CREOSOTE-DELSON AND CREOFOS

“INDICATIONS: Scrofula, Coryza, Hay Fever Necrosis, Bronchial and Throat Affections, Catarrhal Pneumonia, Glandular enlargements of the Spleen, Thyroid, and Lymphatics, Rickets and Syphilis.”

The following claims are therapeutic exaggerations:

“The Ideal Alterative”“... indicated in all cases where an alterative is desired...”“The association of Bromin with Iodin in Brom-I-Phos materially enhances the product in the treatment of chronic affections of the skin, depraved conditions of the mucous membranes, tertiary syphilis, glandular enlargements, etc.”

“The Ideal Alterative”

“... indicated in all cases where an alterative is desired...”

“The association of Bromin with Iodin in Brom-I-Phos materially enhances the product in the treatment of chronic affections of the skin, depraved conditions of the mucous membranes, tertiary syphilis, glandular enlargements, etc.”

In that it suggests that the phosphorus in Brom-I-Phos is more readily assimilated than ordinary phosphate, the following is misleading:

“The Phosphorus contained in Brom-I-Phos is readily assimilated and at once acts as a nutrient to the nervous and osseous structures of the body, stimulates metabolism and increases mental activity.”

The recommendation: “Your specification of Brom-I-Phos in the treatment of Syphilitic cases will immediately prove beneficial to the patient” is not supported by evidence. The name does not indicate that Brom-I-Phos is an alcoholic preparation with iodid as its essential constituent, but suggests that phosphorus is an important constituent, whereas the amount of phosphate or phosphite, produced by the action of iodin on elementary phosphorus (if the amount of phosphorus used in making the preparation is correctly stated) is insignificant.

The combination of bromin, iodin and phosphorus, or bromid, iodid and phosphate, is irrational because these elements are not of mutual assistance to each other in the conditions for which Brom-I-Phos is advertised.

The Council’s report was submitted to the manufacturer of Brom-I-Phos for comment; the reply contained nothing to permit a revision of the previous conclusions.

The Council declared Brom-I-Phos inadmissible to New and Nonofficial Remedies.—(From The Journal A. M. A., June 30, 1917.)

Creosote-Delson and Creofos, or Creosote with Hypophosphites, were submitted by the Delson Chemical Co., Inc., New York City. Creosote-Delson is said to be “beechwood creosote from which the irritating and caustic properties are removed by fractional distillation.” It is claimed that Creofos contains “2 grains of Creosote-Delson and 33⁄5grains of the combined Hypophosphites in each fluidrachm of the mixture or emulsion, the lime salt predominating.” It is also claimed that “the primary object of the hypophosphites in this preparation is that of maintaining the refined creosote in a pure, unoxidized state, and that no particular claim for therapeutic action on their part is advanced.” It is explained further, however, “the addition of the lime was prompted by the belief... that the fundamental cause of pulmonary tuberculosis is lime starvation....”

The assertions are made that Creosote-Delson is superior to the official creosote because it can be taken “abundantly and persistently without harm to or interference with stomach and kidneys” and can be “taken uninterruptedly and indefinitely,” while the dosage is “unlimited by any former knowledge of Creosote Therapy.” Creosote-Delson is not on the market except in the combination Creofos, although it is supplied on request.

Creofos is advised in the treatment of tuberculosis, whooping cough, measles, “Grippe and Colds,” bronchitis, asthma, “Intestinal Affections (Colitis, Summer Diarrhoea, etc.),” while its use is suggested for the “prevention of thespread of contagious diseases,” and for “preventing contagion in minor contagious diseases at any rate, in schools and families.”

The following advertisement has recently appeared in theNew York Medical Journaland in theTherapeutic Gazette:

is the successful development of the most advanced practice in the treatment of infectious diseases. It destroys completely the causative organisms by a bactericide many times more powerful than phenol, yet absolutely harmless to animal life.Unlike serums, its activity is not confined to any specific disease, and its use insures against sequelae (as pneumonia following grippe).Especially valuable in the treatment of infants and patients of delicate constitution and in cases where time is of importance.

Unlike serums, its activity is not confined to any specific disease, and its use insures against sequelae (as pneumonia following grippe).

Especially valuable in the treatment of infants and patients of delicate constitution and in cases where time is of importance.

The Delson Chemical Co. was requested to supply information regarding the identity of Creosote-Delson and to support the claim that although it is “the whole drug” its dosage is “unlimited by any former knowledge of Creosote Therapy.” The reply was virtually an admission that the toxic, caustic, phenolic components of creosote were present in Creosote-Delson just as in the official creosote.

The referee of the Committee on Therapeutics in submitting his report to the Council pointed out that it is difficult to discuss the pharmacologic merits of a semisecret preparation, like Creosote-Delson, claimed to be more acceptable to the human organism than the official product it is intended to supplant, when the action of the parent drug is still questioned or disputed by eminent clinicians.

Absorption experiments have been carried out with creosote and creosote compounds, such as creosote with hypophosphites or calcium or creosote carbonate, chiefly by a study of the elimination products in the urine. But any evidence so far offered that these combinations increase absorption and lessen the irritating, caustic or toxic properties has been wholly inconclusive. The evidence offered by the Delson Chemical Co. presented no control experiments with the official creosote and did not prove that either Creosote-Delson or Creofos was less toxic than a corresponding amount of ordinary beechwood creosote.

The referee concluded that no proof had been offered that these preparations are materially superior to ordinary creosote preparations from the pharmacologic or therapeutic standpoint, and that the claims made for Creosote-Delson and Creofos are unwarranted in the light of our knowledge of the properties of creosote. The advertisement quoted above is an example of unproved and unwarranted claims.

On the recommendation of the referee, the Council declared Creosote-Delson and Creofos inadmissible to New and Nonofficial Remedies, for conflict with the rules as follows:

Creosote-Delson: The information so far available is not sufficient to define the nature, or composition, of Creosote-Delson, or to indicate in how far this product differs, if at all, from the official creosote (conflict with Rule 1). No methods are furnished for determining the identity or composition of Creosote-Delson (conflict with Rule 2). The available information does not show that Creosote-Delson has advantages over creosote (conflict with Rule 6).

Creofos: The composition of Creosote-Delson not having been furnished, the statement concerning the composition of Creofos is also unsatisfactory (conflict with Rule 1). The therapeutic claims are unsubstantiated and grossly exaggerated (conflict with Rule 6). The name is not descriptive of its composition as is required for pharmaceutical mixtures (conflict with Rule 8). There is no evidence that hypophosphites prevent decomposition of creosote (if thisoccurs). Hence the inclusion of hypophosphites must be considered irrational (conflict with Rule 10).

The Council’s report was sent to the Delson Chemical Co. for consideration. The firm’s reply contained nothing to warrant a revision of the report, and the Council voted that Creosote-Delson and Creofos were inadmissible to New and Nonofficial Remedies and authorized the publication of this report.—(From The Journal A. M. A., July 7, 1917.)

Triner’s American Elixir of Bitter Wine is a wine to which bitter drugs and laxatives have been added. Though evidently intended for public consumption, it is also advertised to physicians, and consequently the Council publishes this report.

Some recent advertisements read:

“It Acts Well and Is Very Palatable. These are the reasons why so many physicians recommendTRINER’S AMERICAN ELIXIR OF BITTER WINE. Free from any chemicals. Prepared from bitter herbs roots and barks of eminent medicinal value and pure natural red wine. A safe relief in auto-intoxication, constipation, weakness, etc. Price $1.00. At drug Stores. Samples gratis upon request only to physicians.”“A Laxative Tonic. In cases of constipation and its sequelæ, autointoxication, weakness and nervousness you should tryTriner’s American Elixir of Bitter Wine. This preparation consists of Cascara Sagrada, Dandelion, Gentian Root, with Licorice in Pure Red Wine as a base, with Aromatics.”

“A Laxative Tonic. In cases of constipation and its sequelæ, autointoxication, weakness and nervousness you should tryTriner’s American Elixir of Bitter Wine. This preparation consists of Cascara Sagrada, Dandelion, Gentian Root, with Licorice in Pure Red Wine as a base, with Aromatics.”

Triner’s American Elixir of Bitter Wine is put up in bottles said to hold 1 pint, 51⁄3fluidounces. The label declares the presence of from 16 to 18 per cent. alcohol by volume, and states that “no special tax is required by the laws of the U. S. for the sale of this medicinal preparation.” The circular contains the following recommendations for its use:

“... It should be used in all cases calling for a safe evacuation of the bowels, without weakening the body or causing any pain or other discomfort; in loss of appetite, nervousness and weakness.”“Triner’s American Elixir of Bitter Wine consists of two principal ingredients, viz., Red Wine and Medicinal Herbs.”“Red Wine strengthens the intestines and regulates their work. It also increases the appetite, stimulates and strengthens the body.”“Use Triner’s American Elixir of Bitter Wine always when a thorough cleaning out of the intestines is needed. Arrange the dose to suit your condition and habits.”“In Chronic Constipation the dose of Triner’s American Elixir of Bitter Wine should be increased or taken oftener.”“Many Female Troubles are caused or aggravated by constipation and ladies should always pay good attention to this fact.”

“Triner’s American Elixir of Bitter Wine consists of two principal ingredients, viz., Red Wine and Medicinal Herbs.”

“Red Wine strengthens the intestines and regulates their work. It also increases the appetite, stimulates and strengthens the body.”

“Use Triner’s American Elixir of Bitter Wine always when a thorough cleaning out of the intestines is needed. Arrange the dose to suit your condition and habits.”

“In Chronic Constipation the dose of Triner’s American Elixir of Bitter Wine should be increased or taken oftener.”

“Many Female Troubles are caused or aggravated by constipation and ladies should always pay good attention to this fact.”

In addition to Triner’s Elixir of Bitter Wine, the circular—in English, Polish, Russian, Spanish and other languages—advises the use of Triner’s Angelica Bitter Tonic, Triner’s Red Pills, Triner’s Liniment and Triner’s Cough Sedative.

The composition of this “wine”—some bitter drugs, a laxative and a tannin-containing, constipating red wine—and advertising propaganda all tend to the continued use of this alcoholic stimulant and thus to the unconscious formation of a desire for alcoholic stimulation. As the medical journal advertisements may lead physicians to prescribe this secret and irrational preparation and thus unconsciously lead to alcoholism, the Council authorized publication of this report.—(From The Journal A. M. A., July 14, 1917.)

Trimethol is the trade name for a substance said to be trimethyl-methoxy-phenol of the formula C6H(CH3)3(OCH3).OH—1:2:4:5:6, originated by J. T. Ainslie Walker. It is sold as a nontoxic germicide, having a Rideal-Walker phenol-coefficient of 40, even in the intestinal canal. It is described as insoluble in water and not to be decomposed in the alimentary tract, and to be excreted unchanged in the feces.

Trimethol itself is not obtainable. Pharmaceutical preparations—Trimethol Syrup, Trimethol Capsules and Trimethol Tablets, said to contain Trimethol—are prepared by The Walker-Leeming Laboratories and sold by Thos. Leeming and Co., New York.

Trimethol preparations are advertised for use in all conditions dependent on intestinal putrefaction. The advertising claims made are very extensive and some of them give to “Trimethol” the scope of a panacea. For example:

“Physicians are constantly reporting cases where Trimethol has been especially efficient, and describing conditions (until recently not associated with intestinal infection) which have been distinctly benefited by its use. This would seem to bear out the contentions of Charcot and Metchnikoff that 90% of all human ailments have their origin in intestinal infection.“The careful practitioner, when in doubt, will bear this in mind, now that we have a really efficient and non-toxic intestinal germicide—not a mere antiseptic.”

“The careful practitioner, when in doubt, will bear this in mind, now that we have a really efficient and non-toxic intestinal germicide—not a mere antiseptic.”

The Walker-Leeming Laboratories have not formally requested the Council to consider the Trimethol preparations, though in a personal letter to a member of the Council J. T. Ainslie Walker invited an investigation of his compound.

For the investigation of Trimethol and its preparation the Council secured the aid of a bacteriologist who has given much attention to the study of the intestinal flora. The Walker-Leeming Laboratories and J. T. Ainslie Walker were both asked to submit details of experimental studies and also to furnish a supply of the pure “Trimethol.” But the only data sent that had any definiteness set forth the bacterial counts made of plate cultures of stools of one patient before and after the administration of Trimethol Capsules.

The request for the pure substance was refused, on the grounds that the substance was not used in the undiluted form. The failure to furnish the chemical substance claimed as the essential constituent of the Trimethol preparations is to be deprecated if indeed it has not greater significance. At least it made it impossible for the Council’s expert to express his results in terms of absolute Trimethol of established composition. The data obtained apply only to the market preparations claimed to contain Trimethol. So far as the investigation and report go, “Trimethol” is a hypothetical substance.

Clinical or animal tests of the asserted intestinal antiseptics have hitherto given equivocal results because it is impossible, on the one hand, to predict the course of any intestinal infection, or, on the other hand, to determine what effect, if any, was produced by administration of the medicament. It therefore seemed unwise to undertake this line of investigation until the more direct laboratory bacteriologic methods had been exhausted. Consequently the investigator checked, in the first place, the phenol coefficient of one of the Trimethol preparations and then also determined its “penetrability” coefficient. Although by both methods Trimethol was found to be a germicide, the results did not indicate any remarkable potency or other properties suggesting that the drug possessed special therapeutic value. From the results obtained it appeared inadvisable to proceed further with the work until more definite evidence ofthe nature and of the value of the substance should be at hand. The report of the bacteriologic investigation follows:

“I have made no attempt to study the effects of internal administration of Trimethol on the intestinal flora. The methods available at the present time of enumerating the numbers ofviablebacteria in the feces are probably not accurate within 100 per cent. and the precision of such determinations is equally variable. The physiologic factors involved are so complex that they would appear to make a really valuable assay a question of many months’ careful study. If it were possible to administer known amounts of Trimethol, as such, the problem might be worth while; inasmuch as the available reactive substance is not at present quantitatively assayable, this phase of the investigation barely seems practicable.

“ ‘Trimethol Syrup,’ as such, appears to be about 10 per cent. as efficient in its germicidal value as carbolic acid. If the assay,3⁄4m. Trimethol per drm. (as the label indicates), is correct, the substance would appear to possess germicidal merit provided enough could be administered, if it is not influenced by passage through the stomach.

“A package containing four four-ounce bottles labeled ‘Trimethol, A Non-Toxic Germicide SYRUP Representing3⁄4m. Trimethol per drm., Alcohol 11⁄2per cent.’ was received at the laboratory Dec. 15, 1916. Later a smaller package containing, according to the label, 100 Trimethol tablets, each 5 gr., representing 11⁄4m. Trimethol, was received. The tablets were apparently chocolate coated.

“Two separate series of tests were made upon the syrup. (a)Phenol coefficient, using the method outlined inBulletin No. 82, Hygienic Laboratory, Method of Standardizing Disinfectants With and Without Organic Matter. (b) APenetrability coefficientby the method of Kendall and Edwards,Journal of Infectious Diseases,8, 250.

“The former method compares the viability of naked germs in a 1 per cent. carbolic acid solution as a standard, with various dilutions of the germicide to be tested. The latter measures the relative diffusibility and germicidal power of carbolic acid and various dilutions of the germicide to be tested uponBacillus colisuspended in 1.2 per cent. agar which is molded in cylinders of one centimeter diameter after infection with the organism.

“The first method—phenol coefficient—possesses advantages and disadvantages which are well known and need no mention here. It is worthy of notice, however, that as the death rate of the bacteria increases during the progress of the test, it becomes increasingly difficult to maintain a uniform suspension of living organisms so that each loopful removed shall exactly represent the developmental potentiality of the residual organisms.

“The second method theoretically covers the possibility because all the organisms are immobilized and are exposed to the germicide in direct proportion to its diffusibility until the center of the agar mass is reached, where the residual viable bacteria are presumably located. Inasmuch as the penetrability of an intestinal mass is involved in a discussion of intestinal germicides, the propriety of utilizing this ‘penetrability coefficient’ in this connection is obvious, in spite of its patent shortcomings.

“It is unnecessary to discuss the technique—the standard broth mentioned in the Hygienic Bulletin, a temperature of 70 F., a standard 4 mm. loop and careful attention to dilutions (using distilled water) were all observed. The various dilutions of Trimethol Syrup were made with accurate volumetric pipettes, measuring flasks and distilled water was used as a diluent.

“The results of several determinations, using Trimethol Syrup from three separate bottles, were in sufficient accord to warrant the statement that a dilution of1⁄10of Trimethol Syrup was equivalent to a1⁄100dilution of carbolic acid, usingBacillus typhosusas the test organism. Both solutions—the Trimethol and phenol—killed the organism in the interval between 71⁄2minutes and 10 minutes’ exposure. That is to say, our observations indicate that under standard conditions as defined above, a 10 per cent. solution of Trimethol Syrup is equivalent in germicidal powers, as defined by the phenol coefficient to a 1 per cent. solution of phenol. Naturally, no predictions can be drawn from these observations indicative of the value as an intestinal germicide of Trimethol itself.

“ThePenetrability coefficientresulted as follows: A 5 per cent. solution of phenol killedBacillus coli, suspended uniformly throughout a cylinder of 1.2 per cent. agar in the interval between 60 and 90 minutes. A 1 per cent. solution of phenol killed the same organisms under the same conditions in the interval between two and one half and three hours. An undiluted solution of Trimethol Syrup killed the organisms in the interval between two and one half and three hours. A 10 per cent. solution (nine volumes of distilled water to one volume of Trimethol Syrup) failed to kill the organisms in four hours. It would appear that undiluted Trimethol Syrup has the same combined penetrability and germicidal value as a 1 per cent. phenol solution.

“ThePhenol coefficient: A 10 per cent. solution of Trimethol Syrup in distilled water (nine volumes of distilled water to one volume of Trimethol Syrup) possesses the same germicidal power as a 1 per cent. solution of carbolic acid. This coefficient takes no cognizance of theactual amount of Trimethol as such—it merely indicates the relative germicidal power of the Trimethol Syrup as sold.”

The preceding report shows that Trimethol Syrup has a phenol coefficient of1⁄10, and, assuming Trimethol Syrup contains the amount of Trimethol declared, the substance Trimethol would have a phenol coefficient of 81⁄3instead of 40, as is claimed. According to Kendall and Edwards’ method, the penetrability-germicidal value of the syrup is equal to a 1 per cent. solution of phenol.

The report of the bacteriologist was submitted to The Walker-Leeming Laboratories for comment. The following reply was received from J. T. Ainslie Walker:

(May 22, 1917) “In reply to your letter of the 15th inst., which has just been placed before me on my return to town, I have to inform you that the potent constituent of Trimethol Tablets and Trimethol Syrup is not fully available as a bactericide until it comes in contact with the pancreatic fluid.“As you will see from the enclosed extracts from clinical reports, the therapeutic value of Trimethol has been well established.“As regards penetrability, no claim has ever been made for Trimethol in this connection; and, as I pointed out in my original paper (American Medicine, September, 1914), when referring to the independent tests made by Dr. Frederick Sondern, ‘No attempt was made to determine the bacterial content of the solid particles, as in the opinion of the writer sterilization of the interior of these particles is not only absolutely impossible, but wholly unnecessary. The fact of the fluid contents of the canal being sterile may be taken to indicate that the exterior of all solid particles is in a like condition, and therefore harmless. It is the organisms in the fluid portions only that produce the deadly effects through the chemical substances they secrete; those in the interior of the solid portions (i. e., as evacuated) may be disregarded, as they are not available for good or evil.’“I must confess to no little surprise on learning that your investigator is still using the Hygienic Laboratory method of determining phenol coefficients. I would respectfully suggest that you call his attention to the critical comparison of the Hygienic Laboratory and R.-W. Tests, which he will find in the enclosed reprint from theNew York Medical Journalof March 11, 1916: ‘Instead of being an improvement upon the standard R.-W. Test, the so-called Hygienic Laboratory Method is so defective as to be wholly unreliable, and incapable of furnishing results of any scientific or practical value whatever.’ ”

“As you will see from the enclosed extracts from clinical reports, the therapeutic value of Trimethol has been well established.

“As regards penetrability, no claim has ever been made for Trimethol in this connection; and, as I pointed out in my original paper (American Medicine, September, 1914), when referring to the independent tests made by Dr. Frederick Sondern, ‘No attempt was made to determine the bacterial content of the solid particles, as in the opinion of the writer sterilization of the interior of these particles is not only absolutely impossible, but wholly unnecessary. The fact of the fluid contents of the canal being sterile may be taken to indicate that the exterior of all solid particles is in a like condition, and therefore harmless. It is the organisms in the fluid portions only that produce the deadly effects through the chemical substances they secrete; those in the interior of the solid portions (i. e., as evacuated) may be disregarded, as they are not available for good or evil.’

“I must confess to no little surprise on learning that your investigator is still using the Hygienic Laboratory method of determining phenol coefficients. I would respectfully suggest that you call his attention to the critical comparison of the Hygienic Laboratory and R.-W. Tests, which he will find in the enclosed reprint from theNew York Medical Journalof March 11, 1916: ‘Instead of being an improvement upon the standard R.-W. Test, the so-called Hygienic Laboratory Method is so defective as to be wholly unreliable, and incapable of furnishing results of any scientific or practical value whatever.’ ”

As to the statement that the potent constituent of Trimethol Tablets and Trimethol Syrup is not fully available as a bactericide until it comes in contact with the pancreatic fluid, attention is called to a leaflet, which accompanies each bottle of Trimethol Syrup, that reads:

“Trimethol is insoluble in water, but when properly emulsified has a Rideal-Walker co-efficient of 40; that is to say, it is 40 times more efficient as a germicide than phenol (pure carbolic acid).”

The Trimethol Syrup which was used in the investigation, when mixed with water produced an almost perfectly transparent solution, which justifies the assumption that the proper physical conditions were observed and that this objection is not well founded.

As regards the relation of pancreatic fluid to bactericidal availability of Trimethol, there is little to say, other than that the published statements in the advertising accompanying the packages make no mention of this point. It would be interesting to know what, if any, relation the pancreatic fluid has to this substance, in view of the statement that it “has a Rideal-Walker coefficient of 40.”

The Trimethol “literature” does not throw light on the question, What is the germicidal value of Trimethol Syrup as compared with phenol? The only available method of determining the germicidal value of a liquid disinfectant is to make a direct comparison of the substance in question with phenol under similar conditions. Given parallel conditions, not obviously prejudicial to the substance tested in contrast to the standard solution, the results are comparable, and furnish a basis for estimating the relative germicidal power of the two substances. In the investigation, Trimethol Syrup and phenol were thus compared.

As regards the contention that the bacteria within fecal masses are harmless, this may be granted. But it must also be admitted that these intestinal masses are constantly being reformed so that buried micro-organisms do not remain in the interior. For this reason, the determination of the penetrability coefficient of a germicide is pertinent.

Regarding the respective merits of the old Rideal-Walker and the newer U. S. Hygienic Laboratory method of determining the phenol coefficient, the Rideal-Walker method was found to possess certain drawbacks, and in an attempt to overcome these the “LancetMethod” was evolved; this method in turn was improved in the U. S. Hygienic Laboratory and led to the United States Public Health Service Hygienic Laboratory method for the determination of the phenol coefficient of disinfectants (published inHygienic Laboratory Bulletin 82). In 1913 this method was formally adopted by the Council for the valuation of disinfectants or germicides of the phenol type, and the method is now in general use for this purpose in the United States.119In this connection Hiss and Zinsser may be quoted (Ed. 2, page 80): “The most precise method of standardizing disinfectants is that now in use in the United States Public Health Service.” Stitt, director of the United States Naval Medical Schools, in his Practical Bacteriology, Blood Work and Parasitology (Ed. 4, page 473) says: “In the United States disinfectants are rated according to the Hygienic Laboratory Phenol Coefficient.”

The Council adopted the recommendation of the Committee on Pharmacology to the effect that the claims made for Trimethol are unsupported by acceptableevidence. Accordingly, Trimethol and the pharmaceutical preparations said to contain it—Trimethol Syrup, Trimethol Capsules, and Trimethol Tablets—were held ineligible for New and Nonofficial Remedies.—(From The Journal A. M. A., Aug. 11, 1917.)

E. Fougera & Co., Inc., New York, acting as agent for The British Drug Houses, Ltd., London, advertise “Ferrivine,” “Intramine” and “Collosol Iodine” to the medical profession. A circular entitled “Ferrivine, The New Anti-Syphilitic Remedy” begins:

“FERRIVINE is the name given to ferric tri-para-amino-benzene sulphonate. This iron compound was first prepared by Mr. J. E. R. McDonagh, F. R. C. S., by whom it has been both biologically and clinically tested. It is slightly soluble in water, the solution having an acid reaction.“INDICATIONS“According to Mr. J. E. R. McDonagh’s researches, the phases of theLeucocytozoon syphilidsare killed by the lipoid-globulin molecules of the serum, which possess a stereochemical molecular configuration homologous to those of the lipoid-globulin molecules of the parasite. The process is one of absorption, a chemico-physical reaction which is in part dependent upon the supply of active oxygen. Active oxygen is formed directly by oxidation processes and the peroxide necessary for its formation directly by reducing processes. Oxidation is increased by metals and reduction by non-metals. The non-metal which acts in the body as the normal reducing agent is sulphur, hence the discovery of Intramine (see separate pamphlet). The metal which acts in the body as the normal oxidising agent, is iron, hence the discovery of Ferrivine.”

“INDICATIONS

“According to Mr. J. E. R. McDonagh’s researches, the phases of theLeucocytozoon syphilidsare killed by the lipoid-globulin molecules of the serum, which possess a stereochemical molecular configuration homologous to those of the lipoid-globulin molecules of the parasite. The process is one of absorption, a chemico-physical reaction which is in part dependent upon the supply of active oxygen. Active oxygen is formed directly by oxidation processes and the peroxide necessary for its formation directly by reducing processes. Oxidation is increased by metals and reduction by non-metals. The non-metal which acts in the body as the normal reducing agent is sulphur, hence the discovery of Intramine (see separate pamphlet). The metal which acts in the body as the normal oxidising agent, is iron, hence the discovery of Ferrivine.”

A circular, “Intramine, a New Non-Toxic Compound for the Treatment of Protozoal and Chronic Bacterial Diseases,” expounds Mr. McDonagh’s ideas of the treatment of syphilis with Ferrivine and Intramine by means of the oxidising action of Ferrivine and the reducing action of Intramine and asserts:

“As the ultimate administration of oxidising and reducing agents will benefit almost any infection, it may be said that Intramine is indicated in all protozoal diseases, and in all chronic bacterial diseases, especially in tuberculosis, presumably in leprosy and possibly in malignant disease [cancer?]. To the administration of Intramine there are no contraindications.”

We are also told that:

“Intramine is useful injected into the urethra.... In cases of chronic urethritis and perifolliculitis... invaluable as a local application to chronic ulcers...”

The Intramine circular includes a “Scheme of Treatment for Syphilis” which advises, in addition to Intramine, Ferrivine or salvarsan, mercury and iodids, the use of another proprietary called “Collosol Iodine.” An inquiry addressed to Fougera & Co. in regard to the character and composition of this preparation, brought the reply that the firm had no knowledge of its identity.

This “scheme of treatment” is objectionable in that it advises the “stock” treatment of a disease which demands individualization and further in that whatever beneficial effects may result from the use of mercury and iodid is likely to be ascribed to the preparations “Intramine,” “Ferrivine” and “Collosol Iodine.”

The advertising for Ferrivine and Intramine sent out by Fougera & Co. contains no experimental or clinical data on which an estimate of their value may be based. Apparently in England, where these products were originated, little has been published regarding them.

There is, however, one report which may be accepted as a carefully controlled clinical trial. In theLancet(June 17, 1916, p. 1214) L. W. Harrison, D.S.O.,M.B., Ch.B.Glasg., and C. H. Mills, M.R.C.S., L.R.C.P.Lond., report on “The Effect of Ferrivine and Intramine on Syphilis.” After briefly reviewing the theories which form the basis of McDonagh’s proposed treatment of syphilis with his discoveries “Ferrivine” and “Intramine” the authors point out:

“... that Mr. McDonagh’s biological discoveries... have not been publicly confirmed by any biologist of standing...”

While:

“... eminent chemists have confessed themselves unable to understand his chemistry.”

The authors explain:

“Recognizing that this might prejudice our practical tests of Intramine and Ferrivine, we have taken particular care to guard against their influence, cross-checking our observations and submitting them to others for confirmation or otherwise.”

Harrison and Mills chose for a test three ordinary cases of secondary syphilis, cases with well marked lesions, the clinical progress of which could easily be watched and from which it was easy to obtain specimens for microscopic examination. After a detailed account of the three cases—which records grave conditions resulting from the treatment and which shows the inefficiency of the drugs—they write:

“From the above account it will be seen that the local and general reactions which follow the injection of these preparations are by no means pleasant. In the case of Intramine the pain is undiluted torture and lasts so for two or three days. One of us had previously treated four cases with Intramine and the same local reaction occurred in these. In two of them abscesses have burst outwardly, one of which is still discharging necrotic débris, ten weeks after the injection, and will take many more weeks to close. In those cases where no abscess has yet burst it is easy to feel by the gap in the muscles that considerable necrosis has occurred. None of these effects can be ascribed to sepsis, as most rigid aseptic precautions were taken. Further, particular care was taken to make the injections strictly intramuscular. The constitutional symptoms which follow immediately upon the injection of Ferrivine are distinctly alarming, and such as would cause one to hesitate before injecting this remedy into any but robust patients.”

Harrison and Mills estimate the therapeutic effects of these drugs thus:

“1. That Ferrivine entirely failed to causeS. pallidato disappear from the lesions of three well-marked cases of secondary syphilis.“2. After the failure of Ferrivine to cause the disappearance ofSpirochaeta pallidafrom a mucous patch a single dose of 0.3 gm. salvarsan effected this in 18 hours, and the patch, which had hitherto been uninfluenced, had healed within 48 hours.“3. Clinically we were unable to detect any influence of either or both these compounds on syphilitic lesions, although each of them was of the variety which heals in a week or ten days under salvarsan treatment.“4. Further syphilitic lesions appeared immediately after the treatment in one of the two cases treated with both Ferrivine and Intramine. A mucous patch appeared on one tonsil as well as further syphilitic papules from which spirochetes were obtained. The other case developed nephritis, with albumin and epithelial casts; which was not present prior to the injections.”

“1. That Ferrivine entirely failed to causeS. pallidato disappear from the lesions of three well-marked cases of secondary syphilis.

“2. After the failure of Ferrivine to cause the disappearance ofSpirochaeta pallidafrom a mucous patch a single dose of 0.3 gm. salvarsan effected this in 18 hours, and the patch, which had hitherto been uninfluenced, had healed within 48 hours.

“3. Clinically we were unable to detect any influence of either or both these compounds on syphilitic lesions, although each of them was of the variety which heals in a week or ten days under salvarsan treatment.

“4. Further syphilitic lesions appeared immediately after the treatment in one of the two cases treated with both Ferrivine and Intramine. A mucous patch appeared on one tonsil as well as further syphilitic papules from which spirochetes were obtained. The other case developed nephritis, with albumin and epithelial casts; which was not present prior to the injections.”

While from these cases the obvious conclusion was drawn that Intramine and Ferrivine “have no specific effect on early syphilis,” these authors subsequently treated a case of tertiary syphilis with the drugs. An Intramine injection caused pain for several days but did not stop the progress of the disease. Ferrivine was then administered “not without a feeling of grave responsibility” in view of their previous experiences. They state that “the reaction which resulted in this instance was the most severe” they ever experienced after an intravenous injection of any of the antisyphilitic remedies with which they had previously worked. It is stated that “for a period of someminutes there was grave doubt as to the patient’s survival.” After resuscitation the patient passed a disturbed night, and rigors which ensued lasted until the following afternoon. The author’s report that in this case also no clinical improvement occurred and that the Intramine-Ferrivine treatment was replaced by a course consisting of salvarsan, potassium iodid and mercurial inunction.

Ferrivine, Intramine and Collosol Iodine were declared inadmissible to New and Nonofficial Remedies.—(From The Journal A. M. A., Sept. 8, 1917.)

For the information of the profession the Council has prepared and authorized for publication the following report on Eskay’s Neuro Phosphates.

W. A. Puckner, Secretary.

Eskay’s Neuro Phosphates (Smith, Kline & French Co., Philadelphia) is offered to physicians under the claims that it contains alcohol, 17 per cent., and sodium glycerophosphate, 2 grains, calcium glycerophosphate, 2 grains, and strychnin glycerophosphate,1⁄64grain, in each dessertspoonful. It is called a “Nerve Tissue Reconstructive,” and its advertising claims are based on the discredited theories that certain disorders are due to a deficiency of phosphorus in the nerve structure of the body, and that glycerophosphates are assimilated more readily than ordinary phosphates. This assumption was based on the knowledge that the lecithins, which form a part of the nerve structure, contained the glycerophosphate radical in the molecule. In line with this, Smith, Kline & French Co. aver:

“Eskay’s Neuro Phosphates is of marked value in many acute and chronic conditions, in nervous exhaustion following mental and physical strain, neurasthenia, paralysis, anemia, tuberculosis, marasmus, debility and wasting diseases generally, and the nerve-weakness of the aged. It is particularly useful in convalescence from acute diseases and in the nervous condition following la grippe.”

In its report on “The Therapeutic Value of the Glycerophosphates” (The Journal, Sept. 30, 1916, p. 1033) the Council pointed out that the therapeutic use of the glycerophosphates was based on the assumption that the inorganic phosphates cannot supply the body’s needs of phosphorus or that the use of organic compounds “spared” the system the necessity of making such synthesis. The report presented evidence to show that the glycerophosphates are not absorbed as such, but that they are split into inorganic phosphates before absorption. The Council showed that there was convincing evidence that the animal organism synthesizes its complex organic phosphorus constituents from inorganic phosphates, and that organic phosphorus is of no more value as a food than inorganic. Despite this the Neuro Phosphates advertising makes use of the fallacious assumption regarding the action of the glycerophosphates.

Pleading for the particular mixture represented by the proprietary, it is asserted that:

“Sodium glycerophosphate is of special value in neurasthenia, Addison’s disease, phosphaturia and phthisis.”

and that calcium glycerophosphate “is employed in bone fracture, rachitis, tuberculosis and various wasting diseases.”

The phosphorus content of1⁄64grain of strychnin glycerophosphate is ridiculously small. Yet it is asserted that this strychnin salt is of superior value because it combines the effects of strychnin with a “food-like form of phosphorus.”Eskay’s Neuro Phosphates has an acid reaction which is capitalized, thus:

“Experiments have shown that the acid glycerophosphates are more rapidly absorbed and are more efficient than the neutral salts.”

And as a further illustration of extravagant claims:

“As a glycerophosphoric acid in the form of lecithin is normally present in spermatozoids, it is but natural that the glycerophosphates should exhibit aphrodisiac effects (as has been observed), but this result does not seem to obtain in all cases.”

Is this a clumsy attempt to exploit this “nerve phosphate” as a “lost manhood” cure?

The Council held Eskay’s Neuro Phosphates ineligible for New and Nonofficial Remedies because unwarranted therapeutic claims are made for it and because the administration of strychnin, calcium, phosphate and alcohol is not conducive to rational therapeutics, particularly when such a mixture is marketed under a name which indicates but one of its constituents.—(From The Journal A. M. A., Sept. 29, 1917.)

Because of inquiries received, the Council has authorized publication of the following report declaring K-Y Lubricating Jelly inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

K-Y Lubricating Jelly (Van Horn and Sawtell, New York), originally advertised as a lubricant for instruments and the hands, is now also recommended as a therapeutic agent. If the claims for “K-Y” were limited strictly to such effects as result from the purely mechanical properties of a lubricant, it might be held that it would not come under the purview of the Council. The preparation, however, while introduced as a lubricant, is now offered for a broader field of use, and the manufacturers make claims which are not supported by any evidence available to the Council. Evidence the following, taken from a circular that accompanies the package:

“K-Y allays smarting and burning at once through its pronounced soothing and cooling effects, and thus makes an admirable dressing for burns.”“Many physicians make a practice of anointing the bodies of their measle and scarlet fever patients with ‘K-Y,’ in this way affording gratifying relief from itching and irritation, and effectively preventing dissemination of infectious material.”

“K-Y allays smarting and burning at once through its pronounced soothing and cooling effects, and thus makes an admirable dressing for burns.”

“Many physicians make a practice of anointing the bodies of their measle and scarlet fever patients with ‘K-Y,’ in this way affording gratifying relief from itching and irritation, and effectively preventing dissemination of infectious material.”

And this from another circular:

“I had one of the most troublesome cases of pruritus vulvæ that I had ever seen. I guess I must have tried everything and the case had been referred to me by another man, who had previously tried everything, including cauterization. Well, one day I was examining her, and of course K-Y on the speculum—the irritation seemed to quiet down, and the following day she said she felt no effects from it at all. Then later on, it returned, and I couldn’t imagine what had done so much good, unless it could have been the lubricant, so I told her to buy a tube, which she did. Every once in a while she has a return of it slightly, but she just applies K-Y and clears it all up.”

The manufacturers state that they do not know why K-Y is so soothing, but suggest:

“Possibly the cooling action of the combination, and the effect of the 4% boric acid contained, are factors that enter. Be all that as it may, the fact certainly remains that oftentimes, after other local measures fail, ‘K-Y’ lubricating Jelly gives relief.”

Elsewhere it is claimed to be germicidal, and to give relief in other conditions, thus:

“Diabetic and uremic irritations, not only of the genitalia, but of other parts, have been found fully as amenable as pruritus vulvae to the soothing influence of ‘K-Y’ Lubricating Jelly, especially if the previous application is removed with water every time a new one is put on.”

The foregoing citations are obviously intended largely for the public, and make it plain that “K-Y” Jelly is not in the class of nonmedical and harmless external applications; on the contrary, these claims tend to create the impression that the spread of measles and scarlet fever can bepreventedin the stage of desquamation. To place such statements in the hands of the patient supported by the tacit endorsement of a prescription is to create a false and dangerous sense of security and to lead to a failure to observe other and more important means of preventing dissemination of these diseases.

The Council held K-Y Lubricating Jelly in conflict with Rules 1, 4, 6 and 10, and authorized publication of this report.—(From The Journal A. M. A., Sept. 29, 1917.)

Ziratol (Bristol-Myers Company, New York), in compliance with the federal “insecticide law,” is declared to contain 32 per cent. water and 30 per cent. glycerin as inert constituents. Regarding its active constituents the manufacturer makes the following and meaningless statement:

“Ziratol is prepared from Phenols of the Naphthalene series and consists of a solution of such Phenols in a mixture of soap, water and glycerin.”

In response to inquiry, the A. M. A. Chemical Laboratory examined Ziratol and reported that its essential constituent appears to be alpha-napthol,120and that it has, essentially, the following composition by weight: Alpha-napthol 18 per cent., soap 20 per cent., glycerin and water sufficient to make 100 per cent.

A Ziratol advertising circular gives a tabulated report of germicidal tests, said to have been made according to the method of the Hygienic Laboratory of the U. S. Public Health Service. When this work was done is not stated. According to these tests Ziratol possesses a phenol-coefficient of 13.66. The claim that Ziratol is ten times more efficient than carbolic acid (phenol) is evidently based on this report.

These claims of high germicidal value are contradicted by an examination made for the Council. A specimen purchased in the open market was examined independently by two operators, to determine the Hygienic Laboratory phenol-coefficient. One observer found the phenol coefficient to be 2.54. The other reported it to be 3.09. Evidently the germicidal value of Ziratol is greatly exaggerated in the advertising claims and, in fact, does not exceed that of the official compound solution of cresol (Liquor Cresolis Compositus, U. S. P.) for which a phenol-coefficient of about three has been established. (See New and Nonofficial Remedies, 1917, p. 82.) The claim that Ziratol is “the Universal Antiseptic and Germicide” is manifestly an unwarranted exaggeration.

The referee in submitting this report to the Council recommended that Ziratol be held in conflict with Rule 1 (secrecy of composition) and Rule 6 (unwarranted and exaggerated claims). After the report had been submitted, it was found that a new advertising circular, accompanying a trade package, no longer contained the claim that “Ziratol is ten times more efficient than Carbolic Acid.” The older circular made the following statement:

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