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Targeting triblock copolymer containing morpholine-2,5-dione derivative copolymer, preparation method and application

A technology of copolymers and derivatives, applied in the field of targeted triblock copolymers and preparation, achieves the effects of low cytotoxicity, high transfection rate and improved stability

Active Publication Date: 2016-02-10
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, at present, REDV polypeptides are used to prepare ECs-targeted gene vectors, which carry the target gene (ZNF580 gene) into endothelial cells, thereby promoting the rapid proliferation of endothelial cells, inhibiting smooth muscle proliferation, and finally achieving rapid endothelialization. Such research has not been reported so far.

Method used

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  • Targeting triblock copolymer containing morpholine-2,5-dione derivative copolymer, preparation method and application
  • Targeting triblock copolymer containing morpholine-2,5-dione derivative copolymer, preparation method and application
  • Targeting triblock copolymer containing morpholine-2,5-dione derivative copolymer, preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0054] A method for preparing a targeted tri-block copolymer containing morpholine-2,5-dione derivative copolymer, comprising the steps of:

[0055] (1) take morpholine-2,5-diketone derivative monomer and L-lactide according to the ratio of 20:80 according to the molar ratio, add initiator and stannous octoate catalyst, under the condition of isolated air, React at 150°C for 1h, then react at 120°C for 48h to obtain the mixture; the amount of stannous octoate added is 2% of the sum of the mass of morpholine-2,5-dione derivative monomer and L-lactide; The agent is 1,8-octanediol, and the addition amount of 1,8-octanediol is 7% of the sum of the mass of morpholine-2,5-dione derivative monomer and L-lactide.

[0056] The structure of morpholine-2,5-diketone derivative monomer is formula (I-a):

[0057]

[0058] (2) Dissolve 25g of the mixture obtained in step (1) in 50mL dimethyl sulfoxide to make a solution, add 150mL of anhydrous ether, separate, remove unreacted monomers, ...

Embodiment 2

[0063] A method for preparing a targeted tri-block copolymer containing morpholine-2,5-dione derivative copolymer, comprising the steps of:

[0064] (1) Take by weighing morpholine-2,5-dione derivative monomer and D-lactide in the ratio of 10:90 by molar ratio, add initiator and tin octoate, under the condition of isolated air, at 140 After reacting at 100°C for 2 hours, and then reacting at 100°C for 72 hours, the mixture was obtained; the amount of tin octoate added was 0.001% of the sum of the mass of morpholine-2,5-dione derivative monomer and D-lactide; the initiator was 1,9-nonanediol, the amount of 1,9-nonanediol is 8% of the sum of the mass of morpholine-2,5-dione derivative monomer and D-lactide;

[0065] The structure of morpholine-2,5-diketone derivative monomer is formula (I):

[0066] where R 1 :-H;R 2 :-CH(CH 3 )-CH 2 -CH 3 ;

[0067] (2) 5g of the mixture obtained in step (1) was dissolved in 10mL of chloroform to make a solution, added 50mL of anhydrous et...

Embodiment 3

[0072] A method for preparing a targeted tri-block copolymer containing morpholine-2,5-dione derivative copolymer, comprising the steps of:

[0073] (1) Take morpholine-2,5-diketone derivative monomer and D,L-lactide in the ratio of 25:75 by molar ratio, add initiator and dibutyltin oxide, in the isolated air Under the conditions, react at 155°C for 0.5h, then react at 130°C for 12h to obtain a mixture; the amount of dibutyltin oxide added is morpholine-2,5-dione derivative monomer and D,L-lact 5% of the sum of ester mass; the initiator is 1,10-decanediol, and the mass of 1,10-decanediol is the mass of morpholine-2,5-dione derivative monomer and D,L-lactide 0.16% of the sum;

[0074] The structure of morpholine-2,5-diketone derivative monomer is formula (I):

[0075] where R 1 :-CH 3 ; 2 :-CH 2 C(CH 3 ) 2 ;

[0076] (2) 25g of the mixture obtained in step (1) was dissolved in 50mL of dichloromethane to make a solution, added 150mL of n-hexane, separated, removed unrea...

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Abstract

The invention discloses a targeting triblock copolymer containing a morpholine-2,5-dione derivative copolymer, a preparation method and application. The targeting triblock copolymer containing the morpholine-2,5-dione derivative copolymer is a copolymer which is composed of the morpholine-2,5-dione derivative copolymer, polyethyleneimine and CREDVW and possesses the molecular weight of 3600-98000. Experiments prove that the triblock copolymer containing the morpholine-2,5-dione derivative copolymer is low in cytotoxicity and high in transfection rate and possesses endothelial-cell targeting function. The method is simple and free of pollution, and a nanoparticle prepared from the triblock copolymer containing the morpholine-2,5-dione derivative copolymer possesses good biocompatibility, is capable of effectively carrying a gene and entering a cell and posseses blood-vessel endothelial-cell targeting property.

Description

technical field [0001] The invention belongs to the technical field of gene carrier materials, and specifically relates to a targeting triblock copolymer containing morpholine-2,5-diketone derivative copolymer, a preparation method and application thereof. Background technique [0002] Artificial blood vessels are generally made of high molecular polymers. Compared with natural blood vessels, the biggest difference between artificial blood vessels is the lack of functionalized endothelial cells (ECs) layer on their inner surfaces. At the same time, there are poor hydrophilicity or cell-free recognition sites on the inner surface of artificial blood vessels formed by polymers. These differences often lead to postoperative restenosis of artificial blood vessels, which is the main cause of clinical death of patients. [0003] The endothelial cell layer, the innermost layer of natural blood vessels, provides a non-thrombogenic inner surface while also playing an important role i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00C12N15/87
Inventor 冯亚凯石长灿任相魁李茜于丽
Owner TIANJIN UNIV
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