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Application of colchicin in preparing cholestatic liver disease drug

A technology of cholestasis and colchicine, which is applied in the application field of colchicine in the preparation of drugs for the treatment of cholestatic liver disease, can solve the problems of no colchicine, etc., protect bile duct epithelial cells, reduce liver damage, alleviate The effect of liver cell necrosis

Inactive Publication Date: 2010-09-08
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0027] There is no report about colchicine in the treatment of cholestatic liver disease in the literature, and the inventor first discovered that colchicine can treat cholestatic liver disease

Method used

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  • Application of colchicin in preparing cholestatic liver disease drug
  • Application of colchicin in preparing cholestatic liver disease drug
  • Application of colchicin in preparing cholestatic liver disease drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1, to α-naphthalene isothiocyanate (ANIT) induced rat cholestasis effect

[0048] The cholestasis model induced by α-naphthalene isothiocyanate (ANIT) is a classic model for studying intrahepatic cholestasis. ANIT-induced cholestasis in rats occurred after 12 hours of intragastric administration of ANIT 50-100mg / kg, and liver damage and jaundice occurred 24 hours later. Experimental scheme: 30 220-250g male Wistar rats were randomly divided into 5 groups, 6 in each group: normal control group, model group (ANIT 50mg / kg gavage), melatonin 50mg / kg gavage treatment group, autumn Narcisine 50 and 100μg / kg intraperitoneal injection treatment group. The treatment group was given prophylactic administration for 5 days, fasted overnight after the 5th day, and was given ANIT for modeling, and then 0.5ml of orbital blood was collected 48 hours after the modeling to measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP...

Embodiment 2

[0051] Embodiment 2, to 17α-ethinyl estradiol (EE)-induced rat cholestasis effect

[0052] The cholestasis induced by 17α-ethinylestradiol (EE) was used to establish the model. EE modeling is a commonly used animal model for studying cholestasis during pregnancy. Subcutaneous injection of EE 5mg / kg for 5 consecutive days will cause cholestasis. Experimental scheme: 30 male rats were randomly divided into the following 5 groups according to body weight, 6 rats in each group: normal control group, model group (EE 5mg / kg, sc), ursodeoxycholic acid 50mg / kg gavage treatment group, Colchicine 50 and 100μg / kg intraperitoneal injection treatment group. Among them, EE was administered for 5 days for modeling, colchicine was given 1 hour before modeling, fasted overnight after the last administration, and 1ml of orbital blood was collected to measure ALT, AST, ALP, GGT, TBIL and TBA. The livers were fixed in neutral formalin, embedded in paraffin to make tissue sections, and the expre...

Embodiment 3

[0055] Example 3. Effect on extrahepatic cholestasis caused by bile duct ligation

[0056] The extrahepatic cholestasis induced by bile duct ligation was used to establish the model. Cholestatic jaundice occurs on the second day after common bile duct ligation in rats. The rat bile duct ligation model is a commonly used animal model for studying extrahepatic stasis jaundice. Experimental scheme: 32 SD rats, half male and half female, were anesthetized by intraperitoneal injection of 400 mg / kg chloral hydrate. Incision was made along the abdominal linea alba, the common bile duct was separated, double ligated and cut from the middle, and 6 rats in the control group were sham-operated. Method, only the bile duct was separated without ligation, and sutured with surgical thread. Twenty-four survived two days later. Divided into: control group, model group, ursodeoxycholic acid 50mg / kg intragastric administration treatment group, colchicine 50 and 100μg / kg intraperitoneal injecti...

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Abstract

The invention relates to application of colchicin in preparing drugs, in particular to application of colchicin in pharmacotherapy of cholestatic liver disease, the application of colchicin in preparing a cholestatic liver disease drug, and the application of colchicin in preparing the drug for treating gestation intrahepatic cholestasis syndrome, inner primary cirrhose biliaire, primary sclerosing cholangitis severe jaundice or immunity jaundice cholestatic liver disease. The colchicin can effectively lower liver injury and cholestasis caused by cholestatic liver disease, i.e. the colchicin can effectively treat cholestatic liver disease. The colchicin can effectively lighten hepatic cell necrosis, inflammatory cell infiltration and bile capillary hyperplasia caused by cholestasis. The colchicin can effectively increase bile acid, bilirubin and expression of phospholipid transporters BSEP, MRP2 and MDR3 in a bile duct, accelerates excretion of bile acid, bilirubin and phospholipid deposited in the body and reduces liver damage.

Description

technical field [0001] The invention relates to the application of colchicine in pharmaceuticals, in particular to the application of colchicine in drug treatment of cholestatic liver disease. Background technique [0002] Source of colchicine: colchicine is the main active ingredient and toxic ingredient in colchicine, a tropolone alkaloid. In addition to the colchicum of the Liliaceae, other genera of the same family, including Gloriosa, Iphigenia, Auguillaria and Arisaema, also contain autumn Narcissus alkaloids. Chemical name: N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxo-benzo[a]heptatriene-7 -yl)acetamide, CAS: 64-86-8. [0003] structure: [0004] [0005] The main pharmacological effects of colchicine are briefly summarized as follows: [0006] 1. Anti-gout [0007] At present, colchicine is mainly used for acute gout. Colchicine has a selective anti-inflammatory effect on acute gouty arthritis, but is ineffective on general pain, inflammation and chron...

Claims

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Application Information

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IPC IPC(8): A61K31/165A61P1/16
Inventor 王涛尚靖张陆勇江振洲周植星
Owner CHINA PHARM UNIV
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