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Polypeptide, polypeptide derivative, medicinal salt of polypeptide and pharmaceutical composition

A technology of peptide derivatives and compositions, which is applied in the field of polypeptides and their derivatives, pharmaceutically acceptable salts and pharmaceutical compositions, can solve the problems of short plasma half-life, achieve long plasma half-life, good stability, and improve pancreatic islet The effect of the function

Inactive Publication Date: 2014-09-17
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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  • Polypeptide, polypeptide derivative, medicinal salt of polypeptide and pharmaceutical composition
  • Polypeptide, polypeptide derivative, medicinal salt of polypeptide and pharmaceutical composition
  • Polypeptide, polypeptide derivative, medicinal salt of polypeptide and pharmaceutical composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 Production of Polypeptides

[0115] This example describes the production of polypeptides

[0116] All peptides used in this study were synthesized using 9-fluorenylmethyl chloroformate (Fmoc) solid-phase synthesis. Simply put: Dissolve a weighed amount of 2-chlorotrityl chloride resin (1.6mmol / g) 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 DMF solutio...

Embodiment 2

[0120] Embodiment 2 Stability experiment of peptide

[0121] This example describes stability experiments of peptides under various conditions.

[0122] 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 base sulfoxide (DMSO), and diluted to 10mM, the above two solutions as the stock solution. 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.

[0123] In the stability test, the polypeptide and eucatropine were respectively injected into the plasma, mixed evenly, and 100 μL of each mixed solution was...

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Abstract

The invention provides a polypeptide. The polypeptide solves the problem that the existing polypeptide for promoting islet neogenesis has a short plasma half-life and low activity. The invention also discloses a derivative of the polypeptide, a medicinal salt of the polypeptide and a pharmaceutical composition. The polypeptide has high stability in blood and a long half life.

Description

[0001] This application is based on, and claims priority from, an earlier PCT international application (application number PCT / CN2013 / 072771) filed on March 15, 2013, the entire content of which is hereby incorporated by reference into this application. 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 patient needs to be treated with daily insulin. Type 2 diabetes is caused by insulin resistance, which means that the body's cells cannot use insulin properly. At present, there are many proven and effective non-insulin t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47A61K38/17A61P3/10C12N5/071C12N5/079
CPCC07K14/4733A61K38/00C07K14/474C12N5/0618C12N5/067C12N5/0676C12N2501/998
Inventor 刘利平白茹
Owner SHENZHEN HIGHTIDE BIOPHARM
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