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Application of 13-methylamino-18-thiomatrine compound in the preparation of anti-hepatic fibrosis or other tissue and organ fibrosis drugs

A technology of thiomatrine and anti-hepatic fibrosis, applied in the field of medicine

Inactive Publication Date: 2011-11-30
SHANGHAI HUFENG BIOLOGICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent decades, although some progress has been made in the research of anti-hepatic fibrosis drugs, many drugs are still in the preclinical or clinical trial stage, such as TGFβ1 antagonists, hepatocyte growth factor, S-adenosylmethionine, pirfenib, etc. Ketones, etc., but there is no chemical drug approved for the treatment of human liver fibrosis

Method used

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  • Application of 13-methylamino-18-thiomatrine compound in the preparation of anti-hepatic fibrosis or other tissue and organ fibrosis drugs
  • Application of 13-methylamino-18-thiomatrine compound in the preparation of anti-hepatic fibrosis or other tissue and organ fibrosis drugs
  • Application of 13-methylamino-18-thiomatrine compound in the preparation of anti-hepatic fibrosis or other tissue and organ fibrosis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Cell proliferation test: 1×104 rat hepatic stellate cells HSC-T6, glomerular mesangial cells, lung fibroblasts, cardiac fibroblasts were added to each well of a 96-well cell culture plate, and placed in a 37°C CO2 incubator After incubation for 24 hours, 100 μl of DMEM culture solution or drug-free culture solution containing different drug concentrations and 10% newborn calf serum (NCS) was added, and after 48 hours of continuous cultivation, a thiazolium (MTT) microplate reader was added to measure the absorbance at 570 nm.

[0013] Determination of collagen synthesis: using 3H-proline isotope method. Adjust the cell concentration to 2.5×105 cells / ml, add 100 μl to each well of a 96-well plate, and culture for 24 hours to form a monolayer to eliminate the influence of cell growth on collagen synthesis. Then add the drug containing 50 μg.ml-1 vitamin C and 10% NCS or transforming growth factor β1 (TGFβ1) and culture for another 48 hours, and add 18.5 kBq of [3H]-prolin...

Embodiment 2

[0023] 90 ICR mice, half male and half male, weight 20±2g. Randomly divided into 9 groups, 10 in each group. Group 1 is the normal control group. Groups 2-5 are intraperitoneally injected with 0.5% carbon tetrachloride-olive oil 10 / kg to create a carbon tetrachloride acute liver injury model, and groups 6-9 are injected with D-galactosamine 800 mg / kg intraperitoneally. Create D-galactosamine acute liver injury model. Groups 2 and 6 were the model control group, and groups 3 and 7 were given 200 mg / kg bifendate by intragastric administration as the positive control group. Groups 4 and 8 were given 50 mg / kg of 13-methylamino-18-thiomatrine compound (I) by intragastric administration as the experimental group, and groups 5 and 9 were given 50 mg / kg of matrine by intragastric administration as the experimental control group. Modeling was made after 3 days of administration in each of the above groups, blood and liver were taken 48 hours later, and alanine aminotransferase (ALT) ...

Embodiment 3

[0028] (1) Bile duct ligation (BDL) liver fibrosis model

[0029]60 male SD rats, weighing 150g-200g, clean grade, provided by Shanghai Animal Experiment Center, Chinese Academy of Sciences, were randomly divided into 6 groups, 10 rats in each group. After intraperitoneal injection of chloral hydrate solution for anesthesia, the common bile duct was ligated to prepare the liver fibrosis model with common bile duct ligation. Assuming sham operation group, model control group, 13-methylamino-18-thiomatrine compound (I) (25, 50mg / kg), matrine control group (50mg / kg), matrine injection positive Control group (50mg / kg). The rats were intragastrically administered 2 days after the operation, and the rats were sacrificed 3 weeks after the model was established. The inferior vena cava was punctured to draw blood, and an automatic blood biochemical analyzer was used to detect serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the alkaline hydrolysis method...

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Abstract

The invention relates to the technical field of medicine, in particular to the use of 13-methylamino-18-thiomatrine compound (I) and its salts in the preparation of anti-fibrosis drugs. The present invention proves from cytological tests that 13-methylamino-18-thiomatrine can inhibit proliferation and activation of extracellular matrix producing cells hepatic stellate cells, and inhibit fibrotic liver epithelial cell-mesenchymal transition. In addition, it also has inhibitory effects on various other extracellular matrix-producing cells that lead to organ or tissue fibrosis. Animal experiments have proved that 13-methylamino-18-thiomatrine has a very significant anti-hepatic fibrosis effect. The results show that 13-methylamino-18-thiomatrine has definite anti-hepatic fibrosis or fibrosis of other tissues and organs, and can be used to prepare medicines for preventing and treating liver fibrosis or fibrosis of other tissues and organs.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of 13-methylamino-18-thiomatrine compound and pharmaceutically acceptable salts thereof in the preparation of anti-fibrosis drugs. Background technique [0002] Liver fibrosis is the liver's repair response to chronic liver injury caused by various etiologies, and its main feature is the excessive deposition of extracellular matrix (ECM). Liver fibrosis is a common pathological feature of various chronic liver diseases, and it is the main intermediate link in the further development of liver cirrhosis, and even malignant transformation and death. Because the treatment of liver cirrhosis is very difficult and the mortality rate is high, it is currently believed that liver fibrosis is reversible, so blocking or delaying the occurrence and development of liver fibrosis has important applications for the treatment of various chronic liver diseases accompanied by live...

Claims

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Application Information

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IPC IPC(8): A61K31/4375A61P1/16A61P11/00A61P43/00
Inventor 张俊平王绍展胡宏岗李婕李云华
Owner SHANGHAI HUFENG BIOLOGICAL TECH CO LTD
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