Method for preparing cross-linking agent modified hyaluronic acid-polyaspartic acid in-situ cross-linking type hydrogel

A technology of polyaspartic acid and hyaluronic acid, which is applied in the field of hydrogel series, can solve the problems of poor mechanical strength of hydrogel and limit the application of hydrogel, and achieve mild reaction process, simple preparation process, biophase good capacitive effect

Inactive Publication Date: 2014-02-05
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage is that the fast crosslinking time leads to poor mechanical strength of the hydrogel, which limits the application of the hydrogel.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Weigh 0.015 g of ethylenediamine and dissolve it in 50 mL of disodium hydrogen phosphate-sodium dihydrogen phosphate buffer solution (pH=5.0, concentration 0.2 mol / L) to obtain a buffer solution of ethylenediamine.

[0039] Weigh 0.01g of formylated hyaluronic acid and 0.01g of polyaspartic acid hydrazide and dissolve them in 1mL of the above buffer solution of ethylenediamine. After they are completely dissolved, mix 1mL of formylated hyaluronic acid solution and 0.5mL of polyaspartic acid The aspartazide solution was then placed in a water bath at 10°C at a constant temperature, and the hydrogel was obtained at rest. The gelation time was 25min20.43s, and the elastic modulus was 4009Pa.

Embodiment 2

[0041] Weigh 0.02g of aldylated hyaluronic acid and 0.02g of polyaspartazide and dissolve them in 1mL of citric acid-sodium hydroxide-hydrochloric acid buffer solution (pH=6.0, concentration 0.1mol / L), and wait until they are completely dissolved Finally, mix 1mL of aldylated hyaluronic acid solution and 1mL of polyaspartazide solution, then add 0.006g of ethylenediamine to it, and finally place it in a water bath at 20°C to keep the temperature, and stand still to make a hydrogel. The gelation time is It is 13min58.09s, and the modulus of elasticity is 5991Pa.

Embodiment 3

[0043] Weigh 0.012 g of pentamethylenediamine and dissolve it in 50 mL of Tris-hydrochloric acid buffer solution (pH=7.4, concentration 0.05 mol / L) to obtain a buffer solution of pentamethylenediamine.

[0044] Weigh 0.05 g of aldylated hyaluronic acid and dissolve it in 1 mL of Tris-hydrochloric acid buffer (pH=7.4, concentration 0.05 mol / L) to obtain a buffer solution of aldylated hyaluronic acid.

[0045] Weigh 0.045g of polyaspartazide and dissolve it in 0.9mL of the above-mentioned buffer solution of pentamethylenediamine, place it in a water bath at 30°C, react for 48 hours, mix it with 0.3mL of the buffer solution of aldylated hyaluronic acid, and place Keep the temperature in a water bath at 30°C, and statically prepare the hydrogel, the gelation time is 25min37s, and the elastic modulus is 3432Pa.

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Abstract

The invention discloses a method for preparing cross-linking agent modified hyaluronic acid-polyaspartic acid in-situ cross-linking type hydrogel. According to the method, a modified cross-linking agent which is a substance with dialdehyde radical or diamine radical is added into a buffer solution successively or simultaneously to gelatinize polyaspartic acid derivative with dialdehyde radical and hyaluronic acid derivative with diamine radical through a condensation reaction. The hydrogel has the advantages of controllable mechanical strength, short gelatinization time, stable performance, good biocompatibility and biodegradation, and can be used in the fields of tissue engineering, embolism materials and medicine controlled-release by virtue of an injection means.

Description

technical field [0001] The invention belongs to the hydrogel series, and relates to hyaluronic acid and polyaspartic acid in-situ cross-linked gel modified by a cross-linking agent. Background technique [0002] Hydrogel is a material formed of high molecular polymers, with a water content of more than 90% and a three-dimensional network structure. This material is soft in texture and has good biocompatibility, and is currently widely used in the field of biomedicine. [0003] Injectable in situ crosslinked hydrogels have also received increasing attention in recent years. The injectable in situ cross-linked hydrogel is characterized in that it is in a flowable liquid state before injection, and when injected into the target site, it can form a colloid that completely matches the shape of the target site. This injectable feature not only makes the operation process simple and convenient, but also avoids the pain caused by the implantation operation and greatly reduces the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08J3/075C08L5/08C08L79/08C08K5/17C08K3/28C08K5/07C08K5/1545A61L27/52A61L27/26A61L31/14A61L31/06A61L31/04A61K47/36A61K47/34
Inventor 谭天伟刘敏曹辉张睿孙天玉
Owner BEIJING UNIV OF CHEM TECH
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