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New application of compound Compound C

A technology of compounds and drugs, applied in the new application field of compound CompoundC

Inactive Publication Date: 2019-05-31
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Based on this, it is necessary to provide a new application of Compound C for the treatment of fatty liver, impaired glucose tolerance, insulin resistance and type 2 diabetes

Method used

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  • New application of compound Compound C
  • New application of compound Compound C
  • New application of compound Compound C

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Compound C promotes the expression of UCP1 in white adipocytes and brown adipocytes in a dose-dependent manner in vitro.

[0034] 1. Isolation of White Adipose-Mesenchymal Cells from the Groin

[0035] 1) Take an adult UCP1-2A-luciferase mouse about 10 weeks old, kill it by neck dislocation, immerse it in 75% alcohol for 5 minutes, then transfer it to the operating table, and remove the white fat in the groin.

[0036]2) Wash 3 times with PBS, cut up the adipose tissue with scissors, add 10ml collagenase I solution (prepared with D-Hanks solution, add 0.1g collagenase I to 100ml) for 1g adipose tissue, and place it at 37°C for 40 minutes for digestion.

[0037] 3) Filter with a 250 μm filter membrane, add cell culture medium, then transfer to a centrifuge tube, and centrifuge at 1000 rpm for 3 minutes.

[0038] 4) The supernatant layer after centrifugation is mature adipocytes, which is transferred to a centrifuge tube filled with PBS solution, mixed evenly a...

Embodiment 2

[0059] Example 2 10-week-old mice were fed with high-fat diet and fed with Compound C (10 mg / kg body weight), and the mice in the control group were fed with PBS of the corresponding dose, and weighed every week. After 8 weeks, the mice were dissected In mice, the expression of UCP1 in white adipose tissue in the groin (iWAT) and brown adipose tissue in the scapular muscle (iBAT) and the changes in fatty liver were detected.

[0060] 1 Luciferase signal detection in adipose tissue

[0061] Weigh 50 mg of the adipose tissue isolated from the mouse, then add 200 μL of HEPES, break it up with an electric homogenizer, and then transfer it to an EP tube; the rest of the steps are the same as the method for measuring the luciferase activity of the cells in Example 1.

[0062] 2 Liver pathological section detection

[0063] After the mice were fasted overnight, the mice were dissected, and the liver tissue was separated and fixed in formalin solution. Paraffin sections and HE staini...

Embodiment 3

[0068] Example 3 10-week-old mice were fed with a high-fat diet while being fed with Compound C (10 mg / kg body weight), and mice in the control group were fed with a corresponding dose of PBS. After 8 weeks, glucose tolerance and insulin sensitivity were tested. experiment.

[0069] 1 Glucose Tolerance Test (IGTT)

[0070] Prepare 20% glucose solution with physiological saline, then inject mice according to the dose of 2g glucose / kg body weight, and intraperitoneally inject mice that have fasted for 12 hours (9 o'clock in the evening to 9 o'clock in the morning of the next day). The blood glucose concentration of mice at different time points (15 minutes, 30 minutes, 60 minutes, 120 minutes) before injection (0 minute) and after injection was monitored with a blood glucose meter, and the time error was controlled within 5 seconds.

[0071] 2 Insulin Tolerance Test (ITT)

[0072] The insulin dose was 0.5 unit / kg body weight, but the fasting time was 6 hours (9:00 am to 3:00 p...

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Abstract

The invention relates to a new application of a compound Compound C, which is the application of the compound Compound C in the preparation of a medicament for promoting the expression of adipocyte UCP1. The browning of adipocytes is promoted, that is, the expression of brown adipocytes marker gene uncoupling protein 1 (UCP1) is enhanced, excess fat can be effectively consumed in the form of calories, glucose uptake and fatty acid oxidation can be promoted, the number and vitality of mitochondria can be improved, and the levels of glucose and lipid metabolism and energy metabolism in the bodycan be enhanced, thereby effectively treating fatty liver, impaired glucose tolerance, insulin resistance and type 2 diabetes. Therefore, the compound Compound C has an effect of promoting the expression of the adipocyte UCP1, and can effectively prevent and treat the fatty liver, the impaired glucose tolerance, the insulin resistanceand the type 2 diabetes.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a new application of Compound C. Background technique [0002] Adipose tissue in mammals is divided into white adipose tissue (WAT) and brown adipose tissue (BAT), and WAT is further divided into subcutaneous WAT and visceral WAT. Adipose tissue is composed of a large number of mature adipocytes and a small number of preadipocytes, macrophages and immune cells, as well as fibrous connective tissue, blood vessels, and nerve tissue. There are obvious differences between WAT and BAT in shape, distribution, and function. The specific manifestations are as follows: white adipocytes contain a large lipid droplet, which occupies most of the cytoplasmic volume, while brown adipocytes contain multiple small lipid droplets. lipid droplets; white adipocytes contain relatively few mitochondria, while brown adipocytes contain a large number of mitochondria; WAT is mainly distribu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/519A61P3/10A61P1/16A61P5/50
Inventor 吴东海毛刘锋雷雯雯刘晓敏
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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