Volume 1 / Part 1 — FOREWORD (continued 2)
Reading edition
AlfalfaWheat
Potash49.7912.52
Phosphoric Acid 8.27 9.08
Lime43.51 2.95
Nitrogen44.0122.30”
“... The abundance of muscle and bone producing material in Alfalfa makes this crop especially good.”
Thus estimates of the value of a farm crop and cattle fodder are made to do service as testimonials to its therapeutic merit for human beings! Has the “patent medicine” promoter ever dared to insult the intelligence of his patrons by a cruder absurdity? Yet it is not to the nontechnical and unscientific public, but to a profession presumably scientifically trained in pharmacology and therapeutics that this concern presumes to offer its fodder tincture on the basis of testimony to the agricultural value of the fodder plant.
Alfatone is a worthless alcoholic cordial. The audacity of the attempt to promote its sale by a discourse on the merits of a well-known fodder plant is the sole reason for devoting any attention to it. It is recommended that Alfatone be held ineligible for New and Nonofficial Remedies, and that this report be published.
[Editorial Note.—What a comment on American medicine that a concern can even contemplate the possibility of making a commercial success of the sale of such a silly nostrum as Alfatone! And yet, when one remembers that a proprietary in which oats constitutes one ingredient (“Pas-Avena”) for years has been advertised to physicians and presumably prescribed by them, it is not altogether inexplicable that business men should get the impression that the medical profession is “easy” enough to “fall for” anything in the line of proprietary mixtures. Perhaps we may look forward to being offered proprietaries based on other cheap and well-known fodder plants. Tincture of Timothy Hay, Blue Grass Tonic, Cornhusk Wine! Why not? The enterprising companies that may put them out can easily publish tables to show the digestible nutrients in each and indubitable testimony can be furnished to prove the excellence of any of them as stock feed. If a pitchforkful of timothy hay makes a good fattening ration for a growing steer why should not a teaspoonful of tincture of timothy hay make a “reconstructive tonic and nutrient” dose for a man? If an arm load of thistles (carduus) makes a luscious food for equus asinus why should not a pinch of thistle in alcohol and water be a good “tonic”? Great are the possibilities! They are limited only by the gullibility of the medical profession and the public. Certain it is that some proprietary manufacturers are firmly convinced that no combination can be too preposterous to be worth trying on the medical profession.]—(From The Journal A. M. A., Aug. 7, 1915.)
ARTICLES REFUSED RECOGNITION
Report of the Council on Pharmacy and Chemistry
Below appear abstracts of the Council’s actions on articles refused recognition which were not deemed of sufficient importance to require lengthy reports.
Uricsol
Uricsol is marketed by the Uricsol Chemical Company, formerly of Los Angeles, now of Boston. Regarding its composition only vague statements are made. In an advertising pamphlet it is promised that the formula will be sent to physicians on request. Such a request from a physician elicited the following statement:
“URICSOL is a non-irritating, alkaline solution, containing Lithium Citrate, Acid Citric and Potassium Nitrate, together with a saline laxative in the form of Glycero Sodium Phosphate, with Vegetable Tonics added.”
The Association Laboratory has made an examination of Uricsol to determine its composition and reports as follows:
LABORATORY REPORT
A trade package purchased in March, 1915, from a wholesale drug house was labeled:
“Uricsol Rheumatic Remedy, Uric Acid Solvent, Kidney and Liver Stimulant, Manufactured by the Uricsol Chemical Co., Los Angeles, Cal.”
This package was wrapped in a circular entitled “The Great California Remedy—Uricsol.” The preparation is a viscid, slightly turbid light brown liquid, with a faintly aromatic odor and a salty, bitter taste. The diluted solution is acid in reaction toward litmus and phenolphthalein and alkaline toward methyl orange.
Qualitative tests showed a presence of phosphate, citrate, nitrate, sodium, glycerin, and a small amount of lithium in aqueous solution. Besides these a small amount of some organic, nonalkaloidal substance was found, which from its bitter taste suggested gentian. From the qualitative tests it appeared that the phosphate was the predominating ingredient and accordingly a phosphate determination was made. The results, calculated to sodium phosphate, U. S. P., indicated the presence of 64.20 gm. per 100 c.c., held in solution by citric acid and sodium nitrate.
Uricsol evidently is a solution containing a large amount of sodium phosphate with small amounts of lithium, nitrate, citric acid and glycerin, with probably some vegetable extract.
In general Uricsol is similar to the once widely exploited proprietary “Melachol,” which has been frequently imitated. A preparation essentially identical is in the United States Pharmacopeia, under the title “Compound Solution of Sodium Phosphate.”
The Uricsol Company calls its preparation
“... the latest word in the treatment of Rheumatism and that allied group of ailments which is caused by an excess of Uric Acid.”
Hay fever, bronchial asthma and neuritis are conditions in which it is recommended. The claim is made that
“Uricsol quickly controls Vasomotor Rhinitis and eliminates such conditions from the system.” “In fact, it will correct FAULTY METABOLISM.”
To a few practitioners of an older generation the pharmacologic basis of a remedy for rheumatism was sufficiently defined by saying that it increased the solubility of uric acid or affected it in some way. This theory is obsolete; there is not, and never was, any reliable evidence on which to base the theory that rheumatism is in any way caused by uric acid. The exploitation of Uricsol as a “uric acid solvent” is merely another illustration of the way in which nostrum manufacturers play on disproved theories. Of course the claim that sodium phosphate has any particular power to control vasomotor rhinitis, hay fever, asthma, and to correct faulty metabolism is foolish.
To summarize: Uricsol is a mixture of well-known drugs, marketed with false claims as to therapeutic action, with misleading and meaningless statements as to composition and under a name which invites uncritical prescribing. Uricsol is held ineligible to inclusion in New and Nonofficial Remedies.
Jubol
The following ridiculous statements are addressed, not to the laity, but to the medical profession:
DO YOU SUFFER FROM Constipation—Hemorrhoids—Enteritis—Mucous discharge—Pituita—Acidity of the stomach—Vertigo—Sick Headache—Disturbed Sleep—Insomnia—Sallow Complexion—Coated Tongue—Offensive breath—Fatigue and depression—Boils—Pimples?
“ONE of these symptoms alone shows that there is defective or insufficient function of the intestines, even if the stools are regular.
“Excrements remain too long in the intestine and set up fermentation. The harmful poisons and Ptomains which they produce are re-absorbed by the blood and poison the whole system.
“The Intestines must be cleared and re-educated with JUBOL.
“Jubolise your Intestines.”
Jubol tablets are sold in the United States by Geo. J. Wallau, Inc., New York, and are said to be prepared by J. L. Chatelain, Paris, France. The following incomplete and nonquantitative “formula” is furnished:
“... compounded chiefly [!] of Agar-Agar, Biliary Extracts and pure Extracts from all the intestinal Glands.”
It is asserted that
“The tablets are coated with a protective covering in order that they may act on the intestine only.”
The tablets contained in a regular-size trade package, obtained direct from the agent, readily separated into two halves and disintegrated within a few minutes when agitated with water. It is thus evident that, under ordinary conditions, the intestinal ferments in Jubol (if they are present, as claimed) would be destroyed during their passage through the stomach. In direct tests, however, practically no tryptic activity was demonstrated.
The composition of Jubol is not declared; grossly unwarranted and incorrect claims are made for its therapeutic actions; the name does not indicate the alleged ingredients and so much of the composition as is declared indicates an unscientific mixture. The Council decided that Jubol should be held ineligible for New and Nonofficial Remedies, and that this report should be published.
Urodonal
Urodonal is said to be “produced in the laboratory of J. L. Chatelain,” Paris, France. It is marketed in this country by Geo. J. Wallau, Inc., New York.
The preparation is claimed to be a chemical compound, and the advertising matter furnishes a “formula,” which consists of the formulas of lysidin, sidonal and hexamethylenamin, connected by plus signs:
That the substance is a chemical compound is highly improbable, and no evidence has been submitted to substantiate the claim. On the contrary, in the following statement the phrase “based on” is a virtual admission that the preparation is merely a mixture:
“Urodonal ... is a granular effervescent preparation based on methylglyoxalidine [Lysidine], quinate of diethylene-diamine [Sidonal] and hexamethylene-tetramine [Formin, urotropine].”
Mystery is added by the mention of undefined “special products” in the following:
“The fact of combining these two salts [lysidin and sidonal] in Urodonal, in strictly determined proportions and in the presence of special products, gives this preparation very considerable power in dissolving uric acid.”
These contradictory statements of composition conflict with Rule 1.
Urodonal is marketed in typical “patent medicine” style: the name “Urodonal” is blown in the bottle and the label contains a list of “Indications,” including rheumatism, gout and gravel (Rule 4). That this form of marketing has introduced it to the public is suggested by the following in an advertising circular:
“... Urodonal is now popular—even classic—throughout the world, where thousands of doctors and millions of patients agree in asserting that ‘Urodonal is to rheumatism what quinine is to fever.’ ”
There are also other indications that the mixture is to be exploited to the laity. For instance, the U. S. distributor sends out a portrait of Sarah Bernhardt bearing the legend:
“I am positive that URODONAL preserves youth’s freshness with clearness and strength to brain and heart. I have taken it for two years with the greatest benefit. Sarah Bernhardt.”
A circular advises this mixture
“For all who suffer from Arthritis, Rheumatism, Arterio-Sclerosis, Renal and Bilious Lithiasis, Headache, Gout, Gravel, Lumbago, Sciatic Pains, Neuralgia and all uric acid troubles.”
“In fact, Urodonal is five times more active than piperazine, and thirty-seven times more active than lithia. We are, therefore, entitled to say that no other eliminator of uric acid can be compared with it.”
“Being 37 times more active than lithia, it clears the heart valves of any sandy substances which may clog them, and checks the atheromatous degeneration of the blood vessels.”
These extracts indicate sufficiently the extravagant tone of the advertising (Rule 6): None of the ingredients are notably active in dissolving uric acid when administered by mouth. None produce any marked increase of uric acid elimination. No intelligent physician would use a uric acid solvent for “bilious lithiasis”; and their usefulness in the other conditions is open to doubt, to put it mildly.
Although the preparation is a simple mixture, the name does not indicate the components, but inclines to therapeutic suggestion (Rule 8).
Nothing is to be gained by combining several drugs which are useless, severally, for the purpose intended, as in the present case (Rule 10).
Urodonal is marketed under inconsistent statements of composition and with exaggerated therapeutic claims; the name is nondescriptive and the mixture is unscientific. The Council decided that the preparation should be declared ineligible for conflict with Rules 1, 4, 6, 8 and 10 and that this report should be published.—(From The Journal A. M. A., Aug. 14, 1915.)
FORMAMINT
Report of the Council on Pharmacy and Chemistry
The following report has been authorized for publication.
W. A. Puckner, Secretary.
Formamint is a proprietary medicine manufactured by the A. Wulfing Company (New York, London and Berlin), which is affiliated with the Bauer Chemical Company.
It has been widely advertised in Europe for several years, and is now on the American market;14 it is advertised in this country both in newspapers and medical journals.
Following is a brief review of the more important alleged investigations that have been reported from time to time in various European journals.
In “The Therapeutical Value of Foramint in Septic Affections of the Oro-Pharynx,” De Santi15 quotes Rosenberg,16 who reports the successful use of Formamint in cases of streptococcus infections, tonsillitis and acute symptoms of chronic sore throat. According to Seifert,17 Formamint is a chemical combination of formaldehyd and milk sugar. When the tablets are dissolved in the saliva, 0.01 per cent. of formaldehyd in its “status nascendi” is liberated and exercises a strong disinfectant action. Seifert states that the preparation is markedly palatable, since it contains a little citric acid to render the taste cool and refreshing. In some experiments with streptococci, pneumococci, typhoid and diphtheria bacilli, Seifert found that a solution of one tablet in 10 c.c. of water destroyed these germs in from five to ten minutes. A solution of the same strength was also added to culture tubes of broth, agar, and gelatin, with the result that no growth occurred in them, while distinct and characteristic development of the bacteria took place in control tubes. He does not state, however, how much Formamint solution was added to the mediums.
Daus18 reports successful treatment of tonsillitis, mumps and middle ear diseases. In these cases no other gargles or mouth washes were used. He states that no indication of irritant or other injurious action made its appearance even after large doses. In the same article, F. Levy reports experiments as follows: Agar plates were prepared with a culture of streptococcus from a severe case of quinsy. One half of the plate was rubbed with saliva containing Formamint in solution. (The strength of the solution used is not given.) In twenty-four hours streaks of growth had appeared on one portion of the plates while the part on which the Formamint saliva had been rubbed remained sterile. Daus also found that agar and broth cultures of streptococcus shaken with Formamint saliva remained sterile.
Rheinboldt,19 investigating the effects of Formamint and of ordinary formaldehyd on animals, concludes that formaldehyd is toxic in action while Formamint is not.
How the exploiters of Formamint capitalize the medical profession. Miniature reproductions of typical Formamint advertisements appearing in the newspapers.
Rosenberg20 corroborates this statement. He also found that agar plates of Bacillus prodigiosus were killed by Formamint solutions in about four hours. He fails, however, to give the strength of his Formamint solutions.
Wingrave21 suggests the use of Formamint for infants! He recommends that a tablet be crushed and wrapped in “butter cloth.” The ends of the cloth are to be tied with thread, the Formamint is to be moistened, and the packet is to be held in the mouth of the baby several times each day.
Young22 published the results of some experiments by himself and Delépine on the human throat. They dissolved a tablet in the mouth and made swab cultures with the following results:
Immediately after taking the tablet 0 colonies
10 minutes after taking the tablet 35 colonies
30 minutes after taking the tablet150 colonies
They found no staphylococci at any time. Other results of swabbing various parts of the throat before and after the use of Formamint, reported by these investigators, show enormous reductions in the count, claimed to be due to the action of Formamint. The count was made on agar at 37 C., but they fail to state the time elapsing between taking the Formamint and making the swab. Young also reports favorable clinical results in cases of scarlet fever, diphtheria, sore throat, and the like. It must be noted, however, that they state that the mouth and fauces must first be thoroughly cleansed by swabbing and douching before Formamint is used.
THE “CHEMICAL COMPOUND” CLAIM
The claims made in the advertising literature of Formamint are very extravagant. Many are highly improbable. These statements will be discussed later.
The statement is made that Formamint is a new chemical compound:
“Formamint is Pentamethanallactose, 5 CHOH + C12H22O11. It is an original combination of Formaldehyde with Lactose, a definite chemical compound. The Formaldehyde molecule is locked up in it until solution in the saliva takes place, when the Formaldehyde is liberated in its nascent state and is therefore active without being irritant.”
Furthermore the makers contend that this new chemical compound is entirely harmless. For example, Daus,18 in an article on “The Disinfectant Action of Formic Aldehyde on Mucous Membranes,” declares:
“No indication of irritant or other injurious action made its appearance even after large doses. The urine remained free from albumin and sugar.”
Such statements as these are found in the advertising literature:
“Formamint tablets are absolutely harmless and innocuous, even to little children.”
“When dissolved in the saliva, Formamint Tablets liberate slowly Nascent Formaldehyde in a most active yet non-irritant form.”
They maintain that Formamint is not only absolutely harmless, but actually beneficial to the tissues. It may be used “to tone up and strengthen the tissues, prevent hoarseness, and allay irritation in singers, public speakers,” etc.
The claims urged as to its germicidal power are indeed glittering. This “new chemical compound” is claimed to liberate formaldehyd in some new and peculiar condition which, while it has a soothing and tonic effect on the cells of the human tissues, can at the same time quickly kill any form of bacterial life.
“Dissolving readily, it releases its germicidal, antiseptic qualities, which impregnate the saliva and are carried naturally and easily around the mouth and in the deepest crevices of the throat—destroying the germs where they are causing the mischief. Formamint prevents and destroys infectious germ life in a soothing grateful way.”
“In the saliva it frees a germicide, fatal to germs but harmless to the most delicate membranes. And flowing into every tiny corner of the gums, tonsils and throat, into places where no gargle ever reaches, it most effectively disinfects the throat.”
The claims as to the preventive and curative effects of the preparation cover a large portion of the category of human ailments and distresses. The following quotations indicate some of its supposed properties:
“... it is therefore self-evident that Formamint should be looked upon as a necessary part of the treatment of all forms of tonsillitis.”
“The value of Formamint is equally great in diphtheric tonsillitis, or as a prophylactic ...”
“The extraordinary success which I had with Formamint in a school epidemic of scarlet fever during May and June, 1907, was the determining factor which induced me to abandon the use of inhalations, gargles, local applications in the treatment of diseases of the throat, and to use Formamint exclusively for the future.”
“There are naturally many similar conditions in which Formamint may be used as a prophylactic, notably scarlet fever, mumps, streptococcal and staphylococcal sore throats, ‘milk outbreaks’ of sore throat, drain throats, hospital throats, and the like.”
“Formamint Tablets are indicated in Angina, Tonsillitis, Pharyngitis, Stomatitis, Gingivitis, Glossitis, ulceration, spongy or bleeding gums, Pyorrhea Alveolaris, ‘Smoker’s Sore Throat,’ Abscess or Boils, etc.”
“As a Prophylactic against Diphtheria, Scarlet Fever, Influenza, Measles, Epidemic poliomyelitis, and other pathogenic micro-organisms. To neutralize putrefaction products in and about the teeth, correct fermentative processes, deodorize and purify the breath, etc.”
“To tone up, and strengthen the tissues, prevent hoarseness and allay irritation in singers, public speakers, neutralize the effects of dust-infection or disinfect the saliva or sputum in Influenza, Tuberculosis, etc.”
One man declares that along with specific constitutional treatment he “had the best results from the use of Formamint tablets” in a case of syphilitic ulceration of the tongue.
In short, Formamint is recommended for the treatment or prevention of almost everything, from a bad breath to such grave conditions as scarlet fever, diphtheria and tuberculosis, conditions in which a delay in proper treatment—for instance, in diphtheria, a failure to administer antitoxin—may result in the death of the patient.
A series of investigations was therefore undertaken in order to discover whether the extravagant claims regarding the germicidal power of Formamint could be verified.
Experimental Data
Two fifty-cent bottles of Wulfing’s Formamint were purchased in the open market and were kept well stoppered to prevent deterioration.
Qualitative tests showed the presence of formaldehyd and the amount was determined quantitatively by the hydrogen peroxid method as given by Sutton.23 The results were respectively, 1.99 per cent. and 2.03 per cent. of formaldehyd.
Two Formamint advertisements reproduced in miniature typical of those appearing in a certain type of medical journals.
Some determinations were made of the germicidal power of Formamint in vitro, that is, under controlled laboratory conditions. A twenty-four-hour plain agar culture of Staphylococcus aureus was washed off in 10 c.c. of sterile 0.85 per cent. sodium chlorid solution. A 1:100,000 dilution of this was made in each of three flasks containing 100 c.c. of sterile saliva. Flask 1 contained 1 per cent. of Formamint, Flask 2, 5 per cent.; Flask 3, containing no Formamint, was kept as a control. At intervals samples were removed and dilutions made and plated in duplicate on standard agar. The plates were incubated twenty-four hours at 37 C., and plates containing less than 200 colonies were counted. The results are given in Table 1. After seven days there was no appreciable difference in the plates.
TABLE 1.—SHOWING TIME IN WHICH CULTURES OF STAPHYLOCOCCUS AUREUS WERE KILLED BY DIFFERENT AMOUNTS OF FORMAMINT
Amount of Formamint in Saliva (Per Cent.)Period of Standing at 37 C. (Hours)Average Count When PlatedCount on Flask of Saliva Without Formamint
13323200*
1607000*
51Few5000*
5204100*
5303200*
5607000*
* The last two observations were made at the same time as on the 1 per cent. solutions.
Another test was made by adding a 1 per cent. Formamint solution to plain agar plates inoculated with B. coli. A twenty-four-hour plain agar culture of B. coli was washed off in 10 c.c. of sterile 0.85 per cent. sodium chlorid solution. A 1:1,000,000 dilution was made of this and 1 c.c. added to each plate. Varying amounts of 1 per cent. solution of Formamint were added to each plate. They were incubated seventy-two hours at 37 C. After seven days’ incubation the count was the same. The results are given in Table 2.
TABLE 2.—COUNT OF B. COLI CULTURES WITH DIFFERENT AMOUNTS OF FORMAMINT
No. c.c. of 1 per cent. Formamint00.10.30.50.71.01.52.03.0
Count1603339261512200
Another experiment was made thus: One loopful of a twenty-four-hour plain agar culture of Streptococcus lacticus was mixed with a tube of North medium. One loopful from the inoculated tube was mixed with a second tube of North medium. Both tubes were poured into Petri dishes and allowed to cool. One half of each plate was well smeared with a 10 per cent. solution of Formamint in saliva. After twenty-four hours’ incubation at 37 C., only a few colonies appeared on the side to which the Formamint had been applied, while the other half was thickly covered with colonies.
This work so far corroborates that reported in the literature quoted by the manufacturers. But the fact that a compound is a germicide when brought into intimate contact with bacteria in a solution or medium in a test tube or flask does not prove that it will be effective when used in the human throat.
THE ALLEGED GERMICIDAL ACTION
An attempt was made to discover whether or not the claims advanced by the manufacturers as to the perfect germicidal action of Formamint in all the nooks and crannies of the mouth and throat could be confirmed.
The first step in attacking this problem was to make comparative counts of the number of bacteria in the throat before and after the use of Formamint. The methods employed were as follows: The throat was gargled with 50 c.c. of sterile 0.85 per cent. sodium chlorid solution. In each case the same length of time, as far as possible, was used in the process. The liquid was collected in a sterile flask. The gargling in a series of experiments was begun not less than two hours after a meal. After some preliminary work the following dilutions of the 50 c.c. of salt solution were found sufficient: 1:1,000, 1:10,000 and 1:100,000. Plates were made in duplicate from each dilution and incubated seventy-two hours at 37 C. The counts were made on plates containing less than 200 colonies. Except where otherwise noted standard agar was used. The mediums were always prepared in the same way.
All the work was carried out under conditions as nearly natural as possible. The Formamint was taken according to the directions accompanying the trade package. Every opportunity was given the Formamint to penetrate all the crypts and recesses about the mouth and throat. The tablet was allowed to dissolve as slowly as possible, the time usually being five to six minutes, and saliva was thoroughly forced around the mouth before being swallowed. Plating was always done immediately after gargling so that no growth could occur in the salt solution. The results are given in Table 3. The numbers are average counts from several plates and calculated to show the number of bacteria washed out by the 50 c.c. of salt solution.
TABLE 3.—SHOWING THAT FORMAMINT DOES NOT GREATLY DECREASE THE NUMBER OF BACTERIA IN THE THROAT
Conditions of Test Time Since Preceding TestAmount of Formamint UsedNo. Found in Throat Before Use of FormamintNo. Found in Throat After Use of Formamint
Normal...015,600,000...
Normal1 hour038,500,000...
Normal1 hour030,500,000...
Normal...012,500,000...
Normal1 hour014,500,000...
1 hour023,500,000...
Tablet dissolved in mouth and throat gargled one hour later6 days1 tablet...15,000,000
Throat again gargled two hours after Formamint was used1 hour0...10,050,000
Normal7 days062,000,000...
Normal1 hour072,500,000...
Normal......61,000,000...
Tablets were taken, one per hour, and throat gargled one hour after last tablet was taken2 days12...39,100,000
Throat was again gargled 2 hours after taking last tablet1 hour0...59,000,000
Normal5 days035,000,000...
Normal1 hour062,000,000...
Normal1 hour072,000,000...
One tablet was taken each half hour for twelve hours consecutively. Throat was gargled one hour after last tablet was taken4 days 24 tablets ...175,000,000
Throat was again gargled two hours after last tablet was taken1 hour0...168,750,000
Normal3 days0129,600,000...
Normal1 hour0177,000,000...
Normal1 hour0147,000,000...
Normal3 days079,000,000...
One tablet was taken immediately after preceding gargle. Throat was again gargled at end of one hour1 hour1...83,200,000
Throat was again gargled two hours after tablet was taken1 hour0...134,750,000
Normal conditions except that mouth and teeth were throughly washed with soap just before gargling 19 days032,600,000...
Same as above1 hour033,125,000...
Same as above1 hour040,375,000...
Teeth were not washed. Otherwise normal conditions2 days033,500,000...
Same as above1 hour043,330,000...
Same as above1 hour054,000,000...
Same as above1 hour050,000,000...
Same as above1 hour067,000,000...
Mouth and teeth thoroughly washed with soap just before throat was gargled2 days05,270,000...
Same as above1 hour010,916,000...
Same as above1 hour08,275,000...
Normal conditions, but 1 c.c. of sterile rabbit’s blood was added to each plate3 days0228,750,000...
Count from the same gargle as above. No blood used in the plates0060,625,000...
Normal conditions, but count was made on blood agar1 hour0 431,250,000...
Count from the same gargle as above. No blood used in the plates0059,625,000...
Normal conditions, count was made on blood agar2 days0 683,300,000...
Same gargle as above, but count was made on plain agar0058,500,000...
One tablet was taken just after preceding gargle. After one hour throat was again gargled. Count on blood agar1 hour1 tablet...558,300,000
Same gargle as above, but count was made on plain agar01 tablet...55,875,000
Normal conditions2 days079,125,000...
One tablet was taken just ten minutes before gargle was made1 hour 16 min.1 tablet...56,250,000
Normal conditions2 days046,750,000...
One tablet was taken just ten minutes before throat was gargled1 hour1 tablet...38,500,000
Teeth and mouth were thoroughly washed with soap just before gargle was made5 days047,370,000...
Teeth washed as above and one tablet taken ten minutes before gargle was made1 hour1 tablet...21,225,000
Finally a determination was made of the number of streptococci in the throat before and after the use of Formamint. The throat was gargled in the manner previously described. The streptococcus count was made by the dilution method as given by Heinemann.24 Culture tubes were used instead of fermentation tubes. One per cent. dextrose broth was the medium employed. One cubic centimeter was added to each of a series of ten tubes for each dilution and the following dilutions were used: 1:10,000, 1:100,000 and 1:1,000,000.
The results given in Table 4 are the average count from a number of dilutions and are reported as the total number washed out by the 50 c.c. of salt solution.
TABLE 4.—SHOWING THAT FORMAMINT FAILS TO REDUCE THE NUMBER OF STREPTOCOCCI IN THE THROAT
Conditions of TestTime Since Preceding TestAmount of Formamint UsedNo. Found in Throat Before Use of FormamintNo. Found in Throat After Use of Formamint
Normal...01,200,000...
One tablet was taken and throat gargled one hour later4 days1 tablet...14,750,000
Normal3 days09,950,000...
One tablet was taken and throat gargled ten minutes later1 hour1 tablet...8,000,000
Discussion
The contention that Formamint contains formaldehyd was confirmed by analysis.
The manufacturers also maintain that Formamint is a new, definite chemical compound, consisting of five molecules of formaldehyd and one molecule of lactose, and that when dissolved in the saliva the formaldehyd is liberated in some new and peculiar form, which they call nascent formaldehyd. This new kind of formaldehyd is, according to the advertising literature, especially powerful in its germicidal properties and at the same time has absolutely no irritating or harmful effects.
NOT A CHEMICAL COMPOUND
Thoms,25 retained as an expert by the German government, decided, after a series of chemical investigations, that Formamint was not a definite chemical compound, but that it was probably a solid solution of formaldehyd in lactose. He proved that when the process of manufacture was carried out in exactly the way called for by the Formamint patents, compounds containing a greater or less per cent. of formaldehyd could be made while the other properties remained similar to those of Formamint. The composition of the final product depended on the proportion of the components used in the process. Therefore Formamint did not form a safe means of uniform dosage.
As a result of Thoms’ work the German courts held that Formamint was not a new chemical compound. Consequently the Formamint patent (Number 189036) was annulled in Berlin, Nov. 29, 1913.
Again the contention that formaldehyd in the nascent or active condition is less poisonous and irritating than in its ordinary form is contrary to what would be expected from the behavior of such compounds. If it were liberated, as claimed, in the “nascent” condition, it would be, for that very reason, not only more active but also more harmful.
As a matter of fact, Formamint did have an irritant effect on the worker who carried out these investigations. When one tablet was taken each hour for twelve consecutive hours, marked irritation of the intestinal tract resulted. There was almost sufficient nausea to cause vomiting and uneasiness in the alimentary canal following the experiment. When the twenty-four tablets were taken the results were similar but more pronounced. This is decidedly in contradiction to the assertions of the manufacturers.
Otto Seifert,26 moreover, cites the following:
“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.
HAS NO SELECTIVE ACTION
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.
SUMMARY
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 unwarranted claims 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
Report of the Council on Pharmacy and Chemistry
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.”
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.”
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
Report of the Council on Pharmacy and Chemistry
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 remedy for “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.”
Thiarféine is said to be
“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.”
And that
“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.”
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 Opotherapy completely restores unhealthy 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.)
LACTOPEPTINE AND ELIXIR LACTOPEPTINE
Report of the Council on Pharmacy and Chemistry
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 in The 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 in The 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 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 in The 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”).
Manufacturers’ Protest and Council’s Answer
The foregoing was submitted, together with the findings of the two referees, to the manufacturers. They protested again, alleging that:
AGE OF SPECIMENS
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, 1908
2301 (Powder)June, 1909
2312 (Powder)December, 1909
2348 (Powder)October, 1911
2352 (Powder)December, 1911
2364 (Powder)July, 1912
2374 (Powder)March, 1913
2383 (Powder)October, 1913
1638 (Tablets)October, 1911
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 market supply 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.
REPORTS OF OTHER CHEMISTS
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.27 Dr. 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.
CONCLUSIONS
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.
Report of Referee A
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 appreciable physiologic activity, in view of the daily dose recommended, 10 to 20 grains of the powder.
Report of Referee B
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
AmylasePepsinRenninTrypsinLipase
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 of fresh fibrin in acid media.
Rennin: curdling of milk in moderate excess.
Trypsin: solution of small shreds of fresh fibrin in neutral and alkaline media, and tryptophan test.
Lipase: coloration of litmus-milk; exact color controls.
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.)
IODUM-MILLER AND IOD-IZD-OIL (MILLER’S)
Report of the Council on Pharmacy and Chemistry
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.”
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.”
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....”
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.”
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 only 1⁄20 grain 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 (from 1⁄2 to 20 drops) is equivalent to from 1⁄40 to 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.
REFEREE’S REPORT
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.”
“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.”
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
“... gives the Greatest Bactericidal and Therapeutic Action, whether used Internally, Externally, Hypodermically or Intravenously.”
In the light of the preceding report of the Chemical Laboratory of the Association, these claims require little comment. The laboratory has shown that the free iodin content (and consequently the germicidal efficiency) of Iodum-Miller is less than half that of Lugol’s solution, and less than a third of that of the official tincture of iodin. As for the advice to use Iodum-Miller internally in diseases ranging from pneumonia to syphilis and from typhoid to tuberculosis, in order to be convinced of its dangerous character, it is necessary only to recall that this treatment is equivalent to the administration of small doses of iodid—from 1⁄40 to 1 grain of potassium iodid. The mystery being removed from the composition of Iodum-Miller, the absurd extravagance of the claims made for it becomes manifest. The criticisms of the Council on the recommendations for Burnham’s Soluble Iodine (The Journal A. M. A., May 15, 1915, p. 1673) apply in almost every particular to Iodum-Miller.
Unwarranted therapeutic claims are made for Iodum-Miller; incorrect statements are made with regard to its composition and that of Iod-Izd-Oil (Miller’s); and the application of a trade name to both of these products is unjustifiable, since neither is original. It is therefore recommended that Iodum-Miller and Iod-Izd-Oil (Miller’s) be held ineligible for New and Nonofficial Remedies—(Abstracted in The Journal A. M. A., Oct. 2, 1915.)
ELIXIR IODO-BROMIDE OF CALCIUM COMP. “WITHOUT MERCURY” AND “WITH MERCURY”
Report of the Council on Pharmacy and Chemistry
The Tilden Company, New Lebanon, N. Y., and St. Louis, Mo., sells “Elixir Iodo-Bromide of Calcium Comp. without Mercury” and “Elixir Iodo-Bromide of Calcium Comp. with Mercury.” The latter is said to contain, in addition to the ingredients of the former, 1⁄100 grain mercuric chlorid in each fluidram. According to the label the formula of the elixir “without mercury” is:
“Formula—Salts of Iodine, Bromine, Potassium, Sodium, Calcium, Magnesium with Stillingia, Sarsaparilla, Rumex, Dulcamara, Lappa, Taraxacum, Menispermum.”
A recent circular declares that the elixir contains:
“... a number of the most powerful alteratives of the pharmacopeia such as chemically pure iodin, magnesium, potassium with sarsaparilla, stillingia, prickly ash, burdock, taraxacum, etc. ... Each fluidounce contains seventy-two grains of the combined salts.”
The same circular also alleges that each dram of the preparation contains:
“... the equivalent of one and one-half grains of the combined iodids, potassium and calcium ...”
It will be observed that, (1) the two statements quoted from the circular make no reference to bromids; (2) the statement that each dram contains “the equivalent” of 11⁄2 grains of the combined iodids, potassium and calcium, accounts for but 12 of the 72 grains of “the combined salts” per fluidounce declared in the preceding quotation; (3) the circular mentions the presence of a drug—prickly ash—not declared on the label and, finally (4) none of the “formulas” gives the quantities of all of the several constituents.
It is evident from these “formulas” that the Tilden Company continues its policy of concealment and mystification as exemplified in the cases of Hydrocyanate of Iron, Tilden (discussed in The Journal, June 19, 1909, p. 2008), Febrisol (The Journal, June 29, 1912, p. 2043) and Respirazone (The Journal, June 14, 1913, p. 1899).
In the circular just quoted (“The Conquest of Syphilis”), all hope for the syphilitic is declared to rest in mercury and iodin, and it is implied that only through Elixir Iodo-Bromide of Calcium Comp. is it possible to obtain the greatest good from these drugs.
“Were the cleansing influences of these two drugs [mercury and iodin] unavailable to the luetic patient, he, truly, would be as pitiable an object as the leper ...
“Modern Pharmacy has devised no better means of utilizing these anti-syphilitics than Elixir Iodo-Bromide of Calcium Comp. (Tilden) with or without mercury.... The Elixir, in proper dosage, acts in specific fashion and is adapted for use in all stages of the disease.
“In the early months ... Elixir Iodo-Bromide of Calcium Comp. (Tilden) with mercury is a trustworthy weapon and the physician need have no fear but that it will subjugate the disease ...
“When ... the virulent stage is passed ... Elixir Iodo-Bromide of Calcium Comp. (Tilden) without mercury may be given the patient with every assurance that medicine’s most aggressive measures are being resorted to ... From time to time, up to the very end of the time honored three years’ period of treatment, it is well to put the patient back on the bichloride, using for this purpose the form of the Elixir administered in the first stages of the disease ...
“This regime ... will indubitably antidote the virus of syphilis and eradicate from the organism its every vestige.”
While it seems incredible that any physician would jeopardize the health—even the life—of a patient by accepting this boastful magniloquence as sound therapeutic advice, still the fact that certain medical journals lend their advertising pages to advertisements for Tilden’s Elixir with the caption “The Conquest of Syphilis” makes it incumbent on the Council to record its condemnation of the employment of this unscientific, semisecret mixture.
It is recommended that Elixir Iodo-Bromide of Calcium Comp. “without mercury” and “with mercury” be held in conflict with Rule 1 (secrecy of composition), Rule 6 (unwarranted therapeutic claims) and Rule 10 (unscientific composition).—(From The Journal A. M. A., Nov. 6, 1915.)
LECITHIN PREPARATIONS OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report was sent to the manufacturers of the various lecithin preparations mentioned therein. As the replies of the manufacturers were obviously written from the commercial point of view and did not affect the Council’s conclusion that lecithin, when indicated, would be given more advantageously in the form of yolk of egg than in the less pure manufactured product, the Council directed that the report be published, together with extracts from the replies of the manufacturers.
W. A. Puckner, Secretary.
Commercial lecithin preparations are at best very impure substances; all are more or less altered from the original composition. Even with great care, the methods of extraction and drying always produce considerable decomposition; and in some cases the phosphorus and nitrogen contents bear but little relation to the theoretical values. (Long, J. H.: Jour. Am. Chem. Soc., xxx, 881. McLean, Hugh: Chem. Abstracts, May 20, 1915). There is not the slightest reliable evidence that commercial lecithin has any advantage over the lecithin contained in natural foods; the weight of probability is on the other side.
The doses recommended, moreover, are absurdly small; and the amount thus administered is without practical value. Why administer a few milligrams of a more or less decomposed lecithin when it is possible to give a far larger weight of a purer substance in the form of yolk of egg?
In view of these considerations the Council voted that the following proprietary products be omitted from the next edition of N. N. R.:
Glycerole of Lecithin Lecibrin Lecithin Solution Lecithol Neuro-Lecithin-Abbott
and that the general article on “Lecithin Preparations” be transferred to the annual Council Reports as a matter of record.
The report was submitted to the manufacturers. Their replies were evidently based on commercial consideration, and called for no modification in the report.
The referee recommended that the preceding report be published together with the following extracts from the replies of the manufacturers:
From Armour and Company:
“We are selling a good deal of Lecithol and it seems to be giving satisfactory results in some quarters.... We shall continue to advertise Lecithol along the lines we have employed heretofore.”
From the Abbott Laboratories:
“We can assure you of our confidence in the therapeutic value of Neuro-Lecithin. This has been attested by the reports of favorable results sent us by many physicians, as well as by the periodical literature of the last few years which contains a considerable number of very encouraging references to lecithin therapy.”
From Fairchild Bros. & Foster:
“We would like simply to say that the physician and the Council must be aware of the circumstances and the purposes which actuated us in placing lecithin at disposal, viz., the studies—research—of lecithin and the properties attributed to it and which led to inquiry for and consideration of it. The quantities proposed for medicinal use were not suggested by us; the suggestion of lecithin in small quantities as a therapeutic agent was obviously directed by those who proposed it.... The question whether lecithin, per se, has therapeutic properties in contrast to lecithin as naturally contained in food substances, is something we do not undertake to decide. The Council, on purely theoretical grounds, decides in the negative notwithstanding clinical experience—internal and hypodermic—and thus would deny lecithin the status of a new and nonofficial remedy, worthy of at least tentative progressive clinical consideration. We can only say that we offered bona fide lecithin and that we did not make the investigation of lecithin a pretext for the sale of all sorts of lecithin ‘jumbles’ with lecithin in small proportions, taking their name and making their bid on lecithin.”
Below appears the general article which has been omitted from N. N. R.:
Lecithin Preparations
Lecithins are fat-like bodies belonging to the group of phosphatides. They all consist of glyceryl esters containing two fatty acid radicals and the phosphoric acid radical in which one of the residual hydrogens is replaced by the choline group. The fatty acid may be palmitic, oleic or stearic and various combinations are known to exist; for example, distearyl lecithin, stearyl palmityl lecithin and so on. The commercial lecithins usually include the closely related kephalins.
On saponification the lecithins split more or less readily into choline, the fatty acids and glycerophosphoric acid, and by fusion with alkali nitrate and carbonate they yield alkali phosphate. They occur, free or in combination as lecithoproteins, most abundantly in certain animal tissues, but there are also vegetable lecithins. The lecithins of commerce are obtained usually from yolks of eggs or from calves’ or sheep’s brains.
Numerous processes have been devised for the preparation of lecithin from egg-yolk or animal tissue. From egg-yolk it may be obtained by making an alcoholic extract and precipitating by cadmium chloride. The precipitate is washed with alcohol and ether, mixed with 80 per cent. alcohol and warmed with the proper amount of ammonium carbonate to remove the cadmium. After filtering hot and concentrating the filtrate the lecithin is thrown down by cooling to a low temperature—10 C. or below. The precipitate is taken up in chloroform and reprecipitated by acetone.
From tissues it is obtained by extracting with warm alcohol and ether, concentrating the extract, precipitating with acetone and repeating the operations.
Pure lecithin is white, but the commercial preparations are yellowish-brown wax-like solids, which are not soluble in water but form milky emulsions which exhibit the myeline figures under the microscope. The solubility in cold alcohol or ether is slight, but heat aids it. Lecithins are not soluble in acetone. They are hygroscopic and the water mixtures undergo decomposition on standing. They darken on exposure to air and light.
The alcoholic solution is precipitated by platinum or cadmium chloride. It is decomposed by alkalies with the formation of choline and trimethylamine. The ash contains phosphoric acid. The different lecithins contain from 3.84 to 4.12 per cent. of phosphorus and 1.73 to 1.86 per cent. of nitrogen. The ratio of nitrogen to phosphorus should be at 1 to 2.21.
Lecithin is incompatible with alkalies; it should be kept in well-stoppered bottles and should be protected from the light.
The content of lecithin (plus kephalin) in tissues is about as follows:
Per Cent.
Egg-yolk8 to 12
Egg-white0.1 to 0.2
Liver2.0 to 3.0
Kidney2.0 to 3.6
Lung2.0 to 3.0
Pancreas2.0 to 3.0
Actions and Uses.—The lecithin preparations have been recommended in many pathologic conditions, especially in malnutrition and sexual debility. Moderate doses are said to bring about a marked retention of nitrogen and phosphorus, but satisfactory proof of this is lacking. It is extremely unlikely that the small doses which have been recommended in pill or tablet form or in emulsions can have any perceptible action, in view of the fact that many of our natural foods contain much greater weights of available lecithins than the medicinal doses provide. There is no good basis for the statement that the free lecithin has a greater food value or is more readily assimilated than is the substance as found in eggs or tissue. The reverse proposition is much more likely to be true, especially when it is considered that the commercial preparations are usually somewhat altered or decomposed in the process of separation.
Dosage.—Given by the mouth in the form of pills, tablets or glycero-alcoholic emulsions. The amount of actual lecithin ingested in this way is usually small because of the doubtful purity of the original preparation. Several doses, as commonly administered, would be required to furnish the amount of lecithin present in a small egg.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 122.)
PROPRIETARY NAMES FOR LIQUID PETROLATUM
Report of the Council on Pharmacy and Chemistry
The Council has accepted the following report and authorized its publication.
W. A. Puckner, Secretary.
A former report of the Council (Liquid Petrolatum or “Russian Mineral Oil,” Report Council Pharm. and Chem., The Journal, May 30, 1914, p. 1740) called attention to the large number of concerns that were placing on the market liquid petrolatum as a proprietary under coined names. Since then the number of such products has increased. The Council has been requested by several concerns to consider their products put out under proprietary brand names.
The rules of the Council affirm that “the application of ‘trade names’ to official or established nonproprietary substances tends to confusion and fosters many abuses.” In accordance with this general ruling, the Council has invariably refused to countenance proprietary names applied to liquid petrolatum. The Council holds that proprietary or coined names for this substance are detrimental to medical progress, since they are sure to foster the impression that the particular product is different from liquid petrolatum. Manufacturers have been advised that there is no objection to distinguishing their products by the addition of their firm name or the initial representing the firm name; for instance, “Liquid Petrolatum, A. B. and Co.” or “Liquid Petrolatum, Smith.” The Council also believes that such designations as “Star Liquid Petrolatum” or “Liquid Petrolatum, Anchor Brand,” may be regarded as unobjectionable, provided that the words “Liquid Petrolatum” are always used in connection with the brand designation and given equal prominence.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 127.)
SENG
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
Seng (Sultan Drug Co., St. Louis) is called by the manufacturers:
“... a palatable preparation of Panax (Ginseng) in an aromatic vehicle.”
Regarding ginseng (Panax quinquefolia) the United States Dispensatory, nineteenth edition, page 1603, says:
“The extraordinary medicinal virtues formerly ascribed to ginseng had no other existence than in the imagination of the Chinese. It is little more than a demulcent, and in this country is not employed as a medicine.”
No discussion of ginseng is to be found in the more recently published books on pharmacology, materia medica and therapeutics, evidently because their authors agree with this estimate.
On the other hand, physicians are told through the medium of advertisements appearing in medical journals that Seng is:
“An efficient remedy in all affections in which the gastro-intestinal glands need stimulating.
“Exceptionally useful in atonic indigestion, malnutrition, convalescence from the acute diseases, and all digestive disorders characterized by deranged or depressed functions.” (Woman’s Medical Journal, July, 1914.)
According to the label, Seng is indicated in “indigestion,” “malassimilation,” “malnutrition” and “wasting diseases.” It is also stated—though the preparation is admitted to contain 18 per cent. of alcohol—that to give babies “ten to fifteen drops in water or milk during feeding” is a proper procedure and that “For Colic, Flatulency, etc., the dose for an adult or child may be repeated every half hour until relieved.”
The following are some of the exaggerated therapeutic claims made for this preparation of a worthless drug:
“As a result of its administration the gastro-intestinal secretions are augmented, the digestion of food is substantially increased, and fermentative processes are promptly overcome.”
“Seng will specifically encourage the secretion of the juices in the entire alimentary tract ...”
The formula furnished for Seng is non-quantitative and therefore meaningless. The preparation is exploited in a manner to encourage its ill-advised use by the public, and exaggerated and unwarranted therapeutic claims are made for it. The use of an inefficient or worthless drug like ginseng, moreover, is detrimental to rational therapeutics. The Council therefore voted that Seng be refused recognition for conflict with Rules 1, 4, 6 and 10.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 129.)
FROSST’S BLAUD CAPSULES
Report of the Council on Pharmacy and Chemistry
Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine Capsules were submitted to the Council by C. E. Frosst & Co., Montreal, Canada. This firm claims, on the authority of the report of a firm of analytical chemists, that:
“... of three leading Blaud preparations bought by us on the open market, the iron in Frosst’s Blaud Capsules showed the highest percentage of Ferrous carbonate.”
The Chemical Laboratory of the American Medical Association found this claim unjustified. The laboratory reported that there was no especial difference in the ferrous iron content of the various Blaud pills found on the market, and that among ten specimens examined, the total iron content was the lowest in the Frosst specimen. In view of this the Council refused recognition to Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine Capsules.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 164.)
TYREE’S ELIXIR OF BUCHU AND HYOSCYAMUS COMPOUND
Report of the Council on Pharmacy and Chemistry
Each dessertspoonful of this preparation is said to represent
Buchu Leaves31⁄2 grains
Uva Ursi11⁄8 grains
Pareira Brava11⁄8 grains
Hyoscyamus11⁄2 grains
Hops11⁄2 grains
Acetate Potash71⁄2 grains
Spirits Nitre5 grains
Alcohol5 per cent. (by volume)”
The manufacturer, J. S. Tyree, Washington, D. C., offers this formula to the medical profession with the following claim:
“Approximate composition made [sic] by quantitative and qualitative analysis of the finished product.”
It is also claimed that
“An even greater advantage of Tyree’s Buchu and Hyoscyamus Compound over other drugs, lies in the fact that every constituent of the former is required to conform to a fixed standard of active principle strength; hence the results derivable from it are absolutely uniform.”
These pretentious claims of scientific accuracy look rather absurd to chemists. Many of the substances present in buchu, hops, hyoscyamus, uva ursi and pareira brava are also present in other drugs; hence it would never occur to a pharmaceutical chemist to try to ascertain the composition of such a mixture as Tyree’s Elixir by “quantitative and qualitative analysis of the finished product,” much less to determine the “active principle strength” of each ingredient, for no methods are known by which this can be done.
It is claimed that, because of the care exercised in making Tyree’s Elixir
“... the results derivable from it are absolutely uniform.”
A moment’s reflection, however, must compel any physician to attribute this statement, on the most charitable construction, to sheer ignorance. Of course, even a definite chemical principle, such as quinin, does not exert uniform clinical action, for clinical conditions vary, and accordingly the patient may or may not be cured. It is simply preposterous to claim that the clinical results obtained from such substances as hops, pareira brava, buchu and uva ursi are absolutely uniform.
A peculiarly vicious claim is that the elixir renders the mucous surfaces of the genito-urinary tract “hostile to the multiplication of the gonococci.” Since infection with the gonococcus produces the direst results, any claim which means in plain English that the remedy assists in producing a cure or in preventing infection with that organism cannot be condemned too strongly. Uva ursi, to be sure, has some slight antiseptic action but it is devoid of any curative action in gonorrhea and the minute amounts that are present in the Tyree elixir are of no more protective value against gonorrheal infection than a grain of hexamethylenamin would be.
It is further claimed that the elixir is a “specific” for “Inflammation of the Bladder, Bright’s Disease, Renal Colic, Suppurative Nephritis, Acute Cystitis, Urethritis, Catarrh of the Bladder [it would be interesting to know what distinction the manufacturer draws between ‘Inflammation of the Bladder,’ ‘Cystitis’ and ‘Catarrh of the Bladder’], Acidemia, Edema, Vesical Catarrh of Old Age, Lithemia” and that ascites and anasarca “can be reduced greatly to the satisfaction of the patient, and honor of the physician” by using a mixture of Tyree’s Elixir and infusion of digitalis. Such claims as these do not merit serious discussion, for they carry their own refutation.
It is recommended that Tyree’s Elixir of Buchu and Hyoscyamus Compound be held in conflict with Rules 5, 6 and 10 and that publication of this report be authorized.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 167.)
HYDROLEINE
Report of the Council on Pharmacy and Chemistry
Hydroleine (Charles N. Crittenton Company, New York) is a cod liver oil emulsion said to contain 45 per cent. of cod liver oil, a trace of salicylic acid and 181⁄2 grains of “Pancreatin, Etc.,” per ounce. The advertising claims are based largely on the theory that cod liver oil is “that particular fat which dietetic experience and physiological chemistry have proved to be most digestible.” As a matter of fact, while the superior digestibility of cod liver oil over other oils has often been asserted, neither “dietetic experience” nor “physiological chemistry” have “proved” this by definite observations. The Crittenton Company claims that it is more readily split than other oils. This is probably not true, easy emulsification of the raw oil being often confounded with easy splitting. This latter claim, however, is offered in justification of the name “Hydroleine,” which the Crittenton Company interprets as “hydrated oil.” A circular wrapped around the bottle contains the assertion that “Cod Liver Oil has long been held in high esteem by the medical profession for the treatment of a large number of serious diseases.” This recommendation is likely to lead the public to place undue reliance on Hydroleine in the grave conditions mentioned.
The preparation is in conflict with the rules of the Council inasmuch as its name does not indicate its composition, unwarranted therapeutic claims are made for it, and the exploitation is likely to give the public unwarranted confidence in its value. The Council therefore held Hydroleine ineligible for New and Nonofficial Remedies.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 171.)
CURATIVE VACCINE, BRUSCHETTINI
Report of the Council on Pharmacy and Chemistry
Curative Vaccine, Bruschettini, manufactured by A. Bruschettini, Genoa, Italy, is claimed to have the properties “of acting directly on the tubercular bacillus, bringing directly into the field and determining a hyperproduction of antibacillar and antitoxic substances.” The use of the preparation is said to be indicated in “all forms of tuberculosis.”
A referee reported to the Council that he had examined the available information and believed that the use of this product had no satisfactory experimental basis. The method of preparation appears to be based more on theoretical considerations than on experimental basis.
On the recommendation of the Committee on Serums and Vaccines the Council voted that Curative Vaccine, Bruschettini, be not accepted because (1) the method used for the production of the vaccine was not satisfactorily stated; (2) the theory on which its use is based has not been satisfactorily confirmed, and (3) the value of the product is not upheld by satisfactory clinical evidence.
The Council’s findings, in accordance with its procedure, were sent to the manufacturers for comment. His reply was considered by a new referee who found that the matter presented did not warrant a revision of the Council’s conclusions. Accordingly the Council directed publication of its findings.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 176.)
STEARNS’ WINE
Report of the Council on Pharmacy and Chemistry
Frederick Stearns & Co. market a preparation known as “Stearns’ Wine,” “Stearns’ Wine of Cod Liver Ext. with Peptonate of Iron,” and as “Vinum Ext. Morrhuae, Stearns.” The constituents are said to be “concentrated extract of fresh cod livers,” “Peptonate of Iron” and a “fine quality of prime Sherry Wine” containing 18 per cent. of alcohol.
This preparation was at one time marketed through the medical profession, but is now advertised direct to the public in typical “patent medicine” style. The label on a recently purchased bottle of Stearns’ Wine contains the following statements:
“STEARNS WINE is an ideal tonic for elderly people, for weak, pale and delicate children and convalescents.
“STEARNS WINE has for many years been successfully prescribed in the treatment of general or nervous exhaustion, anemia, malnutrition, loss of appetite, loss of sleep, faulty circulation and impoverished blood supply.”
The scope of the recommendations for the preparation is further indicated in a booklet accompanying the bottle, which begins:
“STEARNS’ WINE, What It Is and Why It Is Good for You.”
The conclusion is:
“STEARNS’ WINE is a safe medicine for the young, middle-aged and old. It is a safeguard to the family health.”
It is not necessary to discuss either these all-embracing claims as to the therapeutic efficacy of the mixture or the fallacies presented in favor of cod-liver extract and peptonate of iron. The Council reaffirms the opinion that whatever therapeutic value cod liver may have resides chiefly, if not entirely, in its fatty constituents (The Journal, Oct. 9, 1909; Reports Council Pharm. and Chem., 1909, p. 115). A confirmation of this opinion has recently been furnished by the investigations of Prof. J. P. Street (The Journal A. M. A., Feb. 20, 1915, p. 638) of several cod liver cordials, one of which (Vinol) like Stearns’ Wine, is described as a wine of cod liver extract with peptonate of iron.
Stearns’ Wine is essentially an alcoholic stimulant. It is not “a safe medicine for the young, middle-aged and old.” The unwarranted therapeutic claims and the recommendations for its indiscriminate use bring it into conflict with Rules 4 and 6. The Council voted that Stearns’ Wine be held ineligible for inclusion in N. N. R.—(From Reports of Council on Pharmacy and Chemistry, 1915, p. 177.)
PROTONUCLEIN AND PROTONUCLEIN BETA
Report of the Council on Pharmacy and Chemistry
The Council had adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
Protonuclein, with other products of Reed and Carnrick, was examined by the Council in 1907 and found ineligible for admission to New and Nonofficial Remedies. According to the patent specifications, it is prepared “from the thyroid and thymus glands, brain (pineal glands and pituitary body), bone-marrow, pancreas, spleen, liver, salivary glands, Brunner’s glands, Lieberkühn’s follicles and peptic glands.” These various glandular bodies, it is said, are dried at a temperature below 130 F. (preferably between 100 and 110); the fat is removed by ether, the dried glands disintegrated, the connective tissue removed by sifting and the resulting powder coated with an ether solution of benzoin and mixed with milk sugar. The dose is three to ten tablets (9 to 30 grains) daily.
Protonuclein Beta is said to be produced by the addition to Protonuclein of an equal amount of nucleoplasm and protoplasm of the spleen. The dose is from two cubes (each 5 grains) three times a day to three cubes four times a day (30 to 60 grains daily).
Special advantages over ordinary nuclein are attributed to Protonuclein, in which, it is claimed, certain unaltered cells remain that are more easily assimilated by the leukocytes than are ordinary proteins, thus leading to a multiplication of cells. In the early advertising Protonuclein was claimed to be: