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Cross linking polymer and preparation method thereof

A technology for cross-linking polymers and products, applied in pharmaceutical formulations, genetic material components, gene therapy, etc., can solve the problems of non-degradability, high cytotoxicity, low PEI gene transfer efficiency, etc., to improve gene transfer efficiency and easy to degrade. Effect

Active Publication Date: 2010-11-10
CHANGZHOU INST OF ENERGY STORAGE MATERIALS &DEVICES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, low-molecular-weight PEI gene transfer efficiency is low, while high-molecular-weight PEI has high gene transfer efficiency, but it is cytotoxic and non-degradable

Method used

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  • Cross linking polymer and preparation method thereof
  • Cross linking polymer and preparation method thereof

Examples

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preparation example Construction

[0042] The present invention also provides a kind of preparation method of cross-linked polymer, comprising:

[0043] a) mixing polyethylene glycol diacrylate and aminoethanol, and performing a polymerization reaction under anhydrous and oxygen-free conditions to obtain a first intermediate product;

[0044] b) Mix the first intermediate product with diisocyanate, heat to 50°C-60°C to react to obtain the second intermediate product, the molar ratio of the hydroxyl group on the first intermediate product to diisocyanate is 1:1.1-4 ;

[0045] c) adding the second intermediate product into a polyethyleneimine solution for grafting reaction to obtain a cross-linked polymer with a molecular weight of 5,000-100,000, and the polyethyleneimine has a molecular weight of 100-2,000.

[0046] According to the present invention, polyethylene glycol diacrylate is first mixed with aminoethanol, and a polymerization reaction occurs under anhydrous and oxygen-free conditions to obtain a first...

Embodiment 1

[0072] Under anhydrous and oxygen-free conditions, respectively dissolve 0.61 g of aminoethanol and polyethylene glycol diacrylate (PEGDA) with a molecular weight of 258 in anhydrous dichloromethane, wherein the molar ratio of PEGDA to aminoethanol is 1:1 , to obtain aminoethanol dichloromethane solution and PEGDA dichloromethane solution, mix the two solutions, react at 50°C for 1 day, settle in 1000mL ether, and dry the solid to obtain a light yellow product, which is The molecular weight of polyurethane L-PAE1 with a linear structure was calculated by gel permeation chromatography (GPC). The results are shown in Table 1. Table 1 shows the L-PAE prepared in the examples of the present invention and its molecular weight.

Embodiment 2

[0074] Use the same raw materials and steps as in Example 1 to operate, but the reaction time is 3 days to obtain the light yellow product L-PAE2, calculate the molecular weight with gel permeation chromatography (GPC), the results are shown in Table 1, and Table 1 is the implementation of the present invention Example prepared L-PAE and its molecular weight.

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Abstract

The invention provides a cross linking polymer. Molecules of the cross linking polymer at least comprise a first repeated unit in a structure as a formula (I) and a second repeated unit in a structure as a formula (II), wherein n is greater than 1 and less than 25, Q is alkyl or aryl, R1 is polymine with the molecular weight between 100 and 2000, and the molecular weight of the cross linking polymer is between 5000 and 100000. The invention also provides a preparation method of the cross linking polymer. Compared with the prior art, the cross linking polymer provided by the invention has larger molecular weight because of the two repeated units in the cross linking polymer provided by the invention, so the gene transfer efficiency of the cross linking polymer can be improved. At the same time, both the two repeated units have low cell toxicity. Thereby, the toxicity of the cross linking polymer is low. Experiments show that when the cross linking polymer provided by the invention is used for in-vitro transfection as gene carriers, the transfection efficiency of the cross linking polymer is ten times or even dozens of times higher than that of PE125k.

Description

technical field [0001] The invention relates to the technical field of high molecular polymers, in particular to a cross-linked polymer and a preparation method thereof. Background technique [0002] Gene therapy is an emerging treatment method in recent years. It can treat genetic diseases or cancer by introducing normal genes into patient cells and correcting the defects of disease-causing genes. In gene therapy, the most critical issue is to transfer DNA into the target cell, then into the nucleus, and finally realize the transcription and expression of the gene. At present, the most commonly used vectors for mediating gene delivery are viral vectors, such as adenovirus vectors and herpes simplex virus vectors. Therefore, non-viral vectors that are easy to prepare, inexpensive, non-toxic, and immune-free have become one of the research hotspots. [0003] At present, the prior art discloses a variety of non-viral carriers, such as liposome complexes, cationic polymers, e...

Claims

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Application Information

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IPC IPC(8): C08G81/00C08G73/04C08G18/83C08G18/64A61K48/00
Inventor 陈学思夏加亮田华雨陈磊李非凡陈杰郭兆培林琳
Owner CHANGZHOU INST OF ENERGY STORAGE MATERIALS &DEVICES
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