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New long-acting GLP-1 (glucagonlike peptide-1) compounds

A GLP-1, 1.GLP-1 technology, applied in the field of long-acting GLP-1 compounds, can solve problems such as GLP-1 instability, continuous intravenous infusion or continuous subcutaneous injection

Inactive Publication Date: 2011-10-19
SHANGHAI GENE BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the GLP-1 produced by the human body is very unstable and will soon be degraded by dipeptidyl peptidase IV (DPP-IV) in the body. Therefore, if natural GLP-1 is used to lower blood sugar, continuous intravenous infusion or continuous subcutaneous injection is required. injection

Method used

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  • New long-acting GLP-1 (glucagonlike peptide-1) compounds

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Embodiment 1

[0065] GLP1 analogs can also be cloned and expressed using gene recombination technology. Host cells for expression include prokaryotic cells, yeast cells or higher eukaryotic cells. Applicable prokaryotic host cells include, but are not limited to: G+ or G- bacteria, such as E. coli E. coli. E. coli strains that can be obtained through public channels include: K12 MM294 (ATCC 31,446), X1776 (ATCC 31,537) , W3110 (ATCC 27,325) and K5 772 (ATCC 53,635), etc. Other prokaryotic cells that can be used include, but are not limited to: Erwinia, Klebsiella, Proteus, Salmonella such as Salmonella typhimurium, Serratia ) such as Serratia marcescans, Shigella, B. subtilis, B. licheniformis, Pseudomonas such as Pseudomonas aeruginosa (P. aeruginosa), Streptococcus (Streptomyces). E. coli. W3110 is recommended as preferred because it is often used as a fermentation host for recombinant DNA products.

[0066]In addition to prokaryotic cells, eukaryotic cells such as filamentous fungi o...

Embodiment 2

[0142] Study on the Pharmaceutical Activity of GLP-1 Derivatives

[0143] In one aspect of the present invention, the drug activity test of GLP-1 derivatives uses a stable transfected cell line of GLP1 receptor (glucagon-like peptide 1 receptor (GLP1R) ). The GLP1 receptor is located in human chromosome 6, which is one of the glucagon receptors and is also a typical G-protein coupled receptor. GLP1 receptors are abundantly expressed on beta cells of the pancreas, and the activated GLP1 receptors can promote the adenylyl cyclase pathway, thereby increasing the synthesis and secretion of insulin. Therefore, the GLP1 receptor is regarded as a potential target for the treatment of diabetes.

[0144] G-protein-coupled receptors are an important target in drug screening. G-protein-coupled receptors are divided into several subtypes according to Gα proteins, and Gs-type G-protein-coupled receptors can activate adenylate cyclase and increase cAMP at the cellular level. Therefore, in...

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Abstract

The invention discloses new long-acting GLP-1 (glucagonlike peptide-1) compounds, a medicine composition containing the compounds, wherein the compound is used for (1) treatments of hyperglycemia, type 2 diabetes, type 1 diabetes, impaired glucose tolerance, obesity, hypertension, X syndrome, dyslipidemia, cognitive disorder, myocardial infarction, coronary heart disease and other vascular diseases, apoplexy, dyspepsia and gastric ulcer, (2) or reducing food intake and beta-cell apoptosis, enhancing beta-cell function and beta-cell quantity , and or, recovering the glucose sensitivity of beta-cell.

Description

[0001] technical field [0002] The present invention relates to the field of therapeutic polypeptides, in particular to new and novel long-acting GLP-1 compounds, pharmaceutical compositions containing these compounds and medical applications of the compounds. It specifically relates to new long-acting GLP-1 compounds, pharmaceutical compositions containing these compounds and the compounds (GLP1 analogs) in the treatment of (1) hyperglycemia, type 2 diabetes, type 1 diabetes, impaired glucose tolerance, obesity , hypertension, syndrome X, dyslipidemia, cognitive impairment, myocardial infarction, coronary heart disease and other cardiovascular diseases, stroke, dyspepsia and gastric ulcer (2) or in reducing food intake, reducing β-cell apoptosis, Role in enhancing β-cell function and β-cell mass and or restoring glucose sensitivity of β-cells. Background technique [0003] Chinese name: Glucagon-like peptide 1 [0004] English name: GLP-1 [0005] CAS number: 106612-9...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/605A61K38/26A61K47/48A61K45/00A61P3/10A61P3/04A61P9/12A61P3/06A61P3/00A61P25/00A61P9/10A61P9/00A61P1/04A61P1/14
Inventor 刘恒余佳凌
Owner SHANGHAI GENE BIOLOGICAL TECH
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