Chapter XXIII: Appendix (4)

Cin-U-Form Lozenges, manufactured by McKesson and Robbins, New York City, are marketed in bottles of 24 for 25 cents. They have a strong odor of cinnamon, weigh 15-1/2 grs. each, and are acid in taste and reaction. The label states that they contain:

“Cinnamon, Eucalyptus, Formaldehyde and Menthol--all powerful
germicides against Influenzal bacilli, but not injurious to the
system in this palatable form.”

A circular contains the same statement as to composition and claims further that they:

“... help to prevent the infection of Spanish Influenza, Pneumonia,
Grip Colds and to guard against Sore Throat, Tonsillitis,
Pharyngitis, etc.”

The A. M. A. Chemical Laboratory reported that Cin-U-Form Lozenges contained some formaldehyde (or paraformaldehyde) and no hexamethylenamin. It is obvious that the mouth and throat cannot be “disinfected” by these lozenges. They would be totally ineffective against bacteria that enter through the nose; they cannot prevent influenza, pneumonia, etc.--(_From The Journal A. M. A., Oct. 4, 1919_)

LAVORIS

Report of the Council on Pharmacy and Chemistry

Lavoris was considered by the Council in 1913, and its proprietors--the Lavoris Chemical Company--were advised that the preparation was inadmissible to New and Nonofficial Remedies because of conflict with Rules 1, 4, 6, 8 and 10. No report was published at that time. As the preparation is still widely advertised to physicians, the Council has again examined Lavoris and authorized publication of the following report.

W. A. Puckner, Secretary.

In recent years Lavoris has been widely advertised as “THE IDEAL ORAL ANTISEPTIC,” particularly to the dental profession. A printed card sent out by the Lavoris Chemical Company in 1913 read: “LAVORIS, the Pyorrhea Remedy. The Original ZINC CHLORIDE Mouth Wash. One grain zinc to each ounce.” The card also gave a “formula” to the effect that each pint of Lavoris contained:

Zinc Chloride 1.040
Resorcin 0.520
Menthol 0.400
Saccharin 0.195
Formalin 0.195
Ol. Cassia Zeyl 0.780
Ol. Caryophyl 0.195

Advertisements now appearing in medical journals repeat the older “formula” except that resorcin is omitted. The formula while seemingly frank and open is in reality indefinite and misleading in that no denomination of weight is given for the various constituents. It is uncertain, for example, if the figures in the formula are intended to represent grains, grams or percentages of the several constituents. In view of the indefinite statement of composition, a chemical examination of Lavoris was undertaken in the A. M. A. Chemical Laboratory. The report of the laboratory follows:

_Zinc._--This was determined electrolytically. Fifty c.c. gave 0.026 gm. zinc and 100 c.c. gave 0.0531 gm. zinc. The average is 0.0526 gm. zinc in 100 c.c. This is equivalent to 0.1102 gm. anhydrous zinc chlorid in 100 c.c.

_Chlorid._--After decolorizing some of Lavoris with chlorid-free animal charcoal, the chlorid was determined by the Volhard method. Twenty-five c.c. Lavoris required 4.328 c.c. tenth-normal silver nitrate solution equivalent to 0.01535 gm. chlorid (chloridion) or 0.0614 gm. in 100 c.c. A second 25 c.c. of Lavoris required 4.112 gm. tenth-normal silver nitrate solution equivalent to 0.01458 gm. chlorid (chloridion) or 0.05832 gm. in 100 c.c. Average is 0.05985 gm. This is equivalent to 0.1150 gm. zinc chlorid in 100 c.c. This agrees closely with the foregoing zinc determination.

_Resorcin._--The method of the U. S. Pharmacopeia was used. The total bromin absorption of 25 c.c. Lavoris was 3.68 c.c. tenth-normal bromin solution. This would be equivalent to 0.00675 gm. resorcin in 25 c.c. or 0.02700 gm. in 100 c.c. In a duplicate test, 25 c.c. Lavoris required 3.8 c.c. tenth-normal bromin solution equivalent to 0.00697 gm. resorcin or 0.02788 gm. in 100 c.c. Since oil of cinnamon absorbs bromin, 50 c.c. of Lavoris was boiled until very little or no odor of the oil was noted, keeping the volume nearly constant by adding a little water from time to time, and the bromin absorption then taken. In one experiment, 0.36 c.c. of tenth-normal bromin solution was consumed, and in a duplicate no bromin was absorbed. This shows the absence of resorcin.

_Residue._--On evaporating 25 c.c. Lavoris on a steam bath and subsequent drying of the residue at 100 C., 0.0455 gm. of residue was obtained. This is equivalent to 0.1820 gm. in 100 c.c.

_Saccharin._--Saccharin was detected in the residue and ether-extract of the residue by its intense sweet taste when a little sodium bicarbonate was added to it.

_Formaldehyd._--This could be detected by the Jarrison test. The color was not very pronounced and the quantity of formaldehyd was small.

_Oil of Cinnamon._--The odor and taste of Lavoris is characteristic of cinnamon.

_Menthol and Oil of Cloves._--The odor of menthol and of oil of cloves could not be detected, but no tests were made to demonstrate their presence.

The analysis thus indicates that the Lavoris of today contains no resorcin but does contain a small amount of formaldehyd, a little saccharin, and oil of cinnamon (menthol and oil of cloves could not be detected by the odor, but were not tested for). The analysis showed that the principal constituent of Lavoris is zinc chlorid, of which there is about 0.1 gm. per 100 c.c. (about 1/2 grain to the ounce).

The amount of zinc chlorid given in the published formula, i. e., 1.04, is meaningless because the unit of weight or measure is not given; furthermore, the analysis shows that it is inaccurate for any unit of weight that might be assumed from the published figures. Since the amount of the most active medicinal ingredient is both indefinite and inaccurate, the composition of the preparation is essentially secret. Lavoris is indirectly advertised to the public by having included in the package a circular giving a list of diseases for which the preparation was recommended. The combination of zinc chlorid, formaldehyd and oil of cinnamon (assuming the menthol and oil of cloves to be present as flavors) in a mixture is irrational and likely to lead its users to ascribe a false and exaggerated value to the preparation. The name is objectionable in that it does not indicate the composition of the potent ingredients of the mixture, but instead suggests its use as a mouth wash.

From a standpoint of public safety, the most serious objection to Lavoris, however, lies in the many unwarranted therapeutic claims and suggestions. It is generally held that zinc chlorid solutions which possess a strength of from 1 to 200 up to 1 to 500 exercise a weak antiseptic action. The strength of zinc chlorid in Lavoris is approximately 1 to 1,000. The directions for its use recommend that Lavoris should be diluted. A dilution of 1 to 4 is recommended for a variety of mouth conditions while for cystitis irrigations and as a vaginal douche, it is recommended that one tablespoonful be added to a quart of warm water or salt solution. The strength of zinc chlorid in the last suggested dilution would approximate 1 to 64,000. It is evident that no antiseptic action could be expected from such dilutions.

The recommendation that diluted Lavoris be used for the treatment of coryza, nasal catarrh, hay fever, inflamed eyes, hemorrhoids and leucorrhea is objectionable and irrational. Especially dangerous is the recommendation that members of a family exposed to diphtheria or scarlet fever should use Lavoris freely as a preventive. Such recommendations can but give a false sense of security and lead to the neglect of proved methods for preventing the spread of these diseases. Equally unwarranted is the recommendation that in gonorrhea one teaspoonful of Lavoris to eight of warm water be used with a blunt end syringe.

The use of Lavoris as recommended would not only prove valueless in many instances but might lead to serious consequences because really valuable methods of prevention or treatment might be neglected. For these reasons the preparation is in conflict with Rule 6.

The Council declared Lavoris ineligible for New and Nonofficial Remedies.--(_From The Journal A. M. A., Nov. 1, 1919_)

MEDINAL

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Medinal (Schering and Glatz, Inc.).

W. A. Puckner, Secretary.

Medinal is a proprietary name applied to barbital sodium (sodium diethylbarbiturate) the sodium salt of barbital (diethylbarbituric acid). The latter was first introduced as Veronal.

Medinal was deleted from New and Nonofficial Remedies in 1916 because the advertising issued by Schering and Glatz (who then acted as agents for Chemische Fabrik auf Actien vorm. E. Schering, the German manufacturer) contained misleading and unwarranted therapeutic claims. The Council did not publish its report because by the time the report was ready for publication the product was practically off the American market, and it was hoped that when Medinal again became available, Schering and Glatz would revise the claims and thus permit its reacceptance.

Medinal, said to be manufactured in the United States, is now marketed by Schering and Glatz, Inc. In October, 1918, the firm sent to the Council a typewritten copy of a proposed circular for Medinal. The firm was informed that this leaflet was subject to the objections that had been raised when Medinal was deleted from New and Nonofficial Remedies. In April, 1919, the firm submitted a printed circular which it was sending out. This contained numerous misleading statements, among them, these:

“MEDINAL removes its [Diethylbarbituric acid] one objectionable
feature--insufficient solubility--and thus fulfills the three
prerequisites of a truly rational hypnotic: Quick absorption,
insuring prompt action, rapid and complete excretion, affording
protection from cumulative toxic after effects, and the choice of
rectal and subcutaneous administration.”

There is no justification for the claim that diethylbarbituric acid (barbital) has only one objectionable feature and that a minor matter of “insufficient solubility.” The Council has called the attention of Schering and Glatz, Inc., to the fact that the difference in the time of absorption between Medinal (barbital sodium) and barbital is, at the most, but one of minutes and that there is no evidence that Medinal is excreted more rapidly than barbital. Hence the claims that the danger of toxic side-actions and that cumulative after-effects are avoided in this product, are wholly unwarranted.

It is also claimed, and the claim is unsupported by satisfactory evidence, that Medinal is useful in the insomnia of tuberculosis in which condition it is said to have a double advantage owing to its favorable effects on the night-sweats. It is claimed that Medinal is used in the withdrawal treatment of morphin addiction with great success; there is no evidence that Medinal has any special usefulness in this treatment of the morphin habit. It is claimed further that success has been reported with Medinal in the treatment of whooping cough. The Council knows of no satisfactory evidence to show that Medinal is of special value in whooping cough; on the contrary, it is capable of doing a great deal of harm. The recommendations that Medinal be used for the control of labor pains and in acute neuralgic pains that resist other forms of treatment are wholly unwarranted as the value of the drug in such conditions is inherently improbable and until satisfactory evidence in support of them is forthcoming, must be deemed misleading.--(_From The Journal A. M. A., Nov. 15, 1919_)

OMISSION OF COTARNIN SALTS (STYPTICIN AND STYPTOL) FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Salts of the base cotarnin have been used as local and systemic hemostatics. The hydrochlorid was first introduced as “Stypticin,” and is now in the pharmacopeia as cotarnin hydrochlorid (_Cotarninae Hydrochloridum, U. S. P._). The phthallic acid salt of cotarnin--cotarnin phthallate--was introduced as “Styptol.” Both Stypticin and Styptol were admitted to New and Nonofficial Remedies. In 1918 the Council voted to omit Stypticin because the former American agents were no longer offering it for sale. Styptol was retained and is described in N. N. R., 1919.

As was pointed out in the description (N. N. R., 1918), the evidence for the usefulness of the cotarnin salts has been contradictory and unsatisfactory; but since the available data against the efficiency were at least equally unreliable, the Council deemed it best to retain them in N. N. R. pending a thorough investigation of the subject. This was undertaken by P. J. Hanzlik, at the suggestion of the Therapeutic Research Committee of the Council.

A reliable judgment of hemostatic efficiency can be formed only on a basis of strictly controlled conditions, which can best be furnished in the laboratory. Hanzlik repeated the principal experiments published by previous investigators, and applied a number of new or improved methods. The results (published in the _Journal of Pharmacology and Experimental Therapeutics_ =10=:523, 1918; =12=:71, 1919) show the following:

_Direct Application to Wounds._--The widely quoted results of the gynecologist K. Abel, on the footpad of cats, were found to be quite unreliable. When the experiment is properly controlled, the results are either negative or the bleeding may be increased. Quantitative experiments on wounds of the footpad of dogs showed that cotarnin invariably _increased_ the bleeding. Equally negative or unfavorable results were obtained with wounds to the comb of roosters, and to the liver and spleen.

_Direct Action on Vessels._--The results of perfusion experiments were variable, but, in general, showed a vasodilation action instead of constriction. This holds true also of the uterine vessels. The vessels in the living animal (rabbit’s ear) were also unaffected.

_Systemic Administration._--The bleeding from an irrigated wound was not modified directly by intravenous injection of cotarnin salts, but varied merely with the state of the blood pressure.

The evidence for the inefficiency of cotarnin salts as hemostatics seemed so conclusive as to warrant the Council in rescinding the acceptance of Styptol, and directing the omission of the general article on cotarnin salts and the description of Styptol from New and Nonofficial Remedies.--(_From The Journal A. M. A., Nov. 22, 1919_)

MICAJAH’S WAFERS AND MICAJAH’S SUPPOSITORIES

Report of the Council on Pharmacy and Chemistry

“Micajah’s Medicated Wafers” and “Micajah’s Suppositories,” sold by Micajah & Co., Warren, Pa., are declared inadmissible to “New and Nonofficial Remedies” because (1) their composition is essentially secret (Rule 1); (2) name of neither of these mixtures is indicative of its composition (Rule 8); (3) of exaggerated and unwarranted therapeutic claims (Rule 6), and (4) the therapeutic advice which accompanies the trade packages constitutes an indirect advertisement to the public (Rule 4).

W. A. Puckner, Secretary.

Micajah’s Medicated Wafers (formerly called “Micajah’s Medicated Uterine Wafers”) were analyzed in the A. M. A. Chemical Laboratory in 1910. They were found to consist essentially of dried (“burnt”) alum, boric acid and borax, in approximately the following proportions:

Alum, dried 59.86 per cent.
Borax, dried 15.62 per cent.
Boric acid 5.67 per cent.
Water of hydration 18.85 per cent.

There are a number of drugs that are more or less effective in the treatment of local lesions of mucous membranes and the skin. They are classed as astringents. Among these are included alum, borax and boric acid. Every physician has used them. To say that a wafer consists of alum, borax and boric acid inspires but little awe. But there is something much more mysterious and impressive in declaring that a wafer “consists of an astringent and antiseptic base, in which are incorporated certain medicaments which both locally and after absorption, contribute to the astringent, antiphlogistic, depletive, soothing and healing action of the product.” This gives the impression that some powerful and almost incomprehensible factors are at work. Yet, after all is said and done, the substances contained in Micajah’s Medicated Wafers are just the homely old alum, boric acid and borax.

In addition to “Micajah’s Medicated Wafers,” Micajah & Co. also put out “Micajah’s Suppositories for Hemorrhoids.” These have been examined in the A. M. A. Chemical Laboratory and, like the “Medicated Wafers” have been found to contain alum, boric acid and borax--and these substances practically alone--incorporated in cocoa butter. The company claims that “to these have been added Ammonii Ichthyosulphonate, Balsam of Peru, Ext. Belladonae.” The A. M. A. chemists report, however, that if extract of belladonna is present at all it is in amounts too small to be detected by the method commonly employed in the chemical examination of alkaloidal drugs. The chemists report further that while ammonium ichthyosulphonate and balsam of Peru both have a decided odor and are dark in color, the suppositories have but little color and the odor of the cocoa butter that forms their base is not covered by these drugs; obviously, therefore, if ammonium ichthyosulphonate and balsam of Peru are present at all it is in amounts utterly insufficient to exert any therapeutic effect.

It would be hard to find better examples of mischievous proprietary medicines than these two products of the Micajah Company. “Twins of Efficiency,” they are called in an advertising pamphlet. The composition is not stated. A physician using the “twins” does so absolutely in the dark. To him they are secret preparations. He is encouraged to use them in a great variety of conditions in which other drugs are much more useful. Inevitably, physicians using them will be likely to overlook, or pass over, new growths, specific infections and diseases that require radical remedial measures.

In addition to misleading and exaggerated claims, there is a reference to a report from the usual “well-known and reliable bacteriological laboratory.” The excerpts published from this report of an unnamed laboratory are sufficiently vague to incriminate no one.

From time to time it is worth while to emphasize facts regarding proprietary medicines that while obvious are sometimes forgotten. For this reason attention is directed to Micajah’s Uterine Wafers and Micajah’s Suppositories.--(_From The Journal A. M. A., Nov. 29, 1919_)

ALKALITHIA

Report of the Council on Pharmacy and Chemistry

Alkalithia was introduced at a time when it was believed that the administration of lithium salts served to remove uric acid from the system. The product was considered by the Council in 1906, and found ineligible for New and Nonofficial Remedies. No report, however, was published at that time.

Because of inquiries received, the Council examined the current claims for Alkalithia, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Keasbey and Mattison Company’s Effervescent Alkalithia is sold with the following statement of composition:

“Each dose or heaping teaspoonful contains 1 grain of Caffeine, 10
grains each of Bi-carbonates of soda and potash, and 5 grains of
Carbonate of Lithia.”

The A. M. A. Chemical Laboratory reports that Alkalithia is an effervescent mixture which contains alkaline carbonates and bicarbonates together with caffein, free tartaric acid and free citric acid. The major portion of the alkali carbonates and bicarbonates is converted into citrates and tartrates when the preparation is dissolved in water--as is done before it is taken. An excess of alkali is present, however, as the solution has an alkaline reaction. Each “heaping teaspoonful” (which was found to be about 4.85 Gm.) contains about 0.044 Gm. of caffein (the manufacturers claim 0.0648 Gm. per heaping teaspoonful). As taken, Alkalithia, therefore, represents caffein in a solution of alkali tartrate, citrate and bicarbonate containing free carbonic acid. If it is assumed that all of the tartrate and citrate in Alkalithia is converted into carbonate in the organism, a “heaping teaspoonful” of Alkalithia would represent about 2.9 Gm. of sodium bicarbonate. This assumption is, however, not correct, for it is known that tartrates are not completely converted into carbonates in the organism.

According to the label on the bottle, this mixture of caffein and alkali salts is “a common sense remedy for the relief and treatment of conditions dependent upon perverted metabolism as manifested by neuralgic, rheumatic, cardiac and renal symptoms.” Wrapped with a trade package is a circular in which is discussed the “uric acid diathesis” as “a cause of Rheumatism in its various forms, Calculus, Gravel and Inflammation of the Bladder and Kidneys, Asthma, Hay Fever, Catarrh, Quinsy and Bronchitis, Eczema, Hives, Itching and Burning of the Skin, Palpitation of the Heart and Cold Hands and Feet, Dizziness, Mental Depression, Melancholia, Neuralgia, Chorea, Hysteria, Numbness and a great variety of purely nervous symptoms.” The arguments for the use of Alkalithia as “a safe and scientific treatment for the uric acid diathesis” found in the circular constitute an indirect appeal to the laity (conflict with Rule 4).

In the circular matter sent direct to the physicians, Keasbey and Mattison claim that in rheumatism, Alkalithia is prescribed by the medical profession more often than any other remedy. The claim is made that, “In five minutes the urine will be discolorized and analysis will show it to be loaded with urates.” The manufacturers further assert:

“You can change the character of the urinary secretion in a few
minutes completely” by Alkalithia, and “In nine cases out of
ten, when the doctor prescribes ‘Alkalithia’ his patient greatly
improves, or gets well.”

The firm advises that “Renal Insufficiency” be determined by the old method of multiplying the ounces of urine in twenty-four hours by the last two numbers of the specific gravity, adding 10, which gives the number of grains of solids excreted in the twenty-four hours. If this is low, no matter what the cause, they advise Alkalithia, “that ideal eliminant.”

The Council declared Alkalithia inadmissible to New and Nonofficial Remedies because the claims made on the label and the circular accompanying the trade package lead the public to its detriment to depend on this preparation (Rule 4); and because the therapeutic claims are unwarranted (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 65_)

ARHOVIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Arhovin is a solution of dephenylamine, thymol benzoate and ethyl benzoate, marketed by Schering and Glatz, Inc. It was omitted from New and Nonofficial Remedies because the therapeutic claims made for the preparation were unwarranted and because the firm had refused to discontinue the distribution of the advertising which contained the objectionable claims prior to Jan. 1, 1919. When the report which appears below explaining the dismissal was submitted to Schering and Glatz, Inc., the firm again promised a revision of its advertising, but refused discontinuance of the objectionable circular before Jan. 1, 1920. Since Arhovin is still marketed with unwarranted therapeutic claims, the Council has authorized publication of this report.

W. A. Puckner, Secretary.

The attention of the firm Schering and Glatz, Inc., was called to misleading statements in its booklet for Arhovin in 1915, and in 1918 the firm was informed that unless the misleading statements were withdrawn before Jan. 1, 1919, Arhovin would be omitted from New and Nonofficial Remedies.

The following quotations are taken from the circular in question, and illustrate the character of the claims to which objection was made:

“Striking also is the antiphlogistic and anesthetic effect
of Arhovin on the inflamed mucosae, an effect which, as all
authorities agree, is far greater than that of all other internal
anti-gonorrheaics.”

“Under its influence vesical and prostatic complications,
gonorrheal arthritis, endocarditis, etc., are rarely incurred.”

References to the indexes of leading textbooks, including those of Meyer and Gottlieb, Cushny, Sollman and Bastedo, fails to show that Arhovin is so much as mentioned by those authors; hence, it is obviously false to state, as is done in the first of the quotations above, that all authors agree concerning the striking effects of Arhovin.

Many of the statements are objectionable by reason of the actions implied, rather than stated directly. The following are examples:

“Arhovin in Gonorrheal Infections of the Male Genito-Urinary
Organs. Anterior Urethritis. This is the class of cases in which
the most favorable results from Arhovin have been reported.”

“Posterior Urethritis.

“Here also the striking effects from Arhovin medication, both
in acute and chronic cases, are rapid decrease of discharge,
disappearance of gonococci from the secretion, and cessation of
subjective difficulties, such as strangury.”

While the firm did not agree to withdraw the objectionable advertising before Jan. 1, 1919, which made necessary the omission of Arhovin from New and Nonofficial Remedies, 1919, it did submit a proposed folder in which the most objectionable of the claims are still made.

The following statement, which was in the proposed “folder” and is included in an advertising pamphlet sent out during 1919, serves to illustrate those points:

“Its action is three-fold:

“Strong antiseptic and bactericidal effect upon the urethral and
vesical mucosae, highly conducive to shortening and palliation of
the acute disease course.”

No evidence has been presented that Arhovin is capable of destroying the gonococcus in the urethra, and consequently, the Council declared the recommendation for the use of Arhovin in the treatment of gonorrhea, by means of claims such as those just cited, is both misleading and dangerous.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 66_)

CHLORON, CHLORAX AND NUMBER “3”

Report of the Council on Pharmacy and Chemistry

The report which appears below was sent to the Chlorine Products Company, Inc., May 14, 1919. In reply to an inquiry sent the Chlorine Products Company, July 8, the company wrote that it could send no reply because the medical director was still in France. However, Chloron and Chlorax are being advertised in medical journals; also essentially the same advertising as that discussed in the report was recently received by a physician from the Chlorine Products Company.

The preceding facts having been reported to the Council, publication of the report was authorized.

W. A. Puckner, Secretary.

Chloron, Chlorax and Number “3” are preparations of essentially similar composition put out by the Chlorine Products Company, Inc., New York.

Chloron

Chloron, according to the label, is “A stable CHLORINE remedy for the reduction of inflammation, relief of pain and for all wounds, burns, scalds and every description of sores except cancer and lupus.” Its composition is given as:

“Free chlorine, 0.200 per cent.; calcium chloride, 0.190 per cent.;
mercurous chloride, 0.030 per cent.; lithium chloride, 0.035 per
cent.; calcium hydrate, 0.010 per cent.; water to 100 parts.”

The Council asked the manufacturers for further information in regard to the composition or preparation of Chloron and received this reply:

“Chlorine gas is prepared in the usual way and purified and passed
into water until a saturated solution is made.

“Water to the extent of three times the volume of the chlorine
solution is used to dissolve the necessary amount of calcium
chloride, and the two solutions are mixed.

“The necessary amounts of Lithium and Mercurous Chloride are then
intimately mixed and made into solution. This solution is then
added to the above and the whole is agitated for some minutes.”

A specimen of Chloron was examined in the A. M. A. Chemical laboratory and the chemists reported:

Qualitatively the presence of the following constituents was confirmed: calcium, mercury, lithium, chlorid, free chlorin. The solution was alkaline. Of course, the declaration that Chloron contains mercurous chlorid (calomel) is obviously incorrect, as mercurous chlorid cannot exist in a solution containing active (free) chlorin, but is oxidized to mercuric chlorid (corrosive sublimate). As the solution was alkaline in reaction, it seemed unlikely that all the active chlorin was present in the free state, as declared on the label. Quantitative determination of free chlorin and of total active (“available”) chlorin gave: free chlorin, 0.036 gm. per hundred c.c.; total “available” chlorin, 0.330 gm. per hundred c.c., or 165 per cent. of the claimed amount.

A comparison of the information sent to the Council with the analytic findings leads to the conclusion that Chloron is not of reliable composition.

As evidence of the therapeutic value of Chloron, the following “case reports” were submitted:

“In a case of second degree burn involving the most of one leg
from the middle of the calf down, CHLORON was the only dressing
used. The burn was a bad one and the patient in a rundown anaemic
condition, at no time was there any appearance of pus, the surface
looked clean and bright and the healing was accomplished with
practically no scar whatever. The burn was kept wet with the
solution by hourly applications day and night. The skin which has
grown on the wound is clear, healthy and firm.

In another case of Varicose veins of long standing, the result was
surprising. The patient told of two years vibrating from Hospital
to Hospital and getting no real relief. Each leg had large open
running sores, the only dressing used was wet compresses of this
solution. The pus disappeared at once, the wound began to cicatrise
from the edges and in two weeks the man was discharged from the
hospital practically cured.”

“CHLORON was recently tried at the ---- and ---- Hospital on cases
presenting ulcers and other sores which did not readily yield to
other methods, with good results, in fact were of an indolent type.
In these cases CHLORON proved very valuable.”

“I have used CHLORON on a series of cases (surgical) presenting pus
foci and I have found the application very beneficial and healing,
the pus early disappearing. In cases of Osteomyelitis, Suppurating
Arthritis, Cellulitis and Chronic Ulcers, CHLORON is particularly
valuable, its good effects quickly observed and the time of
restoration to health shortened.”

In the first case report, there is no evidence that Chloron is more efficient in the treatment of burns than any other commonly used procedure might have been. In the case of the varicose ulcers, while there was some apparent benefit from Chloron, no credit is given to rest and the general treatment which is known to be important in the treatment of such conditions. The evidence in the other case reports is quite inconclusive. Consideration of the “case reports” leads to the conclusion that clinical evidence for the value of Chloron is lacking.

Attention should be called to the fact that the amount of active chlorin, claimed to be present in Chloron as well as the amount found by the association laboratory, is less than that considered effective by Dakin, Dunham and others; seemingly in preparing Chloron no attention has been paid to the degree of alkalinity, yet the importance of this factor is now generally recognized.

Chloron fails to comply with the requirements for surgical solution of chlorinated soda (N. N. R., 1919, p. 133), yet the manufacturers make free use of the text of Dakin and Dunham’s Handbook of Antiseptics in their advertising pamphlet. Thus:

From the Chloron pamphlet:

“This ideal antiseptic effects complete sterilization within
its sphere of action without causing any damage to the cells or
tissues. An important method of judging the injurious action of
antiseptics is to investigate their effects on the leucocytes. From
experiments _in vitro_ by Parry Morgan and _in vivo_ by Col. C. J.
Bond with the strength of antiseptics commonly used in surgery, it
has been found that Chlorine antiseptics and mercury salts have
little effect on phagocytosis in comparison with other germicides.

The activity of the leucocytes from wounds which have recently been
treated with CHLORON may be demonstrated experimentally.”

“In addition to its antiseptic action CHLORON is a strong oxidizing
agent and deodorant and possesses to a marked degree the property
of decomposing toxins. In this connection it is interesting
and pertinent to note that Dean, by the regulated action of
hypochlorous acid, has prepared a nontoxic dysentery vaccine and it
is now a common observation that the free use of CHLORON may reduce
the constitutional symptoms arising from septic processes and that
they reappear on discontinuing the antiseptic treatment.”

Dakin and Dunham Handbook of Antiseptics:

“The ideal surgical antiseptic should effect complete sterilization
within its sphere of action without causing any damage to animal
cells. At the moment such a substance does not appear likely to be
found, but on the other hand it is surprising to see how little
damage may be done to animal tissues by some active antiseptics.
An important method of judging of the injurious action of
antiseptics is to investigate the condition of the leucocytes in
wounds recently treated with the substance under consideration.
In general it appears from experiments _in vitro_ that, with the
strength of antiseptics commonly used in surgery, mercury salts
and hypochlorites have relatively little effect on phagocytosis as
compared with phenol (Parry Morgan). It is a regular phenomenon to
observe activity of the leucocytes obtained from wounds which have
been recently treated with hypochlorites.

Ingenious methods for determining the influence _in vivo_ of
antiseptics on the activities of leucocytes have been worked out by
Col. C. J. Bond.

“In addition to their disinfecting action, the Chlorine antiseptics
are strong oxidizing agents and deodorants and moreover possess in
high degree the property of decomposing toxins. By the regulated
action of hypochlorous acid, Dean has prepared a nontoxic dysentery
vaccine and it is a common observation that the free use of
hypochlorites may reduce the constitutional symptoms arising from
septic processes and that they reappear on discontinuing the
antiseptic treatment.”

Chlorax

Chlorax is said to be “A stable CHLORINE solution for internal use,” in “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions.” It is claimed to have the same composition as that of Chloron with the addition of 0.016 per cent. of tincture of opium.

The A. M. A. Chemical Laboratory reported that the free chlorin in Chlorax was 0.01 gm. per hundred c.c. and the total amount of active (“available”) chlorin was 0.25 gm. per hundred c.c., or 125 per cent. of the amount claimed. The laboratory notes that though the chlorin content of Chloron and Chlorax is claimed to be the same, that of Chlorax actually is less. This is not surprising when the presence in Chlorax of reducing substances such as alcohol is borne in mind. The laboratory concludes that Chlorax is not of reliable composition.

The following is typical of the “case reports” submitted to show the value of Chlorax:

“In January last I used Chlorax on a case of Diabetes Mellitus and
with excellent results.

“The patient had been suffering for about nine years and when first
brought to my care Toxemia had set in, he was drowsy, irritable
and unable to leave the house. I prescribed Chlorax in teaspoonful
doses four times a day and am pleased to say that in one week he
showed marked improvement. Soon after he was able to leave the
house and attend to his business and after two months’ treatment
resumed a normal diet and habits apparently without injurious
effects.

“I believe that in this case Chlorax undoubtedly prolonged life.”

No mention is made of the dietary or other measures used. The wide variation in diabetes and its response to proper diet is so well known that the noncommittal statement concerning the beneficial effects of Chlorax amounts to no evidence at all in favor of the preparation.

The other “case reports” furnished by the Chlorine Products Company, Inc., which concern the treatment of gastric ulcers, acute alcoholic gastritis, tonsillitis, etc., are equally unconvincing. In fact, no satisfactory evidence for the clinical value of Chlorax has been presented.

The following from the advertising for Chlorax is unwarranted and absurd:

“Mercurous chloride (calomel) is perhaps the most widely used
internal antiseptic and alterative and has established itself in
the therapy of constipation, cholera, dysentery, cardiac dropsy,
pleurisy, malignant fever, malaria, syphilis, worms, infectious
diseases, gout and rheumatism; lithium chloride is particularly
efficacious in acute and chronic parenchymatous nephritis and in
various lithemic conditions; while Opium has no rival as an anodyne
and can be used to stabilize and conserve the alkaline reserve of
the body against the acidosing influence of infections.”

Further, on page 14 we find:

“In chills and fever malaria and other blood dicrasias, CHLORAX
is indicated as an internal antiseptic and it exerts a beneficial
effect on the course of these diseases.”

The claims made for Chlorax are exaggerated and misleading.

Number “3”

According to the label, Number “3” is “A STABLE CHLORINE remedy for the purification of the blood,” with the composition:

“Free Chlorine, 0.35 per cent.; Calcium Chloride, 0.30 per cent.;
Mercurous Chloride, 0.03 per cent.; Lithium Chloride, 0.04 per
cent.; Calcium Hydrate, 0.01 per cent.; Opium, 0.02 per cent.;
Ethyl Alcohol, 0.10 per cent.; water to 100 parts.”

It will be noticed that the composition claimed for Number “3” is essentially similar to that claimed for Chloron. It differs from Chloron in that the amounts of some of the constituents are somewhat greater, and in that, like Chlorax, it contains some tincture of opium.

The A. M. A. Chemical Laboratory reports that the free chlorin in a specimen of Number “3” was 0.024 gm. in 100 c.c. and the total active (“available”) chlorin 0.173 gm. per hundred c.c., or about 50 per cent. of the claimed amount. The examination indicates that Number “3” is of unreliable composition. The Chlorine Products Company, Inc., submitted no clinical evidence for Number “3” to which it refers as “our Syphilis remedy.” It stated that two physicians had used the preparation “with good results,” and admitted that “the company requires further evidence before pushing it.”

The Council declared “Chloron,” “Chlorax” and “Number ‘3’” in conflict with the rules governing admission to New and Nonofficial Remedies. All are of unreliable composition (conflict with Rule 1). The therapeutic claims made for the preparations are not substantiated by acceptable evidence and are unwarranted and misleading. Chloron is inferior as an antiseptic to the well-known surgical solution of chlorinated soda on account of its low chlorin content and uncontrolled reaction. There is no warrant for the claim that Chlorax is useful in the treatment of “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions,” nor is there warrant for the claim that “Number ‘3’” is a remedy for the purification of the blood or a “Syphilis remedy” (conflict with Rule 6).

The names of these pharmaceutical mixtures are not descriptive of their composition (conflict with Rule 8).

All three preparations are irrational. No evidence has been furnished that the lithium salt is of value in the mixtures. It is not rational to combine an active chlorin preparation and a mercury salt in one mixture, nor is there evidence that the addition of opium to the preparations proposed for internal use is of value or rational. Experimentation with Number “3” as a “Syphilis remedy” is to be severely condemned in that those on whom it is used will in the meantime be deprived of efficient medication (conflict with Rule 10).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 70_)

ELARSON OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report announcing the omission of Elarson from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Elarson, now sold by the Winthrop Chemical Company, Inc., was formerly sold in the United States by the Bayer Co., Inc. It was admitted to New and Nonofficial Remedies in 1914.

The circular issued by the Winthrop Chemical Co. contains several statements markedly at variance with the results of an investigation made, at the request of Fischer, by Joachimoglu (_Arch. f. exper. Path. u. Pharmakol._ 78:1914). The circular states that Elarson contains about 13 per cent. arsenic. Joachimoglu found from 10.8 to 11.1 per cent. to be present. The circular states further:

“The fact that Elarson represents a lipoid-like chemical
combination of arsenic has an important bearing upon its absorption
and utilization in the system ... there is good reason to believe
that when arsenic is administered in a stable, lipoid-like
combination, as in Elarson, it is more readily taken up by the
cells and more completely utilized than when given in the customary
manner.”

“As regards the behavior of Elarson in the system, it has been
shown that its active constituent, chlorarseno-behenol, is almost
completely absorbed in this form, probably as a chlor-behenolate of
sodium or potassium.”

As a matter of fact, Joachimoglu found that very little arsenic was absorbed when Elarson was given to dogs and rabbits; most of it was recovered from the feces; only traces were found in the liver and kidneys and none in the blood and brain. The absence from the latter organs shows that the lipoid solubility does not obtain in the body. It is claimed in the circular that Elarson has the advantage over Fowler’s solution “in that it is free from any irritating action upon the gastro-intestinal tract”; it is stated that as many as sixty tablets have been given to dogs daily without any toxic effects. Joachimoglu, on the other hand, found powdered Elarson to be very irritating to the gastro-intestinal tract; also that the dog could not stand sixty tablets at all (_gar nicht vertragen_), such doses causing vomiting, diarrhea and intestinal hemorrhages; on repeated administration the symptoms became progressively more severe. Joachimoglu also found that, compared on the basis of arsenic content, Elarson, given intravenously, is from ten to twelve times as poisonous as arsenic trioxid. Elarson is recommended for the class of cases in which Fowler’s solution is used.

To sum up: None of the special claims made for Elarson--the arsenic content, ready absorbability, freedom from irritating action on the gastro-intestinal tract and its alleged better adaptation for continued administration--have been substantiated; on the contrary, they have been disproved as well as the theory of its mode of absorption proposed by Fischer and Klemperer. Furthermore, Joachimoglu found that when it actually got into the circulation (intravenous injection) in the form in which Fischer and Klemperer supposed it to be absorbed, it was from ten to twelve times as toxic as arsenic trioxid.

The Council voted to omit Elarson from New and Nonofficial Remedies because it is sold under unproved and consequently unwarranted claims and because it is an unscientific and relatively useless article. Elarson has not been shown to have advantages over Fowler’s solution; on the contrary, in some respects at least, it is inferior.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 75._)

IODIPHOS

Report of the Council on Pharmacy and Chemistry

A report which appears below was sent Charles L. Heffner for consideration. No reply having been received, the Council authorized its publication.

W. A. Puckner, Secretary.

Iodiphos, marketed by Charles L. Heffner, Brooklyn, N. Y., is declared to contain ferric citro-iodine, 6 grains; calcium glycerophosphate, 8 grains; sodium glycerophosphate, 8 grains, and hypophosphorous acid, 2 minims in each fluidounce, and to present “the Metallic and Non-Metallic elements: Iron, Iodine, Phosphorous, Calcium and Sodium (each in separate Basic combination).”

According to the label, Iodiphos is “ALTERATIVE, TONIC, NERVINE and ANTI-TUBERCULAR” and is “For Treatment of BLOOD, NERVES and PULMONARY ORGANS.” An advertising circular[129] asserts that “Iodiphos exerts its Physiological action rapidly in hardening of the Arteries, High Blood Pressure, Anaemia, Glandular Swelling, Neurasthenia, Hypochondria, Phthisis, Bronchitis, Asthma, Pneumonia and as an Intestinal Antiseptic and Appetizer,” and declares it to be “Indispensable as a Tonic and Restorative.”

[129] After publication of the foregoing report had been authorized by the Council, a letter was received from Charles L. Heffner, advising that the distribution of the circulars has been discontinued.

In the advertising circular it is averred that in the production of Iodiphos “Chemistry Again Aids the Modern Physician.” Iodiphos is another instance when a decadent polypharmacy proposes haphazard medication and so obstructs the efforts of modern medicine to establish the use of single drugs to meet definite indications.

Iodiphos is inadmissible to New and Nonofficial Remedies because it is an irrational mixture of drugs sold with therapeutic claims that are unwarranted, and under a name which is not descriptive of its composition.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 81._)

MERVENOL AND ARMERVENOL NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the report which appears below declaring Mervenol and Armervenol, marketed by the Hille Laboratories, inadmissible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Mervenol is stated by the proprietors--The Hille Laboratories, Chicago--to be a hydrosol (colloidal suspension) of the sulphides of mercury and copper, containing sufficient sodium chloride to make it isotonic with blood serum, and “inert proteid” and “carbohydrate” to stabilize the colloidal suspension: each cubic centimeter is stated to contain 0.005 gm. mercury, 0.0016 gm. copper, and 0.0016 gm. sulphur.

It is claimed that this preparation is of value in pneumonia, influenza, and other conditions and diseases requiring increased leukocytosis.

It is further claimed that the properties and therapeutic effects of this preparation are as follows: “Practically non-irritant; practically non-toxic; lower temperature, often crisis like; lower pulse, with better elimination; greatly accelerated recovery from Influenza; fewer Pneumonia complications; lower mortality rate in Influenza and Pneumonia; remarkable Leucocyte stimulation.” Administration by mouth and by intramuscular and intravenous injection are advocated.

In the recent influenza epidemic, it is reported that therapeutic results of some value were obtained at the Great Lakes Training Station and at Fort Sheridan. The reports of certain medical officers indicate that this preparation seemed to have some effect on the course of pneumonia and influenza, on the temperature, and on the leukocyte count. But those conducting the experiments state that it was “absolutely impossible” to fulfil ideal conditions as to controls and other observations at the time the experiments were conducted.

So far as the Council knows, no effort has been made to determine the potent constituent, or constituents, of this preparation; whether the mercury, the copper, or the protein in the mixture was responsible for the claimed benefits is an open question.

These reports were given careful consideration, but it was decided not to accept this preparation because of (1) exaggerated therapeutic claims, conflicting with Rule 6 (aside from the report of its use in influenza and pneumonia at the Great Lakes Training Station and the Post Hospital at Fort Sheridan, which reports are of work done and observations made under conditions which did not permit careful controls, no evidence has been presented to the Council supporting the therapeutic claims) and (2) being an irrational mixture, conflicting with Rule 10--a mixture containing colloidal mercury, copper and sulphur with proteins and carbohydrates in addition, it is difficult to predict the changes which occur in such mixtures on standing.

Samples of Mervenol (two 1-ounce bottles) submitted by the manufacturer, June 5, 1919, were found when opened, Aug. 18, 1919, to have undergone decomposition. A very disagreeable odor had developed, the liquid was turbid, and a large amount of precipitate had formed.

Armervenol is stated by the proprietors--The Hille Laboratories, Chicago--to be a hydrosol (colloidal suspension) of “mercury-copper-sulpharsenite” containing sufficient sodium chlorid to make it isotonic with blood serum and “inert proteid” and “carbohydrate” to stabilize the solution: each cubic centimeter is declared to contain 0.0025 gm. arsenic, 0.005 gm. mercury, 0.0016 gm. copper, and 0.0032 gm. sulphur.

The use of Armervenol as advised by the Hille Laboratories is the same as that of Mervenol, and in addition its use in syphilis is emphasized. The criticisms of this mixture are similar in every respect to those directed against Mervenol--the addition of arsenic introduces still another factor of uncertainty.

After investigating these claims, it was decided not to accept this preparation on the ground (1) that the therapeutic claims are unproved and unwarranted, conflicting with Rule 6, and (2) that the mixture is an irrational one, conflicting with Rule 10.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 82._)

NORMAL PHENOL SERUM (CANO) AND METHYL-PHENOL SERUM (CANO)
NOT ACCEPTED FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following statement declaring Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) ineligible to New and Nonofficial Remedies.

W. A. Puckner, Secretary.

No statement of the composition of these preparations was submitted to the Council and none appears on the labels of the trade packages. However, the advertising circular contains statements such as:

“... normal phenol serum--phenol with methyl blue dissolved in
anaphylactic serum ...”

“... a combination of human or horse serum with Phenol and
Methylene-blue, thereby forming a new chemico-biologic product
which he termed Methyl-phenol Serum or, chemically, Chloride of
Phenol Thionin Tetramethylene-Seric.”

“Methyl-phenol Serum is a chemico-biological product in which
Phenol is the chief factor. Each ampule of 10 c.c. contains the
therapeutic equivalent of 0.5 gm. (7.5 grains) of Phenol.”

From the foregoing it appears that both preparations contain phenol and methylthionine chloride (methylene blue) and that the second does not contain methyl phenol (cresol) as the name would indicate.

No definite evidence for the value of these preparations is brought forward and even the manufacturer is constrained to caution, “We assume no responsibility for the therapeutic action of the serum....” On the other hand there are a great many statements in the papers of Cano and his colleagues to which exception must be taken. Of these, from among many similar, the following statements are to be cited and commented on:

“Accepting that the gonorrheal infection gives systemic toxemia
from absorption of the toxins ...”

It is the general opinion that in the majority of instances there is no systemic toxemia.

“The technique of intraprostatic injection, while less simple than
that of the intravenous, is by no means so difficult or complicated
as to place it exclusively in the category of the urologist.”

This obviously is an attempt to encourage the general use of these preparations and to minimize the necessity for careful study and special skill in their employment. It is most unwise for one to attempt intraprostatic injections unless he is specially trained in the technique of this procedure.

“This injection to be performed after the 5th or 6th intravenous
injection of Methyl-phenol Serum....”

Intravenous injections have a place in sane therapy only when the medicament to be so administered is of known composition and when evidence is available which gives assurance that definite results shall follow its use. In the absence of these conditions it is manifestly unwise and even unexcusable to employ any medicament in this manner, and its repeated use is reprehensible.

“Intravenous injection of Methyl-phenol Serum alternating with
intravenous injections of mercury should be given every 48 hours
until infection is under control.”

This quotation further emphasizes that the treatment, as advised, carries with it a certain element of danger.

“Methylene blue prevents the phenol from exerting its usual action
upon the red blood corpuscles, and ensures rapid elimination
through healthy kidneys. It preserves the antiseptic power of
the phenol and prevents the phenol from interfering with the
chemico-biological function of the white and red blood cells. The
serum component favors chemotaxis, it strengthens bodily defense,
it prevents anaphylaxis even in debilitated patients, and it
replaces the resistance which has been impaired by the demands that
have already been made upon it.”

No evidence is submitted to substantiate these claims. It seems strange that phenol should lose its power and that this should be restored by the methylene blue.

“It has a refractory chemico-biological action, and exercises no
vicious effect on the red blood corpuscles in the circulation, but,
on the contrary, by its inoffensive presence, it wholly preserves
all of the physiological properties of the blood.”

What “a refractory chemico-biologic action” is, is not clear, but there is no evidence that this preparation has any action which might be defined as “refractory chemico-biological,” that its presence is inoffensive or that it wholly preserves all the physiologic properties of the blood.

“The treatment of gonorrhea by Cano’s theory ... is firmly
based upon chemico-biological facts and accepted authoritative
theories and bears the same relation to gonorrhea that intravenous
injections of arsenicals bear to syphilis.”

Quite an exaggerated and unwarranted statement. In the same way, objection is taken to the following quotations:

“Phenol administered intravenously in combination with methylene
blue, to protect the red-blood globule, undergoes no change, and
preserves all of its actual antiseptic effect on the gonococcus and
its toxins as though employed in the test tube.”

“When thus introduced into the human body its elimination is
unique, effective, antiseptic, germicidal, being completely and
exclusively thrown off through the kidneys in a period varying from
one-half to twelve hours without local injury or disturbance to the
general economy.”

“Combinations of phenol are unstable, but they do have the
advantage of mitigating direct action on the cells and globules.
It is also known that ordinary phenol has a _coagulant action_ on
the albumins and an _oxidizing power_ on the tissues, which power,
if permanent, produces gangrene. By virtue of this dual action it
therefore acts as a _modifier_; by its oxidizing power on the germ
it is germicidal, and prevents the growth of the gonococcus; and
by its coagulant power on the toxins it relieves paragonococcal
lesions (mono- and poly-arthritides) and affections of the serous
organs (endo- and pericarditis, meningitis), and some definite
systemic disturbances, the pathology of which is often confused
with that of other infections.”

“Lymphocytosis is often persistent in some individuals in whom
the internal secretions and the processes of assimilation and
disassimilation are deficient; and because of the lack of these the
organic physiological ferments are insufficient for the mechanism
of nutrition and the phenomena of hematopoiesis.”

Until proof is available showing that phenol, administered intravenously in the quantities employed in Cano’s Normal Phenol Serum and Cano’s Methyl-Phenol Serum, acts as a germicide and methylthionine chloride (“methylene blue”) prevents the deleterious effects of phenol on the red blood corpuscles; that repeated intravenous injections of phenol and mercury are without danger; that there is no danger of anaphylaxis; that the physiologic properties of the blood are preserved by these medicaments; and, finally, that these preparations have an effect on gonorrhea and its complications, these substances Normal Phenol Serum (Cano) and Methyl-Phenol (Cano), are inadmissible to New and Nonofficial Remedies.

The following quotations taken from the circular are admissions that these preparations are not innocuous: