Cubeba. U. S. (Br.)

Cubeba. U. S. (Br.)

Cubeb. Cubeb. [Cubebs]

Preparation: Oil of Cubeb

"The dried, full-grown, unripe fruits of Piper Cubeba Linne filius (Fam. Piperaceae), without the presence or admixture of more than 5 per cent. of stems or other foreign matter." U. S. "Cubebs are the dried full-grown unripe fruits of Piper Cubeba, Linn. fil." Br.

Cubebae Fructus, Br.; Fructus (s. Baceae) Cubebae, Piper Caudatum; Cubeba, Tailed Pepper; Cubebe, Cubebe ou Poivre a Queue, Fr. Cod.; Cubebae, P. G.; Kubeben, G.; Pepe Cubebe, Cubebe, It.; Cubeba, Sp.; Kebabeh, Ar.

Piper Cubeba is a climbing perennial plant, with a smooth, flexuous, jointed stem, and entire, petiolate, oblong or ovate-oblong, acuminate leaves, rounded or obliquely cordate at the base, strongly nerved, coriaceous, and very smooth. The flowers are dioecious and in spikes, with peduncle's about as long as the petioles. The fruit is a globose, pedicelled drupe. This species of Piper is a native of Java, Penang, and probably other parts of the East Indies. It is extensively grown in the coffee plantations, supported by the trees which are used for shade, and has been introduced into Ceylon. The dried unripe fruit is the official portion. Our knowledge of the false cubeb of commerce up to 1894 was epitomized in the 17th edition of the U. S. D., p. 457. To this account the reader is referred for historical details. (See also U. S. D., 19th ed., p. 410.)

Properties.—Cubeb is officially described as follows: "Upper portion globular, from 3 to 6 mm. in diameter, with a straight, slender stem-like portion, from 5 to 7 mm. in length; pericarp externally grayish, brownish, or bluish-black; coarsely reticulate; about 0.3 mm. in thickness, easily cut, 1-locular, 1-seeded; the immature seed attached at the base of the pericarp; odor aromatic, characteristic; taste strongly aromatic and pungent. Under the microscope, sections of Cubeb show an epidermal layer of tabular cells with thickened, undulate outer walls, the contents being olive-green; 1 or 2 rows of parenchyma cells, the contents resembling those of the epidermal cells; a continuous layer of radiately elongated, thick-walled stone cells having numerous pores; a few layers of collapsed cells near which may occur an occasional small group of bast-fibers; a middle layer of 10 rows of cells composed chiefly of parenchyma, scattered among which are numerous secretions cells containing a volatile oil and occasionally crystals in the form of short rods, the contents of the secretion cells being colored a deep crimson upon the addition of sulphuric acid; an endocarp of small, somewhat isodiametric or polygonal stone cells with very thick porous walls; seed-coat of several rows of reddish-brown, tangentially elongated, more or less collapsed cells; perisperm of numerous thin-walled parenchyma, the cells being more or less polygonal in shape and containing either small compound starch grains, or globules of a fixed oil or occasionally a crystal of calcium oxalate. The powder is light brown to blackish-brown, consisting of a more or less even distribution of starch-bearing cells of the perisperm and fragments of the pericarp with stone cells; starch grains numerous, single or compound, from 0.002 to 0.012 mm. in diameter; stone cells numerous in palisade-like groups, in surface view rounded or polygonal with rather prominent dark lumina and yellowish porous walls; secretion cells with a yellowish, oily content, becoming reddish on the addition of sulphuric acid; fragments of stalk few, with spiral trachea and groups of sclerenchymatous fibers from 0.05 to 1 mm. in length with blunt, rounded, or very much attenuated ends, the walls strongly lignified and with numerous oblique pores. Cubeb yields not less than 10 per cent. of volatile extractive, soluble in ether (see Part III, Test No. 12). Cubeb yields not more than 8 per cent. of ash." U. S.

"Nearly globular, about four millimetres in diameter, greyish-brown or nearly black. Pericarp reticulately wrinkled, thin, brittle, and abruptly prolonged at the base into a slender, rounded stalk about one and a half times as long as the globular portion. Seed almost spherical, sometimes much shrivelled, attached by the base. In the' transverse section of the pericarp two layers of sclerenchymatous cells, one near the outer, the other near the inner surface, those of the latter being radially elongated and usually arranged in a single row. Strong, aromatic, and characteristic odor; taste warm, aromatic, and somewhat bitter. When 2 grammes of powdered Cubebs are macerated with 20 millilitres of ether for twenty-four hours, and shaken occasionally, 10 millilitres of the clear ethereal solution, allowed to evaporate in a flat-bottomed dish, yield a residue which, dried for one hour in a desiccator over sulphuric acid, weighs not less than 0.200 gramme." Crushed Cubebs impart a crimson color to sulphuric acid. Ash not more than 8 per cent." Br.

Commercial cubebs are not infrequently admixed with and entirely substituted by other fruits, some of which contain volatile oils which possess very different properties from the genuine oil of cubeb, being in some instances highly toxic. Hartwich (Arch. d. Pharm., 1898, Heft 3; also p. 172) gives the following classification for the identification of spurious fruits:

I. Fruits of the Piperaceae having slender stalks.

STONE CELLS IN EPICARP, ENDOCARP AND DISTRIBUTED IN THE MESOCARP:

Piper ribesioides Wallich (identical with Padang Cubeb). Fruits not colored red with sulphuric acid.

STONE CELLS ONLY PRESENT IN THE EPICARP AND ENDOCARP:

Stone cells of the endocarp radially elongated.

Piper Cubeba L. f. Seed attached only at the base of the pericarp.

a Rinoe Katoentjor, the official variety, which is colored red with sulphuric acid.

ß Rinoe badak, distinguished by not being colored red with sulphuric acid.

Stone cells of the endocarp of iso-diametric form.

Piper crassipes Korthals. Sections not colored red with sulphuric acid.

Stone cells of the endocarp thickened like a. horseshoe.

Piper a court pedicelle. Origin unknown.

STONE CELLS PRESENT ONLY IN THE EPICARP:

Fruit with stem 3 cm. in length, the stem-like portion being alone 17 mm. long.

Piper mollissimum Blume (Keboe Cubeb. Karbauw berries) sections not colored red with sulphuric acid.

The fruits and stems much smaller, but distinguished by having radially elongated stone cells.

Piper venosum DC. colored red with sulphuric acid.

STONE CELLS ABSENT IN THE PERICARP:

African varieties:

Fruit without stem 5 to 6 mm. long, stem-like portion equally long.

a Piper clussi DC., sections colored red with sulphuric acid.

ß Piper guineense Schum. sections not colored red with sulphuric acid.

Fruits 4 mm. long, 2 to 3 mm. thick and stems 6 mm. long.

Piper borbonense DC. (Cubebe du pays) sections not colored red with sulphuric acid.

Indian varieties: None of which are colored red with sulphuric acid.

Stems flattened.

Piper Lowong Blume. Secretion cells colored bluish-green with sulphuric acid.

Ceylon pepper. Secretion cells colored yellow with sulphuric acid.

ß Stem-like portion cylindrical.

Piper canium Blume and P. phyllostitum DC.

II. Fruits of the Piperaceae without stalks.

STONE CELLS PRESENT IN EPICARP AND ENDOCARP:

Piper nigrum L. Stone cells of epicarp radially elongated and sections colored red with sulphuric acid.

Cubebe de Jaba sauvage. Stone cells of the epicarp not radially elongated.

STONE CELLS ONLY IN THE EPICARP:

Dangdang boeroeng. A fruit obtained from Java, the origin of which is unknown.

STONE CELLS ABSENT IN PERICARP.

Cubeb from Bangil, origin unknown. Sections at first colored red with sulphuric acid, then becoming brown.

III. Fruits obtained from plants belonging to other families than the Piperaceae.

Xanthoxylum Budrunga Wall. (Fagara Budrunga Roxb.) (Rutaceae).

Bridelia tomentosa Bl. (Euphorbiaceae).

Tetranthera citrata N. v. Esenbeck (Litsea citrata Bl.) (Lauraceae).

Daphnidium Cubeba Nees. (Lauraceae).

Pericampylus incanus Miers. (Menispermaceae).

Xylopia frutescens Graertner. (Anonaceae).

Helicteres hirsuta Bl. (Sterculiaceae).

Grewia tomentosa Juss. (Tiliaceae).

Constituents.—The most obvious constituent of cubeb is the volatile oil, the proportion of which yielded by the drug varies from 4 to 13 per cent. It is, as shown by Oglialoro, a mixture of a terpene, C₁₀H₁₆, boiling at 158° to 163° C. (316.4°-325.4° F.), which is present in very small amount, and is probably pinene or camphene, some dipentene, and two oils of the formula C₁₅H₂₄, boiling at 262° to 265° C. (503.6°-509° F.). One of these, known as cadmene, is strongly laevogyrate, and yields a crystallized compound having the formula, C₁₅H₂₄₂HCl, and melting at 118° C. (244.4° F.), while the other is less laevogyrate, and does not combine with HCl.

The oil distilled from old cubeb on cooling at length deposits large transparent inodorous octahedra of camphor of cubeb, C₁₅H₂₅O. E. Schmidt found that this camphor melts at 66.5° C. (152° F.); simply by standing over sulphuric acid, more rapidly on heating, it gave up water and passed into that fraction of cubeb oil which boils at 260° C. (500° F.), of which it is, therefore, simply the hydroxide. Another constituent of cubeb is cubebin. This is an inodorous substance, crystallizing in small needles or scales, melting at 125° C. (257° F.), having a bitter taste in alcoholic solution, it dissolves freely in boiling alcohol, but deposits on cooling, and is abundantly soluble in chloroform. Its composition, according to Weidel (1877), is C₁₀H₁₀O₃, and its structural formula,

shows a close relationship to safrol,

Fused with potassium hydroxide it yields proto-catechuic acid. The resin extracted from cubeb consists of an indifferent portion, nearly 3 per cent., and of cubebic acid, C₁₃H₁₄O₇, amounting to about 1 per cent. (Pharmacographia, 2d ed., p. 587.)

The formula of cubebic acid as just given is that of .Schmidt. Schultze (Jahresbericht, 1873, p. 863), on the other hand, gives to it the formula C₂₈H₃₀O₇ +H₂O. According to Capitaine and Soubeiran, cubebin is best obtained by expressing cubeb from which the oil has been distilled, preparing from the marc an alcoholic extract, treating this with a solution of potassium hydroxide, washing the residue with water, and purifying it by repeated crystallizations in alcohol. In the official oleoresin of cubeb a deposit takes place consisting chiefly of cubebin, which may be obtained by washing the deposit with a small quantity of cold alcohol to remove adhering resin and oil, and then dissolving repeatedly in boiling alcohol, and crystallizing until the product is white. E. Schaer calls attention to the similarity in reaction between cubebin and veratrine, aconitine, morphine, and digitalin. (A. Pharm., 1887, p. 531.) The volatile oil is official. (See Oleum Cubebae.) By practical trial Bernatzik has satisfied himself that the peculiar virtues of cubeb as a remedy in gonorrhea depend not on the cubebin or the volatile oil, but on the cubebic acid. When the ethereal extract of cubeb is deprived of its volatile oil by evaporation on a water bath, and of cubebin and wax by deposition, a soft resin is left, the cubebic acid of Bernatzik, in which, according to F. V. Heydenreich, who experimented with it as a physiological agent, the diuretic properties reside, the cubebin being without apparent effect, and the volatile oil, though stimulant and carminative, having no diuretic action. The soft resin, which was of the consistence of honey, of a dark olive-green color,. and some remaining odor of cubeb, when taken in the dose of ten grains every two hours for six hours, acted as a laxative, and gave the urine a peculiar odor, without increasing its quantity; but in the dose of a drachm, once repeated at an interval of three hours, while it produced the same effects as the smaller dose, it considerably augmented the urine. In still larger doses it produced decided irritation of the urinary passages. (A. J. P., Jan., 1868.) Heydenreich's experiments are confirmatory of Bernatzik's conclusion as to the peculiar active principles of cubeb. Cubeb gradually deteriorates by age, and in powder becomes rapidly weaker, in consequence of the escape of its volatile oil. It should be kept whole, and pulverized when dispensed. The powder is said to be sometimes adulterated with that of pimenta.

Uses.—Cubeb is generally stimulant, with a special direction to the urinary organs. In considerable quantities it excites the circulation, increases the heat of the body, and sometimes occasions headache and giddiness. At the same time it frequently produces an augmented flow of the urine, to which it imparts a peculiar odor. Among its effects are also occasionally nausea and moderate purging, and it is said to cause a sense of coolness in the rectum during the passage of the feces. We have no evidence that it was known to the ancients. It was probably first brought into Europe by the Arabians, and was formerly employed for similar purposes as black pepper, but it was found much less powerful and fell into disuse. In India it has long been used in gonorrhea and gleet, and as a grateful stomachic and carminative in disorders of the digestive organs, and it is at present very frequently given both in this country and in Europe in gonorrhea, after the subsidence of the first active inflammatory symptoms. It has been given also in leucorrhea, cystorrhea, the urethritis of women and female children, abscess of the prostate gland, piles, and chronic bronchitis. In connection with copaiba it has been especially recommended in affections of the neck of the bladder and the prostatic portion of the urethra.

It is best administered in powder, of which the dose in gonorrhea is from one to three drachms (3.9-11.6 Gm.) three or four times a day. The volatile oil may be substituted, in the dose of ten or twelve minims (0.6-0.7 mil), suspended in water by means of sugar, although the oleo-resin is generally preferred. (See Oleoresina Cubebae.) An infusion, made in the proportion of an ounce of cubeb to a pint of water, has been employed as an injection in discharges from the vagina.

Dose, of powdered cubeb, ten grains to one drachm (0.65-3.9 Gm.).

Off. Prep.—Fluidextractum Cubebae, N. F.; Oleoresina Cubebae, U. S.; Tinctura Cubebae, Br.; Trochisci Cubebae (from Oleoresin), U. S.; Elixir Buchu Compositum (from Compound Fluidextract of Buchu), N. F.; Fluidextractum Buchu Compositum, N. F.; Pilulae Antiperiodicae, N. F.; Pilulae Antiperiodicae sine Aloes, N. F.; Tinctura Antiperiodica, N. F.; Tinctura Antiperiodica sine Aloes, N. F.; Tinctura Cubebae, N. F.

The Dispensatory of the United States of America, 1918, was edited by Joseph P. Remington, Horatio C. Wood and others.