Preparation method and application of controllable multi-level cross-linked injectable thermally induced phase change hydrogel

A technology of thermally induced phase change and hydrogel, which is applied in the direction of medical preparations, pharmaceutical formulas, and prostheses of non-active ingredients, which can solve the problems of poor mechanical properties of hydrogels and hinder applications, and achieve the goal of overcoming micro-gap and Poor fluidity, thermally sensitive response, and strong controllability

Active Publication Date: 2022-04-19
UNIV OF SCI & TECH BEIJING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

If β-glycerophosphate is used as a physical cross-linking agent, chitosan can be endowed with temperature-responsive properties, allowing it to undergo a sol-gel transition near human body temperature, such as the patent published by Sun Guangwei et al. However, the chitosan hydrogel prepared by this method has a disadvantage, that is, the mechanical properties of the hydrogel are extremely poor, which hinders its application in tissue engineering.

Method used

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  • Preparation method and application of controllable multi-level cross-linked injectable thermally induced phase change hydrogel
  • Preparation method and application of controllable multi-level cross-linked injectable thermally induced phase change hydrogel

Examples

Experimental program
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Effect test

example 1

[0038] Step 1: Dispersion of chitosan and its derivatives and preconditioning of reaction environment

[0039] Weigh the chitosan matrix phase and dissolve it in the buffer solution at a solute ratio of 50:1. Sonicate for 10 minutes, heat and stir for 1 hour to fully disperse in the solution.

[0040] Step 2: Nucleophilic Substitution of Matrix Phase

[0041] Add 10% amine salts to the uniformly dispersed composite hot solution as a reaction aid. Sonicate for 10 minutes, heat and stir to make it fully dissolved, keep stirring after 1 hour and slowly add 20% polyamine compound, speed up the speed, after the compound is fully dissolved, add acetic acid solution drop by drop, and use a pH meter to detect until The pH of the solution is adjusted to be weakly acidic, heated and stirred for 6 hours, and the multi-activation group amino group is grafted to the branch chain on the sixth or third carbon of the chitosan molecule through a nucleophilic substitution process.

[0042] S...

example 2

[0053] Example 2: Step 1: Preconditioning of the reaction environment and nucleophilic substitution of the matrix phase

[0054] Step 1: Dispersion of chitosan and its derivatives and preconditioning of reaction environment

[0055] Weigh the chitosan matrix phase and dissolve it in the buffer solution at a solute ratio of 50:1. Sonicate for 20 minutes, heat and stir for 2 hours to fully disperse in the solution.

[0056] Step 2: Nucleophilic Substitution of Matrix Phase

[0057] Add 2% amine salts to the uniformly dispersed composite hot solution as a reaction aid. Sonicate for 30 minutes, heat and stir to make it fully dissolved, keep stirring after 2 hours and slowly add 50% polyol compound, etc., speed up the speed, after the compound is fully dissolved, add acetic acid solution drop by drop, and use an acidity meter to detect, Until the pH of the solution is adjusted to be weakly acidic, heat and stir for 3 hours, and through a nucleophilic substitution process, multip...

example 3

[0070] Step 1: Dispersion of chitosan and its derivatives and preconditioning of reaction environment

[0071] A pH buffer solution of a certain concentration is prepared, and the chitosan matrix phase with a solute ratio of 50:1 is weighed and dissolved in the buffer solution. Sonicate for 20 minutes, heat and stir for 2 hours to fully disperse in the solution.

[0072] Step 2: Nucleophilic Substitution of Matrix Phase

[0073] Add 5% amine salts to the uniformly dispersed composite hot solution as a reaction aid. Sonicate for 30 minutes, heat and stir to make it fully dissolved, keep stirring after 2 hours and slowly add 20% polyamine compound, etc., speed up the speed, after the compound is fully dissolved, add acetic acid solution drop by drop, and use an acidity meter to detect, Until the pH of the solution is adjusted to be weakly acidic, heat and stir for 3 hours, and multiple activated groups such as amino groups are grafted to the branched chain on the sixth or thir...

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Abstract

A preparation method and application of a controllable multi-stage cross-linked injectable thermally induced phase change hydrogel. Activated grafting of chitosan with multifunctional groups through nucleophilic substitution reaction, purification, refinement and functionalization of nano whiskers, chitosan matrix and functionalized nano whiskers form a first-level cross-linked network, which promotes thermal induction. The activation and formation of the agent-guided secondary cross-linking network jointly promote the final completion of the nanowhisker-reinforced controllable multi-level cross-linking injectable thermally induced phase change hydrogel. By changing the reaction parameters in the system, various properties such as the degradation of the composite gel can be regulated. The preparation process of the present invention is simple and feasible, and the process is green and environmentally friendly. The prepared thermally induced phase change hydrogel is an injectable implant with excellent biocompatibility, mechanical properties, injectability, in vivo degradability, and antibacterial properties. Repair materials can be used for pulp reconstruction, cartilage repair, heart repair and anticoagulant materials, drug release carriers, immobilized enzyme carriers, artificial skin, bone filling materials, soft tissue filling, anti-adhesion materials, etc.

Description

technical field [0001] The invention relates to a preparation method and application of a controllable multi-level cross-linked injectable thermally induced phase change hydrogel reinforced by nano whiskers, in particular to activated grafting of chitosan, and the use of thermally induced agents and functionalized biological Preparation of controllable multilevel crosslinked injectable thermally induced phase change hydrogels by active nanowhiskers. [0002] technical background [0003] Chitosan is a natural polysaccharide chitin deacetylated product, many sources, and cheap and easy to obtain. Moreover, due to the strong reactivity of the amino group in the molecular structure of chitosan, it has excellent biological functions and can perform chemical modification reactions, such as the Schiff base reaction; chitosan itself also has antibacterial, hemostatic, and wound healing properties. specialty. It has the characteristics of good biocompatibility and biodegradability ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/20A61L27/14A61L27/24A61L27/50A61L27/52A61L27/54A61L27/58A61L27/60A61L31/04A61L31/14A61L31/16A61K9/06A61K47/36A61K47/38A61K47/42C08J3/075C08L5/08C08L1/02
CPCA61L27/20A61L27/14A61L27/24A61L27/50A61L27/52A61L27/58A61L27/54A61L27/60A61L31/042A61L31/044A61L31/04A61L31/14A61L31/145A61L31/148A61L31/16A61K9/06A61K9/0024A61K47/36A61K47/38A61K47/42C08J3/075C08J2305/08C08J2401/02A61L2300/232A61L2300/404A61L2300/604A61L2430/02A61L2430/06A61L2430/12A61L2430/20A61L2430/34C08L5/08
Inventor 郑裕东杨惠仪谢亚杰刘旭东乔堃
Owner UNIV OF SCI & TECH BEIJING
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