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A preparation method of multi-dimensional composite cross-linked hyaluronic acid gel and its products and applications

A technology of hyaluronic acid and compound cross-linking, applied in the fields of medical cosmetology and biomedicine, can solve the problems that the cross-linking uniformity of the reaction system cannot be guaranteed, the anti-degradation ability of products varies greatly, and the reaction process cannot be consistent, etc., so as to reduce degradation. and the possibility of side reactions, the uniform mixing of the reaction system, the effect of shortened time

Active Publication Date: 2022-03-29
BLOOMAGE BIOTECHNOLOGY CORP LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But this method directly adjusts system pH after alkaline crosslinking to carry out acidic crosslinking, the pH of the reaction system is uneven, the pH difference between the center of the reaction system and the surface layer is relatively large, the reaction process cannot be consistent, and the crosslinking uniformity of the reaction system cannot be guaranteed. The resistance to degradation is quite different

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  • A preparation method of multi-dimensional composite cross-linked hyaluronic acid gel and its products and applications
  • A preparation method of multi-dimensional composite cross-linked hyaluronic acid gel and its products and applications
  • A preparation method of multi-dimensional composite cross-linked hyaluronic acid gel and its products and applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1 investigates high temperature crosslinking temperature

[0044] Follow the steps below to prepare multidimensional composite cross-linked hyaluronic acid gel:

[0045] (1) Dissolve 0.032g of 1,4-butanediol diglycidyl ether in 20g of sodium hydroxide solution with a pH value of 9 to 13, mix well and add 4g of sodium hyaluronate with a molecular weight of 2 million Daltons (Based on pure product), mix well until the gel is clear and transparent, control the reaction temperature: A 35°C, B 50°C and C 65°C, respectively react for 2 hours to obtain gel I.

[0046] (2) Dissolve 0.048g of 1,4-butanediol diglycidyl ether in 16g of glacial acetic acid solution with a pH value of 3 to 5, mix well and add 4g of sodium hyaluronate with a molecular weight of 2 million Daltons ( Based on the pure product), mix well until the gel is clear and transparent, control the reaction temperature: A 35°C, B 55°C and C 65°C, and react for 2 hours respectively to obtain Gel II.

...

Embodiment 2

[0051] Embodiment 2 investigates high temperature crosslinking time

[0052] Follow the steps below to prepare multidimensional composite cross-linked hyaluronic acid gel:

[0053] (1) Dissolve 0.032g of 1,4-butanediol diglycidyl ether in 20g of sodium hydroxide solution with a pH value of 9 to 13, mix well and add 4g of sodium hyaluronate with a molecular weight of 2 million Daltons (Based on pure product), mix well until the gel is clear and transparent, control the reaction temperature at 50°C, and react separately: A for 0.5h, B for 2h and C for 12h to obtain Gel I.

[0054] (2) Dissolve 0.048g of 1,4-butanediol diglycidyl ether in 16g of glacial acetic acid solution with a pH value of 3 to 5, mix well and add 4g of sodium hyaluronate with a molecular weight of 2 million Daltons ( Calculated as a pure product), mix well until the gel is clear and transparent, control the reaction temperature at 55°C, and react separately: A0.5h, B 2h and C12h to obtain gel II.

[0055] (...

Embodiment 3

[0059] Embodiment 3 investigates cross-linking agent consumption

[0060] Follow the steps below to prepare multidimensional composite cross-linked hyaluronic acid gel:

[0061] (1) Dissolve 1,4-butanediol diglycidyl ether: 0.006g of A, 0.016g of B, and 0.2g of C in 10g of sodium hydroxide solution with a pH value of 9 to 13, mix well and add 2g of molecular weight Sodium hyaluronate (calculated as pure product) is 2 million daltons, mixed evenly until the gel is clear and transparent, the reaction temperature is controlled at 50°C, and reacted for 2 hours to obtain gel I.

[0062] (2) Dissolve 1,4-butanediol diglycidyl ether: A 0.006g, B 0.028g, C 0.2g in 8g of glacial acetic acid solution with a pH value of 3~5, mix well and add 2g of Sodium hyaluronate (calculated as a pure product) of 2 million daltons was mixed evenly until the gel was clear and transparent, the reaction temperature was controlled at 55°C, and the reaction was carried out for 2 hours to obtain gel II.

...

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Abstract

The invention discloses a preparation method of a multi-dimensional composite cross-linked hyaluronic acid gel, the product and its application. The method comprises: 1) high-temperature alkaline cross-linking to obtain gel I; 2) high-temperature acid cross-linking to obtain gel II; 3) Mix Gel I and Gel II at low temperature to obtain Gel III; 4) Dialyze and granulate to obtain the final product. The present invention cross-links under acidic and alkaline conditions to form a cross-linking direction respectively, and then further cross-links the gel formed by two different cross-linking directions through low-temperature reaction, which reduces the degradation and occurrence of hyaluronic acid at higher temperatures. The possibility of side reactions also reduces the use of cross-linking agents, making the reaction system more evenly mixed and the resulting product performance more stable. The obtained multidimensional composite cross-linked hyaluronic acid gel has excellent viscoelasticity, enzymolysis resistance and cohesion, and can be used in cosmetics, joint cavity injections, and tissue fillers, especially the excellent tissue filling and shaping ability, is A very ideal tissue filler.

Description

technical field [0001] The invention relates to a preparation method of a multi-dimensional composite cross-linked hyaluronic acid gel and the obtained product and application, belonging to the technical fields of medical cosmetology and biomedicine. Background technique [0002] Hyaluronic acid (Hyaluronic acid, HA), also known as hyaluronic acid, is a long-chain polymer composed of D-glucuronic acid and N-acetylglucosamine alternately arranged, with good hydrophilicity, viscoelasticity, lubricity and biophase Capacitance, and has been widely used in the medical field, such as ophthalmic viscoelastic surgery, arthritis treatment, prevention of postoperative tissue adhesion, sustained release of drugs, etc. [0003] Due to the shortcomings of natural HA, such as poor stability, sensitivity to hyaluronidase and free radicals, short retention time in the body, and lack of mechanical strength in water systems, it limits its development and application in the field of biomedicin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/075C08J3/24C08L5/08C08K5/1515
CPCC08J3/075C08J3/246C08J2305/08C08K5/1515
Inventor 吴万福苏江伟张燕刘建建郭学平
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD