A kind of Thymofaxin polyethylene glycol polymer, its pharmaceutical composition and application

A new technology of polyethylene glycol and thymus method, which is applied in the directions of drug combinations, medical preparations containing active ingredients, thymosin, etc., to achieve the effect of improving half-life, mild reaction conditions and easy industrialization

Active Publication Date: 2021-03-23
广州维奥康药业科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the inventor also prepared a polymer of Tɑ1 by coupling cysteine ​​to the end of Tɑ1, and then coupling it with polyethylene glycol maleimide, but the research results showed that the half-life of the polymer was less than Conjugates at other sites

Method used

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  • A kind of Thymofaxin polyethylene glycol polymer, its pharmaceutical composition and application
  • A kind of Thymofaxin polyethylene glycol polymer, its pharmaceutical composition and application
  • A kind of Thymofaxin polyethylene glycol polymer, its pharmaceutical composition and application

Examples

Experimental program
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Effect test

Embodiment 1

[0052] Tɑ1 was synthesized by solid-phase synthesis, and the last step of acetylation was converted to adding maleimide group-containing carboxylic acid derivatives and coupling reagents, specifically including the following steps: 4ml of 25% piperidine solution was mixed, and shaken at room temperature for 15min Remove the resin Fmoc protecting group (resin 0.1mmol), filter and replace with a new piperidine solution and repeat once, use DMF, methanol, DCM to wash the resin 3 times each, then drain the resin, add 3-maleimido propionic acid (1 mmol) and condensing agent (1.1 ml of 8% Cl-HOBt and DICDMF solution) were shaken at room temperature for 2 hours, centrifuged, washed twice with DCM, methanol, DMF, and DCM successively, and sucked dry. Add cutting reagent (TFA 10ml; Benzole 0.5ml; Phenol 0.5g; Tis 0.5ml; Water 0.5ml) and react at room temperature for 2 hours, filter the reaction solution into a 50ml centrifuge tube, wash the resin with a small amount of TFA, combine the ...

Embodiment 2

[0068] Tɑ1 was synthesized by solid-phase synthesis, and 6-maleimidocaproic acid and coupling reagent were added before deprotection and protection cleavage. Its synthetic method is with embodiment 1, and synthetic route is as follows:

[0069]

[0070] The molecular weight of the thymus method new polyethylene glycol polymer was determined by LC-MS, and the molecular weight was 3259.3, which was consistent with the target molecular weight. The purification process was the same as in Example 1. After purification, the average molecular weight of the polymer was measured by MALID-TOF-MS. The average molecular weight of the polymer was 8.1 kDa, which was consistent with the target molecular weight.

Embodiment 3

[0072] Tɑ1 was synthesized by solid-phase synthesis, and 11-maleimido undecanoic acid and coupling reagent were added before deprotection and protection cleavage. Its synthetic method is with embodiment 1, and synthetic route is as follows:

[0073]

[0074] The molecular weight of the new polyethylene glycol polymer of the thymus method was determined by LC-MS, and the molecular weight was 3329.4, which was consistent with the target molecular weight. The purification process was the same as in Example 1. After purification, the average molecular weight of the polymer was measured by MALID-TOF-MS. The average molecular weight of the polymer was 8.2 kDa, which was consistent with the target molecular weight.

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Abstract

The invention discloses a thymalfasin (T[alpha]1) polyethylene glycol polymer, a medicine composition including same, and an application thereof. The T[alpha]1 polyethylene glycol polymer is represented as the following general formula. In the invention, the T[alpha]1 is synthesized through a regular solid phase synthesis method, wherein the last one step, acetylation, is replaced by introducing a maleimide active group, which can be specifically coupled with monosulfydryl polyethylene glycol at room temperature to prepare a polymer. The T[alpha]1 polyethylene glycol polymer not changes the biostructure of T[alpha]1 and also not changes the bioactivity of the T[alpha]1, and significantly increases the half-life period of the polymer. The method has simple process, is easy to industrialize, has gentle reaction conditions, is more than 95% in molar yield and has excellent market prospect.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a thymofaxin polyethylene glycol polymer, a pharmaceutical composition containing the same and application thereof. Background technique [0002] Thymus fasin (abbreviated as Tɑ1) is a 28-peptide isolated from bovine thymosin fraction 5 (TF5) by Goldstein et al. Its relative molecular weight is 3108.3 and its isoelectric point is about 4.2. It is a product of nitrogen-terminal acetylation, and thymofasin used in the present invention refers to non-acetylated thymofasin. Tɑ1 is widely distributed in various organs of mammals, with the highest concentration in thymus tissue. The protein structure of Tɑ1 was the same in various tissues and organs. Human Tɑ1 sequence has high homology with Tɑ1 of pig, cow, mouse and other animals. Using protein databases such as NCBI, PIR, and SWISS-PROT, the protein sequence alignment of known Tɑ1 was performed, and it was found that the amino...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/575A61K38/22A61K47/60A61P37/02A61P37/04
CPCA61K38/00C07K14/57581
Inventor 彭贵子
Owner 广州维奥康药业科技有限公司
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