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Cross-linked hyaluronan sponge and preparation method for same

A technology of cross-linking hyaluronic acid and hyaluronic acid, which is applied in the medical field, can solve the problems of unsatisfactory hemostatic effect and uneven cross-linking degree of the product, and achieve the benefits of wound healing, prolonging the retention time, and preventing the formation of adhesions Effect

Inactive Publication Date: 2012-07-11
上海白衣缘生物工程有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are literatures (Mi Pengcheng et al., Preparation and biocompatibility of divinyl sulfone cross-linked sodium hyaluronate gel, Chinese Tissue Engineering Research and Clinical Rehabilitation, 2008, 12(14): 2675-2678) (hereinafter Document A) describes the method for preparing cross-linked sodium hyaluronate gel with divinyl sulfone as a cross-linking agent, and confirms that divinyl sulfone cross-linked hyaluronic acid has biocompatibility. The preparation method of sulfone cross-linked sodium hyaluronate gel is to directly add alkaline solution to the hyaluronic acid raw material, stir for 30 minutes, and then add a cross-linking agent to react, which will lead to uneven cross-linking degree of the product
The foreign product HylaSine is a gel preparation composed of divinyl sulfone cross-linked hyaluronic acid. It is clinically used to cover the mucosal surface of the nasal cavity or sinuses after nasal surgery or injury, and plays a role in hemostasis and anti-adhesion, but the hemostatic effect is not ideal.

Method used

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  • Cross-linked hyaluronan sponge and preparation method for same
  • Cross-linked hyaluronan sponge and preparation method for same
  • Cross-linked hyaluronan sponge and preparation method for same

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preparation example Construction

[0035] The preparation method prepared by the present invention or the obtained cross-linked hyaluronic acid sponge has the following advantages:

[0036] (1) When preparing cross-linked hyaluronic acid, the present invention first swells (dissolves) the hyaluronic acid with water, and then adjusts the pH value to be alkaline, which prevents the hyaluronic acid molecular chain from being degraded by alkali in an alkaline environment for a long time. This means that only a small amount of cross-linking agent needs to be added to obtain a product with a higher degree of cross-linking.

[0037] Hyaluronic acid molecules are degraded into hemiacetals and aldehydes at the reducing end of N-acetylglucosamine under alkaline conditions above pH 10. The α-hydrogen atom on the aldehyde group is very unstable under strong alkaline conditions. , The glycosidic bond is easily broken and further degrades to form glucuronic acid with a reducing end. Therefore, hyaluronic acid molecules are easil...

Embodiment 1

[0070] Weigh 2g of hyaluronic acid raw material dry powder into a beaker, add 35ml of distilled water, stir well with a glass rod, seal, store in a refrigerator at 4℃ for 5 days, after hyaluronic acid is fully swelled in distilled water, add 5ml of 2M sodium carbonate solution, Stir uniformly, place at room temperature for 0.5h, and measure the pH of the solution to be 11.5. Add 0.05ml of divinyl sulfone and stir evenly, then pour them into glass dishes with a thickness of about 2mm, and place them in a constant temperature oven at 40°C for 2 hours. , You can get water-insoluble cross-linked hyaluronic acid gel block. Wash the gel in distilled water. When the pH of the cleaning solution is 6.8, drain the water, transfer the cross-linked gel block to the freezer, put it in the freezer at -60℃ for 48h, and then freeze it with a freeze dryer After drying for 48 hours, the cross-linked hyaluronic acid sponge can be obtained, packaged and sealed with aluminum foil, and sterilized by...

Embodiment 2

[0072] Weigh 2g of hyaluronic acid raw material dry powder in a beaker, add 35ml of distilled water, stir well with a glass rod, seal, store in a refrigerator at 4℃ for 1 day, after hyaluronic acid is fully swelled in distilled water, add 5ml of 2M sodium carbonate solution, Stir evenly and place at room temperature for 0.5h. The measured pH value of the solution is 11.2. Add 0.05ml of divinyl sulfone and stir evenly, then pour them into glass plates with a thickness of about 2mm. Place them in a 37℃ thermostat for 4 hours. , You can get water-insoluble cross-linked hyaluronic acid gel block. Put the gel in distilled water for washing. When the pH of the washing solution is 7.1, drain the water, transfer the cross-linked gel block to the freezer, put it in the freezer at -60℃ for 48h, and then freeze it with a freeze dryer After drying for 48 hours, the cross-linked hyaluronic acid sponge can be obtained, packaged and sealed with aluminum foil, and sterilized by gamma rays.

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Abstract

The invention provides a method for preparing a cross-linked hyaluronan sponge, and the sponge obtained by the method. The method comprises the following steps of: (1) swelling a hyaluronan raw material in water to obtain a hyaluronan gel fluid; (2) adjusting the hyaluronan gel fluid to be alkaline, adding a cross-linking agent, and performing cross-linking reaction to obtain a cross-linked hyaluronan gel; and (3) cleaning the cross-linked hyaluronan gel, and freeze-drying at a low temperature to obtain the cross-linked hyaluronan sponge. The cross-linked hyaluronan sponge prepared by the method provided by the invention is low in the content of the cross-linking agent, good in biocompatibility, consistent in in-vivo degradation cycle and tissue healing cycle, and good in blood-stopping and anti-adhesion functions.

Description

Technical field [0001] The invention relates to a medical, especially cross-linked hyaluronic acid sponge for hemostasis and anti-adhesion, and a preparation method thereof. Background technique [0002] Local bleeding and tissue adhesion after surgery are a common clinical phenomenon, and its occurrence may lead to serious clinical complications. Ideal hemostatic and anti-adhesion materials generally have the following characteristics: good biocompatibility, no obvious toxic and side effects; bioabsorbability; the rate of degradation in the body is synchronized with wound healing; rapid blood application, accurate hemostatic effect; good tissue adhesion It has a good effect on preventing postoperative adhesion, can promote the rapid healing of the wound, and has light mucosal damage. [0003] Studies have shown that after hyaluronic acid (HA) is made into sponges or membranes, its hemostatic and anti-adhesion effects are relatively ideal. Patent application CN 101912633A uses unc...

Claims

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Application Information

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IPC IPC(8): C08J9/28C08J3/24C08L5/08C08K5/41
Inventor 韩韦红
Owner 上海白衣缘生物工程有限公司
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