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Peptide, peptide derivatives, medicinal salts of peptide, medicine composition and application of peptide and peptide derivatives

A technology of peptide derivatives and compositions, applied in the direction of drug combinations, microorganisms, biochemical equipment and methods, etc., can solve the problems of short plasma half-life, achieve long plasma half-life, good stability, and improve the function of islets of pancreas

Inactive Publication Date: 2015-05-27
SHENZHEN HIGHTIDE BIOPHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a polypeptide for the short plasma half-life of INGAP-PP in the prior art

Method used

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  • Peptide, peptide derivatives, medicinal salts of peptide, medicine composition and application of peptide and peptide derivatives
  • Peptide, peptide derivatives, medicinal salts of peptide, medicine composition and application of peptide and peptide derivatives
  • Peptide, peptide derivatives, medicinal salts of peptide, medicine composition and application of peptide and peptide derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0128] The production of embodiment 1 polypeptide

[0129] This example describes the production of polypeptides

[0130] All peptides used in this study were synthesized using 9-fluorenylmethyl chloroformate (Fmoc) solid-phase synthesis. Briefly, a weighed amount of 2-chlorotrityl chloride resin (1.6 mmol / g) was dissolved in dichloromethane (DCM). For C-terminally amidated peptides of interest, use Rink amide resin instead of 2-chlorotrityl chloride resin. For coupling reactions in the presence of hydroxybenzotriazole (Sigma Chemicals, Inc., St. Louis, MO, USA) in dimethylformamide (DMF), preactivated Fmoc-amino acids were used. The entire synthesis process uses an excess of amino acids. Deprotection of the Fmoc group in 20% piperidine in DMF leads to chain extension reactions. When the chain extension reaction was completed, the Fmoc protecting group was removed from the N-terminus of the polypeptide using DMF containing 25% piperidine, and then washed four times with DM...

Embodiment 2

[0134] Stability experiment of embodiment 2 peptide

[0135] This example describes stability experiments of peptides under various conditions.

[0136] Test the stability of the peptide in mouse and rat plasma. A brief description is as follows: Accurately weigh a certain amount of polypeptide and eucatropine (positive control), dissolve the compound to be tested in 50% methanol-water solution, and dilute to 20mg / mL, dissolve eucatropine in dimethylformamide Diluted to 10 mM in DMSO, the above two solutions were used as stock solutions. The eucatropine stock solution was diluted to 0.2 mM with DMSO as a working solution. Prepare an acetonitrile solution containing 200 ng / mL midazolam and tolbutamide as a working stop solution. Add 300 μL of stop solution to each well of a 96-well plate pre-cooled on ice.

[0137] In the stability test, the polypeptide and eucatropine were respectively injected into the plasma, mixed evenly, and 100 μL of each mixed solution was transferre...

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Abstract

The invention provides a peptide to solve the problems of shorter plasma half-lives and lower activities of insulinotropic nascent peptides in the prior art. The peptide has a sequence as follows: Ac-IGLHDPTQGTEPAGE-OH (No.52), Ac-IGLHDPTQGTEPAG-NH2 (No.60), Ac-IGLHDPTQGTEPAGE-NH2 (No.62) or Ac-IGLHDPTQGTEPAGC-NH2 (No.72). Meanwhile, the invention also discloses peptide derivatives, medicinal salts of the peptide, a medicine composition and an application of the peptide and the peptide derivatives. The peptide provided by the invention has high stability and long half-life in blood.

Description

[0001] This application is based on the Chinese patent application (application number CN201410096539.1, titled a polypeptide, a polypeptide derivative, a pharmaceutically acceptable salt of a polypeptide, and a pharmaceutical composition) submitted on March 14, 2014 as the parent case. Divisional application. The parent case is based on an earlier PCT international application (application number PCT / CN2013 / 072771) filed on March 15, 2013, and claims priority from it. technical field [0002] The present invention mainly relates to the fields of medicine and pharmacy, especially a polypeptide, derivatives of the polypeptide, pharmaceutically acceptable salts and pharmaceutical compositions. Background technique [0003] More than 300 million people worldwide suffer from and suffer from diabetes mellitus (DM). There are two main types of diabetes: type 1 diabetes (T1D) and type 2 diabetes (T2D). Type 1 diabetes is caused by the body's inability to produce insulin and the p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K38/17A61P3/10A61P1/16A61P25/00A61P29/00C12N5/071C12N5/079
CPCC07K14/47A61K38/00C12N5/0613C12N5/0618C12N5/067
Inventor 刘利平白茹
Owner SHENZHEN HIGHTIDE BIOPHARM
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