SYRUP LEPTINOL (FORMERLY SYRUP BALSAMEA)
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on “Syrup Leptinol” (formerly “Syrup Balsamea”). The product is inadmissible to “New and Nonofficial Remedies,” first, because the manufacturers fail to give the profession information regarding either the amount of the potent ingredient or the method of determining its identity and uniformity; second, because of the unwarranted recommendation for its use in such infectious diseases as pneumonia and epidemic influenza and for lack of satisfactory supporting evidence of its alleged therapeutic efficacy in other diseases and, third, because the recommendations for its use appearing on and in the trade package constitute an indirect advertisement to the public.
W. A. Puckner, Secretary.
Syrup Leptinol is sold by the Balsamea Co. of San Francisco. It was first introduced as Syrup Balsamea. In recent advertising, Syrup Leptinol is also referred to simply as “Leptinol.”
According to the statements of the Balsamea Co., Syrup Leptinol is prepared from the root of a species of Leptotaenia (a plant belonging to the parsnip family) which grows in Nevada and which has heretofore not been used in medicine. The manufacturer states that the botanists who have been consulted have been unable to agree on the botanical classification of the plant. The dried root of this unclassified species of Leptotaenia is extracted with alcohol and from the extract so obtained the syrup is made, but no information has been furnished to show how the alcohol-soluble material is incorporated in the syrup. Further, the manufacturer has not announced tests whereby the identity and uniformity of the finished preparation may be determined.
A booklet contains the following:
“The species of Leptotaenia from which Leptinol is produced was first used in medicine by Dr. E. T. Krebs, who, after thorough laboratory investigation and clinical application over a period of several months, which resulted in the perfecting of Leptinol, prescribed the preparation for Influenza during the epidemic of that disease in 1918 with remarkably good results. Since this first use, Leptinol has been exhaustively tested by clinicians in private practice and in hospitals in the treatment of Pneumonia, Influenza Bronchitis, etc., and has been universally endorsed.”
In a circular letter it is asserted that the use of “Leptinol” during the “influenza epidemic” of 1918–1919 “demonstrated its almost specific action in respiratory affections”; that “during this epidemic it proved to be five times as efficacious as any other treatment in pneumonia ...”; and that “it is now as firmly fixed in the mind of many doctors for respiratory diseases as quinine is for malaria and the salicylates for rheumatism.”
In the booklet it is further stated that the therapeutic action of the preparation is primarily that of a “stimulating expectorant” and secondarily as a “sedative expectorant”; that “its antiseptic action in the respiratory tract is prompt”; that it “is an effectual cardiac tonic where the tone of the heart muscle is impaired by fever”; that “in acute pulmonary conditions it effectively improves the respiratory action and allays cerebral irritation due to fever and toxins”; that it acts “as a vital stimulant and nerve sedative”; that “it stimulates the excretion of acid by the skin and in fever it has a strongly diaphoretic and antipyretic action without depressing the circulation or the central nervous system”; that it is “mildly diuretic” and “slightly augments the biliary flow” and that “it increases the gastric and intestinal secretions and allays intestinal fermentation.”
No evidence has been presented to the Council which shows that Syrup Leptinol has the actions ascribed to it. The reports of clinical trial are little more than chance observations and lack all control. This applies also to the following, stated to be a quotation from the report of the Tonopah Mines Hospital Association:
“In the spring of 1919 a recurrence of the Influenza epidemic of the previous winter was experienced. During the first period of this second epidemic, prior to April 15th, there were treated one hundred sixteen cases of Influenza, fourteen of which developed Influenzal Pneumonia, with six deaths. The Pneumonia was of the very virulent type which prevails in this high altitude.... After April 15th, when the clinical use of Leptinol was inaugurated, three hundred and sixty-eight cases of Influenza were treated and not a single case developed Pneumonia. Twenty-two cases of Influenzal Pneumonia were received and treated with Leptinol, with a consequent one hundred per cent. recovery....
“In the cases where Leptinol was used the treatment was the same as had been previously followed, as to diet, fresh air, etc., but the medication was confined to Leptinol. Syrup Leptinol was started immediately in one-dram doses at one-hour intervals, in cases with high temperatures, and this was continued until temperature and pulse subsided. It was then used in one-dram doses at three-hour intervals as recovery progressed. On admission to the hospital, calomel in 1⁄4 grain doses, was given at fifteen minute intervals for eight doses. The last calomel was followed in six hours by 1⁄2 ounce Magnesium Sulphate in saturated solution. The second day 1⁄10 grain of calomel was given at one-hour intervals for ten doses....”
Medical journals are replete with reports of remarkable results obtained with the most varied forms of treatment instituted at the time that the “influenza epidemic” had been reached. In these cases it is more than probable that the lessened virulence of the causative factor of the disease, the gradually established resistance of those stricken with it in the latter period and the improved management resulting from experience deserve the credit for the successful outcome of the treatment, rather than the particular form of medication employed.
The report of the Tonopah Mines Hospital Association directly implies that Syrup Leptinol prevents the development of pneumonia in practically all cases of influenza in which it would develop and that it entirely abolishes the mortality of that disease. However, it is well known that innumerable remedies have been recommended as specifics in the treatment of pneumonia on the basis of the treatment of a limited number of cases which recovered, and that eventually these asserted specifics have been discarded as of little value. In the present instance, the recovery of twenty-two cases in succession afford prima facie evidence that those cases were not the virulent type of pneumonia in which the death rate is very high under any methods of treatment. While no effort appears to have been made to determine the nature of the infecting organism, the records show fairly conclusively that they belonged to those causing the milder type of pneumonia.
The Council finds Syrup Leptinol (formerly Syrup Balsamea) inadmissible to New and Nonofficial Remedies because: (1) the information in regard to composition does not state the amount of potent ingredient, nor permit the determination of its identity and uniformity; (2) the recommendation for its use in such infectious diseases as pneumonia and epidemic influenza is unwarranted and its claimed therapeutic efficacy in other diseases is without satisfactory supporting evidence; and (3) the recommendations for its use which appear on the label and the circular wrapped with the trade package constitute an indirect advertisement to the public.
The Council accepts the explanation of the manufacturer that he has been unable to obtain a satisfactory classification of the plant from which Syrup Leptinol is made. It would be undesirable to exclude from therapeutic use a valuable drug simply because its botanical character has not been determined or because an exhaustive chemical examination had so far not been made. However, in the absence of such information the manufacturer should give full information with regard to the preparation or standardization of his remedy and the therapeutic claims made for it should be accompanied by indisputable, thoroughly controlled clinical evidence. In the case of Syrup Leptinol, there is no satisfactory evidence available showing that the preparation has any value in the treatment of epidemic influenza, pneumonia, whooping cough, etc. While it is probable that a balsamic syrup, such as Syrup Leptinol, has palliative properties in coughs, such action does not at all justify the claim that it is useful in the contagious diseases for which it is proposed. The Council cannot recognize a syrup presenting an unknown plant in uncertain proportions which is recommended in a variety of dangerous contagious diseases in which it ultimately may be harmful, even though in early stages of these diseases it may serve to allay some of the milder symptoms.
Concerning the composition of the plant from which Syrup Leptinol is prepared, the Balsamea Company states that it contains “Alkaloids, acids, glucosides, volatile and fixed oils, gums and resins.” This information is valueless, since no information is given concerning the character, amounts or pharmacologic action of the ingredients. Further, it is unreliable as far as the presence of alkaloids is concerned since the A. M. A. Chemical Laboratory has been unable to find any alkaloids in the specimen of the crude drug furnished by the manufacturers.
In accordance with its regular procedure, the Council submitted the preceding statement to the manufacturer.
In reply the Balsamea Company stated that it is more than ever of the belief that Syrup Leptinol is deserving of recognition by the Council, basing this opinion on further clinical experience with it in the treatment of influenza.
The manufacturer stated that the use of the words “Leptinol” and “Syrup Leptinol” interchangeably was due to an oversight and promised to limit the use of the word “Leptinol” to an alcoholic extract of the plant.
Concerning the method of preparation of this alcoholic extract and the amount used in the preparation of Syrup Leptinol the Balsamea Company replied as follows:
“The alcoholic extract of the Leptotaenia, which we have termed ‘Leptinol’ is a preparation of definite and uniform strength, as determined by two methods: (a) the gravity test using the U. S. Hydrometer Scale for spirits, by which Leptinol registers 52 degrees at 60 degrees F., and (b) by gentle evaporation of the alcohol content and the measuring of the active constituents, which measures twenty-five per cent. by weight.
“The alcoholic extract ‘Leptinol’ is glycerinated in a machine, using one part of the alcoholic concentration to four parts of glycerin. This is then added to eleven parts of a heavy syrup, containing 71⁄2 pounds of sugar to the gallon of syrup, and thoroughly mixed in an agitating machine. Leptinol is the sole active ingredient of Syrup Leptinol. Syrup Leptinol is a preparation of uniform strength. It is far more uniform in strength than most of the syrups of the U. S. P. made from fluid extracts which are made from crude drugs which are not uniform in strength.”
This claim cannot be allowed as meeting the conflict with Rule 1. It is well known that plants vary in their composition at different times of the year; under different conditions of cultivation and growth; and under other conditions; hence the claim that alcoholic extracts of equal specific gravity insure uniformity of composition in active principles must be considered entirely illogical, especially since the exact nature of the active principles, if any be present, is unknown. If these are known their nature should be stated and tests for their identity be given. If they are unknown it is manifestly misleading to state that the preparation is of uniform strength.
It is evident that the Council cannot approve of the use of a preparation of unknown composition without satisfactory evidence of its value, especially when it is recommended in a variety of serious infectious diseases such as influenza and pneumonia. The mere fact that a small number of patients who have received the drug recover is no evidence of its curative value, and until carefully controlled clinical tests of the preparation are made, it is not entitled to the consideration of physicians.—(From The Journal A. M. A., June 5, 1920.)