Chapter XXI: Appendix (2)

The Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of the individual patients without which there can be no drug therapy. On the contrary, with the use of such mixtures, therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10, concerning the recognition of mixtures, with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture, it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer warrant for the admission of complex mixtures to New and Nonofficial Remedies, or for the retention of any that have been admitted, unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision, several mixtures now described in New and Nonofficial Remedies will be omitted at the expiration of the three year period for which articles are accepted.

Granular Effervescent Bromide and Acetanilid Compound-Mulford is listed in the Appendix to New and Nonofficial Remedies. Each 100 Gm. of the mixture contains sodium bromide, 5 Gm., and acetanilid, 1.5 Gm. According to the label, an amount containing acetanilid, 6.5 grains, and sodium bromide, 22 grains, is to be taken at a dose, to be repeated in half an hour if necessary. For “children,” half this dose is advised.

The Council has considered the available evidence for mixtures of this sort, and has reached the conclusion that they are inimical to rational medicine and the public, and therefore in conflict with Rule 10. It holds that the use of mixtures of acetanilid and sodium bromide in fixed proportion is irrational and prone to induce their indiscriminate use by the public. Despite the perfectly frank declaration of the composition of this mixture that is made by the Mulford Company, the “directions” will be followed blindly and the preparation will be given to “children” and “repeated in half an hour, if necessary” in cases in which it would be held unwarranted to administer a dose of 3 grains of acetanilid to a child.

The period of acceptance having expired for Granular Effervescent Bromide and Acetanilid Compound-Mulford, the Council directed its omission from New and Nonofficial Remedies for conflict with Rule 10.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 58._)

HOLADIN AND BILE SALT MIXTURES

Holadin and Bile Salts-Fairchild; Capsules of Bile Salts, Succinate of Soda and Phenolphthalein-Fairchild; Capsules of Holadin, Bile Salts and Phenolphthalein-Fairchild; Capsules of Holadin, Succinate of Soda and Bile Salts-Fairchild.

Report of the Council on Pharmacy and Chemistry

To explain the omission from New and Nonofficial Remedies of certain mixtures, the Council has authorized publication of the matter which appears below.

W. A. Puckner, Secretary.

The Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible accurately to determine the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because the practice of prescribing such mixtures tends to discourage careful consideration of the special needs of individual patients without which there can be no rational drug therapy. On the contrary, with the use of such mixtures, therapeutic treatment becomes haphazard and mere guesswork.

The Council, appreciating that long established customs cannot be changed at once, has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer any warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted unless definite evidence of the therapeutic value of such combinations is available. In accordance with this decision, several mixtures now described in New and Nonofficial Remedies will be omitted as soon as the three year period for which articles are accepted has expired.

The following preparations are included in New and Nonofficial Remedies, 1918:

Holadin and Bile Salts-Fairchild.--A mixture of holadin, 5 parts, with bile salts-Fairchild, 1 part, put up in 3 grain capsules.

Capsules of Bile Salts, Succinate of Soda and Phenolphthalein.--Each capsule contains bile salts-Fairchild, 0.065 Gm. (1 grain); sodium succinate exsiccated, 0.2 Gm. (3 grains), and phenolphthalein, 0.03 Gm. (1/2 grain).

Capsules of Holadin, Bile Salts and Phenolphthalein.--Each capsule contains holadin, 0.13 Gm. (2 grains); bile salts-Fairchild, 0.03 Gm. (1/2 grain), and phenolphthalein, 0.065 Gm. (1 grain).

Capsules of Holadin, Succinate of Soda and Bile Salts.--Each capsule contains holadin, 0.20 Gm. (3 grains); sodium succinate exsiccated, 0.20 Gm. (3 grains), and bile salts-Fairchild, 0.03 Gm. (1/2 grain).

Oxbile has long been credited with a cholagogue action, which, however, has probably been greatly overestimated. When pure bile salts were placed on the market some years ago, they and their compounds were admitted to N. N. R.

Holadin is said to represent all the constituents of the pancreas and to possess great potency in respect to the several enzymes, trypsin, amylopsin, lipase, and the milk-curdling ferment.

It is not clear when such a substance is indicated therapeutically. While it may be useful when there is a deficiency of pancreatin and gastric secretion, it should be used alone.

It is also quite possible that bile salts may have a distinct, though limited, field of usefulness when there is a deficiency of biliary secretion; but the bile salts are best administered alone, or in combination with such laxatives as may be deemed necessary by the physician while keeping in mind the fact that different patients show the widest difference in their reaction to laxatives, making combinations of these agents in fixed proportion irrational.

Phenolphthalein was popularized by nostrum makers; and while it has some therapeutic value, this has been greatly overestimated, and it should be used only in amounts deemed necessary for each patient, preferably alone.

Succinate of sodium was introduced as a saline cathartic, with the claim that it exerts an antiseptic action on the biliary passages and gallbladder. There is no satisfactory evidence to substantiate this claim.

The Council maintains a liberal attitude toward new preparations, but it feels that it is impossible to determine the value of the several constituents of such complex mixtures when used as such; it holds that these mixtures are superfluous and that the several substances of which they are composed should be used singly or at most with greater attention to the individual requirements of the patient than is possible when these fixed mixtures are prescribed.

Despite the fact that these mixtures have been in use for more than nine years, there is no satisfactory evidence that they possess any advantage over the simple laxatives or the preparations of bile or pancreatic extract. They are therefore held to be in conflict with Rule 10, and the Council has directed that they be not included in N. N. R. after Dec. 31, 1918.

Having adopted the preceding report, the Council, in accordance with its regular procedure, submitted this to Fairchild Bros. and Foster for comment.

The following reply was received:

We are entirely at variance with you in the arbitrary conclusion
expressed concerning the inimical influence of mixtures on
therapeutic progress, the practice of medicine and the public
welfare.

If the combinations of Holadin and Bile Salts, etc., in capsules,
were ever properly within the scope of New and Nonofficial
Remedies, they should be retained. If, however, complex mixtures
are to be held as, a priori, unworthy of consideration, the
rejection of all would naturally be a logical proceeding.

We believe that the particular combination of Holadin and
Bile Salts etc., have been clearly in the line of therapeutic
progress--a natural evolution, improvement and development.

For many years combinations of pancreatic extract and ox gall had
naturally suggested themselves.

When we realized the fact that the bile salts were quite clearly
the active principles of the bile, and that they must necessarily
exist in greatly varying percentages in the official inspissated
or ox gall, and also because these ox gall products of pharmacy
were of extremely varying density, even from that of treacle
to resin--and of other objectionable character, we undertook to
prepare bile salts.

These combinations are now further justified in view of
physiological considerations, the simultaneous secretion of the
pancreas and bile, and the state of our knowledge of the function
of bile salts, and as co-ferments, promoting and supplementing the
pancreas enzymes.

The question suggested as to whether the cholagogic action of ox
gall (and bile salts) has been overestimated seems to us no clear
purport. The bile salts are obviously employed as the means of
administering and thus realizing whatever properties this secretion
may have in medicine, of which the cholagogic action is by no means
the only consideration.

As for phenolphthalein, which is credited with purely laxative
properties, we are at a loss to see any bearing in the remark that
phenolphthalein was popularized by nostrum makers. We cannot see
that the physician’s or chemist’s estimate of phenolphthalein, its
properties and uses, can be in the least degree influenced one
way or the other by the statement that “phenolphthalein has been
popularized by nostrum makers.”

The phenolphthalein and succinate of soda combinations were
originally both prescribed, and we have simply placed them at the
service of the physician without other exploitation of them than
that designed to call attention to their use in the conditions
indicated.

These combinations are offered in a form which may be administered
by the mouth with the best promise of introducing the substance
more directly in the intestinal tract during the digestion period
or at such interval after or prior to, the digestion period, as
would best, in the judgment of the physician, meet the indications.

These particular combinations are especially desirable in these
“fixed forms” since they are stable and reliable resources at the
command of the physicians, the enzymes retaining their stability
and potency without material deterioration for many years, and they
naturally possess the advantages which are obviously due to the
character of the particular pancreas and bile products used in the
combinations.

Furthermore, the hygroscopic and soluble organic substances in
admixture cannot extemporaneously be so prepared in sealed capsules
as to be readily available under the practical requirements of
prescribing and dispensing. And we do not believe that those
who practice medicine will be in accord with your view that the
pancreas substance should necessarily be administered alone, or the
bile substance alone.

It now appears that these combinations are to be dropped from New
and Nonofficial Remedies in consequence of the view, so stated,
that in clinical experience “for more than nine years there is no
satisfactory evidence that they possess any advantage over the
simple laxatives or preparations of bile or pancreatic extract.”

In reply to this we would simply make the following comment:

During these “nine years” these combinations have inevitably been
put to an informing clinical trial, because of the fact that they
have been employed with success in disorders of the pancreas and
bile functions and often in chronic and serious cases where the
clinical conditions were obvious and unmistakable.

The reports of these cases come to us from physicians widely
separated and each of his own independent initiative. It would
seem gratuitous, to say the least, to state that the observers are
“disinterested,” since it is quite clear that there is no other
interest than that of the practitioner and his patient.

It is not a case of a new drug or combinations of new remedies,
but simply resources which, upon well grounded reasons, both from
a theoretical and material standpoint, justify clinical trial, and
with results which would seem from any ordinary human standpoint to
be satisfactory clinical evidence.

As to the interpretation of competent clinical evidence by the
Council, we would, in view of the circumstances and without
comment, ask to embody in this text this rule:

“Clinical Evidence.”--“To be acceptable, the clinical evidence
must offer objective data with such citation of authority as
will enable the Council to confirm the facts and establish the
scientific value of the conclusions drawn. Clinical data are
worthless when the author is not cited. The facts on which
claims with regard to the value of a remedy are based must have
been rendered accessible for investigation and confirmation by
disinterested observers, either through publication or through
the records of a hospital or other institution.”

To discredit these combinations would seem to us not only
unjustified, but sterile of any real advancement in medicine, or of
anything in the way of helpfulness to the patient in the class of
cases in which these products have been resorted to with benefit;
this on no other ground really than the opinion “that they have no
advantage over the simple preparations themselves.”

Naturally we shall continue to prepare these products and shall
continue to take such action as we deem best to bring them to the
attention of the physician, for the conduct of our business must
remain in the hands of those who are personally responsible for it.

And it is now forty years since we took up this line of work and
with the declared intention of devoting ourselves to the applied
science of the digestive ferments and “to their development and
practical application in every useful purpose in medicine.”

We have been consistently in sympathy with the fundamental purpose
of the Council, which must first rest upon fact as to the character
of the products offered as medicinal agents. The weight of
evidence justifies the position that these particular products
rationally should be, and as a matter of fact are, of important
special service in the utilization of these organic secretions in
medicine.

As explained in the preceding report, the Council holds that complex mixtures of remedial agents are from every point of view inimical to therapeutic progress and therefore to the public welfare. They are especially objectionable because it is impossible to determine accurately the effects which follow the simultaneous administration of a number of drugs having dissimilar actions, and because such a practice tends strongly to discourage careful consideration of the special needs of individual patients without which there can be no therapeutic progress. On the contrary, with their use, therapeutic treatment becomes haphazard and mere guesswork.

The dismissal of the holadin and bile salts mixtures does not involve the question of the usefulness of holadin or of bile salts alone; on the contrary, the possible usefulness of these preparations is admitted in the report. It is the combination of holadin, bile salts, sodium succinate and phenolphthalein to which objection is made.

The statement of Fairchild Bros. and Foster that “these combinations are now further justified in view of physiological considerations” is somewhat misleading. It is true that bile and the pancreatic secretion cooperate in intestinal digestion, but there is no evidence that in every case in which there is a deficiency of one of these secretions there is also a deficiency of the other, and it is an axiom of scientific therapeutics that no drug or remedial agent should be administered except to fill a definite want. Otherwise the practice of therapeutics becomes mere empiricism.

The properties of phenolphthalein are not in the least influenced by the manner of its introduction, as Messrs. Fairchild Bros. and Foster emphasize; but the important fact in this connection is that the popular conception of their actions is greatly influenced by the mode of introduction, and phenolphthalein has been widely advertised in a variety of conditions, so that the popular notion concerning it is not that of scientific therapeutics.

In short, the entire argument of Messrs. Fairchild Bros. and Foster concerning the exploitation of these preparations may be summed up by saying that they have been used by clinicians who believe that good results have followed their use, and that the firm will therefore continue to supply the demand. The tendency of some to use anything brought to their notice, and the readiness of manufacturers to market anything that physicians will use, presents the greatest obstacle to therapeutic progress. There was never a nostrum so irrational or worthless that honest but undiscriminating clinicians could not be found who reported wonderful results from its use.

According to Fairchild Bros. and Foster, these holadin and bile salts mixtures have been in use for some nine years. Yet the Council is not aware of any investigation of their merits that meets the requirements of scientific research.

The Council is not acquainted with a single clinical investigation of their action under conditions which afford satisfactory evidence of their therapeutic value.

It is obviously wholly insufficient for a clinician to report that the use of a mixture was followed by good results. The fallacy of such arguments was demonstrated long ago. He must make a comparison of the results obtained with the remedial agent with those obtained in as nearly similar conditions as possible except for the use of the agent. We are not aware that any such study of the mixtures in question has been made. It is in the last degree irrational to hold that because bile salts are the active constituents of bile, therefore such complex mixtures as these are necessary.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 59_)

LIQUOR SANTAIVA, S. & D., OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Liquor Santaiva, S. & D., has been authorized for publication.

W. A. Puckner, Secretary.

So far the Council has applied Rule 10 concerning the recognition of mixtures with the greatest leniency compatible with consistency. When there has been a reasonable doubt concerning the value of a mixture, it has frequently directed that Rule 10 should not apply, pending further clinical trial of such mixture.

In no instance has subsequent experience shown that a strict interpretation of the rule would have worked hardship or injustice. The Council feels that there is no longer any warrant for the admission of complex mixtures to New and Nonofficial Remedies or for the retention of any that have been admitted, unless definite evidence of the therapeutic value of such combinations is available.

The Council being engaged in the annual revision of New and Nonofficial Remedies, the referee in charge of santal preparations reported that the three year period of acceptance had expired for Liquor Santaiva (Sharp & Dohme).

The referee held that Liquor Santaiva, S. & D., declared to be a solution of santal oil and copaiba with aromatic oils, in a mixture of alcohol and water, is plainly in conflict with the current interpretation of Rule 10, because there was no sound evidence to indicate that any useful end is gained by the simultaneous administration of santal oil and copaiba in any proportion, and that so, of course, there is no evidence of the special advantage in the fixed proportions represented by the mixture. He pointed out that the formula is essentially a survival of the discredited shotgun gonorrhea mixtures and therefore recommended that its acceptance be not continued.

The Council agreed to the recommendation of the referee and directed that Liquor Santaiva, S. & D., be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 66_)

MALTZYME, MALTZYME WITH CASCARA SAGRADA, MALTZYME WITH COD LIVER OIL,
MALTZYME FERRATED AND MALTZYME WITH YERBA SANTA
OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of the Maltzyme preparations has been authorized for publication.

W. A. Puckner, Secretary.

In 1916, the Council voted to omit Maltzyme with Hypophosphites, and Maltzyme with Phosphate of Iron, Quinine and Strychnine. At that time the labels used on the Maltzyme preparations still in New and Nonofficial Remedies contained a list of Maltzyme combinations which included those which had been dismissed. As the Council does not permit an accepted article to be used as a means of advertising an article not accepted, it voted to continue the following preparations for a period of three years on condition that reference to the deleted articles be omitted from the labels when those then in stock had been used up: Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa. While the Maltzyme Company made no definite agreement to revise its advertising propaganda in accordance with the Council’s requirements, the Maltzyme preparations were retained in the belief that in due time the required revision of the labels would be made.

The Council being engaged in preparing the 1919 edition of New and Nonofficial Remedies, the referee in charge of malt extracts reported that the Maltzyme Company had not revised its labels in accordance with the stipulation of the Council. The referee further reported he had become convinced that the claim that Maltzyme is “rich in malt enzymes” is unwarranted and that the term “Maltzyme” (malt plus enzyme) is misleading; this because of the recognized instability of malt extracts (Jour. A. M. A., March 30, 1912, p. 954) and because the Maltzyme Company makes no definite statement with regard to the diastase (malt enzyme) content of its preparations.[126] For this reason it had been the referee’s intention to propose the deletion of all Maltzyme preparations when their period of acceptance expired in 1919. As, however, the present Maltzyme preparations are in contravention with the Council’s requirements, he recommended that the acceptance of these preparations be canceled now.

[126] Manufacturers are warned by the Department of Agriculture, through the Bureau of Chemistry, that combinations claiming to contain digestive enzymes must be active when sold. If preparations tend to deteriorate in a short time, each lot should be dated and not sold after the period when they become inactive. While every manufacturer must be considered innocent until proved guilty, and ignorant until proved knowing, it is a matter of knowledge that manufacturers have marketed their various digestive mixtures with full appreciation of their worthlessness.--(Jour. A. M. A., Dec. 19, 1914, p. 2234.)

The Council agreed to the recommendation of the referee and directed that Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver Oil, Maltzyme Ferrated, and Maltzyme with Yerba Santa be omitted from N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 67_)

METHAFORM OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Methaform has been authorized for publication.

W. A. Puckner, Secretary.

Methaform is the proprietary name applied by F. Stearns & Co. to chlorbutanol.

Being engaged in the annual revision of New and Nonofficial Remedies, and the term of acceptance for Methaform having expired, a trade package was purchased to determine if the product was marketed in compliance with the rules of the Council. It was then found that a circular was wrapped with the trade package which advertised Methaform Inhalant, a preparation not accepted for New and Nonofficial Remedies.

For obvious reasons, the Council does not countenance the use of an accepted article as a means of advertising an article not accepted. Accordingly F. Stearns & Co. was advised that the Council would be obliged to withdraw the acceptance of Methaform unless the objectionable circular was omitted from the Methaform packages. Stearns & Co. did not give the requested assurance, and therefore the Council directed that Methaform be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 68_)

PINEAL GLAND, RED BONE-MARROW AND THYMUS GLAND AND THEIR PREPARATIONS
OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of pineal gland, red bone-marrow and thymus gland and their preparations has been authorized for publication.

W. A. Puckner, Secretary.

Pineal gland, red bone-marrow and thymus gland were admitted to New and Nonofficial Remedies when these products gave promise of having therapeutic value.

The term of acceptance for the preparations of pineal gland, red bone-marrow and thymus gland having expired, the referee in charge of animal organ preparations recommended in his report for the annual revision of N. N. R. that these products and the general articles describing them be omitted from New and Nonofficial Remedies. He held that the experimental and clinical experience with them leads to the conclusion that they are without value.

In accordance with the recommendation of the referee, the Council voted that the following preparations be omitted from New and Nonofficial Remedies: Desiccated Pineal Gland-Armour; Pineal Gland Tablets-Armour; Extract of Red Bone-Marrow-Armour; Desiccated Thymus-Armour; Thymus Tablets-Armour.

As a matter of record, the descriptive articles for pineal gland, red bone-marrow and thymus gland, which appeared in New and Nonofficial Remedies, 1918, are given below.

Pineal Gland

The functions of this gland have not yet been established but there is some pathological and some experimental evidence that there is a relation between the gland and some processes of development and growth; the nature of this relation is unknown. Adiposis is a frequent sign of disturbed pineal function, but observers are not agreed whether to interpret this as indicating hypofunction or hyperfunction, or possibly a concurrent disturbance of the pituitary. In some instances intravenous injections of pineal extract have seemed to cause a distinct fall in blood pressure. It has been inferred from observations in cases of pineal tumors in the young that the gland in young individuals furnishes a secretion which inhibits growth, particularly the development of the reproductive glands, but the results of experimental administration of pineal substance orally have led other observers to infer that the pineal secretion favors physical and possibly mental and sexual development. It has been suggested that, as all evidence points to the fact that the function of the pineal gland is one of early life, extract of adult pineal glands might be expected to be inert. Experiment has also indicated greater activity in glands obtained from young animals than in those obtained from older ones. The Council has decided to admit preparations of pineal gland to New and Nonofficial Remedies simply for experimental purposes.

Red Bone-Marrow

Red bone-marrow consists largely (more than 90 per cent.) of fat. In new-born animals a third or more of this fat consists of lecithin. The marrow of the bones of new-born animals contains iron (up to 1 per cent. or more) in various forms of organic combination. Both lecithin and iron decrease rapidly in the first weeks after birth. The commercial preparations contain very variable amounts of these constituents.

_Actions and Uses._--Red bone-marrow is supposed to stimulate the formation of red blood corpuscles; whatever action it may have in this direction is probably due largely to the iron and lecithin which it contains.

It is said to be useful in simple and pernicious anemias.

Thymus Gland

Little is known as to the functions of the thymus, but it is believed to have an important relation to growth. There also seems to be some relation between the thymus and thyroid, for the former is frequently abnormal in diseases involving the latter (hyperthyroidism).

The use of thymus is purely empirical. It has been employed in the treatment of hyperthyroidism, rickets, tuberculosis, hemophilia, and infantile marasmus and atrophy; its use in the latter conditions is said to be the most promising. It is claimed on very doubtful grounds to exert a somewhat favorable effect in certain cases of cancer.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 69_)

PIPERAZINE AND LYCETOL OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Nonofficial Remedies of Piperazine and Lycetol has been authorized for publication.

W. A. Puckner, Secretary.

Piperazine (diethylenediamene) and Lycetol (a methyl derivative of diethylenediamene) were accepted for New and Nonofficial Remedies in 1906. Both Piperazine and Lycetol were asserted to be efficient uric acid solvents and efficacious remedies in the treatment of gout and rheumatism. These products have been retained until now because there was no investigation which definitely showed their uselessness as uric acid solvents, though their use is generally admitted to have been disappointing.

From an exhaustive and critical study of the available evidence, Hanzlik (Jour. Lab. & Clin. Med., February, 1917) concluded that scientific evidence, though limited, and clinical opinion indicate that Piperazine is valueless in gout and that there is sufficient scientific evidence to indicate the worthlessness of Lycetol.

The referee in charge of Piperazine and Lycetol recommended that these products be omitted from New and Nonofficial Remedies for the reason that they have been sufficiently tried to justify the conclusion that they are not of value. The period of acceptance having expired, the Council directed that Piperazine and Piperazine Tablets (The Bayer Company, Inc.) and Lycetol (The Bayer Company, Inc.) be omitted from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 70._)

STANOLIND LIQUID PARAFFIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

As explained in the report which follows, “Stanolind Liquid Paraffin” was omitted from New and Nonofficial Remedies at the request of the proprietors. Announcement of this omission was made in the preface to New and Nonofficial Remedies, 1918, but publication of the Council’s report was postponed pending actual conflict with the rules. The Council now authorizes publication of the report because a circular indirectly advertising the product to the public was found enclosed with the trade package of Stanolind Liquid Paraffin.

W. A. Puckner, Secretary.

Stanolind Liquid Paraffin was admitted to New and Nonofficial Remedies in 1916, when its method of marketing conformed to the rules of the Council. This brand of liquid petrolatum, by action of the Council, has been omitted from New and Nonofficial Remedies on request of the Standard Oil Company of Indiana, its manufacturer, who wrote to the Secretary of the Council stating that:

“In order that our facilities for the manufacture of this oil shall
be constantly engaged, it will be necessary for us to find sales
on a larger scale than in the past. To do this under our present
advertising and marketing arrangement we feel will be impossible.”

This letter, in addition, suggested “that physicians are not prescribing Stanolind Liquid Paraffin in any considerable proportion of their orders” and “that the situation which now confronts us would not be materially helped if Stanolind was specified in all such prescriptions.” Further, the Council is asked to consider whether it “might be willing to declare this preparation as not a Council product,” on the alleged grounds that “liquid paraffin is not medicinal in its action and passes through the digestive tract in practically unaltered condition.”

The Council holds that Stanolind Liquid Paraffin is a drug, and that, therefore, its direct advertising to the public is in contravention of the Council’s rules. Constipation should be treated by dietary and hygienic means. Evacuants are only temporary measures. Liquid petrolatum is medicinal; it greatly modifies the intestinal flora; it acts as a lubricant and emollient; it modifies the absorptive powers of the intestinal mucous membrane; it is capable of influencing the digestion of fats. In short, liquid petrolatum, being a drug, its indiscriminate and excessive use should not be encouraged.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 72_)

WESTERFIELD’S DIGITALIS TABLETS

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Westerfield’s Digitalis Tablets (The Westerfield Pharmacal Co., Dayton, Ohio) are claimed to represent a fat free tincture of digitalis and to be “enteric coated.” It is claimed that because of this coating these tablets pass the stomach unchanged and dissolve in the intestine, and that this obviates any possibility of gastric disturbance.

The circular which sets forth the asserted advantages of the tablets states that digitalis contains a fat which is an irritant to the gastric membrane. It also contains the following:

“We feel no hesitation in saying that if this remedy is given a
fair trial where it is properly indicated, the result obtained will
be a gratifying surprise.

“It is a common expression from physicians who have tried this
remedy to say, ‘Surely I have never used Digitalis before.’”

If these quotations mean anything, they imply that these tablets present a distinct advance in digitalis therapy. There is no warrant for such a claim. The statement with reference to the occurrence of an oil in digitalis is partly false and partly misleading. Tincture of digitalis, which the tablets are claimed to represent, is fat free; the fixed oil that is present in the drug is not soluble in 70 per cent. alcohol, the menstruum used for the preparation of the official tincture of digitalis. Furthermore, a fairly large amount of this oil (such as is present in 100 therapeutic doses of the drug) is incapable of causing gastric disturbance. Gastric disturbance is a side action that is inseparable from slight overdosage with all true digitalis bodies and is not in any way due to local gastric action. The claim that such action is prevented by the use of enteric pills or tablets is obviously false and misleading.

The alleged “common expression from physicians who have tried this remedy” does not constitute acceptable evidence of the value of the preparation.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Nonofficial Remedies because unwarranted therapeutic claims are made for this product.

When the preceding report was submitted to the Westerfield Pharmacal Co., a reply was received indicating that the firm did not know that progressive manufacturers had discontinued the claim that “fat free” digitalis preparations were devoid of gastric effects. It also submitted a revised circular, which, however, reiterated the claim that the tablet presented a distinct advance in digitalis therapy in that it was “fat free,” and coated to prevent disintegration in the stomach.

Since tincture of digitalis and extract of digitalis are practically devoid of fatty material, and since it is now well known that the fat does not cause gastric disturbance and that therapeutic doses of digitalis do not exert a local irritant action on the stomach, the manufacturer’s product and the claims made for it merely tend to perpetuate old errors.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Nonofficial Remedies on the ground that this presents an unessential modification of pills of an official substance. It directed publication of its report with this explanation.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 75_)

XEROFORM-HEYDEN AND BISMUTH TRIBROMPHENATE-MERCK
OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Bismuth Tribromphenate-Merck and Xeroform-Heyden. These two products were found not to comply with the standards for bismuth tribromphenate adopted for New and Nonofficial Remedies, and hence could not be retained. As the manufacturers of both products announce that efforts toward the production of a satisfactory product are continued, the omission of the two brands is without prejudice to their reacceptance when a satisfactory product becomes available.

W. A. Puckner, Secretary.

The referee in charge of bismuth preparations submitted the following report of the A. M. A. Chemical Laboratory which shows that Xeroform-Heyden and Bismuth Tribromphenate-Merck do not comply with the adopted standards for bismuth tribromphenate.

Some time ago a request was received from the Medical Section
of the National Council of Defense for a report on a brand of
bismuth tribromphenate. In accordance with this request the firm’s
product was examined, and at the same time and for comparison, an
examination was also made of a specimen of bismuth tribromphenate
received from Merck and Company, October, 1915, and of another
specimen of bismuth tribromphenate “Xeroform-Heyden” obtained from
the Chicago branch of the Heyden Chemical Works in April, 1918.

The examination brought out that the bismuth tribromphenate
submitted to the national Council of Defense contained a large
amount of uncombined tribromphenol, while the specimen of
Xeroform-Heyden contained an excessive quantity of bismuth.

When the latter finding was submitted to the Heyden Chemical Works,
the firm stated: “The product had to be made in this country after
importations from Europe became impossible and the first lots were
not fully up to the standard ...” The firm stated that it could now
furnish a product which it considered fully equal to that which
was previously imported, and offered to submit “samples of the new
material.”

Having been requested to do so, a specimen of Xeroform-Heyden was
received from the Heyden Chemical Works, New York. This and a
second specimen, purchased from a Chicago wholesale drug house,
were examined. Whereas the standards for bismuth tribromphenate
which had been formulated by the Laboratory and accepted by the
Heyden Chemical Works required that the product should contain
from 40 to 49 per cent. of bismuth and contain not more than 3.3
per cent. of uncombined tribromphenol, the specimen purchased in
Chicago contained 67.7 per cent. of bismuth, while the specimen
received direct from the Heyden Chemical Works contained 24 per
cent. of uncombined tribromphenol. When this result was reported to
the Heyden Chemical Works, the firm replied:

“It seems that we are not yet in a position to supply a product
that answers a uniform standard and that we have to continue our
efforts in this direction.

“We will take this matter up with you again as soon as we have
been successful ...”

At the time when the preceding examination was being made,
bismuth tribromphenate-Merck could not be obtained from the
Chicago wholesale houses. A request sent to Merck and Company
for a specimen of the market supply brought the information that
the product was temporarily unavailable. Though unable to supply
the product, the firm gave valuable advice for a revision of the
somewhat loosely drawn tests for bismuth tribromphenate in New and
Nonofficial Remedies, 1918.

Recently (November, 1918) Merck and Company sent a specimen of its
product labeled “Bismuth Tribromphenate-Merck” “Merck and Company,
New York, Distributors and Guarantors,” and wrote “... You will
notice this sample conforms in nearly all details to the tests we
submitted with our letter of June 4th. We have been able to produce
better goods, but just at present unsatisfactory starting material
confronts us. The sample conforms to N. N. R., 1918, but will not
meet the test for uncombined tribromphenol submitted by you in your
letter of September 4th ...”

Examination of the specimen demonstrated that it was soluble to a
considerable extent in alcohol (the N. N. R., 1918, description
provides that it should be only slightly soluble in alcohol)
and according to the standards adopted for New and Nonofficial
Remedies, 1919, contains 18 per cent. uncombined tribromphenol
(more than five times the permitted amount).

In view of the Laboratory’s report, the referee recommended that the acceptance of Xeroform-Heyden and Bismuth Tribromphenate-Merck be withdrawn, without prejudice to their reinstatement when satisfactory products are again offered for sale. The Council adopted the recommendation of the referee, and accordingly Xeroform-Heyden and Bismuth Tribromphenate-Merck are omitted from New and Nonofficial Remedies, 1919.

When the Laboratory’s findings with regard to Xeroform-Heyden and the action of the Council deleting the article from New and Nonofficial Remedies was reported to the Heyden Chemical Works, the firm expressed regret that efforts to produce a product equal to that formerly obtained from Germany had so far not been successful and announced that it had decided to withdraw Xeroform-Heyden from the market for the present.

When Merck and Company was advised in regard to the report of the Laboratory and the Council’s action, this firm questioned the feasibility of producing a product meeting the Council’s standards and suggested that the test for free tribromphenol be revised to permit as much as 15 per cent. of this constituent. When Merck and Company was reminded that its product, submitted in 1915, essentially complied with the adopted standards and that the estimate of the therapeutic value of bismuth tribromphenate is based on a product essentially free from alcohol-soluble material, the firm replied:

“As stated in our letter of the 12th inst. we do not wish to market
the chemical unless it meets all legitimate requirements of the
physicians that use it. If, therefore, your standard proves to be
good and it is commercially possible to make supplies conforming to
it, we shall do so. We shall discontinue the article unless it is
of suitable quality.”

--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 76._)

CREAM OF MUSTARD REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Cream of Mustard, The Cream of Mustard Co., South Norwalk, Conn., is said to be made by mixing 2 drachms of oil of mustard and 2 drachms of oil of turpentine with one pound of white petrolatum. According to the label it is “for Tonsillitis, Rheumatism, Sore Muscles, Croup, Pleurisy, Frosted Feet, Sore Throat, Neuralgia, Sprains, Bronchitis, Headache, Chilblains, Stiff Neck, Congestion, Bruises, Asthma, Lumbago, Pains and Aches, Colds in Chest.”

The Council refused recognition to Cream of Mustard:

Because it is a simple pharmaceutical mixture of well-known ingredients and has no advantage over established rubefacients which every physician knows how to prescribe and every pharmacist to compound. Incidentally, the name “Cream of Mustard” is misleading and not descriptive of the composition of this pharmaceutical of oils of mustard and turpentine.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 79_)

“PLURIGLANDULAR” MIXTURES

Caps. Adreno-Spermin Comp., Caps. Antero-Pituitary Comp.,
Caps. Placento-Mammary Comp., Caps. Thyro-Ovarian Comp.,
Caps. Hepato-Splenic Comp., Caps. Pancreas Comp., and
Caps. Thyroid Comp., Not Admitted to N. N. R.

Report of the Council on Pharmacy and Chemistry

After considering the evidence for the several “pluriglandular” mixtures described below, the Council declared them inadmissible to New and Nonofficial Remedies. The Council’s action was communicated to the manufacturer, Henry R. Harrower, in accordance with the usual procedure. After giving due consideration to the manufacturer’s reply the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

With the offer “to supply you with as much literature as may be necessary and as little of the actual remedies as may be desired” if “the prospects for the inclusion of these formulas in N. N. R. are good,” Henry R. Harrower sent the Council a booklet descriptive of his preparations and labels for the following mixtures:

_Caps. Adreno-Spermin Comp._, each said to contain “Adrenal Gland
(total) gr. 1/4, Thyroid Gland (U. S. P.) gr. 1/12, Spermin
Extr. (from Gonads), Brain and Spinal Cord aa gr. 1, Calc.
Glycerophosphate q. s. ad gr. 5.”

_Caps. Antero-Pituitary Comp._, each said to contain “Anterior
Pituitary Body gr. 2, Thymus Gland gr. 1, Thyroid Gland (U. S. P.)
gr. 1/12, Calcium-phosphorus Comp. q. s. ad gr. 5.”

_Caps. Placento-Mammary Co._, each said to contain “Desiccated
Placenta gr. 2, Mammary Substance gr. 1-1/2, Pituitary Body (total)
gr. 1/3, Calcium-phosphorus Comp. q. s. ad. gr. 5.”

_Caps. Thyro-Ovarian Comp._, each said to contain “Desic. Corpora
Lutea Ovarian Substance gr. 2-1/2, Thyroid Gland (U. S. P.) gr.
1/12, Pituitary Gland (total) gr. 1/8, Calcium-phosphorus Comp. q.
s. ad gr. 5.”

_Caps. Hepato-Splenic Comp._, each said to contain “Liver
Parenchyma, Spleen Substance aa gr. 2, Powd. Bile Salts gr. 1/2,
Adreno-Spermin Co. (No. 1) gr. 1.”

_Caps. Pancreas Comp._, each said to contain “Adrenal Gland,
Pituitary Gland (total) aa gr. 1/2, Ovarian Substance gr. 1,
Pancreas Substance q. s. ad gr. 5.”

_Caps. Thyroid Comp._, each said to contain “Desic. Thyroid Gland
(U. S. P.) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”

The Council declared these preparations inadmissible to New and Nonofficial Remedies, for reasons which follow:

1. Each of the mixtures contains one ingredient or more, which is neither recognized in the U. S. Pharmacopeia nor admitted to New and Nonofficial Remedies, namely: “Spermin Extract,” “Brain,” “Spinal Cord,” “Desiccated Placenta,” “Liver Parenchyma,” “Spleen Substance,” “Pancreas Substance” and “Calcium Phosphorus Comp. (Each 100 gm. represents Magnes. Phos. 1; Calc. glycerophos. 4; Potas. bicarb. 15; Sod. bicarb. 22 and Sod. chlor. q. s.).” For obvious reasons the Council does not accept a mixture containing an indefinite ingredient and hence it would be necessary as a preliminary for the consideration of any one of the mixtures that their unofficial ingredients be made eligible for New and Nonofficial Remedies by the submission of evidence that such ingredient is of uniform composition and that it is therapeutically valuable when given by mouth. There is no evidence that many of these organs have any value whatever when administered by the mouth or in any other way.

2. In the light of our knowledge the administration of gland mixtures in the host of conditions enumerated in the advertising circular is irrational and on a par with the use of the shotgun mixtures once in vogue.

Be it a pharmaceutical mixture, a “mixed” vaccine, or a “pluriglandular” product, the combination of two medicinal ingredients in a mixture must be considered contrary to rational therapy unless a good reason exists for such combination. Such mixtures are held in conflict with Rule 10 unless the manufacturer presents acceptable evidence for the value of his combination. A physician may prescribe any mixture which he considers indicated in a given case, but the marketing of mixtures of drugs in fixed proportions is in most instances irrational and a detriment to sound therapy.--(_From The Journal A. M. A., Jan. 18, 1919_)

CERELENE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report declaring Cerelene inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Cerelene, a paraffin preparation for the treatment of burns, was submitted to the Council by the Holliday Laboratories, with the statement that it was composed of 84 per cent. paraffin, 15 per cent. myricyl palmitate, and 1 per cent. purified elemi gum to which is added oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was explained:

“Myricyl Palmitate is a purified form of Beeswax, free from all
impurities, acids, etc., which is solely manufactured by this
Company....”

It was also stated that on “special order” Cerelene has been made containing oil of eucalyptus and resorcin, oil of eucalyptus and picric acid, and picric acid alone. The following report on the preparation was presented to the Council by the referee to whom Cerelene had been assigned:

Cerelene is another compound wax for the treatment of burns.
According to the work of Sollmann (J. A. M. A., 68:1799, 1917) it
is highly improbable that compound mixtures have any advantage over
simple paraffin of low melting point. Cerelene must therefore be
considered as an unessential modification of paraffin, and as in
conflict with Rule 10; unless definite evidence of superiority is
submitted. Cerelene mixtures containing medicinal ingredients also
appear unscientific since the evidence that the ingredients do not
leave the wax has not been successfully contradicted. Finally, the
claims made for Cerelene are rather extreme, and would need some
revision before they could be accepted.

The A. M. A. Chemical Laboratory reports:

The physical properties of Cerelene are as follows:

Melting point 50.0 C. by U. S. P. method.
Ductility limit 30.5 C.
Plasticity limit 26.4 C.
Not strong at 38 C.

Adheres moderately well; detaches with “pulling.” On heating,
readily loses eucalyptol, and a small amount of resinous substance
forms in the bottom of the beaker. If Cerelene is heated to 145 C.
and cooled, the resulting product no longer has the properties of
the original Cerelene.

It is recommended that the preceding report be sent to the Holliday Laboratories, and that unless its superiority over simple paraffins is demonstrated and the unwarranted claims abandoned, Cerelene be declared inadmissible to New and Nonofficial Remedies for conflict with Rules 6 and 10.

This report was submitted to the Holliday Laboratories with the information that it had been adopted, Oct. 3, 1917. It was also explained that before Cerelene could be accepted, the unofficial and unstandardized constituent “myricyl palmitate” would have to be considered and accepted for New and Nonofficial Remedies since, for obvious reasons, the Council does not accept a preparation which contains an unofficial and unstandardized substance not in N. N. R.

The Holliday Laboratories acknowledged receipt of the Council’s report and asked that the matter be held in abeyance until the requested evidence had been obtained. Later the Council was advised that the advertising circulars for Cerelene had been withdrawn with the exception of one giving directions for its use. Five months later, the firm stated that experiments were being made “to determine the actual strength of Cerelene in comparison with other paraffin waxes....” Nothing further has been heard from the Holliday Laboratories and no reply has been received to an inquiry made Oct. 12, 1918. The Council therefore authorizes publication of its report declaring Cerelene inadmissible to New and Nonofficial Remedies.--(_From the Journal A. M. A., Feb. 15, 1919_).

COLLOSOL COCAINE NOT ADMITTED TO N. N. R

Report of the Council on Pharmacy and Chemistry

The report which appears below was adopted by the Council and sent to the Anglo-French Drug Co., Ltd., New York, for comment in December, 1918. No explanation has been received from the manufacturer. For the information of the profession the Council has now authorized publication of the report.

W. A. Puckner, Secretary.

“Collosol Cocaine” was submitted to the Council in October, 1918, by the Anglo-French Drug Co., Ltd., New York, under the claim that it was an “absolute colloid” and that it contained “1 per cent. cocain.” The label on the submitted specimen declares:

“Collosol Cocaine 1-100”

“... the Cocaine exists as the pure alkaloid in the Colloidal
state--the condition in which it is isomorphic with the protein
of the body fluids. The effect is more prolonged than that of
a molecular Cocaine Solution and being _non-toxic_ absorption
presents no practical danger.”

The product was assigned to the Committee on Pharmacology for consideration. The following report was submitted and its adoption by the Council recommended by the committee:

“Collosol Cocaine” is said to be a colloidal form of cocain and
is alleged to possess a remarkably low toxicity. The subjoined
report of the A. M. A. Chemical Laboratory, however, shows that the
preparation does not have the composition claimed for it and it is,
in effect, misbranded. In fact, the English manufacturers concede
that it is not an “absolute colloid” and that the declaration with
regard to the percentage of cocain is incorrect.

It is recommended that, without considering other conflicts with
the rules of the Council at this time, “Collosol Cocaine” be
declared inadmissible to New and Nonofficial Remedies for conflict
with Rule 1 which requires that the composition of an article
must be correctly declared. The report of the A. M. A. Chemical
Laboratory is appended.

REPORT OF THE A. M. A. CHEMICAL LABORATORY

Simpson, Hewlett and Eyre (_Lancet_, April 28, 1917, p. 660) reported “Collosol Cocaine” to be much less toxic than cocain. These writers, however, did not verify the statements as to the composition and in the light of subsequent chemical examination it is not to be wondered at that “Collosol Cocaine 1.0 per cent.” was much less toxic than a solution containing 1.0 per cent. of cocain hydrochlorid.

Barger, Dale and Durham report from the Department of Biochemistry and Pharmacology, Medical Research Committee (_Lancet_, Dec. 1, 1917, p. 825), that they examined “Collosol Cocaine” and found it to contain but 0.25 per cent. of cocain. They also found that the cocain was not present in a colloidal form. Discussing the low toxicity claimed by the manufacturers, these investigators state:

“In the samples which we examined the toxicity was, indeed, much
lower than that of an ordinary 1 per cent. solution of a cocain
salt; but the local anesthetic action was low to a corresponding
degree, and both actions corresponded satisfactorily with the
proportion of cocain chemically recoverable from the solution.”

Stroud, of the Crookes Laboratory (which manufactures the preparation), who apparently had been informed of this work in advance of publication, admits the correctness of it, and states (_British Medical Journal_, Nov. 24, 1918, p. 710) that “whilst the colloidal protective apparently absorbs a portion of the cocain, the remainder is found not to exhibit the attributes of a colloid,...”

The specimen of “Collosol Cocaine” submitted to the Council and labeled “Collosol Cocaine 1-100” was found to contain at most 0.4 per cent. cocain. The examination was made in accordance with the method used by Barger, Dale and Durham and calculated as cocain. This method, however, probably would not distinguish between cocain and basic decomposition products, but would include all as cocain in the amount found. The specimen of “Collosol Cocaine” examined was neutral or slightly acid, a fact which tends to confirm the conclusion of the British investigators that “Collosol Cocaine” contains cocain in noncolloidal form and precludes an increased physiologic effect due to alkalinity.