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Applications of benzenesulfonamido benzamide compound in treatment of non-alcoholic fatty liver diseases

A fatty liver disease, non-alcoholic technology, applied in the field of medicine

Pending Publication Date: 2018-12-07
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although NAFL was considered to be a benign stage in the disease process of NAFLD with a good prognosis in the past, recent studies have shown that NAFL is not static, and some patients can still progress to NASH and liver fibrosis

Method used

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  • Applications of benzenesulfonamido benzamide compound in treatment of non-alcoholic fatty liver diseases
  • Applications of benzenesulfonamido benzamide compound in treatment of non-alcoholic fatty liver diseases
  • Applications of benzenesulfonamido benzamide compound in treatment of non-alcoholic fatty liver diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0222] In this example, oleic acid was used to induce the establishment of HL-7702 cell steatosis model and in vitro screening of benzenesulfonylaminobenzamide compounds for the treatment of nonalcoholic fatty liver disease

[0223] 1.1 Establishment of oleic acid-induced steatosis model in HL-7702 cells

[0224] HL-7702 cells were routinely cultured in 1640 medium containing 10% FBS and double antibodies (10U / mL penicillin + 100U / mL streptomycin) at 37°C with 5% CO 2 cultured in an incubator. Before each experiment, the cells were divided into 2 × 10 5 Each well was inoculated into a 6-well plate, and when the confluence reached 70%-80%, it was replaced with a serum-free medium, and the experiment was performed after 24 hours of starvation. Oleic acid (oleic acid, OA) was dissolved in sterilized phosphate-buffered saline (PBS) + 5% BSA, prepared as a stock solution with a concentration of 20 mmol / L, and stored at -20°C. In the experiment, OA was diluted 50 times (0.4mmol / L...

Embodiment 2

[0228] This example is the regulatory effect of compound IMB17-15 on the therapeutic target of non-alcoholic fatty liver disease in HL-7702 cells.

[0229] 2.1 Administration of HL-7702 cells

[0230]HL-7702 cells according to 2×10 per well 5 After 24 hours of culture, different concentrations of compound IMB17-15 were added, the concentrations were 5 μmmol / L and 10 μmmol / L respectively, and a control group (without compound IMB17-15 treatment) was set up, and the culture was continued for 24 hours. After receiving samples.

[0231] 2.2 Western blot experiment

[0232] The total protein of HL-7702 cells was extracted with RAPI lysate (containing 1% PMSF), and the protein concentration was determined by BCA method. The sample was loaded at 20 μg / 20 μL, electrophoresed on polyacrylamide gel, transferred to membrane, blocked with 5% skim milk, incubated with primary antibody, rinsed with PBST three times, incubated with secondary antibody, and developed with ChemiImager 5500 i...

Embodiment 3

[0239] This example is for the preparation of high-fat feed for golden hamsters and the establishment of a model of non-alcoholic fatty liver disease induced by high-fat feed for golden hamsters.

[0240] 3.1 Preparation of high-fat feed for golden hamsters

[0241] High-fat feed formula: 60% basic feed, 10% sucrose, 10% casein, 15% lard, 1% cholesterol, 1% bile salt, 1% mineral salt, 1% cellulose, 1% edible salt, 0.5% L-methionine, 0.5% multivitamins.

[0242] The high-fat feed was prepared by the Experimental Animal Center of the Academy of Military Medical Sciences of the Chinese People's Liberation Army.

[0243] 3.2 Construction of a model of non-alcoholic fatty liver disease in golden hamsters induced by high-fat diet

[0244] Select 18 male golden hamsters with a body weight of 80-100g, and randomly divide them into a control group (basic feed), a model group (high-fat feed), a cholestyramine administration group (high-fat feed+cholestyramine 1.2g / kg), IMB16-4 admin...

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Abstract

The invention belongs to the technical field of medicine, and relates to applications of a benzenesulfonamido benzamide compound in preparation of medicines used for treatment of non-alcoholic fatty liver diseases. It is confirmed through study on influences on golden hamster weight and liver and kidney index, influences on the contents of ALT and AST in golden hamster serum, influences on goldenhamster serum and blood fat relates indexes, influences on the content of fat in golden hamster livers, and influences on golden hamster liver tissue pathogeny structures that the benzenesulfonamido benzamide compound possesses excellent activity in treatment of non-alcoholic fatty liver diseases, and it is promising for the benzenesulfonamido benzamide compound to be developed into medicines usedfor treatment of non-alcoholic fatty liver diseases.

Description

field of invention [0001] The invention belongs to the technical field of medicine. In particular, the present invention relates to the use of benzenesulfonamidobenzamide compounds for preventing and / or treating non-alcoholic fatty liver disease, or improving liver function, or improving serum blood lipid indicators, or reducing liver lipid deposition, or improving liver Use to index, or improve high-fat-induced liver pathological changes, or prevent and / or treat intrahepatic inflammatory reactions, use to regulate (for example, reduce) triglyceride content in liver tissue, use to regulate non-alcoholic fat The use of the treatment target for chronic liver disease, the use of regulating (for example, inhibiting) the expression level of inflammatory factors in tissues. Background of the invention [0002] Non-alcoholic fatty liver disease (NAFLD) refers to a clinicopathological syndrome characterized by diffuse bullous steatosis and fat deposition in hepatic parenchymal cell...

Claims

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Application Information

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IPC IPC(8): A61K31/18A61K31/63A61P3/06A61P1/16A61P29/00
CPCA61K31/18A61K31/63
Inventor 邵荣光何红伟葛茂旭王菊仙王玉成蔡世英任金凤赵午莉刘虹赵跃张镱萱牛伟晓
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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