Хенодезоксихолевой кислота

Описание

Chenodeoxycholic acid is the first agent to be introduced into the US market for the treatment of radiolucent gallstones. Large scale clinical trials have demonstrated the safety and efficacy of this agent. Chenodeoxycholic acid reduces the biliary concentration of cholesterol relative to that of bile acids and phospholipid, reducing the saturation and thus the lithogenicity of the bile. Success rates in dissolving gallstones are in the range of 50-70% within 4-24 months of treatment. Continuation of the drug after stone dissolution may be required to prevent reoccurrence. Chenodeoxycholic acid is the 7α-isomer of ursodeoxycholic acid which was introduced into the European market in 1978.

chenodeoxycholic acid structure

Химические свойства

Off-White Solid

История

Chenodeoxycholic acid was isolated in 1924 from goose gall by Adolf Windaus and human gall by Heinrich Wieland.Its complete structural configuation was elucidated by Hans Lettre at the University of Gottingen.
In 1968, William Admirand and Donald Small at Boston University Medical School established that in patients with gallstones their bile was saturated with cholesterol, sometimes even exhibiting microcrystals, whereas this was not the case in normal people.It was then found that biliary levels of cholic acid and chenodeoxycholic acid were lower in patients with cholesterol gallstones than in normal people. Leslie Thistle and John Schoenfield at the Mayo Clinic in Rochester, Minnesota, then administered individual bile salts by mouth for four months and found that chenodeoxycholic acid reduced the amount of cholesterol in the bile.This led to a national collaborative study in the United States, which confirmed the effectiveness of chenodeoxycholic acid in bringing about dissolution of gallstones in selected patients. However, recent developments such as laparoscopic cholecystectomy and endoscopic biliary techniques have curtailed the role of chenodeoxycholic acid and ursodeoxycholic acid in the treatment of cholelithiasis.

Использование

A major bile acid in many vertebrates, occurring as the N-glycine and/or N-taurine conjugate. With other bile acids, forms mixed micelles with lecithin in bile which solubilize cholesterol and thus fa cilitates its excretion. Fcilitates fat absorption in the small intestine by micellar solubilization of fatty acids and monoglycerides. Anticholelithogenic. Epimeric with Ursodiol.

Всемирная организация здравоохранения(ВОЗ)

Chenodeoxycholic acid was introduced in 1975 for the treatment of cholelithiasis. It is available in several countries and the World Health Organization is not aware that registration has been refused in any other country.

Общее описание

Chenodeoxycholic acid is a bile acid synthesized in the liver from cholesterol.

Методы очистки

This major bile acid in vertebrates (~80mg) is chromatographed on silica gel (5g) and eluted with CHCl3/EtOAc (3:2) and crystallised from EtOAc/hexane. It has IR: max 1705 cm-1(CHCl3). It also crystallises from EtOAc, EtOAc/heptane after purifying via the poorly soluble Na and K salt if necessary. [Kametani et al. J Org Chem 4 7 2331 1982, Beilstein 10 IV 1604.]