FERRIVINE, INTRAMINE AND COLLOSOL IODINE

Report of the Council on Pharmacy and Chemistry

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

“FERRIVINE is the name given to ferric tri-para-amino-benzene sulphonate. This iron compound was first prepared by Mr. J. E. R. McDonagh, F. R. C. S., by whom it has been both biologically and clinically tested. It is slightly soluble in water, the solution having an acid reaction.

“INDICATIONS

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

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

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

We are also told that:

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

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

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

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

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

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

While:

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

The authors explain:

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

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

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

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

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

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

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

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

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

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