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Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof

A technology of transgenic vector and linear polymer, applied in the field of transgenic vector and its preparation, can solve the problems of weak escape ability of complexes, poor biocompatibility, low transfection efficiency, etc., so as to increase endosome escape ability and synthesis conditions Mild effect with simple preparation method

Inactive Publication Date: 2015-05-13
樊世田
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, cationic polymers have become an important part of non-viral gene carriers, but when cationic polymers are used as gene carriers, there are still some problems, such as poor biocompatibility, toxicity, and the formation of complexes from the connotation. The ability of body escape is weak and the transfection efficiency is low

Method used

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  • Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof
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  • Histamine-modified agmatine-based linear-polymer transgenic carrier and preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Take a 50ml round bottom flask, add agmatine sulfate (1.71g, 7.5mmol), histamine dihydrochloride (0.46g, 2.5mmol) and water (10ml) into the flask (ie agmatine sulfate The molar ratio with histamine dihydrochloride is 3 / 1), and stir it until it becomes a transparent liquid. Add about 1ml of sodium hydroxide solution (4M) dropwise to adjust the pH of the reaction system to about 10. Under strong stirring, 1 ml of glycidyl methacrylate (ρ=1.074 g / ml, 7.6 mmol) was slowly dropped into the reaction system, and the reaction was carried out at 35°C for 24 hours. The reaction solution was extracted with ether, the lower layer was collected in a 50ml round bottom flask, the pH of the system was adjusted to about 5 with 1ml hydrochloric acid solution (4M), and ammonium persulfate (12mg, 0.05mmol) was added at 65°C without oxygen and nitrogen Random polymerization for 24 hours under protective conditions. The reaction product was dialyzed in deionized water with a dialysis bag (m...

Embodiment 2

[0030] Take a 50ml round bottom flask, add agmatine sulfate (1.14g, 5mmol), histamine dihydrochloride (0.92g, 5 mmol) and water (10ml) into the flask (ie agmatine sulfate and The molar ratio of histamine dihydrochloride is 2 / 2), and stir evenly until it becomes a transparent liquid. About 2ml of sodium hydroxide solution (4M) was added dropwise to adjust the pH of the reaction system to about 10. Under strong stirring, 1 ml of glycidyl methacrylate (ρ=1.074 g / ml, 7.6 mmol) was slowly dropped into the reaction system, and the reaction was carried out at 35°C for 24 hours. The reaction solution was extracted with ether, the lower layer was collected in a 50ml round bottom flask, the pH value of the system was adjusted to about 5 with 2ml hydrochloric acid solution (4M), and ammonium persulfate (12mg, 0.05mmol) was added at 65°C without oxygen and nitrogen Random polymerization for 24 hours under protective conditions. The reaction product was dialyzed in deionized water with a ...

Embodiment 3

[0033] Take a 50ml round bottom flask, add agmatine sulfate (0.57g, 2.5mmol), histamine dihydrochloride (1.38g, 7.5mmol) and water (10ml) into the flask (ie agmatine sulfate The molar ratio with histamine dihydrochloride is 1 / 3), and stir it until it becomes a transparent liquid. Add about 3ml of sodium hydroxide solution (4M) dropwise to adjust the pH of the reaction system to about 10. Under strong stirring, 1 ml of glycidyl methacrylate (ρ=1.074 g / ml, 7.6 mmol) was slowly dropped into the reaction system, and the reaction was carried out at 35°C for 24 hours. The reaction solution was extracted with ether, the lower layer was collected in a 50ml round bottom flask, the pH value of the system was adjusted to about 5 with 2ml hydrochloric acid solution (4M), and ammonium persulfate (12mg, 0.05mmol) was added at 65°C without oxygen and nitrogen Random polymerization for 24 hours under protective conditions. The reaction product was dialyzed in deionized water with a dialysis ...

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Abstract

The invention discloses a histamine-modified agmatine-based linear-polymer transgenic carrier and a preparation method and applications thereof. The transgenic carrier is prepared through reacting open loops of epoxy groups of glycidyl methacrylate with amino end groups of agmatine and histamine, chaining the agmatine and the histamine to the glycidyl methacrylate through chemical bonds, initiating a modified glycidyl methacrylate monomer to carry out free-radical atactic polymerization, and finally chaining the electropositive agmatine and the histamine with a proton buffering function to macromolecule chains. The agmatine carrier has good biocompatibility and promotes the transmembrane capacity of composites. The modification of the histamine increases the endosome escape capability of composites on the premise of not affecting the cell toxicity of the carrier, thereby effectively improving the efficiency and properties of the agmatine as a transgenic carrier; and the carrier can be used as an efficient non-viral gene carrier for gene therapy, realizes the improvement on the gene transfection efficiency of the agmatine carrier, and extends the role of the in-vivo circulation time.

Description

Technical field [0001] The invention relates to a transgenic carrier and a preparation method thereof, and more specifically, to a histamine-modified agmatine-based linear polymer transgenic carrier and a preparation method thereof. Background technique [0002] Gene therapy refers to the introduction of normal human genes or therapeutic genes into human target cells in a certain way to correct gene defects or exert therapeutic effects. The vectors used in gene therapy mainly include viral vectors and non-viral vectors. Viral vectors have made some breakthroughs in gene therapy, but in the process of clinical application, their immunogenicity and potential carcinogenicity are still major hidden dangers that are difficult to overcome. As another way of gene delivery, non-viral vectors have been widely studied, which mainly include naked DNA, liposomes, cationic polymers and so on. [0003] As a kind of non-viral vector, cationic polymer has the advantages of non-viral vector (that...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/87C08F220/36
Inventor 刘文广李咏懋杨建海王玮
Owner 樊世田
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