Cross-linked hyaluronic acid gel and preparation method thereof

A technology of cross-linked hyaluronic acid and hyaluronic acid, which is applied in the field of cross-linked hyaluronic acid gel and its preparation, and can solve the problem of cross-linked hyaluronic acid gel with reduced viscoelasticity, non-softness, and easy to cause inflammatory reactions in the body, etc. problems, to achieve good tissue compatibility and biodegradability, good filling effect, and easy injection

Inactive Publication Date: 2009-09-23
SHANGHAI HAOHAI BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, when administered to a living body, the residual cross-linking agent is likely to cause an inflammatory reaction in the body. If the amount of cross-linking agent used is reduced by conventional methods, the viscoelasticity of the obtained cross-linked hyaluronic acid gel will be reduced, and it will not be soft. Unsatisfactory effect or unsatisfactory maintenance time when used as a drug sustained-release preparation

Method used

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  • Cross-linked hyaluronic acid gel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Put 3.3g of hyaluronic acid fine powder with a molecular weight of 2 million Daltons in a container filled with 30ml of 0.25M NaOH solution, and stir and mix for 3 hours;

[0031] During stirring, add 0.3ml of 1,4-butanediol diglycidyl ether (BDDE), and then place the solution in a water bath at 45°C for 5 hours to form a cross-linked hyaluronic acid gel;

[0032] Subsequently, 500 mL of PBS buffer solution with a pH of 7.3 was added, soaked and washed repeatedly for 6 times, and washed for 2.5 days.

[0033] Then put the hyaluronic acid gel in the pressure extrusion device, set the hole diameter to 500 μm, pressurize 7kg / cm 2 , Extrude the hyaluronic acid gel into a microgel.

[0034] Then stir and mix the particulate hyaluronic acid gel and hyaluronic acid to obtain a product, wherein the final concentration of hyaluronic acid is 2 mg / ml. Filling and autoclaving (121° C., 30 minutes).

Embodiment 2

[0036] Put 4g of hyaluronic acid fine powder with a molecular weight of 2 million Daltons in a container containing 30ml of 0.25M NaOH solution, and stir and mix for 4 hours;

[0037] During stirring, add 0.4ml 1,4-butanediol diglycidyl ether (BDDE), and then place the solution in a water bath at 50°C for 5 hours to form a cross-linked hyaluronic acid gel;

[0038] Then add 500mL deionized water to soak and wash repeatedly 8 times, and wash for 3 days.

[0039] Then put the hyaluronic acid gel in the pressure extrusion device, set the hole diameter to 550 μm, pressurize 8kg / cm 2 , Extrude the hyaluronic acid gel into a microgel. Then stir and mix the particulate hyaluronic acid gel with hyaluronic acid, and the final concentration of hyaluronic acid is 2mg / ml. Filling and autoclaving (121° C., 30 minutes).

Embodiment 3

[0041] Put 2.6g of hyaluronic acid fine powder with a molecular weight of 2 million Daltons in a container filled with 30ml of 0.25M NaOH solution, and stir and mix for 4 hours;

[0042] During stirring, add 0.3ml of 1,4-butanediol diglycidyl ether (BDDE), and then place the solution in a water bath at 40°C for 3 hours to form a cross-linked hyaluronic acid gel;

[0043] Then add 500mL deionized water to soak and wash 6 times repeatedly for 2.5 days.

[0044] Then put the hyaluronic acid gel in the pressure extrusion device, set the hole diameter to 550 μm, pressurize 8kg / cm 2 , Extrude the hyaluronic acid gel into a microgel.

[0045] Then stir and mix the particulate hyaluronic acid gel with hyaluronic acid, and the final concentration of hyaluronic acid is 1mg / ml. Filling and autoclaving (121° C., 30 minutes).

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Abstract

The invention provides a cross-linked hyaluronic acid gel and a preparation method thereof. A preparation contains cross-linked hyaluronic acid and uncrosslinked hyaluronic acid, and the cross-linked hyaluronic acid is prepared by reacting a cross-linking agent and hyaluronic acid molecules to form the cross-linked hyaluronic acid gel in the alkaline environment, and then removing the cross-linking agent. The cross-linked hyaluronic acid gel has excellent biocompatibility and long half-life, and is suitable for tissue filling, bone joint lubricating or medicament slow-releasing preparation, and the like.

Description

technical field [0001] The invention relates to a cross-linked hyaluronic acid gel and a preparation method thereof. Background technique [0002] Hyaluronic Acid (HA) gel is widely used in ophthalmology, orthopedics, gynecology, plastic surgery and other fields. It has been in clinical practice for more than ten years, and its safety and effectiveness have been recognized by all medical circles. generally accepted. Natural exogenous hyaluronic acid has a molecular weight of about 100,000 to 5 million Daltons, and its retention time in the body is about 3 to 15 days, which largely limits its application in certain fields. For example, it is used for tissue filling to improve facial wrinkles and creases, improve lip shape and correct facial contours, etc.; or for bone and joint lubrication, the effect duration is too short and continuous injection is required. [0003] Cross-linked hyaluronic acid gel is a cross-linked product of hyaluronic acid and a cross-linking agent, w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08L5/08C08J3/075C08J3/24C08K5/06
Inventor 侯永泰孔淑静毛振琴朱澄
Owner SHANGHAI HAOHAI BIOLOGICAL TECH
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