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GLP-1 analogs, and preparation method and application thereof

A technology of GLP-1 and analogs, which can be used in drug combinations, pharmaceutical formulations, animal/human proteins, etc., can solve the problems of inconvenient clinical use, not meeting clinical standards, and short half-life of liraglutide

Inactive Publication Date: 2014-12-17
TIANJIN JIAHONG TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the serum half-life of GLP-1(7-37) is only 3-5 minutes, and multiple injections per day are very inconvenient in clinical use
[0003] At present, many studies have used GLP-1 analog fusion protein technology to solve the retention time of GLP-1 analogs in the body (CN90101167.3, CN200710018734.2, CN200410054397.9, CN01820232.2, CN200380110152.7, CN200510039265.3, CN200610127237.1, CN200910009642.7), however, the existing technology is still far from the ideal clinical goal, generally has not yet reached the clinical standard, Liraglutide, recently produced by Novo Norisk, is a GLP-1 analogue, which modifies GLP-1 with palmitic acid, and was launched in the United States in 2009
However, liraglutide also has the problem of short half-life, and its dosage form still needs daily injections
[0004]Therefore, there is currently a need for methods that address the short in vivo half-life of GLP-1

Method used

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  • GLP-1 analogs, and preparation method and application thereof
  • GLP-1 analogs, and preparation method and application thereof
  • GLP-1 analogs, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0193] Example 2: Hypoglycemic function related to GLP-1 analogs (general formula II)

[0194] In this embodiment, the polypeptides used are as follows:

[0195] SEQ ID NO 7: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GAA;

[0196] SEQ ID NO 8: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GAAAAAA;

[0197] SEQ ID NO 9: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GYY;

[0198] SEQ ID NO 10: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GYYYYYYYY;

[0199] SEQ ID NO 11: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GYYYYYYYYYY;

[0200] SEQ ID NO 12: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKK;

[0201] SEQ ID NO 13: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKKKK;

[0202] SEQ ID NO 14: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKKKKKK;

[0203] SEQ ID NO 15: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKKKKKKKK;

[0204] SEQ ID NO 16: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKKKKKKKKKK;

[0205] SEQ ID NO 17: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKKKKKKKKKKKK;

[0206] SEQ ID NO 18: HAEGT FTSDVS CYLEGQACK EFIAW LVKGR GKKKKKKKKKKKKKKKK;

[0207...

Embodiment 3

[0226] Example 3: The hypoglycemic function related to GLP-1 analogs (general formula III).

[0227] In this embodiment, the polypeptides used are as follows:

[0228] SEQ ID NO 37: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GRR;

[0229] SEQ ID NO 38: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GRRRR;

[0230] SEQ ID NO 39: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GRRRRR;

[0231] SEQ ID NO 40: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GRRRRRRR;

[0232]SEQ ID NO 41: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GRRRRRRRRR;

[0233] SEQ ID NO 42: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GAA;

[0234] SEQ ID NO 43: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GAAAA;

[0235] SEQ ID NO 44: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GAAAAAA;

[0236] SEQ ID NO 45: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GAAAAAAAA;

[0237] SEQ ID NO 46: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GAAAAAAAAAAA;

[0238] SEQ ID NO 47: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GYY;

[0239] SEQ ID NO 48: HAEGT FTSDVS SYLEGQA AK EFICW LCKGR GYYYY;

[0240] ...

Embodiment 4

[0257] Example 4: Hypoglycemic function related to GLP-1 analogs (general formula IV)

[0258] In this embodiment, the polypeptides used are as follows:

[0259] SEQ ID NO 65: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRA;

[0260] SEQ ID NO 66: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRY;

[0261] SEQ ID NO 67: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRK;

[0262] SEQ ID NO 68: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRI;

[0263] SEQ ID NO 70: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRM;

[0264] SEQ ID NO 71: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRAA;

[0265] SEQ ID NO 72: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRRRAA;

[0266] SEQ ID NO 73: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRRRRRYY;

[0267] SEQ ID NO 74: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRRRRRKKKK;

[0268] SEQ ID NO 75: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRRRRIIIIII;

[0269] SEQ ID NO 76: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRRRRMM;

[0270] SEQ ID NO 77: HAEGT FTSDVS SYLEGQA AK EFIAW LCKGR CRRRRRRMMMMM;

[0271] SE...

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Abstract

The invention discloses GLP-1 analogs, and a preparation method and an application thereof. The GLP-1 analogs have a following general formula A: <7>HAEX10TFTSDVSX18YLEX22QAX25KEFIX30WLX33KGRG<37>n1X1n2X2. With the GLP-1 analogs provided by the invention, GLP-1 blood half-life period can be effectively increased, such that a situation that GLP-1 cannot be clinically used due to short half-life period can be overcome. The GLP-1 analogs have application prospects in fields of medicines used for treating diabetes and obesity. The invention also discloses the preparation method and the application of the GLP-1 analogs.

Description

technical field [0001] The present invention relates to the field of drugs related to diabetes, in particular, the present invention relates to a GLP-1 analogue with prolonged in vivo half-life of glucagon-like peptide-1 (GLP-1). The present invention also relates to the preparation method of the GLP-1 analog and its application in the preparation of diabetes drugs. Background technique [0002] The GLP-1 amino acid (glucagon-likepeptide-1, hereinafter referred to as: GLP-1) involved in the present invention is a polypeptide composed of 37 mainly secreted by small intestinal L cells, and its active form is GLP-1(7-37) OH and GLP-1(7-36)NH2 (Mojsov S, J Clin Invest. 1987 Feb; 79(2): 616-9). GLP-1 significantly reduces blood sugar after meals, stimulates the production of insulin, and also has a certain weight loss effect, and will not cause hypoglycemia (Drucker D J, Diabetes. 1998 Feb; 47(2): 159-69 ). Recent studies have also shown that GLP-1 has a role in pancreatic reg...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/605A61K38/26A61P3/10A61P3/04
Inventor 李瑛
Owner TIANJIN JIAHONG TECH
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