and chloroform, is decomposed and dissolved by sulphuric acid, produces no signs of vesication after forty-eight hours' contact with the skin under adhesive plaster, and is most probably the same volatile principle that has been noticed by Orfila.

The long glass tube was then examined for a sublimate, by rinsing it thoroughly with chloroform, which, on evaporation, afforded more of the same substance obtained from the distilled water, and like it did not produce vesication.

This experiment shows conclusively that cantharidin does not volatilize to an appreciable extent with water evaporating from cantharides.

b. More water was added to the residue in the flask, again boiled for fifteen minutes and thrown on a displacing filter, and water added to the solid residue, after the decoction had ceased to pass, until the absorbed liquid was displaced. The decoction was much less odorous than the distilled water, and had a deep reddishbrown colour. Half of this was agitated repeatedly with chloroform. The latter decanted and evaporated yielded a crop of crystals intermixed with some colouring matter. A part of these heated in a tube over a lamp, gave immediately the brilliant crystalline sublimate of cantharidin well marked; another portion applied to the skin produced vesication in a few hours.

The other half of the decoction was evaporated to a soft extract by direct heat. This produced specdy and deep vesication, more effectual than that of pure cantharidin, as in the extract that principle was in a soluble state by virtue of the yellow matter of the flies.

c. The residual flies were then dried carefully and exhausted with ether, which assumed a deep green colour. A green semifluid fatty oil was obtained by evaporation, from which a fluid yellow oil separated by standing, which produced a tardy vesication, not comparable with the aqueous extract.

d. One hundred grains of flies in powder were introduced into a test tube so as not to soil the sides. This was then kept at the temperature of 212° F. during six hours, by causing it to dip into a vessel of boiling water through a tin plate. The hygrometric water was removed as it condensed above. At the end of the experiment a minute deposit of microscopic crystals less than one-thirtieth of a grain, was observed above the flies on the sides of the tube.

e. Two hundred grains of flies were introduced into a two ounce retort, which they half filled, adapted to a two ounce receiver, and this again connected with a third vessel. The retort heated by a mercurial bath, was kept at 225° F. for two hours, without any product except a little odorous hygrometric water. The heat was then raised to 412° F., when a colourless oily matter flowed slowly into the receiver, mixed with water, whilst a crystalline matter mixed with oil collected in the neck. This crystalline matter mixed with the oil produced vesication when applied to the skin. The heat was now rapidly increased so as to produce brown vapours, from which was condensed a dark coloured empyreumatic oil, abundant crystals of an ammoniacal salt collected in the tubes and on the sides of the receiver, whilst the aqueous liquor in the receiver was strongly ammoniacal. Neither the dark oil nor the crystals produced vesication, the high temperature having probably decomposed the cantharidin.

From these experiments it must be admitted that cantharidin is less volatile than has been asserted. The effect produced on the eye of the pupil of Robiquet who was watching the crystallization of cantharidin during the evaporation of an ethereal solution, may be accounted for by the mechanical action of the dense ethereal vapour escaping near his eye, as he watched the process with a lens, carrying off some particles of cantharidin; and the readiness with which this principle may be brought mechanically in contact with the skin of the face, during a series of experiments, by want of care, will easily account for the occasional testimony of writers in favour of its volatility at low temperatures based on that kind of evidence. During the whole of the experiments detailed in this paper, the author has not experienced any inconvenience to his eyes or face except in two instances, once when decomposing cantharides by destructive distillation, during which some of the vapours escaped near his person, and again where a small capsule containing aqueous extract of cantharides was accidentally exposed to high temperature over a lamp so as to partially decompose it; he suffered slight pain for a few hours in the conjunctiva of both eyes.

It must also be admitted that the heat ordinarily employed in making the

blistering cerate of the United States Pharmacopoeia, does not injure the preparation by volatilising the cantharidin, and that the recommendation to digest the flies in the melted vehicle on a water-bath is not only not injurious, but decidedly advantageous, as it increases, many fold, the solvent power of the fatty matter.

2nd Having ascertained the solvent powers of olive oil, oil of turpentine, and acetic acid, on pure cantharidin, the following experiments were made with those menstrua, and with water, on the flies in substance:

a. 100 grains of powdered cantharides were mixed with 200 grains of olive oil in a large test tube, which was corked, and the mixture heated in a boiling water bath during four hours, with occasional agitation. The contents of the tube were then poured into a small glass displacement apparatus, surrounded with water kept hot by a lamp, and the saturated oil gradually displaced, without cooling, by the addition of fresh portions of oil. The oily liquid thus obtained had a deep green colour, smelled strongly of the flies, and when applied to the skin produced full vesication in about twelve hours contact. After standing twenty-four hours shining needles of cantharidin gradually separated, but not in quantity.

b. 100 grains of powdered flies were mixed with 200 grains of pure oil of turpentine in a closed tube, heated in a boiling water-bath four hours, and displaced while hot as in the preceding experiment. The terebinthinate solution had a dull yellow colour, and was perfectly transparent as it passed, but in a short time numerous minute stellated crystals commenced forming, which increased in quantity by standing. The saturated cold solution, separated from the crystals after standing twenty-four hours, did not blister when applied to the skin.

c. 100 grains of powdered flies were digested in a close vessel, at the temperature of boiling water, in 300 grains of acetic acid, sp. gr. 1.041, for six hours, and then subjected to displacement in the hot filter above noticed. A dark reddish-brown transparent liquid passed, which had very little odour of flies, even when a portion was exposed until the acetic acid had nearly all evaporated. A portion of this liquid applied to the skin produced complete vesication in about ten hours. After standing a few hours, numerous minute granular crystals were deposited, which gradually increased in amount and size.

These three experiments prove that hot fatty matter is a good solvent for cantharidin as it exists in the flies, and that it retains more on cooling than either turpentine or acetic acid. That hot oil of turpentine is a good solvent for extracting cantharidin, although it does not retain much on cooling, and that officinal acetic acid at the temperature of 212° F. will remove cantharidin readily from Spanish flies, but retains but a part on cooling.

d. 500 grains of recently powdered flies, contained in a flask, were boiled in a pint of water, for an hour, and the clear decoction decanted, the residue again treated with half a pint of water, so as to remove all matter soluble in that liquid. The decoctions were mixed, filtered, and evaporated carefully to dryness. The extract was exhausted by repeated treatment with boiling alcohol, which left a dark coloured pulpy matter, very soluble in water, from which it is precipitated by subacetate of lead. The alcoholic solution was now evaporated to a syrup, and on cooling yielded a yellow extract like mass interspersed with numerous minute foursided prisms. By washing a portion with water, the yellow matter was removed, leaving the crystals white and pure. The aqueous washings yielded by evaporation a residue of crystals, and does not vesicate. When the alcoholic extract was treated with chloroform the crystals were dissolved, and the yellow matter left. On evaporating the chloroform solution the crystals were re-obtained with all the characters of cantharidin. The matter left by chloroform was now treated with water, in which it dissolved, except a trace of dark substance, and was again evaporated carefully. It afforded a yellow honey-like residue, thickly interspersed with crystals and strongly acid to litmus, without vesicating power.

A portion of the yellow matter separated from the alcoholic extract by water was boiled with some cantharidin, filtered and evaporated. The residue treated with chloroform afforded no cantharidin; hence it would appear that although the yellow matter enables the cantharidin to dissolve in water and cold alcohol, when once separated its solvent power ceases.

Having now studied the effects 'of the ordinary solvents on cantharidin in a free state, and in the condition in which it exists in the insect, we are prepared to

consider with some clearness, the pharmaceutical preparations of the Spanish fly, and their action as vesicants.

a. If one-thirtieth of a grain of pure cantharidin, in fine powder, be placed on the skin of the arm and covered with a piece of warmed adhesive plaster, active vesication occurs in eight hours, with pain. If the same quantity of cantharidin be put on the other arm, a small piece of paper be laid over it, and then a piece of adhesive plaster with a circular hole in it be applied, so as to hold on the paper, no vesication occurs in sixteen hours, the powder remaining dry. If then a large piece of plaster be put over the whole, at the end of eight hours more no blistering action will have taken place. If now a trace of olive oil be applied to the back of the paper covering the cantharidin, and the plaster replaced, speedy vesication will occur. These experiments prove that cantharidin must be in solution to have its vesicating action, and that oily matter is a proper medium.

b. When powdered flies are stirred into the ordinary vehicle of resin, wax, and lard, so as to chill it almost immediately as was formerly directed, but little of the cantharidin is dissolved by the fatty matter, and when applied to the skin the process of vesication is retarded. If, however, the cerate be kept fluid for a length of time, say for half an hour, by a water-bath or other regular heat, no loss of cantharidin occurs by the heat, the active principle is in great measure dissolved by the fat, and every part is impregnated and active. In the foregoing experiments it has been shown that twenty parts of olive oil will dissolve one of cantharidin when hot. If we admit with Thierry that cantharides contain but four thousandths of their weight of cantharidin, the quantity contained in a pound of cerate is about eight grains, whilst the lard in the same weight of cerate is 1600 grains, or two hundred times the weight of that principle, not to speak of the influence of the wax and resin, which, in union with the melted lard, act as solvents. Hence the whole of the cantharidin may be dissolved by the vehicle. Another advantage of employing a continued heat in digestion is the removal of the hygrometric water from the flies, which is the source of the mouldiness to which the cerate is prone in certain conditions.

In a former essay (Amer. Journ. Pharm., vol. xiii, p. 302), I have advocate:1 digestion in making this cerate (a recommendation also made by Mr. Donovan, of Dublin, about the same time), and also the use of a portion of the oil of turpentine to facilitate the solution of the cantharidin, but the foregoing experiments prove that fatty matter is quite as good, if not a better solvent alone, than with turpentine. c. It has been asserted long ago by Beaupoil, Robiquet, and others, that water will perfectly extract the active matter from Spanish flies, which these experiments corroborate. Hence it is easy to understand how the condensed perspiration may facilitate the action of a blister, especially when, as was formerly much the case, its surface is coated with the dust of the flies and the skin moistened.

It is also clear why the Unguentum Cantharidis of the U.S. Pharmacopoeia is active although made with a decoction of flies, yet, in this preparation, care should be observed not to evaporate all the water, as on the existence of the aqueous extract in a soft state depends much of the efficiency of the preparation as an irritant dressing.

d. In the Linimentum Cantharidis, U. S. Pharm., in which an ounce of flies is digested in eight fluid ounces of oil of turpentine, the cantharidin is to the menstruum as I to 1500, a proportion probably quite sufficient to retain it in solution. The importance of the officinal direction to digest is evident. It is quite doubtful whether this liniment, as made by the process of Dr. Jos. Hartshorne, one part of flies to three parts of oil, will retain all the cantharidin after standing awhile.

e. The Acetum Cantharidis, (Lond. Ph.) made by macerating an ounce of flies in ten fluid ounces of acetic acid, 1.48, has been criticised by Mr. Redwood, (Pharm. Journal, Oct. 1841,) who arrived at the conclusion that it owed its vesicating power almost solely to the acid, he not being able to discover cantharidin in it. The inefficiency of cold acetic acid as a solvent for pure cantharidin has been proven by the above experiments, and its efficiency when hot equally shown. There can be little doubt that the London preparation would be much improved by digesting the flies in the acid for an hour in a close glass vessel at the temperature of boiling water. f. The cantharidal collodion of M. Ilisch has been considerably used as a vesicant in this country. Ether being a good solvent for cantharidin readily keeps that

principle in solution. When applied to the skin, the escape of the ether leaves a coating of ethereal extract of cantharides, admixed with collodion. This preparation sometimes fails from a deficiency of cantharidin, at other times from want of a sufficient body in the collodion excipient, and it has been found more advantageous to treat the cantharides with ether till exhausted, distil off the ether, and add the oily residue to collodion of the proper consistence. The addition of a little olive oil, and of Venice turpentine, as recommended by Mr. Rand, will give more activity to the preparation, especially if a piece of oiled silk or adhesive plaster be applied over the part.

g. Besides these, many other epispastic preparations are made in France and other countries. The acetic alcoholic extract of cantharides of Ferrari is made by digesting four parts of cantharides in sixteen parts of alcohol 36° B. mixed with one part of acetic acid 10° B. In the opinion of the author, the acetic acid tends to prevent the crystallization of the cantharidin, a statement rendered doubtful by the above experiments, as that principle separates in crystals from an acetic solution of cantharides. The alcohol dissolves the green oil which gives to the extract a butyraceous consistence. This is undoubtedly an efficient preparation, and is used by spreading it on paper with a brush, and applying to the skin. Nearly all the French preparations direct digestion of from two to six hours, showing evidently that the experience of Pharmaceutists is opposed to the opinion that cantharides is "a very volatile substance, even at common temperatures."

The vesicating tafeta of the Codex, is that proposed by Messrs. Henry and Guibourt, and is made by fusing together one part of the ethereal extract of cantharides and two of wax, and spreading it on waxed paper or linen in the manner of adhesive plaster. This preparation is said to lose its efficiency by exposure to the air. How can this occur in view of the results which have been detailed above? admitting the fact, is it not probable that the change lies in the strong tendency of the cantharidin to separate in crystals? a change easily observable in the ethereal extract. This is the chief objection to some otherwise excellent preparations of cantharides for vesication, and it is far more probably the true explanation than that volatility should be the cause.

The recently prepared and soft aqueous extract of cantharides has been shown to be a powerful epispastic. Will this extract of the consistence of honey, associated with sufficient acetic acid, alcohol, or acetone, to preserve it, keep without the gradual separation of the cantharidin? If so, it will undoubtedly prove one of the very best blistering agents, as by simply applying a covering of it over the surface of waxed paper, or adhesive plaster, with a camel's-hair-brush, a perfect blistering plaster can be made quickly and neatly, and all tendency to change of aggregation by the action of the air on the menstruum avoided. This is a question now under trial, and should it result favourably, a formula will be published. The extraordinary tendency of cantharidin t crystallize, even under the most adverse circumstances, taken in connection with its insolubility, per se, has hardly received sufficient attention from Pharmaceutists as a cause of the deterioration of cantharidal preparations, and the discovery of a menstruum, that will retain that principle in solution for an indefinite period, is a problem yet to be solved, and worthy the attention of pharmaceutical investigators.-American Journal of Pharmacy.

Philadelphia, September, 1852.

ON THE OIL OF THE ARGEMONE MEXICANA AS A REMEDY
FOR ASIATIC CHOLERA.

BY W. HAMILTON, M.B.

ASIATIC cholera rarely makes its attacks without previous warning, and, if individuals would only pay reasonable attention to the premonitory symptoms, much, if not the whole, of the fearful mortality which has already, upon two occasions, desolated our land, might be prevented. The premonitory symptoms usually point to a disturbance of some kind or other in the organs of digestion, which, from whatever cause it may arise, calls for active interference to subdue.

The most obvious mode of answering this indication, is to keep the first passages free, and thus prevent the accumulation of that feculent matter whose irritation, produces the premonitory symptoms, and ultimately leads to that spasmodic action which is among the most painful accompaniments of Asiatic, or, as it has been more aptly designated, spasmodic cholera.

To relieve the abdominal irritation by carrying off the feculent matter which occasions it, purgatives of the milder and least irritating or drastic character should be carefully administered in combination with some anti-spasmodic, to modify their action, and counteract the strong and painful tendency to spasm or cramp, as it is commonly termed.

Now both these objects may be attained by the most moderate doses of the oil obtained from the seeds of the Argemone Mexicana, a plant which flourishes spontaneously in the greatest abundance in waste places, and among rubbish throughout I believe the whole of the West Indian Archipelago, where it may be found blossoming and loaded with seed in every stage to maturity throughout the year.

It is now above eight years since I first endeavoured to direct medical attention to this valuable but neglected plant, through the pages of the Pharmaceutical Journal, in the fourth and fifth volumes of which communications on this subject will be found at pages 167 and 23.

In the passages referred to, we have the testimony of two experienced Practitioners of Jamaica to the valuable aperient, anodyne, and hypnotic effects of these seeds; properties which are also possessed by the oil which they yield, in a more convenient and less bulky form, the dose being restricted to a few drops. The oil will be best obtained from the recent seeds, on the spot where they grow spontaneously; and, as the Pharmaceutical Society numbers among its Members residents in the regions in which the argemone flourishes and yields its harvests throughout the year, individuals, it is to be hoped, may be found philanthropic enough to prepare some of the oil with care, so as to guard against the possibility of adulteration, and transmit it to the Council of the Society for a trial of its effects, before we are again subjected to the decimating scourge of that strange and fearful malady which has slain its thousands on the continent of Europe during the past season, and will, not improbably, visit our own shores before another year completes its circle.

It is idle to object that cholera has destroyed its victims in the very island in which both Affleck practised and Barham wrote, unchecked and unmitigated by the remedy proposed, although found at the thresholds of the sufferers. Prejudice is often stronger than reason, and a prepossession in favour of old and what are reputed to be orthodox remedies, too often indisposes us to view with favour those which are unstamped by the signet of time, however strong and however conclusive the testimony of their value.

But the present is an age of inquiry and of research; we are progressively rising above the mists of past ignorance, and learning to withhold our condemnation till assured of its being merited.

Cholera is at hand; and, however potent sanitary measures may be in mitigating its ravages, the science of medicine cannot be dispensed with, and when the destroyer comes-as we have too just ground for fearing he will come-the addition of this little article to the artillery of the Pharmaceutist may avert death from thousands, and add a fresher laurel to the triumphs of art.

14, Octagon, Plymouth, 10th November, 1852.

ON THE MANUFACTURE OF VINEGAR.

Extracted from a Report of a Chemical Examination of the Vinegars manufactured by Messrs. Hill, Evans, and Co., of Worcester.

BY PROFESSORS GRAHAM, HOFMANN, AND PLAYFAIR.

THE processes which are usually followed in the manufacture of the acid of vinegar, that is, acetic acid, although greatly varied in their details, appear to involve only two important chemical principles. When billets of wood enclosed in an iron cylinder