Santoninum (U. S. P.)—Santonin.

Preparations: Trochisci Santonini (U. S. P.)—Troches of Santonin. - Trochisci Santonini Composita.—Compound Troches of Santonin. - Trituration of Santonin and Podophyllin
Related entry: Santonica (U. S. P.)—Santonica

"A neutral principle obtained from Santonica. Santonin should be kept in dark, amber-colored vials, and should not be exposed to light"—(U. S. P.).

History and Preparation.—Santonin, the vermifuge principle of santonica, was discovered, in 1830, by Kahler and Alms, simultaneously. The British Pharmacopoeia (1885) gives detailed directions for its preparation, which consists in boiling the bruised santonica seeds in water with addition of slaked lime, concentrating the solution of calcium santonate, adding hydrochloric acid, and allowing it to stand for 5 days. Wash the precipitated santonin (santonic anhydride) with water and ammonia water, which removes resin, and recrystallize from alcohol after treating the solution with animal charcoal. Another method consists in boiling out a mixture of santonica seeds and slaked lime with alcohol of 60 per cent (by volume), and decomposing the calcium santonate with carbonic acid (see Flückiger, Pharmacognosie des Pflanzenreichs, 3d ed., 1891, p. 822). (Also see detailed Bibliography on Santonin, by A. Van Zwaluwenburg, Pharm. Arch., 1899, pp. 1-11.)

Description.—Santonin occurs "in colorless, shining, flattened, prismatic crystals, odorless and nearly tasteless when first put in the mouth, but afterward developing a bitter taste; not altered by exposure to air, but turning yellow on exposure to light. Nearly insoluble in cold water; soluble in 40 parts of alcohol at 15° C. (59° F.), in 250 parts of boiling water, and in 8 parts of boiling alcohol; also soluble in 140 parts of ether, in 4 parts of chloroform, and in solutions of caustic alkalies. When heated to 170° C. (338° F.), santonin melts, and forms, if rapidly cooled, an amorphous mass, which instantly crystallizes oil coming in contact with a minute quantity of one of its solvents. At a higher temperature, it sublimes partly unchanged, and, when ignited, it is consumed, leaving no residue. Santonin is neutral to litmus paper moistened with alcohol. Santonin yields, with an alcoholic solution of potassium hydrate, a bright pinkish-red liquid, which gradually becomes colorless. From its solution in caustic alkalies, santonin is completely precipitated by supersaturation with an acid"—(U. S. P.).

Santonin (C15H18O3) is the anhydride of santonic acid (C15H20O4), which is a derivative of dimethyl-naphtalene (C10H6[CH3]2). Santonin dissolves in alkalies with formation of salts of this acid. Santonin, in acetic acid solution, when exposed to sunlight for about a month, is converted into (colorless) photosantonic acid (C15H22O5). The ethyl-ester of the latter is obtained when an alcoholic solution of santonin is exposed to sunlight (Sestini). The yellow coloration developed upon exposure of santonin to light, is believed to be due to a red resin. Santonin is optically laevo-rotatory.

Adulterations and Tests.—Santonin has been adulterated by boric acid; this substance may be recognized by being insoluble in chloroform, or by not being volatilized when heated on platinum foil. If the residue is dissolved in water, and the solution acidulated with hydrochloric acid, a strip of yellow turmeric paper is colored brown by it. Santonin, turned yellow from exposure to light, has been mistaken for picric acid; the latter is easy of detection, being soluble in cold and hot water with yellow color (J. M. Maisch, Amer. Jour. Pharm., 1874, p. 52); or the white crystals of santonin might be mistaken for strychnine, the latter, however, may readily be distinguished by the violet coloration it produces with sulphuric acid and potassium dichromate (see Strychnina). Other substitutions, e. g., salicin, may be recognized by the following U. S. P. directions for santonin: "Its solution in cold, concentrated sulphuric acid is at first colorless (absence of easily carbonizable, organic substances), but, after some time, turns yellow, then red, and finally brown. If water be added, immediately after it is dissolved without color in sulphuric acid, it will be completely precipitated, and the supernatant liquid should not have a bitter taste, nor should it be altered upon the addition of potassium dichromate T.S. (absence of brucine or strychnine), or of mercuric potassium iodide T.S. (absence of alkaloids in general)"—(U. S. P.). D. Lindo's test for santonin is as follows: Dissolve, in a test-tube, a small quantity of santonin in strong sulphuric acid, add a few drops of a highlydiluted solution of ferric chloride; upon warming in the flame of a Bunsen burner, a beautiful violet coloration is developed.

Action, Medical Uses, and Dosage.—Santonin is an active agent, and, in improper doses, is capable of producing serious symptoms, and even death. As small a dose as 2 grains is said to have killed a weakly child of 5 years, and 5 grains produced death in about ½ hour in a child of the same age. Among the toxic effects may be mentioned gastric pain, pallor and coldness of the surface, followed by heat and injection of the head, tremors, dizziness, pupillary dilatation, twitching of the eyes, stertor, copious sweating, hematuria, convulsive movements, tetanic cramps stupor, and insensibility. Occasionally symptoms resembling cholera morbus have been produced, and in all cases the urine presents a characteristic yellowish or greenish-yellow hue. We have observed convulsions caused by the administration of "worm lozenges." Death from santonin is due to respiratory paralysis, and post-mortem examination revealed in one instance a contracted and empty right ventricle, and about an ounce of liquid, black blood in the left heart, an inflamed duodenum, and inflamed patches in the stomach (Kilner). The chief form of treatment of poisoning by santonin is by artificial respiration. Internal and external stimulation should also be resorted to, inhalations of ether or chloroform, to control the convulsions, should be given, and a purgative administered to remove remaining traces of the poison from the bowels. Santonin often produces a singular effect upon the vision, causing surrounding objects to appear discolored, as if they were yellow or green, and occasionally blue or red; it also imparts a yellow or green color to the urine, and a reddish-purple color if that fluid be alkaline. Prof. Giovanni was led to believe that the apparent yellow color of objects observed by the eye, when under the influence of santonin, did not depend upon an elective action on the optic nerves, but rather to the yellow color which the drug itself takes when exposed to the air. Santonin colored by the air does not produce this effect, which only follows the white article. The air gives the yellow color to santonin, to passed urine containing it, and to the serum of the blood when drawn from a vein, and, according to Giovanni, it is owing to its direct action upon the aqueous humor, where it is carried by absorption, that objects present this color. The view now held, however, is that of Rose, that the alkaline serum dissolves the santonin, which then acts upon the perspective centers of the brain, producing the chromatopsia or xanthopsia. Santonin has been advantageously given in amaurosis following acute inflammation of some of the internal parts of the eye; also in subacute and chronic retinitis and choroiditis. It is said to have materially benefited cases of noncongenital color-blindness, being administered in 1/20 or 1/10 grain doses (Foltz).

Santonin is the chief remedy now used for the expulsion of the roundworm or ascaris lumbricoides. It acts less effectually upon rectal ascarides, and not at all upon the tapeworm. As a rule, when a single dose is to be given, it should be administered upon an empty stomach, and the patient should refrain from eating for a short time afterward. A purgative should precede and follow its use. Another method, which has found much favor in the Eclectic school, is that of giving santonin, in divided doses, as follows: Rx Santonin, grs. v; podophyllin, grs. j; milk-sugar, ʒi. Mix. Divide into 10 powders, and administer 1 powder 3 times a day.

Santonin is an important nerve stimulant. It relieves many of those nervous phenomena which simulate the conditions produced by worms—picking at the nose, starting in sleep, intestinal irritation, etc. Its effects upon troubles of the urinary apparatus, due to disordered or deficient innervation, make it one of our best specific remedies. In retention of urine, due to atony of the bladder, no remedy surpasses it, and when this occurs as a symptom of the advanced stage of acute diseases of children, indicating an unfavorable prognosis, unless the urinary function can be restored, santonin may be given in ¼ to ½- grain doses (triturated with sugar), every hour, until a free urinary flow is established. Retention of urine, caused by opium preparations, is corrected by it. Being strongly diuretic, it may be administered in in renal colic. It relieves urethral irritation, dysuria, strangury, nocturnal enuresis, chronic vesical catarrh, and vesical tenesmus. It acts promptly in the urethral irritation, with pain and scalding, associated with uterine disorders, and in large, but unsafe, doses (10 grains), it has been recommended in uterine colic and amenorrhoea (Berthey). It relieves the difficult micturition and urinal retention following parturition, when not due to long-continued pressure of the child's head upon the parts. Many of the unpleasant urinary symptoms of albuminuria and chronic nephritis are relieved by santonin, and it is a remedy for impaired breathing and tympanitis due to deficient spinal innervation. The dose of santonin for an adult ranges from 1/10 to 4 grains; for a child, 1/20 to 2 grains, always avoiding the larger dose when possible; 2 x trituration, 2 or 3 grains, for its effects upon the urinary apparatus.

Specific Indications and Uses.—To remove all kinds of intestinal worms but the tapeworm; retention of urine from atony; nocturnal enuresis from atony; urethral irritation, with pain and scalding, accompanying uterine disorders, retention of urine in fevers; deficient spinal innervation, as evidenced by impaired respiration and tympanitis; vesical tenesmus and strangury; retention of urine from the use of opiates.

Related Products.—SANTONINOXIME (C15H19NO3, or C15H18O2:N.OH). Said to be a safe substitute for santonin, and the dose given may be 3 times as large. P. Guici (1889) prepared it by the interaction of santonin (5 parts), hydroxylamine hydrochloride (4 parts), strong alcohol (50 parts), and precipitated calcium carbonate (4 parts). These were digested for 3 or 4 days at about 80° C. (176° F.). It forms white silky, laevogyre needles, very sparingly soluble in hot water. It fuses at near 217° C. (442.6° F.).

Santolina chamaecyparissus (Compositae).—Popular in Scotland as a remedy for roundworm. Half ounce of the plant may be boiled with 1 pint of water for 30 minutes, strained, and brought to the measure to 1 pint when finished. Of this decoction, 2 ½ ounces may be given to children, or 5 ounces to adults for 4 successive days, and may be followed with an active cathartic. Maben finds in the plant a bitter body, which he believes to be the active substance, resin, and an essential oil (Pharm. Jour. Trans., Vol. XVI).

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