サントニン

外観

白色～ほとんど白色粉末～結晶

解説

サントニン．セスキテルペンの一種．キク科Artemisia cinaのつぼみなどに1～4％ 含まれているが，わが国ではミブヨモギA.maritimaから単離している．回虫の頭部神経にはたらくけいれん毒で，駆虫薬として用いられる．α-サントニンは，融点171～172 ℃．[α]_D－173°(エタノール)．11位の異性体であるβ-サントニンは，融点216～218 ℃．[α]_D－137.2°(クロロホルム)．LD50 900 mg/kg(マウス，経口)．

効能

駆虫薬

来源

キク科の植物であるシナヨモギ、ミブヨモギ、クラムヨモギの開花直前のつぼみにもっとも多く含まれており、これらの植物の種子状をした小花頭をシナ花（通称セメンシナsemen cina）といい、これから1830年にドイツで結晶として初めて抽出され、メルク社からサントニンの名で発売された。かつて、日本ではセメンまたはセメン円(えん)とよばれた。ミブヨモギは、日本新薬がヨーロッパ産の種子を入手して、京都市の壬生(みぶ)で試作したのでこの名がついた。

説明

Santonin is a lactone compound extracted from the flower bud of Artemisia cina Berg in Compositae, crown daisy chrysanthemum or other plants in Artemisia. It has been recorded in ancient China . Its English name is santonica wormseed, Chinese alias is ‘quhaosu’ and Latin name is Seriphidium cinum (Berg ex Poljak.) Pol-jak. . Santonica wormseed, a variant name for Artemisia cina Berg, is the leaf and anthotaxy of Artemisia cina Berg in sagebrush plants in Compositae. There are more than 100 plus in sagebrush, in which about 30 plus live in China, and parts of them can be used medicinally.
Santonica wormseed, used as raw material to extract and manufacture santonin, lives in cold, dry sandy loam. The place of origin is the Southern Central Asia in the former Soviet Union. China introduced the earliest cultivation in Xinjiang, and now it is introduced and cultivated in the North, Northeast and Northwest China. Santonica wormseed mainly contains hispidulin, quercetin and caffeic acid, and its flower contains 1–3.5% α-santonin, 1–3% artemisinin and volatile oil (mainly is 1, 8-cineole) and so on. Leaf also contains a small amount of α-santonin. In addition, it also contains β-cintonin, 3,4,5,7-tetrahydroxy-3-methoxyflavone7- glucoside and aglucone.

物理的性質

Appearance: a colourless prism crystal or white crystalline powder, odourless, a little taste bitter and turning yellow in the sunlight. Solubility: hardly soluble in water, sparingly soluble in ethanol, freely soluble in boiling ethanol and chloroform and slightly soluble in diethyl ether. Melting point: 170–174 °C. Specific optical rotation: ?170 to ?175°, determined on 1% ethanol solution at 25 °C.
Santonin is a kind of ketolide with two double bonds. It forms a salt by the ring opening when dissolving in alkaline solutions and reforms ketolide by acidification.

来歴

The study on the chemical properties and structure of santonin was carried out at the end of the nineteenth century all the earliest research works were from the Italian scholars, such as Cannizzaro, Andreocci, Gucci, Francesconi, etc. The chemical structures determined before 1910 were all not exactly correct. Until 1929–1930, British scholars, Clemo, Haworth and Walton, finally determined the exact structure of santonin for the transformation from synthesized santonin into desmotroposanto nin and santonous acid. However, until 1940, there were no reports on structural configuration. Chinese scholars, Huang Minglong et al., basically completed the research work on the structural configuration of santonin in 1951, and the results were proved by Japanese scholars, Abe, Y. and Harukawa et al. in 1954.

使用

(-)-Santonin is a sesquiterpene lactone derivative which acts as an anti-pyretic agent when tested with subjects antagonized by haloperidol. Causes a decrease in temperature of mammals.

定義

ChEBI: A santonin that is 3a,5,5a,9b-tetrahydronaphtho[1,2-b]furan-2,8(3H,4H)-dione substituted by methyl groups at positions 3, 5a and 9.

適応症

As a kind of deworming drug, santonin was effective for the treatment of human roundworm infection, but it is no longer in use at present because of the development of more effective medicines.

副作用

副作用として黄視症がみられ、頭痛、悪心(おしん)、腹痛などが現れ、肝障害のあるところから、アメリカでは使用していない。

世界保健機関（WHO）

Santonin, a crystalline lactone obtained from flowerheads of species of Artemisia, was formerly used as an anthelminthic. Its use was associated with a range of adverse effects, mainly involving the sense organs and the central nervous system, some of which were fatal. It has been superseded by other less toxic and more effective anthelminthics.

一般的な説明

(?)-α-Santonin is a sesquiterpene lactone. It is found in the genus Artemisia.

薬理学

Santonin has a roundworm-expelling effect. It can excite worm’s ganglion which leads the worm not to be adsorbed in the intestinal wall, and then the worm is excreted out of the body after using laxatives. The effect is limited to the round worm, and it has little effect on other helminth. Excessive application can cause toxic effect. When it is excreted in urine, it can make the urine dark yellow or pink. It can be used in the treatment of ascariasis. During the medication, grease should be avoided, and laxative needs to be used such as salts. Patients with hepatosis, nephrosis and acute gastritis must contraindicate its use. The lethal dose 50 (LD50) injected under the skin of mice is 250–400 mg/kg.

臨床応用

Santonin has been used for a long time as a kind of deworming drug. Its mechanism is between inhibitory effect on γ-GABA and excitatory effect of cholinergic func tion. It also acts on the human central nervous system and can cause some adverse effects, such as dizziness, leipopsychia, headache, epilepsy, xanthopsia, paresthesia and so on
Santonin is easily dissolved and absorbed in the intestine due to alkaline intesti nal fluid and solvent effect of bile salts. Especially, it can cause severe toxic reaction more easily for increasing absorption because intake of fatty food promotes bile production, secretion and release.
Santonin has obvious central nervous system toxicity. A small amount can cause colour deficiency, and a large amount can cause epileptiform, excessive excitement turning into severe repression and even coma. Santonin is a highly toxic substance. Children’s lethal dose is 0.15 g; adults’ lethal dose is about 1 g. Santonin has already been phased out for the toxicity.