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Injectable temperature-sensitive hydrogel and preparation method thereof

A room temperature, reaction temperature technology, applied in the field of physical hydrogel and its preparation, can solve problems such as easy plugging of needles, and achieve the effects of easy injection, small hydrodynamic volume, and mild reaction conditions

Inactive Publication Date: 2012-02-08
NORTHWEST UNIV(CN)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the polylactic acid injectable hydrogels with temperature sensitivity mainly include: (1) poly(lactic acid-glycolic acid)-polyethylene glycol-poly(lactic acid-glycolic acid) (PLGA-PEG-PLGA). The starting temperature of gelation is too low, it is easy to block the needle during injection (US Patent P6004573)

Method used

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  • Injectable temperature-sensitive hydrogel and preparation method thereof
  • Injectable temperature-sensitive hydrogel and preparation method thereof
  • Injectable temperature-sensitive hydrogel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Weigh 20g of L-lactide and 0.945g of pentaerythritol into a round bottom flask, add 0.03% stannous octoate, and react at 160°C for 8 hours under normal pressure; after the reaction, add 40ml of DMSO to dissolve it, then add 4.17g of succinic anhydride, 4ml of triethylamine and 0.5g of DMAP were reacted at room temperature, and then the product was added into water until the precipitation was complete to obtain light yellow solid PET-PLLA-SA with a viscosity average molecular weight of 2270. Weigh a certain amount of PET-PLLA-SA and mPEG 350 Dissolve in chloroform, add DMAP and DCC, react overnight at room temperature, dissolve the product in water, heat up until a precipitate forms, filter to obtain a four-arm PLLA-mPEG block copolymer with a viscosity-average molecular weight of 3760; from HNMR It can be seen from the spectrum ( figure 1 ), the original two peaks of pentaerythritol, one is 4.688 (CC H 2 OH), 3.488 (CCH 2 o H ), after polymerization, peak 3.488 has...

Embodiment 2

[0032] Weigh 20g of L-lactide and 0.945g of pentaerythritol into a round bottom flask, add 0.03% zinc lactate, replace with N2 gas, and react at 120°C for 8 hours under normal pressure; after the reaction, add 40ml of DMSO to make it Dissolve, then add 4.17g succinic anhydride, 4ml triethylamine and 0.5g DMAP, and react at 25°C; then add the reactant to water to obtain light yellow solid PET-PLLA-SA with a viscosity average molecular weight of 2340. Weigh a certain amount of PET-PLLA-SA and mPEG 350 Dissolve in dichloromethane, add DMAP and DCC, react overnight at room temperature, dissolve the product in water, heat up until a precipitate forms, filter to obtain a four-armed PLLA-mPEG block copolymer with a viscosity-average molecular weight of 3660; PLLA-mPEG was added to water under low conditions to obtain an aqueous copolymer solution, which gelled rapidly at a temperature of 37°C.

Embodiment 3

[0034] Weigh 20g of L-lactide and 0.9615g of glycerol in a round-bottomed flask, add 0.03% stannous octoate, replace with N2 gas, and react at 160°C for 8 hours; after the reaction, add 40ml of DMSO to make After it was dissolved, 5.208g of succinic anhydride, 4ml of triethylamine and 0.5g of DMAP were added and reacted at 25°C; then the reactant was added into water to obtain a light yellow solid with a viscosity-average molecular weight of 2770. Weigh a certain amount of light yellow solid and mPEG 500 Dissolve in dichloromethane, add DMAP and DCC, react overnight at room temperature, dissolve the product in water, heat up until a precipitate forms, filter, and obtain a three-arm PLLA-mPEG block copolymer with a viscosity-average molecular weight of 4310; It can be seen from the HNMR spectrum ( figure 2 ), glycerol and L-lactide polymerization, HNMR peak area analysis, 4.38 [OCO(C H )OH] is 11, 4.25 (C H ) is 4, the ratio of the two is about 3, indicating that the polyme...

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Abstract

The invention discloses a star-type polylactic acid-polyethylene glycol monomethyl ether copolymer. The preparation method of the star-type polylactic acid-polyethylene glycol monomethyl ether copolymer comprises the following steps of: initiating lactide to carry out ring opening polymerization to form star-type polylactic acid by using propanetriol or pentaerythritol as an initiator, adding organic base and a basic catalyst by using butanedioic anhydride as an acylating agent and dimethyl sulfoxide as a solvent and carrying out carboxylation on the tail end of the star-type polylactic acid;adding the star-type polylactic acid of which the tail end is subjected to carboxylation in an organic solvent; then adding the polyethylene glycol monomethyl ether, a condensing agent and a catalystfor reacting; and after the reacting, filtering, dissolving a product in water and gradually raising the temperature until precipitation is generated and obtaining the star-type polylactic acid-polyethylene glycol monomethyl ether copolymer. The hydrogel disclosed by the invention is in a solution state at normal temperature or at the temperature lower than normal temperature and can be quickly gelated at 37DEG C; the formed hydrogel can be degraded in the body and has favorable biocompatibility; and the invention has the advantages of simple synthetic method, mild reaction conditions and suitability for industrial production.

Description

technical field [0001] The invention relates to a thermosensitive and degradable physical hydrogel and a preparation method thereof, belonging to the field of biomedical polymer materials. Background technique [0002] In recent years, the slow-release and controlled-release technology of drugs has developed rapidly. The sustained and controlled release system plays an important role in reducing drug side effects and administration times, reducing blood drug concentration fluctuations and gastrointestinal irritation. At present, some sustained-release systems such as implants and microspheres have entered clinical application, but implants also have some shortcomings, such as surgical implantation often brings pain to patients; microsphere sustained-release systems have less drug loading, including The sealing rate is not high, the sudden release effect is relatively large, and it is difficult to industrialized production. The injectable temperature-sensitive hydrogel has ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G63/664C08G63/78C08J3/075
Inventor 郝红王君莲张粉艳赵亚玲王凯王斌
Owner NORTHWEST UNIV(CN)
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