the physician adjusts the dosage to the individual patient and
with obvious evidence of the efficiency of the adjustment. As
we understand it, the employment of alkaline carbonates is not
based on purely chemic considerations--a definite known quantity
of acid of the gastric juice is to be neutralized; the whole
literature and practice dealing with the alkaline carbonates show
them to be accredited with a much wider field of use and repute in
gastro-intestinal disorders.
The pancreatic extract in Carminzym is designed to be diffusible in
the stomach, the tablet is preferable to be crushed in the mouth
before swallowing, and we believe the pancreatic extract to be an
effective constituent as administered in Carminzym.
You comment as follows:
“Ipecac has a well defined though limited field of usefulness.
When it is used it should be given with due regard to the amount
needed by the patient and the frequency of the repetition of the
dose.”
This in a sense may be said of any of the most useful drugs, but not
in the least special degree does it apply to ipecac, which is, on
the contrary, of quite characteristic, peculiar range of therapeutic
properties, useful in varying combinations and in widely varying
proportions and doses according to the purpose for which it is
employed.
Ipecac in well known official alkaline, carminative, laxative
preparations occurs in the “average dose” in the varying quantities
of 1/14, 1/10, 1/8, and 3/16 of a grain.
The ipecac in combination with the other ingredients in Carminzym is
designed for a tablet which shall carry a minimal quantity whilst
capable of adequate remedial action, thus admitting of increase of
dosage or repetition as occasion requires. The quantity of ipecac
was not taken at random, but chosen after long trial and
consideration.
We believe that Carminzym possesses carminative properties in
a superior degree and that, furthermore, in consequence of its
composition it directly stimulates the gland secretions and thus
exerts a beneficial action upon the whole digestive functions.
Carminzym is for use as occasion requires, and this is to be
especially noted. Thus it is not only of direct benefit, but helpful
in promoting systematic therapeutic measures and regimen.
The Council takes the ground that complex mixtures of remedial
agents are so wrong that there is no longer warrant for their
admission into New and Nonofficial Remedies; and that Carminzym
is an irrational mixture.
We hold that certain desirable therapeutic properties may rationally
be attributable to Carminzym; and that these are manifested in
practice.
During the time since the description was sent and the receipt of
the statement of the action of the Council, some ten months,
Carminzym has proved of constantly increasing service.
The statement in the letter of Fairchild Bros. and Foster “The
long established custom of the use of mixtures of remedial agents
rests on considerations well known and generally accepted” might
well be paraphrased to read: The one-time prevalent custom of using
ill-considered combinations of remedial agents has been thoroughly
discredited and is generally abandoned by progressive practitioners.
Such arguments as that “laxatives, tonics, carminatives, diuretics are
combined with distinct advantage” have led to the use of irrational
mixtures such as the compound syrup of hypophosphites and the electuary
of theriaca. The Council is confident that no one who has studied the
causes and treatment of digestive disorders will find occasion to
prescribe at one time all the ingredients stated to be contained in
Carminzym, and certainly not in the fixed proportions present therein.
The comments in the Council’s report concerning ipecac certainly
does apply to all active therapeutic agents. Ipecac was mentioned in
the report because the several constituents of Carminzym were under
discussion and hence it was necessary to point out the futility of the
small dosage of ipecac in this mixture.
The announcement that “Carminzym has proved of constantly increasing
service” is not convincing. The Council does not know of a single
clinical study of the action of Carminzym under conditions which would
have afforded satisfactory evidence of its therapeutic value.--(_From
The Journal A. M. A., Sept. 28, 1918._)
PHILLIPS’ PHOSPHO-MURIATE OF QUININE COMP.
Report of the Council on Pharmacy and Chemistry
The following report on Phillips’ Phospho-Muriate of Quinine Comp. has
been adopted by the Council and authorized for publication.
W. A. Puckner, Secretary.
Phillips’ Phospho-Muriate of Quinine Comp.[125] is sold by the Charles
H. Phillips Chemical Co., New York. According to the published formula,
each fluidram contains:
Phosphoric Acid 2 minims
Potassium Phosphate }
Magnesium Phosphate }
Calcium Phosphate } 2-1/4 grains
Ferric Phosphate }
Quinin Muriate (equal to nearly 1/2 gr. Bi-Sulph.) 1/4 grain
Strychnin 1/120 grain
Flavoring, Glycerin and Syrup, _q. s._
[125] The evolution of “Phillips’ Phospho-Muriate of Quinine Comp.”
from “Phillips’ Wheat Phosphates” may be interesting. Every one
knows that therapeutics tends to fashions, and “Phillips’ Wheat
Phosphates” appears to have had its inception as the result of the
observation that super-refined white flour contains less phosphates
than the corresponding amount of wheat. It was assumed that such
flour must be deficient in an essential constituent, and the Wheat
Phosphates preparation was apparently designed to fill the want. It was
exploited for the relief of numerous conditions that were supposed,
without satisfactory evidence, to result from this deficiency. When
iron, quinin and strychnin mixtures became the vogue a quarter of a
century ago, it was only natural to ride on the wave of popularity
and the already widely advertised “Wheat Phosphates” was further
enhanced--commercially--by the addition of the iron, quinin and
strychnin, the amount of alkaloid added being practically negligible.
Those who are not familiar with the various phases of the phosphorus,
phosphoric acid, lactophosphate, lecithin, nuclein and glycerophosphate
propaganda are referred to a report of the Council on Pharmacy and
Chemistry in The Journal A. M. A., Sept. 30, 1916, p. 1033.
Some typical claims made for the preparation are:
“With marked beneficial action upon the nervous system. To be
relied on where a deficiency of the phosphates is evident.”
“... brace those tired nerves and aid that worn stomach with
Phillips’ Phospho-Muriate of Quinine.”
“The maintenance of a satisfactory blood pressure level free from
intervals of depression may be accomplished by the use of Phillips’
Phospho-Muriate of Quinine Compound in appropriate doses.”
“The quantities of quinin and strychnin in this preparation are so
well balanced that they relieve the depression and fatigue from
mental or physical exertion, without the necessity of recourse to
alcoholic stimulation.”
“The other ingredients of Phillips’ Phospho-Muriate of
Quinine--phosphoric acid, and the phosphates of potash, magnesia,
lime, and iron--are the most rational as well as convenient
means of administering these tissue remedies, and of introducing
phosphorus--the vitalizing constituent of the nervous system--into
the organism.”
The action of such a mixture as a whole is practically that of the sum
of the actions of its constituents. The therapeutic action of strychnin
and quinin are described in every text-book of therapeutics, but it
is necessary to distinguish carefully between the various conditions
in which these alkaloids have been used without discrimination, and
those conditions in which they have been proved to be of value.
While both have been widely used in a great variety of conditions,
neither is of proved value in more than a distinctly limited range
of diseases. The manufacturers of Phillips’ Phospho-Muriate of
Quinine Comp. seem to appeal to the less discriminating who use these
alkaloids without any definite conception of exactly what they seek
to accomplish with them. Quinin, although used by the uncritical in a
host of diseases, has a definite field of usefulness in the treatment
of malaria, both prophylactic and curative, but the required dose in
the treatment of malaria is many times larger than that recommended in
the Phillips’ preparation. The claim that the “strychnin and quinin
in this preparation are so well balanced that they produce a mild,
buoyant effect, so advantageous, instead of alcoholic stimulation, to
relieve depression and fatigue from mental or physical exertion” is
nonsensical, if, indeed, it is not mendacious balderdash.
Calcium and potassium have important functions in the body, but any
deficiency that may arise is usually attributable to an inability of
the body to utilize that which is supplied, for there is seldom any
deficiency of these salts in the food, and when they are needed they
are best supplied as simple solutions of the salts in appropriate doses
without all of the other constituents of Phillips’ Phospho-Muriate of
Quinine Comp.
Phosphoric acid exerts practically the same actions as other mineral
acids, hydrochloric being usually preferred for internal administration
in certain forms of indigestion, aside from which they are seldom used
as such.
In the more recent literature for Phillips’ Phospho-Muriate of Quinine
Comp., we find the attempt to utilize the well known craze about
phosphorus, which has been through so many phases, every one of which
has had its day and has been discarded.
The phosphoric acid and phosphates present in Phillips’ Phospho-Muriate
of Quinine are of no more value in nervous diseases than is simple
sodium phosphate which does not require the addition of a host of other
ingredients for its action. As a matter of fact, the phosphates of
calcium and potassium present in a dose of Phillips’ Phospho-Muriate of
Quinine are probably devoid of appreciable effect in practically all
conditions.
To pretend that one who suffers from physical and nervous exhaustion
can be materially benefited by this mixture is sheer nonsense and is
unworthy of a moment’s consideration by a clinician who is called on to
treat such patients.
Iron is useful in anemia, as every one knows. Iron has practically no
other field of usefulness in therapeutics. When it is indicated it
should be administered in a simple form, such as the pill of ferrous
carbonate, for example, and not in a “shotgun” mixture that is quite as
likely to do harm as good.
The claim that a satisfactory level of blood pressure can be maintained
by Phillips’ Phospho-Muriate of Quinine is mentioned only to condemn
as the limit of impudent therapeutic claims. It is an insult to the
intelligence of any practitioner to pretend that any known agent or
combination of remedial agents can maintain a uniform blood pressure in
any one of innumerable conditions.
In short, Phillips’ Phospho-Muriate of Quinine Comp. is a complex and
irrational mixture exploited by means of unwarranted claims. It is
a survival of the old days of therapeutic chaos when impossible and
fantastic chemical formulas were gravely published and as solemnly
accepted without question, and also without the slightest understanding
on the part of many; when the most eminent of practitioners did not
hesitate to give glowing testimonials for lithia waters that contained
no more lithium than ordinary river water; when no therapeutic claim
was too preposterous to receive acceptance, no theory too nonsensical
to justify the use of all manner of claptrap mixtures for all manner of
conditions.--(_From The Journal A. M. A., Oct. 19, 1918._)
B. IODINE AND B. OLEUM IODINE
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on “B.
Iodine” and “B. Oleum Iodine,” together with the reply submitted by the
manufacturer and a discussion thereon by the referee in charge of the
preparations.
W. A. Puckner, Secretary.
Specimens of B. Iodine and B. Oleum Iodine (B. Iodine Chemical Company)
and an advertising pamphlet were sent to the Council by John Bohlander,
A.M., M.D., with the declaration:
“Well knowing the value of Iodin in surgical operations and
dressings, prompted me for the benefit of my fellow physicians
as well as myself, and for Humanity’s sake, to make Iodin my
master-piece in chemistry.
“After several years of diligent work in my private laboratory I
succeeded in discovering a new product of Iodin--Nitrogen, hydrate
of Iodin.”
While “B. Iodine” is said to be nitrogen hydrate of iodin and “B. Oleum
Iodine” a 5 per cent. solution thereof, the examination made by Prof.
A. H. Clark of the University of Illinois, School of Pharmacy (working
in the A. M. A. Chemical Laboratory), indicates that the first is a
simple mixture of iodin and ammonium iodid, and the second a solution
of iodin in liquid petrolatum. The Council adopted the report of the
A. M. A. Chemical Laboratory (which appears below) and declared B.
Iodine and B. Oleum Iodine inadmissible to New and Nonofficial Remedies
because:
1. The composition is incorrectly declared. B. Iodine is not a newly
discovered iodin compound, “Nitrogen Hydrate of Iodine,” but a mixture
of iodin and ammonium iodid. B. Oleum Iodine is not a 5 per cent.
solution of B. Iodine as suggested by the statement on the label and
in the advertising, but a solution of iodin in liquid petrolatum
containing about 0.85 per cent. of iodin.
2. Since B. Iodine is a mixture of Iodin and ammonium iodid, its
solution in water will have the properties of other solutions of iodin
made by the aid of iodid, such as a dilution of tincture of iodin or of
compound solution of iodin (Lugol’s solution). Hence, the therapeutic
claim that B. Iodine “being of a colloidal nature has the advantage of
being more readily absorbed and taken up by all cellular structure,
thus getting a perfect cellular medication of Iodine,” is unwarranted.
3. The names “B. Iodine” and “B. Oleum Iodine” are not descriptive of
the pharmaceutical mixtures to which they are applied.
4. B. Iodine and B. Oleum Iodine are unessential modifications of
established articles. B. Iodine has no advantage over tincture of iodin
or compound solution of iodin. (As more convenient of transportation,
the Medical Department of the U. S. Army supplies its field hospitals
with a mixture of iodin and iodid ready for solution in water, either
in tablet form or in powdered form in tubes.) Solutions of iodin in
liquid petrolatum may be readily prepared (Reports Council Pharm. and
Chem., 1917, p. 88).
[Contribution from the A. M. A. Chemical Laboratory]
B. IODINE PRODUCTS
A. H. Clark, Ph.G., B.S.
“B. Iodine” products are marketed by the B. Iodine Chemical Company,
Cincinnati, Ohio; John Bohlander, A.M., M.D., is said to be the
discoverer. They consist of “B. Iodine,” “B. Oleum Iodine,” and “B.
Aqua Iodine.” B. Iodine and B. Oleum Iodine were submitted to the
Council.
In a circular submitted by the B. Iodine Chemical Company, B. Iodine is
said to be “Nitrogen Hydrate of Iodin.” It is claimed that “coming in
contact with water, H₂O, a chemical change takes place forming Hydro
Oxid of Iodin, the Nitrogen of the Nitrogen Hydrate of Iodin escaping,
the balance taking up one of oxygen of the water. Its companion, the
H₂, escaping at the same time with the Nitrogen then combining with the
remainder of the water to form the solution of Hydrogen Oxid of Iodin;
so you can readily see that you really have a pure water of Iodin,
nothing but the H, the O and the I.”--(_From the Journal A. M. A., Feb.
1, 1919._)
B. IODINE
According to the circular, B. Iodine is soluble in alcohol, chloroform,
and ether. Also it:
“Has odor, taste, melting and boiling point, same as regular
Iodin, has a great affinity for water and will respond to all
the tests of Iodin. Appears in a Bluish Black Granulated mass or
Powder. When heated in vaporating dish will throw off large purple
volumes of Iodin leaving a slight white crystalline precipitate,
which on continuous heating will entirely disappear. With careful
manipulation you can get prismatic needle point like crystals,
looking like spores of glass, these dissolving in water will yield
pure Iodin coloring the water Iodin.
“PHARMACOLOGIC, THERAPEUTICAL AND PHYSIOLOGICAL ACTION: Same as
Iodin, being of a colloidal nature has the advantage of being more
readily absorbed and taken up by all cellular structure, thus
getting a perfect cellular medication of Iodin.”
A sample of B. Iodine, marked “Nitrogen Hydrate of Iodin” was submitted
by the manufacturers and this sample was examined.
B. Iodine was found to be a granular powder, almost black with a purple
cast. It has an odor of iodin and dissolves in water readily. It is
also quite soluble in alcohol, but not entirely soluble in chloroform
and ether. Ether quickly dissolves iodin from B. Iodine, leaving a
residue of a white granular substance. Chloroform acts the same as
ether except that the iodin is dissolved out with some difficulty. On
heating B. Iodine, vapors of iodin escape. If the heating is done on
a water bath, a residue of a white granular substance, subsequently
identified as ammonium iodid, remains. If heated in a bunsen flame, no
residue remains. These tests all indicate that iodin is held in the
form of a simple mixture.
_Ammonia_: B. Iodine when mixed with an excess of sodium hydroxid and
warmed, evolves ammonia.
_Iodine_: 0.1567 gm. B. Iodine dissolved in water required 5.88 c.c.
tenth-normal sodium thiosulphate solution indicating 48.28 per cent.
iodin. 0.3721 gm. B. Iodine required 14.18 c.c. tenth-normal sodium
thiosulphate solution indicating 48.37 per cent. iodin. The average is
48.33 per cent. iodin.
_Ammonium Iodide_: 0.3453 gm. of the residue after heating B. Iodine on
a water bath until all iodin had volatilized was dissolved in water,
acidulated with phosphoric acid, and hydrogen dioxid solution added.
The liberated iodin was extracted with chloroform and titrated with
tenth-normal sodium thiosulphate. 23.78 c.c. were required indicating
0.3447 gm., or 99.83 per cent., ammonium iodid.
A mixture of 5 gm. iodin and 5 gm. ammonium iodid has the properties of
B. Iodine mentioned above.
The conclusion is that B. Iodine is essentially a mixture of iodin and
ammonium iodid in equal parts, the two substances being finely powdered
and intimately mixed.
B. OLEUM IODINE
The following regarding B. Oleum Iodine is quoted from the circular
submitted:
“B. OLEUM IODINE: Iodine soluble in mineral oil 5 and 10% for
Nasal, Pharyngeal, Laryngeal, Bronchial, Rectal, etc., and all
meucoid affections and abnormal conditions of the mucous membrane.”
A sample of B. Oleum Iodine was submitted by the manufacturer and
examined. The label on the bottle states that it is 5 per cent. B.
Oleum Iodine in mineral oil. This sample has the characteristics of
a solution of iodin in liquid petrolatum. It is oily and has the
characteristic violet color.
_Ammonia_: B. Oleum Iodine, since it is presumed to be a solution of B.
Iodine, was examined for ammonium compounds. A small quantity was mixed
with an equal volume of strong sodium hydroxid solution and heated. No
ammonia was evolved. A few crystals of ammonium chlorid were added to
a little of B. Oleum Iodine and treated as above. Ammonia was readily
detected.
_Iodine_: 5.255 gm. B. Oleum Iodine was dissolved in chloroform and
placed in a separator. A solution of potassium iodid was added and the
iodin titrated with a tenth-normal sodium thiosulphate solution. It
required 3.5 c.c. indicating 0.85 per cent. iodin.
The conclusion is that B. Oleum Iodine is a simple solution of iodin in
liquid petrolatum to the extent of 0.85 per cent. and not 5 per cent.
as claimed. Furthermore, it is not a solution of B. Iodine since no
ammonium compound is present.
The preceding report was sent to the B. Iodine Chemical Company. The
following reply was received:
Your letter of the 21st inst., received and contents noted and
cannot quite agree with your report.
Reasons why: NH₄I, a Nitro Hydrate Iodide; NH₄I₂, a Nitro Hydrate
Iodate; and NH₄I₂I₂, Per Iodide, a molecular compound, which I
claim, they all being of a NH group, so what can be the objection
of Nitrogen Hydrate of Iodine? Of course when your chemist, with
the aid of heat, drove off all the Iodine, he naturally brought it
back to a NH₄I. There’s where he gets the A.M.. I claim a molecular
compound.
The Oil of Iodine I sent you by mistake was a 1 per cent. and not
a 5 per cent. as marked. I claim it is made from the resublimed
Iodine in mineral oil and not the B. Iodine. I claim a 5 per cent.
has heretofore never been accomplished, so I therefore can claim
something new.
Tr. Iodine contains Alcohol and Potash as a base, the alcohol a
dehydrater and Potash an escharotic, and all other soluble Iodines
like the tincture have a metallic base. Mine has not. My iodine is
compatible almost with all the salts, alkaloids, tannates, and even
the metals. You can’t say that for the tincture or the others. Now
why should mine not be superior to others?
Preparations as yet are not on the market and a few pamphlets were
printed to meet with the requirements of your rulings and approval
and shall be corrected if we only can agree on a proper name as you
may suggest.
Yours very truly,
THE B. IODINE CHEMICAL CO.
By John Bohlander, A.M, M.D.
P.S. We are sending you under separate cover another sample of the
Oil of Iodine which is a 5 per cent. solution, and allowing for
deterioration will test at least four per cent.
The referee in charge of the preparations submitted the above letter to
the Council with the following comments:
The principal statements in the letter are essentially erroneous or
misleading: Mixtures or double salts of ammonium iodid and iodin were
not discovered by Dr. Bohlander, and are nothing new. Watery solutions
of iodin by means of an iodid have long been known and used in the form
of Lugol’s solution.
There is no evidence that ammonium iodid is less irritating than
potassium iodid. On the contrary, ammonium salts are generally more
irritating than the corresponding potassium salts. B. Iodine is not
compatible with alkaloids, but behaves essentially like Lugol’s
solution. The A. M. A. Chemical Laboratory reports that the new sample
of B. Oleum Iodine contains only 1.2 per cent. of free iodin, instead
of the claimed amount. It is therefore somewhat weaker than the iodin
petrolatum prepared by the A. M. A. Chemical Laboratory (Reports
Council Pharm. and Chem., 1917, p. 88).
However good Dr. Bohlander’s intentions may be, the statements that he
makes about his products are misleading or erroneous, and the products
are ineligible for N. N. R.--(_From Reports of Council on Pharmacy and
Chemistry, 1918, p. 44._)
ANTITHYROID PREPARATIONS (ANTITHYROIDIN-MOEBIUS AND
THYREOIDECTIN) OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of antithyroid preparations (Antithyroidin-Moebius and
Thyreoidectin) has been authorized for publication.
W. A. Puckner, Secretary.
New and Nonofficial Remedies, 1918, contains a discussion
of “antithyroid” preparation and describes two of these:
Antithyroidin-Moebius (E. Merck, Darmstadt, Germany) and Thyreoidectin
(Parke, Davis & Company, Detroit, Mich.).
The referee reported that these “antithyroid preparations” evidently
have not realized the expectations of their promoters, and are viewed
with skepticism by practically all critical clinicians.
Consequently, notwithstanding the cautiously worded statements of
claims made by the manufacturers of Thyreoidectin, the Council approved
the recommendation that this preparation (Thyreoidectin) be omitted
from New and Nonofficial Remedies for conflict with Rule 6 (unwarranted
therapeutic claims) and Rule 10 (unscientific and useless articles)
(Antithyroidin-Moebius had already been omitted because it was off
the market). The Council further directed that the general article
“antithyroid preparations” be also omitted.
The Council having adopted the recommendation of the referee,
Thyreoidectin is omitted from N. N. R., while the general article
appears below, as a matter of record:
Antithyroid preparations are obtained from the blood or milk of
animals, after the removal of the thyroid glands.
The use of these preparations is based on the theory that the thyroid
gland secretes products which are toxic, but which neutralize and are
neutralized by, other toxic substances produced elsewhere in the body.
Removal of the thyroid glands would then lead to the accumulation of
these second toxic substances as evidenced by the phenomena of cachexia
strumipriva and myxedema. On the other hand, the blood or milk of
such animals is claimed to be capable of preventing the effects of
hypersecretion of thyroid substance, such as is supposed to occur
in hyperthyroidism (Basedow’s or Graves’ disease--generally called
exophthalmic goiter).
These views are largely hypothetical; attempts to give to them a
rational experimental basis have failed, but some clinical observers
report distinctly beneficial results in the milder forms of the
diseases, and in obscure nervous disorders which are supposedly
connected with thyroid hypersecretion from the administration of
the milk from thyroidectomized goats and also from the use of the
proprietary blood preparations listed below. The value of these
preparations is very doubtful. The reported improvements may only be
psychical or due to associated measures, as is often seen in this
disease. Other measures of treatment should not be neglected.
Improvement is said to occur in two or three weeks and to be indicated
by an amelioration of the nervous symptoms, tremor, palpitation,
insomnia and excitability.
The administration must be long continued. Oral and hypodermic
administration are said to be equally effective, but the former is
usually preferred. These preparations are not known to be toxic, even
when very large doses are used.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 50._)
CEPHAELIN AND SYRUP CEPHAELIN-LILLY OMITTED FROM N. N. R. AND
SYRUP EMETIC-LILLY NOT ACCEPTED
Report of Council on Pharmacy and Chemistry
The Council has authorized publication of the following report, which
explains the omission of cephaelin and Syrup Cephaelin-Lilly from New
and Nonofficial Remedies and the non-acceptance of Syrup Emetic-Lilly.
W. A. Puckner, Secretary.
New and Nonofficial Remedies, 1918, describes cephaelin (an alkaloid
obtained from ipecacuanha root) and lists Syrup Cephaelin-Lilly
(containing 0.088 Gm. cephaelin hydrochlorid per 100 Cc.) as a
pharmaceutical preparation of it.
The period of acceptance for Syrup Cephaelin-Lilly having expired,
Eli Lilly & Company were asked to send the current advertising and
labels so that the Council might determine if the acceptance of this
preparation might be continued. In reply the firm wrote:
“We have changed the name Syrup Cephaeline to Syrup Emetic but the
product remains the same as before. We have no circulars describing
Syrup Emetic and can only send copies of the label.”
The new name “Syrup Emetic” conflicts with the rules of the Council
in that it does not indicate the potent ingredient of this simple
pharmaceutical preparation and in that it is therapeutically
suggestive. Emetics are powerful agents, and physicians should be given
every opportunity of knowing what they prescribe for the purpose.
The name being in conflict with Rule 8, the Council voted to omit Syrup
Cephaelin-Lilly and not to accept Syrup Emetic-Lilly.
As the cephaelin syrup was the only preparation of cephaelin admitted
to New and Nonofficial Remedies, and as the alkaloid appears to have no
important therapeutic field, the Council directed that the description
of cephaelin also be omitted.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 52._)
COLALIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Colalin has been authorized for publication.
W. A. Puckner, Secretary.
Colalin is a bile salt preparation claimed to consist essentially of
hyoglycocholic and hyotaurocholic acids. It is manufactured by Rufus
Crowell and Company, Somerville, Mass., and marketed by Schieffelin and
Company, New York.
An examination of the current advertising by the referee of the Council
in charge of bile salt preparations having revealed that claims were
made for Colalin which were not in harmony with the known action of
bile preparations, Schieffelin and Company were informed that in the
opinion of the referee the Colalin circular matter required radical
revision. In this communication the referee’s objections to the claims
were set forth in detail.
No reply to this letter was received, and hence a copy of the letter
was sent to Schieffelin and Company and also to Rufus Crowell and
Company with the explanation that unless the statements in the Colalin
advertising which the referee had questioned were substantiated by
satisfactory evidence, were suitably revised, or else the advertising
matter withdrawn pending revision, the referee would be obliged
to recommend to the Council that Colalin be omitted from New and
Nonofficial Remedies.
In reply, Schieffelin and Company wrote that they were not “engaged
actively in the introduction of Colalin,” and agreed to the omission of
Colalin from N. N. R.
In view of the failure to substantiate the claims objected to or an
agreement to discontinue them, the Council directed that Colalin and
Colalin Tablets be omitted from New and Nonofficial Remedies for
conflict with Rule 6 (unwarranted therapeutic claims).
The following are the claims which the referee questioned:
“Colalin embodies the physiological function of the bile in the
intestinal canal and also possesses properties of its own which are
intimately connected with the function of the liver.”
The quotation implies that Colalin has properties essentially different
from those of bile salts, a claim which requires substantiation.
“In the liver its action seems to be that of a general stimulant of
all the hepatic functions.”
This is a claim which requires substantiation.
“By the introduction of Colalin it has therefore become possible to
actually utilize the bile for therapeutic purposes.”
This is an unwarranted claim, for bile was used therapeutically before
Colalin was introduced.
“As gall-stones are chiefly composed of cholesterin, experiments
were made to determine whether Colalin would dissolve these
concretions outside of the body. These were completely successful
and were then followed by an extensive series of clinical
investigations on persons suffering with cholelithiasis, which
demonstrated that by the administration of Colalin in many
instances gall-stones were evacuated by the natural passages and
their further formation prevented without resort to surgical
intervention.”
This is misleading in that the context shows that “without surgical
intervention” is meant to imply a connection between the experiments
showing the solvent power of Colalin and the passage of concretions.
“... Colalin not only acts as a solvent of cholesterin calculi, but
prevents their further formation by removing the causes upon which
their development depends.”
This conveys the impression that such solvent action is exerted in
the body, that is, that such concretions in the gallbladder may be
dissolved and evacuated by the use of Colalin. For this claim there is
no evidence.
“To understand the value of Colalin in intestinal disorders it is
necessary to bear in mind the important functions of the bile in
the intestinal canal, namely, its participation in the digestion of
fats, its antitoxic action, and its influence upon the peristalsis.”
“... through its antiseptic influence inhibits the production of
toxins in the intestines.”
The referee believes that there is no satisfactory evidence that bile
or bile salts can inhibit the production of toxins in that part of the
intestine--the colon--in which they are commonly produced.--(_From
Reports of Council on Pharmacy and Chemistry, 1918, p. 52._)
FORAL
Report of the Council on Pharmacy and Chemistry
The following report on Foral, a depilatory preparation, has been
authorized for publication by the Council.
W. A. Puckner, Secretary.
Foral is sold by the Foral Products Company, Pittsburgh, Pa., as an
“antiseptic depilatory” with the special claim for its use for the
removal of hair prior to surgical operation or the dressing of wounds.
In addition to claims made for its hair dissolving action, it is
asserted that, in removing the hair from an open wound, Foral acts as
“an antiseptic, which guarantees against any infection.” It is also
claimed that, though hair will return after its use, “by proper use
it will diminish the growth of hair and cause the hair to grow much
slower, and unlike the razor, the hair will not return coarser and
thicker.”
We are informed by the Foral Products Company that their preparation is
used in many hospitals and that “... one and all are well pleased and a
great satisfaction to do away with the old style razor ...”
Foral is stated to be made according to the following formula:
_To manufacture seventy-five pounds of FORAL_
Starch 35 pounds
Barium-Sulphide 20 pounds
Zinc-Oxide 10 pounds
Calcium-Carbonated-Precip. 10 pounds
Potassium-Permanganate 10 grams
Menthol-Crystallized 10 grams
Carbolic-Acid 1/2 ounce
Lilac or Citronel oil 3 ounces
The four above chemicals are going to a heating process before
mixing or sifting.
In consideration of the preceding, the Council declared Foral
inadmissible to New and Nonofficial Remedies for conflict with its
rules, thus:
1. Foral is an unessential and irrational modification of an
established article.
While its manufacturer states that Foral has been on the market for
eighteen years, the following depilatory formula appears in a book
published thirty-five years ago (A practical Treatise on Diseases of
the Skin, Louis A. Duhring, Ed. 3, 1883) and is to be found in most
books on dermatology:
Barium Sulphid 2 drams
Zinc oxid 3 drams
Starch 3 drams
Permanganates and sulphids mutually destroy each other, and therefore
the addition of the small amount of potassium permanganate cannot
serve any useful purpose. The amounts of phenol, menthol and “Lilac or
Citronel oil” are too small to exercise any effect (other than that of
a flavor) and must be considered unessential additions.
2. Foral is a pharmaceutical mixture marketed under a non-informing
name.
Whereas it is in the interest of rational medicine that physicians
should know the composition of the preparations which they use, the
name of this pharmaceutical mixture fails to indicate that it contains
the well-known and by no means always harmless barium sulphid.
3. Foral is sold under exaggerated and unwarranted claims.
In view of the small amount of phenol present and the method of using
the preparation, the claim that the use of Foral which, when operating
on open wounds, “guarantees against any infection,” is evidently
unwarranted.
There is no evidence for the claim that the use of depilatories such
as Foral retards the growth of hair or renders hair less coarse. On
the contrary, the commonly prevailing opinion is that depilation, like
shaving, makes the hair coarser.
To determine if “one and all” of those who had used Foral were still
using the preparation, four of the testimonials, appearing in an
advertising pamphlet, were investigated. The pharmacist of the
hospital from which the first of these testimonials was stated to have
emanated replied that the person whose name appeared in connection with
it had left the hospital about ten years ago and that no depilatory
preparation has been used in this hospital for some time. So far as
he knew, depilatories were not now in use in the surgical wards of
the hospital. In regard to the second testimonial, the pharmacist of
this hospital wrote that the hospital had not bought the preparation,
but that some of it had been obtained for an elderly deaconness,
who had personal use for a depilatory. The physician signing the
third testimonial replied that the preparation was effectual for the
removal of hair from the scalp, but that “... we have gotten out of
the habit of using it.” In the case of the fourth testimonial, its
asserted author wrote “... if it is applied in too large a quantity
or too concentrated, or permitted to remain on too long, it will
vesicate. It was for this reason chiefly that I discontinued its use.
It is a very bad smelling mixture and patients complain of it very
bitterly.”--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 55._)
GRANULAR EFFERVESCENT BROMIDE AND ACETANILID COMPOUND-MULFORD
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and
Nonofficial Remedies of Granular Effervescent Bromide and Acetanilid
Compound-Mulford has been authorized for publication.
W. A. Puckner, Secretary.
The Council holds that complex mixtures of remedial agents are from
every point of view inimical to therapeutic progress and therefore
to the public welfare. They are especially objectionable because it
is impossible accurately to determine the effects which follow the
simultaneous administration of a number of drugs having dissimilar
actions, and because the practice of prescribing such mixtures tends to
discourage careful consideration of the special needs of the individual
patients without which there can be no drug therapy. On the contrary,
with the use of such mixtures, therapeutic treatment becomes haphazard
and mere guesswork.
The Council, appreciating that long established customs cannot be
changed at once, has applied Rule 10, concerning the recognition of
mixtures, with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture, it
has frequently directed that Rule 10 should not apply, pending further
clinical trial of such mixture.
In no instance has subsequent experience shown that a strict
interpretation of the rule would have worked hardship or injustice.
The Council feels that there is no longer warrant for the admission of
complex mixtures to New and Nonofficial Remedies, or for the retention
of any that have been admitted, unless definite evidence of the
therapeutic value of such combinations is available. In accordance with
this decision, several mixtures now described in New and Nonofficial
Remedies will be omitted at the expiration of the three year period for
which articles are accepted.
Granular Effervescent Bromide and Acetanilid Compound-Mulford is
listed in the Appendix to New and Nonofficial Remedies. Each 100 Gm.
of the mixture contains sodium bromide, 5 Gm., and acetanilid, 1.5 Gm.
According to the label, an amount containing acetanilid, 6.5 grains,
and sodium bromide, 22 grains, is to be taken at a dose, to be repeated
in half an hour if necessary. For “children,” half this dose is
advised.
The Council has considered the available evidence for mixtures of this
sort, and has reached the conclusion that they are inimical to rational
medicine and the public, and therefore in conflict with Rule 10. It
holds that the use of mixtures of acetanilid and sodium bromide in
fixed proportion is irrational and prone to induce their indiscriminate
use by the public. Despite the perfectly frank declaration of the
composition of this mixture that is made by the Mulford Company, the
“directions” will be followed blindly and the preparation will be given
to “children” and “repeated in half an hour, if necessary” in cases in
which it would be held unwarranted to administer a dose of 3 grains of
acetanilid to a child.
The period of acceptance having expired for Granular Effervescent
Bromide and Acetanilid Compound-Mulford, the Council directed its
omission from New and Nonofficial Remedies for conflict with Rule
10.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 58._)
HOLADIN AND BILE SALT MIXTURES
Holadin and Bile Salts-Fairchild; Capsules of Bile Salts, Succinate of
Soda and Phenolphthalein-Fairchild; Capsules of Holadin, Bile Salts and
Phenolphthalein-Fairchild; Capsules of Holadin, Succinate of Soda and
Bile Salts-Fairchild.
Report of the Council on Pharmacy and Chemistry
To explain the omission from New and Nonofficial Remedies of certain
mixtures, the Council has authorized publication of the matter which
appears below.
W. A. Puckner, Secretary.
The Council holds that complex mixtures of remedial agents are from
every point of view inimical to therapeutic progress and therefore
to the public welfare. They are especially objectionable because it
is impossible accurately to determine the effects which follow the
simultaneous administration of a number of drugs having dissimilar
actions, and because the practice of prescribing such mixtures tends
to discourage careful consideration of the special needs of individual
patients without which there can be no rational drug therapy. On the
contrary, with the use of such mixtures, therapeutic treatment becomes
haphazard and mere guesswork.
The Council, appreciating that long established customs cannot be
changed at once, has applied Rule 10 concerning the recognition of
mixtures with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture it
has frequently directed that Rule 10 should not apply, pending further
clinical trial of such mixture.
In no instance has subsequent experience shown that a strict
interpretation of the rule would have worked hardship or injustice. The
Council feels that there is no longer any warrant for the admission of
complex mixtures to New and Nonofficial Remedies or for the retention
of any that have been admitted unless definite evidence of the
therapeutic value of such combinations is available. In accordance with
this decision, several mixtures now described in New and Nonofficial
Remedies will be omitted as soon as the three year period for which
articles are accepted has expired.
The following preparations are included in New and Nonofficial
Remedies, 1918:
Holadin and Bile Salts-Fairchild.--A mixture of holadin, 5 parts, with
bile salts-Fairchild, 1 part, put up in 3 grain capsules.
Capsules of Bile Salts, Succinate of Soda and Phenolphthalein.--Each
capsule contains bile salts-Fairchild, 0.065 Gm. (1 grain); sodium
succinate exsiccated, 0.2 Gm. (3 grains), and phenolphthalein, 0.03 Gm.
(1/2 grain).
Capsules of Holadin, Bile Salts and Phenolphthalein.--Each capsule
contains holadin, 0.13 Gm. (2 grains); bile salts-Fairchild, 0.03 Gm.
(1/2 grain), and phenolphthalein, 0.065 Gm. (1 grain).
Capsules of Holadin, Succinate of Soda and Bile Salts.--Each capsule
contains holadin, 0.20 Gm. (3 grains); sodium succinate exsiccated,
0.20 Gm. (3 grains), and bile salts-Fairchild, 0.03 Gm. (1/2 grain).
Oxbile has long been credited with a cholagogue action, which, however,
has probably been greatly overestimated. When pure bile salts were
placed on the market some years ago, they and their compounds were
admitted to N. N. R.
Holadin is said to represent all the constituents of the pancreas and
to possess great potency in respect to the several enzymes, trypsin,
amylopsin, lipase, and the milk-curdling ferment.
It is not clear when such a substance is indicated therapeutically.
While it may be useful when there is a deficiency of pancreatin and
gastric secretion, it should be used alone.
It is also quite possible that bile salts may have a distinct, though
limited, field of usefulness when there is a deficiency of biliary
secretion; but the bile salts are best administered alone, or in
combination with such laxatives as may be deemed necessary by the
physician while keeping in mind the fact that different patients
show the widest difference in their reaction to laxatives, making
combinations of these agents in fixed proportion irrational.
Phenolphthalein was popularized by nostrum makers; and while it has
some therapeutic value, this has been greatly overestimated, and it
should be used only in amounts deemed necessary for each patient,
preferably alone.
Succinate of sodium was introduced as a saline cathartic, with the
claim that it exerts an antiseptic action on the biliary passages and
gallbladder. There is no satisfactory evidence to substantiate this
claim.
The Council maintains a liberal attitude toward new preparations, but
it feels that it is impossible to determine the value of the several
constituents of such complex mixtures when used as such; it holds
that these mixtures are superfluous and that the several substances
of which they are composed should be used singly or at most with
greater attention to the individual requirements of the patient than is
possible when these fixed mixtures are prescribed.
Despite the fact that these mixtures have been in use for more than
nine years, there is no satisfactory evidence that they possess any
advantage over the simple laxatives or the preparations of bile or
pancreatic extract. They are therefore held to be in conflict with Rule
10, and the Council has directed that they be not included in N. N. R.
after Dec. 31, 1918.
Having adopted the preceding report, the Council, in accordance with
its regular procedure, submitted this to Fairchild Bros. and Foster for
comment.
The following reply was received:
We are entirely at variance with you in the arbitrary conclusion
expressed concerning the inimical influence of mixtures on
therapeutic progress, the practice of medicine and the public
welfare.
If the combinations of Holadin and Bile Salts, etc., in capsules,
were ever properly within the scope of New and Nonofficial
Remedies, they should be retained. If, however, complex mixtures
are to be held as, a priori, unworthy of consideration, the
rejection of all would naturally be a logical proceeding.
We believe that the particular combination of Holadin and
Bile Salts etc., have been clearly in the line of therapeutic
progress--a natural evolution, improvement and development.
For many years combinations of pancreatic extract and ox gall had
naturally suggested themselves.
When we realized the fact that the bile salts were quite clearly
the active principles of the bile, and that they must necessarily
exist in greatly varying percentages in the official inspissated
or ox gall, and also because these ox gall products of pharmacy
were of extremely varying density, even from that of treacle
to resin--and of other objectionable character, we undertook to
prepare bile salts.
These combinations are now further justified in view of
physiological considerations, the simultaneous secretion of the
pancreas and bile, and the state of our knowledge of the function
of bile salts, and as co-ferments, promoting and supplementing the
pancreas enzymes.
The question suggested as to whether the cholagogic action of ox
gall (and bile salts) has been overestimated seems to us no clear
purport. The bile salts are obviously employed as the means of
administering and thus realizing whatever properties this secretion
may have in medicine, of which the cholagogic action is by no means
the only consideration.
As for phenolphthalein, which is credited with purely laxative
properties, we are at a loss to see any bearing in the remark that
phenolphthalein was popularized by nostrum makers. We cannot see
that the physician’s or chemist’s estimate of phenolphthalein, its
properties and uses, can be in the least degree influenced one
way or the other by the statement that “phenolphthalein has been
popularized by nostrum makers.”
The phenolphthalein and succinate of soda combinations were
originally both prescribed, and we have simply placed them at the
service of the physician without other exploitation of them than
that designed to call attention to their use in the conditions
indicated.
These combinations are offered in a form which may be administered
by the mouth with the best promise of introducing the substance
more directly in the intestinal tract during the digestion period
or at such interval after or prior to, the digestion period, as
would best, in the judgment of the physician, meet the indications.
These particular combinations are especially desirable in these
“fixed forms” since they are stable and reliable resources at the
command of the physicians, the enzymes retaining their stability
and potency without material deterioration for many years, and they
naturally possess the advantages which are obviously due to the
character of the particular pancreas and bile products used in the
combinations.
Furthermore, the hygroscopic and soluble organic substances in
admixture cannot extemporaneously be so prepared in sealed capsules
as to be readily available under the practical requirements of
prescribing and dispensing. And we do not believe that those
who practice medicine will be in accord with your view that the
pancreas substance should necessarily be administered alone, or the
bile substance alone.
It now appears that these combinations are to be dropped from New
and Nonofficial Remedies in consequence of the view, so stated,
that in clinical experience “for more than nine years there is no
satisfactory evidence that they possess any advantage over the
simple laxatives or preparations of bile or pancreatic extract.”
In reply to this we would simply make the following comment:
During these “nine years” these combinations have inevitably been
put to an informing clinical trial, because of the fact that they
have been employed with success in disorders of the pancreas and
bile functions and often in chronic and serious cases where the
clinical conditions were obvious and unmistakable.
The reports of these cases come to us from physicians widely
separated and each of his own independent initiative. It would
seem gratuitous, to say the least, to state that the observers are
“disinterested,” since it is quite clear that there is no other
interest than that of the practitioner and his patient.
It is not a case of a new drug or combinations of new remedies,
but simply resources which, upon well grounded reasons, both from
a theoretical and material standpoint, justify clinical trial, and
with results which would seem from any ordinary human standpoint to
be satisfactory clinical evidence.
As to the interpretation of competent clinical evidence by the
Council, we would, in view of the circumstances and without
comment, ask to embody in this text this rule:
“Clinical Evidence.”--“To be acceptable, the clinical evidence
must offer objective data with such citation of authority as
will enable the Council to confirm the facts and establish the
scientific value of the conclusions drawn. Clinical data are
worthless when the author is not cited. The facts on which
claims with regard to the value of a remedy are based must have
been rendered accessible for investigation and confirmation by
disinterested observers, either through publication or through
the records of a hospital or other institution.”
To discredit these combinations would seem to us not only
unjustified, but sterile of any real advancement in medicine, or of
anything in the way of helpfulness to the patient in the class of
cases in which these products have been resorted to with benefit;
this on no other ground really than the opinion “that they have no
advantage over the simple preparations themselves.”
Naturally we shall continue to prepare these products and shall
continue to take such action as we deem best to bring them to the
attention of the physician, for the conduct of our business must
remain in the hands of those who are personally responsible for it.
And it is now forty years since we took up this line of work and
with the declared intention of devoting ourselves to the applied
science of the digestive ferments and “to their development and
practical application in every useful purpose in medicine.”
We have been consistently in sympathy with the fundamental purpose
of the Council, which must first rest upon fact as to the character
of the products offered as medicinal agents. The weight of
evidence justifies the position that these particular products
rationally should be, and as a matter of fact are, of important
special service in the utilization of these organic secretions in
medicine.
As explained in the preceding report, the Council holds that complex
mixtures of remedial agents are from every point of view inimical
to therapeutic progress and therefore to the public welfare. They
are especially objectionable because it is impossible to determine
accurately the effects which follow the simultaneous administration
of a number of drugs having dissimilar actions, and because such a
practice tends strongly to discourage careful consideration of the
special needs of individual patients without which there can be no
therapeutic progress. On the contrary, with their use, therapeutic
treatment becomes haphazard and mere guesswork.
The dismissal of the holadin and bile salts mixtures does not involve
the question of the usefulness of holadin or of bile salts alone; on
the contrary, the possible usefulness of these preparations is admitted
in the report. It is the combination of holadin, bile salts, sodium
succinate and phenolphthalein to which objection is made.
The statement of Fairchild Bros. and Foster that “these combinations
are now further justified in view of physiological considerations”
is somewhat misleading. It is true that bile and the pancreatic
secretion cooperate in intestinal digestion, but there is no evidence
that in every case in which there is a deficiency of one of these
secretions there is also a deficiency of the other, and it is an axiom
of scientific therapeutics that no drug or remedial agent should be
administered except to fill a definite want. Otherwise the practice of
therapeutics becomes mere empiricism.
The properties of phenolphthalein are not in the least influenced by
the manner of its introduction, as Messrs. Fairchild Bros. and Foster
emphasize; but the important fact in this connection is that the
popular conception of their actions is greatly influenced by the mode
of introduction, and phenolphthalein has been widely advertised in a
variety of conditions, so that the popular notion concerning it is not
that of scientific therapeutics.
In short, the entire argument of Messrs. Fairchild Bros. and Foster
concerning the exploitation of these preparations may be summed up by
saying that they have been used by clinicians who believe that good
results have followed their use, and that the firm will therefore
continue to supply the demand. The tendency of some to use anything
brought to their notice, and the readiness of manufacturers to market
anything that physicians will use, presents the greatest obstacle
to therapeutic progress. There was never a nostrum so irrational or
worthless that honest but undiscriminating clinicians could not be
found who reported wonderful results from its use.
According to Fairchild Bros. and Foster, these holadin and bile salts
mixtures have been in use for some nine years. Yet the Council is not
aware of any investigation of their merits that meets the requirements
of scientific research.
The Council is not acquainted with a single clinical investigation of
their action under conditions which afford satisfactory evidence of
their therapeutic value.
It is obviously wholly insufficient for a clinician to report that the
use of a mixture was followed by good results. The fallacy of such
arguments was demonstrated long ago. He must make a comparison of the
results obtained with the remedial agent with those obtained in as
nearly similar conditions as possible except for the use of the agent.
We are not aware that any such study of the mixtures in question has
been made. It is in the last degree irrational to hold that because
bile salts are the active constituents of bile, therefore such complex
mixtures as these are necessary.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 59_)
LIQUOR SANTAIVA, S. & D., OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Liquor Santaiva, S. & D., has been authorized for
publication.
W. A. Puckner, Secretary.
So far the Council has applied Rule 10 concerning the recognition of
mixtures with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture, it
has frequently directed that Rule 10 should not apply, pending further
clinical trial of such mixture.
In no instance has subsequent experience shown that a strict
interpretation of the rule would have worked hardship or injustice. The
Council feels that there is no longer any warrant for the admission of
complex mixtures to New and Nonofficial Remedies or for the retention
of any that have been admitted, unless definite evidence of the
therapeutic value of such combinations is available.
The Council being engaged in the annual revision of New and Nonofficial
Remedies, the referee in charge of santal preparations reported that
the three year period of acceptance had expired for Liquor Santaiva
(Sharp & Dohme).
The referee held that Liquor Santaiva, S. & D., declared to be a
solution of santal oil and copaiba with aromatic oils, in a mixture
of alcohol and water, is plainly in conflict with the current
interpretation of Rule 10, because there was no sound evidence
to indicate that any useful end is gained by the simultaneous
administration of santal oil and copaiba in any proportion, and that
so, of course, there is no evidence of the special advantage in the
fixed proportions represented by the mixture. He pointed out that the
formula is essentially a survival of the discredited shotgun gonorrhea
mixtures and therefore recommended that its acceptance be not continued.
The Council agreed to the recommendation of the referee and directed
that Liquor Santaiva, S. & D., be omitted from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 66_)
MALTZYME, MALTZYME WITH CASCARA SAGRADA, MALTZYME WITH COD LIVER OIL,
MALTZYME FERRATED AND MALTZYME WITH YERBA SANTA
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of the Maltzyme preparations has been authorized for
publication.
W. A. Puckner, Secretary.
In 1916, the Council voted to omit Maltzyme with Hypophosphites, and
Maltzyme with Phosphate of Iron, Quinine and Strychnine. At that
time the labels used on the Maltzyme preparations still in New and
Nonofficial Remedies contained a list of Maltzyme combinations which
included those which had been dismissed. As the Council does not permit
an accepted article to be used as a means of advertising an article
not accepted, it voted to continue the following preparations for
a period of three years on condition that reference to the deleted
articles be omitted from the labels when those then in stock had been
used up: Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod
Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa. While the
Maltzyme Company made no definite agreement to revise its advertising
propaganda in accordance with the Council’s requirements, the Maltzyme
preparations were retained in the belief that in due time the required
revision of the labels would be made.
The Council being engaged in preparing the 1919 edition of New and
Nonofficial Remedies, the referee in charge of malt extracts reported
that the Maltzyme Company had not revised its labels in accordance with
the stipulation of the Council. The referee further reported he had
become convinced that the claim that Maltzyme is “rich in malt enzymes”
is unwarranted and that the term “Maltzyme” (malt plus enzyme) is
misleading; this because of the recognized instability of malt extracts
(Jour. A. M. A., March 30, 1912, p. 954) and because the Maltzyme
Company makes no definite statement with regard to the diastase (malt
enzyme) content of its preparations.[126] For this reason it had
been the referee’s intention to propose the deletion of all Maltzyme
preparations when their period of acceptance expired in 1919. As,
however, the present Maltzyme preparations are in contravention with
the Council’s requirements, he recommended that the acceptance of these
preparations be canceled now.
[126] Manufacturers are warned by the Department of Agriculture,
through the Bureau of Chemistry, that combinations claiming to contain
digestive enzymes must be active when sold. If preparations tend to
deteriorate in a short time, each lot should be dated and not sold
after the period when they become inactive. While every manufacturer
must be considered innocent until proved guilty, and ignorant until
proved knowing, it is a matter of knowledge that manufacturers have
marketed their various digestive mixtures with full appreciation of
their worthlessness.--(Jour. A. M. A., Dec. 19, 1914, p. 2234.)
The Council agreed to the recommendation of the referee and directed
that Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver
Oil, Maltzyme Ferrated, and Maltzyme with Yerba Santa be omitted from
N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 67_)
METHAFORM OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Methaform has been authorized for publication.
W. A. Puckner, Secretary.
Methaform is the proprietary name applied by F. Stearns & Co. to
chlorbutanol.
Being engaged in the annual revision of New and Nonofficial Remedies,
and the term of acceptance for Methaform having expired, a trade
package was purchased to determine if the product was marketed in
compliance with the rules of the Council. It was then found that a
circular was wrapped with the trade package which advertised Methaform
Inhalant, a preparation not accepted for New and Nonofficial Remedies.
For obvious reasons, the Council does not countenance the use of an
accepted article as a means of advertising an article not accepted.
Accordingly F. Stearns & Co. was advised that the Council would
be obliged to withdraw the acceptance of Methaform unless the
objectionable circular was omitted from the Methaform packages.
Stearns & Co. did not give the requested assurance, and therefore the
Council directed that Methaform be omitted from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 68_)
PINEAL GLAND, RED BONE-MARROW AND THYMUS GLAND AND THEIR PREPARATIONS
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of pineal gland, red bone-marrow and thymus gland and their
preparations has been authorized for publication.
W. A. Puckner, Secretary.
Pineal gland, red bone-marrow and thymus gland were admitted to New
and Nonofficial Remedies when these products gave promise of having
therapeutic value.
The term of acceptance for the preparations of pineal gland, red
bone-marrow and thymus gland having expired, the referee in charge of
animal organ preparations recommended in his report for the annual
revision of N. N. R. that these products and the general articles
describing them be omitted from New and Nonofficial Remedies. He held
that the experimental and clinical experience with them leads to the
conclusion that they are without value.
In accordance with the recommendation of the referee, the Council voted
that the following preparations be omitted from New and Nonofficial
Remedies: Desiccated Pineal Gland-Armour; Pineal Gland Tablets-Armour;
Extract of Red Bone-Marrow-Armour; Desiccated Thymus-Armour; Thymus
Tablets-Armour.
As a matter of record, the descriptive articles for pineal gland, red
bone-marrow and thymus gland, which appeared in New and Nonofficial
Remedies, 1918, are given below.
Pineal Gland
The functions of this gland have not yet been established but there
is some pathological and some experimental evidence that there is
a relation between the gland and some processes of development and
growth; the nature of this relation is unknown. Adiposis is a frequent
sign of disturbed pineal function, but observers are not agreed whether
to interpret this as indicating hypofunction or hyperfunction, or
possibly a concurrent disturbance of the pituitary. In some instances
intravenous injections of pineal extract have seemed to cause a
distinct fall in blood pressure. It has been inferred from observations
in cases of pineal tumors in the young that the gland in young
individuals furnishes a secretion which inhibits growth, particularly
the development of the reproductive glands, but the results of
experimental administration of pineal substance orally have led other
observers to infer that the pineal secretion favors physical and
possibly mental and sexual development. It has been suggested that, as
all evidence points to the fact that the function of the pineal gland
is one of early life, extract of adult pineal glands might be expected
to be inert. Experiment has also indicated greater activity in glands
obtained from young animals than in those obtained from older ones. The
Council has decided to admit preparations of pineal gland to New and
Nonofficial Remedies simply for experimental purposes.
Red Bone-Marrow
Red bone-marrow consists largely (more than 90 per cent.) of fat. In
new-born animals a third or more of this fat consists of lecithin.
The marrow of the bones of new-born animals contains iron (up to 1
per cent. or more) in various forms of organic combination. Both
lecithin and iron decrease rapidly in the first weeks after birth.
The commercial preparations contain very variable amounts of these
constituents.
_Actions and Uses._--Red bone-marrow is supposed to stimulate the
formation of red blood corpuscles; whatever action it may have in this
direction is probably due largely to the iron and lecithin which it
contains.
It is said to be useful in simple and pernicious anemias.
Thymus Gland
Little is known as to the functions of the thymus, but it is believed
to have an important relation to growth. There also seems to be some
relation between the thymus and thyroid, for the former is frequently
abnormal in diseases involving the latter (hyperthyroidism).
The use of thymus is purely empirical. It has been employed in the
treatment of hyperthyroidism, rickets, tuberculosis, hemophilia, and
infantile marasmus and atrophy; its use in the latter conditions
is said to be the most promising. It is claimed on very doubtful
grounds to exert a somewhat favorable effect in certain cases of
cancer.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 69_)
PIPERAZINE AND LYCETOL OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Piperazine and Lycetol has been authorized for publication.
W. A. Puckner, Secretary.
Piperazine (diethylenediamene) and Lycetol (a methyl derivative of
diethylenediamene) were accepted for New and Nonofficial Remedies in
1906. Both Piperazine and Lycetol were asserted to be efficient uric
acid solvents and efficacious remedies in the treatment of gout and
rheumatism. These products have been retained until now because there
was no investigation which definitely showed their uselessness as uric
acid solvents, though their use is generally admitted to have been
disappointing.
From an exhaustive and critical study of the available evidence,
Hanzlik (Jour. Lab. & Clin. Med., February, 1917) concluded that
scientific evidence, though limited, and clinical opinion indicate that
Piperazine is valueless in gout and that there is sufficient scientific
evidence to indicate the worthlessness of Lycetol.
The referee in charge of Piperazine and Lycetol recommended that these
products be omitted from New and Nonofficial Remedies for the reason
that they have been sufficiently tried to justify the conclusion that
they are not of value. The period of acceptance having expired, the
Council directed that Piperazine and Piperazine Tablets (The Bayer
Company, Inc.) and Lycetol (The Bayer Company, Inc.) be omitted from
New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 70._)
STANOLIND LIQUID PARAFFIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
As explained in the report which follows, “Stanolind Liquid Paraffin”
was omitted from New and Nonofficial Remedies at the request of the
proprietors. Announcement of this omission was made in the preface to
New and Nonofficial Remedies, 1918, but publication of the Council’s
report was postponed pending actual conflict with the rules. The
Council now authorizes publication of the report because a circular
indirectly advertising the product to the public was found enclosed
with the trade package of Stanolind Liquid Paraffin.
W. A. Puckner, Secretary.
Stanolind Liquid Paraffin was admitted to New and Nonofficial Remedies
in 1916, when its method of marketing conformed to the rules of the
Council. This brand of liquid petrolatum, by action of the Council,
has been omitted from New and Nonofficial Remedies on request of the
Standard Oil Company of Indiana, its manufacturer, who wrote to the
Secretary of the Council stating that:
“In order that our facilities for the manufacture of this oil shall
be constantly engaged, it will be necessary for us to find sales
on a larger scale than in the past. To do this under our present
advertising and marketing arrangement we feel will be impossible.”
This letter, in addition, suggested “that physicians are not
prescribing Stanolind Liquid Paraffin in any considerable proportion
of their orders” and “that the situation which now confronts us would
not be materially helped if Stanolind was specified in all such
prescriptions.” Further, the Council is asked to consider whether
it “might be willing to declare this preparation as not a Council
product,” on the alleged grounds that “liquid paraffin is not medicinal
in its action and passes through the digestive tract in practically
unaltered condition.”
The Council holds that Stanolind Liquid Paraffin is a drug, and that,
therefore, its direct advertising to the public is in contravention
of the Council’s rules. Constipation should be treated by dietary
and hygienic means. Evacuants are only temporary measures. Liquid
petrolatum is medicinal; it greatly modifies the intestinal flora; it
acts as a lubricant and emollient; it modifies the absorptive powers
of the intestinal mucous membrane; it is capable of influencing the
digestion of fats. In short, liquid petrolatum, being a drug, its
indiscriminate and excessive use should not be encouraged.--(_From
Reports of Council on Pharmacy and Chemistry, 1918, p. 72_)
WESTERFIELD’S DIGITALIS TABLETS
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Westerfield’s Digitalis Tablets (The Westerfield Pharmacal Co., Dayton,
Ohio) are claimed to represent a fat free tincture of digitalis and to
be “enteric coated.” It is claimed that because of this coating these
tablets pass the stomach unchanged and dissolve in the intestine, and
that this obviates any possibility of gastric disturbance.
The circular which sets forth the asserted advantages of the tablets
states that digitalis contains a fat which is an irritant to the
gastric membrane. It also contains the following:
“We feel no hesitation in saying that if this remedy is given a
fair trial where it is properly indicated, the result obtained will
be a gratifying surprise.
“It is a common expression from physicians who have tried this
remedy to say, ‘Surely I have never used Digitalis before.’”
If these quotations mean anything, they imply that these tablets
present a distinct advance in digitalis therapy. There is no warrant
for such a claim. The statement with reference to the occurrence of an
oil in digitalis is partly false and partly misleading. Tincture of
digitalis, which the tablets are claimed to represent, is fat free;
the fixed oil that is present in the drug is not soluble in 70 per
cent. alcohol, the menstruum used for the preparation of the official
tincture of digitalis. Furthermore, a fairly large amount of this oil
(such as is present in 100 therapeutic doses of the drug) is incapable
of causing gastric disturbance. Gastric disturbance is a side action
that is inseparable from slight overdosage with all true digitalis
bodies and is not in any way due to local gastric action. The claim
that such action is prevented by the use of enteric pills or tablets is
obviously false and misleading.
The alleged “common expression from physicians who have tried this
remedy” does not constitute acceptable evidence of the value of the
preparation.
The Council declared Westerfield’s Digitalis Tablets inadmissible to
New and Nonofficial Remedies because unwarranted therapeutic claims are
made for this product.
When the preceding report was submitted to the Westerfield Pharmacal
Co., a reply was received indicating that the firm did not know
that progressive manufacturers had discontinued the claim that “fat
free” digitalis preparations were devoid of gastric effects. It also
submitted a revised circular, which, however, reiterated the claim that
the tablet presented a distinct advance in digitalis therapy in that it
was “fat free,” and coated to prevent disintegration in the stomach.
Since tincture of digitalis and extract of digitalis are practically
devoid of fatty material, and since it is now well known that the
fat does not cause gastric disturbance and that therapeutic doses
of digitalis do not exert a local irritant action on the stomach,
the manufacturer’s product and the claims made for it merely tend to
perpetuate old errors.
The Council declared Westerfield’s Digitalis Tablets inadmissible
to New and Nonofficial Remedies on the ground that this presents an
unessential modification of pills of an official substance. It directed
publication of its report with this explanation.--(_From Reports of
Council on Pharmacy and Chemistry, 1918, p. 75_)
XEROFORM-HEYDEN AND BISMUTH TRIBROMPHENATE-MERCK
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on
Bismuth Tribromphenate-Merck and Xeroform-Heyden. These two products
were found not to comply with the standards for bismuth tribromphenate
adopted for New and Nonofficial Remedies, and hence could not be
retained. As the manufacturers of both products announce that efforts
toward the production of a satisfactory product are continued, the
omission of the two brands is without prejudice to their reacceptance
when a satisfactory product becomes available.
W. A. Puckner, Secretary.
The referee in charge of bismuth preparations submitted the following
report of the A. M. A. Chemical Laboratory which shows that
Xeroform-Heyden and Bismuth Tribromphenate-Merck do not comply with the
adopted standards for bismuth tribromphenate.
Some time ago a request was received from the Medical Section
of the National Council of Defense for a report on a brand of
bismuth tribromphenate. In accordance with this request the firm’s
product was examined, and at the same time and for comparison, an
examination was also made of a specimen of bismuth tribromphenate
received from Merck and Company, October, 1915, and of another
specimen of bismuth tribromphenate “Xeroform-Heyden” obtained from
the Chicago branch of the Heyden Chemical Works in April, 1918.
The examination brought out that the bismuth tribromphenate
submitted to the national Council of Defense contained a large
amount of uncombined tribromphenol, while the specimen of
Xeroform-Heyden contained an excessive quantity of bismuth.
When the latter finding was submitted to the Heyden Chemical Works,
the firm stated: “The product had to be made in this country after
importations from Europe became impossible and the first lots were
not fully up to the standard ...” The firm stated that it could now
furnish a product which it considered fully equal to that which
was previously imported, and offered to submit “samples of the new
material.”
Having been requested to do so, a specimen of Xeroform-Heyden was
received from the Heyden Chemical Works, New York. This and a
second specimen, purchased from a Chicago wholesale drug house,
were examined. Whereas the standards for bismuth tribromphenate
which had been formulated by the Laboratory and accepted by the
Heyden Chemical Works required that the product should contain
from 40 to 49 per cent. of bismuth and contain not more than 3.3
per cent. of uncombined tribromphenol, the specimen purchased in
Chicago contained 67.7 per cent. of bismuth, while the specimen
received direct from the Heyden Chemical Works contained 24 per
cent. of uncombined tribromphenol. When this result was reported to
the Heyden Chemical Works, the firm replied:
“It seems that we are not yet in a position to supply a product
that answers a uniform standard and that we have to continue our
efforts in this direction.
“We will take this matter up with you again as soon as we have
been successful ...”
At the time when the preceding examination was being made,
bismuth tribromphenate-Merck could not be obtained from the
Chicago wholesale houses. A request sent to Merck and Company
for a specimen of the market supply brought the information that
the product was temporarily unavailable. Though unable to supply
the product, the firm gave valuable advice for a revision of the
somewhat loosely drawn tests for bismuth tribromphenate in New and
Nonofficial Remedies, 1918.
Recently (November, 1918) Merck and Company sent a specimen of its
product labeled “Bismuth Tribromphenate-Merck” “Merck and Company,
New York, Distributors and Guarantors,” and wrote “... You will
notice this sample conforms in nearly all details to the tests we
submitted with our letter of June 4th. We have been able to produce
better goods, but just at present unsatisfactory starting material
confronts us. The sample conforms to N. N. R., 1918, but will not
meet the test for uncombined tribromphenol submitted by you in your
letter of September 4th ...”
Examination of the specimen demonstrated that it was soluble to a
considerable extent in alcohol (the N. N. R., 1918, description
provides that it should be only slightly soluble in alcohol)
and according to the standards adopted for New and Nonofficial
Remedies, 1919, contains 18 per cent. uncombined tribromphenol
(more than five times the permitted amount).
In view of the Laboratory’s report, the referee recommended that the
acceptance of Xeroform-Heyden and Bismuth Tribromphenate-Merck be
withdrawn, without prejudice to their reinstatement when satisfactory
products are again offered for sale. The Council adopted the
recommendation of the referee, and accordingly Xeroform-Heyden and
Bismuth Tribromphenate-Merck are omitted from New and Nonofficial
Remedies, 1919.
When the Laboratory’s findings with regard to Xeroform-Heyden and the
action of the Council deleting the article from New and Nonofficial
Remedies was reported to the Heyden Chemical Works, the firm expressed
regret that efforts to produce a product equal to that formerly
obtained from Germany had so far not been successful and announced
that it had decided to withdraw Xeroform-Heyden from the market for the
present.
When Merck and Company was advised in regard to the report of the
Laboratory and the Council’s action, this firm questioned the
feasibility of producing a product meeting the Council’s standards and
suggested that the test for free tribromphenol be revised to permit as
much as 15 per cent. of this constituent. When Merck and Company was
reminded that its product, submitted in 1915, essentially complied with
the adopted standards and that the estimate of the therapeutic value
of bismuth tribromphenate is based on a product essentially free from
alcohol-soluble material, the firm replied:
“As stated in our letter of the 12th inst. we do not wish to market
the chemical unless it meets all legitimate requirements of the
physicians that use it. If, therefore, your standard proves to be
good and it is commercially possible to make supplies conforming to
it, we shall do so. We shall discontinue the article unless it is
of suitable quality.”
--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 76._)
CREAM OF MUSTARD REFUSED RECOGNITION
Report of the Council on Pharmacy and Chemistry
Cream of Mustard, The Cream of Mustard Co., South Norwalk, Conn., is
said to be made by mixing 2 drachms of oil of mustard and 2 drachms
of oil of turpentine with one pound of white petrolatum. According to
the label it is “for Tonsillitis, Rheumatism, Sore Muscles, Croup,
Pleurisy, Frosted Feet, Sore Throat, Neuralgia, Sprains, Bronchitis,
Headache, Chilblains, Stiff Neck, Congestion, Bruises, Asthma, Lumbago,
Pains and Aches, Colds in Chest.”
The Council refused recognition to Cream of Mustard:
Because it is a simple pharmaceutical mixture of well-known ingredients
and has no advantage over established rubefacients which every
physician knows how to prescribe and every pharmacist to compound.
Incidentally, the name “Cream of Mustard” is misleading and not
descriptive of the composition of this pharmaceutical of oils of
mustard and turpentine.--(_From Reports of Council on Pharmacy and
Chemistry, 1918, p. 79_)
“PLURIGLANDULAR” MIXTURES
Caps. Adreno-Spermin Comp., Caps. Antero-Pituitary Comp.,
Caps. Placento-Mammary Comp., Caps. Thyro-Ovarian Comp.,
Caps. Hepato-Splenic Comp., Caps. Pancreas Comp., and
Caps. Thyroid Comp., Not Admitted to N. N. R.
Report of the Council on Pharmacy and Chemistry
After considering the evidence for the several “pluriglandular”
mixtures described below, the Council declared them inadmissible to
New and Nonofficial Remedies. The Council’s action was communicated
to the manufacturer, Henry R. Harrower, in accordance with the usual
procedure. After giving due consideration to the manufacturer’s reply
the Council authorized publication of the report which appears below.
W. A. Puckner, Secretary.
With the offer “to supply you with as much literature as may be
necessary and as little of the actual remedies as may be desired” if
“the prospects for the inclusion of these formulas in N. N. R. are
good,” Henry R. Harrower sent the Council a booklet descriptive of his
preparations and labels for the following mixtures:
_Caps. Adreno-Spermin Comp._, each said to contain “Adrenal Gland
(total) gr. 1/4, Thyroid Gland (U. S. P.) gr. 1/12, Spermin
Extr. (from Gonads), Brain and Spinal Cord aa gr. 1, Calc.
Glycerophosphate q. s. ad gr. 5.”
_Caps. Antero-Pituitary Comp._, each said to contain “Anterior
Pituitary Body gr. 2, Thymus Gland gr. 1, Thyroid Gland (U. S. P.)
gr. 1/12, Calcium-phosphorus Comp. q. s. ad gr. 5.”
_Caps. Placento-Mammary Co._, each said to contain “Desiccated
Placenta gr. 2, Mammary Substance gr. 1-1/2, Pituitary Body (total)
gr. 1/3, Calcium-phosphorus Comp. q. s. ad. gr. 5.”
_Caps. Thyro-Ovarian Comp._, each said to contain “Desic. Corpora
Lutea Ovarian Substance gr. 2-1/2, Thyroid Gland (U. S. P.) gr.
1/12, Pituitary Gland (total) gr. 1/8, Calcium-phosphorus Comp. q.
s. ad gr. 5.”
_Caps. Hepato-Splenic Comp._, each said to contain “Liver
Parenchyma, Spleen Substance aa gr. 2, Powd. Bile Salts gr. 1/2,
Adreno-Spermin Co. (No. 1) gr. 1.”
_Caps. Pancreas Comp._, each said to contain “Adrenal Gland,
Pituitary Gland (total) aa gr. 1/2, Ovarian Substance gr. 1,
Pancreas Substance q. s. ad gr. 5.”
_Caps. Thyroid Comp._, each said to contain “Desic. Thyroid Gland
(U. S. P.) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”
The Council declared these preparations inadmissible to New and
Nonofficial Remedies, for reasons which follow:
1. Each of the mixtures contains one ingredient or more, which is
neither recognized in the U. S. Pharmacopeia nor admitted to New and
Nonofficial Remedies, namely: “Spermin Extract,” “Brain,” “Spinal
Cord,” “Desiccated Placenta,” “Liver Parenchyma,” “Spleen Substance,”
“Pancreas Substance” and “Calcium Phosphorus Comp. (Each 100 gm.
represents Magnes. Phos. 1; Calc. glycerophos. 4; Potas. bicarb. 15;
Sod. bicarb. 22 and Sod. chlor. q. s.).” For obvious reasons the
Council does not accept a mixture containing an indefinite ingredient
and hence it would be necessary as a preliminary for the consideration
of any one of the mixtures that their unofficial ingredients be
made eligible for New and Nonofficial Remedies by the submission of
evidence that such ingredient is of uniform composition and that it is
therapeutically valuable when given by mouth. There is no evidence that
many of these organs have any value whatever when administered by the
mouth or in any other way.
2. In the light of our knowledge the administration of gland mixtures
in the host of conditions enumerated in the advertising circular is
irrational and on a par with the use of the shotgun mixtures once in
vogue.
Be it a pharmaceutical mixture, a “mixed” vaccine, or a
“pluriglandular” product, the combination of two medicinal ingredients
in a mixture must be considered contrary to rational therapy unless
a good reason exists for such combination. Such mixtures are held in
conflict with Rule 10 unless the manufacturer presents acceptable
evidence for the value of his combination. A physician may prescribe
any mixture which he considers indicated in a given case, but the
marketing of mixtures of drugs in fixed proportions is in most
instances irrational and a detriment to sound therapy.--(_From The
Journal A. M. A., Jan. 18, 1919_)
CERELENE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
declaring Cerelene inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Cerelene, a paraffin preparation for the treatment of burns, was
submitted to the Council by the Holliday Laboratories, with the
statement that it was composed of 84 per cent. paraffin, 15 per cent.
myricyl palmitate, and 1 per cent. purified elemi gum to which is added
oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was
explained:
“Myricyl Palmitate is a purified form of Beeswax, free from all
impurities, acids, etc., which is solely manufactured by this
Company....”
It was also stated that on “special order” Cerelene has been made
containing oil of eucalyptus and resorcin, oil of eucalyptus and picric
acid, and picric acid alone. The following report on the preparation
was presented to the Council by the referee to whom Cerelene had been
assigned:
Cerelene is another compound wax for the treatment of burns.
According to the work of Sollmann (J. A. M. A., 68:1799, 1917) it
is highly improbable that compound mixtures have any advantage over
simple paraffin of low melting point. Cerelene must therefore be
considered as an unessential modification of paraffin, and as in
conflict with Rule 10; unless definite evidence of superiority is
submitted. Cerelene mixtures containing medicinal ingredients also
appear unscientific since the evidence that the ingredients do not
leave the wax has not been successfully contradicted. Finally, the
claims made for Cerelene are rather extreme, and would need some
revision before they could be accepted.
The A. M. A. Chemical Laboratory reports:
The physical properties of Cerelene are as follows:
Melting point 50.0 C. by U. S. P. method.
Ductility limit 30.5 C.
Plasticity limit 26.4 C.
Not strong at 38 C.
Adheres moderately well; detaches with “pulling.” On heating,
readily loses eucalyptol, and a small amount of resinous substance
forms in the bottom of the beaker. If Cerelene is heated to 145 C.
and cooled, the resulting product no longer has the properties of
the original Cerelene.
It is recommended that the preceding report be sent to the Holliday
Laboratories, and that unless its superiority over simple paraffins is
demonstrated and the unwarranted claims abandoned, Cerelene be declared
inadmissible to New and Nonofficial Remedies for conflict with Rules 6
and 10.
This report was submitted to the Holliday Laboratories with the
information that it had been adopted, Oct. 3, 1917. It was also
explained that before Cerelene could be accepted, the unofficial
and unstandardized constituent “myricyl palmitate” would have to be
considered and accepted for New and Nonofficial Remedies since, for
obvious reasons, the Council does not accept a preparation which
contains an unofficial and unstandardized substance not in N. N. R.
The Holliday Laboratories acknowledged receipt of the Council’s report
and asked that the matter be held in abeyance until the requested
evidence had been obtained. Later the Council was advised that the
advertising circulars for Cerelene had been withdrawn with the
exception of one giving directions for its use. Five months later, the
firm stated that experiments were being made “to determine the actual
strength of Cerelene in comparison with other paraffin waxes....”
Nothing further has been heard from the Holliday Laboratories and no
reply has been received to an inquiry made Oct. 12, 1918. The Council
therefore authorizes publication of its report declaring Cerelene
inadmissible to New and Nonofficial Remedies.--(_From the Journal
A. M. A., Feb. 15, 1919_).
COLLOSOL COCAINE NOT ADMITTED TO N. N. R
Report of the Council on Pharmacy and Chemistry
The report which appears below was adopted by the Council and sent to
the Anglo-French Drug Co., Ltd., New York, for comment in December,
1918. No explanation has been received from the manufacturer. For
the information of the profession the Council has now authorized
publication of the report.
W. A. Puckner, Secretary.
“Collosol Cocaine” was submitted to the Council in October, 1918, by
the Anglo-French Drug Co., Ltd., New York, under the claim that it was
an “absolute colloid” and that it contained “1 per cent. cocain.” The
label on the submitted specimen declares:
“Collosol Cocaine 1-100”
“... the Cocaine exists as the pure alkaloid in the Colloidal
state--the condition in which it is isomorphic with the protein
of the body fluids. The effect is more prolonged than that of
a molecular Cocaine Solution and being _non-toxic_ absorption
presents no practical danger.”
The product was assigned to the Committee on Pharmacology for
consideration. The following report was submitted and its adoption by
the Council recommended by the committee:
“Collosol Cocaine” is said to be a colloidal form of cocain and
is alleged to possess a remarkably low toxicity. The subjoined
report of the A. M. A. Chemical Laboratory, however, shows that the
preparation does not have the composition claimed for it and it is,
in effect, misbranded. In fact, the English manufacturers concede
that it is not an “absolute colloid” and that the declaration with
regard to the percentage of cocain is incorrect.
It is recommended that, without considering other conflicts with
the rules of the Council at this time, “Collosol Cocaine” be
declared inadmissible to New and Nonofficial Remedies for conflict
with Rule 1 which requires that the composition of an article
must be correctly declared. The report of the A. M. A. Chemical
Laboratory is appended.
REPORT OF THE A. M. A. CHEMICAL LABORATORY
Simpson, Hewlett and Eyre (_Lancet_, April 28, 1917, p. 660) reported
“Collosol Cocaine” to be much less toxic than cocain. These writers,
however, did not verify the statements as to the composition and in
the light of subsequent chemical examination it is not to be wondered
at that “Collosol Cocaine 1.0 per cent.” was much less toxic than a
solution containing 1.0 per cent. of cocain hydrochlorid.
Barger, Dale and Durham report from the Department of Biochemistry
and Pharmacology, Medical Research Committee (_Lancet_, Dec. 1, 1917,
p. 825), that they examined “Collosol Cocaine” and found it to contain
but 0.25 per cent. of cocain. They also found that the cocain was not
present in a colloidal form. Discussing the low toxicity claimed by the
manufacturers, these investigators state:
“In the samples which we examined the toxicity was, indeed, much
lower than that of an ordinary 1 per cent. solution of a cocain
salt; but the local anesthetic action was low to a corresponding
degree, and both actions corresponded satisfactorily with the
proportion of cocain chemically recoverable from the solution.”
Stroud, of the Crookes Laboratory (which manufactures the preparation),
who apparently had been informed of this work in advance of
publication, admits the correctness of it, and states (_British Medical
Journal_, Nov. 24, 1918, p. 710) that “whilst the colloidal protective
apparently absorbs a portion of the cocain, the remainder is found not
to exhibit the attributes of a colloid,...”
The specimen of “Collosol Cocaine” submitted to the Council and labeled
“Collosol Cocaine 1-100” was found to contain at most 0.4 per cent.
cocain. The examination was made in accordance with the method used by
Barger, Dale and Durham and calculated as cocain. This method, however,
probably would not distinguish between cocain and basic decomposition
products, but would include all as cocain in the amount found. The
specimen of “Collosol Cocaine” examined was neutral or slightly acid, a
fact which tends to confirm the conclusion of the British investigators
that “Collosol Cocaine” contains cocain in noncolloidal form and
precludes an increased physiologic effect due to alkalinity.
The Council adopted both the report submitted by the committee and that
of the A. M. A. Laboratory and declared “Collosol Cocaine” inadmissible
to New and Nonofficial Remedies.--(_From The Journal A. M. A., April
12, 1919._)
CUPRASE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on
Cuprase, sold by the Anglo-French Drug Co., Ltd. The Council’s
criticisms of the advertising claims were sent to the firm, December,
1918. The firm made no reply and essentially the same claims are
contained in recent advertisements.
W. A. Puckner, Secretary.
“Cuprase” is now being advertised and sold in the United States by the
Anglo-French Drug Co., Ltd., the firm which also markets it in England.
It is said to be “prepared in the Laboratories of F. Ducatte, 8 Place
de la Medeleine, Paris.” According to an advertising circular entitled
“The Medical Treatment of Cancer” “Cuprase” is “chemical colloidal
copper”; in another place it is “a colloidal copper hydroxid,” which is
said to be obtained chemically by the reduction of salts of copper in
the presence of albumosic acid.
A box (price $8.50 less 10 per cent. discount) of “Cuprase-Doctor Gaube
du Gers” was purchased recently from the Anglo-French Drug Co., Ltd.
It contained eight ampules each containing approximately $1 $2$3 of a
brownish fluorescent liquid. No information of composition was given
on the box, except the line: “Chaque ampoule contient: $1 $2$3 .00121
de Cuivre pur” (Each ampule contains O.00121 gr. of pure copper). The
A. M. A. Chemical Laboratory reports that the preparation does contain
a small amount of copper, with some protein material and about 1 per
cent. sodium chlorid.
The therapeutic claims in the advertising circular are those
commonly made for cancer “cures” and are about equally convincing.
The publication of such statements and quotations as the following,
which appear in a pamphlet “The Medical Treatment in Cancer,” cannot
be too strongly condemned in a medicament that at best has only an
experimental status:
“A special preparation, Cuprase, has been introduced into
therapeutics which has been remarkably successful. In the history
of the therapeutics of cancer, nothing has been found which can
compare with the effects produced by means of Cuprase. Clinical
facts carry greater weight than theoretical deductions. It
follows, from the clinical observations which I have collected,
that in the large majority of cases Cuprase effects the diminution
or disappearance of the pains, an improvement in the general
condition, a diminution or arrest of the neoplasms, and finally
in certain cases, a cure has been effected. It should be remarked
that all or nearly all the observations refer to inoperable cases
in which the prognosis was unfavorable at an early date. It is
needless to emphasize the practical importance of a preparation
capable of yielding such results, even relative, in the worst
stages of a disease which has always been regarded as absolutely
resisting the action of all internal remedies.”
“To sum up, Cuprase has given positive results in about 94 per
cent. of the cases in which it has been employed for a sufficiently
long period, and some brilliant results in about 20 per cent. of
these cases. Therefore, it may be affirmed, that among the internal
remedies for cancer, Cuprase is the one which has produced the most
successful results, and can, under certain circumstances, compete
with surgical methods, even, so far as the rapidity of their
results are concerned.”
“It is indicated:
(a) apart from all operation, and as a specific and curative
remedy;
(b) before an operation, in order to give tone to the patient,
mobilise the tumor, destroy its toxins;
(c) after the operation, as a tonic and anti-toxic, and in order
to avoid frequent relapses which are always possible.”
Essentially the same statements are made in the more recent
advertisements (f. i. Urological and Cutaneous Review, Feb., 1919).
Opposed to these loose statements are the results of Richard Weil
(The Journal A. M. A., 1913, Sept. 27, p. 1034; ibid, 1915, April 17,
p. 1283). Weil avoided pitfalls of subjective impressions and used
as the essential criterion of efficiency “the demonstrable reduction
in size of a tumor, of a kind not to be attributed to the natural
processes of evolution of that tumor or of its associated lesions” (l.
c. 1915, p. 1289).
The available evidence for Cuprase is far from meeting this criterion.
That published by the manufacturers and agents presents only vague
generalities, and no definite data. The evidence gathered by Weil
himself permits an estimate of the value of Cuprase and it is entirely
unfavorable. He states (l.c. 1915, p. 1288):
“Colloidal copper has been used in recent time for the same purpose
by Gaube du Gers and by others. I have recently examined the effects
of colloidal copper on malignant tumors in man, and have been unable
to find that it has any therapeutic value. Furthermore, a study of
the distribution of the copper in tumors obtained at operation or by
necropsy from individuals so treated failed to show that the copper had
been deposited therein.”
In view of the extravagant and cruelly misleading therapeutic claims,
and the indefinite statements of composition, the Council voted
Cuprase ineligible to N. N. R., and authorized the publication of this
report.--(_From The Journal A. M. A., April 12, 1919._)
COLLOSOL PREPARATIONS
Report of the Council on Pharmacy and Chemistry
The Council has adopted and authorized publication of the report which
appears below declaring “Collosol Argentum,” “Collosol Arsenicum,”
“Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol
Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin”
and “Collosol Sulphur” inadmissible to New and Nonofficial Remedies,
because their composition is uncertain (conflict with Rule 1). In the
few cases in which the therapeutic claims for these preparations were
examined, the claims were found to be so improbable or exaggerated
(conflict with Rules 6 and 10) as to have necessitated the rejection of
these products.
W. A. Puckner, Secretary
The Anglo-French Drug Co., Ltd., London and New York, in November,
1918, requested the Council to consider the products “Collosol
Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,”
“Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol
Manganese,” “Collosol Quinin” and “Collosol Sulphur.” The term
“Collosol” appears to be a group designation for what are claimed to
be permanent colloidal solutions, marketed by the Anglo-French Drug
Co., Ltd. Were this claim correct, “Collosols” should contain their
active constituents in the form of microscopic or ultramicroscopic
suspensions, protected against spontaneous precipitation by the
presence of proteins or some similar “stabilizers.”
According to the original patent specifications for Collosols, the
metals are precipitated or treated with “peptone,” which acts as the
suspending or stabilizing agent. The method of using the peptone makes
it doubtful, in the first place, whether the major part of the metals
is present in colloidal form, or merely in the form of peptonates,
i. e., as ordinary salts. Moreover, the later patents indicate that the
products have been unsatisfactory; “experience having shown that some
metal colloids under certain conditions not yet fully understood have
the tendency to break down after a certain period” (U. S. patent No.
1,116,247). Phenol, it is claimed has a tendency to counteract this
decomposition, and the patent covers the use of phenol for this purpose.
It is difficult to see how phenol could possibly have such action. In
fact, it obviously does not, for a number of the samples of Collosols
submitted to the Council had separated. For instance, “Collosol
Hydrargyrum” was not a colloidal solution at all, but a suspension
of a coarse powder. The ampules of “Collosol Ferrum” contained a
considerable quantity of flocculent precipitate. If either of these
preparations were injected intravenously as directed, death might
result, making the physician morally if not legally liable.
The recklessness of the claims is further illustrated by the advice
that these indefinite mixtures of poisonous metals can be injected in
unlimited quantities. Thus, Henry Crookes stated (_Chemical News_,
May 7, 1914, p. 218) that Collosols “contain so small a proportion of
metal, viz., 1 in 2000, that even a poisonous body like arsenic can be
used with impunity.” He stated that they may be applied as a lotion,
intramuscular or intravenous injection, and that “one pint or more can
be injected intravenously.”
In the case of “Collosol Cocain,” as was brought out in the Council’s
report published in The Journal, April 12, 1919, the manufacturers have
admitted that the product is not what they have claimed--and still
claim--for it. The report of the A. M. A. Chemical Laboratory showed
that “Collosol Cocain,” instead of containing 1 per cent. cocain as
claimed, contained, in fact, at most not more than 0.4 per cent. cocain.
The report of the A. M. A. Chemical Laboratory on the Collosol products
was sent by the Council to the New York office of the Anglo-French Drug
Co., Ltd., in duplicate in order to facilitate reference to the London
office. This was some months ago. The information which the Council
requested has not yet been received, nor has the Anglo-French Drug Co.,
Ltd., indicated its intention of supplying such information. On the
other hand, claims to which specific objection have been made, continue
to appear in current advertising. Accordingly, the Council authorizes
publication of this report, and declares the Collosol preparations
previously named ineligible to New and Nonofficial Remedies.
Additional Notes on Collosol Evidence
In addition to the preceding the following notes of the referee on the
evidence so far submitted were sent to the Anglo-French Drug Company,
Ltd., for consideration:
_Collosol Iodine_: The leaflet which describes Collosol Iodine contains
claims that are improbable, not in accord with accepted facts nor
substantiated by evidence; for instance:
“This preparation contains Iodine in its most active form ...”
“The disadvantages of ‘iodism’ and nausea frequently associated
with iodides never occur with Collosol Iodine.”
“In the case of Colloidal Iodine the whole of the Iodine is
absorbed and enters into molecular combination with protein to form
an iodo-amino acid and ... exerts a reducing action on the lipoids
producing a different condition of the blood--hence the use of
Iodine as an ‘alterative’.”
“Intravenously the action of Collosol Iodine is more rapid ... in
cases of pyemia ... thus showing its absolute non-toxicity.”
“‘Per se’ Colloidal Iodine is only slightly parasitotropic and
bacteriotropic but micro-organisms are very greatly influenced
by its action, and not only is the effect of a subsequently
administered remedy greatly increased but also the insoluble
colloidal protein of serum itself is reduced to smaller particles,
thus increasing its surface and adsorptive capacity and consequent
germicidal power. In some cases the serum, thus aided, is enabled
to throw off a milk microbial invasion. The above action can be
readily demonstrated ‘in vitro’ by means of the ultramicroscope.”
“In Cancer, the intravenous injection of Collosol Iodine relieves
pain, even where large dosage of morphine is ineffective.”
“In Rheumatism the ionic method of treatment with Collosol Iodine
is strongly advised.”
“In Recovery from Alcoholism the internal administration of
Collosol Iodine restores the normal condition of cell activity,
ensuring rapid recovery.”
_Collosol Hydrargyrum_: This is said to be a preparation of colloidal
mercury and would therefore be similar to Electromercurol (New and
Nonofficial Remedies, 1919, p. 167). Colloidal mercury preparations
have been used to some extent; they appear to have no decided
advantage over other, noncolloidal, mercury compounds. They differ
sufficiently from them, however, to justify acceptance for New and
Nonofficial Remedies, providing that reasonable claims are made for
them. The leaflet advertising Collosol Hydrargyrum contains statements
that cannot be accepted and require thorough revision to make them
acceptable. The following are instances:
“Although--especially locally--the action of mercurials is markedly
antiseptic, when taken internally or injected, it has been stated
by some of the best known authorities, that their action is rather
to increase the natural resisting power of the body to disease,
probably because of stimulation of the oxidases.”
With the soluble mercurials “considerable upset of the normal cell
conditions of the tissues ensues whilst these soluble salts are
being converted to a condition in which the body can make use of
them.”
“The colloidal state ... is stated by some authorities in the case
of mercury to be invariably precedent to absorption.... With the
usual forms of mercury the danger of too great a dose per cell is
considerable, but in the case of colloidal mercury, the diffusion
is extremely rapid and chemical affinity low. Hence the danger
to the individual leucocyte is minimized and the maximum effect
obtained.”
“... absence of pain is usual in the administration of colloidal
preparations and is due to their isomorphism with the colloidal
lipoid and protein of the tissues and body fluids.”
“According to McDonagh,... mercury acts as an oxidizing agent and
that the process of oxidation is more effective in the early stages
of syphilis in producing the death of the causal organism....”
_Collosol Manganese_: The circular submitted to the referee is
a reprint of a paper by Sir Malcolm Morris on “The Treatment of
Furunculosis and Other Deep-Seated Coccogenic Infections by Collosol
Manganese.” It reports four cases of furunculosis, each of which
cleared up after the intramuscular injection of a few doses of Collosol
Manganese. The author seems to attribute the cure to the manganese
but the evidence is not convincing. Even the author admits that, in
the treatment of furunculosis in general “when at last the dismal
procession ends, this often appears to be less the result of treatment
than because the disease has run its natural course.” Unless much
better evidence is in existence, the preparation must be considered
to conflict with Rule 6, which requires therapeutic claims to be
substantiated.
_Collosol Argentum_: The evidence submitted as to actions consists of
a single reprint by Roe, which is not convincing, and this fantastic
statement by Boys:
“A young girl, aged 18, came to my house with acute inflammation of
one eye with an ulcer on the cornea. Two drops of Collosol Argentum
were dropped in the eye at 7 p. m., and a pad placed over the eye.
When she came next morning the eye was quite well; the ulcer had
disappeared, and there was no inflammation.”
There is no evidence that this preparation acts as catalyzer and
assists the natural resisting bodies of the tissues; or that these are
“oxygen carriers.” Unless the claims are supported by better evidence,
they, in the opinion of the referee, could not be accepted.
There have been submitted to the Council samples of the following
metallic Collosols:
COLLOSOL ARGENTUM COLLOSOL FERRUM
COLLOSOL ARSENICUM COLLOSOL HYDRARGYRUM
COLLOSOL CUPRUM COLLOSOL MANGANESE
Also Collosols of Iodine and Sulphur, and finally Collosols of Cocain
and Quinin. Of all the above, except sulphur, only three small ampules
have been submitted. This does not admit of any chemical examination
but a statement of the physical appearance may be of interest.
_Collosol Arsenicum_, 0.2 per cent.: Very turbid with large quantities
of a lemon yellow flocculent precipitate. On shaking does not become
homogeneous and rapidly separates again.
_Collosol Argentum_, 1-2000: The liquid has a slight opalescence. There
is considerable deposit of a heavy black precipitate. Does not become
homogeneous on shaking and the black substance quickly separates again.
_Collosol Cuprum_, 0.5 _per cent._: Dark red somewhat opalescent
liquid. No precipitate. May be colloidal.
_Collosol Ferrum_, 1-2000: Liquid clear. Large quantities of dark brown
flocculent precipitate. The precipitate is not distributed evenly when
the mixture is shaken and settles out quickly on standing.
_Collosol Hydrargyrum, 5 per cent._: Milky liquid. Large quantities of
white deposit mixed with considerable black. The deposit mixes fairly
well but the greater part settles out after standing an hour or two.
_Collosol Manganese_, 2.5-1000: Clear reddish-brown liquid without
deposit of any kind. Is not opalescent or fluorescent.
_Collosol Iodin_, 1-500: Very pale straw colored liquid without
deposit. Has a slight opalescence.
_Collosol Sulphur_, 1-100: Liquid is opalescent. There is some deposit
of yellow particles. A four ounce bottle was also submitted. The liquid
in this bottle is milky with considerable deposit of yellow crystals
like ordinary crystalline sulphur.
_Collosol Cocain_, 1-100: Transparent, colorless liquid with no
deposit. Chemical examination showed 0.4 per cent. of what may have
been cocain. This residue gave alkaloidal tests.
_Collosol Quinin_, 1-100: Slightly opalescent, colorless liquid, with
no deposit. Gives alkaloidal reactions.--(_From The Journal A. M. A.,
June 7, 1919._)
PULVOIDS CALCYLATES COMPOUND
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report, not
so much because the preparation with which it deals is of any great
importance, but as a protest against the large number of similar
irrational complex mixtures which are still offered to physicians.
W. A. Puckner, Secretary.
Pulvoids Calcylates Compound (The Drug Products Co., Inc.) are tablets
each of which is claimed to contain: