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Application of Exenatide in preparing medicament for reversing activation of FFA to P53

A technology of activation and drugs, applied in the direction of drug combinations, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve problems such as β-cell DNA damage

Inactive Publication Date: 2008-10-29
长春百克生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Studies have reported that excessive FFA will cause DNA damage in β-cells

Method used

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  • Application of Exenatide in preparing medicament for reversing activation of FFA to P53
  • Application of Exenatide in preparing medicament for reversing activation of FFA to P53
  • Application of Exenatide in preparing medicament for reversing activation of FFA to P53

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Solid Phase Synthesis of Exenatide

[0022]Weigh 15.4g of Rink Amide MBHA resin and put it into the reaction bottle of the automatic peptide synthesizer, put each amino acid derivative, coupling reagent, and DMF solvent into each solvent bottle, set the reaction program and start the synthesis. The reaction temperature is 25°C, the coupling reaction time is 1 hour, the amino acid α-amino protecting group removal takes 30 minutes, the coupling and Fmoc group removal reaction solvent filling amount is 200ml, and the resin washing frequency is 3 minutes / time×5 Second-rate. When the coupling reaction of the last amino acid is completed, the resin is washed 5 times with methanol, and N 2 Let dry for 30 minutes. After each coupling and deprotection reaction, take out several resins to check the completion of the reaction. The detection reagent is A: the anhydrous ether solution of ninhydrin, the reagent B is the absolute ethanol solution of phenol, and the reagent C is the...

Embodiment 2

[0027] Preparation of free fatty acid FFA (palmitate-pal) compound BSA preparation:

[0028] The free fatty acid salt was mixed with 5% BSA phosphate buffer, and the mixture was added to the cell culture medium containing 10% calf serum, and the molar ratio of free fatty acid to BSA in the culture medium was 6.6:1. After adding the free fatty acid BSA mixture, the pH value of the medium did not change greatly, and the unbound free fatty acid remained in a soluble state during the experiment.

Embodiment 3

[0030] RINm-5F cell culture: Insulinoma cell RINm-5F (ATCC, CRL-11605 TM , USA) in RPMI1640 medium containing 10% fetal bovine serum, 3% (v / v) glutamine, 1 mM ketoglutarate sodium salt, 100 units / ml penicillin, 100 units / ml streptomycin and final glucose concentration Up to 16.8mM culture medium.

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PUM

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Abstract

The invention relates to an application of Exenatide in the preparation of drugs for reversing the activation of FFA on P53, which pertains to the field of medicine. The application of the Exenatide in the preparation of the drugs for reversing the activation of FFA on the sequence specific transcription factor P53 can inhibit the increases of P53, P21 and bax mRNA expressions and the decreases of bcl-2, CyclinD1 and CyclinB2 mRNA expressions caused by FFA. The Exenatide can prevent the occurrence of type II diabetes caused by P53 pathway during the early stage of obesity.

Description

technical field [0001] The present invention relates to the preventive effect of chemical synthetic drug Exenatide on the formation of several diseases through the P53 pathway caused by excessive free fatty acid (FFA) in the early stage of obesity, including the formation of typical type 2 diabetes with insulin resistance And the formation and development of free fatty acid hyperemia, fatty liver disease and cardiovascular complications. Background technique [0002] Exenatide is a new medically valuable drug for the treatment of type 2 diabetes, or glucose regulating activity (Kharroubi, I. et al, Endocrinology, 2004, 145: 5087; EganJ.M, Clocquet A.R, et al, J Clin Endocrinol Metab , 2002, 87: 1282; Kolterman O.G. et al, J Clin Endocrinol Metab, 2003, 88: 3082). The drug can increase insulin gene transcription and insulin secretion, promote β-cell proliferation / new generation and inhibit β-cell apoptosis, restore and increase β-cell number and function (Chepumy O.G.etal, E...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/26A61K38/17A61P3/10
Inventor 李惟陈洁王丽萍
Owner 长春百克生物科技有限公司
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