Ursodeoxycholic acid NEW

Ursodeoxycholic acid can generally be divided into cholelitic agents and liquid cholelitic agents. The former refers to drugs that can promote bile secretion, and the latter refers to drugs that only increase the volume of bile but do not increase the content of bile. At present, the commonly used cholelitic drugs are mainly cholic acids. There are sodium cholate, dehydrocholic acid, goose deoxycholic acid and ursodeoxycholic acid. Ursodeoxycholic acid (URsodeoxycholic acid) is a chemical preparation of natural bile acid isolated from bear bile. It is a differential stereoisomer of goosedeoxycholic acid. Its lithiolysis effect and curative effect are similar to goosedeoxycholic acid, but the course of treatment is short and the dose is small. In the body, it binds to taurine in bile, is a hydrophilic cholic acid, and is a cholesterol stone dissolving agent. It can reduce the liver's secretion of cholesterol, reduce the saturation of cholesterol in bile, promote the secretion of bile acid, increase the solubility of cholesterol in bile, dissolve cholesterol stones or prevent the formation of stones. It can increase the volume of bile secretion, relax the sphincter of bile duct and produce cholelitic effect, which is conducive to the discharge of stones. This product does not dissolve other types of gallstones. Ursodeoxycholic acid is suitable for the treatment of cholesterol lithiasis, hyperlipidemia, biliary dysplasia, primary biliary cirrhosis, chronic hepatitis, bile reflux gastritis and prevention of acute rejection and reaction of liver transplantation. The stone dissolving effect of this product is slightly weaker than that of goodeoxycholic acid.

Pharmacological action

Ursodeoxycholic acid, or 3α, 7β-dihydroxycholic acid, is the 7β-hydroxy differential isomer of goannedeoxycholic acid, and it is this small difference in structure that makes this product hydrophilic. This product can reduce the activity of β-hydroxy-β-methylglutaryl Coenzyme A(HMG-CoA) reductase, which is the rate-limiting enzyme of cholesterol synthesis in liver, and inhibit cholesterol synthesis; And form a stable liquid crystal suspension with cholesterol, so that the cholesterol in the bile is unsaturated, and then promote the cholesterol in the stone precipitation and dissolution. This product can also inhibit intestinal absorption of cholesterol. Ursodeoxycholic acid can also antagonize the cytotoxicity of endogenous hydrophobic bile acids and protect liver cell membrane. This product reduces the overexpression of the major histocompatibility antigen MHC-1 in liver cell membrane; Inhibit the production of interleukin-2, 4, tumor necrosis factor and interferon alpha; Increase the levels of interleukin-10 and 12 in the body; And directly bind to glucocorticoid receptors to play an immunomodulatory role. In addition, ursodeoxycholic acid also has the effects of inhibiting apoptosis, inhibiting inflammation, scavenging free radicals and anti-oxidation. After oral administration, it is mainly absorbed in the upper jejunum by non-ionic passive diffusion and in the ileum by active transport. The first pass effect is large, and 50% ~ 75% of the oral dose is absorbed by the liver. It is mainly distributed in liver, intestine and plasma, and the binding rate of plasma protein is 96% ~ 99%. The concentration of ursodeoxycholic acid in bile increased dose-dependent. When the dose is 20-30 mg/(kg·d), the concentration in bile is more than 60%, which can achieve the best therapeutic effect. Combined with glycine and taurine in the liver, it is metabolized by intestinal bacteria in the colon, a small part of the metabolites are excreted in the urine, and most of them are excreted in the stool. The biological half-life when taken orally is 3.5 to 5.8 days.

Drug interaction

(1) The effect of the combination of the two drugs on the reduction of cholesterol content and saturation in bile was greater than that of the single drug, and also greater than the combined effect of the two drugs.

(2) This product should not be used with cholestyramine or alumina-containing acid-making agent, so as not to affect the absorption.

(3) Oral contraceptives can affect the efficacy of this product. The adverse reaction is smaller than that of andeoxycholic acid and generally does not cause diarrhea. Occasionally constipation, allergy, headache, dizziness, pancreatitis and tachycardia were observed.

Matters needing attention

(1) Use with caution in elderly patients.

(2) Long-term use can increase the number of peripheral blood plates.

(3) If recurrent biliary colic occurs in the treatment of cholesterol stones, the symptoms do not improve or even worsen, or there is obvious calcification of stones, treatment should be discontinued and surgical surgery should be performed.

(4) This product can not dissolve bile pigment stones, mixed stones and non-X-ray stones.

(5) Liver function should be checked regularly during administration.

Application:

1 Gallstone dissolving drug. It is mainly used for cholesterol gallstones that are not suitable for surgical treatment, especially the gallbladder function is basically normal, the stone diameter is below 15mm, X-ray, non-calcified floating cholesterol stones have a high cure rate. It also has certain therapeutic effect on toxic hepatitis, cholecystitis, primary sclerosing cholangitis and primary cholestatic cirrhosis. To improve the therapeutic effect of α-interferon on chronic hepatitis C. Diarrhea, rare constipation, allergic reactions, pruritus, headache, dizziness, stomach pain, pancreatitis and bradycardia. It is contraindicated in patients with complete obstruction of biliary tract and severe hepatic dysfunction and pregnant women.

2 Suitable for the prevention and treatment of cholesterol gallstones, anionic detergent.

3 Anionic detergent for biochemical research.