The Propaganda for Reform in Proprietary Medicines, Vol. 2 of 2 by Council on Pharmacy and Chemistry (American Medical Association)

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THE PROPAGANDA FOR REFORM

IN

Proprietary Medicines

VOLUME 2

Part I Reports of the Council

Part II Contributions from the Laboratory

Part III Journal Contributions: Proprietary Products

Part IV Journal Contributions: Miscellany

PRESS OF AMERICAN MEDICAL ASSOCIATION, FIVE HUNDRED AND THIRTY-FIVE NORTH DEARBORN STREET,--CHICAGO

1922

COPYRIGHT, 1922 BY THE AMERICAN MEDICAL ASSOCIATION

PREFACE TO VOLUME 2

There were nine editions of the first volume of The Propaganda for Reform in Proprietary Medicines. The ninth edition contained the most important reports of the Council on Pharmacy and Chemistry and of the Chemical Laboratory. It contained also those articles from _The Journal of the American Medical Association_ (up to, and including, 1916) which dealt with the problems of proprietaryship in medicine and the furtherance of rational drug therapy.

The present volume contains similar material covering the period from January, 1917, to April, 1922, inclusive. Like Volume 1, this volume is divided into four parts:

Part I. THE COUNCIL ON PHARMACY AND CHEMISTRY: This section presents the principles and rules which govern the Council in the examination of medicaments, together with articles and reports bearing on the work of the Council, and the most important reports of the Council from 1917 to April, 1922, inclusive.

Part II. THE A. M. A. CHEMICAL LABORATORY: This section, besides presenting the aims and objects of the Association’s Chemical Laboratory, also outlines some of the Laboratory’s work which is of particular interest to physicians.

Part III. CONTRIBUTIONS FROM THE JOURNAL: Proprietary Products: This part contains articles on proprietary medicinal preparations and the methods by which they are exploited, which have appeared in _The Journal A. M. A._

Part IV. CONTRIBUTIONS FROM THE JOURNAL: MISCELLANY: In this section are articles dealing with matters of interest to the medical profession but not coming strictly under the classification of proprietary medicinal preparations.

A comparison of the material that has appeared in Volume 1 of The Propaganda for Reform with that which appears in this volume will reveal the changing conditions in the proprietary medicine field. Many of the reports in the first volume brought out the fact that medicinal preparations were at that time foisted on the profession with false claims of composition; reports of this character are less conspicuous in the present volume. Many of the reports in Volume 2 deal with unwarranted therapeutic claims, especially those advanced for animal organ preparations, serums, vaccines, preparations for intravenous medication, etc. The present volume will also be found of interest in its portrayal of the changed conditions in the proprietary medicine business brought about by the World War.

Special attention is directed to the index in this volume. It is, in effect, a bibliography, including references not only to articles in this book but also (1) to articles which appeared in Volume 1; (2) to articles on the same general subject in _The Journal of the American Medical Association_, and (3) to the articles appearing in the annual reports of the Council on Pharmacy and Chemistry and of the A. M. A. Chemical Laboratory, but not reprinted in either volume of the Propaganda for Reform in Proprietary Medicines.

PREFACE TO VOLUME 1: NINTH EDITION

From time to time _The Journal of the American Medical Association_ has published the reports of the Council on Pharmacy and Chemistry and the Chemical Laboratory, as well as other matter on proprietary medicines. Repeated requests for some of the matter have led to the compilation of “The Propaganda for Reform in Proprietary Medicines,” which, in the present volume, attains its ninth edition.

The seventh, eighth and ninth editions have been compiled on slightly different principles from their predecessors. The therapeutic reform work of _The Journal_ and of the Association’s Chemical Laboratory was at first confined almost entirely to the criticism and analysis of the so-called ethical proprietaries. This was right; the medical profession owed it to the public to combat the nostrum evil within its own ranks.

As the more flagrant evils of the “ethical proprietary” question were mitigated, the Association has turned the light on the more widespread and dangerous “patent medicine” evil. The articles devoted to “patent medicines” or quackery being naturally of greater interest to the general public than to the medical profession, the number of inquiries from laymen regarding various quacks and nostrums has steadily increased. It has been thought best, therefore, to publish separately all of the matter from _The Journal_ relative to quackery and to those nostrums exploited only or chiefly to the public, and to include in the Propaganda for Reform practically none of the matter that is of direct interest primarily to laymen. In one or two instances in which the subjects were of equal interest to the profession and to the public, matter that has already appeared in “Nostrums and Quackery” is also given here; but as a general rule the contents of the ninth edition of “The Propaganda for Reform” are of strictly professional interest. Those physicians who are desirous of obtaining in convenient form the matter dealing with “patent medicines” should order the book “Nostrums and Quackery” or the various pamphlets on the same subjects that have been issued since “Nostrums and Quackery” came from the press.

The ninth edition of “Propaganda for Reform” contains a number of new articles, greatly increasing the size of the book. It also contains one novel feature which greatly enhances its value. The index includes references not only to articles in the book, but also to matter on proprietaries not accepted by the Council on Pharmacy and Chemistry which appeared in _The Journal of the American Medical Association_ and elsewhere. This index makes of this edition of “Propaganda for Reform” a very full work of reference on proprietaries which are undeserving of recognition. It should be understood, however, that not all articles indexed are condemned; some are merely discussed and compared.

RESOLUTION ENDORSING THE WORK OF THE COUNCIL ON PHARMACY AND CHEMISTRY

Presented at the San Francisco Session and Signed by All the Members of the House of Delegates in Attendance

+-------------------------------------------------------------------+ | _Resolved_, We, Members of the House of Delegates of the American | | Medical Association, believe that every effort must be made to | | do away with the evils which result from the exploitation of the | | sick for the sake of gain. Earnestly believing that the continued | | toleration of secret, semisecret, unscientific or untruthfully | | advertised proprietary medicines is an evil that is inimical to | | medical progress and to the best interest of the public, we | | declare ourselves in sympathy with, endorse and by our best | | efforts will further, the work which has been, and is being, done | | by the Council on Pharmacy and Chemistry of the American Medical | | Association in the attempt to eliminate this evil. | +-------------------------------------------------------------------+

TABLE OF CONTENTS

PART I: COUNCIL REPORTS

PAGE

Foreword 1

Official Rules of the Council on Pharmacy and Chemistry 3

The Council on Pharmacy and Chemistry, Present and Future 12

“Accepted by the Council on Pharmacy and Chemistry” 19

Helping the Council 20

Delays in Passing on Products 20

Cooperation of the Pharmaceutical Houses 21

Budwell’s Emulsion of Cod-Liver Oil, Nos. 1 and 2 22

Rheumalgine 23

Gray’s Glycerine Tonic 24

Tongaline and Ponca Compound 26

Alfatone 28

Uricsol 30

Jubol 31

Urodonal 32

Formamint 33

Hydragogin 41

Filudine 41

Lactopeptine and Elixir Lactopeptine 43

Iodum-Miller and Iod-Izd-Oil (Miller’s) 49

Elixir Iodo-Bromide of Calcium Comp. “Without Mercury” and “With Mercury” 52

Lecithin Preparations Omitted from N. N. R. 53

Proprietary Names for Liquid Petrolatum 55

Seng 55

Frosst’s Blaud Capsules 56

Tyree’s Elixir of Buchu and Hyoscyamus Compound 57

Hydroleine 58

Curative Vaccine, Bruschettini 58

Stearn’s Wine 59

Protonuclein and Protonuclein Beta 59

Hydropsin 61

Digitalysatum 63

So-Called Secretin Preparations 64

Has Secretin a Therapeutic Value? 65

Radio-Rem 79

Olio-Phlogosis 79

The Hypophosphite Fallacy 80

Pulvoids Calcylates 85

Sulfuryl Monal 86

Mark White Goiter Serum and Mark White Iodinized Oil 87

Kora-Konia 92

The Therapeutic Value of the Glycerophosphates 93

Hydras 96

Bromin-Iodin Compound 97

Ammonium Hypophosphite Omitted from N. N. R. 98

Alphozone Omitted from N. N. R. 99

Calcium Glycerophosphate and Sodium Glycerophosphate Omitted from N. N. R. 99

Gardner’s Syrup of Ammonium Hypophosphite Omitted from N. N. R. 100

Gluten Products Made by the Kellogg Food Company 100

Iodo-Mangan Omitted from N. N. R. 106

Liquid Albolene 106

Naphey’s Medicated Uterine Wafers 107

Nujol 108

Pulvoids Natrium Compound 108

Saloform 110

Secretogen 110

Iron Citrate Green 115

Aspirin 116

Pil. Cascara Compound-Robins 117

Casta-Flora 118

Firwein 119

Firolyptol Plain and Firolyptol with Kreosote 120

Biniodol 121

Comparative Symptoms Resulting from the Use of Several Oily Suspensions of Red Mercuric Iodid (Mercury Biniodid) 123

Corpora Lutea (Soluble Extract), Parke, Davis & Co. 128

Wheeler’s Tissue Phosphates 129

The Claimed Galactagogue Effects of Nutrolactis and Goat’s Rue Not Substantiated 131

The Alleged Galactagogue Action of Galega and Nutrolactis 131

The Russell Emulsion and the Russell Prepared Green Bone 134

Brom-I-Phos 136

Creosote-Delson and Creofos 137

Triner’s American Elixir of Bitter Wine 139

Trimethol 140

Ferrivine, Intramine and Collosol Iodine 144

Eskay’s Neuro Phosphates 146

K-Y Lubricating Jelly 147

Ziratol 148

Gonosan 150

Alcresta Ipecac 153

Iodeol and Iodagol 154

Capsules Bismuth Resorcinol Compound Not Admitted to N. N. R. 157

Dixon’s Tubercle Bacilli Extract and Dixon’s Suspension of Dead Tubercle Bacilli 158

Formosol 158

Iodolene, a Solution of Iodin in Liquid Petrolatum, Inadmissible to N. N. R. 159

Kalak Water 160

Minson’s Soluble Iodin “Kelpidine” Not Admitted to N. N. R. 161

Nutone 162

Tri-Arsenole, L. O. Compound No. 1 and L. O. Compound No. 2 163

Unctol 166

V-E-M (Schoonmaker Laboratories, Inc.) 166

Hemo-Therapin 168

Venosal 169

Secretin-Beveridge and the U. S. Patent Law 170

The Question of the Stability of Secretin 171

Need for Patent Law Revision 177

Surgodine 180

Medeol Suppositories 181

Guaiodine 183

Several “Mixed” Vaccines Not Admitted to N. N. R. 184

Ophthalmol-Lindemann 189

Silvol Ineligible for N.N.R 189

Katharmon 191

Iodinized Emulsion (Scott) and Creosotonic (Scott) 192

Campetrodin and Campetrodin No. 2 193

Carminzym 194

Phillips’ Phospho-Muriate of Quinine Comp 197

B. Iodine and B. Oleum Iodine 198

B. Iodine Products 199

Antithyroid Preparations (Antithyroidin-Moebius and Thyreoidectin) Omitted from N. N. R. 202

Cephaelin and Syrup Cephaelin-Lilly Omitted from N. N. R. and Syrup Emetic-Lilly Not Accepted 203

Colalin Omitted from N. N. R. 203

Foral 204

Granular Effervescent Bromide and Acetanilid Compound-Mulford 206

Holadin and Bile Salt Mixtures 207

Liquor Santaiva, S. & D., Omitted from N. N. R. 211

Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa Omitted from N. N. R. 211

Methaform Omitted from N. N. R. 212

Pineal Gland, Red Bone-Marrow and Thymus Gland and Their Preparations Omitted from N. N. R. 213

Piperazine and Lycetol Omitted from N. N. R. 214

Stanolind Liquid Paraffin Omitted from N. N. R. 214

Westerfield’s Digitalis Tablets 215

Xeroform-Heyden and Bismuth Tribromphenate-Merck Omitted from N. N. R. 216

Cream of Mustard Refused Recognition 218

“Pluriglandular” Mixtures 218

Cerelene Not Admitted to N. N. R. 219

Collosol Cocaine Not Admitted to N. N. R. 221

Cuprase Not Admitted to N. N. R. 222

Collosol Preparations 223

Pulvoids Calcylates Compound 226

Proteogens of the Wm. S. Merrell Company 227

“Arsenoven S. S.” and “Arseno-Meth-Hyd” 231

Hormotone and Hormotone Without Post-Pituitary 234

Formaldehyde Lozenges 235

Lavoris 237

Medinal 239

Omission of Cotarnin Salts (Stypticin and Styptol) from N. N. R. 240

Micajah’s Wafers and Micajah’s Suppositories 241

Alkalithia 242

Arhovin Omitted from N. N. R. 243

Chloron, Chlorax and Number “3” 244

Elarson Omitted from N. N. R. 248

Iodiphos 249

Mervenol and Armervenol Not Admitted to N. N. R. 249

Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) Not Accepted for N. N. R. 251

Soamin Omitted from N. N. R. 253

Some Mixed Vaccines Not Admitted to N. N. R. 254

Somnoform 255

Tablets Formothalates 256

Triple Arsenates with Nuclein 256

“Anti-Pneumococcic Oil” and the Use of Camphor in Pneumonia 257

Dial “Ciba” 259

Apothesine 260

Eumictine 262

Platt’s Chlorides 263

Anti-Tuberculous Lymph Compound (Sweeny) and Anti-Syphilitic Compound (Sweeny) 266

Syrup Leptinol (Formerly Syrup Balsamea) 268

Formitol Tablets, II 271

Sukro-Serum and Aphlegmatol 273

Supsalvs Not Admitted to N. N. R. 274

Hypodermic Solution No. 13, Iron, Arsenic and Phosphorus Compound Not Accepted for N. N. R. 275

Parathesin Not Admitted to N. N. R. 276

Chlorlyptus 277

Aquazone (Oxygen Water) 290

Coagulen-Ciba Omitted from N. N. R. 290

Ferric Cacodylate Omitted from New and Non-Official Remedies 292

Libradol 293

Helmitol Omitted from N. N. R. 295

Spirocide Not Admitted to N. N. R. 296

Digifolin-Ciba Not Admitted to N. N. R. 298

Some of Loesser’s Intravenous Solutions 299

“National Iodine Solution” Not Admitted to N. N. R. 300

Mon-Arsone Not Admitted to N. N. R. 302

Oxyl-Iodide Not Admitted to N. N. R. 304

Quassia Compound Tablets 306

Toxicide 307

Pil. Mixed Treatment (Chichester) 310

Atophan Omitted from N. N. R. 313

Urotropin Omitted from N. N. R. 316

Styptysate Not Admitted to N. N. R. 318

Lipoidal Substances (Horovitz) Not Admitted to N. N. R. 320

Yeast Preparations and Vitamin B Concentrates 321

PART II: CONTRIBUTIONS FROM THE A. M. A. CHEMICAL LABORATORY

The Chemical Laboratory of the American Medical Association 322

The Work of the American Medical Association Chemical Laboratory 322

Lead in “Akoz” 328

Sodium Acetate in Warming Bottles 329

Anti-Syphilitic Compound (Sweeny) 330

“Ambrine” and Paraffin Films 330

The Stability of Iodine Ointments 337

Iodolene and the Solubility of Iodin in Liquid Petrolatum 344

American-Made Synthetic Drugs--I 344

Standardization of Commercial Bismuth Tribromphenate 348

Standardization of Procain and Examination of the Market Supply 355

Deterioration of Sodium Hypochlorite Solutions 358

Syphilodol 359

Cerelene 362

Dr. De Sanctis’ Rheumatic and Gout Pills 363

Iodex and Liquid Iodex 365

PART III: CONTRIBUTIONS FROM THE JOURNAL: PROPRIETARY PRODUCTS

Iodin in Liquid Petrolatum 367

American-Made Synthetic Drugs--II 369

Nostrums in Retrospect 379

Bell-Ans (Pa-Pay-Ans Bell) 380

Anasarcin and Anedemin 383

Pepto-Mangan 387

Cactina Pillets 391

Ammonol and Phenalgin 393

Fellows’ Syrup, and Other Preparations of the Hypophosphites 395

Shotgun Nostrums 398

Tyree’s Antiseptic and Aseptinol 401

Neurosine and the Original Package Evil 404

Anasarcin Advertising 407

Antimeristem-Schmidt 408

Antiphlogistine 409

“Auto-Hemic Serum” 409

“Autolysin” Advertising 413

“Basic Cancer Research” and “Cosmopolitan Cancer Research Society” 414

Seleni-Bascca 416

Bell-Ans (Papayans, Bell) 418

Campho-Phenique 418

“Cinchophen”: Formerly “Atophan” 419

“Collosols”: An Uncritical English Endorsement 420

Cotton Process Ether 421

Dionol 422

The Eli Products of Eli H. Dunn 424

Glover’s Cancer Serum 425

Glyco-Thymoline and Poliomyelitis 427

Glykeron: Cold Storage Testimonials 428

Gray’s Glycerine Tonic: “Whose Bread I Eat His Song I Sing” 429

Hagee’s Cordial of Cod Liver Oil 429

Hypno-Bromic Compound 430

Intravenous Compound (Loffler) 430

Intravenous Specialties 435

Iodex 436

The William F. Koch Cancer Remedy 437

The Lucas Laboratories’ Products 440

“Phylacogens” 441

Pineoleum Advertising Methods 442

“Proteal Therapy” and Henry Smith Williams 443

Proteogens 445

Pulvane 450

Sal Hepatica 451

Salicon 453

So-Called Secretin Preparations 454

Succus Cineraria Maritima 455

Tekarkin 458

Tyree’s Antiseptic Powder Again 462

Wheeler’s Tissue Phosphates 463

Briefer Paragraphs 465

PART IV: CONTRIBUTIONS FROM THE JOURNAL: MISCELLANY

Albert Abrams, A.M., M.D., LL.D., F.R.M.S. 472

Acetylsalicylic Acid, Not Aspirin 480

The Allied Medical Associations of America 486

“Arsenicals” 491

Beer and Cancer Cures 494

Biologic Therapeutics and Its Commercial Domination 496

Capell’s Uroluetic Test 497

Chemotherapy and Tumors 499

The Direct Sales Company 510

Discoveries and Discoverers 511

“Drug Reform” 513

Drug Therapy: The Fallibility of Textbooks 515

Thomas Webster Edgar 515

Glycerophosphates 520

Influenza Vaccine 520

Intravenous Therapy 522

Iodin Fumes 523

Italian Physico-Chemical Company 524

What is Liquid Petrolatum? 526

The Lowenthal Postgraduate Course 527

Medical Society of the United States 531

The National Formulary--A Review of the Fourth Edition 535

Nonspecific Protein Therapy 536

Willard Ealon Ogden 538

“Patents” 542

Pharmaceutical Barnums 545

The Pharmacopeia 546

Physician’s Stock in Prescription Products 548

Pituitary Gland Preparations 549

Proprietorship in Medicine 550

Philip Rahtjen and His Discoveries 553

Sodium Cacodylate in Syphilis 555

Tablets: Dependability of Dosage 556

Therapeutic Evidence: Its Crucial Test 557

“Vaccines in Toxic Conditions” 560

Vitamins: Their Distribution 561

The William A. Webster Co. and the Direct Pharmaceutical Co. 564

Yeast 566

Briefer Paragraphs 570

THE PROPAGANDA FOR REFORM IN PROPRIETARY MEDICINES

PART I

REPORTS OF THE COUNCIL ON PHARMACY AND CHEMISTRY

FOREWORD

THE COUNCIL ON PHARMACY AND CHEMISTRY

The Council on Pharmacy and Chemistry was established by the American Medical Association primarily for the purpose of gathering and disseminating such information as would protect the medical profession--and thus the public--in the prescribing of proprietary medicinal articles.

The Council consists of sixteen members, fifteen appointed for a term of five years without pay, and the sixteenth, a secretary, who is also the director of the Chemical Laboratory of the American Medical Association (see Part II).

At the present time (1921) the membership is:

C. L. Alsberg, A.M., M.D., Chief of the Bureau of Chemistry, U. S. Department of Agriculture, Washington, D. C.

C. W. Edmunds, M.D., Professor of Materia Medica and Therapeutics, University of Michigan Medical School, Ann Arbor.

R. A. Hatcher, Ph.G., M.D., Professor of Pharmacology, Cornell University Medical College, New York City.

A. W. Hewlett, M.D., Professor of Medicine, Leland Stanford Junior University School of Medicine, San Francisco.

John Howland, M.D., Professor of Pediatrics, Johns Hopkins University Medical Department, Baltimore.

Reid Hunt, M.D., Professor of Pharmacology, Medical School, Harvard University, Boston.

W. T. Longcope, A.B., M.D., New York.

G. W. McCoy, M.D., Director of the Hygienic Laboratory, U. S. Public Health Service, Washington, D. C.

Lafayette B. Mendel, Ph.D., Sc.D., Professor of Physiological Chemistry, Sheffield Scientific School, Yale University, New Haven.

F. G. Novy, Sc.D., M.D., Professor of Bacteriology, University of Michigan Medical School, Ann Arbor.

W. W. Palmer, B.S., M.D., Bard Professor of Medicine, Columbia University College of Physicians and Surgeons, New York.

W. A. Puckner, Phar.D., Secretary of the Council, Director of the Chemical Laboratory of the American Medical Association, Chicago.

L. G. Rowntree, M.D., Sc.D., Professor of Medicine, Mayo Foundation, Rochester.

G. H. Simmons, M.D., LL.D., Chairman of the Council, Editor of The Journal of the American Medical Association, Chicago.

Torald Sollmann, M.D., Professor of Pharmacology and Materia Medica, Western Reserve University School of Medicine, Cleveland.

Julius Stieglitz, Ph.D., Sc.D., Chem.D., Professor of Chemistry, University of Chicago, Vice-Chairman of the Council, Chicago.

At its first meeting in 1905, the Council began examining the proprietary and nonofficial medicinal preparations offered to physicians of the United States, and authorized the publication of a book (New and Nonofficial Remedies) containing descriptions of those preparations which were deemed worthy of the consideration of physicians. It also issued reports (Reports of the Council on Pharmacy and Chemistry) to the medical profession on those preparations which were not eligible. The Council adopted a set of rules by which to measure the eligibility of each preparation for admission to New and Nonofficial Remedies. These rules were designed primarily to protect the public--through the medical profession--against fraud, undesirable secrecy and objectionable advertising in connection with proprietary medicinal articles. The rules originally adopted have been subjected to revision from time to time to meet changing conditions. For the information of those who wish to familiarize themselves with the work of the Council the rules which are now in force (1921) follow this introduction. A summary is also to be found in the article, “The Work of the Council on Pharmacy and Chemistry, Present and Future,” page 12.

Since 1906, the Council has issued New and Nonofficial Remedies annually. In each issue are listed and described the articles that stand accepted on January 1 of the year of publication. The book describes proprietary medicinal articles on the American market that are found eligible under the rules, and also such nonproprietary, nonofficial articles as give promise of therapeutic usefulness, listing the acceptable brands. Articles of a similar character are grouped together, and each group is preceded by a general discussion for the purpose of comparison.

Since 1908, the Council has also issued an annual volume, “Reports of the Council on Pharmacy and Chemistry,” which contains reports on proprietary medicines that were found inadmissible to New and Nonofficial Remedies. The reports issued prior to 1916--and deemed of sufficient interest to physicians--were reprinted in the Propaganda for Reform in Proprietary Medicines, ninth edition (1916). The more important reports issued from 1916 to 1921, inclusive, are in this volume.

While it is the chief function of the Council to investigate and report on proprietary medicinal preparations, its work has broadened so that the Council’s work may now be characterized as a propaganda for the rational use of drugs. Thus, its Committee on Therapeutic Research encourages the investigation of questions concerning the actions of drugs. These investigations are brought together in the “Annual Reports of the Therapeutic Research Committee.” The Council also has a committee on medical teaching which has issued the publication “Useful Drugs,” a concise, but thorough and up-to-date, discussion of the more important drugs. In addition, the Council appointed a committee to prepare an “Epitome of the U. S. Pharmacopeia and National Formulary,” in which are presented those portions of the United States Pharmacopeia and the National Formulary that are of interest to physicians and in which is given a concise statement of the therapeutic usefulness of such drugs and preparations.

OFFICIAL RULES OF THE COUNCIL ON PHARMACY AND CHEMISTRY

[May 1, 1921]

Introduction

The following rules have been adopted by the Council primarily with the object of protecting the medical profession and the public against fraud, undesirable secrecy and objectionable advertising in connection with proprietary medicinal articles.

NEW AND NONOFFICIAL REMEDIES.--The book New and Nonofficial Remedies contains a description of proprietary articles which have been accepted as conforming to the rules of the Council; and of such simple nonproprietary and nonofficial substances as seem of sufficient importance to warrant their inclusion.

MIXTURES.--For admission to N. N. R., proprietary pharmaceutical mixtures must comply with the rules; and, to determine such compliance, they will be investigated by the Council. The Council, however, endorses the principle that prescriptions should be written on the basis of the therapeutic effects of the individual ingredients. For this reason, it includes in this book only those mixtures that present some real advantage. There is also an appendix in which are included those proprietary articles which, so far as known to the Council, comply with the rules, but which do not possess sufficient originality to be admitted to the body of the book.

Rules Governing the Admission of Proprietary Articles to the Book New and Nonofficial Remedies

DEFINITION OF PROPRIETARY ARTICLES.--The term “proprietary article,” in this place, shall mean any chemical, drug or similar preparation used in the treatment of diseases, if such article is protected against free competition, as to name, product, composition or process of manufacture, by secrecy, patent, copyright, or by any other means.

_Rule 1._--COMPOSITION.--No article will be accepted for inclusion in the book New and Nonofficial Remedies, or retained therein, unless its composition be furnished to the Council for publication. For simple substances, the scientific name and the chemical formula, rational or structural, if known, should be supplied. For mixtures, the amount of each active medicinal ingredient in a given quantity of the article must be stated. The general composition of the vehicle, its alcoholic percentage, and the identity of the preservatives must be furnished.

_Rule 2._--IDENTIFICATION.--No article will be accepted or retained unless suitable tests for determining its composition are furnished to the Council. In the case of chemical compounds, these shall consist of tests for identity and purity. In the case of mixtures, description of methods for determining the amount and active strength of the potent ingredients shall be furnished, if practicable.

_Rule 3._--DIRECT ADVERTISING.--No article that is advertised to the public will be accepted or retained; but this rule shall not apply to: (_a_) disinfectants, germicides and antiseptics, provided the advertising is limited to conservative recommendations for their use as prophylactic applications to superficial cuts and abrasions of the skin and to the mucous surfaces of the mouth, pharynx and nose (but not to those of the eye, and the gastro-intestinal and genito-urinary tracts) and provided they are not advertised as curative agents (see comments to Rule 3); and (_b_) nonmedicinal food preparations, except when advertised in an objectionable manner.

_Rule 4._--INDIRECT ADVERTISING.--No article will be accepted or retained if the label, package or circular accompanying the package contains the names of diseases in the treatment of which the article is said to be indicated. The therapeutic indications and properties may be stated, provided such statements do not suggest self-medication. Dosage may be indicated. (This rule shall not apply to remedies with which self-medication is altogether improbable, to vaccines and antitoxins or to directions for administering or applying remedies when similar immediate, heroic treatment is indicated.)

_Rule 5._--FALSE CLAIMS AS TO ORIGIN.--No article will be accepted or retained concerning which the manufacturer or his agents make false or misleading statements as to source, raw material from which made, or method of collection or preparation.

_Rule 6._--UNWARRANTED THERAPEUTIC CLAIMS.--No article will be accepted or retained concerning which the manufacturer or his agents make unwarranted, exaggerated or misleading statements as to the therapeutic value.

_Rule 7._--POISONOUS SUBSTANCES.--The principal label on an article containing “poisonous” or “potent” substances must state plainly the amount of each of such ingredients in a given quantity of the product.

_Rule 8._--OBJECTIONABLE NAMES.--Proprietary names for medicinal articles will be recognized only when the Council shall deem the use of such exclusive names to be in the interest of public welfare. Names which are misleading or which suggest diseases, pathologic conditions or therapeutic indications will not be recognized (the provision against therapeutically suggestive names does not apply to serums, vaccines and antitoxins, or to foods). In the case of pharmaceutical preparations or mixtures, the name must be so framed as to indicate the most potent ingredients.

_Rule 9._--PATENTED PRODUCTS AND PROTECTED NAMES.--If the article is patented--either process or product, or both--the number of such patent or patents must be furnished to the Council. Furthermore, if the name of an article is registered, or the label copyrighted, the registration (trademark) number and a copy of the protected label should be furnished the Council. In case of registration in foreign countries, the name under which the article is registered should be supplied.

_Rule 10._--UNSCIENTIFIC AND USELESS ARTICLES.--No article will be accepted or retained which, because of its unscientific composition, is useless or inimical to the best interests of the public or of the medical profession.

Explanatory Comments on the Rules

INTRODUCTION.--The Council on Pharmacy and Chemistry was established in February, 1905, by the American Medical Association, primarily for the purpose of gathering and disseminating such information as will protect the medical profession in the prescribing of proprietary medicinal articles. In pursuance of this object, the Council examines the articles on the market as to their compliance with definite rules designed to prevent fraud, undesirable secrecy and the abuses which arise from advertising directly or indirectly to the laity. Such articles as appear to conform to the rules are accepted; and their essential features are described in the annual publication of the Council, New and Nonofficial Remedies, if they come within the scope of this book. These descriptions are based in part on investigations made by, or under, the direction of the Council, but in part also on evidence or information supplied by the manufacturer or his agents. Such interested statements are examined critically, and are admitted only if they appear to be in conformity with the evidence. It is, however, manifestly impossible for the Council to investigate the composition of every complex pharmaceutical mixture, or to check thoroughly every therapeutic claim; it can give only an unbiased judgment on the available evidence. Criticisms and corrections of the descriptions which may aid in the revision of the matter will be appreciated. The Council judges an article entirely by the facts in evidence at the time of its admission. Previous noncompliance with the rules (short of _intentional_ fraud) does not prevent the favorable consideration of an article which is in accord with existing rules. Infringements of the rules after acceptance of an article for New and Nonofficial Remedies, or the discovery that the Council’s information was incorrect, will cause the acceptance to be reconsidered. An article is accepted for New and Nonofficial Remedies, and will continue to be included in the book, with the understanding that serious violations of the rules, after acceptance, will be followed by the omission of the article and publication of the reasons for such omission. The Council desires physicians to understand that the admission of an article does not imply a recommendation. Acceptance simply means that no conflict with the rules has been found by the Council.

DURATION OF ACCEPTANCE.--Unless an agreement to the contrary is made at the time of acceptance, articles admitted to New and Nonofficial Remedies will be retained for a period of three years, provided that during that period they comply with the rules and regulations which were in force at the time of their acceptance. At the end of this period all articles will be carefully reexamined for compliance with existing rules. Particular weight will be given to the question as to whether recent evidence has substantiated claims as to the therapeutic value of any preparation, this evidence to consist partly of recent statements in the literature and partly of the general esteem in which the preparation is held by clinical consultants of the Council. The reacceptance of articles after such reexamination shall be for three years unless a shorter period is specified. Any amendments to the rules, by specific requirements or by interpretation, which may be made after the acceptance of an article, shall not apply to such article until the period of acceptance has elapsed. At the end of this period the article, if it is not eligible under the amended rules, will be omitted.

THE SCOPE OF NEW AND NONOFFICIAL REMEDIES AND APPENDIX.--To aid physicians and manufacturers in deciding what articles come within the scope of this book, or, in other words, to enable physicians to recognize whether an article which is not described in New and Nonofficial Remedies has been omitted because it does not need admission or because it has been rejected, the Council furnishes the following more detailed definitions:

OFFICIAL ARTICLES.--_Articles official in the U. S. P. or N. F. do not require consideration by the Council if they are marketed under the official name and if no unestablished therapeutic claims are made for them._

These do not require consideration by the Council, since standards for them are provided in these books, and enforced under the provisions of the federal Food and Drugs Act, except that they may be mentioned for information. Consideration by the Council becomes necessary if a U. S. P. or N. F. product is offered for sale under a name other than that, or the synonyms, under which the product is described in one of these books of standards, or if the proprietors or their agents advance claims that the product possesses therapeutic properties other than those commonly accredited to it.

MODIFICATIONS OF U. S. P. AND N. F. PRODUCTS.--A pharmacopeial or National Formulary product which is marketed under the official title or synonym, but with well-founded claims that its purity, permanence, palatability or other physical properties excel the official standard, may, if no extraordinary therapeutic properties are asserted, be considered as an official article and held not to be within the scope of New and Nonofficial Remedies. When such products are marketed under the claim that they possess therapeutic properties other than those commonly accredited to the U. S. P. or N. F. products of which they are modifications, they shall be subject to the consideration of the Council.

SPECIFICALLY EXEMPTED PREPARATIONS.--Foods, in general, unless marketed with the claim that they possess therapeutic properties shall not, at the present time, be considered by the Council. Mechanical appliances, at the present time, shall not be considered by the Council. Mineral waters (natural), at the present time, shall not be considered by the Council. With these exceptions, products which in the judgment of the Council are manufactured and marketed in conformity to the principles underlying the rules of the Council may be accepted for N. N. R. Products which are manufactured and marketed in a manner which does not conform to the principles underlying the rules of the Council shall not be accepted for N. N. R. The burden of proof in establishing claims for therapeutic properties of products considered by the Council shall lie with the proprietor or, when a foreign made product, with the agent who markets the product in the United States. To avoid confusion with nonofficial substances marketed under similar names, the Council recommends that official substances be prescribed by their official titles, followed by the abbreviation “U. S. P.” or “N. F.”; thus: Tinctura Nucis Vomicae, U. S. P.; Elixir Gentianae, N. F.

SUBSTANCES DESCRIBED IN NEW AND NONOFFICIAL REMEDIES.--In the body of the book will be described simple proprietary substances and their preparations; proprietary mixtures if they have originality or other important qualities which, in the judgment of the Council, entitle them to such place, and important, nonproprietary, unofficial articles. The Council recommends that when the latter are prescribed, they be indicated by the abbreviation, “N. N. R.,” thus insuring to the prescriber the quality of these articles laid down in the book.

PROPRIETARY MIXTURES.--A mixture will be considered as proprietary, and therefore requiring consideration by the Council for admission to the book or appendix, if it contains any proprietary article; if it is marketed under a name which is in any way protected, or if its manufacturer claims for it any unusual therapeutic qualities. Proprietary mixtures which are marketed in conformity with the rules are listed in the appendix of the book under the names of the respective manufacturers. Such proprietary mixtures are not admitted to the body of the book, save in the exceptional cases cited in the preceding paragraph.

NONPROPRIETARY MIXTURES OF OFFICIAL SUBSTANCES.--Since the ingredients of such mixtures do not require consideration by the Council, and since the mixtures are not open to the proprietary abuses which call for the work of the Council, it is not necessary that they should be investigated by the Council. The physician must judge whether such mixtures should be directed to be prepared by the pharmacist, or whether he is justified in ordering a ready-made preparation. If he decides to use a ready-made, nonproprietary preparation, he must judge for himself whether it is marketed in accordance with the rules. It should, however, be remembered that the application of a trade name to any substance makes it proprietary.

Explanation of Rule 1: Composition

_Secrecy Objectionable._--It is not only the right but also the duty of the physician to know the essential composition of what he prescribes; the Council cannot compromise on this proposition.

_Vehicles and Preservatives._--In the case of mixtures, not only the potent ingredient, but also the general character of the vehicle, the presence of alcohol, and the identity of preservatives, or of any other substance, whether added or present as an impurity, must be stated if these can under any circumstances affect the therapeutic action of the article. This, as a rule, does not mean the publication of trade secrets, such as flavors or the details of the working formula.

_Trade Secrets._--Furthermore, trade secrets will not be received as confidential by the Council, since it accepts information only with the distinct understanding that this may be freely published, at its discretion.

_Inspection of Factories._--The Council does not accept invitations to inspect factories; its concern is with the finished products.

On the other hand, the Council requires that the information be complete and accurate as to medicinal ingredients.

_Unofficial Constituents._--Unofficial constituents of proprietary mixtures must be presented by the manufacturer in the regular way and must be acted on by the Council before the preparations containing them can be accepted.

_Fraud._--When it appears that a manufacturer has made a _deliberately_ false statement concerning a product, he is asked to furnish an explanation; and if this is not satisfactory, the product will not be accepted, even if the false statement is subsequently corrected or omitted.

_Testimonials._--The foregoing paragraph applies not only to statements made to the Council, but also to statements furnished to physicians by the manufacturer or his agents, even when these statements are in the guise of testimonials.

Explanation of Rule 2: Identification

In order to avoid errors in the case of chemical compounds, and to guard against adulterations, lack of potency or strength, and the mistaking of one chemical for another, it is necessary to have at hand suitable tests.

_Tests, etc._--If these facts have appeared in the literature, or in standard textbooks, reference to them will be sufficient; but with new chemicals, especially synthetics, the manufacturer or his representatives will be required to supply such tests for publication, as will assure an intelligent opinion of these products.

_Physiologic Standardization._--In cases in which chemical methods of identification are unknown or unreliable, physiologic standardization should be employed. The Council considers the phrase “physiologically standardized” or “assayed” as misleading unless the standard and method are published in sufficient detail to permit of their control by independent investigators. It is evident that when no standard is published, it is impossible to know whether the quality is high or low, and the conscientious manufacturer who sets for himself a high standard is placed on a level with the dishonest or careless one who adopts a low standard. Again, if the process of standardization is not published, it is impossible to learn, without actual trial, the relative value of one preparation as compared with that of another manufacturer, or to confirm or disprove the statements of the manufacturer as to the quality of his product.

_Standardization of Disinfectants and Germicides._--No disinfectant or germicide of the phenol type will be accepted for New and Nonofficial Remedies whose phenol coefficient, determined according to the method of the Hygienic Laboratory, U. S. P. H. S., is not stated on the label of the preparation.

Explanation of Rule 3: Direct Advertising

_Lay Advertising._--The impossibility of controlling the irresponsible claims which are usually made in advertisements to the public, the well-known dangers of suggesting by descriptions of symptoms to the minds of the people that they are suffering from the many diseases described, the dangers of the unconscious and innocent formation of a drug habit, and the evils of harmful self-medication, including the dangers of the spread of many infectious and contagious diseases when hidden from the physician, and similar well-known considerations, are the reasons for discouraging, in the interest, and for the safety, of the public, this reprehensible form of exploitation. Advertising in medical journals, etc., distributed solely to physicians, does not come within the scope of this rule.

_Exceptions._--In the case of subjects on which the public should be instructed, as the use of disinfectants, germicides, antiseptics and foods, advertisements to the public, if not in objectionable forms, are considered admissible. In no case shall such advertisements include recommendations for use as curative agents, nor shall the names of any diseases be mentioned in exploitation. If the preparation is sufficiently toxic to require caution in its use to prevent poisoning, this fact shall be stated on the label. On account of the deplorable results which would follow any abuse of this privilege, the conscientious cooperation of manufacturers and their agents in adhering strictly to the limitations laid down is asked; and for the same reason the acceptance of an article which is so advertised as to infringe on these limitations in any essential way (as by naming diseases or by making false and exaggerated claims) shall be summarily rescinded, and the reasons for such action may be published without notice to manufacturer or agent. A disinfectant, germicide or antiseptic will be accepted for description in New and Nonofficial Remedies, and an article of this class which has already been accepted will continue to be included in New and Nonofficial Remedies only on the explicit understanding by the manufacturer and agent that such infringements of the rule will be followed by deletion of the article and by publication of the facts as described.

_Foods._--We may divide the foods into three groups. The first group contains the ordinary foods, including the well-known breakfast foods. These do not come under the supervision of the Council in any way. The second group includes a large and important class of manufactured products, such as invalid and infant foods, which in a sense stand between the first and third groups. The public has the same interest in these foods that the physician has, and usually is supplied with full information concerning them. While the primary recommendation of these articles should naturally come from the physician, it cannot be expected that their continued use should depend on repeated prescriptions. Information concerning this group of foods would come naturally and properly from a physician, and the collection and dissemination of this information may very properly be included in the work of this Council. As the products in this class are used extensively, it is not proper to limit their advertising to medical journals, but the advertising should be permitted in the lay press so long as it is conducted in a manner compatible with the rules of the Council. The third group includes medicinal foods proper, such as predigested foods. These have a relatively low food value and are characterized by a high alcohol or preservative content. They frequently contain strictly medicinal substances, or food substances for which distinct therapeutic properties are claimed. These products should be used only on the advice of the physician, and the advertisements should be restricted as in the case of ordinary medicines.

_Advertisements in Foreign Countries._--The Council deals primarily, in the interest of the public and of the medical profession, with articles proposed for admission to New and Nonofficial Remedies, and, in determining the status of any article, must take into consideration any statements made regarding it or any method of advertising it employed by the manufacturer or his authorized agents or representatives, whether in this country or abroad. The Council will not regard as within its scope, however, questions concerning the marketing of articles (except the matter of direct advertising to the laity and unwarranted claims or misrepresentations) in any country which has a public body corresponding to this Council.

Explanation of Rule 4: Indirect Advertising

_Matter Distributed Solely to Physicians._--It should be remembered that the sole intent of this rule is to protect the physician, so that in prescribing a proprietary medicine he shall not unconsciously advertise proprietary preparations. The rule imposes no restriction on the legitimate methods of bringing a remedy to the attention of the profession, such as advertising in medical journals, circulars and other printed matter distributed solely to physicians. The rule applies only to the package as it may reach the patient.

_Naming Diseases on Labels._--The naming of diseases on the label or package is not necessary, as is shown by the very large number of proprietary products which have been successfully introduced without resorting to this expedient. This method of popularizing a proprietary remedy with the laity is most objectionable, and should not be tolerated in any form. In general, therapeutic indications should be omitted from the label and package. The Council will not insist on this point, however, when such indications are so given as not to promote self-medication, particularly in diseases which require expert diagnosis and supervision. It will be considered an infringement of the rule if an article be marketed in bottles which have the name of the article blown into the glass, or if otherwise the name or initials or other distinctive mark of the article is permanently stamped on the container, on the article itself, or is on the stoppers or seals. Articles which are marketed in any of these ways are not accepted for New and Nonofficial Remedies. Readily removable labels are not objectionable, nor is the permanent affixing of the firm’s initials or name to the trade package if such initials or name is not suggestive of the article. The Council does not countenance the use of an accepted article for advertising other articles which have not been accepted by the Council.

Explanation of Rule 5: False Claims as to Origin

_Source._--No false or misleading statement in regard to an article can be permitted concerning the source of material from which it is made, or the persons by whom it is made. Some glaring frauds of this nature have been perpetrated in the past, and this rule is intended to prevent such imposition.

Explanation of Rule 6: Unwarranted Therapeutic Claims

_Therapeutic Questions._--This rule insists that the claims of manufacturers or agents concerning the therapeutic properties of their products must be compatible with demonstrable facts. Manufacturers will be held responsible for all statements made or quoted in their advertising “literature” regarding their products. Recognizing the existence of honest differences of opinion on many therapeutic questions, the Council desires to be liberal in the application of this rule. It is natural that a manufacturer should be partial toward his own product, and a moderate degree of emphasis in advertising may not be objectionable. The Council, however, will not admit claims which are neither in harmony with already accepted facts nor supported by acceptable evidence. In doubtful cases the Council considers these questions with the advice and cooperation of its staff of clinical consultants.

_Clinical Evidence._--To be acceptable, the clinical evidence must offer objective data with such citation of authority as will enable the Council to confirm the facts and establish the scientific value of the conclusions drawn. Clinical data are worthless when the author is not cited. The facts on which claims with regard to the value of a remedy are based must have been rendered accessible for investigation and confirmation by disinterested observers, either through publication or through the records of a hospital or other institution.

Explanation of Rule 7: Poisonous Substances

_Poisons._--For the information of the pharmacist or dispenser, and to enable him to safeguard the interests of the patient and the physician, all articles containing such potent agents as the poisonous alkaloids and other organic substances and the salts of some of the metals should have the exact amount of these ingredients which is contained in the average adult dose stated on the label.

Explanation of Rule 8: Objectionable Names

_“Coined” Names._--Many of the abuses connected with proprietary medicines arise from “coined” proprietary trade names. Such names will not be recognized by the Council unless in particular instances the Council shall deem their use to be in the interest of public welfare. In every such exception the burden of proof, both for establishing and for continuing the exception, lies with those who market the product.

_Proprietary (“Trade”) Names When Permitted._--In consideration of the benefits which may come from the discovery of a therapeutic agent, the Council concedes to the person or firm which, by right of discovery, controls such a product the right to name it. The Council will offer no opposition to an arbitrary name for such a new product, provided it is not misleading, therapeutically suggestive, or otherwise subversive of scientific pharmacy and therapeutics. If the discovery that a previously known substance has therapeutic value is deemed of sufficient importance, the Council may recognize a name for such a substance if the name is applied by the person who makes the discovery; or, with the consent of the discoverer or in the absence of any protest on his part, the Council may recognize a name applied by the firm which first makes such a product available to physicians. In the interest of rational drug therapy, the Council recommends that trade names be coined so as to indicate the potent element or constituent.

_Scientific Names._--When the proprietary or trade name for an article is considered insufficiently descriptive of its chemical composition or pharmaceutical character, the Council may require as a condition for the acceptance of such articles that a descriptive scientific name satisfactory to the Council appear on the labels, circulars and advertisements for such an article. For all definite chemical substances it is required that the scientific name be given prominence on the labels, in circulars and advertisements.

_Proprietary Names for Unoriginal Articles._--Proprietary names will not be recognized for articles which are included in the U. S. Pharmacopeia or National Formulary or for unessential modifications of such articles. Neither will proprietary names be recognized for substances or mixtures which are described in medical or pharmaceutical publications. In the marketing of unoriginal articles, the legitimate interests of the producer are fully served by identifying such products by appending the name or initials of the manufacturer or agent, or by the use of a general brand mark. No objection will be made by the Council to the use of such brand marks, provided that in no case shall such mark be used as a designation for an individual article.

For any product which, by reason of the absence or lapse of patent rights or for other reasons, is open to manufacture by more than one firm, the Council reserves the right to select a common name and to provide standards of identity, purity and strength, and then will accept such article only if it is marketed under the title adopted as the N. N. R. name or the name under which such article was introduced (to which may be appended the firm’s identifying mark).

_N. N. R. to U. S. P._--When an article which has been accepted for New and Nonofficial Remedies is admitted to the U. S. Pharmacopeia or National Formulary, it will be omitted from New and Nonofficial Remedies one year after such standardization if the name of such article is used in these standards either as the main title for the product or as a synonym. If the name under which the article is described in New and Nonofficial Remedies is not used in these books of standards, the proprietary preparation will be retained provided the official name is given prominence on the labels and in the circulars and advertisements of such article. When the Council adopts a common name for an article that has been admitted under another name, it will be continued under the older name only on condition that the Council name be given prominence on the label and in the circulars and advertisements for such article.

_Pharmaceutical Preparations and Mixtures._--These, with rare exceptions, are not original in composition and there is seldom any reason why they should be endowed with arbitrary names. On the contrary, it is important that the prescriber should be reminded constantly of their potent ingredients.

_Therapeutically Suggestive Names._--Articles bearing therapeutically suggestive names will not be accepted for New and Nonofficial Remedies, first, because they are likely to lead physicians into prescribing names instead of remedies, and second, because they tend to encourage unwarranted self-medication by the laity. Even if the name is at first apparently meaningless to the public, its meaning will soon be understood because patients soon learn the technical names applied to their diseases and symptoms. The prohibition against therapeutically suggestive names is not applied to serums, vaccines and antitoxins, because the accepted nomenclature of the specific organisms used in their preparation makes this unavoidable and because self-medication with them is improbable.

Explanation of Rule 9: Patents, Trademarks, Copyrights, Etc.

_Protection._--This information is important as a means of determining the legal status of medicinal articles and as an aid to their ready recognition in current publications.

Explanation of Rule 10: Unscientific and Useless Articles

_Unscientific Compounds._--The use of articles which are unessential modifications of official or established nonproprietary articles is unscientific and serves no useful purpose. The Council will not accept products which are scientifically unsound and which, therefore, must be considered useless or inimical to the best interest of the medical profession and the public. This class includes compounds or mixtures containing an excessive number of active ingredients; those compounds or mixtures the components of which are of no probable assistance to one another, and those articles which are of no therapeutic value.

_Unessential Modifications of Official Substances._--The subterfuge of obtaining proprietary rights over an official or established nonproprietary product, by introducing unessential modifications, also tends to confusion and abuses, and such articles will not be admitted by the Council. Essential and important modifications, however, will receive recognition. (The Council interprets the term “established nonproprietary product” as applying to a preparation of any formula which has been published through any recognized or reasonably accessible channel of publication, prior to its appropriation or modification by a manufacturer.) Duplicates of biologic products accepted under the name of the manufacturers will not be accepted under the names of the distributors.

THE COUNCIL ON PHARMACY AND CHEMISTRY, PRESENT AND FUTURE[A]

W. A. Puckner, Phar.D.

Secretary, Council on Pharmacy and Chemistry

[A] Read before the Chicago Medical Society, March 26, 1919.

The World War marked an epoch in the existence of the Council on Pharmacy and Chemistry, as it did in all human endeavors. The information and experience which had been accumulated by the Council during its thirteen years’ existence was drawn on by our government, directly or indirectly, and it also received consideration in England, France,[1] Belgium, Holland,[2] Italy,[3] Sweden and elsewhere. In the world wide readjustment that has begun, the efforts of the Council, past and present, will influence the plans of those who engage in the manufacture or sale of medicines, and, undoubtedly, will be the incentive to the establishment of similar bodies in other countries.

[1] “New and Nonofficial Remedies” in France, Foreign News, J. A. M. A. =71=:1331 (Oct. 19) 1918; =70=:1783 (June 8) 1918.

[2] Nederl. Tjdschr. v. Geneesk. Oct. 5, 1918, p. 1201.

[3] An Italian View of the Proprietary Evil, Foreign News, J. A. M. A. =71=:840 (Sept. 7) 1918; The Council on Pharmacy and Chemistry and the Patriotic Medical League in Italy, ibid. =71=:918 (Sept. 14) 1918.

As secretary of the Council almost from the time of its organization in 1905,[4] and knowing the work of its members and its collaborators, I am firmly convinced that this body has deserved the endorsement and support given it by the American medical profession. I welcome this opportunity to present an outline of the Council’s past activities and to speak of some of the problems of the future, because I feel assured that a knowledge of its endeavor to improve drug therapy will increase the profession’s confidence in the Council and add to the number of its supporters.

[4] Although the Council on Pharmacy and Chemistry was established in 1905, it is likely that only a small percentage of physicians know just what the Council is, or have any conception as to its personnel and its ability to judge the available evidence for proprietary medicaments. The personnel has changed from time to time since 1905. At present its membership is: C. L. Alsberg, A.M., M.D., chief of the Bureau of Chemistry, U. S. Department of Agriculture, Washington, D. C.; R. A. Hatcher, Ph.G., M.D., professor of pharmacology, Cornell University Medical College, New York City; A. W. Hewlett, M.D., professor of medicine, Leland Stanford Junior University Medical School, San Francisco; John Howland, M.D., professor of pediatrics, Johns Hopkins University Department of Medicine, Baltimore; Reid Hunt, M.D., professor of pharmacology, Harvard University Medical School, Boston; Henry Kraemer, Ph.D., professor of pharmacognosy, University of Michigan College of Pharmacy, Ann Arbor, Mich.; W. T. Longcope, A.B., M.D., Bard Professor of the Practice of Medicine, College of Physicians and Surgeons of Columbia University, New York City; G. W. McCoy, M.D., director of the Hygienic Laboratory, United States Public Health Service, Washington, D. C.; Lafayette B. Mendel, Ph.D., Sc.D., professor of physiologic chemistry, Sheffield Scientific School, Yale University, New Haven, Conn.; F. G. Novy, M.D., Sc.D., professor of bacteriology, University of Michigan, Ann Arbor, Mich.; W. W. Palmer, B.S., M.D., associate professor of medicine, College of Physicians and Surgeons of Columbia University, New York City; L. G. Rowntree, M.D., professor of medicine, University of Minnesota Medical School, Minneapolis; Torald Sollmann, M.D., professor of pharmacology and materia medica, Medical Department, Western Reserve University, Cleveland; Julius Stieglitz, Ph.D., Sc.D., Chem.D., vice chairman of the Council, professor of chemistry, University of Chicago, Chicago; G. H. Simmons, M.D., LL.D., chairman of the Council, editor of The Journal of the American Medical Association, Chicago, and W. A. Puckner, Phar.D., secretary of the Council, director of the Chemical Laboratory of the American Medical Association, Chicago.

THE COUNCIL’S ACTIVITIES

Organized primarily for the purpose of putting a stop to false declarations with regard to the composition of proprietary medicines, the Council’s activities have broadened until its work may be characterized as “a propaganda for the rational use of drugs.” The following are some of its activities:

1. _New and Nonofficial Remedies._--This is an annual volume, issued by the Council. It describes both proprietary and nonofficial, nonproprietary drugs which are deemed worthy of consideration by the medical profession. To be admitted to this book, a preparation must comply with certain definite rules which stipulate, in effect, that its composition be declared, that no untrue or grossly exaggerated claims be made for it, and that it shall give promise of having therapeutic value.

With the exception of a few which are still under consideration, the Council has considered all proprietaries whose owners or accredited agents have requested that an examination of the products be made, and it has admitted to the book those which were found eligible. In addition, the Council has examined all of the more important or widely exploited proprietaries, even when no examination was requested, and it has admitted those of this group which were found eligible. Further, the Council has admitted to the book certain nonofficial, nonproprietary articles which seemed to give promise of therapeutic usefulness, and it has established standards for the control of their identity and purity, and listed those brands which complied with these standards.

As most proprietary medicines are of a more or less experimental nature, they are accepted for inclusion in New and Nonofficial Remedies only for a limited time--usually a period of three years. At the expiration of the period of acceptance, each preparation is reexamined and retained only if the claims made for it and the present day knowledge of its value permit this action.

Since manufacturers give information only in regard to their own products, New and Nonofficial Remedies groups together articles of a similar character, and includes in each case a general discussion of the group for the purpose of comparison, not only with each other, but also with the established or pharmacopeial drugs which members of the group are intended to supplant.

In brief, New and Nonofficial Remedies is a book in which are described preparations that have been accepted by the Council. The description includes facts that the physician should have. It is a book that should be in the hands of every physician who prescribes medicines, and who wishes to know the facts regarding the newest remedies. It is the only book in which he can find information relative to proprietary medicines that are worthy of his patronage. It will protect the physician who makes use of it against the wiles of the promoters of products not worthy of his patronage. It would certainly be of use to the physician when the detail man calls on him, for if he were being importuned to prescribe or use samples of something which he had not heretofore used and which he was unable to find in N. N. R., he might ask the detail man why. In the nature of things few physicians are sufficiently expert in chemistry and allied sciences to be able unerringly to discriminate between the true and the false as regards many preparations that he is asked to prescribe.

2. _The Reports of the Council on Pharmacy and Chemistry._--A medicament may be inadmissible to New and Nonofficial Remedies for various reasons; it may be worthless or irrational, its composition may be secret or indefinite, or it may be exploited under exaggerated or unwarranted claims or in a way otherwise detrimental to the public health and scientific medicine. Of these various reasons which make an article unacceptable, the manufacturer obviously may remove all except the first, viz., worthlessness or irrationality. Consequently, a preparation which has been presented for admission is not definitely rejected until after its proprietor has been informed of the objections to his product and has failed to bring the preparation in conformity with the Council’s rules. When a preparation is found definitely inadmissible to New and Nonofficial Remedies, that is, when the proprietor cannot or will not make it acceptable, the Council prepares a report for publication. These reports are sent for publication to The Journal of the American Medical Association, and later published in the annual “Reports of the Council on Pharmacy and Chemistry.” The more important of these are also published in the book, “The Propaganda for Reform in Proprietary Medicines.”

3. _Useful Drugs._--Since the domination of proprietary medicines, which was retarding medical advance and threatening therapeutic chaos, had been made possible only by the insufficient and inefficient instruction given in medical schools in subjects having to do with drugs, the Council appointed a Committee on Medical Teaching to secure the cooperation of teachers in materia medica, pharmacology and related branches. This committee has endeavored to effect an improvement in these courses of instruction. One of the results of this work was the selection of a list of drugs to serve as a basis of materia medica instruction and thus insure that medical students shall be better informed with regard to the therapeutic worth of a few well established drugs, rather than, as in the past, leaving school with a smattering of knowledge about many drugs. The outcome of these efforts is the publication of “Useful Drugs,” a concise but thorough and up-to-date discussion of the actions, uses and dosage of the more important drugs. The list of drugs presented in this book is now the basis of instruction in many schools; and many state examining boards are confining their materia medica questions to the drugs in the list.

4. _Epitome of the U. S. P. and N. F._--To encourage the use of official drugs and to make available an estimate of their therapeutic value, a committee of the Council prepared an abstract of the U. S. Pharmacopeia and the National Formulary. This booklet, the “Epitome of the U. S. Pharmacopeia and National Formulary,” presents those portions of these books which are of interest to physicians, and in addition, gives a concise statement of the therapeutic usefulness of the drugs and preparations described in them.

5. _Patent Law Reform._--Some of the worst abuses connected with the exploitation of proprietary medicines have been made possible by our patent and trademark laws and the method of their interpretation and enforcement. The Council, therefore, appointed a committee to study these laws and the various propositions advanced for their improvement. This committee has published, from time to time, reports on various phases of our patent and trademark laws and recently summarized these reports in an address[5] sent to the commissioner of patents and the interested congressional committees. It is hoped that by means of these reports physicians will be enabled to give intelligent support to a revision of the patent and trademark laws when legislation is proposed.

[5] Need for Patent Law Revision, A. M. A. Council on Pharmacy and Chemistry Reports, 1917, p. 130.

6. _Therapeutic Research._--Through its Committee on Therapeutic Research, and with the aid of funds provided by the Board of Trustees of the American Medical Association, the Council has encouraged the investigations of questions which might lead to a better understanding of the action of drugs. These investigations are brought together in the annual reports of the Committee on Therapeutic Research, and are an important addition to our knowledge of drug action.

In the past, the Council has in particular encouraged the investigation of the action and therapeutic value of widely used drugs regarding which our knowledge is still unsatisfactory. These investigations have included a study of the action of strychnin in cardiac disease, a comparison of the action of absorption and excretion of iodid preparations, a study of the pharmacology of the opium alkaloids, etc. Appreciating that the available knowledge of proprietary drugs is one sided in that it comes from investigations made by interested pharmaceutical concerns or from investigations made at the instigation of these firms, the Council is planning a comprehensive study of many of the synthetic drugs that have gained some vogue during recent years.

THE FUTURE

Medical research, and efficient instruction in therapeutics and related subjects, spell a diminishing influence of commercial medicine over rational therapeutics. The fact that the present shortage of German synthetics has not handicapped seriously the practice of medicine should be a lesson to American physicians for many years to come.

On the other hand, it must be remembered that the publicity given to the reports of the Council and to other contributions toward rational therapeutics by The Journal of the American Medical Association, the journals of the state organizations, and a few personally owned publications, is as nothing when compared with the persistent and wide publicity given to the propaganda of the proprietary houses. While a report setting forth the objections to a proprietary is published but once, the firm’s laudatory pronouncement goes forth again and again until the Council’s report is completely overwhelmed and forgotten. Manufacturers of proprietaries not only keep in close touch with the practicing physician by means of house organs, special “literature,” or by traveling representatives, but many of the firms, through the meritorious lines of pills, tablets, tinctures, etc., which they put out, also obtain and hold the good will and confidence of a large proportion of the medical profession.

Furthermore, some of these firms may gain the confidence of the medical profession through these high grade pharmaceuticals, and certain of their proprietaries may be of distinct therapeutic value but may fail to be acceptable for New and Nonofficial Remedies, because they do not conform to the reasonable rules of the Council. These firms do not find it profitable to force the sale of their regular nonproprietary pharmaceuticals by unwarranted claims or objectionable methods, yet they may consider it good business to market certain proprietary products by means of claims which are extravagant and without warrant, and which will lead to indiscriminate use by the profession and the public. In a word, where there is one dollar spent on behalf of rational medicine, thousands are spent for the purpose of increasing the sale of preparations which directly or indirectly are a detriment to the public health, to medicine, and to the pocketbook.

That the day of the secret nostrum of the pseudo-chemical company is not yet past is well illustrated by the recent introduction of an asserted arsphenamin preparation called “Syphilodol.” The A. M. A. Chemical Laboratory proved one form of this asserted French discovery to be essentially a pill of mercurous iodid. Another form of Syphilodol (for intravenous administration) had all the characteristics of water, and appeared devoid of any potent ingredient. Though the advertising sent out by the promoters in regard to its composition was suspiciously evasive, the _Illinois Medical Journal_ published an advertisement of “Syphilodol,” which, possibly by a coincidence, appeared above an appeal to “Our Readers” to use wares advertised in that journal.

While such rank deceptions as “Syphilodol” are not common, there are more subtle deceptions that are even more dangerous. Types of widely exploited remedies of today comprise so-called ethical specialties composed of well known and established drugs (with “jokers” hidden away somewhere) or preparations which have a plausibly fascinating pseudo-scientific background of radiant energy, colloidal chemistry, nonspecific protein reaction, or something of the sort. The latter class of preparations in particular appeal to physicians who are striving hard to keep pace with modern science. Exposure of their fallacies requires most careful consideration on the part of the Council.

Progress toward a rational and scientific drug therapy must continue, and, therefore, it is important that the Council on Pharmacy and Chemistry should continue to make the investigation of proprietary medicines its chief work. Investigation of a proprietary medicine, however, and a report of such investigation are of value in direct ratio only to the number of physicians who read the report, endorse it and act in accordance with its conclusions. In order that you may determine to what extent those preparations which are admitted to New and Nonofficial Remedies deserve your interest and confidence, it will be worth while briefly to outline the rules which govern the Council in the admission of articles to New and Nonofficial Remedies.

RULES GOVERNING THE ACCEPTANCE OF ARTICLES FOR N. N. R.

_Composition._--Rules 1 and 2, and in a measure 5, 7, and 9, deal with the composition of articles. Rule 1 requires that the quantitative composition of an article be furnished the Council for publication. Rule 2 requires that the manufacturer furnish methods whereby the composition of products that are definite chemicals or the potent constituents of mixtures may be determined. The Council does not require that the process of manufacture of an article be declared unless this becomes necessary in order to judge its composition. Rule 5 requires that statements with regard to the origin and source of an article shall be truthful. Rule 7 requires that for the guidance of the dispenser, the amounts of poisonous ingredients of a preparation be placed on the label. Rule 9 requires that if patent rights are claimed for a product, the Council be informed on this point.

That it is not only the right but also the duty of the physician to know the composition of what he prescribes for his patients is so generally admitted that few have attempted to market preparations of avowedly secret composition. When the Council first began its work, it was common to see chemical formulas or statements of composition published which a chemist or a pharmacist was able to pronounce at a glance as impossible.[6] It was not unusual to find that the promoter published “a formula” for his preparation, rather than “the formula.”[7] Today, however, a more prudent, if not more honest, course is pursued. This gives a “formula” which is correct so far as it goes, but which fails to divulge the actual composition of a preparation. When it is considered that many physicians are not any too conversant with the chemistry and pharmacy of drugs, it is not surprising that some administered the proprietary “Venarsen,” regarding the composition of which they had only the vague statement that it was “... a comparatively nontoxic organic arsenic compound, 0.6 gm. representing 247 mg. (3-3/4 grains) of metallic arsenic in chemical combination ...” in the belief that a preparation similar to that first introduced as salvarsan was being used. That “Venarsen” contained its arsenic as sodium cacodylate--a notoriously inactive state of combination--does not justify the intravenous administration of a drug of unknown composition.

[6] Puckner, W. A.: The Abuse of Chemical Formulas, Reports A. M. A. Chemical Laboratory =3=:7, 1910.

[7] The Formula for Glyco-Thymoline, J. A. M. A. =52=:147 (Jan. 9) 1909.

While for the present it probably is not feasible to require, on the part of those who manufacture medicinal preparations, such professional training as is required of those who prescribe and those who dispense them, it certainly is not too much to require, as does Rule 2, that a manufacturer shall be able to demonstrate that his preparation has the composition claimed for it. Nor is it sufficient for him to know that the ingredients claimed as constituents were used in the manufacture. The fallacy of his method of reasoning was furnished by the physician who reported that he had personally added the required amount of mercuric iodid for a batch of “Mercol” which, nevertheless, was devoid of mercury.[8] Acceptance of this rule by manufacturers will permit physicians to have a more accurate knowledge of the composition of preparations such as “Taka-Diastase”[9] and “Iodeol”.[10]

[8] Hunt, Reid, and Seidell, Atherton: Howell’s Mercol, J. A. M. A. =52=:225 (Jan. 16) 1909. Howell’s Mercol Again: Another Analysis Fails to Reveal the Presence of Mercury, J. A. M. A. =52=:1595 (May 15) 1909.

[9] Taka-Diastase and Liquid Taka-Diastase: Report of the Council on Pharmacy and Chemistry, J. A. M. A. =59=:50 (July 6) 1912.

[10] Iodeol and Iodagol: Report of the Council on Pharmacy and Chemistry, J. A. M. A. =69=:1725 (Nov. 17) 1917.

A requirement similar to that of Rule 5 is contained in the Federal Food and Drugs Act and so no objection has been made to this rule which requires a truthful statement of the origin and source of articles. An illustration for the need of the rule was furnished by the one time popular “Vin Mariani”[11] which, though very French in its makeup, was found to be largely of the “made in the United States” variety of tipple.

[11] Vin Mariani: Official Report of Council on Pharmacy and Chemistry--With Comments, J. A. M. A. =47=:1751 (Nov. 24) 1906.

The issuance of a patent for a medicinal product does not prove that such a product presents a discovery or that its owner is entitled to a temporary monopoly, yet it is only fair to physicians and to other manufacturers that notice of such patent claims be given. Hence, the Council publishes in New and Nonofficial Remedies the information bearing on this point.

_Lay Advertising._--Rules 3 and 4 provide against the recognition of articles that are advertised to the public directly or indirectly, exempting from this requirement preparations which the Council believes are safe to be so advertised.

It has been held with some justice that certain shotgun proprietaries are purchased by the public with as much circumspection as they are ordered by those physicians who are addicted to the prescribing of them; but even the exploiters of these mixtures have not denied that the use of medicines by the public on its own initiative is surrounded with many objections. Hence the practice of self medication should not be encouraged by prescribing or using those preparations advertised for public use.

The only objection to the rule has come from a firm which markets a brand of liquid petrolatum, the Standard Oil Company of Indiana. The Council has considered the question of exempting simple laxatives from the restrictions of Rules 3 and 4 as it has exempted antiseptics and nonmedicinal foods. The conclusion was, however, that the excessive use of a simple laxative like a liquid petrolatum, when prompted by newspaper exploitation, is likely to be detrimental to health by overuse as well as by misuse.

The indirect advertisement to the public, which Rule 4 provides against, has been the means of inducing the extensive lay use of “Antikamnia,” “Bromidia” and “Fellows’ Syrup.” Naturally Rule 4 has been bitterly opposed by most proprietary firms. Arguing that many physicians dispense their own drugs, pharmaceutical firms have insisted that every medicinal preparation should bear on its label, not only the dose of the preparation, but also a statement of the diseases in which the article is indicated. Whether manufacturers anticipated the profession’s resentment toward the claim that physicians determine the treatment and perhaps the diagnosis by means of the statements on labels, or because the Shirley amendment to the Food and Drugs Act makes the proprietor responsible for therapeutic claims on the label of a medicine, it is a fact that fewer preparations than formerly need to be refused on account of infringement on this rule. In fact, some thoroughly objectionable proprietaries make a show of being “ethical” by omitting all therapeutic discussion from the labels of their preparations.

_Therapeutic Claims._--Rule 6 makes ineligible for New and Nonofficial Remedies any articles regarding which the manufacturer or his agents make unwarranted, exaggerated or misleading statements as to the therapeutic value. Recognizing the long established custom of therapeutic exaggeration, it has been most difficult to determine the degree of conservatism which might with fairness be required of a manufacturer. In view of the common acceptance of individual impressions as dependable evidence, it is often almost embarrassing to declare as incompetent the statement of some well meaning and all-too-kind-hearted doctor. However, as the pitfalls of haphazard clinical trials become better known and the physician’s mistrust of glowing accounts of marvelous cures more outspoken, the manufacturers’ claims will be more moderate.

_Nomenclature._--Were it possible to enact and enforce a law which would oblige manufacturers to sell their medicinal products under properly descriptive names and which would make it illegal for a physician to prescribe it unless he understood the meaning of such properly descriptive titles, then the Council might safely disband. In that case, physicians would discontinue the use of most proprietary preparations in favor of established drugs, and successful newcomers might each year be counted on the fingers of one hand. Such a rational nomenclature is not to be thought of, at least in our generation. Rule 8 requires that the name of an article shall not be misleading, that it shall not be therapeutically suggestive, and that established drugs shall not be disguised by fanciful titles. It recognizes the right of discoverers of new drugs to name their discoveries, and interposes no objection to arbitrary names for such products so long as such names are not misleading or do not suggest the therapeutic uses of the products. As the rule provides against the recognition of coined names for established nonproprietary drugs, so it requires that mixtures of drugs shall bear names descriptive of their composition. It would be a long step forward if physicians would recognize more fully the objections to the many proprietaries which have, as their only point of originality, a non-descriptive name for an old drug or a mixture of well known drugs. It is an encouraging sign that the Federal Trade Commission, when issuing licenses for the manufacture of synthetic drugs introduced under German patents, stipulated that all manufacturers authorized to make a given drug shall use the same name for it.

_Irrational Articles._--Rule 10 provides against the recognition of an article which, because of its composition, is useless or inimical to the best interests of the public and medical profession. This rule excludes medicaments which (1) are unessential modifications of established articles, or (2) are of no therapeutic value or (3) are irrational. With regard to the recognition of mixtures or compounds containing two or more active ingredients, the Council requires that the manufacturer establish the rationality of its combination. The rule has prevented the recognition of many unnecessary so-called ethical specialties. Though a mass of testimonials was often to be had for them, these contained no evidence that the mixture was superior to its potent ingredient, or that its therapeutic effect had been determined. That there is a healthy tendency to use single drugs for their definite action and to discard combinations (be they shotgun proprietaries or “mixed” vaccines) is perhaps best illustrated by the fact that at the last revision of the U. S. Pharmacopeia a considerable number of complex antiquities were omitted from that book.

Feeling confident that this meets with the endorsement of the profession, the Council is examining more critically the evidence for the value of pharmaceutical mixtures.--(_From The Journal A. M. A., May 10, 1919._)

“ACCEPTED BY THE COUNCIL ON PHARMACY AND CHEMISTRY”

Under the caption given above, the _Journal of the Missouri State Medical Association_, in its July issue, speaks editorially as follows:

The Council on Pharmacy and Chemistry of the American Medical Association is a department of our national organization that has not received the plaudits and encomiums of a wildly joyous medical profession nor the grateful praises of the enthusiastic manufacturer of pharmaceuticals. The Council seems indeed to be the unloved child of the entire family of subsidiary bodies of the association. Perhaps the reason for this may be found in the character of its duties, for the Council must expose fraud, sometimes in high places, and protect the physician from being duped by avaricious persons and by persons who are themselves sometimes the victims of their own credulity. It thus happens that the sale of some proprietary article previously held in high esteem by the practitioner proves valueless, perhaps even fraudulent. The practitioner, however, may have credited much of his success in treating certain conditions to that preparation and the maker has had success in accumulating dollars from its sale and both parties emit a loud and vicious roar against the Council, because they both lose money. Nobody wants to be “protected” against making money--make it honestly, if possible, but make it--but this black sheep among the Councils of the American Medical Association insists on their making their money honestly!

Despite many obstacles thrown into its path, the Council on Pharmacy and Chemistry has serenely pursued its allotted tasks, corrected its mistakes, improved its methods, and today stands as the only medium to which the honest physician may turn for information--not misinformation--regarding proprietary articles. During the war the Council and the chemical laboratory were in close cooperation with the Surgeon-General’s Office, testing and investigating every article offered to the government for the treatment of sick soldiers. The variety and the number of fakish and fraudulent stuff offered to the Surgeon-General was a pitiable exhibit of the mental gymnastics of some people. Just now the Council and the laboratory have a new and important field before them, i. e., to protect the physicians against worthless and useless serums, vaccines and synthetics. It will be the Council’s unpleasant duty to expose the fraudulent and useless among these articles and stamp truth on those found worthy.

We seem to have wandered from the topic in our caption, but not so in reality, because the burden of our thought is to lend our influence to the spread of the motto of the Advertising Clubs of the World, namely, “Truth in Advertising.” It is our purpose to stimulate a larger degree of enthusiasm for the work of the Council on Pharmacy and Chemistry and the Chemical Laboratory, a more generous flow of inquiries concerning articles unfamiliar to the physician, and particularly to urge that the words “Accepted by the Council on Pharmacy and Chemistry of the American Medical Association” be printed on the label and on all advertising circulars of proprietary articles that have been admitted to New and Nonofficial Remedies. Then, when pamphlets and circulars are received by physicians they will read the statements of manufacturers with sympathetic understanding and with full confidence in the verity of the declarations. The importance of creating just that sort of receptivity in the mind of the prospective buyer is so well known to the astute publicity expert that it is needless for us to dwell on its advantages. Every proprietary article advertised in our journal, in The Journal of the American Medical Association, and in the other state association journals, as well as in several well-edited privately owned journals, does in effect say to the reader that the articles so advertised are accepted by the Council because only proprietary articles so accepted are accepted by us. The fact is further acknowledged when these firms are permitted to exhibit their goods at our annual sessions for again the rule is enforced that only proprietary articles which have been approved by the Council may be placed on display.

Why not complete the circle of ideas--it would not be a “vicious circle”--by printing on labels, in advertisements and circulars, the words: “Accepted by the Council on Pharmacy and Chemistry”?--(_From The Journal A. M. A., Aug. 2, 1919._)

HELPING THE COUNCIL

If they were built that way, the members of the Council on Pharmacy and Chemistry of the American Medical Association might become discouraged at the apparent indifference of many members of the medical profession to their efforts. There are many physicians who, while figuratively patting the Council on the back, actually do nothing to aid its efforts. On the other hand, there are men in the profession who give the Council active support instead of merely passive appreciation. The letter that follows was written by such a man to a pharmaceutical concern:

I am receiving circular advertising from you concerning ---- ---- solution, and I am writing to suggest that until these products have been approved by the Council on Pharmacy and Chemistry of the American Medical Association, you are wasting your postage on the practice. Aside from the fact that these products do not appeal to me personally, I feel that I am not in a position to judge the value of such products and I depend entirely on the large clinical opportunities of the Council on Pharmacy and Chemistry of the American Medical Association in addition to their laboratory facilities, in such matters as these. I may, therefore, with all due respect, suggest that ... it will pay you to eliminate my name from your mailing list.

The members of the Council on Pharmacy and Chemistry are working week in and week out without remuneration. Few appreciate how much these scientific men are doing for rational therapeutics; fewer still realize how much has been accomplished through their efforts, or how much more could be accomplished if every physician who at least believes in the work of the Council would give it his full support.--(_Editorial from The Journal A. M. A., Nov. 6, 1920._)

DELAYS IN PASSING ON PRODUCTS

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

The Council frequently receives inquiries--some of them accompanied by expressions of impatience--concerning articles, reports on which appear to be delayed. It therefore seems advisable to make a statement of some of the factors which enter into this problem.

The Council fully realizes the importance of giving prompt information to the profession with regard to proprietary medicines under consideration. It therefore acts as soon as sufficient information is available to justify a definite judgment, and publishes its conclusions as soon as possible. When adequate information is available at the outset, there is no delay in the publication of the Council’s conclusions.

Unfortunately, but very naturally, there are many cases in which the information available at the time the product is submitted is not sufficient to justify the Council in coming to definite conclusions for or against the preparation. In some cases the manufacturer possesses the required information, but to obtain it from him takes time; in other cases the manufacturer does not possess the information--perhaps he did not realize the inadequacy of his evidence until the subject was brought to his attention by the Council.

Such cases might be dealt with in either one of two ways: The Council might at once reject the article because the claims for it are not supported by adequate evidence; or, the Council might suspend judgment and give the manufacturer an opportunity to supply the information.

The first method--immediate rejection--would obviously be felt by manufacturers as a hardship. To afford the fullest possible opportunity for the presentation of the case, the Council follows the second method; that is, it suspends judgment and withholds publication of a report until reasonable time has been afforded for furnishing the required information, provided the manufacturer or agent appears to be making honest and diligent efforts to supply it. The collection and compilation of such information is sometimes a lengthy process, especially when the products are of foreign manufacture.

Although it would be easier for the Council to render an immediate decision than to assist manufacturers to supply the data necessary for the formation of an authoritative judgment, the Council cannot yield to importunities for hasty action. It must rely on the medical profession to bear in mind that the character of a product under consideration by the Council has not yet been determined. The Council holds that, during this stage, a product is suitable, at most, for experimental use.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 119._)

COOPERATION OF THE PHARMACEUTICAL HOUSES

Report of the Council on Pharmacy and Chemistry

In reply to the suggestion made last year by President Bevan that there should be closer cooperation between the large pharmaceutical houses and the Council on Pharmacy and Chemistry, the Council submitted to the Board of Trustees of the American Medical Association the statement which appears below:

“COOPERATION OF THE PHARMACEUTICAL HOUSES: At the opening meeting of the House of Delegates last year, President Arthur Dean Bevan suggested the desirability of greater cooperation between the large pharmaceutical houses and the Council on Pharmacy and Chemistry. The need of such cooperation has been recognized by the Council from the first. In no one direction has the Council made greater effort than in its endeavor to secure the fullest cooperation of the various pharmaceutical houses. The difficulty has been, and always must be, the fundamental antagonism between objectives that are largely commercial on the one hand and purely scientific on the other. Nevertheless, the Council has always believed--and has acted on the belief--that there is a possible middle ground wherein the interests of therapeutics would not be injured but would go hand in hand with a commercial development based on enlightened self-interest.

“The profits to be made by a pharmaceutical house from the sale of a staple drug--a pharmacopeial, National Formulary, or nonproprietary preparation--which enters into free competition with other drugs of the same kind, are moderate; the profits to be made from the sale of a proprietary medicine on which the manufacturer holds a monopoly are usually large--sometimes enormous. There are, broadly, two kinds of proprietary preparations advertised to physicians: One represents laborious research ending in the production of a new medicinal chemical; this product can be patented and the manufacturer can obtain a seventeen-year monopoly on its manufacture and sale. The other represents no research but comprises simple mixtures--frequently of the “shotgun” variety--of well known pharmaceuticals, or biologic products sold under trade names. As these do not represent anything new or original the manufacturer is unable to obtain a patent, but by means of the trade name he can and does obtain a perpetual monopoly. This, from a business standpoint, is more valuable than the limited monopoly granted by a patent. It is not surprising that proprietary remedies of the latter type flourish so long as physicians unthinkingly accept and prescribe them solely on the manufacturer’s valuation.

“The Council has practically the undivided support of manufacturers of medicinal chemicals; that is, of proprietaries of the first mentioned type. But pharmaceutical firms which have found it profitable to promote proprietaries of the second type--“specialties,” unscientific or ordinary mixtures of pharmaceuticals or biologic products sold under trade names--have not supported the Council.

“When the Council was organized, it was hoped and believed that all the large pharmaceutical houses would find it possible and desirable, if not actually more profitable, to shape their business methods so as to make their proprietary and other articles conform to those conservative standards on which the Council bases its rules, and thus render such articles acceptable for New and Nonofficial Remedies. It soon developed, however, that the methods of the pseudochemical companies, whose sales propaganda in the interest of unscientific nostrums with its attending damage to scientific medicine had led to the establishment of the Council, had found their lodgment in most of the pharmaceutical houses. It was a genuine disappointment to the Council to find that some of the large and old-established firms were not only unwilling to cooperate with the Council, but in many instances exhibited a definite antagonism to the Council’s work.

“The object--and duty--of the officers of pharmaceutical houses is primarily to pay dividends to their stockholders. Through skilful advertising or the persuasiveness of “detail men,” they are able to induce physicians to prescribe their controlled products, on which there are large profits, even though such products have not only not been accepted by the Council, but in many instances, have been disapproved. Is it any wonder that concerns which put out such products are indifferent or openly antagonistic to the work of the Council? The matter is largely one of business policy. When the medical profession as a unit will support the Council in its work, then such firms will find it good business policy to accede to Dr. Bevan’s suggestion--but not before.”

Evidently the problem resolves itself into this: The Council, constituted of scientific men, working without remuneration in the interest of scientific medicine and the medical profession, expects--and rightfully--the cooperation and support of the members of that profession. What is needed, therefore, is the active, sympathetic cooperation of physicians; the cooperation of pharmaceutical houses will follow as a matter of course. (_J. A. M. A._ =74=:1235 [May 1] 1920.)

The following is the recommendation of the Reference Committee to which the Report of the Board of Trustees was referred: “A perusal of the Trustees’ Report, ‘Cooperation of the Pharmaceutical Houses’, is well worth the time of every member of the profession, and your committee would emphasize the statement of the Trustees: ‘The Council, constituted of scientific men, working without remuneration in the interest of scientific medicine and the medical profession expects--and rightfully--the cooperation and support of the members of that profession. What is needed, therefore, is the active sympathetic cooperation of physicians; the cooperation of pharmaceutical houses will follow as a matter of course.’

“Your committee would go still further and move that a vote of thanks of the House be extended to those scientific men who have devoted so much valuable time to the welfare of the Association.”

(_J. A. M. A._, =74=:1322 [May 8] 1920; _from Reports of Council on Pharmacy and Chemistry_, 1920, p. 56).

W. A. Puckner, Secretary.

BUDWELL’S EMULSION OF COD-LIVER OIL, NOS. 1 AND 2

Report of the Council on Pharmacy and Chemistry

The Budwell Pharmacal Company, Lynchburg, Virginia, which markets these preparations, claims that “No. 1” contains cod liver oil, “Iodide of Arsenic,” “Iodide of Calcium,” and “Iodide of Manganese.” “No. 2” is said to contain in addition to the ingredients of No. 1, creosote carbonate and guaiacol.

It is known that arsenous iodid is decomposed by contact with water. It is recognized that creosote carbonate is unstable and prone to liberate creosote. Iodide of manganese not being official, the supply on the market is not controlled in any way: Tests of purity are not prescribed by the Pharmacopeia, the National Formulary, New and Nonofficial Remedies or other books of standards. Therefore doubt must be expressed as to the accuracy of the formulas as given. The Council cannot accept such statements of composition without further evidence.

“No. 1” is commended for use in

“Chronic Rheumatism, Glandular Swellings, later forms of Syphilis, convalescence from Scarlet Fever, La Grippe and Malaria, Chronic Malarial Infection, Marasmus, Joint or other suppuration of standing, diseases of skin, chorea, anaemia, neurasthenia, obstinate neuralgia, scrofulous affections in general, and diarrhea or dysentery (subacute or chronic) in childhood.”

“No. 2” is said to be

“Prepared especially for the treatment of Chronic Throat, Nasal, Bronchial and Pulmonary Diseases.”

In the advertising circular statements regarding the various ingredients of Budwell’s Emulsion are quoted from obsolete text books. These statements, for the most part, do not represent modern opinions on the subject. For instance, the circular praises the action of guaiacol as eliminated directly by the lungs, thus exerting a beneficial local effect and causing bacilli to diminish in numbers or to disappear. All of this is directly contradicted in authoritative modern publications on pharmacology, which hold that the excretion of guaiacol by the lungs is infinitesimal and its action on bacilli is nil. The Council held the preparations in conflict with its rules as follows:

1. Many of the therapeutic claims are exaggerations.

2. The method of exploitation amounts to an indirect invitation to the public to use these preparations as “consumption cures.”

3. The preparations are unscientific, they constitute a reprehensible invitation to uncritical prescribing and their use is inimical to the best interests of the profession and the public. It is difficult to imagine in what conditions such a combination would be indicated. These preparations are a remnant of the days of polypharmacy. Their use is not in keeping with present medical thought and practice.--(_From The Journal A. M. A., Feb. 20, 1915._)

RHEUMALGINE

Report of the Council on Pharmacy and Chemistry

Rheumalgine (Eli Lilly & Co., Indianapolis) is put up both in tablet form and as a liquid. Each tablet, or teaspoonful of the liquid, is said to contain:

“Strontium salicylate from Natural Oil 5 gr. Hexamethylenamin 2 gr. Colchicine 1/200 gr.”

The advertising matter contains several statements regarding the individual ingredients to which objection must be made.

It is claimed (quoting from Hare) that strontium salicylate

“... is not so disagreeable to the taste as the corresponding sodium salts, and more important still, it is far less apt to disorder the stomach.”

“Taste” is a difficult subject to dispute; but in the experience of the referee, patients object more to the strontium than to the sodium salt. No evidence is submitted to prove that the strontium salt is less apt to disorder the stomach. In observations made under the direction of the referee, the nauseant and emetic doses are about the same as, or even less than, those of sodium salicylate.

Under hexamethylenamin, the recommendations are not confined to its recognized use as a urinary antiseptic; it is also said to be “unexcelled” as a “germicide,” and to prevent the formation of urate and phosphate deposits. These statements are contrary to facts.

“Rheumalgine ... may be used in all cases where the salicylates are indicated. It is superior to preparations containing sodium salicylate, in that it does not cause nausea or disturb the digestion.”

Both the preceding statements are misleading. The necessity of giving 1/200 grain of colchicin for each 5 grains of salicylate would certainly interfere with the use of adequate doses of the latter. The colchicin would produce digestive disturbance quite apart from the salicylate.

The mixture is described as:

“... ANTIRHEUMATIC, ANTIPYRETIC, URINARY ANTISEPTIC, AND URIC ACID ELIMINANT. Useful in Acute Articular and Chronic Rheumatism, Muscular Pains, Lumbago, Sciatica, Migraine of the Rheumatic, Gout, and in Nervous Irritability of the Gouty or Lithemic.”

The facts are: Salicylates are useful in some of these conditions, colchicin occasionally in a few, hexamethylenamin in none. The combination is conducive to uncritical prescribing. For instance, salicylates are effective in acute articular rheumatism; hexamethylenamin and colchicin are useless; salicylates are of very little use in chronic rheumatism, sciatica and nervous irritability, while hexamethylenamin and colchicin are useless in these conditions; colchicin is sometimes effective in gout, salicylates perhaps also; hexamethylenamin is not.

Attention should also be called to the high dosage of colchicin, namely, 1/100 to 1/50 of a grain of the alkaloid, every three or four hours, the dose then to be “slightly reduced,” but continued for several days; or in chronic cases, 1/100 to 1/30 grain per day, continued indefinitely. This dosage appears high, if a really active preparation is used.

Finally, the name “Rheumalgine” encourages thoughtless and unscientific prescribing. If a mixture is used at all, the prescriber should be constantly reminded of its composition.

It is therefore recommended that Rheumalgine be held in conflict with Rules 6 (unwarranted therapeutic claims), 8 (nondescriptive name) and 10 (unscientific composition).--(_From The Journal A. M. A., June 26, 1915._)

GRAY’S GLYCERINE TONIC

Report of the Council on Pharmacy and Chemistry

The Council adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Gray’s Glycerine Tonic Comp. (Purdue Frederick Company, New York) is a mixture said to be made according to a prescription of the late Dr. John P. Gray, superintendent of the state hospital, Utica, New York. As to the composition, the following statement is furnished by the company:

“This preparation is a combination of Glycerine, Sherry Wine, Gentian, Taraxacum and Phosphoric Acid with carminatives.”

The label declares the presence of 11 per cent. alcohol, and the dose is given at from two teaspoonfuls to a tablespoonful. A study of the ingredients will show that, aside from the alcohol, the mixture contains but one really active drug, gentian. Essentially, then, “Gray’s Glycerine Tonic” is a mixture which, in addition to the narcotic effect of the alcohol, depends on a bitter, gentian, for whatever therapeutic action it may possess.

The bitters, of which gentian is a type, were once credited with many therapeutic virtues which time has shown they do not possess. Pharmacologic research has demonstrated that their utility consists in stimulating the appetite through their action on the taste buds. On this account they were believed also to increase the secretion of the gastric juice by a psychic impression. More recently, however, even this has been questioned--by Carlson, for instance.

These facts are fully understood, presumably, by all physicians. Yet, according to the advertising circular, this “tonic,” which, for all practical purposes, is merely a simple bitter, is good for thirty-two diseases ranging from amenorrhea to whooping cough!

The conditions in which Gray’s Glycerine Tonic is asserted to be especially efficient are described on the label of the bottle and the outside wrapper, in popular terms, more or less typical of “patent medicine” exploitation, such as “catarrhal conditions,” and “stomach derangements.” Similar statements are contained in the leaflet accompanying the trade package. For instance:

“It is, therefore, an effective, reliable tonic in nervous exhaustion, general debility, impoverished conditions of the blood and nervous system, Bright’s disease, diseases of the liver, disorders of the urinary organs, etc.”

“It is an unexcelled restorative in that very common class of cases in which there is no positive organic disease, but the patient complains that he ‘does not feel well’ or ‘is out of sorts.’”

Here are some of the claims made in other advertising matter:

“All stages of bronchitis ... are rapidly improved by the use of Gray’s Glycerine Tonic Comp. This remedy has a direct tonic influence upon the circulation of the respiratory mucous membrane; it relieves congestion and restores tone to weakened blood vessels.”

“... improves the appetite, gives valuable aid to the digestive and absorptive processes, and reinforces cellular nutrition in ways that insure a notable gain in vitality and strength.”

+-----------------------------------------------------------------+ | In Gastro-Intestinal Catarrh | | | | --and other afflictions of the stomach and bowels characterized | | by muscular weakness and glandular insufficiency--there is no | | remedy more prompt and effective in its action than | | | | Gray's Glycerine Tonic Comp. | | | | Under its systematic administration the appetite is restored, | | the alimentary processes greatly improved, the nutrition | | promoted and every vital function throughout the body given a | | new and substantial impetus. As the digestive and assimilative | | functions are restored to their normal efficiency, a notable | | increase in the restorative and recuperative powers of the body | | naturally follow. | | | | THE PURDUE FREDERICK CO. | | 135 Christopher Street, New York City | +-----------------------------------------------------------------+ Mention ILLINOIS MEDICAL JOURNAL when writing to advertisers.

[Illustration: This appeared in a journal owned and controlled by the second largest state medical association of the country.]

Even granting that gentian may improve the appetite, how absurd it is to claim that this mixture “relieves congestion,” “restores tone to weakened blood vessels,” “gives aid to the absorptive processes,” “reinforces cellular nutrition,” or increases vitality!

Neither the composition of Gray’s Glycerine Tonic nor the clinical evidence warrants the belief that it has any therapeutic value other than that due to the psychic effect of the bitter drug gentian. Physicians who have prescribed it have done so because of the advertising. This nostrum has been kept so constantly before the eyes of medical men that they think of Gray’s Glycerine Tonic when they cannot remember the official drugs that may be indicated in the case. The moral is that liberal advertising will sell anything.

It is recommended that Gray’s Glycerine Tonic Comp. be declared not eligible for inclusion in New and Nonofficial Remedies on account of conflict with Rules 1, 6, 8 and 10.

[Editorial Note.--An old practice in hospitals--happily now practically obsolete--was to have certain stock mixtures prepared in bulk. Among these there was usually a so-called tonic mixture, used in a more or less haphazard manner when nothing in particular seemed indicated. Such a stock mixture was used in the State Hospital for the Insane at Utica, N. Y., during the many years that Dr. John P. Gray was superintendent (from the early fifties to the early eighties), although it is very doubtful whether he originated the mixture. After the death of Dr. Gray--so the story runs--one of his sons, with a partner, formed the firm of Purdue Frederick Company, and began the exploitation of the elder Dr. Gray’s name, in connection, presumably, with this stock preparation. As indicated in the Council’s report, Gray’s Glycerine Tonic Comp.--and what an absurd name!--is simply a mixture of ordinary drugs, requiring no skill whatever in compounding. If there is a physician living who cannot write a prescription offhand as good as this formula, that physician should either go back to a medical school or change his vocation. There is, and can be, no excuse for prescribing such a ready-made mixture, for every cross-roads drugstore has the ingredients and any pharmacist worthy of the name could compound it. Among the scores of nostrums that disgrace the medical profession of this country, none is more typical of all that is inimical to scientific medicine, to the medical profession and above all to the public--for, after all is said, it is the public that ultimately is humbugged.]--(_From The Journal A. M. A., July 10, 1915._)

TONGALINE AND PONCA COMPOUND

Report of the Council on Pharmacy and Chemistry

The Council, having considered “Tongaline,” “Tongaline Tablets,” “Tongaline and Lithia Tablets,” “Tongaline and Quinine Tablets” and “Ponca Compound Tablets,” found these preparations ineligible for New and Nonofficial Remedies and authorized publication of the following report.

W. A. Puckner, Secretary.

TONGALINE

Tongaline (Mellier Drug Co., St. Louis) is a fancy name given to what is essentially a sodium salicylate mixture. The air of mystery created by the name permits the manufacturers to make claims for the product which would be ludicrous if the medical profession was fully conversant with the very ordinary character of the preparation.

Tongaline receives its name from tonga, an inert, long-discarded mixture of various barks and herbs said to be gathered and prepared by Fiji Islanders. Its constituents evidently tend to vary with the collector. The history of the introduction of this indefinite combination of simples is thus given in The Journal, May 10, 1913.

“A supply of the crude drug was carried to England by a man who had lived for a short time in the Fiji Islands and it was placed in the hands of a retail house in London. This occurred about 1879. In 1880, two English physicians of repute published laudatory articles on the therapeutic value of tonga in neuralgia and rheumatism. This created a demand for the drug which extended to the United States.”

Time showed that tonga was inert therapeutically, and authorities on pharmacology now no longer notice it. As the Council previously reported,[12] the indefinite character of the mixture should, alone, be sufficient to exclude it from practical therapeutics. During the temporary popularity of tonga, the proprietary mixture Tongaline was put on the market for physicians’ use by the Mellier Drug Company, St. Louis. In this, tonga was named as the active ingredient. The commercial interests thus involved have faithfully nourished and kept alive the “tonga” myth.

[12] Reports of the Council on Pharm. and Chem., 1912, p. 40.

In a recent advertising booklet, “The Therapeutic Properties of the Ingredients of Tongaline,” the virtues of tonga, blue cohosh, colchicum, jaborandi and salicylic acid are discussed. The label of a recently purchased bottle reads:

“Tongaline contains Tonga, Cimicifuga Racemosa, Salicylate of Sodium (the salicylic acid being made from pure natural oil) Colchicum and Pilocarpin.”

It will be noticed that Tongaline is “made from the pure, natural oil.” In fact, the statement is repeated in red ink, in large letters running across the face of the label, thus emphasizing the alleged importance of this assertion. In this connection it is only necessary to recall that it has been proved clinically, chemically and physiologically that there is absolutely no difference between the salicylic acid made from the natural oil and the synthetic.

The formula was thus commented on in the article previously quoted from The Journal:

“Tongaline ... is essentially a preparation of sodium salicylate,... The Mellier Drug Company realized the impossibility of creating any marked demand for a nostrum unless it had some real drugs in it--hence the presence of the salicylates. What the actual composition of Tongaline is, no one but the manufacturers know. At one time the following was given as the formula:

Fluid Tonga 30 grains Extract of Cimicifuga Racemosa 20 grains Sodium Salicylate 10 grains Pilocarpin Salicylate 1/100 grain Colchin Salicylate 1/500 grain

“These amounts refer to the quantity of drugs in each fluidram of the preparation. Whether the nostrum still has this composition we do not know, but assuming that it has, it is quite evident that sodium salicylate is the essential and active ingredient.”

The therapeutic indications given on the label of the bottle are:

“Rheumatism, Neuralgia, Grippe, Gout, Nervous Headache, Sciatica, Lumbago, Malaria, Tonsillitis, Heavy Colds, Excess of Uric Acid, and wherever the use of the Salicylates is indicated.”

In a recent booklet this semisecret salicylate mixture is recommended, not only in conditions in which salicylates are indicated, but also combined with aconite for rheumatic fever, with benzoate of soda in the treatment of “grippe,” with potassium bromid in nervous headaches, with gelsemium, glycerin and whisky for “heavy colds,” with ammonium chlorid, stramonium and cimicifuga in “rheumatic dysmenorrhea,” and even with mercury biniodid as a treatment of syphilitic eruptions!

“When administered with good judgment, Tongaline exerts a stimulating effect upon every organ of elimination; cleansing the complex sewerage system and putting it into working order. When this is done, the sluggish blood current begins to flow more freely; the lymphatic and glandular systems to give up and carry off the toxic products, so long retained ...”

TONGALINE TABLETS

Then because of a “desire to put Tongaline in a more compact and convenient form,” the same concern puts on the market Tongaline Tablets. Whether Tongaline Tablets are of the same composition, the doctor who prescribes them is not advised. In this form we have Tongaline and Lithia Tablets, and Tongaline and Quinin Tablets. Presumably those who are attracted by the word “lithia” are sufficiently uncritical to be content with the statement that:

“The addition of Lithia to Tongaline presents a most useful combination which does not rely upon its action on the kidneys alone as is the case with Lithia salts or Lithia waters as administered ...”

And the foregoing quotation, be it remembered, is for the information of the medical profession! Tongaline and Lithia Tablets, we are informed, are:

“... particularly indicated for certain diseases which are caused by deposits of urates in the joints and kidneys, and can be used with much benefit for many people who indulge in generous or intemperate habits of living.”

Tongaline and Quinine Tablets are also exploited without statement of composition. The promoters are probably justified in feeling that physicians who prescribe quinin in combination with “Tongaline” care little about the dosage.

It is unnecessary to discuss the silly claims made for Tongaline and its combinations, although it is worth while to point out that the prescribing of such nostrums by physicians is an imposition, if not a fraud, on the public.

PONCA COMPOUND

Ponca Compound, also made by the Mellier Drug Company, St. Louis, is a “female weakness remedy” in tablet form. The name suggests that “ponca” is a medicinal substance, and, in fact, at one time, “Ext. Ponca” was named as an ingredient. The nature of “Ext. Ponca” was apparently never explained. It is now replaced in the “formula” by “senecin,” and the only information concerning the composition at present given is:

“Ponca Compound Tablets Contain Extract of Mitchella Repens, Senecin, Helonin, Caulophyllin and Viburnin.”

This “formula” is practically meaningless, not only because the amount of each ingredient is not stated, but also because “senecin,” “helonin,” “caulophyllin” and “viburnin” are in themselves variable mixtures of unknown composition.[13]

[13] See Report of the Council on Pharmacy and Chemistry on “Resinoids and Concentrations,” J. A. M. A., Nov. 13, 1909, p. 1655.

Presumably, “senecin,” “helonin,” “caulophyllin” and “viburnin” are extractives of some kind prepared, respectively, from senecio aureus (life root), helonias dioica (false unicorn), calophyllum thalictroides (blue cohosh) and viburnum prunifolium or opulus (black haw or cramp bark). These are, one and all, practically inert drugs. There is no reason to believe that any or all of them can have any beneficial influence in the many and varied conditions for which Ponca Compound is advertised.

The following are excerpts from the advertising matter:

“Ponca Compound is a remedy of a very beneficial character for Functional, Uterine and Ovarian troubles, which will respond to internal treatment, especially when digital examination or surgical interference is undesirable.”

“Ponca Compound is also valuable during gestation and after parturition.”

“Uterine Alterative for Leucorrhoea, Dysmenorrhoea, Amenorrhoea, Metritis, Endometritis, Menorrhagia, Metrorrhagia, Irregular Menstruation, Subinvolution, Painful Pregnancy.”

It is recommended that Tongaline and Ponca Compound and all their preparations be held in conflict with Rule 1, in view of their semisecret and indefinite composition; with Rule 6, for the grossly exaggerated therapeutic claims made for them; with Rule 8, because of their misleading names, and with Rule 10, in view of their unscientific character as irrational combinations. It is also recommended that this report be published.--(_From The Journal A. M. A., July 17, 1915._)

ALFATONE

Report of the Council on Pharmacy and Chemistry

The Council has found Alfatone ineligible for New and Nonofficial Remedies and has authorized publication of the following report.

W. A. Puckner, Secretary.

Alfalfa is good cattle feed but only nostrum exploiters have suggested its use as a medicine for human beings. While it may seem a waste of time to discuss the medicinal value of alfalfa its recent exploitation by the Norwich Pharmacal Company, Norwich, N. Y., as “a reconstructive tonic and nutrient” in the form of a mixture called “Alfatone,” calls for comment. According to the label on the preparation:

“Each fluidounce represents: Alcohol 15 per cent. Medicago sativa (Alfalfa) 120 grains Taraxacum 2-1/2 grains Gentian 1 grain Berberine Hydrochloride 1/40 grain Glycerin and Aromatics.” “Dose.--One to three fluidrams (4 to 12 c.c.) 4 times daily.”

Each maximum dose, therefore, should represent 45 grains of alfalfa, 1 grain of taraxacum (dandelion), 3/8 grain of gentian, 1/100 grain of berberin hydrochlorid, and 27 minims of alcohol. Since the bitter drugs are present in such small amounts that the preparation is almost devoid of bitterness, and as the medicinal value of alfalfa is practically nil, it is evident that whatever action Alfatone may have is due to the stimulant effects of the alcohol.

Some of the claims made for Alfatone are:

“A reconstructive nutritive tonic indicated in general debility, neurasthenia, convalescence, etc.”

“... a Galactagogue of merit as well.”

“... improves the appetite, aids the processes of digestion and assimilation, facilitates elimination and effects gradual but decided gains in strength, vitality and weight.”

It is suggested that:

“... in case of idiosyncrasy the addition of Tr. Nux Vomica 5 to 10 minims to the dose, unless contraindicated, will secure excellent results.”

The Norwich Pharmacal Company naively remarks:

“The dearth of medical literature on Alfalfa has lead us to present below a few of the findings of the Bureau of Plant Industry of the Department of Agriculture ... as well as those from several state experiment stations ...”

Here are the “findings”:

“... Digestible nutrients in 100 pounds of Alfalfa,... Protein, 11.0 pounds; Carbohydrates, 39.6 pounds; Ether Extract, 1.2 pounds.”

“... The high value of Alfalfa is due to the amount of protein that it contains; to the large percentage of protein that is digestible and the palatability of Alfalfa.”

“... Table showing pounds of elements removed from the soil by one ton of crop.

Alfalfa Wheat Potash 49.79 12.52 Phosphoric Acid 8.27 9.08 Lime 43.51 2.95 Nitrogen 44.01 22.30”

“... The abundance of muscle and bone producing material in Alfalfa makes this crop especially good.”

Thus estimates of the value of a farm crop and cattle fodder are made to do service as testimonials to its therapeutic merit for human beings! Has the “patent medicine” promoter ever dared to insult the intelligence of his patrons by a cruder absurdity? Yet it is not to the nontechnical and unscientific public, but to a profession presumably scientifically trained in pharmacology and therapeutics that this concern presumes to offer its fodder tincture on the basis of testimony to the agricultural value of the fodder plant.

Alfatone is a worthless alcoholic cordial. The audacity of the attempt to promote its sale by a discourse on the merits of a well-known fodder plant is the sole reason for devoting any attention to it. It is recommended that Alfatone be held ineligible for New and Nonofficial Remedies, and that this report be published.

[Editorial Note.--What a comment on American medicine that a concern can even contemplate the possibility of making a commercial success of the sale of such a silly nostrum as Alfatone! And yet, when one remembers that a proprietary in which oats constitutes one ingredient (“Pas-Avena”) for years has been advertised to physicians and presumably prescribed by them, it is not altogether inexplicable that business men should get the impression that the medical profession is “easy” enough to “fall for” anything in the line of proprietary mixtures. Perhaps we may look forward to being offered proprietaries based on other cheap and well-known fodder plants. Tincture of Timothy Hay, Blue Grass Tonic, Cornhusk Wine! Why not? The enterprising companies that may put them out can easily publish tables to show the digestible nutrients in each and indubitable testimony can be furnished to prove the excellence of any of them as stock feed. If a pitchforkful of timothy hay makes a good fattening ration for a growing steer why should not a teaspoonful of tincture of timothy hay make a “reconstructive tonic and nutrient” dose for a man? If an arm load of thistles (carduus) makes a luscious food for _equus asinus_ why should not a pinch of thistle in alcohol and water be a good “tonic”? Great are the possibilities! They are limited only by the gullibility of the medical profession and the public. Certain it is that some proprietary manufacturers are firmly convinced that no combination can be too preposterous to be worth trying on the medical profession.]--(_From The Journal A. M. A., Aug. 7, 1915._)

ARTICLES REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Below appear abstracts of the Council’s actions on articles refused recognition which were not deemed of sufficient importance to require lengthy reports.

Uricsol

Uricsol is marketed by the Uricsol Chemical Company, formerly of Los Angeles, now of Boston. Regarding its composition only vague statements are made. In an advertising pamphlet it is promised that the formula will be sent to physicians on request. Such a request from a physician elicited the following statement:

“URICSOL is a non-irritating, alkaline solution, containing Lithium Citrate, Acid Citric and Potassium Nitrate, together with a saline laxative in the form of Glycero Sodium Phosphate, with Vegetable Tonics added.”

The Association Laboratory has made an examination of Uricsol to determine its composition and reports as follows:

LABORATORY REPORT

A trade package purchased in March, 1915, from a wholesale drug house was labeled:

“Uricsol Rheumatic Remedy, Uric Acid Solvent, Kidney and Liver Stimulant, Manufactured by the Uricsol Chemical Co., Los Angeles, Cal.”

This package was wrapped in a circular entitled “The Great California Remedy--Uricsol.” The preparation is a viscid, slightly turbid light brown liquid, with a faintly aromatic odor and a salty, bitter taste. The diluted solution is acid in reaction toward litmus and phenolphthalein and alkaline toward methyl orange.

Qualitative tests showed a presence of phosphate, citrate, nitrate, sodium, glycerin, and a small amount of lithium in aqueous solution. Besides these a small amount of some organic, nonalkaloidal substance was found, which from its bitter taste suggested gentian. From the qualitative tests it appeared that the phosphate was the predominating ingredient and accordingly a phosphate determination was made. The results, calculated to sodium phosphate, U. S. P., indicated the presence of 64.20 gm. per 100 c.c., held in solution by citric acid and sodium nitrate.

Uricsol evidently is a solution containing a large amount of sodium phosphate with small amounts of lithium, nitrate, citric acid and glycerin, with probably some vegetable extract.

In general Uricsol is similar to the once widely exploited proprietary “Melachol,” which has been frequently imitated. A preparation essentially identical is in the United States Pharmacopeia, under the title “Compound Solution of Sodium Phosphate.”

The Uricsol Company calls its preparation

“... the latest word in the treatment of Rheumatism and that allied group of ailments which is caused by an excess of Uric Acid.”

Hay fever, bronchial asthma and neuritis are conditions in which it is recommended. The claim is made that

“Uricsol quickly controls Vasomotor Rhinitis and eliminates such conditions from the system.” “In fact, it will correct FAULTY METABOLISM.”

To a few practitioners of an older generation the pharmacologic basis of a remedy for rheumatism was sufficiently defined by saying that it increased the solubility of uric acid or affected it in some way. This theory is obsolete; there is not, and never was, any reliable evidence on which to base the theory that rheumatism is in any way caused by uric acid. The exploitation of Uricsol as a “uric acid solvent” is merely another illustration of the way in which nostrum manufacturers play on disproved theories. Of course the claim that sodium phosphate has any particular power to control vasomotor rhinitis, hay fever, asthma, and to correct faulty metabolism is foolish.

To summarize: Uricsol is a mixture of well-known drugs, marketed with false claims as to therapeutic action, with misleading and meaningless statements as to composition and under a name which invites uncritical prescribing. Uricsol is held ineligible to inclusion in New and Nonofficial Remedies.

Jubol

The following ridiculous statements are addressed, not to the laity, but to the medical profession:

DO YOU SUFFER FROM Constipation--Hemorrhoids--Enteritis--Mucous discharge--Pituita--Acidity of the stomach--Vertigo--Sick Headache--Disturbed Sleep--Insomnia--Sallow Complexion--Coated Tongue--Offensive breath--Fatigue and depression--Boils--Pimples?

“ONE of these symptoms alone shows that there is defective or insufficient function of the intestines, even if the stools are regular.

“Excrements remain too long in the intestine and set up fermentation. The harmful poisons and Ptomains which they produce are re-absorbed by the blood and poison the whole system.

“The Intestines must be cleared and re-educated with JUBOL.

“Jubolise your Intestines.”

Jubol tablets are sold in the United States by Geo. J. Wallau, Inc., New York, and are said to be prepared by J. L. Chatelain, Paris, France. The following incomplete and nonquantitative “formula” is furnished:

“... compounded chiefly [!] of Agar-Agar, Biliary Extracts and pure Extracts from all the intestinal Glands.”

It is asserted that

“The tablets are coated with a protective covering in order that they may act on the intestine only.”

The tablets contained in a regular-size trade package, obtained direct from the agent, readily separated into two halves and disintegrated within a few minutes when agitated with water. It is thus evident that, under ordinary conditions, the intestinal ferments in Jubol (if they are present, as claimed) would be destroyed during their passage through the stomach. In direct tests, however, practically no tryptic activity was demonstrated.

The composition of Jubol is not declared; grossly unwarranted and incorrect claims are made for its therapeutic actions; the name does not indicate the alleged ingredients and so much of the composition as is declared indicates an unscientific mixture. The Council decided that Jubol should be held ineligible for New and Nonofficial Remedies, and that this report should be published.

Urodonal

Urodonal is said to be “produced in the laboratory of J. L. Chatelain,” Paris, France. It is marketed in this country by Geo. J. Wallau, Inc., New York.

The preparation is claimed to be a chemical compound, and the advertising matter furnishes a “formula,” which consists of the formulas of lysidin, sidonal and hexamethylenamin, connected by plus signs:

{H₂C Az  } CO₂H--C--OH AzH Az {H₂C C--CH₃} + { H₂C CHOH } {H₂C  CH₂} {H₂C CH₂   CH₂} { AzH  } {OHHC CH₂ } {H₂C  CH₂} + {Az.CH₂ Az.CH₂ Az}  { CHO  } { AzH } {  CH₃ }

That the substance is a chemical compound is highly improbable, and no evidence has been submitted to substantiate the claim. On the contrary, in the following statement the phrase “based on” is a virtual admission that the preparation is merely a mixture:

“Urodonal ... is a granular effervescent preparation based on methylglyoxalidine [Lysidine], quinate of diethylene-diamine [Sidonal] and hexamethylene-tetramine [Formin, urotropine].”

Mystery is added by the mention of undefined “special products” in the following:

“The fact of combining these two salts [lysidin and sidonal] in Urodonal, in strictly determined proportions and in the presence of special products, gives this preparation very considerable power in dissolving uric acid.”

These contradictory statements of composition conflict with Rule 1.

Urodonal is marketed in typical “patent medicine” style: the name “Urodonal” is blown in the bottle and the label contains a list of “Indications,” including rheumatism, gout and gravel (Rule 4). That this form of marketing has introduced it to the public is suggested by the following in an advertising circular:

“... Urodonal is now popular--even classic--throughout the world, where thousands of doctors and millions of patients agree in asserting that ‘Urodonal is to rheumatism what quinine is to fever.’”

There are also other indications that the mixture is to be exploited to the laity. For instance, the U. S. distributor sends out a portrait of Sarah Bernhardt bearing the legend:

“I am positive that URODONAL preserves youth’s freshness with clearness and strength to brain and heart. I have taken it for two years with the greatest benefit. Sarah Bernhardt.”

A circular advises this mixture

“For all who suffer from Arthritis, Rheumatism, Arterio-Sclerosis, Renal and Bilious Lithiasis, Headache, Gout, Gravel, Lumbago, Sciatic Pains, Neuralgia and all uric acid troubles.”

“In fact, Urodonal is five times more active than piperazine, and thirty-seven times more active than lithia. We are, therefore, entitled to say that no other eliminator of uric acid can be compared with it.”

“Being _37 times more active than lithia_, it clears the heart valves of any sandy substances which may clog them, and checks the atheromatous degeneration of the blood vessels.”

These extracts indicate sufficiently the extravagant tone of the advertising (Rule 6): None of the ingredients are notably active in dissolving uric acid when administered by mouth. None produce any marked increase of uric acid elimination. No intelligent physician would use a uric acid solvent for “bilious lithiasis”; and their usefulness in the other conditions is open to doubt, to put it mildly.

Although the preparation is a simple mixture, the name does not indicate the components, but inclines to therapeutic suggestion (Rule 8).

Nothing is to be gained by combining several drugs which are useless, severally, for the purpose intended, as in the present case (Rule 10).

Urodonal is marketed under inconsistent statements of composition and with exaggerated therapeutic claims; the name is nondescriptive and the mixture is unscientific. The Council decided that the preparation should be declared ineligible for conflict with Rules 1, 4, 6, 8 and 10 and that this report should be published.--(_From The Journal A. M. A., Aug. 14, 1915._)

FORMAMINT

Report of the Council on Pharmacy and Chemistry

The following report has been authorized for publication.

W. A. Puckner, Secretary.

Formamint is a proprietary medicine manufactured by the A. Wulfing Company (New York, London and Berlin), which is affiliated with the Bauer Chemical Company.

It has been widely advertised in Europe for several years, and is now on the American market;[14] it is advertised in this country both in newspapers and medical journals.

[14] The Journal A. M. A., Feb. 24, 1912, p. 572.

Following is a brief review of the more important alleged investigations that have been reported from time to time in various European journals.

In “The Therapeutical Value of Foramint in Septic Affections of the Oro-Pharynx,” De Santi[15] quotes Rosenberg,[16] who reports the successful use of Formamint in cases of streptococcus infections, tonsillitis and acute symptoms of chronic sore throat. According to Seifert,[17] Formamint is a chemical combination of formaldehyd and milk sugar. When the tablets are dissolved in the saliva, 0.01 per cent. of formaldehyd in its “status nascendi” is liberated and exercises a strong disinfectant action. Seifert states that the preparation is markedly palatable, since it contains a little citric acid to render the taste cool and refreshing. In some experiments with streptococci, pneumococci, typhoid and diphtheria bacilli, Seifert found that a solution of one tablet in 10 c.c. of water destroyed these germs in from five to ten minutes. A solution of the same strength was also added to culture tubes of broth, agar, and gelatin, with the result that no growth occurred in them, while distinct and characteristic development of the bacteria took place in control tubes. He does not state, however, how much Formamint solution was added to the mediums.

[15] De Santi: Medical Magazine =16=:141, 1907.

[16] Rosenberg: Lancet, London =2=:1871, 1905.

[17] Seifert: Pharmakol. u. therap. Rundschau, 1904, No. 14; quoted by De Santi (Note 2).

Daus[18] reports successful treatment of tonsillitis, mumps and middle ear diseases. In these cases no other gargles or mouth washes were used. He states that no indication of irritant or other injurious action made its appearance even after large doses. In the same article, F. Levy reports experiments as follows: Agar plates were prepared with a culture of streptococcus from a severe case of quinsy. One half of the plate was rubbed with saliva containing Formamint in solution. (The strength of the solution used is not given.) In twenty-four hours streaks of growth had appeared on one portion of the plates while the part on which the Formamint saliva had been rubbed remained sterile. Daus also found that agar and broth cultures of streptococcus shaken with Formamint saliva remained sterile.

[18] Daus: Med. Klin. =2=:4110, 1906.

Rheinboldt,[19] investigating the effects of Formamint and of ordinary formaldehyd on animals, concludes that formaldehyd is toxic in action while Formamint is not.

[19] Rheinboldt: Deutsch. med. Wchnschr. =32=:587, 1906.

[Illustration: How the exploiters of Formamint capitalize the medical profession. Miniature reproductions of typical Formamint advertisements appearing in the newspapers.]

Rosenberg[20] corroborates this statement. He also found that agar plates of _Bacillus prodigiosus_ were killed by Formamint solutions in about four hours. He fails, however, to give the strength of his Formamint solutions.

[20] Rosenberg: Therap. d. Gegen. =7=:55, 1905.

Wingrave[21] suggests the use of Formamint for infants! He recommends that a tablet be crushed and wrapped in “butter cloth.” The ends of the cloth are to be tied with thread, the Formamint is to be moistened, and the packet is to be held in the mouth of the baby several times each day.

[21] Wingrave: Lancet, London =2=:1067, 1906.

Young[22] published the results of some experiments by himself and Delépine on the human throat. They dissolved a tablet in the mouth and made swab cultures with the following results:

Immediately after taking the tablet 0 colonies 10 minutes after taking the tablet 35 colonies 30 minutes after taking the tablet 150 colonies

[22] Young: Lancet, London =1=:975, 1908.

They found no staphylococci at any time. Other results of swabbing various parts of the throat before and after the use of Formamint, reported by these investigators, show enormous reductions in the count, claimed to be due to the action of Formamint. The count was made on agar at 37 C., but they fail to state the time elapsing between taking the Formamint and making the swab. Young also reports favorable clinical results in cases of scarlet fever, diphtheria, sore throat, and the like. It must be noted, however, that they state that the mouth and fauces must first be thoroughly cleansed by swabbing and douching before Formamint is used.

THE “CHEMICAL COMPOUND” CLAIM

The claims made in the advertising literature of Formamint are very extravagant. Many are highly improbable. These statements will be discussed later.

The statement is made that Formamint is a new chemical compound:

“Formamint is Pentamethanallactose, 5 CHOH + C₁₂H₂₂O₁₁. It is an original combination of Formaldehyde with Lactose, a definite chemical compound. The Formaldehyde molecule is locked up in it until solution in the saliva takes place, when the Formaldehyde is liberated in its _nascent_ state and is therefore active without being irritant.”

Furthermore the makers contend that this new chemical compound is entirely harmless. For example, Daus,[5] in an article on “The Disinfectant Action of Formic Aldehyde on Mucous Membranes,” declares:

“No indication of irritant or other injurious action made its appearance even after large doses. The urine remained free from albumin and sugar.”

Such statements as these are found in the advertising literature:

“Formamint tablets are absolutely harmless and innocuous, even to little children.”

“When dissolved in the saliva, Formamint Tablets liberate slowly Nascent Formaldehyde in a most active yet non-irritant form.”

They maintain that Formamint is not only absolutely harmless, but actually beneficial to the tissues. It may be used “to tone up and strengthen the tissues, prevent hoarseness, and allay irritation in singers, public speakers,” etc.

The claims urged as to its germicidal power are indeed glittering. This “new chemical compound” is claimed to liberate formaldehyd in some new and peculiar condition which, while it has a soothing and tonic effect on the cells of the human tissues, can at the same time quickly kill any form of bacterial life.

“Dissolving readily, it releases its germicidal, antiseptic qualities, which impregnate the saliva and are carried naturally and easily around the mouth and in the deepest crevices of the throat--destroying the germs where they are causing the mischief. Formamint prevents and destroys infectious germ life in a soothing grateful way.”

“In the saliva it frees a germicide, fatal to germs but harmless to the most delicate membranes. And flowing into every tiny corner of the gums, tonsils and throat, into places where no gargle ever reaches, it most effectively _disinfects_ the throat.”

The claims as to the preventive and curative effects of the preparation cover a large portion of the category of human ailments and distresses. The following quotations indicate some of its supposed properties:

“... it is therefore self-evident that Formamint should be looked upon as a necessary part of the treatment of all forms of tonsillitis.”

“The value of Formamint is equally great in diphtheric tonsillitis, or as a prophylactic ...”

“The extraordinary success which I had with Formamint in a school epidemic of scarlet fever during May and June, 1907, was the determining factor which induced me to abandon the use of inhalations, gargles, local applications in the treatment of diseases of the throat, and to use Formamint exclusively for the future.”

“There are naturally many similar conditions in which Formamint may be used as a prophylactic, notably scarlet fever, mumps, streptococcal and staphylococcal sore throats, ‘milk outbreaks’ of sore throat, drain throats, hospital throats, and the like.”

“Formamint Tablets are indicated in Angina, Tonsillitis, Pharyngitis, Stomatitis, Gingivitis, Glossitis, ulceration, spongy or bleeding gums, Pyorrhea Alveolaris, ‘Smoker’s Sore Throat,’ Abscess or Boils, etc.”

“As a _Prophylactic_ against Diphtheria, Scarlet Fever, Influenza, Measles, Epidemic poliomyelitis, and other pathogenic micro-organisms. To neutralize putrefaction products in and about the teeth, correct fermentative processes, deodorize and purify the breath, etc.”

“To _tone up_, and _strengthen_ the tissues, prevent _hoarseness_ and _allay irritation_ in singers, public speakers, neutralize the effects of dust-infection or _disinfect the saliva or sputum_ in Influenza, Tuberculosis, etc.”

One man declares that along with specific constitutional treatment he “had the best results from the use of Formamint tablets” in a case of syphilitic ulceration of the tongue.

In short, Formamint is recommended for the treatment or prevention of almost everything, from a bad breath to such grave conditions as scarlet fever, diphtheria and tuberculosis, conditions in which a delay in proper treatment--for instance, in diphtheria, a failure to administer antitoxin--may result in the death of the patient.

A series of investigations was therefore undertaken in order to discover whether the extravagant claims regarding the germicidal power of Formamint could be verified.

Experimental Data

Two fifty-cent bottles of Wulfing’s Formamint were purchased in the open market and were kept well stoppered to prevent deterioration.

Qualitative tests showed the presence of formaldehyd and the amount was determined quantitatively by the hydrogen peroxid method as given by Sutton.[23] The results were respectively, 1.99 per cent. and 2.03 per cent. of formaldehyd.

[23] Sutton: Volumetric Analysis, Edition 10, p. 390.

[Illustration: Two Formamint advertisements reproduced in miniature typical of those appearing in a certain type of medical journals.]

Some determinations were made of the germicidal power of Formamint in vitro, that is, under controlled laboratory conditions. A twenty-four-hour plain agar culture of _Staphylococcus aureus_ was washed off in 10 c.c. of sterile 0.85 per cent. sodium chlorid solution. A 1:100,000 dilution of this was made in each of three flasks containing 100 c.c. of sterile saliva. Flask 1 contained 1 per cent. of Formamint, Flask 2, 5 per cent.; Flask 3, containing no Formamint, was kept as a control. At intervals samples were removed and dilutions made and plated in duplicate on standard agar. The plates were incubated twenty-four hours at 37 C., and plates containing less than 200 colonies were counted. The results are given in Table 1. After seven days there was no appreciable difference in the plates.

Another test was made by adding a 1 per cent. Formamint solution to plain agar plates inoculated with _B. coli_. A twenty-four-hour plain agar culture of _B. coli_ was washed off in 10 c.c. of sterile 0.85 per cent. sodium chlorid solution. A 1:1,000,000 dilution was made of this and 1 c.c. added to each plate. Varying amounts of 1 per cent. solution of Formamint were added to each plate. They were incubated seventy-two hours at 37 C. After seven days’ incubation the count was the same. The results are given in Table 2.

Another experiment was made thus: One loopful of a twenty-four-hour plain agar culture of _Streptococcus lacticus_ was mixed with a tube of North medium. One loopful from the inoculated tube was mixed with a second tube of North medium. Both tubes were poured into Petri dishes and allowed to cool. One half of each plate was well smeared with a 10 per cent. solution of Formamint in saliva. After twenty-four hours’ incubation at 37 C., only a few colonies appeared on the side to which the Formamint had been applied, while the other half was thickly covered with colonies.

TABLE 1.--SHOWING TIME IN WHICH CULTURES OF STAPHYLOCOCCUS AUREUS WERE KILLED BY DIFFERENT AMOUNTS OF FORMAMINT

===================+=================+=============+================= Amount of Formamint| Period of |Average Count| Count on Flask in Saliva |Standing at 37 C.| When Plated |of Saliva Without (Per Cent.) | (Hours) | | Formamint -------------------+-----------------+-------------+----------------- 1 | 3 | 32 | 3200 1 | 6 | 0 | 7000 5 | 1 | Few | 5000 5 | 2 | 0 | 4100 5 | 3 | 0 | 3200* 5 | 6 | 0 | 7000* -------------------+-----------------+-------------+-----------------

* The last two observations were made at the same time as on the 1 per cent. solutions.

This work so far corroborates that reported in the literature quoted by the manufacturers. But the fact that a compound is a germicide when brought into intimate contact with bacteria in a solution or medium in a test tube or flask does not prove that it will be effective when used in the human throat.

THE ALLEGED GERMICIDAL ACTION

An attempt was made to discover whether or not the claims advanced by the manufacturers as to the perfect germicidal action of Formamint in all the nooks and crannies of the mouth and throat could be confirmed.

TABLE 2.--COUNT OF B. COLI CULTURES WITH DIFFERENT AMOUNTS OF FORMAMINT

====================================================================== No. c.c. of 1 per cent. Formamint 0 0.1 0.3 0.5 0.7 1.0 1.5 2.0 3.0 Count 160 33 39 26 15 12 2 0 0 ----------------------------------------------------------------------

The first step in attacking this problem was to make comparative counts of the number of bacteria in the throat before and after the use of Formamint. The methods employed were as follows: The throat was gargled with 50 c.c. of sterile 0.85 per cent. sodium chlorid solution. In each case the same length of time, as far as possible, was used in the process. The liquid was collected in a sterile flask. The gargling in a series of experiments was begun not less than two hours after a meal. After some preliminary work the following dilutions of the 50 c.c. of salt solution were found sufficient: 1:1,000, 1:10,000 and 1:100,000. Plates were made in duplicate from each dilution and incubated seventy-two hours at 37 C. The counts were made on plates containing less than 200 colonies. Except where otherwise noted standard agar was used. The mediums were always prepared in the same way.

All the work was carried out under conditions as nearly natural as possible. The Formamint was taken according to the directions accompanying the trade package. Every opportunity was given the Formamint to penetrate all the crypts and recesses about the mouth and throat. The tablet was allowed to dissolve as slowly as possible, the time usually being five to six minutes, and saliva was thoroughly forced around the mouth before being swallowed. Plating was always done immediately after gargling so that no growth could occur in the salt solution. The results are given in Table 3. The numbers are average counts from several plates and calculated to show the number of bacteria washed out by the 50 c.c. of salt solution.

TABLE 3.--SHOWING THAT FORMAMINT DOES NOT GREATLY DECREASE THE NUMBER OF BACTERIA IN THE THROAT

==========================+=========+=========+===========+=========== | | |No. Found |No. Found | Time |Amount of|in Throat |in Throat Conditions of Test | Since |Formamint| Before | After |Preceding| Used | Use of | Use of | Test | |Formamint |Formamint --------------------------+---------+---------+-----------+----------- Normal | ... | 0 | 15,600,000| ... Normal | 1 hour | 0 | 38,500,000| ... Normal | 1 hour | 0 | 30,500,000| ... Normal | ... | 0 | 12,500,000| ... Normal | 1 hour | 0 | 14,500,000| ... | 1 hour | 0 | 23,500,000| ... Tablet dissolved in mouth | 6 days | 1 tablet| ... | 15,000,000 and throat gargled one | | | | hour later | | | | Throat again gargled two | 1 hour | 0 | ... | 10,050,000 hours after Formamint | | | | was used | | | | Normal | 7 days | 0 | 62,000,000| ... Normal | 1 hour | 0 | 72,500,000| ... Normal | ... | ... | 61,000,000| ... Tablets were taken, one | 2 days | 12 | ... | 39,100,000 per hour, and throat | | | | gargled onehour after | | | | last tablet was taken | | | | Throat was again gargled 2| 1 hour | 0 | ... | 59,000,000 hours after taking last | | | | tablet | | | | Normal | 5 days | 0 | 35,000,000| ... Normal | 1 hour | 0 | 62,000,000| ... Normal | 1 hour | 0 | 72,000,000| ... One tablet was taken each | 4 days | 24 | ... |175,000,000 half hour for 12 hours | | tablets | | consecutively. Throat was| | | | gargled one hour after | | | | last tablet was taken | | | | Throat was again gargled | 1 hour | 0 | ... |168,750,000 two hours after last | | | | tablet was taken | | | | Normal | 3 days | 0 |129,600,000| ... Normal | 1 hour | 0 |177,000,000| ... Normal | 1 hour | 0 |147,000,000| ... Normal | 3 days | 0 | 79,000,000| ... One tablet was taken | 1 hour | 1 | ... | 83,200,000 immediately after preced-| | | | ing gargle. Throat was | | | | again gargled at end of | | | | one hour | | | | Throat was again gargled 2| 1 hour | 0 | ... |134,750,000 hours after tablet was | | | | taken | | | | Normal conditions except | 19 days | 0 | 32,600,000| ... that mouth and teeth were| | | | throughly washed with | | | | soap just before gargling| | | | Same as above | 1 hour | 0 | 33,125,000| ... Same as above | 1 hour | 0 | 40,375,000| ... Teeth were not washed. | 2 days | 0 | 33,500,000| ... Otherwise normal con- | | | | ditions | | | | Same as above | 1 hour | 0 | 43,330,000| ... Same as above | 1 hour | 0 | 54,000,000| ... Same as above | 1 hour | 0 | 50,000,000| ... Same as above | 1 hour | 0 | 67,000,000| ... Mouth and teeth thoroughly| 2 days | 0 | 5,270,000| ... washed with soap just | | | | before throat was gargled| | | | Same as above | 1 hour | 0 | 10,916,000| ... Same as above | 1 hour | 0 | 8,275,000| ... Normal conditions, but 1  | 3 days | 0 |228,750,000| ... c.c. of sterile rabbit’s | | | | blood was added to each | | | | plate | | | | Count from the same gargle| 0 | 0 | 60,625,000| ... as above. No blood used | | | | in the plates | | | | Normal conditions, but | 1 hour | 0 |431,250,000| ... count was made on blood | | | | agar | | | | Count from the same gargle| 0 | 0 | 59,625,000| ... asabove. No blood used in| | | | the plates | | | | Normal conditions, count | 2 days | 0 |683,300,000| ... was made on blood agar | | | | Same gargle as above, but | 0 | 0 | 58,500,000| ... count was made on plain | | | | agar | | | | One tablet was taken just | 1 hour | 1 tablet| ... |558,300,000 after preceding gargle. | | | | After one hour throat was| | | | again gargled. Count on | | | | blood agar | | | | Same gargle as above, but | 0 | 1 tablet| ... | 55,875,000 count was made on plain | | | | agar | | | | Normal conditions | 2 days | 0 | 79,125,000| ... One tablet was taken just | 1 hour | 1 tablet| ... | 56,250,000 ten minutes before gargle| 16 min. | | | was made | | | | Normal conditions | 2 days | 0 | 46,750,000| ... One tablet was taken just | 1 hour | 1 tablet| ... | 38,500,000 ten minutes before throat| | | | was gargled | | | | Teeth and mouth were thor-| 5 days | 0 | 47,370,000| ... oughly washed with soap | | | | just before gargle was | | | | made | | | | Teeth washed as above and | 1 hour | 1 tablet| ... | 21,225,000 1 tablet taken 10 minutes| | | | before gargle was made | | | | --------------------------+---------+---------+-----------+-----------

Finally a determination was made of the number of streptococci in the throat before and after the use of Formamint. The throat was gargled in the manner previously described. The streptococcus count was made by the dilution method as given by Heinemann.[24] Culture tubes were used instead of fermentation tubes. One per cent. dextrose broth was the medium employed. One cubic centimeter was added to each of a series of ten tubes for each dilution and the following dilutions were used: 1:10,000, 1:100,000 and 1:1,000,000.

[24] Heinemann: Laboratory Guide in Bacteriology, p. 86.

The results given in Table 4 are the average count from a number of dilutions and are reported as the total number washed out by the 50 c.c. of salt solution.

TABLE 4.--SHOWING THAT FORMAMINT FAILS TO REDUCE THE NUMBER OF STREPTOCOCCI IN THE THROAT

==============+===========+===========+===========+========== | | | No. Found | No. Found | Time | Amount of | in Throat | in Throat Conditions | Since | Formamint | Before | After of Test | Preceding | Used | Use of | Use of | Test | | Formamint | Formamint --------------+-----------+-----------+-----------+---------- Normal | .... | 0 | 1,200,000 | .... | | | | One tablet was| | | | taken and | | | | throat gargled| | | | one hour later| 4 days | 1 tablet | .... |14,750,000 | | | | Normal | 3 days | 0 | 9,950,000 | .... | | | | One tablet was| | | | taken and | | | | throat gargled| | | | ten minutes | | | | later | 1 hour | 1 tablet | .... | 8,000,000 ==============+===========+===========+===========+==========

Discussion

The contention that Formamint contains formaldehyd was confirmed by analysis.

The manufacturers also maintain that Formamint is a new, definite chemical compound, consisting of five molecules of formaldehyd and one molecule of lactose, and that when dissolved in the saliva the formaldehyd is liberated in some new and peculiar form, which they call nascent formaldehyd. This new kind of formaldehyd is, according to the advertising literature, especially powerful in its germicidal properties and at the same time has absolutely no irritating or harmful effects.

NOT A CHEMICAL COMPOUND

Thoms,[25] retained as an expert by the German government, decided, after a series of chemical investigations, that Formamint was not a definite chemical compound, but that it was probably a solid solution of formaldehyd in lactose. He proved that when the process of manufacture was carried out in exactly the way called for by the Formamint patents, compounds containing a greater or less per cent. of formaldehyd could be made while the other properties remained similar to those of Formamint. The composition of the final product depended on the proportion of the components used in the process. Therefore Formamint did not form a safe means of uniform dosage.

[25] Thoms: Arb. a. d. Pharm. Inst. d. Universität, Berlin =11=:210, 1914.

As a result of Thoms’ work the German courts held that Formamint was not a new chemical compound. Consequently the Formamint patent (Number 189036) was annulled in Berlin, Nov. 29, 1913.

Again the contention that formaldehyd in the nascent or active condition is less poisonous and irritating than in its ordinary form is contrary to what would be expected from the behavior of such compounds. If it were liberated, as claimed, in the “nascent” condition, it would be, for that very reason, not only more active but also more harmful.

As a matter of fact, Formamint did have an irritant effect on the worker who carried out these investigations. When one tablet was taken each hour for twelve consecutive hours, marked irritation of the intestinal tract resulted. There was almost sufficient nausea to cause vomiting and uneasiness in the alimentary canal following the experiment. When the twenty-four tablets were taken the results were similar but more pronounced. This is decidedly in contradiction to the assertions of the manufacturers.

Otto Seifert,[26] moreover, cites the following:

“By Effects: Only a few patients complain of an unpleasant sharp taste, burning of the tongue (Seifert, Sklarek). Among the general symptoms observed are urticaria-like exanthems (Glaser, Roters), which are accompanied by nausea, vomiting, headache, insomnia and vertigo, burning and irritability especially in the larynx (Meissner); phenomena of poisoning (Geissler); gastric disturbances (Engelmann); renal irritation (Steinhard); unsuited for diabetics (Voit).”

[26] Seifert, Otto: Die Nebenwirkungen der modernen Arzneimittel, 1915.

The contention that Formamint, when mixed directly with mediums and left in contact with bacteria, will kill the organisms was corroborated. Thus the statements and pictures in the booklet, “The Gospel of Prevention,” which is enclosed with each bottle of Formamint, showing the inhibition of growth of air bacteria on plates containing Formamint are no doubt true and authentic.

Finally, the claim that Formamint is an almost perfect throat disinfectant was by no means confirmed, as a glance at the tables will show. One hour after it is taken, even when a tablet was used each half hour for twelve hours, the number of bacteria in the throat was practically the same as when Formamint was not used. Even ten minutes after taking a tablet the number of bacteria in the throat was never greatly reduced, as is maintained by the manufacturers.

HAS NO SELECTIVE ACTION

Formamint exerts no selective action in killing off the very delicate organisms which are more apt to be pathogenic. When the comparative counts were made on blood agar which would favor the growth of the delicate parasitic organisms, no reduction whatever was shown by the use of Formamint.

The number of streptococci was found to be the same, within limits of experimental error, ten minutes after taking a tablet as it was before the tablet was taken.

Therefore it seems that Formamint fails, as any such germicide would be expected to fail, to kill bacteria in the crypts and recesses of the throat, for when dissolved in the mouth it cannot reach and remain in contact with the organisms long enough to kill them before it is swallowed.

SUMMARY

Summed up, the investigation shows:

1. That the claims made for Formamint are extravagant and misleading.

2. That the recommendations for the use of these tablets may be, in some cases, fraught with danger and are a menace, not only to the health of the individual, but also to the safety of the community.

3. That the claim that Formamint is a definite chemical compound is false.

4. That the use of Formamint may produce marked irritation of the intestinal tract.

5. That Formamint is not a throat disinfectant, as the manufacturers maintain, but its action on the bacteria of the throat is an almost negligible one and dependence on Formamint for the prevention of infection and for curing disease is not only unwise but dangerous.

6. That Formamint conflicts with the rules of the Council. False statements are made with regard to its composition (Rule 1); grossly unwarranted claims are made for its therapeutic properties (Rule 6), and therefore its exploitation to the public (Rules 3 and 4) is a public danger.

It is recommended that this report be published, to call attention not only to the falsity of the claims made for, and the danger in the use of, Formamint, but also to emphasize the utter inefficiency of all such methods of “disinfecting” the throat.--(_From The Journal A. M. A., Aug. 28, 1915._)

HYDRAGOGIN

Report of the Council on Pharmacy and Chemistry

Hydragogin (C. Bischoff & Co., New York, selling agents) is advertised as “a most powerful diuretic and cardiac tonic.” The composition given is:

“Fifteen parts of the remedy contain 0.5 parts oxysaponin, 1.5 parts tincture of digitalis, 2.5 parts tincture of strophanthus, scillipicrin and scillitoxin, the active principles of scilla maritima, and alcohol.”

It is not clear from this statement whether 15 parts of Hydragogin contain 2.5 parts of tincture of strophanthus, plus unspecified amounts of scillipicrin and scillitoxin, or 2.5 parts of a mixture, in unspecified proportions, of tincture of strophanthus, scillipicrin and scillitoxin. The activity of strophanthus, after it enters the blood stream, is about fifty times that of digitalis; hence, if the former proportion is the true one, in giving an amount of Hydragogin which ensures the full therapeutic effect of the digitalis, one would administer an almost certainly fatal amount of strophanthus. Whatever the proportion of strophanthus may be, however, the administration of a mixture of digitalis and strophanthus in fixed proportions is indefensible. At times it is advisable to follow one of these drugs with the other in the treatment of cardiac disease. The simultaneous administration of the two continuously in fixed proportions, however, is injudicious, because of the great difference between their rates of absorption and in their activity after they enter the blood stream. The action of digitalis, moreover, persists much longer than does that of strophanthus.

An advertising circular contains the following claim:

“The well-known diuretic properties of digitalis, strophanthus and squills are greatly enhanced by the addition of the oxysaponin.”

This is not true. Saponins are not synergistic with digitalis therapeutically; on the contrary, they exert a purely deleterious action on the heart when they enter the circulation.

The symptoms of cardiac disease are often difficult to distinguish from the toxic actions of the digitalis bodies. Since these bodies must often be given to the point of beginning toxic action in order to induce the full therapeutic effects, it is obvious that the administration of a mixture of digitalis, strophanthus, saponin and active principles of squill is especially liable to induce serious toxic effects which cannot be distinguished from the symptoms of the disease.

Hydragogin is a shotgun mixture of semisecret composition; it is marketed under a therapeutically suggestive name, and advertised by means of unwarranted therapeutic claims. It is therefore in conflict with Rules 1, 6, 8 and 10. The Council held Hydragogin ineligible for New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 4, 1915._)

FILUDINE

Report of the Council on Pharmacy and Chemistry

Filudine is said to be prepared by J. L. Chatelain, Paris, and is sold in this country by Geo. J. Wallau, Inc., New York. It is offered as a remedy for “biliary insufficiency,” “hepatic insufficiency,” “intestinal dyspepsia,” “all affections of the liver (diabetes, cirrhosis, cancer, etc.),” “malaria,” “obesity” and “tuberculosis.”

No quantitative information is furnished as to the composition of the preparation and there are noteworthy discrepancies in the various statements regarding the ingredients. In one number of “Treatment,” a self-styled “Review” of medical literature (actually devoted to advertising the preparations sold by Wallau), we are told that

“This product [Filudine] is a more concentrated and potent extract of the liver, with which is combined an extract of the spleen. The liver and the spleen are so intimately interdependent, that the addition of a splenary extract to the liver extract is a signal improvement from which a synergistic action results. Thiarféine is also added, as it helps somewhat to combat the anaemia from which all diabetics suffer more or less.”

Thiarféine is said to be

“Thiomethylarsinate of Caffein, a new salt discovered by M. Chatelain.”

Another circular, which gives an imposing formula for “thiarféine” or “thiomethylarsinate of caffein,” states that

“Sulphurated methylarsinate is an arsenical preparation devoid of all toxicity on account of the intimate joining of its composing parts.”

And that

“Filudine can never be contraindicated.”

A statement of composition in a later number of “Treatment,” however, says that biliary extracts are components, in addition to the liver and spleen extracts. Moreover, thiarféine, the “new salt discovered by M. Chatelain,” is no longer “thiomethylarsinate,” but “thiocinnamate of caffein”; and a new formula is furnished for it.

We are told that

“Methyl-arsinate cannot be used in cases where fever is present....”

“M. Chatelain at first studied the action of thiomethylarsinate; clinical and physiological experimentation led him, however, to adopt thiocinnamate of caffein, of greater activity and with no contraindications.”

Nevertheless the same absence of contraindications was urged in favor of Filudine when it was said to contain the now discarded thiomethylarsinate of caffein.

The following are some of the unwarranted and even absurd claims:

“Filudine restores the liver’s functions. It is to the liver what digitalis is to the heart; it overcomes the insufficiency and stimulates the debilitated organ.”

In malaria “it is the only true specific when associated with quinine.”

“Filudine is ... the ideal medication for tuberculosis, conforming as it does with the most recent researches in the therapeusis of this affection.”

“We will not go as far as to say that Opotherapy _completely restores_ unhealthy livers, for although the lesions of the hepatic parenchyma may be obliterated by regeneration, the lesions of the connective tissues are permanent, and may be observed at the postmortem examination. The new cells, however, do not present the same unhealthy conditions as those of the former diseased gland which they have replaced, and the liver can therefore function normally, so that the patient lives on; and he is satisfied with that.”

“Therefore, while regenerating the liver with Filudine, we cleanse it and combat its congested state with Urodonal. We cause it to produce urea from the excess of uric acid which it contains.”

“By the judicious and harmonious combination of the beneficial effects of Filudine and Urodonal, physicians not only possess the means of treating by rational methods Cirrhosis of the Liver in its various forms (which is one of the most terrible diseases which can afflict anyone) but what is still better, _they can cure it_.”

“The liver of a person suffering from obesity being incapable of fulfilling its functions in regard to the fatty tissues, the rational and up-to-date method of treatment is therefore to restore to the system, in the form of Filudine, the liver extracts which are lacking.”

Filudine is a mixture of semisecret composition. The therapeutic claims are manifestly unwarranted. The name is not indicative of the composition, whatever that may be, and no rational excuse is offered for the combination of liver and spleen extracts (with or without bile extracts) with “thiomethylarsinate” or “thiocinnamate” of caffein.

The Council therefore held Filudine ineligible for New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 18, 1915._)

LACTOPEPTINE AND ELIXIR LACTOPEPTINE

Report of the Council on Pharmacy and Chemistry

Mixtures of pepsin and pancreatin are therapeutically irrational; the two substances are not indicated in the same conditions, nor can they act together. Under physiologic conditions, such mixtures are chemically impossible: in a liquid medium the ingredients destroy each other.

Lactopeptin is manufactured by the New York Pharmacal Association, Yonkers, N. Y. It is sold under the claim that it contains, pepsin, diastase, pancreatin, lactic acid and hydrochloric acid. This product was among the first proprietary preparations examined by the Council on Pharmacy and Chemistry. The report of the investigation was published in The Journal, March 16, 1907, p. 959. The preparation was found to be practically inert--“essentially a weak saccharated pepsin,” devoid of tryptic activity.

Six years later it was still widely advertised with the same irrational claims. A referee (A) therefore examined Lactopeptine (powdered) for the Council in 1913, and confirmed the previous findings. The referee’s report was published in The Journal, Aug. 2, 1913, p. 358.

Nearly four months after this publication, the manufacturer protested against the report, maintaining, contrary to the findings of the Council, that Lactopeptine possesses pancreatic activity and contains “loosely combined” hydrochloric acid. Referee A therefore repeated his examination, and a second referee (B), independently, examined specimens of Lactopeptine (powder) purchased on the open market for the purpose shortly before.

A few specimens examined by these two referees showed a slight tryptic activity; most of them showed none. The amount of hydrochloric acid present was insignificant.

The reports of the two referees were referred to the manufacturers, who again protested vehemently against these findings, this time on the ground that the specimens were old. The manufacturers also cited the work of three chemists to disprove the findings of the referees, and demanded that the Council reexamine Lactopeptine, making use of fresh specimens. The Council refused for the following reasons:

1. So long as the packages of Lactopeptine are not dated, the activity of specimens known to be fresh is of no practical importance. The activity of the actual market supply is the only question of interest to the profession. The only fair test is that made on specimens representative of the product sold to the ultimate consumer.

2. The evidence presented by the manufacturers did not warrant a reexamination, since the work of two of the chemists cited substantially corroborates the results obtained by the Council’s referees from the fresher specimens. The figures for tryptic activity obtained by the third chemist cited by the manufacturers could not be accepted by the Council, since it was at variance with all other known results of investigations of Lactopeptine.

3. As stated at the outset, whatever the tryptic activity of the mixture, it is therapeutically useless. A demonstration of tryptic activity in a mixture containing both pepsin and pancreatin is of merely theoretical interest.

Such activity, of course, cannot be expected, even on theoretical grounds, in liquid mixtures like Elixir Lactopeptine.

The Council therefore again declared Lactopeptine (powder and tablets) and Elixir Lactopeptine ineligible for New and Nonofficial Remedies and authorized publication of the following statement.

W. A. Puckner, Secretary

_THE COUNCIL’S REPORT_

Lactopeptine powder (New York Pharmacal Association, Yonkers, N. Y.) was examined by the Council in 1907. At that time it was claimed to contain

“... the five active agents of digestion--pepsin, diastase (veg. ptyalin), pancreatin, lactic acid and hydrochloric acid--combined in the proper proportion to insure the best results.”

The examination showed that the preparation was essentially “a weak saccharated pepsin,” containing but small amounts of pepsin, no hydrochloric acid, or mere traces only, and no diastase or pancreatin (The Journal, March 16, 1907).

In 1913, the product was reexamined, because the claims, as to both composition and therapeutic value, were still being made. Samples were tested both of the American product, and of a British product from John Morgan Richards & Sons, London. The original findings were confirmed and the results were published in The Journal, Aug. 2, 1913, p. 358. Nearly four months later (November 24) the New York Pharmacal Association wrote to the Council, objecting to the findings and maintaining that Lactopeptine possesses pancreatic activity and contains (“in loose chemical combination”) hydrochloric acid. In accordance with the custom of the Council, the work was sent back for review to the referee (A), whose conclusions were then tested by a second referee (B), a physiologic chemist, not a member of the Council, selected because of his special knowledge of the subject.

In December, 1913, Referee A made a large number of new tests to determine proteolytic and amylolytic power. His results show that the ferment activity of the preparation is so low as to merit no recognition in practical use. The tests also show that the amount of lactic acid or “loosely combined HCl” (or both) present is too small to have any appreciable physiologic activity and therefore to be of any therapeutic value.

Nine samples of Lactopeptine purchased in the open market in December, 1913, and January, 1914, were examined by Referee B early in 1914. His studies show absence of amylase in all samples; presence of pepsin, giving weak reactions even when compared with those of old pepsin preparations; complete absence of trypsin in seven out of nine samples, tryptic reaction being obtained in two samples, in one of which the reaction, “slight at best and of no practical import,” was obtained only after treatment for twelve hours or more.

The presence of tryptic activity in two out of the nine samples may be due to the fresher condition of these specimens, as indicated by the serial numbers. The evidence shows that it is a commercial impossibility to market mixtures of pepsin, pancreatin and lactic acid so that they can display any material tryptic activity.

It should be reaffirmed that mixtures combining peptic and pancreatic activities are not feasible, because pepsin cannot act except in the presence of acid, and pancreatin is destroyed by acid and by peptic activity. Furthermore, in conditions in which pancreatin is called for, pepsin is not, and vice versa; therefore the administration of mixtures of pepsin and pancreatin would be unjustified, even if both constituents could be expected to exert activity.

The foregoing observations apply to Lactopeptine in powder and tablet form.

While mixtures of pepsin and pancreatin are unscientific and unjustified, theoretically the two substances may coexist in a solid preparation, and the activity of such a preparation is consequently a proper subject of investigation. Theoretically as well as practically, however, pepsin and pancreatin cannot exist together in solution. The claims made for Elixir Lactopeptine and all other liquid preparations sold as mixtures of pepsin and pancreatin are therefore impossible. The Council has previously taken action (The Journal, Feb. 2, 1907, p. 434) refusing to approve for inclusion with New and Nonofficial Remedies such preparations, calling the attention of the medical profession and of manufacturers to their worthlessness, and requesting the American Pharmaceutical Association to instruct its committee on the National Formulary to omit from the next edition of that work a liquid preparation of pepsin and pancreatin recognized under the title of “elixir digestivum compositum.”

It is recommended that the Council reaffirm this previous action, and that Lactopeptine and Elixir Lactopeptine be declared ineligible for New and Nonofficial Remedies because of conflict with Rule 10 (“No article will be admitted which, because of its unscientific composition, is useless or inimical to the best interests of the public or of the medical profession”).

Manufacturers’ Protest and Council’s Answer

The foregoing was submitted, together with the findings of the two referees, to the manufacturers. They protested again, alleging that:

AGE OF SPECIMENS

_First._--The specimens of Lactopeptine examined by the second referee were old. The dates of manufacture corresponding to the several batch numbers are supplied by the manufacturers as follows:

2275 (Powder) September, 1908 2301 (Powder) June, 1909 2312 (Powder) December, 1909 2348 (Powder) October, 1911 2352 (Powder) December, 1911 2364 (Powder) July, 1912 2374 (Powder) March, 1913 2383 (Powder) October, 1913 1638 (Tablets) October, 1911

The manufacturers assert that they do not understand how specimens of these ages could have been purchased on the open market in 1913 and 1914, inasmuch as their agents are and long have been instructed to take up from the druggist all lots of Lactopeptine which, as indicated by the batch numbers, have attained “any appreciable age.” The age of the specimens, the manufacturers declare, deprives the table in the second referee’s report of “all significance or interest.”

As previously stated, however, the specimens of Lactopeptine examined were purchased on the open market in various localities in unbroken packages, in December, 1913, and January, 1914. They thus represent stock used in filling physicians’ prescriptions or sold to the public. Neither the referees nor any one connected with the Council had any means of knowing the age of the specimens until the dates of manufacture were furnished by the New York Pharmacal Association. The first tests of the second referee were made in February, 1914, on Specimens 2374 and 2383, which were then, it would appear, about one year old and four months old, respectively. The Council has repeatedly urged that pharmaceutical substances which are subject to deterioration should be dated by the manufacturer, and a similar suggestion has been made by the Bureau of Chemistry of the U. S. Department of Agriculture concerning mixtures containing enzymes. Notwithstanding the instructions which the New York Pharmacal Association claims to have given its agents, the market supply of Lactopeptine in December, 1913, and January, 1914, was not composed of new stock, and until the manufacturers adopt the practice of dating packages, there can be no assurance that it will be fresh. In this connection, it is of interest to note that the Bureau of Chemistry of the U. S. Department of Agriculture has issued a warning that it will judge such products by the degree of their activity when they reach the consumer, i. e., as they are found on the market.

REPORTS OF OTHER CHEMISTS

_Second._--The New York Pharmacal Association cites the work of several chemists, who have examined Lactopeptine and report the presence of tryptic activity. Dr. S. R. Benedict in December, 1913, reported to the Council “distinct” tryptic activity (digestion in twelve hours by Lactopeptine of 4.2 times its weight of fibrin containing 50 per cent. moisture) in specimens examined by him. These specimens were numbered 2382, and were therefore probably manufactured in October, 1913; compare the dates furnished by the manufacturer for the specimens used by the second referee. No tests against other preparations possessing tryptic activity are reported, and Dr. Benedict expressly disclaims any opinion as to the therapeutic value of the preparation.[27] Dr. P. B. Hawk, whose report was submitted by the manufacturers, found in Lactopeptine by Fermi’s method one-fifth tryptic activity of that of Merck’s pancreatin, and by Grützner’s method an activity of 18 per cent. of the pancreatin. A test for the production of tryptophan was reported positive. The New York Pharmacal Association also submitted a report from Dr. A. W. Balch, who found pepsin, rennin, trypsin, steapsin, amylopsin and lactic acid present in Lactopeptine; also an amount of combined hydrochloric acid in 1 gm. the equivalent of 1.05 c.c. tenth normal solution or 0.00383 gm. hydrochloric acid. (He reports digestion in twenty-four hours by Lactopeptine of 25 times its own weight of fibrin. “An active extract of pancreas reacted exactly like the Lactopeptine solution.”) The serial numbers of the specimens tested by Hawk and Balch are not given, but no doubt they were fresh.

[27] Dr. Benedict’s personal communication to a member of the Council is as follows:

“In the report of the Council upon Lactopeptine which you sent to me, I find the following statement: ‘Careful examination failed to show the presence of either diastase or pancreatin.’ In this connection I will cite to you the following experiment carried out by myself: A package containing a 1-ounce bottle of Lactopeptine (powder) with seal unbroken was purchased in the open market and opened in this laboratory. The label bore the special Number 6 2382. Two hundred milligrams of this product was dissolved in 50 c.c. of a 0.25 per cent. solution of sodium carbonate in water. This solution was divided into two portions of 25 c.c. each. One of these portions was boiled at once, and after cooling was added to 1 gm. of moist fibrin contained in a flask. The other portion (unboiled) was also added to 1 gm. of moist fibrin contained in a flask. Both flasks (after addition of 5 c.c. of toluene to each) were stoppered and placed in an incubator at 37 degrees, and left there for twelve hours. Examination of the two flasks at the end of this period showed that the one to which the unboiled solution of Lactopeptine [powder] had been added contained much less solid protein than did the other. Although this fact was obvious to the naked eye, the exact extent of digestion in the two flasks was determined by heating both to boiling, acidifying with acetic acid, diluting to definite volume, filtering and determining the nitrogen in the filtrate by Kjeldahl’s method. Subtracting the trace of nitrogen contained in the filtrate of the control flask, the results showed that 42 per cent. of the original fibrin present had been dissolved by the unboiled Lactopeptine solution. This can be ascribed only to tryptic activity under the conditions of this experiment. Furthermore, this is not simply a ‘trace’ of activity, but is at least sufficiently marked to warrant a statement that this sample showed a distinct tryptic activity. Inasmuch as I have obtained exactly similar results with two other samples of Lactopeptine (powder) (these being the only ones I have examined), I am inclined to question the correctness of the Council’s statement regarding the absence of trypsin from this preparation. [As noted above, a fresh preparation was used.--Ed.]

“May I again add that I am making no statement regarding therapeutic value of preparation, and that I have no opinion upon that matter one way or the other? My work was undertaken solely out of interest to see whether trypsin could exist in the powder (which gives a markedly acid solution when dissolved in water). The Elixir Lactopeptine could theoretically show no tryptic activity, nor have I found any trace of such activity in one sample of the Elixir examined.

“In making use of any of the contents of my letters kindly include the statement that my work upon Lactopeptine was done without remuneration of any kind, and was done only for the scientific interest attached to the question.”

CONCLUSIONS

The New York Pharmacal Association demanded that the referee reexamine Lactopeptine, making use of fresh specimens. The Council held that this was unnecessary, for the following reasons:

1. The previous finding of the Council, that specimens of Lactopeptine found on the open market are essentially weak saccharated pepsins, is not to be refuted by examination of fresh specimens. Even if it be assumed that all old specimens of Lactopeptine have been withdrawn from the market since the last purchase of specimens for the use of the Council’s referee, there can be no assurance that the stock will be constantly kept fresh. Unless the manufacturers date their product, physicians cannot know that their prescriptions are filled with fresh material. Nor is it reasonable to ask that the Council examine the market supply of any given proprietary at a time selected by the manufacturers.

2. Without entering into all questions of detail in the analyses, the Council is willing to accept the reports of Drs. Benedict and Hawk as representative of fresh Lactopeptine powder. It is therefore unnecessary for the Council to make further experiments along this line. The results of these two chemists in no wise contradict the conclusions of the Council’s referees, being comparable with those obtained by the referee on the fresher specimens used by them. The experiments of Drs. Hawk and Benedict show a degree of tryptic activity which, though chemically not negligible, is quite without significance practically, even if it could be assumed that the trypsin in the fresh Lactopeptine escaped destruction in the stomach. The figures for tryptic activity given by Dr. Benedict do not differ materially from those of the first referee. Those of Professor Hawk show a tryptic activity of from 18 to 20 per cent. of that of commercial pancreatin--and commercial pancreatins ordinarily are of low tryptic activity, if not inert (see Long and Muhleman: _Arch. Int. Med._, February, 1914, p. 314.) The reports of these chemists present no reason for changing the conclusion that “it is a commercial impossibility to market mixtures of pepsin, pancreatin and lactic acid so that they can display any material tryptic activity.”

The results which Dr. Balch obtained in a test for tryptic activity show a marked discrepancy with those obtained by Drs. Hawk and Benedict, not to mention the Council’s referees, and also with the fact that only about 11 per cent. of “pancreatin” is claimed in the published formula of Lactopeptine. The Council is unable to accept Dr. Balch’s result for trypsin or rennin as reliable. His other results are without significance and call for no special comment.

3. Even if tryptic activity were conceded to Lactopeptine, the preparation, like all preparations containing pepsin and pancreatin, would still be, as previously stated, therapeutically irrational.

The Council approved the report.

Report of Referee A

In view of the manufacturer’s reiteration of the claims for Lactopeptine powder, I have carried out further experiments to determine its proteolytic and amylolytic power.

For the proteolytic test I used fresh, well washed fibrin and examined samples of Lactopeptine powder numbered as follows:

No. 1. A part of the English product examined and reported on last spring.

No. 2.--A fresh bottle obtained at a Chicago retail drug store in December, 1913.

No. 3. A fresh bottle obtained at a Chicago retail store in December, 1913.

Portions of 1 gm. each of these samples were mixed with 5 gm. fibrin, 100 mg. of sodium carbonate and 50 c.c. of water in flasks. A little toluene was added to each flask, which was then closed with a tuft of cotton and the mixtures were incubated at 40 degrees through twenty-four hours. At the end of that time there was no marked change in the quantity of the fibrin remaining in each flask, the larger part by far being undigested.

As a control I used the sample of an active commercial trypsin, of which I added 500 mg. to the same quantity of water, fibrin and sodium carbonate. This was digested in the same bath at the same time. The digestion was practically completed in less than ten minutes, only minute flakes of the fibrin remaining.

It is evident that the digestive power of the Lactopeptine must be extremely low, and only a small fraction of that exhibited by a commercially good trypsin.

In an experiment with the English sample carried out through nineteen hours as above, using 2 gm. of fibrin and 100 mg. of ferment, it was found by nitrogen tests on the filtrate that about 12.2 per cent. of the protein had been brought into solution, an amount which is practically without importance in a digestion of such duration.

To test the starch digestive power I have made a large number of experiments. In a series just completed I mixed 1 gm. portions of Samples 1 and 2 with water to make 100 c.c. volumes. Before making up to the final volumes 0.5 c.c. of normal sodium hydroxid was added to neutralize the slight acidity of the ferment as shown by phenolphthalein.

Of these mixtures 4, 6, 8 and 10 c.c. portions were mixed with 50 c.c. of 1 per cent. starch paste and incubated at 40 degrees to find the colorless end-point in the starch digestion, by the iodin test.

At the end of twenty-two hours the iodin reaction was as strong as at the beginning, indicating no appreciable starch digestion.

To the flasks in which no digestion had taken place under these conditions, 5 mg. of a pancreas ferment was added. This gave an almost immediate conversion to the colorless end-point. This ferment was a sample of Holadin which had been in the laboratory about a year. The 5 mg. completed the reaction to the colorless end-point in less than ten minutes.

In a similar test I used 2 gm. of Lactopeptine No. 3, made up to 100 c.c. with 1.2 c.c. of normal alkali. Ten and 15 c.c. portions were incubated with 50 c.c. of 1 per cent. starch paste through twenty hours at 40 degrees with no apparent result. The Holadin then added, 5 mg. being used, completed the conversion in less than ten minutes.

This shows that the medium was a proper one for the test and that the Lactopeptine must be extremely weak. No sugar tests were made because the Lactopeptine contains milk sugar to the extent of about 60 per cent.

Similar results for both protein and starch digestives have been obtained in a large number of experiments. These here quoted show that the ferment activity of the preparation is so low as to merit no recognition practically. The digestion of a few milligrams of fibrin or starch after many hours of contact, while being perhaps scientifically possible, is of no value when we come to a consideration of the use of such bodies as digestive ferments in medicine.

The amount of lactic acid or “loosely combined HCl” present in Lactopeptine is very small, since the total acid which may be titrated by sodium hydroxid and phenolphthalein is measured by 0.5 c.c. of the normal hydroxid for 1 gm. of the Lactopeptine powder, in the mean. In different samples examined the range was found to be from 0.41 c.c. to 0.6 c.c. Tests with methyl orange, methyl red and other indicators showed that the free acidity is but trifling; if the whole of this acid, as measured by phenolphthalein, were calculated to HCl, the amount would be too small to have any appreciable physiologic activity, in view of the daily dose recommended, 10 to 20 grains of the powder.

Report of Referee B

The following table gives a summary of the results of my investigations on Lactopeptine. The numbers in the extreme left-hand column are the manufacturer’s identifying marks. These, it is assumed, run serially, the higher numbers indicating fresher specimens.

TABLE SHOWING ENZYMIC POWER OF LACTOPEPTINE PREPARATIONS

Amylase Pepsin Rennin Trypsin Lipase 2275 - + + - - 2301 - + + - - 2312 - + + - - 2348 - + + - - 2352 - + + - - 2364 - + + +(?) - 2374 - + + - +(?) 2383 - + + + +(?) 1638 (tablets) - + + - - Pancreatin (Old) - .. .. ++ -

The conclusions in the foregoing summary depend on the following criteria:

_Amylase_: removal of starch (paste), _small in proportion to begin with_.

_Pepsin_: solution of small shreds of _fresh_ fibrin in acid media.

_Rennin_: curdling of milk in moderate excess.

_Trypsin_: solution of small shreds of _fresh_ fibrin in neutral and alkaline media, and tryptophan test.

_Lipase_: coloration of litmus-milk; exact _color_ controls.

All tests were suitably controlled. The responses for pepsin were weak even when compared with those of old pepsin preparations.

In the table above, the interrogation points in parentheses (?) refer to results that were obtained after treatment for from twelve to twenty-four hours and indicates that the change was slight at best and of no practical import.--(_From The Journal A. M. A., Oct. 23, 1915, with additions._)

IODUM-MILLER AND IOD-IZD-OIL (MILLER’S)

Report of the Council on Pharmacy and Chemistry

The Council adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

A referee has submitted to the Council the following report of the Chemical Laboratory of the American Medical Association on Iodum-Miller and Iod-Izd-Oil (Miller’s) (Iodum-Miller Co., Kansas City, Mo.):

The unsatisfactory statements made in regard to the composition of Iodum-Miller and the far-reaching therapeutic recommendations for it induced the laboratory to make a chemical examination of the preparation. It claimed more or less directly that the preparation is entirely new and possesses novel characteristics.

It is asserted that

“Iodum-Miller is made from Soot Iodine, which is our own product. This Soot Iodine is SOLUBLE IN WATER before being combined with its base C.P. Glycerine.”

No information regarding “soot iodine” is offered and an inquiry sent to the proprietors by a physician brought only the noncommittal reply that “soot iodine”

“is made from Resublime [resublimed?] Iodine by a chemical process which renders it soluble in water before being combined with its base.”

Iodum-Miller is said to contain

“Active Free Iodine 2.2 grams per 100 c.c., 10. grains per fluid ounce, 1.7% by weight.”

“In addition to the active free iodine ... IODUM-MILLER carries a still greater per cent of Iodine in its basic combination....”

According to the label, the preparation is

“An Iodine for External and Internal use ... 45 drops equals 1 dr. by weight. Each drop equals the per cent. of iodine in 1 gr. potas. iodide.”

Iodum-Miller is a heavy, dark liquid having an odor characteristic of ether (ethyl oxid). Qualitative tests revealed the presence of glycerin, free iodin, iodid and potassium. The specific gravity at 25 degrees was 1.284. Direct titration with sodium thiosulphate solution indicated the presence of 1.68 per cent. of free iodin. A determination of the total iodin content by the Hunter method indicated 3.06 per cent. Subtraction of the amount of free iodin found from the total amount of iodin present, gives 1.38 per cent. combined iodin. Assuming this to be present as potassium iodid, as appears probable from the qualitative examination and from the quantitative determination of potassium, 1.80 per cent. potassium iodid is indicated. From this examination it is concluded that Iodum-Miller is, essentially, a solution of iodin and potassium iodid in glycerin, containing 1.68 per cent. free iodin and 1.80 per cent. potassium iodid. The examination contradicts the assumption that Iodum-Miller is either novel in principle or new. Moreover, accepting the firm’s statement that 45 drops weigh 1 dram (60 grains) the examination shows that one drop equals not “the per cent. of iodine in 1 gr. potas. iodide” but instead, the per cent. of iodin in only 1/20 grain potassium iodid. As the statement that “Each drop equals the per cent. of iodine in 1 gr. potas. iodide” appears on the label of the trade package, Iodum-Miller would seem to be misbranded under the federal Food and Drugs Act.

The recommended internal dosage of Iodum-Miller (from 1/2 to 20 drops) is equivalent to from 1/40 to 1 grain of potassium iodid. Its external efficacy in comparison with that of other iodin preparations may be estimated by comparing the respective free iodin contents, since the germicidal power of combined iodid is negligible. While Iodum-Miller contains 2.15 gm. free iodin in 100 c.c., tincture of iodin contains 7 gm. per 100 c.c. and compound solution of iodin (Lugol’s solution) contains 5 gm. free iodin in 100 gm.

Among the advertising literature is a circular which purports to be a “Certificate from Kansas City Testing Laboratory, by Roy Cross, Secretary.” The “certificate” attempts to prove that Iodum-Miller is vastly superior to the official tincture of iodin as a germicide, asserting that “In the process of dissolving [tincture of iodin] in water, a very large amount of the iodin is lost by precipitation....” This is not true of the tincture of iodin which is now official, though it is true of the tincture official in former editions of the Pharmacopeia. The report ignores completely the widely used aqueous solution of iodin.

Iod-Izd-Oil (Miller’s) is said to be an “Iodine Combination” made “from the same Soluble Soot Iodine as is IODUM-MILLER.” It is said to “liberate Free Soluble Iodine” when applied to the skin, mucous surfaces, etc. It is further defined as “Soluble Iodine combined with water-white Hydrocarbon Oil” and is said to liberate “Soluble Iodine 2 per cent.” While these statements suggest that Iod-Izd-Oil (Miller’s) contains the iodin-potassium iodid combination contained in Iodum-Miller, analysis indicated the oil to be a simple solution of iodin in liquid petrolatum. Quantitative determinations indicated, not 2 per cent. of iodin, as claimed, but only 0.42 per cent. and all of this was present as free iodin.

REFEREE’S REPORT

The following therapeutic claims appear on the label of a bottle of Iodum-Miller:

“EXTERNAL INDICATIONS

“Tuberculosis, Pneumonia, Pleurisy, Cough, Sore Throat, Pyorrhea, Tonsilitis, Rheumatism, Spinal Irritation, Boils, Felons or any Pain. Periostitis, Carbuncles, Fistula in Ano, Goiter, Blood Poison, Diseases of Uterus and appendages (apply full strength on cotton wrapped applicator), Gonorrhea, acute or chronic in both sexes, Orchitis, Bubo, Prostatitis, Swellings, Enlarged Glands, Etc.”

“INTERNAL INDICATIONS

“Pneumonia, Tuberculosis, Pleurisy, Typhoid Fever, Syphilis, Catarrh of Mucous surface of Alimentary Canal, Autotoxemia, Vomiting of Pregnancy, Rheumatism, Chronic Glandular and Organic Affections.”

The “certificate” from the Kansas City Testing Laboratory, mentioned above, states that Iodum-Miller was found to have a germicidal value nineteen times greater than carbolic acid--a somewhat remarkable finding in view of the fact that iodin dissolved by means of potassium iodid in alcohol or water, when tried on the typhoid bacillus has recently been found to possess only four times the germicidal value of carbolic acid in a solution of the same strength (Maben and White: _Chem. and Drug._, Jan. 30, 1915, p. 144). The “certificate” further states that the test “shows available iodine as found in IODUM-MILLER to have the greatest bactericidal power of any substance that we have ever tested that can be used medicinally.” There is no reason to believe that the desire to please its patrons has led the “testing laboratory” astray from the literal truth. The laboratory’s experience may be limited and the statement therefore entirely correct as far as it goes. No mention, however, is made of any tests comparing the germ-destroying power of Iodum-Miller with that of tincture of iodin, which contains 7 per cent. free iodin, unless the casual statement that “Iodum-Miller sterilized [the skin] more quickly” than tincture of iodin, be taken to imply such tests. It is not clear, however, by what means the laboratory was able to determine that there were no bacteria left alive in the skin after application of tincture of iodin and Iodum-Miller; no details are given of the methods used in arriving at this conclusion.

A circular says that Iodum-Miller

“... gives the Greatest Bactericidal and Therapeutic Action, whether used Internally, Externally, Hypodermically or Intravenously.”

In the light of the preceding report of the Chemical Laboratory of the Association, these claims require little comment. The laboratory has shown that the free iodin content (and consequently the germicidal efficiency) of Iodum-Miller is less than half that of Lugol’s solution, and less than a third of that of the official tincture of iodin. As for the advice to use Iodum-Miller internally in diseases ranging from pneumonia to syphilis and from typhoid to tuberculosis, in order to be convinced of its dangerous character, it is necessary only to recall that this treatment is equivalent to the administration of small doses of iodid--from 1/40 to 1 grain of potassium iodid. The mystery being removed from the composition of Iodum-Miller, the absurd extravagance of the claims made for it becomes manifest. The criticisms of the Council on the recommendations for Burnham’s Soluble Iodine (The Journal A. M. A., May 15, 1915, p. 1673) apply in almost every particular to Iodum-Miller.

Unwarranted therapeutic claims are made for Iodum-Miller; incorrect statements are made with regard to its composition and that of Iod-Izd-Oil (Miller’s); and the application of a trade name to both of these products is unjustifiable, since neither is original. It is therefore recommended that Iodum-Miller and Iod-Izd-Oil (Miller’s) be held ineligible for New and Nonofficial Remedies--(_Abstracted in The Journal A. M. A., Oct. 2, 1915._)

ELIXIR IODO-BROMIDE OF CALCIUM COMP. “WITHOUT MERCURY” AND “WITH MERCURY”

Report of the Council on Pharmacy and Chemistry

The Tilden Company, New Lebanon, N. Y., and St. Louis, Mo., sells “Elixir Iodo-Bromide of Calcium Comp. without Mercury” and “Elixir Iodo-Bromide of Calcium Comp. with Mercury.” The latter is said to contain, in addition to the ingredients of the former, 1/100 grain mercuric chlorid in each fluidram. According to the label the formula of the elixir “without mercury” is:

“_Formula_--Salts of Iodine, Bromine, Potassium, Sodium, Calcium, Magnesium with Stillingia, Sarsaparilla, Rumex, Dulcamara, Lappa, Taraxacum, Menispermum.”

A recent circular declares that the elixir contains:

“... a number of the most powerful alteratives of the pharmacopeia such as chemically pure iodin, magnesium, potassium with sarsaparilla, stillingia, prickly ash, burdock, taraxacum, etc. ... Each fluidounce contains seventy-two grains of the combined salts.”

The same circular also alleges that each dram of the preparation contains:

“... the equivalent of one and one-half grains of the combined iodids, potassium and calcium ...”

It will be observed that, (1) the two statements quoted from the circular make no reference to bromids; (2) the statement that each dram contains “the equivalent” of 1-1/2 grains of the combined iodids, potassium and calcium, accounts for but 12 of the 72 grains of “the combined salts” per fluidounce declared in the preceding quotation; (3) the circular mentions the presence of a drug--prickly ash--not declared on the label and, finally (4) none of the “formulas” gives the quantities of all of the several constituents.

It is evident from these “formulas” that the Tilden Company continues its policy of concealment and mystification as exemplified in the cases of Hydrocyanate of Iron, Tilden (discussed in The Journal, June 19, 1909, p. 2008), Febrisol (The Journal, June 29, 1912, p. 2043) and Respirazone (The Journal, June 14, 1913, p. 1899).

In the circular just quoted (“The Conquest of Syphilis”), all hope for the syphilitic is declared to rest in mercury and iodin, and it is implied that only through Elixir Iodo-Bromide of Calcium Comp. is it possible to obtain the greatest good from these drugs.

“Were the cleansing influences of these two drugs [mercury and iodin] unavailable to the luetic patient, he, truly, would be as pitiable an object as the leper ...

“Modern Pharmacy has devised no better means of utilizing these anti-syphilitics than Elixir Iodo-Bromide of Calcium Comp. (Tilden) with or without mercury.... The Elixir, in proper dosage, acts in specific fashion and is adapted for use in all stages of the disease.

“In the early months ... Elixir Iodo-Bromide of Calcium Comp. (Tilden) with mercury is a trustworthy weapon and the physician need have no fear but that it will subjugate the disease ...

“When ... the virulent stage is passed ... Elixir Iodo-Bromide of Calcium Comp. (Tilden) without mercury may be given the patient with every assurance that medicine’s most aggressive measures are being resorted to ... From time to time, up to the very end of the time honored three years’ period of treatment, it is well to put the patient back on the bichloride, using for this purpose the form of the Elixir administered in the first stages of the disease ...

“This regime ... will indubitably antidote the virus of syphilis and eradicate from the organism its every vestige.”

While it seems incredible that any physician would jeopardize the health--even the life--of a patient by accepting this boastful magniloquence as sound therapeutic advice, still the fact that certain medical journals lend their advertising pages to advertisements for Tilden’s Elixir with the caption “The Conquest of Syphilis” makes it incumbent on the Council to record its condemnation of the employment of this unscientific, semisecret mixture.

It is recommended that Elixir Iodo-Bromide of Calcium Comp. “without mercury” and “with mercury” be held in conflict with Rule 1 (secrecy of composition), Rule 6 (unwarranted therapeutic claims) and Rule 10 (unscientific composition).--(_From The Journal A. M. A., Nov. 6, 1915._)

LECITHIN PREPARATIONS OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report was sent to the manufacturers of the various lecithin preparations mentioned therein. As the replies of the manufacturers were obviously written from the commercial point of view and did not affect the Council’s conclusion that lecithin, when indicated, would be given more advantageously in the form of yolk of egg than in the less pure manufactured product, the Council directed that the report be published, together with extracts from the replies of the manufacturers.

W. A. Puckner, Secretary.

Commercial lecithin preparations are at best very impure substances; all are more or less altered from the original composition. Even with great care, the methods of extraction and drying always produce considerable decomposition; and in some cases the phosphorus and nitrogen contents bear but little relation to the theoretical values. (Long, J. H.: _Jour. Am. Chem. Soc._, xxx, 881. McLean, Hugh: _Chem. Abstracts_, May 20, 1915). There is not the slightest reliable evidence that commercial lecithin has any advantage over the lecithin contained in natural foods; the weight of probability is on the other side.

The doses recommended, moreover, are absurdly small; and the amount thus administered is without practical value. Why administer a few milligrams of a more or less decomposed lecithin when it is possible to give a far larger weight of a purer substance in the form of yolk of egg?

In view of these considerations the Council voted that the following proprietary products be omitted from the next edition of N. N. R.:

Glycerole of Lecithin Lecibrin Lecithin Solution Lecithol Neuro-Lecithin-Abbott

and that the general article on “Lecithin Preparations” be transferred to the annual Council Reports as a matter of record.

The report was submitted to the manufacturers. Their replies were evidently based on commercial consideration, and called for no modification in the report.

The referee recommended that the preceding report be published together with the following extracts from the replies of the manufacturers:

From Armour and Company:

“We are selling a good deal of Lecithol and it seems to be giving satisfactory results in some quarters.... We shall continue to advertise Lecithol along the lines we have employed heretofore.”

From the Abbott Laboratories:

“We can assure you of our confidence in the therapeutic value of Neuro-Lecithin. This has been attested by the reports of favorable results sent us by many physicians, as well as by the periodical literature of the last few years which contains a considerable number of very encouraging references to lecithin therapy.”

From Fairchild Bros. & Foster:

“We would like simply to say that the physician and the Council must be aware of the circumstances and the purposes which actuated us in placing lecithin at disposal, viz., the studies--research--of lecithin and the properties attributed to it and which led to inquiry for and consideration of it. The _quantities_ proposed for medicinal use were not suggested by us; the suggestion of lecithin in small quantities as a therapeutic agent was obviously directed by those who proposed it.... The question whether lecithin, per se, has therapeutic properties in contrast to lecithin as naturally contained in food substances, is something we do not undertake to decide. The Council, on purely theoretical grounds, decides in the negative notwithstanding clinical experience--internal and hypodermic--and thus would deny lecithin the status of a new and nonofficial remedy, worthy of at least tentative progressive clinical consideration. We can only say that we offered bona fide lecithin and that we did not make the investigation of lecithin a pretext for the sale of all sorts of lecithin ‘jumbles’ with lecithin in small proportions, taking their name and making their bid on lecithin.”

Below appears the general article which has been omitted from N. N. R.:

Lecithin Preparations

Lecithins are fat-like bodies belonging to the group of phosphatides. They all consist of glyceryl esters containing two fatty acid radicals and the phosphoric acid radical in which one of the residual hydrogens is replaced by the choline group. The fatty acid may be palmitic, oleic or stearic and various combinations are known to exist; for example, distearyl lecithin, stearyl palmityl lecithin and so on. The commercial lecithins usually include the closely related kephalins.

On saponification the lecithins split more or less readily into choline, the fatty acids and glycerophosphoric acid, and by fusion with alkali nitrate and carbonate they yield alkali phosphate. They occur, free or in combination as lecithoproteins, most abundantly in certain animal tissues, but there are also vegetable lecithins. The lecithins of commerce are obtained usually from yolks of eggs or from calves’ or sheep’s brains.

Numerous processes have been devised for the preparation of lecithin from egg-yolk or animal tissue. From egg-yolk it may be obtained by making an alcoholic extract and precipitating by cadmium chloride. The precipitate is washed with alcohol and ether, mixed with 80 per cent. alcohol and warmed with the proper amount of ammonium carbonate to remove the cadmium. After filtering hot and concentrating the filtrate the lecithin is thrown down by cooling to a low temperature--10 C. or below. The precipitate is taken up in chloroform and reprecipitated by acetone.

From tissues it is obtained by extracting with warm alcohol and ether, concentrating the extract, precipitating with acetone and repeating the operations.

Pure lecithin is white, but the commercial preparations are yellowish-brown wax-like solids, which are not soluble in water but form milky emulsions which exhibit the myeline figures under the microscope. The solubility in cold alcohol or ether is slight, but heat aids it. Lecithins are not soluble in acetone. They are hygroscopic and the water mixtures undergo decomposition on standing. They darken on exposure to air and light.

The alcoholic solution is precipitated by platinum or cadmium chloride. It is decomposed by alkalies with the formation of choline and trimethylamine. The ash contains phosphoric acid. The different lecithins contain from 3.84 to 4.12 per cent. of phosphorus and 1.73 to 1.86 per cent. of nitrogen. The ratio of nitrogen to phosphorus should be at 1 to 2.21.

Lecithin is incompatible with alkalies; it should be kept in well-stoppered bottles and should be protected from the light.

The content of lecithin (plus kephalin) in tissues is about as follows:

Per Cent. Egg-yolk 8 to 12 Egg-white 0.1 to 0.2 Liver 2.0 to 3.0 Kidney 2.0 to 3.6 Lung 2.0 to 3.0 Pancreas 2.0 to 3.0

_Actions and Uses._--The lecithin preparations have been recommended in many pathologic conditions, especially in malnutrition and sexual debility. Moderate doses are said to bring about a marked retention of nitrogen and phosphorus, but satisfactory proof of this is lacking. It is extremely unlikely that the small doses which have been recommended in pill or tablet form or in emulsions can have any perceptible action, in view of the fact that many of our natural foods contain much greater weights of available lecithins than the medicinal doses provide. There is no good basis for the statement that the free lecithin has a greater food value or is more readily assimilated than is the substance as found in eggs or tissue. The reverse proposition is much more likely to be true, especially when it is considered that the commercial preparations are usually somewhat altered or decomposed in the process of separation.

_Dosage._--Given by the mouth in the form of pills, tablets or glycero-alcoholic emulsions. The amount of actual lecithin ingested in this way is usually small because of the doubtful purity of the original preparation. Several doses, as commonly administered, would be required to furnish the amount of lecithin present in a small egg.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 122._)

PROPRIETARY NAMES FOR LIQUID PETROLATUM

Report of the Council on Pharmacy and Chemistry

The Council has accepted the following report and authorized its publication.

W. A. Puckner, Secretary.

A former report of the Council (Liquid Petrolatum or “Russian Mineral Oil,” Report Council Pharm. and Chem., The Journal, May 30, 1914, p. 1740) called attention to the large number of concerns that were placing on the market liquid petrolatum as a proprietary under coined names. Since then the number of such products has increased. The Council has been requested by several concerns to consider their products put out under proprietary brand names.

The rules of the Council affirm that “the application of ‘trade names’ to official or established nonproprietary substances tends to confusion and fosters many abuses.” In accordance with this general ruling, the Council has invariably refused to countenance proprietary names applied to liquid petrolatum. The Council holds that proprietary or coined names for this substance are detrimental to medical progress, since they are sure to foster the impression that the particular product is different from liquid petrolatum. Manufacturers have been advised that there is no objection to distinguishing their products by the addition of their firm name or the initial representing the firm name; for instance, “Liquid Petrolatum, A. B. and Co.” or “Liquid Petrolatum, Smith.” The Council also believes that such designations as “Star Liquid Petrolatum” or “Liquid Petrolatum, Anchor Brand,” may be regarded as unobjectionable, provided that the words “Liquid Petrolatum” are always used in connection with the brand designation and given equal prominence.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 127._)

SENG

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Seng (Sultan Drug Co., St. Louis) is called by the manufacturers:

“... a palatable preparation of Panax (Ginseng) in an aromatic vehicle.”

Regarding ginseng (_Panax quinquefolia_) the United States Dispensatory, nineteenth edition, page 1603, says:

“The extraordinary medicinal virtues formerly ascribed to ginseng had no other existence than in the imagination of the Chinese. It is little more than a demulcent, and in this country is not employed as a medicine.”

No discussion of ginseng is to be found in the more recently published books on pharmacology, materia medica and therapeutics, evidently because their authors agree with this estimate.

On the other hand, physicians are told through the medium of advertisements appearing in medical journals that Seng is:

“An efficient remedy in all affections in which the gastro-intestinal glands need stimulating.

“Exceptionally useful in atonic indigestion, malnutrition, convalescence from the acute diseases, and all digestive disorders characterized by deranged or depressed functions.” (_Woman’s Medical Journal_, July, 1914.)

According to the label, Seng is indicated in “indigestion,” “malassimilation,” “malnutrition” and “wasting diseases.” It is also stated--though the preparation is admitted to contain 18 per cent. of alcohol--that to give babies “ten to fifteen drops in water or milk during feeding” is a proper procedure and that “For Colic, Flatulency, etc., the dose for an adult or child may be repeated every half hour until relieved.”

The following are some of the exaggerated therapeutic claims made for this preparation of a worthless drug:

“As a result of its administration the gastro-intestinal secretions are augmented, the digestion of food is substantially increased, and fermentative processes are promptly overcome.”

“Seng will specifically encourage the secretion of the juices in the entire alimentary tract ...”

The formula furnished for Seng is non-quantitative and therefore meaningless. The preparation is exploited in a manner to encourage its ill-advised use by the public, and exaggerated and unwarranted therapeutic claims are made for it. The use of an inefficient or worthless drug like ginseng, moreover, is detrimental to rational therapeutics. The Council therefore voted that Seng be refused recognition for conflict with Rules 1, 4, 6 and 10.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 129._)

FROSST’S BLAUD CAPSULES

Report of the Council on Pharmacy and Chemistry

Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine Capsules were submitted to the Council by C. E. Frosst & Co., Montreal, Canada. This firm claims, on the authority of the report of a firm of analytical chemists, that:

“... of three leading Blaud preparations bought by us on the open market, the iron in Frosst’s Blaud Capsules showed the highest percentage of _Ferrous_ carbonate.”

The Chemical Laboratory of the American Medical Association found this claim unjustified. The laboratory reported that there was no especial difference in the ferrous iron content of the various Blaud pills found on the market, and that among ten specimens examined, the total iron content was the lowest in the Frosst specimen. In view of this the Council refused recognition to Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine Capsules.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 164._)

TYREE’S ELIXIR OF BUCHU AND HYOSCYAMUS COMPOUND

Report of the Council on Pharmacy and Chemistry

Each dessertspoonful of this preparation is said to represent

Buchu Leaves 3-1/2 grains Uva Ursi 1-1/8 grains Pareira Brava 1-1/8 grains Hyoscyamus 1-1/2 grains Hops 1-1/2 grains Acetate Potash 7-1/2 grains Spirits Nitre 5 grains Alcohol 5 per cent. (by volume)”

The manufacturer, J. S. Tyree, Washington, D. C., offers this formula to the medical profession with the following claim:

“Approximate composition made [sic] by quantitative and qualitative analysis of the finished product.”

It is also claimed that

“An even greater advantage of Tyree’s Buchu and Hyoscyamus Compound over other drugs, lies in the fact that every constituent of the former is required to conform to a fixed standard of active principle strength; hence the results derivable from it are absolutely uniform.”

These pretentious claims of scientific accuracy look rather absurd to chemists. Many of the substances present in buchu, hops, hyoscyamus, uva ursi and pareira brava are also present in other drugs; hence it would never occur to a pharmaceutical chemist to try to ascertain the composition of such a mixture as Tyree’s Elixir by “quantitative and qualitative analysis of the finished product,” much less to determine the “active principle strength” of each ingredient, for no methods are known by which this can be done.

It is claimed that, because of the care exercised in making Tyree’s Elixir

“... the results derivable from it are absolutely uniform.”

A moment’s reflection, however, must compel any physician to attribute this statement, on the most charitable construction, to sheer ignorance. Of course, even a definite chemical principle, such as quinin, does not exert uniform clinical action, for clinical conditions vary, and accordingly the patient may or may not be cured. It is simply preposterous to claim that the clinical results obtained from such substances as hops, pareira brava, buchu and uva ursi are absolutely uniform.

A peculiarly vicious claim is that the elixir renders the mucous surfaces of the genito-urinary tract “hostile to the multiplication of the gonococci.” Since infection with the gonococcus produces the direst results, any claim which means in plain English that the remedy assists in producing a cure or in preventing infection with that organism cannot be condemned too strongly. Uva ursi, to be sure, has some slight antiseptic action but it is devoid of any curative action in gonorrhea and the minute amounts that are present in the Tyree elixir are of no more protective value against gonorrheal infection than a grain of hexamethylenamin would be.

It is further claimed that the elixir is a “specific” for “Inflammation of the Bladder, Bright’s Disease, Renal Colic, Suppurative Nephritis, Acute Cystitis, Urethritis, Catarrh of the Bladder [it would be interesting to know what distinction the manufacturer draws between ‘Inflammation of the Bladder,’ ‘Cystitis’ and ‘Catarrh of the Bladder’], Acidemia, Edema, Vesical Catarrh of Old Age, Lithemia” and that ascites and anasarca “can be reduced greatly to the satisfaction of the patient, and honor of the physician” by using a mixture of Tyree’s Elixir and infusion of digitalis. Such claims as these do not merit serious discussion, for they carry their own refutation.

It is recommended that Tyree’s Elixir of Buchu and Hyoscyamus Compound be held in conflict with Rules 5, 6 and 10 and that publication of this report be authorized.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 167._)

HYDROLEINE

Report of the Council on Pharmacy and Chemistry

Hydroleine (Charles N. Crittenton Company, New York) is a cod liver oil emulsion said to contain 45 per cent. of cod liver oil, a trace of salicylic acid and 18-1/2 grains of “Pancreatin, Etc.,” per ounce. The advertising claims are based largely on the theory that cod liver oil is “that particular fat which dietetic experience and physiological chemistry have proved to be most digestible.” As a matter of fact, while the superior digestibility of cod liver oil over other oils has often been asserted, neither “dietetic experience” nor “physiological chemistry” have “proved” this by definite observations. The Crittenton Company claims that it is more readily split than other oils. This is probably not true, easy emulsification of the raw oil being often confounded with easy splitting. This latter claim, however, is offered in justification of the name “Hydroleine,” which the Crittenton Company interprets as “hydrated oil.” A circular wrapped around the bottle contains the assertion that “Cod Liver Oil has long been held in high esteem by the medical profession for the treatment of a large number of serious diseases.” This recommendation is likely to lead the public to place undue reliance on Hydroleine in the grave conditions mentioned.

The preparation is in conflict with the rules of the Council inasmuch as its name does not indicate its composition, unwarranted therapeutic claims are made for it, and the exploitation is likely to give the public unwarranted confidence in its value. The Council therefore held Hydroleine ineligible for New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 171._)

CURATIVE VACCINE, BRUSCHETTINI

Report of the Council on Pharmacy and Chemistry

Curative Vaccine, Bruschettini, manufactured by A. Bruschettini, Genoa, Italy, is claimed to have the properties “of acting directly on the tubercular bacillus, bringing directly into the field and determining a hyperproduction of antibacillar and antitoxic substances.” The use of the preparation is said to be indicated in “all forms of tuberculosis.”

A referee reported to the Council that he had examined the available information and believed that the use of this product had no satisfactory experimental basis. The method of preparation appears to be based more on theoretical considerations than on experimental basis.

On the recommendation of the Committee on Serums and Vaccines the Council voted that Curative Vaccine, Bruschettini, be not accepted because (1) the method used for the production of the vaccine was not satisfactorily stated; (2) the theory on which its use is based has not been satisfactorily confirmed, and (3) the value of the product is not upheld by satisfactory clinical evidence.

The Council’s findings, in accordance with its procedure, were sent to the manufacturers for comment. His reply was considered by a new referee who found that the matter presented did not warrant a revision of the Council’s conclusions. Accordingly the Council directed publication of its findings.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 176._)

STEARNS’ WINE

Report of the Council on Pharmacy and Chemistry

Frederick Stearns & Co. market a preparation known as “Stearns’ Wine,” “Stearns’ Wine of Cod Liver Ext. with Peptonate of Iron,” and as “Vinum Ext. Morrhuae, Stearns.” The constituents are said to be “concentrated extract of fresh cod livers,” “Peptonate of Iron” and a “fine quality of prime Sherry Wine” containing 18 per cent. of alcohol.

This preparation was at one time marketed through the medical profession, but is now advertised direct to the public in typical “patent medicine” style. The label on a recently purchased bottle of Stearns’ Wine contains the following statements:

“STEARNS WINE is an ideal tonic for elderly people, for weak, pale and delicate children and convalescents.

“STEARNS WINE has for many years been successfully prescribed in the treatment of general or nervous exhaustion, anemia, malnutrition, loss of appetite, loss of sleep, faulty circulation and impoverished blood supply.”

The scope of the recommendations for the preparation is further indicated in a booklet accompanying the bottle, which begins:

“STEARNS’ WINE, What It Is and Why It Is Good for You.”

The conclusion is:

“STEARNS’ WINE is a safe medicine for the young, middle-aged and old. It is a safeguard to the family health.”

It is not necessary to discuss either these all-embracing claims as to the therapeutic efficacy of the mixture or the fallacies presented in favor of cod-liver extract and peptonate of iron. The Council reaffirms the opinion that whatever therapeutic value cod liver may have resides chiefly, if not entirely, in its fatty constituents (The Journal, Oct. 9, 1909; Reports Council Pharm. and Chem., 1909, p. 115). A confirmation of this opinion has recently been furnished by the investigations of Prof. J. P. Street (The Journal A. M. A., Feb. 20, 1915, p. 638) of several cod liver cordials, one of which (Vinol) like Stearns’ Wine, is described as a wine of cod liver extract with peptonate of iron.

Stearns’ Wine is essentially an alcoholic stimulant. It is not “a safe medicine for the young, middle-aged and old.” The unwarranted therapeutic claims and the recommendations for its indiscriminate use bring it into conflict with Rules 4 and 6. The Council voted that Stearns’ Wine be held ineligible for inclusion in N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 177._)

PROTONUCLEIN AND PROTONUCLEIN BETA

Report of the Council on Pharmacy and Chemistry

The Council had adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Protonuclein, with other products of Reed and Carnrick, was examined by the Council in 1907 and found ineligible for admission to New and Nonofficial Remedies. According to the patent specifications, it is prepared “from the thyroid and thymus glands, brain (pineal glands and pituitary body), bone-marrow, pancreas, spleen, liver, salivary glands, Brunner’s glands, Lieberkühn’s follicles and peptic glands.” These various glandular bodies, it is said, are dried at a temperature below 130 F. (preferably between 100 and 110); the fat is removed by ether, the dried glands disintegrated, the connective tissue removed by sifting and the resulting powder coated with an ether solution of benzoin and mixed with milk sugar. The dose is three to ten tablets (9 to 30 grains) daily.

Protonuclein Beta is said to be produced by the addition to Protonuclein of an equal amount of nucleoplasm and protoplasm of the spleen. The dose is from two cubes (each 5 grains) three times a day to three cubes four times a day (30 to 60 grains daily).

Special advantages over ordinary nuclein are attributed to Protonuclein, in which, it is claimed, certain unaltered cells remain that are more easily assimilated by the leukocytes than are ordinary proteins, thus leading to a multiplication of cells. In the early advertising Protonuclein was claimed to be:

“... an exact physiological product derived from the lymphoid structures of the body without the use of chemical agents.... So delicate is Protonuclein that any chemical agent is liable to disturb its cellular activity.”

After its examination of the product in 1907 (The Journal, Oct. 5, 1907, p. 1198), the Council concluded that any distinction between the action of Protonuclein and that of ordinary nuclein was purely speculative and highly improbable. “If the active ingredients are really so unstable that they are destroyed by all chemical agents, as claimed, it seems impossible that the activity would be preserved when Protonuclein is given by mouth and therefore subjected to the very profound changes of digestion.”

At that time the importance of thyroid as an ingredient had not been emphasized. The following year, however, Hunt and Seidell (The Journal A. M. A., Oct. 24, 1908) reported the results of an investigation which showed that Protonuclein was a diluted thyroid preparation, as skilfully disguised as in the antifats Rengo and Marmola. Hunt later pointed out (The Journal, Feb. 1, 1913, p. 384) that the amount of nuclein contained in a dose of Protonuclein probably would not have the slightest effect, especially when given by mouth.

The following are extracts from the Protonuclein advertising matter:

“For cancer, infectious fevers (measles, scarlet fever, typhoid and septicaemia) and as a prophylactic.”

“Protonuclein: An ideal prophylactic for all infectious Diseases.”

“A true alterative and tissue builder.”

“The value of Protonuclein depends upon its ability to increase cell power and promote tissue strength. It is therefore needed whenever the organism is below the normal standard, more especially in Anaemia, Typhoid, Neoplasms and as a Prophylactic.”

All the foregoing claims and recommendations are supposed to be based on certain alleged discoveries which the Council has previously characterized as “a tissue of vague speculations ... in direct conflict with the known facts of physiologic chemistry.” As for the third claim, Hunt and Seidell have commented on the danger of recommending thyroid, the most powerful tissue-destroying drug known, as a “tissue builder.”

Protonuclein Beta, it is said:

“... combines the reconstructive action of Protonuclein with the action of the vital principle of the spleen, making it a distinct product for use in all tubercular troubles, including phthisis, localized joint affections and scrofular conditions.”

This product, according to the manufacturers, is based on the work of a certain Dr. Bayle of Cannes, France. Dr. Bayle said that he had treated tuberculous patients with fresh ground up spleen of hogs (25-100 grams per day), mixed with fruit preserve or bouillon; in cases in which this brought on gastro-intestinal disorders, extract of the spleen pulp was administered hypodermically. Bayle reported extraordinary improvements in the physical and mental conditions of his patients even after a few days of this treatment; over 90 per cent. of his tuberculous patients, according to him, improved or were cured. This applied to all types and stages of tuberculosis in man. “With the spleen pulp treatment tuberculous glands disappear like syphilis lesions on administration of mercury and iodids.”

This “spleen specific” of Bayle lacks scientific foundation; Bayle’s own cases were not adequately controlled, and no notice has been taken of Bayle’s report by experts on tuberculosis. Hence it practically lacks both confirmation and contradiction.

The spleen is invaded by tubercle bacilli quite as frequently as are the kidneys and the liver; it has no special toxic action on these bacilli. Nor is there any reason to believe that the end products of gastric and intestinal digestion of spleen pulp, after absorption into the blood, exert such toxic action. It cannot be assumed that these end products indirectly aid the healing processes through improved metabolism, for there is no evidence that they have any specific nutritive or stimulating action after such absorption. Altogether, what we know of the physiology and pathology of the spleen does not warrant us in looking for a “specific” against tuberculosis in this organ.

If, however, the known facts did justify any hope that the spleen might furnish such a specific, manufacturers would not be warranted in exploiting or physicians in prescribing spleen products as a remedy for tuberculosis until control experiments on animals had confirmed the therapeutic value of these products. In a chronic disease like tuberculosis, no conclusions that are scientifically valid can be drawn from clinical cases until many cases have been observed for years under suitable conditions. Right here it may be said that the clinical “evidence” offered in favor of Protonuclein Beta is worthless. The observations which have been reported on this product are not such as to permit any valid final conclusions to be drawn with regard to its value.

The rational method of proving the worth of an alleged new specific such as this is by animal experimentation. So far as we know, neither Dr. Bayle nor the Reed and Carnrick company has performed any such experiments with “spleen pulp” or Protonuclein Beta; nor are we aware that any competent investigator has done so. There is, to the best of our knowledge, no scientific evidence on which to base the claims for Protonuclein Beta.

The Council reaffirms its former action with regard to Protonuclein. The objections made to Protonuclein apply with equal force to Protonuclein Beta. In view of the lack of evidence, the claims for Protonuclein Beta are unwarranted and the product is ineligible to N. N. R. on account of noncompliance with Rules 1, 6 and 8.--(_From The Journal A. M. A., Jan. 1, 1916._)

HYDROPSIN

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Hydropsin is marketed by the Ernst Bischoff Company, Inc., New York. Its composition is thus described:

“Hydropsin is the standardized dialysate of Digitalis purpurea, Betula alba, Scilla maritima, Juniperis communis, and Herniaria glabra; or, stated otherwise, it is the juice of these drugs, dialyzed and physiologically standardized.”

“Each fluid dram represents Digitalysatum 7 gtts., and 2 gtts. each of the dialysates of Betula, Herniaria, Juniper and Scilla.”

The composition of Hydropsin must be considered essentially secret since the amounts of the several constituent drugs in a given amount of “dialysate” are not disclosed. The active principle of juniper is a volatile oil which is practically insoluble in water; it is difficult to believe that the “juice” of juniper submitted to dialysis could contain any material amount of the active constituent. No information is given as to the method used whereby the several dialysates are “physiologically standardized.” It therefore remains to be proved that the manufacturer of Hydropsin possesses any method whereby the dialysates of juniper (Juniperis communis), birch (Betula alba, the common European birch) and knot weed (Herniaria glabra) are so standardized. The claim is made that:

“Herniaria has long been recognized as one of the most valuable drugs in the treatment of dropsical affections due to cardiac impairment.”

On the contrary, Herniaria belongs to that large class of drugs which have been tried, found wanting and abandoned. It is a very old remedy, and the claims made for it are an inheritance from the early herbalists, with whom it was very popular. According to King’s American Dispensatory, it was “principally employed to cure _hernia_ (hence its name) and to increase the flow of urine. It was also said to increase the flow of bile.... Internally and externally, it was praised in _snake-bites_, and the powdered plant was employed to kill maggots on unhealthy _sores_ of horses. It was reputed to ‘crush’ and expel calculi from the kidneys and bladder....”

The Ernst Bischoff Company says that:

“Betula exerts both an antiseptic and stimulating influence on the urinary passages and is particularly serviceable where a catarrhal condition of the bladder exists. When combined with other diuretics, as in Hydropsin, the drug affords highly satisfactory results in the treatment of ascites, cardiac dropsy and hydrothorax.”

Birch is another drug which has been discarded. Few textbooks on materia medica even mention it. That it can materially affect the action of such powerful drugs as squill and digitalis is exceedingly doubtful.

An unwarranted implication--that in this preparation the powerful drugs digitalis and squill have been deprived of their dangerous qualities--is the assertion:

“Dialysis, removing all resins and colloidals, results in better tolerance on part of sensitive patients, and in more rapid absorption and elimination; which, in turn, means early therapeutic effects and little or no fear of toxic accumulation.”

That removal of colloids and resins materially affects the tolerance of these drugs is improbable. To claim that because of their removal, there need be “little or no fear of toxic accumulation” is utterly without warrant. The claim that one preparation containing digitalis is less likely to produce cumulative effect than any other digitalis preparation is contradicted by a mass of evidence.

It is claimed that Hydropsin affects “favorably all forms of dropsy or Edema that are at all amenable to medical treatment.” There can be no question but that squill and digitalis, or, better, either singly, used in suitable cases, may relieve dropsical effusions; but to claim that such a complex mixture as Hydropsin can favorably affect all forms of dropsy that are amenable to medical treatment is on its face unwarranted.

The claim is made that:

“By reason of its unusual potency and relative harmlessness, Hydropsin may be employed to great advantage in all cases where it is desirable to increase the volume of urine without injury to the renal structures.”

On the basis of the claimed composition, the action of Hydropsin must be essentially that of digitalis or of digitalis and squill. Consequently, if it possesses “unusual potency,” it cannot possess “relative harmlessness,” and vice versa. Neither digitalis nor squill should be employed “in all cases” of nephritis, even if it is “desirable to increase the volume of urine.”

The composition claimed for Hydropsin brands it as an irrational mixture in which potent drugs are combined with, and more or less covered up by, others that are obsolete and inefficient. The name, instead of indicating its composition, suggests diseases in which it may be thoughtlessly and indiscriminately used. The claim that the danger of toxic or cumulative action has been removed, if accepted by physicians, tends to uncritical use with possible disastrous results. Hydropsin is ineligible for New and Nonofficial Remedies because of conflict with Rules 1, 2, 6, 8 and 10.--(_From The Journal A. M. A., Jan. 8, 1916._)

DIGITALYSATUM

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Digitalysatum is sold in the United States by Ernst Bischoff Company, Inc., New York. The firm claims that it is a dialysate prepared from the juice of freshly gathered digitalis, containing all the active principles, and representing the fresh plant weight for weight. It is said to be standardized physiologically and to contain 12 per cent. alcohol. Sterisol-Digitalysatum, intended for injection, appears to be the “dialysate” without alcohol, diluted with equal parts of physiologic sodium chlorid solution. The Council some years ago found both products ineligible for New and Nonofficial Remedies because of unwarranted therapeutic claims. The preparations are still being advertised to physicians under claims which imply superiority to all other digitalis preparations. For instance:

“Digitalysatum is the diuretic _par excellence_ in cardiac insufficiency ...”

“Digitalysatum as a diuretic and cardiac stimulant is in a class by itself, being quick of action, uniform in strength, and well tolerated.”

“Digitalysatum differs from other forms of digitalis in these respects:... Digitalysatum is free from fat, resins and colloids, and is therefore well-borne by sensitive patients--the young and the feeble--and is quickly absorbed and eliminated....”

The Council has elsewhere[28] expressed the conviction that tincture of digitalis produces the full therapeutic effects of digitalis; that, when properly made, the tincture is as stable as any liquid preparation of digitalis now available, and that attempts to enhance the reputation of proprietary products by exaggerating the disadvantages of the official preparation are to be deplored. No adequate evidence is offered of the claimed superiority of action of Digitalysatum.

[28] Report on Proprietary Digitalis Preparations, J. A. M. A., Dec. 4, 1915, p. 2024.

By implication, the claim is made that Digitalysatum is superior to other digitalis preparations in respect to toxicity:

“Free from fat, resins and colloidals, it is always well borne and is quickly absorbed and eliminated. No case of toxic accumulation (faulty elimination) has ever been reported.”

That Digitalysatum is free from the dangers of toxic cumulation is highly improbable; in fact, it is inconsistent with the statement that the preparation contains all the constituents found in the fresh plant. Even if instances of cumulative action have not been reported this does not prove that such cumulative action does not occur. The tincture of digitalis has the systemic side-effects of digitalis in no greater degree than the various proprietary preparations. Attempts to create the impression that Digitalysatum possesses all the virtues of digitalis without its chief disadvantage are to be condemned as likely to lead to incautious use of the preparation.

These exaggerated claims are in the main made indirectly, but they are none the less inimical to sound therapy. The Council therefore declared Digitalysatum ineligible for New and Nonofficial Remedies and voted that this report be published.--(_From The Journal A. M. A., Jan. 8, 1916._)

SO-CALLED SECRETIN PREPARATIONS

Report of the Council on Pharmacy and Chemistry

The Council authorized the following report for publication, and voted to endorse the work of Professor Carlson discussed therein.

W. A. Puckner, Secretary.

The Council has not accepted for inclusion in New and Nonofficial Remedies any preparations said to contain secretin or prosecretin as their active ingredient. A report giving the reasons for the rejection of one (the first of the so-called secretin preparations marketed) was published early last year;[29] an article on secretin, based on work undertaken at the request of the Council on Pharmacy and Chemistry, is now published.[30]

[29] Secretogen, J. A. M. A., May 1, 1915, p. 1518.

[30] Carlson, A. J.; Lebensohn, J. E., and Pearlmann, S. J.: Has Secretin a Therapeutic Value? J. A. M. A. =66=:178 (Jan. 15) 1916.

Lest the appearance of this detailed study of secretin, after the rejection of so-called secretin preparations, should be interpreted (as manufacturers whose products have been rejected have endeavored to interpret such action) as a case of first condemning a preparation and then getting the facts, the Council’s methods, and their application in this case, may be briefly stated. The Council maintains that, when a manufacturer places a product on the market, the burden of proof is on that manufacturer to show that the properties of his product are in accordance with his claims for it. As stated in the introduction to N. N. R., “it is ... manifestly impossible for the Council to investigate the composition of every complex pharmaceutical mixture, or to check thoroughly every therapeutic claim; it can give only an unbiased judgment on the available evidence.” Acting on this principle, the Council examined the claims made for Secretogen, an alleged secretin product manufactured by the G. W. Carnrick Company. The conclusion was that these claims were in absolute conflict with the available evidence as to the action of secretin.

It is not necessary to review this subject again. It will suffice to state that the claims made for Secretogen rest on two fundamental propositions: (1) that deficiency of secretin (or, rather, of prosecretin) in the intestinal mucosa is a factor in gastro-intestinal diseases; (2) that secretin given by the mouth is absorbed and produces increased secretion of the pancreatic and intestinal juices and of the bile.

From an examination of the evidence available, including that submitted by the manufacturers, the Council concluded: “1. No evidence has been presented that the absence of secretin is a cause of gastro-intestinal disease. 2. There is no evidence that secretin in any form is physiologically active when administered by mouth.” That these conclusions were justified is shown again by the review given by Carlson of the literature, much of which was also reviewed in the Council’s previous report.

Since the claims of the Carnrick Company were not supported by any satisfactory evidence, no further investigation on the Council’s part was necessary to warrant rejection of the product. The Council did not undertake to determine, for instance, whether or not Secretogen and similar products actually contain secretin; the determination of this point was immaterial here, in view of the conclusiveness of the evidence that secretin given by mouth has no physiologic action.

Since firms other than the G. W. Carnrick Company are manufacturing alleged secretin preparations, and since recommendations for the use of secretin preparations in gastro-intestinal diseases have even crept into textbooks, it seemed desirable to obtain further information on certain points. The Council therefore requested Prof. A. J. Carlson of the University of Chicago to check the results of previous investigators with regard to the action of secretin administered by mouth or directly into the intestine, and, in addition, to investigate the secretin content of certain alleged secretin preparations.

Carlson and his co-workers, like all previous investigators, found that secretin given by mouth, or introduced even in enormous doses directly into the intestine, is entirely inactive. They also found that marked destruction of secretin followed contact for one minute with human gastric juice and that secretin is rapidly oxidized and rendered inert in contact with the air.

Further, they were unable to demonstrate the presence of secretin in samples of Secretogen and another supposed secretin preparation (Duodenin) bought on the open market. In the case of Secretogen there was one exception: one bottle was found which contained a little secretin, but it was necessary to administer (by intravenous injection, of course) the entire contents of the bottle (100 tablets) to obtain “a small but unmistakable secretin reaction.”

In these studies the methods employed were those by which secretin was discovered. It is only by the use of such methods that the presence or absence of secretin can be determined. Apparently the manufacturers who place so-called secretin preparations on the market do not make use of these methods, by which alone even the composition of their products can be determined.

Carlson and his collaborators conclude:

“There is as yet no reliable evidence that lack of secretin is a primary or important factor in any disease. Even should this be established, secretin therapy, to be effective, must be intravenous. Secretin has not yet been prepared in sufficiently pure state to render possible intravenous injection in man without injurious effects. And even when this is attained, the very fleeting action of secretin will in all probability render secretin therapy as futile in all the diseases in which it is theoretically indicated as epinephrin therapy is in Addison’s disease.”

In short, secretin is as ineffective taken by mouth as it would be rubbed on the skin.

The referee recommends that the work of Professor Carlson be endorsed.--(_From The Journal A. M. A., Jan. 15, 1916._)

HAS SECRETIN A THERAPEUTIC VALUE?[B]

A. J. Carlson, Ph.D., J. E. Lebensohn, M.S., and S. J. Pearlman, B.S. Chicago

[B] From the Hull Physiological Laboratory of the University of Chicago.

[B] This investigation was undertaken at the request of the Council on Pharmacy and Chemistry. The following report, having been submitted to the Council, received its endorsement (see preceding report of the Council on Pharmacy and Chemistry, “So-Called Secretin Preparations”).

It is well established that acid chyme in the duodenum is the normal stimulus to the secretion of pancreatic juice.[31] Interaction of the acid with the duodenal mucosa liberates into the blood stream a substance which, circulating through the pancreas, excites the latter to activity. This exciting substance has been termed “secretin.” It can be prepared artificially by macerating duodenojejunal mucosa in 0.4 per cent. hydrochloric acid, neutralizing the boiling mixture, and filtering. A few cubic centimeters of the filtrate injected into a vein produce invariably a powerful secretion of pancreatic juice.[32] That a “chemical messenger” is at the basis of the duodenal acid reflex has been proved by even more crucial experiments--transfusion (Wertheimer,[33] Enriquez and Hallion[34]), cross circulation (Fleig,[35] Matuso[36]), and perfusion of the isolated pancreas (Huston[37]).

[31] Pawlow: The Work of the Digestive Glands, 1912.

[32] Bayliss and Starling: Jour. Physiol. =28=:325, 1902.

[33] Wertheimer: Compt. rend. Soc. de biol. =54=:475, 1902.

[34] Enriquez and Hallion: Compt. rend. Soc. de biol. =55=:233, 363, 1903.

[35] Fleig: Arch. internat. de Physiol., =10=:206, 1910.

[36] Matuso: Jour. Physiol. =45=:477, 1913.

[37] Huston: Ann. et bull. Soc. roy. de sc. méd. et nat. =70=:178, 1912.

PROPERTIES OF SECRETIN

_Prosecretin._--Secretin is soluble in water, yet a watery extract of intestinal scrapings is without action,[32] even after being submitted to acid treatment.[38] Starling therefore holds that secretin exists in the intestinal mucosa in an inactive form, as “prosecretin.” The content of the intestine in prosecretin decreases from the duodenum down, so that one is unable to demonstrate any prosecretin in the last 2-1/2 feet of the ileum. Prosecretin is insoluble in water, acetone, absolute alcohol or ether. Secretin, on the other hand, is readily soluble in water, normal salt solution and diluted alcohol (70 per cent.), but likewise insoluble in absolute alcohol and ether.

[38] Starling: Lancet, London =2=:433, 1905.

_Preparation._--All of the more dissociated acids liberate secretin from intestinal mucosa on boiling. Their action is dependent on the degree of dissociation,[39] carbonic and boric acids being inactive.[40] Secretin can also be prepared with strong soaps (from 10 to 30 per cent. sodium oleate), alcohol (70 per cent.,[41] 0.6 per cent. sodium chlorid[36]). The acid and soap in the duodenum produce secretion; there is no necessary correspondence between the action of a substance in the intestine and that obtained by injection after boiling mucosa with it. The sodium chlorid, bile, maltose and glucose produce some secretion by the latter method yet none by the former.[36] On the other hand, ether, chloral and oil of mustard excite secretion when in the intestine, but no secretin can be prepared from boiled mucosa by their action. The irritation of the lining cell has produced the necessary hydrolysis.[38] In well-controlled experiments, Wertheimer and LePage[42] found that after the introduction of acid, secretion is secreted into the lumen of the intestine. Matuso[36] confirmed their results, and found this a satisfactory method for the preparation of secretin. It is said that secretin can be obtained by merely boiling the mucosa with water, but the results are inconstant.[43]

[39] Frouin and Lalou: Compt. rend. Soc. de biol., =71=:189, 1911.

[40] Camus: Compt. rend. Soc. de biol., 1902, =54=:442, 1902.

[41] Fleig: Jour. de physiol. et de path. gén. =6=:32, 50, 1904.

[42] Wertheimer and LePage: Jour. de physiol. et de path. gén. =4=:1061, 1070, 1902.

[43] Stepp: Jour. Physiol. =43=:441, 1912.

_Action._--Secretin is an excitant not only of the pancreatic juice but also of the liver and the intestinal mucosa. The flow of bile is markedly accelerated (Henri and Portier,[44] Enriquez and Hallion[45]), likewise that of succus entericus (Delezenne and Frouin,[46] Bottazzi and Gabrielli[47]), and intestinal peristalsis is stimulated (Enriquez and Hallion,[48] Falloise[49]). Injections of secretin produce a marked vasodilatation, but the secretory effect is independent of the blood pressure changes. The pancreas is not readily fatigued by secretin. Bayliss and Starling[50] have obtained undiminished flow after eight hours of continuous injection. Our experience confirms this result. Also, equal doses of secretin give corresponding results at various intervals. Moreover, anesthesia does not affect the flow. Secretin is unrecoverable from the glands even after two hours of continuous injection.[51] The juice obtained by secretin has been subject to many studies.[52] It is of high alkalinity (about seventh normal), contains all the pancreatic ferments, and corresponds in all respects to the juice obtained in digestion from permanent pancreatic fistulas.[53]

[44] Henri and Portier: Compt. rend. Soc. de biol. =54=:620, 1902.

[45] Enriquez and Hallion: Presse méd. =1=:105, 1903.

[46] Delezenne and Frouin: Compt. rend. Soc. de biol. =56=:319, 1904.

[47] Bottazzi and Gabrielli: Arch. internat. de physiol. =111=:156, 1905.

[48] Enriquez and Hallion: Bull. gén. de thér. =162=:202, 1911.

[49] Falloise: Bull. de l’Acad. roy. de Belgique =5=:945, 1902.

[50] Bayliss and Starling (Note 2). Matuso (Note 6). Arch. internat. de physiol. =10=:335, 1911.

[51] Dixon and Hamill: Jour. Physiol., 1909, xxxv, 314.

[52] Bayliss and Starling: Jour. Physiol., 1904, xxx, 61. Bierry: Compt. rend. Soc. de biol., 1907, lxii, 433. Bierry and Terroine: Compt. rend. Acad. de sc., 1905, cxli, 146. Lalou: Comp. rend. Acad. de sc., 1910, xxix, 824. Morel: Compt. rend. Soc. de biol., 1909, lxvii, 36. Strassano and Billoro: Compt. rend. Soc. de biol., 1902, liv, 937.

[53] Bayliss and Starling (Note 23).

_Specificity._--In a maceration of the duodenojejunal mucosa, such as we have in secretin, the known substances are proteoses and peptones, acid amins, bile salts, beta-imidazolethylamin, cholin, gelatin and inorganic salts. These substances, individually and severally, together with their derivatives, are devoid of secretory action. Chemically, secretin, is then a specific entity. But like epinephrin, in its distribution, it is nonspecific. Active preparations have been made from an extraordinary variety of animals among the different classes of vertebrates (Camus,[54] Bayliss and Starling,[55] Chapman[56]). It is likewise found in the new-born and in the fetus.[57] Its action, however, like its chemical composition, is markedly specific. It stimulates the flow of pancreatic juice, bile and succus entericus. Its effect on the gastric glands is negative, and on the saliva likewise.[58] On the other hand, no other extracts produce pancreatic secretion. Dr. Koch, who, in collaboration with Dr. Keeton and Dr. Luckhardt, has done the most recent work on gastrin[59] (a substance that most nearly resembles secretin) and has isolated an extremely active preparation, finds that gastrin injection has likewise no effect on the pancreas. Camus and Gley,[60] with crude preparations, had previously obtained a similar result.

[54] Camus: Jour. de physiol. et de path. gén. =4=:998, 1902.

[55] Bayliss and Starling: Jour. Physiol. =29=:174, 1903.

[56] Chapman: Proc. Linnaean Soc., New South Wales =1=:92, 1905.

[57] Camus: Compt. rend. Soc. de biol. =61=:59, 1906. Hallion and Lequex: Compt. rend. Soc. de biol. =61=:33, 1906.

[58] Derouaux: Arch. internat. de physiol. =3=:44, 1905. Lambert and Myer: Compt. rend. Soc. de biol. =54=:1044, 1902. Starling: Lancet, London =2=:501, 1905.

[59] Keeton and Koch: Am. Jour. Physiol. =37=:481, 1915.

[60] Camus and Gley: Compt. rend. Soc. de biol. =54=:648, 1902.

_Lability._--Neutral secretin is but feebly attacked by a temperature of 100 C. If heated in an autoclave (so as to prevent oxidation), this temperature can be continued for thirty minutes without any change in its activity. Increasing the temperature increases the speed of destruction, so that at 140 C. the destructive action is marked.[61] Autoclaving at 15 pounds for fifteen minutes, as an ordinary sterilization of culture mediums, produces, we found, a distinct though not serious decrease in activity. Secretin acidified to fifth-normal with hydrochloric acid loses 60 per cent. of its activity on fifteen minutes boiling. Secretin, alkalinized to fifth-normal with sodium hydroxid loses 95 per cent. of its activity in five minutes’ boiling; decreases to a trace in thirty minutes, and disappears entirely in sixty minutes. At room temperature, with fifth-normal alkalinity, 80 per cent. of secretin is destroyed in eight hours.[61] The destruction probably means a secondary cleavage of the secretin molecule itself.

[61] Lalou (Note 21). May: Jour. Physiol. =30=:400, 1904.

Secretin is oxidized readily. If left standing uncovered for a summer’s day, the preparation will be inactive.[51] Even if kept in the ice-chest (no other precaution being taken), its activity is lost in a very few days. Sunlight undoubtedly hastens the oxidative process. If care is taken as to sterility, however, and the secretin is kept in the ice-chest, well stoppered and in a dark flask, it will retain its activity for several weeks.

Dixon and Hamill[51] claimed that secretin disappears quantitatively on passage through a Berkefeld filter at 5 mm. pressure. Lalou,[62] using higher pressure, was unable to confirm the finding, but obtained a marked decrease in activity. Our results are in accord with those of Lalou.

[62] Launoy: Arch. internat. de Physiol. =3=:62, 1906. Morel and Terroine: Compt. rend. Soc. de biol. =67=:36, 1909. Zunz: Arch. internat. de physiol. =8=:181, 1909. Lalou: Jour. de physiol. =14=:465, 1912.

_Analogy to Epinephrin._--The analogy of secretin to epinephrin does not generally receive enough emphasis. Both substances are nonspecific in distribution, but specific chemically, and especially physiologically, epinephrin acting on the myoneural junctions, secretin on intestinal digestion. They are both relatively simple substances of low molecular weight, and subject to rapid oxidation whereby their properties disappear. The action in both cases is very transient. They are the two examples of what Starling calls the “acute hormones,” in which it is essential that reaction take place immediately, and shall disappear as soon as the exciting cause is removed.[63]

[63] Starling: Proc. Roy. Soc. Med., 8, No. 4, 1914, Therap. and Pharm. Section, p. 29.

CLINICAL USE OF SECRETIN

_Diabetes Mellitus._--Moore, Edie and Abram[64] were the first to suggest a therapeutic value for secretin, having obtained favorable results with secretin administration in diabetes. They argued that the internal secretion of the pancreas _may_ be stimulated by secretin, and that some cases of diabetes _may_ be due to lack of this necessary excitant. Owing to the importance of the question, their announcement was followed quickly by numerous investigations by other observers. Previously, Spriggs, at the suggestion of Starling, had tried intravenous injections of secretin free from depressor substance in a diabetic patient, and had obtained negative results. Moore, Edie and Abram gave their secretin by mouth over long periods. Of the five cases cited in their first paper, two were negative. The third was that of a man, aged 25, who received daily 30 c.c. of secretin. After a latent period of three weeks, the sugar suddenly fell, and after four months the urine was sugar-free. Six months later a relapse occurred with the development of phthisis and death. The other two patients were a boy, aged 7, and a girl, aged 9, whose urine in from three to five weeks became sugar free during the secretin treatment in spite of severe diabetes. One of these patients later relapsed.[65] Bainbridge and Beddard[66] gave secretin a thorough trial in three cases with negative results, and are disposed to attribute the results of Moore to dieting. Dakin and Ransom[67] cited one case, secretin being given for twelve weeks, with negative results; Foster,[65] nine cases, all negative; Charles,[68] three cases, all negative. Crofton,[69] however, gave secretin a trial in one case with favorable results. Moore, Edie and Abram, in a later paper,[70] report a large number of cases tried with the majority of results negative, though in some cases an improvement in the digestion, and in certain cases an increase of weight was noted.

[64] Moore, Edie and Abram: Biochem. Jour., =1=:28, 1906.

[65] Foster: Jour. Biol. Chem., =2=:297, 1906.

[66] Bainbridge and Beddard: Biochem. Jour., =1=:429, 1906.

[67] Dakin and Ransom: Jour. Biol. Chem., =2=:305, 1906.

[68] Charles: Med. Press and Cir., =133=:578, 1906.

[69] Crofton: Lancet, London, =176=:607, 1909.

[70] Moore, Edie and Abram: Biochem Jour., =3=:82, 1908.

One method of testing the basis of Moore’s theory would be by examining the prosecretin content of the intestine in diabetics. Bainbridge and Beddard found, in the paper referred to,[66] that from five of the six cases of diabetics examined postmortem, little or no secretin could be prepared; but in a subsequent report of seven cases,[71] they found only one in which the secretin obtained was scanty. The failure to obtain secretin in some cases they claim is probably due to the rapid postmortem degeneration of diabetic tissue. Evans,[72] in Starling’s laboratory, found that in dogs made recently diabetic by total pancreatectomy, but little secretin could be obtained. Hedon and Lisbonne,[73] and Pemberton and Sweet[74] report, on the contrary, that the duodenum of diabetic dogs is rich in prosecretin. Bainbridge and Beddard,[71] working on a diabetic cat, likewise found prosecretin to be present in normal quantity.

[71] Bainbridge and Beddard: Biochem. Jour. =3=:82, 1908.

[72] Evan: Jour. Physiol. =44=:461, 1912.

[73] Hedon: Compt. rend. Soc. de biol. =74=:375, 1913.

[74] Pemberton, Ralph, and Sweet, J. E.: Further Studies on the Influence of the Ductless Glands on the Pancreas, Arch. Int. Med., May, 1910, p. 466.

_Digestive Disturbances._--Secretin for digestive disturbance was first used in the “acid duodenal medication” of Enriquez.[75] This consisted in the giving of tartaric acid in thick keratin capsules, the acid not being liberated until the duodenum was reached, where it provoked the formation of secretin. “The secretin mechanism,” he says, “is probably capable of pathologic disturbance as would result, for example, with diminished acidity of chyme, disturbance of the normal motility of the stomach or pylorus, or diminished prosecretin in the mucosa. Such a condition would produce disturbance of the pancreatic, biliary and intestinal secretions, and interfere with intestinal movements, with a clinical syndrome of intestinal dyspepsia as a result, among the chief and most constant symptoms of which would be constipation.” “The acid duodenal medication” was submitted to wide clinical use, and very favorable results in certain obstinate cases of constipation were reported. In regard to “diminished prosecretin in the mucosa,” Wentworth[76] has claimed that in infantile atrophy such is the condition, but Sweet and Pemberton[77] have found that the difficulty of preparing secretin from human duodenums is such as to render Wentworth’s findings inconclusive.

[75] Enriquez: Bull. du Lab. de biol. Appliq. 2, No. 2-No. 8, 1904.

[76] Wentworth, A. H.: The Cause of Infantile Atrophy, J. A. M. A., July 20, 1907, p. 204.

[77] Sweet, J. E., and Pemberton, Ralph: Experimental Observations on Secretin, Arch. Int. Med., February, 1908, p. 231.

Beveridge[78] suggests the use of secretin in (_a_) pyloric stenosis, (_b_) pancreatic insufficiency, (_c_) hepatic stimulation and cirrhosis of the liver (_d_) to stimulate peristalsis in colonic stasis, (_e_) in gastro-enterostomy and short-circuiting of the intestines. He claims to have used it in over a hundred cases with “brilliant results,” and cites four typical histories. The G. W. Carnrick Company, which manufactures “Secretogen,” an alleged secretin preparation, cites a number of authorities[79] as also recommending secretin for digestive disorders. Harrower, who is or was connected with the Carnrick Company, in clinical journals[80] has ardently advocated the use of secretin for a large number of maladies.

[78] Beveridge: Am. Med. =20=:255, 1914.

[79] Lockwood, G. R.: Diseases of Stomach, 1913, Chapter on Achylia. Bassler, Anthony: Am. Jour. Gastro-Enter., 1914; Kemp, R. C.: Diseases of Stomach, Intestine and Pancreas, 1912. Reed, Boardman: Am. Jour. Gastro-Enter., October, 1912. Ewald (Therapie der Gegenwart, 1915, p. 5) reports favorable results with Secretogen in one of thirteen cases.

[80] Harrower: Pediatrics =25=:430, 1913; New York M. J. =118=:315, 1913; Arch. f. Verdauungskr. =20=:577, 1914.

PHYSIOLOGIC CONSIDERATIONS

Throughout its clinical use, secretin has been given by mouth; _but its direct introduction into the intestine of a dog under anesthesia in even enormous quantities is without effect_. This fact, first observed by Bayliss and Starling,[32] was confirmed by Fleig,[81] and Matuso,[36] and our personal experiments have convinced us of its truth. Matuso found that ordinary secretin and that obtained from intestinal lumen gave equally negative results. Large quantities of active secretin, moreover, acidified to 0.2 per cent. hydrochloric acid, and left in the ileum for fifteen minutes, were still negative. Wertheimer and Duvillier,[82] in a previous paper on this subject, had likewise found that acid solutions of secretin (which might be considered more normal for the intestine than when neutral), when introduced into the ileum gave negative or inconstant results. They conclude that it is more likely that the pancreas does not respond to such minimal stimuli, than that the secretin is not absorbed.

[81] Flieg: Arch. gén. de méd. =191=:1482, 1903.

[82] Wertheimer and Duvillier: Compt. rend. Soc. de biol. =68=:535, 1910.

_The destructive action of the digestive enzymes leads us to believe that it is in inactive form that secretin is absorbed._ Like epinephrin, it cannot pass through the digestive tract. Bayliss and Starling state that it is destroyed by one hour’s tryptic digestion. Lalou[62] worked with the action on secretin of pepsin, dog’s gastric juice, pancreatic juice, succus entericus and erepsin, and found in each case a destructive effect, even almost after mixing; and after five minutes over 75 per cent. of the activity had disappeared. Matuso[36] introduced 30 c.c. of active secretin into the intestine, removed it five minutes later, and found that no activity remained.

Other methods of administration have been tried. Subcutaneous injections are practically negative (Matuso,[36] Hallion[83]) and intrapleural injections are likewise negligible (Bayliss and Starling[55]).

[83] Hallion: Presse méd. =20=:433, 1912.

Starling[63] finds that continued intravenous injections of secretin in a healthy dog produces after a time severe symptoms of collapse, which, he believes, are due to change in the intestinal mucous membrane caused by the entry and non-neutralization of the strongly alkaline pancreatic juice.

Intestinal digestion seems little affected in achylia gastrica (Stockton,[84] Ehrman and Lederer,[85] Bayliss and Starling[32]). This may be due to other secretin stimulants as fats, or to the action of the nervous mechanisms (Meltzer[86]).

[84] Stockton: In Osier and McCrae’s Modern Medicine =3=:19, 1914.

[85] Ehrman and Lederer: Deutsch. med. Wchnschr. =35=:879, 1909.

[86] Meltzer, S. J.: The Factors of Safety in Animal Structure and Animal Economy, J. A. M. A., Feb. 23, 1907, p. 655.

THE DESTRUCTION OF SECRETIN BY HUMAN GASTRIC JUICE

We have carried out in detail experiments on the digestive effect of human gastric juice on secretin. Our results in every respect confirm the findings of Lalou,[62] who worked with commercial pepsin and dog’s gastric juice, but are even more striking because of the much superior quality of pure human gastric juice.

_Methods._--The human gastric juice was obtained from Mr. V., the gastric fistula case of our laboratory. The chemical and digestive characters of his juice are discussed in a recent paper.[87] In the different experiments, different samples of gastric juice were used. The secretin employed was always freshly prepared. Digestion was carried out in the incubator at 38 C. with the reaction of 0.4 per cent. acid, and the end of the period was marked by either boiling the mixture or (in the first two experiments) by turning the mixture alkaline. The action of the preparation, we proved, was not influenced by the method used. The dogs on which the preparations were tested were prepared for carotid blood pressure, injection into the external jugular vein, and cannula in the pancreatic duct, essentially the methods of Bayliss and Starling[32] being employed. The preparations were injected at body temperature after being neutralized and filtered. Except for the addition of normal salt solution instead of gastric juice, the control injections of secretin were submitted to exactly the same treatment as the other preparations.

[87] Carlson: Am. Jour. Physiol. =38=:248, 1915.

_Results._--Our results are embodied in Table 1. We assured ourselves before beginning the series that incubation of secretin with _boiled_ gastric juice produced no change. It is to be noted in the table that each experiment is a unit complete in itself, beginning and ending with a control injection of secretin. _Special attention is called to the marked destruction that follows contact of human gastric juice with secretin for merely one minute._ In Experiment 4, using 1 c.c. of human gastric juice, the action fell to 14 drops from an original secretion of 21; in Experiment 5, using 8 c.c. of gastric juice, the action fell to 6 drops from an original secretion of 20. Of interest also is the rate at which we get _complete_ destruction of secretin. This is practically 2 hours for 2 c.c. with secretin giving originally 110 drops (Experiment 2, Fig. 1), or 30 minutes for 5 c.c. with a secretin giving originally 53 drops (Experiment 6). These results are practically parallel, though they were obtained with different samples of gastric juice and in different experiments.

TABLE 1.--THE DESTRUCTION OF SECRETIN BY HUMAN GASTRIC JUICE

===================================================================== | | Secretion of Pancreatic Juice in Drops | +--------+--------------------------------------+-------- No. |Quan-|10 C.c.c| The Secretin After Incubation |10 C.c. of | tity|Secretin| with Human Gastric Juice |Secretin Exper-|of |Control +-----+------+-----+------+-----+------+Control iment|Gas- |--Begin-| | | | | | |--End of | tric| ning |Dig. |Secre-|Dig. |Secre-|Dig. |Secre-|Experi- |Juice|Experi- |Time,| tion |Time,| tion |Time,| tion | ment |Used,| ment |Hrs. |Rate |Hrs. |Rate |Hrs. |Rate | |C.c. | | | | | | | | ------+-----+--------+-----+------+-----+------+-----+------+-------- 1 | 2 | 28 |6 | 0 |4 | 0 |2 | 0 | 16 2 | 2 | 110 |2 | 7 |1-1/2| 18 |1 | 18 | 41 3 | 2 | 40 |1 | 7 | 3/4| 7 | 1/4 | 8 | 31 4 | 1 | 21 | 1/2| 11 | 1/4| 12 | 1/60| 14 | 18 5 | 8 | 20 | 1/2| 1 | 1/4| 3 | 1/60| 6 | 18 6 | 5 | 53 | 1/2| 2 | .. | .. | .. | .. | .. ------+-----+--------+-----+------+-----+------+-----+------+--------

We also tried the effect of keeping the digestive time _constant_ and varying the amount of gastric juice employed. Increasing the quantity of gastric juice used increases the quantity of secretin destroyed (Table 2).

TABLE 2.--EXPERIMENT 7*

Pancreatic Preparation Juice Drops 10 c.c. secretin 20 10 c.c. secretin digested with 0.5 c.c. gastric juice 15 10 c.c. secretin digested with 3 c.c. gastric juice 13 10 c.c. secretin digested with 10 c.c. gastric juice 8

* The digestive time was kept constant at fifteen minutes. (The gastric juice used had been _diluted_ with stomach washings.)

The reader will observe in Table 1 that the results obtained from the control injection of secretin at the beginning of the experiment is uniformly greater than that obtained after several injections of digested secretin.

In view of the established fact that equal quantities of secretin can generally be relied on to produce results,[21] one might suggest that the injections of the split products of secretin have inhibited to some degree the action of the pancreas. We can submit the data in Table 3 in support of this view, showing among other things that the action of secretin is not influenced by previous injections of inert depressor substances, though it by the injection of the cleavage products of secretin. (The various injections in the experiments were made at about fifteen-minute intervals).

We have carefully analyzed the reaction in blood pressure that follows the injection of the various preparations. We find no constant effect. Digested secretin gives a fall in blood pressure that is at times less, at times equal, and at other times greater (Fig. 1) than that produced by the original preparation.

Besides the bearing that it has on _the therapeutic use of secretin_, this destructive action of the digestive enzymes is also of prime physiologic interest. Failure to realize it has led to misconceptions as to the intrinsic nature of secretin.

TABLE 3.--EXPERIMENTS 8 AND 9

Pancreatic Preparations Juice Drops

Experiment 8:

10 c.c. secretin, five injections of inert depressor substances 29 10 c.c. secretin, two injections of completely digested secretin 28 10 c.c. secretin, eight injections of inert depressor substances 16 10 c.c. secretin 16

Experiment 9:

10 c.c. secretin (control, beginning of experiment) 21 10 c.c. secretin, after thirty minutes incubation with 1 c.c. _boiled_ gastric juice 27 10 c.c. secretin, after thirty minutes incubation with 1 c.c. _fresh_ gastric juice 11 10 c.c. secretin (control, end of experiment) 18

The findings of Lalou, confirmed by us, explain the anomaly that has led Delezenne[88] to put forward the antisecretin theory.

[88] Delezenne and Pozerski: Jour. de Physiol., =14=:540, 1912.

SECRETIN HAS NO ACTION WHEN GIVEN BY MOUTH

It is a constant claim that so many and complex are the factors concerned in physiologic processes, that it is not unusual for clinical deductions to establish themselves in the face of _a priori_ laboratory dicta. We considered it desirable, therefore, to test the action of secretin, orally administered, in the most direct manner, and the one freest from possible criticism. With this in view, we performed a series of experiments on normal unanesthetized dogs having permanent pancreatic fistulas.

_Method._--In the operations for permanent pancreatic fistulas we followed closely the technic developed by Pawlow,[89] and with excellent results. The dogs maintain themselves in splendid condition if proper care is taken. This consists in feeding them only with bread and milk, and giving sodium bicarbonate daily. The dogs were given this treatment in the evening so that experimental procedure might be carried on in the day with empty stomach under constant conditions. Freshly prepared secretin in large quantities was given by stomach tube to these dogs, and the response of the pancreas studied and compared with the response obtained from control preparations. The same preparation was generally not given on consecutive days.

[89] Pawlow: Ergeb. de Physiol., O., p. 266, 1902.

TABLE 4.--DETAIL OF TYPICAL EXPERIMENTS

Dogs with pancreatic fistulas, showing that secretin given by mouth has no action on the pancreas

=================================================================== | Rate of Secretion of Pancreatic | Juice in C.c. per Hr. +------------------+------------------ | Continuous | Continuous | Secretion | Secretion Material Fed by Stomach Tube | Before Feeding | After Feeding |-----+------+-----+-----+------+----- |First|Second|Third|First|Second|Third |Hour | Hour |Hour |Hour | Hour |Hour -----------------------------+-----+------+-----+-----+------+----- 150 c.c. active secretin, | | | | | | slightly acid | 6.5| 3.6 | 3.9 | 20.0| 6.0 | 8.0 150 c.c. active secretin, | | | | | | slightly alkaline | 13.0| 11.0 | 5.0 | 23.0| 26.0 | 12.0 150 c.c. secretin passed | | | | | | through Berkefeld | 7.8| 7.5 | 7.4 | 23.0| 13.0 | 11.0 150 c.c. extract of colon | 11.6| 12.0 |11.4 | 30.0| 19.6 | 14.8 150 c.c. extract of gastric | | | | | | mucosa | 10.0| 7.0 | 8.0 | 23.0| 7.5 | 4.0 150 c.c. extract of muscle | 6.9| 11.0 | 6.4 | 35.0| 5.0 | 7.0 150 c.c. 0.4% HCl | | | | | | (diluted to 250 c.c.) | 6.0| 8.0 | 4.0 | 33.0| 36.0 | 17.0 -----------------------------+-----+------+-----+-----+------+-----

_Results._--We have data from six dogs with a total of seventy-six experiments. As shown in Table 4, the administration of secretin causes an increase in the flow of pancreatic juice, _but_ the administration of inert substances as extracts of colon, gastric mucosa or muscle causes a like increase. The activity of the secretin may be reduced to a low value by exposure to sunlight, or filtering through a Berkefeld filter, yet the response of the pancreas is not correspondingly reduced. The secretion that occurs in the control cases, every one will admit, is but secondary to the production of gastric juice with its accompanying hydrochloric acid, that is, excited by virtue of the extractives and water in the preparations. Such, we can prove, is the only action of secretin. A mixture of gelatin, peptone and salt water, the chief incidental constituents of a secretin preparation, gives as striking results as ever obtained from secretin administration. Yet the objection may be made that the response of the pancreas that is due to the incidental constituents of secretin is maximal, and that the secretin consequently has no opportunity to display its particular potency. But, as inspection of the accompanying tables illustrate, the administration of hydrochloric acid shows that the response is by no means maximal. Let us cite a striking experiment. For three hours before the administration of hydrochloric acid, the secretion in cubic centimeters was respectively 29.4, 11.75 and 35.4 c.c.; for the three hours after, respectively 88.0, 49.0 and 40.5 c.c.

[Illustration: Fig. 1.--Tracings (reduced two-thirds) showing failure of Secretogen, Elixir Secretogen, and Duodenin to stimulate the flow of pancreatic juice even when administered intravenously in amounts three times greater than that recommended to be given by mouth. Dog: light ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood pressure; _b_, flow of pancreatic juice in drops; _c_, signal showing where the intravenous injections were made. Tracing A: Reading from left to right, the five intravenous injections are: (1) three tablets of Secretogen digested with 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (2) three tablets of Secretogen boiled in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of Secretogen in 15 c.c. 0.9 per cent. sodium chlorid; (4) three tablets of Secretogen in 15 c.c. of 70 per cent. alcohol; (5) 15 c.c. Elixir Secretogen. Tracing B: reading from left to right, the four intravenous injections are: (1) 5 c.c. secretin made fresh from dog’s duodenal mucosa; (2) three tablets of Duodenin digested in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of Duodenin boiled in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (4) three tablets of Duodenin in 15 c.c. sodium chlorid (0.9 per cent.).]

TABLE 5.--SUMMARY OF EXPERIMENTS

Dogs with pancreatic fistula, weight 14 kg. Secretin given by mouth

==================================================================== | |Rate of Secretion| | | of Pancreatic | | | Juice in | No. of | | C.c. Per Hour |Increase Experi-| Material Fed +--------+--------+ in ment | | Three | Three | C.c. | | Hours | Hours | | | Before | After | | |Feeding |Feeding | -------+---------------------------------+--------+--------+-------- 3 |Secretin slightly acid | 5 | 11 | 6 5 |Secretin slightly alkaline | 24 | 30 | 6 4 |Secretin passed through Berkefeld| 18 | 23 | 5 1 |Secretin exposed to sun for 4 hrs| 16 | 29 | 13 2 |Extract of colon (rabbit) | 19 | 29 | 10 3 |Extract of gastric mucosa | 14 | 23 | 9 3 |Extract of muscle | 8 | 16 | 8 2 |Mixture of gelatin, peptone and | 23 | 33 | 10 | salt | | | 1 |1 per cent. peptone solution | 6 | 8 | 2 4 |0.2 per cent. hydrochloric acid | 13 | 37 | 24 3 |Milk and bread | 7 | 20 | 13 -------+---------------------------------+--------+--------+--------

It is possible by large doses of sodium bicarbonate given shortly before the administration of a preparation so to depress the stomach that it does not respond with the usual production of hydrochloric acid. Under these conditions the administration of secretin is uniformly negative, but the administration of hydrochloric acid on the contrary still serves to increase the pancreatic secretion (Table 6).

TABLE 6.--SECRETIN IN EXPERIMENTAL “ACHYLIA GASTRICA”

====+================================================================= | | Rate of Secretion of Pancreatic Juice | | in C.c. Per Hour | +--------------------+------------------- Exp.| Material Fed |Continuous Secretion| Secretion After No. | | Before Feeding* | Feeding | +------+------+------+------+------+----- | |First |Second|Third |First |Second|Third ----+------------------------+------+------+------+------+------+----- 1 |} {| 8.7 | 7.5 | 6.8 | 3.0 | 1.0 | 4.8 2 |} 150 c.c. secretin {| 4.5 | 6.5 | 10.0 | 6.0 | 7.5 | 7.6 3 |} {| 15.6 | 8.1 | 16.0 | 3.9 | 4.9 | 2.9 | | | | | | | 1 |} 150 c.c. 4% HCl {| 9.8 | 7.0 | 6.0 | 65.1 | 28.0 | 7.1 2 |} (diluted to 250 c.c.){| 17.4 | 18.5 | 17.0 | 34.0 | 18.0 | 20.0 ----+------------------------+------+------+------+------+------+-----

* Five gm. Na HCO₃ given at beginning of each first two hours.

COMMERCIAL PREPARATIONS OF SECRETIN

_Secretogen and Elixir Secretogen._--The Carnrick Company offers Secretogen[90] for use in a large number of conditions. The following indications for the use of the preparation purport to be based on clinical tests covering a period of several years: dyspepsia, and the indigestions generally, fermentative disorders, gastric catarrh, flatulence, nausea; pancreatic insufficiency, intestinal indigestion; gastric secretory deficiencies, apepsia; constipation and hepatic torpor; intestinal stasis; diarrhea; infantile diarrhea, “summer complaint,” marasmus, inanition and malnutrition; gastric atony and dilatation; cholecystitis and gallstones; nephritis, neurasthenia, cachexia and cancer; epilepsy and high blood pressure. Testimonials are presented as to results in most of these conditions.

[90] Secretogen, Report of the Council on Pharmacy and Chemistry, J. A. M. A., May 1, p. 1518, 1915.

A quantity of “Secretogen” and “Elixir Secretogen” was bought in the open market, and the preparations were tested on suitably prepared dogs. The tablets were ground, thoroughly macerated with the solvent used (water, normal salt solution, alcohol, or 0.4 per cent. hydrochloric acid), and filtered. If hydrochloric acid was used, the pulverized tablets were boiled with it, in the manner that secretin is made from duodenal mucosa, and the preparations neutralized previous to injection. The injections were made in from 15 to 20 c.c. of the solvent. All the operations were carried on immediately before the experiment, and as rapidly as possible, so as to avoid oxidation. The Elixir Secretogen was injected directly, without dilution.

TABLE 7.--SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF SECRETIN IN “SECRETOGEN” AND “ELIXIR SECRETOGEN” EXCEPT IN OCCASIONAL TESTS WHEN ADMINISTERED IN ENORMOUS DOSES

Dogs under ether anesthesia

======================================================================= | | Secretion of Pancreatic Juice in Drops, | Quantity of | Following Intravenous Injection Exp.| Secretogen +--------+---------------------------+------+-------- No.| and Elixir | | Secretogen in | | | Secretogen |Control +---------+----+-------+----+ |Control | Used* |10 C.c. |Distilled|0.4%| 70% |0.9%|Elixir|10 C.c. | |Secretin| Water |HCl |Alcohol|NaCl| |Secretin ----+-------------+--------+---------+----+-------+----+------+-------- 1 |Secretogen, | | | | | | | | 1 tablet; | 109 | 0 | 0 | 0 | 0 | 0 | 59 | Elixir, | | | | | | | | 15 c.c. | | | | | | | 1 |Secretogen, | | | | | | | | 6 tablets | ... | .. | 0 | .. | .. | .. | .. 2 |Secretogen, | | | | | | | | 3 tablets; | 16 | 0 | 0 | 0 | 0 | 1(?)| 16 | Elixir, | | | | | | | | 15 c.c. | | | | | | | 3 |Secretogen, | | | | | | | | 5 tablets | ... | .. |1(?)| .. | .. | .. | .. 4 |Secretogen, | | | | | | | | 25 tablets | 14 | .. |1(?)| .. | .. | .. | 8 5 |Secretogen, | | | | | | | | 100 tablets | 110 | .. | .. | .. | 21 | .. | 67 6 |Secretogen, | | | | | | | | 100 tablets;| 19 | .. | 5 | .. | 1 | 2(?)| 8 | Elixir, | | | | | | | | 125 c.c. | | | | | | | 7 |Elixir, | | | | | | | | 50 c.c. | ... | .. | .. | .. | .. | 1(?)| .. ----+-------------+--------+---------+----+-------+----+------+--------

* One to three tablets is (according to the label) the therapeutic dose of Secretogen; 4 to 12 c.c. the dose of Elixir Secretogen.

_Results._--In only one case was a slight response obtained, the others gave none. Small and large doses were equally inert (Table 7, Figs. 2, 3). The preparations, though inert, always produced a depression in blood pressure, sometimes even greater than that caused by active secretin. Among our many tests, one bottle was found, however, to be a little different from the rest (Experiment 4). Its entire content, 100 tablets, had been ground and boiled in 0.9 per cent. sodium chlorid. The extract on injection was found to have a small but unmistakable secretin reaction, equivalent to about 2 c.c. of the control secretin used. But repeated experiments were unable to duplicate this result. The “Secretogen” and “Elixir Secretogen” were all supposedly fresh preparations, the retail drug store informing us that a fresh supply was obtained from the wholesale house each week.

Secretogen, then, contains practically no secretin, and even if it did contain secretin, it can have no effect on the pancreas when taken by mouth. The indications for Secretogen, therefore, are based on false premises, and the testimonials are worthless.

[Illustration: Fig. 2.--Tracings (reduced one-half) showing no stimulation of the pancreas by Secretogen, Elixir Secretogen, and Duodenin, even when administered intravenously in quantities one hundred times greater than the therapeutic dose by mouth. Dog: Light ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood pressure; _b_, flow of pancreatic juice in drops. Tracing A: at _x_, intravenous injection of 10 c.c. secretin prepared from duodenal mucosa of dog. Tracing B: at _x_, intravenous injection of 100 tablets of Secretogen digested with 0.4 hydrochloric acid and neutralized. Tracing C: at _x_, intravenous injection of 100 tablets of Secretogen, prepared as in Tracing B. Tracing D: at _x_, intravenous injection of 50 c.c. Elixir Secretogen. Tracing E: at _x_, intravenous injection of 100 tablets of Duodenin (dissolved in 0.9 per cent. sodium chlorid).]

_Duodenin._--This is a preparation manufactured by Armour & Company, which purports to be “secretin plus enterokinase.” The claims for this product are similar to those for Secretogen, but somewhat less sweeping. According to the manufacturers, “Duodenin (Armour) is recommended in the treatment of intestinal disorders where an increased flow of pancreatic, hepatic and intestinal secretion is desired. It is of specific value in proteid digestion on the theory that secretin and enterokinase stimulate the pancreas and activate its secretion.”

[Illustration: Fig. 3.--Tracings (reduced one-half) showing practically complete destruction of secretin by the gastric juice. Dog under light ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood pressure; _b_, record of flow of pancreatic juice in drops. Time, twenty-five minutes. Tracing A: intravenous injection of 10 c.c. secretin (prepared fresh from dog’s duodenal mucosa) at _x_. Tracing B: intravenous injection (at _x_) of 10 c.c. of the same secretin as in Tracing A, after being digested in normal human gastric juice at 37 C. for two hours.]

We bought a quantity of Duodenin in the open market, and carried out on this product the same series of experiments as that used in the case of Secretogen. The results were similarly negative (Table 8).

TABLE 8.--SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF SECRETIN IN “DUODENIN”

Dogs under ether anesthesia

================================================================= | | Secretion of Pancreatic Juice in Drops, | | Following Intravenous Injection Exp.| Number +--------+-------------------------------+---------- No. |Duodenin| Control| Duodenin in | Control | Tablets| 10 C.c.+---------+------+-------+------+ 10 C.c. | Used |Secretin|Distilled| 0.4% | 70% | 0.9% | Secretin | | | Water | HCl |Alcohol| NaCl | ----+--------+--------+---------+------+-------+------+---------- 1 | 3 | 29 | 0 | 0 | 0 | 1(?)| 28 1 | 6 | ... | .. | 1(?)| .. | .. | .. 2 | 18 | 16 | .. | 6 | .. | .. | 16 3 | 5 | 14 | .. | 0 | 0 | 0 | 8 3 | 25 | ... | .. | 1(?)| .. | .. | .. 4 | 100 | 110 | .. | 0 | .. | .. | 67 5 | 150 | 19 | .. | 0 | .. | 0 | 8 ----+--------+--------+---------+------+-------+------+----------

In regard to both Secretogen and Duodenin, we assume that the manufacturers have tried to put secretin in them, but have been unable because they have failed, in all likelihood, to check their methods by physiologic standardization. These firms do not give any details as to the procedure they employed in their manufacture of secretin. Desiccated secretin of extreme potency has been prepared by various physiologists,[91] 1 mg. (1/64 grain) of which is active when given intravenously. It is difficult to conceive that any of these methods were used in the preparation of Secretogen or Duodenin.

[91] Stepp (Note 13). Dale and Laidlow: Jour. Physiol. =44=:11, 1912. Launoy and Ochslin: Comp. rend. Soc. de biol., =74=:338, 1913.

CONCLUSIONS

1. Secretin is quickly destroyed by gastric juice and by trypsin.

2. Secretin is not absorbed in active form from the alimentary tract.

3. The presence of secretin or prosecretin cannot be demonstrated in the commercial preparations “Secretogen,” “Elixir Secretogen” and “Duodenin” even when the therapeutic dose of the preparations is given intravenously. In the case of “Secretogen,” intravenous injection of 100 times the therapeutic dose reveals occasionally an insignificant trace of secretin.

DISCUSSION OF RESULTS

It is, of course, objectionable that preparations containing no secretin should be advertised to the medical profession as containing this substance. The more important blunder, however, consists in the attempt to offer such preparations for oral administration, because even chemically pure secretin would be equally ineffective when taken by mouth. There is as yet no reliable evidence that lack of secretin is a primary or important factor in any disease. Even should this be established, secretin therapy, to be effective, must be intravenous. Secretin has not yet been prepared in sufficiently pure state to render possible intravenous injection in man without injurious effects. And even when this has been attained, the very fleeting action of secretin will in all probability render secretin therapy as futile in all the diseases in which it is theoretically indicated as epinephrin therapy is in Addison’s disease.

But there remains the alleged favorable effect from secretin therapy by mouth in various diseases in man. It is, perhaps, impertinent for laboratory men to comment on these clinical results. The ordinary “testimonials” need not be considered, but we should like to ask the serious worker who thinks he has actually obtained good results from secretin therapy how certain he is of the causal relation between the giving of secretin or alleged secretin and the abatement of the disease.

When a therapeutic measure not only lacks a positive basis in physiology and pathology but runs contrary to all the well-established experimental facts in these fundamental medical sciences, is it too much to ask that positive clinical findings be subjected to more than usual critical analysis before acceptance? “_Clinical tests_,” it is said, “covering a period of several years have proved that neither the condition in the stomach during digestion nor those in the intestine prevent the secretin from entering intact into the circulation.” When we meet claims such as this, should we not scrutinize the “tests” as well as the men who make them?

We are indebted to Dr. J. H. Moorehead for assistance in part of the surgical work.--(_From The Journal A. M. A., Jan. 15, 1916._)

ARTICLES REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Below appear abstracts of the Council’s action on articles refused recognition which were not deemed of sufficient importance to require lengthy reports:

Radio-Rem

The Radium Therapy Company, Schieffelin & Co., selling agents, submitted to the Council radium emanation generators called “Radio-Rem Outfits,” designed to generate respectively 200, 1,000, 2,000, 5,000 and 10,000 Mache units per twenty-four hours.

Those who are well informed on the subject of radium therapy are of the opinion that the administration of small amounts of radium emanation such as generated by certain outfits is without therapeutic value. It has been stated that at the Radium Institute of London the minimum preliminary dose is 185 microcuries (500,000 Mache units), and as many as 555 microcuries (1,500,000 Mache units) are employed.

In consideration of these facts the Council voted not to accept any radium emanation generator which produces less than 2 microcuries of emanation during twenty-four hours. Accordingly, while accepting Radio-Rem Outfit No. 5, claimed to produce 10,000 Mache units (3.7 microcuries) and Radio-Rem Outfit No. 4, claimed to produce 5,000 Mache units (1.8 microcuries), the Council voted not to accept Radio-Rem Outfit No. 3, claimed to produce 2,000 Mache units (0.74 microcurie), Radio-Rem Outfit No. 2, claimed to produce 1,000 Mache units (0.37 microcurie), and Radio-Rem Outfit C, claimed to produce 200 Mache units (0.07 microcurie).

This report having been submitted to Schieffelin & Co. and their reply considered, the Council authorized publication of the report. [See also _Reports of Council on Pharmacy and Chemistry_, 1916, p. 631.]

Olio-Phlogosis

Olio-Phlogosis, a liquid preparation to be applied externally by means of a cotton pad, is advertised by the Mystic Chemical Company, Kansas City, Mo., thus:

“Doctor: Don’t fail to use Olio-Phlogosis liberally for Pneumonia, Bronchitis and Pleurisy. It works quickly. Olio-Phlogosis is as far ahead of all medicated kaolin plasters as these plasters were ahead of the old-time moist and soggy poultices.”

A pamphlet advises the use of Olio-Phlogosis in

“... all cases of Inflammation and Congestion, such as Pneumonia, Bronchitis, Pleurisy, Croup, Boils, Carbuncles, Rheumatism, Swollen Glands, Peritonitis, Ovaritis, as a Surgical Dressing, Mamitis [Mastitis (?)] Vaginitis and Metritis (on cotton tampon to deplete these parts), Septic Wounds, Old Ulcers, Chilblain, Eczema, Neuralgia, Inflammation of the Eyes and Ears, Alveolar Inflammation, Burns, Scalds, Etc.”

According to the information sent to the Council by the Mystic Chemical Company, Olio-Phlogosis has the following composition per gallon:

Ol. Eucalyptus Gaultheria drs. 8 Ol. Abies Canadensis drs. 8 Ol. Abies Canadensis drs. 2 Ol. Thyme (white) drs. 2 Resublimated Iodin crystals grs. 32 Resorcin drs. 1 Acid Boracic C. P. drs. 2 Quinine Bisulphate drs. 4 Sodium Thiosulphate drs. 3-1/2 Glycerin C. P. q. s. ad gal. 1

A nonquantitative formula which appears on the label of a sample bottle sent to a physician enumerates the same ingredients except the sodium thiosulphate.

The A. M. A. Chemical Laboratory reports that no free iodin could be detected in the preparation.

Apparently, then, Olio-Phlogosis is essentially a skin irritant applied by means of cotton; it can be expected to be just about as effective as the old-fashioned cotton pneumonia jacket, used in conjunction with an aromatic skin irritant, such as camphorated oil or wintergreen or menthol ointment. The odor may have some psychic effect, and it is possible that some of the oily matter may be absorbed by the skin. That such small amounts, even if absorbed, can produce any considerable systemic effect, however, is highly improbable, and the advice that this preparation be relied on in pneumonia, pleurisy, peritonitis, etc., is pernicious. In the few cases of pneumonia in which heat is indicated, the plain cotton pad will usually be found sufficient. If the physician consider the addition of a skin irritant desirable, it is easy to select one from the official preparations. It will be far more rational to do so than to invoke the aid of a mystic name and a complex formula to which the patient and his family, at least, will be led to give unmerited credit.

The claims made for Olio-Phlogosis are unwarranted; its composition is complex and irrational, and the nondescriptive but therapeutically suggestive name is likely to lead to uncritical use. The Council voted that the product be refused recognition for conflict with Rules 6, 8 and 10, and that this report be published.--(_From The Journal A. M. A., Aug. 19, 1916._)

THE HYPOPHOSPHITE FALLACY

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

The introduction of hypophosphites into medicine was due to an erroneous and now discarded theory as to the cause of tuberculosis of which one Dr. J. F. Churchill of London, and later of Paris, was the promulgator and propagandist.[92] This theory was that the so-called “tuberculosis diathesis” was due to a deficiency of phosphorus in the blood. Believing that the hypophosphites, while nontoxic, were capable of further oxidation in the organism, Churchill recommended them as the best means of supplying the supposedly lacking phosphorus. It is now known that tuberculosis is not due to a deficiency of phosphorus. Of more importance is the fact, now known, that little phosphorus, if any, is assimilated from the hypophosphites--far less than from phosphorus compounds of ordinary food.[93] There is no justification for giving hypophosphites for the sake of their phosphorus content. For various reasons, however--partly from force of habit and partly because of the power of advertising--many physicians still prescribe hypophosphite preparations, and consequently, they are still included in the Pharmacopeia and in textbooks on materia medica and therapeutics. They are put out in the form of “specialties” and of proprietary preparations, and are lauded extravagantly by the manufacturers of the latter.

[92] Churchill, J. F.: De la cause immédiate et du traitement spécifique de la phthisie pulmonaire et des maladies tuberculeuses, Paris, 1858.

[93] The Hypophosphite Fallacy, J. A. M. A., April 25, 1914, p. 1346.

Although the overwhelming weight of evidence was against the probability that the hypophosphite preparations are of value as therapeutic agents, the Council thought it well to investigate the subject. Dr. W. McKim Marriott of Baltimore was therefore requested to review the evidence for and against the therapeutic usefulness of the hypophosphites and to conduct such experiments as seemed necessary. His report has already appeared in The Journal.[94]

[94] Marriott, W. McKim: The Therapeutic Value of the Hypophosphites, J. A. M. A., Feb. 12, 1916, p. 486.

Dr. Marriott found that nine observers (Paquelin and Joly, Vermeulen, Boddaert, Massol and Gamel, Panzer, Delaini and Berg), who endeavored to test the alleged utilization of the hypophosphites in the organism, reported that there is complete, or practically complete, elimination of hypophosphites in the urine, with little or no effect on the body. Only one experimenter (Patta) claimed that a considerable amount of ingested hypophosphite was retained in the body; however, he used a method now known to be inaccurate and made obvious errors in calculation, so that his conclusions were unwarranted.

Since the evidence was even to this extent contradictory, Marriott performed a series of experiments. The methods of this study and details of results are described in his paper, in which he also discusses the experiments of some other observers. Marriott writes:

“None of the subjects of the experiment [Marriott’s] experienced any effect whatsoever from the administration of the drug.... Almost all of the ingested hypophosphite is promptly eliminated unchanged....

“These experiments [Forbes’] demonstrate conclusively that the hypophosphites possess no specific value as a source of phosphorus for the body. This is not to be wondered at in view of the fact that 85 per cent. of the phosphorus ingested in the form of hypophosphite is excreted unchanged, and there is no proof that even the remaining 15 per cent. is available to the organism. It is doubtful if there are any conditions in which the body suffers from lack of phosphorus. Even should such conditions exist, phosphorus, in the form that it occurs in the ordinary foods, or as phosphates, is more efficient in supplying the deficit than hypophosphites that must be oxidized before utilization and which are only about 15 per cent. oxidized, if at all. For example, half a glass of milk contains more available phosphorus than three large doses of hypophosphites of 15 grains each, as great a dosage as is usually given.

“What, then, is the therapeutic value of hypophosphites? There is no reliable evidence that they exert a physiologic effect; it has not been demonstrated that they influence any pathologic process; they are not ‘foods.’ If they are of any use, that use has never been discovered.”

In view of the foregoing, it seemed to the Council advisable to examine the claims under which a few of the proprietary hypophosphite preparations are marketed. The following are representative:

FELLOWS’ SYRUP OF HYPOPHOSPHITES

No very exact information concerning the composition is furnished by the manufacturers (Fellows Medical Mfg. Co., New York). They say that the product

“... contains the chemically pure hypophosphites of iron, quinin, strychnin, calcium, manganese and potassium, agreeably blended in the form of a bland, stable syrup with a slightly alkaline reaction....

“Each fluid drachm contains the equivalent of 1-64th of a grain of pure strychnin.”

The Fellows’ Hypophosphites advertising furnishes something like a barometer of the popular status of hypophosphites. In one circular (undated, but, from certain references contained in it, presumably issued ten or fifteen years ago) we read:

“It is an indubitable fact that the hypophosphites have earned the distinction of having their therapeutic value more completely established than have any other remedial agents.... it is only by accepting the current view, which was originally advanced by Mr. Fellows, that we can satisfactorily account for the incontestable fact that the hypophosphites are of supreme importance in the treatment of a very extensive variety of affections.... the hypophosphites increase the consumption of oxygen and the elimination of carbon dioxide. In this manner, they stimulate nutrition and promote constructive metamorphosis.... It is now universally conceded that the widespread utility of the hypophosphites is due to the fact that they substantially improve metabolic processes, thus increasing the disease-resisting capacity of all the tissues.”

The circular, continuing, emphasizes the “incomparable phosphorus-contributing properties” of Fellows’ Syrup, its “extraordinary reconstructive properties” and “the magnificent results which invariably attend its employment in the treatment of anemia, chronic bronchitis, chlorosis, neurasthenia, mollities ossium, delayed union of fractures, rickets, convalescence,” etc.

A circular bearing the copyright date 1914, on the other hand, admits that:

“The theories for the favorable action of Fellows Syrup of Hypophosphites have undergone several changes.”

The same circular further maintains, however, that:

“... the fact has never been challenged that in Fellows Syrup of Hypophosphites we have one of the most efficient, most complete, most all-around tonics and roborants in the materia medica.”

No attempt is made to base this assertion on the therapeutic action of the constituents. In other words, the old theory, which formed the basis for the popularity of Fellows’ Syrup, has been thrown overboard, but no substitute is deemed necessary; the momentum already acquired is apparently regarded as sufficient to insure its continued sale.

Fellows’ Syrup of Hypophosphites is a semisecret, unscientific preparation--an affront to sound therapy--exploited by means of extravagant and misleading statements.

SYRUPUS ROBORANS (SYRUP HYPOPHOSPHITES COMP. WITH QUININ, STRYCHNIN AND MANGANESE)

Little information concerning this preparation seems to be furnished at present by the manufacturers, Arthur Peter & Co., Louisville, Ky. According to an old circular, it contains, in each fluidounce,

Grains “Hypophos. Potass. 1-1/2 Hypophos. Manganese 1 Hypophos. Lime 1 Hypophos. Iron 1-1/2 Hypophos. Quinin 6/16 Hypophos. Strichnin 1/16 “1/128 grain Strychnia to Teaspoonful.”

Further, according to the same circular:

“The Hypophosphites are especially useful in all diseases where there is a lack of nutrition.... They are the best of all remedies in Rachitis, non-union of fractures, Osteomalacia and Syphilitic Periostitis.”

As for Syrupus Roborans itself:

“This elegant preparation is ... the best general tonic and reconstructive known.”

The unwarranted therapeutic claims formerly made for it seem to be no longer circulated. Syrupus Roborans is an unscientific, shotgun mixture.

SCHLOTTERBECK’S SOLUTION HYPOPHOSPHITES OF LIME AND SODA (LIQ. HYPOPHOSPHITUM, SCHLOTTERBECK’S)

The Schlotterbeck & Foss Co., Portland, Maine, the manufacturers, say of their preparation:

“This solution contains 30 grains of the combined Hypophosphites of Lime and Soda to the ounce. It contains No Sugar, No Acid and it is Perfectly Neutral.”

“Indications for use.--Galactostasis, Imperfect Metabolism, Neurasthenia, Nervous Dyspepsia, Insomnia, Convalescence, Acetonuria, Cyclic Vomiting in Infants, Diabetes, Starvation, Deficiency of Lime, Mother’s Teeth during Pregnancy, Dentition of Infants, Rachitis, Furunculosis, Vomiting of Pregnancy, Obesity.”

“Migraine is often caused by conditions for which this Solution is one of the most satisfactory remedies:”

“In Insomnia due to advancing age, it will often act as a hypnotic....”

Of the hypophosphites the Schlotterbeck & Foss Company say:

“If ‘damning it with faint praise’ on the part of some of the leading medical authorities, or utterly condemning it as useless, on the part of others, would kill a medicine, the Hypophosphites would long since have disappeared as medicinal agents. Negative testimony in regard to the value of a drug does not settle anything.”

Of their own preparation they say:

“When we get the results that ought to follow the administration of Hypophosphites, we have proved that Schlotterbeck’s Solution enters the system unchanged.”

“This Solution is primarily a blood and nerve tonic and chemical food.”

Schlotterbeck’s Solution of Hypophosphites of Lime and Soda is a semisecret preparation marketed under claims that are both unwarranted and misleading.

ROBINSON’S HYPOPHOSPHITES

According to the manufacturers, the Robinson-Pettet Company, Louisville, Ky., each fluidounce of this preparation contains:

“Hypophosphites Soda 2 gr. Hypophosphites Lime 1-1/2 gr. Hypophosphites Iron 1-1/2 gr. Hypophosphites Quinin 3/4 gr. Hypophosphites Strychnine 1/16 gr.”

It is claimed to be

“Nutritive, Tonic Alterative. A Standard Remedy in the treatment of Pulmonary Phthisis, Bronchitis, Scrofulous Taint, General Debility, etc. Stimulates Digestion, promotes Assimilation.”

The declared composition of the preparation is unscientific, and the therapeutic claims are unwarranted.

EUPEPTIC HYPOPHOSPHITES

Nelson, Baker & Co., Detroit, Mich., who market Eupeptic Hypophosphites, call this preparation:

“A superior combination containing the Hypophosphites of Potassium, Calcium, Iron and Manganese, and the bitter tonics, Quinin and Strychnin, agreeably associated with natural digestive ferments of the pancreatic secretion. It is thus a general reconstructive tonic.... The remedy is of especial value in the treatment of mental and nervous affections.... It is indicated in pulmonary tuberculosis, in all wasting diseases, in debilitated conditions generally and in all exhaustion from over work.”

On the basis of the manufacturer’s statement, Eupeptic Hypophosphites must be regarded as a semisecret, unscientific, shotgun preparation, exploited through unwarranted therapeutic claims.

MCARTHUR’S SYRUP OF THE HYPOPHOSPHITES COMP. (LIME AND SODA)

So far as the recent literature and trade package are concerned, no information as to the composition of this product is furnished beyond what is conveyed in the name. The advertising for McArthur’s Syrup, like that for Fellows’ Syrup and Peters’ Syrupus Roborans, has been modified as time has passed. A few years ago it was advertised under such claims as the following:

“... Has Stood the Test during many years for unequaled efficacy in the treatment of Tuberculosis.... Indicated also as a Tonic and Tissue Builder in convalescence from Fevers, in Nervous Diseases, Rickets, Senile Debility and Bronchitis.”

“Its use is indicated in ... diseases of the chest, chronic cough, throat affections, general debility, brain exhaustion, cholera infantum and wasting diseases of children.”

At present no definite claims seem to be made for it; the manufacturers evidently find the magic name of hypophosphites sufficient to evoke the spell for which the advertisement writer’s aid was once sought. A testimonial contained in a circular which seems to be still used illustrates both the kind of aura which surrounds hypophosphites in the minds of physicians who are still living in the past, and the kind of logic which has made the reputation of this and many other equally worthless preparations.

“Just about six years ago I had a severe attack of La Grippe which almost killed me. Left me with Asthma (Catarrh) and a severe cough. Did not get out of the house for three months. Took over a dozen bottles McArthur’s Hypophos.--came out all right and since then worked hard, but last Fall took another cold, but worked on, used McArthur’s Hypophos., am using it now, am on my 12th bottle.

“I have five or six patients whom I have put on McArthur’s Hypophos., but I do not prescribe the single bottle, but _wholesale_ no less than half dozen bottles. One patient is on his 24th bottle with orders to get another half dozen and keep it up all winter. I have given the same order to all (keep it up all winter) and I myself intend to do the same, for with its use I have lost no time--rain or shine I am doing my work. I know what it has done for me and what it is doing for my patients.”

It would be hard to find a more characteristic example of the naïve mental processes of the simple folk who in all good faith write testimonials for worthless medicines. This well-meaning practitioner (a homeopath, by the way), because he “came out all right” after an attack of grip, returns all praise to McArthur’s Hypophosphites, which he has taken “wholesale.” Not the faintest doubt of the validity of his _post hoc ergo propter hoc_ argument seems to glimmer across his consciousness.

McArthur’s Syrup of the Hypophosphites is an irrational preparation. While its faults are fewer and less glaring than those of some other proprietaries, the circulation of such a testimonial as the one just quoted is sufficient of itself to cast suspicion on the product.

BORCHERDT’S MALT OLIVE WITH HYPOPHOSPHITES, MALTZYME WITH HYPOPHOSPHITES AND MALTINE WITH OLIVE OIL AND HYPOPHOSPHITES

These preparations are now described in the appendix to New and Nonofficial Remedies. Borcherdt’s Malt Olive with Hypophosphites (Borcherdt Malt Extract Company, Chicago) is said to contain in each 100 c.c., 0.64 gm. each of calcium and sodium hypophosphites, with malt extract, olive oil and glycerine. Maltzyme with Hypophosphites (Malt-Diastase Company, New York) is said to contain, in each 100 c.c., 0.4 gm. each of calcium, sodium and potassium hypophosphites and 0.005 gm. each of iron and manganese hypophosphites, with maltzyme. Maltine with Hypophosphites (Maltine Company, Brooklyn, N. Y.) is said to contain in each 100 c.c., 0.64 gm. each of calcium and sodium hypophosphites and 0.42 gm. of iron hypophosphite, with maltine. Maltine with Olive Oil and Hypophosphites (Maltine Company, Brooklyn, N. Y.) is said to contain, in each 100 c.c., 0.6 gm. each of calcium and sodium hypophosphites, with maltine and olive oil. In general, no therapeutic claims are made for these mixtures so far as the hypophosphites are concerned. The addition of hypophosphites to such mixtures is irrational and, since it tends to perpetuate the hypophosphite fallacy, detrimental to sound therapeutics.

THE COUNCIL’S ACTION

The Council endorsed the conclusions of the work of Dr. Marriott referred to above, and noted: (1) that the therapeutic use of hypophosphites (except possibly in some cases as a convenient means of administering the positive element in the salt, as ammonium in ammonium hypophosphite or calcium in calcium hypophosphite) is irrational; (2) that the merits of each hypophosphite salt submitted for consideration under the foregoing exception must be judged individually, and (3) that Fellows’ Syrup of Hypophosphites, Peters’ Syrupus Roborans, Schlotterbeck’s Solution Hypophosphites of Lime and Soda, Robinson’s Hypophosphites, the Eupeptic Hypophosphites of Nelson, Baker & Co., and McArthur’s Syrup of the Hypophosphites are ineligible for inclusion in New and Nonofficial Remedies, and that Borcherdt’s Malt Olive with Hypophosphites, Maltzyme with Hypophosphites, Maltine with Hypophosphites, and Maltine with Olive Oil and Hypophosphites be deleted from the appendix of N. N. R. Of these preparations, all are in conflict with Rule 10; Fellows’ Syrup, Schlotterbeck’s Solution, Robinson’s Hypophosphites and Nelson, Baker & Co.’s Eupeptic Hypophosphites are in conflict with Rule 6; the Fellows, Schlotterbeck, and Nelson, Baker preparations are also in conflict with Rule 1.--(_From The Journal A. M. A., Sept. 2, 1916._)

PULVOIDS CALCYLATES

Report of the Council on Pharmacy and Chemistry

Pulvoids Calcylates 5 grains was submitted by the Drug Products Company, Inc., New York, under the following claims as to composition:

“When ingested represents the following chemical formulas: OH) C₆H₄ COO)₂ Ca.2H₂O + Sr.(C₇H₅O₃)₂ + 2H₂O.”

“Strontium Di-Salicylate 2-1/2 grs. and our especially prepared Salt of Calcium and Acid Salicylic adjusted in such nascent form, that these pulvoids upon ingestion will promptly form Calcium Neutral Di-Salicylate 2-1/2 gr.”

“A combination of Calcium and Strontium Di-Salicylate, in seemingly true chemical union.”

These statements are rather vague, possibly because they are an attempt to mystify. The product, however, may be assumed to be a mixture (not a chemical combination) of calcium salicylate and strontium salicylate. The therapeutic claims made for the preparation are:

“Superior to ordinary salicylates. Can be taken continuously and indefinitely without gastric irritation, insuring maximum efficiency.”

“Reports show surprisingly good results, even where the sodium salt fails.”

As there is no evidence to show that strontium salicylate, calcium salicylate or a mixture of the two salts has any advantage over sodium salicylate, these claims cannot be accepted. The name and the statement of composition are objectionable in that they do not reveal the identity of the drugs in “Calcylates” and in suggesting that this preparation possesses radical advantages over salicylates in other forms.

The Drug Products Company was told that the facts just mentioned rendered “Pulvoids Calcylates” ineligible for New and Nonofficial Remedies. The company in its reply objected to the Council’s conclusions, and in support of its position submitted testimonials from a number of physicians. The reply of the company embodied no facts or arguments which had not been considered by the Council’s referee, and the testimonials from physicians contained no evidence to show that the combination has any real advantage over sodium salicylate.

The Council therefore declared “Pulvoids Calcylates” ineligible for New and Nonofficial Remedies for the following reasons: Unwarranted therapeutic claims are made for the mixture (Rule 6); the name does not describe the composition (Rule 8), and the mixture is an unessential modification of an established remedy (sodium salicylate) (Rule 10).--(_From The Journal A. M. A., Sept. 9, 1916._)

SULFURYL MONAL

Report of the Council on Pharmacy and Chemistry

Sulfuryl Monal is said to be manufactured by Monal Frères, manufacturing chemists of Nancy, France. It is sold in the United States by George J. Wallau, Inc., New York City. According to the label:

{Contains: Sulfuryl (combined polysulphurets) { = 0.35 centigr.” “Each Pastille { {Liberates: Nascent sulphurretted Hydrogen { = 2 cub. cent.”

The Chemical Laboratory of the American Medical Association was requested to check the amount of available hydrogen sulphid. An original bottle of Sulfuryl Monal was used; this contained tablets having the taste of licorice extract and an odor of hydrogen sulphid. The tablets were found to liberate about 6 c.c. hydrogen sulphid to each tablet.

Among the claims made for the preparation are:

“Dissolved by the saliva, Sulfuryl Monal reaches the stomach where, under the influence of the gastric juice, it generates nascent sulphuretted hydrogen. Professor Albert Robin’s remarkable researches have proven that it is in the nascent state that drugs produce the greatest effect with the smallest dose.... Being thus eliminated by the entire respiratory tract: the lungs, bronchi and the throat, the sulphurretted hydrogen passes from the interior to the exterior, that is to say, goes right through these organs which are, as a consequence, thoroughly cleansed, antisepticized and freed of the pathogenic micro-organisms.... Then, again, part of the sulphuretted hydrogen, liberated in the stomach, is eliminated by the mouth and acts as an antiseptic and disinfectant of the mucous membranes of the throat and mouth. Hence Sulfuryl Monal is a perfect protective agent against contagious diseases.... Numerous clinical tests have demonstrated its real efficacy in diseases of the throat and of the respiratory tract: laryngitis, pharyngitis, hoarseness, granulations, tonsillitis, colds, bronchitis, pulmonary catarrh, asthma, emphysema, grippe, whooping cough, simple and infectious pneumonia, and in the first stage of pulmonary tuberculosis.”

The sulphids are practically ignored in modern textbooks. There is a rather extensive clinical literature on the subject, particularly in connection with sulphur waters; this, however, offers no good evidence for the therapeutic value of sulphids. Probably the tradition in their favor is largely due to the old popular idea that a disagreeable taste or odor is a mark of a good remedy.[95]

[95] Liquid Sulphur--Sulphume, J. A. M. A., Dec. 2, 1911, p. 1853.

When hydrogen sulphid is introduced into the body, the small amounts that appear in the expired air are insufficient for quantitative demonstration and it is highly improbable that the amount thus excreted has any germicidal action, or that enough is excreted in the lungs to cause irritation and a reaction. The claim that Sulfuryl Monal is “a perfect protective agent against contagious diseases” is unwarranted; the recommendation for its use in “simple and infectious pneumonia, and in the first stage of pulmonary tuberculosis” is dangerous and vicious. The Council declared Sulfuryl Monal ineligible for New and Nonofficial Remedies and authorized publication of this report.

[Editorial Note..--With one exception, this product does not appear to be advertised in medical journals. We find, however, in the gallery of nostrums that grace the advertising pages of the _International Journal of Surgery_, that Sulfuryl Monal has its place. According to an advertisement that has been running some months in this publication, “affections of the throat and respiratory organs respond promptly” to Sulfuryl Monal whose “effects are rapid and certain” even in “incipient tuberculosis.” This preposterous pronouncement is no worse than many others appearing in the same journal, but it is bad enough to indicate how uncritical must be the physicians who support--by subscription or contribution--publications that are still debasing scientific medicine.]--(_From The Journal A. M A., Sept. 16, 1916._)

MARK WHITE GOITER SERUM AND MARK WHITE IODINIZED OIL

Report of the Council on Pharmacy and Chemistry

The “Mark White Goiter Serum Laboratories” of Chicago asked the Council to consider its products “Mark White Goiter Serum” and “Mark White Iodinized Oil.” The “serum” was claimed to be an “antibody blood serum from a goat with thyroidosis” while the “Iodinized Oil” was said to contain “about 4 grains of iodin” to “each c.c.” The therapeutic indications for the treatment were given as:

“Simple or Exophthalmic Goiter, Hyperthyroidism-dosis, Thyrosis, Thyroidosis, Thyrotoxicosis, Dementia.”

An ampule (2 c.c.) of the “serum” is to be injected into the thyroid to be followed one week later by an ampule (2 c.c.) of the “Iodinized Oil.” Repetition of this “treatment” once or twice a month is advised.

The Council asked for more specific information as to the composition of the remedies, particularly as to the preparation and nature of the serum; it also asked for evidence of the therapeutic value of the preparations. In reply, Mark White wrote:

“All that I can say regarding the serum is that it is made from the blood of goats with thyroid affection, and it has been found that the serum from these goats has antibodies which control, or has curative effect upon thyroid affections when injected into thyroid glands of either humans or animals. As to the iodinised oil, it is only an adjunct or side treatment which is not always used or indicated, and will only be furnished to the physician for use in case in his judgment his patient needs it. We shall also advise the use of quinin ... when indicated....”

The Council was referred for further information to a paper by Rachel Watkins, M.D., published in the _Illinois Medical Journal_. It is to be noted, incidentally, that the letterheads used by White in his correspondence bore in one corner the notation “Rachel Watkins, M.D., Practice Limited to Goiter and Other Disorders of the Thyroid Glands,” and in the other, “Mark White, Goiter Research.”

The information regarding the composition of this goiter treatment, as furnished in Dr. Watkins’ paper, was to this effect:

“The medical treatment consists of the administration of a blood serum derived from a thyrodized goat. Formula: Iodine 0.16 grams [according to a correction by Mark White, this should read 0.26 gm.], oil 0.25 c.c., serum q. s. 1 c.c.”

This description of the treatment differs from that furnished to the Council by Mark White in that here the iodin and oil appear to be combined with the serum. Dr. Watkins’ “formula” implies that the iodin is a routine medication, thus contradicting White’s statement, which, in turn, is at variance with the statements made in submitting the treatment.

[Illustration: Photographic reproductions (greatly reduced) of some of the letterheads used by the Mark White concern during the past five years.]

The Council does not accept any biologic product until its sale in interstate commerce has been authorized by the secretary of the treasury in accordance with the federal law regulating the sale of viruses, serums, toxins and analogous products. The sale of the Mark White Goiter Serum has not been so authorized; consequently even if the preparation complied with other rules of the Council it could not be accepted.

In addition, however, this treatment conflicts with other Council rules. The statements regarding its composition are indefinite and contradictory (Rule 1); the evidence presented to support the therapeutic claims is insufficient in itself and does not appear to have been checked by any disinterested authority (Rule 6). Moreover, the recognized variation in the morphology and pathology of the types of goiter render it impracticable to treat cases of goiter by any routine procedure.

The foregoing report was submitted to the Mark White Goiter Serum Laboratory. In reply, a letter signed “Mark White, V.M.D.,” was received, which read, in part:

“... we hope at some future time to be able to give you more detailed information, but as you possibly appreciate that we have experienced for some time a demand on the part of many physicians that we furnish to them our therapy, which necessitates us furnishing it before all the detailed work has yet been accomplished, and I trust that you will be so kind as to bear patiently with us until we are better in a position to make a complete scientific application and report to you.”

White wrote further:

“The serum and iodized oil may be mixed for immediate use, but could not be put up only separate for the use of the profession and the therapy furnished Dr. Watkins she mixed as used.”

This statement throws no light on the discrepancies in the statements with regard to the place of the iodinized oil in the treatment, namely: (_a_) the original statement that the oil was to be given a week after the serum; (_b_) White’s statement (quoted earlier in this report) that the oil “is only an adjunct or side treatment” and “is not always used or indicated”; (_c_) the statement in Dr. Watkins’ paper that the oil and the serum are given in combination.

The Council declared the Mark White Goiter Serum and Mark White Iodinized Oil ineligible for New and Nonofficial Remedies and authorized publication of this report.

Editorial Note on the Mark White “Serum”

As some of our readers will remember, on April 26, 1913, The Journal called attention to the Mark White preparation which at that time was being exploited from Denver. The Propaganda Department has in its files a number of letters sent out from the Mark White concern at various times. One mailed in May, 1911, on the embossed stationery of “The Mark White Goiter Institute,” Exchange Building, Denver, was evidently a general letter sent to physicians, calling their attention to “the most important medical discovery of the age.” “Dr. Mark White, a graduate of the University of Pennsylvania,” said the letter, had discovered “a simple and harmless remedy” that would cure goiter. “Because of the desire to preserve the secrecy of this remedy it is given only at the office here.” It was then suggested that the doctor might send those of his patients who were suffering from thyroidism to the “Mark White Goitre Institute.” If he would do so he would be “given a commission of $10, in cases of the $50 fee with the additional $5 for each $50 increase.” It closed with some casuistic arguments, presumably for the purpose of overcoming the physician’s scruples, summing up the matter with the statement:

“No right thinking man will allow a narrow and self-seeking system of ethics to stand between him and his duty to the sick and suffering.”

About 1912 the name of the concern seems to have been changed, for we have in our files a letter addressed to a layman on the stationery of the “Mark White Goitre Treatment Company.” According to this letterhead the product this concern had for sale was “Goitreine” discovered by Mark White, “President and General Manager.” Mr. White’s letter to the sufferer from goiter assured him that if he would take “Goitreine” he might “be practically sure of an immediate and permanent cure.” “Goitreine,” according to White, “has absolutely and permanently cured 90 per cent.” of all cases of goiter in which it has been used--“and the other ten showed remarkable improvement.” It was efficacious for all forms of goiter and “cannot possibly harm.”

The person who received this assurance might have had his confidence in it shaken had he seen a copy of the Denver _News_ for May 23, 1911, in which was reported a case of collapse and death in a woman following an injection given in White’s office. The paper stated that the death certificate was signed by one W. A. Gray and gave “fatty degeneration of the heart and goiter” as the cause of death. Gray, it seems, was the licensed physician employed by Mark White to administer “Goitreine”--if that is what White happened to be calling his product at that time. For here it may be stated, parenthetically, that Mark White is not a physician; he is a veterinarian.

In February, 1913, Mark White sent a circular letter to a number of medical publications with the request that it be printed in full in the next issue, “to cover one full page of space.” The letter White wanted printed was addressed to doctors offering to “enter into a copartnership agreement” with such physicians who would be willing to treat “patients with goiter affections on a 50 per cent. commission basis.”

“You would be expected to make a cash charge to the patient for the treatment, remitting on the same day our 50 per cent. to us, when ordering the treatment, giving the treatment in no cases for less than $50.00.”

About the same time that Mark White made this “fifty-fifty” offer, he sent in an advertisement to be published in the classified column of The Journal. At that time he was told his advertisement was not acceptable; we now reprint it, however, free of charge. Here it is:

“WANTED--ONE OR MORE PHYSICIANS in each vicinity to administer and represent our new medical treatment for GOITER. Good margin of profit. Write for copy of contract. The Mark White Goitre Treatment Co., Denver, Colo.”

In 1914, White moved to Chicago. At least the card which we reproduce so indicates. At that time, as will be seen, “Dr. Mark White” was “personally associated” with Peter S. Clark, M.D. According to the same card Dr. F. D. Paul of Rock Island, Ill., seems to have been his “associate” for that particular locality. In this connection, it is worth noting that a Rock Island paper, in one of its issues during July, 1913, devoted a good deal of space to “Dr. Mark White” who was at that time in Rock Island “directing Dr. Frank D. Paul in the administering of the treatment.” There was nothing to indicate that this notice was an advertisement or that the editorial appearing in the same issue puffing White’s “important cure,” was paid for.

[Illustration: When exploited from Denver the Mark White “goiter cure” was advertised in the daily papers. Here is a photographic reproduction (reduced) of an advertisement that appeared in the Denver _Post_, Sept. 1, 1912.]

Dr. W. A. Gray, who has already been mentioned as White’s associate in Denver, seems to have been doing business in Illinois some time in 1913 and a Princeton (Ill.) paper had some uncomplimentary things to say about him. Finally in July, 1913, this item appeared in a Princeton paper.

“Dr. W. A. Gray, the goiter specialist who operated last winter at Princeton and Walnut until he became embroiled with Dr. Mark White, a Denver veterinary and originator of the cure, over a division of the spoils, has opened a goiter institute in Chicago under his own name. Advertisements of the Dr. Gray Goiter Institute appeared Sunday morning in the Chicago _Examiner_ and other morning papers. Dr. Gray and Mark White broke off their relations after their disagreement at Walnut, and Dr. Gray slightly changed the ingredients of the goiter cure and started off on his own hook.”

One of Gray’s advertisements in Chicago newspapers made the claim that “Dr. Gray’s New Medical Treatment removes the cause of goiter in seven days.”

[Illustration: Photographic reproduction (reduced) of the “professional” card used by “Dr. Mark White” after he came to Chicago.]

The Tulsa (Okla.) associate of “Dr.” White seems to have been Dr. J. H. Morgan and the Tulsa papers of June, 1914, tell of “Dr.” White’s visit to that city “for the purpose of instructing Dr. J. H. Morgan in the technique of his new medical treatment for nervous disorders and goiter.” Some months later--in December, 1915--the following little item appeared in a Tulsa paper:

“Dr. Mark White was found guilty in the county court yesterday of practicing medicine without a license and was fined $50. Doctor White is a goiter specialist.”

In September, 1915, Mr. Thomas S. Hogan, the efficient counsel for the Illinois State Board of Health, instituted action against Mark White for practicing medicine without a license. The case was tried Oct. 15, 1915, and the jury, after being out four hours, returned a verdict of “not guilty.” Attorney Hogan attributes the failure to obtain a conviction to the testimony of Dr. Rachel Watkins, who said she had a partnership arrangement with White in carrying on the medical business. It was about this time that Mark White seems to have issued some new letterheads. These bore in their upper left hand corner the device “Rachel Watkins, M. D., Practice Limited to Goiter and Other Disorders of the Thyroid Glands,” while the upper right hand corner read “Mark White, Goiter Research.”

On Dec. 9, 1915, Rachel Watkins, M. D., of Chicago, read a paper entitled “A Serum Treatment for Physiologically Defective Thyroids, With Clinical Reports” before the Stock Yards Branch of the Chicago Medical Society. The “serum treatment” discussed was Mark White’s “Goitreine” which, in the course of its checkered career, had lost its original name by the wayside. This paper appeared in the December, 1915, issue of the _Illinois Medical Journal_.

Probably emboldened by the ease with which a component part of the American Medical Association “fell for” a paper exploiting a “goiter cure,” Dr. Watkins requested that she be permitted to read a paper on the same subject before the Section on Pharmacology and Therapeutics at the Detroit meeting of the American Medical Association last June. The request was refused. Dr. Watkins is apparently no longer connected with White and in fact has protested against the use of her name by White in connection with his “goiter cure.”

[After the above was in type and ready for the pages of The Journal, attention was called to the _Official Bulletin of the Chicago Medical Society_ of Sept. 16, 1916. This _Bulletin_ contained a full page advertisement of the Mark White “goiter cure.” The advertiser referred to the preparation as having been “announced to the Chicago Medical Society” and declared it to be “an ethical therapeutic agent.” Mark White was described as “a medical research student” but no hint was given that he is a veterinarian. After again emphasizing that “this therapy is ethically proven” physicians were invited to “visit our goats when convenient” and the advertisement closed with the modest claim that “this thyroid therapy has equal curative therapeutic value in these cases as quinin in malaria.” And this sort of pseudo-scientific claptrap is presented to a presumably learned profession through its own official Bulletin--but what’s the use of commenting!]--(_From The Journal A. M. A., Sept. 23, 1916._)

KORA-KONIA

Report of the Council on Pharmacy and Chemistry

Kora-Konia is a “dusting powder” which at present is advertised to the medical profession through medical journals, circulars, post cards and sample packages. It is put out by the “House of Mennen,” which sells various toilet preparations such as talcum powder, shaving soap, etc. On the trade package is the statement:

“Indicated in the treatment of Acne, Dermatitis, Eczema Intertrigo; in obstinate cases of chafing, prickly heat, nettle rash, chicken pox, measles, scarlatina and irritations of the skin; as a soothing absorbent and antiseptic dusting powder and as an umbilical dressing.”

While a circular asserts that:

“Kora-konia is indicated in the treatment of acne, dermatitis, eczema and eczematous conditions of the utmost severity,... eruptive fevers,...”

What purports to be a physician’s testimonial reads:

“I used Kora-Konia in a new born case of inherited syphilis and the eruption soon cleared up.”

Germicidal powers are claimed for Kora Konia in a medical journal advertisement. In view of the various claims made and the fact that it is advertised to the medical profession, the Chemical Laboratory of the American Medical Association was asked to analyze Kora-Konia. This was done and the chemists reported as follows:

LABORATORY REPORT

Kora-Konia is a white powder, slightly greasy to the touch. Qualitative tests showed the presence of boric acid, zinc, magnesium, a solid fatty acid and material insoluble in hydrochloric acid containing magnesium and aluminum. Starch was not found. Quantitative determinations gave the following results:

Acid-insoluble material (talc) 48.3 per cent. Magnesium (Mg++) soluble in dilute acid 1.2 per cent. Zinc (Zn++) 4.5 per cent. Stearic acid (impure) 39.2 per cent. Boric acid 3.0 per cent. Carbon dioxide (CO₂)   1.5 per cent.

From this analysis it is concluded that Kora-Konia has essentially the following composition:

Zinc stearate U. S. P. 44 per cent. Talc 48 per cent. Magnesium carbonate U. S. P. 5.0 per cent. Boric acid 3.0 per cent.

Essentially this dusting powder consists of the well-known substances talc and zinc stearate in about equal proportions to which small quantities of magnesium carbonate and boric acid have been added. Inasmuch as the claim is made, by inference at least, that Kora-Konia represents original investigation carried out “with the cooperation of the medical profession” it should be stated that the preparation of commercial zinc stearate was described and recommended as a dusting and toilet powder nearly twenty-five years ago.[96]

[96] Proc. Am. Pharm. A. =40=:488, 1892.

There is nothing new or original in any one of these substances or in the combination. The extravagant and unwarranted claims made for this simple dusting powder are undoubtedly leading the public as well as some thoughtless physicians, to place undeserved confidence in it. In view of the small amount of boric acid present in the powder, its antiseptic powers must be slight and its germicidal powers almost nil. The Council declared Kora-Konia ineligible for New and Nonofficial Remedies and authorized publication of this report.--(_From The Journal A. M. A., Sept. 30, 1916._)

THE THERAPEUTIC VALUE OF THE GLYCEROPHOSPHATES

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Glycerophosphates are the salts of glycerophosphoric acid, H₂[C₃H₅(OH)₂]PO₄. This acid is produced by the interaction of glycerin and phosphoric acid. In general, only sodium glycerophosphate, Na₂[C₃H₅(OH)₂]PO₄ + 5-1/2H₂O, and calcium glycerophosphate, Ca[C₃H₅(OH)₂]PO₄ + H₂O, are used in medicine, though the glycerophosphates of lithium, potassium, manganese, magnesium, iron, quinin and strychnin are claimed as constituents of proprietary preparations. At a time when certain disorders were assumed to be due to a deficiency of phosphorus in the nerve structure in the body, glycerophosphates were introduced as “nerve foods” and “tonics” on the theory that they would be assimilated more readily than hypophosphites or ordinary phosphates. What led to this assumption was the fact that the lecithins, which form a part of the nerve structure, were known to contain the glycerophosphate radical in the molecule. The belief that inorganic phosphates cannot supply the body’s need of phosphorus is implied or expressed in most of the “literature” devoted to proprietary phosphorus preparations.

Thus, Schering and Glatz quote G. Meillière as saying that “the organism is incapable of assimilating inorganic forms of phosphorus.”

Again, when exploiters of glycerophosphates admit that the body can synthesize its phosphorus compounds from inorganic phosphates, they attempt to counterbalance the admission by contending that the use of organic compounds “spares” the system the necessity of making such synthesis. This assumption rests on the theory that the organic phosphorus compounds are absorbed and stored as such.

This theory is contradicted by evidence which has been presented[97] that the organic phosphorus compounds are split up into inorganic phosphates before absorption.

[97] McCollum and Hart, Grosser and Husler, Plimmer, and Bayliss and Plimmer, quoted by Marshall (Note 2).

The Council requested E. K. Marshall, Jr., to review the evidence for and against the therapeutic value of organic phosphorus compounds. Marshall’s study[98] brings out the following points:

[98] Marshall, E. K.: The Therapeutic Value of Organic Phosphorus Compounds, J. A. M. A., Feb. 13, 1915, p. 573.

1. In various tissues of the animal body, enzymes have been found which hydrolyze complex organic phosphorus compounds so as to liberate the phosphorus in the form of inorganic phosphates.

2. Metabolism studies of the phosphorus balance with diets containing inorganic phosphorus compounds, as compared with diets containing organically bound phosphorus, are somewhat conflicting in their results. The balance of evidence, however, is in favor of the view that there is no difference between organically combined phosphorus and inorganic salts with respect to the phosphorus balance.

3. Experiments indicate that the organism thrives on and supplies its phosphorus needs quite as well from inorganic phosphorus compounds as from organically bound phosphorus.

Marshall concludes:

“We see that the evidence is very convincing of the view that the animal organism can synthesize its complex organic phosphorus constituents from inorganic phosphates, and that organic phosphorus is of no more value as a food than inorganic.”

In view of this report, the Council deemed it advisable to take up the consideration of certain glycerophosphate preparations on the market. As the therapeutic claims are all similar, it is not necessary to quote them extensively.

TONOLS (SCHERING’S GLYCEROPHOSPHATES)

Tonols (Schering and Glatz, New York) comprise iron, lime, lithium, magnesium, manganese, potassium, quinin, sodium and strychnin “Tonols” or glycerophosphates; also Duotonol Tablets, said to contain equal parts of calcium and sodium glycerophosphates; Triotonol Tablets, each said to contain “Sodium Tonol 2-1/2 grains, Lime-Tonol 2-1/2 grains, Strychnine-Tonol 1/60 grain”; Quartonol Tablets, said to contain “Sodium and Lime-Tonols, each 2-1/4 grains, Quinine Tonol 1/2 grain, Strychnine-Tonol 1/200 grain”; Sextonol Tablets, said to contain “Sodium and Lime-Tonols, each 2 grains, Iron-Tonol, 1/2 grain, Manganese and Quinine-Tonols, each 1/4 grain, Strychnine-Tonol, 1/200 grain.”

The name “Tonols” is objectionable in that it is not only nondescriptive of the composition, but also therapeutically (and falsely) suggestive. The composition of the more elaborate Tonols is particularly unscientific; there is no justification for combining quinin, strychnin, iron, manganese, etc., in one formula.

PHOSPHORCIN COMPOUND

Phosphorcin Compound, called “The Elementary Phosphorus indicated in all forms of Nervous Diseases” and the “Perfect Formula,” is said to be manufactured by the Organic Products Company, Wetzlar an der Lahn, Germany, and Greenwich, Conn. It is sold in the United States by Eimer and Amend, New York, according to whom:

“Each two fluidrachms contain: “Acidulated Bone Phosphor O. P. Co. 2 grains “Calcium Glycerinophosphate, Merck & Co. 1-1/2 grains “Magnesium Glycerinophosphate, Merck & Co. 1-1/2 grains “Sodium Glycerinophosphate, Merck & Co. 2-1/2 grains “Lactated Pepsin 2 grains “Ignatia Extract 1/20 grain “C. P. Glycerin (Special Process) O. P. Co. 50 per cent.

“Acidulated bone phosphor” presumably is acid phosphate of calcium. This formula is an unscientific shotgun combination.

ROBINOL

Robinol, manufactured by John Wyeth and Brother, Philadelphia, is called a “Universal Tonic.” It is said to be:

“A preparation of the glycerophosphates of lithium, calcium, sodium, iron, manganese, quinine, with 1-16 gr. strychnine glycerophosphate in each fluidounce.”

This is a semisecret preparation, since the quantities of most of the ingredients are not given and the vehicle is not named. This complex combination, too, is unwarranted.

PHOSPHOGLYCERATE OF LIME (CHAPOTEAUT)

This is said to be prepared by the Laboratories de Pharmacologie Générale, Dr. Ph. Chapelle, Paris and New York. It is sold in this country by E. Fougera and Co., Inc., New York. It is offered in several forms, especially in that of wine, which is called the “Medicinal Wine and Tonic Par Excellence.” The alcohol is no doubt the constituent to which this preparation is indebted for such popularity as it has attained, for it is much more freely advertised than the syrup, capsules or granulated form. The usual claims are made with regard to the efficacy of calcium glycerophosphate “during convalescence, in cases of enfeebled vitality, and nervous affections associated with an excessive elimination of phosphates.”

ELIXIR GLYCEROPHOSPHATES, NUX VOMICA AND DAMIANA

This is manufactured by Sharp and Dohme, Baltimore. The manufacturers’ statement of composition is:

“Each fluidounce represents Nux Vomica 8 grains, Damiana 64 grains, combined with Glycerophosphates of Calcium and Sodium.”

“Alcohol 20 per cent.”

Sharp and Dohme call this mixture a “Reconstructive Nerve Stimulant, Aphrodisiac,” and claim that:

“Phosphorus in elemental form has long been prescribed under the title of Elixir Phosphorus, Nux Vomica and Damiana, but due to the rapidity of chemical change occurring in preparations containing this form of Phosphorus, much of the Physiologic action is lost. The Glycerophosphates present Phosphorus in its most available form--the form in which it exists in the brain and nervous system. They powerfully stimulate the functions of nutrition and are rapidly assimilated by the system.

“Nux Vomica is a general Nerve Tonic. Damiana exerts a stimulant effect upon the sexual appetite and function.”

The claim that the glycerophosphates may be substituted for elementary phosphorus is, at least, novel.

The elixir is an unscientific semisecret combination.

RECOMMENDATIONS

All of the preparations mentioned violate Rule 6 (unwarranted therapeutic claims). In addition, Robinol and Elixir Glycerophosphates, Nux Vomica and Damiana violate Rule 1 (secrecy of composition) in that not all the quantities of the ingredients are declared; Tonols, Phosphorcin Compound and Robinol violate Rule 8 (objectionable names). It is recommended that the Council endorse Marshall’s findings[98] and declare that Tonols (Schering and Glatz), Phosphorcin Compound (Eimer and Amend), Robinol (John Wyeth and Brother), Phosphoglycerate of Lime Chapoteaut (E. Fougera and Co.), and Elixir Glycerophosphates, Nux Vomica and Damiana (Sharp and Dohme) are ineligible for New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 30, 1916._)

HYDRAS

Report of the Council on Pharmacy and Chemistry

Hydras, sold by John Wyeth and Brother, Philadelphia, is one of the many proprietary, so-called “uterine tonics.” It is said to contain “Cramp Bark, Helonias Root, Hydrastis, Scutellaria, Dogwood and Aromatics,” but as the amounts of the several ingredients are not given the statement regarding its composition is valueless. The label declares the presence of 24 per cent. alcohol.

The name “Hydras,” taken in connection with the statement of composition, would suggest that hydrastis (golden-seal) is an important constituent. The report of the Chemical Laboratory of the American Medical Association, however, indicates that hydrastis is present in unimportant amounts:

“The hydrastin content of Hydras was determined by extraction with immiscible solvents (_Pharm. Review_, May, 1908, p. 132). Twenty-five c.c. was found to yield an alkaloid residue of 0.0160 gm. The preparation contains, therefore, not more than 0.064 gm. ‘hydrastin’ per 100 c.c. Inasmuch as hydrastis is required to contain about 2.5 per cent. ‘hydrastin,’ hydras contains an equivalent of not more than 2.56 gm. hydrastis (golden seal) in 100 c.c. and the stated dose of Hydras--one dessertspoonful (8 c.c.)--represents not more than 0.2 gm. or 1/10 of the U. S. P. average dose of hydrastis.”

The label of a recently purchased bottle of Hydras bears the following recommendations for its use:

“Indicated in treatment of Dysmenorrhea, Menorrhagia Anti-Abortive, with anodyne and tonic properties.”

“For dysmenorrhea, suppressed menses, etc., a dessertspoonful three times daily, before or after meals.”

“To relieve pain due to uterine disorders, a dessertspoonful every three hours, or increased to a tablespoonful, at the discretion of the attending physician.”

A circular wrapped around the bottle declares that Hydras is:

“A valuable preparation to the physician in the treatment of dysmenorrhea, colic, cramps, spasm, palpitation incident to pregnancy, and the various pains resulting from diseases of the female sexual organs.”

It is further claimed that:

“In the dysmenorrhea of young girls due to some mechanical difficulty, as anteflexion or of a congestive character, of suppressed menses from exposure to cold and other causes of a similar character, Hydras will prove efficient and can be administered freely without danger.”

The value of hydrastis in the treatment of the diseases and conditions mentioned is problematical at best, and the small amount present in Hydras is wholly useless. As for the other constituents, cramp bark (_Viburnum opulus_), helonias (false unicorn--_Chamælirium luteum_ or _Helonias dioica_) and scutellaria (skullcap--_Scutellaria lateriflora_) are drugs which are practically ignored by most writers on materia medica and therapeutics.[99] Dogwood (_Cornus florida_) is a mildly astringent aromatic bitter for the use of which there is no scientific evidence.[100]

[99] See reports of the Council, J. A. M. A., Jan. 9, 1915, p. 165; Jan. 23, 1915, p. 359; Nov. 27, 1919, p. 1836; March 27, 1915, p. 1093.

[100] See Reports Council Pharm. and Chem., 1912, p. 36.

To sum up: Of the five ingredients of Hydras (aside from alcohol and aromatics), one (hydrastis), which apparently gives the preparation its name, is present in unimportant amounts; three (cramp bark, helonias and scutellaria) are therapeutically unimportant; the fifth (dogwood) has never been shown to have any specific action on the uterus. The potent constituent, therefore, appears to be the alcohol.

But, even if every one of the several drugs said to be contained in Hydras were possessed of distinct therapeutic properties, and if each were present in known and therapeutically active amounts, still the combination in fixed proportion would be irrational. No one could foresee the joint effect of the five drugs in the several conditions for which the mixture is advertised. Hydras is evidently meant to appeal to the thoughtless and to be used at random; witness the suggestion made in the advertising that

“Owing to its palatability, it is acceptable to patients with impaired digestion, and will serve as a stomachic tonic, promoting appetite and digestion.”

A useless alcoholic nostrum “administered freely” to women and girls is as dangerous as the recommendation for such administration is reprehensible.

This preparation is semisecret. The recommendations for its use in specified diseases which appear on the label and in the advertising accompanying the bottle are sure to lead to its ill-advised use by the public. The claims made for its curative properties are exaggerated and unwarranted. The name, in view of the small content of hydrastis, is misleading. Finally, the combination of five drugs, even if individually they were of therapeutic value, is irrational. Hydras, consequently, is inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 4, 6, 8 and 10, and publication of this report is authorized.

[Editorial Comment.--Products like “Hydras” are the bane of scientific medicine. The physician who prescribes them could with just as much reason prescribe any of the various alcoholic “patent medicines” of the “women’s tonic” type. In fact, his patients would be running less risk of contracting the alcohol habit if he prescribed the “patent medicines,” as these nostrums usually have less alcohol than is contained in their “ethical” prototypes--and alcohol is the only really important drug in practically all of them. Whatever one may think of reputable pharmaceutical houses who put out products of the “Hydras” type, the fault really lies with the profession which tolerates such therapeutic monstrosities.]--(_From The Journal A. M. A., Oct. 7, 1916._)

BROMIN-IODIN COMPOUND

Report of the Council on Pharmacy and Chemistry

“Bromin-Iodin Compound,” according to the Bromin-Iodin Chemical Company, San Diego, Calif., has the following “formula”:

Iodin Gr. 1 Bromin Gr. 1/4 Phosphorus Gr. 1/100 Thymol Gr. 2/3 Menthol Gr. 2/3 Sterilized Oil Gr. 1

The only statement regarding its method of preparation is the line “Solution in Cod Liver Oil, Norwegian.” According to the promoters, “Bromin-Iodin” is:

“A Powerful Anti-Tubercular Agent for Hypodermic Use in Pulmonary and Laryngeal Tuberculosis. Useful in other forms of Tubercular Diseases, and in Non-Tubercular Pulmonary Diseases of a Sub-Acute or Chronic Nature.”

The “formula,” in the form in which the manufacturers publish it, is either impossible or meaningless, according to the interpretation that may be given. It is impossible if it is intended to indicate the actual composition of the product because that would mean that the oil is alleged to contain free or uncombined iodin, bromin and phosphorus. Both on theoretical grounds and also in the light of the findings of the Chemical Laboratory of the American Medical Association, it is not possible that all these constituents can be present in the free state. The formula is meaningless if it is intended to convey the idea, merely, that iodin, bromin, phosphorus, thymol, menthol and sterilized oil are combined to form “Bromin-Iodin.” In the absence of any details of the method of manufacture, it is futile to attempt to pass judgment on the actual composition of the preparation.

The use of an almost identical product (said, however, to contain only 1/2 grain iodin to each fluidram) was described in 1908 by Dr. Ingraham of Binghamton, N. Y., in “Five Years Successful Experience with a Special Mode of Treating Pulmonary Tuberculosis.” In 1910 The Journal[1] characterized the preparation as “one of the innumerable ‘treatments’ for pulmonary tuberculosis that have arisen, had their day and, more or less gracefully, retired.” If the preparation had value for the purpose for which it is recommended, its use during these twelve years should have secured its general recognition. There is no satisfactory evidence of its therapeutic efficacy. The Council refused recognition to Bromin-Iodin Comp. and, after submitting this report to the Bromin-Iodin Chemical Company, authorized its publication.--(_From The Journal A. M. A., Dec. 23, 1916._)

AMMONIUM HYPOPHOSPHITE OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Ammonium hypophosphite was admitted to New and Nonofficial Remedies in 1908 as a preliminary step in the consideration of a preparation containing it--“Gardner’s Syrup of Ammonium Hypophosphite”--because the Council standardizes unofficial products before considering preparations or mixtures of these.

The therapeutic use of hypophosphites being irrational (see, “The Hypophosphite Fallacy,” Report of the Council on Pharmacy and Chemistry, The Journal, Sept. 2, 1916, p. 760), the salt, ammonium hypophosphite, deserves continued recognition only on condition that this salt of ammonium is superior to other salts from which may be obtained the effect of the ammonium radical. It has been claimed that ammonium hypophosphite has a less objectionable taste than other ammonium salts used for similar purposes. This claim would merit serious consideration if in addition to being less objectionable to the taste, the effects of ammonium hypophosphite were equal to or more desirable than the official ammonium salts. There is no evidence that this condition is met by the hypophosphite salt.

Ammonium hypophosphite has long been known, yet it is not official in the Austrian, Belgian, British, French, German, Hungarian, Italian, Swedish, Swiss or United States Pharmacopeias. Neither is it mentioned in the leading textbooks on materia medica, pharmacology or therapeutics. In short it appears to be an instance of an obscure and superfluous salt selected for proprietary exploitation.

Since the continued recognition of ammonium hypophosphite would tend to perpetuate the hypophosphite fallacy, and because there is no evidence supporting its advantage as a means of securing the effect of ammonium salts the Council directed its omission from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 51._)

ALPHOZONE OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following advertisement appeared in the _New Idea_ (September, 1916), a house organ of Frederick Stearns & Co., the proprietors of Alphozone:

[Illustration]

In the light of our present knowledge the claim that Alphozone is a preventive of infantile paralysis is without warrant and the advice that the public depend on it for this purpose is reprehensible and dangerous. Therefore, the Council directed that Alphozone be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 50._)

CALCIUM GLYCEROPHOSPHATE AND SODIUM GLYCEROPHOSPHATE OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Calcium glycerophosphate and sodium glycerophosphate were accepted for New and Nonofficial Remedies chiefly in order that these products might be standardized. These mixtures now being defined in the new edition of the U. S. Pharmacopeia, this reason for including them in N. N. R. no longer exists. The report of Marshall (The Journal, Feb. 13, 1915, p. 573) which has the endorsement of the Council (The Journal, Sept. 30, 1916, p. 1033) shows that organic phosphorus compounds are split up into inorganic phosphates before absorption, that the animal organism can synthesize its complex organic phosphorus constituents from inorganic phosphates and consequently that the glycerophosphates, so far as their phosphorus value is concerned, are not superior to other phosphates. In fact, sodium and phosphate are more effectively administered as neutral or acid phosphate. It is evident that sodium glycerophosphate is a superfluous pharmaceutical preparation, particularly when the difficulty of obtaining a pure product and its high price is considered. So far as its calcium value is concerned, calcium glycerophosphate has no advantages over such calcium salts as the carbonate, phosphate, lactate, or chlorid. In view of the foregoing, the Council directed that sodium glycerophosphate and calcium glycerophosphate be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry_, 1916, p. 52.)

GARDNER’S SYRUP OF AMMONIUM HYPOPHOSPHITE OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

In recognition of the considerable revision of the therapeutic claims made by the manufacturer, Gardner’s Syrup of Ammonium Hypophosphite was retained in New and Nonofficial Remedies, 1916, and the proprietor advised of this provisional retention.

In the most recent advertising for this ammonium hypophosphite syrup the claim is made:

“Besides being an active expectorant Syrup of Ammonium Hypophosphite (Gardner) is useful as an alterative and resolvent and by virtue of its phosphorus element, which is in the form of a hypophosphite, PH₂O₂, has a tonic value.”

As detailed in the report of the Council “The Hypophosphite Fallacy” (The Journal, A. M. A., Sept. 2, 1916, p. 760) careful studies show that the hypophosphites are devoid of the “alterative” and “tonic” actions claimed by the manufacturer of Gardner’s Syrup of Ammonium Hypophosphite. Accordingly the Council voted to omit Gardner’s Syrup of Ammonium Hypophosphite from New and Nonofficial Remedies and authorized publication of this report.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 55._)

GLUTEN PRODUCTS MADE BY THE KELLOGG FOOD COMPANY

Report of the Council on Pharmacy and Chemistry

For over two years the Council has had under consideration certain products offered for the use of diabetics by the Kellogg Food Company of Battle Creek, Mich. These are:

Pure Gluten Biscuit. Pure Gluten Meal. 40 per cent. Gluten Biscuit. 40 per cent. Gluten Flour. 40 per cent. Gluten Meal. 20 per cent. Gluten Meal.

The Council found these products ineligible for New and Nonofficial Remedies because the statements of composition (particularly of starch content) were insufficient and because the exploitation of the products to the laity was objectionable. June 21, 1915, the company promised to place a statement of the starch content on the package of each gluten product, to place on the gluten flour sacks a caution that diabetics use the flour only on the advice of their physicians, and to revise its advertising in accordance with the suggestions of the Council. Nothing further having been heard from the company, in April, 1916, specimens of the product were obtained, through a layman, direct from the Kellogg Food Company. These specimens, together with the advertising matter received at the same time, and also a letter of advice from the company to another layman, were sent to the Council’s referee, whose report follows. As will be seen, the referee finds that the amounts of carbohydrates contained in Pure Gluten Flour, 40 per cent. Gluten Flour and Pure Gluten Meal are greater than the amounts claimed in the company’s published analyses; that in the two first mentioned the amounts of protein are less than the amounts claimed; that exaggerated claims are made on all the labels and in the advertising literature, and that the company prescribes directly to the patient.

The following report was sent to the Kellogg Food Company for consideration. In reply the firm stated that a revision of its advertising was under consideration but would make no statement as to how soon this revision would be carried into effect. As the consideration had already consumed two years, the Council decided to give the profession the facts and authorized publication of the report. At the same time the Kellogg Food Company was advised that its products would be considered further whenever any submitted evidence warranted this.

W. A. Puckner, Secretary.

Referee’s Report

I submit herewith my report on certain foods offered by the Kellogg Food Company for the use of diabetics. I shall discuss these products from the standpoint of the claims made on the label, from the standpoint of the company toward nonmedical treatment as revealed in a letter to a layman, and lastly, on the basis of the claims made for the foods in the company’s literature.

CLAIMS MADE ON THE LABEL

PURE GLUTEN BISCUIT Referee Company Water 8.30 5-10 Ash 2.04 1-2 Protein (N × 5.7) 73.87 75-80 Fiber 0.12 2.4-3 Carbohydrates 14.84 0-5 Fat 0.81 0.25-0.70 Starch 4.02 0-5

The sample analyzed does not contain the amount of protein claimed for it. It also contains more starch than one might suspect from the company’s analysis. A more conservative claim would be “starch less than 5 per cent.” The company makes the error of using the terms “starch” and “carbohydrates” as synonymous. If the maximum figures of the company’s analysis are used, the carbohydrates would amount to 5 per cent., whereas I find 14.84 per cent. The claim on the label “Guaranteed to contain less than 5 per cent. of carbohydrates” is incorrect. The next claim, “Each ounce of this gluten contains 23 grams of protein and represents 95 calories” is approximately correct, as my analysis shows 20.9 grams of protein and 103 calories.

The following remarks under “Vegetable Proteins” are in my judgment exaggerated:

“Leading authorities are now agreed that meat, fish, eggs and other animal proteins are greatly inferior to vegetable proteins in diabetes, often increasing the sugar output and the dangerous acidosis which leads to diabetic coma.... After many years of experimentation, we have succeeded in perfecting a process whereby the carbohydrates are excluded.”

In this connection, von Noorden, whom the company constantly quotes, says:

“In the slighter forms (of diabetes), the influence of meat albumins is not great and it is difficult to demonstrate the reaction of the patient to different forms of albumin. It may be necessary to add more albumin than the patient can actually take before glycosuria indication is reacted.... Once a medium amount of albumin is exceeded, say 70 to 80 grams, the glycosuria increases, no matter what the type of albumin is.”

My analysis also shows that the carbohydrates are not excluded from this food as claimed above.

40 PER CENT. GLUTEN BISCUIT Referee Water 8.50 Ash 1.48 Protein (N × 5.7) 41.15 Fiber 0.08 Carbohydrates 47.81 Fat 0.98 Starch 36.98

No analysis is supplied by the company, but this may be called properly a “40 per cent. Gluten Biscuit.” The company claims, however, that this is “Best for Diabetics,” which is not true.

Here, as in the case of “40 per cent. Gluten Flour,” the company’s label attributes to “Dr. Wm. Osler in ‘Practice of Medicine,’” the following quotation: “Of Gluten Foods, many are very unpalatable, others are frauds. A Good Gluten Flour is made by the Battle Creek Sanatarium Co., Mich.” I have no way of knowing to which gluten flour of the company Dr. Osler had reference. The “Pure Gluten Meal” might be called properly a “good gluten flour,” but this “40 per cent. Gluten Flour” is no better, and no worse, than the average gluten flour on the market. The quotation from Osler gives an entirely false impression.

40 PER CENT. GLUTEN FLOUR Referee Company Water 8.62 5-10 Ash 0.89 0.5-1 Protein (N × 5.7) 33.63 40-45 Fiber 0.08 1-3 Carbohydrates 55.35 40-45 Fat 1.43 0.2-0.5 Starch 48.04 ...

My analysis shows 6.37 per cent. less protein than the company’s minimum, and 10.35 more carbohydrates than their maximum. In past years I have found the protein in this brand to range from 35.0 to 42.9 per cent. (using the factor 5.7). It is true that the manufacturer does not state what protein factor is used in his reported analysis, but as in four other brands 5.7 is used, it is fair to assume that the same factor applies to this as well. At least such should be the case, as otherwise the manufacturer’s analyses would be meaningless. Even using the factor 6.25 this later sample contains only 36.88 per cent. of protein.

The following statement, in my judgment, as applied to a food containing over 48 per cent. of starch, does not hold water: “This food is of special service in cases of Glycosuria and in the milder forms of Diabetes.” With this brand as with “40 per cent. Gluten Biscuit” the manufacturer again uses the misleading quotation from Osler.

40 PER CENT. GLUTEN MEAL

Referee Company Water 7.30 5-10 Ash 1.36 1-2 Protein (N × 5.7) 41.55 40-45 Fiber 0.10 1-2 Carbohydrates 48.58 40-45 Fat 1.11 0.2-0.5 Starch 36.59 40-45

The claimed analysis is justified by my findings. I must take exception, however, to the following statement: “Prepared with great care from a good grade of Spring Wheat, by our special process, which preserves the natural food properties of the product.” The company evidently tries to carry water on both shoulders, on the one hand claiming a reduction in the starch content, while on the other claiming the preservation of all “the natural food properties.”

20 PER CENT. GLUTEN MEAL

Referee Company Water 7.65 5-10 Ash 1.22 1-2 Protein (N × 5.7) 24.68 20-30 Fiber 0.12 1-2 Carbohydrates 65.41 65-70 Fat 0.92 1-2 Starch 51.24 65-70

The company’s analysis is confirmed. As the company claims directly that this is “Not A Diabetic Food,” any criticism of its use for that purpose is disarmed. However, again exception must be taken to the statement that “the natural food properties of the product” are preserved.

PURE GLUTEN MEAL

Referee Company Water 4.60 5-10 Ash 0.96 1-2 Protein (N × 5.7) 76.78 75-80 Fiber 0.08 1-3 Carbohydrates 16.77 0-5 Fat 0.81 0.25-0.70 Starch 6.77 0-5

The minimum claim as to protein is justified. Again the company confuses carbohydrates and starch, and the food instead of containing from 0 to 5 per cent. of “carbohydrates (starch)” actually contains 16.77 per cent. of carbohydrates, of which 6.77 per cent. is starch. Once more the statement that “the natural food properties” are preserved is untrue as applied to a wheat product deprived of most of its starch.

In justice to the company, it should be noted that on the labels of “Pure Gluten Biscuit” and “Pure Gluten Meal” appears the warning: “Every person suffering from diabetes should be under the care of an experienced physician,” and on the label of “40 per cent. Gluten Meal,” “Persons suffering from diabetes should use this food only on the advice of a physician.” On the other hand, the suggestion on the label of “Pure Gluten Meal,” “Write for a copy of Diabetic Foods and How to Use Them” is a more or less direct invitation to self-treatment. Moreover, a letter dated May 9, 1916, apparently dictated for the Kellogg Food Company by one Ruth French, in reply to an inquiry from a layman, gives direct advice with no reference whatever to a physician.

CLAIMS MADE IN A LETTER TO A LAYMAN

In addition to this inconsistent attitude the letter makes certain clear misstatements, as follows:

“40 per cent. Gluten Flour actually contains 40 per cent. of pure Gluten, making it a perfectly safe article of diet in all but the gravest cases of diabetes. From our Gluten Flour excellent bread, gems and puffs are made that perfectly satisfy the craving for bread with no harmful results.” This flour contains 33.63 per cent. of gluten, not 40 per cent.; it is not “a perfectly safe article of diet in all but the gravest cases of diabetes,” for if one reads the literature correctly, starch restriction is more necessary in mild than in severe cases of diabetes. Furthermore, the bread, gems and puffs made from such a flour do not “satisfy the craving for bread with no harmful results.”

In the next paragraph of the letter, undue emphasis is laid on the “objectionable properties” of flesh foods, a statement only in accord with the tenets of extreme vegetarians. I also doubt very much whether the statement is true that “under a diet of our diabetic foods the thirst to which diabetics are so often subject is usually very much relieved.”

In the next paragraph the assertion is made that “The diet indicated ... is in keeping with the ideas of the highest medical authorities.... Meat is entirely excluded from the dietary.” My reading of the literature does not show that the leading authorities take any such position. Later on reference is made to von Noorden’s claim as to the superiority of vegetable over animal proteins, which I have already discussed under “Pure Gluten Biscuit.” (Certain detached sentences of von Noorden might justify such a statement, but a reading of all he says on the subject leads to a very different conclusion.)

CLAIMS MADE IN AN ADVERTISING BOOKLET

The whole booklet is written from the standpoint of an extreme vegetarian, and therefore is often misleading in its conclusions.

Page 5. “The researches of Ogata and others have shown that cane sugar is a less wholesome food than the natural sugars found in fruits and produced in the body by the digestion of starch, that is, fruit sugars and malt sugars.” In opposition to this I quote from von Noorden, their own authority, “Die Zuckerkrankheit und ihre Behandlung,” Berlin, 1910, page 270:

“That levulose, milk sugar and inulin are more useful than the other carbohydrates is a common opinion, but the importance of their use in practice does not correspond with the theory. In light cases the form of carbohydrates makes little difference; in severe cases the advantage from using levulose, milk sugar, etc., is only slightly greater than from using bread and flour.... Only in certain cases does it appear to me that the special form of carbohydrates possesses any particular significance.”

On page 92 of the same work von Noorden tells us that of the carbohydrates dextrose is the worst, with maltose almost as bad (in spite of the fact that Kellogg exploits his “Meltose,” the “new carbohydrate,” as of special value for diabetics). He also says that levulose increases glycosuria only about half as much as dextrose, when used occasionally, but with long use it is as bad as dextrose and starch.

Page 5. The company refers to sugar as “possibly also causing diabetes.” Sugar or any other carbohydrate may under diabetic conditions cause an increase of glucose in the urine, but I do not believe that any food or any diet can cause diabetes.

Page 7. “That the large use of meat and eggs is not only detrimental but positively dangerous in many cases of diabetes is now a well known and recognized fact.” The dietaries of well known authorities on diabetes are not in harmony with this statement.

Page 13. “It has been discovered that the complete suppression of carbohydrates from the dietary is not only unnecessary but is highly detrimental and even dangerous.” “The complete suppression of carbohydrates from the dietary” is the only means the physician has to determine the diabetic’s carbohydrate tolerance. If carbohydrate-poor foods are so “highly detrimental and even dangerous,” why does the company exploit foods like “Pure Gluten Flour” and “Pure Gluten Biscuit,” whose chief claim to excellence is their comparative freedom from carbohydrates?

Page 17. “Cream is an emulsion, and, with the exception of egg yolk, is the only form in which animal fat is found in an emulsified state.” Milk, Nature’s most wonderful emulsion, is apparently overlooked.

Page 19. “... these foods ... will be found of great value ... especially as substitutes for the breads and meats which are the most objectionable features of the ordinary diet, and which should, as far as possible, be interdicted in this class of cases.” This is simply special pleading for the Kellogg vegetarian diet.

Page 19. “Our glutens ... are all thoroughly standardized, so that in their use the physician and the patient know just the amount of starch eaten.” This standardization is largely mythical. For instance, “Pure Gluten Biscuit” claims 0 to 5 per cent. “carbohydrates (starch),” whereas I find 14.84 per cent. carbohydrates with 4.02 per cent. starch. “40 per cent. Gluten Flour” claims 40 per cent. gluten and 40 to 45 per cent. carbohydrates, whereas I find 33.63 and 55.35 per cent., respectively. “Pure Gluten Meal” claims 0 to 5 per cent. “carbohydrates (starch)” whereas I find 16.77 per cent. carbohydrates and 6.77 per cent. starch. I have a record of six analyses each of “40 per cent. Gluten Flour” and “40 per cent. Gluten Biscuit,” which show the hollowness of this claim of “standardization.” The flour showed 33.6, 35.0, 42.9, 36.8, 35.6, and 40.9 per cent. of protein, with from 40.8 to 55.4 per cent. of carbohydrates; the biscuits 32.7, 33.2, 39.5, 43.3, 33.9, and 41.2 per cent. of protein, with from 41.1 to 54.0 per cent. of carbohydrates. In fact, my experience shows that the Kellogg products are more poorly “standardized” than most of the diabetic foods on the market.

Page 20. “May be made to carry a large amount of fat in the form of butter, a most desirable thing in the treatment of diabetes,” while on page 16 the company claims that in an experiment of Minkowski on a dog, butter “passed through the body without change, none being absorbed”; these are certainly contradictory statements. The explanation is that on the one page the company is exploiting its biscuits, and on the other its nut preparations.

Page 20. Again the incorrect claim is made for “40 per cent. Gluten Flour” that “we believe this to be the only standardized gluten flour made.”

Page 21. The claim is made that flesh foods are “objectionable on account of the large amounts of ptomains and toxins which they contain.” I was not aware that fresh meats contained any ptomains whatever. On the same page the claim is again made that by the use of the Kellogg nut foods “diabetics lose their thirst,” a claim which I think is more than doubtful.

Page 22. “Nuts are a whole food, containing all the elements required for the perfect nutrition of the body.” A marked characteristic of nuts is that they are not “a whole food,” as with the exception of a few varieties, such as the chestnut, they are extremely poor in carbohydrates, which fact gives them their value in the diabetic diet.

Page 23. “With the exception of the potato, the beet and the carrot, vegetables contain little sugar or starch.” Corn, beans and peas are all vegetables which are relatively high in carbohydrates, and for this reason are specifically excluded from the diabetic’s dietary.

From the foregoing considerations I would recommend that the company’s analyses of “40 per cent. Gluten Biscuit,” “40 per cent. Gluten Meal,” and “20 per cent. Gluten Meal” be accepted as correct. Before the Council can accept any of these products, the following steps should be taken:

The company on all its labels should correct the impression that “carbohydrates” and “starch” are synonymous terms.

The labels of all the preparations examined should be changed in accordance with the criticisms given above.

In all cases in which analytic data are given, it would be preferable to state only the minimum of protein and the maximum of carbohydrates.

The booklet, “Practical Suggestions About Diet in Diabetes,” should be radically changed along the lines noted above.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 56._)

IODO-MANGAN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Iodo-Mangan, made by the Chemische Fabrik Helfenberg A. G., near Dresden, Germany, and sold in the United States by the Reinschild Chemical Company, New York, is a solution said to contain iron, manganese and iodin in combination with peptone. It is claimed to be a reconstructive tonic and blood-making adjuvant, with favorable action in affections of the glandular system. It was admitted to New and Nonofficial Remedies in 1907, before the Council had adopted the present Rule 10, which provides that no article shall be admitted to New and Nonofficial Remedies which, because of its unscientific composition, is useless or inimical to the best interests of the public or of the medical profession. In 1911 the Council considered the question whether or not this product was still eligible and decided in the end to retain it as probably having some merit. To determine if Iodo-Mangan was eligible for New and Nonofficial Remedies, 1917, the Reinschild Chemical Company was requested to send in the current advertising matter. As this advertising was not sent in and as apparently the product was not marketed at the present time, the Council on Pharmacy and Chemistry voted to omit Iodo-Mangan from New and Nonofficial Remedies. At the same time the Reinschild Chemical Company was informed that the preparation might be submitted for reconsideration at any time.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 64._)

LIQUID ALBOLENE

Report of the Council on Pharmacy and Chemistry

As now marketed, Liquid Albolene (McKesson and Robbins, New York), is claimed to be made only from genuine Russian oil and hence to possess distinct advantages over

“... Oils purporting to be Russian, most of which are imperfectly purified and many of which are positively dangerous for continued use.”

On the other hand, a short time ago, McKesson and Robbins claimed that Liquid Albolene was then available.

“... Of as high a quality as we had supplied before the European War. Thanks to the research and scientific achievement of Our Chemists, we are now able to offer LIQUID ALBOLENE, using as a base a specially refined Domestic Oil that is in every way suitable for medicinal purposes, and having the same viscosity as Russian Oil.”

The advertising matter suggests the promiscuous, thoughtless and irrational use of Liquid Albolene and of a number of Albolene preparations by extravagant claims, such, for example, as the following:

“Albolene will never fail to bring a free, easy stool, no matter what condition may be present, from obstinate atony of the bowel to fissure, fistula, or even malignant disease, and in spite of the failure of ordinary purgatives to which the patient may have become habituated....

“Aromatic Liquid Albolene is actually the first laxative presented to the medical profession that seems to have no drawback....

“It will not have been lost upon the physician who has read the remarks on the use of Aromatic Liquid Albolene to regulate the bowels in surgical cases, that there are many instances where it would prove equally valuable during the treatment of acute diseases. In the exanthemata, in pneumonia, for example, to cite only a few of the conditions where it may be used to advantage, an absolutely reliable laxative that will not in any way weaken or distress the patient, presents obvious superiority to any of the agents heretofore in common use.”

The Council held Liquid Albolene ineligible because the product is marketed in a way to encourage its indiscriminate and irrational use by the public (Rule 4) and because unwarranted therapeutic claims are made for it (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 65._)

NAPHEY’S MEDICATED UTERINE WAFERS

Report of the Council on Pharmacy and Chemistry

Naphey’s Medicated Uterine Wafers were submitted to the Council by the manufacturers, Naphey & Co., some years ago and were rejected. Naphey & Co. has recently requested reconsideration of the preparation, and has submitted advertising matter, trade packages and sample packages. The label of the trade package contains the following:

“Naphey’s Wafers. For the local treatment of diseases of women, indicated in catarrhal conditions of the vagina, and of the uterine cervix. As a [_sic!_] adjuvant for the physician to use in carrying out treatment of disease of the uterus.”

“Zinc Sulphate, 3-3/4 gr., Sodium Sulphate, 3-1/2 gr., Sodium Borate, 4 gr., Boric Acid, 3/4 gr.”

“Naphey & Co., Warren, Pa., U. S. A.”

“Each box contains 25 wafers, sufficient for three months’ treatment. Price per box, 25c.”

In name, composition, and general appearance of the package, Naphey’s Medicated Uterine Wafers bear a strong resemblance to Micajah’s Medicated Uterine Wafers (The Journal, A. M. A., March 26, 1910, p. 1070). An advertising pamphlet reads:

“In every form of leucorrhea Naphey’s Medicated Uterine Wafers are indicated ...”

“What is true of leucorrhea is also true of all other functional troubles affecting the female genital canal; they are all treated best by astringents and antiseptics. And these, to be effective, must be applied in prolonged contact.”

The implication that all “functional troubles affecting the female genital canal” are best treated by astringent tablets like Naphey’s Medicated Uterine Wafers is an absurdity. The naming of disease conditions on the label, the manifestly unwarranted and exaggerated therapeutic claims, the name, which is non-descriptive of composition but suggestive of use, and the fixed formula, which cannot rationally be expected to give uniformly satisfactory results in the wide range of conditions for which the product is recommended, render Naphey’s Medicated Uterine Wafers ineligible for New and Nonofficial Remedies under Rules 4, 6, 8 and 10.

The report having been sent to Naphey & Co., the manufacturer offered, on condition that the preparation be accepted, to revise the advertising matter in minor particulars, to remove disease names from the trade package and to adopt the name Naphey’s Wafers or Naphey’s Tablets. The Council advised Naphey & Co. that the proposed names do not conform to the requirements for acceptance in New and Nonofficial Remedies because they do not indicate the composition of this pharmaceutical mixture, and moreover, that the routine use of a complex formula such as that of these tablets is irrational.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 66._)

NUJOL

Report of the Council on Pharmacy and Chemistry

Nujol, a liquid petrolatum (Standard Oil Company of New Jersey, Bayonne, N. J.), was submitted to the Council by the manufacturers. The Council advised the company that, before Nujol could be made eligible for New and Nonofficial Remedies, the advertising claims made for it must be revised to conform to the rules of the Council and the term “liquid petrolatum” must be used in connection with the brand designation and given equal prominence on the labels, advertisements and all circulars. The company thereupon submitted a label on which the name “Nujol” appeared in large red letters and under it in small letters the words “Liquid Petrolatum.” This did not meet the Council’s requirement with regard to the name. Moreover, Nujol continued to be advertised to the public under exaggerated and unwarranted claims.

The foregoing report was sent to the Standard Oil Company of New Jersey, which thereupon submitted revised advertising copy. This copy was decidedly less objectionable than the previous advertising but still contained exaggerated statements. The copy for use in lay journals particularly evidenced exaggeration. Observation on many occasions of a similar fact has convinced the Council of the inexpediency of admitting to New and Nonofficial Remedies any article which is advertised to the public.[101]

[101] Since publication of this report the Council on Pharmacy and Chemistry has revised its rule against recognition of articles advertised to the public so that this shall not apply (_a_) to disinfectants, germicides and antiseptics, provided the advertising be limited to conservative recommendations for their use as prophylactic applications to superficial cuts and abrasions of the skin and to the mucous surfaces of the mouth, pharynx and nose, and provided they are not advertised as curative agents, and (_b_) to non-medicinal food preparations, except when advertised in an objectionable manner.

The Council held that conflict with Rules 3, 6 and 8 prevented the acceptance of Nujol and authorized the publication of this report.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 68._)

PULVOIDS NATRIUM COMPOUND

Report of the Council on Pharmacy and Chemistry

Pulvoids Natrium Compound was submitted to the Council by the Drug Products Company, Inc., New York, with the statement that each pulvoid (coated tablet, said to be made to dissolve in the intestinal tract) represents the equivalent of:

Potassium Nitrate 2-1/2 grs. Sodium Nitrite 1/2 gr. Sodium Bicarbonate 2 grs. Fl. Ext. Crataegus Oxycantha 1 min. Nitroglycerin 1/250 gr.

According to the advertisements the tablets are “indicated in the treatment of high blood pressure and all forms of hypertension of the cardio-vascular system.” It is claimed that the tablets “will not irritate the kidneys.”

The Council, having submitted its objections to the manufacturer and considered the firm’s reply, held that Pulvoids Natrium Compound was inadmissible to New and Nonofficial Remedies for the following reasons:

1. The claim is made that the tablets disintegrate in the intestines; experiments conducted by the Council indicated that in most cases they would be broken up in the stomach. It was found that the tablets were visibly changed immediately after being put into gastric juice or even into distilled water; they disintegrated within from three to four hours, not only in gastric juice (obtained from a dog) at 37 C., but also in distilled water. It is quite usual for solids to remain in the stomach for more than three hours. If they make their way out of the stomach in less than that time the gastric movements must be so vigorous as further to hasten the disintegration of the tablets.

2. The rules of the Council require that the name of a pharmaceutical mixture shall indicate the potent ingredients. The name of this mixture does not indicate the presence of the nitrites, the potassium nitrate, the bicarbonate or the extract of hawthorne and the nondescriptive name is likely to lead physicians to use the tablets without fully realizing what they are giving.

3. No evidence was submitted that the tablets, as found on the market, contained the amount of sodium nitrite and nitroglycerin claimed. That is, it does not appear that the manufacturer checks the sodium nitrite and nitroglycerin content by analysis. The Council did not determine the nitrite content of the tablets. It maintains that when a manufacturer places a product on the market the burden of proof is on that manufacturer to show that the facts are in accordance with his claims for his product. Further, the examination by the Council of one or several specimens of any commercial product (particularly in the case of nitroglycerin preparations) would not be a guarantee of the constancy of its composition so long as the manufacturer does not himself control the composition by analysis. The necessity of such control of tablets containing nitroglycerin is evident from the report[102] of L. F. Kebler of the U. S. Bureau of Chemistry. Dr. Kebler said:

[102] J. A. M. A., Nov. 2, 1912, p. 1604.

“... nitroglycerin tablets have in a majority of cases been found deficient in the nitroglycerin content declared.”

“... these commodities are manufactured largely by rule of thumb. Little checking obtains in their manufacture and generally no analyst is employed.”

A further proof that nitroglycerin tablets are likely to be deficient in strength is contained in the convictions under the Food and Drugs Act of manufacturers who sold tablets below the declared strength, recorded from time to time (Notices of Judgments Nos. 3405, 2059, 1843, 1799).

4. There is no good evidence, experimental or clinical, to justify the simultaneous administration in fixed proportion of two vasodilators like sodium nitrite and glyceryl trinitrate (nitroglycerin). Also there is no rational excuse for combining extract of hawthorne, which is said to have a tonic effect on the heart muscle, with nitrites, which cause relaxation of the vascular system, or for the combination with these constituents of potassium nitrate or of sodium bicarbonate.

In the absence of evidence for the combination, Pulvoids Natrium Compound must be considered an irrational mixture, the use of which is a detriment to sound drug therapy and, hence, not admissible to New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 69._)

SALOFORM

Report of the Council on Pharmacy and Chemistry

A referee submitted the following report of the American Medical Association Chemical Laboratory to the Council:

ANALYSIS OF SALOFORM

Saloform (Flexner) is advertised by the Robinson-Pettet Company of Louisville, Ky. In the advertisements for the product it is stated that:

“Saloform is a definite chemical compound the component parts of which are _Hexamethylene Tetramine_, _Salicylic Acid_ and Lithia.”

“As a Uric Acid Solvent it is indicated in _Rheumatism_, _Gout_, in _Phosphaturia_, in _Gravel_, and in _Renal Colic_.”

“As a Genito-Urinary Antiseptic it limits suppuration anywhere along the Urinary Tract, from the Kidneys down to the orifice of Urethra.”

As, even after diligent search, no description of a compound of hexamethylenamine (hexamethylenetetramine), salicylic acid and lithia was found in chemical literature, it seemed probable that Saloform is merely a mixture of hexamethylenamine and lithium salicylate. Accordingly the separation of Saloform into its component parts by means of selected solvents was attempted. By triturating the powder with chloroform, filtering and evaporating the filtrate, a residue was obtained which gave satisfactory tests for hexamethylenamine but contained only traces of salicylic acid or lithium salicylate. The portion insoluble in chloroform was dissolved in water. The solution gave satisfactory tests for lithium salicylate but not for hexamethylenamine. From these tests it is evident that Saloform is a simple mixture of hexamethylenamine and lithium salicylate. Quantitative examination indicated that the two ingredients, hexamethylenamine and lithium salicylate, are present in approximately equal amounts.

REFEREE’S RECOMMENDATION

The report of our Chemical Laboratory shows that Saloform is not a definite compound as claimed, but a simple mixture of hexamethylenamin and lithium salicylate. It is therefore in conflict with Rule 1. It is also in conflict with Rule 6, for neither hexamethylenamin, lithium, nor salicylate are therapeutically effective “uric acid solvents”; nor would any of these have any effect on “phosphaturia.”

The mixture also conflicts with Rule 10; for it is inadvisable to administer the ingredients in fixed, but unknown proportions.

It is recommended that Saloform be deemed inadmissible to N. N. R.

The Council adopted the recommendation of the referee and authorized publication of this report.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 71._)

SECRETOGEN

Report of the Council on Pharmacy and Chemistry

About a year ago the Council declared Secretogen,[103] a product the active ingredient of which was stated to be “pancreatic secretin” and advertised as a remedy for certain conditions of defective digestion and assimilation, to be ineligible for New and Nonofficial Remedies. The reasons for this decision were stated at the time as follows:

[103] J. A. M. A., May 1, 1915, p. 1518.

“1. No evidence has been presented that the absence of secretin is a cause of gastro-intestinal diseases. It is usually present, and if not present, as in achylia gastrica, there is evidently some compensating arrangement by which the pancreas is stimulated to perform its regular functions.

“2. There is no evidence that secretin in any form is physiologically active when administered by mouth.”

Since Secretogen was not the only so-called secretin preparation on the market, and since the use of secretin preparations was recommended by certain writers, notwithstanding the lack of evidence of its value, the Council caused an experimental investigation of the question to be made. This was carried out by Prof. A. J. Carlson of the University of Chicago.

No secretin was found in the commercial products examined, namely, Secretogen Tablets, Secretogen Elixir and Duodenin. Furthermore, Carlson’s results[104] confirmed the Council’s previous conclusion as to the inertness of secretin administered by mouth. The Council endorsed Professor Carlson’s findings.[105]

[104] Carlson. A. J.; Lebensohn, J. E., and Pearlman, S. J.; Has Secretin a Therapeutic Value? J. A. M. A., Jan. 15, 1916, p. 178. Reports Council on Pharm. and Chem., 1915, p. 98.

[105] So-Called Secretin Preparations, J. A. M. A., Jan 15, 1916, p. 208; Reports Council on Pharm. and Chem., 1915, p. 96.

The G. W. Carnrick Company has replied to the publication of this report in the letter printed below. (A portion of this letter, which consists of a communication from an unnamed correspondent of the G. W. Carnrick Company and the company’s comment thereon, has been omitted.) The Council offered to publish this if the Carnrick Company would furnish the name of the writer. This it has not done. As will be seen, the company now shifts ground, abandoning entirely the claim that Secretogen contains secretin. The Council has authorized publication of the letter (omitting the part just mentioned), together with the comment that follows.

W. A. PUCKNER, Secretary.

“_The Council on Pharmacy and Chemistry of the American Medical Association._

“Gentlemen:--The opinion of the Council and the contribution by Professor Carlson which appeared in The Journal of the American Medical Association for Jan. 15, 1916, have been read by us with interest. The column of Current Comment dealing with ‘Tiger-Bone Therapy and Clinical Experience’ has appealed to our good nature and, under the circumstances, our sense of humor.

“Professor Carlson seems to have quite well established that the so-called secretin preparations do not contain secretin to any appreciable extent, and that they are inert in laboratory experiments on normal animals. At the same time, to do away with an apparent discrimination on the part of the management of the Council, it would have been well if Professor Carlson had included the so-called secretin preparations belonging to another well-known firm which markets such a product. This discrimination has already been referred to by us.

“Had Professor Carlson stopped at the determination of the therapeutic availability of secretin given by mouth, his work might have been accepted without comment, even if we should have thought it advisable to object to the matter published by the Council. But the professor went beyond his province entirely when, in commenting on the findings obtained by using Secretogen clinically, he said: ‘It is, perhaps, impertinent for laboratory men to comment on these clinical results.’ It is. His point was well taken and it is a profound pity that Professor Carlson did not observe his own ruling.

“In the words of a correspondent of The Journal of the American Medical Association, in discussing Professor Carlson’s criticism of Dr. Crile’s ‘Kinetic Drive,’ ‘it behooves the laboratory man to be circumspect in his criticism of clinical theories, since going beyond the bounds of well-established things weakens his position, not merely with reference to the particular subject under discussion, but with reference to clinical phenomena in general.’ Clinical results have definitely established the value of Secretogen. As the matter now stands this statement is beyond criticism.

“When Secretogen was first introduced we assumed that it depended on secretin for results produced. In this assumption we were in good company, as witnessed by the testimony of Moore, Edie and Abram when, in the course of their investigations as to the value in diabetes of _a secretin-bearing extract given by mouth_,[106] they said: ‘In the majority of these cases ... there has been no appreciable fall in the output of sugar ... in some of these negative cases there has been noted, however, improvement in the digestion and, in certain cases, the patient’s weight has increased.’ They also state that the secretin-bearing product ‘_appears to stimulate the functional activity_ of the duodenum.’[106] They give a most significant report.[107] We quote from the paper as follows:

[106] All italics are ours. G. W. Carnrick Company.

[107] Bio-Chem. Jour. =1=:28, 1906.

“‘The patient had been under observation for six months before treatment and the sugar was not reducible by diet. _Almost at once the dyspepsia from which he was suffering was relieved and his general nutrition improved to such an extent that he regained over eighteen pounds in weight, which he had previously lost, and this improvement was accompanied by complete recovery_ of his physical and mental energies.’[106]

“Inasmuch as this improvement could not have been due to the contained secretin it must have been due to some other principle contained in the extract. Our experience and that of the physicians who have used Secretogen establish the fact that Moore, Edie and Abram made no mistake when they came to the conclusion that what they termed a secretin-bearing extract stimulates the functional activity of the duodenum and improves the digestion.

“When Professor Carlson was investigating Secretogen he must have realized that he was dealing essentially with an extract of the duodenal mucosa. It is, therefore, all the more surprising, considering his extensive researches into the literature, that he should have ignored the testimony of some of his own authorities, particularly Hallion, as to the value of extracts of the duodenal mucosa in duodenal insufficiencies. The meticulous carefulness with which this evidence was avoided is hardly worthy of the best traditions of physiology, a science which has truth for its first and last aim.

“Hallion in his ‘La Pratique de l’Opothérapie’ says that the ‘aims of duodenal opotherapy are: 1, To supply deficient duodenal juice. 2, Above all to stimulate and to relieve this organ--_notably to aid the production of secretin_[4]--and so profit by the stimulating action which duodenal extract exercises on the duodenal mucosa which action we, Enriquez and myself, believe and have experimentally proved, conforms to the general principles of opotherapy. 3, By means of the production of secretin, to reinforce the biliary, pancreatic and intestinal secretions. 4, To stimulate intestinal peristalsis.

“‘Principal indications: Intestinal dyspepsias, intestinal autointoxications, certain forms of constipation and duodenal insufficiency.’

“At the International Congress of Medicine, Madrid, 1903, Hallion said that he felt justified in stating that _duodenal opotherapy correctly carried out must be classed under the very best methods of treating dyspepsia_.[106] The results had been satisfactory and, in many cases, remarkable. It had been nil in a few cases but it had never been harmful in any degree. He pointed out that Marfan was the first to employ this substance clinically. Marfan had had particularly excellent results in children of 15 months to 4 years suffering with marked malnutrition, anorexia and constipation. _Marfan prescribed the duodenal extract given in milk._[106] Hallion further remarks that, as he is not a practitioner, he had had only one opportunity to test duodenal opotherapy clinically. The case was that of a man of 26 years with obstinate intestinal dyspepsia and severe constipation which had persisted from childhood. This patient had been treated by enemas, laxatives, diet, etc. _Treatment with duodenal extract resulted in a complete cure._[106] Hallion points out _that the most satisfactory aspect of duodenal opotherapy is the permanent effect produced_,[106] which bears out his statement that these extracts have the power to aid in the restoration of function and structure of an organ.

“This has been so well established that the principle is now embodied in a law which is frequently referred to as ‘Hallion’s Law’: ‘Extracts of an organ exert on the same organ an exciting influence which lasts for a longer or shorter time. When the organ is insufficient it is conceivable that this influence augments its action and, when it is injured, that it favors its restoration.’

“In ‘La Pratique de l’Opothérapie’ Hallion points out that ‘the opotherapeutic product which corresponds to the affected organ represents in some way the stimulating and elective food for that organ, and if we supply the organ with a food which is more complete than it necessarily needs, the affected organ can exercise its elective action and take up only those substances of which it is in need.’

“Hallion’s observations on this point are beautifully borne out by the classic work of J. W. Draper, as reported in The Journal of the American Medical Association, Sept. 26, 1914. This report gives results in both laboratory and clinical experiments.

“In order to show that fed jejunal and ileac epithelium exercise some special detoxicating power, not yet understood but definitely recognizable, Draper fed a control series of dogs with intestinal obstruction, experimentally produced, on emulsified cells of liver, spleen, pancreas and muscle tissue. These animals lived a few hours longer than not-fed controls, but Draper says that it is evident that these cells had either no detoxicating action, or a very feeble one compared with intestinal epithelium. He used jejunal and ileac epithelium clinically in two instances: 1st, In a female dog which had had ‘chronic stomach trouble’ for six months. When Draper saw her she had had complete intestinal obstruction for five days, with symptoms of tachycardia, extreme nervousness and great weakness in the hind legs. Draper removed a pebble from her intestine but her condition was still grave.

“She was immediately put on small-intestine epithelium derived from two dogs of different breed. Draper says that from a long experience with duodenally obstructed dogs, he should not have expected her to recover, but the symptoms gradually subsided and she lived. The second instance in which he used the epithelium therapeutically was in the case of a man who suffered from an annular cancer of the intestine with definite symptoms of obstruction. After the operation, and realizing that the patient was in a desperate condition, he fed him an emulsion of intestinal epithelium from a dog. The pulse improved and the patient lived.

“Some of Draper’s conclusions are as follows:

“‘Autotoxemia in intestinal obstruction undoubtedly arises from an interference with cellular reactions of the intestinal epithelium.... When small-intestine epithelial cells of healthy animals are _placed in the stomach_[106] of duodenally obstructed animals, such animals have lived nearly twice as long as not-fed controlled animals. This evidence is strongly opposed to the bacterial theory of origin of toxins.’

“The point to be emphasized is this: If this emulsion of intestinal epithelium had been fed to a normal dog and a normal man, what would have happened? Absolutely nothing. On the other hand, given as it was to a dog and a man in desperate need it exercised a potent effect.

“Abundant clinical testimony can be cited in support of the opinions of Moore, Edie and Abram, Hallion, Marfan and Draper as to the value of extracts of the intestinal mucosa given by mouth in pathological conditions. We have previously cited the published favorable opinions of such gastroenterologists as Anthony Bassler, Lewis Brinton, G. R. Lockwood, and R. C. Kemp, so there is no need to recapitulate their experiences with what they honestly believed to be secretin-bearing extracts, but which were essentially extracts of the duodenal mucosa.

“Supplementing the evidence of these men as to the value of these extracts we submit an excerpt from a letter from one of the best known physicians of Edinburgh:

“‘I can speak in very high praise of Secretogen, which I have used in both tablet form and as the elixir. There is no doubt about its value in a certain class of intractable indigestion which refuses to be benefited by any other remedy. On several occasions I have been much gratified by the definite relief obtained in this class of cases. It hits the mark also in some types of obstinate constipation--I think those cases where the trouble is wrapped up in impaired enervation of the intestine, and where stasis occurs at certain segments of the canal.’

“Hallion very pertinently points out[108] that it is now accepted that opotherapy is not substitutive, but homostimulative and he remarks further that it is well to bear in mind that the so-called active substances which make the extract efficacious need not necessarily be the hormones. ‘It may be the elements of tissue structure which may come to the aid of the injured organ. The hormone should not therefore be looked on as the only active agent of opotherapy and, while its action is important, it need not necessarily be preponderant. The chemical isolation of the hormones is, of course, of interest but may not be as vital to organotherapy as we have thought.’ ...”

[108] Presse Médicale, 1912, p. 433.

COMMENT BY THE COUNCIL ON PHARMACY AND CHEMISTRY

The G. W. Carnrick Company, which formerly claimed that Secretogen was efficacious because it contained secretin, now admits this claim to be unfounded. Notwithstanding, the manufacturers still call their product Secretogen and make for it practically the same therapeutic claims as before. They now base these claims on vague “principles of opotherapy” and on so-called “clinical testimony.” The burden of proof rests on them to show that these old claims, already discredited but put forth again on new grounds, are justified. Have they done so?

The “clinical te stimony” is not convincing. So much of it as is definite enough to permit of criticism has already been dealt with. The remainder consists of mere assertions; it is not through reliance on such evidence that the Council can discharge its trust. On this side of the question there is nothing new to be said--reassertion of a refuted argument does not constitute fresh proof.

Nor is the case better on the experimental side. The statements of Hallion, Enriquez, Zuelzer and others[109] as to the existence of a “peristaltic hormone” not only have failed of confirmation, but also have been positively discredited. With regard to Draper’s work, which dealt with acute intestinal obstruction, it is difficult to see what is its relevance to the present issue, particularly since Draper’s results were obtained with a product derived from the mucosa of the jejunum and ileum and _not with an extract of the duodenum_ such as Secretogen purports to be.

[109] Cf. interal. Schagindweit, E.: Experimentelle Versuche mit Hormonal, Arch. Internat. de Pharmacod., 1913, p. 77.

The innuendo that the Council discriminates in favor of certain manufacturers, is itself a confession of weakness.

In publishing this correspondence the Council’s sole object is to put the medical profession in possession of the exact facts of the case. These may fairly be summed up as follows:

1. Secretogen was originally marketed as a preparation containing secretin. None was found in it.

2. Notwithstanding proof of this fact, the G. W. Carnrick Company retain the original name of the product, knowing that, by its association with their former erroneous assertions concerning Secretogen, this name must inevitably convey to a physician using the product the impression that he is administering secretin. In the advertising literature no hint is given that this original statement was erroneous.

3. The product called “Secretogen” has not been shown, either experimentally and by sound clinical evidence, to possess useful therapeutic properties.

Under these circumstances the Council reaffirms its decision.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 72._)

IRON CITRATE GREEN

Report of the Council on Pharmacy and Chemistry

H. K. Mulford Company and E. R. Squibb and Sons submitted to the Council ampules containing solutions of iron citrate green. It thus became necessary to consider the eligibility of iron citrate green itself for admission to New and Nonofficial Remedies. As the rules of the Council provide that nonessential modifications of official or nonproprietary preparations will not be recognized, the above named firms were asked to state what advantages, if any, the so-called iron citrate green had over the official iron and ammonium citrate. In reply the H. K. Mulford Company wrote that it had come to the conclusion that iron citrate green and ampules thereof would undoubtedly be considered by the Council as a nonessential modification of an official product, adding:

“It seems to differ from the official ferric citrate so far as essentials go only in color, but custom, which is exceedingly hard to change in South America, demands that this green variety of ampules be used in place of the official product.”

In reply to a similar letter of inquiry E. R. Squibb and Sons wrote:

“Iron citrate green (iron and ammonium citrate green) differs from the U. S. P. iron and ammonium citrate in that it contains less iron and more citric acid and more ammonium citrate than does the latter. It is of course a modification of the official salt and is supplied to meet a real demand. Its reaction is quite decidedly acid and our present stock contains Fe slightly below the U. S. P. requirements for iron, assaying 15.74 per cent. instead of 16 per cent. Fe. The tests used to control its quality are those for the official product except as before indicated, it is always acid instead of neutral, as the U. S. P. requires for that salt.”

The smaller iron content (98 per cent. of the U. S. P. requirement) of the green variety referred to by E. R. Squibb and Sons is so small as to be negligible. Further, the low iron content as well as the acidity of the green salt would appear to be detriments rather than advantages. Inasmuch as no evidence has been presented to show that iron citrate green is superior in any way to the well-known iron and ammonium citrate the Council held that iron citrate green, and with it the dosage forms, was ineligible to N. N. R.

The preceding report was submitted to the Mulford Company and to E. R. Squibb and Sons for comment before publication. The former firm replied that in the present case it felt bound to supply the existing demand, the latter replied that, to give the Council its support in this matter, the sale of iron citrate green and ampules thereof would be discontinued.--(_From The Journal A. M. A., Jan. 13, 1917._)

ASPIRIN

Report of the Council on Pharmacy and Chemistry

The referee’s report on Aspirin-Bayer which follows was submitted to the Council and adopted by it and, in accordance with the referee’s recommendation, was sent to the Bayer Company, Inc. The company’s reply contained nothing to warrant the continued recognition of this product by the Council. It was accordingly directed that Aspirin-Bayer be omitted from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

REFEREE’S REPORT

The referee’s attention has been called to the systematic campaign of advertising aspirin to the public. He is informed that tablets have been marketed for some time in “vest-pocket” boxes, bearing the name “Aspirin” permanently affixed, which is in technical conflict with the Council’s rule against indirect advertising to the public. More recently, conspicuous advertisements have appeared in daily papers. These are technically in conflict with the rule against direct advertising to the public.

In addition to the plain technical conflicts with the Council’s rules there is a feature of the case which has not hitherto been raised and which should be fully considered: It may be remarked that the advertisements contain no therapeutic recommendation, and do not, on their face, urge the public to employ aspirin but apparently merely tell the public how it may protect itself against sophistication. In substance, they say: “If you are a user of aspirin, this is how you may obtain the genuine.” It might be said that this is not an attempt to increase the use or sale of aspirin--the ordinary object of advertising--but that the means of protection against adulteration is a “subject on which the public should be instructed.” The principle of such exceptions is stated in the comments to Rule 3 (New and Nonofficial Remedies, 1916, p. 15); and although the present case does not come under the exceptions specified under these comments, it may be urged that the exceptions need to be increased as occasion arises. The notorious adulteration of aspirin may well be urged as establishing a need for a similar exception in its use.

The general principle of protecting the public against fraud, adulteration and substitution is directly in line with the objects of the Council, and deserves commendation and support. It is obvious, however, that the means adopted for this end must be efficient, that they must not open the door to other, perhaps greater evils and that they must be used in good faith. The policy of advertising “Aspirin-Bayer” must be examined in these respects.

In the first place, the acceptance of a product by the Council implies an agreement by the manufacturers or agents that they will adhere strictly to the Council’s rules and will not depart from the letter or spirit of these rules without notice to the Council. This principle has been grossly infringed in the present case. There can be no doubt that the agents were aware that their advertisements conflicted, at least with the letter of Rule 3. Nevertheless, they did not, in any way, inform the Council of the change in policy. In this respect, at least, they have not acted in good faith.

Secondly, the wording of the advertisement implies that only the tablets stamped with “The Bayer Cross” are genuine. This is misleading, since every druggist has the right to make unstamped tablets of aspirin, fully as genuine as those stamped with the cross.

Thirdly, the cross itself cannot be considered an efficient protection; for people who imitate aspirin will not hesitate to imitate the stamp. The remedy, in either case, and as with any other drug, is the examination of trade samples, and the vigorous prosecution of those guilty of violating the law.

Fourthly, the permanent affixing of the name “Aspirin” to the vest-pocket boxes is also inefficient as a protection, and serves mainly as an advertisement.

Fifthly, whatever may have been the motives of the advertisers, and however carefully the advertisements are worded, they will inevitably tend to increase the use of aspirin by the public, and this is directly against the interests of public health. The public does not know, as physicians do, that headaches are merely symptoms of other, sometimes very serious conditions; and that they are often the signal for the need of a thorough physical examination and diagnosis. It is true that they are often also the symptoms of very minor derangements, which will right themselves spontaneously; and that, in such cases, drugs like aspirin may give relief and may do no harm. The patient, however, is not educated to distinguish one class from the other, and therefore anything that tends to promote the indiscriminate use of such remedies as aspirin is detrimental to the public health. Furthermore, aspirin itself is not always harmless. Alarming idiosyncrasies are sufficiently common that the use of the first doses, at least, should require medical supervision. With these considerations in mind, the referee is of the opinion that the direct and indirect advertising of aspirin is to be condemned.--(_From The Journal A. M. A., Jan. 20, 1917._)

PIL. CASCARA COMPOUND-ROBINS

Report of the Council on Pharmacy and Chemistry

A circular issued by the A. H. Robins Company of Richmond, Va., contains the following statement:

“PIL. CASCARA COMPOUND-ROBINS is a rational therapeutic formula, composed of CASCARA, PODOPHYLLIN, COLOCYNTH and HYOSCYAMUS, which promotes a natural flow of secretions, which is, in turn, the physiologic stimulant of peristalsis. Thus, a normal evacuation is produced without subsequent inhibition.

“They contain no Mercury, Strychnia nor Belladonna.

“An ideal aid to any remedial agent, when a Mild, Medium or Strong alimentary stimulant is needed [_sic_].

“Made in two strengths, the dosage may be easily regulated so as to obtain the effects of an Anti-Dyspeptic, Aperient, Laxative or Cathartic, as desired. They never cause discomfort unless given in larger dose than needed.”

This preparation is another example of the innumerable mixtures of well-known drugs having nothing in the way of originality or of special therapeutic value to recommend them.

The advertising implies that this particular combination has a special action on the secretions of the gastro-intestinal tract; otherwise it would be hard to explain the claim that the preparation is antidyspeptic, if that means anything more than a laxative or cathartic.

The claim is made that this preparation contains no belladonna--yet it admittedly contains hyoscyamus! This manifests either ignorance on the part of the manufacturers, or an effort to impose on the medical profession. Both belladonna and hyoscyamus contain variable amounts of similar alkaloids, chiefly hyoscyamin. Hyoscyamus is feebler than belladonna in its action, as it contains less alkaloid. The qualitative differences between the two drugs, with reference to their use as laxatives, is so slight as to make the company’s claim for hyoscyamus appear either deliberately misleading or to be the result of crass ignorance. Promoting this mixture of well-known laxatives and cathartics as an “ideal aid to any remedial agent when a mild, medium or strong alimentary stimulant is needed” is a slur on the intelligence of physicians.

Pil. Cascara Compound-Robins is not acceptable for New and Nonofficial Remedies.--(_From The Journal A. M. A., Jan. 27, 1917._)

CASTA-FLORA

Report of the Council on Pharmacy and Chemistry

Casta-Flora is one of those complex preparations which are offered to the medical profession, with plausible arguments in support of the claims made. It is put out by the Wm. S. Merrell Chemical Co., Cincinnati. Each fluidounce is said to represent:

“Castanea, fresh leaves, 40 gr.; Passiflora, fresh plant, 40 gr.; Gelsemium, green tincture, 8 minims; Inula, represented by the camphoraceous stearoptene Helenin, 20 grs.; Iodized Lime, 8 grs.; Menthol, 1-4 grs.; Aromatic Syrup Yerba Santa, 60 minims.”

It is said to be:

“A new combination of well-tried remedies of especial value in pertussis and other spasmodic coughs. It is composed of astringent, antispasmodic, sedative and expectorant agents, that control the paroxysms, relieve the irritation, promote expectoration, and give tone to mucous membranes involved.”

Still more exaggerated claims are made for the individual constituents of Casta-Flora, partly by direct statement, partly by inference. For example:

“Castanea is almost a specific in whooping cough and other spasmodic coughs.

“Passiflora is a narcotic, sedative and antispasmodic without habit-forming properties, nor does it lock up the secretions and upset digestion like opiates.

“Inula (elecampane) has been employed as a cough remedy in England for centuries. Its action is similar to guaiacol and creosote. Its active principle, helenin, is destructive of tubercle bacilli in dilutions of 1 to 10,000.

“Iodized Lime, Menthol, and Yerba Santa are too well known as expectorants and antiseptics to require more than passing mention.”

That Casta-Flora is a “new” combination may be admitted; it is improbable that exactly this combination of obsolete drugs was ever before selected for any purpose whatever, but the statement is misleading in that no new principle of therapeutics is involved. On the contrary, the combination is just what might be expected from haphazard choosing of discarded and nearly forgotten drugs. It seems incredible that a reputable firm of manufacturing pharmacists would make the positive statement that castanea is _almost_ a specific in whooping cough. Why not say it is a specific? It would be about as true. A specific or “almost specific” for this disease would rank among great medical discoveries; but castanea is merely a slightly astringent drug neither better nor worse than scores of other astringent drugs that have been tried, found valueless and discarded.

Hardly less surprising are the statements regarding passiflora. This herb has been on the market about three quarters of a century. Not only has it never established itself in scientific medicine, but it is not even mentioned in modern standard works on therapeutics.

Of all the statements made in the circular perhaps the most remarkable, in that it is so dangerously misleading, is that regarding helenin, the active principle of elecampane. The statement that this principle (helenin) is destructive of tubercle bacilli in dilutions of 1-10,000 can only mean that it is of extraordinary value in the treatment of tuberculosis; in fact, it is definitely stated that the action of elecampane is similar to that of guaiacol and creosote.

It is obvious that any drug which would destroy the tubercle bacilli in the human lungs without exerting a toxic action on the patient would be a great contribution to medicine. But although elecampane may have been used for centuries it has proved to have little, if any, merit, and even the National Standard Dispensatory, p. 848, says: “Elecampane was formerly employed as a tonic, stimulant, diuretic, diaphoretic, expectorant, and emmenagogue, but has now largely fallen into disuse.” One looks in vain in the standard textbooks on therapeutics for a description of the uses of inula (or elecampane), and of its so-called “active principle,” helenin.

The circular to which reference has been made says, referring to the use of castanea and passiflora in the treatment of whooping cough:

“Gelsemium, when made from the fresh, green plant--as is Merrell’s--is an excellent adjuvant to the above drugs, and allays the nervous irritability so frequently present.”

H. C. Wood, Jr. (Pharmacology and Therapeutics, 1916, p. 160), says of gelsemium: “Gelsemium was originally employed as an arterial sedative and febrifuge in the malarial fevers of the South, and subsequently in sthenic fevers. It appears in some way to depress the bodily temperature, but it does not appear probable that any advantage to be derived from it will counterbalance the danger attending its employment in the large doses required. In asthma, spasmodic laryngitis, whooping cough, and nervous cough it has been recommended by Bartholow, but is little used.”

That is about as favorable a statement for the drug as is to be found in the textbooks, and it serves to illustrate how little new there is in this mixture of obsolete drugs that Merrell seeks to market as one possessing extraordinary therapeutic value.

Even though the ingredients, or certain of them, were singly useful in the treatment of those conditions for which Casta-Flora is recommended, no one could possibly foresee the effect in any given case of such a jumble of drugs, both active and inert, as is said to be represented in this preparation. The prescribing of such mixtures, the action of which cannot in any way be foreseen, is plain charlatanism.

In addition, the various drugs in Casta-Flora are present in such proportions that the dose of each of the several ingredients bears no relation to the commonly accepted dose.

Casta-Flora is not acceptable for New and Nonofficial Remedies.--(_From The Journal A. M. A., Jan. 27, 1917._)

FIRWEIN

Report of the Council on Pharmacy and Chemistry

Firwein is a product of The Tilden Company, New Lebanon, N. Y. It is sold under the claim that when swallowed it has a “predilection” both for the bronchial mucosa and also for the genito-urinary organs. To quote:

“Expectorant, Sedative, Antispasmodic in the Treatment of Inflammations of the Bronchial and Genito-Urinary Mucosæ.”

“Firwein being a bland, soothing balsam possesses a wide range of adaptability and increased potency because of its healing virtues and usefulness as an expectorant, sedative and antispasmodic in bronchitis, and inflammation and catarrh of nose, throat and lungs.”

“Firwein has a special predilection for mucosæ, this being as marked in diseases of the genito-urinary system as it is in the respiratory organs. In inflammatory diseases of the genito-urinary organs, its bland, curative properties are exerted in a gratifying degree. In cystitis and uritis it is clearly indicated....”

Little information is given concerning the composition of Firwein. An old circular says:

“Firwein contains Phosphorus, Iodin and Bromin finely blended with a balsameous elixir made from the fir tree.”

From a more recent circular we quote:

“Firwein is prepared from the inside fresh green bark of the fir tree ...”

The label on the product reads:

“Firwein is pleasantly and effectively blended with salts of iodin and bromin, held in solution with 20 per cent. alcohol.”

The therapeutic claims made for Firwein and the mystery enshrouding its composition make it obvious that the product is intended to appeal to those who are either thoughtless or ignorant. This is emphasized by the suggestion that Firwein be combined with (1) cod liver oil (under the claim that it will “promote the efficiency of the oil”), with (2) whisky for the treatment of bronchorrhea of the aged, and with (3) syrup of hypophosphites for the treatment of persistent bronchitis.

As the composition of Firwein is secret, the therapeutic claims unwarranted, and its use irrational, the Council declared it inadmissible to New and Nonofficial Remedies.--(_From Journal A. M. A., Feb. 17, 1917._)

FIROLYPTOL PLAIN AND FIROLYPTOL WITH KREOSOTE

Report of the Council on Pharmacy and Chemistry

Firolyptol, another product of The Tilden Company, is, we are told, composed of eucalyptol 10 drops, cottonseed oil 1/2 ounce and Firwein enough to make 1 ounce. As the composition of Firwein is secret, it is evident that the composition of Firolyptol is also unknown, except to the manufacturers. “Firolyptol with Kreosote” is said to contain, in addition to whatever may be the component parts of Firolyptol, 10 minims of creosote to each ounce. According to an advertisement, Firolyptol with Kreosote is “antituberculous, antistrumous” and “contains all the desired features of cod liver oil and is readily assimilated.”

The advertisements of “Firolyptol Plain” and “Firolyptol with Kreosote” seem to have for their key-note the assertion that cottonseed oil is a particularly valuable nutriment and that when combined with constituents of Firolyptol and Firolyptol with Kreosote becomes particularly valuable to the tuberculous. To quote from an advertising circular:

“Now that the reconstructive properties of cottonseed oil are better appreciated by the profession, the advantages that follow the administration of a palatable emulsion of this strengthening and fattening food product are being demonstrated in hundreds of cases where formerly reliance would have been placed in cod liver oil.... A recent writer says that pure cottonseed oil is the greatest and purest vegetable oil known to chemistry, and will do much toward revolutionizing the treatment of the GREAT WHITE PLAGUE.... If the treatment of tuberculosis could resolve itself into the administration of a fatty substance in a readily assimilated form, there would be no need for any part of FIROLYPTOL but the Cottonseed Oil.... The toxic material constantly produced in the system by the germs of tuberculosis tend to expose it more and more to the ravages of the disease, and the physiologic functions of the body suffer a constant depression. To neutralize this germ activity with a consequent production of toxins it seems most logical to employ such agents as have demonstrated their suitability for such purposes, for which reason Eucalyptol and Kreosote with Firwein are incorporated in FIROLYPTOL.”

The assertion that cottonseed oil is an especially valuable form of fat is without warrant, but even if it were true the fat is available in cheap and palatable forms in numerous other cottonseed oil products. It is unnecessary to discuss the problematic value of creosote in the treatment of tuberculosis or the value of eucalyptol (now generally abandoned), or even of the secret mixture Firwein. Food and fresh air, not drugs, constitute the fundamentals of the treatment of tuberculosis, and it is both irrational and detrimental to the interests of the tuberculous to administer various potent agents in fixed and unknown amounts with such simple articles of food as cottonseed oil. Neither of these products is acceptable for New and Nonofficial Remedies.

Editorial Note.--Firwein[110] has been advertised to physicians for twenty-five or thirty years and it is a sad commentary on the intelligence of our profession that a preparation sold under such obviously false and misleading, not to say silly, claims, should still be in existence. Firwein is claimed to “prevent waste of tissue” in tuberculosis. If it had this power, it would have found its place long ago among the few great agents in drug therapy. As a matter of fact, Firwein has gained virtually no recognition outside of the “literature” of the Tilden concern. The claims made for Firwein are a peculiar mixture of studied candor--when the truth is not likely to hurt its sale--and inane vaporing--when the facts would not redound to its credit. The Tilden Company declares that “Firwein stands without a peer in its class.” But the company adds 10 drops of eucalyptol and some cottonseed oil to this peerless product and an improvement is born--“Firolyptol”! Then, to perfect the already perfectly perfected, 10 drops of creosote are added to “Firolyptol” and the profession is offered “Firolyptol with Kreosote”! In just what verbal pyrotechnics the Tilden Company might indulge, should it decide to add ten drops of something else to “Firolyptol with Kreosote,” one shudders to contemplate.

[110] Three other Tilden products have been the subject of deserved and unfavorable comment in the J. A. M. A: “Narkine” in the issue of Oct. 24, 1908, “Hydrocyanate of Iron-Tilden” in the issue of June 19, 1909, and “Febrisol,” in the issue of June 29, 1912. The first two articles are reprinted in the latest (9th) edition of “The Propaganda for Reform.”

If we are accused of exhibiting undue levity in discussing a therapeutic problem, we can only answer that it is impossible to consider seriously the Charlie Chaplins of the nostrum world.--(_From The Journal A. M. A., Feb. 17, 1917._)

BINIODOL

Report of the Council on Pharmacy and Chemistry

In accordance with the usages of the Council, the report which appears below along with the reports of the clinical investigation by Drs. Cole and Keidel upon which the recommendations of the referee were based were sent to the manufacturer for comment. The reply of the manufacturer contained no evidence which justified the Council in modifying the action already taken. Publication of the report was therefore authorized.

W. A. Puckner, Secretary.

Biniodol was submitted to the Council by the manufacturer, Charles C. Yarbrough, Memphis, Tenn. The manufacturer claims the product is a solution of 1 per cent. of red mercuric iodid and 2.75 per cent. of guaiacol in bland vegetable oil. It is marketed with the implication that it is new and superior to other oil solutions of mercuric iodid. For instance:

“... it is a straight solution of this mercurial compound, as no alkaline iodide or other chemical is used to bring about the solution.” “... It is probably the first and only one-percent oil solution of straight mercury biniodide made in America....”

[The manufacturer, in a letter addressed to the secretary of the Council, explains: “By straight solution, I mean that the solution of the red mercuric iodid is effected without the aid of any alkaline iodid or other chemicals.... Biniodol was first offered early in 1912 ...”]

“Biniodol is, therefore, superior and much to be preferred to other mercurials used for like purposes. It is highly active therapeutically, producing the desired effects, usually without the inevitable disadvantages of other mercurials. It rarely causes salivation, diarrhea, or other symptoms of mercurial intolerance, even when pushed to full therapeutic effect and when given for a considerable period of time. Nor does it produce anemia.”

The Chemical Laboratory of the American Medical Association found that Biniodol contained 1 per cent. of mercuric iodid and 2.5 per cent. of guaiacol; hence the composition is essentially as claimed. It is not true, however, that Biniodol is the “first and only one-percent solution of straight mercury biniodide made in America.” As shown in The Journal A. M. A., Dec. 9, 1914, p. 2247, formulas by Lemaire and Dunning for making a “straight” solution of mercuric iodid were published in this country in 1909 and 1910, respectively. Moreover, a 1 per cent. solution of mercuric iodid in oil is on the market and is described in New and Nonofficial Remedies.

To determine whether or not Biniodol is “superior and much to be preferred to other mercurials used for like purposes,” the Council secured the cooperation of the Department of Dermatology and Syphilology of the Western Reserve University cooperating with the Cleveland City Hospital, and of the Johns Hopkins Hospital. Each received three samples, labeled respectively, 1, 2 and 3: 1 contained Biniodol; 2, a 1 per cent. solution of mercuric iodid in oil; 3, a solution made up according to the formula of Biniodol, namely, 1 per cent. of mercuric iodid and 2.5 per cent. of guaiacol in oil. All the solutions were sterile. The investigators were not informed which preparation was designated by the respective numbers, but they were asked to use the preparations when intramuscular injections of a 1 per cent. oily solution of mercuric iodid were indicated, and to note what differences, if any, were observed following the use of the different solutions regarding pain, discomfort, induration and any other evidences of effects of the medicaments.

The Cleveland investigator reports that the patients were more or less confused in their replies to inquiries and gave rather indefinite and conflicting answers. After carefully tabulating the replies, however, the following summary resulted:

1 was worse than 2 or 3 in 6 cases. 2 was worse than 1 or 3 in 5 cases. 3 was worse than 2 or 1 in 1 case.

The report from Johns Hopkins records a series of 117 injections followed by the estimated reactions recorded below:

1. Severe, 13; mild, 14; none, 4; unrecorded, 8 = 39 2. Severe, 5; mild, 15; none, 16; unrecorded, 5 = 41 3. Severe, 7; mild, 25; none, 3; unrecorded, 2 = 37

That is, when recorded in percentages:

1. (Biniodol) severe, 33.3; mild, 35.9; none, 10.3; unrecorded, 20.5. 2. (Without guaiacol) severe, 12.2; mild, 36.8; none, 39.0; unrecorded, 12.2. 3. (With guaiacol) severe, 18.9; mild, 67.5; none, 8.1; unrecorded, 5.5.

The manufacturer of Biniodol supplied the names of several physicians who have used that preparation in their practice. Correspondence with these elicited the following statements:

One had used Biniodol in forty-eight cases and states that “only a few patients complain of pain at all and then only of a general soreness in the muscle.” This physician reports a limited experience with the use of another manufacturer’s “mercury biniodide oil solution” (apparently six cases), but severe pain following the injections made it necessary to abandon that preparation.

Another of these physicians named by the manufacturer, without reference to any series of cases, reports that “Biniodol is superior to any [oily solution of mercury biniodid] that I have tried.”

A third physician has “used it [Biniodol] a few times” and is “convinced that it has no special action or virtue” over “any red mercuric iodide in oil.”

This evidence, in its most favorable estimate, shows Biniodol to be a good 1 per cent. solution of mercuric iodid in oil, but fails to justify attributing to the preparation any unique characteristics. The preparations made in the laboratory were as satisfactory, or better than the Biniodol, and the presence or absence of the guaiacol was of no consequence.

Biniodol conflicts with Rule 6, since claims of superior therapeutic efficiency made for it are not established; and with Rules 8 and 10, since it is an unessential modification of an established nonproprietary article marketed under a proprietary name.

In view of the foregoing, the referee recommends that Biniodol be not accepted for New and Nonofficial Remedies, and that this report, including the clinical investigations of Drs. Cole and Keidel, be authorized for publication.

COMPARATIVE SYMPTOMS RESULTING FROM THE USE OF SEVERAL OILY SUSPENSIONS OF RED MERCURIC IODID (MERCURY BINIODID)

Report of Dr. H. N. Cole[C]

[C] From the Department of Dermatology and Syphilology of the Western Reserve University and of the Cleveland City Hospital.

At the request of Prof. Torald Sollmann of the Council on Pharmacy and Chemistry of the American Medical Association, we made a comparative study of several oily preparations of red mercuric iodid for intramuscular injections in syphilis.

The information, concerning the preparations submitted to the investigators, was as follows:

OILY SOLUTION OF RED MERCURIC IODID

“It is desired to ascertain whether there is any difference between three preparations, each containing 1 per cent. of mercuric iodid, as to pain, discomfort, induration, etc. The preparations will be labeled “1,” “2” and “3.” They will be sterile.

“One of these preparations will be a plain solution in oil; another will contain, in addition, 2.5 per cent. of guaiacol; the third will be a proprietary preparation containing the guaiacol.

“It is also desirable to know how the oily solution compares with the plain watery solution; but this is of secondary importance.”

The preparations all had the same appearance. The patients were taken indiscriminately, and we attempted to keep them on the injections as long as possible, in order to compare symptoms. Owing, however, to discharge from hospital, symptoms of mercury intoxication, etc., we were unable in all cases to give a thorough trial with each preparation.

In all, eleven patients were treated and seventy-one injections given--by which time our experimental supply was exhausted.

In each case the drug was given intramuscularly in the buttocks and the patients carefully observed for subjective symptoms of pain and for objective symptoms of swelling, induration, abscess formation, etc. The details are given in Table 1.

As will be noted, in several of the cases the patients were more or less confused and gave rather indefinite and conflicting answers. In attempting to compare the results from the different drugs, by careful tabulation one finds that symptoms were more marked with the respective sample as follows:

Preparation 1 was worse than Preparation 2 or 3 in six cases.

Preparation 2 was worse than Preparation 1 in two cases.

Preparation 2 was worse than Preparation 3 in five cases.

Preparation 3 was worse than Preparations 2 or 1 in one case.

TABLE 1.--DETAILS OF INVESTIGATION BY DR. COLE* ====+===+===+============+=======+======+===============+============== | | | | | | Symptoms | | | |Prepar-|Dose, +---------------+-------------- Case|Age|Sex| Date | ation | Grain| Induration-- | Objective | | † | | | | Pain | | | | | | | | ----+---+---+------------+-------+------+---------------+-------------- 1 | 25| ♂ | 6/11/16 | 2 | 1/5 |None |Still painful | | | 6/12/16 | 1 | 1/4 |None |None | | | 6/13/16 | 2 | 1/5 |None |Quite painful | | | 6/14/16 | 2 | 1/4 |Hurt for some |Very tender | | | | | | time | | | | 6/16/16 | 2 | 1/5 |Hurt for some |Very tender | | | | | | time | | | | 6/17/16 | 3 | 1/5 |Not so painful |Less tender | | | | | | | than with | | | | | | | Prepar- | | | | | | | ation 2. | | | 6/18/16 | 3 | 1/5 |Not so painful | Can sit on | | |Discontinued| | | | area; as | | |(salivation)| | | | needle prick | | | | | | | is only place | | | | | | | that it hurts | | | 6/22/16 | 2 | 1/4 |Hurt, but not |Slight indur- | | | | | | so long | ation and | | | | | | | slight | | | | | | | tenderness | | | 6/24/16 | 2 | 1/4 |Hurt, but not |Pain “dead | | | | | | so long | stinging” | | | | | | | lasts 1 hour | | | 6/25/16 | 1 | 1/4 |Not so bad |About the same ----+---+---+------------+-------+------+---------------+-------------- 2 | 32| ♂ | 6/24/16 | 2 | 1/4 |Some pain |No induration | | | 6/25/16 | 1 | 1/4 |More pain |Slight indur- | | | | | | | ation ----+---+---+------------+-------+------+---------------+-------------- 3 | ..| ♂ | 6/12/16 | 1 | 1/5 |No symptoms |Painful | | | 6/13/16 | 2 | 1/4 |No symptoms |Painful | | | 6/14/16 | 2 | 1/4 |Says the last |Painful | | | 6/16/16 |Arseno-| | two have hurt | | | | |benzol | | the more | | | | 6/17/16 | 3 | 1/5 |More pain than |Small painful | | | | | | previously | area | | | 6/17/16 | 3 | 1/5 | | | | | 6/18/16 | 3 | 1/5 |Not so much |Some indur- | | | | | | pain: in | ation at site | | | 6/19/16 | 3 | 1/5 | fact, patient | of injections | | | 6/20/16 | 3 | 1/4 | says he is | | | | 6/21/16 | 3 | 1/4 | over it in a | | | | | | | very short | | | | | | | while; com- | | | | | | | plained of | | | | | | | last one | | | | 6/22/16 | 2 | 1/4 |Some pain |Considerable | | | | | | | tenderness | | | 6/24/16 | 2 | 1/4 |Not so much as | now after so | | | | | | previously | many injec- | | | 6/25/16 | 1 | 1/4 | | tions ----+---+---+------------+-------+------+---------------+-------------- 4 | 36| ♂ | 6/22/16 | 2 | 1/4 |No pain |No tenderness | | | 6/24/16 | 2 | 1/4 |Some pain |Some tender- | | | | | | | ness | | | 6/25/16 | 1 | 1/4 |Could not sleep|Some tender- | | | | | | at night | ness; slight | | | | | | | induration ----+---+---+------------+-------+------+---------------+-------------- 5 | 32| ♂ | 6/20/16 | 3 | 20 |Some pain |No induration | | | | |minims| | | | | 6/21/16 | 3 | 25 |Some pain | | | | | |minims| | | | | 6/23/16 | 2 | 1/4 |Worse pain |No induration | | | 6/24/16 | 2 | 1/4 |Worse pain | | | | 6/25/16 | 1 | 1/4 |Worse than any |Slight tender- | | | | | | |ness ----+---+---+------------+-------+------+---------------+-------------- 6 | 20| ♂ | 6/ 8/16 | 1 | 1/6 |Very little | | | | 6/10/16 | 1 | 1/5 |Very little | | | | 6/13/16 | 1 | 1/4 |Very little | | | | 6/14/16 | 2 | 1/4 |Bothered more | | | | | | | than others | | | | 6/17/16 | 2 | 1/5 |Quite a little |Still some | | | | | | pain | soreness | | | 6/18/16 | 2 | 1/5 |Quite a little |Still some | | | | | | pain | soreness | | | 6/19/16 | 3 | 1/4 |Considerably |Very little | | | | | | less pain than| tenderness | | | 6/20/16 | 3 | 1/4 | with Prepar- | | | | 6/21/16 | 3 | 1/4 | ation 2 | ----+---+---+------------+-------+------+---------------+-------------- 7 | 30| ♂ | 6/12/16 | 1 | 1/5 |Little pain |None | | | 6/13/16 | 2 | 1/4 |No pain | | | | 6/14/16 | 2 | 1/5 |Some pain | | | | 6/16/16 |Arseno-| | | | | | |benzol | | | | | | 6/17/16 | 3 | 1/5 |Not so much |No tenderness | | | 6/18/16 | 3 | 1/5 |Not so much |No tenderness | | | 6/19/16 | 3 | 1/5 |Very little |Only slight | | | | | | pain | amount of | | | 6/20/16 | 3 | 1/4 | | induration | | | 6/21/16 | 3 | 1/4 | | | | | 6/22/16 | 2 | 1/4 |Some pain |Some little | | | | | | | induration | | | 6/24/16 | 2 | 1/4 |Considerable |Some indura- | | | | | | pain | tion | | | 6/25/16 | 1 | 1/4 |“Fine” |Slight indura- | | | | | | | tion ----+---+---+------------+-------+------+---------------+-------------- 8 | 28| ♂ | 6/13/16 | 2 | 1/5 |Little pain |Little pain | | | | | | | afterward | | | 6/15/16 | 2 | 1/5 |Little pain |Little pain | | | | | | | afterward ----+---+---+------------+-------+------+---------------+-------------- 9 | 28| ♀ | 6/17/16 | 2 | 1/5 |Some complaint |Very little | | | | | | of pain. | induration | | | 6/18/16 | 2 | 1/5 | Fairly severe | | | | 6/19/16 | 3 | 1/5 |Some pain; says|Very slight | | | | | | these have | induration | | | 6/20/16 | 3 | 1/4 | hurt very much| | | | 6/21/16 | 3 | 1/4 | less than | | | | | | | others | ----+---+---+------------+-------+------+---------------+-------------- 10 | 37| ♂ | 6/12/16 | 1 | 1/5 |No symptoms |None | | | 6/13/16 | 1 | 1/4 |No symptoms |None | | | 6/14/16 | 1 | 1/5 |No symptoms |None | | | 6/15/16 | 3 | 1/5 |No symptoms |None | | | 6/16/16 |Arseno-| | | | | | |benzol | | | | | | 6/17/16 | 3 | 1/5 |“Much less pain|None | | | | | | than biniodid | | | | | | | or grey oil” | | | | 6/18/16 | 3 | 1/5 |No complaint |None | | | 6/19/16 | 3 | 1/5 |Says he is over|Some indura- | | | 6/20/16 | 3 | 1/4 | it in one hour| tion at site | | | 6/21/16 | 3 | 1/4 | | of injection ----+---+---+------------+-------+------+---------------+-------------- 11 | 30| ♀ | 6/11/16 | 1 | 20 |Considerable; |Considerable | | | | |minims| not so much | pain and | | | 6/12/16 | 2 | 20 | | tenderness on | | | | |minims| | palpation | | | | | | | over area | | | 6/13/16 | 1 | 25 |Not much pain |Indurated area | | | | |minims| | at pt. of | | | | | | | each. | | | | | | | Painful | | | 6/14/16 | 1 | 25 |Not much pain |Slight indura- | | | | |minims| | tion ----+---+---+------------+-------+------+---------------+--------------

* The diagnosis in Case 5 was primary syphilis, and in the other cases, secondary syphilis.

† In this column, ♂ indicates male, and ♀ female. In no case did Wassermann become negative.

The criticism may be raised that the number of cases and of injections is too small to permit the drawing of any just conclusions. Even should we grant it, the statistics certainly do not prove any marked superiority of any one of the preparations over the others. We wish to thank Dr. Sollmann for advising and directing us in this work, and Drs. Bailey, Bernstein, Markus and Reycraft for assistance in carrying it out.

Report of Dr. Albert Keidel

Twenty cases were chosen at random from the syphilitic patients attending the clinic. They were given intramuscular injections of the three solutions, in amounts varying from 1 to 2 c.c., at intervals (in most instances) of two days. The injections were invariably made into the gluteal muscles, at depths of from 2 to 2-1/2 inches, and ordinary care exercised to preserve asepsis. After injection the patient was allowed to depart, and the result was recorded at the succeeding visit. The result was determined from the patient’s statement and our examination. Some patients received injections of only one solution; some were treated with first one and later with another, and one patient received all three at different times. The solutions were never mixed for a single injection, of course.

TABLE 2.--REACTIONS IN TWENTY CASES REPORTED BY DR. KEIDEL

================================================================== Preparation Reactions Number of ┌────────────┴────────────┐ Injections Severe Mild None Undetermined 1 13 14 4 8 39 2 5 15 16 5 41 3 7 25 3 2 37 --- 117 ------------------------------------------------------------------

The solutions are understood to contain a 1 per cent. solution of red mercuric iodid in oil, two of them containing in addition 2.5 per cent. of guaiacol, one of these being a proprietary preparation. The solutions are designated as Preparations 1, 2 and 3, respectively, corresponding to the numbers on the labels of the bottles in which they were originally received. The local reactions are recorded as “severe” (S), “mild” (M), “none” (O) and “Undetermined” (U). By “severe” is meant very severe pain lasting for from several hours to several days; by “mild” is meant slight pain or numbness for several hours, or less than an hour; “none” indicates that there was no local reaction, and “undetermined,” that the patient has failed to return after the last injection.

In Table 3 all the details of the investigation are recorded. Under “Local Reaction,” the letters represent the type of reaction after each injection, in the order in which they were given; when two solutions were used in the same case, the letters represent the reactions following the solution opposite which they stand. In the fifth column the plus and minus symbols indicate the Wassermann reaction; plus indicates a completely positive, and minus a completely negative reaction. When there is only one sign, it refers to the reaction at the end of treatment; when there are two, to the reaction before and after. The seventh column shows the clinical result at the end of treatment; when no note is made, it means that there was no change noted. In the eighth column are noted any objective results observed at the time of examinations of the patients.

The injections were made and the result charted by Dr. E. L. Zimmermann, of my staff, under my directions and supervision.--(_Abstracted in The Journal A. M. A., Feb. 24, 1917._)

TABLE 3.--DETAILS OF INVESTIGATION BY DR. KEIDEL

====+===+=======+=========+========+======+=======+==========+==========+============ | | | | Total |Dura- |Effect | | | Case|No.|Prepar-| Local | Amount | tion | on | Type of | Result | General | | ation |Reaction |Solution| of |Wasser-| Case | | Remarks | | | | Given, |Treat-| mann | | | | | | | C.c. | ment | | | | ----+---+-------+---------+--------+------+-------+----------+----------+------------ 1 | 3 | 2 | OOO | 3 | 6 da.| + |Latent | | 2 | 5 | 2 | MOSMS | 5.6 | 9 da.| + |Gummas....|Marked | 3 | 7 | 1 | MMM; | 9.5 | 3 mo.|- to + |Latent | improve- | | | | others U| | | | | ment | | 3 | 2 | UUU | | | | | | 4 | 1 | 2 | U | 0.75 | ... | + |Latent | | 5 | 4 | 1 | SSSM | 4.4 | 9 da.| - |Gummas....|..........|After 4th | | | | | | | | | injection, | | | | | | | | | developed | | | | | | | | | diarrhea; | | | | | | | | | melena 6 | 9 | 1 |OOUMSOSMU| 9.1 | 1 mo.| - |Latent | | 7 | 2 | 3 | MM | 3.8 | 2 da.| + |Latent |..........|Well | | | | | | | | | tolerated 8 | 7 | 2 | OOOOMOU | 9.6 |17 da.|+ to + |Primary...|Primary | | | | | | | | | healed | 9 | 4 | 1 | SMMU | 5.5 | 9 da.| |Gumma.....|Improved | 10 | 3 | 3 | MSS | 3 | 6 da.| + |Palmar |Markedly | | | | | | | | syphilis;| improved | | | | | | | | tertiary | | 11 | 7 | 3 | MSMMMMM | 10.6 |13 da.|+ to + |Latent | | 12 | 3 | 2 | MMO | 5.4 |14 da.| + |Secondary |Rash |Developed | 2 | 1 | SM | | | | (papular)| disap- | toxic ery- | | | | | | | | pearing.| thema on | | | | | | | | | thighs. | | | | | | | | | Cleared up | | | | | | | | | on stopping | | | | | | | | | HgCl₂ and | | | | | | | | | under local | | | | | | | | | treatment 13 |10 | 3 | MMMMMMMM| 12.6 |20 da.|+ to + |Secondary |Rash |Small | | | MMU | | | | (lichen | not | induration | | | | | | | syph.) | improved.| following | | | | | | | | | injection | | | | | | | | | of 1.2 c.c. 14 | 6 | 2 | OOMSMM | 7.2 |17 da.|+ to + |Old |..........|Responded to | 2 | 1 | SM | | | | cerebro- | | doses of | | | | | | | spinal | | 1 c.c. with | | | | | | | syphilis | | salivation; | | | | | | | | | fever after | | | | | | | | | injection | | | | | | | | | of 1.2 c.c. 15 | 4 | 1 | SOMS | 4.2 | 7 da.|+ to + |Secondary |No | | | | | | | | (condyl- | improve- | | | | | | | | omas) | ment | 16 | 9 | 3 |OMOMMSMSO| 10.4 |12 da.| + |Secondary |Pustules |Slight | 2 | 2 | SO | | | | (pustular| dried up;| gingivitis | | | | | | | syph.) | headache | following | | | | | | | | and fever| dose of | | | | | | | | gone | 1.5 c.c. 17 | 5 | 1 | SSMSU | 13.3 |18 da.|+ to + |Tertiary; |General | | 2 | 2 | MS | | | | aortitis.| condition| | 2 | 3 | MS | | | | | improved | 18 | 4 | 2 | OOMM | 9.5 |13 da.|- to + |Latent | | | 2 | 1 | MM | | | | |Markedly | | | | | | | | | improved | 19 | 2 | 3 | MU | 2.5 | 5 da.| + |Gumma.....| | 20 | 5 | 2 | MMMMO | 9 |14 da.|+ to + |Latent....|Marked |Small | 2 | 3 | MS | | | | | general | induration | | | | | | | | improve- | following | | | | | | | | ment | No. 3 ----+---+-------+---------+--------+------+-------+----------+----------+------------

CORPORA LUTEA (SOLUBLE EXTRACT), PARKE, DAVIS & CO.

Report of the Council on Pharmacy and Chemistry

Following inquiries, the Council took up for consideration “Corpora Lutea (Soluble Extract),” marketed by Parke, Davis & Co. in the form of ampules and proposed for hypodermic administration. The report which appears below was submitted to the Council by a committee, and was adopted by the Council. Corpora Lutea (Soluble Extract) was declared inadmissible to New and Nonofficial Remedies, and publication of the report authorized.

W. A. Puckner, Secretary.

Corpora Lutea (Soluble Extract) has not been submitted by the manufacturer. The information of the referee is based, therefore, on the claims made in the trade package, and on the statements in the price list. These show that the product is essentially secret and claims made for the actions and uses of the preparation do not make clear the essentially experimental status of the article, and are therefore misleading.

_Conflict with Rule 1._--No definite statement of composition appears beyond the indefinite claim that it is an aqueous solution of “soluble Corpora Lutea Extract,” each ampule corresponding to 0.2 Gm. of desiccated gland. How these soluble products are obtained, whether they represent _all_ the water-soluble principles, or whether some have been eliminated, are questions that are not answered. Yet such information is essential to intelligent and scientific use, for, as there is no method of standardization, the method of preparation is the only mark of identity. For instance, we do not know at this time whether proteins have anything to do with the supposed value of corpora lutea. It is, therefore, essential to know whether or not the proteins have been eliminated.

_Conflict with Rule 6._--The circular in the package advises the hypodermic use of this extract, not only in functional amenorrhea and the ordinary reflex consequences of physiologic or artificial menopause, but also in:

“‘neurasthenic’ symptoms during menstrual life”;

“sterility, not due to pyogenic infection or mechanical obstruction”;

“repeated abortions, not due to disease or mechanical factors”;

“hyperemesis in the early months of pregnancy.”

These are not stated merely as conditions in which various enthusiasts have tried corpus luteum, but as conditions “for which it will be found serviceable.”

It is not necessary to inform the medical profession that this statement is calculated to raise expectations which cannot possibly be fulfilled. Even the manufacturers seem to realize this; at least they speak somewhat indefinitely of “suitable cases,” “good judgment,” “real indications,” etc. But they proceed to nullify this warning--if it was intended as a warning--by their illustrations of unsuitable cases, for instance, “amenorrhea due to extreme anemia, dysmenorrhea due to cervical stenosis,” etc. Finally, they sum up the case:

“Therefore, additional emphasis on the necessity for the proper selection of cases is essential in order that this useful preparation may not be unjustly discredited.”

How these cases of sterility, abortions, etc., are to be selected is not revealed. In other words, the restriction is no more than a convenient device by which every improvement is to be attributed to the medicine, and every failure to the physician.

The referee recommends that Corpora Lutea (Soluble Extract), Parke, Davis & Co., be held ineligible to N. N. R., because it is a secret preparation advertised under extravagant claims.

[Editorial Comment.--Was it not in Weir Mitchell’s “Adventures of François” that the itinerant promised to pull teeth without any pain, _if the patient would hold absolutely still_? And, _mirabile dictu_, the ones who suffered were those who had not held absolutely still!]--(_From The Journal A. M. A., April 7, 1917._)

WHEELER’S TISSUE PHOSPHATES

Report of the Council on Pharmacy and Chemistry

The Council held that the contribution from the A. M. A. Chemical Laboratory, “Wheeler’s Tissue Phosphates,” demonstrates that this is a semisecret, complex and irrational preparation, sold with misleading claims concerning its medicinal constituents and therapeutic properties.

The Council directed that the report be included with the Annual Council Reports and declared Wheeler’s Tissue Phosphates in conflict with Rules 1, 6, 8 and 10.

W. A. Puckner, Secretary.

WHEELER’S TISSUE PHOSPHATES

L. E. Warren, Ph.C., B.S.

“Wheeler’s Tissue Phosphates,” known also as “Compound Elixir of Phosphates and Calisaya,” is advertised as a nerve food and a nutritive tonic. The label states that it contains calcium, iron, sodium trihydrogen phosphates, alkaloids of Peruvian bark with 12-1/2 per cent. of alcohol. The preparation is sold by the T. B. Wheeler, M. D. Co., of Rouses Point, New York. According to the manufacturer, Wheeler’s Tissue Phosphates

“... is an _inorganic_ combination of the phosphates of iron and calcium and hydrogen (phosphoric acid) together with hydrochloric acid, hydrocyanic acid, and quinine, cheerful coloring, and a delicious, cordial-like flavoring.”

“... The iron is the green, inorganic phosphate and the calcium the simple white phosphate of your early student days....”

The preparation is a red liquid, having an acid reaction, a sweet-bitter taste and the odor of wild cherry. Qualitative tests indicated the presence of calcium, iron, a phosphate, a chlorid, a sulphate, quinin or cinchona alkaloids, alcohol, sodium, cochineal coloring and invert sugar. Ammonium salts, glycerol, citrates or lactates were not found. From the quantitative values obtained the preparation may be taken to represent:

Sp. gr at 25C./25C. 1.1087 Alcohol (per cent, by volume) 11.35

Gm. per 100 c.c. Calcium phosphate [Ca₃(PO₄)₂]*  0.397 Iron phosphate (FePO₄.4H₂O)* 0.068 Chlorid (as hydrochloric acid) 0.407 Sodium sulphate (Na₂SO₄.10H₂O)  0.043 Quinin sulphate (U. S. P.) 0.041 Sodium phosphate (Na₂HPO₄.12H₂O)  0.065 Invert sugar 26.824 Water, cochineal and flavor, to make 100 c.c.

* It should be understood that the calcium and iron salts are held in solution by the hydrochloric acid.

The dose of Wheeler’s Tissue Phosphates recommended by the manufacturer is a tablespoonful or about 15 c.c. (1/2 oz.). The total calcium in a dose of the preparation is equivalent to about one-sixth of an average dose of the official calcium chlorid, and the total phosphate to each dose is equivalent to about one-fourth of a dose of the official diluted phosphoric acid. Each prescribed dose of the preparation contains about 0.01 gm. (2/13 grain) of iron phosphate or about one twenty-fifth of the average dose, and to obtain a Pharmacopeial dose of iron phosphate the patient would be obliged to take three-fourths of the contents of an entire bottle--or 12 ounces--of the preparation. If it be assumed that all of the chlorid present is in the form of free hydrochloric acid, each dose of the preparation contains the equivalent of about two-thirds of one Pharmacopeial dose of diluted hydrochloric acid. Each dose of the preparation contains about 0.0062 gm. (1/10 grain) of quinin sulphate, or about one-sixteenth of the average tonic dose. In other words, to obtain the amount of quinin sulphate given in the U. S. Pharmacopeia as the tonic dose, the patient would be required to swallow 7-1/2 fluidounces of the proprietary preparation, or the contents of nearly half a bottle. The fallacy of prescribing Wheeler’s Tissue Phosphates either for its quinin or its iron content is apparent.

Wheeler’s Tissue Phosphates is, then, a mildly bitter flavored syrup which contains nearly 12 per cent. of alcohol, small quantities each of calcium phosphate and hydrochloric acid and insignificant amounts of iron and quinin salts. In other words, essentially it is a sweetened solution of small quantities of calcium phosphate in very dilute hydrochlorid acid together with 12 per cent. of alcohol.

Bearing in mind the analysis of the preparation, how ludicrous some of the claims appear:

“_Tissue Phosphates_ is not a hypophosphite preparation; it is not a combination of glycerophosphates or other organic salts, or so-called peptonates and manganates, all recently condemned by the best therapeutic opinion here and in Europe, as much slower and less active than the simpler salts. The iron is the green, inorganic phosphite and the calcium the simple white phosphate of your early student days. Nature takes these simple salts and builds them rapidly into lecithin, bone, and other tissue, without the delay incurred by splitting up the organic salts before she can recombine them.”

“Tissue phosphates is in fact a _chemical food_.”

“The formula, suggested by Professor Dusart, of Paris, combines in an easily assimilable and agreeable cordial; medium medicinal doses of Phosphorus, the Generator of Nerve Force; Calcium Phosphate, for Cell Development and Nutrition; Sodium Phosphate, a stimulant of Liver and Pancreas and Corrective of Acid Fermentation in the Alimentary Canal; Iron, generating in the Blood, Heat and Motion, Phosphoric Acid, Tonic in Sexual Debility; Alkaloids of Calisaya, Antimalarial and Antipyretic; Extract of Wild Cherry, Tonic, yet Calming Irritation and Diminishing Nervous Excitement; Ethyl Alcohol 12.5%; and Aromatics.”

Although the claim is made that the “formula” of Wheeler’s Tissue Phosphates has been “suggested by Professor Dusart,” such of Dusart’s papers as were available in this country[111] failed to disclose any “formula” that was at all comparable to this product.

[111] Dusart, L.: Recherches expérimentales sur le rôle physiologique et thérapeutique du phosphate de chaux, Paris, 1870; Quel est l’acide du suc gastrique? Lille, 1874, unbound, 8 pages; Notice sur l’emploi et les proprietés du lacto-phosphate de chaux, Clichy, 1868, unbound, 8 pages. Dusart and Blache: Recherches sur l’assimilation du phosphate de chaux, Paris, 1868, unbound, 15 pages.

[Editorial Note.--The investigation verifies facts that must be obvious to every physician who has given the matter thought. “Wheeler’s Tissue Phosphates” is an unscientific, shotgun mixture whose most active and powerful drug is the alcohol it contains. That it was not years ago relegated to the realms of obsolete and discarded preparations is a commentary alike on the lack of scientific discrimination and the persuasive power of advertising. While in the past “Wheeler’s Tissue Phosphates” has been advertised extensively in medical journals, it seems that now the chief, if not the only beneficiary of the advertising appropriation for this product is the _New York Medical Journal_, which weekly heralds the “Delicious” and “Sustaining” qualities of “The Ideal Tonic for Fastidious Convalescents.”]--(_From The Journal A. M. A., May 5, 1917._)

THE CLAIMED GALACTAGOGUE EFFECTS OF NUTROLACTIS AND GOAT’S RUE NOT SUBSTANTIATED

Report of the Council on Pharmacy and Chemistry

Specific lactagogues--drugs which stimulate the secretion of milk--are unknown to science. Yet medical publications give space to advertisements of a proprietary--“Nutrolactis”--which is said to increase the milk supply of nursing mothers. Since dependence on a preparation of this kind is likely to cause neglect of the only means of increasing a scanty milk supply of nursing mothers--care of the general health and a sufficient quantity of proper food--this proprietary and the drug “goat’s rue,” (_Galega officinalis_) which the proprietors hint as being the potent constituent, were subjected to a critical study to determine their possible influence on milk secretion. For this purpose the Council secured the help of A. J. Carlson, Ph.D., professor of physiology, University of Chicago. Dr. Carlson, with the aid of A. Woelfel, M.D., and Marian Lewis, Sc.M., undertook to estimate the effect of Nutrolactis and of goat’s rue on nursing dogs and goats with the intention of extending the study to nursing mothers if the animal experiments so warranted. The contribution, “The Alleged Galactagogue Action of Galega and Nutrolactis,” by Marian Lewis and A. J. Carlson from the Hull Physiological Laboratory of the University of Chicago, which appears below, shows that Nutrolactis and goat’s rue are without influence on the milk secretion in nursing animals.

The Council endorsed the work of Lewis and Carlson and held that the claimed galactagogue effects of Nutrolactis and goat’s rue are not substantiated.

W. A. Puckner, Secretary.

THE ALLEGED GALACTAGOGUE ACTION OF GALEGA AND NUTROLACTIS[D]

Marian Lewis, Sc.M., and A. J. Carlson, Ph.D.

CHICAGO

[D] From the Hull Physiological Laboratory of the University of Chicago.

[D] This investigation was begun in 1915 by Drs. A. Woelfel and A. J. Carlson.

It is well established that the food best adapted to the energy and growth requirements of the infant is normal mother’s milk. Any decrease in quantity or deterioration in quality of the maternal secretion is soon followed by a parallel impairment of growth, loss of weight, or lowered resistance to infection in the infant. The widespread occurrence of deficient milk secretion is a matter of common knowledge. The discovery of true lactagogues, or specific substances which increase the quantity and quality of the milk on being administered to nursing mothers, would therefore be of very great importance. In view of this great medical and economic interest in true lactagogues it is not surprising to find that the medical and biologic literature records discoveries of lactagogues based on hope rather than demonstration, and that spurious lactagogues are on the market.

Some of the factors known to affect milk secretion are general health, food supply, psychic state, and heredity. The mechanism of secretion and the method by which these factors affect it are imperfectly understood. In general it has been observed that milk yield improves both in quantity and in quality with improvement in general health, better food supply, and more favorable psychic state. The influence of heredity is taken advantage of by dairymen who are well acquainted with the potential milk production of the different breeds of cattle.

Among the substances which have been reported to stimulate milk secretion may be mentioned the extract of the posterior lobe of the hypophysis. But pituitary extract is not a true lactagogue, because its action is confined to the smooth musculature of the gland ducts, causing a more or less complete ejection of the milk already formed; it has no effect on the gland cells or the actual secretory process in the direction of increasing the milk yield. Extracts of thymus, corpus luteum, ovaries, uterus, placenta, fetus, and the mammary gland itself have also been reported to have a temporary stimulating effect on the quantity of milk secreted, but when these extracts are given by mouth they are apparently without specific influence on the mammary gland.

Galega, or goat’s rue (_Galega officinalis_), is an herb described in the National Formulary as being slightly bitter and astringent. In 1873, Gillet-Damotti,[112] in a communication to the French Academy, stated that this plant when fed to cows increases the secretion of milk from 35 to 50 per cent. Other French writers have affirmed that goat’s rue is a lactagogue. In Germany, Fragner[113] made a preparation called Galegal, using galega as the active principle and combining it with lactose to give it a pleasant taste and make it soluble in water, milk, coffee, and tea. This preparation was reported on favorably by Scherer,[114] who asserts that he obtained positive results in fifty-four of the eighty cases in which he used it.

[112] Gillet-Damotti: Comp. rend. Acad. d. Sc., July 7, 1873.

[113] Fragner: Wien. med. Wchnschr. =60=:1033-1036, 1910.

[114] Scherer: Wien. med. Wchnschr. =60=:1033-1036, 1910.

More recently Huët[115] tested the effects of Theinhardt’s Hygiama lactogene on four lactating women. This preparation is said to be composed of hygiama,[116] galega and anise. Analysis showed that it contains albumins, fat, soluble and insoluble carbohydrates, salts and water. Huët could not observe any influence from the use of this preparation, either on the quantity or on the composition of the milk secreted.

[115] Huët: Nederlandsch Tijdschr. v. Geneesk. =1=:1353-1370, 1914.

[116] Hygiama is said to be a food consisting of condensed milk, with (fatless) cocoa and cereals added to it (Encyclopedia and Dictionary of Medicine and Surgery, 1907).

Nutrolactis[117] is a commercial preparation sold by the Nutrolactis Company of New York at $1 a bottle. The label states that it contains 5 per cent. of alcohol; that it contains fluid extracts of the family of “galactagogic plants,” and that it is intended to “increase the supply of mother’s milk.” It is recommended to maintain “quality and quantity until the end of normal lactation.” Nutrolactis is also recommended for a mother debilitated by lactation. It is claimed that “Nutrolactis does not _force_ the secretion of milk but merely assists such secretion.” Years ago Millbank[118] reported good results from the use of Nutrolactis. After more than a year’s use he concluded that it was more satisfactory than any other lactagogue hitherto employed by him, which is not saying very much, as specific lactagogues are as yet unknown. Nutrolactis is still (1916) extensively advertised in various medical journals as a lactagogue.

[117] The North Dakota Agricultural Experiment Station has recently published (Bulletin 22, 1915, p. 386) a complete chemical analysis of Nutrolactis. It contains only 0.60 per cent. solids (including strychnin and emodin). It has a bitter taste. The alcohol content was 3.5 per cent. The report concludes: “a little strychnin, a little alcohol, and a little laxative is about all there is to cause an increase in the milk secretion.”

[118] Millbank: New York M. J. =50=:544, 1889.

METHODS OF INVESTIGATION

The alleged lactagogue action of galega and Nutrolactis was tested on lactating dogs and goats. In these animals the psychic factors, or suggestion, are largely eliminated. If the results had been positive or had indicated lactagogue action, the test would have been extended to nursing women. The puppies and kids were weighed before and after nursing and a record kept of the amount of milk obtained at each nursing (the animals nursing from three to five times daily). The mothers were fed with varying doses of the drugs, and the milk yield compared with that of a control period during which no drugs were administered. An effort was made to keep the conditions of the experiments uniform throughout.

The galega was ground and mixed with the food. The Nutrolactis was mixed with food given by the stomach tube, or in some cases with a spoon. Galega was tested on two goats and Nutrolactis on one goat and nine dogs. The results are given herewith:

GALEGA

_Goat 1_: Control period, 1,600 gm., milk av. daily yield for 7 days.

Galega period (30 gm. galega mixed with oats), 860 gm., milk av. daily yield for 8 days. Kids weaned at end of period.

_Goat 2_: Control period, 1,161 gm. milk av. daily yield for 9 days.

Galega period (30 gm. galega mixed with oats), 860 gm. milk av. daily yield for 8 days. (25 gm. galega in same way), 810 gm. milk av. daily yield for 10 days.

Control period, 896 gm. milk av. daily yield for 6 days.

NUTROLACTIS

_Goat 3_: Control period, 896 gm. milk av. daily yield for 6 days.

Nutrolactis period (30 c.c. Nutrolactis mixed with oats), 658 gm. milk av. daily yield for 9 days.

Control period, 666 gm. milk av. daily yield for 5 days.

_Dog 1_: Control period, 176 gm. milk av. daily yield for 7 days.

Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 55 gm. milk av. daily yield for 12 days.

_Dog 2_: Control period, 189 gm. milk av. daily yield for 6 days.

Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 72 gm. milk av. daily yield for 11 days.

_Dog 3_: Control period, 93 gm. milk av. daily yield for 8 days.

Nutrolactis period (8 c.c. Nutrolactis on bread), 17 gm. milk av. daily yield for 5 days.

_Dog 4_: Control period, 28 gm. milk av. daily yield for 7 days.

Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 47 gm. milk av. daily yield for 6 days.

(10 c.c. Nutrolactis by stomach tube), 43 gm. milk av. daily yield for 8 days.

Control period, 41.5 gm. milk av. daily yield for 6 days.

Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33.5 gm. milk av. daily yield for 4 days.

_Dog 5_: Control period, 67 gm. milk av. daily yield for 6 days.

Nutrolactis period (10 c.c. Nutrolactis on bread), 81 gm. milk av. daily yield for 6 days.

_Dog 6_: Control period, 40 gm. milk av. daily yield for 5 days.

Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33 gm. milk av. daily yield for 8 days.

Control period, 26 gm. milk av. daily yield for 4 days.

_Dog 7_: Control period, 283 gm. milk av. daily yield for 9 days.

Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 155 gm. milk av. daily yield for 15 days.

(15 c.c. Nutrolactis by stomach tube), 82 gm. milk av. daily yield for 6 days.

Control period, 33 gm. milk av. daily yield for 3 days.

_Dog 8_: Control period, 238 gm. milk av. daily yield for 8 days.

Nutrolactis period (20 c.c. Nutrolactis on bread), 223 gm. milk av. daily yield for 4 days.

(20 c.c. Nutrolactis on bread), 46 gm. milk av. daily yield for 6 days.

_Dog 9_: Control period, 223 gm. milk av. daily yield for 6 days.

Nutrolactis period (10 c.c. Nutrolactis on bread), 178 gm. milk av. daily yield for 15 days.

(15 c.c. Nutrolactis on bread), 146 gm. milk av. daily yield for 5 days.

COMMENT AND CONCLUSION

Goat 1 had already been lactating for over two months, and the yield was gradually decreasing at the time the observations were begun. The administration of galega did not check this decrease. Goat 2 should have been a very favorable subject, for the kid was about a week old at the time the observations were begun. Both galega and Nutrolactis caused a decrease in milk yield of this animal. This decrease is perhaps partly due to the animal’s distaste for the drugs and her consequent failure to eat as well as during the control periods.

Administration of Nutrolactis was accompanied by an increase in milk in only two animals, Dog 4 and Dog 5. A detailed examination of the records of these two dogs shows that in both cases _there was a progressive increase in milk yield during the control period_ and that administration of the drug failed to accelerate this increase. On the contrary, the curve for Dog 5 takes a sudden drop immediately after the first administration of the drug.

The records of Dogs 6 and 7 show that the yield during the second control period is lower than that of the preceding periods. Although the administration of the drug in both cases was followed by a decrease in the yield, it may be urged that the drug has some lactagogue action, for its discontinuance was followed by a decrease in yield. This effect, however, is also apparent rather than real, for the data show a gradual falling off in yield during the period of administration of the drug, which decrease was not accelerated by withdrawing the drug.

Our data show that galega and Nutrolactis, when taken by mouth, and the elements of suggestion excluded, had no beneficial effect on lactation--at least in so far as the quantity of milk is concerned.--(_From The Journal A. M. A., May 26, 1917._)

THE RUSSELL EMULSION AND THE RUSSELL PREPARED GREEN BONE

Report of the Council on Pharmacy and Chemistry

The following report on “The Russell Emulsion” and “The Russell Prepared Green Bone,” marketed by the Standard Emulsion Company, was submitted to the Council by a referee. The Council endorsed the report and authorized its publication.

W. A. Puckner, Secretary.

The Russell Emulsion is put up in a neat package and advertised in an attractive pamphlet, on the cover of which we are told: “Truth Always Justifies The Superlative Degree.” As what follows in the booklet and in the printed circulars certainly does not lack superlatives, this is doubtless a warning.

In addition to the pamphlet and circular advertising, the product seems to be systematically boomed by a lecture scheme in which one Dr. Hague talks before medical societies and distributes advertising matter. The lecture is succeeded by a follow-up letter scheme through which matter is sent to members of the society. Hague ostensibly discusses “lime starvation in tuberculosis,” but medical societies soon learned to estimate his work as essentially to advertise the Russell products. Last April the Medical Society of the State of Pennsylvania sent out a circular letter to its county organizations on the subject of the Russell-Hague propaganda which opens in this way:

“You have doubtless received a letter from Dr. William Grant Hague of New York, offering to address your county society on Tuberculosis. After due investigation, it is respectfully suggested that it may not be desirable to ask him to address your society....”

The statements in the pamphlet and circular published are typical of the whole method of exploitation. For example, can such claims as these be surpassed by the veriest quack?

“SCIENCE cannot improve the means employed in producing THE RUSSELL EMULSION.”

“GENIUS has not devised better methods than are used in manufacturing THE RUSSELL EMULSION.”

“MONEY cannot buy better products than are used in THE RUSSELL EMULSION.”

“EXPERIENCE cannot suggest a more nutritious combination of fats than we use in THE RUSSELL EMULSION.”

The emulsion is said to be made of equal parts of beef-fat, coconut, peanut and cottonseed oils, held in suspension by albumin. The latter we are told is applied to each globule of the emulsion by an “elaborate technical process” devised by Dr. Russell. The mixture is everywhere spoken of as a “physiological” emulsion, but the word is always in quotation marks. Why it is called “physiological” is not clear, but the term may be counted on to impress the unthinking or the unscientific.

Numerous false and exaggerated statements are made about this “physiological” emulsion with reference to food value. For instance:

“The nutritional value of fats differ; the nutritional value of these fats and their increased efficiency by combination over all others have been determined by extensive clinical observation.”

And also:

“The Russell Emulsion is approximated in food value by no other emulsion or food product in existence.”

“A ‘physiological’ emulsion is a predigested food. It is absorbed with little assistance from the digestive juices, and with no waste of energy. It is, therefore, the ideal food....”

These are sample statements found in the pamphlet and accompanying circular. A dozen or more pathologic conditions are mentioned in which this “ideal food” is specifically indicated; but we find, also, this curious statement: “Patients can rarely take this dose [speaking of the maximum dose of 2 ounces night and morning] for more than three or four weeks without showing symptoms of over-feeding.” This unguarded remark about an ingestion of 48 grams of fat daily prompts one to ask what is wrong with the “ideal predigested food.”

Russell is wedded to the idea that “lime starvation” is the main factor in tuberculosis, and insists on the importance of large amounts of fat for the “lime starved.”

“Dr. Russell was the original interpreter of the Lime Starved State and originated The Lime Starvation Treatment in Tuberculosis. He also first pointed out and emphasized the therapeutic importance of regarding the combination of lime phosphate and casein, as brought down by the rennet enzyme, as a chemical union.”

This overworked lime-starvation theory certainly lacks any tangible confirmation (see in this connection a recent paper by Halverson, Mohler and Bergeim, in The Journal, May 5, 1917), and to urge it to promote the sale of a fat preparation is preposterous. On the uninitiated the exaggerated pseudo-scientific language of the pamphlet and circular advertisement will probably make some impression. Unfortunately such things count not only with the layman who, having no technical knowledge of physiology, cannot be expected to weigh the evidence but also with those medical men who, while scientifically educated, are influenced by unscientific claims when plausibly presented. The pamphlet is a striking example of a style which is dangerous because it smacks of science.

The Russell Company sells also a mixture called “Prepared Green Bone,” said to be made by partially digesting ground chicken bones with hydrochloric acid and pepsin and adding glycerin at the end of the digestion. The product is a sticky, unappetizing looking mass, put up in little earthenware boxes and advertised as a lime food, apparently to go along with the fat emulsion. The greater value of a few glasses of milk daily is evidently overlooked.

“The Russell Emulsion” and “The Prepared Green Bone” were declared inadmissible to New and Nonofficial Remedies.

[Editorial Comment.--There are always those who are ready to exploit the unfortunate tuberculous. It is, unfortunately, a fact that many physicians accept as true, statements clothed with obscure and voluminous quasi-scientific verbiage. Such men would laugh at the bald claim that the moon is made of green cheese; when, however, one plausibly and with due solemnity, affirms that the nocturnal luminous earthly satellite is composed of an infinite aggregation of molecules of bewildering and awe-compelling complexity, built up from the recently discovered polypeptids, the whole being of a verdant tint, the person addressed looks impressed and opines that it sounds reasonable! The advertising for The Russell Emulsion and The Russell Prepared Green Bone is dangerous because it appeals to the thoughtless--layman and physician, alike.]--(_From The Journal A. M. A., June 23, 1917._)

BROM-I-PHOS

Report of the Council on Pharmacy and Chemistry

Brom-I-Phos (National Drug Company, Philadelphia) was submitted to the Council with a label bearing the following statement:

“‘ALCOHOL 25 PER CENT.’ COMPOSITION--Per Fluidounce

Iodin 1 gr. Bromin 1 gr. Phosphorus 8-100 gr. Aromatic Base q. s.”

A request for further information in regard to the composition of Brom-I-Phos was sent to the National Drug Company. It was suggested that since the preparation cannot contain the stated amounts of free bromin, free iodin and free phosphorus, the form of combination in which these elements are present should be set forth. In reply, the firm said, first, that “Brom-I-Phos consists of Bromin, Iodin, Phosphorus, Glycerin, Wine, Water and Volatile Oils. The Iodin is rubbed up with a small percentage of Potassium Iodid and 95 per cent. Alcohol, which solution is mixed with a solution of Bromine and Spirits of Phosphorus which are combined with the base and aromatics.” The manufacturer also admitted that phosphorus reacts with bromin and iodin and that other reactions might occur, but maintained that it was “justified in assuming the greater part, if not all of these elements, are actually existent in the nascent state,” and asserted that its “printed formula complies with our working formula in point of quantities involved as well as existence of elements in an uncombined state.”

The A. M. A. Chemical Laboratory reported, on the contrary, that no free phosphorus, free bromin or free iodin could be found in Brom-I-Phos, and that no bromate or iodate could be found; bromid and iodid were present. The addition of silver nitrate to an acidulated portion, diluted with water, gave an amount of silver halid roughly agreeing with that which would be obtained had the claimed amount of bromin and iodin (together with some potassium iodid) been used in the preparation of Brom-I-Phos and in the process of manufacture become converted to bromid and iodid.

The Council declared Brom-I-Phos inadmissible to New and Nonofficial Remedies, for conflict with Rules 1, 4, 6, 8 and 10.

The statement of composition is unsatisfactory and misleading in that it suggests that the preparation contains bromin, iodin and phosphorus in the free (elementary) state. The presence of the potent elementary phosphorus is especially suggested by the small amounts of “phosphorus” declared.

The following statement on the label of the trade package constitutes an indirect advertisement to the public:

“INDICATIONS: Scrofula, Coryza, Hay Fever Necrosis, Bronchial and Throat Affections, Catarrhal Pneumonia, Glandular enlargements of the Spleen, Thyroid, and Lymphatics, Rickets and Syphilis.”

The following claims are therapeutic exaggerations:

“The Ideal Alterative”

“... indicated in all cases where an alterative is desired ...”

“The association of Bromin with Iodin in Brom-I-Phos materially enhances the product in the treatment of chronic affections of the skin, depraved conditions of the mucous membranes, tertiary syphilis, glandular enlargements, etc.”

In that it suggests that the phosphorus in Brom-I-Phos is more readily assimilated than ordinary phosphate, the following is misleading:

“The Phosphorus contained in Brom-I-Phos is readily assimilated and at once acts as a nutrient to the nervous and osseous structures of the body, stimulates metabolism and increases mental activity.”

The recommendation: “Your specification of Brom-I-Phos in the treatment of Syphilitic cases will immediately prove beneficial to the patient” is not supported by evidence. The name does not indicate that Brom-I-Phos is an alcoholic preparation with iodid as its essential constituent, but suggests that phosphorus is an important constituent, whereas the amount of phosphate or phosphite, produced by the action of iodin on elementary phosphorus (if the amount of phosphorus used in making the preparation is correctly stated) is insignificant.

The combination of bromin, iodin and phosphorus, or bromid, iodid and phosphate, is irrational because these elements are not of mutual assistance to each other in the conditions for which Brom-I-Phos is advertised.

The Council’s report was submitted to the manufacturer of Brom-I-Phos for comment; the reply contained nothing to permit a revision of the previous conclusions.

The Council declared Brom-I-Phos inadmissible to New and Nonofficial Remedies.--(_From The Journal A. M. A., June 30, 1917._)

CREOSOTE-DELSON AND CREOFOS

Report of the Council on Pharmacy and Chemistry

Creosote-Delson and Creofos, or Creosote with Hypophosphites, were submitted by the Delson Chemical Co., Inc., New York City. Creosote-Delson is said to be “beechwood creosote from which the irritating and caustic properties are removed by fractional distillation.” It is claimed that Creofos contains “2 grains of Creosote-Delson and 3-3/5 grains of the combined Hypophosphites in each fluidrachm of the mixture or emulsion, the lime salt predominating.” It is also claimed that “the primary object of the hypophosphites in this preparation is that of maintaining the refined creosote in a pure, unoxidized state, and that no particular claim for therapeutic action on their part is advanced.” It is explained further, however, “the addition of the lime was prompted by the belief ... that the fundamental cause of pulmonary tuberculosis is lime starvation....”

The assertions are made that Creosote-Delson is superior to the official creosote because it can be taken “abundantly and persistently without harm to or interference with stomach and kidneys” and can be “taken uninterruptedly and indefinitely,” while the dosage is “unlimited by any former knowledge of Creosote Therapy.” Creosote-Delson is not on the market except in the combination Creofos, although it is supplied on request.

Creofos is advised in the treatment of tuberculosis, whooping cough, measles, “Grippe and Colds,” bronchitis, asthma, “Intestinal Affections (Colitis, Summer Diarrhoea, etc.),” while its use is suggested for the “prevention of the spread of contagious diseases,” and for “preventing contagion in minor contagious diseases at any rate, in schools and families.”

The following advertisement has recently appeared in the _New York Medical Journal_ and in the _Therapeutic Gazette_:

CREOFOS MEDICATION

is the successful development of the most advanced practice in the treatment of infectious diseases. It destroys completely the causative organisms by a bactericide many times more powerful than phenol, yet absolutely harmless to animal life.

Unlike serums, its activity is not confined to any specific disease, and its use insures against sequelae (as pneumonia following grippe).

Especially valuable in the treatment of infants and patients of delicate constitution and in cases where time is of importance.

The Delson Chemical Co. was requested to supply information regarding the identity of Creosote-Delson and to support the claim that although it is “the whole drug” its dosage is “unlimited by any former knowledge of Creosote Therapy.” The reply was virtually an admission that the toxic, caustic, phenolic components of creosote were present in Creosote-Delson just as in the official creosote.

The referee of the Committee on Therapeutics in submitting his report to the Council pointed out that it is difficult to discuss the pharmacologic merits of a semisecret preparation, like Creosote-Delson, claimed to be more acceptable to the human organism than the official product it is intended to supplant, when the action of the parent drug is still questioned or disputed by eminent clinicians.

Absorption experiments have been carried out with creosote and creosote compounds, such as creosote with hypophosphites or calcium or creosote carbonate, chiefly by a study of the elimination products in the urine. But any evidence so far offered that these combinations increase absorption and lessen the irritating, caustic or toxic properties has been wholly inconclusive. The evidence offered by the Delson Chemical Co. presented no control experiments with the official creosote and did not prove that either Creosote-Delson or Creofos was less toxic than a corresponding amount of ordinary beechwood creosote.

The referee concluded that no proof had been offered that these preparations are materially superior to ordinary creosote preparations from the pharmacologic or therapeutic standpoint, and that the claims made for Creosote-Delson and Creofos are unwarranted in the light of our knowledge of the properties of creosote. The advertisement quoted above is an example of unproved and unwarranted claims.

On the recommendation of the referee, the Council declared Creosote-Delson and Creofos inadmissible to New and Nonofficial Remedies, for conflict with the rules as follows:

_Creosote-Delson_: The information so far available is not sufficient to define the nature, or composition, of Creosote-Delson, or to indicate in how far this product differs, if at all, from the official creosote (conflict with Rule 1). No methods are furnished for determining the identity or composition of Creosote-Delson (conflict with Rule 2). The available information does not show that Creosote-Delson has advantages over creosote (conflict with Rule 6).

_Creofos_: The composition of Creosote-Delson not having been furnished, the statement concerning the composition of Creofos is also unsatisfactory (conflict with Rule 1). The therapeutic claims are unsubstantiated and grossly exaggerated (conflict with Rule 6). The name is not descriptive of its composition as is required for pharmaceutical mixtures (conflict with Rule 8). There is no evidence that hypophosphites prevent decomposition of creosote (if this occurs). Hence the inclusion of hypophosphites must be considered irrational (conflict with Rule 10).

The Council’s report was sent to the Delson Chemical Co. for consideration. The firm’s reply contained nothing to warrant a revision of the report, and the Council voted that Creosote-Delson and Creofos were inadmissible to New and Nonofficial Remedies and authorized the publication of this report.--(_From The Journal A. M. A., July 7, 1917._)

TRINER’S AMERICAN ELIXIR OF BITTER WINE

Report of the Council on Pharmacy and Chemistry

Triner’s American Elixir of Bitter Wine is a wine to which bitter drugs and laxatives have been added. Though evidently intended for public consumption, it is also advertised to physicians, and consequently the Council publishes this report.

Some recent advertisements read:

“It Acts Well and Is Very Palatable. These are the reasons why so many physicians recommend TRINER’S AMERICAN ELIXIR OF BITTER WINE. Free from any chemicals. Prepared from bitter herbs roots and barks of eminent medicinal value and pure natural red wine. A safe relief in auto-intoxication, constipation, weakness, etc. Price $1.00. At drug Stores. Samples gratis upon request only to physicians.”

“A Laxative Tonic. In cases of constipation and its sequelæ, autointoxication, weakness and nervousness you should try _Triner’s American Elixir of Bitter Wine_. This preparation consists of Cascara Sagrada, Dandelion, Gentian Root, with Licorice in Pure Red Wine as a base, with Aromatics.”

Triner’s American Elixir of Bitter Wine is put up in bottles said to hold 1 pint, 5-1/3 fluidounces. The label declares the presence of from 16 to 18 per cent. alcohol by volume, and states that “no special tax is required by the laws of the U. S. for the sale of this medicinal preparation.” The circular contains the following recommendations for its use:

“... It should be used in all cases calling for a safe evacuation of the bowels, without weakening the body or causing any pain or other discomfort; in loss of appetite, nervousness and weakness.”

“Triner’s American Elixir of Bitter Wine consists of two principal ingredients, viz., Red Wine and Medicinal Herbs.”

“Red Wine strengthens the intestines and regulates their work. It also increases the appetite, stimulates and strengthens the body.”

“Use Triner’s American Elixir of Bitter Wine always when a thorough cleaning out of the intestines is needed. Arrange the dose to suit your condition and habits.”

“In Chronic Constipation the dose of Triner’s American Elixir of Bitter Wine should be increased or taken oftener.”

“Many Female Troubles are caused or aggravated by constipation and ladies should always pay good attention to this fact.”

In addition to Triner’s Elixir of Bitter Wine, the circular--in English, Polish, Russian, Spanish and other languages--advises the use of Triner’s Angelica Bitter Tonic, Triner’s Red Pills, Triner’s Liniment and Triner’s Cough Sedative.

The composition of this “wine”--some bitter drugs, a laxative and a tannin-containing, constipating red wine--and advertising propaganda all tend to the continued use of this alcoholic stimulant and thus to the unconscious formation of a desire for alcoholic stimulation. As the medical journal advertisements may lead physicians to prescribe this secret and irrational preparation and thus unconsciously lead to alcoholism, the Council authorized publication of this report.--(_From The Journal A. M. A., July 14, 1917._)

TRIMETHOL

Report of the Council on Pharmacy and Chemistry

Trimethol is the trade name for a substance said to be trimethyl-methoxy-phenol of the formula C₆H(CH₃)₃(OCH₃).OH--1:2:4:5:6, originated by J. T. Ainslie Walker. It is sold as a nontoxic germicide, having a Rideal-Walker phenol-coefficient of 40, even in the intestinal canal. It is described as insoluble in water and not to be decomposed in the alimentary tract, and to be excreted unchanged in the feces.

Trimethol itself is not obtainable. Pharmaceutical preparations--Trimethol Syrup, Trimethol Capsules and Trimethol Tablets, said to contain Trimethol--are prepared by The Walker-Leeming Laboratories and sold by Thos. Leeming and Co., New York.

Trimethol preparations are advertised for use in all conditions dependent on intestinal putrefaction. The advertising claims made are very extensive and some of them give to “Trimethol” the scope of a panacea. For example:

“Physicians are constantly reporting cases where Trimethol has been especially efficient, and describing conditions (until recently not associated with intestinal infection) which have been distinctly benefited by its use. This would seem to bear out the contentions of Charcot and Metchnikoff that 90% of all human ailments have their origin in intestinal infection.

“The careful practitioner, when in doubt, will bear this in mind, now that we have a really efficient and non-toxic intestinal germicide--not a mere antiseptic.”

The Walker-Leeming Laboratories have not formally requested the Council to consider the Trimethol preparations, though in a personal letter to a member of the Council J. T. Ainslie Walker invited an investigation of his compound.

For the investigation of Trimethol and its preparation the Council secured the aid of a bacteriologist who has given much attention to the study of the intestinal flora. The Walker-Leeming Laboratories and J. T. Ainslie Walker were both asked to submit details of experimental studies and also to furnish a supply of the pure “Trimethol.” But the only data sent that had any definiteness set forth the bacterial counts made of plate cultures of stools of one patient before and after the administration of Trimethol Capsules.

REFUSE TO FURNISH TRIMETHOL

The request for the pure substance was refused, on the grounds that the substance was not used in the undiluted form. The failure to furnish the chemical substance claimed as the essential constituent of the Trimethol preparations is to be deprecated if indeed it has not greater significance. At least it made it impossible for the Council’s expert to express his results in terms of absolute Trimethol of established composition. The data obtained apply only to the market preparations claimed to contain Trimethol. So far as the investigation and report go, “Trimethol” is a hypothetical substance.

Clinical or animal tests of the asserted intestinal antiseptics have hitherto given equivocal results because it is impossible, on the one hand, to predict the course of any intestinal infection, or, on the other hand, to determine what effect, if any, was produced by administration of the medicament. It therefore seemed unwise to undertake this line of investigation until the more direct laboratory bacteriologic methods had been exhausted. Consequently the investigator checked, in the first place, the phenol coefficient of one of the Trimethol preparations and then also determined its “penetrability” coefficient. Although by both methods Trimethol was found to be a germicide, the results did not indicate any remarkable potency or other properties suggesting that the drug possessed special therapeutic value. From the results obtained it appeared inadvisable to proceed further with the work until more definite evidence of the nature and of the value of the substance should be at hand. The report of the bacteriologic investigation follows:

THE BACTERIOLOGIST’S REPORT

“I have made no attempt to study the effects of internal administration of Trimethol on the intestinal flora. The methods available at the present time of enumerating the numbers of _viable_ bacteria in the feces are probably not accurate within 100 per cent. and the precision of such determinations is equally variable. The physiologic factors involved are so complex that they would appear to make a really valuable assay a question of many months’ careful study. If it were possible to administer known amounts of Trimethol, as such, the problem might be worth while; inasmuch as the available reactive substance is not at present quantitatively assayable, this phase of the investigation barely seems practicable.

“‘Trimethol Syrup,’ as such, appears to be about 10 per cent. as efficient in its germicidal value as carbolic acid. If the assay, 3/4 m. Trimethol per drm. (as the label indicates), is correct, the substance would appear to possess germicidal merit provided enough could be administered, if it is not influenced by passage through the stomach.

“A package containing four four-ounce bottles labeled ‘Trimethol, A Non-Toxic Germicide SYRUP Representing 3/4 m. Trimethol per drm., Alcohol 1-1/2 per cent.’ was received at the laboratory Dec. 15, 1916. Later a smaller package containing, according to the label, 100 Trimethol tablets, each 5 gr., representing 1-1/4 m. Trimethol, was received. The tablets were apparently chocolate coated.

“Two separate series of tests were made upon the syrup. (_a_) PHENOL COEFFICIENT, using the method outlined in _Bulletin No. 82_, Hygienic Laboratory, Method of Standardizing Disinfectants With and Without Organic Matter. (_b_) A PENETRABILITY COEFFICIENT by the method of Kendall and Edwards, _Journal of Infectious Diseases_, 8, 250.

“The former method compares the viability of naked germs in a 1 per cent. carbolic acid solution as a standard, with various dilutions of the germicide to be tested. The latter measures the relative diffusibility and germicidal power of carbolic acid and various dilutions of the germicide to be tested upon _Bacillus coli_ suspended in 1.2 per cent. agar which is molded in cylinders of one centimeter diameter after infection with the organism.

“The first method--phenol coefficient--possesses advantages and disadvantages which are well known and need no mention here. It is worthy of notice, however, that as the death rate of the bacteria increases during the progress of the test, it becomes increasingly difficult to maintain a uniform suspension of living organisms so that each loopful removed shall exactly represent the developmental potentiality of the residual organisms.

“The second method theoretically covers the possibility because all the organisms are immobilized and are exposed to the germicide in direct proportion to its diffusibility until the center of the agar mass is reached, where the residual viable bacteria are presumably located. Inasmuch as the penetrability of an intestinal mass is involved in a discussion of intestinal germicides, the propriety of utilizing this ‘penetrability coefficient’ in this connection is obvious, in spite of its patent shortcomings.

“It is unnecessary to discuss the technique--the standard broth mentioned in the Hygienic Bulletin, a temperature of 70 F., a standard 4 mm. loop and careful attention to dilutions (using distilled water) were all observed. The various dilutions of Trimethol Syrup were made with accurate volumetric pipettes, measuring flasks and distilled water was used as a diluent.

“The results of several determinations, using Trimethol Syrup from three separate bottles, were in sufficient accord to warrant the statement that a dilution of 1/10 of Trimethol Syrup was equivalent to a 1/100 dilution of carbolic acid, using _Bacillus typhosus_ as the test organism. Both solutions--the Trimethol and phenol--killed the organism in the interval between 7-1/2 minutes and 10 minutes’ exposure. That is to say, our observations indicate that under standard conditions as defined above, a 10 per cent. solution of Trimethol Syrup is equivalent in germicidal powers, as defined by the phenol coefficient to a 1 per cent. solution of phenol. Naturally, no predictions can be drawn from these observations indicative of the value as an intestinal germicide of Trimethol itself.

“The PENETRABILITY COEFFICIENT resulted as follows: A 5 per cent. solution of phenol killed _Bacillus coli_, suspended uniformly throughout a cylinder of 1.2 per cent. agar in the interval between 60 and 90 minutes. A 1 per cent. solution of phenol killed the same organisms under the same conditions in the interval between two and one half and three hours. An undiluted solution of Trimethol Syrup killed the organisms in the interval between two and one half and three hours. A 10 per cent. solution (nine volumes of distilled water to one volume of Trimethol Syrup) failed to kill the organisms in four hours. It would appear that undiluted Trimethol Syrup has the same combined penetrability and germicidal value as a 1 per cent. phenol solution.

“The PHENOL COEFFICIENT: A 10 per cent. solution of Trimethol Syrup in distilled water (nine volumes of distilled water to one volume of Trimethol Syrup) possesses the same germicidal power as a 1 per cent. solution of carbolic acid. This coefficient takes no cognizance of the _actual amount of Trimethol as such_--it merely indicates the relative germicidal power of the Trimethol Syrup as sold.”

The preceding report shows that Trimethol Syrup has a phenol coefficient of 1/10, and, assuming Trimethol Syrup contains the amount of Trimethol declared, the substance Trimethol would have a phenol coefficient of 8-1/3 instead of 40, as is claimed. According to Kendall and Edwards’ method, the penetrability-germicidal value of the syrup is equal to a 1 per cent. solution of phenol.

WALKER’S REPLY TO CRITICISM

The report of the bacteriologist was submitted to The Walker-Leeming Laboratories for comment. The following reply was received from J. T. Ainslie Walker:

(_May 22, 1917_) “In reply to your letter of the 15th inst., which has just been placed before me on my return to town, I have to inform you that the potent constituent of Trimethol Tablets and Trimethol Syrup is not fully available as a bactericide until it comes in contact with the pancreatic fluid.

“As you will see from the enclosed extracts from clinical reports, the therapeutic value of Trimethol has been well established.

“As regards penetrability, no claim has ever been made for Trimethol in this connection; and, as I pointed out in my original paper (_American Medicine_, September, 1914), when referring to the independent tests made by Dr. Frederick Sondern, ‘No attempt was made to determine the bacterial content of the solid particles, as in the opinion of the writer sterilization of the interior of these particles is not only absolutely impossible, but wholly unnecessary. The fact of the fluid contents of the canal being sterile may be taken to indicate that the exterior of all solid particles is in a like condition, and therefore harmless. It is the organisms in the fluid portions only that produce the deadly effects through the chemical substances they secrete; those in the interior of the solid portions (_i. e._, as evacuated) may be disregarded, as they are not available for good or evil.’

“I must confess to no little surprise on learning that your investigator is still using the Hygienic Laboratory method of determining phenol coefficients. I would respectfully suggest that you call his attention to the critical comparison of the Hygienic Laboratory and R.-W. Tests, which he will find in the enclosed reprint from the _New York Medical Journal_ of March 11, 1916: ‘Instead of being an improvement upon the standard R.-W. Test, the so-called Hygienic Laboratory Method is so defective as to be wholly unreliable, and incapable of furnishing results of any scientific or practical value whatever.’”

As to the statement that the potent constituent of Trimethol Tablets and Trimethol Syrup is not fully available as a bactericide until it comes in contact with the pancreatic fluid, attention is called to a leaflet, which accompanies each bottle of Trimethol Syrup, that reads:

“Trimethol is insoluble in water, but when properly emulsified has a Rideal-Walker co-efficient of 40; that is to say, it is 40 times more efficient as a germicide than phenol (pure carbolic acid).”

The Trimethol Syrup which was used in the investigation, when mixed with water produced an almost perfectly transparent solution, which justifies the assumption that the proper physical conditions were observed and that this objection is not well founded.

As regards the relation of pancreatic fluid to bactericidal availability of Trimethol, there is little to say, other than that the published statements in the advertising accompanying the packages make no mention of this point. It would be interesting to know what, if any, relation the pancreatic fluid has to this substance, in view of the statement that it “has a Rideal-Walker coefficient of 40.”

The Trimethol “literature” does not throw light on the question, What is the germicidal value of Trimethol Syrup as compared with phenol? The only available method of determining the germicidal value of a liquid disinfectant is to make a direct comparison of the substance in question with phenol under similar conditions. Given parallel conditions, not obviously prejudicial to the substance tested in contrast to the standard solution, the results are comparable, and furnish a basis for estimating the relative germicidal power of the two substances. In the investigation, Trimethol Syrup and phenol were thus compared.

As regards the contention that the bacteria within fecal masses are harmless, this may be granted. But it must also be admitted that these intestinal masses are constantly being reformed so that buried micro-organisms do not remain in the interior. For this reason, the determination of the penetrability coefficient of a germicide is pertinent.

Regarding the respective merits of the old Rideal-Walker and the newer U. S. Hygienic Laboratory method of determining the phenol coefficient, the Rideal-Walker method was found to possess certain drawbacks, and in an attempt to overcome these the “_Lancet_ Method” was evolved; this method in turn was improved in the U. S. Hygienic Laboratory and led to the United States Public Health Service Hygienic Laboratory method for the determination of the phenol coefficient of disinfectants (published in _Hygienic Laboratory Bulletin 82_). In 1913 this method was formally adopted by the Council for the valuation of disinfectants or germicides of the phenol type, and the method is now in general use for this purpose in the United States.[119] In this connection Hiss and Zinsser may be quoted (Ed. 2, page 80): “The most precise method of standardizing disinfectants is that now in use in the United States Public Health Service.” Stitt, director of the United States Naval Medical Schools, in his Practical Bacteriology, Blood Work and Parasitology (Ed. 4, page 473) says: “In the United States disinfectants are rated according to the Hygienic Laboratory Phenol Coefficient.”

[119] Those who are interested in the relative merits of the Rideal-Walker, the _Lancet_ and the Hygienic Laboratory methods for the valuation of disinfectants, should read the following: Method of Standardizing Disinfectants with and without Organic Matter, J. A. M. A., Aug. 24, 1912, p. 667; Standardization of disinfectants, Report of the Council on Pharmacy and Chemistry, J. A. M. A., April 26, 1913, p. 1316; Standardizing Disinfectants, J. A. M. A., Sept. 30, 1916, p. 883.

The Council adopted the recommendation of the Committee on Pharmacology to the effect that the claims made for Trimethol are unsupported by acceptable evidence. Accordingly, Trimethol and the pharmaceutical preparations said to contain it--Trimethol Syrup, Trimethol Capsules, and Trimethol Tablets--were held ineligible for New and Nonofficial Remedies.--(_From The Journal A. M. A., Aug. 11, 1917._)

FERRIVINE, INTRAMINE AND COLLOSOL IODINE

Report of the Council on Pharmacy and Chemistry

E. Fougera & Co., Inc., New York, acting as agent for The British Drug Houses, Ltd., London, advertise “Ferrivine,” “Intramine” and “Collosol Iodine” to the medical profession. A circular entitled “Ferrivine, The New Anti-Syphilitic Remedy” begins:

“FERRIVINE is the name given to ferric tri-para-amino-benzene sulphonate. This iron compound was first prepared by Mr. J. E. R. McDonagh, F. R. C. S., by whom it has been both biologically and clinically tested. It is slightly soluble in water, the solution having an acid reaction.

“INDICATIONS

“According to Mr. J. E. R. McDonagh’s researches, the phases of the _Leucocytozoon syphilids_ are killed by the lipoid-globulin molecules of the serum, which possess a stereochemical molecular configuration homologous to those of the lipoid-globulin molecules of the parasite. The process is one of absorption, a chemico-physical reaction which is in part dependent upon the supply of active oxygen. Active oxygen is formed directly by oxidation processes and the peroxide necessary for its formation directly by reducing processes. Oxidation is increased by metals and reduction by non-metals. The non-metal which acts in the body as the normal reducing agent is sulphur, hence the discovery of Intramine (see separate pamphlet). The metal which acts in the body as the normal oxidising agent, is iron, hence the discovery of Ferrivine.”

A circular, “Intramine, a New Non-Toxic Compound for the Treatment of Protozoal and Chronic Bacterial Diseases,” expounds Mr. McDonagh’s ideas of the treatment of syphilis with Ferrivine and Intramine by means of the oxidising action of Ferrivine and the reducing action of Intramine and asserts:

“As the ultimate administration of oxidising and reducing agents will benefit almost any infection, it may be said that Intramine is indicated in all protozoal diseases, and in all chronic bacterial diseases, especially in tuberculosis, presumably in leprosy and possibly in malignant disease [cancer?]. To the administration of Intramine there are no contraindications.”

We are also told that:

“Intramine is useful injected into the urethra.... In cases of chronic urethritis and perifolliculitis ... invaluable as a local application to chronic ulcers ...”

The Intramine circular includes a “Scheme of Treatment for Syphilis” which advises, in addition to Intramine, Ferrivine or salvarsan, mercury and iodids, the use of another proprietary called “Collosol Iodine.” An inquiry addressed to Fougera & Co. in regard to the character and composition of this preparation, brought the reply that the firm had no knowledge of its identity.

This “scheme of treatment” is objectionable in that it advises the “stock” treatment of a disease which demands individualization and further in that whatever beneficial effects may result from the use of mercury and iodid is likely to be ascribed to the preparations “Intramine,” “Ferrivine” and “Collosol Iodine.”

The advertising for Ferrivine and Intramine sent out by Fougera & Co. contains no experimental or clinical data on which an estimate of their value may be based. Apparently in England, where these products were originated, little has been published regarding them.

There is, however, one report which may be accepted as a carefully controlled clinical trial. In the _Lancet_ (June 17, 1916, p. 1214) L. W. Harrison, D.S.O., M.B., Ch.B.Glasg., and C. H. Mills, M.R.C.S., L.R.C.P.Lond., report on “The Effect of Ferrivine and Intramine on Syphilis.” After briefly reviewing the theories which form the basis of McDonagh’s proposed treatment of syphilis with his discoveries “Ferrivine” and “Intramine” the authors point out:

“... that Mr. McDonagh’s biological discoveries ... have not been publicly confirmed by any biologist of standing ...”

While:

“... eminent chemists have confessed themselves unable to understand his chemistry.”

The authors explain:

“Recognizing that this might prejudice our practical tests of Intramine and Ferrivine, we have taken particular care to guard against their influence, cross-checking our observations and submitting them to others for confirmation or otherwise.”

Harrison and Mills chose for a test three ordinary cases of secondary syphilis, cases with well marked lesions, the clinical progress of which could easily be watched and from which it was easy to obtain specimens for microscopic examination. After a detailed account of the three cases--which records grave conditions resulting from the treatment and which shows the inefficiency of the drugs--they write:

“From the above account it will be seen that the local and general reactions which follow the injection of these preparations are by no means pleasant. In the case of Intramine the pain is undiluted torture and lasts so for two or three days. One of us had previously treated four cases with Intramine and the same local reaction occurred in these. In two of them abscesses have burst outwardly, one of which is still discharging necrotic débris, ten weeks after the injection, and will take many more weeks to close. In those cases where no abscess has yet burst it is easy to feel by the gap in the muscles that considerable necrosis has occurred. None of these effects can be ascribed to sepsis, as most rigid aseptic precautions were taken. Further, particular care was taken to make the injections strictly intramuscular. The constitutional symptoms which follow immediately upon the injection of Ferrivine are distinctly alarming, and such as would cause one to hesitate before injecting this remedy into any but robust patients.”

Harrison and Mills estimate the therapeutic effects of these drugs thus:

“1. That Ferrivine entirely failed to cause _S. pallida_ to disappear from the lesions of three well-marked cases of secondary syphilis.

“2. After the failure of Ferrivine to cause the disappearance of _Spirochaeta pallida_ from a mucous patch a single dose of 0.3 gm. salvarsan effected this in 18 hours, and the patch, which had hitherto been uninfluenced, had healed within 48 hours.

“3. Clinically we were unable to detect any influence of either or both these compounds on syphilitic lesions, although each of them was of the variety which heals in a week or ten days under salvarsan treatment.

“4. Further syphilitic lesions appeared immediately after the treatment in one of the two cases treated with both Ferrivine and Intramine. A mucous patch appeared on one tonsil as well as further syphilitic papules from which spirochetes were obtained. The other case developed nephritis, with albumin and epithelial casts; which was not present prior to the injections.”

While from these cases the obvious conclusion was drawn that Intramine and Ferrivine “have no specific effect on early syphilis,” these authors subsequently treated a case of tertiary syphilis with the drugs. An Intramine injection caused pain for several days but did not stop the progress of the disease. Ferrivine was then administered “not without a feeling of grave responsibility” in view of their previous experiences. They state that “the reaction which resulted in this instance was the most severe” they ever experienced after an intravenous injection of any of the antisyphilitic remedies with which they had previously worked. It is stated that “for a period of some minutes there was grave doubt as to the patient’s survival.” After resuscitation the patient passed a disturbed night, and rigors which ensued lasted until the following afternoon. The author’s report that in this case also no clinical improvement occurred and that the Intramine-Ferrivine treatment was replaced by a course consisting of salvarsan, potassium iodid and mercurial inunction.

Ferrivine, Intramine and Collosol Iodine were declared inadmissible to New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 8, 1917._)

ESKAY’S NEURO PHOSPHATES

Report of the Council on Pharmacy and Chemistry

For the information of the profession the Council has prepared and authorized for publication the following report on Eskay’s Neuro Phosphates.

W. A. Puckner, Secretary.

Eskay’s Neuro Phosphates (Smith, Kline & French Co., Philadelphia) is offered to physicians under the claims that it contains alcohol, 17 per cent., and sodium glycerophosphate, 2 grains, calcium glycerophosphate, 2 grains, and strychnin glycerophosphate, 1/64 grain, in each dessertspoonful. It is called a “Nerve Tissue Reconstructive,” and its advertising claims are based on the discredited theories that certain disorders are due to a deficiency of phosphorus in the nerve structure of the body, and that glycerophosphates are assimilated more readily than ordinary phosphates. This assumption was based on the knowledge that the lecithins, which form a part of the nerve structure, contained the glycerophosphate radical in the molecule. In line with this, Smith, Kline & French Co. aver:

“Eskay’s Neuro Phosphates is of marked value in many acute and chronic conditions, in nervous exhaustion following mental and physical strain, neurasthenia, paralysis, anemia, tuberculosis, marasmus, debility and wasting diseases generally, and the nerve-weakness of the aged. It is particularly useful in convalescence from acute diseases and in the nervous condition following la grippe.”

In its report on “The Therapeutic Value of the Glycerophosphates” (The Journal, Sept. 30, 1916, p. 1033) the Council pointed out that the therapeutic use of the glycerophosphates was based on the assumption that the inorganic phosphates cannot supply the body’s needs of phosphorus or that the use of organic compounds “spared” the system the necessity of making such synthesis. The report presented evidence to show that the glycerophosphates are not absorbed as such, but that they are split into inorganic phosphates before absorption. The Council showed that there was convincing evidence that the animal organism synthesizes its complex organic phosphorus constituents from inorganic phosphates, and that organic phosphorus is of no more value as a food than inorganic. Despite this the Neuro Phosphates advertising makes use of the fallacious assumption regarding the action of the glycerophosphates.

Pleading for the particular mixture represented by the proprietary, it is asserted that:

“Sodium glycerophosphate is of special value in neurasthenia, Addison’s disease, phosphaturia and phthisis.”

and that calcium glycerophosphate “is employed in bone fracture, rachitis, tuberculosis and various wasting diseases.”

The phosphorus content of 1/64 grain of strychnin glycerophosphate is ridiculously small. Yet it is asserted that this strychnin salt is of superior value because it combines the effects of strychnin with a “food-like form of phosphorus.” Eskay’s Neuro Phosphates has an acid reaction which is capitalized, thus:

“Experiments have shown that the acid glycerophosphates are more rapidly absorbed and are more efficient than the neutral salts.”

And as a further illustration of extravagant claims:

“As a glycerophosphoric acid in the form of lecithin is normally present in spermatozoids, it is but natural that the glycerophosphates should exhibit aphrodisiac effects (as has been observed), but this result does not seem to obtain in all cases.”

Is this a clumsy attempt to exploit this “nerve phosphate” as a “lost manhood” cure?

The Council held Eskay’s Neuro Phosphates ineligible for New and Nonofficial Remedies because unwarranted therapeutic claims are made for it and because the administration of strychnin, calcium, phosphate and alcohol is not conducive to rational therapeutics, particularly when such a mixture is marketed under a name which indicates but one of its constituents.--(_From The Journal A. M. A., Sept. 29, 1917._)

K-Y LUBRICATING JELLY

Report of the Council on Pharmacy and Chemistry

Because of inquiries received, the Council has authorized publication of the following report declaring K-Y Lubricating Jelly inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

K-Y Lubricating Jelly (Van Horn and Sawtell, New York), originally advertised as a lubricant for instruments and the hands, is now also recommended as a therapeutic agent. If the claims for “K-Y” were limited strictly to such effects as result from the purely mechanical properties of a lubricant, it might be held that it would not come under the purview of the Council. The preparation, however, while introduced as a lubricant, is now offered for a broader field of use, and the manufacturers make claims which are not supported by any evidence available to the Council. Evidence the following, taken from a circular that accompanies the package:

“K-Y allays smarting and burning at once through its pronounced soothing and cooling effects, and thus makes an admirable dressing for burns.”

“Many physicians make a practice of anointing the bodies of their measle and scarlet fever patients with ‘K-Y,’ in this way affording gratifying relief from itching and irritation, and effectively preventing dissemination of infectious material.”

And this from another circular:

“I had one of the most troublesome cases of pruritus vulvæ that I had ever seen. I guess I must have tried everything and the case had been referred to me by another man, who had previously tried everything, including cauterization. Well, one day I was examining her, and of course K-Y on the speculum--the irritation seemed to quiet down, and the following day she said she felt no effects from it at all. Then later on, it returned, and I couldn’t imagine what had done so much good, unless it could have been the lubricant, so I told her to buy a tube, which she did. Every once in a while she has a return of it slightly, but she just applies K-Y and clears it all up.”

The manufacturers state that they do not know why K-Y is so soothing, but suggest:

“Possibly the cooling action of the combination, and the effect of the 4% boric acid contained, are factors that enter. Be all that as it may, the fact certainly remains that oftentimes, after other local measures fail, ‘K-Y’ lubricating Jelly gives relief.”

Elsewhere it is claimed to be germicidal, and to give relief in other conditions, thus:

“Diabetic and uremic irritations, not only of the genitalia, but of other parts, have been found fully as amenable as pruritus vulvae to the soothing influence of ‘K-Y’ Lubricating Jelly, especially if the previous application is removed with water every time a new one is put on.”

The foregoing citations are obviously intended largely for the public, and make it plain that “K-Y” Jelly is not in the class of nonmedical and harmless external applications; on the contrary, these claims tend to create the impression that the spread of measles and scarlet fever can be _prevented_ in the stage of desquamation. To place such statements in the hands of the patient supported by the tacit endorsement of a prescription is to create a false and dangerous sense of security and to lead to a failure to observe other and more important means of preventing dissemination of these diseases.

The Council held K-Y Lubricating Jelly in conflict with Rules 1, 4, 6 and 10, and authorized publication of this report.--(_From The Journal A. M. A., Sept. 29, 1917._)

ZIRATOL

Report of the Council on Pharmacy and Chemistry

Ziratol (Bristol-Myers Company, New York), in compliance with the federal “insecticide law,” is declared to contain 32 per cent. water and 30 per cent. glycerin as inert constituents. Regarding its active constituents the manufacturer makes the following and meaningless statement:

“Ziratol is prepared from Phenols of the Naphthalene series and consists of a solution of such Phenols in a mixture of soap, water and glycerin.”

In response to inquiry, the A. M. A. Chemical Laboratory examined Ziratol and reported that its essential constituent appears to be alpha-napthol,[120] and that it has, essentially, the following composition by weight: Alpha-napthol 18 per cent., soap 20 per cent., glycerin and water sufficient to make 100 per cent.

[120] Alpha-napthol was also found to be the basis of the nostrum Benetol. See The Journal, April 15, 1911, p. 1128.

A Ziratol advertising circular gives a tabulated report of germicidal tests, said to have been made according to the method of the Hygienic Laboratory of the U. S. Public Health Service. When this work was done is not stated. According to these tests Ziratol possesses a phenol-coefficient of 13.66. The claim that Ziratol is ten times more efficient than carbolic acid (phenol) is evidently based on this report.

These claims of high germicidal value are contradicted by an examination made for the Council. A specimen purchased in the open market was examined independently by two operators, to determine the Hygienic Laboratory phenol-coefficient. One observer found the phenol coefficient to be 2.54. The other reported it to be 3.09. Evidently the germicidal value of Ziratol is greatly exaggerated in the advertising claims and, in fact, does not exceed that of the official compound solution of cresol (Liquor Cresolis Compositus, U. S. P.) for which a phenol-coefficient of about three has been established. (See New and Nonofficial Remedies, 1917, p. 82.) The claim that Ziratol is “the Universal Antiseptic and Germicide” is manifestly an unwarranted exaggeration.

The referee in submitting this report to the Council recommended that Ziratol be held in conflict with Rule 1 (secrecy of composition) and Rule 6 (unwarranted and exaggerated claims). After the report had been submitted, it was found that a new advertising circular, accompanying a trade package, no longer contained the claim that “Ziratol is ten times more efficient than Carbolic Acid.” The older circular made the following statement:

“1. Strong Activity.--Compared with the bactericidal action of Carbolic Acid by the method of the Hygienic Laboratory of the Marine Hospital Service, ZIRATOL has the Carbolic Acid Coefficient of more than TEN, that is, ZIRATOL is TEN times more efficient than Carbolic Acid,--a strength unapproached by any other of its class. ZIRATOL in dilution of 1:1400 kills the Typhoid Bacillus in 2-1/2 minutes, thus proving that it is strongly active even in very weak solutions.”

The new advertising circular reads:

“1. Strong Activity--Extensive bacteriological investigations on many pathogenic organisms, conducted in the Lederle Laboratories of New York, prove conclusively the high bactericidal value of Ziratol in extremely dilute solutions. (A copy of the complete report will be mailed upon request.)”

In response to a request, the Bristol-Myers Company sent a copy of the bacteriologic investigations of Ziratol, said to have been made by the Lederle Laboratories. The organisms employed for these tests were _Staphylococcus aureus_, _Staphylococcus albus_, _Streptococcus_, Green pus bacillus, _B. coli_, and saliva. No tests are given with the typhoid bacillus. The conclusion is reached that “in all the tests the solutions of Ziratol have several times greater killing efficiency than those of phenol.” The “coefficients” or comparative values which can be calculated from the results after exposure of 15 minutes to the disinfectants range from 2.0 to 4.0. This is in substantial accord with the referee’s findings as regards the phenol-coefficient with _B. typhosus_ as the test object. While the new advertising circular avoids the former claim that Ziratol is ten times more efficient than carbolic acid, in germicidal value, it still makes the unwarranted claims that Ziratol is the “universal disinfectant.”

The Council declared Ziratol inadmissible to New and Nonofficial Remedies (1) because its composition is secret (Rule 1); (2) because the phenol coefficient, determined according to the method of the Hygienic Laboratory, U. S. P. H. S., is not stated on the label (Rule 2); (3) because the label and the circular accompanying the trade package advises its use by the public as a “vaginal douche” (Rule 3); and (4) because the claim that Ziratol is the “universal disinfectant” is exaggerated and unwarranted (Rule 6).

Before authorizing publication of the preceding report the Council submitted it to the Bristol-Myers Company in order to give that company the opportunity of revising its method of marketing Ziratol. In reply the company enlarged on its withdrawal (on “our own initiative”) of the claim that Ziratol had a phenol-coefficient of over ten when this claim was shown to be incorrect “by authoritative sources.” One wonders whether this is a euphemistic reference to the proceedings of the federal authorities under the Insecticide Act against the Bristol-Myers Company, just made public,[121] because of the false claims made for the germicidal efficiency of Ziratol. This prosecution resulted in the seizure and condemnation of two lots of this proprietary which had passed in interstate commerce.

[121] U. S. Dept. of Agric., Insecticide and Fungicide Board, Service and Regulatory Announcements, No. 16, issued Aug. 8, 1917. _No. 244_, Misbranding of “Ziratol.” U. S. _v._ 100 bottles, more or less, of “Ziratol”; consent decree of condemnation and forfeiture; product ordered released on bond, p. 248. _No. 256_, Misbranding of “Ziratol.” U. S. _v._ 936 bottles and 6 jugs of Ziratol, consent decree of condemnation and forfeiture; product ordered released on bond, p. 260.

The Bristol-Myers Company in replying to the Council’s report made no offer to declare the exact composition of Ziratol, to state the actual phenol-coefficient, or to remove the other objections pointed out in the report of the Council. In other words, the Bristol-Myers Company has abandoned a definite but false claim of high germicidal power--a claim which subjected the firm to federal prosecution--and has substituted therefor indefinite statements which do not define the actual germicidal efficiency of Ziratol.--(_From The Journal A. M. A., Oct. 6, 1917._)

GONOSAN

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report on Gonosan and authorized its publication.

W. A. Puckner, Secretary.

Gonosan (Riedel and Company, Inc., New York City) comes in the form of capsules, each said to contain 5 minims of a mixture composed of oil of sandalwood 80 per cent., and 20 per cent. of alpha- and beta-resin of kava, isolated by a patent process. The mixture, as the name implies, is intended for the treatment of gonorrhea.

This proprietary preparation was under consideration by the Council at various times from 1905 to 1910. During this time, the Council agreed to accept the preparation if the suggestive name was changed, the therapeutic exaggerations abandoned, and the drug kava admitted to New and Nonofficial Remedies. The name was not changed, the other questions were left open, and the preparation was not accepted.

Recent and more objectionable advertising of Gonosan makes it advisable for the Council to take action and to publish a report. The tone of this advertising is reflected by the following quotation from a recent advertising circular:

“The old-established balsamic treatment of gonorrhea, for some years neglected in favor of the local injection of organic silver and other germicidal salts, has, with the increasing knowledge and attention paid to the composition and purity of the balsams, regained to a large extent the confidence formerly reposed in them.

“It may now be said that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy.”

Any one conversant with current medical literature and practice would stamp these statements as misleading exaggerations. The balsams, oleoresins and volatile oils may have some value as minor adjuvants in the treatment of gonorrhea, but that is all. The position in this respect has not changed materially in recent years. These agents do not have a value equal to that of local treatment, as the quoted statement implies.

The claims made for Gonosan might with equal force be made for oil of santal alone. Kava kava, the other constituent, belongs to the pepper family; it had a temporary vogue some two or three decades ago, but has failed to maintain a place. It has never been recognized officially. There is no scientific evidence that it has any value either alone or as an adjuvant to sandal oil. The “clinical reports” quoted in the advertising circulars, rather curiously, nearly all date back ten years or more, viz., to a period when the attitude of the profession toward proprietary remedies was less critical than it is now. It would be interesting to know whether these authors still adhere to their opinion, or whether any of them have subsequently had experiences similar to that of a correspondent who wrote:

“Gonosan, at my hands, did not prove to be of more essential value in the treatment of gonorrhea than any other sandalwood oil preparation. The various claims made for Gonosan, that it possesses sedative and anesthetic properties, that by its continuous use the urethral discharge disappears more rapidly and that, if combined with appropriate diet and rest, it is liable to prevent complications, are, according to my experience, not corroborated by actual results.”

The only experimental work quoted in support of Gonosan, that of Pohl, is not convincing. The doses that Pohl found necessary to influence experimental purulent pleurisy makes it impossible to transfer his work to the clinic. (He found a dosage of oil of santal corresponding to an ounce per day, for man, inefficient; positive results were obtained only with 2 ounces per day.)

In order to learn the estimate placed on the therapeutic value of the “balsams,” an inquiry was sent to the authors of the papers presented to the section of Genito-Urinary Diseases at the recent meeting of the American Medical Association in New York. The inquiry read:

“_Dear Doctor_:--An advertising circular for Gonosan ‘Riedel’ which is now being distributed begins thus:

‘The old-established balsamic treatment of gonorrhea, for some years neglected in favor of the local injection of organic silver and other germicidal salts, has, with the increasing knowledge and attention paid to the composition and purity of the balsams, regained to a large extent the confidence formerly reposed in them.’

‘It may now be said that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy.’

“Is the statement correct that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy? Your reply to the above will be appreciated by the Council.”

Seventeen replies were received. They bear out the position that has been outlined. Only one writer considered the statement even approximately justified, and this in the sense that “the majority of cases receive no other treatment” than a combination of local applications and systemic medication. Another stated that, “in a general way their statement is true though a trifle too sweeping,” and then added that the field of the balsams is rather restricted. With the exception of these qualified endorsements the remaining (fifteen) replies characterized the statement as incorrect and misleading. The replies are a valuable contribution to the status of the “balsam” treatment of gonorrhea, and extracts of them are appended to this report.

It is recommended that the Council declare Gonosan inadmissible to New and Nonofficial Remedies, because the therapeutic claims are exaggerated (Rule 6); because there is no evidence that the combination of kava resin with oil of santal is superior to oil of santal alone (Rule 10); and because the therapeutically suggestive name is conducive of indiscriminate and unwarranted use of the preparation both by the profession and the public (Rules 4 and 8).

Appendix

The extracts from replies received to the inquiry above referred to, follow:

Dr. B., Penn., wrote:

“In my practice I have found that local injections are very valuable in the treatment of gonorrhea, but I have never found that the internal administration of natural balsamics dominated modern gonorrheal therapy; while it is an aid, I consider the quoted statement to be very erroneous.”

Dr. F., D. C., wrote:

“While it is doubtless true that acute urethritis, gonorrheal, is now generally treated by local injections of solutions of organic silver salts, and that santal oil is often used, it is not true, as one would infer from the quotation, that the balsams are now considered more efficacious than they were formerly. So far as I know they have not lost or regained anything during the past dozen years in the way of confidence reposed in them. The indications for their use is very definite and very limited.”

Dr. B., Ga., wrote:

“... In recent years I have almost abandoned the use of balsams, etc., in the treatment of gonorrhea. Patients, who are properly treated otherwise, seem to get along as well without such drugs as with them, in fact apparently better for they have no gastric disturbance. It is important for patients to drink freely of water and when so doing the balsams are so diluted that I cannot conceive of their doing much good. Formerly my patients often lost weight during the treatment of gonorrhea; now, without balsams and with plenty of water, they usually gain in weight.”

Dr. S., Mich., wrote:

“... we believe that in a general way their statement is true though a trifle too sweeping. We do not ordinarily use the balsams in uncomplicated anterior urethritis. We do however, find indication for their administration in from sixty to seventy five per cent. of all cases of acute gonorrhea at some time during the course of the disease.”

Dr. L., Mo., wrote:

“I would say that the statement that, ‘The combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy,’ is far from representing the facts. While the balsamics may occasionally have an indirect soothing effect on the mucous membranes involved, the dominant factor is local treatment, aiming at disinfection and restoration to normal of the inflamed tissues.”

Dr. R., Mich., wrote:

“Regarding your request although I am willing to reply it is difficult to do so because if I should do so in the affirmative that could apply only to certain acute cases without complication of any kind and such cases are rare. In such, however, the advertiser is not far from right--since vaccine therapy has proven absolutely worthless we must fall back on antiseptics in acute urethritis when there are no objections to such treatment ...”

Dr. K., Ill., wrote:

“I am under the impression that the internal administration of balsamics is used only when complications arise, such as acute posterior urethritis. Personally I use the balsamics very, very rarely. From my observation, however, I am led to believe that many men still use internal drugs in the treatment of gonorrhea, and during the past few years, I should say the use of hexamethylenamin has been on the increase, and the use of the balsams on the decrease. I do not believe that hexamethylenamin is of any value in the treatment of gonorrhea, and am simply citing this as my observation of the widespread use of this drug in the treatment of gonorrhea.”

Dr. T., Penn., wrote:

“... I believe that more men use salol or hexamethylenamin, or no urinary antiseptic whatsoever, than use the balsamics.”

Dr. B., Ind., wrote:

“... The only systemic treatment that is considered necessary today is rest, plenty of water and neutralize the acidity of the urine with bicarbonate of soda or some sodium salt.”

Dr. Y., Mass., wrote:

“Sandal wood oil during the acute stage of gonorrhea certainly tends to make the patient more comfortable and undoubtedly does lend some (tho I believe slight) gonococcidal action. That it plays any _considerable_ part in actual cure I think is doubtful. The statement as quoted is true in so far as it states that local treatment plus internal medication with a balsam comprises most of the modern treatment of gonorrhea but it is grossly misleading in that it lets one draw the inference that the balsam plays a large if not the principal part.”

Dr. H., New York, wrote:

“For a period of at least three years in my hospital, dispensary and private practice, I conscientiously tried out most of the balsamics on the market (including Gonosan, which I favored for some time) both alone, and combined with local injections. As a result of this study, I have come to the conclusion that the balsamics have little, if any value in the treatment of gonorrhea. During the past few years I have relied almost entirely on local therapy, and seldom prescribed any of the balsams in my private practice, certainly in not more than 5 per cent. of the cases. My results I find are just as satisfactory, and my patients appreciate the fact that they are not loaded up with disagreeable medication. Instead of the balsamics, I am using sodium bicarbonate more and more, and feel convinced that the proper use of this drug is of more value than all of them combined.”

Dr. K., Cal., wrote:

“The statement that the combined treatment with local injections and internal administration of natural balsamic products completely eliminates modern gonorrheal therapy, would at present not be justifiable even with reference to the initial or acute stage of gonorrhea, while in the subacute and chronic forms of the disease local injections and balsams play an almost insignificant rôle as compared with various other recognized therapeutic measures.”--(_From The Journal A. M. A., Oct. 13, 1917_).

ALCRESTA IPECAC

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

In 1915 Alcresta Ipecac Tablets (Eli Lilly and Co.) were admitted to New and Nonofficial Remedies as a preparation of ipecac that is insoluble in the stomach but soluble in the intestines. It was supposed that this property would permit the administration of ipecac without the accompanying nausea and vomiting, and that this would be of especial advantage when using the drug in amebic dysentery. The systemic effects, of course, would be those of ipecac.

More recently, the manufacturers of Alcresta Ipecac have been advising its use in conditions which were not contemplated by the Council when the preparation was accepted for New and Nonofficial Remedies. They now claim that ipecac alkaloids have been shown to be useful in the treatment of typhoid fever, flatulence, diarrhea and constipation and that Alcresta Ipecac has these properties. Such a statement is misleading. While it is true that at one time ipecac was used promiscuously against “flatulence, diarrhea and constipation” there never has been and is not now any scientific evidence of its efficiency in such conditions except, of course, in diarrhea of the amebic type. As to the alleged usefulness of ipecac in typhoid fever: This has not even the sanction of tradition and the claim certainly should not be accepted until there is strong evidence to support it.

The advertising matter on Alcresta Ipecac also contained statements to the effect that ipecac alkaloids have a demonstrated usefulness in pyorrhea. Such an unequivocal statement is unwarranted. In spite of the enthusiastic advocacy, in the past, of ipecac alkaloids as a specific in pyorrhea alveolaris the preponderance of scientific evidence indicates that ipecac is of questionable value in this condition. Neither is there any substantial evidence to warrant the claim that ipecac alkaloids, when absorbed through the intestines, are demonstrably useful in amebic infections of the tonsils.

The reputation of the best drugs, whether unofficial or official, is bound to suffer if extravagant claims for them are permitted to go unchallenged. The referee of the Council, therefore, believed it necessary to call the attention of the manufacturers of Alcresta Ipecac Tablets to the statements made for the product and suggested that they submit evidence to substantiate the claims. This the manufacturers have refused to do. Their attitude in the matter, as well as their attitude toward the Council’s work is expressed in the following letter:

“Responding to your letter of March 10th, we beg to suggest that literature covering the different matters at issue are readily available to your referee, and all statements emanating from us are made advisedly.

“If you cannot satisfy yourselves that this preparation is a scientific product, ethically advertised, and a desirable advance in therapeutics, you can only delete it from your next issue of New and Nonofficial Remedies.”

It is to be regretted that Eli Lilly and Co. refuse either to withdraw or modify their claims or to substantiate these claims by scientific evidence. The statements as they stand are exaggerated, misleading and harmful. As such they conflict with Rule 6 of the Council and necessitate the omission of Alcresta Ipecac from New and Nonofficial Remedies. The referee recommended the adoption and publication of this report.--(_From The Journal A. M. A., Oct. 20, 1917._)

IODEOL AND IODAGOL

Report of the Council on Pharmacy and Chemistry

Iodeol and Iodagol (formerly called Iodargol) are products of Viel and Company, Rennes, France, widely advertised in this country by David B. Levy, Incorporated, New York. The claim made for both preparations is that they depend on “colloidal iodin” for their action. They are put up in a number of forms, for instance:

“Iodeol Ampoules each containing 1 c.c. (20 centigrammes colloidal iodin in an oily vehicle).”

“Iodeol External, containing 50 per cent. colloidal iodine.”

“Iodagol Ampoules, each containing 2 c.c. (50 centigrammes colloidal iodine in an oily vehicle).”

The claim is, that, the iodin being in the colloidal state, it has the properties of elementary iodin and thus the preparations may be used in concentrations and under conditions which would make the use of free iodin impossible. The products have been extensively and extravagantly advertised for use in a wide range of conditions. Thus Iodeol has been proposed in the treatment of:

“Pulmonary Tuberculosis” “Laryngeal Tuberculosis,” “Glandular Tuberculosis” “Tuberculosis of the Bones” “Pneumonia, Broncho-pneumonia, and Congestive Conditions” “Whooping Cough, Influenza, Asthma” “Typhoid Fever” “Syphilis” “Obesity.”

Iodagol, which is for external use, has been advised in the treatment of:

“Gonorrhea and its Sequelæ” “Cystitis” “Tetanus” “Wounds complicated by gaseous gangrene” “Burns” “Old Suppurations, ulcers, abscesses, etc.” “Articular rheumatism” “Abscess Alveolar” “Pyorrhea Alveolaris” “Stomatitis (Canker-Sores).”

Nearly two years ago the American agents requested the Council to consider Iodeol and Iodagol for admission to New and Nonofficial Remedies. The information submitted in regard to their character and composition was vague and indefinite, the pharmacologic information practically nil and the clinical data as voluminous as it was unconvincing.

On the basis of chemical, pharmacologic, bacteriologic and clinical investigation carried out under the direction of the referee and a study of the submitted evidence, the referee reported:

1. Iodeol and Iodagol do not contain the amount of iodin claimed.

2. The iodin is not present as elementary iodin, but instead the preparations behave similarly to the well-known organic iodin compounds such as iodized fats.

3. The therapeutic claims made for the preparations are exaggerated and unwarranted.

In view of his findings he recommended that Iodeol and Iodagol be declared inadmissible to New and Nonofficial Remedies for conflict with Rules 1 and 2 (misleading statements regarding composition and identification) and Rule 6 (unwarranted therapeutic claims). The Council adopted the recommendation of the referee, directing inclusion of the full report in the annual Council reports after submission to the manufacturer, and recommending publication of an abstract of this report in The Journal.

This report was brought to the attention of the American agent, David B. Levy, Inc., and through them to the French manufacturers, E. Viel and Company. The manufacturers have intimated that they will not file a reply to the report. The firm of David B. Levy, Inc., has decided to sever its connection with these products and to discontinue their sale.

W. A. Puckner, Secretary.

Summary of Referee’s Report

Iodeol and Iodagol were submitted to the Council nearly two years ago as “electro-colloidal iodine” and with the claim that they produced all the antiseptic and other effects of ordinary iodin without any of its side actions. The referee has done much work on the subject, conducted a large amount of correspondence and has contended with long delays. He feels that the consideration of these products should be brought to a conclusion and accordingly he submits this report of their consideration. The following is a summary of the report, which is appended:

_I. Discrepancy in Iodin Percentage._--The examination at the Chemical Laboratory of the American Medical Association, as well as that of the referee, shows that the various samples of Iodeol and Iodagol examined contained a little less than one-half of the total iodin claimed. These facts were reported to the American agent. After a lengthy delay a reply was received which presented a double excuse: (1) that the full amount of iodin had been added, whatever had become of it later; (2) that the claims were made for “colloidal iodin” and that this is not elementary iodin in the colloidal state, but a preparation of iodin containing only 50 per cent. of real iodin. Neither explanation can be taken seriously, as they are obvious quibblings. The referee concludes that the preparations are falsely labeled as to iodin content.

_II. Nature of the Iodin Compound in Iodeol and Iodagol._--In the information sent the Council, Iodeol and Iodagol were defined as “A suspension of electro-chemical colloidal iodin in a vehicle of purified oil.” Numerous inquiries have failed to elicit more specific information from the manufacturer or his agent. The statement of composition can mean only that the preparations contain free iodin (but in colloidal form) suspended in oil. No evidence to substantiate this claim has been submitted. (There is evidence that the preparations contain colloidal particles, but it does not indicate if this colloidal material is iodin, or a combination of iodin or indeed whether the colloidal component contains any iodin.) The recent statements of the agent seem to concede that what they call “electro-colloidal iodin” contains only about 50 per cent. of real iodin, in other words that it is not “colloidal iodin” at all, but a mixture or combination of iodin with some other unnamed substance. This, of course, is something very different.

Certain results reported from the American Medical Association’s Chemical Laboratory suggest that the so-called “colloidal iodin” of Iodeol may be a combination of iodin with a volatile oil. The investigations of the referee indicate that the iodin exists in a rather resistant form or combination behaving altogether differently from ordinary free iodin, and rather resembling the behavior of iodin substitution products, such as iodized fats or phenols. Briefly then the recent admissions of the agents indicate that Iodeol does not contain “colloidal iodin” in a chemical sense, and there are indications that it does contain its iodin in a rather firm (chemical) combination.

_III. Chemical Properties of Iodeol._--From a study of different specimens of Iodeol, the referee concludes that fresh specimens contain no free iodin and that old ones contain small amounts as a result of decomposition. Iodeol has the solubility characteristics of fats and fat-like compounds. The examination, as a whole, shows that Iodeol contains a peculiar and rather resistant form or combination of iodin. There is nothing in the chemical data that suggests that it could act differently from ordinary iodin compounds, such as iodized fats. It would not act as ordinary iodin.

_IV. Pharmacologic Data._--The pharmacologic statements which were submitted were loose and apparently meaningless or misleading. In reply to questions submitted by the referee, the manufacturer finally had some work done and submitted a report by Jean Laumonnier. The referee was unable to confirm some of this work, and as a whole it does not appear materially to elucidate the action of Iodeol. From a consideration of the submitted evidence, and as a result of his own work, the referee concludes that Iodeol does not behave like elementary iodin; it does not coagulate proteins and therefore is not irritant. It is presumably absorbed, but quite probably after chemical change; it is changed into iodid and, like organic iodids, is excreted somewhat more slowly than when inorganic iodids are administered, but the difference does not appear important.

_V. Antiseptic and Bactericidal Action._--Elementary iodin is considered a fairly powerful agent in these respects. The activity is presumably due to changes in the proteins, etc., of the bacteria, analogous to the effects which produce pain, irritation and necrosis of the tissue cells. Since the latter effect is not produced by Iodeol, it seems highly improbable, if not impossible, that it should act on bacteria like elementary iodin. It is entirely unjustifiable to credit the known antibacterial qualities of ordinary iodin to “colloid” iodin. This misrepresentation is especially prominent in the circular “Notable New Therapeutic Agents,” as will be seen, for instance, from the following citations:

“Iodine has long been universally recognized as an antiseptic of extraordinary potency. Not only is it rapid and certain in its germ-destroying action, but it also possesses an attribute denied many other antiseptic agents, namely, the power to penetrate and impregnate the tissues. Other antiseptics, as is well known, act on the surface epithelium only.”

“According to Kinnaman (J. A. M. A., Aug. 26, 1905), iodine is far superior to bichloride of mercury, a two per cent. solution killing streptococcus pyogenes in two minutes. Iodine does not coagulate albumin, and is very penetrating.”

The citations imply that this “colloidal iodin” of Iodeol and Iodagol acts as an antiseptic like ordinary iodin, except that it is claimed to be more efficient by “diffusing” more readily. This is entirely unjustified and misleading. If Iodeol and Iodagol are really antiseptic, they must act by some other mechanism than that through which elementary iodin acts, and such antiseptic action would have to be demonstrated by direct observation and not assumed from the known action of free iodin.

Antiseptic and bactericidal effects are easily estimated by laboratory methods. Yet no evidence on this point appeared to have been available until the Council called for this. Laumonnier then carried out some experiments which were in turn submitted to bacteriologic control. The bacteriologist failed to obtain any results with some of the tests, and considered the other data of little value.

The claim that Iodeol and Iodagol have the antiseptic and bactericidal action of free iodin lacks proof and must be considered unwarranted and misleading in the extreme.

_VI. Clinical Trials._--The manufacturers and agents of Iodeol presented many letters from physicians; but few, if any, of these gave evidence of careful, critical, controlled observations. They could not, therefore, be considered as acceptable evidence. The more important claims, letters and published papers, however, were submitted to clinical specialists collaborating with the Council, with the request that they examine these and conduct some clinical trials, if they considered it advisable. The results obtained in these preliminary trials did not appear sufficient to warrant further experimentation.

From a consideration of the evidence presented, the referee concludes that the claims made for Iodeol and Iodagol are unwarranted, exaggerated and misleading. He recommends that Iodeol and Iodagol be declared ineligible for New and Nonofficial Remedies for conflict with Rules 1 and 2 (misleading statements as to composition and identification) and with Rule 6 (unwarranted and misleading therapeutic claims). He further recommends that the Council authorize publication of the preceding summary of the consideration of Iodeol and Iodagol in The Journal and inclusion of the full report in the annual Council reports after submission to the manufacturer.--(_From The Journal A. M. A., Nov. 17, 1917._)

CAPSULES BISMUTH RESORCINOL COMPOUND NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

In response to inquiries received, the Council took up the consideration of Capsules Bismuth Resorcinol Compound (The Gross Drug Company, Inc., New York City). The label, sent by the Gross Drug Company, bore the following:

CAPSULES BISMUTH RESORCINOL COMPOUND

Bismuth Subgallate 2 grs. Resorcinol 1 gr. Beta Naphthol 1/2 gr. Creosote (Beechwood) 1 m.

This combination is of acknowledged value in reducing the value in reducing the intes- tinal putrefaction and fermentation, allaying the pain and discomfort of flatulent conditions in the intestinal tract.

DOSE.--One or two capsules before or after meals repeated in two hours if necessary.

The Gross Drug Company, Inc. 20 Laight Street, New York

The Council held this preparation inadmissible to New and Nonofficial Remedies or the Appendix, because (1) the claim “acknowledged value in reducing the intestinal putrefaction and fermentation, allaying the pain and discomfort of flatulent conditions in the intestinal tract” is an unwarranted, exaggerated and misleading claim of therapeutic value (Rule 6); because (2) the name does not indicate the identity of the bismuth salt contained in the capsules, nor declare the presence of betanaphthol and creosote (Rule 8); and because (3) the combination of bismuth subgallate, resorcinol, betanaphthol and creosote in fixed proportions is irrational (Rule 10).--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 139._)

DIXON’S TUBERCLE BACILLI EXTRACT AND DIXON’S SUSPENSION OF DEAD TUBERCLE BACILLI

Report of the Council on Pharmacy and Chemistry

New and Nonofficial Remedies, 1917, contains general descriptions of Dixon’s Tubercle Bacilli Extract and Dixon’s Suspension of Dead Tubercle Bacilli; the products of these manufactured by the H. M. Alexander Company being listed as dosage forms. It having become necessary to omit the preparations of the Alexander Company (see page 138) the referee recommended that the general articles of “Dixon’s Tubercle Bacilli Extract” and “Dixon’s Suspension of Dead Tubercle Bacilli” also be omitted. He reported that no other firm appears to be marketing these products and that they had not been shown to be of special value.

The Council accepted the recommendation and directed the omission as proposed. In accordance with the procedure of the Council, these have been transferred to the annual Council Reports for reference and appear below.

W. A. Puckner, Secretary.

=Dixon’s Tubercle Bacilli Extract.=--An extract of tubercle bacilli dissolved in normal saline solution. (See “Fluid of Dixon,” _Medical News_, Jan. 17, 1891.)

=Dixon’s Suspension of Dead Tubercle Bacilli.=--A suspension in physiologic salt solution of dead tubercle bacilli which have been defatted by prolonged treatment with alcohol and ether. (See “Possibility of Establishing Tolerance for Tubercle Bacilli,” _Medical News_, Oct. 19, 1889.)--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 140._)

FORMOSOL

Report of the Council on Pharmacy and Chemistry

Sunshine’s Formosol (The Formosol Chemical Company, formerly the Sunshine Chemical Company, Cleveland, Ohio) is claimed to contain 18 per cent. formaldehyd in a solution of soap. It is therefore very similar to Veroform Germicide which was deleted from New and Nonofficial Remedies because of the low phenol coefficient reported by the Hygienic Laboratory of the United States Public Health Service (The Journal, Nov. 22, 1913, p. 1920.) The Council voted that in view of the Hygienic Laboratory’s finding that formaldehyd has a low germicidal value, the manufacturers of Formosol be required to produce definite evidence of the degree of germicidal value for this product.

In submitting the preparation to the Council, it was claimed that Formosol had “all properties peculiar to Formaldehyde.” This conservative tone was, however, not maintained in the form-letters submitted. These contain the following unwarranted statements:

“As the name implies, FORMOSOL is a formaldehyde preparation, which embodies all the innate antiseptic merits and eliminates all the ill features of the world’s greatest disinfectant.”

“The elimination of all the destructive elements and the incorporation of all the established therapeutic virtues of formaldehyde, have been scientifically blended in FORMOSOL.”

“FORMOSOL is unique in the sphere of antisepsis because of its peculiar healing properties as diametrically opposed to irritation to the tissue of mucous membrane.”

“FORMOSOL may be used for the thousand niceties of modern antisepsis, but is _specific_ in Gynecology and Obstetrics and is indicated in Dermatology.” [Italics not in original.]

“The constant use of FORMOSOL is to develop a habit sympathetic to ethics.”

“To prescribe FORMOSOL is a great step toward Personal Hygiene, a _duty of the medical fraternity_ to the laity.” [Italics not in original.]

The trade package recommends the use of Formosol “for cuts, wounds, ulcers, abscesses ...” This is a conflict with Rule 4. The Council held Formosol in conflict with Rules 4 and 6, and advised the manufacturers that Formosol is refused admission to New and Nonofficial Remedies until they submit evidence establishing the degree of antiseptic and germicidal efficiency, and justify the quotations listed above; or until these and any other existing conflicts with the Rules have been removed.

After submission of this report to The Formosol Chemical Company the Council authorized its publication.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 145._)

IODOLENE, A SOLUTION OF IODIN IN LIQUID PETROLATUM, INADMISSIBLE TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council was asked to consider a solution of iodin in liquid petrolatum, said to be prepared from Gulf Coast petroleum by a special process. It was to be marketed as “Iodolen” provided the Council found the preparation admissible to New and Nonofficial Remedies. The preparation was claimed to contain over 1.5 per cent. free iodin. The following claims were made:

“It is less irritating in its use on the skin, or in wounds.” “Will kill pathogenic micro-organisms present.” “Is a suitable medium for cell proliferation.” “Will penetrate a useful distance into the walls of a wound.” “Facilitates an easier, less painful and better method of dressing wounds or ulcers.”

Examination in the American Medical Association Chemical Laboratory showed a submitted sample to contain 1.32 per cent. free iodin and to emit a strong odor of hydrogen sulphid. A specimen of liquid petrolatum, said to be composed chiefly of hydrocarbons of the naphthene series, after saturation with iodin at room temperature was found to contain 1.42 per cent. free iodin. Another specimen of liquid petrolatum, said to be composed chiefly of saturated hydrocarbons, after saturation at room temperature was found to contain 1.30 per cent. free iodin.

The preparation having been shown to be an unoriginal, simple solution of iodin in liquid petrolatum, the Council declared the name “Iodolene” unacceptable (Rule 8) and the therapeutic claims made for the preparation unwarranted (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 148._)

KALAK WATER

Report of the Council on Pharmacy and Chemistry

The following report, submitted by a member of the Council’s committee on chemistry, was endorsed by the committee and adopted by the Council:

Kalak Water, sold by the Kalak Water Company, Inc., New York, is an artificial mineral water said to be made by adding certain salts to carbonated, distilled water and supersaturating with the gas under pressure. Such merit as it may possess by virtue of sodium bicarbonate and sodium phosphate is quite insufficient to warrant the extravagant claims made in the advertising pamphlets.

According to the analysis furnished, the water contains, in 1,000,000 parts (milligrams per liter) the following:

Sodium carbonate 4049.0 Sodium phosphate 238.5 Sodium chloride 806.3 Calcium carbonate 578.2 Magnesium carbonate 48.9 Potassium chloride 47.9

Among the many misleading statements found in the advertising pamphlet bearing the title “A Brief for Physiological Alkalescence” these may be quoted:

“The calcium content of Kalak is over 100% greater than ever before placed in solution in any vehicle, a fact of supreme importance when the unique alkalinizing power of the alkaline salts of this metal is considered; the ratio of calcium metabolism to its enormous waste in pregnancy, the diseases of infancy and childhood and the rapidly growing group of ‘acidoses’ make its availability in Kalak of double value.”

The first part of this statement is untrue; the last part is muddled and without much meaning. Evidently the “acidosis” fad is to be overworked as was the old “uric acid diathesis,” of unsavory memory. Again this:

“One of the most important characteristics of Kalak is the close approximation of its formula to the correlation of the contained salts as they occur in the human body, together with its freedom from salts foreign to the human economy. Another is its almost unbelievable palatability, considering its high degree of alkalinity, it being eleven times greater than any other known mineral water, artificial or natural.”

These statements are false. The salts dissolved here bear no discernible relation to the needs of the body, as disclosed by the composition of the blood or solid tissues or as shown by the character of the urinary excretion. The last statement concerning the high alkalinity is neither clear nor accurate. Then, this warning and remedy:

“It seems to be an unappreciated fact that the degree of urinary acidity, checked with the acidity of the saliva, is in direct ratio to the existing acid toxemia, and a urine acid to methyl red should be the signal for immediate and adequate alkalinizing treatment....

“Startling clinical results have been observed by physicians who have used Kalak thoughtfully and sufficiently in the more serious types of acidosis associated with diabetes, nephritis, rheumatism, gout and the acute infections. There is also evidence of its good effect in acute alcoholism and the respiratory edemas; in fact a certain few have hailed Kalak as a possible solution of the annual hay fever problem. Of perhaps supreme importance, however, is the use of Kalak throughout pregnancy as preventive medicine against the inevitable ‘toxemia of pregnancy.’”

Also this:

“Kalak has accomplished certain unexplainable things for the diabetic and nephritic, and if, in future years, diabetes and nephritis should prove to be constitutional diseases, based upon functionation or its lack, Kalak therapy, the embodiment of physiological alkalescence may come into its own, for if acidity retards, alkalinity must normalize functionation.”

It is not necessary to quote further. In order to insure that everyone will recognize the great need of Kalak it is advised to test the urine for acidity by means of a group of indicator solutions sent out to the physicians. Methyl red is one of these and any urine showing an acid reaction with this is said to be open to suspicion. Paranitrophenol is another of the indicators and the explanations given of the behavior of the two and the conclusions to be drawn are questionable. The methyl red solution furnished is too concentrated for proper use and perfectly normal urines from normal individuals have given a rather marked color with it. This indicator gives some color at [H+] = 1.2 × 10^{-6} and a strong reaction at 3 × 10^{-3}. To condemn a urine on such a finding is entirely unwarranted.

Sodium bicarbonate is the main constituent of the water. The value of the phosphate in such a combination, with so much calcium, is problematical. In case an alkaline reaction in the intestine is reached some of it would be left as insoluble phosphate. A few grams of bicarbonate daily would have equal therapeutic value with this water. The advice based on the indications of methyl red and the urine is bad.

The committee’s report was sent to the Kalak Water Company for comment. The company promised to withdraw the advertising circular referred to in the report and disclaimed responsibility for the accuracy and value of the set of indicators which it sent out, but, on the whole, the previous advertising claims were insisted on.

In view of the absurd and false claims made for the product the Council declared Kalak Water inadmissible to N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 148._)

MINSON’S SOLUBLE IODIN “KELPIDINE” NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

Minson’s Soluble Iodin “Kelpidine” was submitted to the Council by J. J. Minson, Washington, D. C., trading as the Kelpidine Company, with the statement that in future “literature” it was to be known as Minson’s Soluble Iodin, only. The following statement of composition was furnished:

“Minson’s Soluble Iodin is somewhat of an indefinite character, chemically. Its formula is, Iodin 4 per cent., Distilled Water 6 per cent., and Absolute Alcohol _q. s._ 100 per cent. By a process of chilling and heating an iodid of uncertain character is produced, and because of the extreme sensitiveness of the product to chemical tests, it is hard to determine. So far as I have been able to judge, however, the result is about 3 or 3-1/2 per cent. free iodin and from 1/2 per cent. to 1 per cent. iodid, possibly ethyl and hydrogen iodid in combination.”

The A. M. A. Chemical Laboratory reports that the preparation is an alcoholic solution containing free iodin and iodid, probably hydrogen iodid and ethyl iodid, but that the free iodin content was only 2.69 gm. per 100 c.c.

It is claimed that the “therapeutic indications” of Minson’s Soluble Iodin are the “same as those of all iodin and iodid preparations, internally, externally, hypodermically and intravenously; excepting, however, counter irritation.” It is admitted that there are no “clinical reports” as to the hypodermic and intravenous use, but the belief is expressed “that in an emergency it is a safe remedy under proper dilution.” It is further claimed that “for all practical purposes it is nontoxic and nonirritating” and that “it has none of the undesirable features such as is the case with the iodids and the organic preparations of iodin, proprietary or otherwise.”

It was assigned for consideration to the Committee on Pharmacology, whose referee reported:

“According to the information submitted, this is a tincture of iodin; differing from the official tincture in that it is more dilute and in that hydrogen and ethyl iodid is the solvent in place of potassium iodid. It is practically immaterial for internal administration, whether the cation of the solvent iodid is hydrogen, ethyl, potassium or sodium. It would certainly be inadvisable to inject a preparation containing free iodin hypodermically. It is not ‘a safe remedy’ for intravenous injection and it would not be nonirritant. The statement that ‘it has none of the undesirable features’ of other iodin compounds is inherently impossible. Apparent freedom of any iodin preparation from undesirable effects is generally due to the use of small doses. Such claims are plainly therapeutic exaggerations and therefore in conflict with Rule 6. Even should these be removed, the preparation must be held an unessential modification of the official tincture, and therefore in conflict with Rule 10.”

The report was agreed to by the committee and adopted by the Council and Minson’s Soluble Iodin “Kelpidine” declared inadmissible to New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 152._)

NUTONE

Report of the Council on Pharmacy and Chemistry

NuTone (NuTone Company, Lowell, Mass.) is a “nutritive tonic” said to have the following complex composition:

Cod Liver Oil, Pure Norwegian, 25 per cent. Malt Extract, 9-1/3 per cent. Beef juice, Glycerine, Hypophosphite Lime, Hypophosphite Soda, Chemically pure, 1-1/2 grs. each to the oz. Fl. Ext. Nux Vomica, 3/64 of a minimum in each teaspoonful.

It is advertised with claims that will lead thoughtless physicians and a confiding public to depend on it in cases in which fresh air, hygienic surroundings and nutritious food are of prime importance.

A sample package (the phrase “as recommended by your physician” and other statements suggest that it is expected to be given the patient by the physician and thus effectively advertise NuTone to the public) describes NuTone as an “Agreeable Concentrated Nutritive Tonic Emulsion of Malt Extract, Beef Juice and Cod Liver Oil, Combined with Nerve Tonics and Bone Nutrients.” Emphasizing the nutritive value of this “Malt Extract, Beef Juice, and Cod Liver Oil” preparation, it is advised, “As NuTone is rich in nutritive properties, it is well to begin with one-fourth teaspoonful, gradually increasing to regular dose, which is: Adults, 1 to 2 teaspoonfuls after meals and at bedtime. Children according to age.” It thus appears that adults are to take this preparation as a “nutritive” in doses which represent from 3 to 12 grains of sugar (on the assumption that malt extract may contain as much as 50 per cent. sugar) and 8 to 30 minims of cod liver oil with unstated, but probably equally small, amounts of beef juice.

A consideration of the negligible food value of NuTone as well as of the inefficiency of the other components and the claim that it is indicated in “malnutrition,” “wasting diseases” and “incipient phthisis” classes NuTone with that large group of shotgun mixtures which do harm in that dependence is placed on them in conditions in which the patient will probably be restored to health if proper medical and hygienic measures are adopted in time.

The Council declared NuTone inadmissible to New and Nonofficial Remedies because it is an irrational shotgun mixture advertised indirectly to the public with unwarranted therapeutic claims and a nondescriptive therapeutically suggestive name.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 154._)

TRI-ARSENOLE, L. O. COMPOUND NO. 1 AND L. O. COMPOUND NO. 2

Report of the Council on Pharmacy and Chemistry

=Tri-Arsenole.=--According to the advertising of the Medical Supply Company of Atlanta, Ga., “Tri-Arsenole” is “Merco-Arseno-Benzo-Chloride,” and the claim is made:

“This compound is the result of many years’ research. The toxicity has been fully tested upon animals before using clinically, the latter having proven such complete success, we take pleasure in presenting it to the public ...”

“The manufacturers of TRI-ARSENOL, before placing it upon the market, tested it biologically.”

Tri-Arsenole is “recommended and suitable for the treatment of primary, secondary, tertiary and hereditary syphilis. It has also been found very useful in pellagra and malaria.” The preparation is supplied in ampules containing varying amounts of the dry substance. It is to be dissolved in water and is to be administered intravenously. In the advertising attention is called to the yellow color of Tri-Arsenole; this, and the style of package suggest that it is a preparation similar to salvarsan.

In reply to a request sent the Medical Supply Company for the quantitative composition and chemical formula of the compound “Merco-Arseno-Benzo-Chloride” and for the details of the biologic test by which its toxicity is claimed to have been determined and evidence for its efficiency, the following statement was received:

“Tri-Arsenole No. 1 equals to each Ampoule, gr.

Sodium chlorid 4-1/2 Hydrarg chlor.-cor. 1/4 Arsenous acid 1/4 Sodium benzoate 4 Hydrastin (resinoid) 2

Tri-Arsenole No. 2 equals to each Ampoule,

Sodium chlorid 4 Hydrarg chlor.-cor. 1/2 Arsenous acid 1/2 Sodium benzoate 4 Hydrastin (resinoid) 2

Tri-Arsenole No. 3 equals to each Ampoule,

Sodium chlorid 3-1/2 Hydrarg chlor.-cor. 3/4 Arsenous acid 3/4 Sodium benzoate 4 Hydrastin (resinoid) 2

Tri-Arsenole No. 4 equals to each Ampoule,

Sodium chlorid 3 Hydrarg chlor.-cor. 1 Arsenous acid 1 Sodium benzoate 4 Hydrastin (resinoid) 2

The request for information regarding the animal experiments said to have determined the toxicity was ignored, nor were references supplied to clinical reports demonstrating the value of the product.

The Council declared Tri-Arsenole inadmissible to New and Nonofficial Remedies because of conflict with the rules as follows:

In the absence of details of the method used, the claim that the preparation has been tested biologically is in conflict with Rule 2, which requires that for preparations claimed to be physiologically standardized the method of testing must be published so as to permit of control by independent investigators.

The claims that “Merco-Arseno-Benzo-Chloride” is “the result of many years research,” that its “toxicity has been fully tested upon animals before using clinically” and that clinical use has “proven such complete success” have not been substantiated by evidence and must be held as unwarranted.

The name is in conflict with Rule 8, which requires that pharmaceutical mixtures shall bear names descriptive of their composition. Further, the name “Tri-Arsenole” by its similarity to Diarsenol, the Canadian brand of arseno-phenolamin hydrochlorid, suggests that this pharmaceutical mixture is a chemical compound similar to salvarsan. Moreover, the danger of confusion is increased by the addition of the hydrastis preparation which imparts a yellow color like that of salvarsan to the solution obtained when the colorless mercury and arsenic compounds of the mixture are dissolved. Again, the synonym “Merco-Arseno-Benzo-Chloride” conveys the false impression that Tri-Arsenole is a definite chemical compound.

The label does not declare the poisonous constituents claimed to be contained in the mixture; namely, “arsenous acid” and corrosive mercuric chlorid (Rule 7).

There is no evidence that arsenous acid (arsenic trioxid) used intravenously is efficient and safe as a spirocheticide, and the administration of this drug in conjunction with mercuric chlorid in fixed proportion is irrational and dangerous--particularly so because of the implied similarity of Tri-Arsenole to arsenphenolamin hydrochlorid (Salvarsan, Diarsenol) (Rule 10).

=L. O. Compound No. 1 and L. O. Compound No. 2.=--In submitting these preparations to the Council, the Medical Supply Company stated that “No. 1” was “composed of the following ingredients; chloral, camphor, menthol, iodin, and oil of gualtheria, incorporated in a fatty base. Each ounce contains fifteen grains of chloral hydrate, nine grains of resublimed iodine.” “No. 2” was said to have the same composition as “No. 1” except that the oil of gaultheria had been omitted. The Medical Supply Company was informed that the rules of the Council required declaration of the amounts of each therapeutic constituent of pharmaceutical mixtures and that, therefore, in addition to the information furnished the amounts of camphor, menthol and oil of gualtheria should be given for “No. 1” and the amount of camphor and menthol for “No. 2.” The following reply was received:

“L. O. Compound No. 1 equals to each Tube, Chloral hydrate gr. 15 Camphor gr. 22 Menthol gr. 7-1/2 Iodin (resublime) gr. 3-2/3 Oil of gaultheria m. 3 Petrolatum, q. s. oz. 1 L. O. Compound No. 2,

The same as above formula for L. O. C. No. 1, except the oil of gaultheria which is omitted.”

It should be noted that when the preparations were submitted each ounce of the preparation was claimed to contain 9 grains of iodin, while in the subsequent letter the company declares that they contain only 3-2/3 grains to the ounce. If it be assumed that the unit intended is the avoirdupois ounce, the preparation should contain 2.06 per cent. of iodin according to the first statement and 0.84 per cent. of iodin according to the second statement. While the dark color of the preparations suggested the presence of appreciable amounts of free iodin, the A. M. A. Chemical Laboratory reported that an examination of the specimens submitted by the Medical Supply Company showed that “No. 1” and “No. 2” each contained but 0.033 per cent. of free iodin; hence both preparations are in conflict with Rule 1.

For both preparations the labels suggest their use for the treatment of “septic wounds, burns, pustular processes of all varieties, and especially bronchial troubles.” This constitutes a conflict with Rule 4. Regarding No. 1 the advertising circular included with the trade package asserts:

“Its merits have been practically demonstrated in the following conditions. We invite your especial attention to its use in diseases of the thoracic cavity, especially Bronchitis and Pneumonia, Rheumatism, Lumbago, Migraine, Neuralgia, Orchitis, Balanitis, enlarged glands or any disturbance of the lymphatic system, anti-galactagogue, or wherever analgesic action is required.”

“No. 2” is said to be especially adapted to the needs of the surgeon, it “can be applied in any wound either aseptic or infected.” It is asserted that the usual method of preparing patients for operation may be discarded and that patients may be operated on after application of this ointment:

“... We have no other preparation to-day which serves the purpose of L. O. Compound in operative and post operative treatment.

“It is a powerful antiseptic and germicide combining anesthetic, analgesic and alterative properties.”

After attempting to discredit the approved methods of preparing the field for surgical operations, the advertising circular continues:

“Method of today: A liberal amount of L. O. Compound No. 2 is applied to the intended area of operation, massage thoroughly until absorption is complete. Patient is ready for operation ...”

Both products are in conflict with Rule 6. Further, as the names of these pharmaceutical mixtures are not descriptive of their composition, they also conflict with Rule 8.

The use of complex mixtures such as these is irrational and leads to misplaced confidence on the part of the physician; particularly when, as in this case, neither the label nor the advertising matter gives the necessary information regarding the composition of the preparations further than that, in accordance with the requirements of the Federal Food and Drugs Act, the amount of chloral is declared (Rule 10).

The Council declared L. O. Compound No. 1 and L. O. Compound No. 2 inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 4, 6, 8 and 10.

The Council’s consideration of Tri-Arsenole, L. O. Compound No. 1 and L. O. Compound No. 2 was based on information received from the Medical Supply Company, the correspondence being signed “Medical Supply Co., per Dr. H. E. Pontius.” The findings having been sent to the Medical Supply Company, the following reply was received:

(June 27, 1917) “Replying to your registered letter of this A. M. relative to the Medical Supply Company’s products, will state that the party furnishing you with such information as you have in hand was misinformed. He is no longer with this company and whereabouts unknown.

Respectfully,

Medical Supply Company, (Signed) W. B. Lingo, President.”

The Medical Supply Company then was asked to point out any statements occurring in the report, as submitted, which the company considered to be inaccurate; but no reply has been received to this request. The advertising sent out by the Medical Supply Company during the last part of August contained essentially the same statements and claims as those to which reference is made in the preceding report. A qualitative examination of Tri-Arsenole made in the A. M. A. Chemical Laboratory indicated the presence of sodium, mercury, arsenic, chlorid, benzoate and a hydrastis preparation. Quantitative determinations were not made as there was no guarantee that an analysis of the present supply would indicate the composition of that marketed later on.

In view of the statement of the president of the company, that the information submitted in the letters from the Medical Supply Company was inaccurate, Tri-Arsenole and L. O. Compound must definitely be placed with preparations, the composition of which is not divulged by their owners; hence Tri-Arsenole as well as L. O. Compound No. 1 and L. O. Compound No. 2 are in conflict with Rule 1.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 156._)

UNCTOL

Report of the Council on Pharmacy and Chemistry

Unctol, sold by the R. R. Rogers Chemical Company, San Francisco, is a paste stated to contain approximately 40 per cent. of metallic mercury in a soap base. It is claimed that a part of the mercury is “precipitated mercury” and a part “mechanically comminuted mercury.” Unctol is sold as a substitute for mercurial ointment and is to be rubbed into the skin with the aid of water. The claim is made for Unctol that “It is more active than blue ointment because the mercury in it (40 per cent.) is more finely divided and the lathering still further subdivides the mercury particles and hence promotes absorption.”

No evidence was presented to the Council in support of the claimed superior efficacy of mercury soap paste over the official mercurial ointment. On the other hand, a consultant of the Council who has studied the absorption of mercury and mercury compounds, when applied to the skin, reported that he had used mercury preparations in which soap was the base, and that in his opinion Unctol could have no advantage over the official mercurial ointment from the standpoint of therapeutic effect. Moreover, the Council is advised that some trials with Unctol at the skin clinic of Leland Stanford University Junior School of Medicine did not confirm the claim that Unctol is more active than mercurial ointment.

The Council declared Unctol inadmissible to New and Nonofficial Remedies because: 1. The claim of superiority over mercurial ointment is not substantiated, and constitutes an unwarranted therapeutic claim (Rule 6). 2. The name does not indicate the composition of this pharmaceutical mixture (Rule 8). 3. The circular wrapped with the trade package advertises proprietary preparations not accepted by the Council (Rule 4).--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 162._)

V-E-M (SCHOONMAKER LABORATORIES, INC.)

Report of the Council on Pharmacy and Chemistry

Because of inquiry received, the Schoonmaker Laboratories, Inc., New York, were requested to submit information in regard to the “V-E-M” products.

According to information received, these products have the following composition:

V-E-M Unguentum Eucalyptol Compound Menthol 5 grs. Eucalyptol (Sander’s) 15 gtts. White Vaseline 1 oz.

V-E-M with Ichthyol Menthol 2-1/2 grs. Eucalyptol (Sander’s) 15 gtts. Ichthyol 10 grs. White Vaseline 1 oz.

V-E-M with Stearate of Zinc Menthol 2-1/2 grs. Eucalyptol (Sander’s) 15 gtts. Stearate of Zinc 1 drm. White Vaseline 1 oz.

V-E-M with Camphor Camphor 15 grs. Eucalyptol (Sander’s) 15 gtts. White Vaseline 1 oz.

V-E-M with Boric Acid Pulv. Boric Acid 1/2 drm. Eucalyptol (Sander’s) 15 gtts. White Vaseline 1 oz.

In an advertising circular this claim is made:

“V-E-M Unguentum Eucalyptol Compound Combining, in well-balanced proportions, the cooling, soothing and healing virtues of Menthol with the antiseptic and deodorizing properties of Eucalyptol, in a base of pure, neutral white Vaseline. Furnished in five formulas as follows:

“V-E-M Unguentum Eucalyptol Compound: Menthol, Eucalyptol (Sander’s), White Vaseline.

“V-E-M with Ichthyol: Menthol, Eucalyptol (Sander’s), Ichthyol, White Vaseline.

“V-E-M with Stearate of Zinc: Menthol, Eucalyptol (Sander’s), Stearate of Zinc, White Vaseline.

“V-E-M with Camphor: Camphor, Eucalyptol (Sander’s), White Vaseline.

“V-E-M with Boric Acid: Pulv. Boric Acid, Eucalyptol (Sander’s), White Vaseline.

“For local application in the treatment of affections of the nose and throat.

“The efficacy of these combinations of remedial agents is so well established as to preclude the necessity of more than passing mention. What is obvious is that in acute coryza, in chronic and acute nasal catarrh, in dry catarrhal conditions especially, in both forms of chronic rhinitis--atrophic and hypertrophic--in the latter stages of the prevailing grippe colds, and even in hay fever, V-E-M Unguentum Eucalyptol Compound affords pronounced relief and proves a most grateful application....”

Though the identity and purity of eucalyptol are provided for by the standards of the U. S. Pharmacopeia, the claim is made that the product contained in these preparations “transcends in purity and efficiency all other brands.”

A package of V-E-M Unguentum Eucalyptol Compound, recently sent to a physician, contains the following:

“If your head is all stuffed up to-night, or you feel a cold coming on, use V-E-M just before going to bed. It will break up the cold, and you’ll wake up in the morning, with your head clear and feeling fine all over.

“If you suffer with chronic or acute catarrh, use V-E-M regularly night and morning. You’ll be agreeably surprised at the relief it will give you in a short time.

“There is nothing quicker, nothing surer to alleviate rhinitis, grippe-colds, or hay fever.

“In a word--V-E-M is the best antiseptic ointment for all diseased conditions of the nose....”

The Council declared these preparations in conflict with its rules because unwarranted therapeutic claims were made for them (Rule 6); because the public was advised to depend on them in the treatment of diseases (Rule 4), and because these combinations of ingredients, in fixed proportions, under proprietary names, are irrational (Rules 8 and 10).--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 163._)

HEMO-THERAPIN

Report of the Council on Pharmacy and Chemistry

The following report on Hemo-Therapin has been adopted by the Council, and its publication authorized.

W. A. Puckner, Secretary.

According to the Hemo-Therapin Laboratories of New York City:

“Hemo-Therapin is a combination of highly refined creosols and phenols (which have been detoxicated by special processes) with salts of iron, potassium, sodium, phosphorus and calcium in minute but physiologic proportions--the solution as a whole being designed to approximately closely in various fundamental details the chemistry of the blood.”

No statement is made as to the quantities of the several ingredients, nor is any information given as to the identity of the “creosols” and “phenols,” nor the nature of the processes whereby these are “detoxicated.” It is further claimed that it is:

“... The composite character of Hemo-Therapin, the relative proportion and balance of its several ingredients, and the action of the compound as a whole, to which its potency is due.”

And it is suggested that:

“It will be apparent that the ingredients which enter into the composition of Hemo-Therapin, a remedy used intravenously exclusively, have been selected with the utmost care with the object of assuring not only maximum therapeutic potency but also _absolute safety and freedom from all dangers of toxic or other unpleasant or harmful action_.” [Italics in the original.]

The advertising does not explain, however, why the complex preparation should be therapeutically efficient or why the intravenous administration of this mixture should be absolutely safe and free from toxic or harmful action. Of the origin of Hemo-Therapin it is said:

“For many years Dr. E. B. Witte, a prominent physician of Trenton, N. J. [apparently owner of the Hemo-Therapin Laboratories] has devoted himself to the study of the blood. As a result of his researches, he early determined that when the blood is close to normal standards, the body is well nourished, the natural waste products are properly eliminated, an effective resistance is offered to the invasion of pathogenic bacteria, and the various functions of the body are kept normally active. But when, for one reason or another, the blood falls away from normal standards, the nutrition of the body suffers, the elimination of waste products is impaired, the resistance to germ attack is weakened, and the various functions of the body become sadly deranged and perverted. In other words, instead of the physiologic processes of the body being normally active, as soon as the blood is depreciated, they become depressed or deranged, with a loss of the physiologic harmony or equilibrium that constitutes a state of health.

“Recognizing the relation of clinical conditions to these various phenomena, Dr. Witte reached the conclusion that the correction of many aberrant or diseased conditions depended on restoring the blood to as near to its normal state as possible. He accordingly applied himself especially to investigation of the chemistry of the blood, with the object of evolving a substance in liquid form that would so closely approximate normal blood in its essential chemical characteristics that when introduced into the circulation it would bring the blood nearer to the condition in which it exists in health.”

After the usual “many years of hard painstaking labor,” Dr. Witte elaborated a “fluid meeting the foregoing conditions” and now the Hemo-Therapin Laboratories inform us that 5 to 10 c.c. of this synthetic blood administered once in one, two or three days in “acute affection” and at longer intervals in “chronic ills”--once a week is said to be usually sufficient--will restore blood to a normality and empower it to overcome most ills. While disclaiming that “Hemo-Therapin is an infallible panacea,” the medical profession is asked to believe that:

“In erysipelas, septicemia, pyemia, the acute fevers, puerperal infection, furunculosis, carbuncles, malaria, acute rheumatism, pneumonia, typhoid fever, and in various skin diseases, such as eczema, psoriasis, herpes zoster, etc., the results have been prompt and gratifying.”

It is “no less effective” in such “chronic ailments” as:

“... diabetes, chronic Bright’s disease, goiter, pulmonary tuberculosis, chronic rheumatism, the severe anemias, arterio-sclerosis [_sic_], various nervous disorders, locomotor ataxia, varicose and indolent ulcers....”

Evidence of the virtues of Hemo-Therapin is submitted as a series of “case reports”--unsigned--which bear a striking likeness to the testimonials of “patent medicine” almanacs. A specimen of the “case reports” is the following:

“_Blood Poisoning due to Snake Bite._--Case 9.: Mrs. ----; age, 52; was bitten by a poisonous snake--a copperhead--seventeen years ago. On the anniversary of the bite the arm would swell to more than twice its normal size and there would be pain, chills and fever. After a month of this the acute symptoms would disappear and the arm would show large scaly blotches which upon being removed would disclose a thin mucous liquid. Throughout the seventeen years pain was constant, being particularly acute in midsummer around the anniversary of the bite. This patient had consulted many physicians during the seventeen years of suffering without any relief. Large doses of narcotic remedies were necessary each day to subdue the pain. Twenty-four hours after the first injection of Hemo-Therapin all pain was dissipated. After four treatments the patient was considered well and there has been no return of any of the symptoms since the last treatment six months ago.”

Hemo-Therapin is sold in ampules: 6 for $5 and 12 for $10, and a circular sent to a physician contained this typewritten note:

“FEES.--While the physician’s fee is not regulated by this company, the physicians who use Hemo-Therapin get $5.00 and $10.00 for each treatment.”--(_From The Journal A. M. A., Jan. 5, 1918._)

VENOSAL

Report of the Council on Pharmacy and Chemistry

The following report on Venosal has been adopted by the Council, and its publication authorized.

W. A. Puckner, Secretary.

“Venosal” is one of the products of the Intravenous Products Company, Denver, Colo. Its composition has been variously, and obscurely, described:

“Venosal is a sterile solution representing 1 gm. (15.4 gr.) of salicylates in combination, together with colchicum.”

“This is a product for intravenous use. The composition of which is Sodium Salicylate, 15.4 grs. (1 gm.), Iron Salicylate a minute quantity and the equivalent of approximately 2 grs. Dried Colchicum Root.”

None of these “formulas” gives the quantity of the product containing the 1 gm. of salicylate, etc., but presumably it refers to the contents of 1 ampule or 20 c.c. This inference is in accord with the analysis of the product made in the Chemical Laboratory of the American Medical Association. The analysis also brought out the fact that the amount of iron in a given ampule was 0.0008 gm. (about 1/80 grain). This trace of iron in the presence of salicylate gives the product a purple color.

Venosal is recommended for the treatment of “rheumatism,” meaning, the context would indicate, infectious rheumatic fever. As colchicum has no special action on this disease and as there is no apparent reason for the employment of the trace of iron present, these additions in fixed proportions are unscientific, if not absurd. According to the advertising matter:

“Venosal ... eliminates unpleasant digestive disturbances which frequently forbid the use of salicylates by mouth and, in addition, insures their full therapeutic value.”

The statement is misleading, as the cases in which the oral administration of the salicylates is contraindicated are not “frequent” but exceptional and there is no evidence to justify the implication that the “full therapeutic value” of salicylates cannot readily be attained by their oral use. Still more astonishing is the following claim:

“Venosal is a combination carrying the true salicylates (sodii) in doses much larger than given by mouth. With this preparation given intravenously, there is no nausea or disagreeable digestive after-effects, tinnitus aurium, or the accumulating effects of the drug; yet the specific action of the salicylates seems to be increased many-fold, according to reports received.”

What are the facts? By mouth sodium salicylate is given in doses of from 3 to 15 gm. in a day; whereas Venosal is advised as 1 gm., in from one to three day intervals; as a matter of elementary arithmetic it is plain that these doses of Venosal are smaller instead of being “much larger.” The absence of digestive ill effects, tinnitus, etc., is explained by the small dosage. That the specific action of the salicylates should be increased by intravenous administration is surprising when it is remembered that the drug is absorbed rapidly and completely from the intestines; in fact, the quoted statement is incredible.

The company further alleges that, on the basis of “clinical reports” it has received, it does not “hesitate to recommend this product for routine use in all streptococcic infections.” Such a therapeutic suggestion is, to put it conservatively, gross exaggeration.

The whole question of the justification of using salicylates intravenously is open to grave doubt. Since it is possible to obtain the salicylate effects promptly and certainly by oral administration, the inherent dangers of intravenous medication render its routine employment unwarranted. A further objection to Venosal, especially at this time when economy is a national policy, is the unnecessarily high expense of Venosal itself and of its administration.

The referee recommends that Venosal be declared ineligible to New and Nonofficial Remedies because of conflicts with Rule 1 (indefinite chemical composition), Rule 6 (therapeutic exaggerations) and Rule 10 (unscientific composition).--(_From The Journal A. M. A., Jan. 5, 1918._)

SECRETIN-BEVERIDGE AND THE U. S. PATENT LAW

Report of the Council on Pharmacy and Chemistry

Two years ago the Council published reports on two proprietary preparations said to contain secretin, namely, “Secretogen,” sold by the G. W. Carnrick Company (The Journal A. M. A., May 1, 1915, p. 1518), and “Duodenin,” sold by Armour and Company (The Journal A. M. A., Aug. 14, 1915, p. 639). These reports explained that there was no evidence to indicate that an insufficient amount of secretin was the cause of gastro-intestinal diseases, and further that there was no evidence that secretin in any form was physiologically active when administered by the mouth.

Subsequently, A. J. Carlson and his co-workers, at the request of the Council, studied the question of the stability of secretin and demonstrated (The Journal A. M. A., Jan. 15, 1916, pp. 178 and 208) that commercial secretin preparations contained no secretin and, further, that secretin given both by the mouth and even in enormous doses directly into the intestine is entirely inactive.

Shortly after the publication of Professor Carlson’s work the attention of the Council was called to a U. S. patent issued, May 2, 1916, to James Wallace Beveridge, “Means for and Method of Stabilizing Secretin.” In this patent Beveridge claimed to have invented “The process of producing secretin in stable form as a commercial article for therapeutic use ...” that is, a process for preparing preparations which would contain secretin when they reach the consumer and in a form resisting destruction in its passage through the stomach.

In view of the demonstrated instability of secretin, the Council asked Professor Carlson to investigate the validity of the claims of the Beveridge patent. The study on “The Question of the Stability of Secretin,” by A. J. Carlson, A. E. Kanter and I. Tumpowski, which appears below, shows that the Beveridge patent furnishes no process for the manufacture of commercially stable secretin preparations, nor any means for preventing the destruction of secretin by the gastric juice when administered orally. It further demonstrates that the preparation made by Beveridge was devoid of secretin.

The Council adopted the report of Carlson and his co-workers, and declared Secretin-Beveridge inadmissible to New and Nonofficial Remedies.

The Council directed that the report of Carlson and his collaborators be sent to the Commissioner of Patents with a protest against the granting of patents without competent and thorough investigation of the claims advanced therein.

W. A. Puckner, Secretary.

THE QUESTION OF THE STABILITY OF SECRETIN

A. J. Carlson, A. E. Kanter and I. Tumpowski

[From the Hull Physiological Laboratory of the University of Chicago]

In a letters patent, filed May 6, 1914, the patent granted May 2, 1916, James W. Beveridge, M.D., makes certain claims concerning the stability and physiologic activity of secretin prepared according to the method patented by him.

In brief, Dr. Beveridge claims that secretin prepared by digesting intestinal mucosa with a weak acid at a temperature slightly below boiling, and mixed with 0.2 per cent. to 2 per cent. blood serum, albumin or peptone (1) remains active for at least six months, (2) stimulates the pancreas when given by mouth, and (3) “may be injected intravenously in man, if desired.” The only thing in the letters patent in support of these claims is the statement: “I have found out by actual tests that the preparation maintains its stability for five or six months.”

Here are the claims in detail:

“For the source of secretin I preferably use that part of the alimentary tract of any lower animal--such as a hog or sheep--including the gastric pylorus, the duodenum and the jejunum. This part is split open and washed with a normal saline solution to clean the mucosa or mucous membrane of any detritus which may be present. The mucosa with the epithelial cells is then removed or separated from the muscular wall by scraping with a blunt knife or in any other suitable way. The scrapings or cuttings, which contain the secretin, are then macerated or broken up.”

“The macerated mass is placed in a suitable vessel and subjected to the action of an acid solution until digested. The time for the digestion of the mass will, of course, depend upon the strength and temperature of the acid solution employed. The stronger the solution and the higher the temperature, the shorter the time necessary for complete digestion. This period may vary from several minutes to several hours. In my experiments I found that the best results were obtained with hydrochloric acid solution of one-tenth to five-tenths of one per cent. in strength, although as high as eight-tenths per cent. might be used. The mixture is brought to a temperature of approximately 210 F., and it may even for a few moments exceed that temperature, but it should be kept below the boiling point, for excessive heat injures or breaks down the secretin molecule and impairs or destroys its activity. Although I prefer to use hydrochloric acid, I would have it understood that other acids--both organic or inorganic--may be employed, provided that the percentage of acidity is regulated to prevent a chemical change in the secretin, and further provided, of course, that the acid has no injurious effect on the human system.”

“After the mass has been digested in the heated solution, the decoction is decanted, and after being allowed to cool is passed through a suitable filter until the filtrate is clear. I found that by filtering the decoction from four to six times through a carbon filter, I obtained a clear colorless filtrate. This is a solution of secretin and the acid which was used, and the clearness of the solution shows that it is practically free from albumoses, gelatin and other impurities (such as cell tissues, etc.) present in the raw material under treatment.”

“To the solution of pure and active secretin prepared as above explained, there is added a suitable quantity of blood serum--say from one-fifth to two per cent. or any equivalent medium--such as albumin solution or a peptone solution--which will aid and sustain the activating power of secretin as provided by the blood. That is to say, any medium having the same power, similar quality or chemical composition that the blood-stream possesses in combining with secretin to stimulate the pancreas. The addition of such a medium to the active secretin solution increases the potency of the secretin and its degree of stability by preventing oxidation or deterioration thereof. If this strengthening or fortifying medium, as it may be properly termed, is alkaline, it performs the additional function of lowering the acidity of the secretin filtrate. It is preferable that the final product be just faintly acid. If desired, the final product may be made into an elixir by the addition of aromatics.”

“Any desired strength of secretin solution may be obtained according to the quantity of acid solution. In my experiments I used from ten to fourteen duodena to a pint of acid solution.”

“The solution of secretin prepared as above described is characterized by its ability to resist oxidation or deterioration for a sufficient period of time to render the solution available as a commercial article, and is furthermore characterized by freedom from poisonous and irritable chemical substances, whereby the secretin is chemically adapted to the human system to stimulate the pancreas to increased secretion.”

“As previously stated, the secretin prepared according to my method may be administered orally to produce the desired physiological action. Of course, if desired, the secretin might be injected intravenously, but this more or less dangerous procedure is not at all necessary, and I merely mention it here to point out that when I refer to the oral administration of my new secretin preparation, I do not mean to exclude its administration by injection.”

“As to the commercial stability of the secretin prepared according to my method, I may say that I have found by actual tests that the preparation maintains its stability for as long a period as five or six months. When I refer to my product as being “commercially stable,” I mean that it resists oxidation or deterioration for a sufficient period to render the same available as a commercial article. This period may vary from several weeks to several months, depending upon certain commercial factors well understood by the manufacturer. So, roughly speaking, I should say that secretin is commercially stable when it retains its activity from one to six months. I do not wish to be understood, however, as limiting myself to these exact figures.”

That active secretin may be extracted from macerated intestinal mucosa by weak acids below the temperature of boiling is well known. In fact, weak acids at body temperature in contact with the duodenal mucosa lead to the formation of secretin. The claims that secretin given by mouth reaches the blood and acts on the pancreas has been made for other preparations of secretin. It has also been shown that these claims are erroneous.[122] Thus it would appear that the only novel element in Dr. Beveridge’s patented secretin is the addition of serum, soluble proteins or peptones. What reason is there for believing that this will render the secretin stable for months, and physiologically active when taken by mouth? We do not believe Dr. Beveridge ever injected his secretin--protein mixture--intravenously in man or animals not under anesthesia, otherwise he would not have stated: “Of course, if desired, the secretin may be injected intravenously.”

[122] Carlson, Lebensohn and Pearlman, The Journal, Jan. 15, 1916, p. 178.

BEVERIDGE’S PATENTED SECRETIN IS NOT STABLE

I. _The Samples of Secretin Sent Us by Dr. Beveridge._--Physiological tests were made on four quart bottles of the secretin kindly sent us by Dr. Beveridge June 26, 1916. According to a letter from Dr. Beveridge of July 20, 1916, those samples of secretin were prepared June 20, that is, only six days before received by us. The material came in dark colored bottles. It was kept in the original bottles and placed in the ice box immediately on receipt. Dr. Beveridge stated the secretin “should remain active until the month of November, 1916, at least.”

Tests were made on three out of the four bottles. The fourth bottle was not opened, as we desired to learn what change it might undergo in the way of protein precipitation and bacterial decomposition. There is nothing in the Beveridge method of preparation that insures a sterile secretin unless it is passed through a Berkefeld filter. In all our crucial experiments the animals (dogs) were kept under light ether anesthesia, a cannula inserted into the pancreatic duct, the blood pressure recorded from the carotid artery and the various secretin preparations injected intravenously. When inactive secretin preparations were encountered, control tests were always made with active solutions of secretin to eliminate possible individual peculiarities of the animal. Thus when the pancreas of a dog reacts to the injection of preparation _A_, but not to preparation _B_, it is evident that absence of response to _B_ is due to this preparation and not to the animal or to the experimental conditions.

[Illustration: Fig. 1.--Records of carotid blood pressure and secretion of pancreatic juice on intravenous injection of Beveridge’s secretin in dogs. _X_, injection of 10 c.c. secretin; _b_, record of flow of pancreatic juice in drops. Tracing _A_, injection of 10 c.c. of one sample secretin (ten days old) furnished by Dr. Beveridge. Tracing _B_, injection of 10 c.c. of second sample of secretin (ten days old) furnished by Dr. Beveridge. Tracing _C_, injection of 10 c.c. of secretin (twenty hours old) made by us according to the Beveridge method. Showing that the secretin preparations sent us by Dr. Beveridge contained no secretin.]

Each of the three samples of secretin sent us by Dr. Beveridge was tested in the above manner on five dogs. The first tests were made June 27, 28 and 29, respectively, that is, within nine days of the preparation of these samples of secretin. _None of the samples was active (Fig. 1), even when injected intravenously in quantities up to 50 c.c._: 40-50 c.c. of Beveridge’s secretin mixture may kill a dog by too great lowering of the blood pressure. A good secretin preparation yields a copious secretion of pancreatic juice on intravenous injection of a few cubic centimeters.

It is not difficult to prepare a secretin, by the original Bayliss or Starling method or by the Beveridge method, that retains some activity for a longer period than nine days. Hence we cannot account for the absolute inactivity of these preparations except on the assumption that they did not contain any secretin to start with; that is, faulty preparation and absence of physiologic standardization.

The sample kept intact in its original container for six months became gradually cloudy, a large mass of amorphous precipitate settled to the bottom and the odor showed bacterial decomposition. It is reprehensible, to say the least, to state concerning such a mixture: “Of course, if desired, it may be injected intravenously.” The fact that Beveridge’s secretin may be rendered clear by filtering through carbon is not sufficient evidence that it is “pure secretin,” free from bacteria and other injurious substances.

II. _Beveridge Secretin Mixture Is Rapidly Rendered Inactive by Human Gastric Juice._--We prepared active secretin solutions by the Beveridge method, using 0.2 per cent. serum as the protein “stabilizer” (?). The addition of the serum does not appear to affect the activity of the fresh secretin preparation. If Beveridge’s secretin is able to act on the pancreas when given by mouth, it is obvious that it must run the gamut of gastric digestion, except in cases of complete achlorhydria. It has been repeatedly demonstrated that all other secretin preparations are rapidly destroyed by pepsin-hydrochloric acid digestion. Is Beveridge’s secretin an exception? What is there in a little serum, native albumin, or peptones to protect secretin against gastric digestion?

The pure human gastric juice used in these tests was secured from the fistula case (Mr. F. V.) that has been under observation in our laboratory for years.[123]

[123] Carlson: The Control of Hunger in Health and Disease, Chicago, 1916.

BEVERIDGE’S SECRETIN AND BAYLISS-STARLING SECRETIN PREPARED Sept. 29, 1916

================================================================ Response of Pancreas (No. of Drops of Secretin) Date of Test Quantity of ┌───────────┴───────────┐ Secretin Bayliss-Starling Beveridge Injected, C.c. Secretin Secretin Sept. 29. 10 75 78 Oct. 2. 10 61 61 Oct. 6. 10 28 17 Oct. 13. 10 25 31 Oct. 27. 10 5 6 Nov. 3. 10 7 6 Nov. 17. 10 4 5 Nov. 30. 10 3 4 Dec. 4. 10 2 2 Dec. 20. 10 0 0 ----------------------------------------------------------------

_Two cubic centimeters of fresh gastric juice added to 8-10 c.c. Beveridge secretin, the mixture being kept at body temperature (38 C.), renders the secretin completely inactive in from 5 to 8 minutes_ (Fig. 2). There is no exception to this rule, as we have repeated the test on many different secretin preparations and using different samples of human gastric juice. The secretin of Beveridge is just as vulnerable as the secretin of Bayliss and Starling to pepsin-hydrochloric acid digestion. On what kind of tests does Beveridge base his claim that his secretin mixture acts on the pancreas when given by mouth?

III. _The Relative Rate of Deterioration of the Secretin Solutions Prepared According to Bayliss and Starling and According to Beveridge._--Six different preparations of the two kinds of secretin were made, kept in dark stoppered bottles in the ice box, and tested by intravenous injection in dogs under ether anesthesia from time to time until all influence on the pancreas had been lost. One typical series of these tests is given by the way of illustration. (See Table on page 126.)

[Illustration: Fig. 2.--Records of carotid blood pressure and flow of pancreatic juice on intravenous injection of secretin prepared by us according to the Beveridge method. _X_, injection of 10 c.c. of the secretin; _b_, record of flow of pancreatic juice in drops. Tracing _A_, the 10 c.c. of Beveridge’s secretin injected had been digested for five minutes with 3 c.c. of human gastric juice. Tracing _B_, injection of 10 c.c. of the same secretin preparation not subjected to gastric digestion. Showing rapid and complete destruction of Beveridge’s secretin by human gastric juice.]

It will be seen that the rate of deterioration (oxidation or decomposition) of the secretin is practically the same whether prepared according to Bayliss and Starling or according to Beveridge (Figure 3). In both preparations the rate of deterioration is most rapid the first few days after preparation. It is scarcely necessary to point out that secretin preparations not kept constantly at low temperature and in the dark, as in the above experiments, will deteriorate more rapidly.

[Illustration: Fig. 3.--Records of carotid blood pressure and flow of pancreatic juice on intravenous injection of secretin preparations. _X_, injection of 10 c.c. secretin; _b_, record of flow of pancreatic juice in drops. Tracing _A_, secretin prepared according to the Beveridge method September 30. _I_, injection of 10 c.c. October 2. _II_, injection of 10 c.c. November 30. Tracing _B_, secretin prepared by the Bayliss-Starling method September 30. _III_, injection of 10 c.c. October 2; _IV_, injection of 10 c.c. November 30. Showing no greater stability of Beveridge’s secretion over that of Bayliss and Starling.]

Why can we hope that the addition of serum or any solution of protein will render secretin more stable? In the intact man or animal under normal conditions of digestion, secretin reaches the pancreas by way of the blood, that is, it is in solution in blood. Does that fact render the secretin stable? By no means. The reader is familiar with the fact that the response of the pancreas to a single intravenous administration of secretin is very transitory (5-15 min.). The cessation of activity is due, not to fatigue of the pancreas, as a second injection of secretin gives a prompt response of pancreatic secretion, but to the disappearance of active secretin from the blood. In fact, secretin left in the test tube or in the bottle remains active over a much longer period of time than when introduced into the blood stream.

IV. _Beveridge’s Secretin Given by Mouth to the Intact Animal Has No Specific Action on the Pancreas._--Active secretin prepared according to the method of Beveridge was fed on an empty stomach to a small dog (5 kilo) with permanent fistula of one of the pancreatic ducts. On control days we gave the dog (_a_) equal quantities of n/10 HCl, and (_b_) bread and milk. The Beveridge secretin was prepared with 0.3 per cent. HCl and the addition of 0.2 per cent. serum. The results may be stated by the following summary:

GIVING BEVERIDGE’S SECRETIN BY MOUTH

================================================================ Secretin of the Number of Pancreas for Three Material Fed Tests Hours Following the Feeding

150 c.c. Beveridge Secretin 6 10.2 c.c. 150 c.c. n/10 HCl 5 22.7 c.c. Bread soaked in milk 4 6.6 c.c. ----------------------------------------------------------------

The Control experiments with pure hydrochloric acid show that the secretion of pancreatic juice following the introduction of Beveridge’s secretin into the stomach is due to the acid factor and the protein content.

CONCLUSIONS

The patented secretin of Beveridge is rendered inactive by gastric juice, is without effect when given by mouth, and exhibits no greater stability or keeping qualities than the secretin prepared according to Bayliss and Starling. It has no merit as a therapeutic agent. It should under no conditions be administered intravenously in man, as it contains deleterious protein split products and living bacteria.--(_From The Journal A. M. A., Jan. 12, 1918._)

NEED FOR PATENT LAW REVISION

Report of the Committee on Patent-Law Revision of the Council on Pharmacy and Chemistry of the American Medical Association

At the present critical time when the efficiency of this nation must be raised to the highest point, it is essential that the United States government should lead in the efforts tending to such increased efficiency. To bring this about the government must protect and stimulate science, art and industry and at the same time curb or prevent waste of the country’s resources. In this field the United States Patent Office has unlimited power for good and evil--good, in the issuance of patent grants for novel devices and substances which go to increase national efficiency; evil, in the granting of patent protection where such protection is not in the interest of national efficiency, conservation of energy and material resources.

For years the American Medical Association, in common with the national pharmaceutical bodies, has been urging amendment of the law which governs the issuance of patents on medicinal preparations and more particularly revision of the procedure under which such patents are issued. At the Chicago (1908) meeting of the American Medical Association a special committee of five was appointed by the House of Delegates to study the questions involved, and to cooperate with the Association’s committee on medical legislation in preparing and securing the enactment of a bill which would correct the abuses connected with the enforcement of our patent laws (The Journal A. M. A., June 13, 1908, p. 2003). This committee presented a comprehensive report at the Atlantic City (1909) meeting of the American Medical Association (The Journal A. M. A., June 19, 1909, p. 2063). A further report was presented at the St. Louis (1910) meeting of the American Medical Association (The Journal A. M. A., June 18, p. 2079). In 1911 (The Journal A. M. A., Nov. 25, 1911, p. 1780) the Council on Pharmacy and Chemistry of the American Medical Association issued a report which set forth the inadequacy of our patent laws as they are administered in relation to medical products particularly.

AGAINST PUBLIC INTEREST

Since that time the Council has continued its study of the U. S. Patent law as it applies to medicine and has become convinced that in many instances the patent law or its enforcement is contrary to the best interest of the public, both as concerns health and prosperity. The Council feels it a duty at this time to protest against the provisions of our patent law, or the methods of its enforcement, which permit the granting of patents without thorough and scientific investigation of the claims advanced in such letters patent. As one means of improving conditions the Council urges that the U. S. Public Health Service, the Bureau of Chemistry, U. S. Department of Agriculture and other scientific departments of the United States government conversant with medicines and related subjects be consulted before the issuance of patents on medicinal preparations.

In support of the Council’s contention that the patent law procedure requires revision, the following is offered: In 1912 a U. S. Patent (No. 1,031,971) was granted on a cresol derivative, metacresyl acetate, a product described in chemical literature in 1903. When the Council inquired as to the grounds for the issuance of a patent for a substance known to science, the Patent Office replied that it was not familiar with the publication in which metacresyl acetate had been described. It seems evident that this patent would not have been issued had the application first been submitted to a government department familiar with chemical literature.

An illustration of the granting of a patent on the use of well-known chemical bodies which present no discovery or originality, is the patent issued for the use of peroxids, perborates and percarbonates as ingredients of tooth powders (U. S. Patents Nos. 760,397 and 802,099). Regarding these patents The Journal of the American Medical Association (Sept. 20, 1913, p. 978) commented:

“The patents held by McKesson and Robbins give this firm the exclusive right of manufacturing tooth powders containing peroxids, perborates and percarbonates. It is another illustration of the unfair monopolies that may be secured under our present patent laws.”

GRANTING A PATENT TO A NOSTRUM

Again in 1913 U. S. Patent No. 1,081,069 was granted to a citizen of Switzerland (a country which does not grant patents on medicinal preparations) for a “composition which is intended to be used internally and which confers to the organisms immunity against the following microbial infectious illnesses: _diphtheria, pneumonia, typhus, scarlet fever, influenza, septic infections, cerebral-spinal meningitis, syphilis, pest, cholera and tuberculosis; it is also effective in another kind of disease, viz., goiter_.” (Italics not in original). The patent specification states that “The principal of these substances is creatinin ...,” but offers no evidence whatever that this well-known chemical body has the extensive and miraculous powers claimed for it. In publishing a notice of this patent The Journal of the American Medical Association (Jan. 3, 1914, p. 54) explained:

“It appears that the inventor is dead, and that his estate took out the patent. Since this great benefactor should have been, by the use of his preparation, immune to practically all diseases, he must have died of senility, although this seems hardly to have been the case.”

and held:

“Assuredly granting patents on such claims ought to be sufficient to show the need of a change in the methods of granting patents--at least of the methods governing the issuance of patents for medicinal products.”

We submit, that had the department of the government entrusted with the enforcement of the federal Food and Drugs Act been consulted as to the claims of this patent, it would probably have advised that, if the absurd and palpably fraudulent claims set forth in this application for a patent were made on the label of a preparation of creatinin offered for sale in interstate commerce or in the District of Columbia, the vendor would be prosecuted.

In 1914 there was issued U. S. Patent No. 1,086,339. Here the “inventor” declared:

“It is the object of my invention to destroy parasitic micro-organisms, particularly on living tissue without injuring the latter, by progressively evolving sodium hydroxid contiguous to said tissue, from and in a moist mixture of calcium hydroxid, sodium carbonate, aluminum sulfate and boric acid....”

In a word, this patent apparently was granted for the production of sodium hydroxid by a chemical reaction which had been in use for several centuries. Because the patentee had twisted the granting of this patent into a quasi-endorsement of his nostrum, the Council’s consideration of this preparation was sent the Patent Office as a protest against the present law which authorizes the granting of patents on unproved and improbable medical claims. At that time the Council was informed by the Patent Office that reforms in the issuance of patents for medicinal substances had been instituted, and that “the trouble will not be so pronounced in the future as it has been in the past.”

FLAVORING EPSOM SALT A “DISCOVERY”

There was issued early in 1917 U. S. Patent No. 1,212,888 for a method of flavoring Epsom salt--yet this “discovery” is a procedure which has been practiced ever since the cathartic action of this bitter salt has been known. Not only does the patent describe a process long known to physicians and pharmacists, but it sets forth claims that the flavored cathartic salt produced by the process cures flatulency, indigestion, sick and sour stomach, colic and destroys worms. In commenting on this patent The Journal of the American Medical Association (June 23, 1917, p. 1914) was constrained to remark:

“The splendid conception of the framers of our constitution in providing a plan for promoting progress in science and useful arts by granting to inventors for a limited time the exclusive use of their inventions, in exchange for the publication of full knowledge thereof, is being debased. No branch of our government is of greater importance to the progress of the country than the patent office, provided that office is intelligently administered. When the patent office is used, however, for an extension of the nostrum business, founded on the abuse of patent and trade-mark laws, it becomes a menace to the public health. The objects of the patent law are being defeated by the practices of the patent office.”

Still further, attention is called to U. S. Patent No. 1,226,394 for a process of making hexamethylenamin tetraiodid and on the product so produced. This patent was issued after the Council had notified the Patent Office that hexamethylenamin tetraiodid had been discovered in 1888 and that a process identical in principle with that for which patent application appeared to have been made was published in 1916. On the basis of claims for which no evidence is produced this patent is issued for a well-known substance on the ground that as previously produced it contained a little free iodin or that the known processes were less economical. This patent appears to be an illustration of our patent procedure which obliged American users of acetylsalicylic acid to pay an exorbitant price because this country granted a patent which gave to the patentee, a foreigner, the exclusive right to the manufacture of the substance, whereas no such patent was issued in the patentee’s own country nor, so far as we can learn, in any other country. It forcibly illustrates the need for a revision either of our patent laws or of their methods of enforcement or both.

THE BEVERIDGE PATENT

In further justification of the Council’s protest against the provisions of our present law, or the methods of its enforcement, which permit the granting of patents without thorough and scientific investigation of the claims advanced in such letters patent, the Council calls attention to the report, appearing above, of an investigation made by A. J. Carlson, A. E. Kanter and I. Tumpowski, “The Question of the Stability of Secretin,” which relates to U. S. Patent No. 1,181,424, issued to James Wallace Beveridge.

Whereas the regulations governing the issuance of patents demand that the processes shall be described in such detail that one versed in the sciences can confirm the claims made by the patentee, no pretense whatever of fulfilling this requirement is made in the patent specifications of this patent. The substance of the first three paragraphs of this patent has long been general knowledge. Nearly every sophomore medical student has himself performed, or seen performed such “experiments” as are therein described. The claims of novelty evidently are confined to the assertion that the preparation is able to “resist oxidation or deterioration”; that it is free from “poisonous and irritable chemical substances”; that it “may be administered orally to produce the desired physiological action.” etc., etc. Not the slightest hint is given as to how any person can substantiate these claims. As a matter of fact, the investigation of Professor Carlson and his co-workers has shown that a preparation having the properties claimed cannot be made by the process described in this patent. Any one familiar with the subject could have demonstrated readily that the applicant was withholding information concerning essential features of his process, assuming that he had any information on the subject (which he probably did not have) and would have advised against the issuance of the Beveridge patent.--(_From The Journal A. M. A., Jan. 12, 1918_.)

SURGODINE

Report of the Council on Pharmacy and Chemistry

The following report submitted by a referee was adopted by the Council and authorized for publication.

W. A. Puckner, Secretary.

Surgodine (Sharp and Dohme, Baltimore, Md.), according to an advertising pamphlet, is a solution of 2-1/4 per cent. of iodin in alcohol, containing no alkaline iodid, but miscible with water in all proportions. The A. M. A. Chemical Laboratory reports that Surgodine is an alcoholic liquid (containing 91.8 per cent. alcohol by volume) containing free iodin, combined iodin and free acid, probably hydrogen iodid (hydriodic acid). Quantitative estimations gave 2.51 gm. free iodin per 100 c.c. and 1.78 gm. combined iodin (the greater part apparently was present as hydrogen iodid).

It is therefore similar to several other iodin preparations already considered by the Council. Like these, it is essentially similar to the official tincture of iodin, except that it is considerably weaker, and instead of potassium iodid it presumably contains hydrogen iodid and probably ethyl iodid to render the iodin water-soluble. Its composition, however, is secret.

There would be no objection to the use of ethyl iodid or hydrogen iodid, except perhaps the acidity of the latter, as a solvent agent rather than of potassium iodid. But neither is there any important advantage, and these preparations would have to be considered as unessential modifications of official preparations, and therefore ineligible for New and Nonofficial Remedies.

The attempt to make these modifications commercially profitable, however, seems inevitably to lead to exaggerations and misstatements. In an advertising pamphlet the following claims for Surgodine are unsupported by any evidence:

“But from the surgical viewpoint the addition of this potassium salt is most objectionable because when such solutions as the official tincture are used locally in the antiseptic treatment of open and often infected wounds the Potassium Iodide acts as an irritant to the wound and therefore produces a localized irritation which is not only objectionable from the surgical standpoint but also materially lessens the antiseptic power of the Iodine itself.”

“It has been demonstrated repeatedly that Iodine without the admixture of any alkaline iodide is much more efficient as a surgical antiseptic than any iodine solution that contains such an addition.”

“Iodine does not produce ‘iodism’ as quickly as the alkaline iodides do because it is eliminated more quickly and more perfectly than the alkaline iodides.”

The next statement intimates that iodin taken by mouth enters the intestinal tract unchanged and is there free to combine with various gases:

“Iodine in the presence of phosphorated or sulphurated gases in the gastro-intestinal tract unites with their hydrogen and thus breaks up these noxious compounds.”

This is certainly untrue at least for ordinary doses.

It is recommended that Surgodine be held inadmissible to New and Nonofficial Remedies because its composition is secret (Rule 1); because the therapeutic claims made for it are exaggerated and unwarranted (Rule 6); and because it is an unessential modification of the official tincture of iodin (Rule 10).

[Editorial Comment.--Surgodine is a good illustration of the economic waste inseparable from most proprietary medicines. A hospital pharmacist writes that whereas his hospital obtains tincture of iodin at less than 82 cents a pint, Surgodine costs $2.13 a pint. This means that while the free-iodin strength of Surgodine is only about one-third that of the official tincture, its price is between two and three times as high.]--(_From The Journal A. M. A., Jan. 26, 1918_)

MEDEOL SUPPOSITORIES

Report of the Council on Pharmacy and Chemistry

The following report on Medeol Suppositories has been adopted by the Council, and its publication authorized.

W. A. Puckner, Secretary.

“Medeol Suppositories” (Medeol Company, Inc., New York) appear to be an imitation of “Anusol Suppositories” which, in 1907, were found to be inadmissible to New and Nonofficial Remedies. A comparison of the composition and of the claims made for the two preparations will be of interest in the present consideration of Medeol Suppositories:

ANUSOL SUPPOSITORIES (1909) MEDEOL SUPPOSITORIES (1917)

Anusoli 7.5 Medeol 0.25 Zinc oxid 6.0 Zinc oxid 0.5 Balsam Peru 1.5 Acid. tannic 0.15 Ol. theobrom. 19.0 Bals. Peru 0.16 Ungt. cerat. 2.5 Cocoa butter and wax _q. s._ for 12 suppositories. for 1 suppository.

“Anusol” was formerly said to be bismuth iodoresorcinsulphonate. The A. M. A. Chemical Laboratory published a report in 1909 showing that the suppositories contained only 1 per cent. of the iodin declared in the “formula,” and were greatly deficient in bismuth and sulphur. After the publication of the report the American agents for the product disclaimed that “Anusol” was a definite chemical compound. Today Anusol Suppositories are said to contain unstated amounts of the indefinite “bismuth oxyiodid and resorcinsulphonate.”

“Medeol” is said to be “resorcinated iodo bismuth,” but no information is vouchsafed as to the character or composition of the ingredient. The therapeutic claims made for the two preparations are similar, as the following, taken from circulars, show:

ANUSOL SUPPOSITORIES

An innocuous, non-irritant remedy for anal, rectal and vaginal inflammatory affections, especially for HEMORRHOIDS!

The local medicinal treatment of hemorrhoidal and other inflammatory ano-rectal conditions has always been unsatisfactory. The usual media cannot be applied in effective concentration without producing intense inflammatory reactions; they are either ineffective or intolerable....

Anusol suppositories are absolutely free from narcotic, caustic or other injurious ingredients and may unhesitatingly be used by both sexes, at any age and under all conditions.

MEDEOL SUPPOSITORIES

An innocuous, Non-irritant, Efficient Antiphlogistic for use in inflammatory diseases of the rectum, anus and vagina especially in HEMORRHOIDS.

Hitherto most of the local remedies used in these conditions have either been too irritating to be employed in sufficient concentration to be efficient or they have lacked efficiency per se....

Medeol suppositories do not contain any narcotic or any caustic or other constituent having violent action; their blandness permits of their use in either sex and at all ages.

The claims made for these preparations--as for instance “that surgical treatment ... should rarely be undertaken until Medeol Suppositories have been given a thorough trial”--are misleading in that they create the inference that the limitations in the palliative treatment of piles have been overcome. It is altogether untrue that these mixtures can be expected to “relieve the most obstinate cases,” as stated in a Medeol circular. This, from an Anusol circular, is equally misleading:

“If dietetic and other requirements are complied with, even the most obstinate chronic cases will frequently readily yield to treatment with Anusol Suppositories.”

The Council declared Medeol Suppositories inadmissible to New and Nonofficial Remedies because their composition is secret (Rules 1 and 2); because unwarranted therapeutic claims are made for these (Rule 6); because the name is objectionable (Rule 8), and because the combination is unscientific (Rule 10).

In those cases of hemorrhoids in which palliative measures may be expected to enable the patient to avoid surgical interference and afford relief from attacks, the object should be to secure cleanliness, to avoid irritation, whether it be by friction or irritating fecal matter, to reduce inflammation by astringents and, when necessary, to relieve pain by analgesics. If an antiseptic dusting powder is desired, boracic acid in impalpable powder with talc may be employed; if an astringent, finely powdered oxid of zinc may be added; if a local analgesic is necessary, a little extract of belladonna may be incorporated with petrolatum or other ointment base. The main reliance, in any event, should be to effect normal bowel movements by regulating the diet rather than by the use of purgatives; the use of warm water to insure cleanliness; the avoidance of irritation, especially that caused by friction and secretions; a mild astringent to reduce inflammation.--(_From The Journal A. M. A., March 9, 1918_)

GUAIODINE

Report of the Council on Pharmacy and Chemistry

The following report on Guaiodine, marketed by the Intravenous Products Company, Denver, has been adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

A referee of the Committee on Pharmacology, in submitting to the Council a report from the A. M. A. Chemical Laboratory on Guaiodine, advises that the Laboratory’s examination shows that instead of containing free “colloidal” iodin as claimed, the preparation is essentially an iodated fatty oil, containing only combined iodin. Equally misleading, in view of the Laboratory’s findings, are the implied claims that the antiseptic action of Guaiodine corresponds to that of free iodin.

Guaiodine is advertised mainly for the treatment of gonorrhea. While it may be true that the guaiacol contained in Guaiodine has some beneficial effect, especially when preceded by potassium permanganate irrigation as advised, the advertised claim that “Guaiodine acts as a specific for gonorrhea in a majority of cases” is utterly false.

The “case records” offered to establish the therapeutic value of Guaiodine are in themselves sufficient to condemn the “evidence.” The following are fair samples:

“The second boy came a day or so later with a slight discharge with the characteristic burning and itching, and with symptoms of a beginning gonorrhea, and judging from the source of the infection, it was believed to be so. Two injections of Guaiodine were given when the discharge ceased.”

“I have several cases that were completely cured in a very short time. I note this, that the first dose causes a cessation of the discharge and the second seems to increase the flow, but the color is changed. I give three doses, and then use a mild wash, and in ten days they are well. I am very pleased with this preparation and very truly believe that it is the best there is to date for the positive cure of gonorrhea.”

REPORT OF THE CHEMICAL LABORATORY

Guaiodine is manufactured by the Intravenous Products Company, Denver, Colorado. The “literature” which accompanies the product describes Guaiodine as:

“... an electro-chemically prepared iodin, suspended in oil, containing iodin, the same strength as the U. S. P. tincture of iodin, or 7 per cent., together with a therapeutic dose of guaiacol.”

The Intravenous Products Company claims that Guaiodine is made by an “electro-chemical process of preparing colloidal iodine,” discovered by one E. B. Page, and that by this process the tendency of iodin to produce iodism has been “overcome.” It is said to be “pre-eminently an antiseptic and germicide.” Guaiodine is a dark brown, oily liquid with a specific gravity of 0.9845 at 15.6 C. and an odor suggestive of guaiacol. Its solubilities were those of a fat. Free iodin was absent in the recently purchased specimen (traces were present in an older one). Steam distillation indicated that the product consisted of volatile and nonvolatile constituents. The volatile matter was concluded to consist, in the main, of guaiacol or some guaiacol-like body, and the nonvolatile matter to be an iodized fatty oil. Quantitative determinations indicated that Guaiodine contained about 7.25 per cent. of iodin in combination, and that it is composed approximately of 3 per cent. volatile matter and 97 per cent. nonvolatile matter. Hence Guaiodine appears to be an iodized fatty oil to which a small amount of guaiacol or some guaiacol-like substance has been added.

THE COUNCIL’S ACTION

On the recommendation of the referee, the Council voted that Guaiodine be declared inadmissible to New and Nonofficial Remedies because of false statements as to composition and action.--(_From The Journal A. M. A., April 6, 1918._)

SEVERAL “MIXED” VACCINES NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The “mixed” vaccines which are discussed in the reports that follow were considered by the Council during the past year because inquiries had been received in regard to them.

In publishing these reports it is desirable that the attitude of the Council toward “mixed” vaccines again be stated. In view of the rapid development of bacterial therapy, the possibility for harm that attends the use of bacterial vaccines and the skepticism among experienced clinicians as to the value of vaccines representing a combination of organisms, the Council has felt that it should scrutinize the claims for such agents with exceptional care and that there should be admitted to New and Nonofficial Remedies only those vaccine mixtures for which there is acceptable evidence to indicate that the use of the particular mixtures is rational.

In considering the subject the Council has borne in mind the fact that in many institutions in which cases are studied and the results of therapeutic measures carefully observed and controlled, vaccines of any sort are practically never used--certainly here the stock mixed vaccine has no recognition. Experienced clinicians have generally come to the conclusion that mixed vaccines have no specific action and that any effect they may produce is due to a non-specific protein reaction.

As set forth in the reports, in no case was the evidence submitted by the proprietors sufficient to establish the claims made for the preparations. Hence none was accepted for New and Nonofficial Remedies.

The preparations that form the basis for the accompanying reports are only a few of the many that are being made and sold by some biological houses. Doubtless many of those not dealt with in this report are equally irrational and sold under claims equally--or probably even more--unwarranted than those with which the present report deals.

W. A. Puckner, Secretary.

Mixed Vaccines-Abbott

In response to inquiry the Council undertook a consideration of the following “mixed{”} vaccines sold by the Abbott Laboratories:

_M. Catarrhalis-Combined-Bacterin_, said to contain killed Micrococcus catarrhalis, Bacillus Friedländer, Pneumococci, Streptococci, Staphylococcus aureus and Staphylococcus albus.

_B. Coli-Combined-Bacterin_, said to contain killed Streptococcus viridans, Streptococcus hemolyticus and Bacillus coli.

_Pertussis-Combined-Bacterin_, said to contain killed Bacillus pertussis, Pneumococci, Streptococci, Staphylococcus albus, Staphylococcus aureus and Micrococcus catarrhalis.

_Streptococcus-Rheumaticus-Combined-Bacterin_, said to contain killed “Streptococci (Rheumaticus, Viridans, etc.)” and Pneumococci.

_Streptococcus-Viridans-Combined-Bacterin_, said to contain killed Streptococcus viridans, Streptococcus hemolyticus, Pneumococcus and Staphylococcus albus.

The Abbott Laboratories were asked to assist in the investigation of these products and to submit evidence to establish their eligibility for admission to New and Nonofficial Remedies. The manufacturer was informed that the Council accepts “mixed” vaccines or bacterins, provided the usefulness of these products is established by acceptable clinical evidence, and references to the literature bearing on the value of the preparations were requested.

The Abbott Laboratories submitted specimens of the products, the advertising matter therefor and a considerable list of references to current literature; all of which was transmitted to the Committee on Serums and Vaccines for consideration. In due time a referee of the committee submitted the following report:

THE COMMITTEE’S REPORT

The referee has studied the literature covered by the references submitted. In general the articles are favorable to the use of vaccines, though many of these papers do not consider “mixed” vaccines; indeed, a number of the articles do not discuss treatment at all, but are devoted entirely to the consideration of etiology of the disease. Many of the papers are by those who are obviously overenthusiastic on the subject of the use of biologic preparations. One paper--not included in the references submitted by the Abbott Laboratories--records an alarming reaction following a dose of mixed vaccine; no claim is made that improvement followed.

The following comments on the submitted references are offered:

_M. Catarrhalis-Combined-Bacterin._--Only four of the nine references given deal with the therapeutic use of the vaccine. The reported results in general were favorable, but sometimes in the discussion evoked by certain of the papers, views the reverse of those expressed by the author were brought forward. The enthusiasm of one writer is shown in his statement that following the use of vaccine in cases of carbuncle complicating diabetes the sugar in the urine disappeared or was reduced. One observer, who reports excellent results in nasal pharyngeal catarrh, speaks of certain vaccines as “bulk goods,” while another considers “----’s No. 7” as the proper thing. It is evident that the reports are not based on careful, scientific data, or such unscientific definition of the product employed would not be used.

_B. Coli-Combined-Bacterin._--In the references cited in support of this preparation the following general statements are noted: One enthusiastic writer says, “It must be recognized that we have no satisfactory explanation of the action of vaccines, and their use at present is empirical.” One author dwelt on the superiority of autogenous vaccines but admits that occasionally stock vaccines are indicated. One vaccine therapist in concluding an article states, “It is simply impossible to practice modern urology without our modern biologic products.” Yet it is a well-known fact that many successful and capable genito-urinary surgeons avoid the use of vaccines, mixed or simple.

_Pertussis-Combined-Bacterin._--These reports are uniformly favorable, but are not controlled and their value is not to be compared with a recent report from the New York City Department of Health which indicates that the vaccine is practically valueless. It is noted, further, that one of the articles cited which dealt rather fully with the treatment of pertussis did not mention vaccines.

_Streptococcus-Rheumaticus-Combined-Bacterin._--The references cited in support of the preparations by the manufacturer give no support whatever for the use of mixed stock vaccines. The first reference deals with the relation of Streptococcus viridans to arthritis deformans and endocarditis and reports the following cases:

_Case 1._--Vaccine case--improvement after eight months. _Case 2._--Slight improvement following use of vaccine. _Case 3._--Slight improvement following use of vaccine. _Case 4._--Marked improvement. _Case 5._--Prompt improvement. _Case 6._--Vaccine not mentioned. _Case 7._--Vaccine followed by slight improvement.

In each of the cases other methods of treatment were used. The paper shows the etiologic relation of Streptococcus viridans rather than the value of vaccines. There is no indication that stock vaccines were used, though the paper is not clear on this point. The second paper deals with the application of vaccine therapy in the treatment of arthritis. This paper is by a man who is avowedly an enthusiast on vaccine therapy. The indications are that he generally used a mixed autogenous vaccine, but the reports of cases are not always clear. This writer apparently makes no serious attempt at the classification of the joint conditions he treats. The third reference is a purely experimental study and has no bearing on the use of vaccines in treatment. The fourth article was admitted by the manufacturer to be “negative as regards evidence.” The fifth reference specifically states that “the vaccine must be autogenous.” The sixth reference deals with the experimental production of appendicitis by the use of diplococci, and has not the most remote bearing on the use of vaccines in the treatment of rheumatism.

_Streptococcus-Viridans-Combined-Bacterin._--The article which bears evidence of more care than the others admits that we are not in position to state the value of vaccines in pyorrhea but the author believes they may have value supplementary to local treatment.

It is not surprising that a large number of favorable reports can be accumulated when we appreciate how promptly men report what they consider to be their successes and how commonly they leave their failures unrecorded. Bearing in mind the fact that these stock mixed vaccines, though before the profession for many years, have not been used, or continued in use, in hospitals where work is rigidly controlled and that they are used practically not at all in the large government hospital service, a candid critic must hold that there is no substantial evidence in favor of the therapeutic use of a mixed vaccine, certainly not for stock “goods” and that probably there is but a limited field for the employment of autogenous vaccines.

The referee calls attention to a shift in the advertising matter on vaccines--the tendency to recommend vaccines to be used in conjunction with drugs. A heading in the Abbott booklet reads, “The Biologics Do Not Replace Drugs”; and the paragraph speaks of serums and bacterins as “new tools, supplemental to those we already have, but not replacing them.” ... “We need them both.”

The referee recommends that the several mixed vaccines discussed in this report be not accepted on the grounds that satisfactory evidence of their value is wanting.

Having been endorsed by the Committee on Serums and Vaccines the Council adopted the report and declared M. Catarrhalis-Combined-Bacterin, B. Coli-Combined-Bacterin, Pertussis-Combined-Bacterin, Streptococcus-Rheumaticus-Combined-Bacterin and Streptococcus-Viridans-Combined-Bacterin ineligible for admission to New and Nonofficial Remedies.

Catarrhal Vaccine Combined-Lilly and Influenza Mixed Vaccine-Lilly

Because of inquiry received, the Council requested Eli Lilly and Company to aid in determining the acceptability of the following products for New and Nonofficial Remedies: “Catarrhal Vaccine Combined,” said to contain killed cultures of the Bacillus of Friedländer, Micrococcus catarrhalis, Staphylococcus aureus and albus, Pneumococcus and Streptococcus; “Influenza Mixed Vaccine,” said to contain killed cultures of Staphylococcus albus and aureus, Streptococcus, Pneumococcus, Micrococcus catarrhalis and Bacillus influenzae.

Lilly and Company sent the circulars, etc., used in advertising these products. A circular for “Catarrhal Vaccine Combined” contained the following claim:

“Catarrhal Vaccine has been especially useful in many respiratory infections, including bronchitis, pharyngitis, rhinitis, chronic catarrh and in the mixed infections of pulmonary tuberculosis.”

A circular for “Influenza Mixed Vaccine” contained the following:

“The vaccine is useful in the treatment of influenza and ordinary colds, and in any infection in which the Bacillus influenzae is the causative agent.”

An advertising pamphlet contained the following:

“Catarrh, Acute and Chronic; Colds, Influenza.--The micro-organisms capable of producing catarrhal conditions of the nose and pharynx and most commonly isolated are B. Friedländer, M. catarrhalis, staphylococcus, pneumococcus (in infections beginning in the larynx), _B. influenza_ and streptococcus. These organisms are found normally in the respiratory passages and acquire virulence only when resistance has been lowered through overwork, exposure to cold, etc.

“The results following the use of Catarrhal Vaccine Combined (in the non-epidemic forms) and influenza Mixed Vaccine (in the epidemic types) have been very satisfactory, due to the great vascularity of the tissues. Acute attacks are aborted altogether or shortened in duration and the danger of complications greatly minimized.”

No evidence was submitted which warrants the preceding claims nor is the Council aware of any reliable testimony to indicate that the administration of the mixture here discussed is warranted or desirable. On the recommendation of the Committee on Serums and Vaccines the Council voted that “Catarrhal Vaccine Combined-Lilly” and “Influenza Mixed Vaccine-Lilly” be not included in New and Nonofficial Remedies because satisfactory evidence of their value is wanting.

Influenza Serobacterin Mixed-Mulford

Because of inquiry received, the Council took up the consideration of “Influenza Serobacterin Mixed-Mulford,” and requested the Mulford Company to present evidence to establish the admissibility of the preparation to New and Nonofficial Remedies. The Mulford Company sent specimens of the serobacterin in question, an advertising circular and a letter by the director of its Biologic Laboratories.

According to the label on the package, the preparation is made from the following organisms: Bacillus influenzae, Staphylococcus aureus, Staphylococcus albus, Streptococcus, Pneumococcus and Micrococcus catarrhalis (group). This mixture is recommended by the manufacturer:

“For the prophylaxis and Treatment of Common Colds, Mixed Infections of the Respiratory Mucous Membranes, Acute and Chronic Catarrhal Conditions of the Nose, Throat and Respiratory Passages.”

No evidence is submitted for this recommendation except that in “colds and bronchitis and the other common infections of the upper respiratory passages ... five or six bacteria are very commonly present--two or more of them are nearly always present ...” and the letter by the director of the Mulford Biologic Laboratories expressing the belief that in his own case the use of the mixed vaccine has aborted or prevented colds.

As regards the use of this complex biologic preparation:

First, the cause of common colds is, at the present time, quite unknown. One of the most striking things is that at the beginning of a cold the organisms to be cultivated from the nasal mucous membrane are very few in number and there is no uniformity in the type of organism found. If someone of the well-known organisms (Streptococcus, Staphylococcus, Pneumococcus, Micrococcus Catarrhalis, Influenza Bacillus, etc.) were responsible, we should expect to find one of them preponderating and in overwhelming numbers. This is far from the case. After the duration of the cold for a day or two with the increased production of mucus and apparently with the infection of a mucous membrane whose powers of resistance have been greatly lowered, bacteria of all kinds are to be found in immense numbers. There is considerable reason for believing that an ultramicroscopic organism is responsible for this condition (See Foster, _Journal of Infectious Diseases_ =21=:451 [Nov.] 1917).

Second, there is no acceptable clinical evidence that vaccination with the influenza bacillus, the Streptococcus, the Pneumococcus or the Micrococcus Catarrhalis will influence the course of an infection due to one or the other of these organisms. It has been repeatedly found that a staphylococcus vaccine is of a certain degree of value when the infection with the staphylococcus is localized, but it is well known that general systemic infections with the staphylococcus are not at all benefited.

Third, the letter submitted as evidence by the Mulford Company is not convincing. The Council is not prepared to accept evidence of this sort unless it is in volume large enough to justify a definite conclusion.

Holding that there is no evidence for the value of this mixture, the Council declared “Influenza Serobacterin Mixed-Mulford” inadmissible to New and Nonofficial Remedies because its use is illogical.

Sherman’s Mixed Vaccine No. 40

Because of inquiry received the Council decided to consider this preparation and requested the manufacturer, G. H. Sherman, Detroit, Mich., to submit evidence in support of the claims made for it.

This vaccine is said to be made from killed cultures of Streptococcus, Pneumococcus, Micrococcus catarrhalis, Staphylococcus aureus, and Staphylococcus albus. In the printed matter sent out by G. H. Sherman this vaccine is recommended for hay-fever, in which it is stated that some of the symptoms are due to bacterial invasion of the respiratory mucosa; for tonsillitis, both as a remedy and as a prophylactic against rheumatic and other sequelae; for “throat infections”; for rhinitis with the claims that acute coryza can be aborted within twenty-four hours; for pneumonia in which it is advised for all stages; for laryngitis, for bronchitis, and for asthma.

No acceptable evidence was submitted as to the value of the product in the treatment of any of the foregoing conditions. In view of what is known about non-specific reactions, it seems likely that any influence which this vaccine may have on the diverse conditions enumerated by the manufacturer, is due to this, rather than to the combination of organisms used in its preparation.

On the recommendation of the Committee on Serums and Vaccines, the Council declared “Sherman’s Mixed Vaccine No. 40” ineligible to New and Nonofficial Remedies because the therapeutic claims made for it are unwarranted (Rule 6) and because the combination, in view of its complexity, is irrational and detrimental to sound therapy (Rule 10).--(_From The Journal A. M. A., June 23, 1918._)

OPHTHALMOL-LINDEMANN

Report of the Council on Pharmacy and Chemistry

Ophthalmol-Lindemann was taken up for consideration by the Council because of inquiries received. The following report, declaring Ophthalmol inadmissible to New and Nonofficial Remedies, was adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

Ophthalmol-Lindemann (Innis, Speiden and Co., New York) is advertised as a treatment for eye diseases by “hyperemia.” The circular advertising the product is written somewhat in the style of “patent medicine” advertisements. It contains testimonials of dubious value. The principle underlying the use of Ophthalmol is that employed to a considerable extent by ophthalmologists, through the use of ethylmorphine (“dionin”), etc., viz., the production of conjunctival irritation in inflammatory eye diseases. Ophthalmol is, therefore, merely a special agent for the production of such ophthalmic irritation.

The advertising circular contains no evidence that Ophthalmol is in any respect superior to the established agents for producing conjunctival hyperemia. On the other hand, there are obvious objections to the use in the eye of a substance of unknown and apparently indefinite composition and uncertain activity. Ophthalmol is said to be an oily solution of “glandular extract of the fish Cobitis Fossilis.” _Cobitis fossilis_ is a small fish said to be common in Germany. According to Kochs, who analyzed Ophthalmol (_Arb. a. d. Pharm. Inst. d. Univ. Berl._, =4=:140, 1907), this fish is popularly believed to predict weather, but medical virtues are not ascribed to it. This “fishy” extract is indefinite, to say the least.

The activity of the preparation is described by the manufacturer thus: “It seems probable that the typical action of Ophthalmol is due to certain organic acids which may have formed during manufacture through the decomposition of protein bodies contained in the crude material.” The profession is not told whether this important decomposition is, or, in fact, can be controlled so as to produce a material of uniform activity.

Kochs concluded from his analysis that Ophthalmol had the properties of rancid olive oil containing about 6 to 7 per cent. mineral oil. The oil contained no nitrogen, left no ash on ignition and though traces of iodin were claimed to be present, no iodin could be found.

It is recommended that Ophthalmol be rejected first, because the use in the eye of an irritant of secret composition and uncertain activity is unscientific and against the interest of public health; second, because Ophthalmol is of secret composition (the composition claimed being practically meaningless), and, third, because no evidence has been submitted to substantiate its claimed superiority over established methods of treatment. The Council declared Ophthalmol inadmissible to New and Nonofficial Remedies.--(_From The Journal A. M. A., July 6, 1918._)

SILVOL INELIGIBLE FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report on Silvol (Parke, Davis & Company) was adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

The Council took up the consideration of Silvol (Parke, Davis & Company) because of inquiries received. The following report was submitted by the referee in charge of silver preparations:

Silvol (Parke, Davis & Company) is a silver-protein preparation of the Argyrol type. Like Argyrol, it is said to contain about 20 per cent. of silver. The referee finds that, like Argyrol, it is nonirritant to the nasal mucosa in a 10 per cent. solution; does not precipitate with chlorid; dissolves in water readily; a 25 per cent. solution has a high specific gravity (Silvol, 1.137 at 20 C.; Argyrol, 1.147 at 20 C.), and is not very viscid (viscosity, 1.25). A 1:1,000 solution of Silvol is clear and about 50 per cent. deeper in color than a solution of Argyrol of the same strength.

Silvol differs from Argyrol mainly in that its solutions yield a fine precipitate with egg albumin (under suitable conditions), while Argyrol is nonprecipitant; and in that Silvol solutions are not so effectively decolorized by Lloyd’s reagent.

The manufacturers did not reply to an inquiry with regard to the basis for the claims made for Silvol (see Appendix). The referee was therefore obliged to deduce these claims from the firm’s advertising matter. About the same claims are made for the local use of Silvol as are generally made for Argyrol. These may be accepted without detailed evidence in view of the similarity of the two preparations.

Its usefulness, as suggested in the advertising, when given by mouth “in the treatment of acute or chronic gastritis, gastric ulcer, or gastro-enteritis,” or the efficacy of very dilute solutions (0.2 per cent.) against dysentery, etc., is doubtful and requires substantiation by evidence. The claims that Silvol is astringent, though nonirritant and noncoagulant, that it is a “powerful germicide” or even that it is a “powerful antiseptic,” and that it may be used with advantage wherever “a silver salt is indicated,” need substantiation. There is no proof of the assertions that Silvol is “the most efficacious of silver salts”; “the most efficient antiseptic,” and “the most remarkable organic silver compound ...”

As the manufacturers have not presented any evidence for their highly improbable claims, and as they have not signified any intention of making their claims agree with substantiated facts, it is recommended that Silvol be declared inadmissible to New and Nonofficial Remedies.

The Council adopted the report of its referee and authorized its publication.

APPENDIX

The following letter from the Secretary of the Council was sent to Parke, Davis & Company, March 20, 1917. No reply to it has been received:

The referee of the Council who is conducting an investigation of silver preparations asked me to inquire if you are willing to submit your evidence for the following claims which are made in your circulars for Silvol:

1. How it is possible for the solution to be astringent, and at the same time nonirritant and noncoagulant?

2. That intestinal irrigation with a Silvol solution containing 10 to 15 grains to the pint is sufficiently bactericidal to “be used in the abortive treatment of such infectious processes as dysentery, cholera infantum, and colitis.”

3. What evidence have you as to the degree of antiseptic and germicidal power of Silvol solutions?

4. What evidence have you as to the degree of antiseptic and germicidal power of 5 per cent. Silvol Ointment?

A reply to the above questions and any other information in regard to Silvol will receive careful consideration.--(_From The Journal A. M. A., July 13, 1918._)

KATHARMON

Report of the Council on Pharmacy and Chemistry

Following inquiries, the Council took up “Katharmon” for consideration and authorized publication of the following report.

W. A. Puckner, Secretary.

The Katharmon Chemical Company of St. Louis in advertising its Katharmon appeals especially to a profession whose members, should they live up to their ethical code, could not prescribe it.[124] In 1893 (when the publication of “a formula” for proprietary preparations was thought to satisfy the requirements of scientific medicine) an advertisement in The Journal of the American Medical Association gave the following “formula” for Katharmon:

[124] “... it is equally unethical to prescribe or dispense secret medicines or other secret remedial agents,...” Sec. 6, Art. I, Chapter II, _Principles of Medical Ethics_.

“Hydrastis Canadensis, Phytolacca Decandra, Acid Salicylous C. P. (from Oil of Wintergreen), Acid Boric C. P., Mentha Arvensis, Thymus Vulgaris, Dist. Ext. Hamamelis Virg. Conc.”

In 1907 an advertisement in the Kansas City _Medical Index-Lancet_ declared that:

“Katharmon represents in chemical combination the active principles of Hydrastis Canadensis, Gaultheria Procumbens, Hamamelis Virginica, Phytolacca Decandra, Mentha Arvensis, Thymus Vulgaris, with two grains C. P. Boric Acid to each fluid drachm.”

Now the advertisements which appear in some medical journals state:

“KATHARMON represents in combination Hydrastis Canadensis, Thymus Vulgaris, Mentha Arvensis, Phytolacca Decandra, 10-1/2 grains Acid Borosalicylic, 24 grains Sodium Pyroborate to each fluid ounce of Pure Distilled Extract of Witch Hazel.”

A comparison of these so-called formulas shows that they have not only varied from time to time, but that in no instance was a quantitative statement with regard to all the asserted ingredients given.

The Chemical Laboratory of the A. M. A. reports: Katharmon has an alkaline reaction and therefore cannot contain boric acid, salicylic acid or “borosalicylic acid” (the latter is unknown to medical literature except as loosely applied to a simple mixture of boric and salicylic acids). The solution gives tests for sodium, borate, and salicylate and therefore probably contains sodium borate and sodium salicylate. Examined by the methods used for the determination of hydrastin in goldenseal preparations, a residue giving only a faint test for alkaloid was obtained; if present at all, hydrastis canadensis (goldenseal) is there only in very small amounts.

A circular wrapped with the trade package of Katharmon contained the following, palpably unwarranted, claims:

“INTERNALLY it is very useful in acute indigestion, Gastric Catarrh, Diarrhoea and Cholera Infantum.”

“... it has demonstrated its remarkable curative effects, not only in preventing unhealthy conditions of fresh wounds, but also in correcting the decaying of putrefactive processes peculiar to the body under certain circumstances. It has, further, a remarkable efficacy in surface inflammations, whether produced by accident or disease, and is an indispensable remedy in the affections of the mucous membranes of the nose, mouth, stomach, bowels, vagina, uterus, urethra, bladder and rectum.”

Katharmon is in conflict with Rules 1 and 4 of the Council on Pharmacy and Chemistry because of its indefinite and secret composition and the method of advertising it indirectly to the public; it is in conflict with Rules 10, 6 and 8, in that it is an irrational shotgun mixture sold under unwarranted therapeutic claims and under a name nondescriptive of its composition.--(_From The Journal A. M. A., Aug. 10, 1918._)

IODINIZED EMULSION (SCOTT) AND CREOSOTONIC (SCOTT)

Report of the Council on Pharmacy and Chemistry

“Iodinized Emulsion (Scott)” and “Creosotonic (Scott)” are proprietary preparations of the Dawson Pharmacal Company, Dawson Springs, Ky. The latter preparation used to be known as “Iodinized Emulsion (Scott) with Hypophosphites, Guaiacol and Creosote.” In 1907 these preparations were considered by the Council and found inadmissible to New and Nonofficial Remedies. Examination of the preparations having been again requested, the Council considered them anew because the composition and claims had been changed somewhat and because at the previous consideration no report was published.

The reports which appear below were sent to the Dawson Pharmacal Company for comment before publication. In reply the company offered to revise its claims for the preparations. The Council replied that the report sent explained that both preparations are irrational mixtures, and hence a revision of the claims would not make them eligible for New and Nonofficial Remedies. It advised that publication of the report would be withheld sixty days and that it would be revised if new information or evidence was submitted permitting such revision. After expiration of the stipulated postponement, the Dawson Pharmacal Company wrote that no new advertising matter had been prepared, but that the old circulars were not being sent out.

As these irrational preparations were still sold and advertised to the medical profession and presumably used by some physicians, the Council directed publication of its report with this explanation.

W. A. Puckner, Secretary.

Iodinized Emulsion (Scott)

The label for Iodinized Emulsion (Scott) declares:

“Each fluidram contains: Alcohol, m. 4-3/4; Rectified Ol. of Turpentine, m. 3-1/2; Iodin, gr. 1/8; Phenol, gr. 1/2; Glycerine and Elixir Lactated Pepsin with Aromatic Oils in the form of a perfect emulsion.”

A circular which gives what is asserted to be the composition of Iodinized Emulsion, declares that, among other ingredients, each fluidram contains “one and three quarters m. Tincture of Iodine.” Both the statement on the label that the preparation contains “iodin” and the one in the circular that tincture of iodin is present in the product are incorrect, for the A. M. A. Chemical Laboratory reports that no free iodin could be detected in the preparation, and that it responded to tests for iodid instead.

An advertising circular for Iodinized Emulsion (Scott) makes unwarranted claims for the therapeutic properties of the constituents. For example:

“... the great usefulness of Turpentine in diseases, especially of the Intestinal Infection, such as the Meteorism and Tympanites of Typhoid.”

And this absurdity:

“... where Turpentine, Carbolic Acid or Iodine or even Pepsin is indicated, that it will give satisfaction in each and every case.”

Iodinized Emulsion (Scott) is not a “pharmaceutical triumph”; it is an irrational mixture--a reminder of a decadent polypharmacy--sold under misleading and unwarranted claims. It is inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 6, 8 and 10.

Creosotonic (Scott)

Creosotonic (Scott), advertised as a “reconstructive tonic” for the tuberculous, according to the label, contains in each fluidram:

“Alcohol, m. 2-1/2; Creosote and Guaiacol sulphonates of each, gr. 1; Compound Hypophosphites, gr. 1 (including Quinine Hypophosphites, gr. 1/36 and Strychnine Hypophosphites, gr. 1/256), with Iodinized Emulsion (Scott) m. 30.”

As in the case of Iodinized Emulsion (Scott), the advertising makes exaggerated therapeutic claims for the individual constituents of the preparation and for the heterogeneous mixture of guaiacol and creosote sulphonates, hypophosphites, quinin, strychnin, turpentine, phenol, iodin, “lactated pepsin,” etc. Thus, while it is well established that in guaiacol sulphonate and creosote sulphonate the phenolic constituent is bound so firmly that, when administered, but very little is split off in the organism, yet the advertising claims “that the system can be saturated in a shorter time and with smaller doses of creosote and guaiacol sulphonates than with any other form of these drugs” and that (on the false premise that the guaiacol and creosote from these drugs will permeate the tissues of the lungs) “they help to clear up the local infection and thus aid in returning to normal the diseased mucous membrane.”

In the advertising pamphlet, following a discussion of the effect of climate and food in the treatment of the tuberculous, we read:

“While admitting the great importance of the foregoing points, we are firmly of the opinion that proper medication is a great aid in the treatment of pulmonary tuberculosis, and, with this in view, we offer to the profession Creosotonic (Scott) believing that in it we have a superior preparation for this purpose.”

This is unwarranted. Of course suitable medication to meet special conditions is proper in the treatment of tuberculosis, but the routine administration of a complex and irrational mixture such as Creosotonic (Scott) is bound to cause inattention to the prime requisites for the proper treatment of the tuberculous--hygienic surroundings and good food.

Creosotonic (Scott) is an irrational mixture, sold under misleading and unwarranted claims. It is inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 6, 8 and 10.--(_From The Journal A. M. A., Aug. 24, 1918._)

CAMPETRODIN AND CAMPETRODIN NO. 2

Report of the Council on Pharmacy and Chemistry

The following report on Campetrodin and Campetrodin No. 2 has been adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

The following report of the A. M. A. Chemical Laboratory on “Campetrodin” and “Campetrodin No. 2,” sold by the A. H. Robins Company, Richmond, Va., was submitted to the Council by a referee of the Committee on Pharmacology:

Campetrodin and Campetrodin No. 2, Double Strength, are called “ethical medicinal specialties” by the A. H. Robins Company, Richmond, Va., which sells them. An advertisement in the _Maryland Medical Journal_ (December, 1917) contains the following claim for composition:

“CAMPETRODIN (Made in Two Strengths of Iodine). This preparation is an Oleaginous Solution of Iodine in Camphor.”

A booklet describing the “specialties” of the Robins Company contains the following in reference to Campetrodin: “Composition: Camphor, Iodine Element, Oleaginous Solvent.” From this it appears that the preparations are claimed to contain elementary (free) iodine in an “oleaginous solvent.” Since free iodin, as is well known, readily combines with fats, it was decided to determine the form in which the iodin was present in these preparations. The examination demonstrated that both preparations contained but a trace of free iodin. On steam distillation there was obtained from both preparations a distillate amounting to about 35 per cent. by volume which had an odor strongly suggestive of turpentine, while the residue contained the iodin and had the characteristics of an iodized fatty oil.

Quantitative determinations indicated that Campetrodin contained approximately 0.03 per cent. of free iodin and 1.3 per cent. of iodin in combination with the fatty oil. Campetrodin No. 2, Double Strength, contained approximately 0.03 per cent. free iodin and 2 per cent. of iodin in combination with the fatty oil.

Thus, contrary to the published statements, Campetrodin is _not_ a preparation of free (elementary) iodin and Campetrodin No. 2, Double Strength, does _not_ contain twice as much iodin as Campetrodin.

The report of the Chemical Laboratory shows that the statements made in regard to the composition of Campetrodin and Campetrodin No. 2 are incomplete in some respects and false in others. In view of the Laboratory’s findings it appears superfluous to inquire into the therapeutic claims made for the preparations: It is evident, however, that a solution containing practically no free iodin is not, as claimed by the Robins Company, “adapted for use wherever ... iodin is indicated externally....”

It is recommended that Campetrodin and Campetrodin No. 2 be declared inadmissible to New and Nonofficial Remedies because of false statements as to chemical composition and therapeutic action, constituting conflicts with Rules 1 and 6.

The Council adopted the recommendation of the referee and authorized publication of this report.--(_From The Journal A. M. A., Sept. 21, 1918._)

CARMINZYM

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following which explains why Carminzym was not accepted for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Carminzym is a tablet sold by Fairchild Bros. and Foster, New York. Each tablet contains, according to claims made, approximately 32 mg. of an extract of pancreas, 50 mg. sodium bicarbonate, 172 mg. prepared chalk, 1.5 mg. powdered ipecac and “aromatics _q. s._” Without considering other possible conflicts with its rules, the Council held the preparation inadmissible to New and Nonofficial Remedies for conflict with Rule 10 which holds that unscientific or useless articles are not acceptable products.

The Council holds that complex mixtures of remedial agents are, from every point of view, inimical to therapeutic progress and therefore to the public welfare. Such mixtures are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions; because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of individual patients without which there can be no rational drug therapy. On the contrary, with the use of such mixture therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture it has frequently directed that Rule 10 should not apply pending further clinical trial of such mixture. In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision several mixtures now described in New and Nonofficial Remedies will be omitted at the expiration of the three year period for which articles are accepted.

Reverting to the Carminzym tablet: When it is desired to obtain the effects of pancreatic extract by oral administration it must be administered with a view of preventing its destruction by the gastric fluid. With this end in view an antacid should be administered to decrease the acidity of the gastric juice. The amount of alkali may be supplied in the form of any of the official preparations, but the amount must be adjusted to the individual patient for the reason that no two successive patients are likely to have the same degree of gastric acidity.

Ipecac has a well defined though limited field of usefulness. When it is used, it should be given with a due regard to the amount needed by the patient and the frequency of the repetition of the dose. There is no reason to suppose that any two successive patients will require ipecac and extract of pancreas in a fixed proportion and with equal frequency. As a matter of fact, the amount of ipecac in Carminzym is so small that no definite therapeutic action can be assigned to it and its use in this combination is purely empirical.

In a word, the employment of mixtures of pancreatic extract, alkalis, ipecac and carminatives in fixed proportion leads to slipshod treatment and irrational therapeutics. Carminzym is an irrational mixture the use of which is detrimental to therapy.

The preceding report was sent to Fairchild Bros. and Foster for comment in accordance with the Council’s usual procedure. The following reply was received:

The long established custom of the use of mixtures of remedial agents rests upon considerations well known and generally accepted. This is equally true of combinations of drugs of similar and dissimilar properties. The drugs of these combinations, especially those of marked therapeutic action, are well known and used by themselves when indicated.

In fact, dissimilarity of action is a cause of combination, an essential of synergism.

Drugs classed as similar are by no means alike in action; laxatives, tonics, carminatives, diuretics are combined with distinct advantage, economy of dose, enhanced effect, potency not obtainable with the single drug.

Your sweeping arbitrary conclusions that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress is not, it seems to us, sustained by fact and experience. There is therapeutic progress in the considerate use and observation of combinations as well as in the use of a single drug. Indeed, in the production of a synthetic chemical substance as a therapeutic agent, the combination of potent and dissimilar elements is worked out to mitigate and correct an objectionable side effect, and promote desirable action.

As for ourselves, at the very outset in our line of work we quite voluntarily declared our principles and our intentions as opposed to incompatible and therefore unstable or inert combinations of the enzymes; and against the “unnecessary multiplication of preparations”--see Fairchild’s Hand-Book of the Digestive Ferments.

Is not this after all the crux of the whole matter--does a combination contain the ingredients stated, does it possess the demonstrable properties which are to be attributed to it in consequence of this composition; and if for a certain purpose, is it well designed therefor?

Carminzym presents certain agents of well known properties, not in the least of incompatible or antagonistic action, but indeed especially suitable for the particular purpose designed; its efficacy not to be measured and judged by theory or opinion as to the efficiency of a certain dosage of a particular drug by itself. That the doses as contained are minimal and effective is distinctly advantageous.

The alkaline carbonates are in Carminzym in stated quantities; the physician adjusts the dosage to the individual patient and with obvious evidence of the efficiency of the adjustment. As we understand it, the employment of alkaline carbonates is not based on purely chemic considerations--a definite known quantity of acid of the gastric juice is to be neutralized; the whole literature and practice dealing with the alkaline carbonates show them to be accredited with a much wider field of use and repute in gastro-intestinal disorders.

The pancreatic extract in Carminzym is designed to be diffusible in the stomach, the tablet is preferable to be crushed in the mouth before swallowing, and we believe the pancreatic extract to be an effective constituent as administered in Carminzym.

You comment as follows:

“Ipecac has a well defined though limited field of usefulness. When it is used it should be given with due regard to the amount needed by the patient and the frequency of the repetition of the dose.”

This in a sense may be said of any of the most useful drugs, but not in the least special degree does it apply to ipecac, which is, on the contrary, of quite characteristic, peculiar range of therapeutic properties, useful in varying combinations and in widely varying proportions and doses according to the purpose for which it is employed.

Ipecac in well known official alkaline, carminative, laxative preparations occurs in the “average dose” in the varying quantities of 1/14, 1/10, 1/8, and 3/16 of a grain.

The ipecac in combination with the other ingredients in Carminzym is designed for a tablet which shall carry a minimal quantity whilst capable of adequate remedial action, thus admitting of increase of dosage or repetition as occasion requires. The quantity of ipecac was not taken at random, but chosen after long trial and consideration.

We believe that Carminzym possesses carminative properties in a superior degree and that, furthermore, in consequence of its composition it directly stimulates the gland secretions and thus exerts a beneficial action upon the whole digestive functions.

Carminzym is for use as occasion requires, and this is to be especially noted. Thus it is not only of direct benefit, but helpful in promoting systematic therapeutic measures and regimen.

The Council takes the ground that complex mixtures of remedial agents are so wrong that there is no longer warrant for their admission into New and Nonofficial Remedies; and that Carminzym is an irrational mixture.

We hold that certain desirable therapeutic properties may rationally be attributable to Carminzym; and that these are manifested in practice.

During the time since the description was sent and the receipt of the statement of the action of the Council, some ten months, Carminzym has proved of constantly increasing service.

The statement in the letter of Fairchild Bros. and Foster “The long established custom of the use of mixtures of remedial agents rests on considerations well known and generally accepted” might well be paraphrased to read: The one-time prevalent custom of using ill-considered combinations of remedial agents has been thoroughly discredited and is generally abandoned by progressive practitioners. Such arguments as that “laxatives, tonics, carminatives, diuretics are combined with distinct advantage” have led to the use of irrational mixtures such as the compound syrup of hypophosphites and the electuary of theriaca. The Council is confident that no one who has studied the causes and treatment of digestive disorders will find occasion to prescribe at one time all the ingredients stated to be contained in Carminzym, and certainly not in the fixed proportions present therein.

The comments in the Council’s report concerning ipecac certainly does apply to all active therapeutic agents. Ipecac was mentioned in the report because the several constituents of Carminzym were under discussion and hence it was necessary to point out the futility of the small dosage of ipecac in this mixture.

The announcement that “Carminzym has proved of constantly increasing service” is not convincing. The Council does not know of a single clinical study of the action of Carminzym under conditions which would have afforded satisfactory evidence of its therapeutic value.--(_From The Journal A. M. A., Sept. 28, 1918._)

PHILLIPS’ PHOSPHO-MURIATE OF QUININE COMP.

Report of the Council on Pharmacy and Chemistry

The following report on Phillips’ Phospho-Muriate of Quinine Comp. has been adopted by the Council and authorized for publication.

W. A. Puckner, Secretary.

Phillips’ Phospho-Muriate of Quinine Comp.[125] is sold by the Charles H. Phillips Chemical Co., New York. According to the published formula, each fluidram contains:

Phosphoric Acid 2 minims Potassium Phosphate } Magnesium Phosphate } Calcium Phosphate } 2-1/4 grains Ferric Phosphate } Quinin Muriate (equal to nearly 1/2 gr. Bi-Sulph.) 1/4 grain Strychnin 1/120 grain Flavoring, Glycerin and Syrup, _q. s._

[125] The evolution of “Phillips’ Phospho-Muriate of Quinine Comp.” from “Phillips’ Wheat Phosphates” may be interesting. Every one knows that therapeutics tends to fashions, and “Phillips’ Wheat Phosphates” appears to have had its inception as the result of the observation that super-refined white flour contains less phosphates than the corresponding amount of wheat. It was assumed that such flour must be deficient in an essential constituent, and the Wheat Phosphates preparation was apparently designed to fill the want. It was exploited for the relief of numerous conditions that were supposed, without satisfactory evidence, to result from this deficiency. When iron, quinin and strychnin mixtures became the vogue a quarter of a century ago, it was only natural to ride on the wave of popularity and the already widely advertised “Wheat Phosphates” was further enhanced--commercially--by the addition of the iron, quinin and strychnin, the amount of alkaloid added being practically negligible. Those who are not familiar with the various phases of the phosphorus, phosphoric acid, lactophosphate, lecithin, nuclein and glycerophosphate propaganda are referred to a report of the Council on Pharmacy and Chemistry in The Journal A. M. A., Sept. 30, 1916, p. 1033.

Some typical claims made for the preparation are:

“With marked beneficial action upon the nervous system. To be relied on where a deficiency of the phosphates is evident.”

“... brace those tired nerves and aid that worn stomach with Phillips’ Phospho-Muriate of Quinine.”

“The maintenance of a satisfactory blood pressure level free from intervals of depression may be accomplished by the use of Phillips’ Phospho-Muriate of Quinine Compound in appropriate doses.”

“The quantities of quinin and strychnin in this preparation are so well balanced that they relieve the depression and fatigue from mental or physical exertion, without the necessity of recourse to alcoholic stimulation.”

“The other ingredients of Phillips’ Phospho-Muriate of Quinine--phosphoric acid, and the phosphates of potash, magnesia, lime, and iron--are the most rational as well as convenient means of administering these tissue remedies, and of introducing phosphorus--the vitalizing constituent of the nervous system--into the organism.”

The action of such a mixture as a whole is practically that of the sum of the actions of its constituents. The therapeutic action of strychnin and quinin are described in every text-book of therapeutics, but it is necessary to distinguish carefully between the various conditions in which these alkaloids have been used without discrimination, and those conditions in which they have been proved to be of value. While both have been widely used in a great variety of conditions, neither is of proved value in more than a distinctly limited range of diseases. The manufacturers of Phillips’ Phospho-Muriate of Quinine Comp. seem to appeal to the less discriminating who use these alkaloids without any definite conception of exactly what they seek to accomplish with them. Quinin, although used by the uncritical in a host of diseases, has a definite field of usefulness in the treatment of malaria, both prophylactic and curative, but the required dose in the treatment of malaria is many times larger than that recommended in the Phillips’ preparation. The claim that the “strychnin and quinin in this preparation are so well balanced that they produce a mild, buoyant effect, so advantageous, instead of alcoholic stimulation, to relieve depression and fatigue from mental or physical exertion” is nonsensical, if, indeed, it is not mendacious balderdash.

Calcium and potassium have important functions in the body, but any deficiency that may arise is usually attributable to an inability of the body to utilize that which is supplied, for there is seldom any deficiency of these salts in the food, and when they are needed they are best supplied as simple solutions of the salts in appropriate doses without all of the other constituents of Phillips’ Phospho-Muriate of Quinine Comp.

Phosphoric acid exerts practically the same actions as other mineral acids, hydrochloric being usually preferred for internal administration in certain forms of indigestion, aside from which they are seldom used as such.

In the more recent literature for Phillips’ Phospho-Muriate of Quinine Comp., we find the attempt to utilize the well known craze about phosphorus, which has been through so many phases, every one of which has had its day and has been discarded.

The phosphoric acid and phosphates present in Phillips’ Phospho-Muriate of Quinine are of no more value in nervous diseases than is simple sodium phosphate which does not require the addition of a host of other ingredients for its action. As a matter of fact, the phosphates of calcium and potassium present in a dose of Phillips’ Phospho-Muriate of Quinine are probably devoid of appreciable effect in practically all conditions.

To pretend that one who suffers from physical and nervous exhaustion can be materially benefited by this mixture is sheer nonsense and is unworthy of a moment’s consideration by a clinician who is called on to treat such patients.

Iron is useful in anemia, as every one knows. Iron has practically no other field of usefulness in therapeutics. When it is indicated it should be administered in a simple form, such as the pill of ferrous carbonate, for example, and not in a “shotgun” mixture that is quite as likely to do harm as good.

The claim that a satisfactory level of blood pressure can be maintained by Phillips’ Phospho-Muriate of Quinine is mentioned only to condemn as the limit of impudent therapeutic claims. It is an insult to the intelligence of any practitioner to pretend that any known agent or combination of remedial agents can maintain a uniform blood pressure in any one of innumerable conditions.

In short, Phillips’ Phospho-Muriate of Quinine Comp. is a complex and irrational mixture exploited by means of unwarranted claims. It is a survival of the old days of therapeutic chaos when impossible and fantastic chemical formulas were gravely published and as solemnly accepted without question, and also without the slightest understanding on the part of many; when the most eminent of practitioners did not hesitate to give glowing testimonials for lithia waters that contained no more lithium than ordinary river water; when no therapeutic claim was too preposterous to receive acceptance, no theory too nonsensical to justify the use of all manner of claptrap mixtures for all manner of conditions.--(_From The Journal A. M. A., Oct. 19, 1918._)

B. IODINE AND B. OLEUM IODINE

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on “B. Iodine” and “B. Oleum Iodine,” together with the reply submitted by the manufacturer and a discussion thereon by the referee in charge of the preparations.

W. A. Puckner, Secretary.

Specimens of B. Iodine and B. Oleum Iodine (B. Iodine Chemical Company) and an advertising pamphlet were sent to the Council by John Bohlander, A.M., M.D., with the declaration:

“Well knowing the value of Iodin in surgical operations and dressings, prompted me for the benefit of my fellow physicians as well as myself, and for Humanity’s sake, to make Iodin my master-piece in chemistry.

“After several years of diligent work in my private laboratory I succeeded in discovering a new product of Iodin--Nitrogen, hydrate of Iodin.”

While “B. Iodine” is said to be nitrogen hydrate of iodin and “B. Oleum Iodine” a 5 per cent. solution thereof, the examination made by Prof. A. H. Clark of the University of Illinois, School of Pharmacy (working in the A. M. A. Chemical Laboratory), indicates that the first is a simple mixture of iodin and ammonium iodid, and the second a solution of iodin in liquid petrolatum. The Council adopted the report of the A. M. A. Chemical Laboratory (which appears below) and declared B. Iodine and B. Oleum Iodine inadmissible to New and Nonofficial Remedies because:

1. The composition is incorrectly declared. B. Iodine is not a newly discovered iodin compound, “Nitrogen Hydrate of Iodine,” but a mixture of iodin and ammonium iodid. B. Oleum Iodine is not a 5 per cent. solution of B. Iodine as suggested by the statement on the label and in the advertising, but a solution of iodin in liquid petrolatum containing about 0.85 per cent. of iodin.

2. Since B. Iodine is a mixture of Iodin and ammonium iodid, its solution in water will have the properties of other solutions of iodin made by the aid of iodid, such as a dilution of tincture of iodin or of compound solution of iodin (Lugol’s solution). Hence, the therapeutic claim that B. Iodine “being of a colloidal nature has the advantage of being more readily absorbed and taken up by all cellular structure, thus getting a perfect cellular medication of Iodine,” is unwarranted.

3. The names “B. Iodine” and “B. Oleum Iodine” are not descriptive of the pharmaceutical mixtures to which they are applied.

4. B. Iodine and B. Oleum Iodine are unessential modifications of established articles. B. Iodine has no advantage over tincture of iodin or compound solution of iodin. (As more convenient of transportation, the Medical Department of the U. S. Army supplies its field hospitals with a mixture of iodin and iodid ready for solution in water, either in tablet form or in powdered form in tubes.) Solutions of iodin in liquid petrolatum may be readily prepared (Reports Council Pharm. and Chem., 1917, p. 88).

[Contribution from the A. M. A. Chemical Laboratory]

B. IODINE PRODUCTS

A. H. Clark, Ph.G., B.S.

“B. Iodine” products are marketed by the B. Iodine Chemical Company, Cincinnati, Ohio; John Bohlander, A.M., M.D., is said to be the discoverer. They consist of “B. Iodine,” “B. Oleum Iodine,” and “B. Aqua Iodine.” B. Iodine and B. Oleum Iodine were submitted to the Council.

In a circular submitted by the B. Iodine Chemical Company, B. Iodine is said to be “Nitrogen Hydrate of Iodin.” It is claimed that “coming in contact with water, H₂O, a chemical change takes place forming Hydro Oxid of Iodin, the Nitrogen of the Nitrogen Hydrate of Iodin escaping, the balance taking up one of oxygen of the water. Its companion, the H₂, escaping at the same time with the Nitrogen then combining with the remainder of the water to form the solution of Hydrogen Oxid of Iodin; so you can readily see that you really have a pure water of Iodin, nothing but the H, the O and the I.”--(_From the Journal A. M. A., Feb. 1, 1919._)

B. IODINE

According to the circular, B. Iodine is soluble in alcohol, chloroform, and ether. Also it:

“Has odor, taste, melting and boiling point, same as regular Iodin, has a great affinity for water and will respond to all the tests of Iodin. Appears in a Bluish Black Granulated mass or Powder. When heated in vaporating dish will throw off large purple volumes of Iodin leaving a slight white crystalline precipitate, which on continuous heating will entirely disappear. With careful manipulation you can get prismatic needle point like crystals, looking like spores of glass, these dissolving in water will yield pure Iodin coloring the water Iodin.

“PHARMACOLOGIC, THERAPEUTICAL AND PHYSIOLOGICAL ACTION: Same as Iodin, being of a colloidal nature has the advantage of being more readily absorbed and taken up by all cellular structure, thus getting a perfect cellular medication of Iodin.”

A sample of B. Iodine, marked “Nitrogen Hydrate of Iodin” was submitted by the manufacturers and this sample was examined.

B. Iodine was found to be a granular powder, almost black with a purple cast. It has an odor of iodin and dissolves in water readily. It is also quite soluble in alcohol, but not entirely soluble in chloroform and ether. Ether quickly dissolves iodin from B. Iodine, leaving a residue of a white granular substance. Chloroform acts the same as ether except that the iodin is dissolved out with some difficulty. On heating B. Iodine, vapors of iodin escape. If the heating is done on a water bath, a residue of a white granular substance, subsequently identified as ammonium iodid, remains. If heated in a bunsen flame, no residue remains. These tests all indicate that iodin is held in the form of a simple mixture.

_Ammonia_: B. Iodine when mixed with an excess of sodium hydroxid and warmed, evolves ammonia.

_Iodine_: 0.1567 gm. B. Iodine dissolved in water required 5.88 c.c. tenth-normal sodium thiosulphate solution indicating 48.28 per cent. iodin. 0.3721 gm. B. Iodine required 14.18 c.c. tenth-normal sodium thiosulphate solution indicating 48.37 per cent. iodin. The average is 48.33 per cent. iodin.

_Ammonium Iodide_: 0.3453 gm. of the residue after heating B. Iodine on a water bath until all iodin had volatilized was dissolved in water, acidulated with phosphoric acid, and hydrogen dioxid solution added. The liberated iodin was extracted with chloroform and titrated with tenth-normal sodium thiosulphate. 23.78 c.c. were required indicating 0.3447 gm., or 99.83 per cent., ammonium iodid.

A mixture of 5 gm. iodin and 5 gm. ammonium iodid has the properties of B. Iodine mentioned above.

The conclusion is that B. Iodine is essentially a mixture of iodin and ammonium iodid in equal parts, the two substances being finely powdered and intimately mixed.

B. OLEUM IODINE

The following regarding B. Oleum Iodine is quoted from the circular submitted:

“B. OLEUM IODINE: Iodine soluble in mineral oil 5 and 10% for Nasal, Pharyngeal, Laryngeal, Bronchial, Rectal, etc., and all meucoid affections and abnormal conditions of the mucous membrane.”

A sample of B. Oleum Iodine was submitted by the manufacturer and examined. The label on the bottle states that it is 5 per cent. B. Oleum Iodine in mineral oil. This sample has the characteristics of a solution of iodin in liquid petrolatum. It is oily and has the characteristic violet color.

_Ammonia_: B. Oleum Iodine, since it is presumed to be a solution of B. Iodine, was examined for ammonium compounds. A small quantity was mixed with an equal volume of strong sodium hydroxid solution and heated. No ammonia was evolved. A few crystals of ammonium chlorid were added to a little of B. Oleum Iodine and treated as above. Ammonia was readily detected.

_Iodine_: 5.255 gm. B. Oleum Iodine was dissolved in chloroform and placed in a separator. A solution of potassium iodid was added and the iodin titrated with a tenth-normal sodium thiosulphate solution. It required 3.5 c.c. indicating 0.85 per cent. iodin.

The conclusion is that B. Oleum Iodine is a simple solution of iodin in liquid petrolatum to the extent of 0.85 per cent. and not 5 per cent. as claimed. Furthermore, it is not a solution of B. Iodine since no ammonium compound is present.

The preceding report was sent to the B. Iodine Chemical Company. The following reply was received:

Your letter of the 21st inst., received and contents noted and cannot quite agree with your report.

Reasons why: NH₄I, a Nitro Hydrate Iodide; NH₄I₂, a Nitro Hydrate Iodate; and NH₄I₂I₂, Per Iodide, a molecular compound, which I claim, they all being of a NH group, so what can be the objection of Nitrogen Hydrate of Iodine? Of course when your chemist, with the aid of heat, drove off all the Iodine, he naturally brought it back to a NH₄I. There’s where he gets the A.M.. I claim a molecular compound.

The Oil of Iodine I sent you by mistake was a 1 per cent. and not a 5 per cent. as marked. I claim it is made from the resublimed Iodine in mineral oil and not the B. Iodine. I claim a 5 per cent. has heretofore never been accomplished, so I therefore can claim something new.

Tr. Iodine contains Alcohol and Potash as a base, the alcohol a dehydrater and Potash an escharotic, and all other soluble Iodines like the tincture have a metallic base. Mine has not. My iodine is compatible almost with all the salts, alkaloids, tannates, and even the metals. You can’t say that for the tincture or the others. Now why should mine not be superior to others?

Preparations as yet are not on the market and a few pamphlets were printed to meet with the requirements of your rulings and approval and shall be corrected if we only can agree on a proper name as you may suggest.

Yours very truly, THE B. IODINE CHEMICAL CO. By John Bohlander, A.M, M.D.

P.S. We are sending you under separate cover another sample of the Oil of Iodine which is a 5 per cent. solution, and allowing for deterioration will test at least four per cent.

The referee in charge of the preparations submitted the above letter to the Council with the following comments:

The principal statements in the letter are essentially erroneous or misleading: Mixtures or double salts of ammonium iodid and iodin were not discovered by Dr. Bohlander, and are nothing new. Watery solutions of iodin by means of an iodid have long been known and used in the form of Lugol’s solution.

There is no evidence that ammonium iodid is less irritating than potassium iodid. On the contrary, ammonium salts are generally more irritating than the corresponding potassium salts. B. Iodine is not compatible with alkaloids, but behaves essentially like Lugol’s solution. The A. M. A. Chemical Laboratory reports that the new sample of B. Oleum Iodine contains only 1.2 per cent. of free iodin, instead of the claimed amount. It is therefore somewhat weaker than the iodin petrolatum prepared by the A. M. A. Chemical Laboratory (Reports Council Pharm. and Chem., 1917, p. 88).

However good Dr. Bohlander’s intentions may be, the statements that he makes about his products are misleading or erroneous, and the products are ineligible for N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 44._)

ANTITHYROID PREPARATIONS (ANTITHYROIDIN-MOEBIUS AND THYREOIDECTIN) OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of antithyroid preparations (Antithyroidin-Moebius and Thyreoidectin) has been authorized for publication.

W. A. Puckner, Secretary.

New and Nonofficial Remedies, 1918, contains a discussion of “antithyroid” preparation and describes two of these: Antithyroidin-Moebius (E. Merck, Darmstadt, Germany) and Thyreoidectin (Parke, Davis & Company, Detroit, Mich.).

The referee reported that these “antithyroid preparations” evidently have not realized the expectations of their promoters, and are viewed with skepticism by practically all critical clinicians.

Consequently, notwithstanding the cautiously worded statements of claims made by the manufacturers of Thyreoidectin, the Council approved the recommendation that this preparation (Thyreoidectin) be omitted from New and Nonofficial Remedies for conflict with Rule 6 (unwarranted therapeutic claims) and Rule 10 (unscientific and useless articles) (Antithyroidin-Moebius had already been omitted because it was off the market). The Council further directed that the general article “antithyroid preparations” be also omitted.

The Council having adopted the recommendation of the referee, Thyreoidectin is omitted from N. N. R., while the general article appears below, as a matter of record:

Antithyroid preparations are obtained from the blood or milk of animals, after the removal of the thyroid glands.

The use of these preparations is based on the theory that the thyroid gland secretes products which are toxic, but which neutralize and are neutralized by, other toxic substances produced elsewhere in the body. Removal of the thyroid glands would then lead to the accumulation of these second toxic substances as evidenced by the phenomena of cachexia strumipriva and myxedema. On the other hand, the blood or milk of such animals is claimed to be capable of preventing the effects of hypersecretion of thyroid substance, such as is supposed to occur in hyperthyroidism (Basedow’s or Graves’ disease--generally called exophthalmic goiter).

These views are largely hypothetical; attempts to give to them a rational experimental basis have failed, but some clinical observers report distinctly beneficial results in the milder forms of the diseases, and in obscure nervous disorders which are supposedly connected with thyroid hypersecretion from the administration of the milk from thyroidectomized goats and also from the use of the proprietary blood preparations listed below. The value of these preparations is very doubtful. The reported improvements may only be psychical or due to associated measures, as is often seen in this disease. Other measures of treatment should not be neglected.

Improvement is said to occur in two or three weeks and to be indicated by an amelioration of the nervous symptoms, tremor, palpitation, insomnia and excitability.

The administration must be long continued. Oral and hypodermic administration are said to be equally effective, but the former is usually preferred. These preparations are not known to be toxic, even when very large doses are used.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 50._)

CEPHAELIN AND SYRUP CEPHAELIN-LILLY OMITTED FROM N. N. R. AND SYRUP EMETIC-LILLY NOT ACCEPTED

Report of Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, which explains the omission of cephaelin and Syrup Cephaelin-Lilly from New and Nonofficial Remedies and the non-acceptance of Syrup Emetic-Lilly.

W. A. Puckner, Secretary.

New and Nonofficial Remedies, 1918, describes cephaelin (an alkaloid obtained from ipecacuanha root) and lists Syrup Cephaelin-Lilly (containing 0.088 Gm. cephaelin hydrochlorid per 100 Cc.) as a pharmaceutical preparation of it.

The period of acceptance for Syrup Cephaelin-Lilly having expired, Eli Lilly & Company were asked to send the current advertising and labels so that the Council might determine if the acceptance of this preparation might be continued. In reply the firm wrote:

“We have changed the name Syrup Cephaeline to Syrup Emetic but the product remains the same as before. We have no circulars describing Syrup Emetic and can only send copies of the label.”

The new name “Syrup Emetic” conflicts with the rules of the Council in that it does not indicate the potent ingredient of this simple pharmaceutical preparation and in that it is therapeutically suggestive. Emetics are powerful agents, and physicians should be given every opportunity of knowing what they prescribe for the purpose.

The name being in conflict with Rule 8, the Council voted to omit Syrup Cephaelin-Lilly and not to accept Syrup Emetic-Lilly.

As the cephaelin syrup was the only preparation of cephaelin admitted to New and Nonofficial Remedies, and as the alkaloid appears to have no important therapeutic field, the Council directed that the description of cephaelin also be omitted.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 52._)

COLALIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Colalin has been authorized for publication.

W. A. Puckner, Secretary.

Colalin is a bile salt preparation claimed to consist essentially of hyoglycocholic and hyotaurocholic acids. It is manufactured by Rufus Crowell and Company, Somerville, Mass., and marketed by Schieffelin and Company, New York.

An examination of the current advertising by the referee of the Council in charge of bile salt preparations having revealed that claims were made for Colalin which were not in harmony with the known action of bile preparations, Schieffelin and Company were informed that in the opinion of the referee the Colalin circular matter required radical revision. In this communication the referee’s objections to the claims were set forth in detail.

No reply to this letter was received, and hence a copy of the letter was sent to Schieffelin and Company and also to Rufus Crowell and Company with the explanation that unless the statements in the Colalin advertising which the referee had questioned were substantiated by satisfactory evidence, were suitably revised, or else the advertising matter withdrawn pending revision, the referee would be obliged to recommend to the Council that Colalin be omitted from New and Nonofficial Remedies.

In reply, Schieffelin and Company wrote that they were not “engaged actively in the introduction of Colalin,” and agreed to the omission of Colalin from N. N. R.

In view of the failure to substantiate the claims objected to or an agreement to discontinue them, the Council directed that Colalin and Colalin Tablets be omitted from New and Nonofficial Remedies for conflict with Rule 6 (unwarranted therapeutic claims).

The following are the claims which the referee questioned:

“Colalin embodies the physiological function of the bile in the intestinal canal and also possesses properties of its own which are intimately connected with the function of the liver.”

The quotation implies that Colalin has properties essentially different from those of bile salts, a claim which requires substantiation.

“In the liver its action seems to be that of a general stimulant of all the hepatic functions.”

This is a claim which requires substantiation.

“By the introduction of Colalin it has therefore become possible to actually utilize the bile for therapeutic purposes.”

This is an unwarranted claim, for bile was used therapeutically before Colalin was introduced.

“As gall-stones are chiefly composed of cholesterin, experiments were made to determine whether Colalin would dissolve these concretions outside of the body. These were completely successful and were then followed by an extensive series of clinical investigations on persons suffering with cholelithiasis, which demonstrated that by the administration of Colalin in many instances gall-stones were evacuated by the natural passages and their further formation prevented without resort to surgical intervention.”

This is misleading in that the context shows that “without surgical intervention” is meant to imply a connection between the experiments showing the solvent power of Colalin and the passage of concretions.

“... Colalin not only acts as a solvent of cholesterin calculi, but prevents their further formation by removing the causes upon which their development depends.”

This conveys the impression that such solvent action is exerted in the body, that is, that such concretions in the gallbladder may be dissolved and evacuated by the use of Colalin. For this claim there is no evidence.

“To understand the value of Colalin in intestinal disorders it is necessary to bear in mind the important functions of the bile in the intestinal canal, namely, its participation in the digestion of fats, its antitoxic action, and its influence upon the peristalsis.”

“... through its antiseptic influence inhibits the production of toxins in the intestines.”

The referee believes that there is no satisfactory evidence that bile or bile salts can inhibit the production of toxins in that part of the intestine--the colon--in which they are commonly produced.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 52._)

FORAL

Report of the Council on Pharmacy and Chemistry

The following report on Foral, a depilatory preparation, has been authorized for publication by the Council.

W. A. Puckner, Secretary.

Foral is sold by the Foral Products Company, Pittsburgh, Pa., as an “antiseptic depilatory” with the special claim for its use for the removal of hair prior to surgical operation or the dressing of wounds. In addition to claims made for its hair dissolving action, it is asserted that, in removing the hair from an open wound, Foral acts as “an antiseptic, which guarantees against any infection.” It is also claimed that, though hair will return after its use, “by proper use it will diminish the growth of hair and cause the hair to grow much slower, and unlike the razor, the hair will not return coarser and thicker.”

We are informed by the Foral Products Company that their preparation is used in many hospitals and that “... one and all are well pleased and a great satisfaction to do away with the old style razor ...”

Foral is stated to be made according to the following formula:

_To manufacture seventy-five pounds of FORAL_

Starch 35 pounds Barium-Sulphide 20 pounds Zinc-Oxide 10 pounds Calcium-Carbonated-Precip. 10 pounds Potassium-Permanganate 10 grams Menthol-Crystallized 10 grams Carbolic-Acid 1/2 ounce Lilac or Citronel oil 3 ounces

The four above chemicals are going to a heating process before mixing or sifting.

In consideration of the preceding, the Council declared Foral inadmissible to New and Nonofficial Remedies for conflict with its rules, thus:

1. Foral is an unessential and irrational modification of an established article.

While its manufacturer states that Foral has been on the market for eighteen years, the following depilatory formula appears in a book published thirty-five years ago (A practical Treatise on Diseases of the Skin, Louis A. Duhring, Ed. 3, 1883) and is to be found in most books on dermatology:

Barium Sulphid 2 drams Zinc oxid 3 drams Starch 3 drams

Permanganates and sulphids mutually destroy each other, and therefore the addition of the small amount of potassium permanganate cannot serve any useful purpose. The amounts of phenol, menthol and “Lilac or Citronel oil” are too small to exercise any effect (other than that of a flavor) and must be considered unessential additions.

2. Foral is a pharmaceutical mixture marketed under a non-informing name.

Whereas it is in the interest of rational medicine that physicians should know the composition of the preparations which they use, the name of this pharmaceutical mixture fails to indicate that it contains the well-known and by no means always harmless barium sulphid.

3. Foral is sold under exaggerated and unwarranted claims.

In view of the small amount of phenol present and the method of using the preparation, the claim that the use of Foral which, when operating on open wounds, “guarantees against any infection,” is evidently unwarranted.

There is no evidence for the claim that the use of depilatories such as Foral retards the growth of hair or renders hair less coarse. On the contrary, the commonly prevailing opinion is that depilation, like shaving, makes the hair coarser.

To determine if “one and all” of those who had used Foral were still using the preparation, four of the testimonials, appearing in an advertising pamphlet, were investigated. The pharmacist of the hospital from which the first of these testimonials was stated to have emanated replied that the person whose name appeared in connection with it had left the hospital about ten years ago and that no depilatory preparation has been used in this hospital for some time. So far as he knew, depilatories were not now in use in the surgical wards of the hospital. In regard to the second testimonial, the pharmacist of this hospital wrote that the hospital had not bought the preparation, but that some of it had been obtained for an elderly deaconness, who had personal use for a depilatory. The physician signing the third testimonial replied that the preparation was effectual for the removal of hair from the scalp, but that “... we have gotten out of the habit of using it.” In the case of the fourth testimonial, its asserted author wrote “... if it is applied in too large a quantity or too concentrated, or permitted to remain on too long, it will vesicate. It was for this reason chiefly that I discontinued its use. It is a very bad smelling mixture and patients complain of it very bitterly.”--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 55._)

GRANULAR EFFERVESCENT BROMIDE AND ACETANILID COMPOUND-MULFORD

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Granular Effervescent Bromide and Acetanilid Compound-Mulford has been authorized for publication.

W. A. Puckner, Secretary.

The Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of the individual patients without which there can be no drug therapy. On the contrary, with the use of such mixtures, therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10, concerning the recognition of mixtures, with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture, it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer warrant for the admission of complex mixtures to New and Nonofficial Remedies, or for the retention of any that have been admitted, unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision, several mixtures now described in New and Nonofficial Remedies will be omitted at the expiration of the three year period for which articles are accepted.

Granular Effervescent Bromide and Acetanilid Compound-Mulford is listed in the Appendix to New and Nonofficial Remedies. Each 100 Gm. of the mixture contains sodium bromide, 5 Gm., and acetanilid, 1.5 Gm. According to the label, an amount containing acetanilid, 6.5 grains, and sodium bromide, 22 grains, is to be taken at a dose, to be repeated in half an hour if necessary. For “children,” half this dose is advised.

The Council has considered the available evidence for mixtures of this sort, and has reached the conclusion that they are inimical to rational medicine and the public, and therefore in conflict with Rule 10. It holds that the use of mixtures of acetanilid and sodium bromide in fixed proportion is irrational and prone to induce their indiscriminate use by the public. Despite the perfectly frank declaration of the composition of this mixture that is made by the Mulford Company, the “directions” will be followed blindly and the preparation will be given to “children” and “repeated in half an hour, if necessary” in cases in which it would be held unwarranted to administer a dose of 3 grains of acetanilid to a child.

The period of acceptance having expired for Granular Effervescent Bromide and Acetanilid Compound-Mulford, the Council directed its omission from New and Nonofficial Remedies for conflict with Rule 10.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 58._)

HOLADIN AND BILE SALT MIXTURES

Holadin and Bile Salts-Fairchild; Capsules of Bile Salts, Succinate of Soda and Phenolphthalein-Fairchild; Capsules of Holadin, Bile Salts and Phenolphthalein-Fairchild; Capsules of Holadin, Succinate of Soda and Bile Salts-Fairchild.

Report of the Council on Pharmacy and Chemistry

To explain the omission from New and Nonofficial Remedies of certain mixtures, the Council has authorized publication of the matter which appears below.

W. A. Puckner, Secretary.

The Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of individual patients without which there can be no rational drug therapy. On the contrary, with the use of such mixtures, therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer any warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision, several mixtures now described in New and Nonofficial Remedies will be omitted as soon as the three year period for which articles are accepted has expired.

The following preparations are included in New and Nonofficial Remedies, 1918:

Holadin and Bile Salts-Fairchild.--A mixture of holadin, 5 parts, with bile salts-Fairchild, 1 part, put up in 3 grain capsules.

Capsules of Bile Salts, Succinate of Soda and Phenolphthalein.--Each capsule contains bile salts-Fairchild, 0.065 Gm. (1 grain); sodium succinate exsiccated, 0.2 Gm. (3 grains), and phenolphthalein, 0.03 Gm. (1/2 grain).

Capsules of Holadin, Bile Salts and Phenolphthalein.--Each capsule contains holadin, 0.13 Gm. (2 grains); bile salts-Fairchild, 0.03 Gm. (1/2 grain), and phenolphthalein, 0.065 Gm. (1 grain).

Capsules of Holadin, Succinate of Soda and Bile Salts.--Each capsule contains holadin, 0.20 Gm. (3 grains); sodium succinate exsiccated, 0.20 Gm. (3 grains), and bile salts-Fairchild, 0.03 Gm. (1/2 grain).

Oxbile has long been credited with a cholagogue action, which, however, has probably been greatly overestimated. When pure bile salts were placed on the market some years ago, they and their compounds were admitted to N. N. R.

Holadin is said to represent all the constituents of the pancreas and to possess great potency in respect to the several enzymes, trypsin, amylopsin, lipase, and the milk-curdling ferment.

It is not clear when such a substance is indicated therapeutically. While it may be useful when there is a deficiency of pancreatin and gastric secretion, it should be used alone.

It is also quite possible that bile salts may have a distinct, though limited, field of usefulness when there is a deficiency of biliary secretion; but the bile salts are best administered alone, or in combination with such laxatives as may be deemed necessary by the physician while keeping in mind the fact that different patients show the widest difference in their reaction to laxatives, making combinations of these agents in fixed proportion irrational.

Phenolphthalein was popularized by nostrum makers; and while it has some therapeutic value, this has been greatly overestimated, and it should be used only in amounts deemed necessary for each patient, preferably alone.

Succinate of sodium was introduced as a saline cathartic, with the claim that it exerts an antiseptic action on the biliary passages and gallbladder. There is no satisfactory evidence to substantiate this claim.

The Council maintains a liberal attitude toward new preparations, but it feels that it is impossible to determine the value of the several constituents of such complex mixtures when used as such; it holds that these mixtures are superfluous and that the several substances of which they are composed should be used singly or at most with greater attention to the individual requirements of the patient than is possible when these fixed mixtures are prescribed.

Despite the fact that these mixtures have been in use for more than nine years, there is no satisfactory evidence that they possess any advantage over the simple laxatives or the preparations of bile or pancreatic extract. They are therefore held to be in conflict with Rule 10, and the Council has directed that they be not included in N. N. R. after Dec. 31, 1918.

Having adopted the preceding report, the Council, in accordance with its regular procedure, submitted this to Fairchild Bros. and Foster for comment.

The following reply was received:

We are entirely at variance with you in the arbitrary conclusion expressed concerning the inimical influence of mixtures on therapeutic progress, the practice of medicine and the public welfare.

If the combinations of Holadin and Bile Salts, etc., in capsules, were ever properly within the scope of New and Nonofficial Remedies, they should be retained. If, however, complex mixtures are to be held as, a priori, unworthy of consideration, the rejection of all would naturally be a logical proceeding.

We believe that the particular combination of Holadin and Bile Salts etc., have been clearly in the line of therapeutic progress--a natural evolution, improvement and development.

For many years combinations of pancreatic extract and ox gall had naturally suggested themselves.

When we realized the fact that the bile salts were quite clearly the active principles of the bile, and that they must necessarily exist in greatly varying percentages in the official inspissated or ox gall, and also because these ox gall products of pharmacy were of extremely varying density, even from that of treacle to resin--and of other objectionable character, we undertook to prepare bile salts.

These combinations are now further justified in view of physiological considerations, the simultaneous secretion of the pancreas and bile, and the state of our knowledge of the function of bile salts, and as co-ferments, promoting and supplementing the pancreas enzymes.

The question suggested as to whether the cholagogic action of ox gall (and bile salts) has been overestimated seems to us no clear purport. The bile salts are obviously employed as the means of administering and thus realizing whatever properties this secretion may have in medicine, of which the cholagogic action is by no means the only consideration.

As for phenolphthalein, which is credited with purely laxative properties, we are at a loss to see any bearing in the remark that phenolphthalein was popularized by nostrum makers. We cannot see that the physician’s or chemist’s estimate of phenolphthalein, its properties and uses, can be in the least degree influenced one way or the other by the statement that “phenolphthalein has been popularized by nostrum makers.”

The phenolphthalein and succinate of soda combinations were originally both prescribed, and we have simply placed them at the service of the physician without other exploitation of them than that designed to call attention to their use in the conditions indicated.

These combinations are offered in a form which may be administered by the mouth with the best promise of introducing the substance more directly in the intestinal tract during the digestion period or at such interval after or prior to, the digestion period, as would best, in the judgment of the physician, meet the indications.

These particular combinations are especially desirable in these “fixed forms” since they are stable and reliable resources at the command of the physicians, the enzymes retaining their stability and potency without material deterioration for many years, and they naturally possess the advantages which are obviously due to the character of the particular pancreas and bile products used in the combinations.

Furthermore, the hygroscopic and soluble organic substances in admixture cannot extemporaneously be so prepared in sealed capsules as to be readily available under the practical requirements of prescribing and dispensing. And we do not believe that those who practice medicine will be in accord with your view that the pancreas substance should necessarily be administered alone, or the bile substance alone.

It now appears that these combinations are to be dropped from New and Nonofficial Remedies in consequence of the view, so stated, that in clinical experience “for more than nine years there is no satisfactory evidence that they possess any advantage over the simple laxatives or preparations of bile or pancreatic extract.”

In reply to this we would simply make the following comment:

During these “nine years” these combinations have inevitably been put to an informing clinical trial, because of the fact that they have been employed with success in disorders of the pancreas and bile functions and often in chronic and serious cases where the clinical conditions were obvious and unmistakable.

The reports of these cases come to us from physicians widely separated and each of his own independent initiative. It would seem gratuitous, to say the least, to state that the observers are “disinterested,” since it is quite clear that there is no other interest than that of the practitioner and his patient.

It is not a case of a new drug or combinations of new remedies, but simply resources which, upon well grounded reasons, both from a theoretical and material standpoint, justify clinical trial, and with results which would seem from any ordinary human standpoint to be satisfactory clinical evidence.

As to the interpretation of competent clinical evidence by the Council, we would, in view of the circumstances and without comment, ask to embody in this text this rule:

“Clinical Evidence.”--“To be acceptable, the clinical evidence must offer objective data with such citation of authority as will enable the Council to confirm the facts and establish the scientific value of the conclusions drawn. Clinical data are worthless when the author is not cited. The facts on which claims with regard to the value of a remedy are based must have been rendered accessible for investigation and confirmation by disinterested observers, either through publication or through the records of a hospital or other institution.”

To discredit these combinations would seem to us not only unjustified, but sterile of any real advancement in medicine, or of anything in the way of helpfulness to the patient in the class of cases in which these products have been resorted to with benefit; this on no other ground really than the opinion “that they have no advantage over the simple preparations themselves.”

Naturally we shall continue to prepare these products and shall continue to take such action as we deem best to bring them to the attention of the physician, for the conduct of our business must remain in the hands of those who are personally responsible for it.

And it is now forty years since we took up this line of work and with the declared intention of devoting ourselves to the applied science of the digestive ferments and “to their development and practical application in every useful purpose in medicine.”

We have been consistently in sympathy with the fundamental purpose of the Council, which must first rest upon fact as to the character of the products offered as medicinal agents. The weight of evidence justifies the position that these particular products rationally should be, and as a matter of fact are, of important special service in the utilization of these organic secretions in medicine.

As explained in the preceding report, the Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible to determine accurately the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because such a practice tends strongly to discourage careful consideration of the special needs of individual patients without which there can be no therapeutic progress. On the contrary, with their use, therapeutic treatment becomes haphazard and mere guesswork.

The dismissal of the holadin and bile salts mixtures does not involve the question of the usefulness of holadin or of bile salts alone; on the contrary, the possible usefulness of these preparations is admitted in the report. It is the combination of holadin, bile salts, sodium succinate and phenolphthalein to which objection is made.

The statement of Fairchild Bros. and Foster that “these combinations are now further justified in view of physiological considerations” is somewhat misleading. It is true that bile and the pancreatic secretion cooperate in intestinal digestion, but there is no evidence that in every case in which there is a deficiency of one of these secretions there is also a deficiency of the other, and it is an axiom of scientific therapeutics that no drug or remedial agent should be administered except to fill a definite want. Otherwise the practice of therapeutics becomes mere empiricism.

The properties of phenolphthalein are not in the least influenced by the manner of its introduction, as Messrs. Fairchild Bros. and Foster emphasize; but the important fact in this connection is that the popular conception of their actions is greatly influenced by the mode of introduction, and phenolphthalein has been widely advertised in a variety of conditions, so that the popular notion concerning it is not that of scientific therapeutics.

In short, the entire argument of Messrs. Fairchild Bros. and Foster concerning the exploitation of these preparations may be summed up by saying that they have been used by clinicians who believe that good results have followed their use, and that the firm will therefore continue to supply the demand. The tendency of some to use anything brought to their notice, and the readiness of manufacturers to market anything that physicians will use, presents the greatest obstacle to therapeutic progress. There was never a nostrum so irrational or worthless that honest but undiscriminating clinicians could not be found who reported wonderful results from its use.

According to Fairchild Bros. and Foster, these holadin and bile salts mixtures have been in use for some nine years. Yet the Council is not aware of any investigation of their merits that meets the requirements of scientific research.

The Council is not acquainted with a single clinical investigation of their action under conditions which afford satisfactory evidence of their therapeutic value.

It is obviously wholly insufficient for a clinician to report that the use of a mixture was followed by good results. The fallacy of such arguments was demonstrated long ago. He must make a comparison of the results obtained with the remedial agent with those obtained in as nearly similar conditions as possible except for the use of the agent. We are not aware that any such study of the mixtures in question has been made. It is in the last degree irrational to hold that because bile salts are the active constituents of bile, therefore such complex mixtures as these are necessary.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 59_)

LIQUOR SANTAIVA, S. & D., OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Liquor Santaiva, S. & D., has been authorized for publication.

W. A. Puckner, Secretary.

So far the Council has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture, it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer any warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted, unless definite evidence of the therapeutic value of such combinations is available.

The Council being engaged in the annual revision of New and Nonofficial Remedies, the referee in charge of santal preparations reported that the three year period of acceptance had expired for Liquor Santaiva (Sharp & Dohme).

The referee held that Liquor Santaiva, S. & D., declared to be a solution of santal oil and copaiba with aromatic oils, in a mixture of alcohol and water, is plainly in conflict with the current interpretation of Rule 10, because there was no sound evidence to indicate that any useful end is gained by the simultaneous administration of santal oil and copaiba in any proportion, and that so, of course, there is no evidence of the special advantage in the fixed proportions represented by the mixture. He pointed out that the formula is essentially a survival of the discredited shotgun gonorrhea mixtures and therefore recommended that its acceptance be not continued.

The Council agreed to the recommendation of the referee and directed that Liquor Santaiva, S. & D., be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 66_)

MALTZYME, MALTZYME WITH CASCARA SAGRADA, MALTZYME WITH COD LIVER OIL, MALTZYME FERRATED AND MALTZYME WITH YERBA SANTA OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of the Maltzyme preparations has been authorized for publication.

W. A. Puckner, Secretary.

In 1916, the Council voted to omit Maltzyme with Hypophosphites, and Maltzyme with Phosphate of Iron, Quinine and Strychnine. At that time the labels used on the Maltzyme preparations still in New and Nonofficial Remedies contained a list of Maltzyme combinations which included those which had been dismissed. As the Council does not permit an accepted article to be used as a means of advertising an article not accepted, it voted to continue the following preparations for a period of three years on condition that reference to the deleted articles be omitted from the labels when those then in stock had been used up: Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa. While the Maltzyme Company made no definite agreement to revise its advertising propaganda in accordance with the Council’s requirements, the Maltzyme preparations were retained in the belief that in due time the required revision of the labels would be made.

The Council being engaged in preparing the 1919 edition of New and Nonofficial Remedies, the referee in charge of malt extracts reported that the Maltzyme Company had not revised its labels in accordance with the stipulation of the Council. The referee further reported he had become convinced that the claim that Maltzyme is “rich in malt enzymes” is unwarranted and that the term “Maltzyme” (malt plus enzyme) is misleading; this because of the recognized instability of malt extracts (Jour. A. M. A., March 30, 1912, p. 954) and because the Maltzyme Company makes no definite statement with regard to the diastase (malt enzyme) content of its preparations.[126] For this reason it had been the referee’s intention to propose the deletion of all Maltzyme preparations when their period of acceptance expired in 1919. As, however, the present Maltzyme preparations are in contravention with the Council’s requirements, he recommended that the acceptance of these preparations be canceled now.

[126] Manufacturers are warned by the Department of Agriculture, through the Bureau of Chemistry, that combinations claiming to contain digestive enzymes must be active when sold. If preparations tend to deteriorate in a short time, each lot should be dated and not sold after the period when they become inactive. While every manufacturer must be considered innocent until proved guilty, and ignorant until proved knowing, it is a matter of knowledge that manufacturers have marketed their various digestive mixtures with full appreciation of their worthlessness.--(Jour. A. M. A., Dec. 19, 1914, p. 2234.)

The Council agreed to the recommendation of the referee and directed that Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated, and Maltzyme with Yerba Santa be omitted from N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 67_)

METHAFORM OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Methaform has been authorized for publication.

W. A. Puckner, Secretary.

Methaform is the proprietary name applied by F. Stearns & Co. to chlorbutanol.

Being engaged in the annual revision of New and Nonofficial Remedies, and the term of acceptance for Methaform having expired, a trade package was purchased to determine if the product was marketed in compliance with the rules of the Council. It was then found that a circular was wrapped with the trade package which advertised Methaform Inhalant, a preparation not accepted for New and Nonofficial Remedies.

For obvious reasons, the Council does not countenance the use of an accepted article as a means of advertising an article not accepted. Accordingly F. Stearns & Co. was advised that the Council would be obliged to withdraw the acceptance of Methaform unless the objectionable circular was omitted from the Methaform packages. Stearns & Co. did not give the requested assurance, and therefore the Council directed that Methaform be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 68_)

PINEAL GLAND, RED BONE-MARROW AND THYMUS GLAND AND THEIR PREPARATIONS OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of pineal gland, red bone-marrow and thymus gland and their preparations has been authorized for publication.

W. A. Puckner, Secretary.

Pineal gland, red bone-marrow and thymus gland were admitted to New and Nonofficial Remedies when these products gave promise of having therapeutic value.

The term of acceptance for the preparations of pineal gland, red bone-marrow and thymus gland having expired, the referee in charge of animal organ preparations recommended in his report for the annual revision of N. N. R. that these products and the general articles describing them be omitted from New and Nonofficial Remedies. He held that the experimental and clinical experience with them leads to the conclusion that they are without value.

In accordance with the recommendation of the referee, the Council voted that the following preparations be omitted from New and Nonofficial Remedies: Desiccated Pineal Gland-Armour; Pineal Gland Tablets-Armour; Extract of Red Bone-Marrow-Armour; Desiccated Thymus-Armour; Thymus Tablets-Armour.

As a matter of record, the descriptive articles for pineal gland, red bone-marrow and thymus gland, which appeared in New and Nonofficial Remedies, 1918, are given below.

Pineal Gland

The functions of this gland have not yet been established but there is some pathological and some experimental evidence that there is a relation between the gland and some processes of development and growth; the nature of this relation is unknown. Adiposis is a frequent sign of disturbed pineal function, but observers are not agreed whether to interpret this as indicating hypofunction or hyperfunction, or possibly a concurrent disturbance of the pituitary. In some instances intravenous injections of pineal extract have seemed to cause a distinct fall in blood pressure. It has been inferred from observations in cases of pineal tumors in the young that the gland in young individuals furnishes a secretion which inhibits growth, particularly the development of the reproductive glands, but the results of experimental administration of pineal substance orally have led other observers to infer that the pineal secretion favors physical and possibly mental and sexual development. It has been suggested that, as all evidence points to the fact that the function of the pineal gland is one of early life, extract of adult pineal glands might be expected to be inert. Experiment has also indicated greater activity in glands obtained from young animals than in those obtained from older ones. The Council has decided to admit preparations of pineal gland to New and Nonofficial Remedies simply for experimental purposes.

Red Bone-Marrow

Red bone-marrow consists largely (more than 90 per cent.) of fat. In new-born animals a third or more of this fat consists of lecithin. The marrow of the bones of new-born animals contains iron (up to 1 per cent. or more) in various forms of organic combination. Both lecithin and iron decrease rapidly in the first weeks after birth. The commercial preparations contain very variable amounts of these constituents.

_Actions and Uses._--Red bone-marrow is supposed to stimulate the formation of red blood corpuscles; whatever action it may have in this direction is probably due largely to the iron and lecithin which it contains.

It is said to be useful in simple and pernicious anemias.

Thymus Gland

Little is known as to the functions of the thymus, but it is believed to have an important relation to growth. There also seems to be some relation between the thymus and thyroid, for the former is frequently abnormal in diseases involving the latter (hyperthyroidism).

The use of thymus is purely empirical. It has been employed in the treatment of hyperthyroidism, rickets, tuberculosis, hemophilia, and infantile marasmus and atrophy; its use in the latter conditions is said to be the most promising. It is claimed on very doubtful grounds to exert a somewhat favorable effect in certain cases of cancer.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 69_)

PIPERAZINE AND LYCETOL OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Piperazine and Lycetol has been authorized for publication.

W. A. Puckner, Secretary.

Piperazine (diethylenediamene) and Lycetol (a methyl derivative of diethylenediamene) were accepted for New and Nonofficial Remedies in 1906. Both Piperazine and Lycetol were asserted to be efficient uric acid solvents and efficacious remedies in the treatment of gout and rheumatism. These products have been retained until now because there was no investigation which definitely showed their uselessness as uric acid solvents, though their use is generally admitted to have been disappointing.

From an exhaustive and critical study of the available evidence, Hanzlik (Jour. Lab. & Clin. Med., February, 1917) concluded that scientific evidence, though limited, and clinical opinion indicate that Piperazine is valueless in gout and that there is sufficient scientific evidence to indicate the worthlessness of Lycetol.

The referee in charge of Piperazine and Lycetol recommended that these products be omitted from New and Nonofficial Remedies for the reason that they have been sufficiently tried to justify the conclusion that they are not of value. The period of acceptance having expired, the Council directed that Piperazine and Piperazine Tablets (The Bayer Company, Inc.) and Lycetol (The Bayer Company, Inc.) be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 70._)

STANOLIND LIQUID PARAFFIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

As explained in the report which follows, “Stanolind Liquid Paraffin” was omitted from New and Nonofficial Remedies at the request of the proprietors. Announcement of this omission was made in the preface to New and Nonofficial Remedies, 1918, but publication of the Council’s report was postponed pending actual conflict with the rules. The Council now authorizes publication of the report because a circular indirectly advertising the product to the public was found enclosed with the trade package of Stanolind Liquid Paraffin.

W. A. Puckner, Secretary.

Stanolind Liquid Paraffin was admitted to New and Nonofficial Remedies in 1916, when its method of marketing conformed to the rules of the Council. This brand of liquid petrolatum, by action of the Council, has been omitted from New and Nonofficial Remedies on request of the Standard Oil Company of Indiana, its manufacturer, who wrote to the Secretary of the Council stating that:

“In order that our facilities for the manufacture of this oil shall be constantly engaged, it will be necessary for us to find sales on a larger scale than in the past. To do this under our present advertising and marketing arrangement we feel will be impossible.”

This letter, in addition, suggested “that physicians are not prescribing Stanolind Liquid Paraffin in any considerable proportion of their orders” and “that the situation which now confronts us would not be materially helped if Stanolind was specified in all such prescriptions.” Further, the Council is asked to consider whether it “might be willing to declare this preparation as not a Council product,” on the alleged grounds that “liquid paraffin is not medicinal in its action and passes through the digestive tract in practically unaltered condition.”

The Council holds that Stanolind Liquid Paraffin is a drug, and that, therefore, its direct advertising to the public is in contravention of the Council’s rules. Constipation should be treated by dietary and hygienic means. Evacuants are only temporary measures. Liquid petrolatum is medicinal; it greatly modifies the intestinal flora; it acts as a lubricant and emollient; it modifies the absorptive powers of the intestinal mucous membrane; it is capable of influencing the digestion of fats. In short, liquid petrolatum, being a drug, its indiscriminate and excessive use should not be encouraged.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 72_)

WESTERFIELD’S DIGITALIS TABLETS

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Westerfield’s Digitalis Tablets (The Westerfield Pharmacal Co., Dayton, Ohio) are claimed to represent a fat free tincture of digitalis and to be “enteric coated.” It is claimed that because of this coating these tablets pass the stomach unchanged and dissolve in the intestine, and that this obviates any possibility of gastric disturbance.

The circular which sets forth the asserted advantages of the tablets states that digitalis contains a fat which is an irritant to the gastric membrane. It also contains the following:

“We feel no hesitation in saying that if this remedy is given a fair trial where it is properly indicated, the result obtained will be a gratifying surprise.

“It is a common expression from physicians who have tried this remedy to say, ‘Surely I have never used Digitalis before.’”

If these quotations mean anything, they imply that these tablets present a distinct advance in digitalis therapy. There is no warrant for such a claim. The statement with reference to the occurrence of an oil in digitalis is partly false and partly misleading. Tincture of digitalis, which the tablets are claimed to represent, is fat free; the fixed oil that is present in the drug is not soluble in 70 per cent. alcohol, the menstruum used for the preparation of the official tincture of digitalis. Furthermore, a fairly large amount of this oil (such as is present in 100 therapeutic doses of the drug) is incapable of causing gastric disturbance. Gastric disturbance is a side action that is inseparable from slight overdosage with all true digitalis bodies and is not in any way due to local gastric action. The claim that such action is prevented by the use of enteric pills or tablets is obviously false and misleading.

The alleged “common expression from physicians who have tried this remedy” does not constitute acceptable evidence of the value of the preparation.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Nonofficial Remedies because unwarranted therapeutic claims are made for this product.

When the preceding report was submitted to the Westerfield Pharmacal Co., a reply was received indicating that the firm did not know that progressive manufacturers had discontinued the claim that “fat free” digitalis preparations were devoid of gastric effects. It also submitted a revised circular, which, however, reiterated the claim that the tablet presented a distinct advance in digitalis therapy in that it was “fat free,” and coated to prevent disintegration in the stomach.

Since tincture of digitalis and extract of digitalis are practically devoid of fatty material, and since it is now well known that the fat does not cause gastric disturbance and that therapeutic doses of digitalis do not exert a local irritant action on the stomach, the manufacturer’s product and the claims made for it merely tend to perpetuate old errors.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Nonofficial Remedies on the ground that this presents an unessential modification of pills of an official substance. It directed publication of its report with this explanation.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 75_)

XEROFORM-HEYDEN AND BISMUTH TRIBROMPHENATE-MERCK OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Bismuth Tribromphenate-Merck and Xeroform-Heyden. These two products were found not to comply with the standards for bismuth tribromphenate adopted for New and Nonofficial Remedies, and hence could not be retained. As the manufacturers of both products announce that efforts toward the production of a satisfactory product are continued, the omission of the two brands is without prejudice to their reacceptance when a satisfactory product becomes available.

W. A. Puckner, Secretary.

The referee in charge of bismuth preparations submitted the following report of the A. M. A. Chemical Laboratory which shows that Xeroform-Heyden and Bismuth Tribromphenate-Merck do not comply with the adopted standards for bismuth tribromphenate.

Some time ago a request was received from the Medical Section of the National Council of Defense for a report on a brand of bismuth tribromphenate. In accordance with this request the firm’s product was examined, and at the same time and for comparison, an examination was also made of a specimen of bismuth tribromphenate received from Merck and Company, October, 1915, and of another specimen of bismuth tribromphenate “Xeroform-Heyden” obtained from the Chicago branch of the Heyden Chemical Works in April, 1918.

The examination brought out that the bismuth tribromphenate submitted to the national Council of Defense contained a large amount of uncombined tribromphenol, while the specimen of Xeroform-Heyden contained an excessive quantity of bismuth.

When the latter finding was submitted to the Heyden Chemical Works, the firm stated: “The product had to be made in this country after importations from Europe became impossible and the first lots were not fully up to the standard ...” The firm stated that it could now furnish a product which it considered fully equal to that which was previously imported, and offered to submit “samples of the new material.”

Having been requested to do so, a specimen of Xeroform-Heyden was received from the Heyden Chemical Works, New York. This and a second specimen, purchased from a Chicago wholesale drug house, were examined. Whereas the standards for bismuth tribromphenate which had been formulated by the Laboratory and accepted by the Heyden Chemical Works required that the product should contain from 40 to 49 per cent. of bismuth and contain not more than 3.3 per cent. of uncombined tribromphenol, the specimen purchased in Chicago contained 67.7 per cent. of bismuth, while the specimen received direct from the Heyden Chemical Works contained 24 per cent. of uncombined tribromphenol. When this result was reported to the Heyden Chemical Works, the firm replied:

“It seems that we are not yet in a position to supply a product that answers a uniform standard and that we have to continue our efforts in this direction.

“We will take this matter up with you again as soon as we have been successful ...”

At the time when the preceding examination was being made, bismuth tribromphenate-Merck could not be obtained from the Chicago wholesale houses. A request sent to Merck and Company for a specimen of the market supply brought the information that the product was temporarily unavailable. Though unable to supply the product, the firm gave valuable advice for a revision of the somewhat loosely drawn tests for bismuth tribromphenate in New and Nonofficial Remedies, 1918.

Recently (November, 1918) Merck and Company sent a specimen of its product labeled “Bismuth Tribromphenate-Merck” “Merck and Company, New York, Distributors and Guarantors,” and wrote “... You will notice this sample conforms in nearly all details to the tests we submitted with our letter of June 4th. We have been able to produce better goods, but just at present unsatisfactory starting material confronts us. The sample conforms to N. N. R., 1918, but will not meet the test for uncombined tribromphenol submitted by you in your letter of September 4th ...”

Examination of the specimen demonstrated that it was soluble to a considerable extent in alcohol (the N. N. R., 1918, description provides that it should be only slightly soluble in alcohol) and according to the standards adopted for New and Nonofficial Remedies, 1919, contains 18 per cent. uncombined tribromphenol (more than five times the permitted amount).

In view of the Laboratory’s report, the referee recommended that the acceptance of Xeroform-Heyden and Bismuth Tribromphenate-Merck be withdrawn, without prejudice to their reinstatement when satisfactory products are again offered for sale. The Council adopted the recommendation of the referee, and accordingly Xeroform-Heyden and Bismuth Tribromphenate-Merck are omitted from New and Nonofficial Remedies, 1919.

When the Laboratory’s findings with regard to Xeroform-Heyden and the action of the Council deleting the article from New and Nonofficial Remedies was reported to the Heyden Chemical Works, the firm expressed regret that efforts to produce a product equal to that formerly obtained from Germany had so far not been successful and announced that it had decided to withdraw Xeroform-Heyden from the market for the present.

When Merck and Company was advised in regard to the report of the Laboratory and the Council’s action, this firm questioned the feasibility of producing a product meeting the Council’s standards and suggested that the test for free tribromphenol be revised to permit as much as 15 per cent. of this constituent. When Merck and Company was reminded that its product, submitted in 1915, essentially complied with the adopted standards and that the estimate of the therapeutic value of bismuth tribromphenate is based on a product essentially free from alcohol-soluble material, the firm replied:

“As stated in our letter of the 12th inst. we do not wish to market the chemical unless it meets all legitimate requirements of the physicians that use it. If, therefore, your standard proves to be good and it is commercially possible to make supplies conforming to it, we shall do so. We shall discontinue the article unless it is of suitable quality.”

--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 76._)

CREAM OF MUSTARD REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Cream of Mustard, The Cream of Mustard Co., South Norwalk, Conn., is said to be made by mixing 2 drachms of oil of mustard and 2 drachms of oil of turpentine with one pound of white petrolatum. According to the label it is “for Tonsillitis, Rheumatism, Sore Muscles, Croup, Pleurisy, Frosted Feet, Sore Throat, Neuralgia, Sprains, Bronchitis, Headache, Chilblains, Stiff Neck, Congestion, Bruises, Asthma, Lumbago, Pains and Aches, Colds in Chest.”

The Council refused recognition to Cream of Mustard:

Because it is a simple pharmaceutical mixture of well-known ingredients and has no advantage over established rubefacients which every physician knows how to prescribe and every pharmacist to compound. Incidentally, the name “Cream of Mustard” is misleading and not descriptive of the composition of this pharmaceutical of oils of mustard and turpentine.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 79_)

“PLURIGLANDULAR” MIXTURES

Caps. Adreno-Spermin Comp., Caps. Antero-Pituitary Comp., Caps. Placento-Mammary Comp., Caps. Thyro-Ovarian Comp., Caps. Hepato-Splenic Comp., Caps. Pancreas Comp., and Caps. Thyroid Comp., Not Admitted to N. N. R.

Report of the Council on Pharmacy and Chemistry

After considering the evidence for the several “pluriglandular” mixtures described below, the Council declared them inadmissible to New and Nonofficial Remedies. The Council’s action was communicated to the manufacturer, Henry R. Harrower, in accordance with the usual procedure. After giving due consideration to the manufacturer’s reply the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

With the offer “to supply you with as much literature as may be necessary and as little of the actual remedies as may be desired” if “the prospects for the inclusion of these formulas in N. N. R. are good,” Henry R. Harrower sent the Council a booklet descriptive of his preparations and labels for the following mixtures:

_Caps. Adreno-Spermin Comp._, each said to contain “Adrenal Gland (total) gr. 1/4, Thyroid Gland (U. S. P.) gr. 1/12, Spermin Extr. (from Gonads), Brain and Spinal Cord aa gr. 1, Calc. Glycerophosphate q. s. ad gr. 5.”

_Caps. Antero-Pituitary Comp._, each said to contain “Anterior Pituitary Body gr. 2, Thymus Gland gr. 1, Thyroid Gland (U. S. P.) gr. 1/12, Calcium-phosphorus Comp. q. s. ad gr. 5.”

_Caps. Placento-Mammary Co._, each said to contain “Desiccated Placenta gr. 2, Mammary Substance gr. 1-1/2, Pituitary Body (total) gr. 1/3, Calcium-phosphorus Comp. q. s. ad. gr. 5.”

_Caps. Thyro-Ovarian Comp._, each said to contain “Desic. Corpora Lutea Ovarian Substance gr. 2-1/2, Thyroid Gland (U. S. P.) gr. 1/12, Pituitary Gland (total) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”

_Caps. Hepato-Splenic Comp._, each said to contain “Liver Parenchyma, Spleen Substance aa gr. 2, Powd. Bile Salts gr. 1/2, Adreno-Spermin Co. (No. 1) gr. 1.”

_Caps. Pancreas Comp._, each said to contain “Adrenal Gland, Pituitary Gland (total) aa gr. 1/2, Ovarian Substance gr. 1, Pancreas Substance q. s. ad gr. 5.”

_Caps. Thyroid Comp._, each said to contain “Desic. Thyroid Gland (U. S. P.) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”

The Council declared these preparations inadmissible to New and Nonofficial Remedies, for reasons which follow:

1. Each of the mixtures contains one ingredient or more, which is neither recognized in the U. S. Pharmacopeia nor admitted to New and Nonofficial Remedies, namely: “Spermin Extract,” “Brain,” “Spinal Cord,” “Desiccated Placenta,” “Liver Parenchyma,” “Spleen Substance,” “Pancreas Substance” and “Calcium Phosphorus Comp. (Each 100 gm. represents Magnes. Phos. 1; Calc. glycerophos. 4; Potas. bicarb. 15; Sod. bicarb. 22 and Sod. chlor. q. s.).” For obvious reasons the Council does not accept a mixture containing an indefinite ingredient and hence it would be necessary as a preliminary for the consideration of any one of the mixtures that their unofficial ingredients be made eligible for New and Nonofficial Remedies by the submission of evidence that such ingredient is of uniform composition and that it is therapeutically valuable when given by mouth. There is no evidence that many of these organs have any value whatever when administered by the mouth or in any other way.

2. In the light of our knowledge the administration of gland mixtures in the host of conditions enumerated in the advertising circular is irrational and on a par with the use of the shotgun mixtures once in vogue.

Be it a pharmaceutical mixture, a “mixed” vaccine, or a “pluriglandular” product, the combination of two medicinal ingredients in a mixture must be considered contrary to rational therapy unless a good reason exists for such combination. Such mixtures are held in conflict with Rule 10 unless the manufacturer presents acceptable evidence for the value of his combination. A physician may prescribe any mixture which he considers indicated in a given case, but the marketing of mixtures of drugs in fixed proportions is in most instances irrational and a detriment to sound therapy.--(_From The Journal A. M. A., Jan. 18, 1919_)

CERELENE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report declaring Cerelene inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Cerelene, a paraffin preparation for the treatment of burns, was submitted to the Council by the Holliday Laboratories, with the statement that it was composed of 84 per cent. paraffin, 15 per cent. myricyl palmitate, and 1 per cent. purified elemi gum to which is added oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was explained:

“Myricyl Palmitate is a purified form of Beeswax, free from all impurities, acids, etc., which is solely manufactured by this Company....”

It was also stated that on “special order” Cerelene has been made containing oil of eucalyptus and resorcin, oil of eucalyptus and picric acid, and picric acid alone. The following report on the preparation was presented to the Council by the referee to whom Cerelene had been assigned:

Cerelene is another compound wax for the treatment of burns. According to the work of Sollmann (J. A. M. A., 68:1799, 1917) it is highly improbable that compound mixtures have any advantage over simple paraffin of low melting point. Cerelene must therefore be considered as an unessential modification of paraffin, and as in conflict with Rule 10; unless definite evidence of superiority is submitted. Cerelene mixtures containing medicinal ingredients also appear unscientific since the evidence that the ingredients do not leave the wax has not been successfully contradicted. Finally, the claims made for Cerelene are rather extreme, and would need some revision before they could be accepted.

The A. M. A. Chemical Laboratory reports:

The physical properties of Cerelene are as follows:

Melting point 50.0 C. by U. S. P. method. Ductility limit 30.5 C. Plasticity limit 26.4 C. Not strong at 38 C.

Adheres moderately well; detaches with “pulling.” On heating, readily loses eucalyptol, and a small amount of resinous substance forms in the bottom of the beaker. If Cerelene is heated to 145 C. and cooled, the resulting product no longer has the properties of the original Cerelene.

It is recommended that the preceding report be sent to the Holliday Laboratories, and that unless its superiority over simple paraffins is demonstrated and the unwarranted claims abandoned, Cerelene be declared inadmissible to New and Nonofficial Remedies for conflict with Rules 6 and 10.

This report was submitted to the Holliday Laboratories with the information that it had been adopted, Oct. 3, 1917. It was also explained that before Cerelene could be accepted, the unofficial and unstandardized constituent “myricyl palmitate” would have to be considered and accepted for New and Nonofficial Remedies since, for obvious reasons, the Council does not accept a preparation which contains an unofficial and unstandardized substance not in N. N. R.

The Holliday Laboratories acknowledged receipt of the Council’s report and asked that the matter be held in abeyance until the requested evidence had been obtained. Later the Council was advised that the advertising circulars for Cerelene had been withdrawn with the exception of one giving directions for its use. Five months later, the firm stated that experiments were being made “to determine the actual strength of Cerelene in comparison with other paraffin waxes....” Nothing further has been heard from the Holliday Laboratories and no reply has been received to an inquiry made Oct. 12, 1918. The Council therefore authorizes publication of its report declaring Cerelene inadmissible to New and Nonofficial Remedies.--(_From the Journal A. M. A., Feb. 15, 1919_).

COLLOSOL COCAINE NOT ADMITTED TO N. N. R

Report of the Council on Pharmacy and Chemistry

The report which appears below was adopted by the Council and sent to the Anglo-French Drug Co., Ltd., New York, for comment in December, 1918. No explanation has been received from the manufacturer. For the information of the profession the Council has now authorized publication of the report.

W. A. Puckner, Secretary.

“Collosol Cocaine” was submitted to the Council in October, 1918, by the Anglo-French Drug Co., Ltd., New York, under the claim that it was an “absolute colloid” and that it contained “1 per cent. cocain.” The label on the submitted specimen declares:

“Collosol Cocaine 1-100”

“... the Cocaine exists as the pure alkaloid in the Colloidal state--the condition in which it is isomorphic with the protein of the body fluids. The effect is more prolonged than that of a molecular Cocaine Solution and being _non-toxic_ absorption presents no practical danger.”

The product was assigned to the Committee on Pharmacology for consideration. The following report was submitted and its adoption by the Council recommended by the committee:

“Collosol Cocaine” is said to be a colloidal form of cocain and is alleged to possess a remarkably low toxicity. The subjoined report of the A. M. A. Chemical Laboratory, however, shows that the preparation does not have the composition claimed for it and it is, in effect, misbranded. In fact, the English manufacturers concede that it is not an “absolute colloid” and that the declaration with regard to the percentage of cocain is incorrect.

It is recommended that, without considering other conflicts with the rules of the Council at this time, “Collosol Cocaine” be declared inadmissible to New and Nonofficial Remedies for conflict with Rule 1 which requires that the composition of an article must be correctly declared. The report of the A. M. A. Chemical Laboratory is appended.

REPORT OF THE A. M. A. CHEMICAL LABORATORY

Simpson, Hewlett and Eyre (_Lancet_, April 28, 1917, p. 660) reported “Collosol Cocaine” to be much less toxic than cocain. These writers, however, did not verify the statements as to the composition and in the light of subsequent chemical examination it is not to be wondered at that “Collosol Cocaine 1.0 per cent.” was much less toxic than a solution containing 1.0 per cent. of cocain hydrochlorid.

Barger, Dale and Durham report from the Department of Biochemistry and Pharmacology, Medical Research Committee (_Lancet_, Dec. 1, 1917, p. 825), that they examined “Collosol Cocaine” and found it to contain but 0.25 per cent. of cocain. They also found that the cocain was not present in a colloidal form. Discussing the low toxicity claimed by the manufacturers, these investigators state:

“In the samples which we examined the toxicity was, indeed, much lower than that of an ordinary 1 per cent. solution of a cocain salt; but the local anesthetic action was low to a corresponding degree, and both actions corresponded satisfactorily with the proportion of cocain chemically recoverable from the solution.”

Stroud, of the Crookes Laboratory (which manufactures the preparation), who apparently had been informed of this work in advance of publication, admits the correctness of it, and states (_British Medical Journal_, Nov. 24, 1918, p. 710) that “whilst the colloidal protective apparently absorbs a portion of the cocain, the remainder is found not to exhibit the attributes of a colloid,...”

The specimen of “Collosol Cocaine” submitted to the Council and labeled “Collosol Cocaine 1-100” was found to contain at most 0.4 per cent. cocain. The examination was made in accordance with the method used by Barger, Dale and Durham and calculated as cocain. This method, however, probably would not distinguish between cocain and basic decomposition products, but would include all as cocain in the amount found. The specimen of “Collosol Cocaine” examined was neutral or slightly acid, a fact which tends to confirm the conclusion of the British investigators that “Collosol Cocaine” contains cocain in noncolloidal form and precludes an increased physiologic effect due to alkalinity.

The Council adopted both the report submitted by the committee and that of the A. M. A. Laboratory and declared “Collosol Cocaine” inadmissible to New and Nonofficial Remedies.--(_From The Journal A. M. A., April 12, 1919._)

CUPRASE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Cuprase, sold by the Anglo-French Drug Co., Ltd. The Council’s criticisms of the advertising claims were sent to the firm, December, 1918. The firm made no reply and essentially the same claims are contained in recent advertisements.

W. A. Puckner, Secretary.

“Cuprase” is now being advertised and sold in the United States by the Anglo-French Drug Co., Ltd., the firm which also markets it in England. It is said to be “prepared in the Laboratories of F. Ducatte, 8 Place de la Medeleine, Paris.” According to an advertising circular entitled “The Medical Treatment of Cancer” “Cuprase” is “chemical colloidal copper”; in another place it is “a colloidal copper hydroxid,” which is said to be obtained chemically by the reduction of salts of copper in the presence of albumosic acid.

A box (price $8.50 less 10 per cent. discount) of “Cuprase-Doctor Gaube du Gers” was purchased recently from the Anglo-French Drug Co., Ltd. It contained eight ampules each containing approximately $1 $2$3 of a brownish fluorescent liquid. No information of composition was given on the box, except the line: “Chaque ampoule contient: $1 $2$3 .00121 de Cuivre pur” (Each ampule contains O.00121 gr. of pure copper). The A. M. A. Chemical Laboratory reports that the preparation does contain a small amount of copper, with some protein material and about 1 per cent. sodium chlorid.

The therapeutic claims in the advertising circular are those commonly made for cancer “cures” and are about equally convincing. The publication of such statements and quotations as the following, which appear in a pamphlet “The Medical Treatment in Cancer,” cannot be too strongly condemned in a medicament that at best has only an experimental status:

“A special preparation, Cuprase, has been introduced into therapeutics which has been remarkably successful. In the history of the therapeutics of cancer, nothing has been found which can compare with the effects produced by means of Cuprase. Clinical facts carry greater weight than theoretical deductions. It follows, from the clinical observations which I have collected, that in the large majority of cases Cuprase effects the diminution or disappearance of the pains, an improvement in the general condition, a diminution or arrest of the neoplasms, and finally in certain cases, a cure has been effected. It should be remarked that all or nearly all the observations refer to inoperable cases in which the prognosis was unfavorable at an early date. It is needless to emphasize the practical importance of a preparation capable of yielding such results, even relative, in the worst stages of a disease which has always been regarded as absolutely resisting the action of all internal remedies.”

“To sum up, Cuprase has given positive results in about 94 per cent. of the cases in which it has been employed for a sufficiently long period, and some brilliant results in about 20 per cent. of these cases. Therefore, it may be affirmed, that among the internal remedies for cancer, Cuprase is the one which has produced the most successful results, and can, under certain circumstances, compete with surgical methods, even, so far as the rapidity of their results are concerned.”

“It is indicated:

(a) apart from all operation, and as a specific and curative remedy;

(b) before an operation, in order to give tone to the patient, mobilise the tumor, destroy its toxins;

(c) after the operation, as a tonic and anti-toxic, and in order to avoid frequent relapses which are always possible.”

Essentially the same statements are made in the more recent advertisements (f. i. Urological and Cutaneous Review, Feb., 1919). Opposed to these loose statements are the results of Richard Weil (The Journal A. M. A., 1913, Sept. 27, p. 1034; ibid, 1915, April 17, p. 1283). Weil avoided pitfalls of subjective impressions and used as the essential criterion of efficiency “the demonstrable reduction in size of a tumor, of a kind not to be attributed to the natural processes of evolution of that tumor or of its associated lesions” (l. c. 1915, p. 1289).

The available evidence for Cuprase is far from meeting this criterion. That published by the manufacturers and agents presents only vague generalities, and no definite data. The evidence gathered by Weil himself permits an estimate of the value of Cuprase and it is entirely unfavorable. He states (l.c. 1915, p. 1288):

“Colloidal copper has been used in recent time for the same purpose by Gaube du Gers and by others. I have recently examined the effects of colloidal copper on malignant tumors in man, and have been unable to find that it has any therapeutic value. Furthermore, a study of the distribution of the copper in tumors obtained at operation or by necropsy from individuals so treated failed to show that the copper had been deposited therein.”

In view of the extravagant and cruelly misleading therapeutic claims, and the indefinite statements of composition, the Council voted Cuprase ineligible to N. N. R., and authorized the publication of this report.--(_From The Journal A. M. A., April 12, 1919._)

COLLOSOL PREPARATIONS

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below declaring “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur” inadmissible to New and Nonofficial Remedies, because their composition is uncertain (conflict with Rule 1). In the few cases in which the therapeutic claims for these preparations were examined, the claims were found to be so improbable or exaggerated (conflict with Rules 6 and 10) as to have necessitated the rejection of these products.

W. A. Puckner, Secretary

The Anglo-French Drug Co., Ltd., London and New York, in November, 1918, requested the Council to consider the products “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur.” The term “Collosol” appears to be a group designation for what are claimed to be permanent colloidal solutions, marketed by the Anglo-French Drug Co., Ltd. Were this claim correct, “Collosols” should contain their active constituents in the form of microscopic or ultramicroscopic suspensions, protected against spontaneous precipitation by the presence of proteins or some similar “stabilizers.”

According to the original patent specifications for Collosols, the metals are precipitated or treated with “peptone,” which acts as the suspending or stabilizing agent. The method of using the peptone makes it doubtful, in the first place, whether the major part of the metals is present in colloidal form, or merely in the form of peptonates, i. e., as ordinary salts. Moreover, the later patents indicate that the products have been unsatisfactory; “experience having shown that some metal colloids under certain conditions not yet fully understood have the tendency to break down after a certain period” (U. S. patent No. 1,116,247). Phenol, it is claimed has a tendency to counteract this decomposition, and the patent covers the use of phenol for this purpose.

It is difficult to see how phenol could possibly have such action. In fact, it obviously does not, for a number of the samples of Collosols submitted to the Council had separated. For instance, “Collosol Hydrargyrum” was not a colloidal solution at all, but a suspension of a coarse powder. The ampules of “Collosol Ferrum” contained a considerable quantity of flocculent precipitate. If either of these preparations were injected intravenously as directed, death might result, making the physician morally if not legally liable.

The recklessness of the claims is further illustrated by the advice that these indefinite mixtures of poisonous metals can be injected in unlimited quantities. Thus, Henry Crookes stated (_Chemical News_, May 7, 1914, p. 218) that Collosols “contain so small a proportion of metal, viz., 1 in 2000, that even a poisonous body like arsenic can be used with impunity.” He stated that they may be applied as a lotion, intramuscular or intravenous injection, and that “one pint or more can be injected intravenously.”

In the case of “Collosol Cocain,” as was brought out in the Council’s report published in The Journal, April 12, 1919, the manufacturers have admitted that the product is not what they have claimed--and still claim--for it. The report of the A. M. A. Chemical Laboratory showed that “Collosol Cocain,” instead of containing 1 per cent. cocain as claimed, contained, in fact, at most not more than 0.4 per cent. cocain.

The report of the A. M. A. Chemical Laboratory on the Collosol products was sent by the Council to the New York office of the Anglo-French Drug Co., Ltd., in duplicate in order to facilitate reference to the London office. This was some months ago. The information which the Council requested has not yet been received, nor has the Anglo-French Drug Co., Ltd., indicated its intention of supplying such information. On the other hand, claims to which specific objection have been made, continue to appear in current advertising. Accordingly, the Council authorizes publication of this report, and declares the Collosol preparations previously named ineligible to New and Nonofficial Remedies.

Additional Notes on Collosol Evidence

In addition to the preceding the following notes of the referee on the evidence so far submitted were sent to the Anglo-French Drug Company, Ltd., for consideration:

_Collosol Iodine_: The leaflet which describes Collosol Iodine contains claims that are improbable, not in accord with accepted facts nor substantiated by evidence; for instance:

“This preparation contains Iodine in its most active form ...”

“The disadvantages of ‘iodism’ and nausea frequently associated with iodides never occur with Collosol Iodine.”

“In the case of Colloidal Iodine the whole of the Iodine is absorbed and enters into molecular combination with protein to form an iodo-amino acid and ... exerts a reducing action on the lipoids producing a different condition of the blood--hence the use of Iodine as an ‘alterative’.”

“Intravenously the action of Collosol Iodine is more rapid ... in cases of pyemia ... thus showing its absolute non-toxicity.”

“‘Per se’ Colloidal Iodine is only slightly parasitotropic and bacteriotropic but micro-organisms are very greatly influenced by its action, and not only is the effect of a subsequently administered remedy greatly increased but also the insoluble colloidal protein of serum itself is reduced to smaller particles, thus increasing its surface and adsorptive capacity and consequent germicidal power. In some cases the serum, thus aided, is enabled to throw off a milk microbial invasion. The above action can be readily demonstrated ‘in vitro’ by means of the ultramicroscope.”

“In Cancer, the intravenous injection of Collosol Iodine relieves pain, even where large dosage of morphine is ineffective.”

“In Rheumatism the ionic method of treatment with Collosol Iodine is strongly advised.”

“In Recovery from Alcoholism the internal administration of Collosol Iodine restores the normal condition of cell activity, ensuring rapid recovery.”

_Collosol Hydrargyrum_: This is said to be a preparation of colloidal mercury and would therefore be similar to Electromercurol (New and Nonofficial Remedies, 1919, p. 167). Colloidal mercury preparations have been used to some extent; they appear to have no decided advantage over other, noncolloidal, mercury compounds. They differ sufficiently from them, however, to justify acceptance for New and Nonofficial Remedies, providing that reasonable claims are made for them. The leaflet advertising Collosol Hydrargyrum contains statements that cannot be accepted and require thorough revision to make them acceptable. The following are instances:

“Although--especially locally--the action of mercurials is markedly antiseptic, when taken internally or injected, it has been stated by some of the best known authorities, that their action is rather to increase the natural resisting power of the body to disease, probably because of stimulation of the oxidases.”

With the soluble mercurials “considerable upset of the normal cell conditions of the tissues ensues whilst these soluble salts are being converted to a condition in which the body can make use of them.”

“The colloidal state ... is stated by some authorities in the case of mercury to be invariably precedent to absorption.... With the usual forms of mercury the danger of too great a dose per cell is considerable, but in the case of colloidal mercury, the diffusion is extremely rapid and chemical affinity low. Hence the danger to the individual leucocyte is minimized and the maximum effect obtained.”

“... absence of pain is usual in the administration of colloidal preparations and is due to their isomorphism with the colloidal lipoid and protein of the tissues and body fluids.”

“According to McDonagh,... mercury acts as an oxidizing agent and that the process of oxidation is more effective in the early stages of syphilis in producing the death of the causal organism....”

_Collosol Manganese_: The circular submitted to the referee is a reprint of a paper by Sir Malcolm Morris on “The Treatment of Furunculosis and Other Deep-Seated Coccogenic Infections by Collosol Manganese.” It reports four cases of furunculosis, each of which cleared up after the intramuscular injection of a few doses of Collosol Manganese. The author seems to attribute the cure to the manganese but the evidence is not convincing. Even the author admits that, in the treatment of furunculosis in general “when at last the dismal procession ends, this often appears to be less the result of treatment than because the disease has run its natural course.” Unless much better evidence is in existence, the preparation must be considered to conflict with Rule 6, which requires therapeutic claims to be substantiated.

_Collosol Argentum_: The evidence submitted as to actions consists of a single reprint by Roe, which is not convincing, and this fantastic statement by Boys:

“A young girl, aged 18, came to my house with acute inflammation of one eye with an ulcer on the cornea. Two drops of Collosol Argentum were dropped in the eye at 7 p. m., and a pad placed over the eye. When she came next morning the eye was quite well; the ulcer had disappeared, and there was no inflammation.”

There is no evidence that this preparation acts as catalyzer and assists the natural resisting bodies of the tissues; or that these are “oxygen carriers.” Unless the claims are supported by better evidence, they, in the opinion of the referee, could not be accepted.

There have been submitted to the Council samples of the following metallic Collosols:

COLLOSOL ARGENTUM COLLOSOL FERRUM COLLOSOL ARSENICUM COLLOSOL HYDRARGYRUM COLLOSOL CUPRUM COLLOSOL MANGANESE

Also Collosols of Iodine and Sulphur, and finally Collosols of Cocain and Quinin. Of all the above, except sulphur, only three small ampules have been submitted. This does not admit of any chemical examination but a statement of the physical appearance may be of interest.

_Collosol Arsenicum_, 0.2 per cent.: Very turbid with large quantities of a lemon yellow flocculent precipitate. On shaking does not become homogeneous and rapidly separates again.

_Collosol Argentum_, 1-2000: The liquid has a slight opalescence. There is considerable deposit of a heavy black precipitate. Does not become homogeneous on shaking and the black substance quickly separates again.

_Collosol Cuprum_, 0.5 _per cent._: Dark red somewhat opalescent liquid. No precipitate. May be colloidal.

_Collosol Ferrum_, 1-2000: Liquid clear. Large quantities of dark brown flocculent precipitate. The precipitate is not distributed evenly when the mixture is shaken and settles out quickly on standing.

_Collosol Hydrargyrum, 5 per cent._: Milky liquid. Large quantities of white deposit mixed with considerable black. The deposit mixes fairly well but the greater part settles out after standing an hour or two.

_Collosol Manganese_, 2.5-1000: Clear reddish-brown liquid without deposit of any kind. Is not opalescent or fluorescent.

_Collosol Iodin_, 1-500: Very pale straw colored liquid without deposit. Has a slight opalescence.

_Collosol Sulphur_, 1-100: Liquid is opalescent. There is some deposit of yellow particles. A four ounce bottle was also submitted. The liquid in this bottle is milky with considerable deposit of yellow crystals like ordinary crystalline sulphur.

_Collosol Cocain_, 1-100: Transparent, colorless liquid with no deposit. Chemical examination showed 0.4 per cent. of what may have been cocain. This residue gave alkaloidal tests.

_Collosol Quinin_, 1-100: Slightly opalescent, colorless liquid, with no deposit. Gives alkaloidal reactions.--(_From The Journal A. M. A., June 7, 1919._)

PULVOIDS CALCYLATES COMPOUND

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, not so much because the preparation with which it deals is of any great importance, but as a protest against the large number of similar irrational complex mixtures which are still offered to physicians.

W. A. Puckner, Secretary.

Pulvoids Calcylates Compound (The Drug Products Co., Inc.) are tablets each of which is claimed to contain:

“Calcium and Strontium Disalicylate, 5 grs.; Resin Guaiac, 1/2 gr.; Digitalis, 1/4 gr.; Cochium [colchicum?] Seed, 1/4 gr.; Squill, 1/4 gr.; Cascarin, 1/16 gr. with aromatics.”

“Pulvoids Calcylates Compound (Sugar coated orange color)” is advertised (_Medical Times_, January, 1919) as being “Analgesic-Antipyretic and Diuretic,” and is included in the preparations designated by the advertiser as “Approved Remedies for LaGrippe and ‘Flu.’” The claim that “Their tolerance is remarkable” refers not to the physicians who tolerate such products, but to the alleged fact that Pulvoids Calcylates are tolerated remarkably well. The advertisement continues:

“May be given persistently and continuously without gastric disturbances.”

“They are uniformly efficient. More certain in effect than the ordinary Salicylates.”

It would be difficult to find an advertisement of equal length containing a greater number of misleading or directly false statements than are found in this one. The Journal (April 22, 1916, p. 1307) has called attention to the lack of justification for this absurd mixture of drugs and has discussed the preparation with especial reference to its use in acute rheumatism, in which the salicylates occupy a special field. The advertisement just quoted mentions La Grippe and “Flu” (or Influenza) as special fields of usefulness for this preparation. This, apparently, is merely an attempt to spread the sail for any breeze. Salicylates have a field of usefulness in influenza in that they often afford relief from pain. There is no reason to suppose that a mixture containing calcium and strontium salicylates--the “Calcium and Strontium Disalicylate” of Pulvoids Calcylates is probably a mixture of calcium and strontium salicylate[127]--has any greater salicylic effect than an equal amount of sodium salicylate. On the other hand, it is worse than useless to give colchicum, squill and digitalis for the relief of such pains.

[127] See report, The Journal, Sept. 9, 1916, p. 827.

Should cardiac dilatation develop, and digitalis medication be required it would be impossible to adjust the dose of such a mixture with special reference to the digitalis action, which alone would be indicated for that condition. No educated physician at present would think of giving resin of guaiac merely because his patient required digitalis, nor would he administer “cascarin,” whatever that may be, in fixed doses, every time he gave a dose of salicylate.

It is impossible to recognize the several effects induced by this therapeutic omneity, and the medical profession should consider it an insult to be offered mixtures such as Pulvoids Calcylates Compound.

Pulvoids Calcylates Compound is, per se, of no great importance; it is one of a type. It has been selected as one of the utterly irrational and therefore potentially dangerous mixtures, that may be found by the score or the hundred in the catalogues of practically every pharmaceutical manufacturing firm in the United States.--(_From The Journal A. M. A., June 14, 1919._)

PROTEOGENS OF THE WM. S. MERRELL COMPANY

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the statement which appears below, declaring Proteogen No. 1 (Plantex) for Cancer, Proteogen No. 2 for Rheumatism, Proteogen No. 3 for Tuberculosis, Proteogen No. 4 for Hay Fever and Bronchial Asthma, Proteogen No. 5 for Dermatoses, Proteogen No. 6 for Chlorosis, Proteogen No. 7 for Secondary Anemia, Proteogen No. 8 for Pernicious Anemia, Proteogen No. 9 for Goitre, Proteogen No. 10 for Syphilis, Proteogen No. 11 for Gonorrhea, and Proteogen No. 12 for Influenza and Pneumonia inadmissible to New and Nonofficial Remedies because their composition is secret; because the therapeutic claims made for them are unwarranted; and because the secrecy and complexity of their composition makes the use of these preparations irrational.

The Council took up the consideration of the Merrell Proteogens because of inquiries received, and on January 27 invited the Merrell Company to aid in the proposed investigation by submitting information in regard to the composition of the preparations, submitting the current advertising, and presenting evidence for the claims that were made for the preparations. While the Merrell Company agreed to submit the requested information, this had not been received at the time the report of the referee to whom the products had been assigned (Referee 1), was adopted. This report was sent to the company on April 4. In reply the Merrell Company protested against the conclusions of the report and submitted considerable material in an attempt to support the claims made for the products. This material was examined by the first referee and then transmitted to a second referee (Referee 2) for consideration. The second referee concluded that the matter submitted offered no evidence that would justify the Council in modifying the report first adopted, and hence recommended that its publication be authorized.

In accordance with this recommendation (report of Referee 2) the Council authorized the publication of the reports of both the first and second referees.

W. A. Puckner, Secretary.

Report of First Referee on Proteogens

“Proteogens,” according to the William S. Merrell Co., are “Polyvalent Proteins of Non-Toxic Plant Origin.” The subject of Proteogens can best be approached by recalling the history of “Autolysin,” an alleged remedy for cancer, originated by A. S. Horowitz, Ph.D. This was exploited some years ago, and was finally shown to be worthless. Proteogens are said to be prepared “under the personal supervision of the originator, Dr. A. S. Horowitz.” The composition of the different Proteogens is essentially secret. The assertion was made at one time, but is not found in the present advertising matter, that Plantex--now called “Proteogen No. 1”--is similar to Autolysin. Now the Proteogens are said to be “prepared by a special process employing various combinations of plants.” Further:

The biologic principles present are chlorophyll, chromoplast, lipoids and vitamines; these are ferments or enzymes. The vegetable acids, metalloids and metals present in all plants in colloid form act biochemically. Among the metalloids are hydrogen, carbon, manganese, oxygen, sulphur, phosphorus and chlorine; the heavy metals are iron, potassium, sodium, magnesium and copper. These biochemic principles are always present in plants as colloids.”

It is claimed by the Merrell Company that:

“Proteogens stimulate the cytogenic mechanism to higher activity; therefore, indirectly cleave the invading microorganism and eliminate their special toxins. Proteogens swing the disturbed metabolism back to normal and, by natural processes, build up effective defenses against recurrent bacterial attacks.”

Proteogen No. 1 was first introduced as “Plantex,” and at that time the Merrell Company referred to a preparation that was the result of “a series of studies” carried out by a “noted biologist” with a view of “evolving a Cancer remedy” that was “to be autolytic in character,” and announced:

“The House of Merrell always interested in the progress of plant therapy, began pharmacological experimentations to reproduce this same substance. The qualitative and quantitative analysis of the substance as used in New York having been published simplified matters. A somewhat similar remedy has now been prepared. It consists of the following substances--Menyanthes trifoliata [Buckbean], Melilotus officinalis [Yellow sweet clover], Mentha crispa [Curled mint], Brassica alba [White mustard], Anemone hepatica [Liver leaf], Viola tricolor [Pansy], Anthemis [Roman chamomile], Fructus colocynthidis [Colocynth], Lignum quassiæ [Quassia], Urtica dioica [Nettle], Radix rhei [Rhubarb root], Hedge hyssop. These substances are in approximately equal proportions with the exception of the mustard which forms 20 per cent. of the mixture, and the colocynth fruit which is 5 per cent.”

With respect also to the other Proteogens listed above, study of medical literature revealed no evidence establishing their therapeutic value; in fact, no evidence was found other than that appearing in the advertising matter of the manufacturer. The range of diseases in which Proteogens are recommended is so wide as to make obvious the lack of scientific judgment which characterizes their exploitation. A circular letter, received January, 1919, reminded the physician that about a year ago his attention had been directed to Proteogen No. 1 for cancer, that later developments enabled the firm to recommend for his consideration “a series of Proteogens (Nos. 2 to 9),” and that now “In response to an insistent demand, Dr. A. S. Horowitz has prepared two new Proteogens--No. 10 for Syphilis and No. 11 for Gonorrhea.” A postscript to this circular letter announced another preparation, “Proteogen No. 12 for Influenza and Pneumonia,” a “development out of the present influenza epidemic,” and admitted that “It has not had the clinical experimentation that precedes our introduction of a new product.”

The introduction of No. 12 was effected by means of a special bulletin which consists exclusively of clinical reports from seven physicians, all from Chicago save one, and all purporting to show most favorable results from No. 12. They describe cases which any physician with experience with influenza can duplicate without any special treatment.

It is difficult to give serious consideration to a set of alleged remedies when the only evidence is that furnished by the proponents of the alleged remedies. This is particularly true when the alleged remedy does not make a sufficient appeal to one’s sense of the rational in therapeutics to lead one to feel justified in asking a trial at the hands of careful clinical observers. Considering the grave nature of the diseases for which Proteogens are recommended, particularly cancer, tuberculosis, and pernicious anemia, the want of a rational basis for the method of treatment and the general tenor of the advertising matter, it appears safe to conclude that these agents do not represent any definite advance in therapeutics.

As the use of preparations, secret in composition, and of no established value, is contrary to rational therapy, it is recommended that the Proteogen preparations be declared in conflict with Rules 1, 6 and 10.

Report of Second Referee Reviewing Manufacturers’ Reply

The report declaring the Proteogens of the William S. Merrell Company inadmissible to New and Nonofficial Remedies was adopted by the Council, but before publication it was sent to the Merrell Company for such comments as it might desire to make. In due time the reply of the firm was received. It consisted of two volumes bound in limp morocco, each stamped in gold: “Report Proteogen Therapy Requested by the American Medical Association, 1919; The Wm. S. Merrell Company.” The first volume contained 79 pages of typewritten material; the second volume contained 76 pages of typewritten material and a number of advertising booklets put out by the Wm. S. Merrell Company, exploiting the Proteogens.

Among the typewritten material was a 14-page report on “Proteogen Therapy” by its originator, A. S. Horowitz. Following this there are several pages devoted to what is termed “a short qualitative description of the ingredients of major importance in Proteogens.” Then follows a page describing the advertising of Proteogens, and the remainder of the two books is devoted to testimonials, lauding the benefit of Proteogens in diseases such as cancer, tuberculosis, rheumatism, asthma, influenza, enlarged prostate, rheumatic endocarditis, syphilis, eczema, psoriasis, diabetes, secondary anemia, gonococcic infections, etc. Finally, there are attached samples of advertising pamphlets.

The dissertation by A. S. Horowitz contains little actual information concerning these substances, but is concerned principally with discussion of foreign proteins, “antiferments,” “non-specific proteins,” “anti-virolins” and speculations on their hypothetical actions and interactions on each other and on the organs of the body and on bacteria. The report contains many questionable statements.

One finds in this report but few definite statements of facts which are known to be accurate or which could be accepted without question. The qualitative description of the proteins and their components is as vague as the previous discussion. The differentiation between the various Proteogens is extremely indefinite; that for Tuberculosis, No. 3 is described as “polyvalent, non-specific protein which rapidly attacks the acid-fast, encapsulated tubercle bacilli”; Proteogen No. 10 for syphilis is said to be a combination of “non-specific plant proteins and different chemicals which has the power to paralyze and destroy living spirochete.” It is stated that Proteogens are scientific preparations based on standard ingredients and that the standardization is more accurate than in serums, vaccines or toxins, etc. The report gives no proof of such statements.

The testimonials that are submitted are typical of “reports” that manufacturers are able to obtain from some physicians, to prove the efficacy of almost any preparation in any disease. Each consists, practically, of the opinion of the individual who has employed the Proteogens or the opinion of the patient who has been treated. Few data are given in these reports from which an impartial conclusion might be drawn. A few of the testimonials presented by the William S. Merrell Company follow. The valuelessness of such material as scientific evidence is obvious:

RHEUMATISM:--_Proteogen No. 2._--The Doctor has one case being treated with No. 2. She has improved so rapidly she cannot express her pleasure, and will continue for some time on the treatments. She is a patient who was confined during the time she suffered from a rheumatic illness, and it seemed to affect her mental condition. This condition is clearing up also, very much to the pleasure of both patient and doctor.--November 27, 1918.

INFLUENZA:--_Proteogen No. 12._--First day, temperature 102, gave 1 c.c. Proteogen No. 12; second day, temperature 100, gave 1 c.c. Proteogen No. 12; third day, temperature 98.8, gave 1 c.c. Proteogen No. 12, and then discharged the case as recovered.--October 31, 1918.

ASTHMA:--_Proteogen No. 4._--Splendid results obtained from a sample of Proteogen No. 4. Three ampoules affected [effected?] complete recovery.--October 9, 1918.

CANCER:--_Proteogen No. 1._--Mrs. B. pronounced recovered from Cancer by Dr. O. W. A., of Catlin, after having injections of Proteogen No. 1 for some time.--October 4, 1918.

ECZEMA:--_Proteogen No. 5._--Tried No. 5 on a patient with eczema, and with happy results. Have not done anything for him for about five months--and he is now at his business. Proteogen No. 5 also RELIEVED HIM OF CONSTIPATION AND WHAT HE CLAIMED A TRAUMATIC STRICTURE OF THE LOWER PORTION OF SIGMOID FLEXURE. He is sure pleased and recommending them to his friends. (Proteogens).--February 17, 1919.

SYPHILIS:--_Proteogen No. 10._--I am getting such excellent results with the No. 10 Proteogen for Syphilis that I am badly in need of more, as I am treating so many cases. Please send me four dozen C. O. D.--October 9, 1918.

ENLARGED PROSTATE:--_Proteogen No. 1._--Have used Plantex in four cases, with good results in each case. One of them his father, an elderly man.--April 25, 1918.

LOBAR PNEUMONIA:--_Proteogen No. 12._--The only case I have used Proteogen No. 12, was a man who had Lobar Pneumonia of left lung following Influenza. After crisis came, patient continued to have slight rise in temperature, cough, and after using 10 doses of your Proteogen No. 12, temperature was normal, cough very much better, patient began to take on flesh and is still improving.--December 26, 1918.

TUBERCULOSIS:--_Proteogen No. 3._--The Doctor writes: The Proteogen No. 3 sent me worked wonders in my patient. The case came under my care when he was too far gone for anything to benefit him a great deal, but the Proteogen did for him more than anyone could have expected, yet he died leaving me with a few ampoules to try on the next patient.--September 20, 1918.

GONORRHEAL CYSTITIS:--_Proteogen No. 11._--My patient has taken two boxes of your Proteogen No. 11 given for gonorrheal cystitis of probably two years’ standing and at this writing I consider her almost, if not entirely, cured which I think speaks very highly of your remedy. I expect to use more of your preparations in the future.--April 12, 1919. [This testimonial, either by clerical error, or because the results were considered remarkable, was repeated elsewhere in the material submitted by the Merrell Company.]

ACUTE GONORRHEA:--_Proteogen No. 11._--Mr. A. E. R., age 65, weight 140 pounds. First attack. Had had no previous treatment. Came to me January 2, 1919. Had discharge, all acute symptoms, burning, etc. Gave seventeen injections of Proteogen No. 11, also mild antiseptic urethral wash. Discharged on February 15, 1919, clinically cured.--April 11, 1919.

EPITHELIOMA OF BUTTOCK.--_Proteogen No. 1._--I used Proteogen No. 1 on an epithelioma of buttock some six months ago with favorable results and no return of symptoms as yet.--April 13, 1919.

It is obvious that the Proteogen preparations are in conflict with Rules 1, 6 and 10, and should not be admitted to “New and Nonofficial Remedies.” It is recommended that the previous action of the Council be allowed to stand and that publication of both reports be authorized.--(_From The Journal A. M. A., July 12, 1919_)

“ARSENOVEN S. S.” AND “ARSENO-METH-HYD”

Report of the Council on Pharmacy and Chemistry

The Council authorizes publication of the following report. This report declares Arsenoven S. S. of the S. S. Products Company and Solution of Arsenic and Mercury (formerly called Arseno-Meth-Hyd) of the New York Intravenous Laboratory, inadmissible to New and Nonofficial Remedies. The Council takes this opportunity to repeat its warning against the abuses--often dangerous--to which patients are frequently subjected when “intravenous therapy” is employed.

W. A. Puckner, Secretary.

Because of inquiries received, the Council took up the consideration of Arsenoven S. S. and Arseno-Meth-Hyd (now sold as Solution of Arsenic and Mercury). The preparations having been referred to a committee for consideration, this committee reported:

ARSENOVEN S. S.

“Arsenoven S. S.” is a preparation put out by the S. S. Products Company, Philadelphia. The claims are made that it is “a simplified office treatment for syphilis” and is “a combination of arsenic and mercury for office use, offering maximum efficiency, safety and convenience.” According to the company, “Arsenoven S. S.” contains Dimethylarsenin 15.4 grains, Mercury biniodid 1/10 grain, Sodium iodid 1/2 grain. With regard to the identity of “dimethylarsenin” the company claims: “This product is a compound of cacodylic acid similar to sodium cacodylate but with a more pronounced therapeutic action.” The committee recommends to the Council that “Arsenoven S. S.” be declared inadmissible to New and Nonofficial Remedies because of unwarranted therapeutic claims.

ARSENO-METH-HYD

“Arseno-Meth-Hyd,” is sold by the New York Intravenous Laboratory, New York City, for the treatment of syphilis. It comes in three dosages, 2 gm., 1.5 gm., and 0.7 gm., respectively. The claim is made that “Arseno-Meth-Hyd 2 gm.” contains “2 gm. (31 grains) of Sodium Dimethylarsenate (Cacodylate), U. S. P.. and Mercury Iodid 5 mg. (1/12 grain)” in 5 c.c. of solution. Physicians are told:

“In primary and early secondary case administer Arseno-Meth-Hyd 2 gm. every sixth day and Mercury Oxycyanide .008 (1/8 grain) intravenously between each injection.”

“In Tertiary cases and those of long standing alternate with intravenous injection of Sodium Iodid 2 gm.”

The following claims are made for the alleged effectiveness and safety of the cacodylate:

“This methyl compound of arsenic has come into almost universal use for syphilis. On account of lack of toxicity an aggressive routine can be carried on. The simple technic and absence of reactions make it most desirable for the regular practitioner. This large dose gives more uniform results both as healing manifestations and negative Wassermann’s.”

“Much discussion has surrounded the use of Methyl Compounds of Arsenic and it has been demonstrated beyond doubt that Cacodylate of Soda proves an effective remedy for syphilis provided that it is properly administered.” [sic]

“The low toxicity of this Methyl compound of arsenic is remarkable. It is contraindicated only where a decided idiosyncrasy for even small doses of arsenic exists.”

These statements are essentially false and misleading. Cacodylate has _not_ come into universal use in the treatment of syphilis, nor has its usefulness been “demonstrated beyond doubt.” On the contrary, H. N. Cole (The Journal, Dec. 30, 1916, p. 2012) has shown that doses so large as to produce renal injury were almost totally ineffective against syphilis. Obviously, “effective doses” if such exist, are not harmless. The dosage advised for Arseno-Meth-Hyd may not produce acute toxic symptoms; nevertheless smaller doses have produced nephritic phenomena. The “Arseno-Meth-Hyd” treatment includes the intravenous injection of about 1/4 grain of a mercury salt. Although this is less than the usual dose (about 1 grain per week), the mercury is probably more effective than the cacodylate.

The committee recommends to the Council that, because of the unwarranted therapeutic claims, “Arseno-Meth-Hyd” be held inadmissible to New and Nonofficial Remedies.

The Council adopted both reports of the committee and declared “Arsenoven S. S.” and “Solution of Arsenic and Mercury” (“Arseno-Meth-Hyd”) inadmissible to New and Nonofficial Remedies. The committee’s reports on these two products impel the Council again to call attention to the undesirable and dangerous abuses to which “Intravenous Therapy” lends itself. There is a distinct field for the intravenous administration of drugs in those cases in which immediate drug action is necessary, or when the medicament is likely to be changed if absorbed through the ordinary channels. Unless such indications exist, however, intravenous administration involves not only inconvenience and expense to the patient, but what is more important, unnecessary danger. The fact that indiscriminate intravenous administration is peculiarly profitable to certain manufacturing houses makes it all the more necessary for the medical profession to be on its guard in this matter.

In this connection it is well worth while to quote the closing paragraph from an editorial on “Intravenous Therapy” that appeared in The Journal, Nov. 11, 1916. It is as true today as when it appeared:

“Intravenous therapy will be most securely advanced if its employment is restricted to such well defined fields. [As those mentioned above.] These fields can be satisfactorily determined only by a scientific pharmacologic study of the action of these drugs when so administered in animals, as well as in man, under conditions in which the results are carefully controlled. The intravenous method is an impressive one, approaching in preparation almost to that which goes with a surgical operation. The patient is usually interested and impressed by this new, and, to him, mysterious method. There is a psychic element in his reaction to the injection which is not a factor in his reaction to the same drug when given by mouth. The intravenous injection of a complex mixture would appear to be particularly reprehensible. Little is known, as has been stated, of the results to be expected from intravenous therapy, even with simple substances. The use of complex mixtures will without doubt react against the proper use of the method.”

After the report on Arseno-Meth-Hyd had been presented to the Council, a letter was received from the New York Intravenous Laboratory announcing that the preparation “Arseno-Meth-Hyd” was now called “Solution of Arsenic and Mercury” and expressing a desire to have its products accepted for inclusion in New and Nonofficial Remedies. In view of this letter, the committee’s report on “Arseno-Meth-Hyd” and the Council’s protest against promiscuous intravenous therapy were sent the New York Intravenous Laboratory for consideration.

The reply of the New York Intravenous Laboratory contained nothing which permitted a revision of the preceding report. The change of the name of “Arseno-Meth-Hyd” to “Solution of Arsenic and Mercury” means little as the name still does not disclose the important fact that the arsenic is present as sodium cacodylate, nor does it tell the character of the mercury compound. The Council voted that “Solution of Arsenic and Mercury” and “Arsenoven S. S.” be declared inadmissible to New and Nonofficial Remedies because the therapeutic claims advanced for them are unwarranted (Rule 6) and because the names of these pharmaceutical preparations are not descriptive of their composition (Rule 8).

In filing its reply with the Council, the New York Intravenous Laboratory announced that that document would be circulated to the medical profession. This is of course the firm’s privilege. The Council notes, however, with interest, that the reply is devoted almost entirely to points which were not raised by the Council and that it fails to discuss the objections which were actually made.

The reply constantly confuses the efficiency of cacodylate in anemia and in syphilis. The Council’s report on “Arseno-Meth-Hyd” does not discuss or even touch on the question of cacodylates in anemia. It is confined to a discussion of the disappointing results obtained with cacodylates as such (i. e., without mercury) in the treatment of syphilis. This attempt on the part of the New York Intravenous Laboratory to confuse the issue and to attribute to the Council an opinion that it has never stated or held is an inexcusable misrepresentation. The company in its reply said:

“We believe that you have previously stated that a solution cacodylate of soda possesses no more action than so much water. In other words, it was inert. Now you try to show that it produces renal injury.”

The Council has never declared that cacodylates are inert. In the report it is merely stated “that doses so large as to produce renal injury were almost totally ineffective against syphilis.” Neither has the Council stated that cacodylate is “peculiarly dangerous.” In fact the absolute toxicity of cacodylates is low but Cole’s results were quoted as a caution that “effective” doses are not harmless. A great portion of the remainder of the reply is devoted to disparaging arsphenamin--a product that is not involved in this action of the Council, and one about which the physician is amply informed.

Amongst other wholly extraneous matters, the firm’s “reply” tried to resurrect the pepsin pancreatin controversy. This also has nothing to do with the efficiency or harmlessness of sodium cacodylate. In order to dispose of the matter, however, it may be pointed out that the implications are entirely misleading. The work which is quoted against the Council was undertaken by the Council itself, to clarify obscurities in the older data. The outcome of these new investigations showed the essential correctness of the deductions from the older work, namely, that pancreatin is destroyed by pepsin-hydrochloric acid. Dr. Long’s work to which the firm’s reply evidently refers, showed that under favorable conditions, namely, when protected by an excess of protein, some trypsin may escape destruction in the stomach; but it fully confirmed the original conclusion that pepsin and pancreatin mixtures as ordinarily administered are practically worthless (J. H. Long, _Jour. Amer. Pharmaco. Assoc._, Sept. 19, 1917).

As regards the editorial on intravenous therapy, a concession may be made the New York Intravenous Laboratory: intravenous injections are no longer quite as “impressive” as in 1916, but that does not alter the fact that they should be used only when a distinct advantage is to be gained.--(_From The Journal A. M. A., Aug. 2, 1919_)

HORMOTONE AND HORMOTONE WITHOUT POST-PITUITARY

Report of the Council on Pharmacy and Chemistry.

“Hormotone,” of the G. W. Carnrick Company, is advertised as “A pluriglandular tonic for asthenic conditions.” “Hormotone Without Post-Pituitary” is recommended for use “in neurasthenic conditions associated with high blood pressure.” These preparations are sold in the form of tablets for oral administration. The Council declares these preparations inadmissible to New and Nonofficial Remedies because: (1) Their composition is semisecret (Rule 1); (2) the therapeutic claims are unwarranted (Rule 6); (3) they are sold under names not descriptive of their composition but suggestive of indiscriminate use as “tonics” (Rule 8); (4) in the light of our present knowledge the routine administration of polyglandular mixtures is irrational (Rule 10). In explanation of this action, the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Each tablet of “Hormotone” (G. W. Carnrick Co., New York City) is said to contain 1/10 grain of desiccated thyroid and 1/20 grain of entire pituitary, together with the hormones of the ovary and testes--the amounts and the form in which the latter are supposed to be present are not given. From this it will be seen that the only definite information given to the medical profession regarding the composition of Hormotone is that it is a weak thyroid and a still weaker pituitary preparation.

What results can be anticipated from one or two tablets three times daily (the recommended dose of Hormotone) each containing 1/10 grain of thyroid and 1/20 grain entire pituitary? Such doses of thyroid may, of course, have a beneficial action in a limited number of cases of myxedema and cretinism. An extract of the posterior lobe of the pituitary (Liquor Hypophysis, U. S. P., for example) will, _when injected subcutaneously or intramuscularly_, have a pronounced effect on the parturient uterus; its action on certain other forms of smooth muscle will be much less certain. But the _oral administration_ (for which Hormotone is recommended) of the posterior lobe of the pituitary has not been shown to have any such effect. The use of the anterior lobe in doses of 1 to 4 grains (doses very many times larger than those recommended for the entire gland in Hormotone) is in the experimental stage and its only probable value seems to be in those cases of known gland deficiency.

As to the other alleged ingredients of Hormotone--hormones of the ovary and testes, amounts not stated: all physicians know the uncertainties attending the use of ovarian preparations and the serious question as to whether testicular extracts have any therapeutic value. Whatever may be the physicians views as to the probable therapeutic value of these organs, the first thing he desires to know is how much of the substance he is giving and from what part of the gland it is obtained.

So much for the facts; yet the physician is asked to jump from this region of solid fact into a sea of hypothesis; to believe that small amounts of the well-known drugs thyroid and pituitary, plus an unknown amount of unknown hormones of the testes and ovary are of great value in conditions that in themselves are often purely hypothetical. He is asked to believe that this combination has virtues in such conditions as “hypofunction of the adrenal system,” neurasthenia, the “fatigue syndrome,” amenorrhea, dysmenorrhea, “natural and artificial menopause,” sexual neuroses, cold extremities, cardiac asthenia, low blood pressure, infantilism, sterility, melancholic conditions, obesity, anorexia, anemia, slow metabolism, constipation, psychasthenia, lowered virility and the sexual neuroses of the unmarried, hysteria following functional exhaustion of the nerve centers, frigidity, etc., etc., especially if he guesses that the trouble is due to a “pluriglandular disturbance,” “glandular hypofunction,” an “adreno-pituitary deficiency,” suboxidation, etc.

The physician is invited to use Hormotone because, among other reasons, each alleged constituent is said to be “in physiologic sympathy and therapeutic harmony with the others,” and further, because:

“Pluriglandular therapy has the endorsement of high authorities, is both logical and effective and Hormotone is a splendid example of it. It will be seen at its best where the patient lacks snap and vim and vigor. Asthenic conditions necessarily indicate hypofunction of the adrenal system ...” etc.

“The use of gland extracts in the treatment of aplasias of the pluriglandular system has become an established therapeutic measure of miraculous potency (Bayard Holmes: The Internal Secretory Glands, _Lancet-Clinic_, Sept. 19, 1914).”

The G. W. Carnrick Company also advertises a “Hormotone Without Post-Pituitary,” each tablet of which is said to contain 1/10 grain desiccated thyroid, and to “present” “hormone bearing extracts of thyroid, anterior pituitary, ovary, and testes.” This product is just as irrational as “Hormotone.”--(_From The Journal A. M. A., Aug. 16, 1919_)

FORMALDEHYDE LOZENGES

Report of the Council on Pharmacy and Chemistry

The Council has voted Hex-Iodin (Daggett and Miller Co., Inc., Providence, R. I.), Formitol Tablets (E. L. Patch Co., Boston), and Cin-U-Form Lozenges (McKesson and Robbins, New York City) inadmissible to New and Nonofficial Remedies, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Some years ago, the Council published (The Journal A. M. A., Aug. 28, 1915, p. 816) a report on Formamint, a proprietary medicine widely exploited as a peculiar chemical compound of sugar of milk and formaldehyde. The formaldehyde was said to be liberated slowly by the action of the saliva, and because of this liberation of formaldehyde, Formamint was claimed to be a powerful germicide. Extravagant claims were made for its curative and prophylactic effects. The Council found that the therapeutic claims were grossly unwarranted and that its exploitation to the public was a public danger.

During the recent epidemic of influenza, a variety of tablets or lozenges were advertised, and are still being advertised, having formaldehyde, in some form or other, as the nucleus around which revolve the therapeutic claims. In some cases, the advertising clearly indicates the character of the formaldehyde compound that is claimed to be present; in others the statements are vague and indefinite or misleading.

It is hardly necessary to remind physicians that the use of tablets containing hexamethylenamin or other formaldehyde compounds can neither cure respiratory infections, nor even confer protection against such infections. To be effective, formaldehyde would need to be supplied to the entire respiratory tract continuously for some time or else in concentrations that would be distinctly irritant and damaging to the tissues. Saliva-dissolved tablets, obviously cannot reach the nasal or tracheal mucosae directly; and the application of quickly acting concentrations of formaldehyde is out of the question. This altogether aside from the fact that hexamethylenamin, the basis of some of these tablets, does not liberate formaldehyde in the mouth, and for this reason alone would be quite useless for this purpose! (See Hanzlik and Collins, _Archives of Internal Medicine_, November, 1913.)

An inefficient antiseptic is more than merely useless; it is a menace to public safety, in that it tends to lead to the neglect of rational and effective protective measures. It therefore seems advisable for the Council again to call the attention of physicians to the subject. Accordingly, three specimens of these products were purchased and examined in the Association’s Chemical Laboratory.

Hex-Iodin

Hex-Iodin (Hexamethylenetetramine and Iodum) Lozenges are manufactured by Daggett and Miller Company, Inc., Providence, R. I. They weigh 15-1/2 grs. each, are sweetened and are flavored with mint or menthol. The package and circulars do not contain a definite statement of composition. The rather indefinite synonyms “Hexameth. and Iodine Comp.” and “Hexamethylenetetramine and Iodum” suggest that the lozenges contain hexamethylenamin and free iodin. The further statement that they “contain the combined medicinal antiseptic and prophylactic properties of Hexamethylenetetramine and Iodum” is also rather indefinite. The therapeutic action claimed for the lozenges, however, could only be produced by free iodin and by liberated formaldehyde.

It is unnecessary to discuss in detail the extravagant claims made for these lozenges. The inefficiency of hexamethylenamin has already been referred to; the limitations of iodin, free or combined, in lozenge form, need not be discussed because the examination made in the A. M. A. Chemical Laboratory showed that Hex-Iodin lozenges contained no free iodin, and only traces of combined iodin. Neither formaldehyde nor paraformaldehyde was present; hexamethylenamin was present but, the lozenges being neutral no formaldehyde is generated in contact with water or with the alkaline saliva.

Thus Hex-Iodin is shown to be worthless for the purpose for which it is advertised. Of the two important ingredients said to be present, iodin and hexamethylenamin, only traces could be found of the former while the latter, as has been shown, is incapable of exerting any effect when used as the manufacturers direct.

Formitol Tablets

These tablets are prepared by the E. L. Patch Co., Boston. Each tablet weighs 13-1/2 grs. They have the odor of thymol or menthol and an acid taste and reaction. They are, according to the label:

“For the throat and mouth. Soothing, Astringent, Antiseptic. Rapidly destroys germs of infection, preventing and relieving sore throat and mouth.”

In a circular, it is stated, that one of the qualities of Formitol:

“... is the generation of formaldehyde when in contact with water or the saliva.”

“Besides generating formaldehyde, Formitol, Patch contains astringent, demulcent and soothing ingredients which render the combination unusually effective.”

A bacteriologic report is given in this circular in which it is stated that, in 2-1/2 minutes one Formitol Tablet rendered sterile a plate culture of a “characteristic throat micrococci.” The instructions are to dissolve a tablet in the mouth, slowly, once an hour or a half-tablet every half hour.

The A. M. A. Chemical Laboratory reported that Formitol Tablets contained formaldehyde (or paraformaldehyde), and ammonium compound, and some hexamethylenamin. It is probable that the formaldehyde (or paraformaldehyde) was produced by the decomposition of hexamethylenamin originally present in the tablets but decomposed by long contact with the acid.[128]

[128] The E. L. Patch Company declares that “no hexamethylenamine has ever been used in the manufacture of Formitol tablets,” and that ammonium chloride and paraformaldehyde are among the ingredients used in the manufacture of these tablets. The hexamethylenamine present in the tablets, therefore, must have been produced by interaction of the paraformaldehyde and ammonium chloride. This does not alter the laboratory findings regarding the composition of the tablets, namely, that they “contain formaldehyde (or paraformaldehyde), an ammonium compound and some hexamethylenamine.”

These tablets differ from Hex-Iodin in that they really contain active formaldehyde and, therefore, possibly produce antiseptic effect in test-tube cultures. The conditions in the mouth, however, are very different from those in the test-tube, since in the mouth the formaldehyde would be immediately “bound” or absorbed. The claimed absence of irritation indicates sufficiently the absence of efficient quantities of formaldehyde under clinical conditions.

Cin-U-Form Lozenges

Cin-U-Form Lozenges, manufactured by McKesson and Robbins, New York City, are marketed in bottles of 24 for 25 cents. They have a strong odor of cinnamon, weigh 15-1/2 grs. each, and are acid in taste and reaction. The label states that they contain:

“Cinnamon, Eucalyptus, Formaldehyde and Menthol--all powerful germicides against Influenzal bacilli, but not injurious to the system in this palatable form.”

A circular contains the same statement as to composition and claims further that they:

“... help to prevent the infection of Spanish Influenza, Pneumonia, Grip Colds and to guard against Sore Throat, Tonsillitis, Pharyngitis, etc.”

The A. M. A. Chemical Laboratory reported that Cin-U-Form Lozenges contained some formaldehyde (or paraformaldehyde) and no hexamethylenamin. It is obvious that the mouth and throat cannot be “disinfected” by these lozenges. They would be totally ineffective against bacteria that enter through the nose; they cannot prevent influenza, pneumonia, etc.--(_From The Journal A. M. A., Oct. 4, 1919_)

LAVORIS

Report of the Council on Pharmacy and Chemistry

Lavoris was considered by the Council in 1913, and its proprietors--the Lavoris Chemical Company--were advised that the preparation was inadmissible to New and Nonofficial Remedies because of conflict with Rules 1, 4, 6, 8 and 10. No report was published at that time. As the preparation is still widely advertised to physicians, the Council has again examined Lavoris and authorized publication of the following report.

W. A. Puckner, Secretary.

In recent years Lavoris has been widely advertised as “THE IDEAL ORAL ANTISEPTIC,” particularly to the dental profession. A printed card sent out by the Lavoris Chemical Company in 1913 read: “LAVORIS, the Pyorrhea Remedy. The Original ZINC CHLORIDE Mouth Wash. One grain zinc to each ounce.” The card also gave a “formula” to the effect that each pint of Lavoris contained:

Zinc Chloride 1.040 Resorcin 0.520 Menthol 0.400 Saccharin 0.195 Formalin 0.195 Ol. Cassia Zeyl 0.780 Ol. Caryophyl 0.195

Advertisements now appearing in medical journals repeat the older “formula” except that resorcin is omitted. The formula while seemingly frank and open is in reality indefinite and misleading in that no denomination of weight is given for the various constituents. It is uncertain, for example, if the figures in the formula are intended to represent grains, grams or percentages of the several constituents. In view of the indefinite statement of composition, a chemical examination of Lavoris was undertaken in the A. M. A. Chemical Laboratory. The report of the laboratory follows:

_Zinc._--This was determined electrolytically. Fifty c.c. gave 0.026 gm. zinc and 100 c.c. gave 0.0531 gm. zinc. The average is 0.0526 gm. zinc in 100 c.c. This is equivalent to 0.1102 gm. anhydrous zinc chlorid in 100 c.c.

_Chlorid._--After decolorizing some of Lavoris with chlorid-free animal charcoal, the chlorid was determined by the Volhard method. Twenty-five c.c. Lavoris required 4.328 c.c. tenth-normal silver nitrate solution equivalent to 0.01535 gm. chlorid (chloridion) or 0.0614 gm. in 100 c.c. A second 25 c.c. of Lavoris required 4.112 gm. tenth-normal silver nitrate solution equivalent to 0.01458 gm. chlorid (chloridion) or 0.05832 gm. in 100 c.c. Average is 0.05985 gm. This is equivalent to 0.1150 gm. zinc chlorid in 100 c.c. This agrees closely with the foregoing zinc determination.

_Resorcin._--The method of the U. S. Pharmacopeia was used. The total bromin absorption of 25 c.c. Lavoris was 3.68 c.c. tenth-normal bromin solution. This would be equivalent to 0.00675 gm. resorcin in 25 c.c. or 0.02700 gm. in 100 c.c. In a duplicate test, 25 c.c. Lavoris required 3.8 c.c. tenth-normal bromin solution equivalent to 0.00697 gm. resorcin or 0.02788 gm. in 100 c.c. Since oil of cinnamon absorbs bromin, 50 c.c. of Lavoris was boiled until very little or no odor of the oil was noted, keeping the volume nearly constant by adding a little water from time to time, and the bromin absorption then taken. In one experiment, 0.36 c.c. of tenth-normal bromin solution was consumed, and in a duplicate no bromin was absorbed. This shows the absence of resorcin.

_Residue._--On evaporating 25 c.c. Lavoris on a steam bath and subsequent drying of the residue at 100 C., 0.0455 gm. of residue was obtained. This is equivalent to 0.1820 gm. in 100 c.c.

_Saccharin._--Saccharin was detected in the residue and ether-extract of the residue by its intense sweet taste when a little sodium bicarbonate was added to it.

_Formaldehyd._--This could be detected by the Jarrison test. The color was not very pronounced and the quantity of formaldehyd was small.

_Oil of Cinnamon._--The odor and taste of Lavoris is characteristic of cinnamon.

_Menthol and Oil of Cloves._--The odor of menthol and of oil of cloves could not be detected, but no tests were made to demonstrate their presence.

The analysis thus indicates that the Lavoris of today contains no resorcin but does contain a small amount of formaldehyd, a little saccharin, and oil of cinnamon (menthol and oil of cloves could not be detected by the odor, but were not tested for). The analysis showed that the principal constituent of Lavoris is zinc chlorid, of which there is about 0.1 gm. per 100 c.c. (about 1/2 grain to the ounce).

The amount of zinc chlorid given in the published formula, i. e., 1.04, is meaningless because the unit of weight or measure is not given; furthermore, the analysis shows that it is inaccurate for any unit of weight that might be assumed from the published figures. Since the amount of the most active medicinal ingredient is both indefinite and inaccurate, the composition of the preparation is essentially secret. Lavoris is indirectly advertised to the public by having included in the package a circular giving a list of diseases for which the preparation was recommended. The combination of zinc chlorid, formaldehyd and oil of cinnamon (assuming the menthol and oil of cloves to be present as flavors) in a mixture is irrational and likely to lead its users to ascribe a false and exaggerated value to the preparation. The name is objectionable in that it does not indicate the composition of the potent ingredients of the mixture, but instead suggests its use as a mouth wash.

From a standpoint of public safety, the most serious objection to Lavoris, however, lies in the many unwarranted therapeutic claims and suggestions. It is generally held that zinc chlorid solutions which possess a strength of from 1 to 200 up to 1 to 500 exercise a weak antiseptic action. The strength of zinc chlorid in Lavoris is approximately 1 to 1,000. The directions for its use recommend that Lavoris should be diluted. A dilution of 1 to 4 is recommended for a variety of mouth conditions while for cystitis irrigations and as a vaginal douche, it is recommended that one tablespoonful be added to a quart of warm water or salt solution. The strength of zinc chlorid in the last suggested dilution would approximate 1 to 64,000. It is evident that no antiseptic action could be expected from such dilutions.

The recommendation that diluted Lavoris be used for the treatment of coryza, nasal catarrh, hay fever, inflamed eyes, hemorrhoids and leucorrhea is objectionable and irrational. Especially dangerous is the recommendation that members of a family exposed to diphtheria or scarlet fever should use Lavoris freely as a preventive. Such recommendations can but give a false sense of security and lead to the neglect of proved methods for preventing the spread of these diseases. Equally unwarranted is the recommendation that in gonorrhea one teaspoonful of Lavoris to eight of warm water be used with a blunt end syringe.

The use of Lavoris as recommended would not only prove valueless in many instances but might lead to serious consequences because really valuable methods of prevention or treatment might be neglected. For these reasons the preparation is in conflict with Rule 6.

The Council declared Lavoris ineligible for New and Nonofficial Remedies.--(_From The Journal A. M. A., Nov. 1, 1919_)

MEDINAL

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Medinal (Schering and Glatz, Inc.).

W. A. Puckner, Secretary.

Medinal is a proprietary name applied to barbital sodium (sodium diethylbarbiturate) the sodium salt of barbital (diethylbarbituric acid). The latter was first introduced as Veronal.

Medinal was deleted from New and Nonofficial Remedies in 1916 because the advertising issued by Schering and Glatz (who then acted as agents for Chemische Fabrik auf Actien vorm. E. Schering, the German manufacturer) contained misleading and unwarranted therapeutic claims. The Council did not publish its report because by the time the report was ready for publication the product was practically off the American market, and it was hoped that when Medinal again became available, Schering and Glatz would revise the claims and thus permit its reacceptance.

Medinal, said to be manufactured in the United States, is now marketed by Schering and Glatz, Inc. In October, 1918, the firm sent to the Council a typewritten copy of a proposed circular for Medinal. The firm was informed that this leaflet was subject to the objections that had been raised when Medinal was deleted from New and Nonofficial Remedies. In April, 1919, the firm submitted a printed circular which it was sending out. This contained numerous misleading statements, among them, these:

“MEDINAL removes its [Diethylbarbituric acid] one objectionable feature--insufficient solubility--and thus fulfills the three prerequisites of a truly rational hypnotic: Quick absorption, insuring prompt action, rapid and complete excretion, affording protection from cumulative toxic after effects, and the choice of rectal and subcutaneous administration.”

There is no justification for the claim that diethylbarbituric acid (barbital) has only one objectionable feature and that a minor matter of “insufficient solubility.” The Council has called the attention of Schering and Glatz, Inc., to the fact that the difference in the time of absorption between Medinal (barbital sodium) and barbital is, at the most, but one of minutes and that there is no evidence that Medinal is excreted more rapidly than barbital. Hence the claims that the danger of toxic side-actions and that cumulative after-effects are avoided in this product, are wholly unwarranted.

It is also claimed, and the claim is unsupported by satisfactory evidence, that Medinal is useful in the insomnia of tuberculosis in which condition it is said to have a double advantage owing to its favorable effects on the night-sweats. It is claimed that Medinal is used in the withdrawal treatment of morphin addiction with great success; there is no evidence that Medinal has any special usefulness in this treatment of the morphin habit. It is claimed further that success has been reported with Medinal in the treatment of whooping cough. The Council knows of no satisfactory evidence to show that Medinal is of special value in whooping cough; on the contrary, it is capable of doing a great deal of harm. The recommendations that Medinal be used for the control of labor pains and in acute neuralgic pains that resist other forms of treatment are wholly unwarranted as the value of the drug in such conditions is inherently improbable and until satisfactory evidence in support of them is forthcoming, must be deemed misleading.--(_From The Journal A. M. A., Nov. 15, 1919_)

OMISSION OF COTARNIN SALTS (STYPTICIN AND STYPTOL) FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Salts of the base cotarnin have been used as local and systemic hemostatics. The hydrochlorid was first introduced as “Stypticin,” and is now in the pharmacopeia as cotarnin hydrochlorid (_Cotarninae Hydrochloridum, U. S. P._). The phthallic acid salt of cotarnin--cotarnin phthallate--was introduced as “Styptol.” Both Stypticin and Styptol were admitted to New and Nonofficial Remedies. In 1918 the Council voted to omit Stypticin because the former American agents were no longer offering it for sale. Styptol was retained and is described in N. N. R., 1919.

As was pointed out in the description (N. N. R., 1918), the evidence for the usefulness of the cotarnin salts has been contradictory and unsatisfactory; but since the available data against the efficiency were at least equally unreliable, the Council deemed it best to retain them in N. N. R. pending a thorough investigation of the subject. This was undertaken by P. J. Hanzlik, at the suggestion of the Therapeutic Research Committee of the Council.

A reliable judgment of hemostatic efficiency can be formed only on a basis of strictly controlled conditions, which can best be furnished in the laboratory. Hanzlik repeated the principal experiments published by previous investigators, and applied a number of new or improved methods. The results (published in the _Journal of Pharmacology and Experimental Therapeutics_ =10=:523, 1918; =12=:71, 1919) show the following:

_Direct Application to Wounds._--The widely quoted results of the gynecologist K. Abel, on the footpad of cats, were found to be quite unreliable. When the experiment is properly controlled, the results are either negative or the bleeding may be increased. Quantitative experiments on wounds of the footpad of dogs showed that cotarnin invariably _increased_ the bleeding. Equally negative or unfavorable results were obtained with wounds to the comb of roosters, and to the liver and spleen.

_Direct Action on Vessels._--The results of perfusion experiments were variable, but, in general, showed a vasodilation action instead of constriction. This holds true also of the uterine vessels. The vessels in the living animal (rabbit’s ear) were also unaffected.

_Systemic Administration._--The bleeding from an irrigated wound was not modified directly by intravenous injection of cotarnin salts, but varied merely with the state of the blood pressure.

The evidence for the inefficiency of cotarnin salts as hemostatics seemed so conclusive as to warrant the Council in rescinding the acceptance of Styptol, and directing the omission of the general article on cotarnin salts and the description of Styptol from New and Nonofficial Remedies.--(_From The Journal A. M. A., Nov. 22, 1919_)

MICAJAH’S WAFERS AND MICAJAH’S SUPPOSITORIES

Report of the Council on Pharmacy and Chemistry

“Micajah’s Medicated Wafers” and “Micajah’s Suppositories,” sold by Micajah & Co., Warren, Pa., are declared inadmissible to “New and Nonofficial Remedies” because (1) their composition is essentially secret (Rule 1); (2) name of neither of these mixtures is indicative of its composition (Rule 8); (3) of exaggerated and unwarranted therapeutic claims (Rule 6), and (4) the therapeutic advice which accompanies the trade packages constitutes an indirect advertisement to the public (Rule 4).

W. A. Puckner, Secretary.

Micajah’s Medicated Wafers (formerly called “Micajah’s Medicated Uterine Wafers”) were analyzed in the A. M. A. Chemical Laboratory in 1910. They were found to consist essentially of dried (“burnt”) alum, boric acid and borax, in approximately the following proportions:

Alum, dried 59.86 per cent. Borax, dried 15.62 per cent. Boric acid 5.67 per cent. Water of hydration 18.85 per cent.

There are a number of drugs that are more or less effective in the treatment of local lesions of mucous membranes and the skin. They are classed as astringents. Among these are included alum, borax and boric acid. Every physician has used them. To say that a wafer consists of alum, borax and boric acid inspires but little awe. But there is something much more mysterious and impressive in declaring that a wafer “consists of an astringent and antiseptic base, in which are incorporated certain medicaments which both locally and after absorption, contribute to the astringent, antiphlogistic, depletive, soothing and healing action of the product.” This gives the impression that some powerful and almost incomprehensible factors are at work. Yet, after all is said and done, the substances contained in Micajah’s Medicated Wafers are just the homely old alum, boric acid and borax.

In addition to “Micajah’s Medicated Wafers,” Micajah & Co. also put out “Micajah’s Suppositories for Hemorrhoids.” These have been examined in the A. M. A. Chemical Laboratory and, like the “Medicated Wafers” have been found to contain alum, boric acid and borax--and these substances practically alone--incorporated in cocoa butter. The company claims that “to these have been added Ammonii Ichthyosulphonate, Balsam of Peru, Ext. Belladonae.” The A. M. A. chemists report, however, that if extract of belladonna is present at all it is in amounts too small to be detected by the method commonly employed in the chemical examination of alkaloidal drugs. The chemists report further that while ammonium ichthyosulphonate and balsam of Peru both have a decided odor and are dark in color, the suppositories have but little color and the odor of the cocoa butter that forms their base is not covered by these drugs; obviously, therefore, if ammonium ichthyosulphonate and balsam of Peru are present at all it is in amounts utterly insufficient to exert any therapeutic effect.

It would be hard to find better examples of mischievous proprietary medicines than these two products of the Micajah Company. “Twins of Efficiency,” they are called in an advertising pamphlet. The composition is not stated. A physician using the “twins” does so absolutely in the dark. To him they are secret preparations. He is encouraged to use them in a great variety of conditions in which other drugs are much more useful. Inevitably, physicians using them will be likely to overlook, or pass over, new growths, specific infections and diseases that require radical remedial measures.

In addition to misleading and exaggerated claims, there is a reference to a report from the usual “well-known and reliable bacteriological laboratory.” The excerpts published from this report of an unnamed laboratory are sufficiently vague to incriminate no one.

From time to time it is worth while to emphasize facts regarding proprietary medicines that while obvious are sometimes forgotten. For this reason attention is directed to Micajah’s Uterine Wafers and Micajah’s Suppositories.--(_From The Journal A. M. A., Nov. 29, 1919_)

ALKALITHIA

Report of the Council on Pharmacy and Chemistry

Alkalithia was introduced at a time when it was believed that the administration of lithium salts served to remove uric acid from the system. The product was considered by the Council in 1906, and found ineligible for New and Nonofficial Remedies. No report, however, was published at that time.

Because of inquiries received, the Council examined the current claims for Alkalithia, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Keasbey and Mattison Company’s Effervescent Alkalithia is sold with the following statement of composition:

“Each dose or heaping teaspoonful contains 1 grain of Caffeine, 10 grains each of Bi-carbonates of soda and potash, and 5 grains of Carbonate of Lithia.”

The A. M. A. Chemical Laboratory reports that Alkalithia is an effervescent mixture which contains alkaline carbonates and bicarbonates together with caffein, free tartaric acid and free citric acid. The major portion of the alkali carbonates and bicarbonates is converted into citrates and tartrates when the preparation is dissolved in water--as is done before it is taken. An excess of alkali is present, however, as the solution has an alkaline reaction. Each “heaping teaspoonful” (which was found to be about 4.85 Gm.) contains about 0.044 Gm. of caffein (the manufacturers claim 0.0648 Gm. per heaping teaspoonful). As taken, Alkalithia, therefore, represents caffein in a solution of alkali tartrate, citrate and bicarbonate containing free carbonic acid. If it is assumed that all of the tartrate and citrate in Alkalithia is converted into carbonate in the organism, a “heaping teaspoonful” of Alkalithia would represent about 2.9 Gm. of sodium bicarbonate. This assumption is, however, not correct, for it is known that tartrates are not completely converted into carbonates in the organism.

According to the label on the bottle, this mixture of caffein and alkali salts is “a common sense remedy for the relief and treatment of conditions dependent upon perverted metabolism as manifested by neuralgic, rheumatic, cardiac and renal symptoms.” Wrapped with a trade package is a circular in which is discussed the “uric acid diathesis” as “a cause of Rheumatism in its various forms, Calculus, Gravel and Inflammation of the Bladder and Kidneys, Asthma, Hay Fever, Catarrh, Quinsy and Bronchitis, Eczema, Hives, Itching and Burning of the Skin, Palpitation of the Heart and Cold Hands and Feet, Dizziness, Mental Depression, Melancholia, Neuralgia, Chorea, Hysteria, Numbness and a great variety of purely nervous symptoms.” The arguments for the use of Alkalithia as “a safe and scientific treatment for the uric acid diathesis” found in the circular constitute an indirect appeal to the laity (conflict with Rule 4).

In the circular matter sent direct to the physicians, Keasbey and Mattison claim that in rheumatism, Alkalithia is prescribed by the medical profession more often than any other remedy. The claim is made that, “In five minutes the urine will be discolorized and analysis will show it to be loaded with urates.” The manufacturers further assert:

“You can change the character of the urinary secretion in a few minutes completely” by Alkalithia, and “In nine cases out of ten, when the doctor prescribes ‘Alkalithia’ his patient greatly improves, or gets well.”

The firm advises that “Renal Insufficiency” be determined by the old method of multiplying the ounces of urine in twenty-four hours by the last two numbers of the specific gravity, adding 10, which gives the number of grains of solids excreted in the twenty-four hours. If this is low, no matter what the cause, they advise Alkalithia, “that ideal eliminant.”

The Council declared Alkalithia inadmissible to New and Nonofficial Remedies because the claims made on the label and the circular accompanying the trade package lead the public to its detriment to depend on this preparation (Rule 4); and because the therapeutic claims are unwarranted (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 65_)

ARHOVIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Arhovin is a solution of dephenylamine, thymol benzoate and ethyl benzoate, marketed by Schering and Glatz, Inc. It was omitted from New and Nonofficial Remedies because the therapeutic claims made for the preparation were unwarranted and because the firm had refused to discontinue the distribution of the advertising which contained the objectionable claims prior to Jan. 1, 1919. When the report which appears below explaining the dismissal was submitted to Schering and Glatz, Inc., the firm again promised a revision of its advertising, but refused discontinuance of the objectionable circular before Jan. 1, 1920. Since Arhovin is still marketed with unwarranted therapeutic claims, the Council has authorized publication of this report.

W. A. Puckner, Secretary.

The attention of the firm Schering and Glatz, Inc., was called to misleading statements in its booklet for Arhovin in 1915, and in 1918 the firm was informed that unless the misleading statements were withdrawn before Jan. 1, 1919, Arhovin would be omitted from New and Nonofficial Remedies.

The following quotations are taken from the circular in question, and illustrate the character of the claims to which objection was made:

“Striking also is the antiphlogistic and anesthetic effect of Arhovin on the inflamed mucosae, an effect which, as all authorities agree, is far greater than that of all other internal anti-gonorrheaics.”

“Under its influence vesical and prostatic complications, gonorrheal arthritis, endocarditis, etc., are rarely incurred.”

References to the indexes of leading textbooks, including those of Meyer and Gottlieb, Cushny, Sollman and Bastedo, fails to show that Arhovin is so much as mentioned by those authors; hence, it is obviously false to state, as is done in the first of the quotations above, that all authors agree concerning the striking effects of Arhovin.

Many of the statements are objectionable by reason of the actions implied, rather than stated directly. The following are examples:

“Arhovin in Gonorrheal Infections of the Male Genito-Urinary Organs. Anterior Urethritis. This is the class of cases in which the most favorable results from Arhovin have been reported.”

“Posterior Urethritis.

“Here also the striking effects from Arhovin medication, both in acute and chronic cases, are rapid decrease of discharge, disappearance of gonococci from the secretion, and cessation of subjective difficulties, such as strangury.”

While the firm did not agree to withdraw the objectionable advertising before Jan. 1, 1919, which made necessary the omission of Arhovin from New and Nonofficial Remedies, 1919, it did submit a proposed folder in which the most objectionable of the claims are still made.

The following statement, which was in the proposed “folder” and is included in an advertising pamphlet sent out during 1919, serves to illustrate those points:

“Its action is three-fold:

“Strong antiseptic and bactericidal effect upon the urethral and vesical mucosae, highly conducive to shortening and palliation of the acute disease course.”

No evidence has been presented that Arhovin is capable of destroying the gonococcus in the urethra, and consequently, the Council declared the recommendation for the use of Arhovin in the treatment of gonorrhea, by means of claims such as those just cited, is both misleading and dangerous.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 66_)

CHLORON, CHLORAX AND NUMBER “3”

Report of the Council on Pharmacy and Chemistry

The report which appears below was sent to the Chlorine Products Company, Inc., May 14, 1919. In reply to an inquiry sent the Chlorine Products Company, July 8, the company wrote that it could send no reply because the medical director was still in France. However, Chloron and Chlorax are being advertised in medical journals; also essentially the same advertising as that discussed in the report was recently received by a physician from the Chlorine Products Company.

The preceding facts having been reported to the Council, publication of the report was authorized.

W. A. Puckner, Secretary.

Chloron, Chlorax and Number “3” are preparations of essentially similar composition put out by the Chlorine Products Company, Inc., New York.

Chloron

Chloron, according to the label, is “A stable CHLORINE remedy for the reduction of inflammation, relief of pain and for all wounds, burns, scalds and every description of sores except cancer and lupus.” Its composition is given as:

“Free chlorine, 0.200 per cent.; calcium chloride, 0.190 per cent.; mercurous chloride, 0.030 per cent.; lithium chloride, 0.035 per cent.; calcium hydrate, 0.010 per cent.; water to 100 parts.”

The Council asked the manufacturers for further information in regard to the composition or preparation of Chloron and received this reply:

“Chlorine gas is prepared in the usual way and purified and passed into water until a saturated solution is made.

“Water to the extent of three times the volume of the chlorine solution is used to dissolve the necessary amount of calcium chloride, and the two solutions are mixed.

“The necessary amounts of Lithium and Mercurous Chloride are then intimately mixed and made into solution. This solution is then added to the above and the whole is agitated for some minutes.”

A specimen of Chloron was examined in the A. M. A. Chemical laboratory and the chemists reported:

Qualitatively the presence of the following constituents was confirmed: calcium, mercury, lithium, chlorid, free chlorin. The solution was alkaline. Of course, the declaration that Chloron contains mercurous chlorid (calomel) is obviously incorrect, as mercurous chlorid cannot exist in a solution containing active (free) chlorin, but is oxidized to mercuric chlorid (corrosive sublimate). As the solution was alkaline in reaction, it seemed unlikely that all the active chlorin was present in the free state, as declared on the label. Quantitative determination of free chlorin and of total active (“available”) chlorin gave: free chlorin, 0.036 gm. per hundred c.c.; total “available” chlorin, 0.330 gm. per hundred c.c., or 165 per cent. of the claimed amount.

A comparison of the information sent to the Council with the analytic findings leads to the conclusion that Chloron is not of reliable composition.

As evidence of the therapeutic value of Chloron, the following “case reports” were submitted:

“In a case of second degree burn involving the most of one leg from the middle of the calf down, CHLORON was the only dressing used. The burn was a bad one and the patient in a rundown anaemic condition, at no time was there any appearance of pus, the surface looked clean and bright and the healing was accomplished with practically no scar whatever. The burn was kept wet with the solution by hourly applications day and night. The skin which has grown on the wound is clear, healthy and firm.

In another case of Varicose veins of long standing, the result was surprising. The patient told of two years vibrating from Hospital to Hospital and getting no real relief. Each leg had large open running sores, the only dressing used was wet compresses of this solution. The pus disappeared at once, the wound began to cicatrise from the edges and in two weeks the man was discharged from the hospital practically cured.”

“CHLORON was recently tried at the ---- and ---- Hospital on cases presenting ulcers and other sores which did not readily yield to other methods, with good results, in fact were of an indolent type. In these cases CHLORON proved very valuable.”

“I have used CHLORON on a series of cases (surgical) presenting pus foci and I have found the application very beneficial and healing, the pus early disappearing. In cases of Osteomyelitis, Suppurating Arthritis, Cellulitis and Chronic Ulcers, CHLORON is particularly valuable, its good effects quickly observed and the time of restoration to health shortened.”

In the first case report, there is no evidence that Chloron is more efficient in the treatment of burns than any other commonly used procedure might have been. In the case of the varicose ulcers, while there was some apparent benefit from Chloron, no credit is given to rest and the general treatment which is known to be important in the treatment of such conditions. The evidence in the other case reports is quite inconclusive. Consideration of the “case reports” leads to the conclusion that clinical evidence for the value of Chloron is lacking.

Attention should be called to the fact that the amount of active chlorin, claimed to be present in Chloron as well as the amount found by the association laboratory, is less than that considered effective by Dakin, Dunham and others; seemingly in preparing Chloron no attention has been paid to the degree of alkalinity, yet the importance of this factor is now generally recognized.

Chloron fails to comply with the requirements for surgical solution of chlorinated soda (N. N. R., 1919, p. 133), yet the manufacturers make free use of the text of Dakin and Dunham’s Handbook of Antiseptics in their advertising pamphlet. Thus:

From the Chloron pamphlet:

“This ideal antiseptic effects complete sterilization within its sphere of action without causing any damage to the cells or tissues. An important method of judging the injurious action of antiseptics is to investigate their effects on the leucocytes. From experiments _in vitro_ by Parry Morgan and _in vivo_ by Col. C. J. Bond with the strength of antiseptics commonly used in surgery, it has been found that Chlorine antiseptics and mercury salts have little effect on phagocytosis in comparison with other germicides.

The activity of the leucocytes from wounds which have recently been treated with CHLORON may be demonstrated experimentally.”

“In addition to its antiseptic action CHLORON is a strong oxidizing agent and deodorant and possesses to a marked degree the property of decomposing toxins. In this connection it is interesting and pertinent to note that Dean, by the regulated action of hypochlorous acid, has prepared a nontoxic dysentery vaccine and it is now a common observation that the free use of CHLORON may reduce the constitutional symptoms arising from septic processes and that they reappear on discontinuing the antiseptic treatment.”

Dakin and Dunham Handbook of Antiseptics:

“The ideal surgical antiseptic should effect complete sterilization within its sphere of action without causing any damage to animal cells. At the moment such a substance does not appear likely to be found, but on the other hand it is surprising to see how little damage may be done to animal tissues by some active antiseptics. An important method of judging of the injurious action of antiseptics is to investigate the condition of the leucocytes in wounds recently treated with the substance under consideration. In general it appears from experiments _in vitro_ that, with the strength of antiseptics commonly used in surgery, mercury salts and hypochlorites have relatively little effect on phagocytosis as compared with phenol (Parry Morgan). It is a regular phenomenon to observe activity of the leucocytes obtained from wounds which have been recently treated with hypochlorites.

Ingenious methods for determining the influence _in vivo_ of antiseptics on the activities of leucocytes have been worked out by Col. C. J. Bond.

“In addition to their disinfecting action, the Chlorine antiseptics are strong oxidizing agents and deodorants and moreover possess in high degree the property of decomposing toxins. By the regulated action of hypochlorous acid, Dean has prepared a nontoxic dysentery vaccine and it is a common observation that the free use of hypochlorites may reduce the constitutional symptoms arising from septic processes and that they reappear on discontinuing the antiseptic treatment.”

Chlorax

Chlorax is said to be “A stable CHLORINE solution for internal use,” in “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions.” It is claimed to have the same composition as that of Chloron with the addition of 0.016 per cent. of tincture of opium.

The A. M. A. Chemical Laboratory reported that the free chlorin in Chlorax was 0.01 gm. per hundred c.c. and the total amount of active (“available”) chlorin was 0.25 gm. per hundred c.c., or 125 per cent. of the amount claimed. The laboratory notes that though the chlorin content of Chloron and Chlorax is claimed to be the same, that of Chlorax actually is less. This is not surprising when the presence in Chlorax of reducing substances such as alcohol is borne in mind. The laboratory concludes that Chlorax is not of reliable composition.

The following is typical of the “case reports” submitted to show the value of Chlorax:

“In January last I used Chlorax on a case of Diabetes Mellitus and with excellent results.

“The patient had been suffering for about nine years and when first brought to my care Toxemia had set in, he was drowsy, irritable and unable to leave the house. I prescribed Chlorax in teaspoonful doses four times a day and am pleased to say that in one week he showed marked improvement. Soon after he was able to leave the house and attend to his business and after two months’ treatment resumed a normal diet and habits apparently without injurious effects.

“I believe that in this case Chlorax undoubtedly prolonged life.”

No mention is made of the dietary or other measures used. The wide variation in diabetes and its response to proper diet is so well known that the noncommittal statement concerning the beneficial effects of Chlorax amounts to no evidence at all in favor of the preparation.

The other “case reports” furnished by the Chlorine Products Company, Inc., which concern the treatment of gastric ulcers, acute alcoholic gastritis, tonsillitis, etc., are equally unconvincing. In fact, no satisfactory evidence for the clinical value of Chlorax has been presented.

The following from the advertising for Chlorax is unwarranted and absurd:

“Mercurous chloride (calomel) is perhaps the most widely used internal antiseptic and alterative and has established itself in the therapy of constipation, cholera, dysentery, cardiac dropsy, pleurisy, malignant fever, malaria, syphilis, worms, infectious diseases, gout and rheumatism; lithium chloride is particularly efficacious in acute and chronic parenchymatous nephritis and in various lithemic conditions; while Opium has no rival as an anodyne and can be used to stabilize and conserve the alkaline reserve of the body against the acidosing influence of infections.”

Further, on page 14 we find:

“In chills and fever malaria and other blood dicrasias, CHLORAX is indicated as an internal antiseptic and it exerts a beneficial effect on the course of these diseases.”

The claims made for Chlorax are exaggerated and misleading.

Number “3”

According to the label, Number “3” is “A STABLE CHLORINE remedy for the purification of the blood,” with the composition:

“Free Chlorine, 0.35 per cent.; Calcium Chloride, 0.30 per cent.; Mercurous Chloride, 0.03 per cent.; Lithium Chloride, 0.04 per cent.; Calcium Hydrate, 0.01 per cent.; Opium, 0.02 per cent.; Ethyl Alcohol, 0.10 per cent.; water to 100 parts.”

It will be noticed that the composition claimed for Number “3” is essentially similar to that claimed for Chloron. It differs from Chloron in that the amounts of some of the constituents are somewhat greater, and in that, like Chlorax, it contains some tincture of opium.

The A. M. A. Chemical Laboratory reports that the free chlorin in a specimen of Number “3” was 0.024 gm. in 100 c.c. and the total active (“available”) chlorin 0.173 gm. per hundred c.c., or about 50 per cent. of the claimed amount. The examination indicates that Number “3” is of unreliable composition. The Chlorine Products Company, Inc., submitted no clinical evidence for Number “3” to which it refers as “our Syphilis remedy.” It stated that two physicians had used the preparation “with good results,” and admitted that “the company requires further evidence before pushing it.”

The Council declared “Chloron,” “Chlorax” and “Number ‘3’” in conflict with the rules governing admission to New and Nonofficial Remedies. All are of unreliable composition (conflict with Rule 1). The therapeutic claims made for the preparations are not substantiated by acceptable evidence and are unwarranted and misleading. Chloron is inferior as an antiseptic to the well-known surgical solution of chlorinated soda on account of its low chlorin content and uncontrolled reaction. There is no warrant for the claim that Chlorax is useful in the treatment of “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions,” nor is there warrant for the claim that “Number ‘3’” is a remedy for the purification of the blood or a “Syphilis remedy” (conflict with Rule 6).

The names of these pharmaceutical mixtures are not descriptive of their composition (conflict with Rule 8).

All three preparations are irrational. No evidence has been furnished that the lithium salt is of value in the mixtures. It is not rational to combine an active chlorin preparation and a mercury salt in one mixture, nor is there evidence that the addition of opium to the preparations proposed for internal use is of value or rational. Experimentation with Number “3” as a “Syphilis remedy” is to be severely condemned in that those on whom it is used will in the meantime be deprived of efficient medication (conflict with Rule 10).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 70_)

ELARSON OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report announcing the omission of Elarson from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Elarson, now sold by the Winthrop Chemical Company, Inc., was formerly sold in the United States by the Bayer Co., Inc. It was admitted to New and Nonofficial Remedies in 1914.

The circular issued by the Winthrop Chemical Co. contains several statements markedly at variance with the results of an investigation made, at the request of Fischer, by Joachimoglu (_Arch. f. exper. Path. u. Pharmakol._ 78:1914). The circular states that Elarson contains about 13 per cent. arsenic. Joachimoglu found from 10.8 to 11.1 per cent. to be present. The circular states further:

“The fact that Elarson represents a lipoid-like chemical combination of arsenic has an important bearing upon its absorption and utilization in the system ... there is good reason to believe that when arsenic is administered in a stable, lipoid-like combination, as in Elarson, it is more readily taken up by the cells and more completely utilized than when given in the customary manner.”

“As regards the behavior of Elarson in the system, it has been shown that its active constituent, chlorarseno-behenol, is almost completely absorbed in this form, probably as a chlor-behenolate of sodium or potassium.”

As a matter of fact, Joachimoglu found that very little arsenic was absorbed when Elarson was given to dogs and rabbits; most of it was recovered from the feces; only traces were found in the liver and kidneys and none in the blood and brain. The absence from the latter organs shows that the lipoid solubility does not obtain in the body. It is claimed in the circular that Elarson has the advantage over Fowler’s solution “in that it is free from any irritating action upon the gastro-intestinal tract”; it is stated that as many as sixty tablets have been given to dogs daily without any toxic effects. Joachimoglu, on the other hand, found powdered Elarson to be very irritating to the gastro-intestinal tract; also that the dog could not stand sixty tablets at all (_gar nicht vertragen_), such doses causing vomiting, diarrhea and intestinal hemorrhages; on repeated administration the symptoms became progressively more severe. Joachimoglu also found that, compared on the basis of arsenic content, Elarson, given intravenously, is from ten to twelve times as poisonous as arsenic trioxid. Elarson is recommended for the class of cases in which Fowler’s solution is used.

To sum up: None of the special claims made for Elarson--the arsenic content, ready absorbability, freedom from irritating action on the gastro-intestinal tract and its alleged better adaptation for continued administration--have been substantiated; on the contrary, they have been disproved as well as the theory of its mode of absorption proposed by Fischer and Klemperer. Furthermore, Joachimoglu found that when it actually got into the circulation (intravenous injection) in the form in which Fischer and Klemperer supposed it to be absorbed, it was from ten to twelve times as toxic as arsenic trioxid.

The Council voted to omit Elarson from New and Nonofficial Remedies because it is sold under unproved and consequently unwarranted claims and because it is an unscientific and relatively useless article. Elarson has not been shown to have advantages over Fowler’s solution; on the contrary, in some respects at least, it is inferior.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 75._)

IODIPHOS

Report of the Council on Pharmacy and Chemistry

A report which appears below was sent Charles L. Heffner for consideration. No reply having been received, the Council authorized its publication.

W. A. Puckner, Secretary.

Iodiphos, marketed by Charles L. Heffner, Brooklyn, N. Y., is declared to contain ferric citro-iodine, 6 grains; calcium glycerophosphate, 8 grains; sodium glycerophosphate, 8 grains, and hypophosphorous acid, 2 minims in each fluidounce, and to present “the Metallic and Non-Metallic elements: Iron, Iodine, Phosphorous, Calcium and Sodium (each in separate Basic combination).”

According to the label, Iodiphos is “ALTERATIVE, TONIC, NERVINE and ANTI-TUBERCULAR” and is “For Treatment of BLOOD, NERVES and PULMONARY ORGANS.” An advertising circular[129] asserts that “Iodiphos exerts its Physiological action rapidly in hardening of the Arteries, High Blood Pressure, Anaemia, Glandular Swelling, Neurasthenia, Hypochondria, Phthisis, Bronchitis, Asthma, Pneumonia and as an Intestinal Antiseptic and Appetizer,” and declares it to be “Indispensable as a Tonic and Restorative.”

[129] After publication of the foregoing report had been authorized by the Council, a letter was received from Charles L. Heffner, advising that the distribution of the circulars has been discontinued.

In the advertising circular it is averred that in the production of Iodiphos “Chemistry Again Aids the Modern Physician.” Iodiphos is another instance when a decadent polypharmacy proposes haphazard medication and so obstructs the efforts of modern medicine to establish the use of single drugs to meet definite indications.

Iodiphos is inadmissible to New and Nonofficial Remedies because it is an irrational mixture of drugs sold with therapeutic claims that are unwarranted, and under a name which is not descriptive of its composition.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 81._)

MERVENOL AND ARMERVENOL NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the report which appears below declaring Mervenol and Armervenol, marketed by the Hille Laboratories, inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Mervenol is stated by the proprietors--The Hille Laboratories, Chicago--to be a hydrosol (colloidal suspension) of the sulphides of mercury and copper, containing sufficient sodium chloride to make it isotonic with blood serum, and “inert proteid” and “carbohydrate” to stabilize the colloidal suspension: each cubic centimeter is stated to contain 0.005 gm. mercury, 0.0016 gm. copper, and 0.0016 gm. sulphur.

It is claimed that this preparation is of value in pneumonia, influenza, and other conditions and diseases requiring increased leukocytosis.

It is further claimed that the properties and therapeutic effects of this preparation are as follows: “Practically non-irritant; practically non-toxic; lower temperature, often crisis like; lower pulse, with better elimination; greatly accelerated recovery from Influenza; fewer Pneumonia complications; lower mortality rate in Influenza and Pneumonia; remarkable Leucocyte stimulation.” Administration by mouth and by intramuscular and intravenous injection are advocated.

In the recent influenza epidemic, it is reported that therapeutic results of some value were obtained at the Great Lakes Training Station and at Fort Sheridan. The reports of certain medical officers indicate that this preparation seemed to have some effect on the course of pneumonia and influenza, on the temperature, and on the leukocyte count. But those conducting the experiments state that it was “absolutely impossible” to fulfil ideal conditions as to controls and other observations at the time the experiments were conducted.

So far as the Council knows, no effort has been made to determine the potent constituent, or constituents, of this preparation; whether the mercury, the copper, or the protein in the mixture was responsible for the claimed benefits is an open question.

These reports were given careful consideration, but it was decided not to accept this preparation because of (1) exaggerated therapeutic claims, conflicting with Rule 6 (aside from the report of its use in influenza and pneumonia at the Great Lakes Training Station and the Post Hospital at Fort Sheridan, which reports are of work done and observations made under conditions which did not permit careful controls, no evidence has been presented to the Council supporting the therapeutic claims) and (2) being an irrational mixture, conflicting with Rule 10--a mixture containing colloidal mercury, copper and sulphur with proteins and carbohydrates in addition, it is difficult to predict the changes which occur in such mixtures on standing.

Samples of Mervenol (two 1-ounce bottles) submitted by the manufacturer, June 5, 1919, were found when opened, Aug. 18, 1919, to have undergone decomposition. A very disagreeable odor had developed, the liquid was turbid, and a large amount of precipitate had formed.

Armervenol is stated by the proprietors--The Hille Laboratories, Chicago--to be a hydrosol (colloidal suspension) of “mercury-copper-sulpharsenite” containing sufficient sodium chlorid to make it isotonic with blood serum and “inert proteid” and “carbohydrate” to stabilize the solution: each cubic centimeter is declared to contain 0.0025 gm. arsenic, 0.005 gm. mercury, 0.0016 gm. copper, and 0.0032 gm. sulphur.

The use of Armervenol as advised by the Hille Laboratories is the same as that of Mervenol, and in addition its use in syphilis is emphasized. The criticisms of this mixture are similar in every respect to those directed against Mervenol--the addition of arsenic introduces still another factor of uncertainty.

After investigating these claims, it was decided not to accept this preparation on the ground (1) that the therapeutic claims are unproved and unwarranted, conflicting with Rule 6, and (2) that the mixture is an irrational one, conflicting with Rule 10.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 82._)

NORMAL PHENOL SERUM (CANO) AND METHYL-PHENOL SERUM (CANO) NOT ACCEPTED FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following statement declaring Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) ineligible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

No statement of the composition of these preparations was submitted to the Council and none appears on the labels of the trade packages. However, the advertising circular contains statements such as:

“... normal phenol serum--phenol with methyl blue dissolved in anaphylactic serum ...”

“... a combination of human or horse serum with Phenol and Methylene-blue, thereby forming a new chemico-biologic product which he termed Methyl-phenol Serum or, chemically, Chloride of Phenol Thionin Tetramethylene-Seric.”

“Methyl-phenol Serum is a chemico-biological product in which Phenol is the chief factor. Each ampule of 10 c.c. contains the therapeutic equivalent of 0.5 gm. (7.5 grains) of Phenol.”

From the foregoing it appears that both preparations contain phenol and methylthionine chloride (methylene blue) and that the second does not contain methyl phenol (cresol) as the name would indicate.

No definite evidence for the value of these preparations is brought forward and even the manufacturer is constrained to caution, “We assume no responsibility for the therapeutic action of the serum....” On the other hand there are a great many statements in the papers of Cano and his colleagues to which exception must be taken. Of these, from among many similar, the following statements are to be cited and commented on:

“Accepting that the gonorrheal infection gives systemic toxemia from absorption of the toxins ...”

It is the general opinion that in the majority of instances there is no systemic toxemia.

“The technique of intraprostatic injection, while less simple than that of the intravenous, is by no means so difficult or complicated as to place it exclusively in the category of the urologist.”

This obviously is an attempt to encourage the general use of these preparations and to minimize the necessity for careful study and special skill in their employment. It is most unwise for one to attempt intraprostatic injections unless he is specially trained in the technique of this procedure.

“This injection to be performed after the 5th or 6th intravenous injection of Methyl-phenol Serum....”

Intravenous injections have a place in sane therapy only when the medicament to be so administered is of known composition and when evidence is available which gives assurance that definite results shall follow its use. In the absence of these conditions it is manifestly unwise and even unexcusable to employ any medicament in this manner, and its repeated use is reprehensible.

“Intravenous injection of Methyl-phenol Serum alternating with intravenous injections of mercury should be given every 48 hours until infection is under control.”

This quotation further emphasizes that the treatment, as advised, carries with it a certain element of danger.

“Methylene blue prevents the phenol from exerting its usual action upon the red blood corpuscles, and ensures rapid elimination through healthy kidneys. It preserves the antiseptic power of the phenol and prevents the phenol from interfering with the chemico-biological function of the white and red blood cells. The serum component favors chemotaxis, it strengthens bodily defense, it prevents anaphylaxis even in debilitated patients, and it replaces the resistance which has been impaired by the demands that have already been made upon it.”

No evidence is submitted to substantiate these claims. It seems strange that phenol should lose its power and that this should be restored by the methylene blue.

“It has a refractory chemico-biological action, and exercises no vicious effect on the red blood corpuscles in the circulation, but, on the contrary, by its inoffensive presence, it wholly preserves all of the physiological properties of the blood.”

What “a refractory chemico-biologic action” is, is not clear, but there is no evidence that this preparation has any action which might be defined as “refractory chemico-biological,” that its presence is inoffensive or that it wholly preserves all the physiologic properties of the blood.

“The treatment of gonorrhea by Cano’s theory ... is firmly based upon chemico-biological facts and accepted authoritative theories and bears the same relation to gonorrhea that intravenous injections of arsenicals bear to syphilis.”

Quite an exaggerated and unwarranted statement. In the same way, objection is taken to the following quotations:

“Phenol administered intravenously in combination with methylene blue, to protect the red-blood globule, undergoes no change, and preserves all of its actual antiseptic effect on the gonococcus and its toxins as though employed in the test tube.”

“When thus introduced into the human body its elimination is unique, effective, antiseptic, germicidal, being completely and exclusively thrown off through the kidneys in a period varying from one-half to twelve hours without local injury or disturbance to the general economy.”

“Combinations of phenol are unstable, but they do have the advantage of mitigating direct action on the cells and globules. It is also known that ordinary phenol has a _coagulant action_ on the albumins and an _oxidizing power_ on the tissues, which power, if permanent, produces gangrene. By virtue of this dual action it therefore acts as a _modifier_; by its oxidizing power on the germ it is germicidal, and prevents the growth of the gonococcus; and by its coagulant power on the toxins it relieves paragonococcal lesions (mono- and poly-arthritides) and affections of the serous organs (endo- and pericarditis, meningitis), and some definite systemic disturbances, the pathology of which is often confused with that of other infections.”

“Lymphocytosis is often persistent in some individuals in whom the internal secretions and the processes of assimilation and disassimilation are deficient; and because of the lack of these the organic physiological ferments are insufficient for the mechanism of nutrition and the phenomena of hematopoiesis.”

Until proof is available showing that phenol, administered intravenously in the quantities employed in Cano’s Normal Phenol Serum and Cano’s Methyl-Phenol Serum, acts as a germicide and methylthionine chloride (“methylene blue”) prevents the deleterious effects of phenol on the red blood corpuscles; that repeated intravenous injections of phenol and mercury are without danger; that there is no danger of anaphylaxis; that the physiologic properties of the blood are preserved by these medicaments; and, finally, that these preparations have an effect on gonorrhea and its complications, these substances Normal Phenol Serum (Cano) and Methyl-Phenol (Cano), are inadmissible to New and Nonofficial Remedies.

The following quotations taken from the circular are admissions that these preparations are not innocuous:

“That the economy will tolerate to a surprising degree substances directly introduced through the blood stream is now well known. By the intravenous injection of 10 c.c. of methyl-phenol serum we throw into the human body a massive dose of an alien substance. The immediate effect of this injection is upon the central nervous system. The recipient usually becomes either pale or suffused, he has a ringing in his ears, has a sensation of great altitude, and occasionally has a dryness of the fauces and a metallic or a garlic taste.”

“In some patients secondary reactions occur in from one to four hours after injection. The phenomena we have observed in these secondary reactions are pronounced chill and rigor ...”

There is no doubt that considerable harm may be done by the intravenous and by the intraprostatic administration of these preparations and until there is good evidence showing the therapeutic value of the treatment, the routine use of these preparations, except perhaps at hospitals in selected and well controlled and carefully guarded cases, is to be strongly discouraged.

When the foregoing statement was sent to the Mulford Company for comment, the firm submitted a letter from Dr. Perry Townsend to the Mulford Company in which he declared that the results obtained with the Cano preparations had been satisfactory and without untoward results. In this letter, Dr. Townsend proposed that a series of injections with these preparations be carried out under the observation of members of the Council and the supervision of Dr. Cano or himself.

The report of the Council, the letter from the Mulford Company and that of Dr. Townsend were sent to a number of urologists for their opinion concerning this whole matter. It was explained that the referee held that no reason had been presented which would warrant the Council to depart from its customary procedure, namely, to require that clinical evidence be submitted in the form of published reports which permit investigation and verification by independent observers but that, before making further recommendation to the Council, he desired the opinion of urologists of recognized standing concerning the report submitted to the Mulford Company. All replies received approved the Council’s position.

The following is one of the replies received:

Your letter in regard to Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) received. I wish to state that I have read the correspondence between the Council and H. K. Mulford Co. and in my opinion the referee and the Council are quite correct in their attitude in the matter. In my opinion I would emphasize the following:

(1) There is absolutely nothing about the remedies directed _specifically_ against the gonococcus and no evidence to show that any action against them is obtained. As we know there are certain states of normal serum which are highly toxic and any normal serum from another animal will produce disturbances in man when injected intravenously--particularly if repeated. The addition of substances to serum normal or otherwise is apt to and frequently does render that serum highly toxic! The substances added in the instances referred to--phenol and methylene blue are not in any way calculated to lessen the toxicity of serum. The element of danger existing in the indiscriminate use of serums intravenously is, in my opinion, increased by the addition of the substances mentioned, and it would be unwise to encourage the general use of any such remedies. Furthermore the products are condemned by the very evidence of the originators and their admissions are quite sufficient to deter anyone from using the products as they suggest.

As to the intraprostatic injections with the serums it does not at all meet my views; although the introduction of serums by this route have been frequently advocated and I have personally carried this mode out I cannot allow the impression to go out that it could be done in a routine manner--nor that no ill results could follow--for I have seen otherwise. Furthermore from theoretical standpoint serums need not be given in this way.

In consideration of the opinion expressed by the Council’s consultants the referee recommended that Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) be declared ineligible for New and Nonofficial Remedies because of conflict with Rule 6 (unwarranted therapeutic claims) without considering possible conflicts with other rules, and that publication of the report be authorized.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 85._)

SOAMIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Soamin is the name under which the firm of Burroughs Wellcome and Company sells its brand of sodium arsanilate. The Council directed the omission of Soamin from New and Nonofficial Remedies and authorized publication of the report which appears below after the proprietors of the product had declined to withdraw or suitably revise the unwarranted therapeutic claims which it made.

W. A. Puckner, Secretary.

The proprietary brand “Soamin” of sodium arsanilate was admitted to New and Nonofficial Remedies several years ago at a time when the therapeutic value of arsanilic acid had not been definitely determined. Experience with this drug has shown that it is far more dangerous and also has a more limited field of usefulness than was at first recognized. The proprietors of the Soamin brand have continued to include in the list of conditions in which it “would seem” to be a “very effective agent” cerebrospinal meningitis and pellagra; in fact, meningitis is the first in the list of conditions mentioned, syphilis the second and pellagra third. In support of their belief in the efficacy of the remedy in meningitis, three reports, published from six to nine years ago, are quoted. In one of these it is stated that two patients “were cured”; in another report, seven of eight patients in whom the clinical, but not the microscopic, diagnosis of meningitis had been made were reported as having recovered; in the third report, fifty-six of ninety cases were reported cured; in this larger series of cases the author neglects to state the method of administration. The firm quotes but one paper (which is a very uncritical report) in regard to pellagra.

It seems to the Council that the evidence of value of sodium arsanilate in these conditions (which are now treated by more rational methods) is too slight to justify the emphasis laid on it by the firm, especially as sodium arsanilate is admittedly a dangerous agent, several cases of blindness having been reported from its use.

For these reasons it was voted to omit Soamin from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 89._)

SOME MIXED VACCINES NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

The consideration of the following “mixed” vaccines was requested by F. I. Lackenbach, San Francisco:

Special Bacterial Vaccine No. 2 (Staph-Strep. Bacterin) containing killed _Staphylococcus albus_, _Staphylococcus aureus_ and streptococcus.

Special Bacterial Vaccine No. 3 (Pneumo-Staph-Strep. Bacterin) containing killed _Staphylococcus albus_, _Staphylococcus aureus_, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 4 (Pneumo-Staph-Strep-Coli Bacterin) containing killed _Staphylococcus albus_, _Staphylococcus aureus_, _Staphylococcus citreus_, _Bacillus coli_, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 5 (Influenza Combined Bacterin) containing killed _Staphylococcus albus_, _Staphylococcus aureus_, _Bacillus Friedländer_, _Bacillus influenzae_, _Micrococcus catarrhalis_, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 11 (Pneumo-Strep. Bacterin) containing killed streptococcus and pneumococcus.

Special Bacterial Vaccine No. 15 (Combined Whooping Cough Bacterin) containing killed _Bacillus pertussis_, _Staphylococcus albus_, _Staphylococcus aureus_, _Micrococcus catarrhalis_, _Bacillus influenzae_, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 16 (Mixed Gonococcus Bacterin) containing killed gonococcus, _Staphylococcus albus_, _Staphylococcus aureus_, _Bacillus coli_, _diphtheroid bacillus_, streptococcus and pneumococcus.

Mr. Lackenbach states that these bacterial mixtures were prepared for him by E. R. Squibb & Sons. Their sale in interstate commerce is permitted under the license granted to the latter firm by the U. S. Treasury Department. However, no evidence of any kind was presented to the Council proving the therapeutic efficacy of the several mixed vaccines. As a mixture of two or more kinds of organisms is accepted for New and Nonofficial Remedies only if there is satisfactory evidence that its therapeutic use is rational, the Council declared the several vaccine mixtures ineligible for New and Nonofficial Remedies (Rule 10).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 90._)

SOMNOFORM

Report of the Council on Pharmacy and Chemistry

The Council examined the available evidence for Somnoform, sold by Stratford-Cookson Company, successors to E. de Trey and Sons, and found the preparation inadmissible to New and Nonofficial Remedies. The Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Somnoform is sold in the United States by Stratford-Cookson Company, successors to E. de Trey and Sons. According to the label on a package of Somnoform sent the Council.

“This mixture contains Chloride of Ethyl, 83 per cent.; Chloride of Methyl, 16 per cent.; Bromide of Ethyl, 1 per cent.”

Although Somnoform has been on the market for a long time, the published reports present no proof that it is superior to ethyl chlorid used alone. Moreover, the published reports and statistics do not necessarily apply to the Somnoform now sold for the reason that mixtures of varying composition have been sold as Somnoform in the past. Thus, when Somnoform was considered by the Council in 1909, it was claimed to be composed of chloride of ethyl, 60 per cent.; chloride of methyl, 35 per cent., and bromide of ethyl, 5 per cent. Federal chemists found, however, that it contained no bromide of ethyl (Notice of Judgment No. 571). It is a question, therefore, whether a given report applies to a mixture containing 5 per cent. bromide of ethyl, 1 per cent. of this substance, or none at all.

The present advertising booklet for Somnoform does not present acceptable evidence of the therapeutic value of the preparation. An ignorance concerning the elementary facts of physiology and pharmacology is evident in the second sentence: when having stated that “Somnoform is the result of several years of study and investigation by Dr. George Rolland, Dean of the Bordeau Dental School,” the pamphlet continues: “He sought an anesthetic which would enter, dwell in, and leave the body in the same manner that oxygen does....”

The claim as to the value of the 1 per cent. of ethyl bromide in the mixture is highly improbable; certainly no evidence in support of the claimed value of this constituent is available to the referee.

No evidence is submitted which proves the claim of superiority of Somnoform over similar preparations, asserted in the following:

“The peculiar manner in which the elements are combined is what makes Somnoform at once so efficient and so safe.”

The Council declared Somnoform inadmissible to New and Nonofficial Remedies because, in the absence of acceptable evidence showing its exceptional safety and value, the claims are unwarranted (Rule 6), and because the name of the mixture is not descriptive of its composition (Rule 8).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 90._)

TABLETS FORMOTHALATES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report which declares Tablets Formothalates (Tailby-Nason Company, Boston, Mass.) ineligible for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Tablets Formothalates are sold by Tailby-Nason Company, Boston, Mass. On the label a formula is given: “Constituents: Acetanilid 2 gr.; phenolphthalein 1/2 gr. In a balanced combination with Hexamene [a name sometimes applied to hexamethylenamin] and Oil of Cinnamon. Indications: Influenza, Colds, Grippe, Headache, Neuralgia, Rheumatism.” The same formula is given in advertisements and in this advertisement it is claimed that they are “For Influenza and Grip” and if “given in the acute stage may avert a serious attack” (_Boston M. & S. J._, Oct. 3, 1918). The dose is given as one to two tablets at 6 p. m. and repeat at bedtimes.

The A. M. A. Chemical Laboratory reported that the tablets weigh an average of 0.4882 Gm., or 7-1/2 grains; that they _have_ the odor and taste of cinnamon; and that they contain hexamethylenamin, are neutral and therefore give up no formaldehyde in the presence of water alone. The Laboratory further reported that they contain phenolphthalein and acetanilid. These tablets were directed to be taken internally and therefore their effect was not intended to be local.

The amount of hexamethylenamin was not determined, but in any case could not exceed 5 grains per tablet. It is evident that 4 grains of acetanilid and 10 grains of hexamethylenamin and 1 grain of phenolphthalein (in two tablets) “if given in the acute stage” of influenza would not “avert a serious attack,” as claimed in the advertisements.

The Council declared Tablets Formothalates inadmissible to New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 92._)

TRIPLE ARSENATES WITH NUCLEIN

Report of the Council on Pharmacy and Chemistry

The Council has declared Triple Arsenates with Nuclein No. 1 and Triple Arsenates with Nuclein No. 2, tablets marketed by the Abbott Laboratories, inadmissible to New and Nonofficial Remedies because unwarranted therapeutic claims (Rule 6) are made for them and because they present an illogical combination of drugs (Rule 10). The publication of the following report has been authorized by the Council.

W. A. Puckner, Secretary.

The following claims are made for Triple Arsenates with Nuclein:

“Puts ‘pep’ and strength back into that patient recovering from Spanish Influenza, pneumonia, typhoid, or surgical operation. An extremely powerful reconstructive tonic. Try it for that ‘run down’ feeling.”

Triple Arsenates with Nuclein is said to contain “Strychnin Arsenate gr. 1/128, Quinin Arsenate gr. 1/64, Iron Arsenate gr. 1/64, Nuclein Solution mins. 4.” A second preparation, of double strength--Triple Arsenates with Nuclein No. 2--is also advertised. The Council voted not to accept these preparations for New and Nonofficial Remedies on the following grounds:

The quantities of quinin, iron and nuclein in the doses represented in these mixtures are negligible; thus, one tablet of Triple Arsenates with Nuclein containing 1/64 grain of quinin arsenate contains only about 1/90 grain of anhydrous quinin; the tablet containing 1/64 grain of iron arsenate contains 1/210 grain of iron; 4 minims of the nuclein solution (assuming it to be the “Nuclein Solution-Abbott”) would contain but 2/5 of a grain of nuclein--a substance which even in large doses is of questionable therapeutic value. The amounts of iron and nuclein contained in doses of this preparation are insignificant in comparison with the amounts present in ordinary foods. The only substances present in even small therapeutic doses are strychnin and arsenic. The effects of arsenic and strychnin are very different and there are comparatively few conditions in which they should be prescribed at the same time. Hence a preparation containing these two in fixed proportions is illogical.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 92._)

“ANTI-PNEUMOCOCCIC OIL” AND THE USE OF CAMPHOR IN PNEUMONIA

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below. This report declares “Anti-Pneumococcic Oil” (a solution of camphor in oil sold by Eimer and Amend, New York) ineligible for New and Nonofficial Remedies because (1) the recommendations for its use in pneumonia are not warranted by the evidence, (2) the name is not descriptive of its composition but is therapeutically suggestive, and (3) the sale of a solution of camphor in oil under a name nondescriptive of its composition is unscientific and a hindrance to therapeutic progress.

W. A. Puckner, Secretary.

The Council having decided to consider Anti-Pneumococcic Oil (Eimer and Amend, New York), the preparation was assigned to the Committee on Therapeutics for report. The report that follows was made by a member of this committee:

According to the advertising, Anti-Pneumococcic Oil is a “twenty-five per cent. solution of camphor in a thin oil” which was “originated” by August Seibert, M.D. The following directions are given for its use:

“10 c.c. (150 minims) to every 100 pounds of body weight, to be injected hypodermically every eight to twelve hours in pneumococcic pneumonia, as soon after the initial chill as possible.”

It is claimed that the prescribed dose one hour before general anesthesia begins, “safeguards against postoperative pneumonia,” and, that “animals can so be immunized against later and otherwise fatal intravenous pneumococcic infection (Boehnke, Institute for Experimental Therapy, Frankfort).” The advice is given:

“In pneumococcic meningitis, endocarditis and pleuritis, 3% of salicylic acid should be added to this oil.”

In an article by Seibert, “Camphor and Pneumococci” (_Medical Record_, April 20, 1912), a reprint of which is used to advertise Anti-Pneumococcic Oil, previous work (_München, med. Wchnschr._, No. 36, 1909) is mentioned as the starting point for the use of camphor in pneumonia. In this article, the author reports his first case, that of a young woman who entered St. Francis’ Hospital on the third day after the initial chill “with the symptoms of severe toxemia (unconscious, temperature 105.5 F., pulse 130, and respiration 40) and involvement of both lower lobes.” “Large doses of camphor,” 12 c.c. of a 20 per cent. solution, were injected hypodermically “every twelve hours, resulting in _gradual_ improvement and recovery by the fourth day, without a crisis.” Seibert reports success in its use in twenty-one cases, but gives no case histories or protocols. He admits, however, that in four out of sixteen cases, following the first twenty-one so reported certain “limitations of this treatment were observed,” and a “sudden rise of temperature in two patients on the second and third days of treatment, respectively, proved to be due to pneumococcic nephritis, promptly subdued by appropriate doses of urotropin, while the camphor injections were continued and resulting in speedy recovery.” He further admits that empyema occurs, and states: “This proves that the camphor brought into the blood cannot prevent the as yet living organisms, constantly entering the blood current from the affected alveoli, from colonizing in the renal and pleural tissue.”

He reports, among thirty-seven patients treated in this manner, one death, that of a man 68 years old, weighing 200 pounds, with a fatty heart. Heart failure was the real cause of death. Seibert also reports some very incomplete experimental work; Dr. Hensel, assistant and pathologist of the German Hospital, found that “1/10,000 part of camphor added to the usual culture media inhibited the growth of pneumococci, while the controls all thrived”; Dr. J. C. Welch, pathologist of the Lying-in Hospital, found that rabbits infected with lethal doses of pneumococcus cultures intravenously were saved by large doses of camphorated oil; fragmentary protocols are given. The assistant pathologist of St. Francis’ Hospital carried on the experimental work, adding salicylic acid to the camphor. No blood cultures are reported. The conclusion reached by Dr. Seibert is that salicylic acid up to 3 per cent., added to the camphorated oil, is effective in preventing pleural infection. In the article by Dr. Seibert, there appear most sketchy reports of cases, recovery being reported without crisis in from three to nine days.

The referee has made a careful search of the literature, with the following results: Boehnke (_Berl. klin. Wchnschr._ 50:818, 1913), using white mice, failed to confirm the experiments reported in Seibert’s paper, unless camphorated oil were given before the pneumococci, and even then, he felt that the results were too irregular to be of great significance. When given with anti-pneumococcic serum, however, he felt that there was some benefit to be seen by the administration of camphor; his protocols, however, are not detailed. There is no report of blood cultures, etc.

Another worker, H. Leo (_Deutsch. med. Wchnschr._ 39:690, 1913), reported that camphor water given intravenously prolonged the lives of thirty-eight rabbits inoculated with pneumococci. Here again there were no adequate protocols and very little evidence of careful experimental work appears.

In the literature of the past ten years, there appear sketchy clinical articles on the value of huge doses of camphor in pneumonia. Markevitch (_Russk. Vrach_, June 27, 1914; abstr., The Journal, Dec. 5, 1914, p. 2081) treated 226 cases of pneumonia with 5 c.c. of camphorated oil hypodermically four times daily, at the same time giving digitalis (amount not stated), with a mortality of 6.6 per cent., whereas, in 322 cases untreated, there was a mortality of 13.3 per cent. He reports 133 grave cases; sixty-six received no camphor; 48 per cent. died. Of sixty-seven treated with camphor, only 22 per cent. died. He reports temperature falling by lysis when camphor is used, and comments on the symptomatic improvement following its use. With the great variation in the clinical course of pneumonia, the above figures, though suggestive, certainly need further support before the routine use of camphor as recommended by Seibert can be sanctioned.

Later articles found on the subject refer to it in a very cursory way, giving no protocols and no cases, and giving the referee the feeling that the conclusions were very impressionistic.

RÉSUMÉ

After a careful search of the literature, the referee concludes that: Huge doses of camphor, to 250 grains in twenty-four hours, may be given to man without serious results. No satisfactory evidence, however, appears that camphor has a specific germicidal action on pneumococci (similar to that of ethylhydrocuprein). The clinical evidence, as found in the literature, is certainly of very little value. It appears that the sale of a simple solution of camphor in oil under the guise of “Anti-Pneumococcic Oil” is to be deplored (a 20 per cent. solution of camphor in cottonseed oil is official in the U. S. Pharmacopeia as camphor liniment). It is recommended that the preparation be held inadmissible to New and Nonofficial Remedies because exaggerated therapeutic claims are advanced for it, and because the name is not descriptive of the composition, but is, instead, therapeutically suggestive.--(_From The Journal A. M. A., Jan. 3, 1920._)

DIAL “CIBA”

Report of the Council on Pharmacy and Chemistry

Dial “Ciba” has not been accepted for “New and Nonofficial Remedies” because, as the report which follows shows, unwarranted claims are made for the product. It is a definite new chemical compound which might be made eligible for N. N. R. if misleading therapeutic claims were eliminated. The Council directed that Dial “Ciba” be included with Articles Described but Not Accepted, so that physicians might be informed with regard to its character and properties.

W. A. Puckner, Secretary.

Dial “Ciba” is a hypnotic manufactured by the Society of Chemical Industry of Basle, Switzerland, and is sold in the United States by A. Klipstein and Company, Inc., New York. Chemically, Dial “Ciba” is diallylbarbituric acid and is, therefore, closely related to diethylbarbituric acid or barbital (“veronal”).

The claims made for Dial “Ciba” are (1), that the “allyl” group in its molecule makes it more readily decomposed by oxidizing agents than barbital, which contains the “ethyl” group; (2) that because of this ease of oxidation, it is more readily decomposed in the body and more rapidly and completely eliminated, and (3) that because of its alleged rapid elimination, it is devoid of the after effects of barbital and other hypnotics.

The Council took up the substance in February, 1918, and referred the matter to the referee in charge of barbital preparations. The referee considered unwarranted the claim that Dial “Ciba” did not have the after-effects of other hypnotics due to its alleged total decomposition in the body. The American agents, A. Klipstein and Company, were informed of the referee’s objections. Their attention was also called to the fact that, notwithstanding the claimed absence of after-effects in one part of the advertising, other parts of the same advertising admitted certain post-hypnotic effects of the product. It was pointed out also that while it was claimed in one of the advertising circulars that lowering of the blood pressure is never observed after administration of Dial “Ciba,” yet two of the authors quoted in the same circular definitely stated that a lowering of the blood pressure followed even small doses of the drug and these authors warn against this very danger in certain conditions.

A year later, a circular letter sent out by A. Klipstein and Company reiterated the claim that the asserted decomposition of Dial “Ciba” in the body prevents after-effects, the drug being still contrasted with barbital (“veronal”). In view of the reiteration of this highly improbable claim, the referee undertook to study the comparative action of Dial “Ciba” as compared with other hypnotics. It was found that the actions of Dial “Ciba” are not distinguishable, qualitatively, from those of barbital, there being no perceptible difference in the after-effects or in the nature of the side actions. In toxic doses, both caused profound depression with the temperature falling to that of the room (or about one degree above), the respiration being extraordinarily slow and shallow as one would expect with lowering of the temperature. There were also the same evidences of nausea that are so frequently seen after toxic doses of the various hypnotics of this group. In view of these results, the Council declared that it is unwarranted to claim freedom from after-effects for Dial “Ciba.”

The Council held that the following statement is unwarranted:

“The therapeutic field for Dial ‘Ciba,’ as shown by tests on rabbits, is just as broad as the field for Diethylbarbituric Acid.”

Tests on rabbits do not and cannot show the breadth of the therapeutic field for a hypnotic. The Council also declared the following statement improbable, and contrary to the evidence obtained by the referee:

“In dogs, the increase of dosage beyond the therapeutic dose to the point of death is decidedly in favor of Dial ‘Ciba,’ which required a larger dose [than diethylbarbituric acid] to produce death.”

The referee’s experiments on cats show that Dial “Ciba” is several times as toxic as hydrated chloral, and more than twice as toxic as diethylbarbituric acid (barbital).

Since the circular to which objection was made in 1918 was still being sent out in December, 1919, the Council held Dial “Ciba” inadmissible to N. N. R. and voted that report of its action in the matter be authorized for publication. The Council further directed that Dial “Ciba” be included with Articles Described but Not Accepted.--(_From The Journal A. M. A., Jan. 24, 1920._)

APOTHESINE

Report of the Council on Pharmacy and Chemistry

Apothesine is a synthetic drug for producing local anesthesia, made by Parke, Davis & Company. In the fall of 1917 the Council wrote to Parke, Davis & Company offering its aid in establishing the identity, purity and therapeutic efficiency of this synthetic local anesthetic with the ultimate object of accepting the product for inclusion in New and Nonofficial Remedies should the facts warrant such acceptance. The Council’s letter was never acknowledged. After Apothesine was put on the market the Council desired to accept it for inclusion in New and Nonofficial Remedies but, unfortunately, was unable to do so because some of the claims made for the product were not justified by acceptable evidence. The manufacturers were notified of the Council’s desire to admit this product to N. N. R. and the wish was expressed that the company would either so modify its claims as to make the product acceptable under the Council’s rules or else would submit evidence to the Council in proof of the claims made and thus permit the Council to revise its conclusions. Parke, Davis & Company were, apparently, either unwilling or unable to submit evidence that would sustain their claims; neither did they offer to modify the claims themselves. The product, therefore, is ineligible to inclusion in New and Nonofficial Remedies; it will, however, be listed in the “Described But Not Accepted” department of New and Nonofficial Remedies. The report on Apothesine that follows has been authorized for publication.

W. A. Puckner, Secretary.

Apothesine, “the hydrochlorid of diethyl-amino-propyl-cinnamate,” is an efficient local anesthetic. It belongs to the procain rather than to the cocain type, that is, it belongs to that type which, while effective for injection anesthesia (especially when combined with epinephrin) is relatively inefficient when applied to mucous membranes. Apothesine may also be used for spinal anesthesia. Its absolute toxicity is less than that of cocain (as 20 is to 15, see table below) but about twice that of procain (as 20 is to 40, see table below). It is non-irritant, is easily soluble and makes a stable solution so that it may readily be sterilized.

The Council took exception to certain claims made by Parke, Davis & Company for their product on the ground that these claims were not supported by acceptable scientific evidence. One of the claims was that Apothesine is applicable in any case in which any other local anesthetic is used. This statement, made in many advertisements, is distinctly misleading as used. When applied to mucous membranes Apothesine is far inferior to cocain and to some other local anesthetics, yet the claim obviously suggests that Apothesine is an efficient substitute for any local anesthetic.

The manufacturers claimed, too, that Apothesine is as potent as cocain. The claim would lead the physician to think that Apothesine had the same anesthetic potency as cocain in solution of equal strength. This statement, so far as it refers to the drug when applied to mucous membranes, is not in accord with the facts and is true for injection anesthesia only when stronger solutions are used. The only support for the claim of equal efficiency appears to be the experiments with intracutaneous injections made by H. C. Hamilton[130] in Parke, Davis & Company’s laboratory. These differed considerably from the results of Sollmann.[131] A further series of experiments were made by Sollmann to compare still further the diverse results previously reported by him and Hamilton. The latest series, while showing considerable variations in the susceptibility of different skin areas, especially toward Apothesine, demonstrated in every case that the efficiency of Apothesine is unmistakably lower than that of cocain, being at best one half. The series also showed that the potency of Apothesine was never greater than procain and averaged considerably below it.

[130] The Comparative Values of Some Local Anesthetics by H. C. Hamilton, Detroit, Mich., from the Research Laboratory of Parke, Davis & Co., J. Lab. & Clin. M. =4=:60 (Nov.) 1918.

[131] Comparative Efficiency of Local Anesthetics, V, by T. Sollmann, from the Pharmacological Laboratory of the School of Medicine, Western Reserve University, J. Pharmacol. & Exper. Therap. =11=:69 (Feb.) 1918.

Another claim made for Apothesine which the Council holds is not supported by evidence is that of superior safety. This claim is made on the basis of hypodermic injections in guinea-pigs carried out in the laboratory of Parke, Davis & Company. Such experiments prove little because of the fact--well known to laboratory workers--that the use of rodents in toxicity tests made by injecting a drug into the subcutaneous tissues does not give a reliable index of the relative toxicity of such a drug for man. This is due partly to the peculiar resistance of rodents to poisons and partly to the great importance of the rate of absorption. The organism destroys most local anesthetics so rapidly that the rate of absorption is more important than the absolute dose. The absorption from hypodermic injections into guinea-pigs differs, of course, from that in clinical accidents, especially where the drug has been applied to mucous membranes. One cannot, therefore, reliably estimate the degree of clinical danger on animals.

It has been shown that when toxicity tests of local anesthetics are made on cats these animals seem to respond to the drugs in a manner more closely approximating humans and it is a suggestive fact that the more toxic of local anesthetics, as shown by tests on cats, have been found the most dangerous in clinical use. The _absolute_ toxicity of Apothesine has been measured by Eggleston and Hatcher[132] by the intravenous injection in cats. The fatal doses, in terms of milligrams per kilogram ranged as follows:

Alypin, Holocain 10 Beta Eucain 12.5 Cocain 15 Apothesine 20 Tropacocain 20-25 Stovain 25-30 Nirvanin 30-35 Procain 40-45

[132] A Further Contribution to the Pharmacology of the Local Anesthetics by Eggleston and Hatcher, from the Department of Pharmacology, Cornell University Medical College, New York City, J. Pharmacol. & Exper. Therap. =13=:433 (Aug.) 1919.

The _absolute_ toxicity of Apothesine is, therefore, only a little lower than that of cocain, and is twice as great as that of procain. The _clinical_ dangers cannot be predicted by either method, since clinical accidents depend, in most instances, on idiosyncrasies, or the technic of application.--(_From The Journal A. M. A., Jan. 24, 1920._)

EUMICTINE

Report of the Council on Pharmacy and Chemistr