Chapter XXVI: Appendix (7)

EXPERIMENT 1.--_1.56 c.c._; injected VI.24.19: Rather restless for an
hour. Active during next four hours and following twenty-four. Eats
well, reflexes good. Acts normal on VII.1.19 and since VI.26.19.

EXPERIMENT 2.--_3.75 c.c._; injected VI.24.19: More quiet; active
during next twenty-four hours. Reflex all right. Eats well; normal
VII.1.19, since VI.26.19.

EXPERIMENT 3.--_5 c.c._; injected VI.24.19: Quiet; defecation in four
hours. Rather quiet for six hours. Eats well. Reflexes good; normal
VII.1.19, since VI.26.19.

EXPERIMENT 4.--_6.25 c.c._; injected VI.24.19: Quiet and breathing
labored in four hours; active after twenty-four hours. Eats well.
Somewhat depressed on VI.26.19; pain reflex present. On VI.26.19,
eats well and fairly active. Active and eats, VI.27.19. Appears
normal, VII.1.19.

EXPERIMENT 5.--_8.75 c.c._; injected VI.30.19: Rather quiet during
next two hours. Morning of VII.1.19, lies on stomach; quiet; does not
eat very much. Pain reflexes good. VII.2.19, still depressed; does
not eat. Appears normal, VII.3.19.

EXPERIMENT 6.--_12.5 c.c._; injected VI.25.19: Quiet, but reflexes
good; more quiet and depressed after several hours. Some loss of oil
from wound. Died night of VI.25.19 (one day). Tail stiff. Temperature
low.

Postmortem: Lungs markedly congested. Spleen and liver dark red. One
kidney congested. Other viscera normal.

EXPERIMENT 7.--_12.5 c.c._; injected VII.9.19: Quiet for one-half
hour; 1.5 hours twitching of muscles of whole body, lies on side,
ataxia present. Died night of VII.9.19 (one day).

EXPERIMENT 8.--_18.75 c.c._; injected VI.25.19: Quiet; reflexes good
(three hours). Some loss of oil. Depressed and turns on side (six
hours). Died night of VI.25.19 (one day).

Postmortem: Lungs congested. Spleen and liver very dark red. Right
kidney much darker red. Viscera normal.

D. REPORT OF DR. D. RIVAS

The following are the results of experiments conducted by me, during the past four months, on the germicidal action of chlorlyptus (chlorinated oil of eucalyptus, principal constituent C₁₀H₁₇OCl₂) in vitro and in vivo, and comparison also with carbolic acid, oil of eucalyptus and dichloramine in test for irritation and toxicity.

_Germicidal Action._--Based on the results obtained, chlorlyptus when used in a 5 per cent. paraffin oil solution was found to be a mild germicidal against typhoid B, streptococcus and staphylococcus when these organisms were suspended in ordinary bouillon culture or sterile salt solutions.

The germicidal action was found stronger when these micro-organisms were suspended in a sterile oily or lipoid substance, such as olive oil. The results of these experiments were not constant, owing probably to the imperfect suspension of the bacteria. Thus, while in some of the experiments chlorlyptus in 1 per cent. oil solution destroyed these micro-organisms, in other cases the same strength solution failed to give same result in same time.

The increased germicidal action of chlorlyptus on bacterial suspensions in olive oil may be accounted for by the fact that chlorlyptus is soluble in olive oil and not an admixture, as in the case of paraffin oil.

Chlorlyptus is not a coagulant, as are germicides of the phenol or hypochlorite types, and the germicidal action is therefore not strictly comparable.

The germicidal action of chlorlyptus oil solution, on pathogenic bacteria, on streptococcus and staphylococcus, suspended in pus, was found to be stronger than when these micro-organisms were suspended in ordinary bouillon culture or sterile salt solution. In one of the experiments, similar results were obtained when these micro-organisms were suspended in olive oil, chlorlyptus showing marked germicidal action.

_Irritation and Toxicity._--The irritating action was found to be relatively mild in tests on laboratory animals. Thus, from 0.5 to 1 c.c. of chlorlyptus in paraffin oil 5 per cent. solution, injected into peritoneal or pleural cavities of guinea-pigs weighing 400 gm. was found to be without any appreciable disturbance in the health of the animal, and in some cases the injection of as much as 2 c.c. did not kill the animal.

_Therapeutic Action._--Guinea-pigs were inoculated with purulent material containing streptococcus, staphylococcus and _B. coli_ in peritoneal and pleural cavities respectively, and after six hours 1 c.c. of chlorlyptus 5 per cent. in paraffin oil solution was injected. Other infected animals were similarly treated twenty-four hours after inoculation, and another series forty-eight hours after inoculation. In some of these cases the animals died from shock but in a clearly defined series in which the injection of 1 c.c. of the chlorlyptus solution was made in the peritoneum of the guinea-pigs twenty-four hours after the inoculation, the animals lived. The control animal, inoculated with the purulent material and not treated with chlorlyptus oil solution, died.

In consideration that the injection of chlorlyptus oil solution [sic, referee] were made [? referee] in the peritoneal cavity this substance is apt to affect the vital organs in the abdominal cavity. It is my belief that in case of wall abscess of chronic inflammation, by limiting the action of chlorlyptus to the infected area, preventing at the same time the infection of the vital organs, chlorlyptus, because of its non-irritating quality, can be used effectively as an antiseptic.

CONCLUSIONS

1. Chlorlyptus is a mild and relatively nonirritating antiseptic of marked action on pus and suppuration.

2. When bacteria were suspended in olive oil or in pus, chlorlyptus showed marked germicidal action.

3. Chlorlyptus can be injected into the peritoneum or the pleural cavities of guinea-pigs in the proportion of 1 c.c. per 400 gm. of body weight without detriment to the animal.

4. Chlorlyptus in 5 per cent. oil solution (taking Clause 3 as comparison) can perhaps be injected in man as an antiseptic agent when there is a walled-in abscess in the peritoneum or pleural cavity where there is drainage, in the proportion of 0.5 to 1 c.c. per pound of body weight with good result.

REPORT ON THE GERMICIDAL ACTION OF CHLORLYPTUS ON PATHOGENIC
BACTERIA IN VITRO AND IN VIVO

EXPERIMENT 1.--_The germicidal action of eucalyptus oil._--Typhoid
bacillus was destroyed in less than five minutes when exposed to the
action of a 5 per cent. suspension of oil of eucalyptus. The exposure
for four hours in a 5 per cent. suspension of chlorlyptus in paraffin
oil was without effect on typhoid bacillus. It requires an exposure
of two to four hours in a 10 per cent. suspension of chlorlyptus in
paraffin oil to destroy typhoid bacillus.

EXPERIMENT 2.--_Bacilliary action of chlorlyptus on the growth of
pathogenic bacteria._--Typhoid and anthrax bacilli were selected for
the experiment. Two series of five tubes each were made. The culture
medium used was nutrient bouillon. Chlorlyptus was added in the
following proportions: Tube 1, 1:10; Tube 2, 1:100; Tube 3, 1:1,000;
Tube 4, 1:10,000, and Tube 5, 1:100,000. One series was inoculated
with typhoid bacillus. All tubes were incubated for three days at
37 C.

Chlorlyptus inhibited the growth of typhoid bacillus when added
to the bouillon in the proportions of 1:10. The growth of anthrax
bacillus was inhibited by chlorlyptus when it was added in the
proportions of 1:10, 1:100 and 1:1,000, as shown in the accompanying
table. [The table was not submitted.--Ed.] In one instance the growth
was markedly inhibited by chlorlyptus when added in the proportion of
1:10,000.

EXPERIMENT 3.--_Germicidal action of chlorlyptus on typhoid
bacillus._--Bouillon cultures of typhoid bacillus forty-eight hours
old, and a suspension of forty-eight-hour agar cultures of typhoid
bacillus in sterile salt solution were used for the experiment.
Chlorlyptus was added in the proportion of 1:1,000; 1:1,500; 1:100;
2 per cent.; 3 per cent.; 4 per cent.; 5 per cent. and 10 per cent.,
respectively.

Inoculations were made in trypsinized peptone bouillon after the
addition of chlorlyptus at different intervals, namely: at once,
after five minutes, after ten minutes, after fifteen minutes, after
thirty minutes, after one hour and after two hours, and tubes
incubated at 37 C. for forty-eight hours.

Result: Growth was shown in all tubes except those in which
chlorlyptus was added in the proportion of 10 per cent. and after the
action of the antiseptic for two hours or longer.

EXPERIMENT 4.--_Inhibitory action of chlorlyptus in the growth
of typhoid bacillus._--Chlorlyptus was added to sterile bouillon
in the proportion of 1:100, 1:1,000, 1:10,000 and 1:100,000, and
incubated for forty-eight hours at 37 C. to eliminate any possible
contamination of the bouillon during the manipulations. All tubes
were found sterile and inoculated with typhoid bacillus.

Result: All tubes were found sterile again after being inoculated
with typhoid bacillus and incubated at 37 C. for forty-eight hours,
which shows chlorlyptus inhibited and the growth of typhoid bacillus
in bouillon when this antiseptic was added in the proportions of
1:100 to 1:100,000.

Remarks: In another experiment made, chlorlyptus showed a weaker
inhibitory action on the growth of typhoid bacillus.

EXPERIMENT 5.--_Germicidal action of carbolic acid._--The technic was
the same as that outlined in Experiment 1. except that carbolic acid
was used instead of chlorlyptus.

Result: Carbolic acid showed a distinct germicidal action on
typhoid bacillus in the proportions of 1 per cent. in ten minutes.

EXPERIMENT 6.--_Action of nitrogen gas on the growth of typhoid
bacillus in bouillon and nutrient agar when chlorlyptus was added to
this culture medium._--Chlorlyptus was added to the bouillon in the
proportions of 1:100, 1:1,000, 1:10,000 and 1:100,000, as outlined in
Experiment 2; also to agar kept melted at 45 C. Tubes were inoculated
with typhoid bacillus; plates were made of the inoculated agar tubes;
all plates and tubes were incubated at 37 C. for forty-eight hours in
an atmosphere of nitrogen gas.

Duplicate experiments were made with cultures of typhoid bacillus
as above in bouillon and agar plates containing the same amount of
chlorlyptus and incubated at 37 C. in ordinary atmosphere as control.

Result: Nitrogen gas did not show any appreciable increase of the
germicidal action of typhoid bacillus when grown in medium containing
chlorlyptus. Growth was about the same in cultures supplied with
nitrogen gas as in those growing in ordinary atmosphere.

EXPERIMENT 7.--_Germicidal action of chlorlyptus on pyogenic bacteria
suspended in an oily medium._--Experiment with streptococcus:
Cultures of streptococcus in blood agar three days old were suspended
in olive oil (sterile), and chlorlyptus was added in the proportions
of 1, 5 and 10 per cent. and inoculated in trypsinized bouillon at
different intervals, namely: at once, after five minutes, after ten
minutes, after fifteen minutes, after thirty minutes, and after one
hour. Tubes were incubated at 37 C. for forty-eight hours.

Result: All tubes remained sterile. The germicidal action of
chlorlyptus on streptococcus suspended in oil was almost at once and
with certainty after five minutes when added in the proportion of 1,
5 and 10 per cent.

EXPERIMENT 8.--_Germicidal action of chlorlyptus on staphylococcus,
suspended in sterile olive oil._--The technic employed was the same
as in Experiment 5, except that a culture of staphylococcus was used.

Result: All tubes remained sterile. The germicidal action of
chlorlyptus was almost at once in the proportions of 1, 5 and 10 per
cent.

Remarks: By repeating this experiment the result showed some
variations. The discrepancy was probably due to an imperfect
suspension of the micro-organism in the oil.

EXPERIMENT 9.--_Germicidal action of carbolic acid on streptococcus
suspended in olive oil._--The technic employed was the same as
in Experiment 5, except that carbolic acid was used instead of
chlorlyptus.

Result: The germicidal action of carbolic acid of streptococcus
suspended in olive oil was almost at once in the proportions of 1, 5
and 10.

EXPERIMENT 10.--_Germicidal action of chlorlyptus on
staphylococcus._--The technic employed was the same as in Experiment
6 except that the carbolic acid was used instead of chlorlyptus.

Result: The germicidal action of carbolic acid on staphylococcus
suspended in olive oil was almost at once, in proportions of 1, 5 and
10 per cent.

EXPERIMENT 11.--_Germicidal action of chlorlyptus on pyogenic
bacteria suspended in pus._--Chlorlyptus was added to sterile pus in
the proportions of 1, 5 and 10 per cent., and then inoculated with
staphylococcus and cultures were made in bouillon at once, after
five minutes, after ten minutes, after fifteen minutes, after thirty
minutes, after one hour and after two hours, respectively, and tubes
incubated for forty-eight hours at 37 C.

Result: Growth was shown in all tubes except those inoculated from
tubes in which chlorlyptus was added in the proportions of 10 per
cent. after one hour.

EXPERIMENT 12.--_Germicidal action of chlorlyptus on streptococcus
suspended in sterile human blood serum._--Staphylococcus culture
in agar forty-eight hours old was suspended in sterile human blood
serum, and to the suspension chlorlyptus 5 per cent. in paraffin oil
was added in the proportions of 1, 5 and 10 per cent. Inoculations
were made at intervals, at once, after five minutes, after ten
minutes, after fifteen minutes and after one hour in trypsinized
bouillon. Tubes were incubated at 37 C. for forty-eight hours.

Result: Chlorlyptus showed inhibitory action on the growth of
staphylococcus in the strength of 10 per cent., but did not produce
complete sterilization. Similar results were shown with the 5 per
cent., and in the 1 per cent. chlorlyptus did not show any inhibitory
action at all.

EXPERIMENT 13.--_Germicidal action of carbolic acid on staphylococcus
suspended in human blood serum (sterile)._--The technic employed
was the same as in Experiment 10 except that carbolic acid was used
instead of chlorlyptus.

Result: Carbolic acid produced a complete sterilization in the
strength of 10 per cent. almost at once, and with certainty after
five minutes. Similar results were produced with the 5 per cent. The
1 per cent. carbolic acid did not show any appreciable germicidal
action on staphylococcus.

EXPERIMENT 14.--_Toxic and irritant action of chlorlyptus._--Six
normal guinea-pigs were used for the experiment. Guinea-Pig 1 was
injected peritoneally with 1 c.c. of chlorlyptus, Guinea-Pig 2 with
2 c.c. of chlorlyptus, Guinea-Pig 3 with 3 c.c. of chlorlyptus,
Guinea-Pig 4 with 4 c.c. and Guinea-Pig 5 with 5 c.c. 5 per cent.
respectively. Guinea-Pig 6 was used as a control and not injected.

Result: Guinea-Pigs 1 and 2 did not show any appreciable disturbance.
Guinea-Pig 3 was sick for four days, after which it gradually
recovered but it became sick again after one week and died ten days
after the injection. Guinea-Pig 4 died over night. Guinea-Pig 5
died six hours after injection. Guinea-Pig 5 was injected at 11:30
with 5 c.c. chlorlyptus. Ten minutes after the injection it was
lying relaxed, respiration and heart normal, conjunctive reflex
present. One hour after the injection the animal seemed to present
symptoms resembling those of narcosis: respiration and heart were
normal. After four hours there was no change in the condition of the
guinea-pig except that the respiration was irregular. Five and a half
hours after it showed prostration with irregular respiration and
heart action. Six hours after injection the animal was dead.

Autopsy: The peritoneum showed a congestion and a fibrinous
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.”