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Meigs in regard to the occasional inactivity of powdered ergot in parturient women : There are conditions of stomach in which you might as well put your medicines in a bladder and hang it up on a nail." So there are conditions of skin wherein absorption is slow and difficult, and in all such, hypodermic medication has great advantages, and it is highly probable that the hypodermic use of these oleates would be effective in such cases.

In reviewing the principal oleates somewhat in detail, it may be useful to begin with oleic acid.

OLEIC ACID.

This is made from the so called "red oil" of the makers of stearin candles. The other fatty acids are separated from the oleic by solidifying at higher temperatures, when they can be filtered out. But they are never completely separated, nor is it necessary, they should be, since this oleic acid for medicinal usesdoes not aim at a high degree of chemical purity. The crude oleic acid is next washed with solution of sulphurous acid, and finally is repeatedly washed with water, and carefully filtered in the cold with the least practicable exposure to air.

It is then an oily liquid of the color of pale sherry wine, having a faint, peculiar, indescribable odor and taste, free from acridity. Its s. g. is .898 to .900, at 15.6° C.=60° F. It is thinner than the oils, and much more easily wiped off of surfaces without leaving them. greasy. Applied to the skin, it wets it almost like water, and if very thinly applied it is so quickly absorbed that it seems as if it had evaporated like water; and it leaves the skin as clean and free from greasiness as though it had been wet with water. The peculiar odor of the acid is much stronger when it is spread upon the skin than when in a bottle. It should be kept from the light and air as much as practicable, although it does not appear to rancidify as easily as fats and oils do. As it has not yet been determined how the oleates keep, it is very good practice to keep the oleic acid on hand, and from it make the oleates as they are required for use-not necessarily each time they are prescribed, but every month or two.

OLEATE OF ACONITIA.

This is made by simply putting the dry alkaloid and the acid together, when the alkaloid, if pure, instantly dissolves and dis

appears. This is, however, only the case with the alkaloid precipi-tated from the "aconitine" of Duquesnel,* (see page 167). With the other aconitias of the market the solution is not quite so prompt, and a little residue is often left undissolved, and has to be filtered out. The oleate should, however, always be made from the best aconitia, although it be thus rendered very expensive. The increased cost is, however, rather apparent than real, since half a drachm of such an oleate is more effective than an ounce made from ordinary aconitia.

There is no pharmacopoeial authority for the strength of this oleate, but usage has started it at two per cent. That is, 2 grains of aconitia in 98 grains of oleic acid. Then, as the aconitia precipitated from "Duquesnel's aconitine" costs at least 40 cents a grain, the 100 grains of this oleate would cost say 82 cents. But the preparation is an exceedingly active and potent one, and is, therefore, required in very small quantity. Remembering that the dose of this aconitia for internal administration is from the one hundredth to the two hundredth of a grain, there will be at least three hundred doses in one hundred grains of the oleate. Hence it will be required, in any probable use of it, in very small quantity, and as it must be a very dangerous substance, it should never be put up or dispensed in larger quantity than about the sixteenth of a fluidounce, or two cubic centimetres, and this quantity would contain. the eighth of a grain. Each minim weighs eight-tenths of a grain,. and contains about one-sixtieth of a grain of aconitia. A drop from the thin lip of the vial in which it is dispensed is about half a minim.

This oleate should be applied by means of the end of the cork which stops the bottle containing it. If twice the quantity which the end of the cork will carry be spread over about half a square inch of the skin on the back of the hand, a glow of warmth in the part. is almost instantly felt. This will continue for some minutes, then become intermittent, and in a half hour will have entirely disappeared. If twice this quantity be then applied to about a square inch of surface, including the first portion, the glow will be more pronounced, and there will be prompt tingling in the nerves which pass under the part down to the ends of the fingers. In a few minutes the glow will have increased to a sense of heat and pricking

*This "aconitine " is a nitrate of aconitia, and requires to be precipitated and dried. As. sold under the name of "Duquesnel's aconitine "it is entirely insoluble in oleic acid.

If,

in the part, and the tingling along the course of the nerves will have increased. In a quarter of an hour there will be slight numbness in the ends of the fingers to which these nerves are distributed. All these sensations will increase slightly and steadily for about half an hour, and will then subside, becoming intermittent with longer intervals, until they disappear at about the end of an hour, when the oleate will have nearly disappeared from the surface. however, at the end of half an hour the dose be repeated on the same surface, all the sensations are promptly increased and extended to the whole hand. In a quarter of an hour a slight glow of warmth is felt throughout the arm, with just perceptible intermittent tingling. This tingling was noticeable with widening intervals for at least ten hours, and on the following day there was itching of the surface.

This much may serve to show the potency of the preparation, and to indicate both the dose and the use. If in trigeminal neuralgia such an application of this oleate be made over the course of the branch involved, or over the point of emergence and distribution of the nerve, it will probably soon do all that aconite can do for the case in a better, safer and more manageable way than by internal administration. The active medication of the whole organism to get at a local nerve at a point of pain seems to be a roundabout way when access can be had directly to it by such means as this oleate, while at the end of a few hours of the above mentioned experiments it seemed quite plain that the aconite influence had extended to the entire organism, for the sensations were distinctly felt in the opposite hand, and although the temperature and pulse' were not taken, they were evidently both reduced.

OLEATE OF ATROPIA.

This oleate is made in exactly the same way as the oleate of aconitia, and by general usage is of the same strength, namely: two per cent. Although an active and potent preparation, it is by no means so active or dangerous as the oleate of aconitia. It has been said that the application of five minims of this oleate to a knee-joint of an adult patient has produced dilatation of the pupils within a quarter of an hour just as a very good belladonna plaster should do, with prompt relief of pain, and if this be true it serves well to indicate the power and the dose of this oleate. There is, beside, considerable loose and scattered testimony to its steady though slow

effect upon the pupil when applied in the neighborhood of the eye. It would seem that it ought to be very manageable and very useful in ophthalmology as a substitute or alternate for instillation of the watery solution, but up to this time it has not attracted much attention so far as any published statements go. Yet there is a good deal of it sold, and judging by the sales its use is increasing, probably mainly as an application to painful joints as a substitute for belladonna plasters.

Each minim contains about one-sixtieth of a grain of atropia, and a drop from a common one-ounce vial is about two-thirds of a minim, or from an homœopathic vial with thin lips about half a minim, or one one-hundred and twentieth grain.

OLEATE OF MORPHIA.

This is made precisely as the preceding oleates, except that as the morphia of the markets is in crystals, their solution in oleic acid is slow, unless the crystals be rubbed into powder before adding them to the acid in the bottle in which the solution is to be made. A little agitation is then all that is needed. This is the only one of the oleates of the alkaloids that within a short time changes much in keeping. When the elements of it are first put together the solution begins to grow darker, and this change progresses until within a year it becomes very dark indeed. This change in keeping does not destroy its efficacy, but whether it diminishes it or not has not been shown. This oleate was introduced by Mr. John Marshall, who made it of the strength of five per cent, or 5 grains of morphia to 95 grains of oleic acid, and this strength has now been generally adopted. This oleate is quite largely used, and yet very little accurate information or observation in regard to it has been published in the ten years that have passed since its introduction. Several good observers within. the writer's personal knowledge have occasionally used it for some years past in special cases, and with alleged success, especially as an anodyne and sedative in infants and children. Five to ten minims applied to the abdomen under oiled silk seems to be about the usual dose for children of one to four years.

As a simple sedative hypnotic it is often applied to the inside of the thighs and arms of infants, one or two drops spread over a large area in each locality so as to get not more than four or five drops in all for infants of six months. It should be dropped onto the surface with care, and be spread by the ball of one finger, and as sometimes

the absorption is slow the dose should not be repeated within an hour if the first one be insufficient. It is is said to have less tendency to constipate than any other opiate. Each ordinary drop contains nearly one-twentieth of a grain of morphia. It is probable that this oleate should be doubled in strength.

OLEATE OF QUINIA.

This, although it has not attracted general attention, is probably one of the most important of the oleates. From the larger quantity of quinia needed in medicine this oleate is made as strong as possible. While a normal oleate of this alkaloid would by calculation contain about 53 per cent. of the alkaloid, it has been found impracticable to dissolve that quantity in the acid. In a series of experiments made some years ago when this oleate was introduced, it was concluded that 25 per cent. was the best proportion. But as the quinia of the market holds some hygrometric moisture, it is better to take 26 grains of the alkaloid and 74 grains of oleic acid as the formula. The alkaloid is simply rubbed to powder, and added to the acid in a bottle. Like the other alkaloids this dissolves so readily that being in much larger proportion, it is liable to clog together and be slow in dissolving. But this clogging together is easily broken up by means of a glass rod. Or the solution may be effected in a capsule and the clogging be prevented by a pestle. In this way it is easily made in a very few minutes. A fluidounce of this oleate weighs about 410 grains, and, therefore, contains about 102 grains of quinia, which is equivalent to about 140 grains of the ordinary sulphate of quinia. Therefore, a fluidrachm contains the equivalent of about 17 grains of the sulphate, and a minim is equivalent to a little more than a quarter of a grain. An hypodermic injection of a fluidrachm will, therefore, carry the equivalent of 17 to 18 grains of sulphate of quinia.

It happens, perhaps oftener with the administration of quinia than most other medicines, that the physician wants to save the stomach. And many conditions need quinia when the stomach will not accept it, or will not utilize it if given by the mouth. These circumstances have long indicated the hypodermic use of quinia, but up to this time no solution has been proposed that is well adapted to hypodermic use, first, because of the large dose required, and again, because of sparing solubility of available quinia salts. Hence this oleate has been sometimes used hypodermically, but with