The referee has made a careful search of the literature, with the

following results: Boehnke (_Berl. klin. Wchnschr._ 50:818, 1913),

using white mice, failed to confirm the experiments reported in

Seibert’s paper, unless camphorated oil were given before the

pneumococci, and even then, he felt that the results were too irregular

to be of great significance. When given with anti-pneumococcic serum,

however, he felt that there was some benefit to be seen by the

administration of camphor; his protocols, however, are not detailed.

There is no report of blood cultures, etc.

Another worker, H. Leo (_Deutsch. med. Wchnschr._ 39:690, 1913),

reported that camphor water given intravenously prolonged the lives of

thirty-eight rabbits inoculated with pneumococci. Here again there were

no adequate protocols and very little evidence of careful experimental

work appears.

In the literature of the past ten years, there appear sketchy clinical

articles on the value of huge doses of camphor in pneumonia. Markevitch

(_Russk. Vrach_, June 27, 1914; abstr., The Journal, Dec. 5, 1914,

p. 2081) treated 226 cases of pneumonia with 5 c.c. of camphorated oil

hypodermically four times daily, at the same time giving digitalis

(amount not stated), with a mortality of 6.6 per cent., whereas, in 322

cases untreated, there was a mortality of 13.3 per cent. He reports

133 grave cases; sixty-six received no camphor; 48 per cent. died. Of

sixty-seven treated with camphor, only 22 per cent. died. He reports

temperature falling by lysis when camphor is used, and comments on the

symptomatic improvement following its use. With the great variation in

the clinical course of pneumonia, the above figures, though suggestive,

certainly need further support before the routine use of camphor as

recommended by Seibert can be sanctioned.

Later articles found on the subject refer to it in a very cursory way,

giving no protocols and no cases, and giving the referee the feeling

that the conclusions were very impressionistic.

RÉSUMÉ

After a careful search of the literature, the referee concludes that:

Huge doses of camphor, to 250 grains in twenty-four hours, may be given

to man without serious results. No satisfactory evidence, however,

appears that camphor has a specific germicidal action on pneumococci

(similar to that of ethylhydrocuprein). The clinical evidence, as

found in the literature, is certainly of very little value. It appears

that the sale of a simple solution of camphor in oil under the guise

of “Anti-Pneumococcic Oil” is to be deplored (a 20 per cent. solution

of camphor in cottonseed oil is official in the U. S. Pharmacopeia

as camphor liniment). It is recommended that the preparation be held

inadmissible to New and Nonofficial Remedies because exaggerated

therapeutic claims are advanced for it, and because the name is not

descriptive of the composition, but is, instead, therapeutically

suggestive.--(_From The Journal A. M. A., Jan. 3, 1920._)

DIAL “CIBA”

Report of the Council on Pharmacy and Chemistry

Dial “Ciba” has not been accepted for “New and Nonofficial Remedies”

because, as the report which follows shows, unwarranted claims are

made for the product. It is a definite new chemical compound which

might be made eligible for N. N. R. if misleading therapeutic claims

were eliminated. The Council directed that Dial “Ciba” be included

with Articles Described but Not Accepted, so that physicians might be

informed with regard to its character and properties.

W. A. Puckner, Secretary.

Dial “Ciba” is a hypnotic manufactured by the Society of Chemical

Industry of Basle, Switzerland, and is sold in the United States by

A. Klipstein and Company, Inc., New York. Chemically, Dial “Ciba”

is diallylbarbituric acid and is, therefore, closely related to

diethylbarbituric acid or barbital (“veronal”).

The claims made for Dial “Ciba” are (1), that the “allyl” group in its

molecule makes it more readily decomposed by oxidizing agents than

barbital, which contains the “ethyl” group; (2) that because of this

ease of oxidation, it is more readily decomposed in the body and more

rapidly and completely eliminated, and (3) that because of its alleged

rapid elimination, it is devoid of the after effects of barbital and

other hypnotics.

The Council took up the substance in February, 1918, and referred the

matter to the referee in charge of barbital preparations. The referee

considered unwarranted the claim that Dial “Ciba” did not have the

after-effects of other hypnotics due to its alleged total decomposition

in the body. The American agents, A. Klipstein and Company, were

informed of the referee’s objections. Their attention was also called

to the fact that, notwithstanding the claimed absence of after-effects

in one part of the advertising, other parts of the same advertising

admitted certain post-hypnotic effects of the product. It was

pointed out also that while it was claimed in one of the advertising

circulars that lowering of the blood pressure is never observed after

administration of Dial “Ciba,” yet two of the authors quoted in the

same circular definitely stated that a lowering of the blood pressure

followed even small doses of the drug and these authors warn against

this very danger in certain conditions.

A year later, a circular letter sent out by A. Klipstein and Company

reiterated the claim that the asserted decomposition of Dial “Ciba”

in the body prevents after-effects, the drug being still contrasted

with barbital (“veronal”). In view of the reiteration of this highly

improbable claim, the referee undertook to study the comparative action

of Dial “Ciba” as compared with other hypnotics. It was found that

the actions of Dial “Ciba” are not distinguishable, qualitatively,

from those of barbital, there being no perceptible difference in the

after-effects or in the nature of the side actions. In toxic doses,

both caused profound depression with the temperature falling to

that of the room (or about one degree above), the respiration being

extraordinarily slow and shallow as one would expect with lowering of

the temperature. There were also the same evidences of nausea that

are so frequently seen after toxic doses of the various hypnotics of

this group. In view of these results, the Council declared that it is

unwarranted to claim freedom from after-effects for Dial “Ciba.”

The Council held that the following statement is unwarranted:

“The therapeutic field for Dial ‘Ciba,’ as shown by tests on

rabbits, is just as broad as the field for Diethylbarbituric Acid.”

Tests on rabbits do not and cannot show the breadth of the therapeutic

field for a hypnotic. The Council also declared the following statement

improbable, and contrary to the evidence obtained by the referee:

“In dogs, the increase of dosage beyond the therapeutic dose to the

point of death is decidedly in favor of Dial ‘Ciba,’ which required

a larger dose [than diethylbarbituric acid] to produce death.”

The referee’s experiments on cats show that Dial “Ciba” is several

times as toxic as hydrated chloral, and more than twice as toxic as

diethylbarbituric acid (barbital).

Since the circular to which objection was made in 1918 was still being

sent out in December, 1919, the Council held Dial “Ciba” inadmissible

to N. N. R. and voted that report of its action in the matter be

authorized for publication. The Council further directed that Dial

“Ciba” be included with Articles Described but Not Accepted.--(_From

The Journal A. M. A., Jan. 24, 1920._)

APOTHESINE

Report of the Council on Pharmacy and Chemistry

Apothesine is a synthetic drug for producing local anesthesia, made

by Parke, Davis & Company. In the fall of 1917 the Council wrote to

Parke, Davis & Company offering its aid in establishing the identity,

purity and therapeutic efficiency of this synthetic local anesthetic

with the ultimate object of accepting the product for inclusion in New

and Nonofficial Remedies should the facts warrant such acceptance.

The Council’s letter was never acknowledged. After Apothesine was

put on the market the Council desired to accept it for inclusion in

New and Nonofficial Remedies but, unfortunately, was unable to do so

because some of the claims made for the product were not justified by

acceptable evidence. The manufacturers were notified of the Council’s

desire to admit this product to N. N. R. and the wish was expressed

that the company would either so modify its claims as to make the

product acceptable under the Council’s rules or else would submit

evidence to the Council in proof of the claims made and thus permit

the Council to revise its conclusions. Parke, Davis & Company were,

apparently, either unwilling or unable to submit evidence that would

sustain their claims; neither did they offer to modify the claims

themselves. The product, therefore, is ineligible to inclusion in New

and Nonofficial Remedies; it will, however, be listed in the “Described

But Not Accepted” department of New and Nonofficial Remedies. The

report on Apothesine that follows has been authorized for publication.

W. A. Puckner, Secretary.

Apothesine, “the hydrochlorid of diethyl-amino-propyl-cinnamate,” is

an efficient local anesthetic. It belongs to the procain rather than

to the cocain type, that is, it belongs to that type which, while

effective for injection anesthesia (especially when combined with

epinephrin) is relatively inefficient when applied to mucous membranes.

Apothesine may also be used for spinal anesthesia. Its absolute

toxicity is less than that of cocain (as 20 is to 15, see table below)

but about twice that of procain (as 20 is to 40, see table below). It

is non-irritant, is easily soluble and makes a stable solution so that

it may readily be sterilized.

The Council took exception to certain claims made by Parke, Davis &

Company for their product on the ground that these claims were not

supported by acceptable scientific evidence. One of the claims was

that Apothesine is applicable in any case in which any other local

anesthetic is used. This statement, made in many advertisements,

is distinctly misleading as used. When applied to mucous membranes

Apothesine is far inferior to cocain and to some other local

anesthetics, yet the claim obviously suggests that Apothesine is an

efficient substitute for any local anesthetic.

The manufacturers claimed, too, that Apothesine is as potent as cocain.

The claim would lead the physician to think that Apothesine had the

same anesthetic potency as cocain in solution of equal strength. This

statement, so far as it refers to the drug when applied to mucous

membranes, is not in accord with the facts and is true for injection

anesthesia only when stronger solutions are used. The only support

for the claim of equal efficiency appears to be the experiments with

intracutaneous injections made by H. C. Hamilton[130] in Parke, Davis &

Company’s laboratory. These differed considerably from the results of

Sollmann.[131] A further series of experiments were made by Sollmann

to compare still further the diverse results previously reported

by him and Hamilton. The latest series, while showing considerable

variations in the susceptibility of different skin areas, especially

toward Apothesine, demonstrated in every case that the efficiency of

Apothesine is unmistakably lower than that of cocain, being at best one

half. The series also showed that the potency of Apothesine was never

greater than procain and averaged considerably below it.

[130] The Comparative Values of Some Local Anesthetics by H. C.

Hamilton, Detroit, Mich., from the Research Laboratory of Parke, Davis

& Co., J. Lab. & Clin. M. =4=:60 (Nov.) 1918.

[131] Comparative Efficiency of Local Anesthetics, V, by T. Sollmann,

from the Pharmacological Laboratory of the School of Medicine, Western

Reserve University, J. Pharmacol. & Exper. Therap. =11=:69 (Feb.) 1918.

Another claim made for Apothesine which the Council holds is not

supported by evidence is that of superior safety. This claim is made

on the basis of hypodermic injections in guinea-pigs carried out in

the laboratory of Parke, Davis & Company. Such experiments prove

little because of the fact--well known to laboratory workers--that the

use of rodents in toxicity tests made by injecting a drug into the

subcutaneous tissues does not give a reliable index of the relative

toxicity of such a drug for man. This is due partly to the peculiar

resistance of rodents to poisons and partly to the great importance of

the rate of absorption. The organism destroys most local anesthetics so

rapidly that the rate of absorption is more important than the absolute

dose. The absorption from hypodermic injections into guinea-pigs

differs, of course, from that in clinical accidents, especially where

the drug has been applied to mucous membranes. One cannot, therefore,

reliably estimate the degree of clinical danger on animals.

It has been shown that when toxicity tests of local anesthetics are

made on cats these animals seem to respond to the drugs in a manner

more closely approximating humans and it is a suggestive fact that the

more toxic of local anesthetics, as shown by tests on cats, have been

found the most dangerous in clinical use. The _absolute_ toxicity of

Apothesine has been measured by Eggleston and Hatcher[132] by the

intravenous injection in cats. The fatal doses, in terms of milligrams

per kilogram ranged as follows:

Alypin, Holocain 10

Beta Eucain 12.5

Cocain 15

Apothesine 20

Tropacocain 20-25

Stovain 25-30

Nirvanin 30-35

Procain 40-45

[132] A Further Contribution to the Pharmacology of the Local

Anesthetics by Eggleston and Hatcher, from the Department of

Pharmacology, Cornell University Medical College, New York City, J.

Pharmacol. & Exper. Therap. =13=:433 (Aug.) 1919.

The _absolute_ toxicity of Apothesine is, therefore, only a little

lower than that of cocain, and is twice as great as that of procain.

The _clinical_ dangers cannot be predicted by either method, since

clinical accidents depend, in most instances, on idiosyncrasies, or the

technic of application.--(_From The Journal A. M. A., Jan. 24, 1920._)

EUMICTINE

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which

appears below. This report declares “Eumictine” ineligible for New and

Nonofficial Remedies because (1) it conflicts with Rule 10 in that it

is unscientific, (2) it conflicts with Rule 6 in that it is sold under

unwarranted therapeutic claims, (3) it conflicts with Rule 4 against

indirect advertising to the public in that the name “Eumictine” is

blown in the bottle for the obvious purpose of bringing the product

to the attention of the public when it is prescribed in the original

package, and (4) because the name is therapeutically suggestive and not

in any way descriptive of its composition.

W. A. Puckner, Secretary.

Eumictine is a preparation from the laboratory of Maurice Le Prince,

Paris, France, and is marketed in this country by George J. Wallau,

Inc., New York. It is claimed that the product is “a balsamo-antiseptic

preparation composed of Santalol, Salol, and Hexamethylene-Tetramine,

in the form of gluten-coated capsules.” Nowhere in the advertising

are the amounts of the ingredients given. According to the

American agent, however, “each capsule is supposed to contain 20

centigrams of Santalol, 5 centigrams of Salol, 5 centigrams of

Hexamethylene-Tetramine.”

Eumictine is advised “in treating genito-urinary diseases (urethritis,

cystitis, prostatitis, pyelitis, etc.).” It is claimed to be “both an

antiphlogistic modifying agent, a well-tolerated diuretic” which “may

be administered for long periods without ill effects.”

The Council declares Eumictine ineligible for New and Nonofficial

Remedies because it is exploited in conflict with the following rules:

It is unscientific (Rule 10). Eumictine is composed of

hexamethylenamin, salol and sanalol in fixed proportions.

Hexamethylenamin may serve a useful purpose in some forms of infection

of the urinary tract, but neither it nor salol is of any considerable

value in gonorrhea. It is now known that the balsamic preparations,

formerly so widely used, do not have the curative effects in gonorrhea

and associated conditions that used to be ascribed to them. To combine

three substances, none of which has any distinct therapeutic value in

the conditions for which Eumictine is proposed, does not enhance their

value. There is nothing original in the combination used in Eumictine,

or in the manner of dispensing it.

It is sold under unwarranted therapeutic claims (Rule 6). These

claims are made not only for the components of Eumictine but for the

combination itself. Though santalol has certain advantages over the

somewhat variable oil of santal and other balsamic resins, it is not

true that santalol “does not cause congestion of the renal epithelium”

or that it does not “produce exanthema as do copaiba, cubebs, and

the ordinary santal oil.” It is not true that salol is “devoid of

toxicity.” Neither is it correct to say that salol “asepticizes and

disinfects the bladder, the prostate and the urethra.” The claim that

hexamethylenamin “is of value when any acute symptoms or tendency to

inflammation subsist” is not justified. The claim that hexamethylenamin

“renders soluble the uric acid and urates” is also without foundation.

The following paragraph is characteristic of the claims made for

Eumictine:

“Anti-gonorrhoic by its Santalol, diuretic, urolytic and analgetic

by its hexamethylenetetramin (Urotropin) antiseptic and antipyretic

by its Salol, Eumictine represents a real therapeutic advance in

the scientific treatment of diseases of the urinary passages.”

Instead of being “a real therapeutic advance” in the treatment of

diseases of the urinary passages, Eumictine presents one of the

complex combinations that have long retarded the scientific treatment

of these diseases. Eumictine also conflicts with Rules 4 and 8 of the

Council.--(_From The Journal A. M. A. Feb. 21, 1920._)

PLATT’S CHLORIDES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on

“Platt’s Chlorides.” It also declares the preparation inadmissible

to New and Nonofficial Remedies because its composition is uncertain

and indefinite and because the claims made for it are exaggerated and

misleading.

W. A. Puckner, Secretary

“Platt’s Chlorides,” marketed by Henry B. Platt, New York, is sold

as a disinfectant and germicide. Only incomplete and contradictory

statements have been made in regard to its composition. Many years

ago (about 1899) the composition of Platt’s Chlorides was given as

“The Chlorids of Zn 40 per cent., Pb 20, Ca 15, Al 15, Mg 5, K 5.” The

statement that the preparation contained 20 per cent. of lead chlorid

is interesting, in view of the fact that lead chlorid is soluble in

water at ordinary temperatures to the extent of less than 1 per cent.

In a booklet, also issued a number of years ago, the following “Formula

of Platt’s Chlorides” was given:

“A saturated solution of Metallic Chlorids combined in the

following proportions:

“Sol. Zinc Chlorid 40 per cent.

“Sol. Aluminum Chlorid 15 per cent.

“Sol. Lead Chlorid 20 per cent.

“Sol. Calcium Chlorid 15 per cent.

“Sol. Magnesium Chlorid 5 per cent.

“Sol. Potassium Chlorid 5 per cent.”

The label on a bottle purchased in 1911, describes Platt’s Chlorides as:

“A Highly Concentrated Solution of the Chlorids of Aluminum,

Calcium, Lead, Zinc, etc.”

The label of a bottle purchased in 1919 reads:

“Contains Inert Material: Water 84.0%. Sodium Chlorid 4.8%. Calcium

Chlorid 0.3%.”

This statement is obviously made to meet the requirements of the

federal Insecticide Act. This law requires either that the identity

and the amounts of potent ingredients in disinfecting preparations be

declared or else that the percentage of the inert ingredients of such

preparations be given. The omission from the label of all statements

with regard to the potent ingredients of the preparation and the

absence of such a statement in recent advertising matter suggests

either that the older statements about its composition were false or

else that the composition has been changed.

Tscheppe published (Pharmaceutische Rundschau =8=:109, 1890) an analysis

of Platt’s Chlorides which has been quoted in other publications as

indicating the composition of the preparation. He reported that he

found each quart of the preparation to contain aluminum sulphate 6

ounces, zinc chlorid 1-1/3 ounces, sodium chlorid 2 ounces, calcium

chlorid 3 ounces.

Some years ago (about 1911) the company made the following statement

relative to the germicidal power (phenol co-efficient) of Platt’s

Chlorides:

“... for some time the carbolic acid co-efficiency of our output

has been from 2.5 to 4.3, the average being about 3; namely about

three times stronger than pure carbolic acid.”

In 1912, the U. S. Public Health and Marine Hospital Service reported

(_Bulletin_ 82, Public Health and Marine Hospital Service, p. 69) that

the phenol coefficient of a sample of Platt’s Chlorides was so low

that it could not be determined and also that the sample was found to

contain some mercuric chlorid. In 1913, the North Dakota Agricultural

Experiment Station reported (_Bulletin_, July, 1913, p. 292), that

Platt’s Chlorides contained principally zinc chlorid, also some

aluminum chlorid, calcium chlorid, and traces of mercuric chlorid. The

phenol coefficient, determined by the Hygienic Laboratory method, was

found to be 0.05.

The preceding suggests that the composition of Platt’s Chlorides had

been changed (without notice to the consumer) and that it had been

fortified by the addition of mercuric chlorid. Years ago part of the

advertising of this product was a testimonial from a health official

which declared that, for disinfection, “bichlorid of mercury is useless

in disinfecting sputum or discharges from the bowels, being rendered

inert by the albumin present” and it lauded Platt’s Chlorides as devoid

of such drawbacks.

RECENT ANALYSES OF PLATT’S CHLORIDES

To determine the present composition of Platt’s Chlorides and to

compare it with that sold formerly, the A. M. A. Chemical Laboratory

has made an analysis of a specimen purchased in 1919 and also of one

purchased in 1911 and since kept unopened in the files of the Council

on Pharmacy and Chemistry. The following table contains the results of

these analyses (all quantities given are Gm. per 100 c.c.):

1911 SPECIMEN 1919 SPECIMEN

Color Colorless Straw Color

Odor None None

Specific Gravity at 25 Cc. 1.1229 1.1313

Total Solids (residue at 100 Cc.) 16.49 18.33

Chlorid (Cl-) 7.60 10.74

Sulphate (SO₄--)  1.11 .16

Aluminum (Al+++) .22 .90

Calcium (Ca++) .19 .13

Zinc (Zn++) 5.11 3.93

Lead (Pb++) .046 Traces

Mercury (Hg++) .. .0086

Sodium (Na+) 1.01 1.39

These quantities transposed to hypothetical combinations would indicate

that Platt’s Chlorides has the following composition:

1911 Specimen 1919 Specimen

Aluminum Sulphate 1.32 .18

Aluminum Chlorid .07 4.29

Calcium Chlorid .54 .37

Zinc Chlorid 10.66 8.19

Lead Chlorid .06 Traces

Mercury Chlorid .. .0116

Sodium Chlorid 2.57 4.81

Hydrogen Chlorid .43 None

In the past, the advertising has suggested, more or less directly,

that, as chlorinated lime (bleaching powder) may be made to give off

chlorin gas which disinfects, so the air in a room may be disinfected

by evaporating Platt’s Chlorides. Thus the label of the 1911 specimen

contains the following:

“FOR STORE ROOMS, Refrigerators, and Closets, keep a sponge

saturated with the pure liquid in a saucer on an upper shelf.”

On the label of the 1919 specimen, the statement reads:

“REFRIGERATORS AND STOREROOMS--As a disinfectant wash regularly

with one part Chlorides to eight of water. As a deodorant, keep in

an open vessel a sponge or cloth saturated with the Chlorides full

strength.”

That the owner of Platt’s Chlorides really believes that the vapors of

the preparation have disinfecting properties is seen from a letter over

the name of Henry B. Platt printed in the New York _Tribune_ in 1916.

This read, in part:

“... by keeping in a dish or saucer on radiators Platt’s Chlorides

diluted one-half, the hot solution will evaporate and purify the

air, thus destroying the grip germ which is the cause of all the

trouble.”

From the analysis of Platt’s Chlorides, it is evident that when the

preparation is evaporated, water vapor only escapes.[133] Whatever

disinfecting or germicidal action the preparation may possess is

exercised only when the solution is brought in direct contact with the

substance to be disinfected.

[133] It is well known that when a solution of mercuric chlorid in

water is evaporated, mercuric chlorid passes off with the water vapors,

but under any condition the amount is but a fraction of the whole. As

in Platt’s Chlorides other metallic chlorids are present, the formation

of complex mercuric compounds which is bound to have occurred, should

retard or prevent the volatilization of mercuric chlorid. That this

actually occurs was confirmed by the following experiment: When 1 gm.

mercuric chlorid was dissolved in 1 liter of water and the solution

distilled, the distillate contained a very small amount of mercury.

Then the experiment was repeated after adding sodium chlorid to the

solution to simulate the conditions in Platt’s Chlorides. In this case

no mercury was found in the distillate. Even were all the mercury in a

bottle of Platt’s Chlorides volatilized in a room 10 by 12 by 9 feet,

this would be equivalent to only about 1/500 grain mercuric chlorid per

cubic foot.

The aluminum and zinc salts present may be useful as deodorants but

they are not effective as germicides. The presence of mercuric chlorid

in a concentration of 1 to 10,000 is hardly to be considered as

materially increasing the efficiency. The directions recommend the use

of a mixture of 1 part of Platt’s Chlorides to 10 parts of water for

rinsing the hands, and a mixture of 1 part to 4 parts of water for the

disinfection of discharges. It is further stated that 1 quart makes 2

gallons sufficiently strong for general use. It is evident that such

dilutions decrease considerably the feeble germicidal action of the

original fluid.--(_From The Journal A. M. A., March 27, 1920._)

ANTI-TUBERCULOUS LYMPH COMPOUND (SWEENY) AND ANTI-SYPHILITIC

COMPOUND (SWEENY)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the reports which appear

below, declaring Anti-Tuberculous Lymph Compound (Sweeny) and

Anti-Syphilitic Compound (Sweeny) ineligible for New and Nonofficial

Remedies.

W. A. Puckner, Secretary.

Anti-Tuberculous Lymph Compound (Sweeny)

“Anti-Tuberculous Lymph Compound (Sweeny)” is put out by the National

Laboratories of Pittsburgh, Dr. Gilliford B. Sweeny, “Medical

Director.” Sweeny has claimed at different times that he became

interested in the subject of von Behring’s efforts to immunize cattle

to tuberculosis at a time when he was an assistant in von Behring’s

laboratory. He claims to have conceived the idea while there of

transferring bovine immunity to tuberculosis to the human subject and

later to have evolved his “treatment” at the Pasteur Institute in Paris.

Just how Anti-Tuberculous Lymph Compound is made today is not

stated--at least so far as one is able to learn from recent

advertising. Some years ago Sweeny declared that his “Anti-Tubercular

Lymph” (as it was then called) was derived from a bullock which had

been immunized to tuberculosis. Then:

“The immunized animal having been slaughtered, the contents of the

lymph reservoirs are carefully collected and an aqueous extract is

made from the grey cerebral substance, spinal cord and the lymph

glands. It is then filtered under high pressure and de-albuminized

by succussion. To this, the lymph, together with a definite

proportion (50 per cent.), of the naturally phosphorized brain fats

is added, with a small amount of chloride of gold (about 1-60 gr.

to the dose), the latter as a preservative.”

It is a fair assumption that however the preparation may have been

made originally, it is not now made in such a manner as to bring it

under the federal laws governing the preparation of serums and similar

preparations. The claims made for Anti-Tuberculous Lymph Compound are

of the usual uncritical and unscientific type. Mainly, of course,

they are of the testimonial class. The physician is told that the

preparation has been carefully tested by men whose judgment is worthy

of consideration; that the verdict has been altogether favorable to the

“Compound.” Thus:

“... the remedy was submitted to a selected body of skilled

physicians, recognized for their skill and care in making

therapeutic observations. These men represented widely varying

conditions, climatic and otherwise. Those who said ten years ago

that Anti-Tuberculous Lymph Compound has a specific immunizing

influence upon the tuberculosis patient, find the same to be true

today.”

Careful reading of the matter just quoted will reveal its ambiguity

and inherent lack of frankness. The inference conveyed is that the

“selected body of skilled physicians” have unqualifiedly endorsed

Anti-Tuberculous Lymph Compound (Sweeny)--but it does not say so!

It is the history of all such preparations, introduced to the medical

profession with the usual blare of trumpets, that a certain number of

favorable testimonials can be obtained. It is also the history of such

products that one has but to wait a few years and the physicians who

had written most enthusiastically regarding the preparation--in the

first flush of their optimism following its use and the perusal of the

manufacturers’ literature--will acknowledge that they were mistaken

in their original estimate and are no longer using the agent. In

this connection an investigation of some of the old testimonials for

Anti-Tuberculous Lymph Compound by the Propaganda department of The

Journal is instructive.

In a somewhat elaborate booklet published in 1907 by Sweeny, an Indiana

physician was said to have reported favorable results following the

administration of the “lymph.” A letter written to this physician in

October, 1919, asking for his present opinion on the product brought

this reply, in part:

“... it being twelve years since using the serum and no reference

or repeated orders since should surely suffice as evidence of my

lack of faith in the serum....”

An Illinois physician was reported in the same booklet to have

described a case of a young man with an active tuberculosis, who was

given injections of the “lymph” in February, 1907. The patient, it was

claimed, showed immediate improvement and the Sweeny booklet (published

in August, 1907) stated that “improvement in this case continued and

terminated in complete recovery.” A letter written to the physician in

October, 1919, brought out the fact that the young man in question,

after receiving “Anti-Tuberculous Lymph Compound” and _other treatment_

was removed “on a stretcher” “to New Mexico, where he remained for

three or four years” and recovered. The doctor adds:

“I do not think that the Anti-Tuberculous Lymph had anything to

do with the man’s recovery, although I realize the difficulty of

definitely analyzing just what did effect the cure. I did since

that time use that preparation in several other cases without

beneficial results so that I gave it up a good many years ago

adding it to that large heap of pharmaceutical material ‘weighed

and found wanting.’”

A physician in Texas also reported in the 1907 booklet as having had

very satisfactory results with the Anti-Tuberculous Lymph Compound in

one case of pulmonary tuberculosis was written to in October, 1919. He

replied:

“I will state that subsequent use of this compound did not bear out

the apparent good results from its use in the first case or two.”

In a “Bulletin” issued by the Sweeny concern in 1912, a Pennsylvania

physician was quoted as having treated three cases with Anti-Tuberculin

Lymph Compound with resultant cures. This physician was written to in

October, 1919, and he replied:

“I have no knowledge of the use of my name by any Pittsburgh

concern and know nothing of a lymph of the name of Sweeny; neither

do I recollect ever curing three cases of tuberculosis with any

lymph.”

The same “Bulletin” quoted the alleged statement by a Delaware

physician to the effect that he believed Anti-Tuberculous Lymph

Compound to be the most successful treatment of tuberculosis extant.

This in 1912. To an inquiry sent in October, 1919, this physician

briefly replied:

“Am not using it now.”

The result of the Propaganda department’s questionnaire was what might

have been expected. Every physician who answered the inquiry regarding

his previous and present opinions of Anti-Tuberculous Lymph Compound

(Sweeny) declared, in effect, that he had long since ceased to have

faith in its value or efficacy.

According to claims made in Sweeny literature, “Anti-Tuberculous Lymph

Compound exercises its immunizing power through a specific action upon

the blood cells.” The statement that “it destroys the tuberculosis

germ when this is present in the system of the patient” is untrue.

The facts are, no serum or lymph has thus far been proved to have

any value in the treatment of tuberculosis even when fortified by “a

small proportion of chloride of gold and soda” as one circular tells

us the “lymph” is. In spite of research by competent investigators, we

are still without any aid in the form of a serum in the treatment of

tuberculosis.

Anti-Tuberculous Lymph Compound (Sweeny) is one of those preparations

that need no elaborate laboratory tests, nor even exact therapeutic

research, to convince any clear-thinking person that it is patently and

obviously worthless. One would hesitate before asking any reputable

clinician to test a preparation of this sort. It is a constant source

of surprise that some physicians allow themselves to be persuaded by

advertising literature that is obviously uncritical and unscientific,

to use preparations which have no more reasonable foundation than this

one.

The Council declares Anti-Tuberculous Lymph Compound (Sweeny) not

acceptable for New and Nonofficial Remedies.

Anti-Syphilitic Compound (Sweeny)

This preparation also is made by or under the direction of the same

Dr. Gilliford B. Sweeny whose researches (?) led to the production and

evolution of the Anti-Tuberculous Lymph Compound (Sweeny). According to

the data at hand, this preparation is made by suspending benzoate of

mercury in lymph from the bullock. Case reports are given of alleged

cures of syphilis after two months of treatment; indeed, the circular

exploiting the agent makes the statement that it is seldom necessary

to continue the treatment beyond two months, which, if one chose to be

credulous, would indicate extraordinary power for the mercury.

Mercury of course has a proper place in the treatment of syphilis,

but that any physician could be induced to place his trust in this

preparation is almost unthinkable though testimonials--which the

“National Laboratories” claim to have received from physicians--are

published. They all stamp the writers as not only gullible but also

incompetent. The tenor of the claims is on a par with those made for

the Anti-Tuberculous Lymph Compound; they do not justify the time

required for detailed consideration.

The Council declares Anti-Syphilitic Lymph Compound (Sweeny) not

acceptable for N. N. R.--(_From The Journal A. M. A., April 3, 1920._)

SYRUP LEPTINOL (FORMERLY SYRUP BALSAMEA)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report

on “Syrup Leptinol” (formerly “Syrup Balsamea”). The product is

inadmissible to “New and Nonofficial Remedies,” first, because the

manufacturers fail to give the profession information regarding either

the amount of the potent ingredient or the method of determining

its identity and uniformity; second, because of the unwarranted

recommendation for its use in such infectious diseases as pneumonia and

epidemic influenza and for lack of satisfactory supporting evidence of

its alleged therapeutic efficacy in other diseases and, third, because

the recommendations for its use appearing on and in the trade package

constitute an indirect advertisement to the public.

W. A. Puckner, Secretary.

Syrup Leptinol is sold by the Balsamea Co. of San Francisco. It was

first introduced as Syrup Balsamea. In recent advertising, Syrup

Leptinol is also referred to simply as “Leptinol.”

According to the statements of the Balsamea Co., Syrup Leptinol is

prepared from the root of a species of Leptotaenia (a plant belonging

to the parsnip family) which grows in Nevada and which has heretofore

not been used in medicine. The manufacturer states that the botanists

who have been consulted have been unable to agree on the botanical

classification of the plant. The dried root of this unclassified

species of Leptotaenia is extracted with alcohol and from the extract

so obtained the syrup is made, but no information has been furnished

to show how the alcohol-soluble material is incorporated in the syrup.

Further, the manufacturer has not announced tests whereby the identity

and uniformity of the finished preparation may be determined.

A booklet contains the following:

“The species of Leptotaenia from which LEPTINOL is produced was

first used in medicine by Dr. E. T. Krebs, who, after thorough

laboratory investigation and clinical application over a period

of several months, which resulted in the perfecting of LEPTINOL,

prescribed the preparation for Influenza during the epidemic of

that disease in 1918 with remarkably good results. Since this first

use, LEPTINOL has been exhaustively tested by clinicians in private

practice and in hospitals in the treatment of Pneumonia, Influenza

Bronchitis, etc., and has been universally endorsed.”

In a circular letter it is asserted that the use of “Leptinol” during

the “influenza epidemic” of 1918-1919 “demonstrated its almost specific

action in respiratory affections”; that “during this epidemic it proved

to be five times as efficacious as any other treatment in pneumonia

...”; and that “it is now as firmly fixed in the mind of many doctors

for respiratory diseases as quinine is for malaria and the salicylates

for rheumatism.”

In the booklet it is further stated that the therapeutic action of

the preparation is primarily that of a “stimulating expectorant” and

secondarily as a “sedative expectorant”; that “its antiseptic action

in the respiratory tract is prompt”; that it “is an effectual cardiac

tonic where the tone of the heart muscle is impaired by fever”; that

“in acute pulmonary conditions it effectively improves the respiratory

action and allays cerebral irritation due to fever and toxins”; that

it acts “as a vital stimulant and nerve sedative”; that “it stimulates

the excretion of acid by the skin and in fever it has a strongly

diaphoretic and antipyretic action without depressing the circulation

or the central nervous system”; that it is “mildly diuretic” and

“slightly augments the biliary flow” and that “it increases the gastric

and intestinal secretions and allays intestinal fermentation.”

No evidence has been presented to the Council which shows that Syrup

Leptinol has the actions ascribed to it. The reports of clinical trial

are little more than chance observations and lack all control. This

applies also to the following, stated to be a quotation from the report

of the Tonopah Mines Hospital Association:

“In the spring of 1919 a recurrence of the Influenza epidemic of

the previous winter was experienced. During the first period of

this second epidemic, prior to April 15th, there were treated one

hundred sixteen cases of Influenza, fourteen of which developed

Influenzal Pneumonia, with six deaths. The Pneumonia was of the

very virulent type which prevails in this high altitude.... After

April 15th, when the clinical use of Leptinol was inaugurated,

three hundred and sixty-eight cases of Influenza were treated

and not a single case developed Pneumonia. Twenty-two cases of

Influenzal Pneumonia were received and treated with LEPTINOL, with

a consequent one hundred per cent. recovery....

“In the cases where LEPTINOL was used the treatment was the same

as had been previously followed, as to diet, fresh air, etc., but

the medication was confined to LEPTINOL. Syrup LEPTINOL was started

immediately in one-dram doses at one-hour intervals, in cases with

high temperatures, and this was continued until temperature and

pulse subsided. It was then used in one-dram doses at three-hour

intervals as recovery progressed. On admission to the hospital,

calomel in 1/4 grain doses, was given at fifteen minute intervals

for eight doses. The last calomel was followed in six hours by 1/2

ounce Magnesium Sulphate in saturated solution. The second day 1/10

grain of calomel was given at one-hour intervals for ten doses....”

Medical journals are replete with reports of remarkable results

obtained with the most varied forms of treatment instituted at the time

that the “influenza epidemic” had been reached. In these cases it is

more than probable that the lessened virulence of the causative factor

of the disease, the gradually established resistance of those stricken

with it in the latter period and the improved management resulting

from experience deserve the credit for the successful outcome of the

treatment, rather than the particular form of medication employed.

The report of the Tonopah Mines Hospital Association directly

implies that Syrup Leptinol prevents the development of pneumonia

in practically all cases of influenza in which it would develop and

that it entirely abolishes the mortality of that disease. However,

it is well known that innumerable remedies have been recommended as

specifics in the treatment of pneumonia on the basis of the treatment

of a limited number of cases which recovered, and that eventually these

asserted specifics have been discarded as of little value. In the

present instance, the recovery of twenty-two cases in succession afford

_prima facie_ evidence that those cases were not the virulent type of

pneumonia in which the death rate is very high under any methods of

treatment. While no effort appears to have been made to determine the

nature of the infecting organism, the records show fairly conclusively

that they belonged to those causing the milder type of pneumonia.

The Council finds Syrup Leptinol (formerly Syrup Balsamea) inadmissible

to New and Nonofficial Remedies because: (1) the information in regard

to composition does not state the amount of potent ingredient, nor

permit the determination of its identity and uniformity; (2) the

recommendation for its use in such infectious diseases as pneumonia

and epidemic influenza is unwarranted and its claimed therapeutic

efficacy in other diseases is without satisfactory supporting evidence;

and (3) the recommendations for its use which appear on the label and

the circular wrapped with the trade package constitute an indirect

advertisement to the public.

The Council accepts the explanation of the manufacturer that he has

been unable to obtain a satisfactory classification of the plant from

which Syrup Leptinol is made. It would be undesirable to exclude

from therapeutic use a valuable drug simply because its botanical

character has not been determined or because an exhaustive chemical

examination had so far not been made. However, in the absence of such

information the manufacturer should give full information with regard

to the preparation or standardization of his remedy and the therapeutic

claims made for it should be accompanied by indisputable, thoroughly

controlled clinical evidence. In the case of Syrup Leptinol, there is

no satisfactory evidence available showing that the preparation has

any value in the treatment of epidemic influenza, pneumonia, whooping

cough, etc. While it is probable that a balsamic syrup, such as Syrup

Leptinol, has palliative properties in coughs, such action does not at

all justify the claim that it is useful in the contagious diseases for

which it is proposed. The Council cannot recognize a syrup presenting

an unknown plant in uncertain proportions which is recommended in a

variety of dangerous contagious diseases in which it ultimately may be

harmful, even though in early stages of these diseases it may serve to

allay some of the milder symptoms.

Concerning the composition of the plant from which Syrup Leptinol is

prepared, the Balsamea Company states that it contains “Alkaloids,

acids, glucosides, volatile and fixed oils, gums and resins.” This

information is valueless, since no information is given concerning the

character, amounts or pharmacologic action of the ingredients. Further,

it is unreliable as far as the presence of alkaloids is concerned since

the A. M. A. Chemical Laboratory has been unable to find any alkaloids

in the specimen of the crude drug furnished by the manufacturers.

In accordance with its regular procedure, the Council submitted the

preceding statement to the manufacturer.

In reply the Balsamea Company stated that it is more than ever of the

belief that Syrup Leptinol is deserving of recognition by the Council,

basing this opinion on further clinical experience with it in the

treatment of influenza.

The manufacturer stated that the use of the words “Leptinol” and “Syrup

Leptinol” interchangeably was due to an oversight and promised to limit

the use of the word “Leptinol” to an alcoholic extract of the plant.

Concerning the method of preparation of this alcoholic extract and the

amount used in the preparation of Syrup Leptinol the Balsamea Company

replied as follows:

“The alcoholic extract of the Leptotaenia, which we have termed

‘Leptinol’ is a preparation of definite and uniform strength, as

determined by two methods: (a) the gravity test using the U. S.

Hydrometer Scale for spirits, by which Leptinol registers 52

degrees at 60 degrees F., and (b) by gentle evaporation of the

alcohol content and the measuring of the active constituents, which

measures twenty-five per cent. by weight.

“The alcoholic extract ‘Leptinol’ is glycerinated in a machine,

using one part of the alcoholic concentration to four parts

of glycerin. This is then added to eleven parts of a heavy

syrup, containing 7-1/2 pounds of sugar to the gallon of syrup,

and thoroughly mixed in an agitating machine. Leptinol is the

sole active ingredient of Syrup Leptinol. Syrup Leptinol is a

preparation of uniform strength. It is far more uniform in strength

than most of the syrups of the U. S. P. made from fluid extracts

which are made from crude drugs which are not uniform in strength.”

This claim cannot be allowed as meeting the conflict with Rule 1. It

is well known that plants vary in their composition at different times

of the year; under different conditions of cultivation and growth;

and under other conditions; hence the claim that alcoholic extracts

of equal specific gravity insure uniformity of composition in active

principles must be considered entirely illogical, especially since the

exact nature of the active principles, if any be present, is unknown.

If these are known their nature should be stated and tests for their

identity be given. If they are unknown it is manifestly misleading to

state that the preparation is of uniform strength.

It is evident that the Council cannot approve of the use of a

preparation of unknown composition without satisfactory evidence of

its value, especially when it is recommended in a variety of serious

infectious diseases such as influenza and pneumonia. The mere fact

that a small number of patients who have received the drug recover

is no evidence of its curative value, and until carefully controlled

clinical tests of the preparation are made, it is not entitled to the

consideration of physicians.--(_From The Journal A. M. A., June 5,

1920._)

FORMITOL TABLETS, II

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following supplementary

report on Formitol Tablets.

W. A. Puckner, Secretary.

In the Council report (The Journal A. M. A., Oct. 4, 1919, p. 1077) on

the ineffectiveness of lozenges claimed either to contain formaldehyd

or to liberate formaldehyd in the mouth, the composition of Formitol

Tablets of the E. L. Patch Co. was briefly discussed in the following

terms:

“The A. M. A. Chemical Laboratory reported that Formitol Tablets

contained formaldehyd (or paraformaldehyd), an ammonium compound,

and some hexamethylenamin. It is probable that the formaldehyd

(or paraformaldehyd) was produced by the decomposition of

hexamethylenamin originally present in the tablets but decomposed by

long contact with the acid.”

At the time this report was published, the label and the advertising

matter contained but vague and indefinite statements with regard to

the composition of Formitol Tablets. In the October, 1919, issue of

_Patchwork_, the house organ of the E. L. Patch Co., it was denied that

these tablets contain hexamethylenamin since none had ever been used in

their manufacture. It was also claimed that the company had a “printed

sheet giving the formula of these tablets.”

The Council advised the E. L. Patch Co. that it desires to publish only

facts about the products which it examines and that if the report on

Formitol Tablets was inaccurate in any way the Council would want to

correct any error it might have unintentionally made. As the Formitol

advertising in the files of the Council contained no information as to

the composition of the tablets, the firm was also requested to send the

printed sheet giving the “formula.”

When this printed “formula” came it was found to be a sheet used by

the E. L. Patch Co. for the purpose of giving its salesmen information

regarding Formitol tablets, to be passed on to the physician. This

printed sheet conveyed the information that Formitol Tablets contain

ammonium chlorid, benzoic acid, citric acid, guaiac, hyoscyamus,

menthol, paraformaldehyd and tannic acid, but it gave no information in

regard to the amount of any of the ingredients except that it declared

that each tablet represents the equivalent of 10 minims of a 1 per

cent. formaldehyd solution.

Because of the nonquantitative, and, therefore meaningless printed

“formula” and because, also, of its complexity, it was thought

desirable to make a more complete analysis of Formitol Tablets.

Experience has shown that frequently the real formula of a thing is

quite different from the alleged formula published by the manufacturer.

The details of the laboratory’s later analysis will appear in the

Annual Reports of the Chemical Laboratory or may be had on request.

The result of the laboratory’s additional experimental work, especially

when taken in connection with investigations made elsewhere on

the interaction of formaldehyd and ammonium chlorid justifies the

conclusion that Formitol Tablets do contain some hexamethylenamin,

even though the amount may be very small. As the E. L. Patch Co.

declare that no hexamethylenamin is put into Formitol Tablets the

conclusion drawn in the Council’s original report to the effect

that the formaldehyd probably was formed by the decomposition of

hexamethylenamin was evidently an error. The hexamethylenamin present

is doubtless produced by the action of the paraformaldehyd on the

ammonium chlorid present.

The analysis also showed that more than 78 per cent. of the weight

of Formitol Tablets was made up of sugars and about 16.5 per cent.

was starch and other material, some of which was talcum or similar

material. This means that about 94 per cent. of the total weight of

the tablets is sugar and starch, neither of which is mentioned in the

printed “formula.” The significance of this is apparent when it is

considered that there are eight ingredients listed in the “formula” for

which therapeutic effects are claimed. Since a tablet weighs about 13.5

grains, the combined weight of all the claimed active ingredients is

less than 1 grain per tablet!

The amount of ammonium chlorid found, as indicated by the total

nitrogen, was not more than 1.0 per cent. or about 1/8 grain per

tablet. The amount of benzoic acid found was 0.34 per cent. or 1/25

grain per tablet. Yet these two drugs are said to exert their peculiar

expectorant action. (The U. S. P. lozenge of ammonium chlorid contains

1-1/2 grains ammonium chlorid or twelve times the amount of this drug

in a Formitol Tablet.)

The tannic acid contained in the tablets could not be determined with

accuracy but it was much less than 1 per cent. (or 1/8 grain per

tablet) yet it is said to add valuable astringent qualities to Formitol

Tablets! (The U. S. P. lozenge of tannic acid contains 1 grain of

tannic acid.)

The quantity of guaiac (as resin) is but a fraction of 1 per cent.

Yet it is said to impart to Formitol Tablets “stimulant resolvent”

properties and it is intimated that there is sufficient to be of value

in “cases of abscess of the throat and inflammation of the tissues.”

The total acidity indicates the presence of about 2 per cent. of

citric acid or 1/4 grain per tablet. Yet this amount is said to be

“antiseptic” and “aids in the general results.”

While the presence of the drug hyoscyamus (henbane) was not positively

identified by microscopic examination, alkaloids were present.

The manufacturers claim that the tablets contain menthol yet only

a suggestion of menthol could be obtained from the odor. However,

the odor of methyl salicylate--a constituent _not_ declared in the

“formula”--predominated throughout the operations of analysis.

Formitol Tablets furnish a good illustration of some well established

but often ignored truths:

1. “Formulas” that are nonquantitative are valueless or worse than

valueless.

2. The fact that a manufacturer puts certain drugs in a mixture, is no

proof that these drugs are there when the mixture reaches the patient.

The physician must be assured that they are there when he prescribes

them.

3. Complex mixtures should be avoided. It is absurd to expect, as

is claimed in the case of Formitol Tablets, anodyne, antiseptic,

astringent, expectorant, and resolvent action all at the same

time.--(_From The Journal A. M. A., June 19, 1920._)

SUKRO-SERUM AND APHLEGMATOL

Report of the Council on Pharmacy and Chemistry

Two years ago, American newspapers contained accounts of an alleged

cure for pulmonary tuberculosis “discovered” by Prof. Domenico Lo

Monaco of Rome, Italy. At that time no reference to the “cure” could

be found in medical journals which had come from Italy and other

European countries (_The Journal A. M. A._, July 13, 1918, p. 142).

Later, reports were published of experiments carried out in Italy,

according to which the intramuscular injection of solutions of sugar

(saccharose--cane sugar) diminished pulmonary secretion and was of

considerable value in the treatment of tuberculosis (_The Journal

A. M. A._, Sept. 28, 1918, p. 1083). On the whole the reports of the

trial of what has been called the Italian Sugar Cure for Consumption

have been unfavorable. At a meeting in Paris in October, 1918, Drs.

Louis Rénon and Mignot reported that they had found that the disease

in guinea-pigs was not modified by the treatment and with humans the

results were also negative (Paris Letter, _The Journal A. M. A._, Nov.

23, 1918, p. 1760).

In view of the exploitation of this treatment in the United States

by the Anglo-French Drug Co., which offers “Sukro-Serum,” and by G.

Giambalvo & Co., which sells “Aphlegmatol,” and because of inquiries

received, the Council has authorized publication of the statement which

follows.

W. A. Puckner, Secretary.

A circular issued by the Anglo-French Drug Co., describes “Sukro-Serum”

as a “Sterilized Solution of lacto-gluco-saccharose.” By reading the

circular to the end, however, one learns that “Sukro-Serum” is not

a “serum” in the ordinary sense but apparently it is a solution of

ordinary sugar (sucrose). “Sukro-Serum is a sterilized, specially

prepared solution of Saccharose.”

Sukro-Serum has been advertised (_N. Y. Med. Jour._, Sept. 6, 1919)

as an “INTRAMUSCULAR INJECTION FOR TUBERCULOSIS” “... ready for use

in cases of Pulmonary and general Tuberculosis” with the assertion

that “It is quite certain that in the near future Sukro-Serum will be

largely used and its value fully recognized.” The circular received

from the Anglo-French Drug Co. contains quotations from an article by

Professor Lo Monaco in the _British Medical Journal_ (Aug. 24, 1918)

setting forth the merits of intramuscular injections of sucrose in

tuberculosis. It is recommended that “Néocaine-Surrénine” (which the

Anglo-French Drug Co. supplies) be used for the control of pain when

Sukro-Serum is injected.

The circular enclosed with a package of “Aphlegmatol,” purchased from

G. Giambalvo & Co., contained the following with reference to the

composition of this preparation:

“A solution of Hydrats of Carbon After the formula of Prof. D. Lo

Monaco, Director of the Institut of Physiological Chemistry of the

University of Rome. Contents: _Sucrose (C₁₂H₂₂O₁₁) Glucose and

Galactose (C₆H₁₂O₆)_.”

The package contained ampules of thin, fragile, brown colored glass,

containing approximately 2-1/2 c.c. of light, clear, amber colored,

thick, sticky fluid, having a distinct caramel odor. Reaction

_p_↓{H} = 5.0. A reducing substance (probably glucose) amounting to 7.4

per cent. was found by using Benedict’s method for estimating glucose

quantitatively; after hydrolysis with hydrochloric acid, 55.5 per

cent. glucose was found. There was no reaction for albumin. No attempt

was made to identify the sugars, as it seemed probable that in the

preparation caramel had been produced.

The circular which accompanied the package of Aphlegmatol contained the

following information (spelling and composition as in original) about

its use and effects:

To be emploied where a large bronchial secretion is present in the

respiratory branches disease. The secretion will diminish and, in

non complicated cases, it will completely disappear.

Fever, cough, hemottisis, night perspiration, vomiting and

difficulty of breathing are, in the meantime, diminuished.

Aphlegmatol acts also as a riconstituent, being itself a nurrishing

composition, improves the digestive function of the body and

increases the arterial pressure.

5 c.c. (2 Phials) of Aphlegmatol per day must be injected

intramuscularly in the Gluteus.

If the patient wishes two injections may be made, one at the right

immediately followed by a second one at the left.

The cure must not be interrupted untill sometime after

expectoration has disappeared, which result may be obtained only

after fifty or sixty days, in the meantime the patient must be

controlled by his home physician, especialy when thermal elevation

of the body takes place.

Improvement will be manifested on or about the tenth day of the

first injection.

In the advertising circular, which is apparently intended for general

distribution, much the same information is given as in the sheet

enclosed with the ampules, except that in the directions we find:

“If the injections are painful--especially in cases where patients

are very emaciated--physicians are advised to inject together with

_Aphlegmatol_, as an anesthetic, a vial with 1 c.c. solution of Stovain

at 3%.” The advertising for Aphlegmatol contains many misspelled words

and appears to be the work of those ignorant of the English language.

Tuberculosis is a widespread disease and a majority of the uninformed

are only too willing and ready to try such a “cure.” The preparations

appear to be nothing more than concentrated solutions of sugar. It

is probable that a small amount of the cane sugar might be inverted

to glucose and fructose, but experiments have shown that cane sugar

subcutaneously administered in the small amounts used in this

instance is largely excreted in the urine unchanged. Less is known

about galactose, but the evidence available would indicate that

galactose is largely excreted in the urine unchanged when given

subcutaneously. Glucose would be absorbed as such, and in the amounts

under consideration, used by the system much the same as when given by

mouth.--(_From The Journal A. M. A., Aug. 21, 1920._)

SUPSALVS NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report

declaring Supsalvs (Anglo-French Drug Company) inadmissible to New and

Nonofficial Remedies.

W. A. Puckner, Secretary.

Supsalvs are advertised by the Anglo-French Drug Company as “stable

suppositories of ‘606’ (of French manufacture)” with the claim that

by the rectal administration of these suppositories the effects of

arsphenamine may be obtained. The asserted efficacy of Supsalvs

medication is based in part on the claim that for these suppositories

an excipient was found which mixes with the cocoa butter base “to form

an assimilable emulsion.”

“The active principle and the vehicle being bound to one another,

the mucous membrane is able to absorb both simultaneously and

progressively in the form of an organic emulsion.”

As no information was furnished the Council by the Anglo-French Drug

Company on the origin or quality of the arsphenamine used in the

preparation of Supsalvs or the character of the vehicle which was

“bound” to the arsphenamine in such a way as to permit the absorption

of this combination in the form of an “organic emulsion,” the firm

was requested to furnish: (1) Evidence that the arsphenamine used in

Supsalvs complies with the N. N. R. standards and that deterioration

of it does not occur in the preparation of the suppositories or on

keeping. (2) The identity of the ingredients composing the suppository.

The Anglo-French Drug Company did not supply the requested evidence

and consequently the Council judged the preparation on the basis of

the information received from the company, and that contained in the

available advertising and circulars. It found Supsalvs inadmissible

to New and Nonofficial Remedies, first because the quality of the

medicament contained in the suppositories has not been established, and

second because the claimed efficacy of this preparation as a means of

securing the effects of arsphenamine lacks substantiating proof.

During the past few years some French physicians have reported

favorably on the intrarectal administration of arsphenamine. Boyd and

Joseph at Panama published (The Journal, Aug. 17, 1918, p. 521) an

enthusiastic report on intrarectal injection of arsphenamine but did

not refer to its use in the form of suppositories. In a comprehensive

report, on the “Treatment of Syphilis” (_Quarterly Journal of Medicine,

July, 1917_) L. W. Harrison stated that arsphenamine (Salvarsan) in the

shape of an enema is definitely less effective than intravenously and

that “Neisser and the vast majority of workers can see no value in the

rectal method.” Schamberg and Hirschler (A Safe and Efficient Intensive

Method of Treating Syphilis, _Therapeutic Gazette_, November, 1919,

p. 761) have given a rather thorough trial of this method; the results

were most disappointing: “A certain or rather uncertain amount of

arsphenamine is absorbed into the blood, but the quantity is obviously

too small to be at all comparable in its effect with the intravenous

administration. Our conclusions are that the rectal administration

of arsphenamine or neoarsphenamine is an extremely feeble method of

administering these drugs.”

The report of the Special Committee on the Manufacture, Biological

History and Clinical Administration of Salvarsan and Other Substances

of the British National Health Insurance Medical Research Committee

contains the following: “The rectal method of administration, either in

the form of solution or as suppositories, has been advocated by a few

observers mainly for cases in which there is difficulty in the adoption

of the intravenous method. The experiments made by Mills at Rochester

Row show that three enemata of ‘606’ (0.6 Gm. in each) on successive

days failed to produce any effect on the spironemes in the lesions.

The general opinion of experienced workers is that the rectal method

is ineffective, and in this view the Committee concur.”--(_From The

Journal A. M. A., Oct. 30, 1920._)

HYPODERMIC SOLUTION NO. 13, IRON, ARSENIC AND PHOSPHORUS

COMPOUND NOT ACCEPTED FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Hypodermic Solution No. 13, Iron, Arsenic and Phosphorus Compound

(Burdick-Abel Laboratory) is said to contain in each c.c.:

Ferrous citrate 0.06 Gm.

Sodium cacodylate 0.06 Gm.

Sodium glycerophosphate 0.1 Gm.

Chloretone 0.005 Gm.

The preparation is advertised as “the old reliable hematinic” which is

“indicated in all forms of anemia, where both red and white cells are

low.” It is for hypodermic or intramuscular administration. The product

is inadmissible to New and Nonofficial Remedies because:

1. It does not contain ferrous citrate as claimed. Instead the iron is

in the ferric condition, apparently in the form of the unofficial and

unstandardized “iron citrate green” for which there is no evidence of

superiority over the official iron and ammonium citrate.[134]

[134] Iron Citrate Green, The Journal A. M. A., Jan. 12, 1917, p. 135;

Reports Council Pharm. and Chem., 1916, p. 42.

2. Its name gives no information on the form in which the iron, the

arsenic and the phosphorus occur therein. The term “arsenic” does

not indicate whether the mild cacodylate or the potent arsenous

oxid is being administered nor does the term “phosphorus” tell the

physician that he is administering the practically inert sodium

glycerophosphate.[135]--(_From The Journal A. M. A., Nov. 13, 1920._)

[135] Glycerophosphates, The Journal A. M. A., Sept. 30, 1916,

p. 1033; Reports Council Pharm. and Chem., 1916, p. 32. Sodium

glycerophosphates. Reports Council Pharm. and Chem., 1916, p. 52.

PARATHESIN 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.

The local anesthetic ethyl paraminobenzoate was first introduced as

“Anesthesin” or “Anæsthesin.” Ethyl paraminobenzoate is not patented

in the United States and it may be manufactured, therefore, by any

firm which chooses to do so. In order that a common name by which to

designate the drug might be available, the Council coined the name

“Benzocaine,” as being short and easily remembered, but yet suggestive

of its composition and character (“benzo” to indicate its derivation

from benzoic acid and “caine” to indicate its cocaine-like properties).

As the term “anesthesin” had become a common name for the drug, the

Council recognized this as a synonym for benzocaine.

One of the accepted brands for benzocaine is “Anesthesin,”

manufactured by the H. A. Metz Laboratories, Inc. (see New and

Nonofficial Remedies, 1920, p. 33). However, on April 19, 1920, the

Metz Laboratories requested that its product be recognized under

the designation of “Parathesin.” As the use of one substance under

several names causes confusion and retards rational therapeutics, the

Council’s rules provide against the recognition of proprietary names

for nonproprietary, established drugs. In view of this and because

the legitimate interests of the manufacturer may be safeguarded

by appending his name or initials to the common name, benzocaine

or anesthesin, the Council voted not to recognize the designation

“Parathesin.”--(_From The Journal A. M. A., Nov. 13, 1920._)

CHLORLYPTUS

Report of the Council on Pharmacy and Chemistry

The condensed report on Chlorlyptus which follows and also a complete

detailed report was sent to the proprietor, Jan. 9, 1920. In reply

he requested that publication be postponed pending the submission of

further clinical evidence. As after nine months this evidence had not

been received the Council has authorized publication of its report.

W. A. Puckner, Secretary.

Chlorlyptus is manufactured by Chas. A. Weeks, trading as the Weeks

Chemical Company, Philadelphia. It is prepared by chlorinating

eucalyptus oil until it has bound 30 per cent. of chlorin, the chlorin

being in relatively stable combination. It is claimed that Chlorlyptus

is a new “chlorinated antiseptic,” highly efficient as a wound

antiseptic and at the same time nonirritant and nontoxic. Chlorlyptus

is offered for use in the treatment of local infections of all types,

as well as of burns, and also as an antiseptic in the alimentary and

genito-urinary tracts.

The claims were based largely on reports of investigations made by

Philip B. Hawk and his collaborators. These reports the referee

of the committee in charge of Chlorlyptus considered incomplete

and unconvincing. Being advised of this Mr. Weeks caused further

investigations to be made. Some of the information was checked and

extended by the A. M. A. Chemical Laboratory and by the referee.

The laboratory side of the investigation may now be considered as

complete. The results show that Chlorlyptus is a feeble antiseptic of

the aromatic oil type, considerably weaker than eucalyptus oil, both

as to therapeutic and toxic qualities. The chlorin contained in it is

bound too firmly to have any action; in fact, the chlorination appears

to have accomplished nothing more than a considerable destruction or

weakening of the eucalyptus oil. As far as the referee can judge, this

object could have been accomplished just as effectively by diluting

ordinary eucalyptus oil with some indifferent solvent.

The manufacturer of Chlorlyptus contends that if the experimental

findings are against his product, it should be judged by the clinical

data. The clinical evidence, however, is not decisive. It shows that

wounds healed and infections were prevented or successfully combated in

cases in which Chlorlyptus was used in combination with good surgery,

but it does not show how much of the result was due to the surgery and

how much, if any, to the use of Chlorlyptus. Even if it were granted

as probable that the Chlorlyptus contributed to the favorable outcome,

it would still be a question whether it equals other established

antiseptics, or whether it possesses any material advantages over

diluted eucalyptus oil. Until these points are established the clinical

reports cannot offset the unfavorable results of the laboratory

investigation.

The manufacturer has endeavored to obtain more convincing clinical

reports, but the lack of success in this direction during the past nine

months gives little encouragement that acceptable clinical evidence

will be available within a reasonable time.

Believing that the information which has been obtained should be made

available to the profession, the Council authorized publication of

this statement and also of the detailed report. The Council voted not

to accept Chlorlyptus for New and Nonofficial Remedies because of the

unfavorable results of the laboratory investigation, but with the

agreement that the product would receive further consideration should

more convincing clinical data become available.

I. DETAILED REPORTS

Summarized Reports

CHEMICAL NATURE OF CHLORLYPTUS

Chlorlyptus is prepared by chlorinating eucalyptus oil until it

has bound 30 per cent. of chlorin. “Chlorlyptol” is prepared in an

analogous manner from eucalyptol. There has been some confusion as to

the composition; but the principal constituent is now stated to be “a

dichloride of eucalyptus oil,” to which the formula C₁₀H₁₆OCl₂ has

been assigned. It differs from the “chlorinated eucalyptus oil,” as

ordinarily used for making dichloramin-T solutions, and which contains

only 2/3 per cent. of chlorin.

AVAILABILITY OF CHLORIN IN CHLORLYPTUS

The chlorin content of chlorlyptus is almost entirely firmly bound,

and therefore not “available,” in contrast to the group of so-called

chlorinated antiseptics (i. e., the hypochlorite and chloramin type).

For instance, it does not directly liberate iodin from iodid. It

contains a very small quantity of free hydrochloric acid, or perhaps

some acid esters, and liberates a little more on prolonged contact with

water; but the total quantity liberated under reasonable conditions is

very small. According to Hawk’s data, they correspond only to 1/8 per

cent. HCl even after standing with water overnight and to only 1/5 per

cent. of HCl after two weeks. The referee has shown that this quantity

of acid has no therapeutic significance.

The “bound” chlorin of chlorlyptus, being chemically inactive, would

have no more practical significance than the bound chlorin in common

salt. The “ozone” said to be used during the preparation, to expel the

HCl, has also practically disappeared, to judge by the slowness with

which iodin is liberated from potassium iodid.

ACID FORMATION

Some constituents of chlorlyptus hydrolyze slowly and to a slight

degree with the liberation of a trace of free hydrochloric acid.

According to the data of Hawk’s report, the free acidity, in term

of HCl, is 1/12 per cent. On standing with water over night, this

increases to 1/8 per cent.

On this basis, Hawk proposed a theory that the claimed antiseptic

effects of chlorlyptus are due to the continuous liberation of

hydrochloric acid.

Experiments by the referee show this to be untenable. The traces of

acid are neutralized and absorbed by the tissues so rapidly that an

acid reaction is not maintained. These experiments are described in the

appendix.

They were submitted to the manufacturers, who in the name of Mr. Weeks

(May 9, 1919) concede this conclusion and state that “there is no

doubt that the referee’s statements as to action in mouth, contact

with living tissue and improbability that the acidity is effectively

antiseptic is correct, and I am willing to accept the referee’s

statement as conclusive in this respect.”

BACTERIAL CULTURE EXPERIMENTS

Mr. Weeks submitted a statement by Hawk to the effect that chlorlyptus

has a phenol coefficient of 2.6, determined by the standard Hygienic

Laboratory procedure.

He also quotes Rockefeller War Hospital that chlorlyptus kills

_Staphylococcus aureus_ in concentra of 1 dram: 1 gallon (about

1:1,000), but not in more dilute solutions.

More recently, he presented a more comprehensive report by Rivas, which

is reproduced in the appendix. The essential results are tabulated

herewith. This tabulation shows that chlorlyptus fails to kill the

organisms after an hour’s exposure of the following concentrations:

Typhoid in bouillon, 10 per cent. of chlorlyptus.

Staphylococci in pus, 5 per cent. of chlorlyptus.

Staphylococci in serum, 1 per cent. of chlorlyptus.

It seems to the referee that a substance that is ineffective with an

hour’s exposure to these concentrations is not at all likely to kill or

check bacteria under clinical conditions. In other words, it is not an

antiseptic in the ordinary sense.

The referee is not impressed by the superior power attributed by Rivas

to chlorlyptus in the presence of pus. Inefficiency of 10 per cent. for

one-half hour or of 5 per cent. for two hours seems a failure rather

than a success. The referee also notes the absence of any data as to

the relative efficiency of chlorlyptus against staphylococci in pus and

in bouillon. The data on serum indicate that chlorlyptus is much weaker

than phenol and show that it is _less effective in the presence of pus_

than in other mediums.

The referee fails to grasp the bearing of the oil experiments on any

clinical condition. Moreover, the inconstant results mentioned by Rivas

suggest the possibility that the incorporation of the bacteria in oil

may have prevented their effective distribution in the culture medium.

If any significance is to be attached to these experiments, they should

be checked by controls, without antiseptics.

SUMMARY OF RIVAS’ IN VITRO EXPERIMENTS

====================================================================

Minimal Maximal

Germicidal Not Germicidal

Concentrations Concentrations

Typhoid Bacilli in Bouillon:

Chlorlyptus (Exp. 3) 10%, 2 to 4 hours 10% for 1 hour

5% for 2 hours

Eucalyptus oil (Exp. 1) 5% within 5 minutes No data

Phenol (Exp. 5) 1% within 10 min. No data

Streptococci and Staphylococci in Olive Oil:

Chlorlyptus

(Exps. 7 and 8) 1%, almost at once, No data

sometimes

Eucalyptus oil No data No data

Phenol (Exps. 9 and 10) 1%, almost at once, No data

Staphylococci in Pus:

Chlorlyptus (Exp. 11) 10% for 1 hour 10% for 1/2 hour

5% for 2 hours

Eucalyptus oil No data No data

Phenol No data No data

Staphylococci in Human Blood Serum:

Chlorlyptus (Exp. 12) 5% in 1 hour 1% in 1 hour

Eucalyptus oil No data No data

Phenol 5% almost at once 1% in 1 hour

--------------------------------------------------------------------

INFECTION EXPERIMENTS IN VIVO

Dr. Rivas reports two series of experiments, in each of which three

guinea-pigs received staphylococcus suspensions in the peritoneum.

One guinea-pig in each series was left untreated; the others received

injections of chlorlyptus into the peritoneum at various intervals.

The following results were obtained:

====================================================

Chlorlyptus Results

Exp. 19, No. 1 None Survived

Exp. 20, No. 1 None Died

Exp. 19, No. 2 At once Died

Exp. 19, No. 3 After 24 hours Survived

Exp. 20, No. 2 After 18 hours Died

Exp. 20, No. 3 After 24 hours Died

----------------------------------------------------

This shows mortalities of:

1 in 2, i. e., 50 per cent., without chlorlyptus.

3 in 4, i. e., 75 per cent., with chlorlyptus.

It is doubtful whether so small a series of experiments on so variable

a phenomenon as is infection should receive any serious consideration.

So far as they go, they would indicate that chlorlyptus is useless or

worse.

TOXICITY

The referee determined the acute toxicity of chlorlyptus by hypodermic

injection of oily solutions into white rats. Comparative experiments

were made with ordinary eucalyptus oil. The details are given in the

appendix. The end-results may be summarized as follows:

==================================================================

Survived Chlorlyptus Eucalyptus Oil

1.56 c.c.

3.75 c.c.

5.00 c.c.

6.25 c.c. 1.25 c.c.

8.65 c.c. 2.5 c.c. (3 days)

Died (in days) 12.5 c.c. (1 day) 3.75 c.c. (3 days)

12.5 c.c. (1 day) 5.00 c.c. (3 days)

18.75 c.c. (1 day) 6.25 c.c. (1-1/2 days)

M. F. D. 8.75 to 12.5 c.c. per kg. 1.25 to 2.5 c.c. per kg.

------------------------------------------------------------------

_Fatality._--The doses are calculated for cubic centimeters of the

undiluted drugs per kilogram of rat.

Dr. Rivas reports a series of toxicity experiments on guinea-pigs.

Assuming a uniform weight of 400 gm. per animal, his results (details

in appendix) may be summarized as:

==================================================================

Minimal Maximal

Fatal Dose Survived Dose

C.c. per Kg. C.c. per Kg.

Chlorlyptus, peritoneal (Exp. 14) 7.5 c.c. 5.0 c.c.

Chlorlyptus, pleural (Exp. 15) 5.0 c.c. 2.5 c.c.

Eucalyptus oil, peritoneal (Exp. 16) 2.5 c.c. No Data

Eucalyptus oil, pleural (Exp. 16) 1.25 c.c. No Data

Dichloramin-T, peritoneal (Exp. 16) 1.25 c.c. No Data

------------------------------------------------------------------

The _comparative toxicity_ in the various series is therefore

approximately as follows:

========================================================

Chlorlyptus : Eucalyptus

Referee, rats, hypodermic 1/5 : 1

Rivas guinea-pig, peritoneal 1/3 : 1

Rivas guinea-pig, pleural 1/4 : 1

--------------------------------------------------------

Evidently, the toxicity of chlorlyptus is about one-fourth of that of

eucalyptus oil. The difference is considerable, but not fundamental.

Moreover, the symptoms of chlorlyptus resemble the characteristics of

eucalyptus oil.

According to the tabulation of Barker and Rowntree,[136] the mean fatal

dose of eucalyptus oil for man, in the twenty-nine clinical cases

reported in the literature, is about 20 c.c. If the toxicity ratio of

the two substances were the same as for the rat experiments (a rather

hazardous assumption), the fatal dose of chlorlyptus for man would be

about 80 c.c.

[136] Barker and Rowntree (Bull. Johns Hopkins Hospital =29=:215, 221

[Oct.] 1918) obtained the following results with eucalyptus oil:

Cat, hypodermic; survived 3 c.c. per kg.; killed by 5.5 c.c. per kg.

Cat, intraperitoneal; killed by 5 c.c. per kg.

Dog, hypodermic; survived 1.3 c.c. per kg.

They quote from Browning that the following doses, c.c. per kilogram,

are not fatal: frogs, 0.5; rabbits, 1 to 5; guinea-pigs, 1.

IRRITATION

Rivas’s Experiment 14 shows that chlorlyptus gives very definite

irritation, apparently similar to that produced in Experiment 16 by

eucalyptus oil in one-fourth the dose.

Incidentally, the referee may add from personal experience that the

“chlorlyptus oil, 5 per cent. Cl” is markedly irritating in the

nostrils, although marked “non-irritating” on the label.

II. APPENDIX: SPECIAL REPORTS

A. COMPARISON OF CHLORLYPTUS WITH CHLORINATED EUCALYPTOL

From the Chemical Laboratory of the American Medical Association

According to the label, “Chlorlyptus” is a “Synthatized Chlorinated

Oil of Eucalyptos, with Acid Reaction, containing approximately 30

per cent. Chlorine and possesses excellent Germicidal Properties,

when made under our special process.” It is manufactured by the Weeks

Chemical Company, Philadelphia, Pa. This product was submitted to the

Council on Pharmacy and Chemistry by the manufacturers, and in turn

the Laboratory was asked to examine it with the idea of comparing it

with the nonproprietary brands of “chlorinated eucalyptol” (used as a

solvent for dichloramine-T; see New and Nonofficial Remedies, 1919,

p. 70). In the submission, certain tests were described, most of which

were followed. Among the statements given under the chemical properties

of chlorlyptus are:

“On distillation, chlorlyptus begins to boil at about 100 C. The

temperature rises as the distillation continues, accompanied by the

decomposition of the chlorlyptus and the evolution of hydrochloric

acid and chlorine.”

“When brought into contact with water, chlorlyptus undergoes a

process of hydrolysis ...”

Notwithstanding the foregoing the statement is made on the label that

chlorlyptus “is a Stable Compound, not affected by heat, light or

water.”

The following comparisons of chlorlyptus, chlorinated eucalyptol-Abbott

and chlorinated eucalyptol-Squibb were made:

Chlorlyptus is a viscous, dark brown liquid, with an acrid odor and

having a specific gravity of 1.2098. Chlorinated eucalyptol-Abbott is a

mobile, light yellow liquid, with a eucalyptus odor, having a specific

gravity of 0.9317. Chlorinated eucalyptol-Squibb is a mobile, colorless

liquid, and its specific gravity is 0.9303.

An alcoholic solution of silver nitrate added to an alcoholic solution

of chlorlyptus yields a heavy precipitate of silver chloride. In the

case of the Abbott chlorinated eucalyptol a slight turbidity is caused

by this test; the Squibb product shows no reaction.

A 10 per cent. solution of potassium iodide is overlaid with an equal

volume of chlorlyptus. Iodine is slowly liberated, being noticeable

in one-half hour. With chlorinated eucalyptol-Abbott, a trace of

free iodine is discernible after four hours, while with chlorinated

eucalyptol-Squibb there is no free iodine present. When the respective

products are shaken with an alcoholic solution of potassium iodide, no

iodine is immediately liberated, thus showing the absence of “active

chlorine” (difference from the hypochlorite derivatives).

When chlorlyptus is dissolved in concentrated sulphuric acid, some

blackening occurs and the odor of hydrogen chloride is very noticeable.

Both the Abbott and Squibb brands of chlorinated eucalyptol give a

reddish mixture, with no perceptible evolution of hydrogen chloride,

and still retain the characteristic eucalyptol odor.

On heating, chlorlyptus decomposes and begins to boil at from 103 to

105 C. Then a higher fraction comes over at 178 C. The distillate has

a sharp odor, is acid, and frees very little iodine from potassium

iodide. Chlorinated eucalyptol-Abbott does not seem to decompose. Some

gaseous substance is given off at 80 C, but the liquid distills at

173 C. The distillate has no acid odor, is neutral, and liberates no

iodine from potassium iodide. (In both cases the distillation was not

carried to completion, approximately only about half of the volume

being distilled over.)

PRELIMINARY TESTS ON CHLORLYPTUS AND CHLORINATED EUCALYPTOL

======================================================================

Chlorinated Chlorinated

Chlorlyptus Eucalyptol-Abbot Eucalyptol-Squibb

Odor Acrid Like eucalyptus Like eucalyptus

Density and Dark brown; Light yellow; Colorless;

color viscous, mobile; lighter mobile; lighter

heavier than water than water

than water

AgNO₃ added Heavy ppt. Slight turbidity Clear

to alcoholic

solution

Equal parts Gives free Gives free iodin No free iodin

with KI iodin slowly, in 4 hours; in 4 hours

solution noticeable not much

in 1/2 hour

Equal parts Much iodin Small amount of No free iodin

with 10% KI, immediately free iodin in in 3 hours

10% KIO₃  few numbers;

solution does not

noticeably

increase

Equal parts Some blackening; Reddish mixture; Same

with conc. odor of HCl no HCl;

H₂SO₄ eucalyptol odor

Alcohol KI No iodin Same Same as Abbott

liberated product

Heating Decomposes and Apparently does not

boils at decompose; some

103-105 C.; gas given off

then higher when T=80; the

fraction comes liquid distilled

over at 178 C.; at 173 C.; the

distillate has distillate did

sharp odor, is not have much

acid, but frees odor; no HCl

very little gas detected;

I₂ from KI;  no I₂ from

distillation KI; distillate

not completed was neutral

(distillation

not completed)

----------------------------------------------------------------------

The addition of chlorlyptus to a mixture of 10 per cent. potassium

iodide, 10 per cent. potassium iodate solution, brings about the

liberation of iodine, increasing perceptibly on standing. This shows

that the hydrogen chloride is gradually split off, and in time will

cause a solution having a considerable degree of acidity. When this

test is carried out on chlorinated eucalyptol-Abbott, a small amount

of iodine is liberated in a few minutes but does not increase, showing

a slight initial acidity without further hydrolysis. Chlorinated

eucalyptol-Squibb yields no free iodine after standing three hours.

When the chlorine content of chlorlyptus is determined according to

the method of Carius, the amount is found to be 29.6 per cent. (The

manufacturers give a method of determining chlorine by Hunter’s fusion

method. It is believed that in this method hydrogen chloride may

be lost, and this opinion is substantiated by the firm’s statement,

“Chlorlyptus analyzed in this manner shows approximately 25 per cent.

of chlorine.”) The chlorine content of chlorinated eucalyptol-Abbott is

found to be 0.67 per cent., and that of the Squibb brand to be 0.62 per

cent. (about one-fiftieth as much as in chlorlyptus).

To sum up: Chlorlyptus differs from chlorinated eucalyptol in odor,

color, density, in reaction to silver nitrate, potassium iodide,

sulphuric acid and the aqueous solution of potassium iodate and

potassium iodide. The distillation of the two products occurs

differently. Chlorlyptus contains nearly 30 per cent. of chlorine,

which is approximately fifty times as much as in chlorinated

eucalyptol. Thus it appears to have considerable chlorine in the

negative form (Cl^-) which may be relatively easily split off as

hydrogen chloride.

B. THE PERSISTENCE OF THE ACID

Reaction of Chlorlyptus in the Body

BY THE REFEREE

This “chlorinated ozonized eucalyptus oil” is distinctly acid to litmus

paper. It is claimed that further quantities of acid are liberated on

contact with water. This is credited with producing a continuous acid

reaction on the surface of tissues to which the oil may be applied and

this in turn is stated to be antiseptic or germicidal.

This theoretical speculation does not take into account the large

quantity of reserve alkali in the body by which it combats attempts to

alter its normal reaction. It is therefore not convincing, unless it is

supported by direct evidence.

In the absence of such data on the part of the promoters of the

preparation, experiments were made to determine whether the oil

preserves its acid reaction in contact with mucous and serous

membranes. The answers were clearly in the negative.

In the mouth, the reaction becomes neutral within ten or fifteen

minutes; in the pleura and peritoneum within half an hour, and probably

in much shorter periods.

More detailed data follow:

SERIES A: BEHAVIOR IN THE MOUTH; HOMO

EXPERIMENT.--Chlorlyptus and to less extent Chlorlyptus Oil, are acid

to litmus. They are applied:

(_a_) Drop to litmus paper and this to gums.

(_b_) Several drops directly to tongue.

(_c_) Same to gums.

The reaction to litmus paper is tried from time to time.

RESULTS.--(_a_) Applied to gums on litmus paper:

Chlorlyptus: Red color becomes gradually feebler and does not spread on

the paper.

Chlorlyptus Oil: Turns blue in a few minutes.

(_b_) Dropped on _tongue_:

Chlorlyptus: Acid taste at once. Does not increase, but on contrary,

becomes less.

Litmus applied after ten minutes: not acid.

Litmus applied after five minutes: distinctly acid.

(_c_) Dropped on inside of _cheek_:

Chlorlyptus, 1/3 c.c.: After six minutes, litmus very red.

After ten minutes, faintly red.

After fifteen minutes, blue.

Chlorlyptus Oil, 1 c.c.

After three minutes, faintly red.

After eight minutes, neutral.

CONCLUSIONS.--On contact with living tissues, the acid of chlorlyptus

is rapidly neutralized and absorbed.

The surface is neutral within ten or fifteen minutes.

It is therefore very improbable that the acidity is effectively

antiseptic.

A comparison of chlorlyptus with dilute acetic acid shows that the

chlorlyptus does not maintain the acidity even as well as 1 per cent.

acetic acid.

=====================================================================

Acetic Acid Chlorlyptus

Tongue, a drop of 5 per cent.; still Neutral between five

slightly acid to litmus after ten minutes; and ten minutes

taste almost gone in two minutes

Gums, a few drops between cheeks and gums: Neutral between ten

Five per cent. still strongly acid in and fifteen minutes

twelve minutes; distinctly acid in

seventeen minutes. One per cent. still

strongly acid in twenty-one minutes

---------------------------------------------------------------------

CHLORLYPTUS: REACTION (LITMUS PAPER) ON CONTACT WITH TISSUE

======================================================================

Serial When Quantity, Time Blue Symptoms or

No. Animal Injected C.c. of Death Litmus Toxicity

1 Rat Pleura 1 1/2 hour Remains blue None; killed;

pleura not

congested;

lung spec. =

21; slight

congestion

2 Rat Pleura <1 1 hour Remains blue Negative

3 Rat Pleura 1 23 min. Remains blue Almost at once

bad gasping

respiration

and died in

23 m.; heart

distend.;

possibly

injection

penetrated

lung

Peritoneum 1 23 min. Turns red

4 Rabbit Pleura 1 .... ...... Died

overnight

5 Dog Pleura 1 1/4 hour Remains blue

20 m. p. m.

Peritoneum 1 1/4 hour Remains blue

20 m. p. m.

6 Dog Pleura 1 3 min. Remains blue

45 m. p. m.

Peritoneum 1 3 min. Remains blue

45 m. p. m.

7 Dog Pleura 1 20 min. Remains blue

20 m. p. m.

Peritoneum 1 20 min. Remains blue

20 m. p. m.

SERIES B: SEROUS MEMBRANES

In these experiments, 1 c.c. of chlorlyptus was injected into the

pleura or peritoneum. After a stated time, the animal was killed, and

the reaction of the pleural or peritoneal surface was tested with blue

litmus paper. The results are shown in the table.

C. TOXICITY EXPERIMENTS

By the Referee

TECHNIC

White rats were injected hypodermically with chlorlyptus or with

eucalyptus oil, diluted with olive oil in the ratio of 1:4. The larger

doses were divided between two or more sites of injection.

DETAILED PROTOCOLS

Hypodermic injections in white rats. Drugs diluted with 3 parts of

olive oil. Doses are given as cubic centimeters of pure drug per

kilogram of rat.

A. EUCALYPTUS SERIES

EXPERIMENT 1.--_1.25 c.c._; injected VII.9.19: Active; walks about.

No depression at any time. VII.10.19. Appears normal.

EXPERIMENT 2.--_2.5 c.c._; injected VI.30.19: Quiet--not very

depressed, reflexes good (six hours).

VII.1.19--Active--reflexes good, eats moderately.

VII.2.19--Animal acts normal--eats moderately, reflexes good; active

(a.m.). Later in day, depressed.

VII.4.19--Died during night of VII.3.19.

EXPERIMENT 3.--_3.75 c.c._; injected VI.24.19: Quiet; depressed;

pain reflex diminished. Animal lay on ventral surface, not supported

by legs. Will get on to feet very sluggishly if turned on side

(twenty-four hours). Does not eat.

VI.26.19--Depressed slightly; pain reflex present.

VI.27.19--Fairly active; eats a little.

VI.28.19--Depressed.

Died during night of VI.29.19 (three days).

EXPERIMENT 4.--_5 c.c._; injected VI.24.19: Quiet; markedly depressed

(one hour). Does not get on feet when turned on side; ataxia well

marked. Slight watery secretion in eyes. Reflexes diminished. Does

not eat (twenty-four hours).

VI.26.19--Heart slowed and arrhythmic. Animal lies on side. Unable to

walk; markedly depressed.

VI.27.19--Lies on side; does not eat. Died during night of VI.27.19

(three days).

EXPERIMENT 5.--_6.25 c.c._; injected VI.24.19: Quiet; very markedly

depressed. Heart and respiration greatly slowed. Lies on side; tears

in eyes; does not eat (twenty-four hours).

VI.25.19--Temperature subnormal; cold to touch; tail stiffened and

straight.

Died during night of VI.25.19 (one and one-half days).

Postmortem: Lungs congested. Liver pale in color. Spleen very dark

red. Kidneys normal. Other organs normal.

B. CHLORLYPTUS EXPERIMENTS

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.