part 22

(1877).

[1654] _Pharm. Journ._ vii. (1866) 496.

=Chemical Composition=—By exhausting the seeds dried at 100° C. with boiling ether, we obtained a thick light brownish oil having an acrid taste and concreting below 18° C. The powdered seeds yielded of this oil 14·4 per cent. Water removes from the seeds a considerable amount of mucilage, some albuminous matter and a little tannic acid. The first is soluble to some extent in dilute spirit of wine, and may be precipitated therefrom by an alcoholic solution of acetate of lead.

The active principle of kaladana is a _resin_, soluble in alcohol, but neither in benzol nor in ether. From the residue of the seeds after exhaustion by ether, treatment with absolute alcohol removed a pale yellowish resin in quantity equivalent to 8·2 per cent. of the seed.

Kaladana resin, which has been introduced into medical practice in India under the name of _Pharbitisin_,[1655] has a nauseous acrid taste and an unpleasant odour, especially when heated. It melts about 160° C. The following liquids dissolve it more or less freely, namely, spirit of wine, absolute alcohol, acetic acid, glacial acetic acid, acetone, acetic ether, methylic and amylic alcohol, and alkaline solutions. It is on the other hand insoluble in ether, benzol, chloroform, and sulphide of carbon. With concentrated sulphuric acid, it forms a brownish yellow solution, quickly assuming a violet hue. This reaction however requires a very small quantity of the powdered resin. If a solution of the resin in ammonia, after having been kept a short time, is acidulated, no precipitate is formed; but the solution is now capable of separating protoxide of copper from an alkaline solution of the tartrate, which originally it did not alter. Heated with nitric acid, the resin affords _sebacic acid_ (see p. 446).

From these reactions of kaladana resin, we are entitled to infer that it agrees with the resin of jalap or _Convolvulin_. To prepare it in quantity, it would probably be best to treat the seeds with common acetic acid, and to precipitate it by neutralizing the solution. We have ascertained that the resin is not decomposed when digested with glacial acetic acid at 100° C., even for a week.

We have had the opportunity of examining a sample of kaladana resin manufactured by Messrs. Rogers and Co., chemists of Bombay and Poona, which we found to agree with that prepared by ourselves. It is a light yellowish friable mass, resembling purified jalap resin, and like it, capable of being perfectly decolorized by treatment with animal charcoal.

=Uses=—Kaladana seeds have cathartic powers like jalap. Besides the resin, an extract, tincture and compound powder have been introduced into the _Pharmacopœia of India_. In many parts of India the natives take the roasted seeds as a purgative.

[1655] _Pharmacopœia of India_, 1868, 156.

SOLANACEÆ.

STIPES DULCAMARÆ.

_Caules Dulcamaræ_; _Bitter-sweet_, _Dulcamara_, _Woody Nightshade_; F. _Douce-amère_, _Morelle grimpante_; G. _Bittersüss_.

=Botanical Origin=—_Solanum Dulcamara_ L., a perennial shrubby plant, having small purple flowers and red berries, occurring throughout Europe, except in the extreme north. It is also found in Northern Africa, and in Asia Minor, and has become naturalized in North America. It is common in moist, shady hedges and thickets.[1656]

=History=—Bitter nightshade, “manyglog,” was an ingredient, together with wild sage and betony, of a drink which the Welsh “Physicians of Myddfai” in the 13th century prepared for the bite of a mad dog.[1657] The stalks of bitter-sweet were also used in the medical practice by the German physicians and botanists of the 16th century, one of whom, Tragus (1552), has figured and described it, under the name of _Dulcis amara_ or _Dulcamarum_.

[1656] _Solanum nigrum_ L. which slightly resembles dulcamara, is a low-growing annual or biennial, with _herbaceous_ stems, and berries usually _black_.

[1657] _Meddygon Myddvai_ (see Appendix) 185. 293. 375.

=Description=—The older stems are woody; the upper and younger are soft and green, long and straggling, attaining by the support of other plants a height of 6 feet or more, and dying back in the winter. For medicinal use, the shoots of a year or two old should be gathered, either late in the year, or early in the spring before the leaves come out. These shoots are several feet long, by about ⅕ of an inch thick, of a light greenish-brown, sometimes cylindrical, at others indistinctly 4-or 5-sided, slightly furrowed longitudinally, or somewhat warty.

The thin, shining cork-bark easily exfoliates, showing beneath it the mesophlœum which is rich in chlorophyll. The stalks are mostly hollow, and partially filled with a whitish pith. The wood when dried is about half or one-third as broad as the hollow centre, and the green bark considerably narrower than the wood; the latter has a radiate structure, and in older stems exhibits two or three sharply-defined annual rings. The stems are usually cut into short lengths before being dried for use.

The odour, which is rather fœtid and unpleasant, is to a great extent dissipated by drying. The taste, at first slightly bitter, is afterwards sweetish. The bitter appears to be more predominant in the spring than in the autumn.

=Microscopic Structure=—The epidermis of younger shoots consists of tabular thick-walled cells, many of them being elevated from the surface as short blunt hairs. The older stems are covered with the usual suberous envelope. The boundary between the mesophlœum and the endophlœum is marked by a ring of strong liber-fibres, some of which also occur in the pith. The woody part is rich in large vessels. In the parenchymatous tissue of bitter-sweet, small crystals of oxalate of calcium, not of a well-defined outline, and minute starch granules are deposited.

=Chemical Composition=—The taste of bitter-sweet appears due, according to Schoonbroodt (1867), to a bitter principle yielding by decomposition, sugar and _Solanine_,—the latter in very small amount. Solanine is an alkaloid; it was first prepared in 1820 by Desfosses, a pharmacien at Besançon, from the berries of _Solanum nigrum_ L., and was subsequently detected by the same chemist in the leaves and stalks of _S. Dulcamara_, and by Peschier in the berries. Winckler (1841) observed that the alkaloid of dulcamara stems can be obtained only in an amorphous state, and that it behaves to platinic and mercuric chlorides differently from the solanine of potatoes. Moitessier (1856) confirmed this observation, and obtained only amorphous salts of the solanine of bitter-sweet.

Zwenger and Kind on the one hand, and O. Gmelin on the other (1859 and 1858), found that solanine, C₄₃H₆₉NO₁₆ (or C₄₂H₈₇NO₁₅, according to Hilger, 1879), is a conjugated compound of sugar and a peculiar crystallizable alkaloid, _Solanidine_, C₂₆H₃₉NO (or C₂₆H₄₁NO₂?). The latter, under the influence of strong hydrochloric acid, gives up water, and is converted into the amorphous and likewise basic compound, _Solanicine_.

Wittstein (1852) stated another alkaloid, dulcamarine, to be present in the stems of bitter-sweet. But Geissler (1875) proved that this substance, when perfectly pure, contains no nitrogen, and is not an alkaloid. Geissler obtained his _Dulcamarin_ by warming an aqueous decoction of the drug with charcoal, which he dried and exhausted with boiling alcohol. This on evaporation afforded a yellowish amorphous matter, which was dissolved in water and mixed with a very little ammonia; a substance containing nitrogen then separated. The liquid was evaporated, the residue again dissolved in alcohol, and the alcohol distilled. Dulcamarin thus obtained is a yellowish powder of at first bitter and subsequently permanently sweet taste. It dissolves in water or alcohol, not in ether, chloroform, bisulphide of carbon. By boiling dulcamarin with dilute acids it splits up according to the following equation:—

C₂₂H₃₄O₁₀ + 2 OH₂ = C₆H₁₂O₆ · C₁₆H₂₆O₆. Dulcamarin. Sugar. Dulcamaretin.

Dulcamaretin, a dark brown, tasteless mass, is soluble in alcohol, not in water or ether.

=Uses=—Dulcamara is occasionally given in the form of decoction, in rheumatic or cutaneous affections; but its real action, according to Garrod, is unknown. This physician remarks[1658] that it does not dilate the pupil or produce dryness of the throat like belladonna, henbane or stramonium. He has given to a patient 3 pints of the decoction _per diem_ without any marked action, and has also administered as much as half a pound of the fresh berries with no ill effect.

[1658] _Essentials of Materia Medica_, 1855. 196.

FRUCTUS CAPSICI.

_Pod Pepper_, _Red Pepper_, _Guinea Pepper_, _Chillies_, _Capsicum_; F. _Piment ou Corail des Jardins_, _Poivre d’Inde ou de Guinée_; G. _Spanischer Pfeffer_.

=Botanical Origin=—The plants, the fruits of which are known as _Pod Pepper_, have for a long period been cultivated in tropical countries, and are now found in such numerous varieties that an exact determination of the original species is a point of great difficulty. Of several species having pungent fruits, the two following are those which supply the spice found in British commerce:—

1. _Capsicum fastigiatum_ Blume,[1659] a small ramous shrub, with 4-sided, fastigiate, diverging branches; fruit-bearing peduncles sub-geminate, slender, erect; fruit very small, subcylindrical, oblong, straight, with calyx obconical and truncate. It occurs apparently wild in Southern India, and is extensively cultivated in Tropical Africa and America.

Roxburgh, who describes this plant under the name _C. minimum_, terms it _East Indian Bird Chilly_ or _Cayenne Pepper Capsicum_. Wight says that it is consumed by the natives of India, but that it is not the sort preferred. It is this species that the authors of the British Pharmacopœia have cited as the source of the _Fructus Capsici_ to be used in medicine, and it certainly furnishes the greater part of the Pod Pepper now found in the London market.

2. _C. annuum_ L., an herbaceous (sometimes shrubby?) plant, with fruit extremely variable in size, form, and colour, in some varieties erect, in others pendulous. According to Naudin, in whose opinion we concur, _C. longum_ DC.[1660] and _C. grossum_ Willd. are not specifically distinct from this plant. It furnishes the larger kinds of Pod Pepper and, as we believe, much of the Cayenne Pepper which is imported in the state of powder.

=History=—All species of _Capsicum_ appear to be of American origin; no ancient Sanskrit or Chinese name for the genus is known, and the Latin and Greek names that have been referred to it are extremely doubtful.[1661]

The earliest reference to the fruit as a condiment that we have met with, occurs in a letter written in 1494 to the Chapter of Seville by Chanca, physician to the fleet of Columbus in his second voyage to the West Indies. The writer in noticing the productions of Hispaniola, remarks that the natives live on a root called _Age_, which they season with a spice they term _Agi_, also eaten with fish and meat.[1662] The first of these words signifies _yam_, the second is the designation of Red Pepper, and still the common name for it in Spanish. Capsicum and its uses are more particularly described by Fernandez, who reached Tropical America from Spain in A.D. 1514.[1663]

[1659] Wight, _Icones Plant. Indiæ Orient._ iv. (1850) tab. 1617; _Capsicum minimum_ Roxb. _Flor. Ind._ i. (1832) 574. Faire has ascertained that this is the _Capsicum frutescens_ of the _Species Plantarum_ of Linnæus, but not that of the _Hortus Cliffortianus_ of the same botanist, to which latter the name _C. frutescens_ is usually applied.

[1660] The chief distinction between _C. annuum_ and _C. longum_ is that the former has an _erect_, the latter a _pendulous_ fruit.

[1661] Dunal in De Cand. _Prodromus_, xiii. i. 412.

[1662] _Letters of Christopher Columbus_, translated by Major (Hakluyt Society), 1870. 68.

[1663] _Historia de las Indias_, Madrid, i. (1851) 275.

In the _Historia Stirpium_ of Leonhard Fuchs, published at Basle in 1542, fol. 733, may be found the first and excellent figures of _Capsicum longum_ DC. under the name of _Siliquastrum_ or _Calicut Pepper_; the author states that the plant has been introduced into Germany from India a few years previously. From this might be inferred an Indian origin; but on the other hand, Clusius asserts that the plant was brought from Pernambuco by the Portuguese, whose commercial intercourse with India would easily explain it being carried thither at an early period. He further states, that the American capsicum had been generally introduced into the gardens at Castille, and that it was used all the year round, green or dried, as a condiment and as pepper. He also saw it cultivated in abundance at Brünn in Moravia in 1585.[1664]

[1664] Caroli Clusii _Curæ posteriores_, Antverp., 1611. 95.

_Capsicum longum_ DC. was grown in England by Gerarde (1597 _et antea_), who speaks of the pods as well known, and sold “in the shops at Billingsgate by the name of Ginnie Pepper.”

=Description=—As already indicated, the Pod Pepper of commerce is of two kinds, namely:—

1. Fruits of _Capsicum fastigiatum_—These are ½ to ¾ of an inch in length, by about ²/₁₀ of an inch in diameter, of an elongated, subconical form, tapering to a blunt point, and slightly contracted towards the base. The calyx, which is not always present, is cup-shaped, 5-toothed, 5-sided, supported on a slender, straight pedicel, ¾ to 1 inch long. The fruits, which are somewhat compressed and shrivelled by drying, and also brittle when old, have a leathery, smooth, shining translucent, thin, dry pericarp, of a dull orange-red, enclosing about 18 seeds, attached in two cells to a thin central

## partition. The seeds have the form of roundish or ovate discs, about

⅛ of an inch in diameter, somewhat thickened at the edges; the embryo is curved, almost into a ring. The taste of the pericarp, and likewise of the seeds, is extremely pungent and fiery. The dried fruit has an odour by no means feeble, which we cannot compare to that of any other substance.

2. Fruits of _Capsicum annuum_ of the commonest variety resemble those of _C. fastigiatum_, except that they are of longer size, being from 2 to 3 or more inches in length, often rather more tapering towards the extremity. The seeds scarcely surpass in size those of _C. fastigiatum_.

=Microscopic Structure=—The pericarp consists of two layers, the outer being composed of yellow thick-walled cells. The inner layer is twice as broad and exhibits a soft shrunken parenchyme, traversed by thin fibro-vascular bundles. The cells of the outer layer especially are the seat of the fine granular colouring matter. If it is removed by an alcoholic solution of potash, a cell-nucleus and drops of fat oil make their appearance. The structural details of this fruit afford interesting subjects for microscopical investigation.

=Chemical Composition=—Bucholz in 1816, and about the same time Braconnot, traced the acridity of capsicum to a substance called _Capsicin_. It is obtained by treating the alcoholic extract of ether, and is a thick yellowish-red liquid, but slightly soluble in water. When gently heated, it becomes very fluid, and at a higher temperature is dissipated in fumes which are extremely irritating to respiration. It is evidently a mixed substance, consisting of resinous and fatty matters.

Felletár in 1869 exhausted capsicum fruits with dilute sulphuric acid, and distilled the decoction with potash. The distillate, which was strongly alkaline and smelt like conine, was saturated with sulphuric acid, evaporated to dryness, and exhausted with absolute alcohol. The solution, after evaporation of the alcohol, was treated with potash, and yielded by distillation a volatile alkaloid having the odour of conine.

From experiments made by one of us (F.) we can fully confirm the observations of Felletár. We have obtained the volatile base in question, and find it to have the smell of conine. It occurs both in the pericarp and in the seeds, but in so small proportion that we were unsuccessful in isolating it in sufficient quantity to allow of accurate examination.

Dragendorff states (1871) that petroleum ether is the best solvent for the alkaloid of capsicum; he obtained crystals of its hydrochlorate, the aqueous solution of which was precipitated by most of the usual tests, but not by tannic acid.

The colouring matter of capsicum fruits is sparingly soluble in alcohol, but readily in chloroform. After evaporation, an intensely red soft mass is obtained, which is not much altered by potash; it turns first blue, then black with concentrated sulphuric acid, like many other yellow colouring substances. By alcohol chiefly _palmitic_ acid is extracted from the fruit, as shown by Thresh in 1877.

The fruits of _Capsicum fastigiatum_ have a somewhat strong odour; on distilling consecutively two quantities, each of 50 lb., we obtained a scanty amount of flocculent fatty matter, which possesses an odour suggestive of parsley. Both this matter, as well as the distilled water, were neutral to litmus paper, and the water tasteless. We separated the latter, and exposed the remaining greasy mass to a temperature of about 50° C., when it for the most part melted. The clear liquid on cooling solidified, and now consisted of tufted crystals, which we further purified by recrystallization from alcohol. Thus about 2 centigrammes were obtained of a neutral white stearoptene, having a decidedly aromatic, not very persistent taste, by _no means acrid_, but rather like that of the essential oil of parsley. The crystals melted at 38° C. On keeping them for some days at the temperature of the water-bath, covered with a watch-glass, some drops of essential oil were volatilized, which had the same taste and did not solidify; the crystals were consequently accompanied by a liquid oil. When kept for some days more in that condition, the crystals themselves began to be volatilized, and the part remaining behind acquired a brownish hue. This no doubt points out another impurity, as we ascertained by the following experiment. With boiling solution of potash, the stearoptene produces a kind of soap, which on cooling yields a transparent jelly. If this is dissolved and diluted, it becomes turbid by addition of an acid. This probably depends upon the presence of a little fatty matter, a suggestion which is confirmed by the somewhat offensive smell given off by our stearoptene if it is heated in a glass tube.

Buchheim’s “Capsicol”[1665] is in our opinion a doubtful substance.

Thresh (1876-1877) succeeded in isolating a well defined, highly active principle, the _Capsaicin_, from the extract which he obtained by exhausting Cayenne pepper with petroleum. From the red liquor dilute caustic lye removes capsaicin, which is to be precipitated in minute crystals by passing carbonic acid through the alkaline solution. They may be purified by recrystallizing them from either alcohol, ether, benzine, glacial acetic acid, or hot bisulphide of carbon; in petroleum capsaicin is but very sparingly soluble, yet dissolves abundantly on addition of fatty oil. The latter being present in the pericarp is the cause why capsaicin can be extracted by the above process.

The crystals of capsaicin are colourless and answer to the formula C₉H₁₄O₂; they melt at 59° C. and begin to volatilize at 115° C., but decomposition can only be avoided by great care. The vapours of capsaicin are of the most _dreadful acridity_, and even the ordinary manipulation of that substance requires much precaution. Capsaicin is not a glucoside; it is a powerful rubefacient, and taken internally produces very violent burning in the stomach.

=Commerce=—Chillies or Pod Pepper are shipped from Zanzibar, Western Africa and Natal, but no general statistics of the quantity imported into Great Britain are accessible.

The exports from Sierra Leone in 1871 reached 7258 lb.[1666] The colony of Natal, which produces Cayenne Pepper in the county of Victoria, where sugar cane and coffee are also grown, shipped in the same year 9072 lb.[1667]

Official returns[1668] show that in 1871 Singapore imported 1071 cwt. (119,952 lb.) of chillies, chiefly from Penang and Pegu. The spice is largely consumed by the Chinese.

Bombay imported of dried chillies in the year 1872-3, 5567 cwt. (623,504 lb.) principally from the Madras Presidency, and exported 3323 cwt.[1669]

=Uses=—Capsicum on account of its pungent properties is often administered as a local stimulant in the form of gargle, and occasionally as a liniment; and internally to promote digestion. In all warm countries it is much employed as a condiment.

RADIX BELLADONNÆ.

_Belladonna Root_; F. _Racine de Belladone_; G. _Belladonnawurzel_.

=Botanical Origin=—_Atropa Belladonna_ L., a tall, glabrous or slightly downy herb, with a perennial stock, native of central and Southern Europe, where it grows in the clearings of woods. The plant extends eastward to the Crimea, Caucasia and Northern Asia Minor. In Britain it is chiefly found in the southern counties, but even of these it is a doubtful native.

[1665] _Jahresbericht_ of Wiggers and Husemann, 1873. 567; also _Yearbook of Pharm._ 1876. 251.

[1666] _Blue Book_ of the Colony of Sierra Leone for 1871.

[1667] Do. of Natal for 1871.

[1668] Do. of the Straits Settlements for 1871.

[1669] _Statement of the Trade and Navigation of Bombay for 1872-73_, pt. ii. 58. 91.

In a few localities in England and France, as well as in North America, the plant is cultivated for medicinal use.

=History=—Although a plant so striking as belladonna can hardly have been unknown to the classical authors, it cannot with certainty be identified in their writings.

Saladinus of Ascoli,[1670] who wrote an enumeration of medicinal plants about A.D. 1450, names the leaves of both _Solatrum furiale_ and _Solatrum minus_, the former of which is probably _Belladonna_. However this may be, the first indubitable notice of it that we have met with, is in the _Grand Herbier_ printed at Paris, probably about 1504.[1671] The plant is also mentioned about this period as _Solatrum mortale_ or _Dolwurtz_, in the writings of Hieronymus Brunschwyg.[1672]

In 1542 belladonna was well figured as _Solanum somniferum_ or _Dollkraut_ by the German botanist Leonhard Fuchs, who fully recognized its poisonous properties.[1673] Yet it was confounded by other writers of this period as Tragus,[1674] who reproduced Fuchs’ figure as “_Solanum hortense_!” _Strygium_ and _Strychnon_ were other names not unfrequently applied to Atropa during the 16th and 17th centuries.

Matthiolus, who terms the plant _Solatrum majus_, states[1675] that it is commonly called by the Venetians _Herba Bella donna_, from the circumstance of the Italian ladies using a distilled water of the plant as a cosmetic. Gesner[1676] was also familiar with the name Belladonna. The introduction of the root of belladonna into British medicine is of recent date, and is due to Mr. Peter Squire of London, who recommended it as the basis of a useful anodyne liniment, about the year 1860.

=Description=—Belladonna has a large, fleshy, tapering root, 1 to 2 inches thick, and a foot or more in length, from which diverge stout branches. Externally the fresh roots are of an earthy brown, rough with cracks and transverse ridges. The bark is thick and juicy, and as well as the more fibrous central portion, is internally of a dull creamy white. A transverse section of the main root shows a distinct radiate structure. The root has an earthy smell with but very little taste at first, but a powerfully acrid after-taste is soon developed.

_Dried root of Belladonna_ is sold in rough irregular pieces of a dirty greyish colour, whitish internally, breaking easily with a short fracture, and having an earthy smell not unlike that of liquorice root. The bark being probably the chief seat of the alkaloid, roots not exceeding the thickness of the finger should be preferred. The drug is for the most part imported from Germany, and is often of doubtful quality. English-grown root purchased in a fresh state (the large and old being rejected), then washed, cut into transverse segments and dried by a gentle heat, furnishes a more reliable and satisfactory article.

[1670] _Compendium Aromatariorum_, 1488.

[1671] _Le Grant Herbier en francoys, contenāt les qualitez, vertus et proprietez des herbes_ etc., Paris (no date) 4°. cap. _De Solastro rustico._

[1672] _Das destillier Buch_ (sub voce _Nachtschet Wasser_). Strassburg, 1521, fol. 93 _b_. The figure probably refers to Atropa, but that given in the edition of the same work of the year 1500 shows _Solanum nigrum_.

[1673] _Historia Stirpium_, Basil. 1542. 689.

[1674] _De Stirpium ... historia_, Argentorati, 1552. 301.

[1675] _Comment. in lib. vi. Dioscoridis_, Venetiis, 1558. 533.

[1676] _De hortis Germaniæ_, Argentorat. 1561, fol. 282.

=Microscopic Structure=—There is a considerable structural difference between the main root and its branches, the former alone containing a distinct pith. This pith is included in a woody circle, traversed by narrow medullary rays. In the outer part of the woody circle, parenchymatous tissue is more prevalent than vascular bundles. The transverse section of the branches of the root exhibits a central vascular bundle instead of a medullary column. The outer vascular bundles show no regular arrangement; and medullary rays are not clearly obvious in the transverse section.

The woody parts, both of the main root and its branches, contain very large dotted vessels accompanied by a prosenchymatous tissue. The cells of the latter, however, are always thin-walled; the absence of proper so-called ligneous tissue explains the easy fracture of the root. Sometimes the prosenchyme in which the vessels are imbedded assumes a brownish hue and a waxy appearance, and such parts exhibit a very irregular structure.

In the cortical portion of belladonna root, many of the cells of the middle layer, and likewise some of the central parts of the root, are loaded with extremely small octahedric crystals of calcium oxalate. But most of the parenchymatous cells are filled up with small starch granules.

=Chemical Composition=—In 1833 Mein prepared from the root, and Geiger and Hesse from the herb, the crystallizable alkaloid _Atropine_. The researches of Lefort (1872) have proved that the roots contain it in very variable proportions, the young being much richer in alkaloid than the old.[1677] The maximum proportion obtained was 0·6 per cent.; this was from root of the thickness of the finger. Large old roots, 7 or 8 years of age, afford from 0·25 to 0·31 per cent. They have besides a smaller proportion of bark than young roots, and it is chiefly in the bark that the alkaloid appears to reside. Manufacturers of atropine employ exclusively the root.

Ludwig and Pfeiffer (1861), by decomposing atropine with potassium chromate and sulphuric acid, obtained benzoic acid and propylamine. Other products are formed when atropine is treated with strong hydrochloric acid, baryta water or caustic soda, thus—_Atropine_, C₁₇H₂₃NO₂ + H₂O = _Tropic Acid_, C₉H₁₀O₃ + _Tropine_, C₈H₁₅NO.

Tropic acid, C₆H₅C(OH) {CH₃ {COOH,

being further boiled with the same agents is converted into

atropic acid, C₆H₅C {CH₂ {COOH,

which, especially by using hydrochloric acid, is gradually transformed into isotropic acid. Both these acids are isomeric to cinnamic acid, C₉H₈O₂, but otherwise remarkably dissimilar.

Tropine is a strongly alkaline body, readily soluble both in water and alcohol, and furnishing tabular crystals by the evaporation of its solution in ether. Neither tropine nor tropic acid, it is stated by Kraut (1863), is present in the leaves and root of belladonna.

Hübschmann (1858) detected in belladonna root a second but uncrystallizable alkaloid, called _Belladonnine_; it has a resinous aspect, is distinctly alkaline, and when heated emits, like atropine, a peculiar odour.

[1677] For Lefort’s process for estimating atropine, see p. 458.

The root further contains, according to Richter (1837) and Hübschmann, a fluorescent substance, as well as a red colouring matter called _Atrosin_.[1678] The latter occurs in greatest abundance in the fruit, and would probably repay further investigation.

=Uses=—Belladonna root is chiefly used for the preparation of atropine, which is employed for dilating the pupil of the eye. A liniment made with belladonna root is used for the relief of neuralgic pains.

=Adulteration=—We may point out that the roots of _Mandragora microcarpa_, _M. officinarum_, and _M. vernalis_ Bertoloni are very nearly allied to the root under notice, both in external appearance and in their structure. They are not likely to be confounded with Belladonna root, their mother plants being indigenous in the South of Europe.

FOLIA BELLADONNÆ.

_Belladonna Leaves_; F. _Feuilles de Belladone_; G. _Tollkraut_.

=Botanical Origin=—_Atropa Belladonna_ L. (p. 455).

=History=—Belladonna Leaves and the extract prepared from them were introduced into the London Pharmacopœia of 1809. For further

## particulars regarding the history of belladonna, see the preceding

article.

=Description=—Belladonna or Deadly Nightshade produces thick, smooth herbaceous stems, which attain a height of 4 to 5 feet. They are simple in their lower parts, then usually 3-forked, and afterwards 2-forked, producing in their upper branches an abundance of bright green leaves, arranged in unequal pairs, from the bases of which spring the solitary, pendulous, purplish, bell-shaped flowers, and large shining black berries.

The leaves are 3 to 6 inches long, stalked, broadly ovate, acuminate, attenuated at the base, soft and juicy; those of barren roots are alternate and solitary. The young shoots are clothed with a soft, short pubescence, which on the calyx is somewhat more persistent, assuming the character of viscid, glandular hairs. If bruised, the leaves emit a somewhat offensive, herbaceous odour which is destroyed by drying. When dried, they are thin and friable, of a brownish-green on the upper surface and greyish beneath, with a disagreeable, faintly bitter taste. Of fresh leaves 100 lb. yield 16 lb. of dried (Squire).

=Chemical Composition=—The important constituent of belladonna leaves is _Atropine_. Lefort (1872)[1679] estimated its amount by exhausting the leaves previously dried at 100° C. by means of dilute alcohol, concentrating the tincture, and throwing down the alkaloid with a solution of iodohydrargyrate of potassium. The precipitate thus obtained was calculated to contain 33·25 per cent. of atropine. Lefort examined leaves from plants both cultivated and growing wild in the environs of Paris, and gathered either before or after flowering. He found cultivation not to affect the percentage of alkaloid,—that the leaves of the young plant were rather less rich than those taken at the period of full inflorescence,—and that the latter (dried) yielded 0·44 to 0·48 per cent. of atropine.

[1678] Gmelin, _Chemistry_, xvii. (1866) 1.

[1679] _Journ. de Pharm._ xv. (1872) 269. 341.

Larger percentages are recorded by Dragendorff;[1680] as much as 0·95 per cent. of atropine as obtained from the dried unripe fruits, 0·83 from the dried leaves, 0·21 from the root. The estimation was performed in nearly the same way as that followed by Lefort.

Belladonna herb yields _Asparagin_, which according to Biltz (1839) crystallizes out of the extract after long keeping. The crystals found in the extract by Attfield (1862) were however chloride and nitrate of potassium. The same chemist obtained by dialysis of the juice of belladonna, nitrate of potassium, and square prisms of a salt of magnesium containing some organic acid; the juice likewise affords ammonia.[1681] The dried leaves yielded us 14·5 per cent. of ash consisting mainly of calcareous and alkaline carbonates.

=Uses=—The fresh leaves are used for making _Extractum Belladonnæ_, and the dried for preparing a tincture. They should be gathered while the plant is well in flower.

HERBA STRAMONII.

_Stramonium_, _Thornapple_; F. _Herbe de Stramoine_; G. _Stechapfelblätter_.

=Botanical Origin=—_Datura[1682] Stramonium_ L., a large, quick-growing, upright annual, with white flowers like a convolvulus, and ovoid spiny fruits. It is now found as a weed of cultivation in almost all the temperate and warmer regions of the globe. In the south of England it is often met with in rich waste ground, chiefly near gardens or habitations.

=History=—The question of the native country and early distribution of _D. Stramonium_ has been much discussed by botanical writers. Alphonse De Candolle,[1683] who has ably reviewed the arguments advanced in favour of the plant being a native respectively of Europe and America or Asia, enounces his opinion thus:—that _D. Stramonium_ L. appears to be indigenous to the Old World, probably the borders of the Caspian Sea or adjacent regions, but certainly not of India; that it is very doubtful if it existed in Europe in the time of the ancient Roman Empire, but that it appears to have spread itself between that period and the discovery of America.

Stramonium was cultivated in London towards the close of the 16th century by Gerarde, who received the seed from Constantinople and freely propagated the plant, of the medicinal value of which he had a high opinion. The use of the herb in more recent times is due to the experiments of Störck.[1684]

[1680] _Werthbestimmung stark wirkender Droguen_, Petersburg, 1876. 28.

[1681] The fresh juice kept for a few days has been known to evolve _red vapours_ (nitrous acid?) when the vessel containing it was opened.—H. S. Evans in _Pharm. Journ._ ix. (1850) 260.

[1682] _Datura_ from the Sanskrit name _D’hustùra_, applied to _D. fastuosa_ L. The origin of the word _Stramonium_ is not known to us.

[1683] _Géographie Botanique_, ii (1855) 731.

[1684] Libellus quo demonstratur _Stramonium_, Hyoscyamum, Aconitum ... esse remedia, Vindob. 1762.

=Description=—Stramonium produces a stout, upright, herbaceous green stem, which at a short distance from the ground, throws out spreading forked branches, in the axil of each fork of which arises a solitary white flower, succeeded by an erect, spiny, ovoid capsule. At each furcation and directed outwards is a large leaf. This arrangement of parts is repeated, and as the plant grows vigorously, it often becomes much branched and acquires in the course of the summer a considerable size.

The leaves of stramonium have long petioles, are unequal at the base, oval, acuminate, sinuate-dentate with large irregular pointed teeth or lobes, downy when young, glabrous at maturity. When fresh they are somewhat firm and juicy, emitting when handled a disagreeable fœtid smell. The larger leaves of plants of moderate growth attain a length of 6 to 8 or more inches.

For medicinal purposes, the entire plants are pulled up, the leaves and younger shoots are stripped off, quickly dried, and then broken and cut into short lengths, so as to be conveniently smoked in a pipe, that being the method in which the drug is chiefly consumed in England. The offensive smell of the fresh plant is lost by drying, being replaced by a rather agreeable tea-like odour. The dried herb has a bitterish saline taste.

=Chemical Composition=—The leaves of stramonium contain, in common with the seeds, the alkaloid _Daturine_ (see p. 461), but in extremely small proportion, not exceeding in fact ²/₁₀ to ³/₁₀ per mille. They are rich in saline and earthy constituents; selected leaves dried at 100° C. yielded us 17·4 per cent. of ash.

=Uses=—Scarcely employed in any other way than in smoking like tobacco for the relief of asthma.—Col. Grant (1871) found the herb to be smoked in pipes by the Nubians for chest-complaint.

=Substitute=—_Datura Tatula_ L.—This plant is closely allied to _D. Stramonium_ L., propagating itself on rich cultivated ground with nearly the same facility; but it is not so generally diffused.

De Candolle is of opinion that it is indigenous to the warmer parts of America, whence it was imported into Europe in the 16th century, and naturalized first in Italy, and then in South-Western Europe. By many botanists it has been united to _D. Stramonium_, but Naudin,[1685] who has studied both plants with the greatest attention, especially with reference to their hybrids, is decidedly in favour of considering them distinct. _D. Tatula_ differs from _D. Stramonium_ in having stem, petiole, and nerves of leaves _purplish_ instead of _green_; and corolla and anthers of a _violet_ colour instead of _white_,—characters which, it must be admitted, are of very small botanical value.

_D. Tatula_ has been recommended for smoking in cases of asthma, on the ground of its being _stronger_ than _D. Stramonium_; but we are not aware of any authority as to the comparative strength of the two species.

[1685] _Comptes Rendus_, lv. (1862) 321.

SEMEN STRAMONII.

_Stramonium Seeds_; F. _Semences de Stramoine_; G. _Stechapfelsamen_.

=Botanical Origin=—_Datura Stramonium_ L., see preceding article.

=Description=—The spiny, ovoid capsule of stramonium opens at the summit in four regular valves. It is bilocular, with each cell incompletely divided into two, and contains a large number (about 400) of flattened, kidney-shaped seeds. The seeds are blackish or dark brown, about 2 lines long and ½ a line thick, thinning off towards the hilum which is on the straighter side. The surface of the seed is finely pitted and also marked with a much coarser series of shallow reticulations or rugosities. A section parallel to the faces of the seed exhibits the long, contorted embryo, following the outline of the testa, and bedded in the oily white albumen. The cylindrical form of the embryo is seen in a transverse section of the seed.

The seeds have a bitterish taste, and when bruised a disagreeable odour. When the entire seeds are immersed in dilute alcohol, they afford a tincture displaying a beautiful green fluorescence, turning yellow on addition of ammonia.

=Microscopic Structure=—The testa is formed of a row of radially extended, thick-walled cells. They are not of a simply cylindrical form, but their walls are sinuously bent in and out in the direction of their length. Viewed in a direction tangential to the surface, the cells appear as if indented one into the other. Towards the surface of the seed the cell-walls are elevated as dark brown tubercles and folds, giving to the seed its reticulated and pitted surface. The albumen and embryo exhibit the usual contents, namely fatty oil and albuminoid substances.[1686]

=Chemical Composition=—The active constituent of stramonium seeds is the highly poisonous alkaloid _Daturine_, of which they afford only about ⅒ per cent., while the leaves and roots contain it in still smaller proportion.[1687] Daturine was discovered in 1833 by Geiger and Hesse, and regarded as identical with atropine by A. von Planta (1850), who found it to have the same composition as that alkaloid. The two bodies exhibit the same relations as to solubility and fusing point (88-90° C.); and they also agree in crystallizing easily. The experiments of Schroff (1852), tending to show that although daturine and atropine act in the same manner, the latter has twice the poisonous energy of the former, raised a further question as to the identity of the two alkaloids. Poehl (1876) also stated solutions of daturine to be levogyrate, those of atropine being devoid of rotatory power. From the observations of Erhard (1866), it would appear that the crystalline form of some of the salts of atropine and daturine is different. In stramonium seeds daturine appears to be combined with malic acid. The seeds yielded to Cloëz (1865) 2·9 per cent. of ash and 25 per cent. of fixed oil.

=Uses=—Stramonium seeds are prescribed in the form of extract or tincture as a sedative or narcotic.

[1686] We have not seen W. G. Mann, _Onderzoek van het zaad van Datura Stramonium_, Enschede, 1875.

[1687] Günther in Wiggers and Husemann’s _Jahresbericht_ for 1869. 54.

SEMEN ET FOLIA DATURÆ ALBÆ.

_Seeds and Leaves of the Indian or White-flowered Datura._

=Botanical Origin=—_Datura alba_ Nees, a large, spreading annual plant, 2 to 6 feet high, bearing handsome, tubular, white flowers 5 to 6 inches long. The capsules are pendulous, of depressed globular form, rather broader than high, covered with sharp tubercles or thick short spines. They do not open by regular valves as in _D. Stramonium_, but split in different directions and break up into irregular fragments.

_D. alba_ appears to be scarcely distinct from _D. fastuosa_ L. Both are common in India, and are grown in gardens in the south of Europe.[1688]

=History=—The mediæval Arabian physicians were familiar with _Datura alba_, which is well described by Ibn Baytar[1689] under precisely the same Arabic name (_Jouz-masal_) that it bears at the present day; they were also fully aware of its poisonous properties.

Garcia de Orta[1690] (1563) observed the plant in India, and has narrated that its flowers or seeds are put into food to intoxicate persons it was designed to rob. It was also described by Christoval Acosta, who in his book on Indian drugs[1691] mentions two other varieties, one of them with yellow flowers, the seeds of either being very poisonous, and often administered with criminal intent, as well as for the cure of disease. Graham[1692] says of the plant that it possesses very strong narcotic properties, and has on several occasions been fatally used by Bombay thieves, who have administered it in order to deprive their victims of the power of resistance.

The seeds and fresh leaves have a place in the _Pharmacopœia of India_, 1868.

=Description=—The seeds of _D. alba_ are very different in appearance from those of _D. Stramonium_, being of a light yellowish-brown, rather larger size, irregular in shape and somewhat shrivelled. Their form has been likened to the human ear; they are in fact obscurely triangular or flattened-pearshaped, the rounded end being thickened into a sinuous, convoluted, triple ridge, while the centre of the seed is somewhat depressed. The hilum runs from the pointed end nearly half-way up the length of the seed. The testa is marked with minute rugosities, but is not so distinctly pitted as in the seed of the _D. Stramonium_; it is also more developed, exhibiting in section large intercellular spaces to which are due its spongy texture. The seeds of the two species agree in internal structure as well as in taste; but those of _D. alba_ do not give a fluorescent tincture.

[1688] Seeds of _D. alba_ sent to us from Madras by Dr. Bidie, were sown by our friend M. Naudin of Collioure (Pyrénées Orientales), and produced the plant under three forms, viz.:—1. The true _D. alba_ as figured in Wight’s _Icones_.—2. Plants with flowers, violet without and nearly white within (_D. fastuosa_).—3. Plants with double corollas of large size and of a yellow colour.

[1689] Sontheimer’s translation, i. 269.

[1690] _Aromatum historia_, 1574, lib. 2. c. 24.

[1691] _Tractado de las Drogas ... de las Indias Orientales_, Burgos, 1578. 85.

[1692] _Catalogue of Bombay Plants_, 1839. 141.

The leaves, which are only employed in a fresh state, are 6 to 10 inches in length, with long stalks, ovate, often unequal at the base, acuminate, coarsely dentate with a few spreading teeth. They evolve an offensive odour when handled.

=Microscopic Structure=—The testa is built up of the same tissues as in _D. Stramonium_, but the thick-walled cells constituting the spongy part are far larger, and distinctly show numerous secondary deposits, making a fine object for the microscope.

=Chemical Composition=—Neither the seeds nor the leaves of _D. alba_ have yet been examined chemically, but there can scarcely be any doubt that their very active properties are due to _Daturine_, for the preparation of which the former would probably be the best source.

=Uses=—The seeds in the form of tincture or extract have been employed in India as a sedative and narcotic, and the fresh leaves, bruised and made into a poultice with flour, as an anodyne application.

FOLIA HYOSCYAMI.

_Henbane Leaves_; F. _Feuilles de Jusquiame_; G. _Bilsenkraut_.

=Botanical Origin=—_Hyoscyamus niger_ L., a coarse, erect herb, with soft, viscid, hairy foliage of unpleasant odour, pale yellowish flowers elegantly marked with purple veins, and 5-toothed bottle-shaped calyx. It is found throughout Europe from Portugal and Greece to Central Norway and Finland, in Egypt, Asia Minor, the Caucasus, Persia, Siberia and Northern India. As a weed of cultivation it now grows also in North America[1693] and Brazil. In Britain it occurs wild, chiefly in waste places near buildings; and is cultivated for medicinal use.

Henbane exists under two varieties, known as _annual_ and _biennial_, but scarcely presenting any other distinctive character.

_Biennial Henbane_ (_Hyoscyamus niger_ var. α. _biennis_) is most esteemed for pharmaceutical preparations. It is raised by seed, the plant producing the first year only a rosette of luxuriant stalked leaves, 12 or more inches in length. In the second, it throws up a flower stem of 2 to 3 feet in height, and the whole plant dies as the fruit matures.

_Annual Henbane_ (_H. niger_ var. β. _annua_, vel _agrestis_) is a smaller plant, coming to perfection in a single season. It is the usual wild form, but it is also grown by the herbalists.[1694]

=History=—Hyoscyamus, under which name it is probable the nearly allied South European species, _H. albus_ L., was generally intended, was medicinal among the ancients, and particularly commended by Dioscorides.

In Europe, henbane has been employed from remote times. Benedictus Crispus, archbishop of Milan, in a work written shortly before A.D. 681, notices it under the name of _Hyoscyamus_ and _Symphoniaca_.[1695] In the 10th century, its virtues were particularly recorded by Macer Floridus[1696] who called it _Jusquiamus_.

[1693] It had become naturalized in North America prior to 1672, as we find it mentioned by Josselyn in his _New England’s Rarities discovered_ (Lond. 1672) among the plants “sprung up since the English planted and kept cattle in New England.”

[1694] _Pharm. Journ._ i. (1860) 414.

[1695] S. de Renzi, _Collectio Salernitana_, Napoli, i. (1852) 74. 84.

[1696] _De Viribus Herbarum_, edited by Choulant, Lips. 1832. 108.

Frequent mention is made of it in the Anglo-Saxon works on medicine of the 11th century,[1697] in which it is called _Henbell_, and sometimes _Belene_, the latter word perhaps traceable in βιλινουντία, which Dioscorides[1698] gives as the Gallic designation of the plant. In the 13th century henbane was also used by the Welsh “Physicians of Myddvai.”

The word _Hennibone_, with the Latin and French synonyms _Jusquiamus_ and _Chenille_, occurs in a vocabulary of the 13th century; and _Hennebane_ in a Latin and English vocabulary of the 15th century.[1699] In the _Arbolayre_, a printed French herbal of the 15th century,[1700] we find the plant described as _Hanibane_ or _Hanebane_ with the following explanation—“Elle est aultrement appeler cassilago et aultrement simphoniaca. La semence proprement a nom jusquiame ou hanebane, et herbe a nom cassilago....” Both _Hyoscyamus_ and _Jusquiamus_ are from the Greek Ὑοσκύαμος, i.e. _Hog-bean_.

Though a remedy undeniably potent, henbane in the first half of the last century had fallen into disuse. It was omitted from the London pharmacopœias of 1746 and 1788, and restored only in 1809. Its re-introduction into medicine was chiefly due to the experiments and recommendations of Störck.[1701]

During the middle ages the seeds and roots of henbane were also much used.

=Description=—The stems of henbane, whether of the annual or biennial form, are clothed with soft, viscid, hairy leaves, of which the upper constitute the large, sessile, coarsely toothed bracts of the unilateral flower-spike. The middle leaves are more toothed and subamplexicaul. The lower leaves are stalked, ovate-oblong, coarsely dentate, and of large size. The stems, leaves, and calyces of henbane are thickly beset with long, soft, jointed hairs; the last joint of many of these hairs exudes a viscid substance occasioning the fresh plant to feel clammy to the touch. In the cultivated plant, the hairiness diminishes.

After drying, the broad light-coloured midrib becomes very conspicuous, while the rest of the leaf shrinks much and acquires a greyish green hue. The drug derived from the flowering plant as found in commerce is usually much broken. The fœtid, narcotic odour of the fresh leaves is greatly diminished by drying. The fresh plant has but little taste.

Dried henbane is sold under three forms, which are not however generally distinguished by druggists. These are 1. _Annual plant_, foliage and green tops. 2. _Biennial plant_, leaves of the first year. 3. _Biennial plant_, foliage and green tops. The third form is always regarded as the best, but no attempt has been made to determine with accuracy the relative merits of the three sorts.

[1697] _Leechdoms etc. of Early England_, iii. (1866) 313.

[1698] Lib. iv. c. 69. (ed. Sprengel).

[1699] Wright, _Volume of Vocabularies_, 1857. 141. 265.

[1700] See p. 148, note 3, also Brunet, _Manuel du Libraire_, i. (1860) 377.

[1701] See p. 459, note 5.

=Chemical Composition=—_Hyoscyamine_, the most important among the constituents of henbane, was obtained in an impure state by Geiger and Hesse in 1833. Höhn in 1871 first isolated it from the seeds, which are far richer in it than the leaves.[1702] The seeds are deprived of the fatty oil (26 per cent.) and treated with spirit of wine containing sulphuric acid, which takes out the hyoscyamine in the form of sulphate. The alcohol is then evaporated and tannic acid added; the precipitate thus obtained is mixed with lime and exhausted with alcohol. The hyoscyamine is again converted into a sulphate, the aqueous solution of which is then precipitated with carbonate of sodium, and the alkaloid dissolved by means of ether. After the evaporation of the ether, hyoscyamine remains as an oily liquid which after some time concretes into wart-like tufted crystals, soluble in benzol, chloroform, ether, as well as in water. Höhn and Reichardt assign to hyoscyamine the formula C₁₅H₂₃O₃. The seeds yield of it only 0·05 per cent.

Hyoscyamine is easily decomposed by caustic alkalis. By boiling with baryta in aqueous solution, it is split into _Hyoscine_, C₆H₁₃N, and _Hyoscinic Acid_, C₉H₁₀O₃. The former is a volatile oily liquid of a narcotic odour and alkaline reaction. By keeping it over sulphuric acid it crystallizes and also yields crystallized salts; hyoscine may be closely allied to conine, C₈H₁₅N. Hyoscinic acid, a crystallizable substance having an odour resembling that of empyreumatic benzoic acid.[1703] It melts, according to Höhn, at 105°; tropic acid (see p. 457), melting at 118°, agrees so very nearly with hyoscinic acid that further researches will probably prove these acids to be identical.

Another process for extracting hyoscyamine is due (1875) to Thibaut. He removes by bisulphide of carbon the fatty oil from the powdered seeds, and exhausts them with alcohol slightly acidulated by tartaric acid. The alcohol being distilled off, the author precipitates the alkaloid by means of a solution containing 6 per cent. of iodide of potassium and 3 per cent. iodine. By decomposing the precipitate with sulphurous acid, hydroiodic acid and sulphate of hyoscyamine are formed. The latter is dried up at 35° with magnesia and the hyoscyamine extracted by alcohol or chloroform. The crystals melt at 90°. Thibaut found the alkaloid thus prepared from seeds differing from that yielded by the leaves, the latter having a somewhat strong odour.

Attfield[1704] has pointed out that extract of henbane is rich in nitrate of potassium and other inorganic salts. In the leaves, the amount of nitrate is, according to Thorey,[1705] largest before flowering, and the same observation applies to hyoscyamine.

=Uses=—Henbane in the form of tincture or extract is administered as a sedative, anodyne or hypnotic. The impropriety of giving it in conjunction with free potash or soda, which render it perfectly inert, has been demonstrated by the experiments of Garrod.[1706] Hyoscyamine, like atropine, powerfully dilates the pupil of the eye.

[1702] From the experiments of Schoonbroodt (1868), there is reason to believe that the active principle of henbane can be more easily extracted from the _fresh_ than from the _dried_ plant.

[1703] I have had the opportunity of examining the above substances as prepared by the said chemists.—F. A. F. July 1871.

[1704] _Pharm. Journ._ iii. (1862) 447.

[1705] Wiggers and Husemann, _Jahresbericht_, 1869. 56.

[1706] _Pharm. Journ._ xvii. (1858) 462; xviii. (1859) 174.

=Substitutes=—_Hyoscyamus albus_ L., a more slender plant than _H. niger_ L., with stalked leaves and bracts, a native of the Mediterranean region, is sometimes used in the south of Europe as medicinal henbane. _H. insanus_ Stocks, a plant of Beluchistan, is mentioned in the _Pharmacopœia of India_ as of considerable virulence, and sometimes used for smoking.

FOLIA TABACI.

_Herba Nicotianæ_; _Tobacco_; F. _Tabac_; G. _Tabakblätter_.

=Botanical Origin=—_Nicotiana Tabacum_ L.—The common Tobacco plant is a native of the New World, though not now known in a wild state. Its cultivation is carried on in most temperate and subtropical countries.

=History=—It is stated by C. Ph. von Martius[1707] that the practice of smoking tobacco has been widely diffused from time immemorial among the natives of South America, as well as among the inhabitants of the valley of the Mississippi as far north as the plant can be cultivated.

The Spaniards became acquainted with tobacco when they landed in Cuba in 1492, and on their return introduced it into Europe for the sake of its medicinal properties. The custom of inhaling the smoke of the herb was learnt from the Indians, and by the end of the 16th century had become generally known throughout Spain and Portugal, whence it passed into the rest of Europe, and into Turkey, Egypt, and India, notwithstanding that it was opposed by the severest enactments both of Christian and Mahommedan governments. It is commonly believed that the practice of smoking tobacco was much promoted in England, as well as in the north of Europe generally, by the example of Sir Walter Raleigh and his companions.

Tobacco was introduced into China, probably by way of Japan or Manila, during the 16th or 17th century, but its use was prohibited by the emperors both of the Ming and Tsing dynasties. It is now cultivated in most of the provinces, and is universally employed.[1708]

The first tolerably exact description of the tobacco plant is that given by Gonzalo Fernandez de Oviedo y Valdés, governor of St. Domingo, in his _Historia general de las Indias_,[1709] printed at Seville in 1535. In this work, the plant is said to be smoked through a branched tube of the shape of the letter =Y=, which the natives call _Tabaco_.

It was not until the middle of the 16th century that growing tobacco was seen in Europe,—first at Lisbon, whence the French ambassador, Jean Nicot, sent seeds to France in 1560 as those of a valuable medicinal plant, which was even then diffused throughout Portugal.[1710]

Monardes,[1711] writing in 1571, speaks of tobacco as brought to Spain a few years previously, and valued for its beauty and for its medicinal virtues. Of the latter he gives a long account, noticing also the methods of smoking and chewing the herb prevalent among the Indians. He also supplies a small woodcut representing the plant, which he states to have white flowers, red in the centre.

[1707] _Beiträge zur Ethnographie und Sprachenkunde Americas, zumal Brasiliens_, i. (1867) 719.

[1708] Mayers in _Hong Kong Notes and Queries_, May, 1867; F. P. Smith, _Mat. Med. and Nat. Hist. of China_, 1871. 219.

[1709] Lib. v. c. 2.

[1710] Nicot, _Thrésor de la langue Françoyse_, Paris, 1606. 429.

[1711] _Segunda parte del libro de las cosas que se traen de nuestras Indias occidentales, que sirven al uso de medicina._ Do se trata del Tabaco ..., Sevilla, 1571, 3.

Jacques Gohory,[1712] who cultivated the plant in Paris at least as early as 1572, describes its flowers as shaded with red, and enumerates various medicinal preparations made from it.

In the _Maison Rustique_ of Charles Estienne, edition of 1583, the author gives a “_Discours sur la Nicotiane ou Petum mascle_,” in which he claims for the plant the first place among medicinal herbs, on account of its singular and almost divine virtues.

The cultivation of tobacco in England, except on a very small scale in a physic garden, has been prohibited by law[1713] since 1660.

=Description=—Amongst the various species of _Nicotiana_ cultivated for the manufacturing of smoking tobacco and snuff, _N. Tabacum_ is by far the most frequent, and is almost the only one named in the pharmacopœias as medicinal. Its simple stem, bearing at the summit a panicle of tubular pink flowers, and growing to the height of a man, has oblong, lanceolate simple leaves, with the margin entire. The lower leaves, more broadly lanceolate, and about 2 feet long by 6 inches wide, are shortly stalked. The stem-leaves are semi-amplexicaul, and decurrent at the base. Cultivation sometimes produces cordate-ovate forms of leaf, or a margin more or less uneven, or nearly revolute.

All the herbaceous parts of the plant are clothed with long soft hairs, made up of broad, ribbon-like, striated cells, the points of which exude a glutinous liquid. Small sessile glands are situated here and there on the surface of the leaf.[1714] The lateral veins proceed from the thick midrib in straight lines, at angles of 40° to 75°, gently curving upwards only near the edge. In drying, the leaves become brittle and as thin as paper, and always acquire a brown colour. Even by the most careful treatment of a single leaf, it is not possible to preserve the green hue.

The smell of the fresh plant is narcotic; its taste bitter and nauseous. The characteristic odour of dried tobacco is developed during the process of curing.

=Chemical Composition=—The active principle of tobacco, first isolated in 1828 by Posselt and Reimann, is a volatile, highly poisonous alkaloid termed _Nicotine_, C₁₀H₁₄N₂. It is easily extracted from tobacco by means of alcohol or water, as a malate, from which the alkaloid can be separated by shaking it with caustic lye and ether. The ether is then expelled by warming the liquid, which finally has to be mixed with slaked lime and distilled in a stream of hydrogen, when the nicotine begins to come over at about 200° C.

[1712] _Instruction sur l’herbe Petum ditte en France l’herbe de la Royne ou Médicée_ ... Paris, 1572.

[1713] 12 Car. II. c. 34; 15 Car. II. c. 7.—For further information on the history of tobacco, see Tiedemann, _Geschichte des Tabaks_, Frankfurt, 1854.—We have not consulted Fairholt, _Tobacco, its History_, Lond. 1859.

[1714] Microscopic structure of tobacco leaves. See Pocklington, _Pharm. Journal_, v. (1874) 301.

Nicotine is a colourless oily liquid, of sp. gr. 1·027 at 15° C., deviating the plane of polarization to the left; it boils at 247° and does not concrete even at -10° C. It has a strongly alkaline reaction, an unpleasant odour, and a burning taste. It quickly assumes a brown colour on exposure to air and light; and appears even to undergo an alteration by repeated distillation in an atmosphere deprived of oxygen. Nicotine dissolves in water, but separates on addition of caustic potash; it occurs in the dried leaves to the extent of about 6 per cent., but is subject to great variation. The seeds of tobacco are stated by Kosutany[1715] as grown in Hungary to contain from 0·28 to 0·67 per cent. of the alkaloid.

It has not been met with in tobacco-smoke by Vohl and Eulenberg (1871), though other chemists assert its occurrence. The vapours were found by the former to contain numerous basic substances of the picolinic series, and ceded to caustic potash, hydrocyanic acid,[1716] sulphuretted hydrogen, several volatile fatty acids, phenol and creasote. There was further observed in the imperfect combustion of tobacco the formation of laminæ fusible at 94° C., and having a composition C₁₉H₁₈. Oxide of carbon is also largely met with.

Tobacco leaves, whether fresh or dried, yield when distilled with water a turbid distillate in which, as observed by Hermbstädt in 1823, there are formed, after some days, crystals of _Nicotianin_ or _Tobacco Camphor_. According to J. A. Barral, nicotianin contains 7·12 per cent. of nitrogen (?). By submitting 4 kilogrammes of good tobacco of the previous year to distillation with much water, we obtained nicotianin, floating on the surface of the distillate, in the form of minute acicular crystals, which we found to be devoid of action on polarized light. The crystals have no peculiar taste, at least in the small quantity we tried; they have a tobacco-like smell, perhaps simply due to the water adhering to them. When an attempt was made to separate them by a filter, they entirely disappeared, being probably dissolved by an accompanying trace of essential oil. The clear water showed an alkaline reaction partly due to _nicotine_; this was proved by adding a solution of tannic acid, which caused a well-marked turbidity. Nicotianine is in our opinion a fatty acid contaminated with a little volatile oil as in the case of Capsicum (see page 454), or Iris (see article Rhizome Iridis).

Among the ordinary constituents of leaves, tobacco contains albumin, resin and gum. In smoking, these substances, as well as the cellulose of the thick midrib, would yield products not agreeable to the consumer. The manufacturer therefore discards the midrib, and endeavours by further preparation to ensure at least the partial destruction of these unwelcome constituents, as well as the formation of certain products of fermentation (ferment-oils), which may perhaps contribute to the aroma of tobacco, especially when saccharine substances, liquorice, or alcohol, are added in the maceration to which tobacco is subjected.

Tobacco leaves are remarkably rich in inorganic constituents, the proportion varying from 16 to 27 per cent. According to Boussingault, they contain when dry about 1 per cent. of phosphoric acid, and from 3 to 5 per cent. of potash, together with 2½ to 4½ per cent. of nitrogen

## partly in the form of nitrate, so that to enable the tobacco plant to

flourish, it must have a rich soil or continual manuring.[1717]

[1715] Dragendorff’s _Jahresbericht_, 1874. 98.

[1716] Poggiale and Marty (1870) stated hydrocyanic acid to be absent.

[1717] For further particulars on the chemistry of tobacco cultivation see Boussingault, _Ann. de Chim. et de Phys._ ix. (1866) 50.

The lime, amounting to between a quarter and a half of the entire quantity of ash, is in the leaf combined with organic acids, especially malic, perhaps also citric. The proportion of potash varies greatly, but may amount to about 30 per cent. of the ash.

=Commerce=—There were imported into the United Kingdom in the year 1872, 45,549,700 lb. of unmanufactured tobacco, rather more than half of which was derived from the United States of America. The total value of the commodity thus imported was £1,563,382; and the duty levied upon the quantity retained for home consumption amounted to £6,694,037. In 1876 the consumption of tobacco had increased to 47,000,000 lb., _i.e._ 1½ lb. per head of the population.

In the United States 559,049 acres of land being in 1875 under cultivation with tobacco yielded a crop of 367,000,000 lb.

=Uses=—Tobacco has some reputation in the removal of alvine obstructions, but it is a medicine of great potency and is very rarely used.

=Substitutes=—Of the other species of _Nicotiana_ cultivated as _Tobacco_, _N. rustica_ L. is probably the most extensively grown. It is easily distinguished by its greenish yellow flowers, and its stalked ovate leaves. In spite of their coarser texture, the leaves dry more easily than those of _N. Tabacum_, and with some care may even be made to retain their green colour. _N. rustica_ furnishes _East Indian Tobacco_, also the kinds known as _Latakia_ and _Turkish Tobacco_.

_N. persica_ Lindl. yields the tobacco of Shiraz. _N. quadrivalvis_ Pursh, _N. multivalvis_ Lindl. and _N. repanda_ Willd. are also cultivated plants, the last named, a plant of Havana, being used in the manufacture of a much valued kind of cigar.

SCROPHULARIACEÆ.

FOLIA DIGITALIS.

_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.

ACANTHACEÆ.

HERBA ANDROGRAPHIDIS.

_Kariyát or Creyat._

=Botanical Origin=—_Andrographis[1727] paniculata_ Nees ab E. (_Justicia Burm._), an annual herb, 1 to 2 feet high, common throughout India, growing under the shade of trees. It is found likewise in Ceylon and Java, and has been introduced into the West Indies. In some districts of India it is cultivated.

[1727] _Andrographis_ from δνὴρ and γραϕὶς, in allusion to the brush-like anther and filament.—Fig. in Bentley and Trimen’s _Med. Plants_,