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Preparation method of difunctional copolymerized nanoparticle inhibitor and application thereof in inhibition and detoxification of amyloid beta protein aggregation

A nanoparticle, dual-function technology, applied in the application field of inhibition and detoxification, can solve the problems of unsatisfactory inhibition and detoxification effects, and achieve the effect of good biocompatibility

Inactive Publication Date: 2017-10-17
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Utilizing the metal chelating performance of IDA, it has been reported in the field of chromatographic separation to apply it to the raw material of ion exchange resin, but it has not been reported in the field of biomedicine
[0007] In addition, the current "metal chelation therapy" method is mainly aimed at inhibiting metal-induced protein aggregation in areas where ions with high metal concentrations exist, thereby delaying the metal-induced aggregation of Aβ protein, but the formation of amyloid fibers and the resulting The inhibition and detoxification effects of toxicity are not ideal

Method used

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  • Preparation method of difunctional copolymerized nanoparticle inhibitor and application thereof in inhibition and detoxification of amyloid beta protein aggregation
  • Preparation method of difunctional copolymerized nanoparticle inhibitor and application thereof in inhibition and detoxification of amyloid beta protein aggregation
  • Preparation method of difunctional copolymerized nanoparticle inhibitor and application thereof in inhibition and detoxification of amyloid beta protein aggregation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: Synthesis of Bifunctional Copolymeric Nanoparticle Inhibitors.

[0034]Copolymer nanoparticles were prepared by free radical copolymerization. (1) Mix N,-N'-methylenebisacrylamide, tert-butylacrylamide, N-isopropylacrylamide and GMA-IDA in molar ratios of 1%, 53%, 41%, and 5%, respectively. In the mixture, 15 mg of surfactant sodium cetyl sulfate was added, and the final volume of the mixed solution was 50 mL. The resulting solution was blown in nitrogen for about 30 minutes to remove the air. Add 60 mg / mL sodium persulfate initiator, and react on a shaker at 25° C. at 160 rpm for 12 hours under nitrogen protection. After the reaction, the resulting polymer was dialyzed against MilliQ water for 14 days (at least two water changes per day) to remove unreacted monomers. Nanoparticles were lyophilized and stored in a refrigerator at 4°C until use. The hydraulic particle diameter of the nanoparticles prepared under this condition is 118±6nm, and the surface Z...

Embodiment 2

[0035] Example 2: Synthesis of Bifunctional Copolymeric Nanoparticle Inhibitors.

[0036] Copolymer nanoparticles were prepared by free radical copolymerization. (1) Mix N,-N'-methylenebisacrylamide, tert-butylacrylamide, N-isopropylacrylamide and GMA-IDA in molar ratios of 2%, 40%, 48%, and 10%, respectively. In the mixture, 10 mg of surfactant sodium cetyl sulfate was added, and the final volume of the mixed solution was 50 mL. The resulting solution was blown in nitrogen for about 60 min to remove the air. Add 60 mg / mL sodium persulfate initiator, and react on a shaker at 25° C. at 160 rpm for 15 h under nitrogen protection. After the reaction, the resulting polymer was dialyzed against MilliQ water for 14 days (at least two water changes per day) to remove unreacted monomers. Nanoparticles were lyophilized and stored in a refrigerator at 4°C until use. The hydraulic particle size of the nanoparticles prepared under this condition is 88±6nm, and the surface Zeta potenti...

Embodiment 3

[0037] Example 3: Synthesis of Bifunctional Copolymeric Nanoparticle Inhibitors.

[0038] Copolymer nanoparticles were prepared by free radical copolymerization. (1) Mix N,-N'-methylenebisacrylamide, tert-butylacrylamide, N-isopropylacrylamide and GMA-IDA in molar ratios of 5%, 38%, 37%, and 20%, respectively. In the mixture, 20 mg of surfactant sodium cetyl sulfate was added, and the final volume of the mixed solution was 50 mL. The resulting solution was blown in nitrogen for about 10 min to remove the air. Add 60 mg / mL sodium persulfate initiator, and react on a shaker at 25° C. at 160 rpm for 10 h under nitrogen protection. After the reaction, the resulting polymer was dialyzed against MilliQ water for 14 days (at least two water changes per day) to remove unreacted monomers. Nanoparticles were lyophilized and stored in a refrigerator at 4°C until use. The hydraulic particle size of the nanoparticles prepared under this condition is 80.0±5nm, and the surface Zeta poten...

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Abstract

The invention relates to a preparation method of difunctional copolymerized nanoparticle inhibitor and application thereof in inhibition and detoxification of amyloid beta protein aggregation. The preparation method includes: using a connection product GMA-IDA of iminodiacetic acid (IDA) and glycidyl methacrylate (GMA) as a monomer; subjecting the monomer to free radical copolymerization reaction with monomers like N-isopropylaccrylamide (NIPAm) and n-tertbutyl acrylamide (TBAm) to synthesize the difunctional nanoparticle inhibitor having metal chelation ability and protein aggregation inhibiting ability. Average particle diameter of difunctional copolymerized nanoparticles synthesized by the method is 80-120nm. Metal ion chelation capacity of the nanoparticles synthesized by the method is higher than 700umol / g, and the nanoparticles can chelate metal ions in environment and inhibit fibrosis aggregation of Abeta42 and are a potential new drug raw material for treating Alzheimer's disease.

Description

technical field [0001] The invention relates to a preparation method of a copolymerized nanoparticle inhibitor with dual functions of metal chelation and inhibition of fibrosis aggregation and its application in the inhibition and detoxification of metal-induced amyloid beta protein aggregation. Background technique [0002] Alzheimer's disease is the most common senile dementia, and its symptoms are manifested as cognitive dysfunction, memory decline, emotional instability and other symptoms. A large number of studies have shown that the pathogenesis of AD is accompanied by the aggregation of amyloid β-protein (Aβ), which produces fibrous plaques in the neuron cells in the brain of patients. Therefore, it is generally believed that there is a close relationship between Aβ aggregation into fibroblasts and the pathogenesis of AD. [0003] Aβ is obtained by cleavage of transmembrane amyloid precursor protein (APP) by β- and γ-secretase successively. However, due to the diffe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F220/54C08F222/38C08F222/22A61P25/28A61K31/785A61P39/02
Inventor 孙彦余林玲董晓燕
Owner TIANJIN UNIV
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