Amphiphilic graft copolymer and application thereof

A graft copolymer and hydrophilic polymer technology, applied in the field of pharmaceutical preparations, can solve the problems of lack of reversibility of intelligent responsive micelles, and achieve the effects of improving stability and targeting efficiency and improving safety.

Active Publication Date: 2021-03-30
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problem of the lack of reversibility of the existing smart responsive micelles, the purpose of the present invention is to provide an amphiphilic graft copolymer which can self-assemble in a neutral or alkaline environment Form a micelle structure. As the pH of the environment changes, the micelle disintegrates in an acidic environment and exists as a stretched chain structure. When the disintegrated micelle monomer re-enters a neutral or alkaline environment, it can self-assemble again form micellar structure

Method used

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  • Amphiphilic graft copolymer and application thereof
  • Amphiphilic graft copolymer and application thereof
  • Amphiphilic graft copolymer and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] 1. Synthesis of γ-PGA-NH-PHis

[0050] (1) γ-PGA-NH 2 Synthesis of γ-PGA: Weigh 100 mg of γ-PGA, add 2 mL of ultrapure water, stir to dissolve, add 345.06 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl) , 207.18mg of N-hydroxysuccinimide (NHS), activated at room temperature for 30min. Weigh 270.45 mg of ethylenediamine (EDA) and add it into the activated γ-PGA solution, and stir at room temperature for 12 hours. After the reaction, the reaction solution was dialyzed with a dialysis bag with a molecular weight cut-off of 3.5 KDa, and freeze-dried for 48 hours to obtain a white loose solid, namely γ-PGA-EDA.

[0051] (2) Synthesis of γ-PGA-NH-PHis: Weigh 67.62 mg of PHis (16), 11.50 mg of EDC.HCl, and 6.9 mg of NHS, dissolve in 2 mL of dimethyl sulfoxide (DMSO), and activate at room temperature for 30 min. Weigh 41.43 mg of γ-PGA-EDA, add 300 μL of ultrapure water to dissolve, dilute to 2 mL with DMSO, add to the activated PHis solution, and ...

Embodiment 2

[0088] Synthesis of PVA-PHis: 20 mg of PHis (16), 6.82 mg of EDC.HCl, and 4.34 mg of DMAP were dissolved in 5 mL of 0.1 M MES buffer (pH=5.8), and activated at room temperature for 30 min. Weigh 10 mg of PVA and dissolve it in 2 mL of MES buffer, add it into the activated PHis solution, and stir at room temperature for 24 hours. The reaction solution was dialyzed and freeze-dried to obtain a white solid, namely PVA-PHis.

[0089] Preparation of micelles: Dissolve an appropriate amount of PVA-PHis in PBS solution with pH 7.4 to form micelles by self-assembly.

[0090] Measure the hydrated particle size of the micellar solution obtained in Example 5 with the technique of dynamic light scattering, adjust the pH of the solution to 6.5, and after standing for half an hour, measure its hydrated particle size again, then adjust the pH of the solution to 7.4, and let it stand After half an hour, measure its hydrated particle size again. The results of hydrated particle size under di...

Embodiment 3

[0095] Synthesis of PEI-PHis: 20 mg of PHis (16), 6.82 mg of EDC.HCl, and 4.08 mg of NHS were dissolved in 5 mL of 0.1 M MES buffer (pH=5.8), and activated at room temperature for 30 min. Weigh 15 mg of PEI and dissolve it in 2 mL of MES buffer, add it into the activated PHis solution, and stir at room temperature for 24 h. The reaction solution was dialyzed and freeze-dried to obtain a white solid, namely PEI-PHis.

[0096] Preparation of micelles: Dissolve an appropriate amount of PEI-PHis in PBS solution with pH 7.4 to form micelles by self-assembly.

[0097] The hydrated particle size of the obtained micellar solution was measured by dynamic light scattering method, the pH of the solution was adjusted to 6.5, and after standing for half an hour, the hydrated particle size was measured again, and the pH of the solution was readjusted to 7.4, and after standing for half an hour , and measure its hydrated particle size again. The results of hydrated particle size under diff...

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Abstract

The invention discloses an amphiphilic graft copolymer and application thereof, belonging to the technical field of pharmaceutical preparations. The amphiphilic graft copolymer comprises a hydrophilicpolymer, wherein an amphiphilic short chain containing an imidazole group is modified on a skeleton of the hydrophilic polymer. The amphiphilic graft copolymer provided by the invention has an amphiphilic short chain containing an imidazole group, so reversible morphological change can be generated in response to pH change, and a micelle structure is formed by self-assembly in a neutral or alkaline environment; in an acid environment, micelle is disintegrated and exists in a stretched chain structure form; and when the micelle is disintegrated and enters a neutral or alkaline environment again, the micelle can be self-assembled again to form the micelle structure.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an amphiphilic graft copolymer and its application. Background technique [0002] In recent years, polymer micelles, as a new type of nano drug delivery system, have attracted more and more attention due to their unique properties, such as good passive targeting, excellent drug loading capacity, stable structure, etc. It is a research hotspot in the field. At present, several nano-micelle preparations have been listed on the market at home and abroad, which have great clinical application value. [0003] At present, polymer micelles mainly use amphiphilic blocks or graft copolymers as carriers, and the hydrophilic components mainly include polyethylene glycol, polyvinyl alcohol, poly(N-vinyl-2-pyrrolidone), polysaccharides, Hyaluronic acid, hydrophilic polyamino acid, etc., whose hydrophilic properties can increase the stability of the preparation...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/00C08G81/02A61K47/34A61K9/107A61K47/64A61K47/69A61K33/243A61K31/337A61P35/00A61P29/00A61P7/02A61K49/00
CPCC08G81/00C08G81/024A61K47/34A61K9/1075A61K47/64A61K47/6907A61K33/243A61K31/337A61P35/00A61P29/00A61P7/02A61K49/00A61K2300/00
Inventor 孙春萌涂家生陈大力伊宸辰嵇梦
Owner CHINA PHARM UNIV
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