part 15

(1876).

[1376] Purchas, _His Pilgrimes_, Lond. iv. (1625),—a treatise of Brasill, written by a Portugall which had long lived there, p. 1311.

Piso and Marcgraf[1377] in their scientific exploration of Brazil met with two kinds of ipecacuanha; the one provided with a brown root is Cephaëlis Ipecacuanha, which they figured. The root of the other variety, which they called _Ipecacuanha blanca_, is that of Richardsonia scabra (see page 376 below). Piso and Marcgraf described the virtues of these roots, apparently supposing them to be much the same as to their action. Although in common use in Brazil, ipecacuanha was not employed in Europe prior to the year 1672. At that date, a traveller named Legras brought from South America a quantity of the root to Paris, some of which came into the possession of the “maître appoticaire” Claquenelle.[1378] It would appear that the root was prescribed from the latter by Legras (said to have been himself acquainted with the practice of medicine[1379]), and also by Jean Adrien Helvetius, a young Dutch physician, then living in Paris. Yet no success at first was obtained, the drug being administered in too large doses. In 1680, a merchant of Paris named Garnier became possessed of 150 lb. of ipecacuanha, the valuable properties of which in dysentery he vaunted to his medical attendant Afforty, and to Helvetius. Garnier on his convalescence[1380] made a present of some of the new drug to Afforty, who attached to it but little importance. Helvetius, on the other hand, was induced to prescribe the root in cases of dysentery, which he did with the utmost success. It is stated by Eloy that Helvetius even caused placards to be affixed to the corners of the streets (about the year 1686), announcing his successful treatment with the new drug, supplies of which he obtained through Garnier from Spain, and sold as a secret medicine. The fame of the cures effected by Helvetius reached the French Court, and caused some trials of the drug to be made at the Hôtel Dieu. These having been fully successful, Louis XIV. accorded to Helvetius the sole right of vending his remedy.[1381] Subsequently several great personages, including the Dauphin of France, having experienced its benefit, the king consulted his physician, Antoine d’Aquin, and the well-known Jesuit Père François de Lachaise, who had become the King’s confessor in 1675. Through them was chiefly negotiated the purchase from Helvetius of his secret, for 1000 louis d’or, and made public in 1688. The right of Helvetius to this payment was disputed in law by Garnier, but maintained by a decision of the Châtelet of Paris.[1382]

The botanical source of ipecacuanha was the subject of much dispute until finally settled by Antonio Bernardino Gomez, a physician of the Portuguese navy, who brought authentic specimens from Brazil to Lisbon in the year 1800.[1383]

[1377] _Hist. nat. Brasil._ 1648. Piso, p. 101, Marcgraf, p. 17.

[1378] Pomet, _Histoire générale des Drogues_, i. (1694) 47.

[1379] Mérat and De Lens, _Dict. de Mat. Méd._ iii. (1831) 644, call Legras a physician, and say that Garnier brought himself the 150 lb. from abroad.

[1380] Eloy, _Histoire générale de la Médecine_. Mons. ii. (1778) 485, mentions a _sick druggist_, who presented Helvetius with the ipecacuanha. Garnier, according to Eloy, was a “Marchand chapelier.”—Leibnitz, in _Ephemerid. Academ. Cæsareo-Leopold_, 1696, Appendix, p. 6, miscalled the merchant Grenier.

[1381] An abstract of the royal patent is given by Leibnitz, _l. c._ 20 (date not added).

[1382] On the history of ipecacuanha, consult also Sprengel, _Geschichte der Arzneykunde_, iv. (1827) 542.—We have not seen the pamphlet quoted by Haller, _Bibl. bot._ ii. 17: Helvetius, _Usage de l’Hipecacoanha_. 4° (no date).

[1383] _Trans. of Linn. Soc._ vi. (1801) 137.

=Collection=[1384]—The ipecacuanha plant, _Poaya_ of the Brazilians, grows in valleys, yet prefers spots which are rather too much raised to be inundated or swampy. Here it is found under the thick shade of ancient trees growing mostly in clumps. In collecting the root, the _poayero_, for so the collector of _poaya_ is called, grasps in one handful if he can, all the stems of a clump, pushing under it obliquely into the soil a pointed stick to which he gives a see-saw motion. A lump of earth enclosing the roots is thus raised; and, if the operation has been well performed, those of the whole clump are got up almost unbroken. The _poayero_ shakes off adhering soil, places the roots in a large bag which he carries with him, and goes on to seek other clumps. A good collector may thus get as much as 30 lb. of roots in the day; but generally a daily gathering does not exceed 10 or 12 lb., and there are many who scarcely get 6 or 8 lb. In the rainy season, the ground being lighter, the roots are removed more easily than in dry weather. The _poayeros_, who work in a sort of partnership, assemble in the evening, unite their gatherings, which having been weighed, are spread out to dig. Rapid drying is advantageous; the root is therefore exposed to sunshine as much as possible, and if the weather is favourable, it becomes dry in two or three days. But it has always to be placed under cover at night on account of the dew. When quite dry, it is broken into fragments, and shaken in a sieve in order to separate adherent sand and earth, and finally it is packed in bales for transport.

The harvest goes on all the year round, but is relaxed a little during the rains, on account of the difficulty of drying the produce. As fragments of the root grow most readily, complete extirpation of the plant in any one locality does not seem probable. The more intelligent _poayeros_ of Matto Grosso are indeed wise enough intentionally to leave small bits of root in the place whence a clump has been dug, and even to close over the opening in the soil.

=Cultivation=—The importance in India of ipecacuanha as a remedy for dysentery, and the increasing costliness of the drug,[1385] have occasioned active measures to be taken for attempting its cultivation in that country. Though known for several years as a denizen of botanical gardens, the ipecacuanha plant has always been rare, owing to its slow growth and the difficulty attending its propagation.

It was discovered in 1869 by McNab, curator of the Botanical Garden of Edinburgh, that if the annulated part of the root of a growing ipecacuanha plant be cut into short pieces even only ¹/₁₆ of an inch thick, and placed in suitable soil, each piece will throw out a leaf-bud and become a separate plant. Lindsay, a gardener of the same establishment, further proved that the petiole of the leaf is capable of producing roots and buds, a discovery which has been utilized in the propagation of the plant at the Rungbi Cinchona plantation in Sikkim.

[1384] Abstracted from the interesting eye-witness account of Weddell, _l. c._

[1385] The following are the average prices at which the drug was purchased wholesale, in London during three periods of ten years each:—

10 years ending 1850, average price 2_s._ 9½_d._ per lb. 10 ” 1860, ” 6_s._ 11½_d._ ” 10 ” 1870, ” 8_s._ 8¼_ d._ ”

In 1871, well-formed fruits were obtained from the ipecacuanha plants growing in the Edinburgh Botanical Garden: this was promoted by artificial fertilization, especially when the flowers of a plant producing _long styles_ were fertilized with the pollen of one having _short_ styles,—for _Cephaëlis_ like _Cinchona_ has dimorphic flowers.

With regard to the acclimatization of the plant in India, much difficulty has been encountered, and successful results are still problematical. The first plant was taken to Calcutta by Dr. King in 1866, and by 1868 had been increased to nine; but in 1870-71, it was reported that, notwithstanding every care, the plants could not be made to thrive. Three plants which had been sent to the Rungbi plantation in 1868, grew rather better; and by adopting the method of root propagation, they were increased by August 1871, to 300. Three consignments of plants, numbering in all 370, were received from Scotland in 1871-72, besides a smaller number from the Royal Gardens, Kew. From these various collections, the propagation has been so extensive, that on 31 March 1873, there were 6,719 young plants in Sikkim, in addition to about 500 in Calcutta, and much more in 1874.

The ipecacuanha plant in India has been tried under a variety of conditions as regards sun and shade, but thus far with only a moderate amount of success. The best results are those that have been obtained at Rungbi, 3000 feet above the sea, where the plants, placed in glazed frames, were reported in May 1873 as in the most healthy condition.[1386]

=Description=—The stem creeps a little below the surface of the soil, emitting a small number of slightly branching contorted roots, a few inches long. These roots when young are very slender and thread-like, but grow gradually knotty and become by degrees invested with a very thick bark, transversely corrugated or ringed. Close examination of the dry root shows that the bark is raised in narrow warty ridges, which sometimes run entirely round the root, sometimes encircle only half its circumference. The whole surface is moreover minutely wrinkled longitudinally. The rings or corrugations of a full sized root number about 20 in an inch; not unfrequently they are deep enough to penetrate to the wood.

The root attains a maximum diameter of about ²/₁₀ of an inch; but as imported, a large proportion of it is much smaller. The woody central

## part is scarcely ¹/₂₀ of an inch in diameter, subcylindrical, sometimes

striated, and devoid of pith.

Ipecacuanha is of a dusky grey hue, occasionally of a dull ferruginous brown. The root is hard, breaks short and granular (not fibrous), exhibiting a resinous, waxy, or farinaceous interior, white or greyish. The bark, which constitutes 75 to 80 per cent. of the entire root, may be easily separated from the less brittle wood. It has a bitterish taste and faint, musty smell; when freshly dried it is probably much more odorous. The wood is almost tasteless. In the drug of commerce the roots are always much broken, and there is often a considerable separation of bark from wood; portions of the non-annulated, woody, subterraneous stem are always present.

[1386] _Annual Report of the Royal Botanical Gardens_, Calcutta, 31 May 1873—from which we have abstracted many of the foregoing particulars. The report for 1876-1877 is by no means favourable to the prospects of Cephaëlis in India.

During the last few years there has been imported into London a variety of ipecacuanha, distinguished as _Carthagena_ or _New Granada Ipecacuanha_, and differing from the Brazilian drug chiefly in being of larger size. Thus, while the maximum diameter of the annulated roots of Brazilian ipecacuanha is about ²/₁₀ of an inch, corresponding roots of the New Granada variety attain nearly ³/₁₀. The latter, moreover, has a distinct radiate arrangement of the wood, due to a greater developement of the medullary rays, and is rather less conspicuously annulated. Lefort (1869) has shown that the New Granada drug is a little less rich in emetine than the ipecacuanha of Brazil.

Mr. R. B. White, of Medellin in the valley of the Cauca, New Granada, near which place the drug has been collected, has been good enough to send us herbarium specimens of the plant with roots attached; they agree entirely with _Cephaëlis Ipecacuanha_.

=Microscopic Structure=—The root is coated with a thin layer of brown cork-cells; the interior cortical tissue is made up of a uniform parenchyme, in which medullary rays cannot be distinguished. In the woody column they are obvious; the prevailing tissue consists of short pitted vessels. The cortical parenchyme and the medullary rays are loaded with small starch granules. Some cells of the interior part of the bark contain however only bundles of acicular crystals of oxalate of calcium.

=Chemical Composition=—The peculiar principles of ipecacuanha are _Emetine_ and _Ipecacuanhic Acid_, together with a minute proportion of a fœtid volatile oil. The activity of the drug appears to be due solely to the alkaloid, which taken internally is a potent emetic.

Emetine, discovered in 1817 by Pelletier and Magendie, is a bitter substance with distinct alkaline reaction, amorphous in the free state as well as in most of its salts; we have succeeded in preparing a crystallized hydrochlorate.

The root yields of the alkaloid less than 1 per cent.; the numerous higher estimates that have been given relate to impure emetine, or have been arrived at by some defective methods of analysis.[1387]

[1387] See the results obtained by Richard and Barruel, by Magendie and Pelletier, and by Attfield, as recorded by the last named chemist in _Proceedings of the British Pharmaceutical Conference_ for 1869. 37-39.

The formula assigned to emetine by Reich (1863) was C₂₀H₃₀N₂O, that given by Glénard (1875) C₁₅H₂₂NO₂, and lastly that found in 1877 by Lefort and F. Würtz, C₂₈H₄₀N₂O₅.

The alkaloid may be obtained by drying the powdered bark of the root with a little milk of lime, and exhausting the mixture with boiling chloroform, petroleum-benzin or ether. It is a white powder turning brown on exposure to light and softening at 70° C. Emetine assumes an intense and permanent yellow colour with solution of chlorinated lime and a little acetic acid, as shown by Power (1877). A solution containing but ¹/₆₀₀₀ of emetine still displays that reaction. We found the alkaloid to be destitute of rotatory power, at least in the chloroform solution.

The above reactions may be easily shown thus:—Take 10 grains of powdered ipecacuanha, and mix them with 3 grains of quicklime and a few drops of water. Dry the mixture in the water bath and transfer it to a vial containing 2 fluid drachms of chloroform: agitate frequently, then filter into a capsule containing a minute quantity of acetic acid, and allow the chloroform to evaporate. Two drops of water now added will afford a nearly colourless solution of emetine, which, placed in a watch-glass, will readily give amorphous precipitates upon addition of a saturated solution of nitrate of potassium, or of tannic acid, or of a solution of mercuric iodide in iodide of potassium. To the nitrate Power’s test may be further applied.

If the _wood_ separated as exactly as possible from the bark is used, and the experiment performed in the same way, the solution will reveal only traces of emetine. By addition of nitrate of potassium, no precipitate is then produced, but tannic acid or the potassico-mercuric iodate afford a slight turbidity. This experiment confirms the observation that the bark is the seat of the alkaloid, as might indeed be inferred from the fact that the wood is nearly tasteless.

_Ipecacuanhic Acid_, regarded by Pelletier as gallic acid, but recognised in 1850 as a peculiar substance by Willigk,[1388] is reddish-brown, amorphous, bitter, and very hygroscopic. It is related to caffetannic and kinic acids; Reich has shown it to be a glucoside.

Ipecacuanha contains also, according to Reich, small proportions of resin, fat, albumin, and fermentable and crystallizable sugar; also gum and a large quantity of pectin. The bark yielded about 30 per cent., and the wood more than 7 per cent. of starch.

=Commerce=—The imports of ipecacuanha into the United Kingdom in 1870 amounted to 62,952 lb., valued at £16,639.[1389]

=Uses=—Ipecacuanha is given as an emetic, but much more often in small doses as an expectorant and diaphoretic. In India it has proved of late a most important remedy for dysentery. Since the year 1858 when the administration of ipecacuanha in large (30 grains) doses began to be adopted, the mortality in the cases treated for this complaint has greatly diminished.[1390]

=Adulteration and Substitutes=—It can hardly be said that ipecacuanha as at present imported is ever adulterated. Although it may contain an undue proportion of the woody stems of the plant, it is not fraudulently admixed with other roots. But it very often arrives much deteriorated by damp: we have the authority of an experienced druggist for saying that at least three packages out of every four offered in the London drug sales, have either been damaged by sea-water or by damp during their transit to the coast.

Several roots have been described as _False Ipecacuanha_, but we know not one that would not be readily distinguished at first sight by any druggist of average knowledge and experience.

In Brazil the word _Poaya_ is applied to emetic roots of plants of at least six genera, belonging to the orders _Rubiaceæ_, _Violarieæ_, and _Polygaleæ_; while in the same country, the name _Ipecacuanha_ is used for various species of _Ionidium_[1391] as well as for _Cephaëlis_.

[1388] Gmelin, _Chemistry_, xv. (1862) 523.

[1389] _Annual Statement of the Trade and Navigation of the U.K. for 1870._—The more recent issues of this return have been simplified to such an extent that drugs are for the greater part included under one head.

[1390] In the Madras Presidency, the death-rate from dysentery was 71 per 1000 cases treated: under the new method of treatment, it has been reduced to 13·5. In Bengal it has fallen from 88·2 to 28·8 per 1000.—_Supplement to the Gazette of India_, January 23, 1869.

[1391] As _Ionidium Ipecacuanha_ Vent., _I. Poaya_ St. Hil., _I. parviflorum_ Vent., the first of which affords the _Poaya branca_ or _White Ipecacuanha_ of the Brazilians.—See C.F.P. von Martius, _Specimen Mat. Med. Bras._ 1824; A. de St. Hilaire, _Plantes usuelles des Brésiliens_, 1827-28.

Some of these roots, which are occasionally brought to Europe under the notion that they may find a market, have been described and figured by pharmacologists. We shall notice only the following:—

1. _Large Striated Ipecacuanha_—This is the root of _Psychotria emetica_ Mutis (_Rubiaceæ_), a native of New Granada. It is considerably stouter than true ipecacuanha, but consists like the latter of a woody column covered with a thick brownish bark. The latter, though marked here and there with constrictions and fissures, is not annulated like ipecacuanha, but has very evident longitudinal furrows. But its most remarkable character is that it remains _soft and moist, tough to the knife_, even after many years; and the cut surface has a dull violet hue. The root has a sweetish taste and abounds in sugar;[1392] its decoction is not rendered blue by iodine, nor is any starch to be detected by means of the microscope. The drug occasionally appears in the London market.

2. _Small Striated Ipecacuanha_—This drug in outward appearance closely resembles the preceding, but is usually of smaller size, sometimes much smaller and in short pieces tapering towards either end. It also differs in being brittle, abounding in starch, and having its woody column provided with numerous pores, easily visible under a lens. Prof. Planchon[1393] of Paris, who has particularly examined both varieties of Striated Ipecacuanha, is of opinion that the drug under notice may be derived from some species of _Richardsonia_.

3. _Undulated Ipecacuanha_—The root thus called is that of _Richardia scabra_ L. (_Richardsonia scabra_ St. Hilaire), a plant of the same order as _Cephaëlis_, very common in Brazil, where it grows in cultivated ground and sandy places, or by roadsides, and even in the less frequented streets of Rio de Janeiro. Authentic specimens have been forwarded to us by Mr. Glaziou of Rio de Janeiro, and Mr. J. Correa de Méllo of Campinas; and we have also had ample supplies of the plant cultivated by us near London and at Strassburg, where Richardsonia succeeds in the open air.

The root in the fresh state is pure white, but by drying becomes of a deep iron-grey. In the Brazilian specimens, there is a short crown emitting as many as a dozen prostrate stems; below this there is generally, as in true ipecacuanha, a naked woody portion, which extends downwards into a thicker root, ²/₁₀ of an inch in diameter, and six or more inches long. This part of the root is marked by deep fissures on alternate sides, which give it a knotty, sinuous, or undulating outline. It has a brittle, very thick bark, white and farinaceous within, surrounding a strong flexible slender woody column. The root has an earthy odour not altogether unlike that of ipecacuanha, and a slightly sweet taste. It affords no evidence of emetine when tested in the manners described at p. 374, and can therefore easily be distinguished from the true drug.

[1392] Attfield in _Pharm. Journ._ xi. (1870) 140.

[1393] _Journ. de Pharm._ xvi. (1872) 405: xvii. 19.

VALERIANACEÆ.

RADIX VALERIANÆ.

_Valerian Root_; F. _Racine de Valériane_; G. _Baldrianwurzel_.

=Botanical Origin=—_Valeriana officinalis_ L., an herbaceous perennial plant, growing throughout Europe from Spain to Iceland, the North Cape and the Crimea, and extending over Northern Asia to the coasts of Manchuria. The plant is found in plains and uplands, ascending even in Sweden to 1200 feet above the sea-level.

In England, valerian is cultivated in many villages[1394] near Chesterfield in Derbyshire, the wild plant which occurs in the neighbourhood not being sufficiently plentiful to supply the demand.

In Vermont, New Hampshire and New York, as well as in Holland, the plant is grown to some extent, but by far the largest supply would appear to be grown in the environs of the German town Cölleda, not far from Leipzig.

Valerian is propagated by separating the young plants which are developed at the end of runners emitted from the rootstock.

The wild plant, according to the situation it inhabits, exhibits several divergent forms. Among eight or more varieties noticed by botanists,[1395] we may especially distinguish α. _major_ with a comparatively tall stem and all the leaves toothed, β. _minor_ (_V. angustifolia_ Tausch) with entire or slightly dentate leaves, and also _V. sambucifolia_ Mikan, having only 4 or 5 pairs of leaflets.

=History=—The plant which the Greeks and Romans called Φοῦ or _Phu_, and which Dioscorides and Pliny describe as a sort of wild nard, is usually held to be some species of valerian.[1396]

The word _Valeriana_ is not found in the classical authors. We first meet with it in the 9th or 10th century, at which period and for long afterwards, it was used as synonymous with _Phu_ or _Fu_.

Thus in the writings of Isaac Judæus[1397] occurs the following:—“_Fu id est valeriana, melior rubea et tenuis et quæ venit de Armenia et est diversa in sua complexione_....”

Constantinus Africanus[1398]—“_Fu, id est valeriana. Naturam habet sicut spica nardi_....”

The word _Valeriane_ occurs in the recipes of the Anglo-Saxon leeches written as early as the 11th century.[1399] _Valeriana_, _Amantilla_ and _Fu_ are used as synonymous in the _Alphita_, a mediæval vocabulary of the school of Salernum.[1400]

Saladinus[1401] of Ascoli directs (_circa_ A.D. 1450) the collection in the month of August of “_radices fu id est valerianæ_.”

[1394] Namely Ashover, Woolley Moor, Morton, Stretton, Higham, Shirland, Pilsley, North and South Wingfield, and Brackenfield. From the produce of these villages, one wholesale dealer in Chesterfield obtained in 1872 about 6 tons (13,440 lb.) of root.

[1395] Regel, _Tentamen Floræ Ussuriensis_, 1862 (_Mém. de l’Académie de St. Pétersbourg_).

[1396] _V. officinalis_ L. and nine other species occur in Asia Minor (Tehihatcheff).

[1397] _Opera Omnia_, Lugd. 1515, cap. 45.—It must be remembered that this is a translation from the Arabic. How the word in question stands in the original we have no means of knowing.

[1398] _De omnibus medico cognitu necessariis_, Basil. 1539. 348.

[1399] _Leechdoms, Wortcunning and Starcraft of early England_, iii. (1866) 6. 136.

[1400] S. de Renzi, _Collectio Salernitana_, iii. (1854) 271-322.

[1401] _Compendium Aromatariorum_, Bonon. 1488.

Valerian was anciently called in English _Setwall_, a name properly applied to _Zedoary_; and the root was so much valued for its medicinal virtues, that as Gerarde[1402] (1567) remarks, the poorer classes in the north of England esteemed “_no broths, pottage, or physicall meats_” to be worth anything without it. Its odour, now considered intolerable, was not so regarded in the 16th century, when it was absolutely the custom to lay the root among clothes as a perfume[1403] in the same way as those of _Valeriana celtica_ L. and the Himalayan valerians are still used in the East.

Some of the names applied to valerian in Northern and Central Europe are remarkable. Thus in Scandinavia we find _Velandsrot_, _Velamsrot_, _Vandelrot_ (Swedish); _Vendelród_, _Venderód_, _Vendingsród_ (Norwegian); and _Velandsurt_ (Danish)—names all signifying _Vandels’ root_.[1404] Valerian is also called in Danish _Danmarks græs_. Among the German-speaking population of Switzerland, a similar word to the last, namely _Tannmark_, is applied to valerian. The _Denemarcha_ mentioned by St. Hildegard,[1405] about A.D. 1160, is the same. These names seem to point to some connexion with Northern Europe which we are wholly unable to explain.

Pentz, a pharmaceutical assistant at Pyrmont, was the first, in 1829, to draw attention to the acid reaction of the distilled water of valerian. Another German assistant, Grote, at Verden, showed in 1831 that the acidity was by no means due to acetic acid, but to a peculiar kind of acid. The latter was identified in 1843 by Dumas with the acid artificially obtained from amylic alcohol and that extracted in 1817 by Chevreul from the fat of dolphins.

=Description=—The valerian root of the shops consists of an upright rhizome of the thickness of the little finger, emitting a few short horizontal branches, besides numerous slender rootlets.[1406] The rhizome is naturally very short, and is rendered still more so by the practice of cutting it in order to facilitate drying. The rootlets, which are generally 3 to 4 inches long, attain ⅒ of an inch in diameter, tapering and dividing into slender fibres towards their extremities. They are shrivelled, very brittle, and, as well as the rhizome, of a dull, earthy brown. When broken transversely, they display a dark epidermis, forming part of a thick white bark which surrounds a slender woody column. The interior of the rhizome is compact, firm and horny, but when old becomes hollow, a portion of the tissue remaining however in the form of transverse septa.

The drug has a peculiar, somewhat terebinthinous and camphor-like odour, and a bitterish, aromatic taste. The root when just taken from the ground has no distinctive smell, but acquires its characteristic odour as it dries.

=Microscopic Structure=[1407]—In the rhizome as well as in the rootlets, the cortical part is separated from the central column by a dark cambial zone; the medullary rays are not distinctly obvious. In old rootstocks, sclerenchymatous cells are met with in the cortical tissue.

[1402] _Herball_, 1636. 1078.

[1403] Turner’s _Herball_,