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Composition comprising glp-1 receptor agonist and glucagon receptor agonist and use thereof

A receptor agonist, GLP-1 technology, applied in the field of medicine, can solve the problems of short half-life and poor activity, and achieve the effects of reducing food intake, increasing energy consumption and preventing weight gain

Active Publication Date: 2021-08-24
PEGBIO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, the half-life of oxyntomodulin in human plasma is very short (8-12 minutes); as a dual-receptor agonist, its activity is poor, and its ability to activate two receptors is much lower than that of the original peptide. The dosage needs to reach the level of mg / kg

Method used

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  • Composition comprising glp-1 receptor agonist and glucagon receptor agonist and use thereof
  • Composition comprising glp-1 receptor agonist and glucagon receptor agonist and use thereof
  • Composition comprising glp-1 receptor agonist and glucagon receptor agonist and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Example 1: Preparation of PB-119 (a conjugate of PB-105 and mPEG-ppMAL-23KD)

[0086] Weigh 10mg of PB-105 (purchased from Chengdu Capgemini Biomedical Technology Development Co., Ltd.) and 65mg of mPEG23KD-ppMAL (produced by Paige Biopharmaceutical Company) in a 50mL glass container bottle (the molar ratio of PB-105 to PEG is 1:1.2 ), dissolved in 5ml of 0.2M PBS buffer solution with pH 6.5, and stirred at room temperature (25°C) for 1 hour, then adjusted the pH to 4.0 with hydrochloric acid to terminate the reaction, and placed at 4°C for purification.

[0087] Dilute the above reaction solution 5 times with ultrapure water, adjust the pH to 4.0 with acetic acid, and load the sample on the cation exchange of 10 mL Macrocap SP equilibrated with buffer A (20 mM pH 4.0 HAc-NaAc) for 3-4 column volumes. Column, after loading, use buffer A (20mM pH 4.0 HAc-NaAc) to elute excess PEG, then use eluent B (20mM pH4.0HAc-NaAc+1M NaCl) to elute 10 column volume gradients Remove ...

Embodiment 2

[0089] Example 2: Preparation of PB-120 (a conjugate of PB-105 and mPEG-ppMAL-25KD)

[0090] Weigh 10mg of PB-105 (purchased from Chengdu Capgemini Biomedical Technology Development Co., Ltd.) and 72mg of mPEG25KD-ppMAL (produced by Paige Biopharmaceutical Company) in a 50mL glass container bottle (the molar ratio of PB-105 to PEG is 1:1.2 ), dissolved in 5ml of 0.2M PBS buffer solution with pH 6.5, and stirred at room temperature (25°C) for 1 hour, then adjusted the pH to 4.0 with hydrochloric acid to terminate the reaction, and placed at 4°C for purification.

[0091] Dilute the above reaction solution 5 times with ultrapure water, adjust the pH to 4.0 with acetic acid, and load the sample on the cation exchange of 10 mL Macrocap SP equilibrated with buffer A (20 mM pH 4.0 HAc-NaAc) for 3-4 column volumes. Column, after loading, use buffer A (20mM pH 4.0 HAc-NaAc) to elute excess PEG, then use eluent B (20mM pH4.0HAc-NaAc+1M NaCl) to elute 10 column volume gradients Remove ...

Embodiment 3

[0092] Example 3: Preparation of PB-107 (a conjugate of PB-105 and mPEG-ppMAL-30KD)

[0093] Weigh 10mg of PB-105 (purchased from Chengdu Capgemini Biomedical Technology Development Co., Ltd.) and 86mg of mPEG30KD-ppMAL (produced by Paige Biopharmaceutical Company) in a 50mL glass container bottle (the molar ratio of PB-105 to PEG is 1:1.2 ), dissolved in 5ml of 0.2M PBS buffer at pH 6.5, and stirred at room temperature (25°C) for 1 hour, then adjusted to pH 4.0 with hydrochloric acid to terminate the reaction, and placed at 4°C for purification.

[0094] Dilute the above reaction solution 5 times with ultrapure water, adjust the pH to 4.0 with acetic acid, and load the sample on the cation exchange of 10 mL Macrocap SP equilibrated with buffer A (20 mM pH 4.0 HAc-NaAc) for 3-4 column volumes. Column, after loading, use buffer A (20mM pH 4.0 HAc-NaAc) to elute excess PEG, then use eluent B (20mM pH4.0HAc-NaAc+1M NaCl) to elute 10 column volume gradients Remove to 30%, collect...

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Abstract

The present invention relates to a composition comprising a GLP-1 receptor agonist and a glucagon receptor agonist and uses thereof. In particular, the present invention relates to a pharmaceutical composition comprising a pharmaceutically effective amount of a GLP-1 receptor agonist and a glucagon receptor agonist, wherein the GLP-1 receptor agonist and the glucagon receptor The body agonist independently forms a conjugate with a hydrophilic polymer or the GLP-1 receptor agonist and the glucagon receptor agonist form a conjugate with a hydrophilic polymer together.

Description

technical field [0001] The present invention relates to the field of medicine. In particular, the present invention relates to a composition comprising a GLP-1 receptor agonist and a glucagon receptor agonist and its use for weight loss and / or lipid lowering. Background technique [0002] With the changes in diet and lifestyle brought about by economic development in recent years, the proportion of obese people has increased year by year. According to the latest statistics from the World Health Organization: the number of obese and overweight people in the world has surged from 857 million in 1980 to 2.1 billion in 2013, accounting for nearly one-third of the world's total population. In 2014, more than 1.9 billion adults aged 18 and over were overweight, of whom 600 million were obese. In 2014, 39 percent of adults aged 18 and over were overweight and 13 percent were obese. Once considered a problem in high-income countries, overweight and obesity are now on the rise in ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K38/17A61K38/26A61K47/60A61P1/16A61P3/04A61P3/06A61P3/10
CPCA61K38/17A61K38/1767A61K38/26A61K45/06A61K2300/00A61P3/04A61P3/06A61P3/10Y02A50/30A61K47/60A61P1/16A61K38/2278
Inventor 徐敏吕玮张映辉罗小苏
Owner PEGBIO
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