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Hydrastis (U. S. P.)—Hydrastis.

[image:12636 align=left hspace=1]Preparations: Tincture of Hydrastis - Compound Tincture of Hydrastis - Compound Infusion of Golden Seal - Extract of Hydrastis - Fluid Extract of Hydrastis - Compound Powder of Golden Seal - Glycerite of Hydrastis - Compound Lotion of Golden Seal - Lotion of Golden Seal and Aconite - Compound Wine of Golden Seal
Related entries: Berberis.—Barberry - Berberis Aquifolium.—Oregon Grape
[Golden seal (Hydrastis) is endangered. Don't use it unless you know it's cultivated, not wildcrafted. --Henriette]

"The rhizome and roots of Hydrastis canadensis, Linné"—(U. S. P).
Nat. Ord.—Ranunculaceae.
COMMON NAMES: (See below.)
ILLUSTRATIONS: Lloyd's Drugs and Med. of N. A., Pl. 8; Bentley and Trimen, Med. Plants, 1; Köhler's Med. Pflanzen, Pl. 180.

[image:12637 align=left hspace=1]Botanical Source.—This indigenous plant has a perennial root or rhizome, which is tortuous, knotty, creeping, internally of a bright-yellow color, with numerous long fibers. The stem is erect, simple, herbaceous, rounded, pubescent upward, from 6 to 12 inches in height, seeming purplish, and bearing 2 unequal terminal leaves. The leaves are 2 only, alternate, palmate, with from 3 to 5 lobes, hairy, dark-green, cordate at base, veiny, the lower leaf petiolate, the other sessile, front 4 to 9 inches wide when full-grown, and the segments serrated. The flowers solitary, terminal, small, white or rose-colored, and borne on a peduncle about 2 inches in length. The calyx consists of 3 segments small, deciduous, broadly-ovate, pale greenish-white, concave, slightly downy sepals, which fall away when the flower opens. The stamens are many, and longer than the pistils. Filaments flat, linear-lanceolate, and having the cells of an anther on their edge at the apex. Pistils several; ovary oval, glabrous and attenuated upward into a short style. Stigma obtuse and scarcely lobed. The fruit resembles a raspberry, is red, and consists of many little 2-seeded drupes collected into a globose bead, each crowned with the persistent style; the seeds are nearly black, obovate, and polished, having a minute embryo at the base of a flesh and oily albumen (L.—W.—G.).

History.—This plant is found growing in shady woods, in rich soil, and damp meadows, in different parts of the United States and Canada, but is more abundant west of the Alleghanies. From about 1847, and especially since the first appearance of the Eclectic Dispensatory of the United States (now American Dispensatory), in 1852, hydrastis has figured conspicuously among the leading Eclectic drugs, and few have been in greater esteem. This plant is well known to botanists as Yellow puccoon and Orange root. The present pharmacopoeial name, Golden seal, was introduced by the Thomsonians, who employed the root to a limited extent. It has reference both to the color of the root and to its seal-like scars produced by the death of the stalk of the plant of the preceding year. It has several other common names, some of them applicable and some being shared by other plants, one in particular, Yellow root, being the commercial drug name for Xanthorrhiza apiifolia. Some of these common names are derived from some physical characteristics of the plant; others from its therapeutic uses; while still others have reference to its resemblance to other substances. The following are some of its popular appellatives: Golden seal, Yellow puccoon, Yellow root, Orange root, Eye balm, Eye root, Ground raspberry, Indian paint, Yellow paint, Indian dye, Yellow eye, Jaundice root, Wild curcuma, Ohio curcuma, Curcuma, Golden root, Mild turmeric, and Indian turmeric. In commerce, both golden seal and yellow root are the terms employed. The other names should be dropped, and only the name of golden seal, as recognized by the Pharmacopoeia, should be retained. The scientific name Hydrastis, given it by Linnaeus, on authority of Ellis, is a misnomer, derived from old English authorities, who supposed that the plant grew in boggy places, an error which also appears in Wood's Class Book of Botany (C. G. Lloyd), whereas the plant is never found in wet or boggy situations, on prairies, or in sterile soil, but rather in rich open woodlands, preferring a hillside richly strewn with leaf mold. An attempt, which unfortunately failed, was made by Miller, in 1759, to change the name to Warneria, in honor of Richard Warner, of Woodford, Essex, England.

In our article on podophyllum, we call attention to the fact that that plant can not easily be exterminated by the advance of agriculture. With hydrastis, however, the opposite is true; the plant disappears as soon as the ground is disturbed by the settler. Once plentiful along the Ohio riverbanks, it is now found only in isolated spots, having suffered extermination as fast as the woodland yielded to the pioneer's axe. At present the geographical center of the plant is around Cincinnati. But four states now grow sufficient hydrastis to make it profitable for gathering for commercial use. These are Ohio, Indiana, Kentucky, and West Virginia. There is one redeeming feature, however, in the fact that in the mountainous parts of the states in which it grows, it is not very likely to disappear soon. These districts are inhabited by a class of individuals commonly known as "white trash," and also by negroes. They are perfectly contented to exist with the least possible exertion on their part, consequently they do not take kindly to cultivation of the soil. These virgin forests of the mountain contain an abundance of medicinal roots, among them hydrastis. While the plow exterminates it forever, simply digging the roots, as is done by these contented, happy root diggers, will never absolutely exhaust the resources of those regions. Hence, we may hope to have a moderate supply of this drug as long as these people are left to enjoy their seclusion; but it must grow scarcer each year, and, if the demand continues in medicine, increasingly more expensive.

Hydrastis is of very rapid growth, so much so that those who are searching for botanical specimens must be on the alert, as the plant, when favored by a continuance of warm weather during May, will, in a week or 10 days, send up a stem and open its blossom. This bloom is white and small, the stamens, on account of their whiteness, being the most conspicuous portion of the flower. The stem of the plant ranges from 6 inches to 1 foot in height, forking near the top, and each art of the division thus made, bears a roundish cordate leaf, each having from 5 to 7 lobes. These leaves, after the flowering periods, often become 6 or 8 inches broad, being but partly developed at the time of flowering. The lower leaf is the larger at this time, while the smaller is sessile at the base of the flower stem, enclosing the bud, and is but partially unfolded when the flower expands. A whole patch of hydrastis, for it grows in patches in rich, hilly woods, will not remain in bloom over a week. The fruit, consisting of several drupes aggregated together, known botanically as an etaerio, matures in July. It resembles somewhat a red raspberry, though larger. Each of the drupes, which are from 8 to 10 in number, contains 1 round, shining, black seed, imbedded in a white, sweetish pulp.

Description.—The rhizome of hydrastis—the part employed in medicine—does not attain a very great size, for after from 4 to 6 years growth, a gradual decay sets in at the end of the root remote from the stem. It consists of a crooked, knotty, wrinkled rootstock, 1 or 2 inches long, giving off a number of yellow fibers. The younger rhizomes are well marked on the upper surface with cup-like depressions, showing where the stems of the previous years were articulated. The cotyloid cavities become less marked as the rhizome advances in age, and it is from these seal-like depressions that the name, golden seal, is derived. Fresh hydrastis is vivid yellow, both within and without, but upon drying, becomes dull-brown. The best rhizome has a large amount of yellow juice, which, in drying may leave the interior yellow or orange-yellow, or, by aggregations of it, the central portion may assume a reddish hue. Dry hydrastis usually, however, is of a lemon-yellow color on fracture, if the root be not old. If old, it may be of a greenish-yellow hue, or even brown, the latter color. being due to the disintegration of the yellow principles. Therefore, specimens of hydrastis, showing a greenish-brown or brown color, should be rejected as being of inferior quality. The juice was used by the Indians to color their clothing, and to stain their faces. Hydrastis has a peculiar odor and a bitter taste, added to which is a persistent acridity, which causes the abundant salivary flow following the chewing of the rhizome. Hydrastis loses about two-thirds of its weight by drying. Its virtues are imparted to water, glycerin, or alcohol. The official drug is thus described: "Rhizome about 4 Cm. (1 1/2 inches) long and 6 Mm. (1/4 inch) thick; oblique, with short branches, somewhat annulate and longitudinally wrinkled; externally brownish-gray; fracture short, waxy, bright reddish-yellow, with a thickish bark, about 10 narrow wood-wedges, broad medullary rays, and large pith. Roots thin, brittle, with a thick, yellow bark and subquadrangular, woody center. Odor slight, taste bitter"—(U. S. P.).

Chemical History and Composition.—The root of hydrastis contains the usual plant constituents, starch, albuminous matter, resin, sugar, fatty matter, inorganic salts, and three alkaloids, berberine, of yellow color, and hydrastine and canadine, both of which are white.

[image:12550 align=left hspace=1]BERBERINE has received different names, according to the botanical sources in which it was discovered, and to this alkaloid the name hydrastine was first affixed. In 1824, Hüttenschmid found a yellow coloring matter in what he believed to be Geoffroya inermis, the Jamaica cabbage-tree, and gave it the name jamaicine. This substance, Wittstein (Organic Principles of Plants), accepts as berberine. In 1826, Chevallier and Pelletan found a rich yellow alkaloid in the bark of Xanthoxylum Clava Herculis (Hercules' club), which they named xanthopicrite. This was subsequently also proved identical with berberine. In 1828, C. S. Rafinesque, whose works were authority with the Eclectic fathers, stated in his Medical Flora of the United States (1828), that the constituents of Hydrastis canadensis were: "Amarin, extractive, several salts, and a peculiar principle, hydrastine, of a yellow color," taking pains to italicize the word hydrastine.

Again, in 1830, Buchner and Herberger obtained from Berberis vulgaris, a purified yellow extract, which they named berberine. In 1839, Dr. George Kemp prepared a salt of berberine and picric acid, and was the first to class berberine among the alkaloids. This name at last superseded the terms jamaicine, xanthopicrite, and Rafinesque's hydrastine, although the latter name clung to it for a long time afterward. Even to this day, the name hydrastine is frequently preferred in America owing to the priority of the appellation given by Rafinesque, and, as an act of right, due to priority, it has been insisted upon by the earlier Eclectics. Hydrastine (berberine), was not the exact substance employed by the members of our school as a medicine, but rather a salt of the above was used—a hydrochlorate of hydrastine (muriate of hydrastine), which was called hydrastine, or neutral hydrastine. It was not shown to be a salt until after Durand (1851) gave a process for making a product similar to that which had long been prepared by Eclectic pharmacists and employed medicinally by Eclectic physicians. As late as 1862, Mr. F. Mahla, of Chicago, proved this Eclectic hydrastine to be an alkaloidal salt, and showed that the base was berberine. Eclectic physicians, however, refused then to change the name of the medicinal salt, and to this day it frequently bears, the old name, hydrastine.

The demand for "concentrated medicines," or so-called "Eclectic concentrations" was the means of introducing muriate of hydrastine (hydrochlorate of berberine) into medicine. Arguing that if podophyllum yielded an active medicinal product by precipitation of its alcoholic preparations with water, the early Eclectics also thought that an active product could be thus obtained from hydrastis. Upon trial, a yellow, bitter, resinous body was obtained and put on the market as a "concentrated powder," under the name, resinoid hydrastin. It soon became evident that this resinous precipitate, or "resinoid," did not possess the medicinal qualities of the crude drug, hence a desire to further investigate led to the method of adding hydrochloric acid to the supernatant liquid after precipitation of the resinoid (which solution was shown to possess the major part of the active properties of the root), with the result of obtaining a very bitter, brilliant yellow precipitate. To distinguish it from the resinoid hydrastin, this yellow salt was called hydrastin (hydrastine) neutral, and was put on the market by three manufacturers under the following names: Muriate of hydrastin, hydrastin neutral, and hydrastine. The name hydrastin neutral being finally dropped, it entered the lists as hydrastine, muriate of hydrastine, and hydrastin, the resinoid of the latter name having gone out of market.

To recapitulate we find: (1) That the yellow alkaloid now known as berberine was the hydrastine of Rafinesque; (2) that the medicinal hydrastine of the Eclectic fathers was hydrochlorate of berberine, and was known to them as hydrastine or neutral hydrastine, or muriate of hydrastin; and still later as hydrastin; (3) that the name hydrastin originally referred to the resinous precipitate prepared by treating the alcoholic tincture with water and drying powdering the precipitate. To make matters still worse a mixture of various substances supposed to represent all the peculiar constituents and virtues of hydrastis was named "combined hydrastin." This is the only drug now known simply as hydrastin, or combined principles hydrastine. Several berberine salts have been used in medicine. For further particulars concerning the early history of berberine, see J. U. and C. G. Lloyd (D. and M. of N. A, Vol. I, p. 96.)

Berberine may be obtained by the following process, recommended by Mr. Wm. Procter, Jr.: "Take the root of Hydrastis canadensis, or of Berberis vulgaris, preferably the former, in coarse powder, exhaust it by repeated decoction or digestion in boiling water, and evaporate the filtered liquid to a soft extract. Treat this with stronger alcohol by digestion in a water-bath still, at several times until it is exhausted (or until a quart of alcohol has been employed for the extract from each pound of the root). Add to the tincture one-fourth of its bulk of water, distill off five-sixths of the alcohol, and add to the hot, watery residue an excess of diluted sulphuric acid, and allow it to cool. The sulphate of berberine crystallizes out, and if necessary, may be drained from the mother liquid, redissolved, in the smallest quantity of boiling water, and again crystallized. The sulphate of berberine thus obtained is dissolved in boiling water, and decomposed by the addition, in excess, of oxide of lead (freshly obtained by precipitation from the acetate or nitrate of lead by liquor potassa, and well washed), the solution being kept hot during the decomposition. When a drop of the hot, clear liquid will not be precipitated by baryta water or acetate of lead, the decomposition is finished. The solution should then be filtered off hot, evaporated, and set aside for crystallization" (Amer. Jour. Pharm., 1864, p. 10).

The authors of D. and M. of N. A. prefer the preparation of berberine by the decomposition of berberine sulphate with a very slight excess of baryta water. Berberine (C20H17NO4, J. Dyson Perrins, 1862) crystallizes in tufts of dark, brown-red needles, soluble in water and alcohol, and practically insoluble in sulphuric ether, chloroform, carbon disulphide, and benzol. It forms crystallizable salts with acids, such as the hydrochlorate, the nitrate, the acid and the neutral sulphate (mono- and di-berberine sulphate), etc. It also forms a crystallizable compound with acetone, called acetone berberine (C20H17NO4.C3H6O) (For the history and description of the salts see D. and M. of N. A.) The graphic formula of berberine was brought to light by W. H. Perkins. Jr., in 1890.

HYDRASTINE, the principal white alkaloid of hydrastis, must not be confused with Rafinesque's hydrastine or with the Eclectic medicine hydrastine muriate. It was discovered in 1850, by Mr. Alfred B. Durand (Amer. Jour. Pharm., Vol. XXIII, p. 13), who described it as being insoluble in water, sparingly so in cold ether and alcohol, more soluble in boiling ether, entirely soluble in chloroform and boiling alcohol, but speaks of the crystals as being of a brilliant yellow color, which was undoubtedly due to contamination with traces of berberine. Mr. J. Dyson Perrins (Pharm. Jour. Trans., May, 1862) was the first to obtain it white. Mr. F. Mahla, of Chicago, prepared it in 1863 (Amer. Jour. Pharm., Vol. XXXV, p. 433), by adding aqua ammoniae in slight excess to the mother liquor from which berberine was previously separated as hydrochlorate, by the addition of hydrochloric acid. The crude hydrastine was then purified by recrystallization from alcohol. Also, see paper by Prof. F. B. Power, on the preparation of hydrastine in Proc. Amer. Pharm. Assoc., 1884, p. 448. Hydrastine (C21H21NO6, Freund and Will, Ber. d. Deutsch. Chem. Ges., 1887, p. 88) is tasteless in the alkaline saliva; it forms salts with acids, which, however are not crystallizable. Its soluble salts are acrid, the hydrochlorate, and occasionally the citrate, being the preferred medicinal salts. Hydrastine salts in solution are decomposed by alkalies, which liberate the alkaloid as a precipitate. A fluorescent body has been found adhering to crystals of hydrastine; its effects are produced in the presence of alkalies (see D. and M. of N. A., Vol. I, p. 143). The melting point of hydrastine, according to Prof. Power, is 132° C. (269.6° F.). By reduction with nascent hydrogen, this author obtained crystallizable tetra-hydro-hydrastine. Hydrastine, when oxidized in acid media, is converted into opianic acid (C6H10O6) and hydrastinine (C11H11NO2), Freund and Will, 1888; also see E. Schmidt and Wilhelm (Archiv der Pharm., 1888, p. 353). In alkaline solution methylamine and hemipinic and nicotinic acids result. An interesting account of the chemical relationship between hydrastine and narcotine on the one hand, and berberine and papaverine on the other, is given by Dr. Alfred R. L. Dohme in the Western Druggist, 1895, p. 58. The statement made by Dr. Freund is also recorded, that hydrastine and berberine exist in the root of golden seal, most probably in the free state.

CANADINE (C20H21NO4). In 1873, Mr. A. K. Hale (Amer. Jour. Pharm., 1873, p. 247), announced the presence of a third alkaloid in hydrastis root, resembling berberine, but being darker in color, and behaving differently toward solvents. Mr. John C. Burt (Amer. Jour. Pharm., 1875, p. 481), confirmed these observations, and gave additional reactions. Again, Mr. Herman Lerchen (Amer. Jour. Pharm., 1879, p. 470), prepared the new base, naming it xanthopuccine, on account of the yellow color of the alkaloid as be obtained it. Lastly, F. Wilhelm, in Prof. Schmidt's laboratory, incidentally obtained minute quantities of a new alkaloid (Archiv der Pharm., 1888, p. 345), which Prof. Schmidt named canadine, and which he believes to be identical with the third alkaloid of hydrastis obtained by his predecessors. More recently, Prof. Schmidt found canadine to be tetra-hydro-berberine, having the formula C20H21NO4 (Archiv der Pharm., 1894, pp. 136-154; also see resumé by Mr. F. X. Moerk, in Amer. Jour. Pharm., 1894, p. 304). Canadine forms an almost insoluble nitrate by means of which the alkaloid was obtained from hydrastis. The free base forms white, acicular crystals melting at 132.5° C. (270.5° F.). It is insoluble in water, soluble in alcohol, ether, chloroform, benzol, and hot petroleum-ether; the hydrochlorate and hydrobromate, especially in excess of acid, are not easily soluble, while the sulphate forms an exception, being soluble in water. When exposed to light, canadine gradually turns yellow, being converted into berberine, especially in sulphuric acid solution.

From the researches of Prof. Schmidt, it becomes probable that hydrastis root contains in addition several alkaloids related to those already known, but occurring only in minute quantity. (For a special dissertation on hydrastis, the reader is referred to Vol. I, of D. and M. of N. A., by J. U. and C. G. Lloyd, from which publication is derived much of the botanical and chemical material embodied in this article on hydrastis.)

Medical History, Action, Uses, and Dosage.—For many years the salts of berberine and powdered hydrastis were the chief forms in which this drug was administered. At the present time these salts and the crude drug are but little used, and in this paper we shall confine ourselves principally to the liquid preparations of hydrastis—chief among which are the specific hydrastis and Lloyd's hydrastis As there have been many preparations of this drug thrown on the market (since Lloyd's was introduced), under the name "colorless hydrastis," and accompanied by the statement that they are preparations of the white alkaloid hydrastine, it is but fair, in speaking of Lloyd's hydrastis, that we should state that it is not merely a solution of hydrastine, which is probably the least valuable constituent of hydrastis, but a preparation containing the combined colorless constituents of the drug. It is a well-known fact, though often overlooked by those who wish to make it appear that the alkaloidal constituents of a plant are alone the valuable and active therapeutic factors, that the combination or association of principles formed naturally in the plant, or held together naturally even when derived from the plant, more completely represents the crude drug than do the isolated and forcibly separated alkaloids, and that medicinal virtues are possessed by the former that can not be even approximated by the latter. Thus it is, that Lloyd's hydrastis is much superior as a remedy, than if it were merely a fluid preparation of the white alkaloid From some experiments made by Prof. J. A. Jeançon (Ec. Med. Jour., 1886, p. 576), with a concentrated solution of the associated colorless principles divested of the alkaloid, hydrastine, it was shown that marked therapeutic effects could be obtained from them alone. It acted principally as an astringent, gradually decreasing and finally arresting hypersecretion. As an intrauterine astringent he preferred it above all others. In determining its physiological effects, he administered it to animals in health, but could not observe any appreciable effect upon temperature, pulse, or respiratory apparatus. These physiological doses, however, produced constipation and anorexia. Thus, we observe, as is very frequently the case, a marked contrast between the almost negative physiological effects and the very positive therapeutic results. In this connection we can state that Prof. Lloyd has been led, from his great experience in observing the results of the uses of hydrastis, to seriously consider the advisability of excluding, to the great extent, the white alkaloid from Lloyd's Hydrastis. Reports, unquestionably reliable, indicate that it is often irritating and objectionable.

The whole drug, including the alkaloid hydrastine, appears to stimulate the respiratory and circulatory apparatus, imparting increased tone and power. Arterial tension is augmented, and blood pressure in the capillaries increased, rendering it valuable, like belladonna and ergot, in overcoming blood stasis. Its action upon the nervous system has been compared to that of strychnine (Ellingwood), though less energetic, but more permanent. Thus the tone imparted to the heart muscle is permanent, rather than intermittent or spasmodic (ibid.). The sensibility of the nerve endings is blunted by hydrastis in excessive doses, and in the lower animals large doses of the alkaloid have produced death. No such toxic action, however, has been observed upon man. Muscular nutrition is increased under the judicious administration of hydrastis, making it a valuable agent in muscular debility, and in altered states of the muscles, particularly of the unstriped variety.

It is a little singular that hydrastis was not mentioned by our earliest writers on indigenous materia medica, for it was in extensive use among certain of the aboriginal tribes of North America, being used both as a medicine and as a coloring material. Prof. Benjamin Smith Barton in his first edition of "Collections for an Essay Toward a Materia Medica of the United States" (1798), refers to the Cherokee use of it as a cure for cancer. Later, he calls attention to its properties as a bitter tonic, and as a local wash for ophthalmia. From that time on it was endorsed by Rafinesque, Hand, Smith, and the various writers of the botanic and of the medical reform schools. The extensive range of uses given by the foregoing writers was not included in the first edition of the American Dispensatory (1852), Prof. King evidently believing the virtues of the drug to have been greatly overdrawn. He gave, however, a careful review of its properties and uses, and thus, for the first time, it became firmly established as an Eclectic medicine. At the present time it is a great favorite with Homoeopathic practitioners and with a large proportion of Allopathic physicians. It was introduced into Homoeopathic medicine by the late Prof. E. M. Hale, M. D., who was familiar with the Eclectic uses of the plant.

Hydrastis is bitter to the taste, and induces increased activity of the salivary glands. It sharpens the appetite and aids digestion when indicated. Schatz has shown that it increases contraction of the muscular fibers of arteries without affecting other muscular tissues of the tubular organs. He has also shown that it decreases congestion of the genito-urinary tract. Rutherford, who investigated it, concluded that it was a hepatic stimulant, and in less degree stimulant to the intestinal tract. Its power as a hepatic stimulant is, however, probably overrated, while as a stimulant of the gastric and intestinal mucous surfaces its action is marked. Hydrastis exerts its chief action upon the mucous and glandular structures, and to some extent, through its white alkaloid, upon the nervous system.

Hydrastis is a valuable drug in disordered states of the digestive apparatus, especially when functional in character. It is not adapted to all classes of cases, but is rather to be considered as indicated in disorders of a sub-acute character and in atonic states with increased flow of mucus. In sub-acute and chronic inflammation with free secretion it will be found to render good service. As a general bitter tonic it resembles, though does not equal calumba and gentian, but is more applicable to debilitated conditions of mucous tissues. Beginning at the mouth, its beneficial action may be traced throughout the alimentary canal. For aphthous stomatitis it is equaled only by coptis and phytolacca. It is not the remedy in this disorder when the mucous secretions are checked, but is best adapted to subacute forms, bordering on a chronic state. As a remedy for various gastric disorders it will take a leading place, especially if it be borne in mind that it is never beneficial, but on the contrary, does harm, in acute inflammatory conditions. When, however, the trouble is subacute and semi-chronic, and especially with mucorrhoea, or even secretion of pus, the drug will give good results. It is indicated in gastric irritability, relieving the irritation, and afterward restoring the tone of the parts. For years the powdered root was made into aqueous infusion, which, when cold, was employed with marked benefit, but now we have pleasanter preparations which give equally as good results without entailing the unpleasantness of swallowing a large quantity of bitter and crude medicine. Lloyd's hydrastis has proved an excellent form of administration in cases of "ice water dyspepsia," a diseased condition said to be peculiarly American, on account of the almost universal practice in this country of drinking ice water and iced tea. The hydrastis should be given in 10-drop doses, before each meal and at bedtime. Chronic gastritis, with increased secretion (chronic gastric catarrh), is often promptly met with this drug. It is very valuable in gastric ulcer. Several physicians have observed that it is a very useful remedy to exhibit in cases of gastric catarrh following the inordinate use of alcoholic stimulants. Prof. Bartholow, who among the "regulars," has made extensive use of hydrastis, goes so far as to state that in sufficient doses (tincture or fluid extract), it is probably the best substitute for alcoholic beverages when it is desired to abandon the use of spirituous stimulants. This statement is ridiculed by the therapeutic editor of the National Dispensatory. However, it is certain that it is valuable in any form of gastric disorder, no matter what its origin may be, if there be irritation, or subacute inflammatory symptoms with increased secretion-a condition of atony. In chronic alcoholism it may be associated with capsicum or strychnine, or both, together with a liberal quantity of beef tea and other easily digested food, regularly administered. Small doses of hydrastis will be found indicated in that form of dyspepsia exhibiting a belching of putrescent gases, and followed by a weakness, or sensation of "goneness" in the pit of the stomach. If great irritability of the stomach is present, minute doses of the fluid preparations or of hydrastine hydrochlorate are to be preferred. When there is less irritation and great inactivity, powdered hydrastis may be used. When the larger doses are employed it should be immediately after meals.

This drug is equally as beneficial in catarrhal states of the intestines and gall ducts. In duodenal catarrh, with jaundice, and in those forms of catarrh of the biliary passages due to accretions of inspissated bile mixed with crystallized cholesterin, the remedy will be found serviceable if continued for a considerable length of time. Hydrastis should be remembered in obstinate constipation. It is especially useful in those disordered states due to hepatic obstruction or to hepatic congestion, accompanied or not with intestinal or biliary catarrh. The constipation best met with hydrastis is that hinging on atonic conditions of the intestinal glands, which may be gently stimulated to normal activity by small doses of either the specific preparation or Lloyd's hydrastis. Prof. King considered it a valuable tonic for enfeebled states of the alimentary tract in infants and children, and recommended it for the same purpose in convalescence from "severe attacks of diarrhoea, dysentery, and other debilitating maladies." Local application, with the internal use of hydrastis, has been resorted to in hemorrhoids, fissured anus, ulcers and eczema of the anus, and prolapsed and ulcerated rectum, with apparent benefit.

For the use of hydrastis in respiratory affections we insert the following from a previous article: "Golden seal is a valuable local agent in affections of the nose and throat. It acts as a subastringent tonic to the parts to which it is applied. Simple catarrhal, follicular, or granular pharyngitis is often cured by it. Syphilitic ulcerations of the vaso-pharyngeal passages are relieved and often cured by it. The colorless hydrastis (Lloyd's) has a beneficial effect in the various forms of sore throat, rhinitis, and also ulcerated or aphthous varieties of tonsillar, pharyngeal, and retro-pharyngeal catarrh. Subacute and naso-pharyngeal catarrh where the mucous membranes are dry and parched, the secretions being altered in quantity and character, is cured by it. In catarrhal hypertrophy, with profuse discharge and thickening of the Schneiderian membrane, this preparation is without an equal. It should be somewhat diluted, and is never the remedy for active, inflammatory lesions" (Felter). For that disagreeable state accompanying nasal and pharyngeal catarrh, in which the mucus forms in gelatinous masses and drops into the throat, hydrastis is probably without an equal. It should be applied locally and also administered internally. Locally, it is especially serviceable in subacute forms of tonsilitis, and occasionally in diphtheria. The drug is more especially indicated in catarrhal affections of any of the mucous membranes if there be also muscular debility.

In aural and ophthalmological practice this drug is a favorite local application. In the earlier history of its use as a medicine, infusion of the root, as employed by the Indians met by Captain Lewis, in 1804 (during the famous Lewis and Clark Expedition), and solutions of berberine salts, as used by the "Eclectic Fathers," were employed in various ophthalmias. These forms gave excellent results, the one objection to their employment being their staining qualities. At the present day these colored preparations are seldom used, but in their stead Lloyd's hydrastis gives fully as great satisfaction therapeutically, as well as being pleasant in taste and much more cleanly as a local application. It may be employed in the proportion of about 1 part in 10 or 20 of pure water in conjunctival diseases. It is only useful in superficial disorders of the eye, having no value in intraocular affections. It is valuable in all conjunctival inflammations, particularly so in the catarrhal forms. Foltz regards it as an excellent remedy in follicular conjunctivitis. Superficial corneal ulcerations are benefited by it, and in ciliary blepharitis it may be employed with confidence. It is well, however, in the latter disorder to wash the edges of the lids thoroughly with a weak solution of potassium bicarbonate, rinse well with pure water, and lastly apply the hydrastis lotion. It has been recommended and used with a degree of success in trachomic lids; but it is not nearly so effective in this complaint as the ointment of non-alcoholic thuja. The principal use of this drug in ear diseases has been for the cure of purulent inflammation of the middle ear, provided granulations do not exist. It may be employed here in both acute and chronic inflammations, and is especially indicated where the discharge is abundant. It may be dropped in the ear, or the ear may be cleansed with water to which a quantity of the medicine has been added. About 10 drops of solution (1 to 6 or 8) is about the proper amount to be employed when instilled into the aural aperture. Excellent results have been obtained by using it in this manner, mixed with specific hamamelis, to which water is added if too much smarting be produced. This combination has served us well in eczema of the aural canal and in irritation due to inspissated cerumen, the latter being readily softened by it.

Prof. Webster (Dynam. Therap.) calls attention to the use of specific hydrastis in cases of myalgic tenderness and soreness. He regards it as indicated where the unpleasant symptoms are masked during rest but aggravated by pressure and by motion. These myalgic symptoms may be due to various causes, often resulting as reflexes from uterine, rectal, and prostatic disorders. He also includes in the category of myalgic complaints, headaches resulting from reflexes in which the scalp-muscles are involved; pectoral tenderness due to lacerated cervix uteri; and the muscular pains caused by anemia, resulting from uterine, hemorrhoidal, and other hemorrhages. The dose recommended is from the fraction of a drop to 1 drop.

Taking advantage of the results of Prof. Schatz's investigation of the action of this drug on the circulation, several physicians have employed it in hemorrhagic conditions and in pathological states upon which hemorrhages are likely to depend. Schatz found it useful in hemorrhage from uterine fibroids (myomata); congestive dysmenorrhoea; hemorrhage in virgins, persisting even after the use of the curette; hemorrhages from subinvolution, endometritis, metritis, parametritis, cicatrices, stenotic conditions, and climacteric hemorrhage. Operations and other means had failed in the cases above mentioned, but hydrastis cured. The dose administered was 20 drops of the tincture 3 times daily. Too small a dose is without this controlling power over the walls of the vessels, according to Schatz, while large doses have an effect further than is desired. It is too slow a remedy for active post-partum hemorrhage, but may be employed for the control of passive hemorrhage. It is useful in metrorrhagia. Like ergot, it may be employed for the relief of chronic cerebral hyperaemia, and other forms of cerebral engorgement. Other observers have seen its beneficial action in the cure of fungoid endometritis, lacerated cervix, and pelvic cellulitis. Locally and internally, excellent results are obtained from hydrastis in leucorrhoea, both vaginal and uterine. For gonorrhoea, Lloyd's hydrastis probably enjoys a more extensive use as a local application than any other drug, and this use of it is not confined to Eclectic practitioners alone. For gleet it is equally as beneficial. For this purpose it may frequently be combined with aqueous thuja. Salts of zinc and lead, in very small amounts, may be added to the solution of hydrastis. If carefully employed, stricture as a result need never be feared. Other preparations of hydrastis will give good results, but their staining qualities condemn them. To Prof. John King must be accorded the first mention of this use of the drug. He also used it successfully in "incipient stricture, spermatorrhoea, and inflammation and ulceration of the internal coat of the bladder." As a remedy for cystitis, it maybe given internally, and used largely diluted to wash out the bladder. Prof. Jeançon, in discussing the concentrated solution of the associated principles of hydrastis (devoid of hydrastine), says: "Formerly, I used to apply locally a tampon or wad of absorbent cotton, well saturated with a solution of the double sulphate of alumina and copper, in cases of cervical erosions and light papillary vegetations. Now I apply the cotton saturated with the concentrated solution of these hydrastis substances, and find that the effect is all that can be desired. The eroded surface becomes smooth, the vegetations disappear, and a fine glistening layer of mucous structure soon makes its appearance.

Hydrastis has been used to some extent in cutaneous diseases. Prof. Jeançon cured a stubborn case of eczema of the scrotum with it. Other cases of eczema, depending upon gastro-intestinal disturbances, have been cured by its internal exhibition alone. Acne, seborrhoea sicca or oleosa, scrofula, acne rosacea, lupus, sycosis, boils, carbuncles, and ulcers, when dependent upon gastric difficulties, have been greatly benefited and some cases cured by the internal use of the drug alone. The local use at the same time hastens the cure. Eczematous manifestations around the outlets of the body also yield to the kindly action of golden seal locally applied. It has been said to cure cancer, though this use of the drug is overrated. Still, many believe it to have a beneficial effect in prolonging life and in mitigating the severity of the disease. On this point Prof. Scudder remarks, "In some cases of cancer with sloughing of tissues, and in malignant ulceration, no application will do more to retard the progress of the disease than an infusion of the crude article or a solution of the alkaloid (berberine). It has been claimed that the internal administration of the remedy alone will prove curative. I am satisfied that in some cases this use of hydrastis will do much to relieve pain and lengthen life, even if it does not prove curative." Hale and others consider the long-continued use of hydrastis internally excellent in retarding scirrhus of the breast, when the tumor is hard and painful, but has not yet advanced to ulceration.

Hydrastis should be remembered in convalescence from diseases having excessive mucoid discharges, or where hemorrhage has played an important part. For malarial disorders it probably has but little to recommend it. It has been used as an anti-malarial drug, but as it has usually been employed with some of the cinchona alkaloids, the beneficial, or at least the antiperiodic effects were probably due to the latter. Hydrastis should not be overlooked, nevertheless in convalescence from general debility, protracted fevers, inflammatory affections, and nervous prostration. Hence it is useful to combine with it capsicum, strychnine, nux vomica, iron salts, and quinine, when there are clear indications for their selection. Prostrating night-sweats are very often controlled by it. In hepatic and stomachic disorders it may be greatly aided by iris, phytolacca, bryonia, arnica, leptandra, chionanthus, and podophyllin, provided any of these are indicated. Powdered hydrastis and the extract are now seldom employed. The usual dose of specific hydrastis ranges from the fraction of a drop to 30 drops; of Lloyd's hydrastis, from 5 drops to 1 drachm; of infusion of hydrastis (℥i to aqua Oj) from 1/2 to 2 fluid ounces; locally, Lloyd's hydrastis, from full strength (ulcerated cervix uteri), to a dilution of 1 in 20 in water. Dose of the powder, from 10 to 30 grains; of the tincture, from 1 to 2 fluid drachms; of the hydro-alcoholic extract, from 2 to 5 grains; of the fluid extract, 10 to 60 minims; hydrastine (Eclectic), 1 to 6 grains; of hydrastinine hydrochlorate, 1/4 to 1 1/2 grains; berberine (see below), 2 to 20 grains; berberine hydrochlorate, 1 to 5 grains; berberine sulphate, 1 to 5 grains.

Specific Indications and Uses.—Hydrastis is specifically indicated in catarrhal states of the mucous membranes, when unaccompanied with acute inflammation. An apparent exception to this is in acute 'purulent otitis media, in which it is said to act better than in chronic conditions; gastric irritability; irritation of parts with feeble circulation; muscular tenderness and soreness, worse under pressure or on motion; passive hemorrhages from uterus and other pelvic tissues; skin diseases depending on a gastric abnormality, indicating hydrastis.

Related Drug.Coelocline polycarpa, A. De Candolle (Unona polycarpa, De Candolle), Yellow-dye tree of Soudan, Berberine tree. An African tree inhabiting Sierra Leone, Soudan, and other points in western Africa, which, when wounded, exudes a juice which leaves an indelible yellow stain upon linen, and tinges the saliva yellow. It is used as a yellow dye by the natives, and imparts both color and bitterness to water. Stenhouse has shown the coloring principle to be berberine. Medicinally, it has been used in decoction and powder by the inhabitants of Sierra Leone, as a topical dressing for obstinate ulcerations.

Preparation of Hydrastis.—LIQUID HYDRASTIS. This is a glycerin preparation introduced by the William. S. Merrell Chemical Company, of Cincinnati, and is properly a specialty of this firm. Fluid hydrastis is employed both externally and internally.

Related Preparations.—BERBERINE AND ITS SALTS. Berberina, Berberine. (For a description of berberine see above.) Berberine is an excellent tonic, and also appears to possess slightly laxative properties. It will be found to exert an efficient action upon all abnormal mucous tissues, and may be employed in cases where barberry or hydrastis is indicated. It may be used in powder, in doses of from 2 to 20 grains; or in water, to which citric, tartaric, or acetic acid has been added to aid its solution. Acetate of berberine will be found a very soluble salt, and of much efficacy.

BERBERINAE HYDROCHLORAS, Berberine hydrochlorate (see above).—Hydrochlorate of berberine is a tonic, with an especial action on diseased mucous tissues; it possesses, in an eminent degree, the tonic virtues of the root, and was formerly much used, and is still employed by some physicians as a substitute for it. It is more beneficial as a tonic during convalescence from exhausting diseases, such as bilious and typhoid fevers, acute hepatitis, gastritis, enteritis, diarrhoea, dysentery, etc. In dyspepsia and chronic inflammation of the stomach it is very valuable, and will be found of especial advantage in the treatment of persons who are intemperate, gradually removing the abnormal condition of the stomach, and in many instances destroying the appetite for liquor; it may be combined in these cases with sulphate of quinine, extract of quassia, or other bitter tonic. In jaundice, a combination of equal parts of hydrochlorate of berberine, extract of bayberry bark, and oleoresin of prickly ash bark, will often prove efficient. Combined with sulphate of quinine and extract of leptandra, it was once considered useful in infantile remittent fever. Equal parts of hydrochlorate of berberine, resin of caulophyllum, and extract of leptandra, form an excellent medicine for aphthae and other ulcerations of the mouth and throat, in infants, as well as adults; it should be administered internally. A pill composed of 1 grain of hydrochlorate of berberine, 1/20 of a grain of alcoholic extract of nux vomica, and sufficient oleoresin of ptelea to form a pill-mass, is found an efficient remedy for some forms of dyspepsia, and loss of appetite; 1 pill to be given for a dose, and repeated 3 times a day. Dose of hydrochlorate of berberine: For an adult, from 1 to 5 grains; for children, from 1/2 a grain to 3 grains; and which may be repeated from 3 to 6 times a day, if required.

BERBERINAE SULPHAS, Berberine sulphate.—Four grains of sulphate of berberine, dissolved in 1 fluid ounce of hot water, forms, when cold, an excellent collyrium in purulent and phlyctenular conjunctivitis, and an efficient injection in otorrhoea, ozoena, leucorrhoea, catarrh of the bladder, chronic gonorrhoea, prostatorrhoea, and relaxed or enfeebled conditions of mucous membranes. Staining of garments, etc., is an objection to the local use of berberine salts.

King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.

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