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Preparation method of injectable in-situ self-assembled sodium hyaluronate hydrogel

A technology of sodium hyaluronate and hyaluronic acid, which is applied in skin care preparations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., and can solve complex purification processes, inability to remove, toxic and side effects, etc. question

Inactive Publication Date: 2016-08-31
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of these hydrogel biomedical materials are prepared by chemical crosslinking first, followed by purification to remove residual crosslinking agents and by-products. This type of process is difficult to ensure complete removal of residual crosslinking agents, or some functional groups The residual cross-linking agent that undergoes cross-linking reaction is covalently fixed in the hydrogel and cannot be removed
This will lead to toxic side effects such as inflammation in clinical use
Its limitation is that complex purification processes are required for product preparation, and at the same time, it increases the risk of clinical use

Method used

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  • Preparation method of injectable in-situ self-assembled sodium hyaluronate hydrogel
  • Preparation method of injectable in-situ self-assembled sodium hyaluronate hydrogel
  • Preparation method of injectable in-situ self-assembled sodium hyaluronate hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Dissolve 0.5 g of cystamine dihydrochloride in 15 mL of water, adjust the pH to 4, weigh 1 g of sodium hyaluronate dry powder (molecular weight 1,300,000 DA), stir well, weigh 1 g of DMTMM, dissolve it completely in 5 mL of water and Adjust the pH value to 4, then add it into the mixture, and react at 4°C for 2 days after complete stirring. After the reacted gel was cut into pieces, it was dialyzed with PBS buffer, and the dialysate was changed every 1 h and weighed until the gel mass no longer increased, and the dialysis was terminated. After the gel was pulverized and granulated, the pH value of the gel was adjusted to 8 with 1 M NaOH aqueous solution, after mixing evenly, 2 g of dithiothreitol was added, and the reaction was carried out overnight at room temperature, and the pH of the obtained reaction solution was adjusted with hydrochloric acid solution After reaching about 3, transfer the solution to a dialysis bag (molecular weight cut-off 10,000), dialyze with 1...

Embodiment 2

[0024] Dissolve 0.25 g of cystamine dihydrochloride in 15 mL of water, adjust the pH to 6, weigh 1 g of sodium hyaluronate dry powder (molecular weight 310,000 DA), stir well, weigh 0.5 g of DMTMM, dissolve it completely in 5 mL of water, and adjust the pH The value was adjusted to 6, and then added to the mixture, and after being completely stirred evenly, it was reacted at room temperature for 1 day. After the reacted gel was cut into pieces, it was dialyzed with PBS buffer, and the dialysate was changed every 1 h and weighed until the gel mass no longer increased, and the dialysis was terminated. After the gel was pulverized and granulated, the pH value of the gel was adjusted to 8 with 1M NaOH aqueous solution, and after mixing evenly, 1.5 g of dithiothreitol was added and reacted overnight at room temperature, and the resulting reaction solution was adjusted to a pH of After 3 or so, transfer the solution to a dialysis bag (molecular weight cut-off 10,000), dialyze with 1...

Embodiment 3

[0028] Dissolve 1 g of cystamine dihydrochloride in 15 mL of water, adjust the pH to 7, weigh 1.2 g of sodium hyaluronate dry powder (molecular weight 710,000 DA), stir well, weigh 1 g of DMTMM, dissolve it completely in 5 mL of water and Adjust the pH value to 7, then add it into the mixture, and react at 4°C for 3 days after complete stirring. After the reacted gel was cut into pieces, it was dialyzed with PBS buffer, and the dialysate was changed every 1 hour and weighed until the gel mass no longer increased, and the dialysis was terminated. After the gel was pulverized and granulated, the pH value of the gel was adjusted to 8 with 1 M NaOH aqueous solution, after mixing evenly, 2.5 g of dithiothreitol was added, and the reaction was carried out overnight at room temperature, and the pH of the obtained reaction solution was adjusted with hydrochloric acid solution After about 3, the solution was transferred to a dialysis bag (molecular weight cut-off 10000), dialyzed with ...

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Abstract

The invention relates to a preparation method of injectable in-situ self-assembled sodium hyaluronate hydrogel. The preparation method comprises that sodium hyaluronate reacts with cystamine to produce a hyaluronic acid derivative under activation action of a coupling reagent 4-(4, 6-dimethoxy-1, 3, 5-triazin-2-yl)-4-methyl morpholinium chloride (DMTMM), the hyaluronic acid derivative is reduced through dithiothreitol (DTT) to produce a hyaluronic acid mercapto derivative, simultaneously, sodium hyaluronate reacts with dopamine under activation action of the coupling reagent DMTMM to produce a catechol functionalized hyaluronic acid derivative and the hyaluronic acid mercapto derivative and the catechol functionalized hyaluronic acid derivative are mixed to form hydrogel without other cross-linking agents.

Description

technical field [0001] The invention relates to the technical field of medical biomaterials, in particular to a method for preparing a self-assembled, injectable, and clickable in-situ cross-linked sodium hyaluronate hydrogel. It has potential application value in injection, joint lubricating fluid, injection beauty and so on. Background technique [0002] Polymer gel is a common type of hydrogel, which contains a lot of water but is insoluble in water. Its three-dimensional cross-linked network is composed of hydrophilic and hydrophobic groups or dissociation groups on the main polymer chain and side chains, and the solvent is fixed in the molecular network. The cross-linked network points of the polymer gel can be chemically cross-linked by covalent bonds, or physically cross-linked, such as electrostatic interaction, hydrogen bond interaction, hydrophobic interaction, etc. [0003] Hydrogels, especially polymer hydrogels prepared from intercellular matrix materials, hav...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08L5/08C08B37/08A61K8/73A61K9/06A61K47/36A61L27/20A61L27/52A61Q19/08A61P39/06
CPCC08J3/246A61K8/735A61K9/06A61K47/36A61K2800/91A61L27/20A61L27/52A61L2400/06A61L2400/10A61Q19/08C08B37/0072C08J3/075C08J2305/08C08J2405/08C08L5/08C08L2203/02C08L2205/025C08L2312/00
Inventor 魏长征吴祎宋瑞瑞蒋丽霞
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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