In preparing foxglove for medicinal use, it is the custom of some druggists to remove the whole of the petiole and the thicker part of the midrib, retaining only the thin lamina, which is dried with a gentle heat.[1724] The fresh leaf has when bruised an unpleasant herbaceous smell, which in drying becomes agreeable and tea-like. The dried leaf has a very bitter taste.
Chemical Composition—Since the beginning of the present century, numerous attempts have been made to prepare the active principle of foxglove, and the name Digitalin has been successively bestowed on widely different substances.
Among the investigators engaged in these researches, we may point out Walz (1846-1858), Kosmann (1845-46, 1860), Homolle partly with Quévenne (1845-61), Nativelle (1872), and especially Schmiedeberg (1874).[1725] The latter has prepared a new, well-defined, crystallizable principle, Digitoxin, from Digitalis. He exhausted with water the leaves previously dried and powdered, and then extracted them repeatedly with dilute alcohol, 50 per cent.; the tincture thus obtained was then mixed with basic acetate of lead as long as it produced a precipitate. The latter being separated, the filtered liquid was concentrated and the deposit now formed, after some days, removed from the aqueous liquid. It was then washed with a dilute solution of carbonate of sodium, by which a yellow matter (chrysophan?) was partly removed. The substance was then dried, and yielded to chloroform a brownish mass, which after the chloroform had been driven off, was purified by benzin. This liquid dissolved the remainder of the yellow or orange matter, and a little fat, leaving crude digitoxin, which is to be purified by recrystallization from warm alcohol, 80 per cent., adding a little charcoal. This purification still yields yellowish crystals, which ought to be washed again with carbonate of sodium, ether or benzin, and then recrystallized from warm absolute alcohol, containing a little chloroform. This process, however, will only afford colourless crystals provided it be so performed as to cause the separation of digitoxin on account of the cooling of the solution, not by the evaporation of the solvent. If the liquid is instead allowed to evaporate it will soon assume a darker coloration. In the way just pointed out, perfectly colourless scales or needle-shaped crystals of pure digitoxin are at length formed, the yield being not more considerable than about one part from 10,000 of dried leaves.
Digitoxin is insoluble in water, to which it does not even impart its intensely bitter taste as displayed in the alcoholic solution. It is likewise insoluble in benzin or bisulphide of carbon, very sparingly soluble in ether, more abundantly so in chloroform, the latter liquid however acting but very slowly on digitoxin. Its best solvent is alcohol, either cold or warm. The composition of digitoxin answers to the formula, C₃₁H₃₃O₇.
Digitoxin warmed with concentrated hydrochloric acid assumes a yellow or greenish hue, the same which is commonly attributed to commercial “digitalin.” Digitoxin is not a saccharogenous matter; in alcoholic solution it is decomposed by dilute acids, and then affords Toxiresin, an uncrystallizable, yellowish substance, which may easily be separated on account of its ready solubility in ether; it appears to be produced also if digitoxin is maintained for some time in the state of fusion at about 240° C. Toxiresin proved to be a very powerful poison, acting energetically on the heart and muscles of frogs. The very specific action of foxglove is due—not exclusively—to digitoxin; it is so highly poisonous that Schmiedeberg thinks it not at all fit for medicinal use, which might rather be confined to other constituents of foxglove, as, for instance, to those obtained from the seeds under the names of digitalin and digitaléin. The latter, however, are of more difficult extraction than digitoxin.
The preparation of digitoxin is similar to that of Nativelle’s crystallized “digitalin;” the former as well as paradigitogenin[1726] are largely found in Nativelle’s digitalin.
The Digitalin of Nativelle—The researches on digitalis of this chemist, for which the Orfila prize of 6000 francs was awarded in 1872, have resulted in the extraction of a crystallized preparation possessing active medicinal properties. It may be obtained by the following process:—
The leaves, previously exhausted by water, are extracted by means of alcohol, sp. gr. ·930. The tincture is concentrated until its weight is equal to that of the leaves used, and then diluted by adding thrice its weight of water. A pitch-like deposit is then formed; digitaléin and other substances remaining in solution. The deposit dried on blotting paper is boiled with double its weight of alcohol, sp. gr. ·907; on cooling, crystals are slowly deposited during some days. They should be washed with a little diluted alcohol (·958) and dried: to purify them, they should be first recrystallized from chloroform, and subsequently from boiling alcohol sp. gr. ·828, some charcoal being used at the same time. Digitalin is thus obtained in colourless needle-shaped crystals. It assumes an intense emerald green colour when moistened with hydrochloric acid, and has an extremely bitter taste. On the animal economy, it displays all the peculiar effects of digitalis, the dose of a milligramme taken by an adult person once or twice a day occasioning somewhat alarming symptoms, but smaller doses exhibiting the sedative power of the herb.
Another body occurring in foxglove is the crystallizable sugar called Inosite, which was detected by Marmé in the leaves, as well as in those of dandelion ([p. 394]). Pectic matters are also present in foxglove leaves.
Uses—Foxglove is a very potent drug, having the effect of reducing the frequency and force of the heart’s action, and hence is given in special cases as a sedative; it is also employed as a diuretic.