Pharmacographia / A history of the principal drugs of vegetable origin, met with in Great Britain and British India

CORTEX ANGOSTURÆ.

Botanical Origin—Galipea Cusparia St. Hilaire (G. officinalis Hancock, Bonplandia trifoliata Willd., Cusparia trifoliata Engler 1874, Flora Brasil. 113), a small tree, 12 to 15 feet high, with a trunk 3 to 5 inches in diameter, growing in abundance on the mountains of San Joaquin de Caroni in Venezuela, between 7° and 8° N. lat., also according to Bonpland[419] near Cumana. According to Hancock,[420] who was well acquainted with the tree, it is also found in the Missions of Tumeremo, Uri, Alta Gracia, and Cupapui, districts lying eastward of the Caroni and near its junction with the Orinoko. The bark is brought into commerce by way of Trinidad.

History—Angostura Bark is said to have been used in Madrid by Mutis as early as 1759[421] (the year before he left Spain for South America,) but it was certainly unknown to the rest of Europe until much later. Its real introducer was Brande, apothecary to Queen Charlotte, and father of the distinguished chemist of the same name, who drew attention to some parcels of the bark imported into England in 1788.[422] In the same year a quantity was sent to a London drug firm by Dr. Ewer of Trinidad, who describes it[423] as brought to that island from Angostura by the Spaniards. The drug continued to arrive in Europe either by way of Spain or England, and its use was gradually diffused. In South America it is known as Quina de Caroni and Cascarilla del Angostura.

Description—The bark occurs in flattish or channelled pieces, or in quills rarely as much as 6 inches in length and mostly shorter. The flatter pieces are an inch or more in width and ⅛ of an inch in thickness. The outer side of the bark is coated with a yellowish-grey corky layer, often soft enough to be removeable with the nail, and then displaying a dark brown, resinous under surface. The inner side is light brown with a rough, slightly exfoliating surface indicating close adhesion to the wood, strips of which are occasionally found attached to it; the obliquely cut edge also shows that it is not very easily detached. The bark has a short, resinous fracture, and displays on its transverse edge sharply defined white points, due to deposite of oxalate of calcium. It has a bitter taste and a nauseous musty odour.

Microscopic Structure—The most striking peculiarity is the great number of oil-cells scattered through the tissue of the bark. They are not much larger than the neighbouring parenchymatous cells, and are loaded with yellowish essential oil or small granules of resin. Numerous other cells contain bundles of needle-shaped crystals of oxalate of calcium or small starch granules. The liber exhibits bundles of yellow fibres, to which the foliaceous fracture of the inner bark is due. The structure of the bark under notice has been very minutely described and figured by Oberlin and Schlagdenhauffen.[424]

Chemical Composition—Angostura bark owes its peculiar odour to an essential oil which it was found by Herzog[425] to yield to the extent of ¾ per cent. It is probably a mixture of a hydrocarbon (C₁₀H₁₆) with an oxygenated oil. Its boiling point is 266° C. Oberlin and Schlagdenhauffen obtained 0·19 per cent. of the oil, and found it to be slightly dextrogyre; it assumes a fine red colour when shaken with aqueous ferric chloride, and turns yellow with concentrated sulphuric acid.

The bitter taste of the bark is attributed to a substance pointed out in 1833 by Saladin and named Cusparin. It is said to be crystalline, neutral, melting at 45° C., soluble in alcohol, sparingly in water, precipitable by tannic acid. The bark is stated to yield it to the extent of 1·3 per cent. Herzog endeavoured to prepare it but without success, nor have Oberlin and Schlagdenhauffen met with it. The latter chemists, on the other hand, isolated an alkaloid Angosturine C₁₀H₄₀NO₁₄. It is in thin prisms, melting at 85° and yielding a crystallized chlorhydrate or sulphate. Angosturine turns red when touched with concentrated sulphuric acid, or green if nitric acid or iodic acid, or other oxydizing substances, have been previously mixed with the sulphuric acid. The alcoholic solution of the alkaloid is of decidedly alkaline reaction. A cold aqueous infusion of angostura bark yields an abundant red-brown precipitate with ferric chloride. Thin slices of the bark are not coloured by solution of ferrous sulphate, so that tannin appears to be absent.

Uses—Angostura bark is a valuable tonic in dyspepsia, dysentery and chronic diarrhœa, but is falling into disuse.

Adulteration—About the year 1804, a quantity of a bark which proved to be that of Strychnos Nux Vomica reached Europe from India, and was mistaken for Cusparia. The error occasioned great alarm and some accidents, and the use of angostura was in some countries even prohibited. The means of distinguishing the two barks (which are not likely to be again confounded) are amply contained in the above-given descriptions and tests, and at length pointed out by Oberlin and Schlagdenhauffen. They also described the bark of Esenbeckia febrifuga Martius (Evodia febrifuga Saint Hilaire), a Brazilian tree belonging to the same natural order. Maisch[426] was the first to draw attention to this “new false Angostura bark.” It is at once distinguished by being devoid of aromatic properties; its taste is purely bitter.

FOLIA BUCHU.

Botanical Origin—The Buchu leaves are afforded by three species of Barosma.[427] The latter are erect shrubs some feet in height, with glabrous rod-like branches, opposite leaves furnished with conspicuous oil-cells on the toothed margin as well as generally on the under surface. The younger twigs and several parts of the flower are also provided with oil-cells. The white flowers with 5-partite calyx, and the fruit formed of five erect carpels, are often found, together with small leafy twigs, in the drug of commerce.

The leaves of the three species referred to may be thus distinguished:—

1. Barosma crenulata Hook. (B. crenata Kunze).—Oblong, oval, or obovate, obtuse, narrowed towards the base into a distinct petiole; margin serrulate or crenulate; dimensions, ¾ to 1½ inches long, ³/₁₀ to ⁴/₁₀ of an inch wide.

2. B. serratifolia Willd.—Linear-lanceolate, equally narrowed towards either end, three-nerved, apex truncate always furnished with an oil-cell; margin sharply serrulate; 1-1½ inches long by about ²/₁₀ of an inch wide.

3. B. betulina Bartling.—Cuneate-obovate, apex recurved; margin sharply denticulate, teeth spreading; ½ to ¾ of an inch long by ³/₁₀ to ⁵/₁₀ wide. Substance of the leaf more harsh and rigid than in the preceding.

B. crenulata and B. betulina grow in the Divisions of Clanwilliam and Worcester, north and north-east of Cape Town, and the former even on Table Mountain close to the capital; B. serratifolia is found in the Division of Swellendam farther south.

History—The use of Buchu leaves was learnt from the Hottentots by the colonists of the Cape of Good Hope. The first importations of the drug were consigned to the house of Reece & Co., of London, who introduced it to the medical profession in 1821.[428] The species appears to have been B. crenulata.

Description—In addition to the characters already pointed out, we may observe that buchu leaves of either of the kinds mentioned are smooth and glabrous, of a dull yellowish-green hue, somewhat paler on the under side, on which oil-cells in considerable number are perceptible.

The leaves of B. crenulata vary in shape and size in different parcels, in some the leaves being larger and more elongated than in others, probably according to the luxuriance of the bushes in particular localities. Those of B. serratifolia and B. betulina present but little variation. Each kind is always imported by itself. Those of B. betulina are the least esteemed, and fetch a lower price than the others, yet appear to be quite as rich in essential oil.

Buchu leaves have a penetrating peculiar odour and a strongly aromatic taste.

Microscopic Structure—The essential oil is contained in large cells close beneath the epidermis of the under side of the leaf. The oil-cells are circular and surrounded by a thin layer of smaller cells; they consequently partake of the character of the oil-ducts in the aromatic roots of Umbelliferæ and Compositæ. The latter, however, are elongated.

The upper side of the leaf of Barosma exhibits an extremely interesting peculiarity[429]. There is a colourless layer of cells separating the epidermis from the green inner tissue (mesophyllum). If the leaves are examined under alcohol or almond oil the colourless layer is seen to be very narrow, and the thin walls of its cells shrunken and not clearly distinguishable. If the transverse sections are examined under water, these cells immediately swell up, and become strongly distended, giving off an abundance of mucilage, the latter being afforded by the solution of the very cell-walls. The mucilage of buchu leaves thus originates in the same way as in flax seed or quince seed, but in the former the epidermis is thrown off without alteration. We are not aware that other mucilaginous leaves possess a similar structure, at least not those of Althæa officinalis and of Sesamum which we examined[430].

Chemical Composition—The leaves of B. betulina afforded us by distillation 1·56 per cent, of volatile oil[431], which has the odour rather of peppermint than of buchu, and deviates the ray of polarized light considerably to the left. On exposure to cold it furnishes a camphor which, after re-solution in spirit of wine, crystallizes in needle-shaped forms. After repeated purification in this manner, the crystals of Barosma Camphor have an almost pure peppermint odour; they fuse at 85° C., and begin to sublime at 110° C. After fusion they again solidify only at 50° C. Submitted to elementary analysis, the crystals yielded us 74·08 per cent. of carbon and from 9 to 10 per cent. of hydrogen[432]. Barosma camphor is abundantly soluble in bisulphide of carbon.

The crude oil from which the camphor has been separated has a boiling point of about 200° C., quickly rising to 210° or even higher. That which distilled between these temperatures was treated with sodium, rectified in a current of common coal gas and submitted to elementary analysis, afforded us 77·86 per cent, of carbon and 10·58 of hydrogen. The formula C₁₀H₁₆O would require 78·94 of carbon and 10·53 of hydrogen.

Wayne’s experiments[433] appear to indicate that the oil also contains a substance capable of being converted into salicylic acid. An aqueous infusion of buchu leaves turns beautifully yellow if it is mixed with alkali.

On addition of perchloride of iron the infusion assumes a dingy brownish-green colour changing to red by an alkali. The infusion added to a concentrated solution of acetate of copper causes a yellow precipitate[434] which dissolves in caustic potash, affording a green solution. This may be due to the presence of a substance of the quercitrin or rutin class.

When the leaves are infused in warm water, the mucilage noticed under the microscope may easily be pressed out. It requires for precipitation a large amount of alcohol, being readily miscible with dilute alcohol. Neutral acetate of lead produces a yellow precipitate in an infusion of the leaves; the liquid affords a precipitate by a subsequent addition of basic acetate of lead. The latter precipitate is (probably) due to the mucilage, that afforded by neutral acetate partly to mucilage and partly, we suppose, to rutin or an allied substance. Yet the mucilage of buchu leaves is of the class which is not properly dissolved by water, but only swells up like tragacanth.

The leaves of B. crenulata afforded us upon incineration 4·7 per cent. of ash. Jones (1879) obtained on an average 4·54 per cent. from the same species; 5·27 from B. serratifolia; and 4·49 from B. betulina. He pointed out the presence of manganate in this ash.

The Diosmin of Landerer[435] is entirely unknown to us.

Commerce—The export of buchu from the Cape Colony in 1872 was 379,125 lb., about one-sixth of which quantity was shipped direct to the United States.[436]

Uses—Buchu is principally administered in disorders of the urino-genital organs. It is reputed diuretic and diaphoretic. In the Cape Colony the leaves are much employed as a popular stimulant and stomachic, infused in water, sherry, or brandy. They are also extensively used in the United States, both in regular medicine and by the vendors of secret remedies.

Substitutes—The leaves of Empleurum serrulatum Ait., a small shrub of the same order as Barosma and growing in the same localities, have been imported rather frequently of late and sold as Buchu. They have the same structure as regards mucilage, and nearly the same form as those of B. serratifolia, but are easily distinguished. They are still narrower, and often longer than those of B. serratifolia, devoid of lateral veins, and terminate in an acute point without an oil-duct. They have a bitterish taste and a less powerful odour than those of Barosma, even in fresh leaves as imported in London. The odour of Empleurum is moreover distinctly different from that of the leaves of Barosma. The flowers of Empleurum are still more distinct, for they are apetalous and reddish-brown. The fruit consisting of a single, compressed, oblong carpel, terminated by a flat-shaped horn, is quite unlike that of buchu.

The leaves of Barosma Eckloniana Berg (regarded by Sonder[437] as a form of B. crenulata) have to our knowledge been imported on one occasion (1873). They are nearly an inch long, oval, rounded at the base, strongly crenate, and grow from pubescent shoots.

We have seen other leaves which had been imported from South Africa and offered as buchu; but though probably derived from allied genera they were not to be mistaken for the genuine drug.

RADIX TODDALIÆ.

Botanical Origin—Toddalia aculeata Pers., a ramous prickly bush,[438] often climbing over the highest trees, common in the southern parts of the Indian peninsula as the Coromandel Coast, South Concans, and Canara, also found in Ceylon, Mauritius, the Indian Archipelago and Southern China.

History—The pungent aromatic properties which pervade the plant, but especially the fresh root-bark, are well known to the natives of India and have been utilized in their medical practice. They have also attracted the attention of Europeans, and the root of the plant is now recognized in the Pharmacopœia of India.

It is from this and other species of Toddalia, or from the allied genus Zanthoxylum,[439] that a drug is derived which under the name of Lopez Root had once some celebrity in Europe. This drug which was more precisely termed Radix Indica Lopeziana or Root of Juan Lopez Pigneiro, was first made known by the Italian physician Redi,[440] who described it in 1671 from specimens obtained by Pigneiro at the mouth of the river Zambesi in Eastern Africa,—the very locality in which in our times Toddalia lanceolata Lam. has been collected by Dr. Kirk.[441] It was actually introduced into European medicine by Gaubius[442] in 1771 as a remedy for diarrhœa, and acquired so much reputation that it was admitted to the Edinburgh Pharmacopœia of 1792. The root appears to have been sometimes imported from Goa, but its place of growth and botanical origin were entirely unknown, and it was always extremely rare andcostly.[443] It has long been obsolete in all countries except Holland, where until recently it was to be met with in the shops. The Pharmacopœia Neerlandica of 1851 says of it “Origo botanica perquam dubia—Patria Malacca?”

Description—The specimen of the root of Toddalia aculeata which we have examined was collected for us by Dr. G. Bidie of Madras whose statements regarding the stimulant and tonic action of the drug may be found in the Pharmacopœia of India, p. 442. It is a dense woody root in cylindrical, flexuous pieces, which have evidently been of considerable length and are from ½ to 1½ inches in diameter, covered with bark ⅒ to ¹/₁₂ of an inch in thickness. The bark has a soft, dull yellowish, suberous coat, wrinkled longitudinally, beneath which is a very thin layer of a bright yellow colour, and still lower and constituting two-thirds or more of the whole, is the firm, brown middle cortical layer and liber, which is the part chiefly possessing the characteristic pungency and bitterness of the drug. The yellow corky coat is however not devoid of bitterness. The wood is hard, of a pale yellow, and without taste and smell. The pores of the wood, which are rather large, are arranged in concentric order and traversed by numerous narrow medullary rays.

In a letter which Frappier[444] wrote to Guibourt from the island of Réunion where Toddalia aculeata is very common, he states that the roots of the plant are of enormous length (longueur incroyable) and rather difficult to get out of the basaltic rock into the fissures of which they penetrate. Mr. J. Horne of the Botanical Garden, Mauritius, has sent us a specimen of the root of this plant, the bark of which is of a dusky brown, with the suberous layer but little developed.

Microscopic Structure—We have examined the root for which we are indebted to Dr. Bidie, and may state that its cortical tissue is remarkable by the number of large cells filled with resin and essential oil; they are scattered through the whole tissue, the cork excepted. The parenchymatous cells are loaded with small starch granules or with crystals of oxalate of calcium. The vessels of younger roots abound in yellow resin.

Chemical Composition—None of the constituents of the Toddalia root of India have yet been satisfactorily examined. The bark contains an essential oil, which would be better extracted from fresh than from dry material. The tissue of the bark is but little coloured by salts of iron. In the aqueous infusion, tannic acid produces an abundant precipitate, probably of an indifferent bitter principle rather than of an alkaloid. We have been unable to detect the presence in the bark of berberine.

Lopez root was examined in Wittstein’s laboratory by Schnitzer[445] who found that the bark contains in addition to the usual substances a large proportion of resin,—a mixture probably of two or three different bodies. The essential oil afforded by the bark had an odour resembling cinnamon and melissa.

Uses—The drug has been introduced into the Pharmacopœia of India chiefly upon the recommendation of Dr. Bidie of Madras, who considers it of great value as a stimulating tonic. The bark rasped or shaved from the woody root is the only part that should be used.

FOLIA PILOCARPI.

Folia Jaborandi.

Botanical Origin—Pilocarpus pennatifolius[446] Lemaire, a slightly branched shrub, attaining about 10 feet in height. It is distributed through the eastern provinces of Brazil.

Pilocarpus Selloanus[447] Engler, occurring in Southern Brazil and Paraguay, appears to be not considerably different from P. pennatifolius.

History—Piso[448] recommended an infusion made with Ipecacuanha and Jaborandi. Plumier,[449] who also mentioned this, figured under the name of Jaborandi two plants of the order Piperaceæ. The introduction of the leaves of Pilocarpus pennatifolius into medical use is due to Dr. Coutinho of Pernambuco, 1874. The plant has been cultivated in European greenhouses since about the year 1847; we have repeatedly seen it flowering at Strassburg. Baillon in 1875 showed the fragments of Jaborandi as supplied by Coutinho to belong to P. pennatifolius, which had been described in 1852 by Lemaire. Holmes (1875) in examining the drug as imported from Pernambuco came to the same conclusion.

Description—The leaves of the species under examination are long-stalked, imparipennate, the opposite leaflets in 2 to 5, in cultivated plants most commonly in 2 pairs, the terminal one longer stalked, while the others are provided with a petiole attaining 1½ inch in length or remaining much shorter. The whole leaf is frequently 1½ feet long, the leaflets being often as much as 5 inches long by 2 inches wide. The latter are entire oblong, tapering or rounded at the base, tapering or obtuse or even emarginate at the apex. The leaflets are coriaceous, with a slightly revolute margin and a prominent midrib below. In transmitted light they show very numerous pellucid oil-glands.

The taste of the leaves of Pilocarpus is at first bitterish and aromatic; they subsequently produce a tingling sensation in the mouth and an abundant flow of saliva.

Microscopic Structure[450]—The oil-glands consist of large cells of the same structure as those occurring generally in the leaves of Rutaceæ, Aurantiaceæ, Myrtaceæ. In Pilocarpus they are largely distributed in the tissue covered on both sides of the leaf by the epidermis; the oil-cells are also abundantly met with in the petiole and in the bark of the stems and branches.

Chemical Composition—The active principle of Jaborandi is the alkaloid Pilocarpine, C₂₃H₃₅N₄O₄ + 4OH₂, discovered in 1875 by Hardy. It is an amorphous soft mass, but yielding crystallized salts, among which the hydrochlorate and the nitrate are now more frequently used than the drug itself. The leaves afford about ½ per cent. of the nitrate.

The occurrence of another peculiar alkaloid in Pilocarpus has been asserted, but not ultimately proved.

The leaves contain about ½ per cent. of essential oil, the prevailing constituent of it being a dextrogyrate terpene, C₁₀H₁₆, boiling at 178°, which forms a crystallized compound C₁₀H₁₆ + 2HCl melting at 49°·5 C.

Uses—Pilocarpine being a powerful diaphoretic and sialagogue, the leaves of Jaborandi are used to some extent in pharmaceutical preparations.

Other Kinds of Jaborandi—This name, as above stated, has originally been given to plants of the order Piperaceæ, some of which are still known in Brazil under the name Jaborandi. The following may be quoted as being used at least in that country: Serronia Jaborandi[451] Gaudichaud, Piper reticulatum L. (Enckea Miquel), Piper citrifolium Lamarck (Steffensia Kunth), Piper nodulosum Link, Artanthe mollicoma Miq.

Aubletia trifolia[452] Richard (Monniera L.) and Xanthoxylum elegans Engler, belonging to the same order as Pilocarpus itself, are also sometimes called Jaborandi.

We are not aware that other leaves than those of Pilocarpus are imported to some extent in Europe under the name of Jaborandi.