Hyaluronic acid crosslinked gel as well as preparation method and application thereof

A technology of hyaluronic acid and cross-linked gel, applied in medical science, prosthesis, tissue regeneration, etc., can solve the problems of unfavorable industrialization, difficult quantification of cross-linking degree, no obvious advantages, etc. The effect of gel properties

Inactive Publication Date: 2017-01-04
BEIJING DATSING BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the secondary cross-linking is achieved through the network interpenetration of hyaluronic acid, and the degree of cross-linking is difficult to quantify, so it is not conducive to large-scale indus

Method used

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  • Hyaluronic acid crosslinked gel as well as preparation method and application thereof
  • Hyaluronic acid crosslinked gel as well as preparation method and application thereof
  • Hyaluronic acid crosslinked gel as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0046] Example 1

[0047] Follow the steps below to prepare sodium hyaluronate cross-linked gel:

[0048] (1) Dissolve sodium hyaluronate with a molecular weight of 1 million daltons in purified water to prepare a solution with a concentration of 1.5%, stir to fully dissolve the sodium hyaluronate; slowly drip into the sodium hyaluronate solution Add 2-chloro-1-methylpyridinium iodide (CMPI) so that the molar ratio of CMPI to sodium hyaluronate is 1:50, stir and mix thoroughly, and let stand at room temperature for 12 hours; use a dialysis bag to perform Dialysis, change the purified water for dialysis regularly, remove CMPI, and freeze-dry to obtain self-crosslinking product;

[0049] (2) Dissolving the self-crosslinking product in 0.5% NaOH to prepare a 4% solution. After heating to 40°C, the crosslinking agent 1,4-butanediol diglycidyl ether (BDDE) was slowly added dropwise so that the molar ratio of BDDE to the initial sodium hyaluronate was 1:100. After fully stirring, let it...

Example Embodiment

[0050] Example 2

[0051] Follow the steps below to prepare sodium hyaluronate cross-linked gel:

[0052] (1) Dissolve sodium hyaluronate with a molecular weight of 1 million daltons in purified water to prepare a solution with a concentration of 2%, stir to fully dissolve the sodium hyaluronate; slowly drip into the sodium hyaluronate solution Add 2-chloro-1-methylpyridinium iodide (CMPI) to make the molar ratio of CMPI to sodium hyaluronate 1:100, stir and mix thoroughly, and let stand at room temperature for 12 hours; use a dialysis bag to perform the mixed solution Dialysis, change the purified water for dialysis regularly, remove CMPI, and freeze-dry to obtain self-crosslinking products;

[0053] (2) Dissolving the self-crosslinked product in 0.5% HCl and preparing a 4% solution. Slowly add carbodiimide (EDC) dropwise so that the molar ratio of EDC to the initial sodium hyaluronate is 1:80, stir well and let stand for 12 hours; use ethanol for precipitation, put the precipitat...

Example Embodiment

[0054] Example 3

[0055] Follow the steps below to prepare sodium hyaluronate cross-linked gel:

[0056] (1) Dissolve sodium hyaluronate with a molecular weight of 1 million daltons in 0.5% NaOH to prepare a solution with a concentration of 4%, stir to fully dissolve the sodium hyaluronate; Slowly add 1,4-butanediol diglycidyl ether (BDDE) to the sodium phosphate solution so that the molar ratio of BDDE to sodium hyaluronate is 1:100, stir thoroughly and mix well, and stir at 50°C for 5 hours; ethanol Precipitation to remove unreacted crosslinking agent, and drying to obtain a crosslinked product;

[0057] (2) Dissolve the cross-linked product in purified water to form a 1% solution, slowly drop 2-chloro-1-methylpyridinium iodide (CMPI) into the solution to make CMPI and sodium hyaluronate The molar ratio is 1:50. After stirring and mixing thoroughly, let it stand at room temperature for 12 hours; use a dialysis bag to dialyze the mixed solution, periodically replace the purified ...

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Abstract

The invention relates to a preparation method of hyaluronic acid crosslinked gel. The method comprises steps as follows: hyaluronic acid or a salt solution thereof is taken as a raw material, a self-crosslinking reaction and an intermolecular crosslinking reaction with a crosslinking agent are performed under the action of a self-crosslinking catalyst, and the sequence of the self-crosslinking reaction and the intermolecular crosslinking reaction is not limited. According to the method, a conventional hyaluronic acid crosslinking technology is combined with a self-crosslinking process, the consumption of the conventional crosslinking agent is effectively reduced, the hyaluronic acid shows excellent gel performance under the use condition that the conventional crosslinking agent is reduced, the hyaluronic acid gel prepared with the method can meet physical and chemical properties and biocompatibility required by tissue filling.

Description

technical field [0001] The invention relates to the field of high molecular polymers, in particular to a hyaluronic acid cross-linked gel and its preparation method and application. Background technique [0002] Hyaluronic acid is a heteropolysaccharide composed of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine. Under normal physiological conditions in the body, the carboxyl group on the uronic acid molecule of hyaluronic acid combines with sodium ions in the body to form sodium hyaluronate. The unique molecular structure and physical and chemical properties enable sodium hyaluronate to display a variety of important physiological functions in the body, such as promoting fibroblast proliferation, cardiovascular formation, lubricating joints, and promoting wound healing. [0003] Unmodified sodium hyaluronate is easily degraded by hyaluronidase in the body, and the degradation and absorption speed is relatively fast, which affects its clinical applicati...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08L5/08A61L27/20A61L27/52
CPCC08J3/24A61L27/20A61L27/52A61L2430/34C08J3/075C08J2305/08C08K5/06C08K5/29C08L2312/00C08L5/08
Inventor 袁源张玉兰张婷婷李湘杰李次会
Owner BEIJING DATSING BIO TECH
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