Santonin

SANTONIN (C₁₅H₁₈O₃), the active principle of wormwood, Artemisia Cina Berg., A. maritima L., A. mexicana and other species, was first found in 1830 by the pharmacist Kaller and independently by Alms in the dried, unopened inflorescences (incorrectly called wormwood seed) of this plant, wild-growing in Kazakhstan, in the Chimkent region. Santonin possesses ketone properties and is simultaneously a lactone of santoninic acid, C₁₅H₁₈O₃, the structure of which is attributed as follows: o-----co CH₃ / I I CH | Cc/V^CH-CH-CH₃^/K/^CH₂ CI₂CH₃ a colorless crystalline powder (rhombic prisms or plates), odorless, slightly bitter taste, soluble in 5,000 parts of cold and 250 parts of boiling water (neutral reaction), in 44 parts of cold and in 3 parts of boiling 90% alcohol, in 75 parts of ether and in 4 parts of chloroform. It also dissolves in fatty and essential oils and in alkalis. Under the influence of light it undergoes a photochemical change, forming the yellow substance chromosantonin, which after crystallization reverts to Santonin. It melts at 170°, subliming. Rotatory power [a]^° = -171.6° for a 2% solution in 90% alcohol. Santonin is produced at the Chimkent pharmaceutical factory. Its extraction from wormwood seed, which contains from 1 to 3.5% Santonin, is based on the fact that when treated with slaked lime it passes into the calcium salt of santoninic acid. Upon addition of hydrochloric acid to an aqueous solution of this salt, Santonin precipitates, which is purified with ammonia and crystallized from alcohol and decolorized with charcoal. Santonin gives a blood-red coloration with a 50% solution of sulfuric acid, heated to 100°, with a drop of ferric chloride. When heated with hydrochloric acid, Santonin is converted into the isomeric desmotroposantonin, obtained in 1930 by synthetic means. In the acidic medium of the stomach, Santonin partially dissolves and is absorbed (more so on an empty stomach). Further, in the small intestines, it dissolves in the alkaline intestinal juice, passing into the sodium salt of Santonin, which is absorbed, manifesting a general action. Santonin is primarily a nervous poison. Most often, a distortion in the perception of colors - xanthopsia - is observed, which is usually explained by a specific action on the retina, but this question has not yet been precisely elucidated. Apparently, Santonin reduces the ability to perceive the most refracted rays of the spectrum. In poisoning with large doses, convulsions are observed; in experimental animals, breathing becomes irregular, slows down, and the animal dies from asphyxia. After the usual doses used in medicine, almost all Santonin is excreted in a colored form, mainly in the urine, the yellow color of which, upon addition of caustic alkalis, turns red. The colored substance was also found in sweat, and upon administration of the potassium salt of Santonin, also in blood plasma and feces. The mechanism of Santonin's action on ascarids is not yet sufficiently clarified. In vitro, ascarids live for a long time in Santonin solutions, which some authors explain by the absence of bile acids, which enhance the effect of Santonin in the body. According to Trendelenburg, Santonin strongly excites the musculature of the worms, causing its strongest contraction, and this phenomenon is specific to Santonin and only relatively to worms. In recent times, the hypothesis has been expressed that Santonin is completely absorbed in the intestine and manifests its action only upon its secondary excretion into the intestine, after it has undergone certain changes in the body. The fact that such excretion into the intestine with subsequent manifestation of an anti-helminthic action does take place is proved by the anti-ascaris efficacy of Santonin upon its subcutaneous administration of its soluble sodium salt (Morinaka and Ischikawa, 1926; Schultz and Abuladze) or with santonin suppositories (Seishin, 1924). Santonin shows no significant action on migrating ascarid larvae (Smirnov, 1931). Santonin is most effective against ascarids (various representatives of the family Ascarididae, parasites of man and other mammals) and pinworms, acts more weakly on whipworms and is completely ineffective against most other nematodes, cestodes, and trematodes. Practically, Santonin finds application in human ascariasis (Ascaris lumbricoides), swine ascariasis (A. suum), and ascariasis of dogs and cats (Toxascaris leonina, Toxocara canis, T. mystax). It is prescribed in the form of powder, cakes, and in an oily solution with a preliminary diet and emptying of the stomach. The subsequent strong laxative (castor oil, calomel) expels the stupefied or dead worms with the feces. In recent years, a number of reports have appeared in the foreign press questioning the anti-ascaris efficacy of Santonin. Special works carried out by the All-Union Institute of Helminthology and NIKhFI have refuted these data, and it has been established that properly applied (mandatory with a laxative) and in correct doses, Santonin removes 70-95% of ascarids. Santonin expels not only adult but also young forms of ascarids. The expulsion of ascarids is noted on the 4th, 5th, and even 6th day after taking Santonin (Shikhobalova and Sokolova). The sensitivity of different individuals to Santonin is very different. With age, tolerance to Santonin increases. The results from the use of Santonin are not always the same, which should be attributed to a number of incidental factors (quantity and quality of the laxative, conditions and technique of administration and dosage). Based on specially conducted work by Shikhobalova and Sokolova, the following conclusion is reached: precise age dosages of Santonin (under the condition of normal physical status) are one of the factors playing a main role in the success of the therapy of ascariasis in children. For wide application, the dose of santonin 0.015 per day per year of the child's life and 0.3 for an adult (per day) can be recommended. The daily dose can be given in three doses with an hourly interval or in two doses with an interval of 2-3 hours. The maximum dose for man according to the pharmacopoeia is 0.1 once and 0.3 daily, but some allow larger dosages. The dose for a pig is 0.03-0.05 per 1 kg of live weight, for a dog 0.03 per 1 kg, for a cat 0.1-0.2 per head. With careless application of Santonin, poisoning can occur. The picture of poisoning and treatment - see Poisoning. Santonin is stored with precautions in a light-protected place in orange glass.

I. Pevinstein. Discovery of santonin in forensic cases. The objects of investigation may be the contents of the stomach and intestines, vomit. Discovery is successful only a short time after poisoning. The investigated material is extracted with water, alkalized with caustic soda upon heating. The solution is extracted with benzene to remove impurities, then acidified with hydrochloric acid and extracted with chloroform. The latter is evaporated and the residue is subjected to the following reactions: 1) a drop of the alcoholic solution of the precipitate is mixed with 1 drop of a 2% alcoholic solution of furfural and 2 cm³ of concentrated sulfuric acid and heated in a porcelain cup in a water bath: a purplish-red coloration appears, turning into violet-blue and blue, giving a black precipitate after a few hours. The reaction occurs when there is an excess of furfural with respect to Santonin. In the absence of the latter, furfural gives only a pale-pink coloration, which quickly turns brown. 2) In sunlight the residue yellows and upon dissolution in caustic alkalis takes on a reddish color, then disappearing.

I. Pevinstein. Discovery of santonin in forensic cases. The objects of investigation may be the contents of the stomach and intestines, vomit. Discovery is successful only a short time after poisoning. The investigated material is extracted with water, alkalized with caustic soda upon heating. The solution is extracted with benzene to remove impurities, then acidified with hydrochloric acid and extracted with chloroform. The latter is evaporated and the residue is subjected to the following reactions: 1) a drop of the alcoholic solution of the precipitate is mixed with 1 drop of a 2% alcoholic solution of furfural and 2 cm³ of concentrated sulfuric acid and heated in a porcelain cup in a water bath: a purplish-red coloration appears, turning into violet-blue and blue, giving a black precipitate after a few hours. The reaction occurs when there is an excess of furfural with respect to Santonin. In the absence of the latter, furfural gives only a pale-pink coloration, which quickly turns brown. 2) In sunlight the residue yellows and upon dissolution in caustic alkalis takes on a reddish color, then disappearing.

I. Pevinstein. Discovery of santonin in forensic cases. The objects of investigation may be the contents of the stomach and intestines, vomit. Discovery is successful only a short time after poisoning. The investigated material is extracted with water, alkalized with caustic soda upon heating. The solution is extracted with benzene to remove impurities, then acidified with hydrochloric acid and extracted with chloroform. The latter is evaporated and the residue is subjected to the following reactions: 1) a drop of the alcoholic solution of the precipitate is mixed with 1 drop of a 2% alcoholic solution of furfural and 2 cm³ of concentrated sulfuric acid and heated in a porcelain cup in a water bath: a purplish-red coloration appears, turning into violet-blue and blue, giving a black precipitate after a few hours. The reaction occurs when there is an excess of furfural with respect to Santonin. In the absence of the latter, furfural gives only a pale-pink coloration, which quickly turns brown. 2) In sunlight the residue yellows and upon dissolution in caustic alkalis takes on a reddish color, then disappearing.