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Method for preparing PVP-PEG-PLA shell-crosslinked nano micelle

A technology of micelle and shell layer, applied in the field of nano drug release carrier preparation, can solve the problems of long circulation time in vivo and narrow particle size distribution, and achieve the effects of large drug loading, simple preparation process and good stability

Inactive Publication Date: 2008-09-17
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Generally only tens of nanometers, and the particle size distribution range is narrow
(3) Long circulation time in the body

Method used

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  • Method for preparing PVP-PEG-PLA shell-crosslinked nano micelle
  • Method for preparing PVP-PEG-PLA shell-crosslinked nano micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Take 10 g of polyethylene glycol with a relative molecular mass of 400, add 30 mg of hydroquinone into the reactor, pass nitrogen gas under ice-bath conditions, add 2.5 g of methacryloyl chloride dropwise, and stir at 150 rpm for 24 hours to obtain polyethylene glycol For the crude product of monomethacrylate, dissolve the crude product in 40ml of deionized water, extract with 10ml of diphenyl ether, and then extract the obtained aqueous phase with 50ml of a mixture of 35.5ml of dichloromethane and 12.5ml of n-hexane , the organic solvent was distilled off to obtain polyethylene glycol monomethacrylate with a yield of 65%.

[0022] Take 4g of polyethylene glycol monomethacrylate, 1g of lactide and 1mg of stannous octoate into the reactor, and react in an anaerobic vacuum at 140°C for 24 hours. The obtained polymer is dissolved in chloroform and precipitated with petroleum ether to obtain The polyethylene glycol monomethacrylate-polylactic acid diblock copolymer has a pr...

Embodiment 2

[0026] Take 15g of polyethylene glycol with a relative molecular mass of 600, add 35mg of hydroquinone into the reactor, pass nitrogen gas under ice-bath conditions, add 2.5g of methacryloyl chloride dropwise, and stir for 24 hours at 150 rpm to obtain polyethylene glycol For the crude product of monomethacrylate, the crude product was dissolved in 60ml of deionized water, extracted with 15ml of diphenyl ether, and the obtained aqueous phase was re-extracted with 80ml of a mixture of 60ml of dichloromethane and 20ml of n-hexane, evaporated The organic solvent was removed to obtain polyethylene glycol monomethacrylate with a yield of 68.4%.

[0027] Take 4g of polyethylene glycol monomethacrylate, 2g of lactide and 2mg of stannous octoate into the reactor, and react in an anaerobic vacuum at 140°C for 24 hours. The obtained polymer is dissolved in chloroform and precipitated in petroleum ether to obtain The polyethylene glycol monomethacrylate-polylactic acid diblock copolymer ...

Embodiment 3

[0031]Take 10 g of polyethylene glycol with a relative molecular mass of 400, add 30 mg of hydroquinone into the reactor, pass nitrogen gas under ice-bath conditions, add 2.5 g of methacryloyl chloride dropwise, and stir at 150 rpm for 24 hours to obtain polyethylene glycol For the crude product of monomethacrylate, dissolve the crude product in 40ml of deionized water, extract with 10ml of diphenyl ether, and then extract the obtained aqueous phase with 50ml of a mixture of 35.5ml of dichloromethane and 12.5ml of n-hexane , the organic solvent was distilled off to obtain polyethylene glycol monomethacrylate with a yield of 65%.

[0032] Take 4g of polyethylene glycol monomethacrylate, 0.8g of lactide and 0.8mg of stannous octoate into the reactor, and react in an anaerobic vacuum at 140°C for 24 hours, and the obtained polymer is dissolved in chloroform and precipitated in petroleum ether , to obtain polyethylene glycol monomethacrylate-polylactic acid diblock copolymer, the ...

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Abstract

The invention discloses a method for preparing a poly-N-vinylpyrrolidone-polyethylene glycol-poly-lactic acid copolymer shell layer cross-linked micelle. The process of the method comprises the following steps: polyethylene glycol monomethacrylate is firstly synthesized, and then the polyethylene glycol monomethacrylate-poly-lactic acid block copolymer which is provided with double bonds at the tail end of a PEG chain segment is prepared by the polymerization with lactide. Polyethylene glycol monomethacrylate-poly-lactic acid block copolymer micelle aqueous dispersion is prepared by the spontaneous emulsion-solvent method, then N-vinyl pyrrolidone is added in the presence of ammonium persulfate and tetramethylethylenediamine, thus obtaining the poly-N-vinylpyrrolidone-polyethylene glycol-poly-lactic acid copolymer shell layer cross-linked micelle. The method has the advantages that, the preparation process is simple; the prepared poly-N-vinylpyrrolidone-polyethylene glycol-poly-lactic acid copolymer shell layer cross-linked micelle has good stability and can be used as a drug release carrier with great drug loading and adjustable release rate.

Description

technical field [0001] The invention relates to a preparation method of poly-N-vinylpyrrolidone-polyethylene glycol-polylactic acid copolymer (PVP-PEG-PLA) shell cross-linked micelles, which belongs to the preparation technology of nano drug release carrier. Background technique [0002] In recent years, biodegradable nanoparticles have attracted extensive attention as an effective drug carrier. Among them, macromolecular micelles with core-shell structure have the characteristics of high efficiency, long-term effect, and safety, and have become a research hotspot in the field of pharmacy. Initially, this macromolecular micelle is mainly composed of amphiphilic (hydrophilic and hydrophobic) block copolymers. The hydrophobic block of the polymer forms the inner core of the micelle through hydrophobic interactions in water, and the hydrophilic block Then the shell of the micelles is formed around the core of the micelles. In addition to this hydrophobic interaction, water-in...

Claims

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Application Information

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IPC IPC(8): C08F290/06C08G65/48C08G63/91C08G63/66C08J3/03A61K47/30C08F226/10
Inventor 姚芳莲汪民马晓燕郭双壮
Owner TIANJIN UNIV
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