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Thermosensitive block copolymer hydrogel as well as preparation method and application thereof

A block copolymer and hydrogel technology, which is applied in the field of thermosensitive block copolymer hydrogel and its preparation, can solve the problems of sudden release of drugs, toxic reactions, low mechanical strength, etc., and achieve good application potential, The effect of strong mechanical strength

Pending Publication Date: 2022-06-17
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the micelles are bound by physical hydrophobic interactions, so the mechanical strength of this type of physical hydrogel is low. When applied in vivo, the gel network often collapses rapidly under the action of body fluid erosion.
The premature collapse of the hydrogel network often results in severe burst release of the drug during the drug delivery process, which not only fails to achieve the expected therapeutic effect, but may also cause toxic reactions due to the high local concentration of the drug.

Method used

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  • Thermosensitive block copolymer hydrogel as well as preparation method and application thereof
  • Thermosensitive block copolymer hydrogel as well as preparation method and application thereof
  • Thermosensitive block copolymer hydrogel as well as preparation method and application thereof

Examples

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preparation example Construction

[0073] The invention also discloses a preparation method of the temperature-sensitive block copolymer hydrogel. The steps are as follows:

[0074] 1. Initiating ring-opening polymerization or thermal polymerization of ester monomers with small molecular monohydric alcohol or polyhydric alcohol under the catalysis of catalyst to obtain linear or star-shaped polyester containing hydroxyl at the end;

[0075] II. Connect the polyethylene glycol block by esterification reaction or coupling bond at the end of the polyester to obtain a block copolymer with active groups at the end of the hydrophilic block;

[0076] III. Dissolving one or more block copolymers in a solvent at low temperature to prepare a copolymer solution; or,

[0077] A copolymer solution is prepared by dissolving a plurality of block copolymers in a solvent, and then mixing the respective solutions.

[0078] In other embodiments, the preparation method comprises the following steps:

[0079] 1. Initiating ring-o...

Embodiment 1

[0085] A block copolymer with a free hydroxyl group at the end of a hydrophilic block, the preparation method of which is as follows:

[0086] (1) Add amyl alcohol to a 250mL three-necked flask, remove water in a vacuum at 120°C for 3 hours, first cool to 80°C with argon, add lactide (LA) corresponding to the weight of the target molecular weight and account for the weight of the monomers 0.15-0.20 wt % stannous octoate, after replacing argon three times, the temperature is raised to 150° C. and stirred for 12 hours to obtain linear one-armed polylactic acid (PLA).

[0087] (2) After the reaction is completed, cool down to room temperature, add succinic anhydride with 1.5 to 2 times the molar amount of hydroxyl on the linear polylactic acid, replace the gas in the reaction flask with argon three times, and add an appropriate amount of anhydrous dichloride to the reaction flask with a syringe Methane, and the polymer was dissolved by magnetic stirring. Subsequently, a dichloro...

Embodiment 2-10

[0090] A block copolymer with a hydrophilic block with an active group, the preparation method of which is similar to that of Preparation Example 1, except that the selected alcohol initiator, the type and molecular weight of the polyester, the polyethylene glycol The molecular weights are shown in Table 1.

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Abstract

The invention belongs to the technical field of high polymer materials and medicines, and particularly relates to thermo-sensitive block copolymer hydrogel as well as a preparation method and application thereof. According to the thermosensitive block copolymer hydrogel disclosed by the invention, a hydrophobic polyester block is positioned in the middle of a block copolymer, a hydrophilic polyethylene glycol block is positioned on the outer side of the block copolymer, and a terminal group is an active chemical group such as hydroxyl, carboxyl or amino, so that contact between functional groups or between the functional groups and an external matrix is facilitated. In addition, free active groups such as hydroxyl, carboxyl or amino and the like at the tail end of the polyethylene glycol block can be further chemically modified and modified. Furthermore, functional groups such as propylene double bonds, catechol groups and phenol groups are modified on terminal active groups of the segmented copolymer through esterification reaction or coupling reaction, the segmented copolymer with the hydrophilic terminal subjected to functional modification is obtained, and therefore the temperature-sensitive hydrogel is endowed with tissue adhesion performance and higher mechanical strength and imaging capacity.

Description

technical field [0001] The invention belongs to the technical field of polymer materials and medicine, and particularly relates to a temperature-sensitive block copolymer hydrogel and a preparation method and application thereof. Background technique [0002] An injectable thermotropic hydrogel composed of polyethylene glycol / polyester block copolymers is widely used in drug delivery due to its good biocompatibility, tunable biodegradability, and convenient injectability. It has shown good application potential in tissue repair, medical imaging, and auxiliary surgery. [0003] Although polyethylene glycol / polyester block copolymer thermotropic hydrogels have been tried to be used in different biomedical fields, for different biomedical applications, it is often necessary to design the polymer molecular structure to achieve hydrogelation Personalized customization of glue properties. Common temperature-sensitive polyethylene glycol / polyester block copolymers are obtained by...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08L87/00C08G81/00A61K9/06A61K47/34A61L26/00A61L27/18A61L27/50A61L27/52
CPCC08J3/075C08G81/00A61K9/06A61K47/34A61L27/18A61L27/52A61L26/008A61L26/0019A61L27/50A61L26/0061C08J2387/00A61L2400/06A61L2400/04A61L2300/412A61L2300/418C08L87/00
Inventor 俞麟杨孝伟丁建东
Owner FUDAN UNIV
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