A kind of composite sodium hyaluronate gel resisting hyaluronidase hydrolysis and preparation method thereof

A technology of hyaluronidase and sodium hyaluronate, used in pharmaceutical formulations, prostheses, drug delivery, etc., can solve the problems of reduced biocompatibility, easy to cause immune response, etc., so as to delay the degradation time and strengthen the anti-enzyme The ability to decompose and improve the effect of biocompatibility

Active Publication Date: 2022-05-27
QINGDAO CHENLAND MARINE BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The degree of cross-linking affects the properties of fillers. Increasing the degree of cross-linking is the main way to prolong the degradation time. The method of adding cross-linking agents is often used. Any residue of cross-linking agents cannot be completely removed under the existing technology. Cross-linking Excessive dosage of the combination will lead to a decrease in biocompatibility, and it is easy to cause an immune response when injected into the human body

Method used

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  • A kind of composite sodium hyaluronate gel resisting hyaluronidase hydrolysis and preparation method thereof
  • A kind of composite sodium hyaluronate gel resisting hyaluronidase hydrolysis and preparation method thereof
  • A kind of composite sodium hyaluronate gel resisting hyaluronidase hydrolysis and preparation method thereof

Examples

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Effect test

Embodiment 1

[0029] A chondroitin sulfate-sodium hyaluronate composite gel resistant to hydrolysis by hyaluronidase is specifically prepared by the following method:

[0030] Weigh 1g of chondroitin sulfate (molecular weight is 10kDa), dissolve it in 50mL NaOH solution (pH=11) and keep stirring, add 5g sodium hyaluronate dry powder (molecular weight is 800kDa), add 1mL BDDE and stir well. The reaction was carried out in an environment with a temperature of 37° C. for 4 h, and the initial cross-linked gel was obtained after the reaction. The gel was precipitated with 95% ethanol, and the precipitate was repeatedly washed with purified water and dried to obtain gel powder.

[0031] Weigh 10g of dry sodium hyaluronate powder (molecular weight 1500kDa) and dissolve it in 50mL of NaOH solution (pH=11), then add 2g of dry powder of primary cross-linked gel and stir evenly, and stir and react at 37°C for 5h. After the reaction, 1 mL of BDDE was added and stirred evenly, and the cross-linking was...

Embodiment 2

[0034] A chondroitin sulfate-sodium hyaluronate composite gel resistant to hydrolysis by hyaluronidase is specifically prepared by the following method:

[0035] Weigh 2g chondroitin sulfate (molecular weight is 10kDa), dissolve it in 50mL NaOH solution (pH=11) and keep stirring, add 5g sodium hyaluronate dry powder (molecular weight is 800kDa), add 1mL BDDE and stir well. The reaction was carried out in an environment with a temperature of 37° C. for 4 h, and the initial cross-linked gel was obtained after the reaction. The gel was precipitated with 95% ethanol, and the precipitate was repeatedly washed with purified water and dried to obtain gel powder.

[0036] Weigh 10g of dry sodium hyaluronate powder (molecular weight 1500kDa) and dissolve it in 50mL of NaOH solution (pH=11), then add 2g of dry powder of primary cross-linked gel and stir evenly, and stir and react at 37°C for 5h. After the reaction, 1 mL of BDDE was added and stirred evenly, and the cross-linking was stre...

Embodiment 3

[0038] A chondroitin sulfate-sodium hyaluronate composite gel resistant to hydrolysis by hyaluronidase is specifically prepared by the following method:

[0039] Weigh 2g chondroitin sulfate (molecular weight is 10kDa), dissolve it in 50mL NaOH solution (pH=11) and keep stirring, add 5g sodium hyaluronate dry powder (molecular weight is 800kDa), add 1mL BDDE and stir well. The reaction was carried out in an environment with a temperature of 37° C. for 4 h, and the initial cross-linked gel was obtained after the reaction. The gel was precipitated with 95% ethanol, and the precipitate was repeatedly washed with purified water and dried to obtain gel powder.

[0040] Weigh 10g of dry sodium hyaluronate powder (molecular weight 1500kDa) and dissolve it in 50mL of NaOH solution (pH=11), then add 2g of dry powder of primary cross-linked gel and stir evenly, and stir and react at 37°C for 5h. After the reaction, 1 mL of BDDE was added to stir evenly, and the cross-linking was streng...

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Abstract

The invention discloses a composite sodium hyaluronate gel resistant to hyaluronidase hydrolysis and a preparation method thereof, belonging to the technical field of composite sodium hyaluronate gel preparation. There are two ways to improve the enzymolysis resistance of sodium hyaluronate gel in the present invention: one is to contain active functional groups, which can be combined into the structure of sodium hyaluronate by grafting; the other is to add it directly to Sodium Hyaluronate Gel. Constructing a gel system with a hyaluronidase activity inhibitor and sodium hyaluronate can delay the degradation time of the gel without adding an excessive amount of cross-linking agent, and prolong the degradation time of the gel in vivo by inhibiting the activity of hyaluronidase. It provides a new idea for facial injection of gel-like functional materials.

Description

technical field [0001] The invention belongs to the technical field of preparation of composite sodium hyaluronate gel, in particular to a composite sodium hyaluronate gel resistant to hydrolysis by hyaluronidase and a preparation method thereof. Background technique [0002] Sodium hyaluronate is a natural macromolecular polysaccharide that exists in various organs and tissues in higher animals, and is an important component of human interstitial, synovial fluid and other tissues. It is composed of glucuronic acid and N-acetylglucosamine, has good biocompatibility, high viscoelasticity, unique molecular structure and physicochemical properties, and shows a variety of important physiological functions in the body. [0003] Injection fillers are one of the most effective ways to treat facial aging wrinkles and depressions at this stage, and the sodium hyaluronate products in injection fillers are relatively stable products. Sodium hyaluronate can be clinically used in most c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/24C08L5/08A61L27/44A61L27/50A61L27/54
CPCC08J3/243A61L27/50A61L27/44A61L27/54C08J2305/08C08J2405/08A61L2400/06C08L5/08
Inventor 林莎莎邹圣灿王宝群姜晓文王君廷
Owner QINGDAO CHENLAND MARINE BIOTECH CO LTD
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