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o-Alkyl carbamate chitosan, transgenic composite particle and preparation method thereof

A technology of alkyl carbamate and ester chitosan, which is used in gene therapy, pharmaceutical formulations, genetic material components, etc., to achieve the effects of low cytotoxicity, broad application prospects and high transfection efficiency

Active Publication Date: 2016-06-22
DALIAN NATIONALITIES UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the research results of the current literature, there is no report on modifying chitosan without occupying the amino group of chitosan, which is easily broken after entering the cell, and compounding it into transgenic complex particles for use

Method used

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  • o-Alkyl carbamate chitosan, transgenic composite particle and preparation method thereof
  • o-Alkyl carbamate chitosan, transgenic composite particle and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] ① Phthalimidization of chitosan amino groups: Disperse chitosan (Mw=40,000) in N,N-dimethylformamide / water (the mass fraction of water is 5%) solvent, Swell for 36h. Add phthalic anhydride in an amount three times that of the chitosan repeating unit, and stir and react for 5 hours under normal pressure, nitrogen atmosphere, and 130° C. reaction temperature to make chitosan aminophthalimide. After the reaction, the reaction solution was poured into ice water, filtered with suction, and the precipitate was collected.

[0031] ②Coupling of chitosan and alkylamine: Disperse the precipitate in step ① into anhydrous N-methylpyrrolidone, add carbonyldiimidazole in an amount equal to 1 times the repeating unit of chitosan, under normal pressure, nitrogen Atmosphere and reaction temperature of 40°C, stirring and reacting for 3h, then adding laurylamine in an amount equal to 1 times of the chitosan repeating unit, stirring and reacting for 3h under normal pressure, nitrogen atmo...

Embodiment 2

[0035] Except that in step ④, the mass ratio of O-alkylcarbamate chitosan, liposome DOTAP and PGFP-N2 plasmids was changed to 2:6:1, the others were the same as in Example 1.

Embodiment 3

[0037] Except that in step ④, the mass ratio of O-alkylcarbamate chitosan, liposome DOTAP and PGFP-N2 plasmids was changed to 4:6:1, the others were the same as in Example 1.

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Abstract

The invention discloses a method for preparing O-alkyl carbamic acid ester chitosan, and also discloses a ternary transgenic compound particle taking the O-alkyl carbamic acid ester chitosan as a carrier. The O-alkyl carbamic acid ester chitosan is prepared through forming phthalimide for chitosan amino, coupling of chitosan and alkylamine, and deprotection of the chitosan amino, so that selective modification of repetitive unit C6 hydroxy of the chitosan is realized, the free amino of the chitosan with biological activity is maintained, C8-C20 linear chain alkylamine is taken as an alkyl donor, the alkyl carbamic acid ester chitosan with an acid sensitive carbamic acid ester bond as a connecting bond is obtained, and the ternary transgenic compound particle prepared by taking the chitosan as the carrier has the transfection characteristics of low cell toxicity and high transfection efficiency, and has a broad application prospect in gene cure field.

Description

technical field [0001] The present invention relates to a carrier of a transgene complex microparticle and a ternary transgene complex microparticle, in particular to a liposome-polymer-DNA ternary transgene complex microparticle and its preparation method, belonging to gene The preparation method and technology of new high-efficiency non-viral gene carrier in the field of treatment. Background technique [0002] Gene therapy introduces foreign genes into the nucleus of target cells to repair defective genes that cause diseases or inhibit harmful genes that cause diseases, so as to restore the body to normal functions and achieve the purpose of treating diseases. The development of molecular biology and the establishment of human gene banks have promoted the clinical application of gene therapy, making it not only play an advantage in the treatment of hereditary congenital diseases and malignant tumors, but also more and more widely used in the treatment of various common di...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/08A61K47/36A61K48/00A61K9/14
Inventor 张树彪陈会英赵轶男崔韶晖王冰
Owner DALIAN NATIONALITIES UNIVERSITY
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