is often alluded to or intended when the words "dermic medication" are used, but this is inaccurate, as the latter expression has been appropriated by the specialists in skin diseases. Such a distinction of terms leaves the word endermic to apply to medication after the cuticle has been removed. Mr. John Marshall, F. R. S., in the London Lancet for May 25, 1872, p. 709, seems to have been the first to show the facility with which an oleate of mercury passes through the sound skin, and the efficacy of the mercury when introduced in this way. He seems to have used the oleic acid simply as a convenient vehicle for the oxide of mercury, and morphia, without thinking, perhaps, that a very useful method of medication through the unbroken skin might and should grow out of his observations. Many persons took up the idea from Mr. Marshall's paper, and among them the present writer, but from that time to this nothing worthy of the name of accurate research or systematic observation has been undertaken. The field is an excellent one, and the object of this note is to try to stimulate some close and accurate observers to take up this subject of epidermic medication, with the hope that its advantages may be brought out and rendered generally available. For some uses, and these, perhaps, not very few, it has great advantages over hypodermic medication. The use of salves and ointments is as old as the earliest days of medicine, and the fats as salts of the fatty acids with glycerin have always been the common vehicles for this kind of medication. But with these merely as vehicles the absorption has been very slow and uncertain, and therefore the utility comparatively small. An oleate of glycerin, say common olive oil for example, when used as a solvent or vehicle for an active medicine, is absorbed or is passed through the skin very slowly and imperfectly; but if the glycerin of the oleate be chemically replaced by a basic medicinal agent by the chemical reaction commonly spoken of as saponification, and if this soap be then dissolved in an excess of the fatty acid, the whole seems to pass more rapidly through the skin by an endosmosis, and the general as well as the local medicinal effect is correspondingly prompt and certain. There seems to be some relation of homology between these liquid fatty acids and the skin which causes the acids to pass in and be absorbed more rapidly and more easily than any other liquids, and to carry in with them anything with which they are chemically combined. Thus the original observations of Marshall showed that any degree of mercurial effect, either local or general, could be promptly and easily procured, with very accurate

limitation, by the local application of very small quantities of oleate of mercury, and also that local pain could be controlled by oleate of morphia, and that the quantities of mercury and morphia required for a given effect were much smaller when locally applied than when given by the mouth. Since then the physiological effects of aconitia, atropia, quinia, strychnia and veratria have all been as easily and as promptly obtained, while the primæ viæ have been saved from disturbance fully as well as by hypodermic medication,. if not better. It has simply been known more or less generally that the application of a little oleate of atropia, for example, without. friction, under oiled silk, around an irritated and painful joint, would not only afford a prompt atropia relief, but the pupils would be as promptly dilated. Then, by direct and unavoidable inference, all similar tissue throughout the whole body everywhere would be similarly effected. But as to any careful or accurate investigation or observation into which quantity, time and quality of action have entered, there seems to have been none, either with this or any other of the oleates. Yet upon the loose and desultory experience handed along in a loose, disjointed way, oleate of mercury has gone into a very extensive use. Next, oleate of morphia has. been pretty largely used, especially as an anodyne for infants and children, while comparatively few of the other oleates, although affording equally definite results, have been much used.

The need seems to be that those who meet with the indications for the use of the alkaloids and the metallic bases should apply them in this form with care, accuracy and close observation, and then publish their results. In this way, in a short time, a method of epidermic medication would either come into definite and established use or go out of use altogether. If any general method of epidermic medication could be established, its many very apparent advantages would soon render it of great general value. While, if there be practical objections to it, these would be brought out, and it would soon cease to complicate an already over-loaded materia medica.

The most that this writer can contribute upon oleic acid in its relation to epidermic medication is the curious circumstance that wood, porcelain or cloth greased with oils, glycerin or oleic acid seem to remain greasy alike for an indefinite length of time. But if the skin be similarly treated, the parts greased with oleic acid will be dry the soonest. All will disappear through the skin in time, but the oleic acid in the shortest time, and indeed in a remarkably short time. A few minims of the acid, or of any oleate,

spread over any portion of the skin and simply covered with oiled. silk or rubber tissue will entirely disappear in half an hour, and as it is irritant to the skin of few persons, this may be repeated as often as may be desired. It seems, from the circumstances, highly probable that mercury may be used in this way with the greatest possible accuracy and safety, for either its local or constitutional effects, or both together, since the quantity can be controlled with great accuracy by a minimum amount of care and skill, while it is least liable to accidental causes of undue activity.

This much then may be said of epidermic medication as it now stands: First, that it is entirely rational, and a legitimate result of inductive progress from the known to that which may become known; and second, that it is not a novelty nor a startling discovery, but has a record of experience which, though indefinite and loose, fully warrants the labor of the more extended and more accurate research that is so much needed by it.

THE MEDICINAL OLEATES.

Chevreul (Recherches Sur les Corps Gras) discovered oleic acid about 1811, and notices of medicinal oleates may be found in the chemistry and pharmacy of France about that time. The first paper met with in the English language, however, is by Professor Attfield. This is "On a Method of Dissolving Alkaloids in Oils," and is published in the British "Pharmaceutical Journal and Transactions" for 1862-3, Vol. IV., p. 388. This paper refers mainly, but not entirely, to the use of oleates for the purpose of rendering their bases soluble in oil, and both in the paper and in the discussion which followed the reading of it, this use of the oleates was discouraged as tending to useless polypharmacy. From this time nothing very definite has been met with until the publication of the paper of Mr. John Marshall in 1872. Since 1872 very general notice has been taken of the subject, in a casual, inexact way, by authors on therapeutics and materia medica, and several papers have appeared upon the chemistry and pharmacy of the oleates. Various methods of preparation have been advocated, but none so good as the direct union of the acid with the dry base without heating. The preparation should always be either a liquid or a semisolid which is easily and completely liquified by the natural temperature of the surface to which it is to be applied, and hence nor

mal oleates undiluted are not applicable to therapeutic uses, but only solutions of the oleates, and these solutions should always be in oleic acid as the solvent rather than in oils, because the acid is more readily absorbed than the oils. In the rare cases where the excess of acid as a solvent of the oleates proves irritant to the skin, dilution with a bland oil becomes admissible. A paper has appeared recently by Dr. John V. Shoemaker, see" The Medical Bulletin" for July, 1882, p. 153, in which it is stated that the oleates as commonly prepared and used are not chemically true oleates, but merely solutions of oxides in oleic acid, and as such will often give negative results. This is a mistake, and is as great an error as it would be to say that mercuric nitrate, made by dissolving mercuric oxide in nitric acid, was not a chemical nitrate, but only a solution of the oxide in the acid. This author also states that the best method of making oleates for medicinal uses is by double decomposition; and this, as a general statement, is also a mistake, as very few oleates are well made in this way, and it is doubtful whether any are best made by double decomposition between solution of oleate of sodium and solution of salts of the bases. At least this is neither the simplest nor the easiest way of making the solutions of the oleates in oleic acid as required for the best and the easiest absorption through the sound or unbroken skin, and it is incorrect to write of preparations made by direct union of the acid and base as "supposed oleates" of "indefinite and unstable character."

The oleates which, up to this time, appear to have been most used, are oleates of aconitia, atropia, mercury, morphia, quinia, strychnia, veratria and zinc. These for general or epidermic use through the skin, while for special or dermic use in diseases of the skin, oleates of copper, lead and zinc are those most frequently heard of

Oleates of the more active alkaloids, namely, aconitia, atropia, strychnia and veratria are usually and properly made of the strength of two per cent. of the alkaloid. The oleate of morphia usually contains five per cent. of that alkaloid, while the oleate of quinia is made as strong as is practicable, and usually contains twenty per cent. of the alkaloid.

All of these are very simply and easily made by putting the weighed quantity of the alkaloid into a mortar, adding a small quantity of the oleic acid, little by little, and triturating until the alkaloid is completely dissolved. The strong solution thus made is then poured into a tared bottle, and the mortar and pestle rinsed

twice into the bottle with small quantities of oleic acid. The proper weight is then made up by the addition of oleic acid. No heat is needed, nor should any be used in the preparation of many oleates, but in some of these the digestion is prolonged, and intervals of trituration are needed. All heating has a great tendency to change their molecular constitution. If well made oleate of morphia be shaken with dilute sulphuric acid, the morphia should be washed out as a sulphate, but it is a singular fact that it cannot all be so recovered as morphia; yet the morphia effect of the oleate is prompt and decided. This appears to show that some change is effected in the alkaloid even by combining it without heat, while if heated the changes are destructive.

The molecular or combining weight of oleic acid is high, namely, 282, but the weights of the alkaloids are still higher. That of aconitia is 645, atropia 239, morphia 285, quinia 324, strychnia 334, and veratria 592. Hence the molecule of the respective oleates would be very complex and very easily split up by any forces tending to decomposition, as heat, light, etc., or by oxidation from undue exposure to air. Hence it is that oleates may not keep well, but should be as freshly made as practicable, and should not be relied upon for their full effect when more than a year old, even if they have been carefully kept in a cool place.

The normal oleates-that is, when the oleic acid is fully saturated by the base-contain the following percentage of the respective bases:

Oleate of aconitia, about 69.6 per cent. of aconitia.

A brief notice of the therapeutic application of some of these oleates may not be without use. In epidermic medication it must be borne in mind that the skin, in common with the mucous membranes of the primæ viæ, does not absorb with equal facility or rapidity at all times. As was forcibly said by Prof. Chas. D.