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Oxidation-reduction stimulus response type nanometer medicine carrier as well as preparation method and application thereof

A nano-drug carrier and stimuli-response technology, which is applied in the direction of pharmaceutical formulations, medical preparations of non-active ingredients, emulsion delivery, etc., to achieve the effect of good application value and simple preparation process

Active Publication Date: 2019-01-08
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, to the best of our knowledge, covalently bonding TEMPO redox groups to amphiphilic polymers and then self-assembling into redox nanoparticles has not been reported.

Method used

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  • Oxidation-reduction stimulus response type nanometer medicine carrier as well as preparation method and application thereof
  • Oxidation-reduction stimulus response type nanometer medicine carrier as well as preparation method and application thereof
  • Oxidation-reduction stimulus response type nanometer medicine carrier as well as preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1: Preparation of mPEG-CDP(IV)

[0038] mPEG(II)(M n =2000, 2.00g, 1mmol), CDP(III) (0.80g, 2mmol), DMAP (0.12g, 1mmol), were added in 100ml dichloromethane; EDC (0.40g, 2mmol) was dissolved in 30mL dichloromethane Add it dropwise to the above system in an ice-bath environment, and react at room temperature for 18 hours. After the reaction is completed, evaporate part of the solvent, add the remaining liquid dropwise to cold ether to wash the precipitate, and repeat the washing for 3 After three times, the precipitate was put into a vacuum drying oven at 40° C. overnight to obtain 2.11 g of the macromolecular RAFT reagent mPEG-CDP(IV), with a yield of 87%.

Embodiment 2

[0039] Embodiment 2: Preparation of PEG-b-PTMPM (V)

[0040] Add mPEG-CDP(IV) (0.48g, 0.2mmol), AIBN (11mg, 0.067mmol), TMPM (0.90g, 4mmol) and 5.5mL of dioxane into a 50mL single-necked round bottom flask respectively. Pass N 2 After 30 minutes, react at 70°C for 24h, precipitate the liquid obtained by the reaction with petroleum ether, put the precipitate in a vacuum drying oven, and dry overnight at 40°C to obtain 1.31g of polymer PEG-b-PTMPM(V). 95%.

Embodiment 3

[0041] Embodiment 3: Preparation of PEG-b-PTMA (VI)

[0042] Add polymer PEG-b-PTMPM (V) (1.0 g, containing 2.92 mmol of secondary amine groups), Na 2 WO 4 2H 2 O (0.24g, 0.73mmol), EDTA (0.12g, 0.41mmol), THF 5mL, stirred at room temperature for 30min, then transferred to 60°C oil bath, slowly added H 2 o 2 3.0 mL, reacted for 24 hours, precipitated the liquid obtained by the reaction with petroleum ether, put the precipitate in a vacuum drying oven, and dried overnight at 40°C to obtain 0.82 g of polymer PEG-b-PTMA(VI), with a yield of 80%.

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Abstract

The invention provides an oxidation-reduction stimulus response type nanometer medicine carrier as well as a preparation method and application thereof. A linear polymer with controllable molecular weight can be prepared by an RAFT active polymerization method, an amphiphilic polymer containing TEMPO nitroxide free radical is prepared by oxidizing the linear polymer, finally the polymer is self-assembled to obtain an oxidation-reduction stimulus response type nanometer micelle, and the nanometer micelle can be applied to a medicine controlled-release carrier; the oxidation-reduction stimulus response type nanometer medicine carrier is simple in preparation process and avoids agglomeration and coagulation; the nitroxide free radical gives oxidation-reduction stimulus responsiveness to the polymer nanometer micelle; and the polymer provides a carrier with good application value for medicine controlled release.

Description

(1) Technical field [0001] The invention relates to a redox stimulus-responsive nano drug carrier and its preparation method and application. (2) Technical background [0002] According to the statistics of the Ministry of Health, cancer has surpassed cardiovascular disease and ranked first in the cause of death. In my country, more than 1.6 million people die from cancer every year, and the treatment cost is as high as 150 billion yuan. Moreover, the annual cancer mortality rate is on the rise. Cancer treatment has thus become the most concerned research field in the world. Drug therapy is currently the main treatment for cancer, but the biggest problem is that anticancer drugs cannot stay locally in the tumor tissue but are distributed in various tissues and organs of the body, resulting in serious damage to other normal tissues while killing cancer cells. . Researchers at home and abroad have been looking for a drug delivery system that can directly deliver drugs to the...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/34C08G65/338
CPCA61K9/1075A61K47/34C08G65/338
Inventor 王建黎沈显波张寿豪
Owner ZHEJIANG UNIV OF TECH
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