Crosslinking hyaluronic acid gel resisting hydrolysis of hyaluronidase

A technology for cross-linking hyaluronic acid and hyaluronidase, applied in the field of materials, can solve problems such as adverse reactions, and achieve the effects of large application potential, large economic benefits, and enhanced maintenance time and plasticity.

Active Publication Date: 2019-05-17
宁夏妙朗生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, to improve the maintenance time of hyaluronic acid gel, only the mode of increasing the degree of chemical cross-linking is used, but the increase of the content of chemical cross-linking agent may lead to subsequent adverse reactions

Method used

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  • Crosslinking hyaluronic acid gel resisting hydrolysis of hyaluronidase
  • Crosslinking hyaluronic acid gel resisting hydrolysis of hyaluronidase
  • Crosslinking hyaluronic acid gel resisting hydrolysis of hyaluronidase

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The names of natural flavin coenzymes and their derivatives are: including riboflavin: Riboflavin, isoalloxazine: isoalloxazine,

[0039] 7-methyl-8-chloro-10-(1′-D-ribityl)isoalloxazine(7-M-8-C),

[0040] 7-bromo-8-methyl-10-(1′-D-ribityl)isoalloxazine(7-B-8-M),

[0041] 7-methyl-8-bromo-10-(1′-D-ribityl)isoalloxazine(7-M-8-B),

[0042] 7-chloro-8-ethyl-10-(1′-D-ribityl)isoalloxazine(7-C-8-E),

[0043] 7,8-diethyl-10-(1′-D-ribityl)isoalloxazine (7,8-D).

Embodiment 2

[0046] Inhibition of human recombinant hyaluronidase activity by natural flavin coenzyme and its derivatives

[0047] The establishment of the reaction system:

[0048] 0.5g of cross-linked hyaluronic acid gel, the content of hyaluronic acid is 28mg / g, add 2mL of PBS buffer solution, pH 6.5-7.5, which contains 250U / mL of human-derived recombinant hyaluronidase; in addition, add a certain amount of Natural flavin coenzyme or its derivative molecule. The entire reaction system was placed in a water bath at 37° C. for 72 hours, samples were taken every 24 hours, centrifuged at 12,000 rpm for 10 minutes, and then the supernatant was removed to determine the content of free hyaluronic acid.

[0049] (1) Determination of the optimal addition amount of FAD

[0050] Determine the maximum amount of ligand molecule added. In the above reaction system, add 0, 0.2, 0.4, 0.6, 0.8, 1.0mmol / L of FAD, in a water bath at 37°C for 72 hours, sample every 24 hours, centrifuge at 12000rpm for 1...

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Abstract

The invention provides crosslinking hyaluronic acid gel resisting hydrolysis of hyaluronidase, and relates to the crosslinking hyaluronic acid gel, natural flavocoenzyme and derivatives of the naturalflavocoenzyme. The derivatives include riboflavin, isoalloxazine, 7-M-8-C, 7-B-8-M, 7-M-8-B, 7-C-8-E and 7,8-D. The invention further provides a method for utilizing the natural flavocoenzyme and thederivatives of the natural flavocoenzyme for lowering the activity of the hyaluronidase, effectively prolonging the maintaining time of the crosslinking hyaluronic acid gel, and effectively improvingthe plasticity effect of the crosslinking hyaluronic acid gel. By means of the method, in an experiment of in-vitro enzymolysis of crosslinking hyaluronic acid, the catalysis efficiency of the hyaluronidase is lowered by 50% or above. The crosslinking hyaluronic acid gel has a large application potential and shows great economic benefits.

Description

technical field [0001] The invention relates to a cross-linked hyaluronic acid gel resistant to hyaluronidase hydrolysis, belonging to the field of materials. Background technique [0002] Hyaluronic acid is a component in the tissue matrix that restricts the diffusion of water and other extracellular substances. Hyaluronidase (HAase; EC 4.2.99.1) is an enzyme that can hydrolyze hyaluronic acid, which can specifically hydrolyze N - the β-1,4-glycosidic bond between acetylglucosamine and D-glucuronic acid, thereby degrading the hyaluronic acid molecule. When used in the human body, it can temporarily reduce the viscosity of the intercellular substance, and can promote the diffusion of subcutaneous infusion, locally accumulated exudate or blood to facilitate absorption. It is an important drug diffusing agent. It is clinically used as a drug penetration agent to promote the absorption of drugs and promote the dissipation of local edema or hematoma after surgery and trauma. I...

Claims

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Application Information

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IPC IPC(8): A61L27/20A61L27/00A61L27/50A61L27/52
Inventor 辛瑜
Owner 宁夏妙朗生物科技有限公司
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