This constitutes by far the most obscure part of the subject of medicinal combination, and must ever continue so until we become better acquainted with the laws which govern the action of medicinal substances upon the living system. That the most valuable effects, however, are really produced by such arrangements, we have the testimony of long experience, and examples are furnished in the valuable and well-known operation of many officinal preparations; thus the “Pulvis Ipecacuanhæ compositus” contains as its active elements, Opium and Ipecacuanha; and yet, in well regulated doses, it neither possesses the narcotic operation of the former, nor the nauseating effects of the latter; they appear to be mutually lost, and converted into a powerful diaphoretic: so again, the emetic operation of Sulphuret of Antimony, and the specific influence of Calomel, are changed by combination with each other, giving rise to a remedy eminently distinguished for its powers as an alterative. Dr. Bree observes that Tincture of Squills combined with Extract of Henbane, and the Nitric Acid, have been proved by much experience to be expectorant and sedative in a paroxysm of asthma, although each article, uncombined, had been given without success. See Form. 139. The efficacy of Hemlock, in quieting Pulmonary irritation, has been frequently adverted to in the course of this work; I have to state, in this place, that its value, on such occasions, is generally enhanced by combination with Ipecacuanha.
It is probable that many of our natural remedies owe their efficacy to the results of a similar species of combination. In the fourth edition of this work it was stated that, according to the assertion of Dr. Chapman, “Kino, when administered in union with Calumba, constituted a pretty certain, and powerful purgative;” since the publication of this fact, I have investigated what, if true, would appear to be a most extraordinary anomaly in the philosophy of medicinal combination, and I find that the statement of Dr. Chapman[[264]] is not borne out by experiment. That we might arrive at a just conclusion upon this subject, I requested the assistance of my friend Dr. John Davy, whose character for experimental accuracy, and whose situation as Superintendant of the Medical Division of the General Military Hospital at Chatham, seemed to point him out as a person peculiarly adapted for such an inquiry; the result of his trials does not establish that of the experiments of Dr. Chapman, but on the contrary it seems to prove, that neither Kino nor Calumba, when taken separately, has a constipating effect, and that in the form of powder (especially the Calumba) each has an aperient quality, which is not increased by exhibiting the two medicines together in a state of mixture. The trials from which these inferences are drawn were made on different individuals in tolerable health, and they were repeated more than once; in some cases they were given separately, and in others, mixed together, in doses varying from a scruple to a drachm of each.
B. By combining Substances which have the property of acting chemically upon each other; the result of which is the formation of new Compounds, or the decomposition of the original Ingredients, and the developement of their more active Elements.
A. The Formation of New Compounds.
It is not necessary to extend our researches beyond the range of the Pharmacopœiæ,[[265]] to collect a variety of interesting and important examples, in illustration of this division of our subject; if we require a striking example of the agency of chemical combination in destroying the identity of the original constituents, and of giving origin to a compound of new powers, it may be exemplified by the well known instance of Sulphate of Potass, a substance possessing but a weak affinity for water, and exerting but little energy upon the animal œconomy; whereas the two ingredients of which it consists are distinguished for the extreme eagerness with which they unite with water, and for the caustic activity which they display in their action upon animal matter.
Under this head the class of metals will also present itself to our consideration, all the individuals of which, with the exception perhaps of iron, are perfectly inert and harmless; even arsenic, lead, copper, and mercury, which in certain states of combination constitute some of the most virulent of known substances, exert no action upon the living system, unless they be in union with some other body; but when so united, how valuable do they become, and what various medicinal effects may they not be made to produce.
The Acetic Acid and Ammonia become neutralized by combination with each other, affording a compound of new virtues. Sulphate of Zinc, and Acetate of Lead, when mixed together in solution, decompose each other, and the Acetate of Zinc which is formed, affords a more valuable remedy than either of the former salts, as an application in ophthalmia. The “Mistura Ferri Composita” of our Pharmacopœia offers another example of the same chemical resource. I also beg the reader to refer to the construction of Formula 82, which presents an instance of a purgative draught being produced by combination, in which the original properties of every element are entirely changed. See also Formula 87, the chemical actions of which are more complicated, but no less instructive than the preceding one; the ingredients of the formula are the Carbonates of Soda and Magnesia,—Sulphate of Iron,—Diluted Sulphuric Acid, and Water—and when mixed together, the following decompositions would appear to take place; the free Sulphuric Acid, together with that which exists in the Sulphate of Iron, being just sufficient to decompose the Carbonates of Soda and Magnesia, forms two neutral Sulphates (viz. Sulphates of Soda and Magnesia,) and thereby disengages a volume of Carbonic Acid gas, which not only increases the purgative operation of the new saline compounds, but, by its excess, holds in solution the Carbonate of Iron, which is formed by the decomposition of the Sulphate, and which in that state displays an effect powerfully tonic.
Before we quit the consideration of medicinal compounds as the results of chemical action, it is expedient to remind the practitioner of the essential difference between Mixture and Combination, a difference which affects the medicinal virtues no less than the chemical characters of bodies; it is determined by ample experience, that substances will produce effects upon the living system when presented in a state of simple mechanical mixture, very different from those which the same medicines will occasion when they are combined by the agency of chemical affinity, as is well exemplified in the comparative effects of alcohol as existing in ardent spirits, and in wine (see Vinum); or in the relative powers of Mercury in the Unguentum Hydrargyri of the London College, and the Unguentum Oxidi Hydrargyri cinerei of the Pharmacopœia of Edinburgh, (see Unguent. Hydrargyri); the former of which is a true chemical compound, whereas the latter is a simple mixture of its ingredients.
B. The Developement of Active Elements.
The accomplishment of such an effect is in many instances the sole object of a pharmaceutical process. It is thus that we obtain pure Citric acid from the juice of the Lemon; Tartaric acid, from Cream of Tartar; Benzoic acid, from the resinous substance known by the name of Gum Benzoin; upon the same principle, the Muriatic and Nitric acids are elicited from the saline compounds in which they exist. Ammonia, in its pungent form, is developed from its inodorous Muriate; and the fixed alkalies are obtained in their caustic state, from the comparatively mild carbonates in which they naturally exist. But a more striking and instructive instance of the effect of chemical action, in developing an active, or useful principle, cannot perhaps be selected than that of the well known stimulant Plaister, composed of Muriate of Ammonia, Soap, and Lead Plaister, in which the alkali of soap enters into combination with the muriatic acid, when the Ammonia, upon which the virtues of the plaister solely depend, is slowly disengaged in the form of gas, producing a powerfully rubifacient and stimulant effect: the “Cataplasma Fermenti,” or “Yeast Poultice,” is indebted for its antiseptic properties to a similar agency, for they do not depend upon any virtue in the ingredients themselves, but upon their decomposition, and the consequent developement of an active element, which is Carbonic Acid. The practitioner unacquainted with the modus operandi of these combinations, would inevitably fall into an error by which their efficacy must be lost; he would hardly apply them as soon as they were formed, nor would he be aware of the necessity of repeating them at short intervals.