Synthesis method of in-situ-enhanced thermosensitive polymer and degradable in-situ-enhanced injectable thermosensitive hydrogel

A temperature-sensitive hydrogel and synthesis method technology, applied in the field of in-situ enhanced synthesis of injectable temperature-sensitive hydrogel, can solve the problems of cell damage, tissue necrosis, cell death, etc., and achieve the effect of enhanced strength and stability

Inactive Publication Date: 2012-06-20
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, toxic photoinitiators and UV light can cause cell death
In addition, the heat released by polymerization will damage cells and lead to local necrosis of biological tissues

Method used

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  • Synthesis method of in-situ-enhanced thermosensitive polymer and degradable in-situ-enhanced injectable thermosensitive hydrogel
  • Synthesis method of in-situ-enhanced thermosensitive polymer and degradable in-situ-enhanced injectable thermosensitive hydrogel
  • Synthesis method of in-situ-enhanced thermosensitive polymer and degradable in-situ-enhanced injectable thermosensitive hydrogel

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preparation example Construction

[0026] A method for synthesizing a temperature-sensitive polymer capable of in situ enhancement, comprising the following steps: in the presence of a hydroxyl group-containing initiator and a catalyst, homopolymerize a cyclic lactone functional monomer containing a double bond, or obtain it from a double-bond-containing functional monomer The cyclic lactone functional monomer is obtained by copolymerization with one of carbonate, lactone and lactide, wherein the double bond functional monomer is a compound shown in structural formula (1)-(3):

[0027]

[0028] The hydroxyl group-containing initiator is preferably Pluronic F127, PLGA-PEG-PLGA, unless otherwise specified, the F127 mentioned below is Pluronic F127.

[0029] Described catalyst is a kind of in metal or metalloid catalyst; Metal catalyst comprises stannous octoate, tin trifluoromethanesulfonate; Nonmetal catalyst comprises aliphatic tertiary amine (comprising triethylamine (TEA), N, N, N',N'-tetramethylethylenedi...

Embodiment 1

[0039] Weigh 1.89g (1.5×10 -4 mol) F127 was dehydrated in a reaction polymerization tube at 120° C. for 4 h under vacuum, protected by Ar and cooled to room temperature. in a vacuum glove box (O 2 Content2 O content -4 mol) TMEDA (N, N, N', N'-tetramethylethylenediamine), 0.364 (3.57×10 -3 mol) TMC (trimethylene carbonate), 0.126g (6.3×10 -4 mol) AC (2-methyl 2-methyl acrylate-1,3 dimethylene carbonate). The polymerization tube was sealed, and after reacting at 60° C. for 45 h, the reaction polymerization tube was placed in an ice bath to terminate the polymerization reaction. The crude product was precipitated using ice anhydrous diethyl ether 8-10 times the volume of THF at room temperature. The anhydrous ether precipitate was then dissolved in THF, dried under reduced pressure at 40°C to constant weight, and stored in a desiccator.

Embodiment 2

[0041] Dissolve 0.06 g of the copolymer obtained in Example 1 in 1 ml of PBS (pH=7.4), and place it in a refrigerator at 4°C for overnight storage, so that the aqueous solution of the hydrogel material reaches an equilibrium state. Add 1mgDTT (dithiothreitol) to the aqueous solution; and react at 40°C for 10min.

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Abstract

The invention discloses a synthesis method of in-situ-enhanced thermosensitive polymer. The synthesis method includes the following steps of homopolymerizing double-bond functional monomer or copolymerizing the double-bond functional monomer, carbonic ester, lactone and lactide on the conditions of hydroxy-containing initiators and amine catalysts, wherein the homopolymerization or copolymerization reaction temperature ranges from 50 DEG C to 80 DEG C, and reaction time ranges from 1 to 4 hours. The hydrogel is in a liquid state at low temperature while is in a gel state at physiological temperature, and can be injected with bioactive molecules and biological signals conveniently and is endowed with special bioactivity. Besides, the hydrogel can be degradable gradually at the physiological environment.

Description

technical field [0001] The invention relates to a synthesis method of an in-situ enhanced thermosensitive polymer and a degradable in-situ enhanced injectable thermosensitive hydrogel. Background technique [0002] As a kind of hydrogel that can be implanted in the human body as a bioactive molecule and drug controlled release carrier and a hydrogel scaffold in the field of tissue engineering, it has good biocompatibility, biodegradability, non-toxicity, environmental stimulus responsiveness and certain mechanical strength. Among them, smart hydrogel has become a research hotspot of biomedical materials due to its intelligent response ability to external environmental stimuli such as temperature, pH, and electric field. In recent years, research on hydrogels has shifted from hydrogel implantation to in situ injectable thermosensitive hydrogels. The in situ injectable thermosensitive hydrogel is in a liquid state at lower temperatures and in a gel state at physiological tem...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G64/02C08G64/30C08G63/08C08G63/64C08G63/91C08G81/00C08J3/075A61K47/34A61K47/36A61K47/42A61L27/18A61L27/20A61L27/22A61L27/24A61L27/52A61L27/50
Inventor 全大萍王涛颜明发
Owner SUN YAT SEN UNIV
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