exudation, amount of liquid increased, some part of which was
probably chlorlyptus unabsorbed. Spleen about normal, liver
congested, kidney about normal, suprarenal glands about normal, lungs
normal, pleural cavity obtained no exudation, heart soft, flabby and
congested.
EXPERIMENT 15.--_Toxic and irritant action of chlorlyptus when
injected into the pleural cavity._--Six normal guinea-pigs used for
the experiment. Chlorlyptus was injected in the pleural cavity as
follows: Guinea-Pig 1, 0.5 c.c.; Guinea-Pig 2, 1 c.c.; Guinea-Pig 3,
2 c.c.; Guinea-Pig 4, 3 c.c., and Guinea-Pig 5, 4 c.c. Guinea-Pig 6
was used as a control.
Result: Guinea-Pigs 1 and 2 recovered about four hours after
injection. Guinea-Pig 3 died three days after and Guinea-Pigs 4 and 5
four and two hours after, respectively.
Conclusions: Guinea-pigs weighing on the average of 400 gm. may be
injected peritoneally with one or two c.c. or intrapleurally with
0.5 to 1 c.c. of chlorlyptus without having fatal results from the
injection.
EXPERIMENT 16.--_Toxic and irritant action of eucalyptus oil._--Three
normal guinea-pigs were used for the experiment. Guinea-Pig 1 was
injected with 1 c.c. of oil of eucalyptus in the peritoneum, and
Guinea-Pig 2 with 0.5 c.c. in the pleural cavity. Guinea-Pig 3 was
used as a control.
Result: Guinea-Pig 1 died about three hours after injection, and
Guinea-Pig 2 about two hours after the injection.
Autopsy: Both guinea-pigs showed marked congestion and a moderate
degree of exudate in the peritoneum.
EXPERIMENT 17.--_Toxic and virulent action of eucalyptus._--Three
normal guinea-pigs were selected for the experiment, as in Experiment
16. The injection was made in the pleural cavity. Guinea-Pig 1 was
injected with 0.5 c.c. and Guinea-Pig 2 with 1 c.c. of eucalyptus oil.
Result: Guinea-Pig 1 died the following day, and Guinea-Pig 2 one
hour after the injection.
EXPERIMENT 18.--_Toxic and irritant action of dichloramin-T, 0.5 per
cent. in chlorcozane._--One guinea-pig was used for each experiment.
Guinea-Pig 1 was injected with 0.5 c.c. and Guinea-Pig 2 with 1 c.c.
of dichloramin-T peritoneally.
Result: Both animals became restless immediately after the injection,
and died twelve hours after of acute hemorrhagic peritonitis.
EXPERIMENT 19.--_Effect of chlorlyptus on staphylococcus suspended in
salt solution and one of that solution injected into the peritoneum
of the guinea-pig._--Three guinea-pigs were used for the experiment.
Guinea-Pig 1 was injected with 0.5 c.c. of staphylococcus suspension
as control. Guinea-Pig 2 was given the same, and immediately after
received 1 c.c. of chlorlyptus. Guinea-Pig 3 was injected with the
same amount, and chlorlyptus was injected twenty-four hours after
injection.
Results: Guinea-Pig 1 was sick and weak with loss of appetite for
some days, but gradually recovered. Guinea-Pig 2 died over night.
Autopsy: There was a large amount of exudate in the peritoneal
cavity, irritation of the intestine, and other signs of acute
inflammation. A moderate degree of congestion; spleen not enlarged;
liver showed cloudy swelling and fibrinous exudate; lungs and heart
about normal except for a moderate degree of congestion but no
exudate. Guinea-Pig 3 was sick for some days, but recovered gradually
one week after.
EXPERIMENT 20.--_Effect of chlorlyptus in vivo on
staphylococcus._--The experiment was conducted in the same way as in
Experiment 17, but 2 c.c. were used instead of 1 c.c.
Result: Guinea-Pig 1 was injected with 2 c.c. staphylococcus
suspension and died over night. Autopsy showed that the animal died
of acute peritonitis. The peritoneum showed some fibrinous exudate
and mesenteric vessels. Guinea-Pig 2 was injected with 2 c.c. of
staphylococcus, and eighteen hours after was injected with 1 c.c. of
chlorlyptus. The animal died two weeks after injection. Guinea-Pig 3
was injected with 2 c.c. staphylococcus suspension, and twenty-four
hours after with 1 c.c. of chlorlyptus. The Guinea-Pig died ten days
after. Autopsy revealed bronchopneumonia of the left lung and acute
miliary abscess in the liver.
--(_From The Journal A. M. A., Nov. 27, 1920, with additions._)
AQUAZONE (OXYGEN WATER)
Report of the Council on Pharmacy and Chemistry
Aquazone is stated by the Aquazone Laboratories, Inc., Los Angeles,
California, to be a supersaturated solution of oxygen in water,
carrying approximately five and one-half times as much dissolved oxygen
as ordinary water. In an advertising booklet, it is suggested that
Aquazone is of value in the treatment of influenza, pneumonia, typhoid,
Bright’s disease and kindred disorders. It was also stated therein
that in the treatment of fevers it lowers the temperature, and that
the administration of three bottles of Aquazone (representing 0.033
gm.--1-1/2 grain--of oxygen) is of value for “preventive and tonic
purposes.”
The evidence which the Aquazone Laboratories submitted did not show
that the effects were other than those which might be obtained from the
administration of ordinary potable water. The Council declared Aquazone
inadmissible to New and Nonofficial Remedies, because the therapeutic
claims made for it were unwarranted, and because its use is irrational
for the reason that oxygen given by stomach in this way is of little
or no value.--(_Abstracted from Reports of Council on Pharmacy and
Chemistry, 1920, p. 50._)
COAGULEN-CIBA OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
announcing the deletion of Coagulen-Ciba from New and Nonofficial
Remedies.
W. A. Puckner, Secretary.
Coagulen-Ciba, a product of the Society of Chemical Industry, Basle,
Switzerland, was admitted to New and Nonofficial Remedies in 1915.
It is stated to be an extract prepared from blood platelets and to
contain thromboplastic substances (cytozym, thrombokinase, thrombozym)
mixed with lactose. Extensive clinical reports appeared to justify its
acceptance for New and Nonofficial Remedies with Fibrin Ferments and
Thromboplastic substances.
In 1918, Dr. Arthur D. Hirschfelder reported to the Council that of
a number of specimens of Coagulen-Ciba examined by him, failed to
accelerate the coagulation time of blood.
In view of Dr. Hirschfelder’s findings, the Therapeutic Research
Committee of the Council invited Dr. P. J. Hanzlik to undertake an
exhaustive investigation of thromboplastic substances, the Council,
in the meantime temporarily retaining Coagulen in New and Nonofficial
Remedies until the investigation was completed.
The following report on the eligibility of Coagulen-Ciba was made to
the Council by Dr. Hanzlik:
_Object_: To test the claims of thromboplastic and hemostatic
activities.
_Claims_: Coagulen is alleged to be a “physiological styptic prepared
from the natural coagulants of animal food contained in the blood
platelets. It has the characteristics of a lipoid.” (If cephalin is
meant it is difficult to understand why platelets should be selected
in preference to other abundantly supplied organs such as brains).
“Coagulen is indicated in all cases of external and internal
hemorrhage due to a deficiency of the coagulating power of the blood:
epistaxis, hemophilia, hemorrhage from gastric or duodenal ulcer,
melaena neonatorum, hemorrhage from the gums, the lungs, the bladder,
the uterus, hemorrhage during or after operations (turbinectomy,
tonsillectomy). It has also been used as a prophylactic before
operations, likely to produce severe hemorrhage.”
“In cases of true hemophilia one application of 5 grains of coagulen
usually suffices to control the hemorrhage.” “In gastric and
intestinal hemorrhage the internal administration of coagulen will be
found effective.” “In bonegrafting, plastic surgery, dentistry and
nose and throat surgery the application of a 10 per cent. solution of
Coagulen will be found to be of valuable assistance in controlling
hemorrhage and oozing.”
“It is a non-toxic and non-irritating powder to which a certain
amount of sugar has been added, with a view to ensuring its prompt
solution in water or physiological sodium chloride solution.”
_Description_: “Coagulen is a yellowish granular powder with but
slight odor, a sweet taste and is readily soluble in water or a
normal salt solution.” The dry Coagulen obtained corresponds to
the description claimed. Old specimens show the presence of dark
brown particles. Coagulen is marketed in 3 forms: (1) as dry powder
containing lactose, which, it is claimed, facilitates solution in
water; (2) as 3 per cent. sterile solution in ampoules;[137] (3)
tablets.
[137] An ampoule labeled as follows: “Coagulen-Ciba, 20 c.c. in
sterile solution ready for use. To be shaken. Importé de Suisse. Op.
No. 968” was found to measure only 15 c.c. Another ampoule with the
same label and Op. No. 9641 contained considerable sediment.
_Methods of Study_: The alleged thromboplastic activity was tested by
the method of Howell and a modification of this method by Fenger as
described in “New and Nonofficial Remedies.” In the Howell method dog
or cat blood is used, while beef blood at body temperature is used in
Fenger’s method. In other respects the methods are essentially the
same. Briefly these consist of noting the acceleration of coagulation
time in a mixture of equal parts of serum and the thromboplastic
agent to which about an equal part of oxalate plasma is added. Under
these conditions cephalin causes clotting in about 1 minute or even
less as compared with 20 to 30 minutes or more of the control.
The effects were compared with freshly prepared cephalin and other
thromboplastic agents, using saline (0.9 per cent. NaCl) as control.
The effect of different concentrations was also studied.
The literature of the manufacturers claims that Coagulen is harmless.
This was tested by making intravenous and subcutaneous injections
into guinea-pigs, using saline and cephalin as controls.
Bloods of 4 different species were used, namely, cat, dog, beef and
human. Dog’s peptonized blood and plasma were also tried.
The 15 different tests that were made in vitro were carried out with
3 different samples of fresh dry Coagulen (from manufacturer), 2
old samples (one from Council on Pharmacy and Chemistry and one of
our own), 3 fresh specimens of sterile solution in ampoules (from
manufacturer), one old specimen and 4 small ampoules (Council on
Pharmacy and Chemistry).
The tablets were not tested since these are made from dry Coagulen
and the results would hardly be expected to show anything different.
_Results_: The results obtained may be briefly summarized as follows:
(1) 0.1 per cent. to 5 per cent. Coagulen did not accelerate the
coagulation time of blood and oxalate plasmas in the majority of
tests any more than the controls of saline, while 0.1 per cent.
cephalin was found to shorten the coagulation time from 1/3 to 1/2.
(2) There was no difference between the behavior of old and fresh
specimens.
(3) No acceleration of coagulation _in vitro_ was observed even with
the highest concentrations tried, namely 25 and 50 per cent.
(4) Irrigations made with fresh dry coagulen in solution and sterile
solution in ampoules on superficial bleeding from the foot-pads of 3
normal and peptonized dogs and local application to hemorrhages from
dissected femoral arteries and bone and liver wounds of 3 dogs showed
that coagulen was no more active than normal saline.
_Toxicity_: Subcutaneous and intravenous injections of different
doses of Coagulen solutions (fresh ampoules) and dry Coagulen
in solution in 8 guinea-pigs produced definite anaphylactoid
symptoms with injury to the circulatory and respiratory systems as
indicated by cardiac dilatation, abdominal congestion and pulmonary
hemorrhages, congestion, distention and sometimes thrombi. On the
other hand, the control animals injected with saline and cephalin
remained practically unharmed.
_Conclusions_: The results obtained justify the following conclusions:
(1) Coagulen is entirely inactive as a thromboplastic and hemostatic
agent.
(2) Coagulen is distinctly injurious when injected systemically.
(3) The claims of hemostatic efficiency and harmlessness for Coagulen
by the manufacturer appear exaggerated and unjustified.
_Recommendations_: Because of its uncertain composition, the
possible dangers when injected systemically, and its inactivity as a
thromboplastic and hemostatic agent when tested by several different
methods, Coagulen merits no recognition as a therapeutic agent for
inclusion in New and Nonofficial Remedies.
The detail evidences used as the basis of this brief report
concerning Coagulen will be published shortly in the _Journal
of Pharmacology_,[138] together with the results with other
thromboplastic agents.
[138] Since the report was sent to the manufacturers, the results
have been published. Hanzlik, P. J., and Weidenthal, C. M., Plasma
and Blood Clotting Efficiency of Thromboplastic Agents in Vitro and
their Stability, J. Pharmacol. and Exper. Therap. =14=:157 (October)
1919; Hanzlik, P. J., Karsner, H. T., and Fetterman, J., Anaphylactoid
Conditions, J. Pharmacol. and Exper. Therap. =14=:189 (Oct.) 1919;
Hanzlik, P. J., Karsner, H. T., and Fetterman, F., Anaphylactoid
Phenomena from Thromboplastic Agents, J. Pharmacol. and Exper. Therap.
=14=:229 (Nov.) 1919.
The preceding report was sent to the American agent for the Society of
Chemical Industry, Sept. 8, 1919.
In reply the American agent, Ciba Co., Inc., on March 22, 1920,
sent the Council “some additional clinical reports on the use of
Coagulen-Ciba in the treatment of Hemorrhages supporting our claims of
the merits of Coagulen-Ciba.”
The material submitted by the Ciba Co., contains no objective evidence
for or against the efficiency of Coagulen-Ciba but merely opinions. As
a rule these opinions are favorable though conditional and hedging and
quite unconvincing. Nothing was submitted to offset or challenge the
findings of Dr. Hanzlik’s report.
Since the evidence indicates that Coagulen-Ciba has little, if any,
efficacy as a hemostatic, the Council directed its omission from New
and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and
Chemistry, 1920, p. 53._)
FERRIC CACODYLATE OMITTED FROM NEW AND NONOFFICIAL REMEDIES
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the report which appears
below, explaining the omission of ferric cacodylate from New and
Nonofficial Remedies.
W. A. Puckner, Secretary.
Iron cacodylate, the ferric salt of cacodylic acid, was admitted to New
and Nonofficial Remedies in 1917. It is required to contain from 39.7
to 44.9 per cent. of arsenic (As).
The following statement of the action, uses and dosage of iron
cacodylate appears in the 1920 edition of New and Nonofficial Remedies:
“Actions and Uses.--Ferric Cacodylate has the properties of iron
salts and of arsenic. Its use has been proposed in conditions
in which the effects of iron and the mild arsenic action of
cacodylates is desired.
“Dosage.--from 0.015 to 0.1 Gm. (1/4 to 1-1/2 grains).”
The period for which the iron cacodylate preparations now in New and
Nonofficial Remedies were accepted coming to an end with the close of
1920, the Council decided to determine if sufficient evidence for the
value of ferric cacodylate has accumulated to warrant its continued
recognition. The following is the report of the referee of the
Committee on Therapeutics to whom the matter was assigned:
“As far as the Referee knows, the only claim that Iron Cacodylate has
as a therapeutic agent is that it forms a convenient method for the
administration of Iron and Cacodylate (while there is no reason why
a drug should not be given by mouth, usually intramuscularly, and
apparently it has recently been given intravenously). The effects to
be expected from its use are those of iron and arsenic.
“Granted that iron and arsenic are valuable therapeutic agents, Iron
Cacodylate is not a satisfactory preparation in which to administer
these drugs for the following reasons:
“1. It would appear that Cacodylates are not the best form in which
to administer arsenic. Cacodylates in therapeutic doses exert but a
feeble action. Small quantities may be reduced to cacodyl (CH₂)₄As₂,
and varying amounts to inorganic arsenic. The amount transformed
to arsenic is apparently unknown and probably varies in different
individuals. On these grounds alone the use of the cacodylates where
an arsenic effect is desired seems dubious.
“2. The amounts of iron and cacodylates contained in the doses
recommended are small when compared with the usual doses of either
iron or cacodylate. The amount of iron in the Iron Cacodylate
preparations is small, about .0036 gram per dose, while the
preparations admitted to ‘Useful Drugs’ contain much larger amounts
per dose recommended. The list follows:
Massa Ferri Carbonates Fe per dose .042 gm.
Pilulae Ferri Carbonates " .058 gm.
Tinctura Ferri Chloride " .022 gm.
Ferri et Ammonii Citrae " .042 gm.
“The approximate amount of arsenic in Iron Cacodylate in the commonly
recommended doses varies from .012 gm. to 0.024 gm., while the amount
of arsenic in Sodium Cacodylate in the recommended doses varies
between .021 and .35 gms. It would seem that a much more rational
method of administration of these two drugs would be separately, in
which case a better control over the dosage is possible.
“3. The Referee has been unable to secure reliable clinical evidence
that Iron Cacodylate is a serviceable preparation. A search of the
available literature for the past fifteen years has been made, also
Drs. Edsall, Longcope, Stengel, Hoover, Phillips and Miller have been
consulted. These physicians know nothing of its use.
“4. In view of the above, it appears to the Referee that Iron
Cacodylate is an irrational and useless method of the administration
of iron and arsenic.”
The Council adopted the report of the referee and directed that iron
cacodylate be omitted from the 1921 edition of New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1920,
p. 62._)
LIBRADOL
Report of the Council on Pharmacy and Chemistry
The Council has authorized for publication the following report which
explains why Libradol was found ineligible for New and Nonofficial
Remedies.
W. A. Puckner, Secretary.
Libradol is manufactured by Lloyd Bros., Cincinnati. According to a
circular (a “readily removable” label) which accompanies the trade
package, its “uses” are: “In colds, croup and acute bronchitis. In
local congestions; in lung trouble, in acute inflammations of this or
any other organ, especially if pain or soreness be present. In lumbago,
sciatica, or in rheumatic pains of the joints or muscles. Applied to
the forehead, it induces sleep.”
Libradol is offered in two forms, “Libradol Mild” for infants and
supersensitive persons which is said to be “destitute of drug energy”
and Libradol “Regular” which is “highly medicated,” the “constituents”
being “DRACONTIUM, SANGUINARIA, CEPHAELIS, MELALEUCA, LOBELIA, LAURUS,
CAPSICUM, TOBACCO.”
According to a circular, “The sanitary plasma Libradol” is a
“homogeneous, highly medicated, and exceedingly potent compound, in
plastic form,” which “carries the energies of its drug constituents
and the high antiseptic qualities of Laurus Camphora and Melaleuca.”
It is stated: “The Drug Influence of Libradol is necessarily different
from that of any known single member of the Materia Medica. But yet,
no mystery either in medicine or of pharmacy is claimed as a part of
its composition or process of manufacture. It is a thing peculiar to
itself, the result of the study of the drugs from which it is derived
and compounded. These drugs may be studied at leisure by whoever cares
to do so....”
The following information bearing on the composition of Libradol was
furnished by Lloyd Brothers in response to a request from the Council
to aid in the consideration of the preparation:
“‘Compound Lobelia Powder’ has been, since 1852, official in the
_American Dispensatory_, in the first edition of which (1852) its
formula is given, as follows:
“‘Take of Lobelia, in powder, twelve ounces; Bloodroot and Skunk
Cabbage, in powder, of each, six ounces; Ipecacuanha, eight ounces;
Capsicus, in powder, two ounces. Mix them.’
“This preparation came increasingly into demand with the Eclectic
profession, the principal use for which it was first employed (as
an emetic), being finally displaced by its local application in
bronchial pneumonia troubles, when sprinkled on a greased cloth and
applied to the chest.”
“In 1898, Dr. Finley Ellingwood petitioned Lloyd Brothers to
make for him, in plasma form, ready for application, a compound
carrying the ingredients of the old ‘Compound Lobelia Powder,’
strengthened by the addition of Melaleuca leucadendron, Laurus
camphora and Nicotiana tabacum. Experiments not very encouraging
in a pharmaceutical sense were made, and it was not until repeated
requests had been made that a product was at last satisfactorily
prepared and forwarded to Dr. Ellingwood (1900), with no thought
other than that of serving him personally in his practice. This
product he used and commended to his professional friends, and
under his commendation it came into professional demand.”
An examination of the information submitted by Lloyd Brothers showed
Libradol to be in conflict with the principles and rules that govern in
the acceptance of articles for New and Nonofficial Remedies as follows:
Composition (Rule 1).--The information which has been received
gives little idea of the actual composition of the preparation; for
example, the statement that Libradol “carries the energies of its drug
constituents and the high antiseptic qualities of Laurus Camphora
and Melaleuca” gives no indication as to the part or parts of the
Laurus Camphora or Melaleuca employed. If the statement is correct,
that Libradol “is a homogeneous, highly medicated, and exceedingly
potent compound,” it is essential that the several potent ingredients
be stated clearly and not merely hinted at by their qualities. Other
conflicts with Rule 1 might be enumerated, but the foregoing citations
state the direct conflict; and this has not been removed, although an
inquiry was sent to Lloyd Brothers for a statement of the amount of
each potent ingredient in a given quantity of Libradol.
Indirect Advertising (Rule 4).--The recommendation for the use of
Libradol in the treatment of colds, bronchitis, lumbago, sciatica and
rheumatic pains, which accompanies the trade package, is prone to
lead the public to depend on it in cases where definite treatment is
imperative.
Unwarranted Therapeutic Claims (Rule 6).--Libradol is recommended in
a great variety of conditions and is especially claimed not only to
relieve pain, but to remove the cause of pain. This is explained as
follows: “In the study of the physiological action of many drugs, it
was found that the constituent remedies in this combination exercised
a most salutary influence, not only upon the sensibility of the nerves
involved, but upon the capillary circulation within the diseased area,
the muscular structures therein included, and, subsequently, upon the
course of the advancement of the congestive and inflammatory processes,
and upon secretion, exudation, adhesion, induration, hypertrophy,
suppuration and excretion.”
Granting, for the sake of argument, that carefully controlled
experimental clinical evidence were available to substantiate this
statement with reference to a single case of pain, the statement
would be misleading when considered as a general explanation of the
preparation’s relieving pain by removing the cause of pain when taken
in connection with the conditions for which it is recommended and in
which pain is even a minor symptom. Still, if pain were relieved in
these cases by removing the cause, the patient would be cured of the
conditions which give rise to the pain, and these include: “Acute
pain in the chest;... acute inflammation in the chest;... persistent
local pain;...” (This might be interpreted as including tuberculosis;
pneumonia; cancer, and appendicitis.) “lumbago; sciatica; articular
rheumatism” (gonorrheal infections?).
Name (Rule 8).--The name, derived from _Dolar_ and _Liber_, suggests
the claimed action of the preparation (the relief of pain) rather than
the drugs said to be presented by it.
Irrational Composition (Rule 10).--It is quite possible that Libradol
will relieve pain in certain instances and that the drug constituents
present in Libradol “Regular” make this more effective than “Libradol
Mild” which is “destitute of drug energy”; this, however, is no
justification for the use by physicians of a cataplasm containing
or made from skunk cabbage, bloodroot, ipecac, melaleuca (oil of
cajeput?), lobelia, laurus comphora (camphor?), capsicum and tobacco.
The combination is thoroughly irrational and a reminder of a past
century. Further, the Council knows of no evidence to support the
following claims:
“As a stimulant Capsicum has the power of neutralizing depressant
remedies like Lobelia and Tobacco.”
“Our association of its desirable constituents with those of
Lobelia, in connection with the modifying influence of Capsicum,
Melaleuca, and Laurus Camphora, permits a more free use in Libradol
than would be possible were it to be employed alone.”
“Capsicum, Melaleuca, and Laurus Camphora in Libradol tend to
counteract the excessive relaxative and depressant effects of
Lobelia.”
“The great value of Melaleuca in Libradol is its quality of
modifying and controlling the action of the associated energetic
constituents of the drugs Tobacco and Lobelia, which reduce
congestion and inflammation, but which would, unsupported, be too
depressant.”
Libradol is inadmissible to New and Nonofficial Remedies because its
composition is complex, irrational and semi-secret, and because its
name and the unwarranted therapeutic recommendations made for it will
lead to its ill-advised use.--(_From Reports of Council on Pharmacy and
Chemistry, 1920, p. 65._)
HELMITOL OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Helmitol is hexamethylenamin methylencitrate. It was introduced with
the claim that it was superior to hexamethylenamin--which acts in acid
fluids only--in that it is equally efficient whether the urine is
alkaline or acid.
In 1918 The Bayer Company, which then marketed the product in the
United States, was notified that the Council questioned the claims made
for Helmitol and desired evidence to substantiate them. In 1919 the
same notification was sent the Winthrop Chemical Company, which in the
meantime had secured control of the product. Pending the submission
of the evidence, the Council continued the acceptance of Helmitol
for New and Nonofficial Remedies with the statement that the actions
and uses of hexamethylenamin anhydromethylencitrate were those of
hexamethylenamin.
W. A. Puckner, Secretary.
The following report on Helmitol was made by the referee in charge of
hexamethylenamin compounds and preparations, adopted by the Council and
sent the Winthrop Chemical Company:
“Helmitol is a compound of anhydromethylencitric acid and
hexamethylenamin. It was introduced with the claim that it would be
antiseptic even in alkaline urine. The Council did not entirely trust
the evidence, but continued to list Helmitol in N. N. R., merely as
a salt of hexamethylenamin, until satisfactory data should become
available. These have now been furnished by Hanzlik (_Journal of
Urology_ =4=:145) who has shown that:
“1. The alkalinity required to split off formaldehyd from
anhydromethylencitric acid is greater than exists in the urine, even in
advanced ammoniacal fermentation.
“2. Even if any formaldehyd were liberated in ammoniacal fermentation,
it would at once become inactive by combining with ammonia.
“3. Urine after the administration of anhydromethylencitric acid
actually putrefies readily.
“4. Less than 5 per cent. of the anhydromethylencitric radical reaches
the urine, the remainder being destroyed in the body.
“The only reason for the existence of Helmitol was this claim of
antiseptic action in alkaline and putrefying urines. Since this has
been disproved, there remains no reason for retaining Helmitol in
N. N. R.; on the contrary, its retention would only tend to continue
the fallacy on which it is based.
“It is, therefore, recommended that Helmitol be no longer listed with
New and Nonofficial Remedies, and that this report be published, after
the usual submission to the manufacturers.”
In accordance with the recommendation of the report, the Council has
directed the omission of Helmitol from New and Nonofficial Remedies
and has authorized the publication of this report.--(_From The Journal
A. M. A., Jan. 22, 1921._)
SPIROCIDE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
“Spirocide” (The Spirocide Corporation of New York) is advertised as a
new and successful treatment of syphilis by fumigation and inhalation.
According to the information presented to the Council, Spirocide is a
mechanical mixture of metallic mercury 25 per cent., copper sulphate 25
per cent., cypress cones 20 per cent., henna 20 per cent., nut gall 5
per cent., and dried pomegranate 5 per cent. It is supplied in the form
of greenish-gray tablets weighing about 10 gm. each, and containing,
therefore, about 2.5 gm. (about 38 grains) of mercury. It is sold in
packages of six tablets.
The following directions for its use are contained in a pamphlet
recently distributed:
“Spirocide is administered by means of fumigation and inhalation.
The patient is disrobed to the waist and placed in a light chair,
preferably with arms. A pastil or tablet of Spirocide is placed on
a small plate, or open receptacle, after being ignited by holding
in a gas or alcohol flame for a minute or so until it begins to
smoulder. The plate with the burning Spirocide is then placed on
the floor between the patient’s feet or just under the chair. A
small shelf or platform between the lower rounds of the chair is
an excellent location for the plate containing the burning mass.
When all is in position a sheet should be thrown over the patient
and arranged to enclose the whole. The patient should breathe
naturally and inhale the vapor, which will rise and fill the canopy
surrounding him. The treatment will require 15 to 30 minutes, or
until the Spirocide is burned up. The patient may complain at first
of a slight choking sensation, and there may be some tendency to
cough. This can be removed by raising the sheet long enough to
let in a little clear air. The eyes should be closed or lightly
bandaged to avoid smarting.”
Experiments conducted in the A. M. A. Chemical Laboratory show that
Spirocide, when ignited, burns slowly with consequent volatilization
of mercury. The several organic constituents serve as fuel and the
copper sulphate possibly acts as a regulator of the combustion. During
the burning process the cypress cones, henna, etc., are consumed but
most, if not all, the copper remains behind, the mercury only being
vaporized. It is asserted in the advertising pamphlet that Spirocide is
indicated in all stages of syphilis, primary, secondary and tertiary,
and in all its complications or sequelae. In these varying conditions
one tablet daily or every other day is recommended until six treatments
have been taken, though it is stated that “occasionally, depending on
the severity or the duration of the disease, it may be wise to give
nine treatments, the last three at intervals of two, three or more
days.”
Some of the results which it is claimed are obtained with Spirocide are:
“At the completion of this course of treatment with Spirocide,
all signs or evidences of syphilis are removed, and in ten days
to three months all Wassermann tests prove negative. Any further
treatments than the original course of fumigations are rarely
needed. Wassermann’s will be found uniformly negative after a
period which, according to the patient, may vary from ten days to
three months. These results have been obtained in cases in which
Salvarsan and kindred preparations have been employed without the
slightest benefit.”
In a letter to the Council the “scientific observer” of the Spirocide
Corporation declared:
“We do not claim that the vaporization method is new. We do claim,
however, that this combination of mercury produces more rapid
volatilization, certain absorption and undoubted effect than any
form of mercury administered by any method known to science without
the usual danger. That this is so we are willing to prove by
comparison with other methods both by ourselves and many observers
scattered over the United States....”
To determine the validity of the claims made for Spirocide, the
Corporation was asked to present the evidence which it offered. In
reply, the corporation’s “scientific observer,” Dr. J. Lewengood,
submitted 83 case reports from a number of different observers,
including those from military hospitals and a state institution, and
also a reprint of an article published by him in the _New York Medical
Journal_, Feb. 21, 1920, wherein were reported eight cases which
received “Spirocide Treatment.” In no case were controls with other
methods of mercury administration carried out.
This material the Council sent to two recognized syphilographers for
an opinion. One of the consultants reported that of the 83 cases,
20 dealt with patients who had also received arsphenamin medication
and, therefore, these 20 cases could not be considered as evidence
concerning the value of Spirocide. As to the remaining cases, he
found on the whole that the history and data furnished were far from
sufficient to warrant the claims made. In many of the cases emphasis
was laid on the Wassermann test, as though this test were the only
thing to be considered in a case of syphilis. He pointed out that in
one case the reaction changed from negative to strongly positive after
six treatments and that in several cases the phenomena reported cannot
be explained by anything else than a desire to get a negative blood
test. For example, one case had Spirocide treatment and a Wassermann,
1 plus, 55 days after; the author then reports that 19 days later the
reaction had become negative and, therefore, the change must be due to
Spirocide. In several of the cases reported it is even questionable
if the patients were syphilitic. The consultant concluded that the
evidence submitted by the Spirocide Corporation failed to prove the
claims made for Spirocide. He pointed out on the other hand that
patients readily become salivated from the use of Spirocide, often
after 8 or 10 treatments.
The second consultant replied that in his opinion the claim that
Spirocide produces more “undoubted effect than any form of mercury
administered by any method known to science without the usual danger,”
was not substantiated. He believed that it was not as effective as some
other methods, that the dosage is not as exact, and, therefore, it is
not as free from danger when the drug is pushed.
The Council’s two consultants were also asked whether or not, in their
opinion, the administration of mercury by inhalation is a method which
the Council should endorse to the extent of recognizing a preparation
based on this principle. This inquiry was also sent to the members of
the editorial board of the _Archives of Dermatology and Syphilology_.
Five replies were received. One advised a thorough study of the
different methods of administering mercury by inhalation. The other
four were opposed to such recognition on the ground that as the dosage
is not exact the effects, therefore, are not certain.
In consideration of the opinions expressed by its consultants, the
Council declared Spirocide inadmissible to New and Nonofficial Remedies
because (1) the claims made for it are unproved and unwarranted, (2)
the routine use of an inexact method for the administration of mercury
is detrimental to sound therapy and (3) the name is not descriptive of
its composition, thus failing to remind the physician who uses these
pastils that he is administering metallic mercury.--(_From The Journal
A. M. A., Jan. 22, 1921._)
DIGIFOLIN-CIBA NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized the publication of the following report,
declaring Digifolin-Ciba inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Digifolin-Ciba is a product of the Society of Chemical Industry
of Basle, Switzerland. It is marketed in the United States by the
Ciba Company, 91 Barclay Street, New York City. It is claimed that
Digifolin-Ciba is “a preparation of digitalis leaves that has been
freed from the useless and harmful principles such as Digitonin
(saponin), coloring and inert matter, etc., but does contain all the
really valuable, therapeutically active constituents of the leaves,
namely: digitoxin and digitalein in their natural proportions.” There
is no evidence that digifolin contains all of the glucosides of
digitalis as they exist in the leaf, and it is extremely improbable
that this is the case because one cannot remove saponin without
altering the other active principles of digitalis.
The Ciba Company sends out the following pamphlets relating to
Digifolin:
“‘Concerning Digifolin-Ciba, A New Preparation of Digitalis,’ by C.
Hartung, M.D., Ph.D. Extracts from the work ‘Ueber Digifolin, Ein
Neues Digitalis-Praeparat’ in the _Munich Medical Weekly_, No. 36,
page 1944, 1912.”
“‘Digitoxin Contents of Digifolin-Ciba,’ by C. Hartung, M.D.,
Ph.D., Basle, Switzerland. Reprints from the _Pharmaceutical Post_,
1913. No. 34, page 357. No. 40, page 431.”
“‘Pharmacological Tests of Digitalis,’ by M. J. Chevalier, Chef Des
Travaux Pratiques de Pharmacologie et Matiere Medicale, Faculte De
Medecine De Paris. Report Presented to the Societe de Therapeutique
at Their Meeting, May 28, 1913.”
In the reprint “Concerning Digifolin, ‘Ciba.’” Hartung lays stress
on the presence of harmful and inert substances present in the leaf
and galenical preparations with the direct or implied statement that
digifolin has an advantage in that these are absent from it. This is
misleading. It is true that Boehm whom Hartung cites, found saponin to
be irritating, but Boehm states that it required 100 mg. per kilogram
of body weight to induce vomiting after its oral administration.
Furthermore, saponin is present in traces only in infusion of
digitalis, so that the therapeutic dose contains a wholly negligible
amount of it.
The following occurs in “Pharmacological Tests of Digitalis,” by M. J.
Chevalier:
“Hartung’s Digifolin merits our attention, especially because
it seems to possess all the pharmacodynamic properties of
galenic preparations of digitalis without showing any of their
disadvantages.”
This claim scarcely needs comment, since it is well established that
the chief “disadvantages” of digitalis are inherent in the principles
which produce the desired effects of digitalis and may be avoided
to a large extent by a carefully regulated dosage of any digitalis
preparation. In short, the advertising for Digifolin asserts that this
digitalis preparation has all the advantages of digitalis itself, but
none of its disadvantages. This claim has been refuted so frequently
that manufacturers must be aware that it is untenable. Further the
claims now made for Digifolin are essentially those made nearly four
years ago at which time the attention of the American agent was called
to their unwarranted character.
The Council declared Digifolin-Ciba inadmissible to New and Nonofficial
Remedies because the therapeutic claims advanced for it are misleading
and unwarranted.--(_From The Journal A. M. A., April 2, 1921._)
SOME OF LOESER’S INTRAVENOUS SOLUTIONS
Report of the Council on Pharmacy and Chemistry
The Council has authorized the publication of the following report
on “Loeser’s Intravenous Solution of Hexamethylenamin,” “Loeser’s
Intravenous Solution of Hexamethylenamin and Sodium Iodid,” “Loeser’s
Intravenous Solution of Sodium Salicylate,” “Loeser’s Intravenous
Solution of Salicylate and Iodid,” “Loeser’s Intravenous Solution of
Sodium Iodid” and “Loeser’s Intravenous Solution of Mercury Bichlorid,”
put out by the New York Intravenous Laboratory, Inc.
W. A. Puckner, Secretary.
The intravenous solutions of “Hexamethylenamin,” “Hexamethylenamin
and Sodium Iodid,” “Sodium Salicylate,” “Sodium Salicylate and Sodium
Iodid,” “Sodium Iodid” and “Mercuric Chlorid” marketed by the New York
Intravenous Laboratory, Inc., are solutions of official substances sold
under their official names. They would, therefore, be outside the scope
of the Council, were it not that special and general therapeutic claims
are made for them. Such special claims, for instance, are contained in
an advertisement in the _Illinois Medical Journal_ for Oct. 20, 1920,
which gives, under the various drugs, a list of diseases in which the
drugs are said to be “indicated.” The Council is unable to agree with
some of these recommendations. The fundamental objection, however, is
the general claim of superiority and safety of the intravenous method.
The intravenous solutions named above would naturally have little sale
if such special claims were not made for them. While the claims may not
be made directly, they are carried by such display phrases as “For the
progressive physician seeking improved clinical results” and “A safe
practical office technique.”
The Council continues to hold that intravenous medication, generally,
is not as safe as oral medication even with relatively harmless
substances (a fact again illustrated by the results of Hanzlik and
Karsner, 1920, _Journal Pharmacology and Experimental Therapeutics_,
14, 379), and that it does not give “improved clinical results” except
under rather narrowly confined circumstances--namely, if the drug
undergoes decomposition in the alimentary tract, if it is not absorbed,
if it causes serious direct local reaction or if time is an urgent
element. Each intravenous preparation for which advantage over oral
administration is claimed, directly or by implication, must be examined
from these points of view.
The Council has recognized intravenous preparations which satisfied
these requirements. It is evident, however, that hexamethylenamin,
sodium iodid and sodium salicylate do not. When given orally they do
not undergo material decomposition in the digestive tract, they are
rapidly absorbed, they cause no direct local reaction, and in the
conditions in which they are used the hour or so which is required for
absorption is immaterial, especially as they are used continuously for
some time. Mercuric chlorid does indeed produce some local irritation,
but there is as yet no convincing evidence that its intravenous
injection causes less injury than oral administration. More experience
under controlled conditions is needed before the intravenous use of
mercuric chlorid can be approved. Especially objectionable are the
fixed proportion mixtures of sodium iodid with sodium salicylate and
with hexamethylenamin. The dosage of all three drugs has to be adapted
to individual conditions. This is impossible when giving them in fixed
proportions.
The Council voted not to accept “Loeser’s Intravenous Solution of
Hexamethylenamin,” “Loeser’s Intravenous Solution of Hexamethylenamin
and Sodium Iodid,” “Loeser’s Intravenous Solution of Sodium
Salicylate,” “Loeser’s Intravenous Solution of Salicylate and Iodid,”
“Loeser’s Intravenous Solution Sodium Iodid” and “Loeser’s Intravenous
Solution of Mercury Bichlorid” for New and Nonofficial Remedies because
they are sold under misleading claims regarding their alleged safety
and efficiency. In view of this fundamental objection the individual
claims for each preparation were not passed on.--(_From The Journal
A. M. A., April 16, 1921._)
“NATIONAL IODINE SOLUTION” NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
“National Iodine Solution” is a proprietary sold by the National Drug
Co., Philadelphia, Pa. From inquiries received by the Council on
Pharmacy and Chemistry it is evident that the product is extensively
brought to the attention of physicians by means of circulars. The name
implies that it is a solution of iodin and the inference is given that
it has the advantages of iodin without the disadvantages.
COMPOSITION
In view of the foregoing, the Council took up the investigation of
“National Iodine Solution,” and in turn asked the A. M. A. Chemical
Laboratory to analyze it. The chemist’s report follows:
According to the label of National Iodine Solution, “each fluidounce
represents three grains Proteo-albuminoid compound of iodin
(National)”; also an alcohol declaration of 7 per cent. is made.
Otherwise no information is given as to the composition either of the
“solution” or of “Proteo-albuminoid compound of Iodine.”
Each bottle contained about 115 c.c. (nearly 4 ounces) of a yellowish
solution, acid in reaction, having an odor resembling witch hazel; its
specific gravity at 25 C. was 0.9860. Qualitative tests indicated the
presence of zinc, alcohol, sulphate, an iodin compound (the solution
gave tests which indicated a very small amount of free iodin; most
of the iodin was in the form of ordinary iodid), a small amount of
vegetable extractives, and traces of aluminum and potassium. If any
protein was present, it was in amounts too small to be identified,
though a small amount of a nitrogenous compound was present. The amount
of solids in “National Iodine Solution” was equivalent to 0.72 per
cent, and the amount of ash, to 0.2 per cent. Quantitative estimations
yielded the following:
Alcohol (by volume) 7.0 per cent.
Zinc (Zn++) 0.096 per cent.
Iodin (free and combined) 0.029 per cent.
Sulphate (SO₄--) 0.146 per cent.
Protein (N × 6.36) 0.012 per cent.
The above findings indicate that each 100 c.c. contains about 7 c.c. of
alcohol, 0.5 gram of zinc sulphate U. S. P. (ZnSO₄+7H₂O.), 0.03 gram
of iodin, 0.01 gram of protein (calculated as such from nitrogen times
the factor 6.36) and some hamamelis water. Expressed in equivalent
apothecary terms, each fluidounce contains essentially:
Zinc sulphate 2-1/3 grains
Iodin (free and combined) 1/8 grain
Protein 1/25 grain
Alcohol 34 minims
This amount of alcohol is equivalent to about 3-1/2 fluidrams of witch
hazel water. Although the label states that each fluidounce contains
three grains of “proteo-albuminoid compound of iodine,” yet the sum of
the protein (calculated from nitrogen content) and iodin components is
equivalent to less than 1/5 grain.
“National Iodine Solution” appears to be very similar to “Gonocol” (The
National Drug Co., Philadelphia, Pa.), which was analyzed by the Bureau
of Chemistry of the U. S. Department of Agriculture. The bureau stated
that “it [Gonocol] consisted essentially of an aqueous solution of zinc
sulphate, hamamelis water, a small amount of alcohol, 0.38 grain of
iodin, and 0.36 grain of protein per fluidounce.”
It is evident that “National Iodine Solution” is not a solution of
free elementary iodin as the name suggests; instead it appears to be
a solution of zinc sulphate in witch hazel water containing less than
0.03 per cent. of combined iodin and _not more than a trace of free
iodin_. “National Iodine Solution” is one more to be added to that
already long list of proprietaries which makes capital of the high
esteem in which physicians hold iodin.
THE CLAIMS
An advertising circular sent to physicians begins:
“_Dear Doctor_: We beg to suggest a line of treatment while using
National Iodine Solution which our many years of experience has
proven to us to give the best and quickest results in the treatment
of inflammation of the urethral tract ...”
In it are given directions for the treatment of “acute gonorrhea,
male,” “anterior urethritis,” “anterior-posterior urethritis,” “ardor
urinæ and chordee,” etc., by means of National Iodine Solution and
other proprietaries of the National Drug Company’s make. In fact the
solution is claimed to be “Indicated in All Conditions of Urethra
Accompanied by a Discharge.”
COMMENT AND CONCLUSIONS
The therapeutic claims made for “National Iodine Solution” are
unwarranted. Such a solution is not indicated in all conditions of the
urethra accompanied by discharge. The advice contained in the circular
is equivalent to mail-order treatment of gonorrhea.
It is of interest to note that the claims for an identical or a
similar solution prepared by the National Drug Company as a treatment
for gonorrhea and intended for use by the laity, has been adjudged
misbranded by the federal authorities (Notice of Judgment No. 8150,
issued Jan. 25, 1921) in that it misled and deceived the purchaser
or purchasers thereof in the statements regarding the therapeutic
or curative effects of the article, which falsely and fraudulently
represent it to be indicated in all conditions of the urethra
accompanied with a discharge, “whereas in truth and in fact it was not.”
The Council would emphasize that if physicians give heed to advertising
such as that sent out by the National Drug Company for this preparation
the medical profession cannot with good grace protest against the
routine treatment of venereal diseases by quacks and “patent medicine”
venders.--(_From The Journal A. M. A., June 4, 1921._)
MON-ARSONE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
Mon-Arsone is offered by the Harmer Laboratories Company as “a new
and non-toxic arsenical for the treatment of syphilis.” In the
advertisements for Mon-Arsone it has been claimed that with this
drug “the toxic, corrosive and uncertain reactions attending the use
of arsphenamine have been entirely eliminated” and that “it has a
therapeutic value equal to arsphenamine, but extensive case reports
fail to record the slightest toxic reaction following its use.”
According to the manufacturers, Mons-Arsone is disodiumethylarsonate,
the sodium salt of ethylarsonic acid, derived from arsenic acid by
replacement of one hydroxyl group by the ethyl group--AsO(CH₂CH₃)(OH)₂.
Mons-Arsone is related to sodium cacodylate, which is the sodium salt
of dimethyl-arsenic acid--AsO(CH₃)₂OH--derived from arsenic acid by
replacement of two hydroxyl groups by two methyl groups. Ethylarsonic
acid and its potassium salt were described by La Coste[139] more than
thirty-five years ago, and the use of the sodium salt of methylarsonic
acid was proposed in France some years ago. The Harmer Laboratories
Company claims originality for Mons-Arsone in that it was the first
to prepare the sodium salt of ethylarsonic acid and to propose its
therapeutic use.
[139] La Coste: Annalen der Chemie (Liebig’s) 208: 34.
It was reported several years ago by Castelli[140] that sodium
cacodylate and the sodium salt of methyl arsenic acid were devoid of
effect on experimental trypanosomiasis and spirochete infections.
Careful clinical observations in this country by H. J. Nichols[141] and
H. N. Cole[142] have demonstrated the inefficacy of sodium cacodylate
in the treatment of human syphilis.
[140] Castelli, G.: Arch. f. Schiffs- u. Tropen-Hyg. 16: 605, 1912.
[141] Nichols, H. J.: Salvarsan and Sodium Cacodylate, J. A. M. A. 56:
492 (Feb. 18) 1911.
[142] Cole, H. N.: A Study of Sodium Cacodylate in the Treatment of
Syphilis, J. A. M. A. 67: 2012 (Dec. 30) 1916.
Animal experiments carried out in the U. S. Hygienic Laboratory by
Voegtlin and Smith[143] show that Mon-Arsone is devoid of any practical
trypanocidal action. Thus the “therapeutic ratio” (the ratio of the
minimal effective dose to the lethal dose) was about 1, that is, it
was effective therapeutically only in approximately fatal doses; the
therapeutic ratio for arsphenamine in similar conditions was 17, and
that of neoarsphenamine, 28.
[143] Voegtlin, Carl, and Smith, H. W.: J. Pharmacol. and Exper.
Therap. 16: 449, 1921.
The findings that sodium dimethylarsenate (sodium cacodylate), sodium
methylarsenate, and sodium ethylarsenate are devoid of any practical
trypanocidal action and the conclusion that sodium cacodylate is
inefficient in the treatment of human syphilis does not prove
that Mon-Arsone is without effect on the disease. These findings,
however, certainly demand convincing therapeutic evidence to warrant
the recommendation for the use of the drug in the treatment of
syphilis--particularly because the drug is proposed as a substitute for
arsphenamine, the value of which is established.
When the Council first took up the consideration of Mon-Arsone, the
only evidence for the claim that it “has a therapeutic value at least
equal to that of arsphenamine” consisted, with one exception, of
reports from those who had experimented with the drug for the Harmer
Laboratories Company, including a report by B. L. Wright, L. A.
Kennell, and L. M. Hussey,[144] the latter of the Harmer Laboratories
Company. These reports appeared to show that the administration of
Mon-Arsone caused less reaction than arsphenamine, and that the
immediate effects, judged by clinical symptoms and the response to the
Wassermann test, appeared to be good. These trials extended over too
short a period of time to permit judgment as to the permanence of the
results. A report by an independent observer seemed to indicate that
Mon-Arsone does not have the sterilizing action on syphilitic lesions
which it is usually believed arsphenamine exercises.
[144] Wright, B. L.; Kennell, L. A., and Hussey, L. M.: M. Rec. 97: 607
(April 10) 1920.
After examining the available evidence, the Council advised the Harmer
Laboratories Company that the claim that Mon-Arsone has a therapeutic
value equal to arsphenamine appeared unwarranted; that, in the opinion
of the Council, Mon-Arsone should not be used except under conditions
that justify the experimental trial of an unproved drug, and should not
be used in a routine way until the permanence of its effects has been
established; and consequently any advertising propaganda for the drug
by the Harmer Laboratories Company was to be deprecated.
In its reply the Harmer Laboratories Company admitted that its
advertising claim, that Mon-Arsone was at least equal to arsphenamine
therapeutically, had been based on reports on fifty cases and on
additional reports that were beginning to come in at that time.
The Harmer Laboratories Company submitted a list of hospitals and
physicians using Mon-Arsone. A letter of inquiry sent by the Council to
those who, according to the names in the list supplied by the Harmer
Laboratories Company, had used Mon-Arsone, brought seven replies.
The clinical evidence contained in these replies was to the effect that
Mon-Arsone had been used in the various types of syphilis and that
there was a certain beneficial effect, both clinically and as shown by
the Wassermann reaction. In certain instances the Wassermann reaction
changed from a four plus to a negative reaction. The reports showed
that the efficiency of Mon-Arsone as compared with that of arsphenamine
preparations has not been adequately studied. One physician who has
used Mon-Arsone extensively reports that in many of the cases treated
there seemed to be nearly as good results from the use of Mon-Arsone as
is frequently obtained in the use of arsphenamine. He reports, however,
that it was necessary in eleven out of one hundred cases to change from
Mon-Arsone to neoarsphenamine.
In view of the fact that there is definite lack of evidence to show
that Mon-Arsone is the equal of arsphenamine therapeutically, and
because of the reports that in some cases it is inferior, Mon-Arsone
should not be used in the treatment of syphilis generally until its
therapeutic status has been more rigidly investigated and conclusive
evidence of its superiority to arsphenamine preparations obtained.
The Council voted not to admit Mon-Arsone to New and Nonofficial
Remedies and reaffirmed its conclusion that the claim that Mon-Arsone
has a therapeutic value equal to that of arsphenamine is premature and
unwarranted; that Mon-Arsone should not be used except under conditions
that justify the experimental trial of an unproved drug; and that the
advertising propaganda for the drug by the Harmer Laboratories Company
is to be deprecated.
* * * * *
When the preceding report was sent to the Harmer Laboratories Company,
the firm submitted a reply in which it was stated:
1. That in certain instances patients improved under Mon-Arsone who,
previously, had not improved under arsphenamine, and that this should
be taken to offset the report of the one hundred cases in which the use
of Mon-Arsone had to be abandoned in 11 per cent. of the cases.
2. That the Harmer Laboratories Company has abandoned the claim that
Mon-Arsone is therapeutically equal to arsphenamine and that it now
furnishes the drug to such men as care to use it simply on the basis of
its special and useful characteristics.
The Council heartily endorses the recent warning against the use
of untried medicaments which was issued by the U. S. Public Health
Service.[145]
[145] J. A. M. A. June 12, 1920, p. 1654.
Since the Council’s report was prepared a report on the effects of
Mon-Arsone on experimental syphilis has been published by Nichols,[146]
from the Division of Laboratories, Army Medical School, which concludes:
1. Disodium-ethylarsinate, or mon-arsone, tested on rabbits infected
with syphilis shows no spirocheticidal power. The tissues are fatally
poisoned as soon as or before the spirochetes are affected.
“2. For its practical use in syphilis there is no such germicidal basis
as exists in case of the arsphenamine group.”--(_From The Journal
A. M. A., June 18, 1921._)
[146] Nichols, H. J.: The Spirocheticidal Value of Disodium Ethyl
Arsenate (Mon-Arsone), J. A. M. A. 76: 1335 (May 14) 1921.
OXYL-IODIDE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
“Oxyl-Iodide” (Eli Lilly and Co.) is said to be the hydroiodid of
cinchophen and the claim is made that it exerts the effects of
cinchophen and of iodid. Because of inquiries which have been received
the Council decided to determine the eligibility of “Oxyl-Iodide” for
New and Nonofficial Remedies. Dr. P. J. Hanzlik--formerly Associate
Professor of Pharmacology at Western Reserve University School of
Medicine, now Professor of Pharmacology at Leland Stanford Junior
University Medical School--who has made a study of the action of
salicylates and cinchophen, was asked to report on the therapeutic
value and the rationality of “Oxyl-Iodide.” This he consented to do and
his report appears below.
After considering Doctor Hanzlik’s report, the Council declared
“Oxyl-Iodide” inadmissible to New and Nonofficial Remedies because it
is an irrational combination, marketed under claims that are unproved
and consequently unwarranted.
W. A. Puckner, Secretary.
“Oxyl-Iodide,” marketed by Eli Lilly & Co., is claimed to be the
hydroiodid of phenylcinchoninic acid, containing 33 per cent. of iodin
and 67 per cent. of phenylcinchoninic acid (cinchophen). Its solubility
resembles that of cinchophen, being low in water and acid mediums, and
higher in the presence of alkalis. Whether “oxyl-iodide” is decomposed
into its constituents in the presence of alkalis does not appear to
have been determined. However, if this were the case, the intestine,
after administration of “oxyl-iodide,” would contain cinchophen and
sodium iodid in the same forms as if these agents were administered
individually so that nothing would be gained by administering
“oxyl-iodide.” Being, like cinchophen, practically insoluble in acid
mediums, “oxyl-iodide” would have no advantage over the latter so far
as gastric irritation is concerned.
DOSAGE
The dosage advised is from one to three tablets containing 3 grains
(0.2 gm.) each of “oxyl-iodide.” The total dosage would depend on
the condition to be treated. In rheumatic fever, which requires a
full therapeutic or so-called, “toxic” dose of cinchophen, about 12
to 13 gm. would be administered intensively. Since each tablet of
“oxyl-iodide” contains 0.13 gm. of cinchophen, the total number of
tablets of “oxyl-iodide” required would be 100, or two and one-half
bottles of forty tablets each. At the same time the patient would
receive 6.6 gm. of iodin (as iodid). This might be distinctly
objectionable because of the production of the disagreeable symptoms of
iodism in some persons, and indicates that the fixed proportion of the
iodin constituent would be objectionable.
Even a smaller dosage, such as 5 gm. of cinchophen, which gives partial
relief in rheumatism and similar conditions, would still require a
patient to take a full bottle, or forty tablets, of “oxyl-iodide,” and
at the same time about 2.7 gm. of iodin would have to be ingested.
Furthermore, rheumatic fever, the arthritides, gout and related
conditions in which cinchophen is indicated do not require iodid.
Therefore, “oxyl-iodide” would not be the remedy of choice in these
conditions, and its use would be irrational and illogical.
ACTIONS
No data on the pharmacologic actions of “oxyl-iodide” are presented
in the manufacturer’s literature. Presumably, the compound would
exhibit the actions of its individual components, i. e., cinchophen and
iodin (as iodid), though probably less efficiently, owing to its low
solubility. This is also indicated by the following statements of the
manufacturer: “The analgesic action of ‘oxyl-iodide’ is gradual. A word
of caution is necessary to those who may expect immediate relief from
pain.” Therefore, why use “oxyl-iodide” in place of more dependable
analgesics, such as salicylate or cinchophen. The following statements
appear far-fetched: “There is a stimulation of the endocrines which
is perhaps more marked in the thyroid gland, although it is probably
shared by the pituitary and other glands which function in a chain-like
control.... There is stimulation of cells with increased flow of
secretion, visibly demonstrated by the nasal mucous membrane after
‘oxyl-iodide’ has been taken for some time. The general action on
mucous membranes favors elimination of toxins and waste products.”
It is probable that “oxyl-iodide” acts as a uric acid eliminant, though
there is no reason to suppose that it is more effective than cinchophen
alone. No data are given for this in the manufacturer’s literature.
USES
Successful use of “oxyl-iodide” is claimed in brachial and sciatic
neuritis, lumbago, muscular rheumatism, arthritis deformans, chronic
arthritis (“... in some instances were apparently cured”), subacute
bronchitis, circumflex neuritis, traumatic orchitis, eczema and
rheumatism. However, a careful reading of the protocols of seven cases,
representing these conditions, gives an unfavorable impression as to
the real contribution to the recovery by, or value received from,
“oxyl-iodide.” Summarized, the opinions as quoted by the manufacturers
in support of their claims for “oxyl-iodide” are briefly as follows:
Case 1. “Of course, the case is not complete yet, but I am looking for
continued betterment.”
Case 2. “For two weeks past her improvement has been marvelous.”
Case 3. “The joints are still enlarged and we do not hope to clear them
entirely....”
Case 4. “Undoubtedly, removal of the kidney had much to do with
improvement.”
Case 5. “I think I have gotten very good results.”
Case 6. “Some apparent benefit.”
Case 7. “She is practically free from pain, and the muscle and joint
stiffness is now slight.”
These inconclusive opinions certainly do not agree with the favorable
impression which other portions of the manufacturer’s literature
create. If the factor of natural recovery in the conditions represented
by these seven cases is given due weight, little, if anything, is
left to the credit of “oxyl-iodide.” Such clinical evidence as is
supplied by the manufacturer indicates that the therapeutic efficiency
of “oxyl-iodide” is doubtful, and not an improvement over either
cinchophen or iodid.
IODISM
Iodism cannot be avoided by the use of “oxyl-iodide,” for the
manufacturer’s literature states that “the dosage of ‘oxyl-iodide’
may be pushed to iodism as manifested by skin symptoms.... To avoid
iodism there should be an occasional interruption of treatment.”
“Oxyl-iodide,” therefore, has no advantage over ordinary sodium iodid
to avoid iodism. Usually, the conditions which require cinchophen
do not require the simultaneous administration of iodids, and vice
versa. If administration of iodid and cinchophen together should be
indicated or desirable, these can be given separately with the added
advantage that the iodid can be easily reduced or withdrawn in case
iodism supervenes, and the cinchophen could be continued if necessary.
Since conditions do not arise frequently enough to warrant the use
of iodid and cinchophen together, the existence of such a product as
“oxyl-iodide” is unwarranted.
Finally, the manufacturer himself recognizes that phenylcinchoninic
acid (cinchophen) can take the place of “oxyl-iodide.” Under
“dosage,” the circular states: “A few patients may be idiosyncratic
to the iodides and find they cannot take ‘oxyl-iodide.’ For the
latter chloroxyl, the hydrochloride of phenylcinchoninic acid, is
recommended.” The action of the hydrochlorid of phenylcinchoninic acid
does not differ, of course, from that of cinchophen. The difficulties
of assigning a clear-cut, definite, therapeutic rôle to “oxyl-iodide”
in order to justify its existence, alongside well-known and tried
remedies are self-evident.
CONCLUSION
“Oxyl-iodide” is pharmacologically and therapeutically an illogical,
irrational and unjustified substitute for cinchophen and iodids. The
conditions which require the administration of cinchophen do not as
a rule require the administration of iodid and vice versa. If it is
desirable to secure the effects of iodid and cinchophen together, these
can be more conveniently and advantageously administered as separate
agents, permitting in that way a better control of their actions. This
cannot be accomplished with “oxyl-iodide,” in which the proportion of
iodid and cinchophen are fixed. Symptoms of iodism cannot be avoided
by the administration of “oxyl-iodide.” The objective evidences for
its actions and uses are totally lacking; and the clinical opinions
concerning its therapeutic benefits in different disease conditions
are inconclusive and hedging, and, if anything, contradictory to the
favorable impressions which the language of the advertising matter is
likely to create.--(_From The Journal A. M. A., July 2, 1921._)
QUASSIA COMPOUND TABLETS
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report,
declaring that Quassia Compound Tablets (Flint, Eaton and Company) are
inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Quassia Compound Tablets, marketed by Flint, Eaton and Company,
Decatur, Ill., according to the label on a trade package submitted to
the Council, contain in each tablet:
Quassia 3/4 grain Aloin 1/4 grain
Chionanthus 1 grain Ipecac 1/16 grain
Wahoo 3/4 grain Podophyllin 1/4 grain
Nux Vomica 1/2 grain Gingerine _q. s._
Cascara 1/3 grain
In the advertising the “Cascara” of the label is replaced by the
indefinite term “Cascarin” and the “Gingerine _q. s._” by “Carminative
Antigripe _q. s._” Flint, Eaton and Company informed the Council that
“Carminative Antigripe is C. P. Sodium Sulphite of which each tablet
contains 1/4 grain.” The tablets were treated with dilute hydrochloric
acid and the odor of sulphur dioxid became apparent. This shows that
the company’s statement to the Council, that the tablets contain a
sulphite, is correct and the formula on the label is incorrect.
In the advertising for this preparation we read:
“A careful study of this formula [which formula? That on the label
or that in the general advertising?--COUNCIL] will reveal the
outstanding fact that, while there are several drugs employed, each
ingredient is there for a purpose and all do splendid teamwork. If
your patient is constipated because the stomach is not sufficiently
energetic, the Quassia stimulates that organ to an increased
secretion of digestive fluids and sets it to working normally.
If the liver be sluggish, the Chionanthus and Wahoo prompt it to
increased activity. Chionanthus has no superior for producing a
sustained healthy hepatic condition. Should the bowels be slow
and uncertain, the small doses of Aloin, Cascarin and Podophyllin
stimulate to free peristaltic action, while the Nux Vomica sets the
nervous system right. We use an effective Antigripe so that there
is no griping.”
It is absurd to suppose that a complex mixture of drugs in fixed
proportions can have the actions claimed for Quassia Compound Tablets.
As regards the claim that “Chionanthus has no superior for producing a
sustained healthy hepatic condition,” it was brought out in a report
of the Council on “Some Unimportant Drugs” (Reports of Council on
Pharmacy and Chemistry, 1912, p. 36) that the “claims for this remedy
[Chionanthus] are not supported by experimental evidence and the
clinical reports of its use fail to show indications of discriminating
critical observation. It is not noticed by most pharmacologic
authorities.”
Of Wahoo (Euonymus N. F.) the “Epitome of the U. S. P. and N. F.”
says: “_Actions and Uses._--Obsolete cathartic; toxic digitalis
effects. _Caption_: the uncertain absorption of this drug makes its use
inadvisable.”
Quassia Compound Tablets (Flint, Eaton and Company) are inadmissible
to New and Nonofficial Remedies because (1) they contain drugs of
unproved value; (2) their composition is needlessly complex, and,
therefore irrational; (3) unwarranted therapeutic claims are made
for them; (4) the name is misleading and not descriptive of their
composition, and (5) the statement of their composition is indefinite
and incorrect.--(_From The Journal A. M. A., July 9, 1921._)
TOXICIDE
Report of the Council on Pharmacy and Chemistry
The Council has authorized the publication of the following report:
W. A. Puckner, Secretary.
Toxicide (Toxicide Laboratories, Chicago) is alleged to be a remedy
which “increases systemic resistance,” is “used for immunizing against
septic infections” and “is indicated in any case of septic infection,
capable of inducing inflammation and pus formation, regardless of
location or kind of tissue involved.” The following statements
bearing on the composition of the preparation are furnished by the
manufacturers:
“Toxicide contains Lachesis 12X, Tarantula 6X, Psorinum (special)
15X, Silicia 6X and Excipient q. s. (the excipient is sweet milk).
“These remedies are combined in the sweet milk and put through a
process of development, which produces the curative agent which we
call ‘Toxicide’ ...
“Put up in tablet form, sugar coated and colored red.”
No information is given as to the proportions, either relative or
actual, of the ingredients. Neither is any information given regarding
the “process of development” to which the mixture is subjected, nor the
amount of the finished mixture which is contained in Toxicide tablets.
The Toxicide Laboratories present the following “theory”:
“In combining these remedies and processing with milk, we develop a
latent immunizing active principle, which usually controls the most
virulently, active, septic infections promptly.”
[Illustration: Photographic reproduction (reduced) of an advertisement
of the “originator” of Toxicide; it ran for many months in the program
of a burlesque theater located in Ruckel’s neighborhood.]
There is no evidence, however, that any effort has been made to
demonstrate the presence of a “latent immunizing active principle” by
scientific methods of modern immunology. The following claims for the
use of Toxicide appear on the label:
“Acne, boils, carbuncles, furuncles and abscesses of the most
virulent types usually begin to show improvement within 4 to 12
hours after beginning administration.
“In badly infected wounds, Toxicide will check the further
destruction of live tissue and should always be given for a few
days before and after operations on pus cases.
“For gunshot wounds and other conditions difficult to sterilize or
drain, Toxicide is the ideal remedy.
“For abscesses existing or threatened in any obscure location, the
middle ear, the mastoid, the frontal or any accessory sinuses,
Toxicide is of inestimable value.
“If administered early, in fractures, compound or simple, or for
laceration and other injuries, inflammation, swelling, soreness and
destruction of tissue will be greatly mitigated.”
In support of these claims there are offered letters from physicians
who have used Toxicide with good results. None of these testimonials
present evidence that the reported effects were due to Toxicide.
The asserted--and highly improbable--action of Toxicide could be
determined only by an extensive series of carefully controlled clinical
trials--and such evidence is entirely lacking. In fact, the claims
appear to have no better basis than the coincidence which is stated to
have led to the discovery of the “remedy”; namely, that a boil on the
neck disappeared shortly after the administration of Toxicide!
The Council finds Toxicide inadmissible to New and Nonofficial Remedies
because (1) the identity and amount of the potent constituent or
constituents have not been furnished; (2) the preparation is advertised
indirectly to the public; (3) the name “Toxicide” is therapeutically
suggestive, and (4) the therapeutic claims, being unsubstantiated by
evidence, are unwarranted.
[Illustration: Photographic reproduction (greatly reduced) of an
advertising circular used some time ago describing the marvels
(alleged) of Toxicide.]
[Editorial Comment.--It seems rather preposterous that a scientific
body, such as the Council on Pharmacy and Chemistry, should have to
waste its time in investigating and reporting on such an obviously
unscientific product as “Toxicide.” So long, however, as there are
physicians who will take preparations of this sort seriously, the
Council feels that it is its duty to report on such products. The
problem, in fact, was well stated in a letter addressed to the
editor some months ago by the secretary of a county medical society
who had just received a visit from a representative of the Toxicide
Laboratories and who sent to The Journal some of the advertising matter
that he had received from the same source. This physician wrote:
“I do not wish to trouble you with this kind of material, usually
deposited safely in my waste paper basket, but the enclosed was handed
to me today by a ‘bird’ who is calling on all the doctors and making
strong statements. When he claimed that ‘Toxicide’ is being used in
the Presbyterian Hospital, Chicago, and that the Council on Pharmacy
and Chemistry is considering it seriously, etc., etc., I wish to know
whether I am missing any real good thing. If it has any real virtue,
I would like to know about it, but if it has not, it seems to me that
something ought to be done to head him off as some doctors are sure to
fall for some of it.”
The Toxicide Laboratories is, apparently, merely a trade name used by
the alleged originator of “Toxicide,” J. F. Ruckel, M.D. According to
our records, Ruckel was born in 1860 and was graduated by the Chicago
Homeopathic Medical College in 1886. He claims to have originated
Toxicide about twenty years ago and to have prescribed it “in over
3,000 cases.” In addition to Toxicide, the Toxicide Laboratories also
put out “Dianasiac for Nymphomania and Satyriasis” and “Somnosine for
Insomnia.”]--(_From The Journal A. M. A., Oct. 8, 1921._)
PIL. MIXED TREATMENT (CHICHESTER)
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report:
W. A. Puckner, Secretary.
“Pil. Mixed Treatment (Chichester)” is a proprietary preparation of
the Hillside Chemical Co., Newburgh, N. Y. It is sold in the form of
pills, each said to contain 1/20 grain of mercuric iodid and 5 grains
of potassium iodid.
In 1907 the Council examined the therapeutic claims advanced for this
preparation and found that they were unwarranted, exaggerated and
misleading. It found, also, many misleading statements in regard to the
product itself. Furthermore, the A. M. A. Chemical Laboratory found the
pills to be “short weight” in potassium iodid content.
At the time that the Council examined Pil. Mixed Treatment
(Chichester), a dermatologist of recognized standing, to whom the
“literature” for this product had been submitted for an opinion, made
the following report:
“Assuming that this pill contains what is claimed for it, one-twentieth
(1/20) of a grain of biniodid of mercury and five (5) grains of
potassium iodid, it presents neither an original nor a very useful
formula.
“The literature furnished by the company abounds in suggestions that
the mixture, as they prepare it, represents some unusual potency which
is not possessed by the ordinary mixture of these same drugs in the
same proportion. These suggestions may of course be dismissed without
consideration. There is nothing mysterious in a mixture of potassium
iodid and biniodid of mercury and this formula is no more entitled
to special consideration than any other pill or tablet of the same
composition prepared by any reputable pharmaceutical firm.
“The formula of this pill, however, does not represent a good
combination. It is offered for use both during the active secondary
period of syphilis and for tertiary lesions. The pill does not contain
enough mercury to be an efficient remedy for secondary syphilis and not
enough potassium iodid to be satisfactory in the treatment of tertiary
lesions. It is neither fish, flesh, fowl, nor good red herring. A
patient with secondary syphilis should not be dosed all the time with
potassium iodid and for the treatment of tertiary lesions he should
have a very much larger quantity of potassium iodid than can be given
in these pills without giving toxic doses of mercury.
“The statement that this pill ‘does not impair the appetite nor disturb
digestion and is well borne by patients who cannot tolerate iodids
otherwise administered’ is a bald claim which cannot be justified by
experience. The most unsatisfactory way of administering potassium
iodid is in solid form. A patient who can stand potassium iodid in pill
form, as it is furnished in this preparation, can stand it in any form
in which it is ever administered.
“In short this preparation is neither agreeable nor efficient. The
greatest objection to it is its inefficiency, for it is offered as
an adequate preparation for the treatment of syphilis in all of its
stages, whereas it is neither satisfactory for the treatment of
secondary syphilis nor of tertiary lesions.”
During the fourteen years which have elapsed since the Council’s first
examination of Pil. Mixed Treatment (Chichester), arsphenamin has
been added to the syphilographer’s armamentarium and much has been
learned about syphilis and its treatment. While there exist differences
of opinion as to the exact value of arsphenamin in the treatment of
syphilis and there are even some who desist from the use of arsenic
compounds of any kind, no syphilographer of standing countenances the
routine treatment of syphilis with a fixed combination of mercuric
iodid and potassium iodid. The use of Pil. Mixed Treatment (Chichester)
is on a par with the use of certain “blood purifiers” which were
advocated at a time when the treatment of syphilis was a baffling
problem.
PRESENT DAY CLAIMS
The present advertising, which reads as if it had been written in the
heyday of proprietary license, is, in effect, an invitation to treat
syphilis in its various stages and manifestations with Pil. Mixed
Treatment (Chichester). If heeded by those who read the advertising of
the Hillside Chemical Co., it will result in much harm to the public
and the profession. For this reason, the present report of the Council
is published as a protest against any advertising propaganda advocating
the routine treatment of a disease which requires that each case be
studied carefully so that prompt and efficient measures may be applied
to the various manifestations of the disease.
The following advertisement appeared recently in several medical
journals:
“Medicine is an Exact Science--on Paper Only!” Every general
practitioner of medicine is called upon to treat Syphilis
occasionally. He cannot depend upon the use of arsenicals alone.
In most cases, “mixed treatment” the giving of mercury and iodides
is required to get satisfactory results. PIL. MIXED TREATMENT
(CHICHESTER) accurately and successfully meets the indications and
assures definite action. Important advantages:
Ready solubility of mercury in combination with Potassium Iodide.
Avoidance of gastric, buccal or intestinal disturbance.
Easy administration, can be taken at any time, anywhere.
Economical, both drugs in one combination.
Accurate adjustment of dosage to each individual case.
Full physiological action--assured by purity of content.
Secrecy--patient or friends do not know nature of medicine. Pil
Mixed Treatment (Chichester) has been time tested and trial proven.
It needs no introduction to the thousands of physicians who
prescribe or dispense it.
While the advertisement does not directly so advise, yet it is a
subtle invitation to the general practitioner to use Pil. Mixed
Treatment (Chichester) and thus save himself and his patient the time
and inconvenience which the rational treatment of syphilis imposes. A
circular “The Treatment of Syphilis Simplified and Improved” begins:
“No therapeutic fact is more conspicuously and decisively
established than that a radical cure of syphilis can be effected by
the continuous administration, from the period of development, of a
proper combination of mercury with iodine.”
Continuing, it is admitted that mercury is the most efficacious drug in
the primary and secondary stages of syphilis and iodin in the tertiary
stage, but it is asserted that:
“... it is now granted by all syphilologists that the antiluetic
action of these drugs is immeasurably augmented by properly
combining them, and that the best results are obtained when they
are conjunctively administered throughout the entire course of the
disease.”
Arguing along the same lines, this circular continues:
“... it was not until mercury and iodine in the form of Pil. Mixed
Treatment (Chichester) was evolved that the marked advantages of
the combined employment of these drugs in the various stages of
syphilis became a scientific certainty.”
Further we are asked to believe that:
“Because of the greatly increased potency of mercury and iodine
when combined, as in Pil. Mixed Treatment (Chichester), the
foremost syphilologists are now agreed that the employment of
these drugs in such form should be enjoined as soon as the disease
develops, and should be thus continued until a cure has been
effected; in other words, Pil. Mixed Treatment (Chichester) should
be made the sole antisyphilitic medication throughout all stages of
the disease.”
The circular illustrates the extent to which our knowledge of drugs may
be distorted and misrepresented and the public health jeopardized in
the exploitation of a proprietary medicine.
[Illustration: One reason scientific medicine lags. Uncritical medical
journals perpetuate--for a price--the use of nostrums.]
PROPRIETARY CLAIMS
In its advertising, the Hillside Chemical Co. claims that Pil.
Mixed Treatment (Chichester) both as to formula and method of
preparation “in the incapsulated powder form” was “brought to the
notice of the profession by Dr. W. R. Chichester of New York, an
eminent Syphilographer and recognized authority in the therapeutics
of Syphilis.” It is claimed that this pill “is perfectly soluble,
tasteless, nonirritant, and therefore well adapted to a sensitive
stomach.” It is claimed that the pill “is always preferable to one
extemporaneously prepared, which, even if identical in composition,
often gives negative results.”
An examination made in the chemical laboratory of the association to
determine if the product now marketed contains the claimed amount of
potassium iodid indicated that this was the case. The chemist who made
this examination commented as follows on the claim that in this pill,
potassium iodid is rendered tasteless, that the pill is “perfectly
soluble” and that extemporaneous pills of “identical ... composition
often give negative results.”
“That the potassium iodid has been rendered tasteless is false,
naturally; the pills when placed in the mouth, after removal of the
coating, have the characteristic taste of alkali iodids. The claim
that the pills are entirely soluble is incorrect; they contain a large
amount of insoluble material, probably kaolin. The assertion that an
extemporaneous compound prescription even if identical in composition
with the Chichester pill is often inert, is absurd and a reprehensible
attack by suggestion of the ideal that the physician shall write his
prescription to meet the individual needs of his patient and that the
pharmacist shall compound the prescriptions of the physician as they
are required. It should also be pointed out that while much is said
about the potassium iodid in the Chichester pill being in powdered
form, the pill mass is solid and very slowly soluble and the claim of
being in powdered form is, if immaterial, also incorrect.”
As to the asserted standing of the alleged discoverer of the formula
for Pil. Mixed Treatment: Dr. William R. Chichester appears to have
lived and practiced in New York since 1886 or longer, but the claim
that he is an “eminent syphilographer” seems to have originated with
the exploiters of “Pil. Mixed Treatment.” Search failed to show the
name of W. R. Chichester among authors of textbooks of syphilis or any
other branch of medicine or among authors of contemporary literature in
the _Index Medicus_ from 1907 down to the present; nor did a search of
the catalogue to the Surgeon-General’s Library reveal W. R. Chichester
as ever having published anything on syphilis or any other subject.
Pil. Mixed Treatment (Chichester) is sold under therapeutic claims
which are unwarranted and misleading. The preparation well illustrates
the abuses which are connected with the exploitation as proprietaries
of established drugs or mixtures of established drugs.--(_From The
Journal A. M. A., Oct. 22, 1921._)
ATOPHAN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
explaining why Atophan has been omitted from New and Nonofficial
Remedies. Schering and Glatz, Inc., the firm which markets this
brand of cinchophen in the United States, has refused to place
either the U. S. Pharmacopeial name, “Phenylcinchoninic Acid (Acidum
Phenylcinchoninicum)” or the N. N. R. name, “Cinchophen,” on the label
and in the advertising matter so as to make the identity of the product
clear to physicians. Furthermore, the product is sold under therapeutic
claims which the Council holds to be exaggerated and unwarranted.
W. A. Puckner, Secretary.
COMMERCIAL HISTORY OF CINCHOPHEN
The substance, 2-phenyl-quinolin-4-carboxylic acid, was described by
Doebner and Gieseke in 1887 (_Ann. d. Chem._ [Liebig’s] =242=:291). The
therapeutic properties of this compound were described by Nicolaier and
Dohrn in 1908 (_Deutsch. Arch. f. klin. Med._ =93=:331). Subsequently
the product was placed on the market and extensively advertised by the
Chemische Fabrik auf Actien (vorm. E. Schering), Berlin, Germany. This
firm also took out a patent in the United States on its production
and in 1911 secured a U. S. trademark on the name “Atophan.” In
1912 Atophan was passed on by the Council and admitted to New and
Nonofficial Remedies.
When the government of the United States took charge of German-owned
patents during the World War, the Federal Trade Commission, and
later the Chemical Foundation, Inc., issued licenses to American
firms whereby these were authorized to manufacture the compound.
In the meantime, Schering and Glatz, Inc., who had been the U. S.
representatives for the Chemische Fabrik auf Actien, also undertook to
supply the drug, but did not obtain a license from the boards in charge
of German patents. Also, this firm secured, in 1919, a trademark of the
word “Atophan,” apparently after the German-owned trademark had been
canceled.
The drug “Atophan” was admitted to the U. S. Pharmacopeia as
“Phenylcinchoninic Acid (Acidum Phenylcinchoninicum).” As this name
proved too cumbersome, the Council on Pharmacy and Chemistry coined the
abbreviated name “Cinchophen” for it, and this name is now used by all
the firms which are marketing the product in the United States, with
the exception of Schering and Glatz, Inc., who use the term “Atophan,”
first owned by the Chemische Fabrik auf Actien.
ATOPHAN, A BRAND OF CINCHOPHEN
Because of the confusion which is bound to arise from giving various
names to one drug, the Council selects a common name and provides
standards of identity, purity and strength for any drug which, by
reason of the absence or lapse of patent rights or for other reason,
is open to manufacture by more than one firm. The Council, then, will
accept such article only if it is marketed under the title adopted
for New and Nonofficial Remedies. The rules provide, however, that
when the Council adopts a common name for an article that has been
admitted under another name, such article will be retained in New and
Nonofficial Remedies under the older name if the Council name is given
prominence on the label and in the circulars and advertisements, in
order to avoid confusion. Accordingly, when the period of acceptance
for Atophan in New and Nonofficial Remedies was about to expire,
Schering and Glatz were notified that Atophan could be retained in
that publication only on condition that the name, “Cinchophen,”
or else the pharmacopeial name, “Phenylcinchoninic Acid (Acidum
Phenylcinchoninicum)” be placed on the label and used in the circulars
and advertising.
UNWARRANTED THERAPEUTIC CLAIMS FOR ATOPHAN
At the time that the Council asked Schering and Glatz to adopt
cinchophen or phenylcinchoninic acid as a synonym for Atophan, the
firm was also requested to omit from future advertising a number of
therapeutic claims to which the Council was obliged to take exception.
Schering and Glatz refused the first request and made no definite
promise with regard to the second. The Council, therefore, directed the
omission of Atophan from New and Nonofficial Remedies, 1921.
The advertising to which the Council took exception does not appear to
be distributed at present. A pamphlet has been sent out, however, which
is equally objectionable. It contains unwarranted therapeutic claims
and suggests that Atophan be used in conditions in which it is not
indicated. For instance:
“No longer the vague, hypothetical, ‘test-tube demonstrated’
principle of uric acid elimination by solution, but a definite,
scientifically and clinically established, physiologic stimulation
of the uric acid excretion. Performed innocuously and controllable
to a nicety by dosage and by urine and blood tests.”
The “innocuousness” of Atophan has not been proved; on the other
hand there is evidence that it is not innocuous, as the recent
investigations of Hanzlik and Scott and their collaborators
(Cinchophen, Neocinchophen and Novaspirin in Rheumatic Fever,
J. A. M. A. 76: 1728 [June 18] 1921) show that it may injure the
kidney.
The circular also contains the following:
“No longer, hit and miss relief of pain at the expense of the
heart, the intestines, the kidneys and the nervous system, but
the promptest and most reliable analgesic, anti-inflammatory and
decongestive action so far known, with notable freedom from heart
depressant, renal irritant, constipating and cumulative toxic
by-effects. No contraindications, except chronic nephritis and the
presence of kidney concretions.”
This is misleading. The drug depresses the circulation, injures the
kidney and produces symptoms of salicylism or “toxicity.” It is _not_
the promptest and most reliable analgesic; morphin is superior and
salicylate is just as efficient. The phrase “decongestive action” is
vague. Treatment of pulmonary congestion from phosgene, and congestion
of the conjunctiva in mustard oil chemosis of cats, with large doses
of Atophan was ineffective; in fact, it proved distinctly harmful.
This was shown by such workers as Laqueur and Magnus, and Heubner
and Gildemeister (_Ztschr. f. d. ges. exper. Med._ =13=:200, 1921). It
is incorrect to ascribe “decongestive” or “anticongestive” action in
the true sense to Atophan (cinchophen). The principal assets of the
salicylate-cinchophen class of drugs in the treatment of rheumatism and
gout are their analgesic and antipyretic qualities.
The claim is made:
“In Rheumatic and Gouty Disorders, whether of the well-known
muscular and arthritic type, or their Eye, Ear, Nose and Throat
manifestations.”
The suggestion that Atophan is indicated in “their Eye, Ear, Nose and
Throat manifestations” is a vague generalization without definite
meaning, but nevertheless calculated to impress physicians and promote
the sale of Atophan for common and minor ailments. Rhinitis and sore
throat are, of course, self-limited conditions which require chiefly
good habits, personal and general hygiene as prophylactic measures,
and simple hot baths with rest, instead of medication, for symptomatic
relief. When it comes to ear and eye conditions, Atophan certainly
would do no good in otitis media, panophthalmitis, choroiditis,
retinitis, etc.
The administration of Atophan is proposed “in Migrains, Hemicrania,
Eyestrain, etc., often vaguely grouped as ‘Headaches.’” Eyestrain and
headaches are vague symptoms often arising from numerous causes that
require no medication, but rather good habits, hygiene and similar
corrective measures. There is always the possibility of habituation
from the use of drugs for such common and vague symptoms, resulting
eventually in more harm than good to the patient.
The use of Atophan is proposed “In Influenza (Grippe) for the ready
alleviation of the respiratory congestion, pain and stiffness of
limbs and back.” Probably the entire claim is without warrant, since
influenza is a self-limited disease. Atophan might relieve pain in
the joints, reduce the fever, etc., but at the same time it would
tend to impair the functional efficiency of the heart, which may be
impaired already by the disease. Cardiac failure is one of the causes
of death in influenza. The recommendation for “alleviating respiratory
congestion” is certainly without warrant, since in actual trial
in pulmonary congestion by Magnus et al., Atophan was found to be
deleterious and not beneficial. Phosgenized cats are probably as good a
test object for the alleged decongestive action of Atophan as anything
could be, since, according to Underhill and Ringer (J. A. M. A.
=75=:1531, 1920) the pathological physiology of the circulation and
respiration in phosgene poisoning and influenza are nearly identical.
Further, Atophan is recommended “In Pyorrhea Alveolaris as a systemic
support to local and specific measures.” Atophan is not indicated here.
Pyorrhea requires local medication, if anything at all. It could exert
no local beneficial effects in this condition; indeed, the employment
of Atophan might lead to irritation. Good dental treatment is more
essential than medication.
Finally, Schering and Glatz advise Atophan “In Eczema, Pruritus
and similar irritant and itching Skin Diseases with lowered blood
alkalinity.” The assumption that blood alkalinity is lowered in
irritant and itching disease is unsupported by evidence in medical
literature and the recommendation is incorrect and misleading. Neither
does Atophan alter the reaction of the blood. Amelioration in these
capricious conditions occurs without medication so that any relief
that might be obtained could not be attributed to Atophan. The entire
paragraph is misleading and will undoubtedly tend to extend the use of
Atophan in conditions for which it is not suited.--(_From Reports of
Council on Pharmacy and Chemistry, 1921, p. 8._)
UROTROPIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Urotropin is a proprietary name applied to the substance which is known
in chemical literature as hexamethylenetetramin and which is designated
hexamethylenamine in the U. S. Pharmacopeia. The Council has authorized
publication of the following report explaining that Urotropin
was omitted from New and Nonofficial Remedies because Schering &
Glatz, Inc. (the firm that markets this brand of hexamethylenamin
in the United States), refused to place the U. S. Pharmacopeia
name Hexamethylenamine (hexamethylenamina) on the label and in its
advertising so as to make clear to physicians the identity of the
product, and, furthermore, because it was sold under therapeutic claims
which the Council held unwarranted.
W. A. Puckner, Secretary.
Commercial History of Hexamethylenamin
This substance which is generally referred to in chemical literature as
hexamethylenetetramin, the cyclic condensation product of formaldehyd
and ammonia, appears to have been described first in 1860 (Butlerow:
_Ann. d. Chem._ =115=:322, 1860). Subsequently, numerous references to
the preparation, properties and constitution of the substance appeared
in chemical literature.
Hexamethylenetetramin is said to have been first used for therapeutic
purposes by G. Bardet, who, in 1894, reported to the Société de
Thérapeutique that he believed this substance to be a uric acid
solvent. At about the same period, A. Nicolaier, who gave Bardet credit
for suggesting the use of hexamethylenetetramin as a uric acid solvent,
announced the discovery of its antiseptic action (_Centralbl. f. d.
med. Wissensch._ =32=:897, 1894; _Deutsche med. Wchnschr._ =21=:541,
1895). Shortly thereafter as a result of Nicolaier’s publication, the
Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, Germany, began
to offer the product to the medical profession under the trademarked
and nondescriptive name “Urotropine.” In the United States, it was
marketed by Schering and Glatz, who then were acting as American agents
for the Schering works of Germany.
It soon became evident that hexamethylenetetramin was a valuable
drug. As the substance was introduced at a time when new “synthetic”
drugs were rapidly appearing and when unlimited and uncritical
confidence was placed in them, and before the medical profession became
skeptical of the claims advanced by manufacturers for their respective
“discoveries,” it was not long before this new drug was placed on the
market by many firms, each applying its own name and often keeping the
chemical character of it in the background. Some of the names which
were thus applied to hexamethylenamin were Cystogen, Aminoform, Formin,
Uritone, Urisol, {and} Cystamine.
In 1907 the late Prof. J. O. Schlotterbeck, then a member of the
Council, protested against the confusion caused by the marketing of a
given drug under different names. He stated that it was not uncommon
for a physician to prescribe two or more of these identical substances
in the same mixture, expecting to get the combined action of different
urinary antiseptics; also, that patients had been treated first with
hexamethylenamin under one name and later by the same substance under
another name (The Journal, Jan. 19, 1907, p. 241).
Hexamethylenetetramin was admitted to the eighth revision of the
U. S. Pharmacopeia. In part because of this official recognition
and standardization and in part because the extravagant reports of
its virtues had been largely discounted, physicians have in general
prescribed the drug by its pharmacopeial name, with one notable
exception: Urotropin. One reason for this is that Urotropin was the
first proprietary brand of hexamethylenetetramin introduced, a second
reason is that through the extensive and persistent advertising of
the proprietary name under which the substance was introduced, it has
become firmly fixed in the minds of many physicians. The other is that
the product was claimed to be of greater purity than the product sold
under the pharmacopeial or other name although no evidence confirmatory
of this claim has ever been published. On the other hand, Daniel
Base, as long ago as 1907, found that hexamethylenamin sold under its
pharmacopeial name is just as pure as when sold under proprietary
names. When, in 1907, urotropin was admitted to New and Nonofficial
Remedies, the published description showed that it was manufactured
by the Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, and
that Schering and Glatz were the United States agents. In 1919, the
description was revised to show that Schering and Glatz were no longer
selling the German product.
As it is the general practice to omit articles that are admitted to
the U. S. Pharmacopeia for the reason that their quality is guaranteed
under the federal Food and Drugs Act and because pharmacopeial
nonproprietary articles are rarely advertised with claims that require
the Council’s control, yet, in the case of Urotropin, it was retained
because it was sold under a name not recognized in the pharmacopeia and
because special (proprietary) claims were made for it.
Urotropin Marketed Under Unwarranted Therapeutic Claims
The period for which Urotropin stood “Accepted” expired with the close
of 1921. To determine its continued eligibility for New and Nonofficial
Remedies, the Council examined the labels and circular matter sent by
Schering and Glatz for the purpose and also a booklet “Urotropin,”
subsequently sent by the firm to physicians.
It was found that the pamphlet contained a number of unwarranted
statements. Particularly objectionable are the claims made for the use
of Urotropin as an antiseptic in body fluids that are alkaline, such as
the cerebrospinal fluid, bile, aqueous humor of the eye, saliva, the
excretions caused by middle ear infection and other excretions of the
nasal, bronchial, laryngeal and mucous membranes. The lack of efficacy
of hexamethylenamin in alkaline secretions is generally admitted and
the clinical references to the use of hexamethylenamin in the pamphlet
are obsolete. In the introduction to the pamphlet, Schering and Glatz
state that they are well acquainted with the scientific research work
discrediting the efficiency of hexamethylenamin in nonacid mediums,
but that they feel that the accumulated evidence for its efficacy in
such conditions should not be “brushed aside.” However, the pamphlet
is not made up of quotations, but of unqualified statements. With one
exception, all references to the antiseptic properties of the drug in
alkaline mediums are previous to 1913, that is, before the importance
of reaction of the medium was fully appreciated. To quote these
earlier articles without regard to the later work, which in most eyes
discredited them, constitutes in effect an exploitation of this brand
of hexamethylenamin under unwarranted therapeutic claims.
Urotropin a Brand of Hexamethylenamine, U. S. P.
In consideration of the confusion which arises from the application
of different names to an identical article, the rules of the Council
provide that when an article which has been accepted for New and
Nonofficial Remedies is admitted to the U. S. Pharmacopeia under
another name, it will be retained, provided the official name is
given prominence on the label and in the advertising of such article.
Neither the label nor the advertising for Urotropin gives prominence
to the pharmacopeial name as a synonym nor indeed does it bring out
the fact that Urotropin is a brand of hexamethylenamine, U. S. P.
Schering and Glatz, Inc., was advised that Urotropin could be retained
in New and Nonofficial Remedies only on condition that the objections
to the therapeutic recommendations were removed and on agreement that
the U. S. P. name appear on the labels and circular matter. The firm
did not offer to make the product eligible for continued recognition;
accordingly the Council directed the omission of Urotropin because of
conflict with Rule 6 (Unwarranted Therapeutic Claims) and with Rule
8 (Objectionable Names).--(_From Reports of Council on Pharmacy and
Chemistry, 1921, p 71._)
STYPTYSATE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report,
declaring Styptysate (Ernst Hischoff Co., Inc.) inadmissible to New and
Nonofficial Remedies.
W. A. Puckner, Secretary.
Styptysate, according to the advertisement of Ernst Bischoff Co., Inc.,
New York, is “obtained by dialysis from Bursa Pastoris (Sheppard’s
[_sic!_] Purse).” It is claimed to be “The Remedy For Hemorrhages,”
to be “Superior to Ergot and Hydrastis,” “of particular advantage
in Menorrhagia and Metrorrhagia” and to have been “found of great
value in vesical hemorrhages and hemorrhages from mucous membranes in
general.” The Styptysate label bears the synonym “Dialysate Herba Bursa
Pastoris”; the statement that it contains “alcohol 11 per cent.” and
that it is “made in Germany.” No other statement of the composition or
strength of “Styptysate” is furnished nor is the name of the German
manufacturer disclosed.
In an advertising circular entitled “Styptysate, a New Reliable
Hemostatic,” it is declared that in recent years the plant, Shepherd’s
Purse (_Capsella bursa pastoris_), “has been submitted to clinical
tests in the form of a concentrated dialysate, known as Styptysate,
by Loewy, Oppenheim, Krummacher and others, and that their reports
coincide in regard to Styptysate as a hemostatic _par excellence_,
particularly in uterine hemorrhages, even in cases where ergot and
hydrastis had failed to produce satisfactory results.” The circular
also reprints some “short clinical reports” without reference to their
authorship; one ascribed to Krummacher and two ascribed to “B.H.M.,
Kansas City, Mo.,” and the following references: “A. Krummacher, M.D.,
_Monthly Review for Obstetrics and Gynecology_, Berlin, Vol. XLIX, 4,
and Vol. LII.” “H. Oppenheim, M.D., _Medical Clinic_, Berlin, 1920, 35.”
Shepherd’s Purse is a weed common in the United States and in Europe.
Like most other herbs, it has some reputation as a folk medicine. It
is used by eclectics and homeopaths, being included in the Homeopathic
Pharmacopeia of the United States. Shepherd’s Purse receives no
consideration at the hands of the authors of standard works on materia
medica, pharmacology or therapeutics.
From an examination of recent German medical publications, it appears
that the use of Shepherd’s Purse was proposed as a substitute for
ergot and hydrastis, when the latter drugs became scarce in Germany.
These publications, in the main, emanate from those in the employ of
pharmaceutical firms and deal with proprietary preparations or they are
written by physicians who used these proprietary preparations at the
solicitation of the manufacturers. For this reason the reported results
must be accepted with reserve.
One of the proprietary preparations discussed in the German
publications is Styptysate, manufactured by Isalfabrik Johannes
Buerger, Wernigerode. It is said to be produced by submitting the juice
of fresh Shepherd’s Purse to dialysis and preserving the dialysate
by the addition of alcohol. There is no statement as to the drug
strength or the chemical or biological standards, if any, used in
its manufacture; hence, the preparation is essentially a secret one.
As first produced, the preparation seems to have been fortified by
the addition of cotarnin: the dose was then given as ten to fifteen
drops. Later, as the cost of cotarnin went up, this drug was omitted,
and the drug strength increased; the dose of the new preparation is
given as twenty-five to thirty drops. Just what relation, if any, the
Styptysate of Ernst Bischoff Co., Inc., bears to that of the Isalfabrik
Johannes Buerger, Wernigerode, cannot be determined from the Bischoff
advertising. If it has any relationship the announcement that no
narcotic order is required when ordering Styptysate would indicate
that the new preparation is supplied; the old one with its addition
of cotarnin would require a narcotic order. On the other hand, the
recommended dose of the cotarnin-free preparation is twenty-five to
thirty-drops, whereas the product sold by Bischoff and Co. is to be
given in doses of ten to fifteen drops--that is, in the amount proposed
for the cotarnin-fortified product.
What justification is there for the claim that Styptysate has been
submitted to clinical tests by Loewy, Oppenheim and Krummacher and
found to be a hemostatic _par excellence_ and efficient even where
ergot had failed to give satisfactory results? Loewy (_Zentralblatt
für Gynäcologie_ =42=:920, 1921) made some pharmacologic tests on
guinea-pigs with the cotarnin-containing preparation, but reported no
clinical trials. Hans Oppenheim (_Medizinische Klinik_, Aug. 29, 1920,
p. 906) reported that he was agreeably surprised at the excellent
results (_vorzueglichem Erfolg_) obtained with the drug but he did not
assert that it is superior to ergot.
Krummacher reported on thirteen cases of profuse menstruation in
which the patients were treated with Styptysate, using for a part,
the preparation containing cotarnin and for the other a preparation
without cotarnin. He reported as good results with the cotarnin-free
preparation in larger dosage, as with the cotarnin-containing
preparation in smaller dosage. Krummacher did not compare Styptysate
with ergot. Some of Krummacher’s cases are quoted, with some
typographical errors, in the Bischoff circular.
On the assumption that the product discussed in German publications
is the Styptysate marketed in the United States, the best that can be
said for it is, that during a shortage of ergot it was used in place
of that established drug. There is no evidence to warrant the use of
this indefinite proprietary in place of the biologically standardized
fluidextract of ergot or other standardized ergot preparations.
Styptysate (Ernst Bischoff and Co., Inc.) is inadmissible to New
and Nonofficial Remedies because its composition is semisecret and
indefinite and there is no evidence that its uniformity and strength
is controlled (Rules 1 and 2); further, it is inadmissible because the
therapeutic claims advanced for it are exaggerated and unwarranted
(Rule 6) and because there is no evidence that it possesses any
advantage over established drugs such as the biologically standardized
fluidextract of ergot or the definite ergot preparations admitted to
New and Nonofficial Remedies.--(_From The Journal A. M. A., Feb. 11,
1922._)
LIPOIDAL SUBSTANCES (HOROVITZ) NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
declaring Lipoidal Substances (Horovitz) inadmissible to New and
Nonofficial Remedies because its composition is essentially secret
and because the curative claims made for it are unsubstantiated and,
therefore, unwarranted.
W. A. Puckner, Secretary.
In the advertising of the Horovitz Biochemic Laboratories Co. (A. S.
Horovitz, president) we read:
“Horovitz proves by careful paralleled investigations of normal
and of pathological tissues, both in addiction disease and in
other diseases, that in patients suffering from narcotic addiction
disease there is an inactivity of the lymph-glands due to the
use of the drug and that the system is not supplied with the
necessary fats.” “Horovitz further found that the lipoidal content
of the cerebro-spinal system varies in strict accordance with the
pathological processes introduced by infection or by alkaloids.
Furthermore, he has found that the lipoids of various other organs,
as well as those of the THERMORnervous system, may be extracted and
consumed by the administration of narcotic alkaloids.”
It is further stated in the advertising that:
“After a long and very careful research investigation, Dr. Horovitz
worked out a method of rational treatment for narcotic addiction
disease which involves the restoration of the lipoids, which have
been lost through the action of the drug, and of the toxins, by
means of a combination of lipoidal substance from various plant
lipoids in the form of a sterile solution. This preparation not
only replaces the lipoids lost by the tissues, but also protects
the nerve tissues, from attacks by the toxins elaborated during the
use of narcotics, and, this by detoxicating the tissues, brings
about permanent freedom from the craving of narcotics, instead of
the temporary relief afforded by other methods of treatment.”
The “combination of lipoidal substance of various plant lipoids” which
was worked out by Horovitz, the Horovitz Biochemic Laboratories offer
as “Lipoidal Substances.” This preparation is supplied in ampoules said
to contain 1 c.c. of solution. The treatment with “Lipoidal Substances”
consists, first, in the complete withdrawal of the narcotic; second,
in free catharsis; and third, in the intramuscular injection of the
preparation. The initial dose is given as 8 to 12 minims repeated with
increase of 3 to 4 minims every three hours during the first day. On
the second, third and fourth day 16 minims is to be given twice a day
and “from the fifth day until the medication is stopped (usually 28 to
35 days) it will be necessary usually to give but 1 injection of 16
minims each day.”
In a request for the admission of its preparation to New and
Nonofficial Remedies, the Horovitz Biochemic Laboratories Co. stated:
“The composition of Lipoidal Substance is (_a_) Lipoids of plant
origin, (_b_) Vitamines (water soluble) of plant origin, (_c_)
Non-specific plant proteins, (_d_) Preservatives--None.”
While the communication abounded in generalities, it gave neither
the identity nor character of the lipoids, of the vitamins nor of
the nonspecific protein, nor their quantities or methods for their
control. The firm presented no evidence that the injection of “Lipoidal
Substances” produced any effect other than by suggestion. Also,
while a long list of references to publications bearing on lipoids
was submitted (many of which had no bearing on the subject under
consideration) there was no reference to the work of Horovitz quoted in
the firm’s advertising.
After examining the information which had been submitted, the Council
requested the manufacturer to supply:
1. Information as to the character (identity) of the several
ingredients contained in the preparation that it marketed, the amount
of each ingredient so far as known and the method used for their
control.
2. Evidence that the administration of “Lipoidal Substances” is of
value in the treatment of drug addiction.
3. Evidence for the claims that the “researches” of Horovitz have
proved that “in patients suffering from narcotic addiction disease
there is an inactivity of the lymph-glands ... and the system is not
supplied with the necessary fats” and that “lipoidal content of the
cerebro-spinal system varies in strict accordance with the pathological
processes introduced by infection or by alkaloids” and that “the
lipoids of various other organs as well as those of the nervous system,
may be extracted and consumed by the administration of narcotic
alkaloids.”
The Horovitz Biochemic Laboratories replied that the requested
information would be supplied in about _two weeks_. At the expiration
of _three months_ the promised information and evidence had not been
received; neither had any reports to show the value of the treatment
come to the attention of the Council. The Council, accordingly,
declared “Lipoidal Substances” (Horovitz Biochemic Laboratories)
inadmissible to New and Nonofficial Remedies because the composition is
essentially secret and because the curative claims are unsubstantiated
and unwarranted.--(_From The Journal A. M. A., Feb. 25, 1922._)
YEAST PREPARATIONS AND VITAMIN B CONCENTRATES
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following principles as a guide in the
consideration of yeast preparations and vitamin B concentrates for New
and Nonofficial Remedies.
W. A. Puckner, Secretary.
1. The claim that deficiency of vitamin B and diseases resulting
therefrom are common conditions in the United States is not at this
time supported by adequate acceptable evidence.
2. The claim that yeast preparations or extracts are, in principle
or in general, essentially more effective or more practical or more
available means of administering vitamins than the commonly available
vitamin-containing foods is not at this time supported by adequate
acceptable evidence. (Any claims for superiority made for such products
proposed for inclusion in New and Nonofficial Remedies must be
presented in detail and passed on specially by the Council.)
3. The claim that therapy with yeast or yeast preparations has as yet
more than an experimental status is not at this time supported by
adequate acceptable evidence.
Preparations for which such claims are made, directly or by implication
or in one-sided quotations, in advertisements or letters or by
salesmen, cannot be admitted to or retained in New and Nonofficial
Remedies.--(_From The Journal A. M. A., April 15, 1922._)