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Preparation method of high-quality cross-linked sodium hyaluronate gel

A technology for cross-linking hyaluronic acid and sodium hyaluronate, applied in the field of sodium hyaluronate gel, can solve the problems of non-softness and reduced gel viscoelasticity, achieve good gel softness, improve anti-degradation, The effect of prolonging the retention time

Inactive Publication Date: 2018-04-24
桂林华诺威生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the conventional crosslinking method, if the amount of crosslinking agent added is reduced, the viscoelasticity of the resulting gel decreases and is not soft.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 1) Dissolve sodium hyaluronate dry powder in sodium hydroxide solution with a mass concentration of 10%, add 1,4-butanediol diepoxy ether with a weight of 0.01% of sodium hyaluronate dry powder, and incubate at 35°C for 5h , get gel X;

[0019] 2) Press the gel X at 500MPa for 1min;

[0020] 3) Adjust the pH value of the compressed gel X to neutral, add phosphate buffer, and swell at 40°C for 18 hours;

[0021] 4) Cool down the swollen gel X to -4°C and keep it warm for 1 hour to obtain a sodium hyaluronate gel.

[0022] 1. Enzyme resistance test method: Accurately weigh the above gel, add 5ml of 0.1mogl / L phosphate buffer (pH7.0) and 5ml of hyaluronidase solution (100U / ml), mix well, and place at 37 ℃ water bath for 24 hours, and then boiled at 100 ℃ for 10 minutes to inactivate. Filter through a 0.45μm microporous membrane, take 1.0ml of the filtrate, add water to make up to 10ml. The content of uronic acid was measured by the improved carbazole chromogenic method...

Embodiment 2

[0035] 1) Dissolve sodium hyaluronate dry powder in sodium hydroxide solution with a mass concentration of 20%, add 1,4-butanediol diepoxy ether with a weight of 0.05% of sodium hyaluronate dry powder, and incubate at 50°C for 8 hours , get gel X;

[0036] 2) Press Gel X at 1000MPa for 3min;

[0037] 3) Adjust the pH value of the compressed gel X to neutral, add phosphate buffer, and swell at 50°C for 36 hours;

[0038] 4) Cool down the swollen gel X to -4°C and keep it warm for 3 hours to obtain a sodium hyaluronate gel.

[0039] Detected according to the method of Example 1, the enzymatic degradation rate of sodium hyaluronate gel was 3.6%, and the kinetic viscosity was 55.0×10 4 mPa·s, the intrinsic viscosity is 4467.8cm 3 / g.

Embodiment 3

[0041] 1) Dissolve sodium hyaluronate dry powder in sodium hydroxide solution with a mass concentration of 15%, add 1,4-butanediol diepoxy ether with a weight of 0.02% of sodium hyaluronate dry powder, and keep warm at 45°C for 6h , get gel X;

[0042] 2) Press Gel X at 800MPa for 2min;

[0043] 3) Adjust the pH value of the compressed gel X to neutral, add phosphate buffer, and swell at 45°C for 24 hours;

[0044] 4) Cool down the swollen gel X to -4°C and keep it warm for 2 hours to obtain a sodium hyaluronate gel.

[0045] Detected according to the method of Example 1, the enzymatic degradation rate of sodium hyaluronate gel was 3.0%, and the kinetic viscosity was 57.4×10 4 mPa·s, the intrinsic viscosity is 4618.4cm 3 / g.

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Abstract

The invention discloses a preparation method of high-quality cross-linked sodium hyaluronate gel. The preparation method comprises the following steps: 1) dissolving sodium hyaluronate dry powder intoa sodium hydroxide solution; adding 1,4-butanediol diepoxy ether which accounts for 0.01 to 0.05 percent of the weight of the sodium hyaluronate dry powder; preserving heat at 35 to 50 DEG C for 5 to8h to obtain gel X; 2) pressing the gel X for 1 to 3min under the pressure of 500 to 1000MPa; 3) regulating the pH (Potential of Hydrogen) value of the pressed gel X to be neutral; adding a phosphatebuffering solution and swelling for 18 to 36h; 4) cooling the swollen gel X to -4 DEG C and carrying out heat-preservation treatment for 1 to 3h to obtain the sodium hyaluronate gel. The cross-linkedsodium hyaluronate gel has a relatively stable net-shaped structure, and can be used for effectively improving the degradation resistance of hyaluronic acid and prolonging the retention time of the hyaluronic acid in a body.

Description

technical field [0001] The invention relates to the technical field of sodium hyaluronate gel, in particular to a preparation method of high-quality cross-linked sodium hyaluronate gel. Background technique [0002] Hyaluronic acid is a linear mucopolysaccharide composed of repeating two-tang structural units β-D-glucuronic acid and N-acetylglucosamine linked to each other. Hyaluronic acid is the main component of connective tissues such as human interstitial cells, eye vitreous body, and joint synovial fluid. It plays important physiological functions in the body such as water retention, maintenance of extracellular space, regulation of osmotic pressure, lubrication, and promotion of cell repair. Because hyaluronic acid has the characteristics of viscoelastic separation, viscoelastic protection and viscoelastic filling, it has been widely used in clinical medicine such as general surgery and obstetrics and gynecology to prevent postoperative adhesions, as well as medical fi...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08J3/075C08J3/00C08L5/08
CPCC08J3/00C08J3/075C08J3/24C08J2305/08
Inventor 韦忠明黄启斌
Owner 桂林华诺威生物科技有限公司
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