preponderance of evidence indicates that whatever therapeutic value
cod liver oil may have depends chiefly, if not entirely, on its fat
(oil). There never was any evidence or scientific authority for the
theory that the therapeutic value of cod liver oil was independent of
its fat content. The fact that the fat is the growth-promoting element
has already been shown, and J. P. Street, chemist for the Connecticut
Agricultural Experiment Station (The Journal A. M. A., Feb. 20, 1915,
p. 638), in a series of experiments on a number of the so-called
extracts of cod liver or cod liver oil (including Hagee’s Cordial) has
conclusively demonstrated that the growth-promoting properties of the
oil are not to be found in the extracts. Street placed rats on a ration
not sufficient to maintain normal nutrition and growth for an extended
period. After the rats had been on this ration for some time and a
failure to maintain weight was indicated, an amount of dealcoholized
Hagee’s Cordial was substituted for a portion of the lard contained in
the ration. Later Hagee’s Cordial was replaced by cod liver oil.
[19] The Journal A. M. A., Oct. 9, 1909, p. 1201.
Street says:
“None of the four rats did well on Hagee’s Cordial; in fact, they
lost 1.2 to 15.4 gm. during feeding periods of from seven to
fourteen days.”
“The rats failed so quickly when put on Hagee’s Cordial that in two
cases the animals did not recover even when put on the full cod
liver oil ration.”
“... the four rats during the Hagee period, instead of gaining the
normal 24 gm., actually lost 36.2 gm., while during the cod liver
oil period instead of gaining 114 gm., they gained 156.4 gm.”
“_The inferiority of Hagee’s Cordial as a reconstructive and a
nutrient compared with ordinary cod liver oil is apparent._”
Hagee’s Cordial of the Extract of Cod Liver Oil Compound has neither
the nutritive qualities nor the reconstructive efficacy of cod liver
oil. This mixture is worthless for the conditions for which it is
advertised, and is marketed under misleading and unwarranted claims.
It is recommended that Hagee’s Cordial be held ineligible for New and
Nonofficial Remedies.--(_From The Journal A. M. A., April 10, 1915._)
WAMPOLE’S PERFECTED AND TASTELESS PREPARATION OF
AN EXTRACT OF COD LIVER[J]
Report of the Council on Pharmacy and Chemistry
[J] See also reports on Hagee’s Cordial preceding and Waterbury’s
Compound following this; also The Comparative Nutrient Value of Cod
Liver Oil and Cod Liver Oil Cordials, p. 442.
Wampole’s Preparation is another of the oil-free “extracts” of
cod liver. The following formula (which, be it observed, is
non-quantitative and therefore practically worthless) is published by
the owners, Henry K. Wampole & Co., Inc.:
“Contains a solution of an extractive obtainable from fresh cod
livers, the oily or fatty portion being afterward eliminated. This
extractive is combined with Liquid Extract of Malt, Fluid Extract
of Wild Cherry and Compound Syrup of Hypophosphites (containing
Calcium, Sodium, Potassium, Iron, Manganese, Quinin and Strychnin).”
An alcohol content of 17 per cent. is declared on the label. The
following claims are typical of those made for the preparation:
“This grease, or oil, is not present in Wampole’s Preparation
of the Extract, which is _palatable_ and, at the same time,
very efficient as a stimulant to the centers of nutrition and
assimilation. It is unsurpassed as a reconstructive tonic ...”
“[Cases] with a marked tendency to pulmonary troubles,... if a
timely impulse be given them will easily shake off the impending
evil. Wampole’s Preparation gives that timely impulse ...”
In the Council’s opinion, as previously expressed,[20] such therapeutic
value as there may be in cod liver oil is chiefly, if not altogether,
due to the fat (oil). Lately, the investigations of J. P. Street
of the Connecticut Agricultural Experiment Station have definitely
disproved the claims made for the Wampole’s and similar preparations.
In Street’s experiments, rats were placed on a ration insufficient for
normal nutrition and growth. After the rats had been on the ration for
a time long enough for inability to maintain weight to become evident,
dealcoholized Wampole preparation was substituted for a portion of
the lard contained in the ration. Later the Wampole preparation was
replaced by cod liver oil. From these experiments it appears that,
although the Wampole preparation is said to contain malt extract and
sugar, it does not show the advantage over ordinary cod liver oil as
a source of nutriment which is claimed for it by the manufacturers.
Street emphasizes that the Wampole preparation does not possess to any
marked degree the reconstructive properties of cod liver oil, butter
fat and egg yolk, on which foods rats gain weight rapidly and steadily
after having been on a deficient diet. Street calls attention to the
fact that the amount of alcohol consumed daily by the user of the
Wampole preparation (the equivalent of 0.7 fluidounces of whiskey)
explains to a considerable extent the asserted tonic virtues of the
preparation.
[20] The Journal A. M. A., Oct. 9, 1909, p. 1201. (See following
report, this volume.)
Though offered as an efficient substitute for cod liver oil, Wampole’s
“Perfected and Tasteless Preparation of an Extract of Cod Liver” lacks
both the nutritive and the reconstructive properties and is marketed
under an indefinite name and unwarranted and untrue claims. It is
recommended that Wampole’s Preparation be held ineligible for New and
Nonofficial Remedies.--(_From The Journal A. M. A., April 10, 1915._)
WATERBURY’S METABOLIZED COD-LIVER OIL COMPOUND[K]
Report of the Council on Pharmacy and Chemistry and Laboratory
Contribution on Which It Is Based
[K] See also preceding reports on Hagee’s Cordial and Wampole’s
Preparation; also Waterbury’s Compound once more, p. 291; The
Comparative Nutrient Value of Cod Liver Oil and Cod Liver Oil Cordials,
p. 422.
The following report has been adopted by the Council and its
publication directed
W. A. Puckner, Secretary.
_To the Council_:--Your committee on pharmacology has read with
interest the contribution from the Association’s laboratory on
Waterbury’s Metabolized Cod-Liver Oil Compound. The report shows that
misleading and false statements are made in regard to the composition
of the product and also that exaggerated and unwarranted claims are
made for its therapeutic value. In view of the attempt of the Waterbury
Chemical Co. to create a false impression in regard to the therapeutic
value of the composition of its product, it is recommended that the
following report be adopted and published:
The Council believes that there is a preponderance of evidence to
indicate that whatever therapeutic value cod-liver oil has, that value
depends chiefly, if not entirely, on its fat (oil). In the opinion of
the Council, the word cod-liver oil should not be used in connection
with any preparation unless it consists to a large extent (25 per cent.
or more) of cod-liver oil. Since Waterbury’s Metabolized Cod-Liver Oil
Compound contains no appreciable quantity of cod-liver oil, the name
is incorrect and misleading, and as a cod-liver oil preparation it is
believed to be wholly valueless. The Council has previously voted that
Waterbury’s Cod-Liver Oil Compound be refused recognition because of
conflict with Rules 1 and 6.--(_From The Journal A. M. A., Oct. 9,
1909._)
[CONTRIBUTION FROM THE CHEMICAL LABORATORY OF THE AMERICAN MEDICAL
ASSOCIATION]
Waterbury’s Metabolized Cod-Liver Oil Compound
W. A. Puckner and L. E. Warren
A full page advertisement of Waterbury’s Metabolized Cod-Liver Oil
Compound appeared in the _Iowa Medical Journal_, March 15, 1909, in
the form of a letter purporting to give the results of an analysis
of the product made for the firm by a Chicago chemist. In this
letter-advertisement the chemist states at the outset that the results
of his examination “are somewhat at variance with the statements made
in The Journal.” These statements he quotes as follows:
1. It is a clear liquid and no globules of oil are seen under the
microscope. It is therefore not an emulsion.
2. It is of acid reaction when mixed with water and remains clear
when strongly acidified. Hence it does not contain a soap, and is
not a saponification of fat.
3. It mixes with water without precipitation, hence, it can not
contain more than traces of a fatty acid.
The chemist admits in his letter to the firm that his analyses verify
statements 1 and 3, but regarding statement 2 he says: “I find that
your preparation is acid in reaction, but when strongly acidified gives
a distinct turbidity within 10 minutes and a voluminous precipitate
within 1 hour. This precipitate is shown to consist of fatty acids of
cod-liver oil, which are thrown down by the splitting of the soaps,
on acidifying either with sulphuric or hydrochloric acid.” From these
results he states that to him it seems that the “preparation does not
deserve the statement that it contains no soap, as there is no question
whatever of the presence of cod-liver oil.”
While in the letter published in this advertisement the chemist claims
to have demonstrated the presence in the product of “saponified
cod-liver oil,” he _omits to mention the quantities_ of the soap
present. In the article that originally appeared in The Journal (Oct.
13, 1906), in addition to the three paragraphs quoted by the chemist,
the following statements were made:
“By these simple tests a physician is easily able to demonstrate
that the preparation does not contain cod-liver oil. It is therefore
valueless for the purpose of nutrition for which we give the oil. More
careful analysis confirms the results of these tests and shows that it
contains no fat or fatty acids (except the merest traces)....”
At the time these statements were published in The Journal, the _St.
Paul Medical Journal_, October, 1906, contained an advertisement for
Waterbury’s Metabolized Cod-Liver Oil Compound, which contained this
statement:
“The only tasteless preparation on the market which contains
Cod-Liver Oil in its entirety. The metabolized product is obtained
by the action of digestive ferments on pure Cod-Liver Oil.”
In the _Ohio Medical Journal_ of Feb. 15, 1907, there appeared in
the form of an advertisement what purported to be an analysis of
Waterbury’s Metabolized Cod-Liver Oil Compound by Prof. C. N. Kinney of
Drake University. While Professor Kinney made a quantitative analysis
of the preparation, the quantities were omitted from the analysis as
published. A footnote added by the Waterbury Chemical Company called
attention to this fact and closed as follows:
“Any physician who is not satisfied with the analysis we will
be only too glad to furnish the complete analysis by our
representatives.”
If this weirdly constructed sentence meant anything, it meant that
the complete analysis would be furnished on request. Such requests
to the company, however, from various sources failed to elicit the
information required nor was the “complete analysis” forthcoming. The
inference to be drawn is fairly plain.
In a circular accompanying the product as sold at present, this
statement occurs:
+------------------------------------------------+
| |
| WATERBURY’S |
| METABOLIZED COD LIVER OIL COMPOUND |
| With Creosote and Guaiacol or Plain |
| |
| DOES CONTAIN COD LIVER OIL |
| DOES ALLAY FERMENTATION |
| DOES AID DIGESTION |
| DOES ASSIST ASSIMILATION |
| BUT DOES NOT DISTURB THE STOMACH |
| |
+------------------------------------------------+
As previous examination disclosed only the merest traces of cod-liver
oil in the product though claims were made that it “represents
cod-liver oil in its entirety,” and in view of the fact, too, that
present advertisements emphatically declare that cod-liver oil is
present in the preparation as now sold, it was thought best to examine
some of the preparation with especial reference to the quantities of
fatty acids from cod-liver oil.
[Illustration: OLD LABEL NEW LABEL
It is interesting in this connection to note that this product is no
longer being sold under the name “Metabolized Cod Liver Oil Compound.”
See the illustrations of the old and new labels.]
The results of the examination are briefly as follows: The total
quantity of acids isolated amounted to about 0.3 per cent., and of this
amount about two-thirds was _salicylic acid_. Thus it appears from
the examination of the specimens bought on the open market that the
preparation contains at most but 0.1 per cent. of the fatty acids from
cod-liver oil, a totally insignificant quantity.
Notwithstanding the protestations by the manufacturers, in the form
of published analyses and circulars, it is seen that the statements
published in The Journal, Oct. 13, 1906, p. 1207, are essentially
substantiated; it is further evident that the product does not deserve
to be designated as a cod-liver oil preparation. To obtain a medicinal
dose of cod-liver oil the patient would be compelled to swallow the
contents of a bottle of this mixture, and as the product contains 11
per cent. alcohol the patient who did so would probably experience a
degree of exhilaration not referable to cod-liver oil.--(_From The
Journal A. M. A., Oct. 9, 1909._)
Declared Misbranded
This product of the Waterbury Chemical Company, of Des Moines, Iowa,
was exposed in The Journal of the American Medical Association, October
9, 1909. In May, 1910, the United States Government issued a notice
of judgment in which it was declared that Waterbury’s Metabolized Cod
Liver Oil Compound was misbranded. The court rendered its decree of
condemnation and forfeiture.--[_Notice of Judgment, No. 303._]
WATERBURY’S COMPOUND
Report of the Council on Pharmacy and Chemistry
The Waterbury Chemical Company having requested that the Council
reconsider its action of four years ago (see preceding report) on the
product then known as Waterbury’s Cod-Liver Oil Compound, now called
Waterbury’s Compound, the matter was submitted to a referee. The
referee reported that the statement now made as to the composition of
this product is as follows:
“Made from Cod Liver Oil, Digestive Ferments, Malt Extract
Unfermented, Hypophosphites Comp. Special, Ext. Cherry, Eucalyptus,
Aromatics, etc.”
He held that the Waterbury Chemical Company has not submitted
satisfactory evidence to indicate that the objections of the Council’s
former unfavorable report have been met; that there is no evidence
that the product is a substitute for cod-liver oil in any way; and
that under the present methods of exploitation it constitutes what
is at least an inferential fraud; and recommended that no further
consideration be given to Waterbury’s Compound. The report was adopted
by the Council.--(_From The Journal A. M. A., March 20, 1915._)
COLCHI-SAL
Report of the Council on Pharmacy and Chemistry
Colchi-Sal, said to be made by the Anglo-American Pharmaceutical Co.,
Ltd., New York, is advertised, sold and “guaranteed” (sic) by E.
Fougera and Co., Inc., New York. According to the label of a recently
purchased specimen:
“Each Capsule contains Cannabis Indica (Active Principle of)
1-500th Grain (1/8 Milligram); Colchicine (Crystallized) 1-250th
Grain (1/4 Milligram); Methyl Salicylate 20 Centigrams.”
The advertising circular around the bottle adds that the mixture also
contains “appropriate aromatic adjuvants.”
It is recommended in “Gouty and Chronic Rheumatic Manifestations,”
“acute cases of Gout,” “intestinal auto-intoxication or dyspepsia,”
“bilious headaches,” etc. Salicylates are generally recognized as
valuable in acute manifestations of acute articular rheumatism;
colchicum is useless in these conditions. Both salicylates and
colchicum are practically useless in chronic rheumatic and in chronic
gouty affections. For dyspepsia, bilious headache, etc., salicylates
are distinctly contra-indicated and the drastic purgation produced by
colchicum would not be thought desirable. Though methyl salicylate
administered internally is not generally considered so efficient as
sodium salicylate, it is asserted that the former
“... is found far more effective than salicylate of soda or other
salicylic derivatives when given in conjunction with colchicine as
Colchi-Sal.”
Further, the highly improbable and unsubstantiated claim is made
that “the active principle of _Cannabis indica_” (whatever that
may be) “corrects any tendency of the colchicine to irritate the
gastro-intestinal tract” and that the “appropriate aromatic adjuvants”
“prevent intolerance of the methyl salicylate.”
Colchi-Sal is put up in a way to appeal to the public; the bottle
has the name “Colchi-Sal” blown in the glass; the label gives full
instruction for the use of Colchi-Sal, and also the price, suggesting
that the preparation may be freely purchased. Wrapped around the bottle
is a circular advising its use in various affections.
The physician who acts on the advice that it is well to “insist on
the pharmacist dispensing original bottles ...” of the “little green
capsules” actually suggests to his patient the use of this preparation
of methyl salicylate and colchicum in conditions in which these drugs
may do much harm and in which proper treatment is imperative.
Colchi-Sal is typical of unscientific ready-to-take proprietaries. It
was held ineligible for New and Nonofficial Remedies because of its
secret composition, viz., the unknown nature of the “active principle
of Cannabis indica” (Rule 1); because the circular in the package
and the name blown in the bottle constitute advertisement to the
laity (Rule 4); because the claim that cannabis indica removes the
gastro-intestinal irritation, and the claim of the superiority of
methyl salicylate are unwarranted therapeutic claims (Rule 6); because
the name does not indicate the presence of the habit-forming cannabis
indica, and because of its unscientific composition (Rule 10).--(_From
The Journal A. M. A., March 20, 1915._)
CYPRIDOL CAPSULES
Report of the Council on Pharmacy and Chemistry
Having voted that Cypridol Capsules be refused recognition, the Council
directed that for the information of physicians publication of the
following report be authorized.
W. A. Puckner, Secretary.
Cypridol Capsules, sold by E. Fougera & Co., New York, are stated to
be “Bottled in the New York Laboratories of Vial, late Rigaud and
Chapoteaut, Paris,” and to contain, in each capsule, 2 mg. (1/32 grain)
mercuric iodid (biniodid of mercury) dissolved in a fatty oil. They
are claimed to permit the administration of mercury without danger of
salivation--an obvious misrepresentation.[21] Cypridol Capsules are
marketed in a way to appeal to the public. If they are once prescribed,
the directions on the bottle and the full instructions for the
treatment of syphilis by means of Cypridol and by other proprietaries
sold by Fougera & Co. is likely to lead the patient to attempt the
treatment of this malady on his own accord, and thus probably to
forfeit his chances of cure. Cypridol is a vicious example of the
“ready-to-take” proprietaries.
[21] Physicians who desire to use a solution of mercuric iodid in oil
should direct their pharmacist to prepare it according to the method
suggested by Lemaire (Repert. pharm., xxi, 97-102, from Chem. Abst.,
1909, p. 1444), viz.: One gm. of mercuric iodid is dissolved in 50 c.c.
sterilized castor oil by warming to about 70 degrees, 3 gm. guaiacol
are added and the solution made up to 100 c.c. with sterilized poppy
oil. Or according to a later suggestion (Dunning: Proc. Am. Pharm.
Assn., 1910, p. 1123): one gm. of mercuric iodid is dissolved in 99 gm.
of a mixture of equal parts of sterilized castor and olive oils, by
warming on the water-bath.
Cypridol Capsules are in conflict with the rules of the Council as
follows:
Rule 4: The dosage, price, etc., on the label, and the name “Cypridol”
blown in the bottle, all tend to a direct self-prescribing by the
public. In addition to the objectionable statements on the bottle
itself, the preparation is put up in patent medicine style and is
accompanied by a circular giving full directions for the use of this
and of other proprietaries for the treatment of syphilis in all of its
stages. The circular states that “a 1 per cent. solution of bin-iodide
of mercury in an aseptic oil” is “An Improved Specific in the Treatment
of Syphilis,” and after lauding the virtues of Cypridol, gives full
directions for the treatment of syphilis in its various stages by
means of Capsules of Cypridol augmented, during periodical cessation
of treatment, by “small doses of iodide of strontium (Paraf-Javal’s
standard solution, thirty grains to the ounce).” Further, the circular
expounds the need of “a toning up of the general system” and by means
of obsolete theories and obviously untrue assertions recommends
“_Chapoteaut’s Wine_ [another of their proprietary preparations], each
ounce of which contains 10 grains of phospho-glycerate of lime. This is
a delicious, nutritive tonic. A pint bottle costs $1.00.”
Rule 6: Whereas it is evident that Cypridol, depending for its effects
on mercuric iodid, the ordinary well-known hydrargyri iodidum rubrum
of the U. S. Pharmacopeia, must naturally have the properties of a
mercuric compound, unwarranted claims such as the following are made:
“CYPRIDOL does not render patients anemic. Ptyalism never follows
the administration of the capsules or injections. On the contrary,
patients rapidly put on flesh and keep well. There are no
diarrhoeas or other symptoms of intolerance even when the dose is
pushed.”
Rule 8: The non-informing name “Cypridol” for a mercuric iodid
preparation is bound to lead to its use without consideration of the
fact that a potent mercury preparation is being used, requiring a
careful adjustment of dosage, a consideration of the needs of the
individual case, a correct diagnosis, etc. While the advertising
propaganda argues that “physicians recognize the advantage of
prescribing this solution of mercuric iodide in an aseptic oil under
the name of ‘Cypridol,’ because it does not betray to the laity the
fact that mercury is being used,” not only the physician but also the
patient has a right to know, and ought to know, the potent character of
the remedy which is being administered.
It is recommended that Cypridol be refused recognition and that
publication of this report be authorized.--(_From The Journal A. M. A.,
Dec. 19, 1914._)
CYSTOGEN, CYSTOGEN APERIENT AND CYSTOGEN-LITHIA[L]
Abstract of Report of the Council on Pharmacy and Chemistry
[L] For the unabridged report of the Council’s action on Cystogen,
Cystogen Aperient and Cystogen-Lithia, see Reports Council Pharm. and
Chem., 1914, p. 66.
Cystogen is the therapeutically suggestive name applied to
hexamethylenamin by the Cystogen Chemical Company. While investigation
has shown that hexamethylenamin yields formaldehyd only in the presence
of an acid and consequently can produce an antiseptic effect only in
the gastric juice and in the urine, it is claimed that Cystogen is
an “intestinal antiseptic” and that it “bears its disinfectant and
antitoxic qualities into well-nigh every important bodily cavity.”
As the sale of a simple drug even with the aid of the most extravagant
claims probably did not offer sufficient opportunity for an extensive
proprietary propaganda, the Cystogen Company has put out two other
preparations, Cystogen Aperient and Cystogen-Lithia, and finds it an
easy matter by means of extravagant claims, unwarranted assertions and
pseudo-scientific arguments to recommend the use of one or another, or
often all three, in a well-nigh endless number of diseases.
As the continued patronage of the medical profession cannot be relied
on for proprietaries of this sort, the Cystogen Chemical Company takes
good care that every Cystogen prescription is likely to spread the
Cystogen gospel among the people. The Council has directed publication
of its report on the Cystogen products to call attention to the way
in which a simple drug of established value may be made the basis of
an extensive proprietary propaganda. A conservative discussion of
the action of hexamethylenamin appears in the Council’s publication,
“Useful Drugs.” The Council therefore refused recognition to Cystogen,
Cystogen Aperient and Cystogen-Lithia.--(_From The Journal A. M. A.,
Dec. 12, 1914._)
CYSTO-SEDATIVE
Report of the Council on Pharmacy and Chemistry
Cysto-Sedative is sold by Strong, Cobb and Company, Cleveland, Ohio,
with the claim:
“Each fluid ounce represents:
Thuja Occidentalis, 3-1/2 grains.
Pichi, 18 grs.
Saw Palmetto berries, 36 grs.
Triticum Repens, 36 grs.
Hyoscyamus 8 grs.
All inert extractive matter being eliminated.”
The therapeutically active constituents of arbor vitæ, pichi, saw
palmetto and couch grass have never been isolated--indeed, it has not
been proved that all of these drugs contain any therapeutically active
constituents. Yet the absurd claims are made that all inert matter
has been eliminated and each lot of drug used in the preparation of
Cysto-Sedative is “tested in reference to its medicinal activity.”
Equally preposterous is the claim:
“In formulating Cysto-Sedative each drug entering into its
composition was subjected to careful study clinically to determine
the exact proportion required when combined to increase their
efficiency as a whole. Cysto-Sedative is scientifically prepared,
the proportion of each individual drug being so finely adjusted as
to increase their therapeutic action in the conditions for which
they are intended, forming a preparation always reliable and of the
very highest medicinal activity.”
Some other extravagant claims made for this complex unscientific
mixture are:
“It gives relief in almost every form of cystitis and
prostatitis....”
“The best results are obtained in the worst chronic cases of
cystitis and prostatitis....”
“In Cystitis, Urethritis, Prostatitis, Inflammation of the Vesicle
Neck, complicated with Gonorrhoea, Enuresis, Painful Micturition,
the action of Cysto-Sedative is prompt.”
The Council voted that Cysto-Sedative be refused recognition.--(_From
The Journal A. M. A., Dec. 12, 1914._)
TAKA-DIASTASE AND LIQUID TAKA-DIASTASE
Report of the Council on Pharmacy and Chemistry
Some time ago it was decided that a reexamination should be made of
Taka-Diastase and Liquid Taka-Diastase, both of which had previously
been rejected, to ascertain whether or not the preparations were in
accord with the claims made for them by the manufacturers. Accordingly,
the matter was referred to a committee of the Council, and an
examination of specimens of these two preparations bought in the market
was made. The referee’s report, which appears below, according to the
usual procedure, and before final confirmation by the Council, was
first submitted to the manufacturers of Taka-Diastase for comment.
The report recommends that the rejection of Taka-Diastase and Liquid
Taka-Diastase be allowed to stand, and that the report be published.
Parke, Davis & Co., in their reply, which is given in full below, claim
that the report is unjust concerning Liquid Taka-Diastase, because the
period of activity of the preparation has been greatly prolonged by
reducing the amount of alcohol from 18 per cent. to 10 per cent. and by
adding glycerin. They reiterate their claims for the digestive power of
Taka-Diastase, but admit that it will not reduce the stated amount of
starch to the colorless end-point in ten minutes (the standard method
for the valuation of diastase). They further state that they would
change the word “digest” on the label to “liquefy.”
The conclusion of the report having been questioned, the entire
matter was referred to a member of the Council’s staff of clinical
consultants. His report, which, also, is given in full below, states
that the material before him was sufficient to decide the matter,
and no further tests were necessary. He concludes that the claims
of the manufacturers regarding the strength and properties of the
material are erroneous and exaggerated; that the literature still sent
out by Parke, Davis & Co. is misleading; and that if substitution
of the word “liquefy” for “digest” were endorsed by the Council
confusion would result which would give an exaggerated and false
value to Taka-Diastase. He therefore recommends that the report of
the reinvestigation of Taka-Diastase be accepted by the Council and
published.
This report of the second referee was referred to Parke, Davis & Co.
with the request that they state more definitely the actual amylolytic
strength of their preparations. To this they replied that they had
no desire to discuss the subject further, or to make any additional
statements.
In accordance with the second referee’s recommendations, the Council
confirmed its provisional action and voted that the rejection of
Taka-Diastase and Liquid Taka-Diastase be allowed to stand, and that
the report which appears below be authorized for publication.
W. A. Puckner, Secretary.
_REFEREE’S REPORT ON TAKA-DIASTASE AND LIQUID TAKA-DIASTASE_
Following is the report of the committee to which was referred the
reexamination of Taka-Diastase and Liquid Taka-Diastase:
Some time ago a comparison was made of the various methods proposed for
the valuation of preparations claimed to have amylolytic power. This
work was reported in The Journal,[22] and the method proposed for the
testing of diastase preparations now appears in New and Nonofficial
Remedies.[23] In view of the incorrect and exaggerated claims made
for Taka-Diastase, the Council in 1908 was obliged to rescind its
acceptance and to direct its omission from New and Nonofficial
Remedies. The report contained the following reference to Taka-Diastase
(Parke, Davis & Company), a product that had been accepted for
inclusion with New and Nonofficial Remedies:
[22] The Journal A. M. A., July 11, 1908, p. 140.
[23] New and Nonofficial Remedies, 1912, p. 68; The Journal A. M. A.,
April 15, 1911, Part 2, p. 18.
“The widest discrepancy between the values as claimed by the
manufacturer and those found by actual tests seems to be shown in
the case of Taka-Diastase. The liquid preparation has been tested a
number of times in different samples and has always been found weak.
Some samples, in fact, were quite inert. This ferment appears to lose
strength very rapidly in solution, as the manufacturers now concede.
The stability of the solid product is also far from satisfactory, and
appears to be less than that of the ferment as marketed some years
ago. The two samples examined recently were weak.”
More than three years have now elapsed since the publication of the
Council’s findings regarding Taka-Diastase--sufficient time, it is
believed, for the manufacturers to modify either their claims or the
product itself, and thus again make it eligible for inclusion with
New and Nonofficial Remedies. With this idea in mind new specimens of
Taka-Diastase and Liquid Taka-Diastase were purchased from a Chicago
drug house and the preparations reinvestigated. The following is the
report of this reinvestigation.
REPORT OF THE REEXAMINATION
In our report on the diastase preparations three years ago, it was
recommended that Taka-Diastase be removed from New and Nonofficial
Remedies, because the examinations showed that it did not have
the digestive strength claimed for it. This was true both for
Taka-Diastase itself and for Liquid Taka-Diastase. So far as the
latter was concerned, the starch-converting power was practically
_nil_ in those preparations which had been in the drug stores for
some months.
During the last few weeks new tests have been carried out with
several samples of the Taka-Diastase preparations and the results
obtained are essentially the same as those obtained in the former
examinations. The liquid preparation is still extremely weak in
starch-converting power, while we found that Taka-Diastase itself
would convert only 16.6 parts of pure anhydrous starch to the
colorless end-point in ten minutes, as explained below.
In our method of experimentation we determine the weight of the
diastase in question which will convert a given weight of starch in
uniform paste to the so-called colorless end-point in ten minutes,
that is to the point where it will no longer give any color reaction
with a standard iodin solution. The standard starch weight in 50 c.c.
always is 1 gm. or 1,000 mg. and to a series of flasks containing
this amount of starch, maintained at a constant temperature of 40 C.,
the diastase dilutions are added. These diastase dilutions are made
by dissolving small, accurately weighed amounts of the sample in
some small, constant volume of water, usually 5 or 10 c.c. and they
are then poured into the starch flasks at the right temperature, and
agitated regularly.
Tests are made by taking a few drops from each flask and mixing
with the iodin solution. The end-point is reached when a dilution
is found which, at ten minutes from the mixing time, gives no color
with the iodin reagent. The first set of tests is taken as a general
guide, and quite accurate results may be obtained in a second set of
dilutions.
We first used a sample of Taka-Diastase bought in the open market. It
was found that 140 mg. were required to convert the gram of starch as
explained. This is equivalent to a conversion of 7.14 parts of starch
by 1 part of the Taka-Diastase.
A new, and possibly fresher, sample was then obtained and the
test repeated. With this new sample it was found that 60 mg. were
necessary to convert the gram of starch to the colorless end-point
in ten minutes, from which it follows that 1 part of the ferment
will convert 16.6 parts of starch to the colorless end-point in
the same time. With a new sample of Liquid Taka-Diastase obtained
simultaneously it was found that 3.5 c.c. were necessary to convert
1 gram of starch to the colorless end-point in ten minutes. As a
fluidounce of this liquid is said to contain 20 grains of the solid
it will be seen that the results approximately agree with those of
the first sample of the solid, and that they are both very low.
In the earlier tests 16 parts of starch converted by 1 part of the
ferment was the value found. These results are in close agreement
with values reported by Sherman (_Jour. Am. Chem. Soc._, xxxii, 1073)
for a sample of recent purchase. He found a conversion of 51 parts of
starch to the colorless end-point in _thirty_ minutes for one sample,
while for another he found 66 parts, in the same time. It will be
noted that our time limit is _ten_ minutes. It is worthy of note
that for a perfectly fresh and specially prepared sample furnished
by Dr. Takamine, a conversion of 278 parts in _thirty_ minutes was
found by Sherman. Taking the time into consideration, it will be seen
that the results are about the same for the market samples as those
found by us and much lower than claimed, as well as much lower than
for other makes of similar products. The difference in the behavior
of fresh specially prepared Taka-Diastase and the market sample is
very clearly shown. No one questions the fact that fresh laboratory
samples of Taka-Diastase may show a moderate converting power on
starch. But we have to deal with the _activity of market samples
only_, and Sherman’s work and our own show the low digesting power of
the product as physicians may secure it on the market.
The marked difference in activity between perfectly fresh and
ordinary market samples of Taka-Diastase is very clearly shown also
in a recent paper published by Wohlgemuth.[24] In the digestion
of starch paste to the “dextrin” stage Wohlgemuth found in the
commercial sample a strength approximately a hundred times less than
that observed in a fresh sample sent him by Dr. Takamine.
[24] Wohlgemuth: Biochem. Ztschr., March 18, 1912.
Wohlgemuth’s results were obtained by a method not essentially
different from ours, with this difference, however, that he digested
through 24 hours in the cases reported, and carried the reaction
to the “dextrin” stage only, in place of to a colorless end-point.
Making the proper reductions, it is evident that the actual values
found by him for the market samples bought in Germany are not greater
than those reported by us.
The reference to the work of Sherman is made because, in a following
paper in the same journal, he recommends the use of salt as an
activator in finding the strength of certain diastase preparations.
It is well known that dialyzed diastase preparations and starch of
highest purity have but slight action on each other; a little salt
increases the activity greatly, and also increases the activity of
commercial diastase preparations. These facts Sherman utilizes in
working out a method for valuation of commercial diastases. The facts
were well known to us at the time of our former report, but it was
not thought best to depart from the general method which had been
in use by all analysts following the general scheme of Roberts.
Quite recently, I. Bang has published a paper on the investigation
of diastase (_Biochem. Ztschr._, xxxii, 417) in which he studies the
behavior of sodium chlorid and other salts on the rapidity of starch
conversion, and finds that a much smaller amount of salt than Sherman
recommends brings the maximum increase.
The method employed in our former tests is a good comparative method,
and this is all that may be claimed at present for any method. By
adding salt to our starch solution the activity of Panase and other
ferments is likewise greatly increased. For Panase, a preparation
possessing rather high starch-converting power, we have recently
found an increase of about 30 per cent. in the converting power,
with salt present. Working to loss of blue color, merely, it is
possible in this way to get a higher value than that claimed by the
manufacturer. There is no practical gain in using the salt for our
purpose as the methods are at best arbitrary, and the results only
comparative.
Taking all the facts into consideration, it is recommended that the
rejection of Taka-Diastase and Liquid Taka-Diastase be allowed to
stand and that, in view of their extensive exploitation, this report
be authorized for publication so that physicians may know the facts.
This report was referred to Parke, Davis & Co., and they made the
following reply:
“The report submitted in your letter of the 23d is, we contend,
erroneous and unjust: first, to our Liquid Taka-Diastase, because
over three years ago we changed our formula, reducing the alcohol
from 18 per cent. to 10 per cent., increasing the glycerin and thus
prolonging greatly the period of activity.
“As for our regular Taka-Diastase, our claim is and has been for
years simply that Taka-Diastase will digest or hydrolyze 150 times
its weight of starch in ten minutes, under proper conditions. We
do not claim, we do not permit our representatives to claim, that
Taka-Diastase will completely transform starch, to the colorless
end-point, into sugars. Taka-Diastase is used to supplement a
deficiency of ptyalin and converts the starch into soluble material
with great rapidity, thus giving the gastric fluid immediate access
to the proteids.
“If in the enclosed labels the word ‘digest’ were replaced with the
word ‘liquefy,’ the claim could not be assailed by the most carping
critic. To save any possible question, we shall therefore make this
change in our label, having it read: ‘Taka-Diastase will liquefy 150
times its weight of starch in ten minutes, under proper conditions.’
Is there the slightest question in your mind that this statement as
just quoted is entirely correct and entirely supported by clinical
experience?
“It is our conviction that Taka-Diastase has a very remarkable power
to hydrolyze starch either in the test-tube or in the stomach, and
that this property is of great utility in clinical work. We do not
claim that its conversion of the starch into sugars is complete, to
the colorless end-point of the Johnson test; and on this point we
have been perfectly frank with the Council, as well as with every
physician who has taken sufficient interest to inquire.”
In view of the above protest, the matter was submitted to a second
referee, who reported as follows:
“Your referee on the matter of Taka-Diastase has made a careful
investigation of the reports and correspondence submitted, and begs
to make the following report:
“The question at issue, viz., whether Taka-Diastase should be
included in New and Nonofficial Remedies, I believe, can be
determined by the material before me, and further tests of the
material are not necessary.
“The letter of the makers of Taka-Diastase admits that the early
claims regarding the strength and properties of the material were
erroneous and exaggerated. Since the product was once admitted to New
and Nonofficial Remedies, it may be claimed that as the Council on
Pharmacy and Chemistry must have been in error then, it may be now.
Your referee does not consider this supposition worth discussing. The
conclusion he draws is that the Council was too hasty in accepting
the preparation, and that the incident shows how much better it would
be in all cases to accept no remedy until sufficient time has been
given for conclusive tests.
“The literature still sent out by Parke, Davis & Co. regarding
Taka-Diastase is misleading and of a kind more appropriate for a
nostrum than a standard chemical substance. What would we think if
morphin, quinin or even heroin were advertised in the same way? I
cite the statement, ‘Taka-Diastase digests starchy food with vigor
and directness.’ It seems to the referee that the proposition to
modify the label to indicate the amount of starch which is liquefied
rather than the amount which is saccharified, in accordance with the
Council’s standard, is bound to lead to confusion and to give an
exaggerated and false value to Taka-Diastase.
“Your referee recommends that the report of the reinvestigation of
Taka-Diastase which has been submitted to me, be made available to
the medical profession, and that the rejection of Taka-Diastase and
Liquid Taka-Diastase be allowed to stand.”
This report of the second referee was submitted to Parke, Davis & Co.,
with the request that they state more explicitly their claims regarding
the activity of Taka-Diastase and Liquid Taka-Diastase, in order that,
if they decided to revise their claims for the preparations, such
revision of claims might be published along with the reports of the
Council. They replied:
“Answering your note of the 15th instant: We have no desire to
discuss further the subject of your letter of February 24, or to make
any statement beyond that set forth in our letter to you of Dec. 27,
1911.”--(_From The Journal A. M. A., July 6, 1912._)
DIGALEN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Digalen is a proprietary said to contain a soluble form (digitoxinum
solubile Cloetta) of digitoxin, the chief active principle of
digitalis. This preparation was accepted[25] by the Council in 1909
for inclusion in New and Nonofficial Remedies. The Council had not
at that time determined whether Digalen contained “soluble amorphous
digitoxin,” as claimed, or not. The product was accepted merely as a
standardized soluble and fairly stable digitalis preparation.
[25] The Journal A. M. A., Sept. 11, 1909, p. 869.
After the acceptance of Digalen, the therapeutic claims made for it by
the manufacturers increased in extravagance. Meanwhile, evidence was
brought forward by various independent investigators which tended not
only to show that these therapeutic claims were unfounded, but also
to discredit the claim that Digalen contained a principle chemically
identical with digitoxin. In view of the obscurity of the whole subject
of the chemistry of the digitalis principles, the latter claim (that
Digalen was a solution of “amorphous digitoxin”) had been an academic
issue at the time of the acceptance of the product. When, however, the
manufacturers of Digalen sought to mislead physicians by increased and
unwarranted therapeutic claims, the Council felt that investigation of
the whole matter was imperatively demanded to decide whether or not
Digalen should be retained in N. N. R.
The questions at issue were: (1) the presence in Digalen of “amorphous
digitoxin”; (2) the constancy of composition and reliability of action
of Digalen, and (3) the claim that it causes less gastric disturbance
than digitoxin. No satisfactory proof has yet been offered that Digalen
contains “amorphous digitoxin.” The mass of evidence tends to show that
Digalen is not constant in composition or reliable in action, and that,
when given in doses corresponding in therapeutic activity, Digalen
causes quite as much gastric disturbance as the official galenical
preparations of digitalis.
The outcome of protracted negotiations between the Council and the
Hoffmann-La Roche Chemical Works may be summed up as follows: 1. The
manufacturers promise to hold in abeyance the claim regarding the
presence of “amorphous digitoxin.” 2. They refuse to concede the
variable composition of Digalen. 3. They reassert the claim that
Digalen is superior to other digitalis products with respect to
liability to cause gastric irritation and consequent vomiting.
In view of the unsatisfactory character of the reply on the second and
third points, the Council voted that Digalen be omitted from N. N. R.
and that publication of the report on Digalen which appears below be
authorized, as well as of the two reports[26] (A and B) referred to
therein.
[26] These reports (A, first report on Digalen and B, examination of
Digalen Tablets) will be published in the 1914 Annual Council Reports.
A reprint of the entire matter dealing with the rejection of Digalen
will be sent on receipt of a two-cent stamp.
W. A. Puckner, Secretary.
Referee’s Report on Digalen
Because of persistent conflict with Rule 6 (unwarranted therapeutic
claims) and Rule 1 (composition) it is recommended that Digalen be
omitted from New and Nonofficial Remedies; also that a copy of the
report be sent to the manufacturers, and that publication of this
report and the two previous reports submitted to the Council be
authorized.
The nature of the problems involved necessitates a somewhat extended
discussion of the subject.
Digalein (liquid) is said to contain 1 part of soluble amorphous
digitoxin Cloetta in 1,000 parts of glycerin and 1,600 parts of water
with 7.5 per cent. of alcohol. One c.c. is said to contain 0.0003 gm.
of the amorphous digitoxin.
Digalen was accepted by the Council[27] and the following footnote
was appended to the description in New and Nonofficial Remedies:
[27] The Journal A. M. A., Sept. 11, 1909, p. 869.
“The Council has not determined whether digalen contains ‘soluble
amorphous digitoxin’ or not, but accepts it simply as a soluble
digitalis preparation.”
Tablets of Digalen were accepted by the Council as a dosage form of
Digalen. Each tablet is said to represent 0.5 c.c. (eight minims) of
Digalen (liquid).
One of the principal considerations which led the Council to accept
Digalen was that it was regarded as affording a fairly constant
and stable preparation of digitalis suitable for intravenous
administration. If Digalen is not fairly stable and of fairly constant
composition it has no obvious advantage over an active soluble
digitalis preparation, such as digitalein.
The evidence now at hand seems to show: 1. Digalen is not of constant
composition or activity. 2. The manufacturers, or their agents,
continue to make misleading statements. 3. It is merely a solution of
certain digitalis principles, probably of digitalen mainly, in impure
form.
COMPOSITION
Cloetta[28] prepared a soluble amorphous substance which he called
“Digitoxinum solubile Cloetta,” but no information concerning the
method of preparation has been published.
[28] Cloetta: München. med. Wchnschr., 1904, No. 33.
Cloetta reported the result of an elementary analysis of his product
which he compared to the analyses of digitoxin (crystalline) made by
Schmiedeberg and by Kiliani, and stated that there could be no doubt
concerning the chemical identity of the two substances.
Kiliani[29] characterized as preposterous Cloetta’s claim that the
active constituent of Digalen is chemically identical with digitoxin
and stated that Digalen was merely an impure digitalein. Kiliani
has recently reiterated the statement that the so-called “amorphous
digitoxin” is not identical with digitoxin.[30]
[29] Kiliani: München. med. Wchnschr., 1907, p. 886.
[30] Kiliani: Am. Jour. Pharm., 1913, lxxxv, 224.
Cloetta’s failure to publish his method of preparing Digalen places
an additional burden of proof on him (or the manufacturers of
Digalen), concerning the identity of the product, and in the face of
Kiliani’s denial of the correctness of Cloetta’s contention we must
have strong corroborative evidence of Cloetta’s claim before we can
accept it as being established.
The difficulties of dealing with the chemistry of digitalis are so
well known that they hardly require further mention here, but under
the circumstances Cloetta cannot be considered as being wholly
unprejudiced, and, while the same might perhaps be said of Kiliani,
such evidence as can be deduced tends strongly to support Kiliani’s
view, and to disprove the contention of Cloetta.
There is much confusion regarding the names which have been applied
to the various principles obtained from digitalis, and while it is
undesirable that an established name should be given to a newly
discovered principle, one might overlook this if no effort were made
to associate the therapeutic actions of the two substances to an
extent which the truth did not justify.
While the Council at that time did not challenge the existence of
“amorphous digitoxin” and made no attempt to determine the identity
with digitoxin of the substance forming the basis of Digalen, the
manufacturers of Digalen have sought to show that Digalen and
digitoxin were identical so far as their therapeutic actions were
concerned, but that Digalen lacked the disadvantages of digitoxin.
What was a purely academic question when the acceptance of Digalen
was under discussion by the Council becomes a matter of very great
practical importance when the manufacturers of Digalen seek to
mislead the physician by these claims.
The evidence which lends support to the view that Digalen and
digitoxin are wholly dissimilar may be summarized as follows: Digalen
differs greatly in its physical properties from digitoxin and in
certain of its physiologic actions, as the manufacturers themselves
state, Digalen being amorphous, and soluble in water, while digitoxin
is crystalline and insoluble in water. The manufacturers state that
Digalen differs from digitoxin in certain of its physiologic actions,
but the two substances do indeed differ far more than they admit.
Cloetta and the manufacturers of Digalen lay especial stress on the
claim that Digalen is cumulative to a far less extent than digitoxin,
and that it has far less tendency to cause gastric disturbance than
the latter. The first of these claims is true; the second is the
very opposite of the truth, as we shall show.
We know nothing of the structure of any of the digitalis principles,
and even though one were to admit (purely for the sake of argument)
that Digalen and digitoxin were chemical isomers, that fact could
not be taken to lend any support to the contention that the two
substances were identical, in the face of the established fact
that they differ physically and physiologically in nearly every
particular, and agree only in that they both cause standstill of the
heart in the same way--an action possessed also by so dissimilar a
substance as barium.
The manufacturers of Digalen support the claim of the identity of
their product with digitoxin by stating that “Digalen is a solution
of the most active glucoside of digitalis.”[31] Of course, it is very
generally admitted that digitoxin is the most active principle of
digitalis, though there is some question concerning its glucosidal
nature.
[31] Clinical Suggestions and Reports, December, 1912, p. 24.
Digalen is in fact far less active than digitoxin, as has been shown
by a number of independent observers[M] (Worth Hale, 1910; Hatcher
and Brody, 1910; Neave, 1907; Miller, 1908; the referee; Weis, 1912).
[M] Owing to lack of space a portion of the report is here omitted. A
detailed discussion of these results is included in the full report
contained in the reprint.
The essential fact which appears from the investigation of Weis is
that _Digalen did not behave like digitoxin in any case_.
Hale also found that Digalen gave atypical actions in which the
effects on the central nervous system became prominent. The referee
can corroborate these observations of Hale’s on frogs, but the
convulsive symptoms were prominent with some specimens of Digalen on
mammals, though not with others, the more recent specimens of the
preparation showing the action prominently.
The results of all these biologic tests, as well as of the physical
tests made by Weis, certainly lend no support to the contention of
Cloetta that the potent constituent of Digalen is identical with
digitoxin, but, on the contrary, they show conclusively that the
two substances differ widely in many essentials, and the continued
claim of the manufacturers that the “amorphous digitoxin” said to be
contained in Digalen is the same as digitoxin, or that it is the most
active glucosid of digitalis, can be considered only as misleading,
and therefore in conflict with the rules of the Council.
CONSTANCY OF COMPOSITION AND ACIDITY
The manufacturers of Digalen continue to claim that it is of constant
and uniform activity,[32] and they imply this even when they do
not state it in those words; for example, a substance cannot be
considered reliable if it is variable in activity. “Digalen is
Absolutely _Reliable_. It is _Standardized_ and consequently _always
uniform_. It _does not produce gastric disturbances_.”
[32] Advertisement Brit. Med. Jour., April 26, 1913.
That the foregoing is absolutely untrue can be shown abundantly.
Hale[33] found digalen not to be uniformly stable; Weis found very
different degrees of activity for Digalen in the liquid and tablet
forms, the tablets being but one-third as active as the liquid, and
the referee found very great variations in the activity of different
specimens of Digalen, one specimen being almost inert. The results
obtained by Miller show that Digalen is sometimes very slightly
active, or not at all so.
[33] Hale: Hyg. Lab. Bull., 74.
The foregoing citations show conclusively that Digalen is not
of uniform activity. When _reliability_ is claimed for Digalen
in contrast to the known variability of digitalis, it must be
considered as tantamount to the claim that Digalen is not subject
to such variability and it must be held that the manufacturers make
misleading statements when they assert that Digalen is absolutely
reliable.
The manufacturers claim that Digalen does not produce gastric
disturbances (see advertisement cited).
It is quite true that when small doses of Digalen are used
therapeutically it fails to produce gastric disturbances because it
is of such slight activity, as previously stated, but when it is used
in amounts which correspond in activity to such doses of the ordinary
galenical preparations of digitalis as commonly cause nausea and
vomiting it does cause gastric disturbances quite as readily as the
latter.
Among the clinicians who have found that Digalen causes gastric
disturbances may be cited: Veiel,[34] Mueller,[35] Eichhorst[36] and
Teichmann.[37]
[34] Veiel: München. med. Wchnschr., 1906, liii, 2140.
[35] Mueller: München. med. Wchnschr., 1909, lvi, 904.
[36] Eichhorst: Deutsch. med. Wchnschr., 1905, xxxi, 49.
[37] Teichmann: Therap. d. Gegenw., 1907, xlviii, 199.
Eggleston and Hatcher[38] compared the emetic and cardiac activity
of Digalen and numerous other digitalis bodies and preparations and
found that the emetic activity of Digalen was decidedly greater in
proportion to its cardiac (or therapeutic) action than was that of
digitalis or digitoxin.
[38] Eggleston, Cary, and Hatcher, Robert, A.: The Emetic Action of
the Digitalis Bodies, The Journal A. M. A., Feb. 15, 1913, p. 499.
In the absence of any evidence to controvert this clinical and
experimental evidence, the continued claim that Digalen does not
disturb the stomach must be looked on as deliberate misrepresentation.
MISLEADING THERAPEUTIC CLAIMS
The recommendation that Digalen be dismissed from N. N. R. is made
with the full appreciation of the fact that the manufacturers of
Digalen and their agents have repeatedly stated that they desired to
comply with the rules of the Council, and that they have withdrawn
several statements to which the Council has taken exception, but
the fact remains that despite these reiterations the advertisements
of Digalen continue to embody statements which the Council can only
consider misleading.
The Council believes that the following advertisements constitute
gross therapeutic exaggerations:
“Digalen a sheet anchor in pneumonia; a strong support to the heart
in this deadliest of infectious diseases among adults. The prompt
action of Digalen, by intravenous or intramuscular injection makes
it possible to save lives which might be otherwise hopelessly
lost. The best digitalis preparation which we have at the present
time.”[39]
[39] Advertisement in Am. Med., January and February, 1913.
“_The_ digitalis for children. Because its dosage can be
controlled. Endorsed by pediatrists everywhere.”[40]
[40] Advertisement in Merck’s Arch., April, 1913.
“The myocarditis of Tuberculosis so frequently encountered,
especially in the advanced stage of the disease, may be controlled
with the aid of Digalen. The standard digitalis preparation.”[41]
[41] South. Medical Journal, January to May, 1913, inclusive.
“Digalen is Absolutely _Reliable_. It is _standardized_ and
consequently _always uniform_. It _does not produce gastric
disturbances._”[42]
[42] Advertisement in Brit. Med. Jour., April 26, 1913.
Digalen is not a sheet anchor in pneumonia, for there is no drug
deserving such a title. Digalen has no action which other digitalis
preparations lack, and cannot save lives otherwise hopelessly lost.
The dosage of Digalen cannot be controlled any better than that of
other digitalis preparations, since its activity is variable. We cannot
control the myocarditis of advanced tuberculosis by this or any other
means.
CLAIMED SUPERIORITY
Various digitalis principles, including digitoxin, digitalin (true)
and digitalein, have been known for many years. Therapeutically they
have been found wanting and there appears to be no basis for the
continued claim that Digalen has any superiority over these several
digitalis principles. On the contrary, the evidence is accumulating
that Digalen has no advantage in any particular over a solution of
digitalein, and misleading claims of the manufacturers and their
agents certainly interfere with the formation of that calm and
unbiased opinion on the part of the general practitioner, which, when
applied to the non-proprietary digitalis principles has caused them
to fall into disuse.--(_From The Journal A. M. A., Sept. 5, 1914._)
DIORADIN REFUSED RECOGNITION
Report of the Council on Pharmacy and Chemistry
A preparation called Dioradin was placed on the market as a cure for
consumption three years ago in Europe and somewhat later in this
country. It was first submitted to the Council in July, 1911. Because
of the manifestly unwarranted claims made for its use in the treatment
of tuberculosis, the Council voted that the product be refused
recognition for conflict with Rule 8, without at that time taking under
consideration the question whether or not it was in conflict with other
rules of the Council.
In June, 1912, further consideration of Dioradin was requested. The
American agent having promised a reform in the methods of advertising,
the Council considered the available evidence regarding the identity
and value of the preparation. Examination of evidence regarding the
composition of Dioradin--claimed to consist of radium chlorid, iodoform
and menthol in an ether-oil solution--showed serious discrepancies
as to the amount of radium as well as to the identity and amounts of
other constituents. It was further found that the experimental evidence
was insufficient and biased. Then, too, in view of the difficulty
of judging the effects of medicines in tuberculosis, the clinical
data were unconvincing. There was nothing to prove that the reported
improvements, even if they actually occurred, were to be ascribed to
the mixture as a whole rather than to any one of its constituents.
As a result of these findings, the Council voted that Dioradin be
refused recognition and that the publication of these facts be
authorized. In accordance with its regular procedure, it also submitted
the report to the agent. In reply the agent submitted evidence which
showed that he was not responsible for the misstatements about Dioradin
but offered no facts that affected the Council’s findings.
The entire matter having been referred to a second referee, minor
modifications of the first draft of the report were authorized. Since
then the Dioradin Company has submitted two reports of examinations
of Dioradin made for the company in Germany showing a higher radium
content than that previously found. These reports do not alter the
facts brought out in the report of the Council that the composition of
Dioradin has been variable, which past variability arouses a feeling of
uncertainty or lack of confidence. In view of this the amended report
was ordered published and appears below.
W. A. Puckner, Secretary.
_FIRST SUBMISSION OF DIORADIN_
Dioradin, a preparation for the treatment of consumption originated
by Dr. R. de Szendeffy, Budapest, Hungary, was submitted to the
Council by Louis Gero, Ltd., New York, with the following statement
of composition:
“A radio-active preparation of Menthol, Iodin and Radium Barium
Chlorid 1/10 of a drop; in ether solution.”
A circular which accompanied the submission stated:
“Preparation No. 3 of Dioradin contains not only terpins but also
iodin salts.... In view of the fact that emanations of the radium
as well as the combinations of the evasive iodin terpins enter into
the organism through the lung....”
Later these indefinite statements of composition were supplemented by
the following:
“In 100 c.c. there are:
1 gr. Iodoform.
5 " Menthol.
10 drops Radium chlorid solution
(1 milligr. in 100 c.c. of water).
5 gr. ether.
90 " Oil (ol. amygd. frig. press).”
In a circular contained in the package these claims were made:
“The preparations of the Dioradin are based on the miraculous
effects which scientific researches have shown in regard to the
different sicknesses treated with radium.
“It is generally known that radium, even if externally employed,
has proved itself to be a bactericidal remedy. Its effect is
multiplied if one employs it internally even in infinitesimal
doses, in consequence of its permanent action of emanation on the
organism.
“The preparations of the Dioradin contain the radium itself. For
this reason their antiseptic and bactericidal effect is much more
intensive than with medicaments which contain only its emanation,
which disappears in a short time.”
In view of the general extravagance of the claims made for its
therapeutic action the preparation was rejected without considering
other possible conflicts with the rules of the Council.
_SECOND SUBMISSION OF DIORADIN_
Having been advised of the rejection by the Council of Dioradin the
American agency, which in the meantime had become the Dioradin Co.,
requested further consideration. The Council therefore took up the
subject again. After certain typographical errors had been corrected
the following was now given as the composition:
“1 gram Iodoform.
5 grams Menthol.
10 drops Radium Chlorid Solution (containing 1 milligram of
radium chlorid in 100 cubic centimeters of water).
5 grams Ether.
89 grams expressed oil of almond.
This liquid is put up in ampules containing one cubic
centimeter of liquid.”
In support of the therapeutic claims for Dioradin the American agent
submitted literature consisting chiefly of articles by Dr. Bernheim
of Paris. Before reporting on the requested reconsideration of
Dioradin the referee directed the secretary of the Council to point
out to the American agent that in the formula given, the amount
of non-volatile matter should be about 90 per cent., whereas the
report of the Lederle Laboratories which accompanied the request for
reconsideration states that but 72.08 per cent. was found in the
analysis. In reply the agent stated that he had called the attention
of Dr. Szendeffy (the originator of Dioradin) to the discrepancies
concerning non-volatile matter and that he felt sure the discrepancy
was wholly accidental (_sic_). In a later communication the agent
submitted a statement of analysis from the Lederle Laboratories
of a new specimen of Dioradin according to which the amount of
non-volatile matter agreed essentially with the amount claimed by the
agent.
The referee, having examined the evidence, is of the opinion that
the statement of composition is misleading and that the therapeutic
claims are unwarranted, thus:
DISCREPANCIES IN RADIUM CONTENT
The chief claims for its therapeutic value are based on the radium
content, yet the discrepancies and contradictions, regarding this are
serious.
In connection with the reconsideration of this product the agent
presented a certificate of chemical examination by the Lederle
Laboratories in which the following statement was made as to the
radio-activity:
“Examination shows the preparation to possess slight radioactivity,
corresponding in activity to less than 1-10,000 of 1 milligram
of radium bromid per ampule. According to the sworn statement of
Dr. A. de Szendeffy, the originator of Dioradin, the preparation
contains 10 drops of radium chlorid solution (1 milligram in
100 cubic centimeters of water) in 100 cubic centimeters of the
preparation. This would correspond to 5-1,000 milligram of radium
chlorid in 100 cubic centimeters, or about 1-20,000 of 1 milligram
per ampule.”
A cursory reading of this paragraph gives the impression that Dioradin
possesses fully the amount of radio-activity claimed by its originator,
Dr. A. de Szendeffy. This impression is greatly strengthened by the
concluding paragraph of the Lederle report, which says:
“In conclusion, our examination shows that the preparation
submitted to us as Dioradin possesses radio-activity, and contains
a fixed oil (apparently expressed oil of almond), iodoform, menthol
and ether, thus confirming the sworn statement of Dr. A. de
Szendeffy in regard to the composition of this product.”
On inquiry as to the method used by the Lederle Laboratories, in
determining radio-activity the agent submitted a further statement
of the Lederle Laboratories which describes the gamma ray test by
which the determination was made and a radium value equivalent to
0.000041 mg. of radium bromid per capsule was obtained. The report then
says:
“The variations of the single measurements from the mean in the
case of the natural leak and the leak with the Dioradin near were
so large that we did not feel justified in assigning much accuracy
to the figure, 0.000041, but stated that the amount of radium per
capsule could not be greater than 0.0001 mg., with the possibility
of there being a much smaller amount present.”
It is evident that the wording of the reports of the Lederle
Laboratories is liable to give the impression that their examination
confirms the claims made for Dioradin.
It is further evident from these reports that the amount of
radio-active matter has not been definitely ascertained but that it
is at the best very small. The unreliability of the claims for radium
content of Dioradin was recently shown by Buechner,[43] who found a
specimen obtained from an apothecary to contain but 1-1,000 of the
amount claimed.
[43] Buechner: Pharm. Weekblad, March 2, 1912, p. 161.
VOLATILE AND NON-VOLATILE MATTER
The varying claims regarding the content of volatile and non-volatile
matter throw doubt on the entire composition of Dioradin, for if the
statement as to these is wrong the rest of the statement regarding
composition cannot be given credence.
In the first submission of Dioradin about 89 per cent. of
non-volatile matter was claimed but in the report of the analysis by
the Lederle Laboratories, which accompanied the resubmission, only
about 72 per cent. was found. Later the Lederle Laboratories reported
that an examination of a new specimen of Dioradin had shown about
90 per cent. of non-volatile matter. The discrepancies between the
composition claimed for Dioradin and that found for the product in
the first Lederle report has shown that the agent was quite ignorant
of the composition of the product which he was selling.
INDEFINITENESS OF THE IODIN CONTENT
The label on the trade package of Dioradin first submitted to the
Council stated that the product contained iodoform; a similar
statement was made in the submission of the product; the circular
accompanying the first submission stated that “iodin salts” were
contained in the product while the iodin content was referred to
further on in this circular as “combinations of evasive iodin
terpins.” In Bernheim’s papers, which have been used to advertise
Dioradin, and which are referred to in the same circular, the iodin
compound is called “iode peptonisé,” which, according to information
stated by the American agent to have come from Budapest, is to be
translated “iodized peptone.” What is the meaning of this confusion?
One would naturally suppose that the preparation to be sold in this
country contains iodoform in an ether-oil solution while the one used
by Bernheim and Dieupart[44] was stated to contain an _ethereal_
solution of “iodized peptone.” This is another mystification, for
an ethereal solution of any kind of peptone would be a novelty. The
matter is of some importance, for Bernheim and Dieupart lay great
stress on the difference between “peptonized iodin” and other iodin
(loc. cit., p. 333) and of the superiority of ethereal over oily
solutions (loc. cit., p. 334). The American agents, however, in
the second submission, state that this is all a mistake; that the
Dioradin used by Bernheim is the same Dioradin which was submitted to
the Council; and that this does not contain, and never did contain,
the ethereal solution of “iode peptonisé” to which Bernheim attached
so great importance. Bernheim (report to Medical Congress of Lyons)
himself has come to the same conclusion; for five months after his
first paper he believes that the “special salt of radium” (_sic_)
is the principal agent; so that the “peptonized iodin” must be
unimportant, and in a cablegram of July 4, 1912, he now informs
the Dioradin Company that the formula was incorrectly given in his
first papers “owing to my ignorance of actual composition,” and that
all the Dioradin used by him was of the composition stated in the
submission to the Council.
[44] Bernheim and Dieupart: Revue Internationale de la Tuberculose,
May, 1911, p. 336.
While this vindicates the good faith of the American Dioradin
Company, it does not clear up the mystery. The question occurs at
once: What led Dr. Bernheim to make such positive statements? Was he
drawing purely on his imagination? If so, why did his imagination
take this peculiar special direction? Or if he did have some reason
to imagine the “iode peptonisé,” who supplied this reason? And if,
at that time, he was given to understand by Szendeffy, who must
have supplied him with the material, that it contained the iodized
peptone, how can he be positive at this time, that it did not contain
it? Has he actually analyzed the old material?
There is also a further question which needs to be answered. Why
has Dr. Szendeffy waited until Dioradin was rejected by the Council
before correcting Bernheim’s serious misapprehension, in the meantime
permitting the circulation of Bernheim’s paper?
Until these questions have been satisfactorily answered, the element
of mystery about the composition of Dioradin cannot be cleared away.
EXPERIMENTAL EVIDENCE
The available experimental evidence regarding “Dioradin” is
restricted to some quotations from its inventor Szendeffy, in the
paper of Bernheim and Dieupart (p. 334). These, if confirmed,
would show that radium alone has practically no effect on cultures
of tubercle or colon bacilli; that 0.1 gm. of “iode-menthol”
(concentration not stated) checks the growth of the acid-fast
organisms; and that this antiseptic efficiency can be nearly doubled
by the addition of a little radium. No quantitative data are given,
so that it is difficult to judge the accuracy of the observation.
Granting that it is correct, it would have little bearing on the
therapeutic actions of Dioradin, for there is nothing to show that
the effective test-tube concentration is reached in the pulmonary
tissues.
It is also claimed that the injection of Dioradin prevents tubercle
infection. The referee believes that the Council and the medical
profession should hesitate to accept this conclusion without further
details; and these would require confirmation by unprejudiced
observers.
CLINICAL EVIDENCE
The Dioradin Company submits considerable clinical data in favor of
Dioradin. It must be remembered that most favorable opinions have
been published, from time to time, about scores of “consumption
cures,” which have mysteriously lost their efficiency when their
novelty wore away. There is no more reason to doubt the good faith
of those who are enthusiastic about Dioradin than of those who have
been enthusiastic about other “cures.” There appear to be features
in the course of tuberculosis which make the judgment of therapeutic
measures peculiarly difficult. It is possible that impartial
clinical trials of Dioradin by tuberculosis experts appointed by the
Council might facilitate judgment as to the actual efficiency of
Dioradin. The referee doubts, however, whether this would advance the
Council very much toward the acceptance of the substance. Such an
investigation would be so lengthy that it should not be undertaken
until the Dioradin Company itself has offered at least presumptive
evidence in this direction, especially in view of the adverse report
recently made by Cecil Wall.[45] Ten tuberculous patients were
treated by Wall in strict accordance with the method outlined to
him by Bernheim, yet Wall concludes that none of the cases, though
treated accurately in accordance with the instructions, can be quoted
to justify any of the claims for the therapeutic efficiency of
Dioradin. The Council cannot undertake lengthy investigations of this
character until it is put in possession of data which would show to
its satisfaction that such investigations would probably be fruitful.
[45] Wall, C.: Brit. Med. Jour., July 20, 1912, p. 109.
CONCLUSIONS
From investigations made, it appears that the claims in regard to
the composition of Dioradin have contained vague statements and
contradictions which arouse a feeling of uncertainty and lack of
confidence. Until this uncertainty is cleared away, Dioradin cannot
be considered as complying with Rule 1. The experimental data are
insufficient and unconvincing. Some favorable clinical reports
have been submitted, but the accuracy of the observations is to be
questioned and they are more than offset by the negative results
observed by Cecil Wall. As might be expected, other negative results,
if observed, have not been submitted and there is nothing in the
manufacturer’s claim to show whether the improvement reported is
really due to the peculiar mixture called Dioradin or to any one of
its ingredients.
It is therefore recommended that Dioradin be not accepted for New and
Nonofficial Remedies. In view of the extensive advertising of this
preparation and because of the admittedly incorrect statements in the
earlier papers it is recommended that publication of this report be
authorized.--(_From The Journal A. M. A., Oct. 26, 1912._)
ECHINACEA
Report of the Council on Pharmacy and Chemistry
The Council has voted to reject several non-proprietary articles
and has recommended that the reasons for their rejection be given
in The Journal; among these is echinacea. The following paper has
been submitted by a subcommittee with the recommendation that it be
published. This recommendation was adopted.
W. A. Puckner, Secretary.
Echinacea
When this drug was first introduced, it was a typical nostrum, with
exaggerations regarding its therapeutic value that were somewhat more
gross than usual. It was later adopted by the eclectic school without
being freed from the stigmata of its origin. It was also pressed
into use as the main ingredient of such proprietary preparations as
Echafolta, Ecthol Eusoma, etc. Efforts have been made to get the
regular profession to use it in these various forms.
According to J. U. Lloyd (_Pharm. Review_, vol. xxii, p. 9-14), the
introduction of echinacea into eclectic medicine is due to the efforts
of Dr. H. F. C. Meyer to increase the sale of Meyer’s Blood Purifier,
a secret remedy containing it. The following is a literal copy of the
label on this nostrum:
+------------------------------------------------------------+
| MEYER’S BLOOD PURIFIER |
| DIRECTIONS |
| This is a powerful drug as an Alterative and Antiseptic |
| cases: _Rheumatism, Sick Headache, Erysipelas, Dyspepsia, |
| Old Sores and Biles, Open Wounds, Dizziness, Scrofula and |
| Sore Eyes._ |
| |
| In case of _Poisoning by Herbs, & C._, take the double |
| dosis, and _Bites of Rattlesnakes_ take three ounces three |
| times a day, until the swelling is gone. This is an |
| absolute cure within 24 hours. |
+------------------------------------------------------------+
After Lloyd had identified the plant, Meyer put the preparation out
under another form with the following label:
+--------------------------------------------------------------+
| ECHINACEA ANGUSTEFOLIA |
| This is a powerful drug as an Alterative and Antiseptic |
| in all tumorous and Syphilitic indications; old chronic |
| wounds, such as fever sores, old ulcers, Carbuncles, Piles, |
| eczema, wet or dry, can be cured quick and active; also |
| Erysipelas. It will not fail in Gangrene. In fever it is a |
| specific; typhoid can be adverted in two to three days; also |
| in Malaria, Malignant, Remittent and Mountain fever it is a |
| specific. It relieves pain, swelling and inflammation, by |
| local use, internal and external. It has not and will not |
| fail to cure Diphtheria quick. It cures bites from the bee |
| to the rattlesnake, it is a specific. Has been tested in |
| more than fifty cases of mad dog bites in human and in every |
| case it prevented hydrophobia. It has cured hydrophobia. It |
| is perfectly harmless, internal and external. |
| |
| Dose.--One half to one fluid-drachm 3 or 4 times a day. |
| |
| Manufactured by H. C. F. Meyer, M.D. |
| Price, $ Pawnee City, Neb., U. S. A. |
| Patent |
+--------------------------------------------------------------+
These absurd claims of an evidently ignorant man have passed into
the more recent proprietary advertising matters and into much of the
eclectic writings. Indeed, the seemingly impossible had been attained
by even surpassing Meyer’s all-but-all-embracing claims. Not content
with endorsing echinacea as a positive and speedy “specific” for
rattlesnake bite, syphilis, typhoid fever, malaria, diphtheria and
hydrophobia, later enthusiasts have credited it with equally certain
curative effects in tuberculosis, tetanus and exophthalmic goiter, and
with the power of retarding the development of cancer.
It is worth noticing--although it is not surprising--that these
far-reaching claims have been made on no better basis than that of
clinical trials by unknown men who have not otherwise achieved any
general reputation as acute, discriminating and reliable observers.
No attempt seems to have been made to verify these claims by accurate
scientific methods, clinical or otherwise, although this could very
easily have been done.
Not one of the eulogistic reporters and exploiters seems to have
considered it worth while to determine by the simplest control
experiments whether the drug possesses any bactericidal or antiseptic
powers whatever. It is therefore not very strange that discriminating
physicians have failed to show much enthusiasm. One of the warmest
endorsers of echinacea, C. S. Chamberlain (who later became the
president of the Eusoma Pharmaceutical Company), complains that he
has been unable to interest regular physicians in the remedy. He
reviews the statements of previous authors and reports eight cases of
infection, only two being acute or extensive, in which he used it with
asserted success.
In view of the lack of any scientific scrutiny of the claims made for
it, echinacea is deemed unworthy of further consideration until more
reliable evidence is presented in its favor.
REFERENCES
Meyer, H. F. C.: _Eclectic Med. Jour._, 1887; Goss: _Chicago Med.
Times_, 1888; Hages: _Eclectic Med. Jour._, 1888; Shelly: _Medical
Gleaner_, 1894; Lloyd, C. G.: _Eclectic Med. Jour._, 1897; Lloyd,
J. U.: _Eclectic Med. Jour._, 1897; Lloyd, J. U.: _Pharm. Review_,
xxii, 9-14; Schnitz, Elsie M.: _Wis. Med. Recorder_, 1898, ii, 202;
White, J. N.: _Texas Med. News_, 1898, viii, 110-113; Stinson,
J. C.: Therap. _Gazette_, 1900; Hale, E.: _Lancet-Clinic_, March,
1901; Thielen, B. F.: Echafolta, Its Uses in Dental Surgery, _Dental
Reg._, 1903, vii, 462-465; Gorse, C. A.: _New Albany Med. Herald_,
1903-4, xxii, 384; Chamberlain, C. S.: _Louisville Monthly Jour.
Med. & Surg._, 1904-5, xi, 219-223; _Lancet-Clinic_, 1905, M. S.,
liv, 279-283; Ellingwood, F.: _Therap. Gazette_, 1905, 3, S., xxi,
298-300; French, J. M.: _Med. Brief_, 1905, xxxiii, 537; Mathews,
A. B.: _Georgia Pract._, 1905, i, 137-140.--(_From The Journal
A. M. A., Nov. 27, 1909._)
ECHTISIA, ECTHOL AND ECHITONE
Report of the Council on Pharmacy and Chemistry
Echtisia (Wm. S. Merrell Chemical Co.), Ecthol (Battle and Co.) and
Echitone (Strong, Cobb and Co.) are proprietary preparations each of
which is alleged to contain echinacea as its chief constituent. In 1909
the Council examined into the claims made for echinacea. This drug has
been claimed to be a “specific” for rattlesnake bite, syphilis, typhoid
fever, malaria, diphtheria and hydrophobia. Enthusiasts have credited
it with equally certain curative effects in tuberculosis, tetanus,
and exophthalmic goiter and with power of retarding the development
of cancer. Of course there is no reliable or trustworthy evidence to
substantiate these claims. Echinacea is not often prescribed under its
own name, but is employed as an ingredient in proprietary preparations
mixed with other little-used or obsolete substances. Thus Echtisia is
said to contain echinacea, wild indigo, arbor vitae and poke root;
Ecthol, to have echinacea and arbor vitae; Echitone, to consist of
echinacea, pansy and blue flag. Naturally the manufacturers of such
proprietaries make use of all available optimistic reports in promoting
their sale, while each manufacturer ascribes special and peculiar
virtues to the combination represented in his particular preparation.
The Merrell Chemical Company claims that baptisia (wild indigo) is a
“destroyer” of devitalizing elements in the blood “a vitalizer of the
blood as well”; that thuja (arbor vitae) is a “perfect antiseptic and a
generator of vital force in disorganized tissues,” and that a long list
of diseases, including diphtheria, syphilitic sciatica and gonorrheal
rheumatism, “are all more or less amenable to full doses” of phytolacca
(poke root). Strong, Cobb and Co. maintain that Iris versicolor (blue
flag) is “one of the most powerful excitants of the biliary, salivary
and pancreatic secretions,” and that the “principal sphere of action of
Viola tricolor [pansy] is in the gastro-intestinal canal and the skin.”
There is no satisfactory evidence that the claims for any of
these substances are any more reliable than those for echinacea.
Notwithstanding, Strong, Cobb and Co. claim for Echitone “not only the
virtues of its constituent parts, but a wider field and a particular
therapeutic value of its own”; Battle and Co., maintain that Ecthol
is the “‘Ideal Corrector’ of depraved conditions of the fluids and
tissues,” while the Merrell Company urges the virtues of Echtisia in a
list of diseases ranging from acne to appendicitis and from gangrene
to rattlesnake bite. The Council refused recognition to these three
products and directed publication of reports to call attention to the
exaggerated, unwarranted and often utterly absurd claims made for these
and similar preparations.--(_From The Journal A. M. A., Jan. 2, 1915._)
ERGOAPIOL[N]
Abstract of Report of the Council on Pharmacy and Chemistry
[N] For abstract of report on a similar mixture, see Apergols, p. 26;
for unabridged report of the Council’s action on Apergols and Ergoapiol
see Reports Council Pharm. and Chem., 1914, p. 64.
Ergoapiol (Martin H. Smith Co., New York) is a mixture put up in
capsules, each of which is said to contain
Apiol (Special M. H. S.) 5 grains
Ergotin 1 grain
Oil Savin 1/2 grain
Aloin 1/8 grain
Examination discloses the fact that, contrary to the claim made, each
capsule, instead of containing 5 grains of apiol, really contains some
liquid preparation of the type of oleoresin of parsley seed. Ergoapiol
is recommended (on the label) for such diseases as “Amenorrhea,
Dysmenorrhea and other Menstrual Disorders,” while a circular enclosed
in the package contains many suggestions that may be counted on to lead
to its indiscriminate and uncritical use.
Ergoapiol is an unscientific, shot-gun mixture of drugs having
widely different therapeutic effects. Where the action of parsley is
desired, the effects of ergot would ordinarily, be contra-indicated;
furthermore, neither aloin or savin would be called for in conditions
that demanded the effects of apiol. It would be impossible to predict
the action of a mixture of this kind in the varying conditions for
which its use is advised by the manufacturers. To combine four drugs
of dissimilar action in fixed proportions for the routine treatment
of conditions which have little in common except that they involve
the female generative organs, is unscientific and absurd. The Council
refused admission to Ergoapiol.--(_From The Journal A. M. A., Dec. 12,
1914._)
ERPIOL (DR. SCHRADER)
Report of the Council on Pharmacy and Chemistry
The original rules of the Council governing the acceptance of articles
have recently been modified, particularly by adoption of Rule 10, which
reads:
“Unscientific and Useless Articles.--No article will be admitted
which, because of its unscientific composition, is useless or
inimical to the best interests of the public or of the medical
profession.”
In view of these modifications, the Council is reconsidering the
articles already accepted with the view of determining their compliance
with the rules as amended. In line with this the Council reconsidered
Erpiol (Dr. Schrader), manufactured by the William S. Merrell Chemical
Company, and from the evidence given below concluded that one of the
constituents, gossypin, is inert and its use unscientific. The Council
therefore voted that Erpiol (Dr. Schrader) be omitted from New and
Nonofficial Remedies and authorized publication of the following report.
W. A. Puckner, Secretary.
Erpiol
In consequence of the more thorough scrutiny now given by the
Council to the therapeutic value of the remedies admitted to New
and Nonofficial Remedies, the Council has reconsidered Erpiol (Dr.
Schrader), previously accepted for New and Nonofficial Remedies. Erpiol
(Dr. Schrader) is the name applied to capsules containing apiol,
ergotin and gossypin, which are sold as an emmenagogue. The first two
ingredients have a recognized value in the treatment of diseases of
the female generative organs. The third, gossypin, is a preparation
from cotton-root bark, belonging to the somewhat indefinite class of
pharmaceutical preparations known as resinoids.
Cotton-root bark (_Gossypii radicis cortex_, U. S. P.) has been
credited by some with pharmacologic and therapeutic properties,
similar to ergot, especially in its action on the uterus; experiments
on pregnant animals do not confirm this view. Most authorities on
gynecology either make no reference whatever to the drug or ascribe
little or no value to it. The preparations from the dried bark are
inert.
From reports made to him, Professor J. U. Lloyd concluded (_Eclectic
Med. Jour._, 1876, xxxvi, 545) that a prime fluidextract of fresh
cotton-root bark is an active therapeutic agent and deserving the
attention of the medical profession, while that of the dry bark is
inert and worthless. The gossypin on the market is made from the dried
bark.
Professor Lloyd, who is considered an authority on eclectic medicine,
says: “Were it left to me to admit or exclude it, by reason of its
therapeutical position, I should exclude it, because, in my opinion, it
has never been demonstrated, in clinical practice, to be worthy of any
therapeutic recognition whatever.”
As the available evidence indicates that gossypin is an inert
preparation, Erpiol (Dr. Schrader) was considered in conflict with Rule
10 and the Council has therefore voted that it be deleted from New and
Nonofficial Remedies.--(_From the Journal A. M. A., June 3, 1911._)
FALSE UNICORN (HELONIAS)
Report of the Council on Pharmacy and Chemistry
The Council voted to refuse to recognize false unicorn as a
non-proprietary article and the following statements, submitted by a
subcommittee, were ordered published.
W. A. Puckner, Secretary.
False Unicorn-Helonias
_Helonias dioica_, or more properly _Chamælirium luteum_, is a plant,
preparations of which enter into various proprietary mixtures for
diseases of the female pelvic organs. In the advertisements of these
preparations it is usually credited with hemostatic powers and is
asserted to be a uterine tonic.
There is practically no reference to this drug in reliable medical
literature, and as there is no evidence worthy of credence to support
the claims made for it, the drug was not considered deserving of a
place in the Pharmacopeia. Hence, it may be regarded as a drug not
worthy of attention of physicians.--(_From The Journal A. M. A., Nov.
27, 1909._)
FORMUROL
Report of the Council on Pharmacy and Chemistry
Formurol, Citrocoll and Aspirophen were submitted to the Council by the
Cellarius Company of San Francisco. The manufacturers having failed
to substantiate the claims they make for these products, the Council
has voted that the preparations be refused recognition. The Council
also authorized the publication of the following report, which deals
particularly with one of the preparations--Formurol.
W. A. Puckner, Secretary.
Formurol is the product of the Chemische Fabrik Falkenberg,
Falkenberg-Gruenau, near Berlin, Germany. The Cellarius Company,
San Francisco, acting as selling agents for the United States,
submitted Formurol (along with Aspirophen and Citrocoll, also made
by the same firm) to the Council, with the statement that it is
“hexamethylentetraminsodium-citrate,” and that it has the following
composition: “C_{6}H_{7}O_{7}Na.C_{6}H_{12}N_{4}.”
Zernik,[46] who examined these products, reported that Aspirophen,
Citrocoll and Formurol do not have the composition that is claimed for
them by the Fabrik Falkenberg. Formurol, he states, is not a definite
chemical compound, but a mixture of hexamethylenamin and sodium
citrate. The agents were advised of this fact by the Council and were
asked to submit evidence to substantiate their claims. No such evidence
was submitted.
[46] Zernik: Arb. a. d. Pharmazeut. Inst. d. Univ. Berlin, 1907, iv, 46.
Since a compound having the composition that is claimed for Formurol
is theoretically possible, the Council requested that the product be
examined in the Association Laboratory to determine whether it still
was the simple mixture reported by Zernik, or whether, perhaps, it now
possessed the formula claimed for it. The following report was made by
the Association chemists:
Formurol, as submitted to the Council, was in the form of tablets
weighing about 1 gm. each and appeared to be composed of a fine
white substance interspersed with some transparent particles.
The tablets were readily soluble in water, were odorless and
possessed a slightly acid taste. The aqueous solution responded
to tests for hexamethylenamin, citrate and sodium. To determine
whether hexamethylenamin was present in the free or the combined
state, the method of Zernik was employed. This consists in the
extraction of Formurol with chloroform, which dissolves out
hexamethylenamin, leaving insoluble sodium citrate. As the use of
the solvent, chloroform, would seem to preclude decomposition of
such a hypothetical compound as “hexamethylenamin-sodium-citrate,”
the extraction of hexamethylenamin from Formurol may be taken to
demonstrate its presence in the free state.
That Formurol is not a compound of hexamethylenamin, but a mixture
of hexamethylenamin and sodium citrate, was further indicated by
the appearance of the crushed tablets described above. Further,
on the low-power microscope the powder was found to be composed
of transparent crystals and white opaque particles which appeared
to be masses of minute crystals. When treated with chloroform the
transparent crystals dissolved, leaving the white masses intact,
demonstrating the presence of two distinct substances, one soluble
and the other insoluble in chloroform. It having been demonstrated
that the residue obtained by evaporation of chloroform could not be
weighed as hexamethylenamin, due to enclosed chloroform, the amount
of this substance in the residue was determined.
The method used has been described in the Report of the Chemical
Laboratory of the American Medical Association, Vol. I, p. 55,
and depends on the decomposition of hexamethylenamin by means of
sulphuric acid to form ammonium sulphate and formaldehyd. From this
solution the ammonia is liberated, distilled and determined by
titration and from the ammonia found the amount of hexamethylenamin
is calculated. By this method Formurol was found to contain (_a_)
35.42 per cent. and (_b_) 35.32 per cent., or an average of 35.37 per
cent. hexamethylenamin. The residue insoluble in chloroform was shown
to consist essentially of disodium hydrogen citrate by determining
the amount of sodium (Na) contained in Formurol. The percentage of
sodium calculated from the amount of sodium sulphate found was (_a_)
11.38 per cent. and (_b_) 11.20 per cent., or an average of 11.29 per
cent., equivalent to 62.50 per cent. disodium hydrogen citrate.
As a check on this determination, the amount of material contained
in Formurol which is insoluble in chloroform was determined. It was
found to be (_a_) 63.23 per cent. and (_b_) 63.49 per cent., making
an average of 63.36 per cent., and thus agreeing fairly well with the
results obtained when the sodium content was assumed to be disodium
hydrogen citrate. From this analysis it appears that Formurol is
not a definite compound of hexamethylenamin and sodium citrate, but
instead is a mixture of these substances consisting approximately of
hexamethylenamin 35.37 per cent. and sodium acid citrate (disodium
hydrogen citrate) 63.36 per cent., practically a mixture of 1 part
hexamethylenamin and 2 parts sodium acid citrate. These results agree
with those reported by Zernik[47] and show that the product now, as
then, is not true to claims.
[47] Therap. d. Gegenw., February, 1909.
In view of the findings of the laboratory, it is recommended that
Formurol be refused recognition. As the exploitation of well-known
remedies under false and misleading names is detrimental to the
progress of medicine, it is recommended that publication of this report
be authorized.
[Editorial Note: This report illustrates once more the value of
the Council on Pharmacy and Chemistry and the Chemical Laboratory
to the medical profession. Before the Council was organized there
was no agency to protect the physician’s interests in the matter
of pharmaceuticals. Under the old régime Formurol would have been
heralded as a new “synthetic” of the most approved made-in-Germany
type--and the claims would have gone unchallenged. To-day its status
is made clear and the profession is informed. Only those who have
closely studied the question can realize what a wonderful power for
commercial probity the Council has proved. Under the _laissez faire_
system of the past, many large pharmaceutical firms gave little
attention to the accuracy of the claims made for their products. If
the advertising gave good “pulling” results, that was all that was
asked or expected. Within the past five years a wonderful change has
taken place in this regard, and firms of the better class have so
modified their advertising as to make it not only conservative in
tone, but to approximate scientific accuracy.]--(_From The Journal
A. M. A., Jan. 21, 1911._)
GASTROGEN TABLETS
Report of the Council on Pharmacy and Chemistry
The Bristol-Myers Co., Brooklyn, N. Y., sells Gastrogen Tablets which
are described as “A Neutralizing Digestive” to be “used in connection
with Sal Hepatica.” Sal Hepatica, it will be remembered, is another
product of the Bristol-Myers Company and has been the subject of
previous unfavorable comment. The label on a recently purchased
package of Gastrogen Tablets contains the following:
“For gastric distress, weak stomach and dyspepsia, one to two
tablets after eating; repeat in half an hour if needed.
“Also indicated in nausea, flatulence, sour stomach and heartburn.”
While these recommendations sound as if they were addressed to the
public, Gastrogen Tablets are advertised in medical publications and
hence come within the scope of the Council. Gastrogen Tablets are said
to be composed of pepsin, calcium carbonate, calcium phosphate and
“aromatics.” As each tablet, according to the label, contains 7 grains
of calcium carbonate (chalk), the recommended dosage would in most
cases be sufficient to neutralize the gastric fluids in the stomach
and would thus tend to prevent the pepsin from exerting its digestive
effects. The means adopted to relieve one symptom of dyspepsia,
in other words, defeats the action of the means for relieving the
indigestion. The fact is that patients who need an antacid do not
need pepsin, while those who need pepsin will be harmed by the
administration of an antacid. Gastrologists hold that, except in rare
cases, the evidence tends to show that wherever there is a sufficiency
of hydrochloric acid there is a sufficiency of pepsin. When pepsin
is lacking it should be administered along with hydrochloric acid to
make it effective. The Council voted that Gastrogen Tablets be refused
recognition.--(_From The Journal A. M. A., Dec. 12, 1914._)
GLYCO-HEROIN, SMITH
Report of the Council on Pharmacy and Chemistry
The following report was submitted to the Council by a referee and
publication authorized.
W. A. Puckner, Secretary.
Glyco-Heroin, Smith (Martin H. Smith Co., New York) is marketed in a
showy “patent-medicine” type of package, the label on which announces
the presence of 1/2 grain of heroin to the fluidounce and admits the
presence of 3.5 per cent. alcohol, an active ingredient that is not
discussed in any way in the literature sent out by the manufacturer.
The composition of Glyco-Heroin, Smith, is given as follows: “Each
teaspoonful represents: Heroin 1/16 grain, White Pine Bark 3-1/2
grains, Ammonium Hypophosphite 3 grains, Balsam Tolu 1/4 grain,
Hyoscyamus 1 grain, Glycerin Q. S.” The alcohol is not mentioned in the
formula.
The advertising matter says of the merits of the formula:
“Despite the fact that heroin, which is universally recognized
as an invaluable respiratory sedative, is a conspicuous element
of Glyco-Heroin, Smith, the other constituents, henbane, ammonia
hypophosphite, balsam tolu and white pine bark are factors of no
less importance; indeed, it is through the concerted action of
its several ingredients that the preparation proves so notably
beneficial in the class of affections in which it is indicated.
The constantly increasing popularity of the preparation in the
treatment of respiratory affections is the best adducible evidence
of its value in such disorders.”
The absurdity of this assertion will be appreciated on comparing the
nature, quantities and activities of the several ingredients. Thus,
while heroin, a potent habit-forming drug, is present in unusually
large proportions, tolu, an innocuous or comparatively harmless
product, is said to be represented by 1/4 grain, a relatively small
quantity, hardly sufficient to impart even a distinctive taste or
flavor. Ammonium hypophosphite, in the amount said to be present, may
be considered to be practically useless, while the dose of hyoscyamus,
an additional narcotic, is fairly large. The white pine bark present
is probably as active as would be a corresponding amount of white pine
shavings or of turpentine sufficient to give the preparation a slight
odor. The vehicle, glycerin, is claimed to be “notably advantageous,”
but not a word occurs in the discussion by the manufacturer in regard
to the presence of alcohol, which is certainly quite as active
medicinally as the balsam of tolu and contributes fully as much to the
flavor or taste of the preparation as does the white pine bark.
In prominent type on the outer label of the trade package we are told
that the preparation is intended for the treatment of “COUGH, ASTHMA,
PHTHISIS, PNEUMONIA, BRONCHITIS, LARYNGITIS, WHOOPING-COUGH AND KINDRED
INFECTIONS.” In much smaller type: “Glyco-Heroin (Smith) is distinctly
a product designed expressly for the use of physicians.” The circular
included with the trade package, however, bears statements which would
tend to encourage self-drugging by the layman, and in view of the
manner in which the preparation is exploited are undoubtedly intended
to do so. For instance:
“_Bronchitis._--In the acute form of bronchitis, Glyco-Heroin
(Smith) acts most happily. It tends to diminish the congestion and
inflammation of the lining of the air passages, relieves the pain
and institutes repair....
“_Phthisis._--In the treatment of the cough of phthisis,
Glyco-Heroin (Smith) is used with the most gratifying results.
It checks the night sweats, acts favorably upon the reflexes,
increases expectoration and induces refreshing sleep.
“_Asthma._--The preparation diminishes the intensity of the
paroxysms and lengthens the intervals between their recurrence.
By the administration of the preparation, asthmatic attacks can
frequently be aborted.
“_Pneumonia._--In the initial stage of pneumonia, the preparation
exercises a calming, antipyretic and sedative effect. In the latter
stages of the disease, the analgesic and expectorant properties of
the product are well displayed.
“_Whooping-Cough._--Administered in doses of from five to ten drops
this preparation affords surprisingly satisfactory results. The
cough rapidly loses its spasmodic character and the frequency of
the paroxysms is considerably diminished.”
How cruelly misleading the literature put out by the manufacturer of
this nostrum is, will be apparent from a comparison of the rather large
dose of heroin in a teaspoonful of the nostrum and the directions on
the package that:
“The adult dose of Glyco-Heroin (Smith) is one teaspoonful repeated
every two hours or at longer intervals, as the case may require.
“Children of 10 or more years, from a quarter to a half-teaspoonful.
“Children of 3 years or more, 5 to 10 drops.”
A WICKED FALSEHOOD
Included in much of the advertising matter that has been put out is the
bare-faced untruth that the preparation does not produce narcotism or
habituation. Here is a quotation from an undated circular:
“Glyco-Heroin (Smith) is decidedly preferable to preparations
containing codeine or morphine, by reason of the fact that it
does not produce narcotism, constipation, gastric disturbance nor
habituation, even though its administration be protracted.”
That this assertion is not in keeping with facts is evidenced by the
recent report of a study on the sale and use of heroin made by the
U. S. Department of Agriculture. From the information gathered it
appears that the sales of heroin and heroin-containing preparations
have increased greatly, particularly in those states which have
rigid laws preventing the indiscriminate sale of morphin and cocain.
Investigation of the subject establishes the fact that many drug
victims who formerly used morphin and cocain, and who under the new
laws find it difficult to obtain these substances, have begun using
heroin, the sale of which is not as yet carefully restricted under
state laws. The drug is said to be fully as dangerous as morphin, and
by many is held to be much worse, for the reason that it occasionally
kills the victim outright, and its habitual use is far harder to
overcome than that of other drugs.
Phillips,[48] in discussing the prevalence of the heroin habit,
reports, among others, the case of a physician aged 60 who began to
take heroin because he suffered from a chronic cough and thought there
was no danger of habit from the use of this drug because he believed
the statements of various manufacturing firms who claimed that there
was no danger of habit.
[48] Phillips, John: Prevalence of the Heroin Habit, The Journal
A. M. A., Dec. 14. 1912, p. 2146.
In a pamphlet now being distributed to the medical profession,
entitled, “Glyco-Heroin (Smith), an exposition of its components
together with references to its value in the treatment of Bronchitis,
Cough, Cough of Phthisis, Laryngitis, Pneumonia and allied disorders of
the Respiratory Tract,” the several alleged uses of the nostrum in the
treatment of cough, “Regardless of the nature of its underlying cause,
... whether of recent origin or of long duration,” are discussed at
length, and eminent practitioners with degrees extending the width of
the printed page are quoted in support of the statements made. While it
may be permissible for a theoretically trained medical tyro who lays
claim to the right of appending the abbreviations M.A., M.D., D.C.L.,
L.R.C.P. to his name to laud a heterogeneous habit-forming cough-syrup
like Glyco-Heroin, Smith, similar testimonials from a man entitled
to append Ph.G., M.S., M.D. to his name makes one doubt the value of
the training, either scientific, pharmaceutical or medical, that has
been given the poor unfortunate who, according to his own statements,
indiscriminately doses a female patient of 7 and a male patient of 40
with huge doses of heroin every two, four or six hours.
The danger of contributing to the spread of the heroin habit by the
use of preparations of this type is indicated by an editorial in The
Journal of the American Medical Association,[49] which points out that
although heroin and its hydrochlorid have been in use but a few years
they have already established themselves among the habit-forming drugs
and have become sufficiently conspicuous in this respect to awaken the
thinking public to the deplorable results for which they may become
responsible. Phillips,[1] in the article mentioned above, quotes
Petty, who reports that in the last 150 cases of drug habit coming
under his care he saw eight cases of heroin addiction. Three of these
were initial cases; in one the patient had been cured of the opium
habit, but following an operation heroin was prescribed, and the habit
followed. The remaining four patients purposely substituted heroin for
morphin, to which they had been addicted.
[49] Facts about Heroin, Current Comment, The Journal A. M. A., Dec.
21, 1912, p. 2262.
THE GROWTH OF HEROIN ADDICTION
The imminent danger of substituting heroin for either morphin or
cocain is shown by the fact, reported by the U. S. Department of
Agriculture, that during the early months of 1913 the coroner’s office
in Philadelphia County, Pa., held inquests on five sudden deaths from
heroin poisoning. In each case the victim was a heroin fiend and took
an overdose. Drug fiends are apparently able to consume relatively
large quantities of morphin or cocain, but any sudden and material
increase in the amount of heroin taken is liable to prove fatal. As
indicating the wide sale of this substance, it is known that one
druggist in Pennsylvania whose store is located in an undesirable
section of his city has been buying heroin tablets in 25,000 lots.
GLYCO-HEROIN, SMITH, A “PATENT MEDICINE”
The popularity of Glyco-Heroin, Smith, as a household nostrum is
suggested by the fact that one of the larger department-store type of
drug-stores in the city of Philadelphia lists this preparation in its
“patent-medicine” catalogue at $1.75 per bottle and sells it freely
to all who care to buy. This is due to the fact that Pennsylvania,
like many other states, does not include heroin in the prohibited
list of habit-forming drugs that can be supplied only on physicians’
prescriptions.
To what extent Glyco-Heroin, Smith, is responsible for developing
the rapidly growing heroin habit is of course problematic. It is
reasonable, however, to suppose that a preparation, each teaspoonful
of which contains so large a dose of heroin as does this nostrum, when
taken as repeatedly and as indiscriminately as is directed by the
manufacturer, would offer possibilities for harm sufficient in number
to induce the thinking medical practitioner to avoid its use altogether
and at least to suggest to even the most commercial dabbler in the
healing art the desirability of carefully considering its potency for
harm before endorsing its use in the treatment of “cough and kindred
affections.”--(_From the Journal A. M. A., June 6, 1914._)
GLYCO-THYMOLINE
Report of the Council on Pharmacy and Chemistry
The Council, having voted that Glyco-Thymoline be refused recognition,
authorized publication of the following report.
W. A. Puckner, Secretary
Glyco-Thymoline (Kress and Owen Company, New York) is a typical example
of a “patent medicine” advertised to the public through the doctors.
Bottles of the mixture with the name blown in the glass are issued to
physicians for distribution to patients, and the circular which comes
around the bottle more or less directly recommends it for use in almost
every form of infectious disease.
COMPOSITION AND VARYING FORMULAS
Different formulas for Glyco-Thymoline have appeared. At one time it
was said to contain:
“Sodium 24, Boric Acid 4, Benzoin 4, Acid Salicylic 0.33,
Eucalyptol 0.33, Thymoline 0.17, Betula Lenta 0.08, Menthol 0.08,
Pini Pumilionis 0.17, Glycerin and solvents, q.s.”
Another formula, which appeared about the same time, was:
“Benzo-Salicyl. Sod. 33.33, Eucalyptol 0.33, Thymol 0.17,
Salicylate of Methyl from Betula Lenta 0.16, Pini Pumilionis 0.17,
Glycerin and solvents q.s.”
A later formula was like the second except that it included “Menthol,
0.08.”
Analysis in the chemical laboratory of the American Medical Association
showed that Glyco-Thymoline contained borax, but no boric acid; sodium
salicylate, but no salicylic acid; sodium benzoate, but no benzoin;
the compound benzo-salicyl. sod. could not be determined, but a
mixture of sodium benzoate and sodium salicylate was demonstrable.[50]
Later Puckner pointed out[51] that while such a combination as
benzo-salicylate of sodium is known, it could not possibly be present
in Glyco-Thymoline because the alkalinity of this mixture would
decompose the compound. As the manufacturers evidently recognize that
false formulas can no longer be made plausible, only vague statements
as to the composition are now offered.
[50] The Formula for Glyco-Thymoline, Pharmacology Department, The
Journal A. M. A., Jan. 9, 1909, p. 147.
[51] Puckner, W. A.: Rep. Chem. Lab., A. M. A., 1910, iii, 7.
Two points should be noted in this connection:
1. Glyco-Thymoline conflicts with Rule 1 of the Council on Pharmacy
and Chemistry, which declares that no article shall be accepted for
inclusion with New and Nonofficial Remedies unless its composition be
furnished.
2. No matter which published formula be accepted as correct, it is
at best a weak antiseptic. The antiseptic ingredients present cannot
act as germicides in the strength in which they are used, or in the
alkaline solution on the unique virtues of which the circular lays so
much stress (“the one antiseptic solution based on the alkalinity and
saline strength of normal blood”). As shown by Verhoeff and Ellis,[52]
undiluted Glyco-Thymoline does not kill _Staphylococcus aureus_ in four
hours. It evidently, they say, “could have but little if any greater
therapeutic value than sterile salt solution.”
[52] Verhoeff, F. H., and Ellis, Edward Keith: The Bactericidal Values
of Some Widely Advertised Antiseptics, The Journal A. M. A., June 29,
1907, p. 2175.
DANGEROUS RECOMMENDATIONS
_In Diphtheria_: “Case-reports” in the advertising pamphlet describe
the treatment of diphtheria with Glyco-Thymoline. It is surely
unnecessary to point out that, whatever the possible merits of
Glyco-Thymoline or its ingredients, they are utterly irrelevant here.
But let a “case-report” be quoted:
“............., M.D., states: ‘I have many an interesting story of
Glyco-Thymoline. I just finished up a family in which I was
treating five cases of diphtheria--two of which presented
diphtheritic membrane in nasal cavity. I decided not to use
antitoxin in these cases. I used only the regular constitutional
treatment and Glyco-Thymoline as a local antiseptic. I believe
the Glyco-Thymoline worked wonders. My cases are all now in good
health, with no after troubles. I think it an ideal antiseptic for
every trouble in nose and throat.’”
Words of denunciation fall flat before the complacent self-revelation
of the physician who “decided not to use antitoxin.” Surely if any
other physicians have been misguided by this example, there must be
many another “interesting story of Glyco-Thymoline” to tell--not to
speak of other families that have been “finished up.”
_In Ophthalmia Neonatorum_: We gain from the same advertising pamphlet
the following information on prophylaxis:
“The treatment in the past has consisted of instillation of silver
nitrate, boric acid, salts of mercury, nucleinated salts of silver
and mercury, etc. ..., but these agents have proved to be failures
as an absolute specific.... During the past few months experiments
have demonstrated the efficacy of a new mode of treatment that
is both rapid and thorough, and devoid of danger in its use.
This method consists of thorough irrigation of the eyes in fully
developed cases of the disease with a solution of Glyco-Thymoline.”
At the very best, Glyco-Thymoline is a weak, a very weak
antiseptic--not a germicide. To assert, or even to imply, that it is
superior to the well-tried and efficacious Credé method of treatment
for ophthalmia in the new-born is cruelly wicked.
_In Consumption_: This from the same pamphlet:
“The indifference of phthisical patients toward the maintenance of
sanitary conditions is proverbial.
“That the environment of all such patients should be absolutely
aseptic both for the good of the patient and for the welfare of
those who are brought into contact with them is a well-established
fact.”
It is, instead, an ill-established fiction. To talk about maintaining
an “absolutely aseptic” environment under any practical conditions of
daily life is to talk nonsense; the thing is impossible, even were it
desirable. But, not to be distracted from the main issue by subsidiary
falsehoods:
“In Glyco-Thymoline we have an antiseptic which, while mild and
soothing ... is still a powerful agent for promoting asepsis, and
a potent factor in the maintenance of sanitary environment in the
sick room.
“Inhaled from a vaporizer or a fine spray atomizer, it will loosen
the mucus in a marvelous manner and in a wonderfully short time,
shorten the paroxysms of coughing to a marked degree, at the same
time reducing the danger of contagion to a minimum.”
And this is the preparation, it will be remembered--this “powerful
agent for promoting asepsis”--which, when applied in undiluted
strength, was unable to kill _Staphylococcus aureus_ in four hours!
It would be a waste of space to cite further evidence to show that
the advertising of Glyco-Thymoline is in conflict with Rule 6 of the
Council, which provides that no article shall be accepted “concerning
which the manufacturer or his agents make unwarranted, exaggerated or
misleading statements as to the therapeutic value.” It is further in
conflict with Rule 4, against indirect advertising by means of the
label, package or circular accompanying the package.
CLAIMS TO ORIGINALITY
Hatcher and Wilbert have pointed out that from a therapeutic point of
view the composition of Glyco-Thymoline is based on the formula of
the widely known “compound solution of sodium borate,” or Dobell’s
solution. For the phenol in the original, a mixture of antiseptic acids
and volatile oils has been substituted.
SUMMARY
Glyco-Thymoline is in conflict with Rules 1 and 4 of the Council on
Pharmacy and Chemistry, because of its indefinite composition and the
method of advertising it to the public. It is in conflict with Rules
10, 6 and 8, in that it is an unscientific, shot-gun mixture sold under
unwarranted therapeutic claims and under a misleading name. Altogether
it must be considered an unscientific heterogeneous mixture, in which
a few valuable ingredients are hidden by the useless shrubbery which
surrounds them.--(_From The Journal A. M. A., Oct. 10, 1914._)
GLYCOZONE
Report of the Council on Pharmacy and Chemistry, with Comments
A number of specimens of Glycozone purchased in the open market were
examined by a subcommittee. The product was found to be a mixture of
approximately 90 per cent. glycerin, 5 per cent. glyceric acid, a small
amount of water and traces of undetermined matter. The absence of
hydrogen peroxid or other peroxids was demonstrated.
In its report the subcommittee held that: (1) The name of the product
is objectionable and misleading; (2) the statements made in regard to
its composition also are misleading; (3) the claims for its therapeutic
value are exaggerated and untrue. Since the objectionable statements
have been given wide publicity among physicians as well as among the
laity, the subcommittee recommended that attention should be called to
the matter in The Journal.
The report of the subcommittee was adopted by the Council.
W. A. Puckner, Secretary.
Comment:--While the name gives the impression that ozone or some
similar substance is an essential constituent of Glycozone, or else
that the preparation is a compound or derivative of ozone, and while
the earlier advertisements stated that Glycozone was “glycerine
combined with ozone,” the examination made by the Council shows that
there is no basis of fact for such inferences.
In the advertisements the “chemical formula” C_{3}H_{6}O_{4} +
C_{3}H_{8}O_{3} appears under the word Glycozone. From the Council’s
report it is apparent that C_{3}H_{6}O_{4} stands for glyceric acid
and the C_{3}H_{8}O_{3} for glycerin, and that these, therefore,
indicate the chief constituents of Glycozone. Few, doubtless, would
recognize the first formula as being that of a glyceric acid, a product
practically unknown in medicine, nor would many associate glycerin with
the second. The evident intent is that physicians should accept the
formula as a badge of respectability.