HYDRAGOGIN

“By Effects: Only a few patients complain of an unpleasant sharp taste, burning of the tongue (Seifert, Sklarek). Among the general symptoms observed are urticaria-like exanthems (Glaser, Roters), which are accompanied by nausea, vomiting, headache, insomnia and vertigo, burning and irritability especially in the larynx (Meissner); phenomena of poisoning (Geissler); gastric disturbances (Engelmann); renal irritation (Steinhard); unsuited for diabetics (Voit).”

“By Effects: Only a few patients complain of an unpleasant sharp taste, burning of the tongue (Seifert, Sklarek). Among the general symptoms observed are urticaria-like exanthems (Glaser, Roters), which are accompanied by nausea, vomiting, headache, insomnia and vertigo, burning and irritability especially in the larynx (Meissner); phenomena of poisoning (Geissler); gastric disturbances (Engelmann); renal irritation (Steinhard); unsuited for diabetics (Voit).”

The contention that Formamint, when mixed directly with mediums and left in contact with bacteria, will kill the organisms was corroborated. Thus the statements and pictures in the booklet, “The Gospel of Prevention,” which is enclosed with each bottle of Formamint, showing the inhibition of growth of air bacteria on plates containing Formamint are no doubt true and authentic.

Finally, the claim that Formamint is an almost perfect throat disinfectant was by no means confirmed, as a glance at the tables will show. One hour after it is taken, even when a tablet was used each half hour for twelve hours, the number of bacteria in the throat was practically the same as when Formamint was not used. Even ten minutes after taking a tablet the number of bacteria in the throat was never greatly reduced, as is maintained by the manufacturers.

Formamint exerts no selective action in killing off the very delicate organisms which are more apt to be pathogenic. When the comparative counts were made on blood agar which would favor the growth of the delicate parasitic organisms, no reduction whatever was shown by the use of Formamint.

The number of streptococci was found to be the same, within limits of experimental error, ten minutes after taking a tablet as it was before the tablet was taken.

Therefore it seems that Formamint fails, as any such germicide would be expected to fail, to kill bacteria in the crypts and recesses of the throat, for when dissolved in the mouth it cannot reach and remain in contact with the organisms long enough to kill them before it is swallowed.

Summed up, the investigation shows:

1. That the claims made for Formamint are extravagant and misleading.

2. That the recommendations for the use of these tablets may be, in some cases, fraught with danger and are a menace, not only to the health of the individual, but also to the safety of the community.

3. That the claim that Formamint is a definite chemical compound is false.

4. That the use of Formamint may produce marked irritation of the intestinal tract.

5. That Formamint is not a throat disinfectant, as the manufacturers maintain, but its action on the bacteria of the throat is an almost negligible one and dependence on Formamint for the prevention of infection and for curing disease is not only unwise but dangerous.

6. That Formamint conflicts with the rules of the Council. False statements are made with regard to its composition (Rule 1); grossly unwarrantedclaims are made for its therapeutic properties (Rule 6), and therefore its exploitation to the public (Rules 3 and 4) is a public danger.

It is recommended that this report be published, to call attention not only to the falsity of the claims made for, and the danger in the use of, Formamint, but also to emphasize the utter inefficiency of all such methods of “disinfecting” the throat.—(From The Journal A. M. A., Aug. 28, 1915.)

Hydragogin (C. Bischoff & Co., New York, selling agents) is advertised as “a most powerful diuretic and cardiac tonic.” The composition given is:

“Fifteen parts of the remedy contain 0.5 parts oxysaponin, 1.5 parts tincture of digitalis, 2.5 parts tincture of strophanthus, scillipicrin and scillitoxin, the active principles of scilla maritima, and alcohol.”

“Fifteen parts of the remedy contain 0.5 parts oxysaponin, 1.5 parts tincture of digitalis, 2.5 parts tincture of strophanthus, scillipicrin and scillitoxin, the active principles of scilla maritima, and alcohol.”

It is not clear from this statement whether 15 parts of Hydragogin contain 2.5 parts of tincture of strophanthus, plus unspecified amounts of scillipicrin and scillitoxin, or 2.5 parts of a mixture, in unspecified proportions, of tincture of strophanthus, scillipicrin and scillitoxin. The activity of strophanthus, after it enters the blood stream, is about fifty times that of digitalis; hence, if the former proportion is the true one, in giving an amount of Hydragogin which ensures the full therapeutic effect of the digitalis, one would administer an almost certainly fatal amount of strophanthus. Whatever the proportion of strophanthus may be, however, the administration of a mixture of digitalis and strophanthus in fixed proportions is indefensible. At times it is advisable to follow one of these drugs with the other in the treatment of cardiac disease. The simultaneous administration of the two continuously in fixed proportions, however, is injudicious, because of the great difference between their rates of absorption and in their activity after they enter the blood stream. The action of digitalis, moreover, persists much longer than does that of strophanthus.

An advertising circular contains the following claim:

“The well-known diuretic properties of digitalis, strophanthus and squills are greatly enhanced by the addition of the oxysaponin.”

“The well-known diuretic properties of digitalis, strophanthus and squills are greatly enhanced by the addition of the oxysaponin.”

This is not true. Saponins are not synergistic with digitalis thera­peutically; on the contrary, they exert a purely deleterious action on the heart when they enter the circulation.

The symptoms of cardiac disease are often difficult to distinguish from the toxic actions of the digitalis bodies. Since these bodies must often be given to the point of beginning toxic action in order to induce the full therapeutic effects, it is obvious that the administration of a mixture of digitalis, strophanthus, saponin and active principles of squill is especially liable to induce serious toxic effects which cannot be distinguished from the symptoms of the disease.

Hydragogin is a shotgun mixture of semisecret composition; it is marketed under a thera­peutically suggestive name, and advertised by means of unwarranted therapeutic claims. It is therefore in conflict with Rules 1, 6, 8 and 10. The Council held Hydragogin ineligible for New and Non­official Remedies.—(From The Journal A. M. A., Sept. 4, 1915.)

Filudine is said to be prepared by J. L. Chatelain, Paris, and is sold in this country by Geo. J. Wallau, Inc., New York. It is offered as a remedyfor “biliary insufficiency,” “hepatic insufficiency,” “intestinal dyspepsia,” “all affections of the liver (diabetes, cirrhosis, cancer, etc.),” “malaria,” “obesity” and “tuberculosis.”

No quantitative information is furnished as to the composition of the preparation and there are noteworthy discrepancies in the various statements regarding the ingredients. In one number of “Treatment,” a self-styled “Review” of medical literature (actually devoted to advertising the preparations sold by Wallau), we are told that

“This product [Filudine] is a more concentrated and potent extract of the liver, with which is combined an extract of the spleen. The liver and the spleen are so intimately interdependent, that the addition of a splenary extract to the liver extract is a signal improvement from which a synergistic action results. Thiarféine is also added, as it helps somewhat to combat the anaemia from which all diabetics suffer more or less.”

“This product [Filudine] is a more concentrated and potent extract of the liver, with which is combined an extract of the spleen. The liver and the spleen are so intimately interdependent, that the addition of a splenary extract to the liver extract is a signal improvement from which a synergistic action results. Thiarféine is also added, as it helps somewhat to combat the anaemia from which all diabetics suffer more or less.”

Thiarféine is said to be

“Thiomethylarsinate of Caffein, a new salt discovered by M. Chatelain.”

“Thiomethylarsinate of Caffein, a new salt discovered by M. Chatelain.”

Another circular, which gives an imposing formula for “thiarféine” or “thio­methyl­arsinate of caffein,” states that

“Sulphurated methylarsinate is an arsenical preparation devoid of all toxicity on account of the intimate joining of its composing parts.”

“Sulphurated methylarsinate is an arsenical preparation devoid of all toxicity on account of the intimate joining of its composing parts.”

And that

“Filudine can never be contraindicated.”

“Filudine can never be contraindicated.”

A statement of composition in a later number of “Treatment,” however, says that biliary extracts are components, in addition to the liver and spleen extracts. Moreover, thiarféine, the “new salt discovered by M. Chatelain,” is no longer “thio­methyl­arsinate,” but “thio­cinnamate of caffein”; and a new formula is furnished for it.

We are told that

“Methyl-arsinate cannot be used in cases where fever is present....”“M. Chatelain at first studied the action of thio­methyl­arsinate; clinical and physiological experimentation led him, however, to adopt thio­cinnamate of caffein, of greater activity and with no contraindications.”

“Methyl-arsinate cannot be used in cases where fever is present....”

“M. Chatelain at first studied the action of thio­methyl­arsinate; clinical and physiological experimentation led him, however, to adopt thio­cinnamate of caffein, of greater activity and with no contraindications.”

Nevertheless the same absence of contraindications was urged in favor of Filudine when it was said to contain the now discarded thio­methyl­arsinate of caffein.

The following are some of the unwarranted and even absurd claims:

“Filudine restores the liver’s functions. It is to the liver what digitalis is to the heart; it overcomes the insufficiency and stimulates the debilitated organ.”In malaria “it is the only true specific when associated with quinine.”“Filudine is... the ideal medication for tuberculosis, conforming as it does with the most recent researches in the therapeusis of this affection.”“We will not go as far as to say that Opotherapycompletely restoresunhealthy livers, for although the lesions of the hepatic parenchyma may be obliterated by regeneration, the lesions of the connective tissues are permanent, and may be observed at the postmortem examination. The new cells, however, do not present the same unhealthy conditions as those of the former diseased gland which they have replaced, and the liver can therefore function normally, so that the patient lives on; and he is satisfied with that.”“Therefore, while regenerating the liver with Filudine, we cleanse it and combat its congested state with Urodonal. We cause it to produce urea from the excess of uric acid which it contains.”“By the judicious and harmonious combination of the beneficial effects of Filudine and Urodonal, physicians not only possess the means of treating by rational methods Cirrhosis of the Liver in its various forms (which is one of the most terrible diseases which can afflict anyone) but what is still better,they can cure it.”“The liver of a person suffering from obesity being incapable of fulfilling its functions in regard to the fatty tissues, the rational and up-to-date method of treatment is therefore to restore to the system, in the form of Filudine, the liver extracts which are lacking.”

“Filudine restores the liver’s functions. It is to the liver what digitalis is to the heart; it overcomes the insufficiency and stimulates the debilitated organ.”

In malaria “it is the only true specific when associated with quinine.”

“Filudine is... the ideal medication for tuberculosis, conforming as it does with the most recent researches in the therapeusis of this affection.”

“We will not go as far as to say that Opotherapycompletely restoresunhealthy livers, for although the lesions of the hepatic parenchyma may be obliterated by regeneration, the lesions of the connective tissues are permanent, and may be observed at the postmortem examination. The new cells, however, do not present the same unhealthy conditions as those of the former diseased gland which they have replaced, and the liver can therefore function normally, so that the patient lives on; and he is satisfied with that.”

“Therefore, while regenerating the liver with Filudine, we cleanse it and combat its congested state with Urodonal. We cause it to produce urea from the excess of uric acid which it contains.”

“By the judicious and harmonious combination of the beneficial effects of Filudine and Urodonal, physicians not only possess the means of treating by rational methods Cirrhosis of the Liver in its various forms (which is one of the most terrible diseases which can afflict anyone) but what is still better,they can cure it.”

“The liver of a person suffering from obesity being incapable of fulfilling its functions in regard to the fatty tissues, the rational and up-to-date method of treatment is therefore to restore to the system, in the form of Filudine, the liver extracts which are lacking.”

Filudine is a mixture of semisecret composition. The therapeutic claims are manifestly unwarranted. The name is not indicative of the composition, whatever that may be, and no rational excuse is offered for the combination of liver and spleen extracts (with or without bile extracts) with “thio­methyl­arsinate” or “thiocinnamate” of caffein.

The Council therefore held Filudine ineligible for New and Non­official Remedies.—(From The Journal A. M. A., Sept. 18, 1915.)

Mixtures of pepsin and pancreatin are thera­peutically irrational; the two substances are not indicated in the same conditions, nor can they act together. Under physiologic conditions, such mixtures are chemically impossible: in a liquid medium the ingredients destroy each other.

Lactopeptin is manufactured by the New York Pharmacal Association, Yonkers, N. Y. It is sold under the claim that it contains, pepsin, diastase, pancreatin, lactic acid and hydrochloric acid. This product was among the first proprietary preparations examined by the Council on Pharmacy and Chemistry. The report of the investigation was published inThe Journal, March 16, 1907, p. 959. The preparation was found to be practically inert—“essentially a weak saccharated pepsin,” devoid of tryptic activity.

Six years later it was still widely advertised with the same irrational claims. A referee (A) therefore examined Lactopeptine (powdered) for the Council in 1913, and confirmed the previous findings. The referee’s report was published inThe Journal, Aug. 2, 1913, p. 358.

Nearly four months after this publication, the manufacturer protested against the report, maintaining, contrary to the findings of the Council, that Lactopeptine possesses pancreatic activity and contains “loosely combined” hydrochloric acid. Referee A therefore repeated his examination, and a second referee (B), independently, examined specimens of Lactopeptine (powder) purchased on the open market for the purpose shortly before.

A few specimens examined by these two referees showed a slight tryptic activity; most of them showed none. The amount of hydrochloric acid present was insignificant.

The reports of the two referees were referred to the manufacturers, who again protested vehemently against these findings, this time on the ground that the specimens were old. The manufacturers also cited the work of three chemists to disprove the findings of the referees, and demanded that the Council reexamine Lactopeptine, making use of fresh specimens. The Council refused for the following reasons:

1. So long as the packages of Lactopeptine are not dated, the activity of specimens known to be fresh is of no practical importance. The activity of the actual market supply is the only question of interest to the profession. The only fair test is that made on specimens representative of the product sold to the ultimate consumer.

2. The evidence presented by the manufacturers did not warrant a reexamination, since the work of two of the chemists cited substantially corroborates the results obtained by the Council’s referees from the fresher specimens. The figures for tryptic activity obtained by the third chemist cited by the manufacturers could not be accepted by the Council, since it was at variance with all other known results of investigations of Lactopeptine.

3. As stated at the outset, whatever the tryptic activity of the mixture, it is thera­peutically useless. A demonstration of tryptic activity in a mixture containing both pepsin and pancreatin is of merely theoretical interest.

Such activity, of course, cannot be expected, even on theoretical grounds, in liquid mixtures like Elixir Lactopeptine.

The Council therefore again declared Lactopeptine (powder and tablets) and Elixir Lactopeptine ineligible for New and Non­official Remedies and authorized publication of the following statement.

W. A. Puckner, Secretary

THE COUNCIL’S REPORT

Lactopeptine powder (New York Pharmacal Association, Yonkers, N. Y.) was examined by the Council in 1907. At that time it was claimed to contain

“... the five active agents of digestion—pepsin, diastase (veg. ptyalin), pancreatin, lactic acid and hydrochloric acid—combined in the proper proportion to insure the best results.”

“... the five active agents of digestion—pepsin, diastase (veg. ptyalin), pancreatin, lactic acid and hydrochloric acid—combined in the proper proportion to insure the best results.”

The examination showed that the preparation was essentially “a weak saccharated pepsin,” containing but small amounts of pepsin, no hydrochloric acid, or mere traces only, and no diastase or pancreatin (The Journal, March 16, 1907).

In 1913, the product was reexamined, because the claims, as to both composition and therapeutic value, were still being made. Samples were tested both of the American product, and of a British product from John Morgan Richards & Sons, London. The original findings were confirmed and the results were published inThe Journal, Aug. 2, 1913, p. 358. Nearly four months later (November 24) the New York Pharmacal Association wrote to the Council, objecting to the findings and maintaining that Lactopeptine possesses pancreatic activity and contains (“in loose chemical combination”) hydrochloric acid. In accordance with the custom of the Council, the work was sent back for review to the referee (A), whose conclusions were then tested by a second referee (B), a physiologic chemist, not a member of the Council, selected because of his special knowledge of the subject.

In December, 1913, Referee A made a large number of new tests to determine proteolytic and amylolytic power. His results show that the ferment activity of the preparation is so low as to merit no recognition in practical use. The tests also show that the amount of lactic acid or “loosely combined HCl” (or both) present is too small to have any appreciable physiologic activity and therefore to be of any therapeutic value.

Nine samples of Lactopeptine purchased in the open market in December, 1913, and January, 1914, were examined by Referee B early in 1914. His studies show absence of amylase in all samples; presence of pepsin, giving weak reactions even when compared with those of old pepsin preparations; complete absence of trypsin in seven out of nine samples, tryptic reaction being obtained in two samples, in one of which the reaction, “slight at best and of no practical import,” was obtained only after treatment for twelve hours or more.

The presence of tryptic activity in two out of the nine samples may be due to the fresher condition of these specimens, as indicated by the serial numbers. The evidence shows that it is a commercial impossibility to market mixtures of pepsin, pancreatin and lactic acid so that they can display any material tryptic activity.

It should be reaffirmed that mixtures combining peptic and pancreatic activities are not feasible, because pepsin cannot act except in the presence of acid, and pancreatin is destroyed by acid and by peptic activity. Furthermore, in conditions in which pancreatin is called for, pepsin is not, and vice versa; therefore the administration of mixtures of pepsin and pancreatin would be unjustified, even if both constituents could be expected to exert activity.

The foregoing observations apply to Lactopeptine in powder and tablet form.

While mixtures of pepsin and pancreatin are unscientific and unjustified, theoretically the two substances may coexist in a solid preparation, and the activity of such a preparation is consequently a proper subject of investigation. Theoretically as well as practically, however, pepsin and pancreatin cannot exist together in solution. The claims made for Elixir Lactopeptine and all other liquid preparations sold as mixtures of pepsin and pancreatin are therefore impossible. The Council has previously taken action (The Journal, Feb. 2, 1907, p. 434) refusing to approve for inclusion with New and Non­official Remedies such preparations, calling the attention of the medical profession and of manufacturers to their worthlessness, and requesting the American Pharmaceutical Association to instruct its committee on the National Formulary to omit from the next edition of that work a liquid preparation of pepsin and pancreatin recognized under the title of “elixir digestivum compositum.”

It is recommended that the Council reaffirm this previous action, and that Lactopeptine and Elixir Lactopeptine be declared ineligible for New and Non­official Remedies because of conflict with Rule 10 (“No article will be admitted which, because of its unscientific composition, is useless or inimical to the best interests of the public or of the medical profession”).

The foregoing was submitted, together with the findings of the two referees, to the manufacturers. They protested again, alleging that:

First.—The specimens of Lactopeptine examined by the second referee were old. The dates of manufacture corresponding to the several batch numbers are supplied by the manufacturers as follows:

2275 (Powder)September, 19082301 (Powder)June, 19092312 (Powder)December, 19092348 (Powder)October, 19112352 (Powder)December, 19112364 (Powder)July, 19122374 (Powder)March, 19132383 (Powder)October, 19131638 (Tablets)October, 1911

2275 (Powder)

2301 (Powder)

2312 (Powder)

2348 (Powder)

2352 (Powder)

2364 (Powder)

2374 (Powder)

2383 (Powder)

1638 (Tablets)

The manufacturers assert that they do not understand how specimens of these ages could have been purchased on the open market in 1913 and 1914, inasmuch as their agents are and long have been instructed to take up from the druggist all lots of Lactopeptine which, as indicated by the batch numbers, have attained “any appreciable age.” The age of the specimens, the manufacturers declare, deprives the table in the second referee’s report of “all significance or interest.”

As previously stated, however, the specimens of Lactopeptine examined were purchased on the open market in various localities in unbroken packages, in December, 1913, and January, 1914. They thus represent stock used in filling physicians’ prescriptions or sold to the public. Neither the referees nor any one connected with the Council had any means of knowing the age of the specimens until the dates of manufacture were furnished by the New York Pharmacal Association. The first tests of the second referee were made in February, 1914, on Specimens 2374 and 2383, which were then, it would appear, about one year old and four months old, respectively. The Council has repeatedly urged that pharmaceutical substances which are subject to deterioration should be dated by the manufacturer, and a similar suggestion has been made by the Bureau of Chemistry of the U. S. Department of Agriculture concerning mixtures containing enzymes. Notwithstanding the instructions which the New York Pharmacal Association claims to have given its agents, the marketsupply of Lactopeptine in December, 1913, and January, 1914, was not composed of new stock, and until the manufacturers adopt the practice of dating packages, there can be no assurance that it will be fresh. In this connection, it is of interest to note that the Bureau of Chemistry of the U. S. Department of Agriculture has issued a warning that it will judge such products by the degree of their activity when they reach the consumer, i. e., as they are found on the market.

Second.—The New York Pharmacal Association cites the work of several chemists, who have examined Lactopeptine and report the presence of tryptic activity. Dr. S. R. Benedict in December, 1913, reported to the Council “distinct” tryptic activity (digestion in twelve hours by Lactopeptine of 4.2 times its weight of fibrin containing 50 per cent. moisture) in specimens examined by him. These specimens were numbered 2382, and were therefore probably manufactured in October, 1913; compare the dates furnished by the manufacturer for the specimens used by the second referee. No tests against other preparations possessing tryptic activity are reported, and Dr. Benedict expressly disclaims any opinion as to the therapeutic value of the preparation.27Dr. P. B. Hawk, whose report was submitted by the manufacturers, found in Lactopeptine by Fermi’s method one-fifth tryptic activity of that of Merck’s pancreatin, and by Grützner’s method an activity of 18 per cent. of the pancreatin. A test for the production of tryptophan was reported positive. The New York Pharmacal Association also submitted a report from Dr. A. W. Balch, who found pepsin, rennin, trypsin, steapsin, amylopsin and lactic acid present in Lactopeptine; also an amount of combined hydrochloric acid in 1 gm. the equivalent of 1.05 c.c. tenth normal solution or 0.00383 gm. hydrochloric acid. (He reports digestion in twenty-four hours by Lactopeptine of 25 times its own weight of fibrin. “An active extract of pancreas reacted exactly like the Lactopeptine solution.”) The serial numbers of the specimens tested by Hawk and Balch are not given, but no doubt they were fresh.

The New York Pharmacal Association demanded that the referee reexamine Lactopeptine, making use of fresh specimens. The Council held that this was unnecessary, for the following reasons:

1. The previous finding of the Council, that specimens of Lactopeptine found on the open market are essentially weak saccharated pepsins, is not to be refuted by examination of fresh specimens. Even if it be assumed that all old specimens of Lactopeptine have been withdrawn from the market since the last purchase of specimens for the use of the Council’s referee, there can be no assurance that the stock will be constantly kept fresh. Unless the manufacturers date their product, physicians cannot know that their prescriptions are filled with fresh material. Nor is it reasonable to ask that the Council examine the market supply of any given proprietary at a time selected by the manufacturers.

2. Without entering into all questions of detail in the analyses, the Council is willing to accept the reports of Drs. Benedict and Hawk as representative of fresh Lactopeptine powder. It is therefore unnecessary for the Council to make further experiments along this line. The results of these two chemists in no wise contradict the conclusions of the Council’s referees, being comparable with those obtained by the referee on the fresher specimens used by them. The experiments of Drs. Hawk and Benedict show a degree of tryptic activity which, though chemically not negligible, is quite without significance practically, even if it could be assumed that the trypsin in the fresh Lactopeptine escaped destruction in the stomach. The figures for tryptic activity given by Dr. Benedict do not differ materially from those of the first referee. Those of Professor Hawk show a tryptic activity of from 18 to 20 per cent. of that of commercial pancreatin—and commercial pancreatins ordinarily are of low tryptic activity, if not inert (see Long and Muhleman:Arch. Int. Med., February, 1914, p. 314.) The reports of these chemists present no reason for changing the conclusion that “it is a commercial impossibility to market mixtures of pepsin, pancreatin and lactic acid so that they can display any material tryptic activity.”

The results which Dr. Balch obtained in a test for tryptic activity show a marked discrepancy with those obtained by Drs. Hawk and Benedict, not to mention the Council’s referees, and also with the fact that only about 11 per cent. of “pancreatin” is claimed in the published formula of Lactopeptine. The Council is unable to accept Dr. Balch’s result for trypsin or rennin as reliable. His other results are without significance and call for no special comment.

3. Even if tryptic activity were conceded to Lactopeptine, the preparation, like all preparations containing pepsin and pancreatin, would still be, as previously stated, thera­peutically irrational.

The Council approved the report.

In view of the manufacturer’s reiteration of the claims for Lactopeptine powder, I have carried out further experiments to determine its proteolytic and amylolytic power.

For the proteolytic test I used fresh, well washed fibrin and examined samples of Lactopeptine powder numbered as follows:

No. 1. A part of the English product examined and reported on last spring.

No. 2. A fresh bottle obtained at a Chicago retail drug store in December, 1913.

No. 3. A fresh bottle obtained at a Chicago retail store in December, 1913.

Portions of 1 gm. each of these samples were mixed with 5 gm. fibrin, 100 mg. of sodium carbonate and 50 c.c. of water in flasks. A little toluene was added to each flask, which was then closed with a tuft of cotton and the mixtures were incubated at 40 degrees through twenty-four hours. At the end of that time there was no marked change in the quantity of the fibrin remaining in each flask, the larger part by far being undigested.

As a control I used the sample of an active commercial trypsin, of which I added 500 mg. to the same quantity of water, fibrin and sodium carbonate. This was digested in the same bath at the same time. The digestion was practically completed in less than ten minutes, only minute flakes of the fibrin remaining.

It is evident that the digestive power of the Lactopeptine must be extremely low, and only a small fraction of that exhibited by a commercially good trypsin.

In an experiment with the English sample carried out through nineteen hours as above, using 2 gm. of fibrin and 100 mg. of ferment, it was found by nitrogen tests on the filtrate that about 12.2 per cent. of the protein had been brought into solution, an amount which is practically without importance in a digestion of such duration.

To test the starch digestive power I have made a large number of experiments. In a series just completed I mixed 1 gm. portions of Samples 1 and 2 with water to make 100 c.c. volumes. Before making up to the final volumes 0.5 c.c. of normal sodium hydroxid was added to neutralize the slight acidity of the ferment as shown by phenolphthalein.

Of these mixtures 4, 6, 8 and 10 c.c. portions were mixed with 50 c.c. of 1 per cent. starch paste and incubated at 40 degrees to find the colorless end-point in the starch digestion, by the iodin test.

At the end of twenty-two hours the iodin reaction was as strong as at the beginning, indicating no appreciable starch digestion.

To the flasks in which no digestion had taken place under these conditions, 5 mg. of a pancreas ferment was added. This gave an almost immediate conversion to the colorless end-point. This ferment was a sample of Holadin which had been in the laboratory about a year. The 5 mg. completed the reaction to the colorless end-point in less than ten minutes.

In a similar test I used 2 gm. of Lactopeptine No. 3, made up to 100 c.c. with 1.2 c.c. of normal alkali. Ten and 15 c.c. portions were incubated with 50 c.c. of 1 per cent. starch paste through twenty hours at 40 degrees with no apparent result. The Holadin then added, 5 mg. being used, completed the conversion in less than ten minutes.

This shows that the medium was a proper one for the test and that the Lactopeptine must be extremely weak. No sugar tests were made because the Lactopeptine contains milk sugar to the extent of about 60 per cent.

Similar results for both protein and starch digestives have been obtained in a large number of experiments. These here quoted show that the ferment activity of the preparation is so low as to merit no recognition practically. The digestion of a few milligrams of fibrin or starch after many hours of contact, while being perhaps scientifically possible, is of no value when we come to a consideration of the use of such bodies as digestive ferments in medicine.

The amount of lactic acid or “loosely combined HCl” present in Lactopeptine is very small, since the total acid which may be titrated by sodium hydroxid and phenol­phthalein is measured by 0.5 c.c. of the normal hydroxid for 1 gm. of the Lactopeptine powder, in the mean. In different samples examined the range was found to be from 0.41 c.c. to 0.6 c.c. Tests with methyl orange, methyl red and other indicators showed that the free acidity is but trifling; if the whole of this acid, as measured by phenol­phthalein, were calculated to HCl, the amount would be too small to have any appreciablephysiologic activity, in view of the daily dose recommended, 10 to 20 grains of the powder.

The following table gives a summary of the results of my investigations on Lactopeptine. The numbers in the extreme left-hand column are the manufacturer’s identifying marks. These, it is assumed, run serially, the higher numbers indicating fresher specimens.

TABLE SHOWING ENZYMIC POWER OF LACTOPEPTINE PREPARATIONS

AmylasePepsinRenninTrypsinLipase2275–++––2301–++––2312–++––2348–++––2352–++––2364–+++(?)–2374–++–+(?)2383–++++(?)1638 (tablets)–++––Pancreatin (Old)–....++–

2275

2301

2312

2348

2352

2364

2374

2383

1638 (tablets)

Pancreatin (Old)

The conclusions in the foregoing summary depend on the following criteria:

Amylase: removal of starch (paste),small in proportion to begin with.

Pepsin: solution of small shreds offreshfibrin in acid media.

Rennin: curdling of milk in moderate excess.

Trypsin: solution of small shreds offreshfibrin in neutral and alkaline media, and tryptophan test.

Lipase: coloration of litmus-milk; exactcolorcontrols.

All tests were suitably controlled. The responses for pepsin were weak even when compared with those of old pepsin preparations.

In the table above, the interrogation points in parentheses (?) refer to results that were obtained after treatment for from twelve to twenty-four hours and indicates that the change was slight at best and of no practical import.—(From The Journal A. M. A., Oct. 23, 1915, with additions.)

The Council adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

A referee has submitted to the Council the following report of the Chemical Laboratory of the American Medical Association on Iodum-Miller and Iod-Izd-Oil (Miller’s) (Iodum-Miller Co., Kansas City, Mo.):

The unsatisfactory statements made in regard to the composition of Iodum-Miller and the far-reaching therapeutic recommendations for it induced the laboratory to make a chemical examination of the preparation. It claimed more or less directly that the preparation is entirely new and possesses novel characteristics.

It is asserted that

“Iodum-Miller is made from Soot Iodine, which is our own product. This Soot Iodine is SOLUBLE IN WATER before being combined with its base C.P. Glycerine.”

“Iodum-Miller is made from Soot Iodine, which is our own product. This Soot Iodine is SOLUBLE IN WATER before being combined with its base C.P. Glycerine.”

No information regarding “soot iodine” is offered and an inquiry sent to the proprietors by a physician brought only the noncommittal reply that “soot iodine”

“is made from Resublime [resublimed?] Iodine by a chemical process which renders it soluble in water before being combined with its base.”

“is made from Resublime [resublimed?] Iodine by a chemical process which renders it soluble in water before being combined with its base.”

Iodum-Miller is said to contain

“Active Free Iodine 2.2 grams per 100 c.c., 10. grains per fluid ounce, 1.7% by weight.”“In addition to the active free iodine... IODUM-MILLER carries a still greater per cent of Iodine in its basic combination....”

“Active Free Iodine 2.2 grams per 100 c.c., 10. grains per fluid ounce, 1.7% by weight.”

“In addition to the active free iodine... IODUM-MILLER carries a still greater per cent of Iodine in its basic combination....”

According to the label, the preparation is

“An Iodine for External and Internal use... 45 drops equals 1 dr. by weight. Each drop equals the per cent. of iodine in 1 gr. potas. iodide.”

“An Iodine for External and Internal use... 45 drops equals 1 dr. by weight. Each drop equals the per cent. of iodine in 1 gr. potas. iodide.”

Iodum-Miller is a heavy, dark liquid having an odor characteristic of ether (ethyl oxid). Qualitative tests revealed the presence of glycerin, free iodin, iodid and potassium. The specific gravity at 25 degrees was 1.284. Direct titration with sodium thiosulphate solution indicated the presence of 1.68 per cent. of free iodin. A determination of the total iodin content by the Hunter method indicated 3.06 per cent. Subtraction of the amount of free iodin found from the total amount of iodin present, gives 1.38 per cent. combined iodin. Assuming this to be present as potassium iodid, as appears probable from the qualitative examination and from the quantitative determination of potassium, 1.80 per cent. potassium iodid is indicated. From this examination it is concluded that Iodum-Miller is, essentially, a solution of iodin and potassium iodid in glycerin, containing 1.68 per cent. free iodin and 1.80 per cent. potassium iodid. The examination contradicts the assumption that Iodum-Miller is either novel in principle or new. Moreover, accepting the firm’s statement that 45 drops weigh 1 dram (60 grains) the examination shows that one drop equals not “the per cent. of iodine in 1 gr. potas. iodide” but instead, the per cent. of iodin in only1⁄20grain potassium iodid. As the statement that “Each drop equals the per cent. of iodine in 1 gr. potas. iodide” appears on the label of the trade package, Iodum-Miller would seem to be misbranded under the federal Food and Drugs Act.

The recommended internal dosage of Iodum-Miller (from1⁄2to 20 drops) is equivalent to from1⁄40to 1 grain of potassium iodid. Its external efficacy in comparison with that of other iodin preparations may be estimated by comparing the respective free iodin contents, since the germicidal power of combined iodid is negligible. While Iodum-Miller contains 2.15 gm. free iodin in 100 c.c., tincture of iodin contains 7 gm. per 100 c.c. and compound solution of iodin (Lugol’s solution) contains 5 gm. free iodin in 100 gm.

Among the advertising literature is a circular which purports to be a “Certificate from Kansas City Testing Laboratory, by Roy Cross, Secretary.” The “certificate” attempts to prove that Iodum-Miller is vastly superior to the official tincture of iodin as a germicide, asserting that “In the process of dissolving [tincture of iodin] in water, a very large amount of the iodin is lost by precipitation....” This is not true of the tincture of iodin which is now official, though it is true of the tincture official in former editions of the Pharmacopeia. The report ignores completely the widely used aqueous solution of iodin.

Iod-Izd-Oil (Miller’s) is said to be an “Iodine Combination” made “from the same Soluble Soot Iodine as is IODUM-MILLER.” It is said to “liberate Free Soluble Iodine” when applied to the skin, mucous surfaces, etc. It is further defined as “Soluble Iodine combined with water-white Hydrocarbon Oil” and is said to liberate “Soluble Iodine 2 per cent.” While these statements suggest that Iod-Izd-Oil (Miller’s) contains the iodin-potassium iodid combination contained in Iodum-Miller, analysis indicated the oil to be a simple solution of iodin in liquid petrolatum. Quantitative determinations indicated, not 2 per cent. of iodin, as claimed, but only 0.42 per cent. and all of this was present as free iodin.

The following therapeutic claims appear on the label of a bottle of Iodum-Miller:

“EXTERNAL INDICATIONS

“Tuberculosis, Pneumonia, Pleurisy, Cough, Sore Throat, Pyorrhea, Tonsilitis, Rheumatism, Spinal Irritation, Boils, Felons or any Pain. Periostitis, Carbuncles, Fistula in Ano, Goiter, Blood Poison, Diseases of Uterus and appendages (apply full strength on cotton wrapped applicator), Gonorrhea, acute or chronic in both sexes, Orchitis, Bubo, Prostatitis, Swellings, Enlarged Glands, Etc.”

“Tuberculosis, Pneumonia, Pleurisy, Cough, Sore Throat, Pyorrhea, Tonsilitis, Rheumatism, Spinal Irritation, Boils, Felons or any Pain. Periostitis, Carbuncles, Fistula in Ano, Goiter, Blood Poison, Diseases of Uterus and appendages (apply full strength on cotton wrapped applicator), Gonorrhea, acute or chronic in both sexes, Orchitis, Bubo, Prostatitis, Swellings, Enlarged Glands, Etc.”

“INTERNAL INDICATIONS

“Pneumonia, Tuberculosis, Pleurisy, Typhoid Fever, Syphilis, Catarrh of Mucous surface of Alimentary Canal, Autotoxemia, Vomiting of Pregnancy, Rheumatism, Chronic Glandular and Organic Affections.”

“Pneumonia, Tuberculosis, Pleurisy, Typhoid Fever, Syphilis, Catarrh of Mucous surface of Alimentary Canal, Autotoxemia, Vomiting of Pregnancy, Rheumatism, Chronic Glandular and Organic Affections.”

The “certificate” from the Kansas City Testing Laboratory, mentioned above, states that Iodum-Miller was found to have a germicidal value nineteen times greater than carbolic acid—a somewhat remarkable finding in view of the fact that iodin dissolved by means of potassium iodid in alcohol or water, when tried on the typhoid bacillus has recently been found to possess only four times the germicidal value of carbolic acid in a solution of the same strength (Maben and White:Chem. and Drug., Jan. 30, 1915, p. 144). The “certificate” further states that the test “shows available iodine as found in IODUM-MILLER to have the greatest bactericidal power of any substance that we have ever tested that can be used medicinally.” There is no reason to believe that the desire to please its patrons has led the “testing laboratory” astray from the literal truth. The laboratory’s experience may be limited and the statement therefore entirely correct as far as it goes. No mention, however, is made of any tests comparing the germ-destroying power of Iodum-Miller with that of tincture of iodin, which contains 7 per cent. free iodin, unless the casual statement that “Iodum-Miller sterilized [the skin] more quickly” than tincture of iodin, be taken to imply such tests. It is not clear, however, by what means the laboratory was able to determine that there were no bacteria left alive in the skin after application of tincture of iodin and Iodum-Miller; no details are given of the methods used in arriving at this conclusion.

A circular says that Iodum-Miller

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