Thermo-sensitive and degradable micro hydrogel as well as preparation method and application thereof

Abstract

The invention discloses a thermo-sensitive and degradable micro hydrogel as well as a preparation method and application thereof. The structure of the micro hydrogel is shown as a formula M3 in the specification. In the formula M3, m represents the repetitive unit number of L-lactic acid, n represents the repetitive unit number of glycol, m=9-21, and n=23-69. The preparation method comprises the following step of conducting radical copolymerization reaction and interlinking reaction on N-alkyl acrylamide, a degradable double-bond blocked cross-linking agent of a poly(L-lactic acid)-polyethylene glycol-poly(L-lactic acid) triblock copolymer and an initiator. The preparation method is simple and easy to control. The obtained micro hydrogel has dual performances of thermo-sensitivity and degradability, high purity and excellent stability. The micro hydrogel can be used in the fields of biological medication and medicine controlled slow release.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, and in particular relates to a temperature-sensitive degradable micro-hydrogel and its preparation and application. Background technique [0002] Microgel is a cross-linked latex particle with colloidal size (1nm-μm) swollen in a good solvent, and its molecular structure is between branched macromolecules and polymer macroscopic network structures. According to different solvents, polymer gels are further divided into hydrogels and organic gels. Among them, micro-hydrogels can be uniformly dispersed in an aqueous solution system, have good swelling properties and responsiveness to external stimuli, so micro-hydrogels have great application prospects in controlled drug release and biosensors. [0003] At present, research on polymer hydrogels, especially stimuli-responsive hydrogels, is quite popular. Typical external stimuli include temperature, pH value, solvent, salt concentration,...

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Problems solved by technology

[0004] So far, there have been many reports on biodegradable polymers and smart hydrogels at home and abroad, but there are still relatively few reports on microgels with both biodegradable and smart responses.

Most of the reported biodegradable hydrogels do not have the performance of intelligent response, and only exist in the form of block bulk hydrogels, it is difficult to have the size controllability of colloidal particles such as microgels and the ability to operate in aqueous media. The characteristics of fluidity, the scope of application is limited; on the other hand, by designing the composition and structure of micro-hydrogels to make them have degradable cross-linking points, researchers at home and abroad are being widely focused

[0005] The Chinese patent No. ZL200410013315.6 discloses a biodegradable temperature-sensitive hydrogel and its preparation method. This macroporous konjac glucomannan hydrogel introduces N-isopropylacrylamide units, and at the same time It has good thermosensitivity and biodegradability, and can adsorb and embed drugs for controlled drug release. However, the hydrogel is a bulk gel and does not have the tiny size of micro-hydrogel colloidal particles. Fluidity in the medium, it is difficult to effectively deliver to the lesion in the body like a micro-hydrogel

[0006] The Chinese patent No. ZL 200610039297.8 discloses a kind of N-isopropylacrylamide and acrylic acid as main monomers, in the presence of a chemical crosslinking agent, triggering polymerization to prepare pH and temperature dual sensitive nano hydrogel method, the particle size of the nano-hydrogel is 30-200nm, but the preparation method also needs to use a surfactant, causing the dialysis purification time of the nano-hydrogel to be as long as 2 weeks, and this kind of micro-hydrogel can be used in medical In the field of medicine, but because it does not have biodegradability, long-term residue in the living body will cause harm to the living body

[0007] The Chinese patent application with the application number 03115319.4 and the Chinese patent with the patent number ZL 200410017390.X disclose a temperature-sensitive degradable microgel and its preparation method. The microgel is completely composed of synthetic polymers and has reverse temperature sensitivity and degradability, and its main degradable components are also polylactide segments, but it needs to use one or more non-ionic surfactants in the preparation process of microgel, that is, emulsifying agent, which is not conducive to the purification of microgels and affects its application in the field of biomedicine

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