_Foxglove Leaves_; F. _Feuilles de Digitale_; G. _Fingerhutblätter_.
=Botanical Origin=—_Digitalis purpurea_ L., an elegant and stately
plant, common throughout the greater part of Europe, but preferring
siliceous soils and generally absent from limestone districts. It is
found on the edges of woods and thickets, on bushy ground and commons,
becoming a mountain plant in the warm parts of Europe. It occurs in the
island of Madeira, in Portugal, Central and Southern Spain, Northern
Italy, France, Germany, the British Isles and Southern Sweden, and in
Norway as far as 63° N. lat.; it is however very unequally distributed,
and is altogether wanting in the Swiss Alps and the Jura.[1718] As a
garden plant it is well known.
=History=—The Welsh “Physicians of Myddvai” appear to have frequently
made use of foxglove for the preparation of external medicines.[1719]
Fuchs[1720] and Tragus[1721] figured the plant; the former gave it
the name of _Digitalis_, remarking that up to the time at which he
wrote, there was none for the plant in either Greek or Latin. At that
period it was regarded as a violent medicine. Parkinson recommended
it in 1640 in the “Theatrum botanicum,” and it had a place in the
London Pharmacopœia of 1650 and in several subsequent editions. The
investigation of its therapeutic powers (1776-9) and its introduction
into modern practice are chiefly due to Withering, a well-known English
botanist and physician.[1722]
[1718] Dr. R. Cunningham found (1868) _Digitalis purpurea_ completely
naturalized about San Carlos in the Island of Chiloe in Southern Chili.
[1719] _Meddygon Myddfai_ (see Appendix) in many places.
[1720] _De Hist. Stirpium_, 1542. 892.
[1721] _De Stirpium ... nomenclaturis_, etc. 1552—“_Campanula
sylvestris seu Digitalis_.”
[1722] Withering (William), _Account of the Foxglove_, Birmingham,
1785. 8°.
The word _foxglove_ is said to be derived from the Anglo-Saxon
_Foxes-glew_, i.e. _fox-music_, in allusion to an ancient musical
instrument consisting of bells hung on an arched support.[1723] In the
Scandinavian idioms the plant bears likewise the name of _foxes bell_.
=Description=—Foxglove is a biennial or perennial, the leaves of which
ought to be taken from the plant while in full flower. The lower
leaves are ovate with the lamina running down into a long stalk; those
of the stem become gradually narrower, passing into ovate-lanceolate
with a short broadly-winged stalk, or are sessile. All have the margin
crenate, crenate-dentate, or sub-serrate, are more or less softly
pubescent or nearly glabrous on the upper side, much paler and densely
pubescent on the under, which is marked with a prominent network of
veins. The principal veins diverge at a very acute angle from the
midrib, which is thick and fleshy. The lower leaves are often a foot or
more long, by 5 to 6 inches broad; those of the stem are smaller.
When magnified, the tip of each crenature or serrature of the leaf is
seen to be provided with a small, shining, wart-like gland. The hairs
of the lower surface are simple, and composed of jointed cells which
flatten in drying; those of the upper surface are shorter.
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.
[1723] Prior, _Popular Names of British Plants_, ed. 2. 1870. 84.
[1724] This method of preparing the leaf was directed in the London
Pharmacopœia of 1851, but it had long been in use. No particular
directions are given in the British Pharmacopœia.
[1725] For further particulars on Schmiedeberg’s very elaborate
researches, the reader may consult my abstract of them in _Pharm.
Journ._ v. (1875) 741.—F. A. F..
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.
[1726] A derivative of _digitoxin_ as extracted by Schmiedeberg from
the seeds of foxglove.
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.
=Adulteration=—The dried leaves of some other plants have occasionally
been supplied for those of foxglove. Such are the leaves of
_Verbascum_, which are easily recognized by their thick coat of
branched stellate hairs; of _Inula Conyza_ DC. and _I. Helenium_ L.,
which have the margin almost entire, and in the latter plant the veins
diverging nearly at a right angle from the midrib; in both plants the
under side of the leaf is less strongly reticulated than in foxglove.
But to avoid all chance of mistake, it is desirable that druggists
should purchase the _fresh flowering plant_, which cannot be confounded
with any other, and strip and dry the leaves for themselves.