Chapter XVII: Introduction: The Council on Pharmacy and Chemistry was established (10)

Report of the Council on Pharmacy and Chemistry

Ziratol (Bristol-Myers Company, New York), in compliance with the federal “insecticide law,” is declared to contain 32 per cent. water and 30 per cent. glycerin as inert constituents. Regarding its active constituents the manufacturer makes the following and meaningless statement:

“Ziratol is prepared from Phenols of the Naphthalene series and consists of a solution of such Phenols in a mixture of soap, water and glycerin.”

In response to inquiry, the A. M. A. Chemical Laboratory examined Ziratol and reported that its essential constituent appears to be alpha-napthol,[120] and that it has, essentially, the following composition by weight: Alpha-napthol 18 per cent., soap 20 per cent., glycerin and water sufficient to make 100 per cent.

[120] Alpha-napthol was also found to be the basis of the nostrum Benetol. See The Journal, April 15, 1911, p. 1128.

A Ziratol advertising circular gives a tabulated report of germicidal tests, said to have been made according to the method of the Hygienic Laboratory of the U. S. Public Health Service. When this work was done is not stated. According to these tests Ziratol possesses a phenol-coefficient of 13.66. The claim that Ziratol is ten times more efficient than carbolic acid (phenol) is evidently based on this report.

These claims of high germicidal value are contradicted by an examination made for the Council. A specimen purchased in the open market was examined independently by two operators, to determine the Hygienic Laboratory phenol-coefficient. One observer found the phenol coefficient to be 2.54. The other reported it to be 3.09. Evidently the germicidal value of Ziratol is greatly exaggerated in the advertising claims and, in fact, does not exceed that of the official compound solution of cresol (Liquor Cresolis Compositus, U. S. P.) for which a phenol-coefficient of about three has been established. (See New and Nonofficial Remedies, 1917, p. 82.) The claim that Ziratol is “the Universal Antiseptic and Germicide” is manifestly an unwarranted exaggeration.

The referee in submitting this report to the Council recommended that Ziratol be held in conflict with Rule 1 (secrecy of composition) and Rule 6 (unwarranted and exaggerated claims). After the report had been submitted, it was found that a new advertising circular, accompanying a trade package, no longer contained the claim that “Ziratol is ten times more efficient than Carbolic Acid.” The older circular made the following statement:

“1. Strong Activity.--Compared with the bactericidal action of
Carbolic Acid by the method of the Hygienic Laboratory of the
Marine Hospital Service, ZIRATOL has the Carbolic Acid Coefficient
of more than TEN, that is, ZIRATOL is TEN times more efficient than
Carbolic Acid,--a strength unapproached by any other of its class.
ZIRATOL in dilution of 1:1400 kills the Typhoid Bacillus in 2-1/2
minutes, thus proving that it is strongly active even in very weak
solutions.”

The new advertising circular reads:

“1. Strong Activity--Extensive bacteriological investigations on
many pathogenic organisms, conducted in the Lederle Laboratories of
New York, prove conclusively the high bactericidal value of Ziratol
in extremely dilute solutions. (A copy of the complete report will
be mailed upon request.)”

In response to a request, the Bristol-Myers Company sent a copy of the bacteriologic investigations of Ziratol, said to have been made by the Lederle Laboratories. The organisms employed for these tests were _Staphylococcus aureus_, _Staphylococcus albus_, _Streptococcus_, Green pus bacillus, _B. coli_, and saliva. No tests are given with the typhoid bacillus. The conclusion is reached that “in all the tests the solutions of Ziratol have several times greater killing efficiency than those of phenol.” The “coefficients” or comparative values which can be calculated from the results after exposure of 15 minutes to the disinfectants range from 2.0 to 4.0. This is in substantial accord with the referee’s findings as regards the phenol-coefficient with _B. typhosus_ as the test object. While the new advertising circular avoids the former claim that Ziratol is ten times more efficient than carbolic acid, in germicidal value, it still makes the unwarranted claims that Ziratol is the “universal disinfectant.”

The Council declared Ziratol inadmissible to New and Nonofficial Remedies (1) because its composition is secret (Rule 1); (2) because the phenol coefficient, determined according to the method of the Hygienic Laboratory, U. S. P. H. S., is not stated on the label (Rule 2); (3) because the label and the circular accompanying the trade package advises its use by the public as a “vaginal douche” (Rule 3); and (4) because the claim that Ziratol is the “universal disinfectant” is exaggerated and unwarranted (Rule 6).

Before authorizing publication of the preceding report the Council submitted it to the Bristol-Myers Company in order to give that company the opportunity of revising its method of marketing Ziratol. In reply the company enlarged on its withdrawal (on “our own initiative”) of the claim that Ziratol had a phenol-coefficient of over ten when this claim was shown to be incorrect “by authoritative sources.” One wonders whether this is a euphemistic reference to the proceedings of the federal authorities under the Insecticide Act against the Bristol-Myers Company, just made public,[121] because of the false claims made for the germicidal efficiency of Ziratol. This prosecution resulted in the seizure and condemnation of two lots of this proprietary which had passed in interstate commerce.

[121] U. S. Dept. of Agric., Insecticide and Fungicide Board, Service and Regulatory Announcements, No. 16, issued Aug. 8, 1917. _No. 244_, Misbranding of “Ziratol.” U. S. _v._ 100 bottles, more or less, of “Ziratol”; consent decree of condemnation and forfeiture; product ordered released on bond, p. 248. _No. 256_, Misbranding of “Ziratol.” U. S. _v._ 936 bottles and 6 jugs of Ziratol, consent decree of condemnation and forfeiture; product ordered released on bond, p. 260.

The Bristol-Myers Company in replying to the Council’s report made no offer to declare the exact composition of Ziratol, to state the actual phenol-coefficient, or to remove the other objections pointed out in the report of the Council. In other words, the Bristol-Myers Company has abandoned a definite but false claim of high germicidal power--a claim which subjected the firm to federal prosecution--and has substituted therefor indefinite statements which do not define the actual germicidal efficiency of Ziratol.--(_From The Journal A. M. A., Oct. 6, 1917._)

GONOSAN

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

Gonosan (Riedel and Company, Inc., New York City) comes in the form of capsules, each said to contain 5 minims of a mixture composed of oil of sandalwood 80 per cent., and 20 per cent. of alpha- and beta-resin of kava, isolated by a patent process. The mixture, as the name implies, is intended for the treatment of gonorrhea.

This proprietary preparation was under consideration by the Council at various times from 1905 to 1910. During this time, the Council agreed to accept the preparation if the suggestive name was changed, the therapeutic exaggerations abandoned, and the drug kava admitted to New and Nonofficial Remedies. The name was not changed, the other questions were left open, and the preparation was not accepted.

Recent and more objectionable advertising of Gonosan makes it advisable for the Council to take action and to publish a report. The tone of this advertising is reflected by the following quotation from a recent advertising circular:

“The old-established balsamic treatment of gonorrhea, for some
years neglected in favor of the local injection of organic silver
and other germicidal salts, has, with the increasing knowledge
and attention paid to the composition and purity of the balsams,
regained to a large extent the confidence formerly reposed in them.

“It may now be said that the combined treatment with local
injections and internal administration of natural balsamic products
completely dominates modern gonorrheal therapy.”

Any one conversant with current medical literature and practice would stamp these statements as misleading exaggerations. The balsams, oleoresins and volatile oils may have some value as minor adjuvants in the treatment of gonorrhea, but that is all. The position in this respect has not changed materially in recent years. These agents do not have a value equal to that of local treatment, as the quoted statement implies.

The claims made for Gonosan might with equal force be made for oil of santal alone. Kava kava, the other constituent, belongs to the pepper family; it had a temporary vogue some two or three decades ago, but has failed to maintain a place. It has never been recognized officially. There is no scientific evidence that it has any value either alone or as an adjuvant to sandal oil. The “clinical reports” quoted in the advertising circulars, rather curiously, nearly all date back ten years or more, viz., to a period when the attitude of the profession toward proprietary remedies was less critical than it is now. It would be interesting to know whether these authors still adhere to their opinion, or whether any of them have subsequently had experiences similar to that of a correspondent who wrote:

“Gonosan, at my hands, did not prove to be of more essential value in the treatment of gonorrhea than any other sandalwood oil preparation. The various claims made for Gonosan, that it possesses sedative and anesthetic properties, that by its continuous use the urethral discharge disappears more rapidly and that, if combined with appropriate diet and rest, it is liable to prevent complications, are, according to my experience, not corroborated by actual results.”

The only experimental work quoted in support of Gonosan, that of Pohl, is not convincing. The doses that Pohl found necessary to influence experimental purulent pleurisy makes it impossible to transfer his work to the clinic. (He found a dosage of oil of santal corresponding to an ounce per day, for man, inefficient; positive results were obtained only with 2 ounces per day.)

In order to learn the estimate placed on the therapeutic value of the “balsams,” an inquiry was sent to the authors of the papers presented to the section of Genito-Urinary Diseases at the recent meeting of the American Medical Association in New York. The inquiry read:

“_Dear Doctor_:--An advertising circular for Gonosan ‘Riedel’ which is now being distributed begins thus:

‘The old-established balsamic treatment of gonorrhea, for some
years neglected in favor of the local injection of organic silver
and other germicidal salts, has, with the increasing knowledge
and attention paid to the composition and purity of the balsams,
regained to a large extent the confidence formerly reposed in them.’

‘It may now be said that the combined treatment with local
injections and internal administration of natural balsamic products
completely dominates modern gonorrheal therapy.’

“Is the statement correct that the combined treatment with local injections and internal administration of natural balsamic products completely dominates modern gonorrheal therapy? Your reply to the above will be appreciated by the Council.”

Seventeen replies were received. They bear out the position that has been outlined. Only one writer considered the statement even approximately justified, and this in the sense that “the majority of cases receive no other treatment” than a combination of local applications and systemic medication. Another stated that, “in a general way their statement is true though a trifle too sweeping,” and then added that the field of the balsams is rather restricted. With the exception of these qualified endorsements the remaining (fifteen) replies characterized the statement as incorrect and misleading. The replies are a valuable contribution to the status of the “balsam” treatment of gonorrhea, and extracts of them are appended to this report.

It is recommended that the Council declare Gonosan inadmissible to New and Nonofficial Remedies, because the therapeutic claims are exaggerated (Rule 6); because there is no evidence that the combination of kava resin with oil of santal is superior to oil of santal alone (Rule 10); and because the therapeutically suggestive name is conducive of indiscriminate and unwarranted use of the preparation both by the profession and the public (Rules 4 and 8).

Appendix

The extracts from replies received to the inquiry above referred to, follow:

Dr. B., Penn., wrote:

“In my practice I have found that local injections are very
valuable in the treatment of gonorrhea, but I have never found that
the internal administration of natural balsamics dominated modern
gonorrheal therapy; while it is an aid, I consider the quoted
statement to be very erroneous.”

Dr. F., D. C., wrote:

“While it is doubtless true that acute urethritis, gonorrheal, is
now generally treated by local injections of solutions of organic
silver salts, and that santal oil is often used, it is not true,
as one would infer from the quotation, that the balsams are now
considered more efficacious than they were formerly. So far as I
know they have not lost or regained anything during the past dozen
years in the way of confidence reposed in them. The indications for
their use is very definite and very limited.”

Dr. B., Ga., wrote:

“... In recent years I have almost abandoned the use of balsams,
etc., in the treatment of gonorrhea. Patients, who are properly
treated otherwise, seem to get along as well without such drugs
as with them, in fact apparently better for they have no gastric
disturbance. It is important for patients to drink freely of
water and when so doing the balsams are so diluted that I cannot
conceive of their doing much good. Formerly my patients often lost
weight during the treatment of gonorrhea; now, without balsams and
with plenty of water, they usually gain in weight.”

Dr. S., Mich., wrote:

“... we believe that in a general way their statement is true
though a trifle too sweeping. We do not ordinarily use the
balsams in uncomplicated anterior urethritis. We do however, find
indication for their administration in from sixty to seventy five
per cent. of all cases of acute gonorrhea at some time during the
course of the disease.”

Dr. L., Mo., wrote:

“I would say that the statement that, ‘The combined treatment with
local injections and internal administration of natural balsamic
products completely dominates modern gonorrheal therapy,’ is far
from representing the facts. While the balsamics may occasionally
have an indirect soothing effect on the mucous membranes involved,
the dominant factor is local treatment, aiming at disinfection and
restoration to normal of the inflamed tissues.”

Dr. R., Mich., wrote:

“Regarding your request although I am willing to reply it is
difficult to do so because if I should do so in the affirmative
that could apply only to certain acute cases without complication
of any kind and such cases are rare. In such, however, the
advertiser is not far from right--since vaccine therapy has proven
absolutely worthless we must fall back on antiseptics in acute
urethritis when there are no objections to such treatment ...”

Dr. K., Ill., wrote:

“I am under the impression that the internal administration of
balsamics is used only when complications arise, such as acute
posterior urethritis. Personally I use the balsamics very, very
rarely. From my observation, however, I am led to believe that many
men still use internal drugs in the treatment of gonorrhea, and
during the past few years, I should say the use of hexamethylenamin
has been on the increase, and the use of the balsams on the
decrease. I do not believe that hexamethylenamin is of any value
in the treatment of gonorrhea, and am simply citing this as my
observation of the widespread use of this drug in the treatment of
gonorrhea.”

Dr. T., Penn., wrote:

“... I believe that more men use salol or hexamethylenamin, or no
urinary antiseptic whatsoever, than use the balsamics.”

Dr. B., Ind., wrote:

“... The only systemic treatment that is considered necessary today
is rest, plenty of water and neutralize the acidity of the urine
with bicarbonate of soda or some sodium salt.”

Dr. Y., Mass., wrote:

“Sandal wood oil during the acute stage of gonorrhea certainly tends to make the patient more comfortable and undoubtedly does lend some (tho I believe slight) gonococcidal action. That it plays any _considerable_ part in actual cure I think is doubtful. The statement as quoted is true in so far as it states that local treatment plus internal medication with a balsam comprises most of the modern treatment of gonorrhea but it is grossly misleading in that it lets one draw the inference that the balsam plays a large if not the principal part.”

Dr. H., New York, wrote:

“For a period of at least three years in my hospital, dispensary
and private practice, I conscientiously tried out most of the
balsamics on the market (including Gonosan, which I favored for
some time) both alone, and combined with local injections. As
a result of this study, I have come to the conclusion that the
balsamics have little, if any value in the treatment of gonorrhea.
During the past few years I have relied almost entirely on local
therapy, and seldom prescribed any of the balsams in my private
practice, certainly in not more than 5 per cent. of the cases.
My results I find are just as satisfactory, and my patients
appreciate the fact that they are not loaded up with disagreeable
medication. Instead of the balsamics, I am using sodium bicarbonate
more and more, and feel convinced that the proper use of this drug
is of more value than all of them combined.”

Dr. K., Cal., wrote:

“The statement that the combined treatment with local injections
and internal administration of natural balsamic products completely
eliminates modern gonorrheal therapy, would at present not be
justifiable even with reference to the initial or acute stage
of gonorrhea, while in the subacute and chronic forms of the
disease local injections and balsams play an almost insignificant
rôle as compared with various other recognized therapeutic
measures.”--(_From The Journal A. M. A., Oct. 13, 1917_).

ALCRESTA IPECAC

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

In 1915 Alcresta Ipecac Tablets (Eli Lilly and Co.) were admitted to New and Nonofficial Remedies as a preparation of ipecac that is insoluble in the stomach but soluble in the intestines. It was supposed that this property would permit the administration of ipecac without the accompanying nausea and vomiting, and that this would be of especial advantage when using the drug in amebic dysentery. The systemic effects, of course, would be those of ipecac.

More recently, the manufacturers of Alcresta Ipecac have been advising its use in conditions which were not contemplated by the Council when the preparation was accepted for New and Nonofficial Remedies. They now claim that ipecac alkaloids have been shown to be useful in the treatment of typhoid fever, flatulence, diarrhea and constipation and that Alcresta Ipecac has these properties. Such a statement is misleading. While it is true that at one time ipecac was used promiscuously against “flatulence, diarrhea and constipation” there never has been and is not now any scientific evidence of its efficiency in such conditions except, of course, in diarrhea of the amebic type. As to the alleged usefulness of ipecac in typhoid fever: This has not even the sanction of tradition and the claim certainly should not be accepted until there is strong evidence to support it.

The advertising matter on Alcresta Ipecac also contained statements to the effect that ipecac alkaloids have a demonstrated usefulness in pyorrhea. Such an unequivocal statement is unwarranted. In spite of the enthusiastic advocacy, in the past, of ipecac alkaloids as a specific in pyorrhea alveolaris the preponderance of scientific evidence indicates that ipecac is of questionable value in this condition. Neither is there any substantial evidence to warrant the claim that ipecac alkaloids, when absorbed through the intestines, are demonstrably useful in amebic infections of the tonsils.

The reputation of the best drugs, whether unofficial or official, is bound to suffer if extravagant claims for them are permitted to go unchallenged. The referee of the Council, therefore, believed it necessary to call the attention of the manufacturers of Alcresta Ipecac Tablets to the statements made for the product and suggested that they submit evidence to substantiate the claims. This the manufacturers have refused to do. Their attitude in the matter, as well as their attitude toward the Council’s work is expressed in the following letter:

“Responding to your letter of March 10th, we beg to suggest that
literature covering the different matters at issue are readily
available to your referee, and all statements emanating from us are
made advisedly.

“If you cannot satisfy yourselves that this preparation is a
scientific product, ethically advertised, and a desirable advance
in therapeutics, you can only delete it from your next issue of New
and Nonofficial Remedies.”

It is to be regretted that Eli Lilly and Co. refuse either to withdraw or modify their claims or to substantiate these claims by scientific evidence. The statements as they stand are exaggerated, misleading and harmful. As such they conflict with Rule 6 of the Council and necessitate the omission of Alcresta Ipecac from New and Nonofficial Remedies. The referee recommended the adoption and publication of this report.--(_From The Journal A. M. A., Oct. 20, 1917._)

IODEOL AND IODAGOL

Report of the Council on Pharmacy and Chemistry

Iodeol and Iodagol (formerly called Iodargol) are products of Viel and Company, Rennes, France, widely advertised in this country by David B. Levy, Incorporated, New York. The claim made for both preparations is that they depend on “colloidal iodin” for their action. They are put up in a number of forms, for instance:

“Iodeol Ampoules each containing 1 c.c. (20 centigrammes colloidal
iodin in an oily vehicle).”

“Iodeol External, containing 50 per cent. colloidal iodine.”

“Iodagol Ampoules, each containing 2 c.c. (50 centigrammes
colloidal iodine in an oily vehicle).”

The claim is, that, the iodin being in the colloidal state, it has the properties of elementary iodin and thus the preparations may be used in concentrations and under conditions which would make the use of free iodin impossible. The products have been extensively and extravagantly advertised for use in a wide range of conditions. Thus Iodeol has been proposed in the treatment of:

“Pulmonary Tuberculosis”
“Laryngeal Tuberculosis,”
“Glandular Tuberculosis”
“Tuberculosis of the Bones”
“Pneumonia, Broncho-pneumonia, and Congestive Conditions”
“Whooping Cough, Influenza, Asthma”
“Typhoid Fever”
“Syphilis”
“Obesity.”

Iodagol, which is for external use, has been advised in the treatment of:

“Gonorrhea and its Sequelæ”
“Cystitis”
“Tetanus”
“Wounds complicated by gaseous gangrene”
“Burns”
“Old Suppurations, ulcers, abscesses, etc.”
“Articular rheumatism”
“Abscess Alveolar”
“Pyorrhea Alveolaris”
“Stomatitis (Canker-Sores).”

Nearly two years ago the American agents requested the Council to consider Iodeol and Iodagol for admission to New and Nonofficial Remedies. The information submitted in regard to their character and composition was vague and indefinite, the pharmacologic information practically nil and the clinical data as voluminous as it was unconvincing.

On the basis of chemical, pharmacologic, bacteriologic and clinical investigation carried out under the direction of the referee and a study of the submitted evidence, the referee reported:

1. Iodeol and Iodagol do not contain the amount of iodin claimed.

2. The iodin is not present as elementary iodin, but instead the preparations behave similarly to the well-known organic iodin compounds such as iodized fats.

3. The therapeutic claims made for the preparations are exaggerated and unwarranted.

In view of his findings he recommended that Iodeol and Iodagol be declared inadmissible to New and Nonofficial Remedies for conflict with Rules 1 and 2 (misleading statements regarding composition and identification) and Rule 6 (unwarranted therapeutic claims). The Council adopted the recommendation of the referee, directing inclusion of the full report in the annual Council reports after submission to the manufacturer, and recommending publication of an abstract of this report in The Journal.

This report was brought to the attention of the American agent, David B. Levy, Inc., and through them to the French manufacturers, E. Viel and Company. The manufacturers have intimated that they will not file a reply to the report. The firm of David B. Levy, Inc., has decided to sever its connection with these products and to discontinue their sale.

W. A. Puckner, Secretary.

Summary of Referee’s Report

Iodeol and Iodagol were submitted to the Council nearly two years ago as “electro-colloidal iodine” and with the claim that they produced all the antiseptic and other effects of ordinary iodin without any of its side actions. The referee has done much work on the subject, conducted a large amount of correspondence and has contended with long delays. He feels that the consideration of these products should be brought to a conclusion and accordingly he submits this report of their consideration. The following is a summary of the report, which is appended:

_I. Discrepancy in Iodin Percentage._--The examination at the Chemical Laboratory of the American Medical Association, as well as that of the referee, shows that the various samples of Iodeol and Iodagol examined contained a little less than one-half of the total iodin claimed. These facts were reported to the American agent. After a lengthy delay a reply was received which presented a double excuse: (1) that the full amount of iodin had been added, whatever had become of it later; (2) that the claims were made for “colloidal iodin” and that this is not elementary iodin in the colloidal state, but a preparation of iodin containing only 50 per cent. of real iodin. Neither explanation can be taken seriously, as they are obvious quibblings. The referee concludes that the preparations are falsely labeled as to iodin content.

_II. Nature of the Iodin Compound in Iodeol and Iodagol._--In the information sent the Council, Iodeol and Iodagol were defined as “A suspension of electro-chemical colloidal iodin in a vehicle of purified oil.” Numerous inquiries have failed to elicit more specific information from the manufacturer or his agent. The statement of composition can mean only that the preparations contain free iodin (but in colloidal form) suspended in oil. No evidence to substantiate this claim has been submitted. (There is evidence that the preparations contain colloidal particles, but it does not indicate if this colloidal material is iodin, or a combination of iodin or indeed whether the colloidal component contains any iodin.) The recent statements of the agent seem to concede that what they call “electro-colloidal iodin” contains only about 50 per cent. of real iodin, in other words that it is not “colloidal iodin” at all, but a mixture or combination of iodin with some other unnamed substance. This, of course, is something very different.

Certain results reported from the American Medical Association’s Chemical Laboratory suggest that the so-called “colloidal iodin” of Iodeol may be a combination of iodin with a volatile oil. The investigations of the referee indicate that the iodin exists in a rather resistant form or combination behaving altogether differently from ordinary free iodin, and rather resembling the behavior of iodin substitution products, such as iodized fats or phenols. Briefly then the recent admissions of the agents indicate that Iodeol does not contain “colloidal iodin” in a chemical sense, and there are indications that it does contain its iodin in a rather firm (chemical) combination.

_III. Chemical Properties of Iodeol._--From a study of different specimens of Iodeol, the referee concludes that fresh specimens contain no free iodin and that old ones contain small amounts as a result of decomposition. Iodeol has the solubility characteristics of fats and fat-like compounds. The examination, as a whole, shows that Iodeol contains a peculiar and rather resistant form or combination of iodin. There is nothing in the chemical data that suggests that it could act differently from ordinary iodin compounds, such as iodized fats. It would not act as ordinary iodin.

_IV. Pharmacologic Data._--The pharmacologic statements which were submitted were loose and apparently meaningless or misleading. In reply to questions submitted by the referee, the manufacturer finally had some work done and submitted a report by Jean Laumonnier. The referee was unable to confirm some of this work, and as a whole it does not appear materially to elucidate the action of Iodeol. From a consideration of the submitted evidence, and as a result of his own work, the referee concludes that Iodeol does not behave like elementary iodin; it does not coagulate proteins and therefore is not irritant. It is presumably absorbed, but quite probably after chemical change; it is changed into iodid and, like organic iodids, is excreted somewhat more slowly than when inorganic iodids are administered, but the difference does not appear important.

_V. Antiseptic and Bactericidal Action._--Elementary iodin is considered a fairly powerful agent in these respects. The activity is presumably due to changes in the proteins, etc., of the bacteria, analogous to the effects which produce pain, irritation and necrosis of the tissue cells. Since the latter effect is not produced by Iodeol, it seems highly improbable, if not impossible, that it should act on bacteria like elementary iodin. It is entirely unjustifiable to credit the known antibacterial qualities of ordinary iodin to “colloid” iodin. This misrepresentation is especially prominent in the circular “Notable New Therapeutic Agents,” as will be seen, for instance, from the following citations:

“Iodine has long been universally recognized as an antiseptic of
extraordinary potency. Not only is it rapid and certain in its
germ-destroying action, but it also possesses an attribute denied
many other antiseptic agents, namely, the power to penetrate and
impregnate the tissues. Other antiseptics, as is well known, act on
the surface epithelium only.”

“According to Kinnaman (J. A. M. A., Aug. 26, 1905), iodine is far
superior to bichloride of mercury, a two per cent. solution killing
streptococcus pyogenes in two minutes. Iodine does not coagulate
albumin, and is very penetrating.”

The citations imply that this “colloidal iodin” of Iodeol and Iodagol acts as an antiseptic like ordinary iodin, except that it is claimed to be more efficient by “diffusing” more readily. This is entirely unjustified and misleading. If Iodeol and Iodagol are really antiseptic, they must act by some other mechanism than that through which elementary iodin acts, and such antiseptic action would have to be demonstrated by direct observation and not assumed from the known action of free iodin.

Antiseptic and bactericidal effects are easily estimated by laboratory methods. Yet no evidence on this point appeared to have been available until the Council called for this. Laumonnier then carried out some experiments which were in turn submitted to bacteriologic control. The bacteriologist failed to obtain any results with some of the tests, and considered the other data of little value.

The claim that Iodeol and Iodagol have the antiseptic and bactericidal action of free iodin lacks proof and must be considered unwarranted and misleading in the extreme.

_VI. Clinical Trials._--The manufacturers and agents of Iodeol presented many letters from physicians; but few, if any, of these gave evidence of careful, critical, controlled observations. They could not, therefore, be considered as acceptable evidence. The more important claims, letters and published papers, however, were submitted to clinical specialists collaborating with the Council, with the request that they examine these and conduct some clinical trials, if they considered it advisable. The results obtained in these preliminary trials did not appear sufficient to warrant further experimentation.

From a consideration of the evidence presented, the referee concludes that the claims made for Iodeol and Iodagol are unwarranted, exaggerated and misleading. He recommends that Iodeol and Iodagol be declared ineligible for New and Nonofficial Remedies for conflict with Rules 1 and 2 (misleading statements as to composition and identification) and with Rule 6 (unwarranted and misleading therapeutic claims). He further recommends that the Council authorize publication of the preceding summary of the consideration of Iodeol and Iodagol in The Journal and inclusion of the full report in the annual Council reports after submission to the manufacturer.--(_From The Journal A. M. A., Nov. 17, 1917._)

CAPSULES BISMUTH RESORCINOL COMPOUND NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

In response to inquiries received, the Council took up the consideration of Capsules Bismuth Resorcinol Compound (The Gross Drug Company, Inc., New York City). The label, sent by the Gross Drug Company, bore the following:

CAPSULES
BISMUTH RESORCINOL COMPOUND

Bismuth Subgallate 2 grs.
Resorcinol 1 gr.
Beta Naphthol 1/2 gr.
Creosote (Beechwood) 1 m.

This combination is of acknowledged value
in reducing the value in reducing the intes-
tinal putrefaction and fermentation, allaying
the pain and discomfort of flatulent conditions
in the intestinal tract.

DOSE.--One or two capsules before or after meals
repeated in two hours if necessary.

The Gross Drug Company, Inc.
20 Laight Street, New York

The Council held this preparation inadmissible to New and Nonofficial Remedies or the Appendix, because (1) the claim “acknowledged value in reducing the intestinal putrefaction and fermentation, allaying the pain and discomfort of flatulent conditions in the intestinal tract” is an unwarranted, exaggerated and misleading claim of therapeutic value (Rule 6); because (2) the name does not indicate the identity of the bismuth salt contained in the capsules, nor declare the presence of betanaphthol and creosote (Rule 8); and because (3) the combination of bismuth subgallate, resorcinol, betanaphthol and creosote in fixed proportions is irrational (Rule 10).--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 139._)

DIXON’S TUBERCLE BACILLI EXTRACT AND DIXON’S SUSPENSION
OF DEAD TUBERCLE BACILLI

Report of the Council on Pharmacy and Chemistry

New and Nonofficial Remedies, 1917, contains general descriptions of Dixon’s Tubercle Bacilli Extract and Dixon’s Suspension of Dead Tubercle Bacilli; the products of these manufactured by the H. M. Alexander Company being listed as dosage forms. It having become necessary to omit the preparations of the Alexander Company (see page 138) the referee recommended that the general articles of “Dixon’s Tubercle Bacilli Extract” and “Dixon’s Suspension of Dead Tubercle Bacilli” also be omitted. He reported that no other firm appears to be marketing these products and that they had not been shown to be of special value.

The Council accepted the recommendation and directed the omission as proposed. In accordance with the procedure of the Council, these have been transferred to the annual Council Reports for reference and appear below.

W. A. Puckner, Secretary.

=Dixon’s Tubercle Bacilli Extract.=--An extract of tubercle bacilli dissolved in normal saline solution. (See “Fluid of Dixon,” _Medical News_, Jan. 17, 1891.)

=Dixon’s Suspension of Dead Tubercle Bacilli.=--A suspension in physiologic salt solution of dead tubercle bacilli which have been defatted by prolonged treatment with alcohol and ether. (See “Possibility of Establishing Tolerance for Tubercle Bacilli,” _Medical News_, Oct. 19, 1889.)--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 140._)

FORMOSOL

Report of the Council on Pharmacy and Chemistry

Sunshine’s Formosol (The Formosol Chemical Company, formerly the Sunshine Chemical Company, Cleveland, Ohio) is claimed to contain 18 per cent. formaldehyd in a solution of soap. It is therefore very similar to Veroform Germicide which was deleted from New and Nonofficial Remedies because of the low phenol coefficient reported by the Hygienic Laboratory of the United States Public Health Service (The Journal, Nov. 22, 1913, p. 1920.) The Council voted that in view of the Hygienic Laboratory’s finding that formaldehyd has a low germicidal value, the manufacturers of Formosol be required to produce definite evidence of the degree of germicidal value for this product.

In submitting the preparation to the Council, it was claimed that Formosol had “all properties peculiar to Formaldehyde.” This conservative tone was, however, not maintained in the form-letters submitted. These contain the following unwarranted statements:

“As the name implies, FORMOSOL is a formaldehyde preparation, which
embodies all the innate antiseptic merits and eliminates all the
ill features of the world’s greatest disinfectant.”

“The elimination of all the destructive elements and the
incorporation of all the established therapeutic virtues of
formaldehyde, have been scientifically blended in FORMOSOL.”

“FORMOSOL is unique in the sphere of antisepsis because of its
peculiar healing properties as diametrically opposed to irritation
to the tissue of mucous membrane.”

“FORMOSOL may be used for the thousand niceties of modern
antisepsis, but is _specific_ in Gynecology and Obstetrics and is
indicated in Dermatology.” [Italics not in original.]

“The constant use of FORMOSOL is to develop a habit sympathetic to
ethics.”

“To prescribe FORMOSOL is a great step toward Personal Hygiene, a
_duty of the medical fraternity_ to the laity.” [Italics not in
original.]

The trade package recommends the use of Formosol “for cuts, wounds, ulcers, abscesses ...” This is a conflict with Rule 4. The Council held Formosol in conflict with Rules 4 and 6, and advised the manufacturers that Formosol is refused admission to New and Nonofficial Remedies until they submit evidence establishing the degree of antiseptic and germicidal efficiency, and justify the quotations listed above; or until these and any other existing conflicts with the Rules have been removed.

After submission of this report to The Formosol Chemical Company the Council authorized its publication.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 145._)

IODOLENE, A SOLUTION OF IODIN IN LIQUID PETROLATUM,
INADMISSIBLE TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council was asked to consider a solution of iodin in liquid petrolatum, said to be prepared from Gulf Coast petroleum by a special process. It was to be marketed as “Iodolen” provided the Council found the preparation admissible to New and Nonofficial Remedies. The preparation was claimed to contain over 1.5 per cent. free iodin. The following claims were made:

“It is less irritating in its use on the skin, or in wounds.” “Will
kill pathogenic micro-organisms present.” “Is a suitable medium for
cell proliferation.” “Will penetrate a useful distance into the
walls of a wound.” “Facilitates an easier, less painful and better
method of dressing wounds or ulcers.”

Examination in the American Medical Association Chemical Laboratory showed a submitted sample to contain 1.32 per cent. free iodin and to emit a strong odor of hydrogen sulphid. A specimen of liquid petrolatum, said to be composed chiefly of hydrocarbons of the naphthene series, after saturation with iodin at room temperature was found to contain 1.42 per cent. free iodin. Another specimen of liquid petrolatum, said to be composed chiefly of saturated hydrocarbons, after saturation at room temperature was found to contain 1.30 per cent. free iodin.

The preparation having been shown to be an unoriginal, simple solution of iodin in liquid petrolatum, the Council declared the name “Iodolene” unacceptable (Rule 8) and the therapeutic claims made for the preparation unwarranted (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 148._)

KALAK WATER

Report of the Council on Pharmacy and Chemistry

The following report, submitted by a member of the Council’s committee on chemistry, was endorsed by the committee and adopted by the Council:

Kalak Water, sold by the Kalak Water Company, Inc., New York, is an artificial mineral water said to be made by adding certain salts to carbonated, distilled water and supersaturating with the gas under pressure. Such merit as it may possess by virtue of sodium bicarbonate and sodium phosphate is quite insufficient to warrant the extravagant claims made in the advertising pamphlets.

According to the analysis furnished, the water contains, in 1,000,000 parts (milligrams per liter) the following:

Sodium carbonate 4049.0
Sodium phosphate 238.5
Sodium chloride 806.3
Calcium carbonate 578.2
Magnesium carbonate 48.9
Potassium chloride 47.9

Among the many misleading statements found in the advertising pamphlet bearing the title “A Brief for Physiological Alkalescence” these may be quoted:

“The calcium content of Kalak is over 100% greater than ever before
placed in solution in any vehicle, a fact of supreme importance
when the unique alkalinizing power of the alkaline salts of this
metal is considered; the ratio of calcium metabolism to its
enormous waste in pregnancy, the diseases of infancy and childhood
and the rapidly growing group of ‘acidoses’ make its availability
in Kalak of double value.”

The first part of this statement is untrue; the last part is muddled and without much meaning. Evidently the “acidosis” fad is to be overworked as was the old “uric acid diathesis,” of unsavory memory. Again this:

“One of the most important characteristics of Kalak is the close
approximation of its formula to the correlation of the contained
salts as they occur in the human body, together with its freedom
from salts foreign to the human economy. Another is its almost
unbelievable palatability, considering its high degree of
alkalinity, it being eleven times greater than any other known
mineral water, artificial or natural.”

These statements are false. The salts dissolved here bear no discernible relation to the needs of the body, as disclosed by the composition of the blood or solid tissues or as shown by the character of the urinary excretion. The last statement concerning the high alkalinity is neither clear nor accurate. Then, this warning and remedy:

“It seems to be an unappreciated fact that the degree of urinary
acidity, checked with the acidity of the saliva, is in direct ratio
to the existing acid toxemia, and a urine acid to methyl red should
be the signal for immediate and adequate alkalinizing treatment....

“Startling clinical results have been observed by physicians who
have used Kalak thoughtfully and sufficiently in the more serious
types of acidosis associated with diabetes, nephritis, rheumatism,
gout and the acute infections. There is also evidence of its good
effect in acute alcoholism and the respiratory edemas; in fact a
certain few have hailed Kalak as a possible solution of the annual
hay fever problem. Of perhaps supreme importance, however, is the
use of Kalak throughout pregnancy as preventive medicine against
the inevitable ‘toxemia of pregnancy.’”

Also this:

“Kalak has accomplished certain unexplainable things for the
diabetic and nephritic, and if, in future years, diabetes and
nephritis should prove to be constitutional diseases, based upon
functionation or its lack, Kalak therapy, the embodiment of
physiological alkalescence may come into its own, for if acidity
retards, alkalinity must normalize functionation.”

It is not necessary to quote further. In order to insure that everyone will recognize the great need of Kalak it is advised to test the urine for acidity by means of a group of indicator solutions sent out to the physicians. Methyl red is one of these and any urine showing an acid reaction with this is said to be open to suspicion. Paranitrophenol is another of the indicators and the explanations given of the behavior of the two and the conclusions to be drawn are questionable. The methyl red solution furnished is too concentrated for proper use and perfectly normal urines from normal individuals have given a rather marked color with it. This indicator gives some color at [H+] = 1.2 × 10^{-6} and a strong reaction at 3 × 10^{-3}. To condemn a urine on such a finding is entirely unwarranted.

Sodium bicarbonate is the main constituent of the water. The value of the phosphate in such a combination, with so much calcium, is problematical. In case an alkaline reaction in the intestine is reached some of it would be left as insoluble phosphate. A few grams of bicarbonate daily would have equal therapeutic value with this water. The advice based on the indications of methyl red and the urine is bad.

The committee’s report was sent to the Kalak Water Company for comment. The company promised to withdraw the advertising circular referred to in the report and disclaimed responsibility for the accuracy and value of the set of indicators which it sent out, but, on the whole, the previous advertising claims were insisted on.

In view of the absurd and false claims made for the product the Council declared Kalak Water inadmissible to N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 148._)

MINSON’S SOLUBLE IODIN “KELPIDINE” NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

Minson’s Soluble Iodin “Kelpidine” was submitted to the Council by J. J. Minson, Washington, D. C., trading as the Kelpidine Company, with the statement that in future “literature” it was to be known as Minson’s Soluble Iodin, only. The following statement of composition was furnished:

“Minson’s Soluble Iodin is somewhat of an indefinite character,
chemically. Its formula is, Iodin 4 per cent., Distilled Water
6 per cent., and Absolute Alcohol _q. s._ 100 per cent. By a
process of chilling and heating an iodid of uncertain character is
produced, and because of the extreme sensitiveness of the product
to chemical tests, it is hard to determine. So far as I have been
able to judge, however, the result is about 3 or 3-1/2 per cent.
free iodin and from 1/2 per cent. to 1 per cent. iodid, possibly
ethyl and hydrogen iodid in combination.”

The A. M. A. Chemical Laboratory reports that the preparation is an alcoholic solution containing free iodin and iodid, probably hydrogen iodid and ethyl iodid, but that the free iodin content was only 2.69 gm. per 100 c.c.

It is claimed that the “therapeutic indications” of Minson’s Soluble Iodin are the “same as those of all iodin and iodid preparations, internally, externally, hypodermically and intravenously; excepting, however, counter irritation.” It is admitted that there are no “clinical reports” as to the hypodermic and intravenous use, but the belief is expressed “that in an emergency it is a safe remedy under proper dilution.” It is further claimed that “for all practical purposes it is nontoxic and nonirritating” and that “it has none of the undesirable features such as is the case with the iodids and the organic preparations of iodin, proprietary or otherwise.”

It was assigned for consideration to the Committee on Pharmacology, whose referee reported:

“According to the information submitted, this is a tincture of iodin; differing from the official tincture in that it is more dilute and in that hydrogen and ethyl iodid is the solvent in place of potassium iodid. It is practically immaterial for internal administration, whether the cation of the solvent iodid is hydrogen, ethyl, potassium or sodium. It would certainly be inadvisable to inject a preparation containing free iodin hypodermically. It is not ‘a safe remedy’ for intravenous injection and it would not be nonirritant. The statement that ‘it has none of the undesirable features’ of other iodin compounds is inherently impossible. Apparent freedom of any iodin preparation from undesirable effects is generally due to the use of small doses. Such claims are plainly therapeutic exaggerations and therefore in conflict with Rule 6. Even should these be removed, the preparation must be held an unessential modification of the official tincture, and therefore in conflict with Rule 10.”

The report was agreed to by the committee and adopted by the Council and Minson’s Soluble Iodin “Kelpidine” declared inadmissible to New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 152._)

NUTONE

Report of the Council on Pharmacy and Chemistry

NuTone (NuTone Company, Lowell, Mass.) is a “nutritive tonic” said to have the following complex composition:

Cod Liver Oil, Pure Norwegian, 25 per cent.
Malt Extract, 9-1/3 per cent.
Beef juice,
Glycerine,
Hypophosphite Lime, Hypophosphite Soda, Chemically pure,
1-1/2 grs. each to the oz.
Fl. Ext. Nux Vomica, 3/64 of a minimum in each teaspoonful.

It is advertised with claims that will lead thoughtless physicians and a confiding public to depend on it in cases in which fresh air, hygienic surroundings and nutritious food are of prime importance.

A sample package (the phrase “as recommended by your physician” and other statements suggest that it is expected to be given the patient by the physician and thus effectively advertise NuTone to the public) describes NuTone as an “Agreeable Concentrated Nutritive Tonic Emulsion of Malt Extract, Beef Juice and Cod Liver Oil, Combined with Nerve Tonics and Bone Nutrients.” Emphasizing the nutritive value of this “Malt Extract, Beef Juice, and Cod Liver Oil” preparation, it is advised, “As NuTone is rich in nutritive properties, it is well to begin with one-fourth teaspoonful, gradually increasing to regular dose, which is: Adults, 1 to 2 teaspoonfuls after meals and at bedtime. Children according to age.” It thus appears that adults are to take this preparation as a “nutritive” in doses which represent from 3 to 12 grains of sugar (on the assumption that malt extract may contain as much as 50 per cent. sugar) and 8 to 30 minims of cod liver oil with unstated, but probably equally small, amounts of beef juice.

A consideration of the negligible food value of NuTone as well as of the inefficiency of the other components and the claim that it is indicated in “malnutrition,” “wasting diseases” and “incipient phthisis” classes NuTone with that large group of shotgun mixtures which do harm in that dependence is placed on them in conditions in which the patient will probably be restored to health if proper medical and hygienic measures are adopted in time.

The Council declared NuTone inadmissible to New and Nonofficial Remedies because it is an irrational shotgun mixture advertised indirectly to the public with unwarranted therapeutic claims and a nondescriptive therapeutically suggestive name.--(_From Reports of Council on Pharmacy and Chemistry, 1917, p. 154._)

TRI-ARSENOLE, L. O. COMPOUND NO. 1 AND L. O. COMPOUND NO. 2

Report of the Council on Pharmacy and Chemistry

=Tri-Arsenole.=--According to the advertising of the Medical Supply Company of Atlanta, Ga., “Tri-Arsenole” is “Merco-Arseno-Benzo-Chloride,” and the claim is made:

“This compound is the result of many years’ research. The toxicity
has been fully tested upon animals before using clinically, the
latter having proven such complete success, we take pleasure in
presenting it to the public ...”

“The manufacturers of TRI-ARSENOL, before placing it upon the
market, tested it biologically.”

Tri-Arsenole is “recommended and suitable for the treatment of primary, secondary, tertiary and hereditary syphilis. It has also been found very useful in pellagra and malaria.” The preparation is supplied in ampules containing varying amounts of the dry substance. It is to be dissolved in water and is to be administered intravenously. In the advertising attention is called to the yellow color of Tri-Arsenole; this, and the style of package suggest that it is a preparation similar to salvarsan.

In reply to a request sent the Medical Supply Company for the quantitative composition and chemical formula of the compound “Merco-Arseno-Benzo-Chloride” and for the details of the biologic test by which its toxicity is claimed to have been determined and evidence for its efficiency, the following statement was received:

“Tri-Arsenole No. 1 equals to each Ampoule, gr.

Sodium chlorid 4-1/2
Hydrarg chlor.-cor. 1/4
Arsenous acid 1/4
Sodium benzoate 4
Hydrastin (resinoid) 2

Tri-Arsenole No. 2 equals to each Ampoule,

Sodium chlorid 4
Hydrarg chlor.-cor. 1/2
Arsenous acid 1/2
Sodium benzoate 4
Hydrastin (resinoid) 2

Tri-Arsenole No. 3 equals to each Ampoule,

Sodium chlorid 3-1/2
Hydrarg chlor.-cor. 3/4
Arsenous acid 3/4
Sodium benzoate 4
Hydrastin (resinoid) 2

Tri-Arsenole No. 4 equals to each Ampoule,

Sodium chlorid 3
Hydrarg chlor.-cor. 1
Arsenous acid 1
Sodium benzoate 4
Hydrastin (resinoid) 2

The request for information regarding the animal experiments said to have determined the toxicity was ignored, nor were references supplied to clinical reports demonstrating the value of the product.

The Council declared Tri-Arsenole inadmissible to New and Nonofficial Remedies because of conflict with the rules as follows:

In the absence of details of the method used, the claim that the preparation has been tested biologically is in conflict with Rule 2, which requires that for preparations claimed to be physiologically standardized the method of testing must be published so as to permit of control by independent investigators.

The claims that “Merco-Arseno-Benzo-Chloride” is “the result of many years research,” that its “toxicity has been fully tested upon animals before using clinically” and that clinical use has “proven such complete success” have not been substantiated by evidence and must be held as unwarranted.

The name is in conflict with Rule 8, which requires that pharmaceutical mixtures shall bear names descriptive of their composition. Further, the name “Tri-Arsenole” by its similarity to Diarsenol, the Canadian brand of arseno-phenolamin hydrochlorid, suggests that this pharmaceutical mixture is a chemical compound similar to salvarsan. Moreover, the danger of confusion is increased by the addition of the hydrastis preparation which imparts a yellow color like that of salvarsan to the solution obtained when the colorless mercury and arsenic compounds of the mixture are dissolved. Again, the synonym “Merco-Arseno-Benzo-Chloride” conveys the false impression that Tri-Arsenole is a definite chemical compound.

The label does not declare the poisonous constituents claimed to be contained in the mixture; namely, “arsenous acid” and corrosive mercuric chlorid (Rule 7).

There is no evidence that arsenous acid (arsenic trioxid) used intravenously is efficient and safe as a spirocheticide, and the administration of this drug in conjunction with mercuric chlorid in fixed proportion is irrational and dangerous--particularly so because of the implied similarity of Tri-Arsenole to arsenphenolamin hydrochlorid (Salvarsan, Diarsenol) (Rule 10).

=L. O. Compound No. 1 and L. O. Compound No. 2.=--In submitting these preparations to the Council, the Medical Supply Company stated that “No. 1” was “composed of the following ingredients; chloral, camphor, menthol, iodin, and oil of gualtheria, incorporated in a fatty base. Each ounce contains fifteen grains of chloral hydrate, nine grains of resublimed iodine.” “No. 2” was said to have the same composition as “No. 1” except that the oil of gaultheria had been omitted. The Medical Supply Company was informed that the rules of the Council required declaration of the amounts of each therapeutic constituent of pharmaceutical mixtures and that, therefore, in addition to the information furnished the amounts of camphor, menthol and oil of gualtheria should be given for “No. 1” and the amount of camphor and menthol for “No. 2.” The following reply was received:

“L. O. Compound No. 1 equals to each Tube,
Chloral hydrate gr. 15
Camphor gr. 22
Menthol gr. 7-1/2
Iodin (resublime) gr. 3-2/3
Oil of gaultheria m. 3
Petrolatum, q. s. oz. 1
L. O. Compound No. 2,