Treatment for biliary cirrhosis through GLP-1R/GCGR double-target-point agonist polypeptide

A technology of biliary cirrhosis and GLP-1R, applied in the field of biochemistry, can solve the problem of no clinical treatment, and achieve the effect of large safety window, small dosage, and easy to scale up production

Inactive Publication Date: 2019-05-14
SHENZHEN TURIER BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although some cytokine preparations have a certain therapeutic effect on the treatment of biliary cirrhosis, none of them can be used in clinical treatment so far.

Method used

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  • Treatment for biliary cirrhosis through GLP-1R/GCGR double-target-point agonist polypeptide
  • Treatment for biliary cirrhosis through GLP-1R/GCGR double-target-point agonist polypeptide
  • Treatment for biliary cirrhosis through GLP-1R/GCGR double-target-point agonist polypeptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Embodiment 1, the synthesized polypeptide compound structure (Table 1) in the embodiment of the present invention:

[0054]

Embodiment 2

[0055] Example 2. In vitro inhibitory effect of GLP-1R / GCGR dual-target agonist polypeptide on liver fibrosis

[0056] The human hepatic stellate cell line LX-2 was selected to study and observe the effect of different doses of the test substance on the expression of the activation marker α-SMA of LX-2 cells.

[0057] Human hepatic stellate cells LX-2 were plated on a 35mm cell culture dish and cultured with DMEM (high glucose) + 10% FBS + 1% double antibody medium (Thermo Fisher) at 37°C, 5% CO 2 Under the conditions, when the cells grow to 70% confluence, there is no serum overnight, and in the morning of the next day, they are treated with the above-mentioned GLP-1R / GCGR dual agonist polypeptide 1-4 (dissolved in PBS) for 48 hours, and then the cell protein is extracted, and Western Blot is performed, and the β -actin was used as an internal reference, and the expression levels of α-SMA and β-actin were analyzed by Image J 1.50i gray scale. Negative control only added the ...

Embodiment 3

[0063] Example 3, GLP-1R / GCGR dual agonist polypeptides improve therapeutic effect on rat liver fibrosis induced by common bile duct ligation (BDL) (rat model of biliary cirrhosis)

[0064] 1. Test drugs: polypeptide compounds 1, 2, 3, 4 and liraglutide. Storage conditions -20°C.

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Abstract

The invention relates to application of a polypeptide compound having a double activation effect on a glucagons-like peptide-1 receptor (GLP-1R) and a glucagons receptor (GCCR). The degree of BDL-induced rat cholestasis-induced liver fibrosis can be obviously decreased, and the effect of treating biliary cirrhosis and other diseases is remarkable. The double-target-point agonist polypeptide can beused for preventing or treating biliary cirrhosis and related liver fibrosis diseases.

Description

technical field [0001] The invention belongs to the technical field of biochemistry, and specifically relates to the application of a GLP-1R / GCGR dual-target agonist polypeptide in the preparation of preventive and / or therapeutic drugs for treating diseases such as biliary liver cirrhosis. Background technique [0002] Liver cirrhosis affects the health of hundreds of millions of people around the world, and cirrhosis can further lead to the occurrence of liver cancer. Every year, liver cirrhosis causes 1.2 million deaths worldwide, and the mortality rate is higher than that of the five major cancers. In 2015, the global death toll due to liver cancer was as high as 810,000 (Fitzmaurice C, Allen C, Barber RM, et al. JAMA Oncol, 2017, 3 :524-548.). [0003] Liver fibrosis is a pathological state caused by chronic liver disease during the repair process. Liver fibrosis is the early stage of liver cirrhosis. If the course of liver cirrhosis exceeds 5 years, about 10% of patien...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/26A61P1/16
CPCC07K14/605A61K38/16A61K38/26A61P1/16
Inventor 王蕾欧阳建梅
Owner SHENZHEN TURIER BIOTECH CO LTD
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