Chapter XI: Introduction: The Council on Pharmacy and Chemistry was established (4)

Iodum-Miller is a heavy, dark liquid having an odor characteristic of ether (ethyl oxid). Qualitative tests revealed the presence of glycerin, free iodin, iodid and potassium. The specific gravity at 25 degrees was 1.284. Direct titration with sodium thiosulphate solution indicated the presence of 1.68 per cent. of free iodin. A determination of the total iodin content by the Hunter method indicated 3.06 per cent. Subtraction of the amount of free iodin found from the total amount of iodin present, gives 1.38 per cent. combined iodin. Assuming this to be present as potassium iodid, as appears probable from the qualitative examination and from the quantitative determination of potassium, 1.80 per cent. potassium iodid is indicated. From this examination it is concluded that Iodum-Miller is, essentially, a solution of iodin and potassium iodid in glycerin, containing 1.68 per cent. free iodin and 1.80 per cent. potassium iodid. The examination contradicts the assumption that Iodum-Miller is either novel in principle or new. Moreover, accepting the firm’s statement that 45 drops weigh 1 dram (60 grains) the examination shows that one drop equals not “the per cent. of iodine in 1 gr. potas. iodide” but instead, the per cent. of iodin in only 1/20 grain potassium iodid. As the statement that “Each drop equals the per cent. of iodine in 1 gr. potas. iodide” appears on the label of the trade package, Iodum-Miller would seem to be misbranded under the federal Food and Drugs Act.

The recommended internal dosage of Iodum-Miller (from 1/2 to 20 drops) is equivalent to from 1/40 to 1 grain of potassium iodid. Its external efficacy in comparison with that of other iodin preparations may be estimated by comparing the respective free iodin contents, since the germicidal power of combined iodid is negligible. While Iodum-Miller contains 2.15 gm. free iodin in 100 c.c., tincture of iodin contains 7 gm. per 100 c.c. and compound solution of iodin (Lugol’s solution) contains 5 gm. free iodin in 100 gm.

Among the advertising literature is a circular which purports to be a “Certificate from Kansas City Testing Laboratory, by Roy Cross, Secretary.” The “certificate” attempts to prove that Iodum-Miller is vastly superior to the official tincture of iodin as a germicide, asserting that “In the process of dissolving [tincture of iodin] in water, a very large amount of the iodin is lost by precipitation....” This is not true of the tincture of iodin which is now official, though it is true of the tincture official in former editions of the Pharmacopeia. The report ignores completely the widely used aqueous solution of iodin.

Iod-Izd-Oil (Miller’s) is said to be an “Iodine Combination” made “from the same Soluble Soot Iodine as is IODUM-MILLER.” It is said to “liberate Free Soluble Iodine” when applied to the skin, mucous surfaces, etc. It is further defined as “Soluble Iodine combined with water-white Hydrocarbon Oil” and is said to liberate “Soluble Iodine 2 per cent.” While these statements suggest that Iod-Izd-Oil (Miller’s) contains the iodin-potassium iodid combination contained in Iodum-Miller, analysis indicated the oil to be a simple solution of iodin in liquid petrolatum. Quantitative determinations indicated, not 2 per cent. of iodin, as claimed, but only 0.42 per cent. and all of this was present as free iodin.

REFEREE’S REPORT

The following therapeutic claims appear on the label of a bottle of Iodum-Miller:

“EXTERNAL INDICATIONS

“Tuberculosis, Pneumonia, Pleurisy, Cough, Sore Throat, Pyorrhea,
Tonsilitis, Rheumatism, Spinal Irritation, Boils, Felons or any
Pain. Periostitis, Carbuncles, Fistula in Ano, Goiter, Blood
Poison, Diseases of Uterus and appendages (apply full strength on
cotton wrapped applicator), Gonorrhea, acute or chronic in both
sexes, Orchitis, Bubo, Prostatitis, Swellings, Enlarged Glands,
Etc.”

“INTERNAL INDICATIONS

“Pneumonia, Tuberculosis, Pleurisy, Typhoid Fever, Syphilis,
Catarrh of Mucous surface of Alimentary Canal, Autotoxemia,
Vomiting of Pregnancy, Rheumatism, Chronic Glandular and Organic
Affections.”

The “certificate” from the Kansas City Testing Laboratory, mentioned above, states that Iodum-Miller was found to have a germicidal value nineteen times greater than carbolic acid--a somewhat remarkable finding in view of the fact that iodin dissolved by means of potassium iodid in alcohol or water, when tried on the typhoid bacillus has recently been found to possess only four times the germicidal value of carbolic acid in a solution of the same strength (Maben and White: _Chem. and Drug._, Jan. 30, 1915, p. 144). The “certificate” further states that the test “shows available iodine as found in IODUM-MILLER to have the greatest bactericidal power of any substance that we have ever tested that can be used medicinally.” There is no reason to believe that the desire to please its patrons has led the “testing laboratory” astray from the literal truth. The laboratory’s experience may be limited and the statement therefore entirely correct as far as it goes. No mention, however, is made of any tests comparing the germ-destroying power of Iodum-Miller with that of tincture of iodin, which contains 7 per cent. free iodin, unless the casual statement that “Iodum-Miller sterilized [the skin] more quickly” than tincture of iodin, be taken to imply such tests. It is not clear, however, by what means the laboratory was able to determine that there were no bacteria left alive in the skin after application of tincture of iodin and Iodum-Miller; no details are given of the methods used in arriving at this conclusion.

A circular says that Iodum-Miller

“... gives the Greatest Bactericidal and Therapeutic Action,
whether used Internally, Externally, Hypodermically or
Intravenously.”

In the light of the preceding report of the Chemical Laboratory of the Association, these claims require little comment. The laboratory has shown that the free iodin content (and consequently the germicidal efficiency) of Iodum-Miller is less than half that of Lugol’s solution, and less than a third of that of the official tincture of iodin. As for the advice to use Iodum-Miller internally in diseases ranging from pneumonia to syphilis and from typhoid to tuberculosis, in order to be convinced of its dangerous character, it is necessary only to recall that this treatment is equivalent to the administration of small doses of iodid--from 1/40 to 1 grain of potassium iodid. The mystery being removed from the composition of Iodum-Miller, the absurd extravagance of the claims made for it becomes manifest. The criticisms of the Council on the recommendations for Burnham’s Soluble Iodine (The Journal A. M. A., May 15, 1915, p. 1673) apply in almost every particular to Iodum-Miller.

Unwarranted therapeutic claims are made for Iodum-Miller; incorrect statements are made with regard to its composition and that of Iod-Izd-Oil (Miller’s); and the application of a trade name to both of these products is unjustifiable, since neither is original. It is therefore recommended that Iodum-Miller and Iod-Izd-Oil (Miller’s) be held ineligible for New and Nonofficial Remedies--(_Abstracted in The Journal A. M. A., Oct. 2, 1915._)

ELIXIR IODO-BROMIDE OF CALCIUM COMP. “WITHOUT MERCURY”
AND “WITH MERCURY”

Report of the Council on Pharmacy and Chemistry

The Tilden Company, New Lebanon, N. Y., and St. Louis, Mo., sells “Elixir Iodo-Bromide of Calcium Comp. without Mercury” and “Elixir Iodo-Bromide of Calcium Comp. with Mercury.” The latter is said to contain, in addition to the ingredients of the former, 1/100 grain mercuric chlorid in each fluidram. According to the label the formula of the elixir “without mercury” is:

“_Formula_--Salts of Iodine, Bromine, Potassium, Sodium, Calcium,
Magnesium with Stillingia, Sarsaparilla, Rumex, Dulcamara, Lappa,
Taraxacum, Menispermum.”

A recent circular declares that the elixir contains:

“... a number of the most powerful alteratives of the pharmacopeia
such as chemically pure iodin, magnesium, potassium with
sarsaparilla, stillingia, prickly ash, burdock, taraxacum, etc. ...
Each fluidounce contains seventy-two grains of the combined salts.”

The same circular also alleges that each dram of the preparation contains:

“... the equivalent of one and one-half grains of the combined
iodids, potassium and calcium ...”

It will be observed that, (1) the two statements quoted from the circular make no reference to bromids; (2) the statement that each dram contains “the equivalent” of 1-1/2 grains of the combined iodids, potassium and calcium, accounts for but 12 of the 72 grains of “the combined salts” per fluidounce declared in the preceding quotation; (3) the circular mentions the presence of a drug--prickly ash--not declared on the label and, finally (4) none of the “formulas” gives the quantities of all of the several constituents.

It is evident from these “formulas” that the Tilden Company continues its policy of concealment and mystification as exemplified in the cases of Hydrocyanate of Iron, Tilden (discussed in The Journal, June 19, 1909, p. 2008), Febrisol (The Journal, June 29, 1912, p. 2043) and Respirazone (The Journal, June 14, 1913, p. 1899).

In the circular just quoted (“The Conquest of Syphilis”), all hope for the syphilitic is declared to rest in mercury and iodin, and it is implied that only through Elixir Iodo-Bromide of Calcium Comp. is it possible to obtain the greatest good from these drugs.

“Were the cleansing influences of these two drugs [mercury and
iodin] unavailable to the luetic patient, he, truly, would be as
pitiable an object as the leper ...

“Modern Pharmacy has devised no better means of utilizing these
anti-syphilitics than Elixir Iodo-Bromide of Calcium Comp. (Tilden)
with or without mercury.... The Elixir, in proper dosage, acts
in specific fashion and is adapted for use in all stages of the
disease.

“In the early months ... Elixir Iodo-Bromide of Calcium Comp.
(Tilden) with mercury is a trustworthy weapon and the physician
need have no fear but that it will subjugate the disease ...

“When ... the virulent stage is passed ... Elixir Iodo-Bromide of
Calcium Comp. (Tilden) without mercury may be given the patient
with every assurance that medicine’s most aggressive measures are
being resorted to ... From time to time, up to the very end of the
time honored three years’ period of treatment, it is well to put
the patient back on the bichloride, using for this purpose the form
of the Elixir administered in the first stages of the disease ...

“This regime ... will indubitably antidote the virus of syphilis
and eradicate from the organism its every vestige.”

While it seems incredible that any physician would jeopardize the health--even the life--of a patient by accepting this boastful magniloquence as sound therapeutic advice, still the fact that certain medical journals lend their advertising pages to advertisements for Tilden’s Elixir with the caption “The Conquest of Syphilis” makes it incumbent on the Council to record its condemnation of the employment of this unscientific, semisecret mixture.

It is recommended that Elixir Iodo-Bromide of Calcium Comp. “without mercury” and “with mercury” be held in conflict with Rule 1 (secrecy of composition), Rule 6 (unwarranted therapeutic claims) and Rule 10 (unscientific composition).--(_From The Journal A. M. A., Nov. 6, 1915._)

LECITHIN PREPARATIONS OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report was sent to the manufacturers of the various lecithin preparations mentioned therein. As the replies of the manufacturers were obviously written from the commercial point of view and did not affect the Council’s conclusion that lecithin, when indicated, would be given more advantageously in the form of yolk of egg than in the less pure manufactured product, the Council directed that the report be published, together with extracts from the replies of the manufacturers.

W. A. Puckner, Secretary.

Commercial lecithin preparations are at best very impure substances; all are more or less altered from the original composition. Even with great care, the methods of extraction and drying always produce considerable decomposition; and in some cases the phosphorus and nitrogen contents bear but little relation to the theoretical values. (Long, J. H.: _Jour. Am. Chem. Soc._, xxx, 881. McLean, Hugh: _Chem. Abstracts_, May 20, 1915). There is not the slightest reliable evidence that commercial lecithin has any advantage over the lecithin contained in natural foods; the weight of probability is on the other side.

The doses recommended, moreover, are absurdly small; and the amount thus administered is without practical value. Why administer a few milligrams of a more or less decomposed lecithin when it is possible to give a far larger weight of a purer substance in the form of yolk of egg?

In view of these considerations the Council voted that the following proprietary products be omitted from the next edition of N. N. R.:

Glycerole of Lecithin
Lecibrin
Lecithin Solution
Lecithol
Neuro-Lecithin-Abbott

and that the general article on “Lecithin Preparations” be transferred to the annual Council Reports as a matter of record.

The report was submitted to the manufacturers. Their replies were evidently based on commercial consideration, and called for no modification in the report.

The referee recommended that the preceding report be published together with the following extracts from the replies of the manufacturers:

From Armour and Company:

“We are selling a good deal of Lecithol and it seems to be giving
satisfactory results in some quarters.... We shall continue to
advertise Lecithol along the lines we have employed heretofore.”

From the Abbott Laboratories:

“We can assure you of our confidence in the therapeutic value of
Neuro-Lecithin. This has been attested by the reports of favorable
results sent us by many physicians, as well as by the periodical
literature of the last few years which contains a considerable
number of very encouraging references to lecithin therapy.”

From Fairchild Bros. & Foster:

“We would like simply to say that the physician and the Council
must be aware of the circumstances and the purposes which actuated
us in placing lecithin at disposal, viz., the studies--research--of
lecithin and the properties attributed to it and which led to
inquiry for and consideration of it. The _quantities_ proposed for
medicinal use were not suggested by us; the suggestion of lecithin
in small quantities as a therapeutic agent was obviously directed
by those who proposed it.... The question whether lecithin, per se,
has therapeutic properties in contrast to lecithin as naturally
contained in food substances, is something we do not undertake
to decide. The Council, on purely theoretical grounds, decides
in the negative notwithstanding clinical experience--internal
and hypodermic--and thus would deny lecithin the status of a new
and nonofficial remedy, worthy of at least tentative progressive
clinical consideration. We can only say that we offered bona fide
lecithin and that we did not make the investigation of lecithin
a pretext for the sale of all sorts of lecithin ‘jumbles’ with
lecithin in small proportions, taking their name and making their
bid on lecithin.”

Below appears the general article which has been omitted from N. N. R.:

Lecithin Preparations

Lecithins are fat-like bodies belonging to the group of phosphatides. They all consist of glyceryl esters containing two fatty acid radicals and the phosphoric acid radical in which one of the residual hydrogens is replaced by the choline group. The fatty acid may be palmitic, oleic or stearic and various combinations are known to exist; for example, distearyl lecithin, stearyl palmityl lecithin and so on. The commercial lecithins usually include the closely related kephalins.

On saponification the lecithins split more or less readily into choline, the fatty acids and glycerophosphoric acid, and by fusion with alkali nitrate and carbonate they yield alkali phosphate. They occur, free or in combination as lecithoproteins, most abundantly in certain animal tissues, but there are also vegetable lecithins. The lecithins of commerce are obtained usually from yolks of eggs or from calves’ or sheep’s brains.

Numerous processes have been devised for the preparation of lecithin from egg-yolk or animal tissue. From egg-yolk it may be obtained by making an alcoholic extract and precipitating by cadmium chloride. The precipitate is washed with alcohol and ether, mixed with 80 per cent. alcohol and warmed with the proper amount of ammonium carbonate to remove the cadmium. After filtering hot and concentrating the filtrate the lecithin is thrown down by cooling to a low temperature--10 C. or below. The precipitate is taken up in chloroform and reprecipitated by acetone.

From tissues it is obtained by extracting with warm alcohol and ether, concentrating the extract, precipitating with acetone and repeating the operations.

Pure lecithin is white, but the commercial preparations are yellowish-brown wax-like solids, which are not soluble in water but form milky emulsions which exhibit the myeline figures under the microscope. The solubility in cold alcohol or ether is slight, but heat aids it. Lecithins are not soluble in acetone. They are hygroscopic and the water mixtures undergo decomposition on standing. They darken on exposure to air and light.

The alcoholic solution is precipitated by platinum or cadmium chloride. It is decomposed by alkalies with the formation of choline and trimethylamine. The ash contains phosphoric acid. The different lecithins contain from 3.84 to 4.12 per cent. of phosphorus and 1.73 to 1.86 per cent. of nitrogen. The ratio of nitrogen to phosphorus should be at 1 to 2.21.

Lecithin is incompatible with alkalies; it should be kept in well-stoppered bottles and should be protected from the light.

The content of lecithin (plus kephalin) in tissues is about as follows:

Per Cent.
Egg-yolk 8 to 12
Egg-white 0.1 to 0.2
Liver 2.0 to 3.0
Kidney 2.0 to 3.6
Lung 2.0 to 3.0
Pancreas 2.0 to 3.0

_Actions and Uses._--The lecithin preparations have been recommended in many pathologic conditions, especially in malnutrition and sexual debility. Moderate doses are said to bring about a marked retention of nitrogen and phosphorus, but satisfactory proof of this is lacking. It is extremely unlikely that the small doses which have been recommended in pill or tablet form or in emulsions can have any perceptible action, in view of the fact that many of our natural foods contain much greater weights of available lecithins than the medicinal doses provide. There is no good basis for the statement that the free lecithin has a greater food value or is more readily assimilated than is the substance as found in eggs or tissue. The reverse proposition is much more likely to be true, especially when it is considered that the commercial preparations are usually somewhat altered or decomposed in the process of separation.

_Dosage._--Given by the mouth in the form of pills, tablets or glycero-alcoholic emulsions. The amount of actual lecithin ingested in this way is usually small because of the doubtful purity of the original preparation. Several doses, as commonly administered, would be required to furnish the amount of lecithin present in a small egg.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 122._)

PROPRIETARY NAMES FOR LIQUID PETROLATUM

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

A former report of the Council (Liquid Petrolatum or “Russian Mineral Oil,” Report Council Pharm. and Chem., The Journal, May 30, 1914, p. 1740) called attention to the large number of concerns that were placing on the market liquid petrolatum as a proprietary under coined names. Since then the number of such products has increased. The Council has been requested by several concerns to consider their products put out under proprietary brand names.

The rules of the Council affirm that “the application of ‘trade names’ to official or established nonproprietary substances tends to confusion and fosters many abuses.” In accordance with this general ruling, the Council has invariably refused to countenance proprietary names applied to liquid petrolatum. The Council holds that proprietary or coined names for this substance are detrimental to medical progress, since they are sure to foster the impression that the particular product is different from liquid petrolatum. Manufacturers have been advised that there is no objection to distinguishing their products by the addition of their firm name or the initial representing the firm name; for instance, “Liquid Petrolatum, A. B. and Co.” or “Liquid Petrolatum, Smith.” The Council also believes that such designations as “Star Liquid Petrolatum” or “Liquid Petrolatum, Anchor Brand,” may be regarded as unobjectionable, provided that the words “Liquid Petrolatum” are always used in connection with the brand designation and given equal prominence.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 127._)

SENG

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

Seng (Sultan Drug Co., St. Louis) is called by the manufacturers:

“... a palatable preparation of Panax (Ginseng) in an aromatic
vehicle.”

Regarding ginseng (_Panax quinquefolia_) the United States Dispensatory, nineteenth edition, page 1603, says:

“The extraordinary medicinal virtues formerly ascribed to ginseng
had no other existence than in the imagination of the Chinese.
It is little more than a demulcent, and in this country is not
employed as a medicine.”

No discussion of ginseng is to be found in the more recently published books on pharmacology, materia medica and therapeutics, evidently because their authors agree with this estimate.

On the other hand, physicians are told through the medium of advertisements appearing in medical journals that Seng is:

“An efficient remedy in all affections in which the
gastro-intestinal glands need stimulating.

“Exceptionally useful in atonic indigestion, malnutrition,
convalescence from the acute diseases, and all digestive disorders
characterized by deranged or depressed functions.” (_Woman’s
Medical Journal_, July, 1914.)

According to the label, Seng is indicated in “indigestion,” “malassimilation,” “malnutrition” and “wasting diseases.” It is also stated--though the preparation is admitted to contain 18 per cent. of alcohol--that to give babies “ten to fifteen drops in water or milk during feeding” is a proper procedure and that “For Colic, Flatulency, etc., the dose for an adult or child may be repeated every half hour until relieved.”

The following are some of the exaggerated therapeutic claims made for this preparation of a worthless drug:

“As a result of its administration the gastro-intestinal secretions
are augmented, the digestion of food is substantially increased,
and fermentative processes are promptly overcome.”

“Seng will specifically encourage the secretion of the juices in
the entire alimentary tract ...”

The formula furnished for Seng is non-quantitative and therefore meaningless. The preparation is exploited in a manner to encourage its ill-advised use by the public, and exaggerated and unwarranted therapeutic claims are made for it. The use of an inefficient or worthless drug like ginseng, moreover, is detrimental to rational therapeutics. The Council therefore voted that Seng be refused recognition for conflict with Rules 1, 4, 6 and 10.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 129._)

FROSST’S BLAUD CAPSULES

Report of the Council on Pharmacy and Chemistry

Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine Capsules were submitted to the Council by C. E. Frosst & Co., Montreal, Canada. This firm claims, on the authority of the report of a firm of analytical chemists, that:

“... of three leading Blaud preparations bought by us on the open
market, the iron in Frosst’s Blaud Capsules showed the highest
percentage of _Ferrous_ carbonate.”

The Chemical Laboratory of the American Medical Association found this claim unjustified. The laboratory reported that there was no especial difference in the ferrous iron content of the various Blaud pills found on the market, and that among ten specimens examined, the total iron content was the lowest in the Frosst specimen. In view of this the Council refused recognition to Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine Capsules.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 164._)

TYREE’S ELIXIR OF BUCHU AND HYOSCYAMUS COMPOUND

Report of the Council on Pharmacy and Chemistry

Each dessertspoonful of this preparation is said to represent

Buchu Leaves 3-1/2 grains
Uva Ursi 1-1/8 grains
Pareira Brava 1-1/8 grains
Hyoscyamus 1-1/2 grains
Hops 1-1/2 grains
Acetate Potash 7-1/2 grains
Spirits Nitre 5 grains
Alcohol 5 per cent. (by volume)”

The manufacturer, J. S. Tyree, Washington, D. C., offers this formula to the medical profession with the following claim:

“Approximate composition made [sic] by quantitative and qualitative
analysis of the finished product.”

It is also claimed that

“An even greater advantage of Tyree’s Buchu and Hyoscyamus Compound
over other drugs, lies in the fact that every constituent of
the former is required to conform to a fixed standard of active
principle strength; hence the results derivable from it are
absolutely uniform.”

These pretentious claims of scientific accuracy look rather absurd to chemists. Many of the substances present in buchu, hops, hyoscyamus, uva ursi and pareira brava are also present in other drugs; hence it would never occur to a pharmaceutical chemist to try to ascertain the composition of such a mixture as Tyree’s Elixir by “quantitative and qualitative analysis of the finished product,” much less to determine the “active principle strength” of each ingredient, for no methods are known by which this can be done.

It is claimed that, because of the care exercised in making Tyree’s Elixir

“... the results derivable from it are absolutely uniform.”

A moment’s reflection, however, must compel any physician to attribute this statement, on the most charitable construction, to sheer ignorance. Of course, even a definite chemical principle, such as quinin, does not exert uniform clinical action, for clinical conditions vary, and accordingly the patient may or may not be cured. It is simply preposterous to claim that the clinical results obtained from such substances as hops, pareira brava, buchu and uva ursi are absolutely uniform.

A peculiarly vicious claim is that the elixir renders the mucous surfaces of the genito-urinary tract “hostile to the multiplication of the gonococci.” Since infection with the gonococcus produces the direst results, any claim which means in plain English that the remedy assists in producing a cure or in preventing infection with that organism cannot be condemned too strongly. Uva ursi, to be sure, has some slight antiseptic action but it is devoid of any curative action in gonorrhea and the minute amounts that are present in the Tyree elixir are of no more protective value against gonorrheal infection than a grain of hexamethylenamin would be.

It is further claimed that the elixir is a “specific” for “Inflammation of the Bladder, Bright’s Disease, Renal Colic, Suppurative Nephritis, Acute Cystitis, Urethritis, Catarrh of the Bladder [it would be interesting to know what distinction the manufacturer draws between ‘Inflammation of the Bladder,’ ‘Cystitis’ and ‘Catarrh of the Bladder’], Acidemia, Edema, Vesical Catarrh of Old Age, Lithemia” and that ascites and anasarca “can be reduced greatly to the satisfaction of the patient, and honor of the physician” by using a mixture of Tyree’s Elixir and infusion of digitalis. Such claims as these do not merit serious discussion, for they carry their own refutation.

It is recommended that Tyree’s Elixir of Buchu and Hyoscyamus Compound be held in conflict with Rules 5, 6 and 10 and that publication of this report be authorized.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 167._)

HYDROLEINE

Report of the Council on Pharmacy and Chemistry

Hydroleine (Charles N. Crittenton Company, New York) is a cod liver oil emulsion said to contain 45 per cent. of cod liver oil, a trace of salicylic acid and 18-1/2 grains of “Pancreatin, Etc.,” per ounce. The advertising claims are based largely on the theory that cod liver oil is “that particular fat which dietetic experience and physiological chemistry have proved to be most digestible.” As a matter of fact, while the superior digestibility of cod liver oil over other oils has often been asserted, neither “dietetic experience” nor “physiological chemistry” have “proved” this by definite observations. The Crittenton Company claims that it is more readily split than other oils. This is probably not true, easy emulsification of the raw oil being often confounded with easy splitting. This latter claim, however, is offered in justification of the name “Hydroleine,” which the Crittenton Company interprets as “hydrated oil.” A circular wrapped around the bottle contains the assertion that “Cod Liver Oil has long been held in high esteem by the medical profession for the treatment of a large number of serious diseases.” This recommendation is likely to lead the public to place undue reliance on Hydroleine in the grave conditions mentioned.

The preparation is in conflict with the rules of the Council inasmuch as its name does not indicate its composition, unwarranted therapeutic claims are made for it, and the exploitation is likely to give the public unwarranted confidence in its value. The Council therefore held Hydroleine ineligible for New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 171._)

CURATIVE VACCINE, BRUSCHETTINI

Report of the Council on Pharmacy and Chemistry

Curative Vaccine, Bruschettini, manufactured by A. Bruschettini, Genoa, Italy, is claimed to have the properties “of acting directly on the tubercular bacillus, bringing directly into the field and determining a hyperproduction of antibacillar and antitoxic substances.” The use of the preparation is said to be indicated in “all forms of tuberculosis.”

A referee reported to the Council that he had examined the available information and believed that the use of this product had no satisfactory experimental basis. The method of preparation appears to be based more on theoretical considerations than on experimental basis.

On the recommendation of the Committee on Serums and Vaccines the Council voted that Curative Vaccine, Bruschettini, be not accepted because (1) the method used for the production of the vaccine was not satisfactorily stated; (2) the theory on which its use is based has not been satisfactorily confirmed, and (3) the value of the product is not upheld by satisfactory clinical evidence.

The Council’s findings, in accordance with its procedure, were sent to the manufacturers for comment. His reply was considered by a new referee who found that the matter presented did not warrant a revision of the Council’s conclusions. Accordingly the Council directed publication of its findings.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 176._)

STEARNS’ WINE

Report of the Council on Pharmacy and Chemistry

Frederick Stearns & Co. market a preparation known as “Stearns’ Wine,” “Stearns’ Wine of Cod Liver Ext. with Peptonate of Iron,” and as “Vinum Ext. Morrhuae, Stearns.” The constituents are said to be “concentrated extract of fresh cod livers,” “Peptonate of Iron” and a “fine quality of prime Sherry Wine” containing 18 per cent. of alcohol.

This preparation was at one time marketed through the medical profession, but is now advertised direct to the public in typical “patent medicine” style. The label on a recently purchased bottle of Stearns’ Wine contains the following statements:

“STEARNS WINE is an ideal tonic for elderly people, for weak, pale
and delicate children and convalescents.

“STEARNS WINE has for many years been successfully prescribed
in the treatment of general or nervous exhaustion, anemia,
malnutrition, loss of appetite, loss of sleep, faulty circulation
and impoverished blood supply.”

The scope of the recommendations for the preparation is further indicated in a booklet accompanying the bottle, which begins:

“STEARNS’ WINE, What It Is and Why It Is Good for You.”

The conclusion is:

“STEARNS’ WINE is a safe medicine for the young, middle-aged and
old. It is a safeguard to the family health.”

It is not necessary to discuss either these all-embracing claims as to the therapeutic efficacy of the mixture or the fallacies presented in favor of cod-liver extract and peptonate of iron. The Council reaffirms the opinion that whatever therapeutic value cod liver may have resides chiefly, if not entirely, in its fatty constituents (The Journal, Oct. 9, 1909; Reports Council Pharm. and Chem., 1909, p. 115). A confirmation of this opinion has recently been furnished by the investigations of Prof. J. P. Street (The Journal A. M. A., Feb. 20, 1915, p. 638) of several cod liver cordials, one of which (Vinol) like Stearns’ Wine, is described as a wine of cod liver extract with peptonate of iron.

Stearns’ Wine is essentially an alcoholic stimulant. It is not “a safe medicine for the young, middle-aged and old.” The unwarranted therapeutic claims and the recommendations for its indiscriminate use bring it into conflict with Rules 4 and 6. The Council voted that Stearns’ Wine be held ineligible for inclusion in N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1915, p. 177._)

PROTONUCLEIN AND PROTONUCLEIN BETA

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

Protonuclein, with other products of Reed and Carnrick, was examined by the Council in 1907 and found ineligible for admission to New and Nonofficial Remedies. According to the patent specifications, it is prepared “from the thyroid and thymus glands, brain (pineal glands and pituitary body), bone-marrow, pancreas, spleen, liver, salivary glands, Brunner’s glands, Lieberkühn’s follicles and peptic glands.” These various glandular bodies, it is said, are dried at a temperature below 130 F. (preferably between 100 and 110); the fat is removed by ether, the dried glands disintegrated, the connective tissue removed by sifting and the resulting powder coated with an ether solution of benzoin and mixed with milk sugar. The dose is three to ten tablets (9 to 30 grains) daily.

Protonuclein Beta is said to be produced by the addition to Protonuclein of an equal amount of nucleoplasm and protoplasm of the spleen. The dose is from two cubes (each 5 grains) three times a day to three cubes four times a day (30 to 60 grains daily).

Special advantages over ordinary nuclein are attributed to Protonuclein, in which, it is claimed, certain unaltered cells remain that are more easily assimilated by the leukocytes than are ordinary proteins, thus leading to a multiplication of cells. In the early advertising Protonuclein was claimed to be:

“... an exact physiological product derived from the lymphoid
structures of the body without the use of chemical agents.... So
delicate is Protonuclein that any chemical agent is liable to
disturb its cellular activity.”

After its examination of the product in 1907 (The Journal, Oct. 5, 1907, p. 1198), the Council concluded that any distinction between the action of Protonuclein and that of ordinary nuclein was purely speculative and highly improbable. “If the active ingredients are really so unstable that they are destroyed by all chemical agents, as claimed, it seems impossible that the activity would be preserved when Protonuclein is given by mouth and therefore subjected to the very profound changes of digestion.”

At that time the importance of thyroid as an ingredient had not been emphasized. The following year, however, Hunt and Seidell (The Journal A. M. A., Oct. 24, 1908) reported the results of an investigation which showed that Protonuclein was a diluted thyroid preparation, as skilfully disguised as in the antifats Rengo and Marmola. Hunt later pointed out (The Journal, Feb. 1, 1913, p. 384) that the amount of nuclein contained in a dose of Protonuclein probably would not have the slightest effect, especially when given by mouth.

The following are extracts from the Protonuclein advertising matter:

“For cancer, infectious fevers (measles, scarlet fever, typhoid and
septicaemia) and as a prophylactic.”

“Protonuclein: An ideal prophylactic for all infectious Diseases.”

“A true alterative and tissue builder.”

“The value of Protonuclein depends upon its ability to increase
cell power and promote tissue strength. It is therefore needed
whenever the organism is below the normal standard, more especially
in Anaemia, Typhoid, Neoplasms and as a Prophylactic.”

All the foregoing claims and recommendations are supposed to be based on certain alleged discoveries which the Council has previously characterized as “a tissue of vague speculations ... in direct conflict with the known facts of physiologic chemistry.” As for the third claim, Hunt and Seidell have commented on the danger of recommending thyroid, the most powerful tissue-destroying drug known, as a “tissue builder.”

Protonuclein Beta, it is said:

“... combines the reconstructive action of Protonuclein with the
action of the vital principle of the spleen, making it a distinct
product for use in all tubercular troubles, including phthisis,
localized joint affections and scrofular conditions.”

This product, according to the manufacturers, is based on the work of a certain Dr. Bayle of Cannes, France. Dr. Bayle said that he had treated tuberculous patients with fresh ground up spleen of hogs (25-100 grams per day), mixed with fruit preserve or bouillon; in cases in which this brought on gastro-intestinal disorders, extract of the spleen pulp was administered hypodermically. Bayle reported extraordinary improvements in the physical and mental conditions of his patients even after a few days of this treatment; over 90 per cent. of his tuberculous patients, according to him, improved or were cured. This applied to all types and stages of tuberculosis in man. “With the spleen pulp treatment tuberculous glands disappear like syphilis lesions on administration of mercury and iodids.”

This “spleen specific” of Bayle lacks scientific foundation; Bayle’s own cases were not adequately controlled, and no notice has been taken of Bayle’s report by experts on tuberculosis. Hence it practically lacks both confirmation and contradiction.

The spleen is invaded by tubercle bacilli quite as frequently as are the kidneys and the liver; it has no special toxic action on these bacilli. Nor is there any reason to believe that the end products of gastric and intestinal digestion of spleen pulp, after absorption into the blood, exert such toxic action. It cannot be assumed that these end products indirectly aid the healing processes through improved metabolism, for there is no evidence that they have any specific nutritive or stimulating action after such absorption. Altogether, what we know of the physiology and pathology of the spleen does not warrant us in looking for a “specific” against tuberculosis in this organ.

If, however, the known facts did justify any hope that the spleen might furnish such a specific, manufacturers would not be warranted in exploiting or physicians in prescribing spleen products as a remedy for tuberculosis until control experiments on animals had confirmed the therapeutic value of these products. In a chronic disease like tuberculosis, no conclusions that are scientifically valid can be drawn from clinical cases until many cases have been observed for years under suitable conditions. Right here it may be said that the clinical “evidence” offered in favor of Protonuclein Beta is worthless. The observations which have been reported on this product are not such as to permit any valid final conclusions to be drawn with regard to its value.

The rational method of proving the worth of an alleged new specific such as this is by animal experimentation. So far as we know, neither Dr. Bayle nor the Reed and Carnrick company has performed any such experiments with “spleen pulp” or Protonuclein Beta; nor are we aware that any competent investigator has done so. There is, to the best of our knowledge, no scientific evidence on which to base the claims for Protonuclein Beta.

The Council reaffirms its former action with regard to Protonuclein. The objections made to Protonuclein apply with equal force to Protonuclein Beta. In view of the lack of evidence, the claims for Protonuclein Beta are unwarranted and the product is ineligible to N. N. R. on account of noncompliance with Rules 1, 6 and 8.--(_From The Journal A. M. A., Jan. 1, 1916._)

HYDROPSIN

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

Hydropsin is marketed by the Ernst Bischoff Company, Inc., New York. Its composition is thus described:

“Hydropsin is the standardized dialysate of Digitalis purpurea,
Betula alba, Scilla maritima, Juniperis communis, and Herniaria
glabra; or, stated otherwise, it is the juice of these drugs,
dialyzed and physiologically standardized.”

“Each fluid dram represents Digitalysatum 7 gtts., and 2 gtts. each
of the dialysates of Betula, Herniaria, Juniper and Scilla.”

The composition of Hydropsin must be considered essentially secret since the amounts of the several constituent drugs in a given amount of “dialysate” are not disclosed. The active principle of juniper is a volatile oil which is practically insoluble in water; it is difficult to believe that the “juice” of juniper submitted to dialysis could contain any material amount of the active constituent. No information is given as to the method used whereby the several dialysates are “physiologically standardized.” It therefore remains to be proved that the manufacturer of Hydropsin possesses any method whereby the dialysates of juniper (Juniperis communis), birch (Betula alba, the common European birch) and knot weed (Herniaria glabra) are so standardized. The claim is made that:

“Herniaria has long been recognized as one of the most valuable
drugs in the treatment of dropsical affections due to cardiac
impairment.”

On the contrary, Herniaria belongs to that large class of drugs which have been tried, found wanting and abandoned. It is a very old remedy, and the claims made for it are an inheritance from the early herbalists, with whom it was very popular. According to King’s American Dispensatory, it was “principally employed to cure _hernia_ (hence its name) and to increase the flow of urine. It was also said to increase the flow of bile.... Internally and externally, it was praised in _snake-bites_, and the powdered plant was employed to kill maggots on unhealthy _sores_ of horses. It was reputed to ‘crush’ and expel calculi from the kidneys and bladder....”

The Ernst Bischoff Company says that:

“Betula exerts both an antiseptic and stimulating influence
on the urinary passages and is particularly serviceable where
a catarrhal condition of the bladder exists. When combined
with other diuretics, as in Hydropsin, the drug affords highly
satisfactory results in the treatment of ascites, cardiac dropsy
and hydrothorax.”

Birch is another drug which has been discarded. Few textbooks on materia medica even mention it. That it can materially affect the action of such powerful drugs as squill and digitalis is exceedingly doubtful.

An unwarranted implication--that in this preparation the powerful drugs digitalis and squill have been deprived of their dangerous qualities--is the assertion:

“Dialysis, removing all resins and colloidals, results in better
tolerance on part of sensitive patients, and in more rapid
absorption and elimination; which, in turn, means early therapeutic
effects and little or no fear of toxic accumulation.”

That removal of colloids and resins materially affects the tolerance of these drugs is improbable. To claim that because of their removal, there need be “little or no fear of toxic accumulation” is utterly without warrant. The claim that one preparation containing digitalis is less likely to produce cumulative effect than any other digitalis preparation is contradicted by a mass of evidence.

It is claimed that Hydropsin affects “favorably all forms of dropsy or Edema that are at all amenable to medical treatment.” There can be no question but that squill and digitalis, or, better, either singly, used in suitable cases, may relieve dropsical effusions; but to claim that such a complex mixture as Hydropsin can favorably affect all forms of dropsy that are amenable to medical treatment is on its face unwarranted.

The claim is made that:

“By reason of its unusual potency and relative harmlessness,
Hydropsin may be employed to great advantage in all cases where it
is desirable to increase the volume of urine without injury to the
renal structures.”

On the basis of the claimed composition, the action of Hydropsin must be essentially that of digitalis or of digitalis and squill. Consequently, if it possesses “unusual potency,” it cannot possess “relative harmlessness,” and vice versa. Neither digitalis nor squill should be employed “in all cases” of nephritis, even if it is “desirable to increase the volume of urine.”

The composition claimed for Hydropsin brands it as an irrational mixture in which potent drugs are combined with, and more or less covered up by, others that are obsolete and inefficient. The name, instead of indicating its composition, suggests diseases in which it may be thoughtlessly and indiscriminately used. The claim that the danger of toxic or cumulative action has been removed, if accepted by physicians, tends to uncritical use with possible disastrous results. Hydropsin is ineligible for New and Nonofficial Remedies because of conflict with Rules 1, 2, 6, 8 and 10.--(_From The Journal A. M. A., Jan. 8, 1916._)

DIGITALYSATUM

Report of the Council on Pharmacy and Chemistry

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

W. A. Puckner, Secretary.

Digitalysatum is sold in the United States by Ernst Bischoff Company, Inc., New York. The firm claims that it is a dialysate prepared from the juice of freshly gathered digitalis, containing all the active principles, and representing the fresh plant weight for weight. It is said to be standardized physiologically and to contain 12 per cent. alcohol. Sterisol-Digitalysatum, intended for injection, appears to be the “dialysate” without alcohol, diluted with equal parts of physiologic sodium chlorid solution. The Council some years ago found both products ineligible for New and Nonofficial Remedies because of unwarranted therapeutic claims. The preparations are still being advertised to physicians under claims which imply superiority to all other digitalis preparations. For instance:

“Digitalysatum is the diuretic _par excellence_ in cardiac
insufficiency ...”

“Digitalysatum as a diuretic and cardiac stimulant is in a class
by itself, being quick of action, uniform in strength, and well
tolerated.”

“Digitalysatum differs from other forms of digitalis in these
respects:... Digitalysatum is free from fat, resins and colloids,
and is therefore well-borne by sensitive patients--the young and
the feeble--and is quickly absorbed and eliminated....”

The Council has elsewhere[28] expressed the conviction that tincture of digitalis produces the full therapeutic effects of digitalis; that, when properly made, the tincture is as stable as any liquid preparation of digitalis now available, and that attempts to enhance the reputation of proprietary products by exaggerating the disadvantages of the official preparation are to be deplored. No adequate evidence is offered of the claimed superiority of action of Digitalysatum.

[28] Report on Proprietary Digitalis Preparations, J. A. M. A., Dec. 4, 1915, p. 2024.

By implication, the claim is made that Digitalysatum is superior to other digitalis preparations in respect to toxicity:

“Free from fat, resins and colloidals, it is always well borne and
is quickly absorbed and eliminated. No case of toxic accumulation
(faulty elimination) has ever been reported.”

That Digitalysatum is free from the dangers of toxic cumulation is highly improbable; in fact, it is inconsistent with the statement that the preparation contains all the constituents found in the fresh plant. Even if instances of cumulative action have not been reported this does not prove that such cumulative action does not occur. The tincture of digitalis has the systemic side-effects of digitalis in no greater degree than the various proprietary preparations. Attempts to create the impression that Digitalysatum possesses all the virtues of digitalis without its chief disadvantage are to be condemned as likely to lead to incautious use of the preparation.

These exaggerated claims are in the main made indirectly, but they are none the less inimical to sound therapy. The Council therefore declared Digitalysatum ineligible for New and Nonofficial Remedies and voted that this report be published.--(_From The Journal A. M. A., Jan. 8, 1916._)

SO-CALLED SECRETIN PREPARATIONS

Report of the Council on Pharmacy and Chemistry

The Council authorized the following report for publication, and voted to endorse the work of Professor Carlson discussed therein.

W. A. Puckner, Secretary.

The Council has not accepted for inclusion in New and Nonofficial Remedies any preparations said to contain secretin or prosecretin as their active ingredient. A report giving the reasons for the rejection of one (the first of the so-called secretin preparations marketed) was published early last year;[29] an article on secretin, based on work undertaken at the request of the Council on Pharmacy and Chemistry, is now published.[30]

[29] Secretogen, J. A. M. A., May 1, 1915, p. 1518.

[30] Carlson, A. J.; Lebensohn, J. E., and Pearlmann, S. J.: Has Secretin a Therapeutic Value? J. A. M. A. =66=:178 (Jan. 15) 1916.

Lest the appearance of this detailed study of secretin, after the rejection of so-called secretin preparations, should be interpreted (as manufacturers whose products have been rejected have endeavored to interpret such action) as a case of first condemning a preparation and then getting the facts, the Council’s methods, and their application in this case, may be briefly stated. The Council maintains that, when a manufacturer places a product on the market, the burden of proof is on that manufacturer to show that the properties of his product are in accordance with his claims for it. As stated in the introduction to N. N. R., “it is ... manifestly impossible for the Council to investigate the composition of every complex pharmaceutical mixture, or to check thoroughly every therapeutic claim; it can give only an unbiased judgment on the available evidence.” Acting on this principle, the Council examined the claims made for Secretogen, an alleged secretin product manufactured by the G. W. Carnrick Company. The conclusion was that these claims were in absolute conflict with the available evidence as to the action of secretin.

It is not necessary to review this subject again. It will suffice to state that the claims made for Secretogen rest on two fundamental propositions: (1) that deficiency of secretin (or, rather, of prosecretin) in the intestinal mucosa is a factor in gastro-intestinal diseases; (2) that secretin given by the mouth is absorbed and produces increased secretion of the pancreatic and intestinal juices and of the bile.

From an examination of the evidence available, including that submitted by the manufacturers, the Council concluded: “1. No evidence has been presented that the absence of secretin is a cause of gastro-intestinal disease. 2. There is no evidence that secretin in any form is physiologically active when administered by mouth.” That these conclusions were justified is shown again by the review given by Carlson of the literature, much of which was also reviewed in the Council’s previous report.

Since the claims of the Carnrick Company were not supported by any satisfactory evidence, no further investigation on the Council’s part was necessary to warrant rejection of the product. The Council did not undertake to determine, for instance, whether or not Secretogen and similar products actually contain secretin; the determination of this point was immaterial here, in view of the conclusiveness of the evidence that secretin given by mouth has no physiologic action.

Since firms other than the G. W. Carnrick Company are manufacturing alleged secretin preparations, and since recommendations for the use of secretin preparations in gastro-intestinal diseases have even crept into textbooks, it seemed desirable to obtain further information on certain points. The Council therefore requested Prof. A. J. Carlson of the University of Chicago to check the results of previous investigators with regard to the action of secretin administered by mouth or directly into the intestine, and, in addition, to investigate the secretin content of certain alleged secretin preparations.

Carlson and his co-workers, like all previous investigators, found that secretin given by mouth, or introduced even in enormous doses directly into the intestine, is entirely inactive. They also found that marked destruction of secretin followed contact for one minute with human gastric juice and that secretin is rapidly oxidized and rendered inert in contact with the air.

Further, they were unable to demonstrate the presence of secretin in samples of Secretogen and another supposed secretin preparation (Duodenin) bought on the open market. In the case of Secretogen there was one exception: one bottle was found which contained a little secretin, but it was necessary to administer (by intravenous injection, of course) the entire contents of the bottle (100 tablets) to obtain “a small but unmistakable secretin reaction.”

In these studies the methods employed were those by which secretin was discovered. It is only by the use of such methods that the presence or absence of secretin can be determined. Apparently the manufacturers who place so-called secretin preparations on the market do not make use of these methods, by which alone even the composition of their products can be determined.

Carlson and his collaborators conclude:

“There is as yet no reliable evidence that lack of secretin is a primary or important factor in any disease. Even should this be established, secretin therapy, to be effective, must be intravenous. Secretin has not yet been prepared in sufficiently pure state to render possible intravenous injection in man without injurious effects. And even when this is attained, the very fleeting action of secretin will in all probability render secretin therapy as futile in all the diseases in which it is theoretically indicated as epinephrin therapy is in Addison’s disease.”

In short, secretin is as ineffective taken by mouth as it would be rubbed on the skin.

The referee recommends that the work of Professor Carlson be endorsed.--(_From The Journal A. M. A., Jan. 15, 1916._)

HAS SECRETIN A THERAPEUTIC VALUE?[B]

A. J. Carlson, Ph.D., J. E. Lebensohn, M.S., and S. J. Pearlman, B.S.
Chicago

[B] From the Hull Physiological Laboratory of the University of Chicago.

[B] This investigation was undertaken at the request of the Council on Pharmacy and Chemistry. The following report, having been submitted to the Council, received its endorsement (see preceding report of the Council on Pharmacy and Chemistry, “So-Called Secretin Preparations”).

It is well established that acid chyme in the duodenum is the normal stimulus to the secretion of pancreatic juice.[31] Interaction of the acid with the duodenal mucosa liberates into the blood stream a substance which, circulating through the pancreas, excites the latter to activity. This exciting substance has been termed “secretin.” It can be prepared artificially by macerating duodenojejunal mucosa in 0.4 per cent. hydrochloric acid, neutralizing the boiling mixture, and filtering. A few cubic centimeters of the filtrate injected into a vein produce invariably a powerful secretion of pancreatic juice.[32] That a “chemical messenger” is at the basis of the duodenal acid reflex has been proved by even more crucial experiments--transfusion (Wertheimer,[33] Enriquez and Hallion[34]), cross circulation (Fleig,[35] Matuso[36]), and perfusion of the isolated pancreas (Huston[37]).

[31] Pawlow: The Work of the Digestive Glands, 1912.

[32] Bayliss and Starling: Jour. Physiol. =28=:325, 1902.

[33] Wertheimer: Compt. rend. Soc. de biol. =54=:475, 1902.

[34] Enriquez and Hallion: Compt. rend. Soc. de biol. =55=:233, 363, 1903.

[35] Fleig: Arch. internat. de Physiol., =10=:206, 1910.

[36] Matuso: Jour. Physiol. =45=:477, 1913.