“Spirocide is administered by means of fumigation and inhalation. The patient is disrobed to the waist and placed in a light chair, preferably with arms. A pastil or tablet of Spirocide is placed on a small plate, or open receptacle, after being ignited by holding in a gas or alcohol flame for a minute or so until it begins to smoulder. The plate with the burning Spirocide is then placed on the floor between the patient’s feet or just under the chair. A small shelf or platform between the lower rounds of the chair is an excellent location for the plate containing the burning mass. When all is in position a sheet should be thrown over the patient and arranged to enclose the whole. The patient should breathe naturally and inhale the vapor, which will rise and fill the canopy surrounding him. The treatment will require 15 to 30 minutes, or until the Spirocide is burned up. The patient may complain at first of a slight choking sensation, and there may be some tendency to cough. This can be removed by raising the sheet long enough to let in a little clear air. The eyes should be closed or lightly bandaged to avoid smarting.”
“Spirocide is administered by means of fumigation and inhalation. The patient is disrobed to the waist and placed in a light chair, preferably with arms. A pastil or tablet of Spirocide is placed on a small plate, or open receptacle, after being ignited by holding in a gas or alcohol flame for a minute or so until it begins to smoulder. The plate with the burning Spirocide is then placed on the floor between the patient’s feet or just under the chair. A small shelf or platform between the lower rounds of the chair is an excellent location for the plate containing the burning mass. When all is in position a sheet should be thrown over the patient and arranged to enclose the whole. The patient should breathe naturally and inhale the vapor, which will rise and fill the canopy surrounding him. The treatment will require 15 to 30 minutes, or until the Spirocide is burned up. The patient may complain at first of a slight choking sensation, and there may be some tendency to cough. This can be removed by raising the sheet long enough to let in a little clear air. The eyes should be closed or lightly bandaged to avoid smarting.”
Experiments conducted in the A. M. A. Chemical Laboratory show that Spirocide, when ignited, burns slowly with consequent volatilization of mercury. The several organic constituents serve as fuel and the copper sulphate possibly acts as a regulator of the combustion. During the burning process the cypress cones, henna, etc., are consumed but most, if not all, the copper remains behind, the mercury only being vaporized. It is asserted in the advertising pamphlet that Spirocide is indicated in all stages of syphilis, primary, secondary and tertiary, and in all its complications or sequelae. In these varying conditions one tablet daily or every other day is recommended until six treatments have been taken, though it is stated that “occasionally, depending on the severityor the duration of the disease, it may be wise to give nine treatments, the last three at intervals of two, three or more days.”
Some of the results which it is claimed are obtained with Spirocide are:
“At the completion of this course of treatment with Spirocide, all signs or evidences of syphilis are removed, and in ten days to three months all Wassermann tests prove negative. Any further treatments than the original course of fumigations are rarely needed. Wassermann’s will be found uniformly negative after a period which, according to the patient, may vary from ten days to three months. These results have been obtained in cases in which Salvarsan and kindred preparations have been employed without the slightest benefit.”
“At the completion of this course of treatment with Spirocide, all signs or evidences of syphilis are removed, and in ten days to three months all Wassermann tests prove negative. Any further treatments than the original course of fumigations are rarely needed. Wassermann’s will be found uniformly negative after a period which, according to the patient, may vary from ten days to three months. These results have been obtained in cases in which Salvarsan and kindred preparations have been employed without the slightest benefit.”
In a letter to the Council the “scientific observer” of the Spirocide Corporation declared:
“We do not claim that the vaporization method is new. We do claim, however, that this combination of mercury produces more rapid volatilization, certain absorption and undoubted effect than any form of mercury administered by any method known to science without the usual danger. That this is so we are willing to prove by comparison with other methods both by ourselves and many observers scattered over the United States....”
“We do not claim that the vaporization method is new. We do claim, however, that this combination of mercury produces more rapid volatilization, certain absorption and undoubted effect than any form of mercury administered by any method known to science without the usual danger. That this is so we are willing to prove by comparison with other methods both by ourselves and many observers scattered over the United States....”
To determine the validity of the claims made for Spirocide, the Corporation was asked to present the evidence which it offered. In reply, the corporation’s “scientific observer,” Dr. J. Lewengood, submitted 83 case reports from a number of different observers, including those from military hospitals and a state institution, and also a reprint of an article published by him in theNew York Medical Journal, Feb. 21, 1920, wherein were reported eight cases which received “Spirocide Treatment.” In no case were controls with other methods of mercury administration carried out.
This material the Council sent to two recognized syphilographers for an opinion. One of the consultants reported that of the 83 cases, 20 dealt with patients who had also received arsphenamin medication and, therefore, these 20 cases could not be considered as evidence concerning the value of Spirocide. As to the remaining cases, he found on the whole that the history and data furnished were far from sufficient to warrant the claims made. In many of the cases emphasis was laid on the Wassermann test, as though this test were the only thing to be considered in a case of syphilis. He pointed out that in one case the reaction changed from negative to strongly positive after six treatments and that in several cases the phenomena reported cannot be explained by anything else than a desire to get a negative blood test. For example, one case had Spirocide treatment and a Wassermann, 1 plus, 55 days after; the author then reports that 19 days later the reaction had become negative and, therefore, the change must be due to Spirocide. In several of the cases reported it is even questionable if the patients were syphilitic. The consultant concluded that the evidence submitted by the Spirocide Corporation failed to prove the claims made for Spirocide. He pointed out on the other hand that patients readily become salivated from the use of Spirocide, often after 8 or 10 treatments.
The second consultant replied that in his opinion the claim that Spirocide produces more “undoubted effect than any form of mercury administered by any method known to science without the usual danger,” was not substantiated. He believed that it was not as effective as some other methods, that the dosage is not as exact, and, therefore, it is not as free from danger when the drug is pushed.
The Council’s two consultants were also asked whether or not, in their opinion, the administration of mercury by inhalation is a method which the Council should endorse to the extent of recognizing a preparation based on this principle. This inquiry was also sent to the members of the editorial board of theArchives of Dermatology and Syphilology. Five replies were received. One advised a thorough study of the different methods of administeringmercury by inhalation. The other four were opposed to such recognition on the ground that as the dosage is not exact the effects, therefore, are not certain.
In consideration of the opinions expressed by its consultants, the Council declared Spirocide inadmissible to New and Nonofficial Remedies because (1) the claims made for it are unproved and unwarranted, (2) the routine use of an inexact method for the administration of mercury is detrimental to sound therapy and (3) the name is not descriptive of its composition, thus failing to remind the physician who uses these pastils that he is administering metallic mercury.—(From The Journal A. M. A., Jan. 22, 1921.)
The Council has authorized the publication of the following report, declaring Digifolin-Ciba inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Digifolin-Ciba is a product of the Society of Chemical Industry of Basle, Switzerland. It is marketed in the United States by the Ciba Company, 91 Barclay Street, New York City. It is claimed that Digifolin-Ciba is “a preparation of digitalis leaves that has been freed from the useless and harmful principles such as Digitonin (saponin), coloring and inert matter, etc., but does contain all the really valuable, therapeutically active constituents of the leaves, namely: digitoxin and digitalein in their natural proportions.” There is no evidence that digifolin contains all of the glucosides of digitalis as they exist in the leaf, and it is extremely improbable that this is the case because one cannot remove saponin without altering the other active principles of digitalis.
The Ciba Company sends out the following pamphlets relating to Digifolin:
“ ‘Concerning Digifolin-Ciba, A New Preparation of Digitalis,’ by C. Hartung, M.D., Ph.D. Extracts from the work ‘Ueber Digifolin, Ein Neues Digitalis-Praeparat’ in theMunich Medical Weekly, No. 36, page 1944, 1912.”“ ‘Digitoxin Contents of Digifolin-Ciba,’ by C. Hartung, M.D., Ph.D., Basle, Switzerland. Reprints from thePharmaceutical Post, 1913. No. 34, page 357. No. 40, page 431.”“ ‘Pharmacological Tests of Digitalis,’ by M. J. Chevalier, Chef Des Travaux Pratiques de Pharmacologie et Matiere Medicale, Faculte De Medecine De Paris. Report Presented to the Societe de Therapeutique at Their Meeting, May 28, 1913.”
“ ‘Concerning Digifolin-Ciba, A New Preparation of Digitalis,’ by C. Hartung, M.D., Ph.D. Extracts from the work ‘Ueber Digifolin, Ein Neues Digitalis-Praeparat’ in theMunich Medical Weekly, No. 36, page 1944, 1912.”
“ ‘Digitoxin Contents of Digifolin-Ciba,’ by C. Hartung, M.D., Ph.D., Basle, Switzerland. Reprints from thePharmaceutical Post, 1913. No. 34, page 357. No. 40, page 431.”
“ ‘Pharmacological Tests of Digitalis,’ by M. J. Chevalier, Chef Des Travaux Pratiques de Pharmacologie et Matiere Medicale, Faculte De Medecine De Paris. Report Presented to the Societe de Therapeutique at Their Meeting, May 28, 1913.”
In the reprint “Concerning Digifolin, ‘Ciba.’ ” Hartung lays stress on the presence of harmful and inert substances present in the leaf and galenical preparations with the direct or implied statement that digifolin has an advantage in that these are absent from it. This is misleading. It is true that Boehm whom Hartung cites, found saponin to be irritating, but Boehm states that it required 100 mg. per kilogram of body weight to induce vomiting after its oral administration. Furthermore, saponin is present in traces only in infusion of digitalis, so that the therapeutic dose contains a wholly negligible amount of it.
The following occurs in “Pharmacological Tests of Digitalis,” by M. J. Chevalier:
“Hartung’s Digifolin merits our attention, especially because it seems to possess all the pharmacodynamic properties of galenic preparations of digitalis without showing any of their disadvantages.”
“Hartung’s Digifolin merits our attention, especially because it seems to possess all the pharmacodynamic properties of galenic preparations of digitalis without showing any of their disadvantages.”
This claim scarcely needs comment, since it is well established that the chief “disadvantages” of digitalis are inherent in the principles which producethe desired effects of digitalis and may be avoided to a large extent by a carefully regulated dosage of any digitalis preparation. In short, the advertising for Digifolin asserts that this digitalis preparation has all the advantages of digitalis itself, but none of its disadvantages. This claim has been refuted so frequently that manufacturers must be aware that it is untenable. Further the claims now made for Digifolin are essentially those made nearly four years ago at which time the attention of the American agent was called to their unwarranted character.
The Council declared Digifolin-Ciba inadmissible to New and Nonofficial Remedies because the therapeutic claims advanced for it are misleading and unwarranted.—(From The Journal A. M. A., April 2, 1921.)
The Council has authorized the publication of the following report on “Loeser’s Intravenous Solution of Hexamethylenamin,” “Loeser’s Intravenous Solution of Hexamethylenamin and Sodium Iodid,” “Loeser’s Intravenous Solution of Sodium Salicylate,” “Loeser’s Intravenous Solution of Salicylate and Iodid,” “Loeser’s Intravenous Solution of Sodium Iodid” and “Loeser’s Intravenous Solution of Mercury Bichlorid,” put out by the New York Intravenous Laboratory, Inc.
W. A. Puckner, Secretary.
The intravenous solutions of “Hexamethylenamin,” “Hexamethylenamin and Sodium Iodid,” “Sodium Salicylate,” “Sodium Salicylate and Sodium Iodid,” “Sodium Iodid” and “Mercuric Chlorid” marketed by the New York Intravenous Laboratory, Inc., are solutions of official substances sold under their official names. They would, therefore, be outside the scope of the Council, were it not that special and general therapeutic claims are made for them. Such special claims, for instance, are contained in an advertisement in theIllinois Medical Journalfor Oct. 20, 1920, which gives, under the various drugs, a list of diseases in which the drugs are said to be “indicated.” The Council is unable to agree with some of these recommendations. The fundamental objection, however, is the general claim of superiority and safety of the intravenous method.
The intravenous solutions named above would naturally have little sale if such special claims were not made for them. While the claims may not be made directly, they are carried by such display phrases as “For the progressive physician seeking improved clinical results” and “A safe practical office technique.”
The Council continues to hold that intravenous medication, generally, is not as safe as oral medication even with relatively harmless substances (a fact again illustrated by the results of Hanzlik and Karsner, 1920,Journal Pharmacology and Experimental Therapeutics,14, 379), and that it does not give “improved clinical results” except under rather narrowly confined circumstances—namely, if the drug undergoes decomposition in the alimentary tract, if it is not absorbed, if it causes serious direct local reaction or if time is an urgent element. Each intravenous preparation for which advantage over oral administration is claimed, directly or by implication, must be examined from these points of view.
The Council has recognized intravenous preparations which satisfied these requirements. It is evident, however, that hexamethylenamin, sodium iodid and sodium salicylate do not. When given orally they do not undergo material decomposition in the digestive tract, they are rapidly absorbed, they cause no direct local reaction, and in the conditions in which they are used the houror so which is required for absorption is immaterial, especially as they are used continuously for some time. Mercuric chlorid does indeed produce some local irritation, but there is as yet no convincing evidence that its intravenous injection causes less injury than oral administration. More experience under controlled conditions is needed before the intravenous use of mercuric chlorid can be approved. Especially objectionable are the fixed proportion mixtures of sodium iodid with sodium salicylate and with hexamethylenamin. The dosage of all three drugs has to be adapted to individual conditions. This is impossible when giving them in fixed proportions.
The Council voted not to accept “Loeser’s Intravenous Solution of Hexamethylenamin,” “Loeser’s Intravenous Solution of Hexamethylenamin and Sodium Iodid,” “Loeser’s Intravenous Solution of Sodium Salicylate,” “Loeser’s Intravenous Solution of Salicylate and Iodid,” “Loeser’s Intravenous Solution Sodium Iodid” and “Loeser’s Intravenous Solution of Mercury Bichlorid” for New and Nonofficial Remedies because they are sold under misleading claims regarding their alleged safety and efficiency. In view of this fundamental objection the individual claims for each preparation were not passed on.—(From The Journal A. M. A., April 16, 1921.)
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
“National Iodine Solution” is a proprietary sold by the National Drug Co., Philadelphia, Pa. From inquiries received by the Council on Pharmacy and Chemistry it is evident that the product is extensively brought to the attention of physicians by means of circulars. The name implies that it is a solution of iodin and the inference is given that it has the advantages of iodin without the disadvantages.
In view of the foregoing, the Council took up the investigation of “National Iodine Solution,” and in turn asked the A. M. A. Chemical Laboratory to analyze it. The chemist’s report follows:
According to the label of National Iodine Solution, “each fluidounce represents three grains Proteo-albuminoid compound of iodin (National)”; also an alcohol declaration of 7 per cent. is made. Otherwise no information is given as to the composition either of the “solution” or of “Proteo-albuminoid compound of Iodine.”
Each bottle contained about 115 c.c. (nearly 4 ounces) of a yellowish solution, acid in reaction, having an odor resembling witch hazel; its specific gravity at 25 C. was 0.9860. Qualitative tests indicated the presence of zinc, alcohol, sulphate, an iodin compound (the solution gave tests which indicated a very small amount of free iodin; most of the iodin was in the form of ordinary iodid), a small amount of vegetable extractives, and traces of aluminum and potassium. If any protein was present, it was in amounts too small to be identified, though a small amount of a nitrogenous compound was present. The amount of solids in “National Iodine Solution” was equivalent to 0.72 per cent, and the amount of ash, to 0.2 per cent. Quantitative estimations yielded the following:
Alcohol (by volume)7.0per cent.Zinc (Zn++)0.096per cent.Iodin (free and combined)0.029per cent.Sulphate (SO4- -)0.146per cent.Protein (N × 6.36)0.012per cent.
Alcohol (by volume)
Zinc (Zn++)
Iodin (free and combined)
Sulphate (SO4- -)
Protein (N × 6.36)
The above findings indicate that each 100 c.c. contains about 7 c.c. of alcohol, 0.5 gram of zinc sulphate U. S. P. (ZnSO4+7H2O.), 0.03 gram of iodin, 0.01 gram of protein (calculated as such from nitrogen times the factor 6.36) and some hamamelis water. Expressed in equivalent apothecary terms, each fluidounce contains essentially:
Zinc sulphate21⁄3grainsIodin (free and combined)1⁄8grainProtein1⁄25grainAlcohol34minims
Zinc sulphate
Iodin (free and combined)
Protein
Alcohol
This amount of alcohol is equivalent to about 31⁄2fluidrams of witch hazel water. Although the label states that each fluidounce contains three grains of “proteo-albuminoid compound of iodine,” yet the sum of the protein (calculated from nitrogen content) and iodin components is equivalent to less than1⁄5grain.
“National Iodine Solution” appears to be very similar to “Gonocol” (The National Drug Co., Philadelphia, Pa.), which was analyzed by the Bureau of Chemistry of the U. S. Department of Agriculture. The bureau stated that “it [Gonocol] consisted essentially of an aqueous solution of zinc sulphate, hamamelis water, a small amount of alcohol, 0.38 grain of iodin, and 0.36 grain of protein per fluidounce.”
It is evident that “National Iodine Solution” is not a solution of free elementary iodin as the name suggests; instead it appears to be a solution of zinc sulphate in witch hazel water containing less than 0.03 per cent. of combined iodin andnot more than a trace of free iodin. “National Iodine Solution” is one more to be added to that already long list of proprietaries which makes capital of the high esteem in which physicians hold iodin.
An advertising circular sent to physicians begins:
“Dear Doctor: We beg to suggest a line of treatment while using National Iodine Solution which our many years of experience has proven to us to give the best and quickest results in the treatment of inflammation of the urethral tract...”
“Dear Doctor: We beg to suggest a line of treatment while using National Iodine Solution which our many years of experience has proven to us to give the best and quickest results in the treatment of inflammation of the urethral tract...”
In it are given directions for the treatment of “acute gonorrhea, male,” “anterior urethritis,” “anterior-posterior urethritis,” “ardor urinæ and chordee,” etc., by means of National Iodine Solution and other proprietaries of the National Drug Company’s make. In fact the solution is claimed to be “Indicated in All Conditions of Urethra Accompanied by a Discharge.”
The therapeutic claims made for “National Iodine Solution” are unwarranted. Such a solution is not indicated in all conditions of the urethra accompanied by discharge. The advice contained in the circular is equivalent to mail-order treatment of gonorrhea.
It is of interest to note that the claims for an identical or a similar solution prepared by the National Drug Company as a treatment for gonorrhea and intended for use by the laity, has been adjudged misbranded by the federal authorities (Notice of Judgment No. 8150, issued Jan. 25, 1921) in that it misled and deceived the purchaser or purchasers thereof in the statements regarding the therapeutic or curative effects of the article, which falsely and fraudulently represent it to be indicated in all conditions of the urethra accompanied with a discharge, “whereas in truth and in fact it was not.”
The Council would emphasize that if physicians give heed to advertising such as that sent out by the National Drug Company for this preparation the medical profession cannot with good grace protest against the routine treatment of venereal diseases by quacks and “patent medicine” venders.—(From The Journal A. M. A., June 4, 1921.)
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
Mon-Arsone is offered by the Harmer Laboratories Company as “a new and non-toxic arsenical for the treatment of syphilis.” In the advertisements for Mon-Arsone it has been claimed that with this drug “the toxic, corrosive and uncertain reactions attending the use of arsphenamine have been entirely eliminated” and that “it has a therapeutic value equal to arsphenamine, but extensive case reports fail to record the slightest toxic reaction following its use.”
According to the manufacturers, Mons-Arsone is disodiumethylarsonate, the sodium salt of ethylarsonic acid, derived from arsenic acid by replacement of one hydroxyl group by the ethyl group—AsO(CH2CH3)(OH)2. Mons-Arsone is related to sodium cacodylate, which is the sodium salt of dimethyl-arsenic acid—AsO(CH3)2OH—derived from arsenic acid by replacement of two hydroxyl groups by two methyl groups. Ethylarsonic acid and its potassium salt were described by LaCoste139more than thirty-five years ago, and the use of the sodium salt of methylarsonic acid was proposed in France some years ago. The Harmer Laboratories Company claims originality for Mons-Arsone in that it was the first to prepare the sodium salt of ethylarsonic acid and to propose its therapeutic use.
It was reported several years ago byCastelli140that sodium cacodylate and the sodium salt of methyl arsenic acid were devoid of effect on experimental trypanosomiasis and spirochete infections. Careful clinical observations in this country by H. J.Nichols141and H. N.Cole142have demonstrated the inefficacy of sodium cacodylate in the treatment of human syphilis.
Animal experiments carried out in the U. S. Hygienic Laboratory by Voegtlin andSmith143show that Mon-Arsone is devoid of any practical trypanocidal action. Thus the “therapeutic ratio” (the ratio of the minimal effective dose to the lethal dose) was about 1, that is, it was effective therapeutically only in approximately fatal doses; the therapeutic ratio for arsphenamine in similar conditions was 17, and that of neoarsphenamine, 28.
The findings that sodium dimethylarsenate (sodium cacodylate), sodium methylarsenate, and sodium ethylarsenate are devoid of any practical trypanocidal action and the conclusion that sodium cacodylate is inefficient in the treatment of human syphilis does not prove that Mon-Arsone is without effect on the disease. These findings, however, certainly demand convincing therapeutic evidence to warrant the recommendation for the use of the drug in the treatment of syphilis—particularly because the drug is proposed as a substitute for arsphenamine, the value of which is established.
When the Council first took up the consideration of Mon-Arsone, the only evidence for the claim that it “has a therapeutic value at least equal to that of arsphenamine” consisted, with one exception, of reports from those who had experimented with the drug for the Harmer Laboratories Company, including a report by B. L. Wright, L. A. Kennell, and L. M. Hussey,144the latter of the Harmer Laboratories Company. These reports appeared to show that the administration of Mon-Arsone caused less reaction than arsphenamine, and that the immediate effects, judged by clinical symptoms and the response tothe Wassermann test, appeared to be good. These trials extended over too short a period of time to permit judgment as to the permanence of the results. A report by an independent observer seemed to indicate that Mon-Arsone does not have the sterilizing action on syphilitic lesions which it is usually believed arsphenamine exercises.
After examining the available evidence, the Council advised the Harmer Laboratories Company that the claim that Mon-Arsone has a therapeutic value equal to arsphenamine appeared unwarranted; that, in the opinion of the Council, Mon-Arsone should not be used except under conditions that justify the experimental trial of an unproved drug, and should not be used in a routine way until the permanence of its effects has been established; and consequently any advertising propaganda for the drug by the Harmer Laboratories Company was to be deprecated.
In its reply the Harmer Laboratories Company admitted that its advertising claim, that Mon-Arsone was at least equal to arsphenamine therapeutically, had been based on reports on fifty cases and on additional reports that were beginning to come in at that time. The Harmer Laboratories Company submitted a list of hospitals and physicians using Mon-Arsone. A letter of inquiry sent by the Council to those who, according to the names in the list supplied by the Harmer Laboratories Company, had used Mon-Arsone, brought seven replies.
The clinical evidence contained in these replies was to the effect that Mon-Arsone had been used in the various types of syphilis and that there was a certain beneficial effect, both clinically and as shown by the Wassermann reaction. In certain instances the Wassermann reaction changed from a four plus to a negative reaction. The reports showed that the efficiency of Mon-Arsone as compared with that of arsphenamine preparations has not been adequately studied. One physician who has used Mon-Arsone extensively reports that in many of the cases treated there seemed to be nearly as good results from the use of Mon-Arsone as is frequently obtained in the use of arsphenamine. He reports, however, that it was necessary in eleven out of one hundred cases to change from Mon-Arsone to neoarsphenamine.
In view of the fact that there is definite lack of evidence to show that Mon-Arsone is the equal of arsphenamine therapeutically, and because of the reports that in some cases it is inferior, Mon-Arsone should not be used in the treatment of syphilis generally until its therapeutic status has been more rigidly investigated and conclusive evidence of its superiority to arsphenamine preparations obtained.
The Council voted not to admit Mon-Arsone to New and Nonofficial Remedies and reaffirmed its conclusion that the claim that Mon-Arsone has a therapeutic value equal to that of arsphenamine is premature and unwarranted; that Mon-Arsone should not be used except under conditions that justify the experimental trial of an unproved drug; and that the advertising propaganda for the drug by the Harmer Laboratories Company is to be deprecated.
When the preceding report was sent to the Harmer Laboratories Company, the firm submitted a reply in which it was stated:
1. That in certain instances patients improved under Mon-Arsone who, previously, had not improved under arsphenamine, and that this should be taken to offset the report of the one hundred cases in which the use of Mon-Arsone had to be abandoned in 11 per cent. of the cases.
2. That the Harmer Laboratories Company has abandoned the claim that Mon-Arsone is therapeutically equal to arsphenamine and that it now furnishes the drug to such men as care to use it simply on the basis of its special and useful characteristics.
The Council heartily endorses the recent warning against the use of untried medicaments which was issued by the U. S. Public Health Service.145
Since the Council’s report was prepared a report on the effects of Mon-Arsone on experimental syphilis has been published by Nichols,146from the Division of Laboratories, Army Medical School, which concludes:
1. Disodium-ethylarsinate, or mon-arsone, tested on rabbits infected with syphilis shows no spirocheticidal power. The tissues are fatally poisoned as soon as or before the spirochetes are affected.
“2. For its practical use in syphilis there is no such germicidal basis as exists in case of the arsphenamine group.”—(From The Journal A. M. A., June 18, 1921.)
“Oxyl-Iodide” (Eli Lilly and Co.) is said to be the hydroiodid of cinchophen and the claim is made that it exerts the effects of cinchophen and of iodid. Because of inquiries which have been received the Council decided to determine the eligibility of “Oxyl-Iodide” for New and Nonofficial Remedies. Dr. P. J. Hanzlik—formerly Associate Professor of Pharmacology at Western Reserve University School of Medicine, now Professor of Pharmacology at Leland Stanford Junior University Medical School—who has made a study of the action of salicylates and cinchophen, was asked to report on the therapeutic value and the rationality of “Oxyl-Iodide.” This he consented to do and his report appears below.
After considering Doctor Hanzlik’s report, the Council declared “Oxyl-Iodide” inadmissible to New and Nonofficial Remedies because it is an irrational combination, marketed under claims that are unproved and consequently unwarranted.
W. A. Puckner, Secretary.
“Oxyl-Iodide,” marketed by Eli Lilly & Co., is claimed to be the hydroiodid of phenylcinchoninic acid, containing 33 per cent. of iodin and 67 per cent. of phenylcinchoninic acid (cinchophen). Its solubility resembles that of cinchophen, being low in water and acid mediums, and higher in the presence of alkalis. Whether “oxyl-iodide” is decomposed into its constituents in the presence of alkalis does not appear to have been determined. However, if this were the case, the intestine, after administration of “oxyl-iodide,” would contain cinchophen and sodium iodid in the same forms as if these agents were administered individually so that nothing would be gained by administering “oxyl-iodide.” Being, like cinchophen, practically insoluble in acid mediums, “oxyl-iodide” would have no advantage over the latter so far as gastric irritation is concerned.
The dosage advised is from one to three tablets containing 3 grains (0.2 gm.) each of “oxyl-iodide.” The total dosage would depend on the condition to be treated. In rheumatic fever, which requires a full therapeutic or so-called, “toxic” dose of cinchophen, about 12 to 13 gm. would be administered intensively. Since each tablet of “oxyl-iodide” contains 0.13 gm. of cinchophen, the total number of tablets of “oxyl-iodide” required would be 100, or two and one-half bottles of forty tablets each. At the same time the patient would receive 6.6 gm. of iodin (as iodid). This might be distinctly objectionable because of the production of the disagreeable symptoms of iodism in some persons,and indicates that the fixed proportion of the iodin constituent would be objectionable.
Even a smaller dosage, such as 5 gm. of cinchophen, which gives partial relief in rheumatism and similar conditions, would still require a patient to take a full bottle, or forty tablets, of “oxyl-iodide,” and at the same time about 2.7 gm. of iodin would have to be ingested.
Furthermore, rheumatic fever, the arthritides, gout and related conditions in which cinchophen is indicated do not require iodid. Therefore, “oxyl-iodide” would not be the remedy of choice in these conditions, and its use would be irrational and illogical.
No data on the pharmacologic actions of “oxyl-iodide” are presented in the manufacturer’s literature. Presumably, the compound would exhibit the actions of its individual components, i. e., cinchophen and iodin (as iodid), though probably less efficiently, owing to its low solubility. This is also indicated by the following statements of the manufacturer: “The analgesic action of ‘oxyl-iodide’ is gradual. A word of caution is necessary to those who may expect immediate relief from pain.” Therefore, why use “oxyl-iodide” in place of more dependable analgesics, such as salicylate or cinchophen. The following statements appear far-fetched: “There is a stimulation of the endocrines which is perhaps more marked in the thyroid gland, although it is probably shared by the pituitary and other glands which function in a chain-like control.... There is stimulation of cells with increased flow of secretion, visibly demonstrated by the nasal mucous membrane after ‘oxyl-iodide’ has been taken for some time. The general action on mucous membranes favors elimination of toxins and waste products.”
It is probable that “oxyl-iodide” acts as a uric acid eliminant, though there is no reason to suppose that it is more effective than cinchophen alone. No data are given for this in the manufacturer’s literature.
Successful use of “oxyl-iodide” is claimed in brachial and sciatic neuritis, lumbago, muscular rheumatism, arthritis deformans, chronic arthritis (“... in some instances were apparently cured”), subacute bronchitis, circumflex neuritis, traumatic orchitis, eczema and rheumatism. However, a careful reading of the protocols of seven cases, representing these conditions, gives an unfavorable impression as to the real contribution to the recovery by, or value received from, “oxyl-iodide.” Summarized, the opinions as quoted by the manufacturers in support of their claims for “oxyl-iodide” are briefly as follows:
Case 1. “Of course, the case is not complete yet, but I am looking for continued betterment.”
Case 2. “For two weeks past her improvement has been marvelous.”
Case 3. “The joints are still enlarged and we do not hope to clear them entirely....”
Case 4. “Undoubtedly, removal of the kidney had much to do with improvement.”
Case 5. “I think I have gotten very good results.”
Case 6. “Some apparent benefit.”
Case 7. “She is practically free from pain, and the muscle and joint stiffness is now slight.”
These inconclusive opinions certainly do not agree with the favorable impression which other portions of the manufacturer’s literature create. If the factor of natural recovery in the conditions represented by these seven casesis given due weight, little, if anything, is left to the credit of “oxyl-iodide.” Such clinical evidence as is supplied by the manufacturer indicates that the therapeutic efficiency of “oxyl-iodide” is doubtful, and not an improvement over either cinchophen or iodid.
Iodism cannot be avoided by the use of “oxyl-iodide,” for the manufacturer’s literature states that “the dosage of ‘oxyl-iodide’ may be pushed to iodism as manifested by skin symptoms.... To avoid iodism there should be an occasional interruption of treatment.” “Oxyl-iodide,” therefore, has no advantage over ordinary sodium iodid to avoid iodism. Usually, the conditions which require cinchophen do not require the simultaneous administration of iodids, and vice versa. If administration of iodid and cinchophen together should be indicated or desirable, these can be given separately with the added advantage that the iodid can be easily reduced or withdrawn in case iodism supervenes, and the cinchophen could be continued if necessary. Since conditions do not arise frequently enough to warrant the use of iodid and cinchophen together, the existence of such a product as “oxyl-iodide” is unwarranted.
Finally, the manufacturer himself recognizes that phenylcinchoninic acid (cinchophen) can take the place of “oxyl-iodide.” Under “dosage,” the circular states: “A few patients may be idiosyncratic to the iodides and find they cannot take ‘oxyl-iodide.’ For the latter chloroxyl, the hydrochloride of phenylcinchoninic acid, is recommended.” The action of the hydrochlorid of phenylcinchoninic acid does not differ, of course, from that of cinchophen. The difficulties of assigning a clear-cut, definite, therapeutic rôle to “oxyl-iodide” in order to justify its existence, alongside well-known and tried remedies are self-evident.
“Oxyl-iodide” is pharmacologically and therapeutically an illogical, irrational and unjustified substitute for cinchophen and iodids. The conditions which require the administration of cinchophen do not as a rule require the administration of iodid and vice versa. If it is desirable to secure the effects of iodid and cinchophen together, these can be more conveniently and advantageously administered as separate agents, permitting in that way a better control of their actions. This cannot be accomplished with “oxyl-iodide,” in which the proportion of iodid and cinchophen are fixed. Symptoms of iodism cannot be avoided by the administration of “oxyl-iodide.” The objective evidences for its actions and uses are totally lacking; and the clinical opinions concerning its therapeutic benefits in different disease conditions are inconclusive and hedging, and, if anything, contradictory to the favorable impressions which the language of the advertising matter is likely to create.—(From The Journal A. M. A., July 2, 1921.)
The Council has authorized publication of the following report, declaring that Quassia Compound Tablets (Flint, Eaton and Company) are inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Quassia Compound Tablets, marketed by Flint, Eaton and Company, Decatur, Ill., according to the label on a trade package submitted to the Council, contain in each tablet:
Quassia3⁄4grainAloin1⁄4grainChionanthus1grainIpecac1⁄16grainWahoo3⁄4grainPodophyllin1⁄4grainNux Vomica1⁄2grainGingerineq. s.Cascara1⁄3grain
Quassia
Aloin
Chionanthus
Ipecac
Wahoo
Podophyllin
Nux Vomica
Gingerine
Cascara
In the advertising the “Cascara” of the label is replaced by the indefinite term “Cascarin” and the “Gingerineq. s.” by “Carminative Antigripeq. s.” Flint, Eaton and Company informed the Council that “Carminative Antigripe is C. P. Sodium Sulphite of which each tablet contains1⁄4grain.” The tablets were treated with dilute hydrochloric acid and the odor of sulphur dioxid became apparent. This shows that the company’s statement to the Council, that the tablets contain a sulphite, is correct and the formula on the label is incorrect.
In the advertising for this preparation we read:
“A careful study of this formula [which formula? That on the label or that in the general advertising?—Council] will reveal the outstanding fact that, while there are several drugs employed, each ingredient is there for a purpose and all do splendid teamwork. If your patient is constipated because the stomach is not sufficiently energetic, the Quassia stimulates that organ to an increased secretion of digestive fluids and sets it to working normally. If the liver be sluggish, the Chionanthus and Wahoo prompt it to increased activity. Chionanthus has no superior for producing a sustained healthy hepatic condition. Should the bowels be slow and uncertain, the small doses of Aloin, Cascarin and Podophyllin stimulate to free peristaltic action, while the Nux Vomica sets the nervous system right. We use an effective Antigripe so that there is no griping.”
“A careful study of this formula [which formula? That on the label or that in the general advertising?—Council] will reveal the outstanding fact that, while there are several drugs employed, each ingredient is there for a purpose and all do splendid teamwork. If your patient is constipated because the stomach is not sufficiently energetic, the Quassia stimulates that organ to an increased secretion of digestive fluids and sets it to working normally. If the liver be sluggish, the Chionanthus and Wahoo prompt it to increased activity. Chionanthus has no superior for producing a sustained healthy hepatic condition. Should the bowels be slow and uncertain, the small doses of Aloin, Cascarin and Podophyllin stimulate to free peristaltic action, while the Nux Vomica sets the nervous system right. We use an effective Antigripe so that there is no griping.”
It is absurd to suppose that a complex mixture of drugs in fixed proportions can have the actions claimed for Quassia Compound Tablets. As regards the claim that “Chionanthus has no superior for producing a sustained healthy hepatic condition,” it was brought out in a report of the Council on “Some Unimportant Drugs” (Reports of Council on Pharmacy and Chemistry, 1912, p. 36) that the “claims for this remedy [Chionanthus] are not supported by experimental evidence and the clinical reports of its use fail to show indications of discriminating critical observation. It is not noticed by most pharmacologic authorities.”
Of Wahoo (Euonymus N. F.) the “Epitome of the U. S. P. and N. F.” says: “Actions and Uses.—Obsolete cathartic; toxic digitalis effects.Caption: the uncertain absorption of this drug makes its use inadvisable.”
Quassia Compound Tablets (Flint, Eaton and Company) are inadmissible to New and Nonofficial Remedies because (1) they contain drugs of unproved value; (2) their composition is needlessly complex, and, therefore irrational; (3) unwarranted therapeutic claims are made for them; (4) the name is misleading and not descriptive of their composition, and (5) the statement of their composition is indefinite and incorrect.—(From The Journal A. M. A., July 9, 1921.)
The Council has authorized the publication of the following report:
W. A. Puckner, Secretary.
Toxicide (Toxicide Laboratories, Chicago) is alleged to be a remedy which “increases systemic resistance,” is “used for immunizing against septic infections” and “is indicated in any case of septic infection, capable of inducing inflammation and pus formation, regardless of location or kind of tissue involved.” The following statements bearing on the composition of the preparation are furnished by the manufacturers: