Chapter XVI: Introduction: The Council on Pharmacy and Chemistry was established (9)

[117] The North Dakota Agricultural Experiment Station has recently published (Bulletin 22, 1915, p. 386) a complete chemical analysis of Nutrolactis. It contains only 0.60 per cent. solids (including strychnin and emodin). It has a bitter taste. The alcohol content was 3.5 per cent. The report concludes: “a little strychnin, a little alcohol, and a little laxative is about all there is to cause an increase in the milk secretion.”

[118] Millbank: New York M. J. =50=:544, 1889.

METHODS OF INVESTIGATION

The alleged lactagogue action of galega and Nutrolactis was tested on lactating dogs and goats. In these animals the psychic factors, or suggestion, are largely eliminated. If the results had been positive or had indicated lactagogue action, the test would have been extended to nursing women. The puppies and kids were weighed before and after nursing and a record kept of the amount of milk obtained at each nursing (the animals nursing from three to five times daily). The mothers were fed with varying doses of the drugs, and the milk yield compared with that of a control period during which no drugs were administered. An effort was made to keep the conditions of the experiments uniform throughout.

The galega was ground and mixed with the food. The Nutrolactis was mixed with food given by the stomach tube, or in some cases with a spoon. Galega was tested on two goats and Nutrolactis on one goat and nine dogs. The results are given herewith:

GALEGA

_Goat 1_: Control period, 1,600 gm., milk av. daily yield for 7 days.

Galega period (30 gm. galega mixed with oats), 860 gm., milk av.
daily yield for 8 days. Kids weaned at end of period.

_Goat 2_: Control period, 1,161 gm. milk av. daily yield for 9 days.

Galega period (30 gm. galega mixed with oats), 860 gm. milk av. daily
yield for 8 days. (25 gm. galega in same way), 810 gm. milk av. daily
yield for 10 days.

Control period, 896 gm. milk av. daily yield for 6 days.

NUTROLACTIS

_Goat 3_: Control period, 896 gm. milk av. daily yield for 6 days.

Nutrolactis period (30 c.c. Nutrolactis mixed with oats), 658 gm.
milk av. daily yield for 9 days.

Control period, 666 gm. milk av. daily yield for 5 days.

_Dog 1_: Control period, 176 gm. milk av. daily yield for 7 days.

Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 55 gm. milk
av. daily yield for 12 days.

_Dog 2_: Control period, 189 gm. milk av. daily yield for 6 days.

Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 72 gm. milk
av. daily yield for 11 days.

_Dog 3_: Control period, 93 gm. milk av. daily yield for 8 days.

Nutrolactis period (8 c.c. Nutrolactis on bread), 17 gm. milk av.
daily yield for 5 days.

_Dog 4_: Control period, 28 gm. milk av. daily yield for 7 days.

Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 47 gm. milk
av. daily yield for 6 days.

(10 c.c. Nutrolactis by stomach tube), 43 gm. milk av. daily yield
for 8 days.

Control period, 41.5 gm. milk av. daily yield for 6 days.

Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33.5 gm.
milk av. daily yield for 4 days.

_Dog 5_: Control period, 67 gm. milk av. daily yield for 6 days.

Nutrolactis period (10 c.c. Nutrolactis on bread), 81 gm. milk av.
daily yield for 6 days.

_Dog 6_: Control period, 40 gm. milk av. daily yield for 5 days.

Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33 gm. milk
av. daily yield for 8 days.

Control period, 26 gm. milk av. daily yield for 4 days.

_Dog 7_: Control period, 283 gm. milk av. daily yield for 9 days.

Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 155 gm.
milk av. daily yield for 15 days.

(15 c.c. Nutrolactis by stomach tube), 82 gm. milk av. daily yield
for 6 days.

Control period, 33 gm. milk av. daily yield for 3 days.

_Dog 8_: Control period, 238 gm. milk av. daily yield for 8 days.

Nutrolactis period (20 c.c. Nutrolactis on bread), 223 gm. milk av.
daily yield for 4 days.

(20 c.c. Nutrolactis on bread), 46 gm. milk av. daily yield for 6
days.

_Dog 9_: Control period, 223 gm. milk av. daily yield for 6 days.

Nutrolactis period (10 c.c. Nutrolactis on bread), 178 gm. milk av.
daily yield for 15 days.

(15 c.c. Nutrolactis on bread), 146 gm. milk av. daily yield for 5
days.

COMMENT AND CONCLUSION

Goat 1 had already been lactating for over two months, and the yield was gradually decreasing at the time the observations were begun. The administration of galega did not check this decrease. Goat 2 should have been a very favorable subject, for the kid was about a week old at the time the observations were begun. Both galega and Nutrolactis caused a decrease in milk yield of this animal. This decrease is perhaps partly due to the animal’s distaste for the drugs and her consequent failure to eat as well as during the control periods.

Administration of Nutrolactis was accompanied by an increase in milk in only two animals, Dog 4 and Dog 5. A detailed examination of the records of these two dogs shows that in both cases _there was a progressive increase in milk yield during the control period_ and that administration of the drug failed to accelerate this increase. On the contrary, the curve for Dog 5 takes a sudden drop immediately after the first administration of the drug.

The records of Dogs 6 and 7 show that the yield during the second control period is lower than that of the preceding periods. Although the administration of the drug in both cases was followed by a decrease in the yield, it may be urged that the drug has some lactagogue action, for its discontinuance was followed by a decrease in yield. This effect, however, is also apparent rather than real, for the data show a gradual falling off in yield during the period of administration of the drug, which decrease was not accelerated by withdrawing the drug.

Our data show that galega and Nutrolactis, when taken by mouth, and the elements of suggestion excluded, had no beneficial effect on lactation--at least in so far as the quantity of milk is concerned.--(_From The Journal A. M. A., May 26, 1917._)

THE RUSSELL EMULSION AND THE RUSSELL PREPARED GREEN BONE

Report of the Council on Pharmacy and Chemistry

The following report on “The Russell Emulsion” and “The Russell Prepared Green Bone,” marketed by the Standard Emulsion Company, was submitted to the Council by a referee. The Council endorsed the report and authorized its publication.

W. A. Puckner, Secretary.

The Russell Emulsion is put up in a neat package and advertised in an attractive pamphlet, on the cover of which we are told: “Truth Always Justifies The Superlative Degree.” As what follows in the booklet and in the printed circulars certainly does not lack superlatives, this is doubtless a warning.

In addition to the pamphlet and circular advertising, the product seems to be systematically boomed by a lecture scheme in which one Dr. Hague talks before medical societies and distributes advertising matter. The lecture is succeeded by a follow-up letter scheme through which matter is sent to members of the society. Hague ostensibly discusses “lime starvation in tuberculosis,” but medical societies soon learned to estimate his work as essentially to advertise the Russell products. Last April the Medical Society of the State of Pennsylvania sent out a circular letter to its county organizations on the subject of the Russell-Hague propaganda which opens in this way:

“You have doubtless received a letter from Dr. William Grant Hague of New York, offering to address your county society on Tuberculosis. After due investigation, it is respectfully suggested that it may not be desirable to ask him to address your society....”

The statements in the pamphlet and circular published are typical of the whole method of exploitation. For example, can such claims as these be surpassed by the veriest quack?

“SCIENCE cannot improve the means employed in producing THE RUSSELL
EMULSION.”

“GENIUS has not devised better methods than are used in
manufacturing THE RUSSELL EMULSION.”

“MONEY cannot buy better products than are used in THE RUSSELL
EMULSION.”

“EXPERIENCE cannot suggest a more nutritious combination of fats
than we use in THE RUSSELL EMULSION.”

The emulsion is said to be made of equal parts of beef-fat, coconut, peanut and cottonseed oils, held in suspension by albumin. The latter we are told is applied to each globule of the emulsion by an “elaborate technical process” devised by Dr. Russell. The mixture is everywhere spoken of as a “physiological” emulsion, but the word is always in quotation marks. Why it is called “physiological” is not clear, but the term may be counted on to impress the unthinking or the unscientific.

Numerous false and exaggerated statements are made about this “physiological” emulsion with reference to food value. For instance:

“The nutritional value of fats differ; the nutritional value of
these fats and their increased efficiency by combination over all
others have been determined by extensive clinical observation.”

And also:

“The Russell Emulsion is approximated in food value by no other
emulsion or food product in existence.”

“A ‘physiological’ emulsion is a predigested food. It is absorbed
with little assistance from the digestive juices, and with no waste
of energy. It is, therefore, the ideal food....”

These are sample statements found in the pamphlet and accompanying circular. A dozen or more pathologic conditions are mentioned in which this “ideal food” is specifically indicated; but we find, also, this curious statement: “Patients can rarely take this dose [speaking of the maximum dose of 2 ounces night and morning] for more than three or four weeks without showing symptoms of over-feeding.” This unguarded remark about an ingestion of 48 grams of fat daily prompts one to ask what is wrong with the “ideal predigested food.”

Russell is wedded to the idea that “lime starvation” is the main factor in tuberculosis, and insists on the importance of large amounts of fat for the “lime starved.”

“Dr. Russell was the original interpreter of the Lime Starved State
and originated The Lime Starvation Treatment in Tuberculosis. He
also first pointed out and emphasized the therapeutic importance of
regarding the combination of lime phosphate and casein, as brought
down by the rennet enzyme, as a chemical union.”

This overworked lime-starvation theory certainly lacks any tangible confirmation (see in this connection a recent paper by Halverson, Mohler and Bergeim, in The Journal, May 5, 1917), and to urge it to promote the sale of a fat preparation is preposterous. On the uninitiated the exaggerated pseudo-scientific language of the pamphlet and circular advertisement will probably make some impression. Unfortunately such things count not only with the layman who, having no technical knowledge of physiology, cannot be expected to weigh the evidence but also with those medical men who, while scientifically educated, are influenced by unscientific claims when plausibly presented. The pamphlet is a striking example of a style which is dangerous because it smacks of science.

The Russell Company sells also a mixture called “Prepared Green Bone,” said to be made by partially digesting ground chicken bones with hydrochloric acid and pepsin and adding glycerin at the end of the digestion. The product is a sticky, unappetizing looking mass, put up in little earthenware boxes and advertised as a lime food, apparently to go along with the fat emulsion. The greater value of a few glasses of milk daily is evidently overlooked.

“The Russell Emulsion” and “The Prepared Green Bone” were declared inadmissible to New and Nonofficial Remedies.

[Editorial Comment.--There are always those who are ready to exploit the unfortunate tuberculous. It is, unfortunately, a fact that many physicians accept as true, statements clothed with obscure and voluminous quasi-scientific verbiage. Such men would laugh at the bald claim that the moon is made of green cheese; when, however, one plausibly and with due solemnity, affirms that the nocturnal luminous earthly satellite is composed of an infinite aggregation of molecules of bewildering and awe-compelling complexity, built up from the recently discovered polypeptids, the whole being of a verdant tint, the person addressed looks impressed and opines that it sounds reasonable! The advertising for The Russell Emulsion and The Russell Prepared Green Bone is dangerous because it appeals to the thoughtless--layman and physician, alike.]--(_From The Journal A. M. A., June 23, 1917._)

BROM-I-PHOS

Report of the Council on Pharmacy and Chemistry

Brom-I-Phos (National Drug Company, Philadelphia) was submitted to the Council with a label bearing the following statement:

“‘ALCOHOL 25 PER CENT.’
COMPOSITION--Per Fluidounce

Iodin 1 gr.
Bromin 1 gr.
Phosphorus 8-100 gr.
Aromatic Base q. s.”

A request for further information in regard to the composition of Brom-I-Phos was sent to the National Drug Company. It was suggested that since the preparation cannot contain the stated amounts of free bromin, free iodin and free phosphorus, the form of combination in which these elements are present should be set forth. In reply, the firm said, first, that “Brom-I-Phos consists of Bromin, Iodin, Phosphorus, Glycerin, Wine, Water and Volatile Oils. The Iodin is rubbed up with a small percentage of Potassium Iodid and 95 per cent. Alcohol, which solution is mixed with a solution of Bromine and Spirits of Phosphorus which are combined with the base and aromatics.” The manufacturer also admitted that phosphorus reacts with bromin and iodin and that other reactions might occur, but maintained that it was “justified in assuming the greater part, if not all of these elements, are actually existent in the nascent state,” and asserted that its “printed formula complies with our working formula in point of quantities involved as well as existence of elements in an uncombined state.”

The A. M. A. Chemical Laboratory reported, on the contrary, that no free phosphorus, free bromin or free iodin could be found in Brom-I-Phos, and that no bromate or iodate could be found; bromid and iodid were present. The addition of silver nitrate to an acidulated portion, diluted with water, gave an amount of silver halid roughly agreeing with that which would be obtained had the claimed amount of bromin and iodin (together with some potassium iodid) been used in the preparation of Brom-I-Phos and in the process of manufacture become converted to bromid and iodid.

The Council declared Brom-I-Phos inadmissible to New and Nonofficial Remedies, for conflict with Rules 1, 4, 6, 8 and 10.

The statement of composition is unsatisfactory and misleading in that it suggests that the preparation contains bromin, iodin and phosphorus in the free (elementary) state. The presence of the potent elementary phosphorus is especially suggested by the small amounts of “phosphorus” declared.

The following statement on the label of the trade package constitutes an indirect advertisement to the public:

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

The following claims are therapeutic exaggerations:

“The Ideal Alterative”

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

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

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

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

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

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

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

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

CREOSOTE-DELSON AND CREOFOS

Report of the Council on Pharmacy and Chemistry

Creosote-Delson and Creofos, or Creosote with Hypophosphites, were submitted by the Delson Chemical Co., Inc., New York City. Creosote-Delson is said to be “beechwood creosote from which the irritating and caustic properties are removed by fractional distillation.” It is claimed that Creofos contains “2 grains of Creosote-Delson and 3-3/5 grains of the combined Hypophosphites in each fluidrachm of the mixture or emulsion, the lime salt predominating.” It is also claimed that “the primary object of the hypophosphites in this preparation is that of maintaining the refined creosote in a pure, unoxidized state, and that no particular claim for therapeutic action on their part is advanced.” It is explained further, however, “the addition of the lime was prompted by the belief ... that the fundamental cause of pulmonary tuberculosis is lime starvation....”

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

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

The following advertisement has recently appeared in the _New York Medical Journal_ and in the _Therapeutic Gazette_:

CREOFOS MEDICATION

is the successful development of the most advanced practice in
the treatment of infectious diseases. It destroys completely the
causative organisms by a bactericide many times more powerful than
phenol, yet absolutely harmless to animal life.

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

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

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

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

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

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

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

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

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

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

TRINER’S AMERICAN ELIXIR OF BITTER WINE

Report of the Council on Pharmacy and Chemistry

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

Some recent advertisements read:

“It Acts Well and Is Very Palatable. These are the reasons why so
many physicians recommend TRINER’S AMERICAN ELIXIR OF BITTER WINE.
Free from any chemicals. Prepared from bitter herbs roots and barks
of eminent medicinal value and pure natural red wine. A safe relief
in auto-intoxication, constipation, weakness, etc. Price $1.00. At
drug Stores. Samples gratis upon request only to physicians.”

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

Triner’s American Elixir of Bitter Wine is put up in bottles said to hold 1 pint, 5-1/3 fluidounces. The label declares the presence of from 16 to 18 per cent. alcohol by volume, and states that “no special tax is required by the laws of the U. S. for the sale of this medicinal preparation.” The circular contains the following recommendations for its use:

“... It should be used in all cases calling for a safe evacuation
of the bowels, without weakening the body or causing any pain or
other discomfort; in loss of appetite, nervousness and weakness.”

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

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

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

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

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

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

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

TRIMETHOL

Report of the Council on Pharmacy and Chemistry

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

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

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

“Physicians are constantly reporting cases where Trimethol has been
especially efficient, and describing conditions (until recently not
associated with intestinal infection) which have been distinctly
benefited by its use. This would seem to bear out the contentions
of Charcot and Metchnikoff that 90% of all human ailments have
their origin in intestinal infection.

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

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

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

REFUSE TO FURNISH TRIMETHOL

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

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

THE BACTERIOLOGIST’S REPORT

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

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

“A package containing four four-ounce bottles labeled ‘Trimethol, A Non-Toxic Germicide SYRUP Representing 3/4 m. Trimethol per drm., Alcohol 1-1/2 per cent.’ was received at the laboratory Dec. 15, 1916. Later a smaller package containing, according to the label, 100 Trimethol tablets, each 5 gr., representing 1-1/4 m. Trimethol, was received. The tablets were apparently chocolate coated.

“Two separate series of tests were made upon the syrup. (_a_) PHENOL COEFFICIENT, using the method outlined in _Bulletin No. 82_, Hygienic Laboratory, Method of Standardizing Disinfectants With and Without Organic Matter. (_b_) A PENETRABILITY COEFFICIENT by the method of Kendall and Edwards, _Journal of Infectious Diseases_, 8, 250.

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

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

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

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

“The results of several determinations, using Trimethol Syrup from three separate bottles, were in sufficient accord to warrant the statement that a dilution of 1/10 of Trimethol Syrup was equivalent to a 1/100 dilution of carbolic acid, using _Bacillus typhosus_ as the test organism. Both solutions--the Trimethol and phenol--killed the organism in the interval between 7-1/2 minutes and 10 minutes’ exposure. That is to say, our observations indicate that under standard conditions as defined above, a 10 per cent. solution of Trimethol Syrup is equivalent in germicidal powers, as defined by the phenol coefficient to a 1 per cent. solution of phenol. Naturally, no predictions can be drawn from these observations indicative of the value as an intestinal germicide of Trimethol itself.

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

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

The preceding report shows that Trimethol Syrup has a phenol coefficient of 1/10, and, assuming Trimethol Syrup contains the amount of Trimethol declared, the substance Trimethol would have a phenol coefficient of 8-1/3 instead of 40, as is claimed. According to Kendall and Edwards’ method, the penetrability-germicidal value of the syrup is equal to a 1 per cent. solution of phenol.

WALKER’S REPLY TO CRITICISM

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

(_May 22, 1917_) “In reply to your letter of the 15th inst., which
has just been placed before me on my return to town, I have to
inform you that the potent constituent of Trimethol Tablets and
Trimethol Syrup is not fully available as a bactericide until it
comes in contact with the pancreatic fluid.

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

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

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

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

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

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

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

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

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

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

[119] Those who are interested in the relative merits of the Rideal-Walker, the _Lancet_ and the Hygienic Laboratory methods for the valuation of disinfectants, should read the following: Method of Standardizing Disinfectants with and without Organic Matter, J. A. M. A., Aug. 24, 1912, p. 667; Standardization of disinfectants, Report of the Council on Pharmacy and Chemistry, J. A. M. A., April 26, 1913, p. 1316; Standardizing Disinfectants, J. A. M. A., Sept. 30, 1916, p. 883.

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

FERRIVINE, INTRAMINE AND COLLOSOL IODINE

Report of the Council on Pharmacy and Chemistry

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

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

“INDICATIONS

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

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

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

We are also told that:

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

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

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

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

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

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

While:

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

The authors explain:

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

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

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

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

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

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

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

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

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

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

ESKAY’S NEURO PHOSPHATES

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

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

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

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

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

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

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

The phosphorus content of 1/64 grain of strychnin glycerophosphate is ridiculously small. Yet it is asserted that this strychnin salt is of superior value because it combines the effects of strychnin with a “food-like form of phosphorus.” Eskay’s Neuro Phosphates has an acid reaction which is capitalized, thus:

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

And as a further illustration of extravagant claims:

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

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

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

K-Y LUBRICATING JELLY

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

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

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

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

And this from another circular:

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

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

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

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

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

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

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

ZIRATOL