no Resins and Resin Combinations

Resins are amorphous products with a Balsams are resinous mixtures that con- complex chemical nature. They are usually tain cinnamic acid, benzoic acid, or both, formed in schizogenous or in schizolysig- or esters of these acids. Benzoin, Peru bal- enous ducts or cavities and are end prod- sam, Tolu balsam, and styrax are typical ucts of metabolism. Physically, resins are balsams. The term "balsam" has been er- usually hard, transparent, ortranent roneously applied to some oleoresins, e.g., and, heated, they soften -andnd- finally balsam of copaiba. This error has occasion- melt Chemically, theyeioiiu ally led to some confusion. tures of rei acids, resin alcohols, resi- In a few cases, resins are found in gly- are cosidal combinations; such combinations insoluble in water, and some investigators are called glucoresins or, more properly, believe resins are oxidation products of the glycoresins. Such glycoresins are found in terpenes. Several resins are used in phar- jalap and podophyllurn. macy and in the arts, among which rosin, guaiac, and mastic are typical examples. Resins often occur in more or less ho- RESINS mogeneous mixtures with volatile oils; the When resins are separated and purified, mixtures are known as oleoresins. Natural they are usually brittle, amorphous solids oleoresins are exemplified by turpentine that fuse readily when heated, after pass- and copaiba; pharmaceutic oleoresins are ing through a preliminary stage of soft- derived from ginger and capsicum. Oleo- ening. They are insoluble in water but dis- resins also occur in mixtures with gums; solve in alcohol or other organic solvents. these mixtures are called oleo-gum-resins. On evaporation these solutions deposit the Because gums are water-soluble carbohy- resin as a varnishlike film. Resins burn drate derivatives, they can be separated with a characteristic, smoky flame. from oleoresins rather easily. Oleo-gum- Resins may be the final products in de- resins include asafetida and myrrh. The structive metabolism. Many are believed to nomenclature of these resinous combina- be oxidation products of the terpenes. tions is, at best, artificial because small They are usually more or less complex mix- amounts of volatile oil are often present in tures and their principal constituents max' resins, and small amounts of gum are often be classified as follows. present in oleoresins. Resin Acids. These contain a large propor- 1 3() 140 RESINS AND RESIN COMBINATIONS

tion of oxyacids, usually combining the Biosynthesis of Resin Components. The exact properties of carboxylic acids and phenols. chemical identity of most constituents of They occur both in the free state and as resin mixtures is unknown; thus, detailed esters. They are soluble in aqueous solu- information on the bios ynthesis of these tions of the alkalies, usually forming soa plant constituents is lacking. Many resin like solutions or colloidal suspensions. components are considered to arise b y ox- Their metallic salts are known as resinates, idation of polymerized terpenoid rnetabo- and some of these resiflates are used ex- lites. Acetate and mevalonate are incor- tensive]v in the manufacture of cheap porated into some resins, and a soaps and varnishes. Examples of resin surprisingly rapid rate of "resin acid" turn- acids are abietic acid in rosin or colophony, over in pine has been suggested by studies copaivic and oxycopaivic acid in copaiba, with 11CO3. and commiphoric acid in myrrh. The aromatic acids in balsams are Un- Resin Alcohols. Complex alcohols of high doubtedly formed by way of the shikimic molecular weight, known as resinotan- acid-phenvipropanoid pathway. It is also nols, give a tannin reaction with iron salts, believed that phenyipropanoid precursors Resinols do not give such a reaction. The are involved in the formation of more corn- resin alcohols occur in the free state and as plex resin components. The lignan, po- esters in combination with simple aromatic dophyllotoxin, which presumably arises acids (benzoic, salicylic, cinnamic, and urn- via an oxidative coupling of 2 cinnamic acid bellic). The following resinotannols have residues (Fig. 6-1), is an example of this been isolated: aloeresinotannol from aloe, type of resin component. This belief is sup- peruresinotannol from balsam of Peru, sia- ported by the observed 1.4% incorporation resinotannol and sumaresinotarinol from of radioactivity into podophyllotoxin dur- henzoin, and toluresinotannol from balsam ing preliminary feeding studies using Of Tolu. The following are examples of res- phe1tvlalanineU_ 14 C and Podophyllum inols: henzoresinol from benzoin and sto- cnwdi. resinol from storax. Resenes. Complex neutral sLibstances de- Rosin void of characteristic chemical properties are called resenes. They do not form salts Rosin or colophony is a solid resin ob- or esters and are insoluble in and resist tamed from Pious patusb'is Miller and other hydrolysis by alkalies. species of Pinus Linné (Fain. Pinaceoe). Glycoresins. These are complex mixtures The commercial grades of rosin vary in yielding sugars and complex resin acids on color from light amber (the finest or hydrolysis, as with the resin of jalap. "water-white" grade) to almost black (and Pharmaceutic Resins. Pharmaceutic resins very dirty); the latter is used principally for are usually obtained (1) by extracting the destructive distillation and the production drug with alcohol and precipitating the of "rosin oils." Rosin has a great variety of resin in water, as with resins of jalap and technical uses. Only the light-colored podophyllum; (2) by separating the oil transparent rosins are used medicinally from oleoresin by distillation, as with rosin Rosin usually occurs a5 shiny, sharp, an- from turpentine and copaivic resin from gular fragments that are translucent, ropaiba; or (3) by collecting the natural amber-colored, and often covered with a product that has exuded a r oleoresin from yellowish dust. Rosin is bard, h'jjtle, and the plant through natural orartificinJ puitc- easily pulverized. Its f cture is tures and from which the natural oil has conchoidai; ]fS and taste are faintly partially evaporated into the atmosphoro, re'br-Th'ote Rosin is soluble in alcohol, as with mastic. ether, betmzoJ carbon disulfide, acetic acid, RESINS AND RESIN COMBINATIONS 141 U COOH COOH -

2 Cinnamic acid Podophyllotoxin Fig. 6-1. Proposed biosynthetic origin of podophyllotoxin. fixed and volatile oils, and in solutions of and from Virginia and North Carolina. The potassium or sodium hydroxide. drug was known to the Indians, who in- The alcoholic solution of rosin becomes troduced it to the early settlers. The drug milky white when added to water. When should not be confused with mandragora, fragments of rosin are heated in water, referred to as mandrake by the ancient they melt, flow together, and form a sticky Greeks and Asiatics (see page 200). mass. Mayapple is an important American bo- Rosin contains from 80 to 90% of the an- tanical drug; the annual production is sev- hydrides of abietic acid (which, on treat- eral hundred tons and supplies both do- ment with alcohol, are changed into Crys- mestic and export demands. talline abietic acid); sylvic acid, which is Podophyllum contains 3.5 to 6% of a probably a decomposition product of resin whose active principles are lign.ans. abietic acid; sapinic acid; pimaric acid and These include podophyllotoxrn (20%).. other acids; and resene, a hydrocarbon. a-peltatin (10%), and -peltatin (5%). A USES. Rosin is used as a stiffening agent number of lignari glycosides are in the in cerates, plasters, and ointments. It is em- plant, but because of their water solubilitv. ploed in veterinary medicine as a diuretic. they are lost during the normal preparatior Commercially, rosin is used in the manu- of the resin. facture of varnishes, varnish and paint The antimitotic and purgative properties dryers, printing inks, soap, sealing wax, of these compounds depend on a lactone floor coverings, and numerous other prod- ring in the trans configuration. Treatment ucts. Rosin is frequently used as an adul- with mild alkali produces epimerization terant of other resinous products. with formation of the stable cis isomers, which are physiologically inactive. Picro- Podophyllum podophylhn is an inactive cis isomer pro- Podophyihim consists of the dried rhi- duced in this wa y from the active trans po- zome and roots of Podophyllum peitatum dophyllotoxin. Linné (Fam. Berheridaceae) (Fig. 6-2). It is Podophyllum yields not less than 5% of also known as mayapple or mandrake. podophvllum resin. The generic name is Greek and means USES. Podophyllum possesses drastic footlike leaf; peltatum means shieldlike. The purgative properties. Its resin is also em- plant is a perennial herb that has a long, ployed as an antimitotic and caustic. ointecI, and branching rhizome. The rhi- ALLIED PLANTS. Indian podophyflum, the zomes are dug either early in the spring or rhizome of Podophyllum emodi Wallich, a in the autumn after the aerial parts have plant growing on the lower slopes of the died down. Most of the commercial sup- Himalayas, is larger and yields 11.4 to 12% plies come from the central United States of resin that contains about twice as much 142 RESINS AND RESIN COMBINATIONS

Fig. 6-2_ A tYpR taIk UI IIIUH ppnH 1 7H/III4)1I peltatu;n plants gruU III In lndlaTV PIlOt,' Courtesy of Dr. Thomas M. Zennie) podophyllotoxin as the resin obtained from inhibiting constituents of poophyIlum P. peltatum. resin. Such compounds include podo- Podophyllum resin is also known as phylloxtoxin, several podophyllotoxin de- podophyllin and is the powdered mixture rivatives, and - and -peltatin. The pci- of resins removed from podophvllum by tatins are responsible for most of the percolation with alcohol and by subse- purgative effects of the drug. quent precipitation from the concentrated PROPRIETARY PRODUCTS. Bilstan , Pod- percolate when added to acidified water. Ben-250, and Podohen° The precipitated resin is washed twice with water and is dried and powdered. it Erodictyon is an amorphous powder that varies in Eriodictyon or yerba Santa is the dried color from light brown to greenish yellow leaf of Eriodictyon californicuni (Hooker et and turns darker when subjected to tem- Arnott) Torrey (Fom. Hydrophyllaceae). peratures exceeding 2.5)'C or when exposed Eriodictyon is Greek and means wooll y, re- to light. It has a slight, peculiar, bitter taste ferring to the hairy leaves. The plant is an and is highly irritating to the eye and to evergreen shrub indigenous to the moun- mucous membranes in general. tains of California and northern Mexico. USES AND DOSE. Podophyllum resin is a The drug has been employed by the Indi- caustic for certain papillomas. It is applied ans of California for many years. topically as a 25% dispersion in compound Eriodictyon contains a resin, eriodictyol benzoin tincture or in a 70 to 96% solution (the aglycone of eriodictin), xanthoeriodic- of alcohol. Podophyllum resin has also tyol, chrysoeriodictyol, homoeriodictyol, been used as a drastic purgative and as a eriodictvonic acid, formic acid, butyric hydragogue cathartic. The dose employed acid, volatile oil, and tannin. was 10 mg. USES AND DOSE. Eriodictyon is a flavor A number of lignans with lactone rings used to disguise the bitterness of certain in the trans configuration are the tumor- preparations, such as those containing qui- RESINS AND RESIN COMBINATIONS 143 nine. It has also been used as a stimulating cus Linné (Fam. Anacardiaceae). Mastic is expectorant in doses of 1 g. Greek and means to chew; Pistacia is from Jalap the Persian pistah, the name of the pistachio Jalap or jalap root is the dried, tuberous tree; lentiscus refers to the lenticular cavities root of Exogonium purga (Wendoroth) Ben- into which the resin is secreted. The plant tham (Fam. Convolvulaceae). Jalap yields is a shrub or small tree indigenous to the Mediterranean region and cultivated in the not less than 9% of resins. Exogonium is Greek and means "outside" and "off- Grecian archipelago, especially on the is- spring," referring to the exserted stamens land of Chios. The resinous juice collects and pistils; Jalapa is the name of the city in cavities in the inner bark. Long incisions in Mexico from which the drug was first are made in the trunk and in larger obtained. The plant is a perennial, twining branches, through which the resin exudes. herb indigenous to the mountains of Mex- The resin finally collects in small tears on ico and cultivated in Mexico, India, and, to the outside. The origin of the use of mastic some extent, in the West Indies. The plant is lost in antiquity; it is mentioned by both possesses thin, horizontal, underground Theophrastus and Pliny. Mastic has long runners. The tuberous roots arise from the been chewed by Oriental women as a nodes of the runners. The roots are usually breath sweetener and is a common article dug in the fall, placed in nets, and dried in Oriental bazaars, Its employment in over open fires. This latter process ac- medicine dates back to about the 13th cen- counts for their empyreumatic odor. Our tury. nation's supply comes entirely from Vera Mastic contains about 90% of a resin, Cruz. consisting of a-resin (mastichic acid), Jalap contains resin, 8 to 12%; volatile oil; which is soluble in alcohol, and 13-resin starch; gum; and sugar. The resin contains (masticin), which is insoluble in alcohol, • number of glycosides, such as ipurganol, and a volatile oil, 1 t 2.5%, which has the • phytosterol glycoside (also found in cer- balsamic odor of the drug and consists tain ipornoea species) and jalapin, a mixture chiefly of (+ )-pinene. A bitter principle is of acidic glycosides. It also contains also present. a-methyl esculetin and palmitic and stearic USE. Mastic is used in the form of a dental acids. varnish to seal cavities. USE AND DOSE. Jalap is a cathartic and is Kava generally considered a hydragogue and a drastic purgative. The usual dose is 1 g. Kava or kava-kava is the dried rhizome Jalap resin is prepared by extracting and roots of Piper methysticurn Forster powdered jalap with an alcohol-water mix- (Fam. Piperaceae). The plant is a large ture. The percolate is concentrated to one shrub widely cultivated in Oceania; its un- fourth the weight of drug used and is then derground parts have been extensively slowly poured into water and constantly used by the natives of these islands in the stirred. The precipitated resin is washed preparation of an intoxicating beverage. with hot water, collected, and dried. OCH Jalap resin occurs as yellowish brown masses or powder. It is a cathartic pos- sessing hydragogue activity. The usual H2C/10 dose is 125 mg Mastic Dihydromethysticin Mastic, mastiche, or mastich is the con- In addition to large quantities of starch, crete resinous exudate from Pistacia lentis- the drug contains about 5 to 10% of a resin 144 RESINS AND RESIN COMBINATIONS from which 6 different, closely related sty- smaller ratios than those just indicated. rylpyrortes have been isolated in pure The hemp leaves contain a small amount form: yangonin, desmethoxyyangonin, ka- of the resin. wain, dihydrokawain, methysticin, and Indian cannabis is prepared rather care- dihydromethysticin. Pharmacologic stud- fully from the pistillate flower heads only ies have shown that all of the kava pyrones and contains relatively few leaves. Mexican are more or less potent, centrally acting and American cannabis consist of the skeletal muscle re1axant. In addition to in- whole upper portion of the stalk of the pis- ducing changes in motor function and re- tillate plant. Indian cannabis may have an flex irritability, they possess antipyretic activity many times greater than that of a and local anesthetic properties. Differences poor quality of American cannabis. (Figure in action are largely quantitative. The cen- 6-4 shows the American cannabis plant; tral nervous and peripheral activities of the Figure 6-5 shows the structural elements kava pvrones are sufficient to account for in powdered cannabis.) the native use of the drug The unusual sensations induced in hu- Cannabis mans by the uncontrolled use of cannabis are obtained more promptly and with less Cannabis. Indian hemp, marihuana, or drug by inhaling the smoke of burning can- pot consists of the dried flowering tops of nabis than by oral dosage. The importation the pistillate plants of Cannabis sativa Linné into the United States of rather crude Mex- (Farn. Moraceae). ican cannabis (marihuana) cigarettes The plant is an annual herb indigenous began several decades ago. As the demand to central and western Asia and is culti- for these cigarettes (reefers) increased and vated in India and other tropical and tem- the habit of smoking them spread to school perate regions for the fiber and seed. Can- children, federal and state narcotic agents nabis is the ancient Greek name of hemp. started a campaign to stamp out their sale. Cannabis was used in China and India, The importation of Indian cannabis was spread slowly through Persia to Arabia prohibited, and even large areas of natu- where the resin was known as hashish, and probably was introduced into Euro- rally growing American hemp were de- pean and American materia medica about stroyed. This campaign continues. The the time of Napoleon. substitution of a poor quality drug for the Through long years of selective cultiva- high quality Indian cannabis and the ma- tion, 2 genetic types of cannabis have rihuana campaign resulted in discontinued evolved. One, designated the drug type, is medicinal use of cannabis in the United rich in THC. The other, referred to as the States. hemp type, contains little active principle Indian cannabis yields 15 to 20% of a (cannabidiol is the predominant cannabi- resin that contains the major active eu- noid) but has the elongated bast fibers de- phoric principle (- )--trans-tetrahydro- sired in the manufacture of rope. cannabinol, commonly referred to as - The amount of resin found in the pistil- THC. This compound was isolated almost late flowering tops of C. sativa markedly simultaneously by 2 teams of investigators. decreases when the plants are grown in the One team viewed the compound as a di- more temperate climates (Fig. 6-3). Thus, benzopyran derivative and assigned the Indian cannabis yields 20% or more of aforementioned name. The other group resin; Mexican cannabis 15% or less; Ken- applied a monoterpene nomenclature, re- tucky hemp 8% or less; Wisconsin hemp sulting in the designation '-trans-tetra- 6% or less. The active principles are found hvdrocannabinol. Both names are com- in the resin in about the same or in even monly found in the literature, but the RESINS AND RESIN COMBINATIONS 145

Fig. 6-3. Scanning electron micrograph of stalked and sessile glandular trichornes on the bract of a fe- male plant of Cannabis .sat lea. The glands contain resin. Magnification 390 X. (Photo, courtesy of Dr. Charles I. Hammond Department of Biology, Wabash Col- lege)

Fig. 6-4 . American cannabis. 146 RESINS AND RESIN COMBINATIONS

I 51 r

a

Fig. 6-5. Powdered cniiahis. of, Epideunis from lower surface of eaves with sinuate vertical walls and n morons oval stomata, and di, Irom upper surface, with straight walls and no stomata; h, nonglandular hairs, numerous, unicellular, rigid, curved, with a slender pointed apex and an enlarged base, usuall y con- laming a cystolith (a,), but ireguentiv broken, and the cvstohth treed; glandular hairs at 2 kinds, 1 with a short i-celled stalk ('hs) and the other with a long multicellular stalk (gui), the head (g/z) in both kinds being globular and consisting of 8 to 16 cells; lit, fragments of bracts and leaves showing yellowish brow fl taticiferous vessels (Jo), numerous rosette aggregates (ag) of calcium oxalate 5 to 30 p. in diameter, strands of spiral (sir) or reticulLc (t,) vessels, and phloern; (ftc), fragments of fruits with palisadelike, norilignified cells with yellowish brown, finely porous walls, tissues 0t embryo and endosperm with numerous oil globules and ateurone grams (a!). the latter 5 to 10 p. in diameter and displayi ng crystalloids and globoids; gel, pollen grains, rnic, photo- inicrograph of leaf fragment showing a rosette aggregate of calcium oxalate cr ystals in nearly every cell, (Drawings b y Paul D. Carpenter.)

(5 dihenzopyran nomenclature is now more binol TetrahvdrocannabinolS and A9- widely used in this countr. THC) possess euphoric activity, cannabi- nol is weakly active, and cannabichromene C13 QH and cannabidiolic acid are sedative prin- ciples. A-THC has been synthesized and the pure compound utilized for physio- logic studies in human beings. It was found H-_\ -o CH 3 OH3 to be more potent when smoked than -THC when taken orally. A-THC is available Other constituents isolated from canna- under the name of dronabinol (Marinol®) bis resin include cannahinol, cannahidiol, for the control of nausea in cancer chem- cannahidiolic acid, cannabichroniene, call- otherapy. nahigerol, and -f raiis-tetrahvdrocanna Cannabis is cultivated to a considerable RESINS AND RESIN COMBIN#TIONS 147 extent for its bast fibers, hemp, and for its The oleoresin is secreted in ducts located fruits, hempseed; the latter contain about directly beneath the cambium in the sap- 20% of a fixed oil that is expressed and used wood. During the spring of the year, bark in the manufacture of paints and soap; the is chipped from the tree by using a "bark cake meal is used as cattle food. hack," a long-handled cutting blade. Fol- lowing removal of the rounded chip, a spray of 50% solution of sulfuric acid is OLEORESINS applied to the freshly cut surface. As the Oleoresins are homogeneous mixtures sap (oleoresin) flows, it is guided by metal of resins and volatile oils. gutters into containers attached directly to There is no sharp line of demarcation the tree trunk; the thick liquid that collects between these various types of resinous is removed periodically and taken to the substances, and classification is sometimes turpentine still. difficult. Small proportions of volatile oils The older method of chipping "deep and are present in many resins. Depending on often" into the wood does not produce as the relative amount of volatile oil in the much flow, requires more man-hours of mixture, oleoresins may be liquid, semi- labor per tree, and, because of the flat sur- solid, or solid. Usually, there is a small face of the face, deteriorates the value of amount of "natural" exudate from oleo- the butt log for lumbering purposes. An- resin-containing trees owing to insect other method of collecting, i.e., making a stings, broken branches, and other inju- "box" in the trunk to collect the sap, is no ries, but the commercial supplies are gen- longer used. erally obtained by artificial incision The acid treatment collapses the thin- through the bark and even into the wood. walled parenchymal cells that line the resin ducts. This allows the duct channels to be- Turpentine come larger, providing a more rapid flow Turpentine, gum turpentine, or gum of oleoresin and reducing the chances of thus is the concrete oleoresin obtained hardened secretions blocking the outlets. from Pin us palustris Miller and from other The acid does not stimulate greater pro- species of Pinus (Fam. Pinaceae). duction of oleoresin by the tree, but it en- "Gum" turpentine or "gum" is a com- ables more oleoresin from the ducts to es- mon name among the collectors and deal- cape, thus prolonging the flow. If applied ers of turpentine but is a misnomer from properly, add treatment does not injure the scientific standpoint. Turpentine is not the tree. This method has been much more related to the true gums and mucilages of successful than the fungous culture carbohydrate origin. method used several years ago. Turpentine is collected from the longleaf The usual turpentining season lasts pine (P. palustris Miller) and from the slash about 32 weeks. The product of the first pine (P. elliottii Engeimann var. elliottii) that year's cutting is superior and,is known as grow in North and South Carolina, Geor- "virgin" turpentine. On steam distillation, gia, and northern Florida. The trees form it yields from 15 to 30% of volatile oil (tur- vast forests and present a characteristic ap- pentine oil, see page 111), whereas the pearance owing to the "face" of the cut product of the second or third year may surface (Fig. 6-6). Turpentine yields de- yield not more than 10% of oil. The hot pend on the treatment and the size of the filtered residue left after distillation con- tree. Large trees measuring 45 to 50 cm in stitutes rosin (see page 140). diameter are preferred, although smaller The United States is the world's largest trees may be turpentined also. If skillfully producer of rosin and turpentine, account- worked, trees yield for 15 to 20 years. ing for about 70% of the supply. This in- 148 RESINS AND RESIN COMBINATIONS

Fig. 6-6. :ipI:. dustry is often referred to as "naval stores" Turpentine occurs as yellowish, opaque trade because the wooden sailing vessels masses that are lighter internally, more or of the 17th century used enormous quan- less glossy, sticky when warm, and brittle tities of tar and pitch obtained from the in the cold. its odor and taste are charac- coniferous forests of Europe. Since then, teristic. It is freely soluble in alcohol, ether, the trade has followed the location of the chloroform, and glacial acetic acid. pine forests, moving from New England The drug constituents are volatile oil and southward as the trees were depleted or resin. It contains not more than 2% of for- became inaccessible. eign organic matter. Living pine trees are just one source of USE. It is employed externally as a coun- turpentine oleoresin. In addition, the prod- terirritant. uct is obtained by steam distilling pine stumps and also by working up the black Capsicum liquor soap produced in the Kraft pulping Capsicum or cayenne pepper is the process. Total production in the United dried, ripe fruit of Capsicum frutescens States has remained nearly constant for al- Linné, known in commerce as African chil- most a century, About 30 million gallons of lies, of C. annum Linné var. conoides Irish, turpentine oil, prepared by distillation of known in commerce as Tabasco pepper, or the oleoresin, and 1 billion lb of rosin are C. uiinuuiu var. 1on'wn Sendt, known in produced annually from all sources. commerce ds Louisiana long pepper, or of RESINS AND RESIN COMBINATIONS 149

a hybrid between the Honka variety of lap- and Louisiana peppers up to 10 times the ailese capsicum and the old Louisiana size of African capsicum. The outer epi- short capsicum, known in commerce as dermis of the pericarp of these peppers Louisiana short pepper (Farn. Solanaceae). consists of irregular (not quadrangular) Capsicum must be labeled to indicate cells with thickened and strongly beaded, which variety is contained in the package. lignified, radial walls. The y also possess a Capsicuin is from the Latin capsa, mean- hypodermis of elongated cells with thick- ing a box, and refers to the partially hollow, ened, strongly beaded radial walls of cel- boxlike fruit; frutescens is Latin and refers lulose or cuticularized cellulose. These fea- to the shrubby character of the plant; and tures readily distinguish these peppers, in anuuuni is Latin and refers to the annual whole or powdered form, from genuine character of the plant. African capsicum. C. frutescens is a small spreading shrub . Capsicum contains capsaicin (about reaching 1 meter in height and is indige- 0.02%), an extremely pungent principle, in nous to tropical America and cultivated in the dissepiments of the fruit. Capsaicin is tropical localities in Africa, India, America, a phenol having the formula: and Japan. Apparently, the more tropical H CH(CH,) the climate, the more pungent the fruit. C. annuum is an herbaceous, annual form cul- CH2NHCO(OH2) H tivated in mildly temperate to semitropical localities in central and southern Europe, Mexico, the United States, and other coun- tries, it is cultivated under the names of OH garden pepper, paprika, pimiento, Mexi- Capsaidri It imparts a distinctly pungent taste to All of these are less pungent than African chillies but are desirable as condiments. water, even when diluted to I part in 11 The medicinal value of capsicum as a rube- million parts of water. Capsicum also con facient depends on its pungency. tains about 1.5% of a volatile oil, a fixe African cayenne comes chiefly from oil, carotenoids, and up to 0.2% of ascorbic Kenya and Tanzania in East Africa and acid (vitamin Q. Sierra Leone in West Africa and is usually USES AND DOSE. Capsicum is an irritant designated in the trade by the port from and a carminative; it is used as a rubefa- which it is shipped. Japanese chillies, usu- cient and also as a stimulant and a condi- ally exported from Kobe, are somewhat ment. The usual dose is 60 mg. Capsicum less pungent than African capsicum but oleoresin has the same properties. The more pungent than Madras or Bombay usual dose is 15 mg. chillies from India. Of the millions of PROPRIETARY PRODUCTS. Capsicum is an Pounds annually imported into the United ingredient in a number of external anal- States, about one half comes from India, gesic preparations, including Absorbent one third from Japan, and one sixth from Rub®, Fleet®, InfraRuh ®, Omega Oil, Africa. and Sloan's®. Capsicum was first mentioned in 1494 by ALLIED DRUGS. Paprika, Hungarian pap- Chauca, a physician who accompanied Co- rika, or Turkish paprika is a large-fruited lumbus on his second voyage to the West pepper obtained from varieties of C. an- Indies. Plants were introduced into India nuum, It apparently is indigenous to Amer- by the Portuguese at an early date and later ica and was first introduced to Spain and into Africa. then to Greece, Turkey, and Hungary. The Tabasco peppers are about twice the size fruits, when fresh, are to 10 cm in length, 150 RESINS AND RESIN COMBINATIONS to the 13th centuries, ginger was a common import from the East. Marco Polo observed it in China and India from 1280 to 1290. Ginger was introduced into Jamaica and other islands of the West Indies by the Spaniards, and drug exports from the West Indies to Spain were made in considerable quantities as early as 1547. Exports from Jamaica to all parts of the world amount to more than 2 million lb annually. Ginger owes its characteristic aroma to Fig. 6-7. Jamaica ginger: Irregularly branched rhi- about ito 3% of a volatile oil, the principal zomes (4 to 16 cm long and 4 to 20 mm thick) from constituents of which are 3 sesquiterpenes: which the cork has been removed, showing de- bisabolene, zingiberene, and zingiberol. pressed stem scars (Sc) at the ends of the branches; the rhizomes are longitudinally striate, somewhat yel- The characteristic pungency of the drug is lowish to light brown in color, break with a short- attributed to ginger oleoresin, from which fibrous, starch-resinous fracture, and have an aro- 2 aromatic ketones, zingerone and sho- matic odor and a pungent, aromatic taste. gaol, have been isolated. In addition, gin- ger contains more than 507c, of starch. 5 to 7 cm in diameter, more or less inflated, USES AND DOSE. Ginger is classed as a and bright red. flavor; it is used as a condiment, an aro- Spanish paprika or pimiento is paprika matic stimulant, and a carminative. The grown in Spain. The succulent pericarp is dose is 0.6 g. Ginger oleoresin has the used for stuffing olives, and the dry pod same properties. Much of the ginger con- is ground as a spice. sumed in the present-day market is used in the manufacture of ginger ale. Ginger Ginger or zingiber is the dried rhizome White Pine of Zingiber officinale Roscoe (Fam. Zin- White pine or white pine bark is the giberaceae), known in commerce as Ja- dried inner bark of Pinus strohus Linné maica ginger, African ginger, and Cochin (Fam. Pinaceae). The white or Weymouth ginger (Fig. 6-7). The outer cortical layers Pine is the principal timber pine of the are often either partially or completely re- northern United States and Canada. The moved. Zingiber is from the Arabic outer corky layer of the bark is removed Zindschebil, meaning root of Zindschi before the inner portion is dried. (India). The specific name refers to its use Pinus is the ancient Latin name, probably as an ingredient of preparations made in akin to pinna, and means a feather, refer- drug shops. ring to the somewhat featherlike foliage of The ginger plant is propagated in Ja- many of the species. The specific name, maica by rhizome cuttings that are planted strobus, pertains to the cones or strobiles. in March and April. The rhizomes are dug The alcoholic extract forms about 30% of and peeled in December and January. As the drug and contains tannic acid and an soon as they are peeled, the rhizomes are oleoresin. The bark contains considerable washed in water for hours, then dried in mucilage and a small quantity of coniferin; the sun for 5 to 6 days. They are covered the latter is usually present in the cambial at night and during rainy weather. layer of all of the species of Pinus as well Ginger was known in China as early as as in other genera of the Pinaceae. the 4th century s.c. It was used as a spice USE AND DOSE. White pine has expecto- by the Greeks and Romans. From the 11th rant properties. The usual dose is 2 g. RESINS AND RESIN COMBINATIONS 151

PROPRIETARY PRODUCTS. Creomulsionr The oleo-gum-resin exudes naturally or and Prunicodeine. from incisions made in the bark; it is at first a yellowish color, but soon hardens in the Copaiba intense heat of these countries, becomes Copaiba or balsam copaibä is an oleo- darker, and is then collected. There are 2 resin derived from South American species principal commercial varieties of myrrh: of Copaifera (Copaiba) (Fam. Leguminosae). Africa or Somali myrrh and Arabian or The oleoresin is formed in schizolysigenous Yemen myrrh. The former is considered cavities in the wood and seems to be a the better of the two. Practically all of the metamorphosed product of the cell walls; commercial supply comes from Somalia. these cavities sometimes contain several li- There are numerous references to myrrh ters of the oleoresin. The trees are tapped in the Old Testament, but it is highly pos- or boxed (see turpentine, page 147) to the sible that the product thus designated was center of the tree and the oleoresin con- bdellium. Myrrh was an ingredient of the ducted directly to containers. A tree embalming material of the Egyptians. It quently yields 20 to 24 liters. use in incense and perfumes in ceremonia It should be noted that the term "bal- religious life since the days of remote an sam" is erroneously applied. Copaiba is an tiquity is well known. Theophrastu. oleoresin and contains neither benzoic nor Pliny, and other early writers mentior cinnamic acid. It consists of a volatile oil, myrrh, and from early times it has beer resin acids, and a small quantity of a bitter valued in domestic medicine for its aro principle. rnatic qualities. USES AND DOSE. Copaiba was used as a Myrrh contains a yellow or yellowish genitourinary disinfectant. It has diuretic, green, rather thick, volatile oil, 2.5 to 87r stimulant, expectorant, and laxative prop- that has the characteristic odor of myrrh erties. The dose is 1 ml. resin, 25 to 40%, composed of several con stituents, among which are resin adds (a- -, and y-commiphoric acids), resenes, an OLEO-GUM-RESINS phenolic compounds, one of which yield Oleo-gum-resins are mixtures of resin, protocatechuic acid and pyrocatechi gum, volatile oil, and, frequently, small gum, about 60%, consisting of soluble an quantities of other substances. The prin- insoluble portions and forming a mucilag' cipal oleo-gum-resins are myrrh and asa- that does not readily ferment (being of th fetida. acacia type) and yielding arabinose as one of the products of hydrolysis; and a bitter Myrrh principle, sparingly soluble in water but Myrrh or gum myrrh is an oleo-gum- soluble in alcohol. resin obtained from Commiphora molmol En- USES. Myrrh is a protective; it has also gler, from C. abyssinica (Berg) Engler, or been employed as a stimulant and a stom- from other species of Cominiphora Jacquin achic. It is used in mouthwashes as an as- (Fam. Burseraceae). The name myrrh is tringent. from the Arabic nzurr, meaning bitter; Corn- PROPRIETARY PRODUCTS. Astring-O-Sol°' rniphora is Greek and means gum bearing; and Odara®. rnohnol is the native Somali name; and abys- sinica refers to the habitat of the plants. The plants are small trees that sometimes attain BALSAMS a height of 10 meters and are found grow- Balsams are resinous mixtures that con- ing on the Arabian peninsula and in Ethio- tain large proportions of benzoic acid, cin- pia and Somalia. namic acid, or both, or esters of these acids. 152 RESINS AND RESIN COMBINATIONS

Benzoin is sometimes referred to as a bal- used mostly in the tobacco industry for fla- samic resin. The medicinal balsams include voring cigarettes. Tolu balsam, Peru balsam, styrax (Levant The early Arabian physicians were ac- and American), and benzoin (Siam and Su- quainted with storax, and it is mentioned matra). as early as the 12th century. Most of the styrax used in pharmacy comes from Tur- Storax key and Honduras. Storax is a balsam obtained, from the Levant storax occurs as a viscid, grayish trunk of Liquidmbar orienti1is Miller, to grayish brown, more or less opaque, known in commerce as Levant storax, or semiliquid mass that deposits a heavier, of L. styraciflua Linné, known in commerce dark brown, oleoresinous stratum on as American storax (Fam. Hammamelida- standing. American storax is a nearly dear, ceae). Storax is also known as liquid storax yellowish brown semiliquid that becomes or styrax. hard, opaque, and darker colored. Storax The term styrax is from the Arabian as- is transparent in thin layers; its odor is sitirax, meaning a sweet-smelling exuda- agreeable and its taste is balsamic. Storax tion; Liquidanibar is from the Latin liquidus, is insoluble in water but almost completely meaning fluid, and from the Arabian soluble in warm alcohol. anthar, meaning amber; orientalis means Levant storax consists of about 50% of 2 pertaining to the Orient; and styraciflua resin alcohols, a-storesiri and -storesin, means to flow storax. which are partly free and partly in com- L. orientalis is a tree that attains a height bination with cinnamic acid. a-Storesin is of about 15 meters and grows in Asia amorphous but forms a crystalline com- Minor. L. styraciflua is a tree that attains a pound with potassium. -5toresin occurs height of up to 40 meters and grows in as white flakes that do not form a crystal- southern North America, Central America, line compound with potassium. Storax also and northern South America. Levant sto- rax is a pathologic product; its formation is contains storesin cinnamate, 10 to 20%; induced by bruising or puncturing the bark styracin or cinnamyl cinnamate, 5 to 10%, of the tree in early summer, thereby caus- in needle-crystals that are colorless, odor- ing the cambium to produce new wood less, and tasteless; phenylpropyl cinna- with balsam-secreting ducts. In autumn, mate, 10%, a liquid with the odor and taste the bark, which is more or less saturated of styrax; volatile oil, 0.5 to 1%; a trace of with balsam, is peeled off and the balsam vanillin; free cinnamic acid, from 2 to 5%; is recovered by pressing. The bark is then and small amounts of several other sub- boiled in hot water and pressed again. The stances. Free cinnamic acid may be ob- balsam is poured into casks or cans and is tairCd from storax by microsublimation usually exported via Smyrna. with a yield of up to 20%. Most of the American storax is produced American storax contains related stores- in Central America where large forests of ins and other principles of Levant storax: L. styraciflua are found. The balsam exudes it yields 7% of volatile oil by steam distil- into natural pockets between the bark and lation and contains about 28% of cinnamic the wood and may be located by excres- acid, 23% of cinnamein, 35% of resin es- cences on the outside of the bark. These ters, and 2% of resin acids. pockets, which contain up to 4 kg of the USES AND DOSE. Storax is a pharmaceutic balsam, are tapped with gutters and the aid for compound benzoin tincture. It has balsam is led into containers. The balsam been used as a stimulant, an expectorant, is exported in tin cans. A large quantity is and an antiseptic. When used internally, also produced in the United States but is the dose is I g. RESINS AND RESIN COMBINATIONS 153

Peruvian Balsam amount of benzyl benzoate; resin esters, 30 to 38%, which are composed mostly of pe- Peruvian balsam, Peru balsam, or bal- ruresjnotannol cinnarnate and benzoate; sam of Peru is obtained from Myrcxylon vanillin; free cinnamic acid; peruviol; and pereirac (Royle) Klostzsch (Fain Legurni- other substances in small amounts. nosae). Myroxdon is from the Greek myron, USES. Peru balsam is a local protectant meaning ointment, and xylon, meaning and rubefacient; it also is a parasjtjcide in wood; pL'reirae is in honor of Jonathan certain skin diseases. It is an antiseptic and Pereira (1804 to 1853), an English phar- vulnerary and is applied externally either macognosist. "Peru" refers to the early im- alone, in alcoholic solution, or in the form portation of the balsam into Spain via of an ointment. Lima, Peru. PROPRIETARY PRODUCTS. The drug is The balsam trees attain a height of about employed for its astringent properties in 25 meters and are especially abundant various preparations used to treat hemor- along the coast of El Salvador in Central rhoids. These include Anusol® supposito- America. The tree has been naturalized in ries and Wyanoid® ointment and suppos- Florida and in Sri Lanka. It was frequently itories. referred to by writers who described the conquest of Guatemala in 1524. In the 17th Tou Balsam century, the drug appeared in German Tolu balsam is a balsam obtained from pharmacy, after which its use became uni- Miiroxylou /aLsamum (Liriné) Harms (Fam. versal. Leguminosac). Tolu balsam is sometimes The balsam is a pathologic product and called balsam of Tolu. is formed by injury to the trees. The tree The balsam trees grow abundantly along is beaten on 4 sides and then scorched with the lower Magdalena River in Colombia. a torch to cause the bark to separate from 'Tolu is a district near Cartagena, where the the trunk. Four intermediate strips are left balsam was once extensively produced. uninjured so as not to kill the tree. Within Balsam of Tolu is usually considered to a week, the bark drops from the trunk and he a pathologic product similar to balsam the balsam begins to exude freely from the at Peru or coniferous oleoresins. V-shaped exposed wood. The areas are then incisions are made through the bark and wrapped with rags that are removed from sap wood, and calabash cups receive the time to time when they become saturated flow of balsam. Similar cuts are made with balsam. The rags are then boiled with higher on the trees; sometimes as many as water and, as the water cools, the balsam 20 incisions are made on a tree. The balsam settles out, is recovered, strained, and is collected from the cups and transferred packed, usually in tin cans. Most of the to tin containers in which it is shipped. commercial supply comes from El Salva- Some balsam of Tolu is also produced in dor, although some is produced in Hon- Venezuela, and trees are now being culti- duras. vated in the West Indies. Tolu balsam was Peruvian balsam occurs as a dark brown, used by the natives in Colombia and Ven- viscid liquid that appears reddish brown ezuela. Monardes (1574) described its col- and transparent in thin la yers. It is free lection, stating that the drug was much es- from stringiness or stickiness and has an teemed by the Indians and later by the empyreumat-ic, aromatic, vanillalike odor Spanish, who introduced it into Europe. and a hitter, acrid, persistent taste. Much of the balsam of Tolu entering the The drug contains cinnamein, about United States comes from Great Britain, 60%, which is a volatile oil consisting where a certain amount of the volatile oil chiefly of benzyl cinnamate and a lesser has been removed. Sufficient oil remains, 154 RESINS AND RESIN COMBINATIONS

however, so that the balsam meets the of- The first tapping of S. henzoin yields the ficial requirements. so-called almond tears. The second tap- Tolu balsam occurs as a plastic solid that ping yields a more fluid substance. The al- gradually hardens, becoming brown or ye!- mond tears and the fluid substance are im- lowish brown. It is transparent in thin lay- ported into Singapore and are admixed ers, brittle when old, dried, or exposed to (possibly with adulterants) to produce cold, and shows numerous crystals of cin- block benzoin. namic acid. Its odor is agreeably aromatic, In Thailand, the separate tears are resembling that of vanilla, and its taste is scraped from the trees. New incisions are aromatic and slightly pungent. continually made until the trees die. The The drug contains resin esters, 75 to tree contains no secretory cells, nor does it 80%, chiefly toluresinotannol cinnamate contain the constituents of the balsamic with a small quantity of the benzoate; vol- resin until it is incised. The bark of the atile oil, 7 to 8%, chiefly benzyl benzoate; normal tree contains considerable tannin. free cinnamic acid, 12 to 15%; free benzoic The resinotannols in benzoiri are probably acid, 2 to 8 1k; vanillin and other constit- produced from this tannin. Benzoin was uents in small quantities. unknown to the Greeks and Romans. It USES. Tolu balsam is a pharmaceutic aid was first mentioned by lbn Batuta, who for compound benzoin tincture. It is some- visited Sumatra in the 14th century. In the times used as an expectorant and is exten- 15th century, it still appeared as a precious sively used as a pleasant flavoring in me- balsam, but in the 16th century it was an dicinal syrups, confectionery , chewing article of Venetian commerce. gum, and perfumery. The use of Siam benzoin is confined al- most entirely to perfumery. The tears of Benzoin Siam berizoin are graded according to size Benzoin is the balsamic resin obtained and color; the smaller tears and sittings are from Styrax benzoin Dryander, S. parallelo- darker in color. In pharmacy, only the Su- neurus Perkins, known in commerce as Su- matra henzoin is used. Before World War matra benzoirt, S. tonkinensis (Pierre) Craib II, Sumatra benzoin was obtained directly ex Hartwich, or other species of the Section from Sumatra; today almost all Sumatra Anthostyrax of the genus Styrax, known in benzoin is imported from Singapore. commerce as Siam benzoin (Fam. Styra- Sumatra benzoin occurs as blocks or ir- ceae). Styrax is the ancient Greek name of regular masses composed of tears of vari- storax applied to a sweet-scented gum and able size imbedded in a translucent or to the tree producing it; benin is from the opaque matrix. It is brittle and internally Arabic ben, meaning fragrant, or the He- the tears are milky white, becoming soft brew ben, meaning a branch, and zoo, an when warmed and gritty when chewed. exudation, meaning the juice of the branch; The matrix is reddish or grayish brown; the tonkinensis is named after Tonkin, the odor is agreeable, balsamic, and resembles northern region of Vietnam, that of styrax; the taste is aromatic and The pits are trees of medium height resinous. that grow in southeastern Asia and the East Siam benzoin occurs mostly in separate Indies. S. henzoin is cultivated throughout concavo-convex tears that are yellowish Sunv ra; S. tonkinensis in Thailand, Viet- brown to rusty brown externally and milky nar' and Laos. Benzoin is a pathologic white on the freshly broken surface. The prduct developed by incising the bark. tears are brittle but become soft when A1ter about 2 months, the exuding bal- warmed and plastic when chewed. Siam .mic resin becons less sticky and firm benzoin has a varii}laljke odor. enough to collect. Siam benzoin consists principally of