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A glutathione-responsive targeting polymer micelle and its preparation method and application

A technology of glutathione and polymer, applied in the field of biomedical materials, can solve the problem that double drug-loaded polymer micelles have not been reported yet.

Active Publication Date: 2020-03-17
苏州永沁泉智能设备有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, glutathione-responsive double drug-loaded polymer micelles prepared by multiple Michael addition reactions have not been reported

Method used

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  • A glutathione-responsive targeting polymer micelle and its preparation method and application
  • A glutathione-responsive targeting polymer micelle and its preparation method and application
  • A glutathione-responsive targeting polymer micelle and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] Example 1: Synthesis of disulfide bond cross-linked polyethyleneimine (PEI-SS)

[0090] Dissolve polyethyleneimine (PEI) in methanol aqueous solution, and slowly drop the methanol solution of N,N'-bis(acryloyl)cystamine (CBA) into the PEI solution under nitrogen and protected from light. The addition time is 30min, the water bath is heated and stirred at 45°C for 4h, and the speed is 400rpm; then a small amount of polyethyleneimine (PEI) solution is added again to make N,N'-bis(acryloyl)cystamine (CBA) fully react. After 2h, add deionized water and return to room temperature to terminate the reaction. Adjust the pH value to 4.0, dialyze for three days, freeze-dry for 24 hours to obtain disulfide bond cross-linked polyethyleneimine (PEI-SS).

[0091] The molar ratio of the polyethyleneimine (PEI) and N,N'-bis(acryloyl)cystamine (CBA) is 6:1; the concentration of the polyethyleneimine (PEI) in the reaction system It is 0.04 mol / L, and the volume of deionized water used to te...

Embodiment 2

[0092] Example 2: Synthesis of disulfide bond cross-linked polyethyleneimine (PEI-SS)

[0093] Dissolve polyethyleneimine (PEI) in methanol aqueous solution, and slowly drop the methanol solution of N,N'-bis(acryloyl)cystamine (CBA) into the PEI solution under nitrogen and protected from light. The addition time is 30min, the water bath is heated and stirred at 45°C for 4h, and the speed is 400rpm; then a small amount of polyethyleneimine (PEI) solution is added again to make N,N'-bis(acryloyl)cystamine (CBA) fully react. After 2h, add deionized water and return to room temperature to terminate the reaction. Adjust the pH value to 4.0, dialyze for three days, freeze-dry for 24 hours to obtain disulfide bond cross-linked polyethyleneimine (PEI-SS).

[0094] The molar ratio of the polyethyleneimine (PEI) and N,N'-bis(acryloyl)cystamine (CBA) is 4:1; the concentration of the polyethyleneimine (PEI) in the reaction system It is 0.02 mol / L, and the volume of deionized water used to te...

Embodiment 3

[0095] Example 3: Synthesis of disulfide bond cross-linked polyethyleneimine (PEI-SS)

[0096] Dissolve polyethyleneimine (PEI) in methanol aqueous solution, and slowly drop the methanol solution of N,N'-bis(acryloyl)cystamine (CBA) into the PEI solution under nitrogen and protected from light. The addition time is 30min, the water bath is heated and stirred at 45°C for 4h, and the speed is 400rpm; then a small amount of polyethyleneimine (PEI) solution is added again to make N,N'-bis(acryloyl)cystamine (CBA) fully react. After 2h, add deionized water and return to room temperature to terminate the reaction. Adjust the pH value to 4.0, dialyze for three days, freeze-dry for 24 hours to obtain disulfide bond cross-linked polyethyleneimine (PEI-SS).

[0097] The molar ratio of the polyethyleneimine (PEI) and N,N'-bis(acryloyl)cystamine (CBA) is 8:1; the concentration of the polyethyleneimine (PEI) in the reaction system It is 0.06mol / L, and the volume of deionized water used to ter...

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Abstract

The invention discloses glutathione response type target polymer micelle and a preparation method and application thereof and belongs to the field of biological medical materials. The preparation method disclosed by the invention is mild and simple and avoids special treatment. The prepared target polymer micelle disclosed by the invention has the advantages of good water solubility and easiness in degradation; furthermore, catabolite of the target polymer micelle has smaller toxicity; ingredients of the target polymer micelle are simple, the raw materials are easy to obtain and have good biocompatibility, and the target polymer micelle is hopeful to be widely applied to the field of biological and medical engineering materials. The polymer micelle can be used for wrapping hydrophobic drug; meanwhile, the material has positive electricity and can adsorb gene through electrostatic interaction to form a gene and medicine double-loading carrier to give play to a synergistic effect. As polypeptide modified polymer is prepared into a tumor targeted gene medicine and hydrophobic medicine double-loading gradual-release system, distribution of the drug-loading gradual-release system at thetumor position is improved; thus, an uptake efficiency and a tumor treating effect of the drug-loading gradual-release system are improved, thus, the target polymer micelle has a wide application prospect in compound chemotherapy for malignant tumors.

Description

Technical field [0001] The invention belongs to the field of biomedical materials, and specifically relates to a glutathione-responsive targeting polymer micelle and a preparation method and application thereof. Background technique [0002] The drug carrier can adjust the rate of drug release, change the distribution of chemotherapeutic drugs in the body, reduce the toxic and side effects of the drugs, and improve their bioavailability, which is of great significance for improving the clinical application of chemotherapeutics. Among the many drug carriers, polymer micelles are popular due to their core-shell structure with high drug loading capacity, a wide range of suitable drugs, small particle size and narrow distribution, and easy surface modification. Extensive attention has great development prospects. In recent years, glutathione-responsive smart drug carriers have attracted great attention due to their high-efficiency drug release effects. [0003] Cao et al. synthesized...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G81/00C08G73/02C08G63/91C08J3/00A61K48/00A61P35/00A61K31/12A61K31/337A61K31/704
CPCA61K31/12A61K31/337A61K31/704A61K48/005C08G63/912C08G73/0213C08G81/00C08J3/00C08J2387/00
Inventor 郭瑞刘璇冯龙宝
Owner 苏州永沁泉智能设备有限公司
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