“Toxicide contains Lachesis 12X, Tarantula 6X, Psorinum (special) 15X, Silicia 6X and Excipient q. s. (the excipient is sweet milk).“These remedies are combined in the sweet milk and put through a process of development, which produces the curative agent which we call ‘Toxicide’...“Put up in tablet form, sugar coated and colored red.”
“Toxicide contains Lachesis 12X, Tarantula 6X, Psorinum (special) 15X, Silicia 6X and Excipient q. s. (the excipient is sweet milk).
“These remedies are combined in the sweet milk and put through a process of development, which produces the curative agent which we call ‘Toxicide’...
“Put up in tablet form, sugar coated and colored red.”
No information is given as to the proportions, either relative or actual, of the ingredients. Neither is any information given regarding the “process of development” to which the mixture is subjected, nor the amount of the finished mixture which is contained in Toxicide tablets.
The Toxicide Laboratories present the following “theory”:
“In combining these remedies and processing with milk, we develop a latent immunizing active principle, which usually controls the most virulently, active, septic infections promptly.”
“In combining these remedies and processing with milk, we develop a latent immunizing active principle, which usually controls the most virulently, active, septic infections promptly.”
Photographic reproduction (reduced) of an advertisement of the “originator” of Toxicide; it ran for many months in the program of a burlesque theater located in Ruckel’s neighborhood.
Photographic reproduction (reduced) of an advertisement of the “originator” of Toxicide; it ran for many months in the program of a burlesque theater located in Ruckel’s neighborhood.
There is no evidence, however, that any effort has been made to demonstrate the presence of a “latent immunizing active principle” by scientific methods of modern immunology. The following claims for the use of Toxicide appear on the label:
“Acne, boils, carbuncles, furuncles and abscesses of the most virulent types usually begin to show improvement within 4 to 12 hours after beginning administration.“In badly infected wounds, Toxicide will check the further destruction of live tissue and should always be given for a few days before and after operations on pus cases.“For gunshot wounds and other conditions difficult to sterilize or drain, Toxicide is the ideal remedy.“For abscesses existing or threatened in any obscure location, the middle ear, the mastoid, the frontal or any accessory sinuses, Toxicide is of inestimable value.“If administered early, in fractures, compound or simple, or for laceration and other injuries, inflammation, swelling, soreness and destruction of tissue will be greatly mitigated.”
“Acne, boils, carbuncles, furuncles and abscesses of the most virulent types usually begin to show improvement within 4 to 12 hours after beginning administration.
“In badly infected wounds, Toxicide will check the further destruction of live tissue and should always be given for a few days before and after operations on pus cases.
“For gunshot wounds and other conditions difficult to sterilize or drain, Toxicide is the ideal remedy.
“For abscesses existing or threatened in any obscure location, the middle ear, the mastoid, the frontal or any accessory sinuses, Toxicide is of inestimable value.
“If administered early, in fractures, compound or simple, or for laceration and other injuries, inflammation, swelling, soreness and destruction of tissue will be greatly mitigated.”
In support of these claims there are offered letters from physicians who have used Toxicide with good results. None of these testimonials present evidence that the reported effects were due to Toxicide. The asserted—and highly improbable—action of Toxicide could be determined only by an extensive series of carefully controlled clinical trials—and such evidence is entirely lacking. In fact, the claims appear to have no better basis than the coincidence which is stated to have led to the discovery of the “remedy”; namely, that a boil on the neck disappeared shortly after the administration of Toxicide!
The Council finds Toxicide inadmissible to New and Nonofficial Remedies because (1) the identity and amount of the potent constituent or constituents have not been furnished; (2) the preparation is advertised indirectly to the public; (3) the name “Toxicide” is therapeutically suggestive, and (4) the therapeutic claims, being unsubstantiated by evidence, are unwarranted.
Photographic reproduction (greatly reduced) of an advertising circular used some time ago describing the marvels (alleged) of Toxicide.
Photographic reproduction (greatly reduced) of an advertising circular used some time ago describing the marvels (alleged) of Toxicide.
[Editorial Comment.—It seems rather preposterous that a scientific body, such as the Council on Pharmacy and Chemistry, should have to waste its time in investigating and reporting on such an obviously unscientific product as “Toxicide.” So long, however, as there are physicians who will take preparations of this sort seriously, the Council feels that it is its duty to report on such products. The problem, in fact, was well stated in a letter addressed to the editor some months ago by the secretary of a county medical society who had just received a visit from a representative of the Toxicide Laboratories and who sent toThe Journalsome of the advertising matter that he had received from the same source. This physician wrote:
“I do not wish to trouble you with this kind of material, usually deposited safely in my waste paper basket, but the enclosed was handed to me today by a ‘bird’ who is calling on all the doctors and making strong statements. When he claimed that ‘Toxicide’ is being used in the Presbyterian Hospital, Chicago, and that the Council on Pharmacy and Chemistry is considering it seriously, etc., etc., I wish to know whether I am missing any real good thing. If it has any real virtue, I would like to know about it, but if it has not, it seems to me that something ought to be done to head him off as some doctors are sure to fall for some of it.”
“I do not wish to trouble you with this kind of material, usually deposited safely in my waste paper basket, but the enclosed was handed to me today by a ‘bird’ who is calling on all the doctors and making strong statements. When he claimed that ‘Toxicide’ is being used in the Presbyterian Hospital, Chicago, and that the Council on Pharmacy and Chemistry is considering it seriously, etc., etc., I wish to know whether I am missing any real good thing. If it has any real virtue, I would like to know about it, but if it has not, it seems to me that something ought to be done to head him off as some doctors are sure to fall for some of it.”
The Toxicide Laboratories is, apparently, merely a trade name used by the alleged originator of “Toxicide,” J. F. Ruckel, M.D. According to our records, Ruckel was born in 1860 and was graduated by the Chicago Homeopathic Medical College in 1886. He claims to have originated Toxicide about twenty years ago and to have prescribed it “in over 3,000 cases.” In addition to Toxicide, the Toxicide Laboratories also put out “Dianasiac for Nymphomania and Satyriasis” and “Somnosine for Insomnia.”]—(From The Journal A. M. A., Oct. 8, 1921.)
The Council has authorized publication of the following report:
W. A. Puckner, Secretary.
“Pil. Mixed Treatment (Chichester)” is a proprietary preparation of the Hillside Chemical Co., Newburgh, N. Y. It is sold in the form of pills, each said to contain1⁄20grain of mercuric iodid and 5 grains of potassium iodid.
In 1907 the Council examined the therapeutic claims advanced for this preparation and found that they were unwarranted, exaggerated and misleading. It found, also, many misleading statements in regard to the product itself. Furthermore, the A. M. A. Chemical Laboratory found the pills to be “short weight” in potassium iodid content.
At the time that the Council examined Pil. Mixed Treatment (Chichester), a dermatologist of recognized standing, to whom the “literature” for this product had been submitted for an opinion, made the following report:
“Assuming that this pill contains what is claimed for it, one-twentieth (1⁄20) of a grain of biniodid of mercury and five (5) grains of potassium iodid, it presents neither an original nor a very useful formula.
“The literature furnished by the company abounds in suggestions that the mixture, as they prepare it, represents some unusual potency which is not possessed by the ordinary mixture of these same drugs in the same proportion. These suggestions may of course be dismissed without consideration. There is nothing mysterious in a mixture of potassium iodid and biniodid of mercury and this formula is no more entitled to special consideration than any other pill or tablet of the same composition prepared by any reputable pharmaceutical firm.
“The formula of this pill, however, does not represent a good combination. It is offered for use both during the active secondary period of syphilis and for tertiary lesions. The pill does not contain enough mercury to be an efficient remedy for secondary syphilis and not enough potassium iodid to be satisfactory in the treatment of tertiary lesions. It is neither fish, flesh, fowl, nor good red herring. A patient with secondary syphilis should not be dosed all the time with potassium iodid and for the treatment of tertiary lesions he should have a very much larger quantity of potassium iodid than can be given in these pills without giving toxic doses of mercury.
“The statement that this pill ‘does not impair the appetite nor disturb digestion and is well borne by patients who cannot tolerate iodids otherwise administered’ is a bald claim which cannot be justified by experience. The most unsatisfactory way of administering potassium iodid is in solid form. A patient who can stand potassium iodid in pill form, as it is furnished in this preparation, can stand it in any form in which it is ever administered.
“In short this preparation is neither agreeable nor efficient. The greatest objection to it is its inefficiency, for it is offered as an adequate preparation for the treatment of syphilis in all of its stages, whereas it is neither satisfactory for the treatment of secondary syphilis nor of tertiary lesions.”
During the fourteen years which have elapsed since the Council’s first examination of Pil. Mixed Treatment (Chichester), arsphenamin has been added to the syphilographer’s armamentarium and much has been learned about syphilis and its treatment. While there exist differences of opinion as to the exact value of arsphenamin in the treatment of syphilis and there are even some who desist from the use of arsenic compounds of any kind, no syphilographer of standing countenances the routine treatment of syphilis with a fixed combination of mercuric iodid and potassium iodid. The use of Pil. Mixed Treatment (Chichester) is on a par with the use of certain “blood purifiers” which were advocated at a time when the treatment of syphilis was a baffling problem.
The present advertising, which reads as if it had been written in the heyday of proprietary license, is, in effect, an invitation to treat syphilis in its various stages and manifestations with Pil. Mixed Treatment (Chichester). If heeded by those who read the advertising of the Hillside Chemical Co., it will result in much harm to the public and the profession. For this reason, the present report of the Council is published as a protest against any advertising propaganda advocating the routine treatment of a disease which requires that each case be studied carefully so that prompt and efficient measures may be applied to the various manifestations of the disease.
The following advertisement appeared recently in several medical journals:
“Medicine is an Exact Science—on Paper Only!” Every general practitioner of medicine is called upon to treat Syphilis occasionally. He cannot depend upon the use of arsenicals alone. In most cases, “mixed treatment” the giving of mercury and iodides is required to get satisfactory results.Pil. Mixed Treatment(Chichester) accurately and successfully meets the indications and assures definite action. Important advantages:Ready solubility of mercury in combination with Potassium Iodide.Avoidance of gastric, buccal or intestinal disturbance.Easy administration, can be taken at any time, anywhere.Economical, both drugs in one combination.Accurate adjustment of dosage to each individual case.Full physiological action—assured by purity of content.Secrecy—patient or friends do not know nature of medicine. Pil Mixed Treatment (Chichester) has been time tested and trial proven. It needs no introduction to the thousands of physicians who prescribe or dispense it.
“Medicine is an Exact Science—on Paper Only!” Every general practitioner of medicine is called upon to treat Syphilis occasionally. He cannot depend upon the use of arsenicals alone. In most cases, “mixed treatment” the giving of mercury and iodides is required to get satisfactory results.Pil. Mixed Treatment(Chichester) accurately and successfully meets the indications and assures definite action. Important advantages:
Ready solubility of mercury in combination with Potassium Iodide.
Avoidance of gastric, buccal or intestinal disturbance.
Easy administration, can be taken at any time, anywhere.
Economical, both drugs in one combination.
Accurate adjustment of dosage to each individual case.
Full physiological action—assured by purity of content.
Secrecy—patient or friends do not know nature of medicine. Pil Mixed Treatment (Chichester) has been time tested and trial proven. It needs no introduction to the thousands of physicians who prescribe or dispense it.
While the advertisement does not directly so advise, yet it is a subtle invitation to the general practitioner to use Pil. Mixed Treatment (Chichester) and thus save himself and his patient the time and inconvenience which the rational treatment of syphilis imposes. A circular “The Treatment of Syphilis Simplified and Improved” begins:
“No therapeutic fact is more conspicuously and decisively established than that a radical cure of syphilis can be effected by the continuous administration, from the period of development, of a proper combination of mercury with iodine.”
“No therapeutic fact is more conspicuously and decisively established than that a radical cure of syphilis can be effected by the continuous administration, from the period of development, of a proper combination of mercury with iodine.”
Continuing, it is admitted that mercury is the most efficacious drug in the primary and secondary stages of syphilis and iodin in the tertiary stage, but it is asserted that:
“... it is now granted by all syphilologists that the antiluetic action of these drugs is immeasurably augmented by properly combining them, and that the best results are obtained when they are conjunctively administered throughout the entire course of the disease.”
“... it is now granted by all syphilologists that the antiluetic action of these drugs is immeasurably augmented by properly combining them, and that the best results are obtained when they are conjunctively administered throughout the entire course of the disease.”
Arguing along the same lines, this circular continues:
“... it was not until mercury and iodine in the form of Pil. Mixed Treatment (Chichester) was evolved that the marked advantages of the combined employment of these drugs in the various stages of syphilis became a scientific certainty.”
“... it was not until mercury and iodine in the form of Pil. Mixed Treatment (Chichester) was evolved that the marked advantages of the combined employment of these drugs in the various stages of syphilis became a scientific certainty.”
Further we are asked to believe that:
“Because of the greatly increased potency of mercury and iodine when combined, as in Pil. Mixed Treatment (Chichester), the foremost syphilologists are now agreed that the employment of these drugs in such form should be enjoined as soon as the disease develops, and should be thus continued until a cure has been effected; in other words, Pil. Mixed Treatment (Chichester) should be made the sole antisyphilitic medication throughout all stages of the disease.”
“Because of the greatly increased potency of mercury and iodine when combined, as in Pil. Mixed Treatment (Chichester), the foremost syphilologists are now agreed that the employment of these drugs in such form should be enjoined as soon as the disease develops, and should be thus continued until a cure has been effected; in other words, Pil. Mixed Treatment (Chichester) should be made the sole antisyphilitic medication throughout all stages of the disease.”
The circular illustrates the extent to which our knowledge of drugs may be distorted and misrepresented and the public health jeopardized in the exploitation of a proprietary medicine.
One reason scientific medicine lags. Uncritical medical journals perpetuate—for a price—the use of nostrums.
One reason scientific medicine lags. Uncritical medical journals perpetuate—for a price—the use of nostrums.
In its advertising, the Hillside Chemical Co. claims that Pil. Mixed Treatment (Chichester) both as to formula and method of preparation “in the incapsulated powder form” was “brought to the notice of the profession by Dr. W. R. Chichester of New York, an eminent Syphilographer and recognized authority in the therapeutics of Syphilis.” It is claimed that this pill “is perfectly soluble, tasteless, nonirritant, and therefore well adapted to a sensitive stomach.” It is claimed that the pill “is always preferable to one extemporaneously prepared, which, even if identical in composition, often gives negative results.”
An examination made in the chemical laboratory of the association to determine if the product now marketed contains the claimed amount of potassium iodid indicated that this was the case. The chemist who made this examination commented as follows on the claim that in this pill, potassium iodid is rendered tasteless, that the pill is “perfectly soluble” and that extemporaneous pills of “identical... composition often give negative results.”
“That the potassium iodid has been rendered tasteless is false, naturally; the pills when placed in the mouth, after removal of the coating, have the characteristic taste of alkali iodids. The claim that the pills are entirely soluble is incorrect; they contain a large amount of insoluble material, probably kaolin. The assertion that an extemporaneous compound prescription even if identical in composition with the Chichester pill is often inert, is absurd and a reprehensible attack by suggestion of the ideal that the physician shall write his prescription to meet the individual needs of his patient and that the pharmacist shall compound the prescriptions of the physician as they are required. It should also be pointed out that while much is said about the potassium iodid in the Chichester pill being in powdered form, the pill mass is solid and very slowly soluble and the claim of being in powdered form is, if immaterial, also incorrect.”
As to the asserted standing of the alleged discoverer of the formula for Pil. Mixed Treatment: Dr. William R. Chichester appears to have lived and practiced in New York since 1886 or longer, but the claim that he is an “eminent syphilographer” seems to have originated with the exploiters of “Pil. Mixed Treatment.” Search failed to show the name of W. R. Chichester among authors of textbooks of syphilis or any other branch of medicine or among authors of contemporary literature in theIndex Medicusfrom 1907 down to the present; nor did a search of the catalogue to the Surgeon-General’s Library reveal W. R. Chichester as ever having published anything on syphilis or any other subject.
Pil. Mixed Treatment (Chichester) is sold under therapeutic claims which are unwarranted and misleading. The preparation well illustrates the abuses which are connected with the exploitation as proprietaries of established drugs or mixtures of established drugs.—(From The Journal A. M. A., Oct. 22, 1921.)
The Council has authorized publication of the following report explaining why Atophan has been omitted from New and Nonofficial Remedies. Schering and Glatz, Inc., the firm which markets this brand of cinchophen in the United States, has refused to place either the U. S. Pharmacopeial name, “Phenylcinchoninic Acid (Acidum Phenylcinchoninicum)” or the N. N. R. name, “Cinchophen,” on the label and in the advertising matter so as to make the identity of the product clear to physicians. Furthermore, the product is sold under therapeutic claims which the Council holds to be exaggerated and unwarranted.
W. A. Puckner, Secretary.
The substance, 2-phenyl-quinolin-4-carboxylic acid, was described by Doebner and Gieseke in 1887 (Ann. d. Chem.[Liebig’s]242:291). The therapeutic properties of this compound were described by Nicolaier and Dohrn in 1908 (Deutsch. Arch. f. klin. Med.93:331). Subsequently the product was placed on the market and extensively advertised by the Chemische Fabrik auf Actien (vorm. E. Schering), Berlin, Germany. This firm also took out a patent in the United States on its production and in 1911 secured a U. S. trademark on the name “Atophan.” In 1912 Atophan was passed on by the Council and admitted to New and Nonofficial Remedies.
When the government of the United States took charge of German-owned patents during the World War, the Federal Trade Commission, and later theChemical Foundation, Inc., issued licenses to American firms whereby these were authorized to manufacture the compound. In the meantime, Schering and Glatz, Inc., who had been the U. S. representatives for the Chemische Fabrik auf Actien, also undertook to supply the drug, but did not obtain a license from the boards in charge of German patents. Also, this firm secured, in 1919, a trademark of the word “Atophan,” apparently after the German-owned trademark had been canceled.
The drug “Atophan” was admitted to the U. S. Pharmacopeia as “Phenylcinchoninic Acid (Acidum Phenylcinchoninicum).” As this name proved too cumbersome, the Council on Pharmacy and Chemistry coined the abbreviated name “Cinchophen” for it, and this name is now used by all the firms which are marketing the product in the United States, with the exception of Schering and Glatz, Inc., who use the term “Atophan,” first owned by the Chemische Fabrik auf Actien.
Because of the confusion which is bound to arise from giving various names to one drug, the Council selects a common name and provides standards of identity, purity and strength for any drug which, by reason of the absence or lapse of patent rights or for other reason, is open to manufacture by more than one firm. The Council, then, will accept such article only if it is marketed under the title adopted for New and Nonofficial Remedies. The rules provide, however, that when the Council adopts a common name for an article that has been admitted under another name, such article will be retained in New and Nonofficial Remedies under the older name if the Council name is given prominence on the label and in the circulars and advertisements, in order to avoid confusion. Accordingly, when the period of acceptance for Atophan in New and Nonofficial Remedies was about to expire, Schering and Glatz were notified that Atophan could be retained in that publication only on condition that the name, “Cinchophen,” or else the pharmacopeial name, “Phenylcinchoninic Acid (Acidum Phenylcinchoninicum)” be placed on the label and used in the circulars and advertising.
At the time that the Council asked Schering and Glatz to adopt cinchophen or phenylcinchoninic acid as a synonym for Atophan, the firm was also requested to omit from future advertising a number of therapeutic claims to which the Council was obliged to take exception. Schering and Glatz refused the first request and made no definite promise with regard to the second. The Council, therefore, directed the omission of Atophan from New and Nonofficial Remedies, 1921.
The advertising to which the Council took exception does not appear to be distributed at present. A pamphlet has been sent out, however, which is equally objectionable. It contains unwarranted therapeutic claims and suggests that Atophan be used in conditions in which it is not indicated. For instance:
“No longer the vague, hypothetical, ‘test-tube demonstrated’ principle of uric acid elimination by solution, but a definite, scientifically and clinically established, physiologic stimulation of the uric acid excretion. Performed innocuously and controllable to a nicety by dosage and by urine and blood tests.”
“No longer the vague, hypothetical, ‘test-tube demonstrated’ principle of uric acid elimination by solution, but a definite, scientifically and clinically established, physiologic stimulation of the uric acid excretion. Performed innocuously and controllable to a nicety by dosage and by urine and blood tests.”
The “innocuousness” of Atophan has not been proved; on the other hand there is evidence that it is not innocuous, as the recent investigations of Hanzlik and Scott and their collaborators (Cinchophen, Neocinchophen and Novaspirin in Rheumatic Fever, J. A. M. A.76:1728 [June 18] 1921) show that it may injure the kidney.
The circular also contains the following:
“No longer, hit and miss relief of pain at the expense of the heart, the intestines, the kidneys and the nervous system, but the promptest and most reliable analgesic, anti-inflammatory and decongestive action so far known, with notable freedom from heart depressant, renal irritant, constipating and cumulative toxic by-effects. No contraindications, except chronic nephritis and the presence of kidney concretions.”
“No longer, hit and miss relief of pain at the expense of the heart, the intestines, the kidneys and the nervous system, but the promptest and most reliable analgesic, anti-inflammatory and decongestive action so far known, with notable freedom from heart depressant, renal irritant, constipating and cumulative toxic by-effects. No contraindications, except chronic nephritis and the presence of kidney concretions.”
This is misleading. The drug depresses the circulation, injures the kidney and produces symptoms of salicylism or “toxicity.” It isnotthe promptest and most reliable analgesic; morphin is superior and salicylate is just as efficient. The phrase “decongestive action” is vague. Treatment of pulmonary congestion from phosgene, and congestion of the conjunctiva in mustard oil chemosis of cats, with large doses of Atophan was ineffective; in fact, it proved distinctly harmful. This was shown by such workers as Laqueur and Magnus, and Heubner and Gildemeister (Ztschr. f. d. ges. exper. Med.13:200, 1921). It is incorrect to ascribe “decongestive” or “anticongestive” action in the true sense to Atophan (cinchophen). The principal assets of the salicylate-cinchophen class of drugs in the treatment of rheumatism and gout are their analgesic and antipyretic qualities.
The claim is made:
“In Rheumatic and Gouty Disorders, whether of the well-known muscular and arthritic type, or their Eye, Ear, Nose and Throat manifestations.”
“In Rheumatic and Gouty Disorders, whether of the well-known muscular and arthritic type, or their Eye, Ear, Nose and Throat manifestations.”
The suggestion that Atophan is indicated in “their Eye, Ear, Nose and Throat manifestations” is a vague generalization without definite meaning, but nevertheless calculated to impress physicians and promote the sale of Atophan for common and minor ailments. Rhinitis and sore throat are, of course, self-limited conditions which require chiefly good habits, personal and general hygiene as prophylactic measures, and simple hot baths with rest, instead of medication, for symptomatic relief. When it comes to ear and eye conditions, Atophan certainly would do no good in otitis media, panophthalmitis, choroiditis, retinitis, etc.
The administration of Atophan is proposed “in Migrains, Hemicrania, Eyestrain, etc., often vaguely grouped as ‘Headaches.’ ” Eyestrain and headaches are vague symptoms often arising from numerous causes that require no medication, but rather good habits, hygiene and similar corrective measures. There is always the possibility of habituation from the use of drugs for such common and vague symptoms, resulting eventually in more harm than good to the patient.
The use of Atophan is proposed “In Influenza (Grippe) for the ready alleviation of the respiratory congestion, pain and stiffness of limbs and back.” Probably the entire claim is without warrant, since influenza is a self-limited disease. Atophan might relieve pain in the joints, reduce the fever, etc., but at the same time it would tend to impair the functional efficiency of the heart, which may be impaired already by the disease. Cardiac failure is one of the causes of death in influenza. The recommendation for “alleviating respiratory congestion” is certainly without warrant, since in actual trial in pulmonary congestion by Magnus et al., Atophan was found to be deleterious and not beneficial. Phosgenized cats are probably as good a test object for the alleged decongestive action of Atophan as anything could be, since, according to Underhill and Ringer (J. A. M. A.75:1531, 1920) the pathological physiology of the circulation and respiration in phosgene poisoning and influenza are nearly identical.
Further, Atophan is recommended “In Pyorrhea Alveolaris as a systemic support to local and specific measures.” Atophan is not indicated here. Pyorrhea requires local medication, if anything at all. It could exert no localbeneficial effects in this condition; indeed, the employment of Atophan might lead to irritation. Good dental treatment is more essential than medication.
Finally, Schering and Glatz advise Atophan “In Eczema, Pruritus and similar irritant and itching Skin Diseases with lowered blood alkalinity.” The assumption that blood alkalinity is lowered in irritant and itching disease is unsupported by evidence in medical literature and the recommendation is incorrect and misleading. Neither does Atophan alter the reaction of the blood. Amelioration in these capricious conditions occurs without medication so that any relief that might be obtained could not be attributed to Atophan. The entire paragraph is misleading and will undoubtedly tend to extend the use of Atophan in conditions for which it is not suited.—(From Reports of Council on Pharmacy and Chemistry, 1921, p. 8.)
Urotropin is a proprietary name applied to the substance which is known in chemical literature as hexamethylenetetramin and which is designated hexamethylenamine in the U. S. Pharmacopeia. The Council has authorized publication of the following report explaining that Urotropin was omitted from New and Nonofficial Remedies because Schering & Glatz, Inc. (the firm that markets this brand of hexamethylenamin in the United States), refused to place the U. S. Pharmacopeia name Hexamethylenamine (hexamethylenamina) on the label and in its advertising so as to make clear to physicians the identity of the product, and, furthermore, because it was sold under therapeutic claims which the Council held unwarranted.
W. A. Puckner, Secretary.
This substance which is generally referred to in chemical literature as hexamethylenetetramin, the cyclic condensation product of formaldehyd and ammonia, appears to have been described first in 1860 (Butlerow:Ann. d. Chem.115:322, 1860). Subsequently, numerous references to the preparation, properties and constitution of the substance appeared in chemical literature.
Hexamethylenetetramin is said to have been first used for therapeutic purposes by G. Bardet, who, in 1894, reported to the Société de Thérapeutique that he believed this substance to be a uric acid solvent. At about the same period, A. Nicolaier, who gave Bardet credit for suggesting the use of hexamethylenetetramin as a uric acid solvent, announced the discovery of its antiseptic action (Centralbl. f. d. med. Wissensch.32:897, 1894;Deutsche med. Wchnschr.21:541, 1895). Shortly thereafter as a result of Nicolaier’s publication, the Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, Germany, began to offer the product to the medical profession under the trademarked and nondescriptive name “Urotropine.” In the United States, it was marketed by Schering and Glatz, who then were acting as American agents for the Schering works of Germany.
It soon became evident that hexamethylenetetramin was a valuable drug. As the substance was introduced at a time when new “synthetic” drugs were rapidly appearing and when unlimited and uncritical confidence was placed in them, and before the medical profession became skeptical of the claims advanced by manufacturers for their respective “discoveries,” it was not long before this new drug was placed on the market by many firms, each applying its own name and often keeping the chemical character of it in the background. Some of the names which were thus applied to hexamethylenamin were Cystogen, Aminoform, Formin, Uritone, Urisol, {and} Cystamine.
In 1907 the late Prof. J. O. Schlotterbeck, then a member of the Council, protested against the confusion caused by the marketing of a given drug under different names. He stated that it was not uncommon for a physician to prescribe two or more of these identical substances in the same mixture, expecting to get the combined action of different urinary antiseptics; also, that patients had been treated first with hexamethylenamin under one name and later by the same substance under another name (The Journal, Jan. 19, 1907, p. 241).
Hexamethylenetetramin was admitted to the eighth revision of the U. S. Pharmacopeia. In part because of this official recognition and standardization and in part because the extravagant reports of its virtues had been largely discounted, physicians have in general prescribed the drug by its pharmacopeial name, with one notable exception: Urotropin. One reason for this is that Urotropin was the first proprietary brand of hexamethylenetetramin introduced, a second reason is that through the extensive and persistent advertising of the proprietary name under which the substance was introduced, it has become firmly fixed in the minds of many physicians. The other is that the product was claimed to be of greater purity than the product sold under the pharmacopeial or other name although no evidence confirmatory of this claim has ever been published. On the other hand, Daniel Base, as long ago as 1907, found that hexamethylenamin sold under its pharmacopeial name is just as pure as when sold under proprietary names. When, in 1907, urotropin was admitted to New and Nonofficial Remedies, the published description showed that it was manufactured by the Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, and that Schering and Glatz were the United States agents. In 1919, the description was revised to show that Schering and Glatz were no longer selling the German product.
As it is the general practice to omit articles that are admitted to the U. S. Pharmacopeia for the reason that their quality is guaranteed under the federal Food and Drugs Act and because pharmacopeial nonproprietary articles are rarely advertised with claims that require the Council’s control, yet, in the case of Urotropin, it was retained because it was sold under a name not recognized in the pharmacopeia and because special (proprietary) claims were made for it.
The period for which Urotropin stood “Accepted” expired with the close of 1921. To determine its continued eligibility for New and Nonofficial Remedies, the Council examined the labels and circular matter sent by Schering and Glatz for the purpose and also a booklet “Urotropin,” subsequently sent by the firm to physicians.
It was found that the pamphlet contained a number of unwarranted statements. Particularly objectionable are the claims made for the use of Urotropin as an antiseptic in body fluids that are alkaline, such as the cerebrospinal fluid, bile, aqueous humor of the eye, saliva, the excretions caused by middle ear infection and other excretions of the nasal, bronchial, laryngeal and mucous membranes. The lack of efficacy of hexamethylenamin in alkaline secretions is generally admitted and the clinical references to the use of hexamethylenamin in the pamphlet are obsolete. In the introduction to the pamphlet, Schering and Glatz state that they are well acquainted with the scientific research work discrediting the efficiency of hexamethylenamin in nonacid mediums, but that they feel that the accumulated evidence for its efficacy in such conditions should not be “brushed aside.” However, the pamphlet is not made up of quotations, but of unqualified statements. With one exception, all references to the antiseptic properties of the drug in alkaline mediums are previous to 1913, that is, before the importance of reaction of the medium wasfully appreciated. To quote these earlier articles without regard to the later work, which in most eyes discredited them, constitutes in effect an exploitation of this brand of hexamethylenamin under unwarranted therapeutic claims.
In consideration of the confusion which arises from the application of different names to an identical article, the rules of the Council provide that when an article which has been accepted for New and Nonofficial Remedies is admitted to the U. S. Pharmacopeia under another name, it will be retained, provided the official name is given prominence on the label and in the advertising of such article. Neither the label nor the advertising for Urotropin gives prominence to the pharmacopeial name as a synonym nor indeed does it bring out the fact that Urotropin is a brand of hexamethylenamine, U. S. P. Schering and Glatz, Inc., was advised that Urotropin could be retained in New and Nonofficial Remedies only on condition that the objections to the therapeutic recommendations were removed and on agreement that the U. S. P. name appear on the labels and circular matter. The firm did not offer to make the product eligible for continued recognition; accordingly the Council directed the omission of Urotropin because of conflict with Rule 6 (Unwarranted Therapeutic Claims) and with Rule 8 (Objectionable Names).—(From Reports of Council on Pharmacy and Chemistry, 1921, p 71.)
The Council has authorized publication of the following report, declaring Styptysate (Ernst Hischoff Co., Inc.) inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Styptysate, according to the advertisement of Ernst Bischoff Co., Inc., New York, is “obtained by dialysis from Bursa Pastoris (Sheppard’s [sic!] Purse).” It is claimed to be “The Remedy For Hemorrhages,” to be “Superior to Ergot and Hydrastis,” “of particular advantage in Menorrhagia and Metrorrhagia” and to have been “found of great value in vesical hemorrhages and hemorrhages from mucous membranes in general.” The Styptysate label bears the synonym “Dialysate Herba Bursa Pastoris”; the statement that it contains “alcohol 11 per cent.” and that it is “made in Germany.” No other statement of the composition or strength of “Styptysate” is furnished nor is the name of the German manufacturer disclosed.
In an advertising circular entitled “Styptysate, a New Reliable Hemostatic,” it is declared that in recent years the plant, Shepherd’s Purse (Capsella bursa pastoris), “has been submitted to clinical tests in the form of a concentrated dialysate, known as Styptysate, by Loewy, Oppenheim, Krummacher and others, and that their reports coincide in regard to Styptysate as a hemostaticpar excellence, particularly in uterine hemorrhages, even in cases where ergot and hydrastis had failed to produce satisfactory results.” The circular also reprints some “short clinical reports” without reference to their authorship; one ascribed to Krummacher and two ascribed to “B.H.M., Kansas City, Mo.,” and the following references: “A. Krummacher, M.D.,Monthly Review for Obstetrics and Gynecology, Berlin, Vol. XLIX, 4, and Vol. LII.” “H. Oppenheim, M.D.,Medical Clinic, Berlin, 1920, 35.”
Shepherd’s Purse is a weed common in the United States and in Europe. Like most other herbs, it has some reputation as a folk medicine. It is used by eclectics and homeopaths, being included in the Homeopathic Pharmacopeia of the United States. Shepherd’s Purse receives no consideration at the hands of the authors of standard works on materia medica, pharmacology or therapeutics.
From an examination of recent German medical publications, it appears that the use of Shepherd’s Purse was proposed as a substitute for ergot and hydrastis, when the latter drugs became scarce in Germany. These publications, in the main, emanate from those in the employ of pharmaceutical firms and deal with proprietary preparations or they are written by physicians who used these proprietary preparations at the solicitation of the manufacturers. For this reason the reported results must be accepted with reserve.
One of the proprietary preparations discussed in the German publications is Styptysate, manufactured by Isalfabrik Johannes Buerger, Wernigerode. It is said to be produced by submitting the juice of fresh Shepherd’s Purse to dialysis and preserving the dialysate by the addition of alcohol. There is no statement as to the drug strength or the chemical or biological standards, if any, used in its manufacture; hence, the preparation is essentially a secret one. As first produced, the preparation seems to have been fortified by the addition of cotarnin: the dose was then given as ten to fifteen drops. Later, as the cost of cotarnin went up, this drug was omitted, and the drug strength increased; the dose of the new preparation is given as twenty-five to thirty drops. Just what relation, if any, the Styptysate of Ernst Bischoff Co., Inc., bears to that of the Isalfabrik Johannes Buerger, Wernigerode, cannot be determined from the Bischoff advertising. If it has any relationship the announcement that no narcotic order is required when ordering Styptysate would indicate that the new preparation is supplied; the old one with its addition of cotarnin would require a narcotic order. On the other hand, the recommended dose of the cotarnin-free preparation is twenty-five to thirty-drops, whereas the product sold by Bischoff and Co. is to be given in doses of ten to fifteen drops—that is, in the amount proposed for the cotarnin-fortified product.
What justification is there for the claim that Styptysate has been submitted to clinical tests by Loewy, Oppenheim and Krummacher and found to be a hemostaticpar excellenceand efficient even where ergot had failed to give satisfactory results? Loewy (Zentralblatt für Gynäcologie42:920, 1921) made some pharmacologic tests on guinea-pigs with the cotarnin-containing preparation, but reported no clinical trials. Hans Oppenheim (Medizinische Klinik, Aug. 29, 1920, p. 906) reported that he was agreeably surprised at the excellent results (vorzueglichem Erfolg) obtained with the drug but he did not assert that it is superior to ergot.
Krummacher reported on thirteen cases of profuse menstruation in which the patients were treated with Styptysate, using for a part, the preparation containing cotarnin and for the other a preparation without cotarnin. He reported as good results with the cotarnin-free preparation in larger dosage, as with the cotarnin-containing preparation in smaller dosage. Krummacher did not compare Styptysate with ergot. Some of Krummacher’s cases are quoted, with some typographical errors, in the Bischoff circular.
On the assumption that the product discussed in German publications is the Styptysate marketed in the United States, the best that can be said for it is, that during a shortage of ergot it was used in place of that established drug. There is no evidence to warrant the use of this indefinite proprietary in place of the biologically standardized fluidextract of ergot or other standardized ergot preparations.
Styptysate (Ernst Bischoff and Co., Inc.) is inadmissible to New and Nonofficial Remedies because its composition is semisecret and indefinite and there is no evidence that its uniformity and strength is controlled (Rules 1 and 2); further, it is inadmissible because the therapeutic claims advanced for it are exaggerated and unwarranted (Rule 6) and because there is no evidence that it possesses any advantage over established drugs such as the biologically standardized fluidextract of ergot or the definite ergot preparations admitted to New and Nonofficial Remedies.—(From The Journal A. M. A., Feb. 11, 1922.)
The Council has authorized publication of the following report declaring Lipoidal Substances (Horovitz) inadmissible to New and Nonofficial Remedies because its composition is essentially secret and because the curative claims made for it are unsubstantiated and, therefore, unwarranted.
W. A. Puckner, Secretary.
In the advertising of the Horovitz Biochemic Laboratories Co. (A. S. Horovitz, president) we read:
“Horovitz proves by careful paralleled investigations of normal and of pathological tissues, both in addiction disease and in other diseases, that in patients suffering from narcotic addiction disease there is an inactivity of the lymph-glands due to the use of the drug and that the system is not supplied with the necessary fats.” “Horovitz further found that the lipoidal content of the cerebro-spinal system varies in strict accordance with the pathological processes introduced by infection or by alkaloids. Furthermore, he has found that the lipoids of various other organs, as well as those of the nervous system, may be extracted and consumed by the administration of narcotic alkaloids.”
“Horovitz proves by careful paralleled investigations of normal and of pathological tissues, both in addiction disease and in other diseases, that in patients suffering from narcotic addiction disease there is an inactivity of the lymph-glands due to the use of the drug and that the system is not supplied with the necessary fats.” “Horovitz further found that the lipoidal content of the cerebro-spinal system varies in strict accordance with the pathological processes introduced by infection or by alkaloids. Furthermore, he has found that the lipoids of various other organs, as well as those of the nervous system, may be extracted and consumed by the administration of narcotic alkaloids.”
It is further stated in the advertising that:
“After a long and very careful research investigation, Dr. Horovitz worked out a method of rational treatment for narcotic addiction disease which involves the restoration of the lipoids, which have been lost through the action of the drug, and of the toxins, by means of a combination of lipoidal substance from various plant lipoids in the form of a sterile solution. This preparation not only replaces the lipoids lost by the tissues, but also protects the nerve tissues, from attacks by the toxins elaborated during the use of narcotics, and, this by detoxicating the tissues, brings about permanent freedom from the craving of narcotics, instead of the temporary relief afforded by other methods of treatment.”
“After a long and very careful research investigation, Dr. Horovitz worked out a method of rational treatment for narcotic addiction disease which involves the restoration of the lipoids, which have been lost through the action of the drug, and of the toxins, by means of a combination of lipoidal substance from various plant lipoids in the form of a sterile solution. This preparation not only replaces the lipoids lost by the tissues, but also protects the nerve tissues, from attacks by the toxins elaborated during the use of narcotics, and, this by detoxicating the tissues, brings about permanent freedom from the craving of narcotics, instead of the temporary relief afforded by other methods of treatment.”
The “combination of lipoidal substance of various plant lipoids” which was worked out by Horovitz, the Horovitz Biochemic Laboratories offer as “Lipoidal Substances.” This preparation is supplied in ampoules said to contain 1 c.c. of solution. The treatment with “Lipoidal Substances” consists, first, in the complete withdrawal of the narcotic; second, in free catharsis; and third, in the intramuscular injection of the preparation. The initial dose is given as 8 to 12 minims repeated with increase of 3 to 4 minims every three hours during the first day. On the second, third and fourth day 16 minims is to be given twice a day and “from the fifth day until the medication is stopped (usually 28 to 35 days) it will be necessary usually to give but 1 injection of 16 minims each day.”
In a request for the admission of its preparation to New and Nonofficial Remedies, the Horovitz Biochemic Laboratories Co. stated: