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Method for preparing crosslinking hyaluronic acid gel

A technology of cross-linked hyaluronic acid and hyaluronic acid, which is applied in the field of pharmacy, can solve the problems of reduced viscoelasticity of cross-linked hyaluronic acid gel, unsatisfactory maintenance time, and unsatisfactory filling effect, etc., so as to broaden the use and application effect, high molecular weight, long retention time effect

Active Publication Date: 2013-04-10
XIAN LIBANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Commonly used cross-linking agents are glutaraldehyde (GTA), diepoxide (DEC), divinyl sulfone (DVS), and 1,4-butanediol glycidyl ether (BDDE). These cross-linking agents form When cross-linked sodium hyaluronate gel is applied to organisms, the residual cross-linking agent is likely to cause inflammatory reactions in the body, and the amount of cross-linking agent used is reduced by conventional methods, and the viscoelasticity of the cross-linked hyaluronic acid gel obtained is reduced. Not soft, the filling effect is not ideal when used as a tissue filler or the maintenance time is not ideal when used as a drug sustained-release preparation

Method used

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  • Method for preparing crosslinking hyaluronic acid gel
  • Method for preparing crosslinking hyaluronic acid gel

Examples

Experimental program
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Effect test

Embodiment 1

[0036] Add 0.22g of diethylene glycol to 4ml of 0.02M NaOH aqueous solution, heat to reflux for 0.5h to make a diethylene glycol alkali solution, and cool to room temperature;

[0037] Add 0.05g of divinyl sulfone into the polyethylene glycol alkali solution, then raise the temperature of the solution to 35°C to initiate the reaction, cool with an ice bath to keep the temperature at about 60°C, stop the heat release, and then heat to 80°C for 5 minutes , cooled to room temperature, to obtain a viscous product, add 10ml of water to dissolve;

[0038] Add 1g of sodium hyaluronate dry powder with a molecular weight of 1 million to 25ml of 0.2M NaOH aqueous solution, stir to dissolve, add to the above product, stir at room temperature for 2 to 3 hours to form a cross-linked sodium hyaluronate gel;

[0039] Then add 160ml of PBS buffer solution (pH7.0) to swell for 24 or 48 hours, remove the buffer, rinse with normal saline and soak until the gel is transparent and homogeneous;

...

Embodiment 2

[0042] Add 1.64g polyethylene glycol 400 to 4ml 0.02M NaOH aqueous solution, heat to reflux for 0.5h to make polyethylene glycol alkali solution, and cool to room temperature;

[0043] Add 0.05g of divinyl sulfone into the polyethylene glycol alkali solution, then raise the temperature of the solution to 35°C to initiate the reaction, cool with an ice bath to keep the temperature at about 60°C, stop the heat release, and then heat to 80°C for 5 minutes , cooled to room temperature, to obtain a viscous product, add 20ml of water to dissolve;

[0044] Add 1g of sodium hyaluronate dry powder with a molecular weight of 1 million to 25ml of 0.2M NaOH aqueous solution, stir to dissolve, add to the above product, stir at room temperature for 2 to 3 hours to form a cross-linked sodium hyaluronate gel;

[0045] Then add 160ml of PBS buffer solution (pH7.0) to swell for 24 or 48 hours, remove the buffer, rinse with normal saline and soak until the gel is transparent and homogeneous;

...

Embodiment 3

[0048] Add 2.52g polyethylene glycol 600 into 4ml 0.02M NaOH aqueous solution, heat to reflux for 0.5h to make polyethylene glycol alkali solution, and cool to room temperature;

[0049] Add 0.05g of divinyl sulfone into the polyethylene glycol alkali solution, then raise the temperature of the solution to 35°C to initiate the reaction, cool with an ice bath to keep the temperature at about 60°C, stop the heat release, and then heat to 80°C for 5 minutes , cooled to room temperature, to obtain a viscous product, add 25ml of water to dissolve;

[0050] Add 1g of sodium hyaluronate dry powder with a molecular weight of 300,000 to 25ml of 0.2M NaOH aqueous solution, stir to dissolve, add to the above product, stir at room temperature for 2 to 3 hours to form a cross-linked sodium hyaluronate gel;

[0051] Then add 160ml of PBS buffer solution (pH7.0) to swell for 24 or 48 hours, remove the buffer, rinse with normal saline and soak until the gel is transparent and homogeneous;

...

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Abstract

The invention provides a crosslinking hyaluronic acid gel and its preparation method. The method is characterized in that divinylsulfone is combined with polyethylene glycol for generating a novel cross-linking agent at first, the novel cross-linking agent is reacted with a hyaluronic acid molecule for producing a crosslinking hyaluronic acid gel. The crosslinking sodium hyaluronate gel obtained in the invention has good biological compatibility and longer half life period, and the particle is small and uniform, and is suitable for beautifying shaping, tissue filling, bone articular lubrication or medicine sustained-release preparation and the like.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a cross-linked hyaluronic acid gel and a preparation method thereof. Background technique [0002] Hyaluronic acid (HA for short) is derived from animal tissue or microbial fermentation, and is widely used in the fields of food, daily chemicals and medicine. The random curling state of HA in solution and its hydrodynamic characteristics endow HA with high viscoelasticity, plasticity, permeability, unique rheological properties and good biocompatibility. It is a bioabsorbable material due to its It is a component of human and animal bodies. It is not only safe and reliable as a medical raw material, but also has no side effects. Therefore, it is a new type of biomedical material that is very popular in today's medical field and has high medical value. However, due to its rapid diffusion and degradation in the body, it is difficult to maintain the desired effect, which largely limits its app...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/075C08J3/24C08L5/08C08L71/08C08G65/48C08K5/41A61L27/52A61L27/20
Inventor 傅经国王艳果庞世毅李涛陈涛
Owner XIAN LIBANG PHARMA
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