FIG. 85.Gentiana lutea growing in the Royal Botanic Society's Gardens (London). (After P6rr6d<*s.

and roots of Gentiana lutea Linne (Fam. Gcntianaceas). Gentian yields not less than 30 per cent of water-soluble extractive and contains not more than 15 per cent of moisture. Gentiana was named after Gentius, king of Illyria, discoverer of the tonic value of the plant; lutea, yellow, refers to the color of the flowers. The plant is a large perennial herb indigenous, - 'to central and southern Europe and .Asia Minor. . The drug is gathered in-he autumn and is cut into pieces of variable length, the more fleshy ones being sliced longitudinally. These are then left in piles -and allowed to ferment, after which they are slowly dried. The rhizomes and roots are difficult to dry thoroughly because of the high sugar content. Prepared in this way the internal, color of the root changes from white to yellowish brown and a con : siderable amount of the gentiopicrin disappears, probably through enzymic action. The drug is packed in burlap bags, most of the commercial supply coming from Marseilles, Bordeaux, Antwerp, Hamburg and Budapest. Gentian was known to Pliny and Dio-scorides. It was commonly used in medicine during the Middle Ages. DESCRIPTION.Nearly cylindrical to irregular pieces, 5 to 40 mm. in diameter; externally light brown, annulate above (rhizome portion), longitudinally wrinkled below (root portion), and with a few buds, stem-and root-scars; fracture short when dry, tough and flexible when damp; internally yellowish brown, with a distinct dark brown cambium zone. ' STRUCTURE. See the National Formulary XL. POWDER.Moderate yellowish brown; odor strong and characteristic; taste persistently and strongly bitter; fragments of

FIG. 85.Gentiana lutea growing in the Royal Botanic Society's Gardens (London). (After Perr6d<*s.)

and roots of Gentiana lutea Linne (Fam. Gcntianaceas). Gentian yields not less than 30 per cent of water-soluble extractive and contains not more than 15 per cent of moisture. Gentiana was named after Gentius, king of IllyTia, discoverer of the tonic value of the plant; lutea, yellow, refers to the color of the flowers. The plant is a large perennial herb indigenous, - 'to central and southern Europe and .Asia Minor. . The drug is gathered in ihe autumn and is cut into pieces of variable length, the more fleshy ones being sliced longitudinally. These are then left in piles -and allowed to ferment, after which they are slowly dried. Tl^e rhizomes and ropts are difficult to dry thoroughly because of the high sugar content. Prepared in this way the internal color of the root changes from white to yellowish brown and a con: sidcrable amount of the gentiopicrin disappears, probably through enzymic action. The drug is packed in burlap bags, most of the commercial supply coming from Marseilles, Bordeaux, Antwerp, Hamburg and Budapest. Gentian was known to Pliny and Dio-scorides. It was commonly used in medicine during the Middle Ages. DESCRIPTION.Nearly cylindrical to irregular pieces, 5 to 40 mm. in diameter; externally light brown, annulate above (rhizome portion), longitudinally wrinkled below (root portion), and with a few buds, stem-and root-scars; fracture short when dry, tough and flexible when damp; internally yellowish brown, with a distinct dark brown cambium zone. ' STRUCTURE. See the National Formulary XL ; POWDERModerate yellowish brown; odor strong and characteristic; taste persistently and strongly bitter; fragments of

Quassia parenchyma tissue with occasional trachea? having simple pores; intermediate fibers non-lignified, the walls being marked with irregular, simple, oblique pores; starch grains or calcium oxalate crystals few or absent; stone cells and bast or wood fibers absent. CONSTITUENTS.Three" bitter glycosides, gentiopicrin,, gentiamarin and gentiin; genti-sin; gentianose; glucose 12 to. 15 per cent; total ash about 3 per cent; acid-insoluble ash about 0.75 per cent. Gentiopicrin forms white, optically levorotatory needles, soluble in water, less so in alcohol, and may be largely destroyed by enzymes during curing and drying of the drug. Gentiamarin is amorphous, with a bitter taste. Gentiin (gentianin) occurs in microscopic yellow needles, gives a greenish black color with solutions of ferric salts and on hydrolysis yields gentienin, xylose and glucose. Gentianose Is a crystalline carbohydrate, occurring in the fresh root, and does not reduce Fehling's solution. Gentism or gentianic acid may be inicrosublimed from powdered gentian to form yellow prismatic crystals, from 10 to 150 microns long, straight or slightly curved, and isolated or in small clusters; they are insoluble in water (hence tasteless), alcohol or ether, but soluble in chloral hydrate or potassium hydroxide solutions. USE AND DOSE.Gentian is classed as a bitter. The dose was formerly listed as 1 Gm. STORAGE.Gentian is liable to insect attack and should be stored in suitable containers with the usual precautions. The followingdrugs belongto theG.entian-aceaj and possess constituents related to those of Gentian: American Gentian or Blue Gentian (Gentiana Catesbsii), Chirata (Swertia Chirayita), Centaury (Erythrxa Ccniaurium), American Centuary .{Sabbatia angularis) and Buckbean or Marsh Trefoil

157

malignant fevers. The drug was at one time almost exclusively obtained from Quassia amara hut now is largely derived from Picrasma exceha from Jamaica. DESCRIPTION AND STRUCTURE.See Figure 86 and the National Formulary X. POWDER.Weak yellow; tracheal fragments with bordered pores; wood fibers long, thin-walled and with oblique simple pores; calcium oxalate in monoclinic prisms 6 to 30 microns in length or in sphenoidal micro-crystals; starch grains few, spheroidal or ellipsoidal, 5 to 15 microns in diameter. When bark is present a few stone cells and cork cells are also found. In the bark of Surinam Quassia stone cells are numerous. CONSTITUENTS.The drug contains up to 0.75 per cent of a bitter crystalline substance, quassin, which consists of two crystalline principles, a-picrasmin and 6-picrasmin; an alkaloidal principle which gives a blue fluorescence in acidified alcoholic solution. Total ash, about 3.75 per cent; acid-insoluble ash, about 0.1 per cent. USES AND DOSE.Quassia is a bitter. Administered as an enema, the drug possesses anthelmintic properties. The dose was formerly listed as 500 mg. Quassin has replaced brucine in the preparation of denatured alcohol. Bitter principles similar to those in Quassia are also found in Quassia Bark, the bark of Picrasma excelsa and of Quassia amara, and also in Simaruba Bark (U.S.P. 1820 to 1873), the bark.of the root of Simaruba officinalis and S. amara. The

(Menyanthes trifoliata). y''

... ' } QUASSIA

. Quassia or Bitter Wood (U.S.P. 1820 to 19S6;.N.F. 1936 to 1960) is the wood of Picrasma excelsa (Swartz) Planchon, known in commerce as Jamaica Quassia, or of Quassia amara LinneV^known in commerce as Surinam Quassia (Fam. Simarubacese).
Qiuls-

^ia is from Quassi, the name of a Surinam

Negro, who first discovered the febrifuge properties of the drug; picrasma is Greek meaning bitter; amara is Latin for bitter; and excehaas from.the Latin meaning surpassing, i.e., the tallest tree in the genus. Picrasma'excelsa is a tree attaining a height of about 25 meters, growing in the \Ye:>t Indies, while Quassia amara is a branching shrub or small tree attaining a height of 2 to 3 meters and found in Venzueia, northern Brazil and the Guianas. The wood is usually cut into logs for shipment. ''Quassia Cups" were formerly turned from the wood and the shavings used as the drug. The drug consists of chips, raspings or shavings. Quassia seems to have been used in Surinam as early as 1714 for the treatment of

FIG. 86. A, Transverse section of Jamaica Quassia. B, Transverse section of Surinam Quassia: trachea?; ft wood fibers; hp, wood parenchyma; o, cells containing calcium oxalate; 7/?, medullar}- ray (After Meyer.)

latter also contains a volatile oil having an odor resembling benzoin. All of these barks have bitter properties.
GLYCYRRKLZA

Glycynhizz or Licorice Root (U.S.P. 1820 to date) is the dried rhizome and roots of Glycyrrhiza glabra Linne var. typica Regel et Herder, known'. in commerce as Spanish;. Licorice, or of Glycyrrhiza glabra Linne var. glandulifera Waldstein et Kit&ibel, known in commerce as ..Russian Licorice (U.S.P. 1890 to date),-or of other varieties of Glycyrrhiza glabra Linne, gelding a yellow and sweet wooa fi|km. Leguminosse) j Glycyrrhiza is of''Greek origin and means sweet root; glabra means smooth, and reTers to the fruit of this species which is a smooth pod. In the species glandulifera the fruit has gland-like swellings. The plant is perennial herb attaining a height of 1 to 1.7* meters.^ The underground portion of the .variety typica (Spanish licorice) consists of several horizontal,

FIG. 87.A bundle of Spanish Licorice root from the Pharmacognosy Museum of the University of Illinois. (Photo by R. S. Adamaon.)

100

Glycosides

spreading rhizomes bearing, buds and Glycyrrhiza of branching roots which penetrate the soil to a depth of several feet. In the variety glandulifera (Russian licorice) the underground portion consists of a large rhizome which gives off long, thick, fusiform roots. Until 1870 Spain produced practically the entire world's supply of licorice root. Now, Greece and Asia Minor supply most of the licorice. 'Experimental lots of licorice root have been produced by cultivation in California and Oregon, where there are great areas well adapted to it; yet until mechanical means reduce the high labor cost, the United States will not become a competitor in the production of licorice. Over 43,000,000 pounds of licorice root and 625,000 pounds of licorice extract were imported in 1957. Propagation of the variety typica is generally by rhizome cuttings which are planted in rows about 4 feet apart. At the end of the 3rd or 4th year the rhizome and roots are dug, preferably in the autumn and from plants which have not borne fruit, so as to insure maximum sweetness of the sap. The washed material is air-dried (4 to 6 months), packed into bales or cut and tied into short cylindrical bundles (see Fig. 87). The large thick roots of Russian licorice are peeled before drying. In southern Italy a considerable amount of the erop is extracted with water, the liquid being clarified and eva-ported, and the resulting extract molded into sticks, etc. DESCRIPTION, HISTOLOGY AND POWDER. See Figures 87, 88 and the U. S. Pharmacopeia XVI. CONSTITUENTS.Glycyrrhiza contains.two* glycosides: .felycvrrgziig (from JTto 12 *per cent) which is 50 times' as sweet as sugar, and liqueritirf; a bitter principle known as glycyramarin which occurs principally in the bark and thus is less abundant in Russian licorice; asparagin, sucrose/ mannite and a yellow coloring matter, ^yjcjvrrhjzin ,has been'shown to have an action similar to ^ ... .d&xy&rpone1 m depressing the output of **A-Cl]H by the pituitary gland. Glycyrrhiza also possesses an appreciable.quantity of an estrogenic hormone similar to estriol.
1 KRAOS, S. D.: Glycjrrrhizin-induced Inhibition of .the Pituitary Adrenal Response, J. Exp. Med., U08t 325-328, 1958.

...

FIG.

88.Spanish

Licorice

in

transverse

section:

Ck, cork of numerous layers of yellowish brown cells; C, cortex, jvith outer rows collenchymatous and inner portion parenchymatous, with groups of .fibers (Sf), more or less surrounded by crystal fibers (Cf); P, phloem with^alternating strands of basj. (Bf) and sjeve. (Si)r th6 cells of the latter wjlh thickened highly retractile walls; MR, medullary rays from 1
to_8 cells wide and definitely radiate, alternating with the phloem; Ca, cambium, narrow and inconspicuous; X, ocylcin.region wiih broad wood wedges containing bundles of wood fibers (Wf) associated with crystal fibers (Cf), large tracheae (Tr) and thinwalled, non-lignified wood parenchjTna (WP); the parenchyma cells of the bark, medullary rays and wood bear an abundance of starch. (Drawing by c* v * Harry Flower.) .

STANDARD. Glycyrrhiza yields not more than 2.5 per cent of acid-insoluble ash. STORAGE.Glycyrrhiza should be preserved from attack by insects. USES. Glycyrrhiza is considered to possess demulcent, expectorant and laxative properties. It is used considerably as a flavoring agent and is frequently employed to mask the taste of bitter drugs such as aloe, ammonium chloride, quinine, etc. Commercially, licorice is added to chewing gums, chocolate candy, cigarettes, smoking mixtures, chewing tobacco and snuff; when it is added to beer, it increases the foaminess; when it is added to root beer, stout a;id porter, it imparts a better taste. Glycyrrhiza Extract, Licorice Root Extract or Licorice (U.S.P. 1820 to 1955; N.F. 1955 to date) is an extract prepared from the rhizome and roots of species of Glycyrrhiza Tournefort ex Linne (Fam. Leguminosx). It is prepared by extracting coarsely ground licorice root, usually the inferior grades, with warm water, clarifying the extract and evaporating it to complete or nearly complete dryness. Spanish licorice is used almost exclusively for preparing this extract. Glycyrrhiza Extract occurs as a brown powder, in flattened, cylindrical rolls, or in

glycyramarih. It has never been substituted f o r the official licorice.

RED SAUNDERS Red Saunders (U.S.P. 1820 to 1950; N.F. 1950 to 1960) is the heartwood of Picrocar-pus sanialinus Linn6 films (Fam. Leguminosdc). The specific name santalinus is probably from the Persian sandul, meaning useful; rub rum is Latin, meaning red. This is a large tree growing in southern India, Ceylon and the Philippines. The heartwood is highly prized for cabinet work, and the Indian Government carefully regulates cutting, new forests being established from time to time to prevent extermination. The light-colored sap-wood is separated anc' only the heartwood is employed. Marco Polo refers t( sandalwood imported into China, distinguishing the variety by the word red. Garcia de Orta of Goa (16th century) distinguishes between the fragrant sandalwood of Timor (see Santalum Album) and the inodorous red sandalwood. In the DESCRIPTION.Usually in a coarse powder of a reddish orange or brownish red color; in transverse section the wood is radiate, with numerous alternate lighter and darker concentric rings; medullary rays one cell wide; fracture hard, fibrous.

black color externally, and a brittle, sharp, Middle Ages red saune'ers was used for color-smooth, conchoidal fracture; the- taste is. ing purposes, a use for which it is employed sweet and characteristic. Not more than -25 * today. masses^ The rolls or masses have a glossy CONSTITUENTS.Santalin (santalic acid), per cent of the extract is insoluble in cold which occurs in red needles that are insoluble water. It contains no foreign starch and yields in water, soluble in jJcohol, forming a deep red notJ more than 5 per ceni|^lwj solution which is colored violet with solutions Extract of licorice is useel as an excipient in of the alkalis; tannin; and several the manufacture of.pillsjmd troches and as a flavoring'and disguising agent in other pharmaceutical preparations." I Much of the commercial supply is used in confectionery and in chewing 'tobacco.? pared by adding fluted ammonia solution to $ an extract* of glycyrrhiza perflated,.wit|f boiling water| The ammoniated -solution is boiled to reduce the volume, then filtered and iminediately evaporated until the residue has a pilular consistence. Pure Glycyrrhiza* extract is _a_ blabk^pilular mass having a characteristic sweet taste. It is a pharmaceutic necessity, being an ingredient in Aromatic Cascara Sagrada Fluidextract. Pure Gjycyrrhiza' Extract or Pure Licorice Root Extract (U.S.P. 1880 to date) is preWild or American Licorice is the root of colorless crystalline principles, STANDARDS AND TESTS.(1) When 500 m*g. of Red Saunders is added to 10 ml. of alcohol, the mixture becomes distinctly reddish brown to reddish orange. (2) When 500 mg. of Red Saunders is added to 10 ml. of ether, the solution assumes a brown color, and when held in a bright light shows a distinct greenish yellow fluorescence. (3) When 500 mg. of Red Saunders is added to IO ml.

Glycyrrhiza lepidota, a perennial herb

indigenous to western North America. The plant is similar to that yielding Spanish licorice. The roots contain 6 per cent of glycyrrhizin and considerable

100

Glycosides

Cochineal of disti'led water, agitated, and filtered, the filtrate is colorless to weak yellow. USE.Red Saunders is used for imparting color. COCHINEAL Cocluneai or Coccus (U.S.P. 1831 to 1955; N.F. 1955 to date) consists of the dried female insects, Coccus cacti Linne (Fatn. CoccuLv), enclosing the young larva:. The gea eric

name Coccus is from the Greek Kokku meaning a grain or berry and refers to ti-appearance of the insect; cacti is from t> Greek Kaktos, meaning a prickly plant, tl insects being cultivated on various specie of cactus. The cochineal insect feeds upon varioi^ species of the Cadacex, more especially ti* Nopal plant, Xopalca cochcnillifcr (OputiU

. FIG. 89.Diagram\of cochineal insect of commerce, showing an ovoid sac-like membranous cradle tL dosing numerous young larvse (I). Parts of {he mother insect: m, mouth part; 6, beak or proboscis; antennae;/, three pairs of legs; r, respiration channels or breathing pores; ^segments in abdominal region \c, wax pores. 11.

Other Coloring Principles

1ST:

coccinellifcra), a native of Mexico and Peru. It few drops of hydrochloric acid have been added.
has spread in Central and South America and has been introduced into the West Indies, East Indies, Canary Islands, southern Spain and Algeria and is said to be found in Florida and California. Most of the supply comes from Peru. The female insect is without wings, about 2 mm. in length and consists of from 9 to 12 segments. It is somewhat globular, becoming later distinctly ovoid. In general appearance, the insect body is convex on the upper (dorsal) surface and somewhat flattened or concave below. It is covered with a protective secretion or wax which is formed as a glandular secretion by the "wax pores" (Fig. 89, w), and wax hairs. The antenna are rather short, consisting of 8 parts. The thread-like beak or proboscis, forming a sucking apparatus, is very fully developed. There are 3 pairs of legs and projecting from the posterior portion of the abdomen there are 2 hairs or bristles. The female insect after fecundation grows larger as the young larvte develop, becoming eventually about twice her original size. The cochineal of commerce consists of the females which are removed by the planters from the Nopal plants. They are then subjected to steam or hot water and dried, or they may be dried by direct heat. DESCRIPTION. It is concavo-convex, about 5 mm. in length, dark garnet in color. The mouth part of the insect with a more or less developed beak or rostrum is always present, the beak sometimes being extended and recurved in an elliptical form in the direction of the abdomen. One or both of the antenna? are frequently present, showing 5 to 7 parts. The joints of the legs are usually more or less detached, the point of insertion usually-being indicated only by large yellowish brown elliptical scars.' Between each of the legs on both sides are situated 2 distinct pores, which resenible in form and color the point of attachment of the legs and which are respiration canals. * In the abdominal region, which . is very large,'the larvae are borne. These are usually seen in several stages of development (Fig. 89). . The following method is useful in destroying the coloring \matter, thus rendering it possible to study the cochineal insect; 10 Gra. of commercial cochineal is macerated with 100 ml. of water containing 2 or 3 per cent of an alkali. The mixture is allowed to stand for an hour or so and then is poured over a piece of wire gauze. The insects remain on the gauze and are then washed with a few liters of water. The insects, from which the coloring matter has been partly removed, are then transferred to 150 ml. of hydrogen peroxide solution and allowed to stand for a few hours with occasional gentle stirring. The mixture is again transferred to the gauze, the excess of hydrogen peroxide washed off and the insects then transferred to a weak alkali solution in which they are macerated for 6 to 8 hours. The mixture is poured upon the wire gauze and washed with water until the filtrate runs practically colorless. The insects on the gauze are then transferred to dilute alcohol to which a

This now renders them translucent and ready for microscopic study. They may be mounted in chloral T.S. and examined. CONSTITUENTS.Cochineal contains from 9 to 10 per cer t of a glycosidal coloring principle, carmin c acid (carmine red). It is methyldioxy'iaphthoquinone and forms crystals, which are very soluble in water, alcohol and ammon.a, partly soluble in ether, and insoluble in nxed and volatile oils. Cochineal also contains a wax, coccerin; myristin; and fats and fatty acids. TESTS.The red color of dilute aqueous solutions of Cochineal is changed to purple by alkalis and to light orange by acids. When whole Cochineal is macerated in water, no insoluble powder separates from the mixture (inorganic matter used for weighting). USE.:The principal use of Cochineal is as a coloring agent. COMMERCIAL GRADES. There is considerable variation in the quality of the commercial article. According to the broker or exporter, several grades of cochineal_are recognized. Broadly speakingTtEe^terms "silver grain," "black grain" and "granilla''. are used, but there are intermediate qualities variously designated as gray, black-gray, silver-gray, silver-black, rosy black, red and foxy, and these again may be qualified by the terms fair, bold, fine and so forth. The com

Glycosides

mercial variety known as "granilla" repres-sents the smaller females in which the larvae usually show but a very slight development. Carmine (N.F. 1910 to 1955) is the aluminum lake of the coloring principle obtained from cochineal. Carmine occurs in irregular, angular, bright red fragments or as a powder, without odor or taste. When burned it emits an odor resembling that of burned feathers. Carmine is slightly soluble in ammonia water or alkaline liquids, forming a dark purplish red solution. It should not contain more than 25 per cent of water and not more than 12 per cent of ash and should be free from tin, lead, and soluble and insoluble barium compounds. Consult the National Formulary IX for methods of testing. USES.Carmine is a coloring agent. Crocus or Spanish Saffron (U.S.P. 1820 to 1905; N.F. 1916 to 1942) is the dried stigma of Crocus sativus Linne (Fam. Iridacex). The plant is a low-growing, perennial herb, producing its flowers in the autumn from buds on the large conn: The flowers are 25 mm. or more across, lily-like, and the three stigmas terminate a long style. The flowering period extends over 2 or 3 weeks, the flowers being gathered as they open; the dark red stigmas are separated by hand and are dried over charcoal fires, with a loss in weight of about 80 per cent. The stigmas from about 100,000 flowers are required to make a kilo of the pure dried drug, hence the price of the drug is very high. The plant is indigenous to the eastern Mediterranean region and is cultivated for the drug in Spain, France, Austria, Germany, Switzerland and Iran. The imports to the United States are largely from Spain. Saffron was known to the Egyptians and was prized by the ancient Greeks and Romans. Even in the Middle Ages it was an expensLvedhig. Saffron seems to have been introduced into Spain about the 10th century. Crocus contains two glycosides: crocin -which is colored yellow and pierocrocin which hydrolyzes to form a volatile oil giving the drug its characteristic odor. Crocus was formerly employed as a diaphoretic and also -to promote eruption in 'cases of measles, but for these purposes, it has largely been abandoned Its prineipi. use today is as a coloring and flavoring ager: in cooking. Carthamus, American Saffron, Safilower Indian safilower (U.S.P. 1820 to 1882) consisu of the tubular florets of Carthamus tijictoriu Linne (Fam. Composite). It is lighter red ir. color than Crocus, but is sometimes adtnLxe: with it and occasionally substituted for it. Carthamus is used for much the same purposes as Crocus; however, the two should not be confused inasmuch as Spanish saffron b much more expensive than American Saffron. NOTE: Safilower Oil (see p. 191) is a fixed oil obtained

from the seed of Carthavus tinctorius Linne (Fam. Composite). OTHER COLORING PRINCIPLES Various types of coloring principles arc contained in the following drugs, some of | which were officially recognized in the pan and some of which are still employed as reagents in the official compendia. Alkanna or Alkanet (U.S.P. 1831 to 1842. is the dried root of Alkanna tinctoria (Fam. Boraginacex). It contains alkannin (also known as anchusin). Brazil Wood (U.S.P. 1894 to 1916) is the wood obtained from Caesalpinia cchinata (Fam. Leguminosx). It contains brazilin. Hematoxylon or Logwood (U.S.P. 1820 to 1916; N.F. 1916 to 1936) is the heartwood of H&matoxylon campechianum (Fam. Legum-inossi). It contains hematoxylin. Hematoxylin (U.S.P. 1905 to 1926; reagent, U.S.P. 1936 to date; reagent, N.F. 192G to 1960) is the chief constituent of Hematoxylon and, chemically, is hydroxybrazilin. It is employed as an indicator, a microscopic stain and in certain dyestuffs. Hematein (reagent, U.S.P. 1916 to date; reagent, N.F. 1936 to date) is an oxidation product of hematoxylin. It is used as an indicator and as a nuclear.stain in. cytologic^ work. : Litmus, Lacmus, - Turnsole or Lacqueblue (reagent, U.S.P. 1926 to 1936, 1942 to date; reagent, N.F. 1942 to 1960) is a blue pigment prepared from various species of Roccella, Lecanora, or other lichens (Fam. Parmel-iacex). The lichens are ground into a pulp with water, treated with dilute ammonia

Other Coloring Principles

1ST:

water and potassium carbonate, and allowed to ferment until the color of the solution reaches the desired tint. The liquid is then mixed with calcium carbonate or gypsum, molded into small cubes and finally dried. Most of the commercial litmus is manufactured in Holland. The familiar litmus paper is made by saturating filter paper strips with litmus solution. The color is, of course, dependent on whether the solution has been rendered basic or acidic. Azolitmin (reagent, U.S.P. 1916 to 1926, 1942 to 1960; reagent, N.F. 1936 to date)is a water-soluble coloring principle obtained from litmus. It is used as an indicator. Orchil or Archil is a coloring substance obtained by the fermentation of Rocclla tinc-toria, R. fuciformis and other lichens (Fam. Parmeliaccx). It is a source of orcinol. Orcinol (reagent, U.S.P. 1916 to 1926; reagent, N.F. 1942 to 1960) is obtained from orchil or is prepared synthetically. By alkaline fermentation it is converted to orcein which forms lavender colored solutions with alkalis. It is used as an indicator. Cudbear (N.F. 191G to 1950) is a powder prepared from species of Rocclla, Lecanom or other lichens (Fam. Parmcliaccx). Its chief constituent is orcein. Cudbear was used as a coloring agent for pharmaceutical preparations and also in the dyeing industry.

IDENTIFICATION TESTS Concentrated sulfuric acid added to picrotoxin produces a golden-yellow solution which changes gradually to reddish brown. For additional tests consult the N.F. XL USES AND DOSE. Picrotoxin is a central stimulant and is used as an antidote for barbiturate poisoning. Usual dose, intravenous, to be determined by the physician according to the needs of the patient. (The dose was formerly given as 2 mg.). Picrotoxin was formerly incorporated into ointments and employed as a parasiticide; however, this is considered dangerous he-cause it is very poisonous. Jamaica Dogwood is the root bark of Pi.s-cidia erythrina (Fam. Leguminosx), a tree growing in the West Indies. The bark has been used for stupefying fish in a manner similar to Cocculus. It contains piscidin and piscidic acid and has been employed in medicine as a narcotic, analgesic and soporific. KHELLTN

Khellin is the aglycone of a glycoside obtained from the fruit of Ammi visnaga Lam. (Fam. UmbcUiferx). The plant grows in Mediterranean countries and has been used for urethral spasm and renal colic. :The fruits contain khellinin, the glycoside of methoxyhydroxymethylfurano-chromone, also called khellol glucoside. PICROTOXJN USES AND DOSE.Khellin is a selective Cocculus, Fishberry, Indian Berry or coronary vasodilator and bronchodilator. It is Cocculus Indicus (N.F. 1916 to 1947) is the used in the treatment of coronary indried ripe fruit of Anamirta Cocmlus (Linne) Wight et Arnott (Fam. Mcnispcrmacex) The plant is a woody climber growing in the mountainous woods of southeastern Asia, particularly along.the Malabar coast. The blackish.brown of reddish brown fruits are commonly used by.the natives to stupefy fish, thus making it possible to catch them by hand'. When ripe they are of a reddish color and are removed from their stalks and dried. The drug seems to deteriprate with .age, and those fruits which are of a dark color having the seeds well preserved, are preferred. CONSTITUENTS;The chief constituent of Cocculus is picrotoxin (1.5 per cent). The drug also contains two tasteless, nontoxic crystailizable alkaloids: mcnisperrainc^ and paramenispermine, as well as about 25 per cent of fixed oil. USE.Cocculus, in the form of the tincture, is used as a parasiticide; however, the drug is a convulsant poison. It should not be administered internally. Picrotoxin or Cocculin (U.S.P. 1882 to 1905, 1942 to 1955; N.F. 1955 to date) is an active principle obtained from Anamirta Cocculus. It is an equimolecular compound of picrotin and picrotoxinin. It occurs as flexible, shining, prismatic crystals or as a microcrystalline powder. It is odorless and stable in air, but is affected by light. The melting point is between 198 and 200 C.

11

Glycoside?

Arnica

in-

sufficiency, angina pectoris, and bronchial was also known to the Greeks and I Romans. It asthma. Usual dose, 50 to 100 mg. 3 times is characterized by its aromatic I odor and its daily; intramuscularly or intravenously, when aromatic, bitter taste. The 1 chief constituents of Calamus are acorin, a I bitter necessary. PRESCRIPTION PRODUCTS.Khellin is rep- glycosidai principle, volatile oil (1.5 b I 3.5 per resented in the products: Ammivin, cent), resin and tannin. Calamus wis I used as a Bene-cardin*, Eskel, Khelisem, Khelltron*. carminative, an aromatic bitter. I and as a flavoring agent. The dose was I formerly listed Khelloyd, and others. as 3 Gm. In a recent study,1 investigators have I ARNICA reexamined the rhizome of Acorus Calcnnu: I to Arnica or Arnica Flowers (U.S.P. 1851 to determine the physical, chemical and I 1926; N.F. 1926 to date) consists of the dried pharmacological properties of the volatile I oil it flower head of A mica montana Linne, known in contains. commerce as European Arnica, or of Arnica fulgens Pursh., Arnicasororia Greene, and Eupatorium, Thoroughwort or Boneset I (U.S.P. Arnica cordifolia Hooker, known in commerce 1820 to 1916; N.F. 1926 to 1950 I consists of the as American Arnica (Fam. Composite). All of dried leaves and flowering I tops of Eupatorium perfoliatum Linne (Fam. I Composite). these perennial herbs are indigenous to cold mountainous regions; A . montana in central Eupatorium was named in I honor of Eupator, Europe and the other species as well as A . King of Pontus, who is said to have used one of montana in northwestern United States and the species in | medicine; perfoliatum means having a sessile, clasping leaf. The plant is a southwestern Canada. perennial herb indigenous to eastern and central Formerly, the commercial drug was obtained from central Europe but during World War II, North America. The drug was used as a domestic when European imports ceased, the American remedy by the early colonists; boneset "tea" was a favorite remedy for many years. The chief arnica met the need. Since World War II the constituent is a bitter, crystalline commercial supply has again been furnished by northern Italy and the American drug has disappeared from the market. Arnica has been used in European medicine since the lGth century. DESCRIPTION, STRUCTURE AND POWDER. See the National Formulary XI. CONSTITUENTS.Arnica contains a bitter, crystalline principle called arnicin (about 4 per cent); resins and various organic acids are also present. ADULTERANTS.Flower heads of other composite plants are sometimes admixed with Arnica Flowers. Frequently the involucre and .torus of the flower heads are injured ou the plant or after collection, by the. larvae of the insect, Trypeta arnicivora. For. this reason, it is advisable to store Arnica in tightly stoppered containers consuming a pledget of cotton saturated with carbon tetrachloride or other insect pre-. ventive substances,. USES.Arnica is listed as a local irritant. In the form of theUincture, it is applied to bruises, sprains, abrasions and slight wounds, its action being that of a vulnerary. Al though it has been used internally as i stimulant to increase temperature arj: secretions, its effects are said to be follower I by transient depression and debility.
Calamus or Sweet Flag (U.S.P. 1820 t I 1916; N.F. 1936 to 1950) is the peeled, driec rhizome of Acorns Calamus Linne (Fam I Aracex). The specific name Calamus mean: I "a reed" and refers to the habitat of tiki plants since they generally grow in swamp;. I land. The rhizomes are collected in &t I autumn, separated from the leaves and rooti. I split longitudinally, and sometimes peelec I before drying. During the drying process I the rhizome shrinks considerably and lose; J about 75 per cent of its weight. A confectior. I is made by "candying" the fresh rhizomes I The drug was employed in India in ancient I times and Investigation! of Volatile Oil, J. Phartn. and Pharmacol., 11 (3), 163-168, 1959.

1 DANDIYA, P-C, BAXTER, R. M., WALKEB, G. C. and CULLUMBINE, H.: Studies on Acorus Cdarnxu, Part II.

glycoside, eupatorin; in addition, a volatile oil and resin are also present. Eupatorium was used as a stimulant and a diaphoretic; in large doses it possesses emetic and cathartic properties. The drug was formerly given in doses of 2 Gm. Other drugs containing glycosides or bitter principles are: Asclepias, Pleurisy Root or Butterfly Weed (U.S.P. 1820 to 1905; N.F. 1916 to 1936). Asclepias Syriaca or Common Milkweed (U.S.P. 1820 to 1863; 1873 to 1882). Baptisia or Wild Indigo Root (U.S.P. 1831 to 1842; N.F. 1916 to 1936). Boldo or Boldus (N.F. 1916 to 1936). Cornus Florida or Common Dogwood Bark (U.S.P. 1820 to 1894; N.F. 1916 to 1936). Cypripedium or Lady Slipper Root (U.S.P. 1863 to 1916; N.F. 1916 to 1936). Euonymus or Wahoo Bark (U.S.P. 1863 to 1916; N.F. 1916 to 1947). (A recent investigation has shown that Euonymus contains a cardiac glycoside called euatroside1.)
Eupatorium Purpureum, Joe-pye Weed or Gravel Root

FI.AGG, J.: Aloe Vera Gel in Dermatological Preparations, Amer. Perf. and Arom., 7!, (4), 27-28, 1959. FltlKDHICtt, H.: The Biosynthesis of Atilhraqm-nones, Planta Medica, 7, 367-382, 1959. GRIFFITH, J. Q. JR., KREWSON, C. S. and NAGHSKI, J., eds.: Rutin and Related Flavonoids, Easton, Pennsylvania, Mack Publishing Company, 1959. JENSEN, K. B. and TENNOE, K.: Paper Chromatography of Cardiac Glycosides and Aglycones from Digitalis lanata, J. Pharm. and Pharmacol., 7, 334-340, 1955. LICHTI, II., VON WARTBURG, A. and RENZ, J.: New Cardio-Active Glycosides from JJrginca ( =Scilla) Altissinia (Liliaceac), Angew. Chem., 72 (2), 85, 1960. LOWN, B.: Current Concepts in Digitalis Therapy, Boston, Little, Brown <k Company, 1954. LYMAN, R. L., BICKOFF, E. M., BOOTH, A. N. and LIVINGSTON, A. L.: Detection of Coumestrol in I.egUminose Plants, Arch. Biochem. Biophys., 80, 61-67, 1959. MARTIN, G. J. and SZKNT-GYORGYI, A.: Bioflavonoids and the Capillary, Annals of the New York Acad. Sci:, 61, 637-736, 1955,. MORRIS, fyt. P., ROARK, B. A. and CANCEL, B.: Simple Procedure for the Routine Asisay of Dios-corea Tubers, J. Agr. Food Chem., 6, 856-858, 1958. MURPHY, J. E.: GitosideA New Digitalis Glycoside, J. Amer. Pharm. Assoc., Sci. Ed., 46 (3) 170-172, 1957.

(U.S.P. 1820 to 1842).

Eupatorium Teucrifolium or Wild Hore-hound

(U.S.P.

1820 to 1842). (N.F. 1916 to 1936). (N.F. 1910 to 1936). Galega or European Goat's Rue (N.F. 1916 to 1930). Hepatica or Liverwort (U.S.P. 1831 to 1882). Hydrangea or Seven Barks (N.F. 1916 to 1926). Juglans or Butte:nut Bark (U.S.P. 1820 to 1905; N.F. 1916 to 1936): Lactuca Elongata or Wild Lettuce (U.S.P. 1820 to 1851). / Lactacarium,(U.S.P 1820 to 1926). Lactu-carium is an ingredient in CosanyK LModen'dron or Tulip-tree Bark (U.S.P. ; 1820 to 1882). .; Magnolia (U.S.P. 1820 to 1894). Marrubium or White Horehound (U.S.P. 1820 to 1915).
Farfara, Tussilago or Coltsfoot Fraxinus or White Ash Bark
1

Euonymus atrojiurpurca Jacq. II. A Study of the Structure

Buss, C. A. and RAMSTAD, R.: Cardiac Glyco-Hidce of

of Euatroside and Euatromonoside, J. Amer. Pharm. Assoc., Sci. Ed., (7), 423-426, 1957. Paracoto or Para-coto Bark (N.F. Pulsatilla or Pasque Flower

1916 to 1926). (U.S.P. 1882 to 1905;

N.F. 1916 to 1947).

Ranunculus or Crowfoot Scutellaria or Skullcap

(U.S.P. 1820 to 1882). (U.S.P. 18G3 to 1910; N.F. 1916 to 1926).

1916 to 1947).
Verbena or America Blue Vervain (N.F.

ADDITIONAL READING REFERENCES

BEGLINCER, E. and LOCKE, E.: Charcoal Its Manufacture BRADLEY, C. E.: Yerbe de la Fleche Arrow and Fish
Poison of the American Southwest, Econ. Bot., 10 (4), 362, 1956. POSE, B. C, VIJAYVARGIYA, R., SAIFI, A. O. and SHARMA, S. K.: Some Aspects of Chemical and Pharmacological Studies of Acorus Calamus Linu6, J. Amer. Pharm. Assoc., Sci. Ed., 9 (1), 32-34, 1960. FERGUSON, T. P. and WEAVING, A. S.: Rutin in Tobacco Grown in a Greenhouse, Nature, ISS, 64, 1959. FIEDLER, K. II. and GISVOLD, 0.: A Preliminary Phytochemical Investigation of Digitalis yrandi-Jlora, J. Amer. Pharm. Assoc., Sci. Ed., /,6 (5), 317-320, 1957. and Use, Econ. Bot., // (2), 160, 1957.

13

Glycoside?

Additional Reading References

PRATT, R. and YUZURIHA, Y.: Antibacterial Activity of the Heartwood of Haematozylon brazil-elto, J. Amer. Pharm. Assoc., Sci. Ed., 48 (1), 69-72, 1959. SCHWARTZ, S. M. and GISVOLD, 0.: A Preliminary Phytochemical Investigation of Digitalis lutea Second Year Growth, J. Amer. Pharm. Assoc., Sci. Ed., 40 (5), 321-329, 1957. THOMPSON, R. H.: Naturally Occurring Quinones, New York, Academic Press, Inc., 1957. WALTER, E. D.: Isolation of a Saponin, Hedcrin, find its Sapogetlin, flederogenin, from Bur Clover (Mcdicago hispida), J. Amer. Pharm. Assoc., \ Ed., 40 (8), -166-167, 1957. ------------- : Note on Saponins and Their Sapogor.^ from Strawberry Clover, J. Amer. Pharm. Assoc Sci. Ed., 40(11), 735-736, 1960. WILLAMAN, J. J.; Some Biological Effects of A Flavonoids, J. Amer. Pharm. Assoc., Sci. K<i . (7), 401-408, 1955. WILLIAMS, L. 0.: Ginseng, Econ. Bot., // (4), 3l< 34S, 1947. WORTH EN, L. R., BENNETT, E. and CZARNECKJ, f. 13.: Chromatographic Boliavior of Afoi'n, ; Pliann. and Pharmacol., //, 384, 1959.

Tannins

Chapter

Tannins
Tannins comprise a large group of complex substances that are widely distributed in the plant kingdom; almost every family of plants embodies species which contain tannins. When tannins occur in appreciable quantities, they are usually localized in specific plant parts such as leaves, fruits, barks or stems. Although often found in immature fruits, tannins usually disappear during the ripening process. It has been theorized that the fruit employs the energy supplied by the oxidation of these tannins in its metabolic processes, also that the tannins are the source of fruit acids. Another theory suggests that since tannins are antiseptic in action, they prevent damage by insects and fungi. This idea probably originated from results of investigations into the occurrence of tannins in insect galls on plants. Obviously, the role of tannins in plant metabolism is somewhat speculative, but they probably serve as a protective to the plant during certain stages of growth, and are finally either destroyed or deposited as end products of metabolism in certain dead tissues of the mature plant, i.e., outer cork, heartwood, and galls. In deciduous trees the leaves that are shed at the end of the growing season generally show the presence of a considerable amount of tannins. If it is assumed that tannins are metabolic waste products''and that they are of little use to the plant, it is logical to believe that such leaves, normally destined to be separated from the stems, would represent a convenient method of tannin release from the plant. Tannins are non-crystallizable chemicals which with water form colloidal solutions j)bssessing an acid reaction and a sharp "puckering'' taste. They cause precipitation of solutions of gelatin as well as of alkaloids, they form d^^^^or CTeenlsh black solubl| compounds^iTirt^rric^RsT^hey produce a
f 168) deep red color with potassium

The ability of tannins to precipitate proteins is also utilized in the process of vege- table tanning by which animal hides are converted to leather. The tannin affects not only the pliancy and toughness of the leather, but being antiseptic, acls as a preservative. Various types of tannins produce a variety of leathers; thus, the ellagic acid type forms a "bloom" while the phlobaphene type causes the "tanner's red." The deeply colored compounds obtained with iron salts have been used in the manufacture of inks on a commercial scale. Because of therr precipitating qualities, solutions of tannins are utilized in the laboratory as reagents for the detection of gelatin, proteins, and alkaloids. In the antidotal treatment of alkaloidal poisoning, tannin solutions are extremely valuable for

ferricyanide and arnmoni|L, and'they are precipitated by salts of copper, lead, and tin, also by strong aqueo'usJpot^lum^^icMbmate (or 1 per cent chromic acid)^solution's. In alkaline solutions many of their derivatives readily absorb oxygen. Tannins precipitate proteins from solution and are able to combine with them rendering them resistant to proteolytic enzymes. When applied to living tissues this action is known as an "astringent" action, and forms the basis for the therapeutic application of tannins. Many tannin-bearing drugs such as nutgall, krameria, gambir, and kino as well as partially purified tannins (tannic acid) and their derivatives (acetyltannic acid) are employed in medicine as astringents, both to the gastrointestinal tract 'and on skin abrasions. tin the treatment of burns, the proteins of the exposed tissues are precipitated forming a mildly antiseptic/-protective coat under which the regeneration of new tissues may take place.

inactivating the alkaloid by the formation of insoluble tannale. Chemically, tannins arc complex substances; they usually occur as mixtures of polyphenols that are very difficult to separate since they do not crystallize. While some tannins may appear to be g!ytt*idic in nature, the majority probably4re not. When hydrolyzed, they yield relatively simple polyhydric phenols (1) gallic acid, which is broken down to pyrogallol; (2) protccatechuic acid, which is broken down to catechol, ..(3) "ellagic acid, etc. The phenolic groups of the tannins are responsible for their astringent and antiseptic actions as well as their coloration with iron salts. on + co2

c. They form a blue color withFeCl3 Ti d. They do not form a precipitate win bromine T.S. Examples of pyrogallotannins are gallo tannin in nutgall, and ellagitannin in oil bark and in pomegranate bark.

HAMAMELIS Hamamelis Leaf or Witch Hazel Leave (U.S.P. 1882 to 1916; N.F. 1916 to 1955) it the dried leaf of Hamamelis Virginia* Linne (Fam.

Hamamelidacex).
Hamamelis Bark or Witch Hazel BiA (U.S.P..1905

to 1916)

consists of the

bar* and

twigs

of

V
COOH Protocatcchuic acid

Hamamelis virginiana. Hamamelis is from the Greek harm, meaning "at the same time" and metis ineafr ing "a fruit"; virginiana indicates that tbt plant
is found in Virginia, although actual habitat ranges from New Brunswi to Minnesota and extends southward Florida and Texas, particularly in low, da woods. The plant is a shrub or small t attaining a height of 8 meters. The flow (see Fig. 90) appear in the fall at the sa time as the ripening period of the frui of the previous year. The leaves collected throughout the summer and dried in the open air, preferably un shade to preserve the green color. Gathe~ terminates at the first sign of frost since this causes the leaves to turn brown, thus d*-creasing their market value. The commercaJ supply comes from the Blue Ridge MounUa region, chiefly from Virginia, North Carol" and Tennessee. The decoction or infusion witch hazel leaves has been in common ua since the days of the early colonists wbtr

+ CO,

Oil HO/V

HOA Catechol
The classification of tannins is based upon the colors obtained with iron salts. Demonstrations have shown that in the presence of ' catechol with its two adjacent phenolic groups, a green color is obtained with ferric iron and in the presence of pyrogallol with its three adjacent phenolic groups, a blue color. In practice,-however, where tannins of both types may be present in the same plant extract,' the one present in larger amount will mask the one present in lesser amount. Then too, tannins of the ellagic acid type, which contain pyrogallol nuclei, may produce a green coloration because two ^adjacent phenolic groups are present on each sideiof the molecule. The usual classification of tannins is as. follows: 1.'Catechol (Pvrvcatecliol/ Tannins or Phlo-batajinitis show thel following characteristics: a. When heated, they yield catechol^ b. When boiled with HC1, they yield insoluble, red phlobaphcncs, c. They form a green color with FeCl, Ti d. Thev form a precipitate with bromir* T.S. Examples of catechol tannins are kinc-tannic acid in kino, and catechutannic acic in gambir.and in catechu. 2. Pyr'ogallotannins show these-charactcrL-tics : a. When heated^ they yield pyrogallol. b. When boiled with HClj they yield gallr acid or ellagic acid, j

Tannins

FIG. 90.Autumn flowers of the Witch Hazel tree. (Photo by Claus.)

learned of the drug from the American Indians. DESCRIPTION, STRUCTURE AND POWDER. See Figure 91 and the National Formulary IX. CONSTITUENTS.Both leaves and bark contain hamamelitannih and a second tannin which appears to be-derived from gallic acid and a hexose sugar, a volatile oil, a bitter principle, gallic acid and calcium oxalate. Hamamelin is an evaporated alcoholic extract of. either the leaves or bark, that of the former being greenish black arid more permanent. USES AND DOSE.Both leaves and bark possess astringent and hemostatic properties. Usual dose, 2 Gni., Hamamelis Water or Distilled Witch Hazel Extract (U.S.P. 196.5 to 1926; N.F. 1888 to 1905, 1926 to date) is prepared as follows: Macerate a weighed amount of the recently cut and partially dried dormant twigs of Hamamelis virginiana for about 24 hours in about twice their weight of water; then distil until not more than 850 ml. of distillate is obtained for each 1000 Gm. of the twigs taken; add 150 ml. of alcohol to each 850 ml. of distillate; mix thoroughly. DESCRIPTION.Hamamelis Water is clear and colorless, having a characteristic odor and taste; it is neutral or slightly acid to litmus paper, and free from methanol, formaldehyde,

acetone, isopropyl alcohol: and tertiary butyl alcohol.

CONSTITUENTS. On evaporation Hamamelis Water yields not more than 0.025 per cent of dry residue. The alcohol content ranges from 14 to 15 per cent by volume, of CHjOH. The identity of the aromatic volatile principle present is not known; it is

17

Tannins

FIG. 91.Hamamelis Leaf: A, transverse section of a midrib from about middle of the leaf-blade, showing an arch-shaped collateral vascular bundle situated near the upper or ventral epidermis and a stele with central pith (7') near the center of the section: Ep, ventral epidermis; Coll, collenchyma; P, palisade celL. St, sclerenchymatous fibers; H, tracheae; L, sieve; T, pith; Ca, calcium oxalate; A, colorless tissue; D, dorsal epidermis. B, transverse section of a thin mesotomc strand of leaf-blade: Ep, ventral epidermis; Coll, collenchyma; P, palisade tissue; St, stone cells; PS, parenchyma sheath; N, loose mesophyll. C, transverse section of leaf-bLade: Ep, ventral epidermis; D, dorsal epidermis; Sc, colorless stone cells (also called idio-blasts); N, loose mesophyll; in figures a and b the palisade and pneumatic tissue are shown with thick-walled ..stone cells, branched in a, penetrating epidermis in-" 6/ in c one end of. a sclereid is entering an epidermal cell, "alid.in d, is shown a surface view of the epidermis with the end of a stone cell. D, basal portion of a 4-brancBed hair from the dorsal epidermis of leaf, showing very thin cross-walls in the branches. E, surface view of dorsal epidermis .of leaf-blade, showing the stomata (S) and oil globules (0). F, transverse sectioD a midrib from near the summit of the leaf-blade; letters as A. (After Holm )

not present in the dry witch hazel bark and may be formed during the maceration of the twigs in the water. USES.Hamamelis Water possesses astringent properties and is applied externally by rubbing or fomentation to relieve congestions, bruises, hemorrhoids, etc. Krameria or Rhatany (U.S.P. 1831 to 1916, 1926 to 1936; N.F. 1916 to 1926, 1936 to 1947) is the dried root of Krameria triandra Ruiz et Pavon, known in commerce as Peruvian Rhatany; or of Krameria argentea Martius, known in commerce as Para or Brazilian Rhatany (Fam. Leguminosx). Krameria was named in honor of J.G.H. and W.H. Kramer, two 18th century German botanists; triandra is Latin, meaning three stamens, and argentea refers to the silvery appearance of the leaves. The plants are low shrubs with spreading branches. Krameria triandra. grows on the sandy slopes of the Bolivian and Peruvian Cordilleras, and Krameria argentea is found mostly in Brazil, being shipped from Para or Rio de Janeiro. Krameria contains from 8 to 20 per cent of tannin, krameric acid, starch, an uncry-stallizable sugar, and calcium oxalate. The tannin is a phlobatanuin and is colored dark green with solutions of ferric salts; it forms the phlobaphenc, krameria-rcd, and. upon further decomposition yields phloroglucin and protocatechuic acid. Krameria is used as an astringent and a tonic. The dose was listed as 1 Gin. ' Chestnut Leaves (U.S.I\ 1873 to 1905; N.F. 1916 to 1947) consist of the dried leaves of Castanea dentata (Marshall) Borkhausen (Fam. Fagacex). The leaves are gathered at the time of flowering of the tree or shortly afterward and are carefully dried. Chestnut leaves cojn^ybj^per^e^^ acid, which is colored green with feme sluts, and a mucilage which is insoluble in alcohol. It is.used as a tonic and an astringent!, Usual .dose, 4 Gm. ^ " '(^mquapin^ark (U.S.P. 1820 to 1851) is the dried bark of Castanea pumtkriMichaux (Fam. Fagacex). '(This bark^ like that of the chestnut, contains! tannin and has been used as an astringent. The seeds are smaller than chestnuts but contain about 45 per cent of starch and 2.5 per cent of protein. Kino (U.S.P. 1820 to 1942; N.F. 1942 to 1950) is the dried juice obtained from the trunk of Pterocarpus Marsupium Roxburgh (Fam. Ijegnminosse). The name Pterocarpus is Greek and signifies a winged carpel or fruit; Marsupium is Latin, meaning a bag or pouch and refers to the shape of the fruit; kino is the native name given the_drug by the Mandingo tribe of West Africa. The plant is.a large timber tree growing in central and eastern India and in Ceylon. The genus is widely distributed over the earth, and astringent drugs from these species, as well as from other plants not even remotely related to

Pterocarpus, have come to be known by the name

kino. The phloem contains secretory cells with a red astringent fluid which exudes from the surface when the bark is injured. Vertical incisions are cut into the bark which terminate at their lower end into an oblique incision from which the juice is collected in cups. This juice is dried in shallow pans in the sun and the drug is shipped from Bombay; that shipped from Madras is known as Malabar or East Indian Kino. The drug has been used as an astringent in India for many centuries. DESCRIPTION.Kino occurs as small, angular, opaque or translucent, glistening, brittle pieces, less than 10 mm. in diameter, and reddish black to dusky brown in color. It has no odor but has a rather sweet taste. It is very astringent and adheres to the teeth when chewed, the saliva being colored red. CONSTITUENTS.Kinotannic acid, 30 to 80 per cent; kinoin, 1.5 per cent; catechol (pyrocatechin); kino-red; gallic acid; resin; gum; pectin; 13 to 15 per cent of moisture; and an oxidase enzyme which may cause gelatinization of galenicals made from kino Iby converting the kinotannic acidinto kino-red, an insoluble, amorphous red phloba-phene. Kino gives a blackish green color and precipitate with ferric chloride solution, and a violet color with solutions of ferrous salts. STANDARDS.Kino yields not less than 60 per cent of alcohol-soluble extractive and not less than 75 per cent of water-soluble extractive.

19

Tannins

Ceanothus USE AND DOSE.Kino is an astringent. Usual dose, 500 mg. Gambir or Pale Catechu (U.S.P. 1905 to 1936; N.F. 1936 to 1950) is the dried aqueous extract prepared from the leaves and twigs of Uncaria Gambir (Hunter) Roxburgh (Fam. Rubiaccx). Gambir is the native Malayan name of the plant. The plant is a climbing shrub growing in the Malay States and in the East Indies. The natives gather the leaves and twigs and extract them by boiling with water. The aqueous extract is evaporated in tubs and when sufficiently thick is cut into cubes that are dark red to light brown in color. These cubes are frequently dried over fires. Most of the drug is produced in Singapore, Bin-tang and British North Borneo. Gambir is one of nic first substances known as catechu (Malay cate, a tree; chu, juice) which were described about the sixteenth century. The catechu of Barbosa (1514) was probably black catechu. The first account of gambir seems to be that of a Dutch trader in 1790. Its production in Singapore dates from 1820. It rarely occurs on the present day market. CONSTITUENTS.Catechutannic acid, 22 to 50 per cent, resembling the tannin in oak bark, kino and krameria; pyrocatcchol, up to 30 per cent; catechin, which crystallizes in silky needles; gambir-fluorescein; catechu red and quercetin. STANDARDS AND TESTS.Gambir yields not less than 60 per cent of alcohol-soluble extractive and not less than 70 per cent of water-soluble extractive. Macerate 1 Gin. of powdered gambir with 50 ml. of distilled water for one hour, filter; separate portions of this filtrate give an intense green color with dilute ferric chloride T.S. and no precipitate with cupric sulfate TS.

1;;

porous, and has a sligli odor and an astringent and sweetish task It contains about 25 per cent of phlobatanni: called catechutannic acid and is used i an astringent. Very little catechu can U found on the market. Substances referred to as "black catechu have been prepared froin many other speei-of plants, particularly from species of Acac-,: and of Cxsalpinia of the Leguminosx. Ceanothus, New Jersey Tea or Red Root t the dried bark of the root of Ceanotk-j americanus (Fam. Rhamnacex) a branch it.; shrub, 6 to 12 dm. high, of the eastern an: central United States and Canada. The larr-woody root with many branches is terminated with a knotty crown product numerous slender stems. The plant has low been used as an astringent; during tlx Revolutionary War the leaves served as I substitute for tea. The drug has been shown to possess marked blood-coagulative powen when administered by mouth.1 Ceanothus contains tannin (10 per cent), phlobaphenes, resin and oil; die blood coagulating substances consist of a mixture o: acids: succinic, oxalic, malonic, malic, ortho-phosphoric and pyf ophosphoric. The drug is
1 LYNCH, T. A., MIYA, T. S. and CARR, C. F.: A Investigation of Blood Coagulating Principles froa Ceanothus americanus, J. Amer. Pharm. Assoc., Sc. Ed., 47, 816-819, 1958. '

(catechutannic acid).

Extract powdered gambir with alcohol and filter; to the filtrate add sodium hydroxide T.S., and, after shaking, a few ml. of petro-. Ieum Senzin; upon standing, the benzin layer shows a strong green fluorescence

(gambir-"Huoresceiri). *

Wet a match stick with an aqueous extract of gambir so diluted as to impart a slight tint to the wood; dry it^ dip it into hydrochloric acid, quickly remove it, and warm it near a flame; a deep purplish red stain is developed (catechin). Compare this test with a sirail-one using a solution of phloroglucinol. USES AND DOSE.Gambir is an astringent It is also employed in tanning and is used u a mordant in dyeing. The dose was formed; listed as 500 mg. Mangrove Extract is prepared from th-bark of the red variety of Rhizophora manga or R. mucronata (Fam. Rhizophoracex) an: contains about 70 per cent of tannic acic It is sometimes sold as catechu. Catechu, Black Catechu or Black Cuta (U.S.P. 1820 to 1905) is an extract prepare: from the heartwood of Acacia catechu (Fart Leguminosx), a tree indigenous to India an: Burma. The wood is extracted with boilirj water, the extract strained, evaporated to i syrupy consistency and allowed to harden The drug occurs in irregular masses, wit: fragments of leaves or mats upon the out-side; it is reddish black, somewhat shin;, brittle, more or less

considered a hemostatic and a blood coagulant. PRESCRIPTION PRODUCT.Ceanothyn*. TANNIC ACID Nutgall (U.S.P. 1820 to 1942; X.F. 1947 to 1955) is the excrescence obtained from the young twigs oiQuerpus infectotfih Olivier and other allied species of Quercus (Fam. Faga-cex). The galls are obtained principally from Aleppo, in Asiatic Turkey. The excrescence (gall) is due to the puncture of a hymenoptcrous insect, Cynips tincioria, and the presence of the deposited ovum; there are several stages in the development of the gall corresponding to the development of the insect: 1. When the larva begins to develop and the gall to enlarge, the cells of the outer and central zones contain numerous small starch grains. 2. When the chrysalis stage is reached, the starch near the middle of the gall is replaced in part by gallic acid, but the peripheral and central cells contain masses of tannic acid. 3. As the winged insect is developed nearly all of the cells contain masses of tannic acid with a slight amount of adhering gallic acid. 4. When the insect emerges from the gall, a hole to the central cavity is formed. Thus, the tannic acid, due to the presence of moisture and air, may be oxidized in part into an insoluble product, and the gall becomes more porous, constituting the so-called White Gall of commerce. The technical and medicinal use of galls was known to the ancient Greeks (450 B.C.). Ever since the Crusades, great quantities of them have been exported from Asia Minor. DESCRIPTION, HISTOLOGY AND POWDER. See the National Formulary IX. .CoNSTrruENTS.The principal constituent is

American nutgalls are formed on Quercus coccinca and Q . imbricaria by Cynips aciculala. When fresh they are globular, 1.5 to 3 cm. in diameter, and of a yellowish, somewhat mottled color. On drying they become yellowish to dark brown and m u c h shriveled. Texas nutgalls are formed on the live oak (Quercus virens) and yield 40 per cent of tannic acid. California oak galls are excrescences on Quercus lobata and contain considerable tannic acid. Tannic Acid, Gallotannic Acid or Tannin (U.S.P. 1842 to 1950; N.F. 1950 to date) is a tannin usually obtained from nutgall. The powdered galls are extracted with a mixture of ether, alcohol and water; the liquid separates into two layers, the aqueous layer containing gallotannin and the ethereal layer the free gallic acid present in the gall. After separation the solution of gallotannin is evaporated, the tannin being purified in various ways. Acetone and other solvents are sometimes used, and it is said that a considerable amount of commercial tannin comes from Chinese and Japanese galls. DESCRIPTION AND TESTS.Amorphous powder, glistening scales or spongy masses, light brown to yellowish white; odor faint; taste strongly astringent. Tannic acid is soluble in water, alcohol and acetone, and insoluble' in ether, chloroform and benzin. An aqueous solution of tannic acid is colored bluish black with ferric chloride T.S., and precipitates alkaloids, albumin and gelatin from solution. Tannic acid loses not more

tannic acid,Vhich is found to the extent a^so con*ams of JjLfe&^QPgr_^f_njjifre ganiclffl?^6*^pe7^itEllagic acid; starch and resin. STANDARDS AND TESTS.An aqueous mixture of powdered nutgall (1 in 10,000) gives a dark blue precipitate with 5 per cent ferric sulfate solution; a- dark brown precipitate with 1 per cent ferric acetate solution; an 6range-brown color and a slight precipitate
with saturated potassium dichromate plus a trace of acetic acid; and a yellowish brown color and a slight precipitate with 1 per cent sodium carbonate solution. USES AND DOSE.Nutgall is the source of tannic aeid'and is used in the tanning and dyeing industry and in the manufacture of ink. Medicinally, i t is used as an astringent. The dose was formerly listed as 500 mg.4 ALLIED PRODUCTS.Japanese and Chinese Galls are formed on Rhus japonica and R. semialata (Fam. Anacardiacex) respectively, due to the stings of certain plant lice ( A p h w ) . These galls arc very rich in tannin, and, as they contain less coloring matter than the oak galls, are used in the manufacture of gallic acid.

21

Tannins

Tannic Acid than 12 per cent of its weight upon drying at 100 C. and yields not more than 0.5 per cent of ash. It should be free from gum, dextrin, and resinous substances. USES AND DOSETannic Acid is an astringent and is used in the treatment of burns. It is an alkaloidal precipitant and, as such, has been employed in cases of alkaloidal poisoning. As an antidote, it was administered in doses of 1 Gm. PROPRIETARY PRODUCTS.Amertan Jelly Hexaltan* Jelly, and Rhulitol contain tannic acid as an ingredient. RELATED SUBSTANCES.Tannic acid is the basis for the following preparations or derivatives: Acetyltannic Acid or Diacetyl Tannic Acid (U.S.P. 1926 to 1942) is a product obtained by the acetylization of tannic acid. Usual dose, 0.6 Gm. Albumen Tannate (U.S.P. 1926 to 1912) is a compound of albumen (usually egg albumen) and tannic acid. Usual dose, 2 Gm. Gallic Acid . (ILS.P. 1851 to 192G; N.F. 193G to 1947; as a reagent, U.S.P. 1926 to 19G0; as a reagent, N.F. I960 to date) is 3,4,5-trihydroxybenzoic acid, crystallizing with, one molecule of water. It occurs in nutgall; in addition, it may be prepared from tannic acid by hydrolysis with dilute acids. It consists of white or fawn-colored silky needles having an astringent, slightly acidu-luous taste; it is soluble in water-and in alcohol but insoluble in chloroform. It neither precipitates nor forms colored solutions with pure ferrous salts, and it should be free from tannic acid. USES.Gallic Acid possess mild astringent properties. The dose was formerly listed as 1 Gm. \ Pyrogallol or Pyrogallic Acid (U.S.P. 1894 to 1942; N.F. 1942 to 1960; as a reagent, U.S.P. I960 to date) is 1,2,3-trihydroxyDenzcnc. It is obtained^by Keating gallic acid. ^ It occurs as white leaflets or fine needles that -are soluble in water, alcohqLarid ether/ Solutions of pyrogallol are rapidly oxidized byair, particularly in thej|resence of alkalis. USES.Pyrogallol is a local irritant-and a local antibacterial, -dt is used externally as an antiseptic in skin infections. r Rose, Red Rose, French Rose or Rosa i Gallica (U.S.P. 1831' to 1936; N.F. 1936 to 1950) is the dried petals of Rosa gallicc Linne (Fam. Rosacex), collected just before the expansion of the flowers. The generk name Rosa is the ancient Latin name for the rose; gallica means "of or pertaining t< Gaul," now France. The plant is a shrul indigenous to southern Europe and prohahl;. western Asia, and extensively cultivated in all parts of the world. The petals are obtained from cultivated plants before the expansion of the flower, the lower clawed portion usually being removed; they are used fresh or are carefully dried and preserved. The chief supply of the drug is obtained froir. southern France. Rosa gallica is said to have been introduced into France in 1241 by the Count of Champagne on his return from the
Crusades.

CONSTITUENTS.The drug contains tannic and gallic, acids, a yellow crystal 1 in-rhamnoside (quercitrin) which yields qucr-cetin and rhamnosc. (NOTE: Rose Oil U.S.P XVI is a volatile oil obtained from the fresh flowers of Rosa gallica and other species See p. 212.) USE.Rose is used as a mild astringent. Rosa Centifolia, Pale Rose or Hundred-leaved Rose (U.S.P. 1820 to 1905) consists of the petal of Rasa centifolia Linne, collected after the expansion of the flowers and carefully dried. This drug was used as an astringent. The fruits of the above species and others of the genus Rosa represent a rich source of natural vitamin C. Many plants contain tannins and a number of these yield drugs which have been recognized officially in the past. Black Oak Bark or Quercitron Bark (U.S.?. 1820 to 1873) is the inner bark of Quercus velutina Lamarck (Fam. Fagaccse). It contains the glycoside, quercitrin, which yields the yellow quercetin. Diospyros or Persimmon (U.S.P. 1820 to 1882) is the unripe fruit of Diospyros virginiana Linne (Fam. Ebenacex). -.The unripe fruit contains a considerable amount of tannin and was used as an astringent. The ripe fruit contains malic acid and sugar and is edible. Geranium or Cranesbill (U.S.P. 1820 to 1916; N.F. 1916 to 1936) is the dried rhizome of Geranium maculatum Linne (Fam. Ger-

anvacex). The drug contains from 15 to 25

per cent of a gallotannin. Geum or Water Avens (U.S.P. 1820 to 1882)
is the dried root of Geum rivalc Linne (Fam.

var. carohmana Gray (Fam. Plumbaginace The root contains about 18 per cent of ta nin. Tormentilla (U.S.P. 1820 to 1882) is t dried rhizome of Potentilla tormentilla Lin (Fam. Rosacese). It contains from 18 to per cent of tannic acid, tormentilla red decomposition product of tannin), ella^ acid, resin and a volatile oil. White Oak Bark (U.S.P. 1820 to 1916; N. 1916 to 1936) is the dried inner bark Quercus alba Linne (Fam. Fagacese). It co tains 10 per cent of tannin "known as qu< citannin. Numerous other plants show the presen of large amounts of tannin in the bark ai have been employed in the tanning industi Among these are: Quebracho Bark, the bark of Aspidospcri quebracho Colorado (Fam. Apocynaccx), whi contains 20 per cent of tannic acid. A coi mercial extract is used in tanning leather. Hemlock Bark, the bark of Tsugacanadcn. (Fam. Pinacex), which is used extensive in the United States. It contains from 10 15 per cent of tannin and a small quanti of volatile oil and resin. It also is of particul use in tanning leather.
ADDITIONAL READING REFERENCES
GtfOBH, R.:

Rosacex). It contains tannins. Hehanthemum,

Frostweed or Frostwort (U.S. P. 1851 to 1882; N.F. 1916 to 1926) is the dried overground plant of Helianthemum canadense (Fam. Cistacex). It contains 10 per cent of tannic acid, a glycoside and a small quantity of volatile oil. Heuchera or Alum Root (U.S.P. 1820 to 1882) is the dried rhizome and roots of Heuchera americana Linne (Fam. Saxifragacex). It contains from 10 to 20 per cent of tannin. Prinos or Black Alder (U.S.P. 1820 to 1894) is the dried bark of Prinos verticillatus Linne (Fam. Aquifoliaccx). It contains tannin and a bitter principle. Rhus Glabra or Sumac Berries (U.S.P. 1S20 to 1916; 1926 to 1936; N.F. 1916 to 1926) is the fruit of Rhus glabra Linne (Fam. Anacar-diacese). It contains about 2 per cent of tannic acid, also gallic acid and calcium and potassium malates. The leaves of Rhus glabra contain from 16 to 25 per cent of tannin; the galls which are formed on the petioles and leaves contain about 60 per cent of tannin. Rubus or Blackberry Bark (U.S.P. 1820 to 1916; N.F. 1916 to 1936) is the dried bark of the rhizome and roots from plants of the section Eubaius of the genus Rubus (Fam. Rosacese). It contains from 10 to 20 per cent of tannin, also gallic acid, and a crystalline glycoside, villosin. Spirea or Hardhack (U.S.P. 1820 to 1882) is the root of Spiraea tomentosa Linne (Fam. Rosacea). It contains tannins. Statice or Marsh Rosemary (U.S.P. 1820 to 1882) is the root of Statice Limonium Linne

Organic Chemistry of Vegetable Tanni

Chapter XL. London, Progress in Leather Scien 1920-1945, British Leather Manufacturers As ciation, 1948. GILBERT, N. W. and BLACK, D. S.: Canaigre Potential Domestic Source of Tannin., Uni States Dept. Agri. Production Res. Rept., SS, 15, 1958. HOWES, F. N.: Vegetable Tanning Materials, L> don, Butterworths Scientific Publications, 1953 THE FARADAY SOCIETY: The Physical Chemistri, Dyeing and Tanning, London, Aberdeen, 1954