“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).”
“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 21⁄2c.c. of light, clear, amber colored, thick, sticky fluid, having a distinct caramel odor. ReactionpH= 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.
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 withAphlegmatol, 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.)
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 parton 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.”
“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.)
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 citrate0.06Gm.Sodium cacodylate0.06Gm.Sodium glycerophosphate0.1Gm.Chloretone0.005Gm.
Ferrous citrate
Sodium cacodylate
Sodium glycerophosphate
Chloretone
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
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.)
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.)
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.
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 C10H16OCl2has been assigned. It differs from the “chlorinated eucalyptus oil,” as ordinarily used for making dichloramin-T solutions, and which contains only2⁄3per cent. of chlorin.
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 to1⁄8per cent. HCl even after standing with water overnight and to only1⁄5per 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.
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, is1⁄12per cent. On standing with water over night, this increases to1⁄8per 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.”
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 killsStaphylococcus aureusin 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 isless effective in the presence of pusthan 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
MinimalGermicidalConcentrationsMaximalNot GermicidalConcentrationsTyphoid Bacilli in Bouillon:Chlorlyptus (Exp. 3)10%, 2 to 4 hours10% for 1 hour5% for 2 hoursEucalyptus oil (Exp. 1)5% within 5 minutesNo dataPhenol (Exp. 5)1% within 10 min.No dataStreptococci and Staphylococci in Olive Oil:Chlorlyptus (Exps. 7 and 8)1%, almost at once,sometimesNo dataEucalyptus oilNo dataNo dataPhenol (Exps. 9 and 10)1%, almost at once,No dataStaphylococci in Pus:Chlorlyptus (Exp. 11)10% for 1 hour10% for1⁄2hour5% for 2 hoursEucalyptus oilNo dataNo dataPhenolNo dataNo dataStaphylococci in Human Blood Serum:Chlorlyptus (Exp. 12)5% in 1 hour1% in 1 hourEucalyptus oilNo dataNo dataPhenol5% almost at once1% in 1 hour
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:
ChlorlyptusResultsExp. 19, No. 1NoneSurvivedExp. 20, No. 1NoneDiedExp. 19, No. 2At onceDiedExp. 19, No. 3After 24 hoursSurvivedExp. 20, No. 2After 18 hoursDiedExp. 20, No. 3After 24 hoursDied
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.
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:
SurvivedChlorlyptusEucalyptus Oil1.56 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. (11⁄2days)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:
MinimalFatal DoseC.c. per Kg.MaximalSurvived DoseC.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 DataEucalyptus oil, pleural (Exp. 16)1.25 c.c.No DataDichloramin-T, peritoneal (Exp. 16)1.25 c.c.No Data
Chlorlyptus, peritoneal (Exp. 14)
Chlorlyptus, pleural (Exp. 15)
Eucalyptus oil, peritoneal (Exp. 16)
Eucalyptus oil, pleural (Exp. 16)
Dichloramin-T, peritoneal (Exp. 16)
Thecomparative toxicityin the various series is therefore approximately as follows:
Chlorlyptus:EucalyptusReferee, rats, hypodermic1⁄5:1Rivas guinea-pig, peritoneal1⁄3:1Rivas guinea-pig, pleural1⁄4:1
Referee, rats, hypodermic
Rivas guinea-pig, peritoneal
Rivas guinea-pig, pleural
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,136the 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.
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.
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...”
“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
ChlorlyptusChlorinated Eucalyptol-AbbotChlorinated Eucalyptol-SquibbOdorAcridLike eucalyptusLike eucalyptusDensity and colorDark brown; viscous, heavier than waterLight yellow; mobile; lighter than waterColorless; mobile; lighter than waterAgNO3added to alcoholic solutionHeavy ppt.Slight turbidityClearEqual parts with KI solutionGives free iodin slowly, noticeable in1⁄2hourGives free iodin in 4 hours; not muchNo free iodin in 4 hoursEqual parts with 10% KI, 10% KIO3solutionMuch iodin immediatelySmall amount of free iodin in few numbers; does not noticeably increaseNo free iodin in 3 hoursEqual parts with conc. H2SO4Some blackening; odor of HClReddish mixture; no HCl; eucalyptol odorSameAlcohol KINo iodin liberatedSameSame as Abbott productHeatingDecomposes and boils at 103–105 C.; then higher fraction comes over at 178 C.; distillate has sharp odor, is acid, but frees very little I2from KI; distillation not completedApparently does not decompose; some gas given off when T=80; the liquid distilled at 173 C.; the distillate did not have much odor; no HCl gas detected; no I2from KI; distillate 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.
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:
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 ontongue:
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 ofcheek:
Chlorlyptus,1⁄3c.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 AcidChlorlyptusTongue, a drop of 5 per cent.; still slightly acid to litmus after ten minutes; taste almost gone in two minutesNeutral between five and ten minutesGums, a few drops between cheeks and gums: Five per cent. still strongly acid in twelve minutes; distinctly acid in seventeen minutes. One per cent. still strongly acid in twenty-one minutesNeutral between ten and fifteen minutes
CHLORLYPTUS: REACTION (LITMUS PAPER) ON CONTACT WITH TISSUE
SerialNo.AnimalWhenInjectedQuantity,C.c.Timeof DeathBlueLitmusSymptomsor Toxicity1RatPleura11⁄2hourRemains blueNone; killed; pleura not congested; lung spec. = 21; slight congestion2RatPleuraLess than 11 hourRemains blueNegative3RatPleura123 min.Remains blueAlmost at once bad gasping respiration and died in 23 m.; heart distend.; possibly injection penetrated lungPeritoneum123 min.Turns red4RabbitPleura1................Died overnight5DogPleura11⁄4hourRemains blue20 m. p. m.Peritoneum11⁄4hourRemains blue20 m. p. m.6DogPleura13 min.Remains blue45 m. p. m.Peritoneum13 min.Remains blue45 m. p. m.7DogPleura120 min.Remains blue20 m. p. m.Peritoneum120 min.Remains blue20 m. p. m.
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.
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.
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.