Chenodeoxycholic acid

Uses

Chenodeoxycholic acid is a bile acid synthesized in the liver from cholesterol. henodeoxycholic acid has been used in a study to assess its effects as a long-term replacement therapy for cerebrotendinous xanthomatosis (CTX). It has also been used in a study to investigate its effects on the small-intestinal absorption of bile acids in patients with ileostomies.

Description

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

Chemical Properties

Off-White Solid

Originator

Rowell (USA)

History

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.

Uses

An apoptosis inducer via PKC-dependent signalling pathway.

Uses

anticholithogenic, antilipemic agent

Uses

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.

Uses

Chenodeoxycholic acid is a bile acid that induces apoptosis through protein kinase C signaling pathways.It is 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 facilitates its excretion.Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress. Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.

1. Chenodeoxycholic acid is widely utilized in therapeutic applications. It is applied in medical therapy to dissolve gallstones. It is employed in the treatment of cerebrotendineous xanthomatosis. It is used to treat constipation and cerebrotendineous xanthomatosis. It acts as a urea receptor in supramolecular chemistry which can contain anions. It is a staining additive commonly used with ruthenium or organic photo-sensitizers in the preparation of staining solutions for dye solar cells.
2. Chenodeoxycholic Acid is a staining additive commonly used with ruthenium or organic photo-sensitizers in the preparation of staining solutions for Dye Solar Cells. This co-adsorbent will prevent dye aggregation on the semiconductor surface, reducing losses in the solar cell's operation.
3. Chenodeoxycholic Acid is a white solid added with the dye powder to the solvent while preparing staining solutions. The concentration of co-adsorbent is typically 10 fold the dye concentration.
4. Chenodeoxycholic acid has been used in a study to assess its effects as a long-term replacement therapy for cerebrotendinous xanthomatosis (CTX).
5. It has also been used in a study to investigate its effects on the small-intestinal absorption of bile acids in patients with ileostomies.
6. Chenodeoxycholic acid (CDCA) is a hydrophobic primary bile acid that activates nuclear receptors involved in cholesterol metabolism.EC50 concentrations for activation of FXR range from 13-34 μM.In cells, CDCA also binds to bile acid binding proteins (BABP) with a reported stoichiometry of 1:2.CDCA toxicity is linked to increased cellular glutathione levels and increased oxidative stress. Exposure of cells to excess CDCA contributes to liver and intestinal cancers.

Definition

ChEBI: Chenodeoxycholic acid is a dihydroxy-5beta-cholanic acid that is (5beta)-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 7 respectively. It has a role as a human metabolite and a mouse metabolite. It is a bile acid, a dihydroxy-5beta-cholanic acid and a C24-steroid. It is a conjugate acid of a chenodeoxycholate.

Manufacturing Process

To 1,400 ml of an approximately 50% water/triglycol solution of the potassium salt of chenodeoxycholic acid, obtained by the Wolff-Kishner reduction (using hydrazine hydrate and potassium hydroxide) from 50 g of 7- acetyl-12-ketochenodeoxycholic acid, 220 ml of dilute hydrochloric acid is added to bring the pH to 2. The solution is stirred and the crude chenodeoxycholic acid precipitates. The precipitate is recovered and dried to constant weight at about 60°C. About 36 g of the crude chenodeoxycholic acid, melting in the range of 126°-129°C, is obtained.
25 g of crude chenodeoxycholic acid so obtained is dissolved in 750 ml of acetonitrile while stirring and heating. 3 g of activated charcoal is added and then removed by suction filtering. The resulting liquid filtrate is cooled, the pure chenodeoxycholic acid crystallizing out. The crystals are recovered by suction filtering and the recovered crystals dried under vacuum. The yield is 19 g of pure chenodeoxycholic acid with a melting range of 168°-171°C.

brand name

CHEWM

Therapeutic Function

Gallostone dissolving agent

World Health Organization (WHO)

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.

General Description

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

Flammability and Explosibility

Non flammable

Purification Methods

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.]