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Pharmaceutical composition for preventing and treating tissue damage caused by metabolic disorder or inflammation

A composition and drug technology, applied in the field of medicine, can solve problems such as undiscovered compounds, achieve the effects of reducing liver/body weight ratio, improving liver inflammation score, and reducing liver fibrosis

Active Publication Date: 2022-05-13
SHENZHEN CHIPSCREEN BIOSCIENCES CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

2-(3,5-Dibromo-4-((4-oxyl-3,4-dihydrophthalazin-1-yl)oxy)phenyl)-3,5-dioxo-2,3 ,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile (compound II) and 2-(3,5-dichloro-4-((4-oxyl-3,4-dihydro Phthalazin-1-yl)oxy)phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile (compound III) is A brand-new TRβ agonist, which is disclosed in the Chinese invention patent application CN202010379605.1, the full content of the Chinese invention patent application CN202010379605.1 is incorporated into the present invention, and compound II and compound III have not been found to have the effect of treating NASH

Method used

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  • Pharmaceutical composition for preventing and treating tissue damage caused by metabolic disorder or inflammation
  • Pharmaceutical composition for preventing and treating tissue damage caused by metabolic disorder or inflammation
  • Pharmaceutical composition for preventing and treating tissue damage caused by metabolic disorder or inflammation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1—Establishment of C57BL / 6J mouse NASH model by high-fat + carbon tetrachloride induction

[0029] 6-8 week old male C57BL / 6J mice (Chengdu Dashuo Animal Experiment Co., Ltd.) were divided into a control diet group and a high-fat + carbon tetrachloride group. The mice in the control diet group were fed with the control diet for 16 weeks. The mice in the high-fat + carbon tetrachloride group were fed with 60% high-fat diet for 16 weeks, and after 8 weeks were injected with carbon tetrachloride twice a week. Orbital blood was collected at 12 weeks, and serum was separated to detect corresponding biochemical indicators, including ALT, AST, HDL-C and LDL-C. 12-16 weeks is the dosing time. The results showed that before the injection of carbon tetrachloride, the body weight of the mice fed with the high-fat diet increased significantly over time compared with the mice in the control diet group. After the injection of carbon tetrachloride, the weight of the mice de...

Embodiment 2

[0030] Example 2—The effect of compound I, compound II and their combination on the liver / body ratio of high-fat+carbon tetrachloride-induced mice

[0031] The model mice obtained in Example 1 were orally administered with vehicle (2% sodium carboxymethyl cellulose + 1% Tween 80), control feed (control feed group was fed control feed, while other groups were fed high-fat feed ), 20 mg / kg Compound I (twice a day), 10 mg / kg Compound II (once a day), or a combination of both. After 4 weeks of dosing, body weight and liver / body weight ratio were measured. The results showed that after 4 weeks of administration, the body weight of each model group was lighter than that of the control feed group. However, there was no significant difference in body weight between the different administration groups. After the 16-week experiment, the liver / body weight ratio of each group was analyzed. It was found that the liver / body ratio of the modeling vehicle group was significantly higher than...

Embodiment 3

[0032] Embodiment 3—the effect of compound I, compound II and their combination on the relevant serum biochemical indexes of mice induced by high-fat + carbon tetrachloride

[0033] Blood was collected from the orbits of the mice after the experiment in Example 2, serum was separated, and relevant biochemical indicators were detected. The results showed that: the high-fat + carbon tetrachloride modeling group significantly increased ALT, AST and LDL-C, and significantly decreased HDL-C compared with the control diet group, which was consistent with the 12-week test results. Compared with the vehicle group, the ALT and LDL-C of the mice in the compound I treatment group (20 mg / kg, twice a day) were significantly decreased, and other indicators had no significant changes. Compared with the vehicle group, the ALT, AST and LDL-C of the mice in the compound II treatment group (10 mg / kg, once a day) were significantly decreased, and there was no significant change in HDL-C. ALT, AS...

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PUM

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Abstract

The invention provides a pharmaceutical composition for preventing and treating tissue damage caused by metabolic disorder or inflammation. The pharmaceutical composition comprises an apoptosis signal-regulating kinase 1 (ASK1) inhibitor and a thyroid hormone receptor beta subtype (TR beta) agonist. The research shows that the apoptosis signal regulating kinase 1 (ASK1) inhibitor, the thyroid hormone receptor beta subtype (TR beta) agonist or the combination of the ASK1 inhibitor and the TR beta agonist can relieve the symptoms of a mouse with non-alcoholic steatohepatitis (NASH) induced by high fat and carbon tetrachloride and improve NASH related indexes, and has potential benefits for NASH patients.

Description

technical field [0001] The present invention belongs to the field of medicine, and relates to medicines or pharmaceutical compositions for preventing and / or treating tissue damage and related diseases caused by abnormal metabolism or inflammation, in particular to a drug or a pharmaceutical composition comprising an apoptosis signal-regulated kinase 1 inhibitor and / or thyroid hormone receptor beta sub-substance A drug or pharmaceutical composition for preventing and / or treating tissue damage and related disorders caused by abnormal metabolism or inflammation. Background of the Invention [0002] Metabolic abnormalities such as hyperlipidemia and hyperuricemia can cause the accumulation and cytotoxicity of unfavorable metabolites in cells, and induce a chronic inflammatory process, which further leads to tissue damage such as vascular damage, and induces cardiovascular and cerebrovascular diseases and other circulatory system-related diseases. On the other hand, cell damage ...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/4439A61K31/53A61P1/16A61P29/00
CPCA61K45/06A61K31/4439A61K31/53A61P1/16A61P29/00A61K2300/00
Inventor 黄圣健鲁先平潘德思杨千姣邓舟王伟廖国强
Owner SHENZHEN CHIPSCREEN BIOSCIENCES CO LTD
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