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Application of a polypeptide in the preparation of drugs for treating diabetic cardiomyopathy

A technology for diabetes and cardiomyopathy, which is applied in the application field of polypeptides in the preparation of drugs for the treatment of diabetic cardiomyopathy, can solve the problems of lack of TRB3 protein inhibitors, etc., and achieve remarkable results

Active Publication Date: 2017-07-28
胡卓伟
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The technical problem to be solved by the present invention is to provide a polypeptide that can specifically bind to TRB3 and its use in the preparation of a drug for treating and / or preventing diabetic cardiomyopathy in view of the current lack of effective TRB3 protein inhibitors. application

Method used

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  • Application of a polypeptide in the preparation of drugs for treating diabetic cardiomyopathy
  • Application of a polypeptide in the preparation of drugs for treating diabetic cardiomyopathy
  • Application of a polypeptide in the preparation of drugs for treating diabetic cardiomyopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 Isolation and cultivation of primary rat cardiomyocytes

[0054] Male rats (6 weeks old) were anesthetized by intraperitoneal injection of 10000U / kg of heparin and 50 mg / kg of intraperitoneal injection of pentobarbital sodium. The heart was quickly opened and immediately put into ice-cold PBS. Clean up the connective tissue and strip the aorta, hang the heart on the Langendorff perfusion device and fix it, keep the temperature around the heart and the perfusate at 37°C, retrogradely perfuse the aorta with Krebs-Henseleit buffer KHB (containing 118mM NaCl, 4.8mM KCl, 25mM HEPES, 1.25mM K 2 PO 4 , 1.25mM MgSO 4 , 11mM glucose and 5mM taurine, pH7.4) for 5 minutes, then change the digestion solution (containing 0.7mg / mL type II collagenase, 0.2mg / mL hyaluronidase, 0.1% BSA and 25μM Ca 2+ ) for 10 minutes of continuous perfusion, the Ca in the digestive juice 2+ The concentration was supplemented from 25 μM to 100 μM and reperfused for 5 minutes. When the hea...

Embodiment 2

[0055] Example 2 Co-immunoprecipitation method to verify the interaction between protein p62 and protein TRB3 in cardiomyocytes

[0056] Co-immunoprecipitation reagents are as follows:

[0057] (1) Lysis solution A: 0.6057g Tris base, 1.7532g NaCl, 0.1017g MgCl 2 ·6H 2 O, 0.0742g EDTA, 10mL glycerin, 10mL 10% NP-40, add deionized water to 150mL, adjust the pH value to 7.6 with HCl, adjust the volume to 191mL, mix well, filter through a 0.45μm membrane filter, and store at 4°C.

[0058] (2) Lysis solution B: 200μL 2M β-glycerol phosphate, 4mL 2.5M NaF, 2mL 100mM NaVO 3 , 2 mL of 100 mM PMSF, 200 μL of 1M DTT, 200 μL each of 1 mg / mL Leu, Pep, and Apr, with a total volume of 9 mL. The mother liquor was stored at -20°C. Before use, thaw the mother solution of each component in solution B, add to solution A according to the above composition ratio and mix well to obtain co-immunoprecipitation lysate.

[0059] (3) Protein A / G Plus-Agarose was purchased from Santa Cruz, USA.

...

Embodiment 3

[0065] Example 3 Streptozotocin (STZ) plus high-fat diet-induced type 2 diabetes mouse model preparation, experimental grouping and administration scheme

[0066] 1. Model preparation

[0067] SPF-grade C57BL / 6J mice (male, 3-4 weeks old) were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., and were bred in the Experimental Animal Center of the Institute of Materia Medica, Chinese Academy of Medical Sciences, with constant temperature and humidity, and free diet. After one week of adaptive feeding, the mice were randomly divided into 2 groups according to body weight: 40 high-fat+STZ groups were given high-fat and high-sugar diet (containing 35% fat, 18% protein, 47% carbohydrates); 10 mice in the control group , continued to give the basal diet (containing 4% fat, 18% protein, 78% carbohydrate) until the end of the experiment. After 4 weeks, the high-fat+STZ group was intraperitoneally injected with streptozotocin STZ solution 100mg / kg (dissolv...

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Abstract

The present invention discloses applications of a polypeptide capable of specifically binding with TRB3 or polypeptide derivatives in preparation of drugs for treatment or prevention of diabetic cardiomyopathy, wherein the amino acid sequence of the polypeptide is one selected from sequences represented by SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and the polypeptide derivative is a chimeric peptide formed by connecting the polypeptide and a cell-penetrating peptide. According to the present invention, the polypeptide or polypeptide derivatives can specifically bind with TRB3 so as to block the interaction between the TRB3 and the P62 protein, and the peptide derivatives such as Pep2-A1, Pep2-A2 and Pep2-A3 can be used for treating the high-fat diet-induced type 2 diabetes.

Description

technical field [0001] The invention relates to the application of a polypeptide and its derivatives in the preparation of medicines for treating and / or preventing diabetic cardiomyopathy. Background technique [0002] Diabetes mellitus is an endocrine and metabolic disorder that seriously threatens human health, characterized by hyperglycemia and hyperlipidemia. Among them, the incidence of type 2 diabetes accounts for more than 90% of diabetic patients, manifested as insulin resistance, accompanied by the occurrence of diabetic complications, and cardiovascular complications secondary to diabetes are the primary cause of death in diabetic patients. Epidemiological survey found that 70-80% of diabetic patients died of cardiovascular complications. Diabetic cardiomyopathy (DCM) is a major cardiac complication in patients with diabetes. The disease is caused by metabolic disorder and microvascular disease, causing extensive focal necrosis and fibrosis of the myocardium, whic...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/10A61K38/16A61P3/10A61P9/00A61P9/04
Inventor 胡卓伟花芳张晓伟
Owner 胡卓伟
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