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Lipid-lowering polypeptide and pharmaceutical application thereof

A lipid-lowering and drug technology, applied in the fields of pharmacy and medicine, can solve problems such as poor stability of GLP-1, and achieve the effects of improving glucose tolerance, inhibiting liver cell damage, and reducing blood lipid levels.

Pending Publication Date: 2020-05-12
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Natural human GLP-1 has poor stability and is easily degraded by dipeptidyl peptidase Ⅳ (DPPⅣ) and quickly cleared by the kidneys, with a half-life of t1 / 2≤2min

Method used

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  • Lipid-lowering polypeptide and pharmaceutical application thereof
  • Lipid-lowering polypeptide and pharmaceutical application thereof
  • Lipid-lowering polypeptide and pharmaceutical application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Example 1: Pharmacodynamic evaluation of P48

[0033] 1. Modeling and grouping of NAFLD model mice

[0034] Fifty 8-week-old male c57 mice (purchased from Nanjing University-Nanjing Institute of Biomedicine, license number: SCXK (Su) 2016-0011) were adaptively fed for 1 week, and then continued to be fed high-fat diet for 28 weeks ( HFD, D12492, purchased from ResearchDiets) was fed to increase the body weight of the mice, and the model was successfully established when the body weight of the mice was greater than 50 g at the 14th week. The modeling mice were randomly divided into 4 groups, 10 in each group, respectively blank control group (Chow, D12450J, purchased from Research Diets, fed with control feed, normal body weight, blank control group), solvent control group (Vehicle, negative control group) ), Liraglutide group (Liraglutide, positive control group, purchased from Nanjing Leon Biotechnology Co., Ltd.), ursodeoxycholic acid group (UDCA, Ursodeoxycholic Aci...

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Abstract

The invention designs a novel lipid-lowering polypeptide P48. The novel lipid-lowering polypeptide P48 is prolonged in a half-life period, plays the role of a GLP-1 receptor agonist and also plays therole of a GLP-1 analogue to adjust the fat content of an individual. The P48 peptide can be used for inhibiting feed intake of a non-alcoholic fatty liver model mouse induced by high-fat diet, remarkably reduce the weight of an obese mouse, lower the blood fat level of the obese mouse, maintain the normal form of the liver, inhibit liver cell injury, reduce accumulation of lipid in the liver andvacuolar deformation of cells, increase the level of adiponectin leptin in blood, and give a play to the blood glucose reducing and blood fat regulating effects of the adiponectin leptin; meanwhile, the P48 peptide obviously improves insulin tolerance and sugar tolerance. The novel lipid-lowering polypeptide P48 of the invention has potential pharmaceutical application in preparation of drugs fortreating and preventing obesity or complications thereof, namely non-alcoholic fatty liver diseases.

Description

technical field [0001] The present invention belongs to related technologies of pharmacy and medicine, and in particular relates to a novel lipid-lowering polypeptide and its application in the preparation of medicines for treating or preventing obesity and its complications. Background technique [0002] As of 2014, 1.9 billion adults worldwide were overweight, of which more than 600 million were obese. When lifestyle intervention is ineffective, that is, when the weight loss cannot be reduced by 5%, and the BMI index is still greater than 28, drug treatment is recommended; for patients who are overweight and have a complication (cardiovascular disease, hypertension, type 2 diabetes, etc.), If life intervention is ineffective, drug treatment is also recommended. More than 1 billion patients worldwide require drug treatment. Changing the lifestyle is the main method of obesity treatment. It is difficult to maintain long-term weight loss only by diet control. Although many ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N9/88A61K38/26A61K38/22A61K38/51A61P3/04A61P1/16
CPCC07K14/605C07K14/57563C12N9/88A61P3/04A61P1/16C12Y401/01015C07K2319/00A61K38/00
Inventor 金亮李凯莹张艳峰潘怡
Owner CHINA PHARM UNIV
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