Chapter XIX: Introduction: The Council on Pharmacy and Chemistry was established (12)

Hitherto most of the local remedies used in these conditions
have either been too irritating to be employed in sufficient
concentration to be efficient or they have lacked efficiency per
se....

Medeol suppositories do not contain any narcotic or any caustic or
other constituent having violent action; their blandness permits of
their use in either sex and at all ages.

The claims made for these preparations--as for instance “that surgical treatment ... should rarely be undertaken until Medeol Suppositories have been given a thorough trial”--are misleading in that they create the inference that the limitations in the palliative treatment of piles have been overcome. It is altogether untrue that these mixtures can be expected to “relieve the most obstinate cases,” as stated in a Medeol circular. This, from an Anusol circular, is equally misleading:

“If dietetic and other requirements are complied with, even the
most obstinate chronic cases will frequently readily yield to
treatment with Anusol Suppositories.”

The Council declared Medeol Suppositories inadmissible to New and Nonofficial Remedies because their composition is secret (Rules 1 and 2); because unwarranted therapeutic claims are made for these (Rule 6); because the name is objectionable (Rule 8), and because the combination is unscientific (Rule 10).

In those cases of hemorrhoids in which palliative measures may be expected to enable the patient to avoid surgical interference and afford relief from attacks, the object should be to secure cleanliness, to avoid irritation, whether it be by friction or irritating fecal matter, to reduce inflammation by astringents and, when necessary, to relieve pain by analgesics. If an antiseptic dusting powder is desired, boracic acid in impalpable powder with talc may be employed; if an astringent, finely powdered oxid of zinc may be added; if a local analgesic is necessary, a little extract of belladonna may be incorporated with petrolatum or other ointment base. The main reliance, in any event, should be to effect normal bowel movements by regulating the diet rather than by the use of purgatives; the use of warm water to insure cleanliness; the avoidance of irritation, especially that caused by friction and secretions; a mild astringent to reduce inflammation.--(_From The Journal A. M. A., March 9, 1918_)

GUAIODINE

Report of the Council on Pharmacy and Chemistry

The following report on Guaiodine, marketed by the Intravenous Products Company, Denver, has been adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

A referee of the Committee on Pharmacology, in submitting to the Council a report from the A. M. A. Chemical Laboratory on Guaiodine, advises that the Laboratory’s examination shows that instead of containing free “colloidal” iodin as claimed, the preparation is essentially an iodated fatty oil, containing only combined iodin. Equally misleading, in view of the Laboratory’s findings, are the implied claims that the antiseptic action of Guaiodine corresponds to that of free iodin.

Guaiodine is advertised mainly for the treatment of gonorrhea. While it may be true that the guaiacol contained in Guaiodine has some beneficial effect, especially when preceded by potassium permanganate irrigation as advised, the advertised claim that “Guaiodine acts as a specific for gonorrhea in a majority of cases” is utterly false.

The “case records” offered to establish the therapeutic value of Guaiodine are in themselves sufficient to condemn the “evidence.” The following are fair samples:

“The second boy came a day or so later with a slight discharge with
the characteristic burning and itching, and with symptoms of a
beginning gonorrhea, and judging from the source of the infection,
it was believed to be so. Two injections of Guaiodine were given
when the discharge ceased.”

“I have several cases that were completely cured in a very short
time. I note this, that the first dose causes a cessation of the
discharge and the second seems to increase the flow, but the color
is changed. I give three doses, and then use a mild wash, and in
ten days they are well. I am very pleased with this preparation and
very truly believe that it is the best there is to date for the
positive cure of gonorrhea.”

REPORT OF THE CHEMICAL LABORATORY

Guaiodine is manufactured by the Intravenous Products Company, Denver, Colorado. The “literature” which accompanies the product describes Guaiodine as:

“... an electro-chemically prepared iodin, suspended in oil,
containing iodin, the same strength as the U. S. P. tincture
of iodin, or 7 per cent., together with a therapeutic dose of
guaiacol.”

The Intravenous Products Company claims that Guaiodine is made by an “electro-chemical process of preparing colloidal iodine,” discovered by one E. B. Page, and that by this process the tendency of iodin to produce iodism has been “overcome.” It is said to be “pre-eminently an antiseptic and germicide.” Guaiodine is a dark brown, oily liquid with a specific gravity of 0.9845 at 15.6 C. and an odor suggestive of guaiacol. Its solubilities were those of a fat. Free iodin was absent in the recently purchased specimen (traces were present in an older one). Steam distillation indicated that the product consisted of volatile and nonvolatile constituents. The volatile matter was concluded to consist, in the main, of guaiacol or some guaiacol-like body, and the nonvolatile matter to be an iodized fatty oil. Quantitative determinations indicated that Guaiodine contained about 7.25 per cent. of iodin in combination, and that it is composed approximately of 3 per cent. volatile matter and 97 per cent. nonvolatile matter. Hence Guaiodine appears to be an iodized fatty oil to which a small amount of guaiacol or some guaiacol-like substance has been added.

THE COUNCIL’S ACTION

On the recommendation of the referee, the Council voted that Guaiodine be declared inadmissible to New and Nonofficial Remedies because of false statements as to composition and action.--(_From The Journal A. M. A., April 6, 1918._)

SEVERAL “MIXED” VACCINES NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The “mixed” vaccines which are discussed in the reports that follow were considered by the Council during the past year because inquiries had been received in regard to them.

In publishing these reports it is desirable that the attitude of the Council toward “mixed” vaccines again be stated. In view of the rapid development of bacterial therapy, the possibility for harm that attends the use of bacterial vaccines and the skepticism among experienced clinicians as to the value of vaccines representing a combination of organisms, the Council has felt that it should scrutinize the claims for such agents with exceptional care and that there should be admitted to New and Nonofficial Remedies only those vaccine mixtures for which there is acceptable evidence to indicate that the use of the particular mixtures is rational.

In considering the subject the Council has borne in mind the fact that in many institutions in which cases are studied and the results of therapeutic measures carefully observed and controlled, vaccines of any sort are practically never used--certainly here the stock mixed vaccine has no recognition. Experienced clinicians have generally come to the conclusion that mixed vaccines have no specific action and that any effect they may produce is due to a non-specific protein reaction.

As set forth in the reports, in no case was the evidence submitted by the proprietors sufficient to establish the claims made for the preparations. Hence none was accepted for New and Nonofficial Remedies.

The preparations that form the basis for the accompanying reports are only a few of the many that are being made and sold by some biological houses. Doubtless many of those not dealt with in this report are equally irrational and sold under claims equally--or probably even more--unwarranted than those with which the present report deals.

W. A. Puckner, Secretary.

Mixed Vaccines-Abbott

In response to inquiry the Council undertook a consideration of the following “mixed{”} vaccines sold by the Abbott Laboratories:

_M. Catarrhalis-Combined-Bacterin_, said to contain killed Micrococcus catarrhalis, Bacillus Friedländer, Pneumococci, Streptococci, Staphylococcus aureus and Staphylococcus albus.

_B. Coli-Combined-Bacterin_, said to contain killed Streptococcus viridans, Streptococcus hemolyticus and Bacillus coli.

_Pertussis-Combined-Bacterin_, said to contain killed Bacillus pertussis, Pneumococci, Streptococci, Staphylococcus albus, Staphylococcus aureus and Micrococcus catarrhalis.

_Streptococcus-Rheumaticus-Combined-Bacterin_, said to contain killed “Streptococci (Rheumaticus, Viridans, etc.)” and Pneumococci.

_Streptococcus-Viridans-Combined-Bacterin_, said to contain killed Streptococcus viridans, Streptococcus hemolyticus, Pneumococcus and Staphylococcus albus.

The Abbott Laboratories were asked to assist in the investigation of these products and to submit evidence to establish their eligibility for admission to New and Nonofficial Remedies. The manufacturer was informed that the Council accepts “mixed” vaccines or bacterins, provided the usefulness of these products is established by acceptable clinical evidence, and references to the literature bearing on the value of the preparations were requested.

The Abbott Laboratories submitted specimens of the products, the advertising matter therefor and a considerable list of references to current literature; all of which was transmitted to the Committee on Serums and Vaccines for consideration. In due time a referee of the committee submitted the following report:

THE COMMITTEE’S REPORT

The referee has studied the literature covered by the references submitted. In general the articles are favorable to the use of vaccines, though many of these papers do not consider “mixed” vaccines; indeed, a number of the articles do not discuss treatment at all, but are devoted entirely to the consideration of etiology of the disease. Many of the papers are by those who are obviously overenthusiastic on the subject of the use of biologic preparations. One paper--not included in the references submitted by the Abbott Laboratories--records an alarming reaction following a dose of mixed vaccine; no claim is made that improvement followed.

The following comments on the submitted references are offered:

_M. Catarrhalis-Combined-Bacterin._--Only four of the nine references given deal with the therapeutic use of the vaccine. The reported results in general were favorable, but sometimes in the discussion evoked by certain of the papers, views the reverse of those expressed by the author were brought forward. The enthusiasm of one writer is shown in his statement that following the use of vaccine in cases of carbuncle complicating diabetes the sugar in the urine disappeared or was reduced. One observer, who reports excellent results in nasal pharyngeal catarrh, speaks of certain vaccines as “bulk goods,” while another considers “----’s No. 7” as the proper thing. It is evident that the reports are not based on careful, scientific data, or such unscientific definition of the product employed would not be used.

_B. Coli-Combined-Bacterin._--In the references cited in support of this preparation the following general statements are noted: One enthusiastic writer says, “It must be recognized that we have no satisfactory explanation of the action of vaccines, and their use at present is empirical.” One author dwelt on the superiority of autogenous vaccines but admits that occasionally stock vaccines are indicated. One vaccine therapist in concluding an article states, “It is simply impossible to practice modern urology without our modern biologic products.” Yet it is a well-known fact that many successful and capable genito-urinary surgeons avoid the use of vaccines, mixed or simple.

_Pertussis-Combined-Bacterin._--These reports are uniformly favorable, but are not controlled and their value is not to be compared with a recent report from the New York City Department of Health which indicates that the vaccine is practically valueless. It is noted, further, that one of the articles cited which dealt rather fully with the treatment of pertussis did not mention vaccines.

_Streptococcus-Rheumaticus-Combined-Bacterin._--The references cited in support of the preparations by the manufacturer give no support whatever for the use of mixed stock vaccines. The first reference deals with the relation of Streptococcus viridans to arthritis deformans and endocarditis and reports the following cases:

_Case 1._--Vaccine case--improvement after eight months.
_Case 2._--Slight improvement following use of vaccine.
_Case 3._--Slight improvement following use of vaccine.
_Case 4._--Marked improvement.
_Case 5._--Prompt improvement.
_Case 6._--Vaccine not mentioned.
_Case 7._--Vaccine followed by slight improvement.

In each of the cases other methods of treatment were used. The paper shows the etiologic relation of Streptococcus viridans rather than the value of vaccines. There is no indication that stock vaccines were used, though the paper is not clear on this point. The second paper deals with the application of vaccine therapy in the treatment of arthritis. This paper is by a man who is avowedly an enthusiast on vaccine therapy. The indications are that he generally used a mixed autogenous vaccine, but the reports of cases are not always clear. This writer apparently makes no serious attempt at the classification of the joint conditions he treats. The third reference is a purely experimental study and has no bearing on the use of vaccines in treatment. The fourth article was admitted by the manufacturer to be “negative as regards evidence.” The fifth reference specifically states that “the vaccine must be autogenous.” The sixth reference deals with the experimental production of appendicitis by the use of diplococci, and has not the most remote bearing on the use of vaccines in the treatment of rheumatism.

_Streptococcus-Viridans-Combined-Bacterin._--The article which bears evidence of more care than the others admits that we are not in position to state the value of vaccines in pyorrhea but the author believes they may have value supplementary to local treatment.

It is not surprising that a large number of favorable reports can be accumulated when we appreciate how promptly men report what they consider to be their successes and how commonly they leave their failures unrecorded. Bearing in mind the fact that these stock mixed vaccines, though before the profession for many years, have not been used, or continued in use, in hospitals where work is rigidly controlled and that they are used practically not at all in the large government hospital service, a candid critic must hold that there is no substantial evidence in favor of the therapeutic use of a mixed vaccine, certainly not for stock “goods” and that probably there is but a limited field for the employment of autogenous vaccines.

The referee calls attention to a shift in the advertising matter on vaccines--the tendency to recommend vaccines to be used in conjunction with drugs. A heading in the Abbott booklet reads, “The Biologics Do Not Replace Drugs”; and the paragraph speaks of serums and bacterins as “new tools, supplemental to those we already have, but not replacing them.” ... “We need them both.”

The referee recommends that the several mixed vaccines discussed in this report be not accepted on the grounds that satisfactory evidence of their value is wanting.

Having been endorsed by the Committee on Serums and Vaccines the Council adopted the report and declared M. Catarrhalis-Combined-Bacterin, B. Coli-Combined-Bacterin, Pertussis-Combined-Bacterin, Streptococcus-Rheumaticus-Combined-Bacterin and Streptococcus-Viridans-Combined-Bacterin ineligible for admission to New and Nonofficial Remedies.

Catarrhal Vaccine Combined-Lilly and Influenza Mixed Vaccine-Lilly

Because of inquiry received, the Council requested Eli Lilly and Company to aid in determining the acceptability of the following products for New and Nonofficial Remedies: “Catarrhal Vaccine Combined,” said to contain killed cultures of the Bacillus of Friedländer, Micrococcus catarrhalis, Staphylococcus aureus and albus, Pneumococcus and Streptococcus; “Influenza Mixed Vaccine,” said to contain killed cultures of Staphylococcus albus and aureus, Streptococcus, Pneumococcus, Micrococcus catarrhalis and Bacillus influenzae.

Lilly and Company sent the circulars, etc., used in advertising these products. A circular for “Catarrhal Vaccine Combined” contained the following claim:

“Catarrhal Vaccine has been especially useful in many respiratory
infections, including bronchitis, pharyngitis, rhinitis, chronic
catarrh and in the mixed infections of pulmonary tuberculosis.”

A circular for “Influenza Mixed Vaccine” contained the following:

“The vaccine is useful in the treatment of influenza and ordinary
colds, and in any infection in which the Bacillus influenzae is the
causative agent.”

An advertising pamphlet contained the following:

“Catarrh, Acute and Chronic; Colds, Influenza.--The micro-organisms
capable of producing catarrhal conditions of the nose and pharynx
and most commonly isolated are B. Friedländer, M. catarrhalis,
staphylococcus, pneumococcus (in infections beginning in the
larynx), _B. influenza_ and streptococcus. These organisms are
found normally in the respiratory passages and acquire virulence
only when resistance has been lowered through overwork, exposure to
cold, etc.

“The results following the use of Catarrhal Vaccine Combined
(in the non-epidemic forms) and influenza Mixed Vaccine (in the
epidemic types) have been very satisfactory, due to the great
vascularity of the tissues. Acute attacks are aborted altogether
or shortened in duration and the danger of complications greatly
minimized.”

No evidence was submitted which warrants the preceding claims nor is the Council aware of any reliable testimony to indicate that the administration of the mixture here discussed is warranted or desirable. On the recommendation of the Committee on Serums and Vaccines the Council voted that “Catarrhal Vaccine Combined-Lilly” and “Influenza Mixed Vaccine-Lilly” be not included in New and Nonofficial Remedies because satisfactory evidence of their value is wanting.

Influenza Serobacterin Mixed-Mulford

Because of inquiry received, the Council took up the consideration of “Influenza Serobacterin Mixed-Mulford,” and requested the Mulford Company to present evidence to establish the admissibility of the preparation to New and Nonofficial Remedies. The Mulford Company sent specimens of the serobacterin in question, an advertising circular and a letter by the director of its Biologic Laboratories.

According to the label on the package, the preparation is made from the following organisms: Bacillus influenzae, Staphylococcus aureus, Staphylococcus albus, Streptococcus, Pneumococcus and Micrococcus catarrhalis (group). This mixture is recommended by the manufacturer:

“For the prophylaxis and Treatment of Common Colds, Mixed
Infections of the Respiratory Mucous Membranes, Acute and Chronic
Catarrhal Conditions of the Nose, Throat and Respiratory Passages.”

No evidence is submitted for this recommendation except that in “colds and bronchitis and the other common infections of the upper respiratory passages ... five or six bacteria are very commonly present--two or more of them are nearly always present ...” and the letter by the director of the Mulford Biologic Laboratories expressing the belief that in his own case the use of the mixed vaccine has aborted or prevented colds.

As regards the use of this complex biologic preparation:

First, the cause of common colds is, at the present time, quite unknown. One of the most striking things is that at the beginning of a cold the organisms to be cultivated from the nasal mucous membrane are very few in number and there is no uniformity in the type of organism found. If someone of the well-known organisms (Streptococcus, Staphylococcus, Pneumococcus, Micrococcus Catarrhalis, Influenza Bacillus, etc.) were responsible, we should expect to find one of them preponderating and in overwhelming numbers. This is far from the case. After the duration of the cold for a day or two with the increased production of mucus and apparently with the infection of a mucous membrane whose powers of resistance have been greatly lowered, bacteria of all kinds are to be found in immense numbers. There is considerable reason for believing that an ultramicroscopic organism is responsible for this condition (See Foster, _Journal of Infectious Diseases_ =21=:451 [Nov.] 1917).

Second, there is no acceptable clinical evidence that vaccination with the influenza bacillus, the Streptococcus, the Pneumococcus or the Micrococcus Catarrhalis will influence the course of an infection due to one or the other of these organisms. It has been repeatedly found that a staphylococcus vaccine is of a certain degree of value when the infection with the staphylococcus is localized, but it is well known that general systemic infections with the staphylococcus are not at all benefited.

Third, the letter submitted as evidence by the Mulford Company is not convincing. The Council is not prepared to accept evidence of this sort unless it is in volume large enough to justify a definite conclusion.

Holding that there is no evidence for the value of this mixture, the Council declared “Influenza Serobacterin Mixed-Mulford” inadmissible to New and Nonofficial Remedies because its use is illogical.

Sherman’s Mixed Vaccine No. 40

Because of inquiry received the Council decided to consider this preparation and requested the manufacturer, G. H. Sherman, Detroit, Mich., to submit evidence in support of the claims made for it.

This vaccine is said to be made from killed cultures of Streptococcus, Pneumococcus, Micrococcus catarrhalis, Staphylococcus aureus, and Staphylococcus albus. In the printed matter sent out by G. H. Sherman this vaccine is recommended for hay-fever, in which it is stated that some of the symptoms are due to bacterial invasion of the respiratory mucosa; for tonsillitis, both as a remedy and as a prophylactic against rheumatic and other sequelae; for “throat infections”; for rhinitis with the claims that acute coryza can be aborted within twenty-four hours; for pneumonia in which it is advised for all stages; for laryngitis, for bronchitis, and for asthma.

No acceptable evidence was submitted as to the value of the product in the treatment of any of the foregoing conditions. In view of what is known about non-specific reactions, it seems likely that any influence which this vaccine may have on the diverse conditions enumerated by the manufacturer, is due to this, rather than to the combination of organisms used in its preparation.

On the recommendation of the Committee on Serums and Vaccines, the Council declared “Sherman’s Mixed Vaccine No. 40” ineligible to New and Nonofficial Remedies because the therapeutic claims made for it are unwarranted (Rule 6) and because the combination, in view of its complexity, is irrational and detrimental to sound therapy (Rule 10).--(_From The Journal A. M. A., June 23, 1918._)

OPHTHALMOL-LINDEMANN

Report of the Council on Pharmacy and Chemistry

Ophthalmol-Lindemann was taken up for consideration by the Council because of inquiries received. The following report, declaring Ophthalmol inadmissible to New and Nonofficial Remedies, was adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

Ophthalmol-Lindemann (Innis, Speiden and Co., New York) is advertised as a treatment for eye diseases by “hyperemia.” The circular advertising the product is written somewhat in the style of “patent medicine” advertisements. It contains testimonials of dubious value. The principle underlying the use of Ophthalmol is that employed to a considerable extent by ophthalmologists, through the use of ethylmorphine (“dionin”), etc., viz., the production of conjunctival irritation in inflammatory eye diseases. Ophthalmol is, therefore, merely a special agent for the production of such ophthalmic irritation.

The advertising circular contains no evidence that Ophthalmol is in any respect superior to the established agents for producing conjunctival hyperemia. On the other hand, there are obvious objections to the use in the eye of a substance of unknown and apparently indefinite composition and uncertain activity. Ophthalmol is said to be an oily solution of “glandular extract of the fish Cobitis Fossilis.” _Cobitis fossilis_ is a small fish said to be common in Germany. According to Kochs, who analyzed Ophthalmol (_Arb. a. d. Pharm. Inst. d. Univ. Berl._, =4=:140, 1907), this fish is popularly believed to predict weather, but medical virtues are not ascribed to it. This “fishy” extract is indefinite, to say the least.

The activity of the preparation is described by the manufacturer thus: “It seems probable that the typical action of Ophthalmol is due to certain organic acids which may have formed during manufacture through the decomposition of protein bodies contained in the crude material.” The profession is not told whether this important decomposition is, or, in fact, can be controlled so as to produce a material of uniform activity.

Kochs concluded from his analysis that Ophthalmol had the properties of rancid olive oil containing about 6 to 7 per cent. mineral oil. The oil contained no nitrogen, left no ash on ignition and though traces of iodin were claimed to be present, no iodin could be found.

It is recommended that Ophthalmol be rejected first, because the use in the eye of an irritant of secret composition and uncertain activity is unscientific and against the interest of public health; second, because Ophthalmol is of secret composition (the composition claimed being practically meaningless), and, third, because no evidence has been submitted to substantiate its claimed superiority over established methods of treatment. The Council declared Ophthalmol inadmissible to New and Nonofficial Remedies.--(_From The Journal A. M. A., July 6, 1918._)

SILVOL INELIGIBLE FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report on Silvol (Parke, Davis & Company) was adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

The Council took up the consideration of Silvol (Parke, Davis & Company) because of inquiries received. The following report was submitted by the referee in charge of silver preparations:

Silvol (Parke, Davis & Company) is a silver-protein preparation of the Argyrol type. Like Argyrol, it is said to contain about 20 per cent. of silver. The referee finds that, like Argyrol, it is nonirritant to the nasal mucosa in a 10 per cent. solution; does not precipitate with chlorid; dissolves in water readily; a 25 per cent. solution has a high specific gravity (Silvol, 1.137 at 20 C.; Argyrol, 1.147 at 20 C.), and is not very viscid (viscosity, 1.25). A 1:1,000 solution of Silvol is clear and about 50 per cent. deeper in color than a solution of Argyrol of the same strength.

Silvol differs from Argyrol mainly in that its solutions yield a fine precipitate with egg albumin (under suitable conditions), while Argyrol is nonprecipitant; and in that Silvol solutions are not so effectively decolorized by Lloyd’s reagent.

The manufacturers did not reply to an inquiry with regard to the basis for the claims made for Silvol (see Appendix). The referee was therefore obliged to deduce these claims from the firm’s advertising matter. About the same claims are made for the local use of Silvol as are generally made for Argyrol. These may be accepted without detailed evidence in view of the similarity of the two preparations.

Its usefulness, as suggested in the advertising, when given by mouth “in the treatment of acute or chronic gastritis, gastric ulcer, or gastro-enteritis,” or the efficacy of very dilute solutions (0.2 per cent.) against dysentery, etc., is doubtful and requires substantiation by evidence. The claims that Silvol is astringent, though nonirritant and noncoagulant, that it is a “powerful germicide” or even that it is a “powerful antiseptic,” and that it may be used with advantage wherever “a silver salt is indicated,” need substantiation. There is no proof of the assertions that Silvol is “the most efficacious of silver salts”; “the most efficient antiseptic,” and “the most remarkable organic silver compound ...”

As the manufacturers have not presented any evidence for their highly improbable claims, and as they have not signified any intention of making their claims agree with substantiated facts, it is recommended that Silvol be declared inadmissible to New and Nonofficial Remedies.

The Council adopted the report of its referee and authorized its publication.