Method for preparing polyethylene glycol-modified alpha-interferon 1b

A polyethylene glycol and interferon technology, applied in interferon, cytokines/lymphokines/interferon, chemical instruments and methods, etc., can solve problems such as shortened biological half-life, reduced product activity, and biological damage, and achieve The effect of simplifying the chemical reaction process and increasing the biological half-life

Inactive Publication Date: 2005-08-17
JIANGSU HENGRUI MEDICINE CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such parenterally administered biomacromolecular drug products usually have the following problems: (1) Biomacromolecular drugs often have sensitization reactions, and antibodies produced in the organism can cause serious damage to the organism and affect The progress of treatment; (2) The biomacromolecule itself is greatly shortened due to the influence of antibodies or the metabolism caused by proteolytic enzymes; (3) The stability of biomacromolecules is poor and storage is difficult
The modification of polyethylene glycol in the prior art often cannot be modified for specific amino acids, causing some amino acids that affect protein activity to be modified by polyethylene glycol, which reduces the activity of the modified product or changes the activity of the protein
[0005] (2) The chemical reaction of polyethylene glycol can only covalently combine polyethylene glycol with a single phase and the same chain length: Sometimes, polyethylene glycol with a single phase and uniform chain length cannot fully increase bioavailability and prolong biological activity purpose of half life
[0006] At present, there is no report to improve or overcome the problems in the above aspects from the perspective of modifying the preparation process of biomacromolecular drugs

Method used

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  • Method for preparing polyethylene glycol-modified alpha-interferon 1b
  • Method for preparing polyethylene glycol-modified alpha-interferon 1b
  • Method for preparing polyethylene glycol-modified alpha-interferon 1b

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1 Preparation of polyethylene glycol 12000 / 20000α-interferon 1b

[0066] Step (1) reaction

[0067] Dissolve 1.0 mg of α-interferon in 1 ml of 100 mM (pH 6.0) sodium phosphate buffer. Take 20 mg of SS-activated linear polyethylene glycol (SS-PEG12000) with a molecular weight of 12,000, quickly add it to the above solution, and shake it properly to completely dissolve the activated linear polyethylene glycol (SS-PEG12000) within 30 seconds. The reaction was carried out at 25°C for 60 minutes, and the reaction solution was rinsed without concentration, and could be further purified or subjected to the second step of reaction.

[0068] The pH range of the (1) step reaction is controlled at 6.0 to 6.5.

[0069] Step (2) reaction

[0070] Add 0.1 ml of 500 mM (pH 8.0) sodium phosphate buffer solution to the solution obtained in the above step 1. Put this solution in a water bath and preheat it to 25°C, and take another 20 mg of activated polyethylene glycol with ...

Embodiment 2

[0072] Example 2 Preparation of polyethylene glycol 20000 / 20000α-interferon 1b

[0073] The same steps as in Example 1 were used to prepare polyethylene glycol 20000 / 2000α-interferon 1b, except that: in the first step, SS-activated linear polyethylene glycol with a linear length range of 30 mg and 20,000 Daltons The diol is contacted with 1 mg of α-interferon 1b, and the length of the linear chain of polyethylene glycol is used for the reaction, that is, the mass ratio of α-interferon 1b to polyethylene glycol is in the range of 1:30.

[0074] In the second step, 30 mg of SS-activated linear polyethylene glycol with a linear length in the range of 20,000 Daltons is contacted with 1 mg of α-interferon 1b, and the reaction uses the length of the linear chain of polyethylene glycol, i.e., polyethylene glycol The mass ratio range of alcohol to α-interferon 1b is 1:30.

Embodiment 3

[0075] Example 3 Preparation of polyethylene glycol 12000 / 20000α-interferon 1b

[0076] Step (1) reaction

[0077] 1.0 mg of α-interferon 1b was dissolved in 1 ml of 100 mM (pH 6.0) sodium phosphate buffer. Take 30 mg of SC-activated linear polyethylene glycol (SC-PEG12000) with a molecular weight of 12,000, quickly add it to the above solution, and shake properly to completely dissolve the activated linear polyethylene glycol (SC-PEG12000) within 30 seconds. The reaction was carried out at 25°C for 60 minutes, and the reaction solution was rinsed without concentration, and could be further purified or subjected to the second step of reaction.

[0078] The pH range of the (1) step reaction is controlled at 6.0 to 6.5.

[0079] Step (2) reaction

[0080] Add 0.1 ml of 500 mM (pH 8.0) sodium phosphate buffer solution to the solution obtained in the above step 1. Put this solution in a water bath and preheat it to 25°C, and take another 20 mg of activated polyethylene glycol ...

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Abstract

The present invention relates to a sort of making method for the Alpha-interferon modified by the covalent bond of the activating polyethyleneglycol. By changing the acid-base scale of the reaction system it can achieve the purpose that modifies the histidine or lysine in the surface of the Alpha-interferon protein. During the course of reaction there is no need to separate the raw material of Alpha-interferon 1 b from the intermediate product, the novel compound which is modified by the polyethyleneglycol of Alpha-interferon 1 b can retain the biological activity of the former Alpha-interferon 1 b, but in pharmacology, immunogen character, medicine substituting character, medicine effect and the like aspects it gains an advantage over the former protein.

Description

technical field [0001] The present invention relates to a novel and simple technology for chemical modification of biological protein macromolecular medicine, as well as the product obtained by the technology and the application of the product. The method can chemically modify specific amino acids on the protein surface through covalent bonds without affecting or reducing the biological activity of biological protein macromolecular drugs. This is a special preparation method of polyethylene glycol-biological macromolecule medicine, especially the preparation method of polyethylene glycol-modified α-interferon 1b. Background technique [0002] Generally speaking, many products (such as interferon, peptide or protein biotechnology drugs) obtained by biotechnology (such as gene recombination), or biomacromolecular pharmaceutical products obtained by natural extraction and purification, are obtained through parenteral It enters the living body through the route of drug administ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K38/21A61K47/34A61K47/48A61P35/00C07K14/56C07K17/08C08G65/00C12P21/00C12P21/02
CPCA61K47/48215C07K14/56A61K38/00A61K47/60A61P35/00
Inventor 孟宪台彭滢孙飘扬
Owner JIANGSU HENGRUI MEDICINE CO LTD
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