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Application of polypeptide to preparation of medicines for preventing or treating metabolic syndromes

A technology for drugs and compositions, applied in metabolic diseases, drug combinations, pharmaceutical formulations, etc., can solve problems such as unsatisfactory curative effects, and achieve the effects of improving abnormal glucose and lipid metabolism, reducing the weight of adipose tissue, and reducing blood sugar

Active Publication Date: 2019-07-23
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previous studies have found that UⅡ receptor antagonist Palosuran【The urotensin-II receptor antagonist palosuran improves pancreaticand renal function in diabetic rats[J].J Pharmacol Exp Ther.2006.316(3):1115-21】can improve glucose and lipid metabolism in diabetes , but withdrew from clinical trials due to unsatisfactory efficacy in clinical trials for diabetic nephropathy
Sanofi-Aventis also conducted clinical trials of other Urotensin II receptor antagonists, but they all withdrew from clinical trials due to unsatisfactory efficacy

Method used

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  • Application of polypeptide to preparation of medicines for preventing or treating metabolic syndromes
  • Application of polypeptide to preparation of medicines for preventing or treating metabolic syndromes
  • Application of polypeptide to preparation of medicines for preventing or treating metabolic syndromes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1. Preparation of polypeptide

[0038] Peptide Glu 1 -Thr 2 -Pro 3 -Asp 4 -Cys 5 -Phe 6 -Trp 7 -Lys 8 -Tyr 9 -Cys 10 -Val 11 (disulfide bond Cys 5 -Cys 10 ) is chemically synthesized (specifically by solid-phase synthesis), and the HPLC purity is greater than 95%. The peptide powder was dissolved in physiological saline to prepare a solution of 1000 μg / ml, and after aliquoting, it was frozen and stored at -80°C for later use. Dilute with normal saline to the corresponding concentration when used.

Embodiment 2

[0039] Embodiment 2. Effect of active polypeptide on normal animals

[0040] 10 C57BL / J male mice (Beijing Huafukang Biotechnology Co., Ltd.), weighing 17-20 g, were fed with complete nutritional feed, without restriction of water. Urotensin 27.8 μg / kg (20 nmol / kg) was administered, and body weight was monitored weekly. Once a day for 14 days. Animals were fasted overnight before glucose and insulin tolerance assays. 2g / kg or 0.75U / kg insulin were administered after measuring basal blood glucose. Blood glucose levels were measured at 15, 30, 60, and 120 minute time points. After the experiment, the visceral index and serum markers were measured.

Embodiment 3

[0041] Example 3. Effect of Active Polypeptides on High Fat Feed Induced Metabolic Syndrome / Type 2 Diabetes / Obesity Animals

[0042] Male C57BL / J mice, weighing 17-20 g, were fed with high-fat diet and were not limited to water. C57BL / J mice of the same age were used as a normal control group, weighing 17-20 g, fed with complete nutrition feed, without water restriction. Monitor body weight weekly. After the high-fat-fed mice were 10 g heavier than the normal control, the mice in the obese group were randomly divided into two groups: the high-fat control group and the Urotensin 2 administration group. The urotensin administration group was intraperitoneally injected with polypeptide 27.8 μg / kg (20 nmol / kg), and the normal and high-fat control groups were intraperitoneally injected with the same volume of normal saline. Continuous administration for 3 weeks. Blood sugar and body weight were measured weekly. Animal deaths were recorded. After the experiment, the visceral in...

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Abstract

The invention relates to the field of biological medical care, in particular to an application of polypeptide (urotensin II) to preparation of medicines for treating and / or preventing metabolic syndromes / type II diabetes / obesity / diabetes complications. The polypeptide disclosed by the invention has significant effects of reducing the proportion and the weight of tissue fat, improving and alleviating insulin resistance and reducing blood sugar. The polypeptide is novel in effects, easy to synthesize and low in dosage, and has good application and development prospects.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to the use of a polypeptide in the preparation of drugs for preventing, alleviating and / or treating metabolic syndrome / type 2 diabetes / obesity / diabetic complications. Background technique [0002] Metabolic syndrome is a group of complex metabolic disorders, which is a pathological state of abnormal aggregation of various metabolic components, and is a risk factor for diabetic cardiovascular and cerebrovascular diseases. It has the following characteristics: ① A variety of metabolic disorders are integrated in one body, including obesity, hyperglycemia, hypertension, and dyslipidemia. These metabolic disorders are the pathological basis of heart and cerebrovascular diseases and diabetes. ② There is a common pathological basis. At present, it is mostly believed that their common cause is insulin resistance and hyperinsulinemia caused by obesity, especially central obesity. ③It can...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/08A61P3/10A61P3/04A61P13/12A61P25/02A61P27/02
CPCA61K38/08
Inventor 杜冠华杨秀颖陈熙陈柏年强桂芬张莉贾伟华殷琳
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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