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Cross-linked hyaluronic acid gel

A technology of cross-linking hyaluronic acid and hyaluronic acid, which is applied in medical science, pharmaceutical formulations, prostheses, etc., and can solve problems such as degradation of hyaluronic acid, failure to meet performance requirements, and harsh process parameters.

Active Publication Date: 2021-06-11
烟台德胜海洋生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, from the process point of view, these process methods are roughly the same, and there is an obvious feature: one or more process parameters used in them are more stringent
The reason is that there is a fundamental defect in this conventional chemical cross-linking process: during the reaction, the non-neutral environment will cause continuous degradation of hyaluronic acid
[0009] To sum up, the fundamental defects of the conventional chemical cross-linking process lead to the existence of one or several disadvantages of relatively harsh reaction conditions in the existing process methods and the adverse effects brought about by them, which cannot realize our aforementioned Performance requirements for superficial and mid-level skin fillers

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0134] The preparation method is as follows, wherein the sodium hyaluronate concentration is 5 w / v%, the sodium hydroxide concentration is 1 w / v%, the heterogeneous system formation temperature is -20°C, the holding time is 2h, the crosslinking reaction temperature is -20°C, and the reaction time is 3 days.

[0135] Prepare 20 ml of 1 w / v% sodium hydroxide aqueous solution, add the cross-linking agent BDDE according to the concentration shown in Table 1, mix well and add 1 g of sodium hyaluronate to it. The solution was stirred until uniform, then kept at -20°C for 2 hours, and then placed at -20°C for 3 days. After the reaction is completed, place the product at room temperature until the ice crystals are completely melted, adjust the pH to neutral with hydrochloric acid solution, put it in PBS buffer solution, dialysis, purify, swell and mechanically homogenize to obtain a cross-linked sodium hyaluronate gel. 20mg / ml.

Embodiment 2

[0148] Example 2: The preparation method is as follows, wherein the crosslinking agent concentration is 1.5 w / w%, the sodium hydroxide concentration is 2 w / v%, the heterogeneous system formation temperature is -25°C, the holding time is 1h, the crosslinking reaction temperature is -20°C, The cross-linking reaction time is 3 days.

[0149] Prepare 5ml of 2 w / v% sodium hydroxide aqueous solution, add the crosslinking agent BDDE according to the concentration shown in Table 2, mix well and add sodium hyaluronate powder to the concentration shown in Table 2. The solution was stirred until homogeneous and kept at -25°C for 1 h, then at -20°C for 3 days. After the reaction is completed, place the product at room temperature until the ice crystals are completely melted, adjust the pH to neutral with hydrochloric acid solution, put it into PBS buffer solution for dialysis purification and mechanical homogenization, and obtain a cross-linked sodium hyaluronate gel. 20 mg / ml. For the ...

Embodiment 3

[0157] Example 3: The preparation method is as follows, wherein the concentration of sodium hyaluronate is 10 w / v%, the concentration of sodium hydroxide is 1 w / v%, the concentration of crosslinking agent BDDE is 1 w / w%, and the heterogeneous system formation temperature is -30°C. The holding time is 2h, and the crosslinking reaction time is 3 days.

[0158] Prepare 10 ml of 1 w / v% sodium hydroxide aqueous solution, add 0.01 g of cross-linking agent BDDE, mix well and add 1 g of sodium hyaluronate. The solution was stirred until uniform, then kept at -30°C for 2h, and then placed at the temperature in Table 3 for 3 days. After the reaction was completed, the product was placed at room temperature until the ice crystals were completely melted, adjusted to neutral pH with hydrochloric acid solution, dialyzed and purified in PBS buffer and mechanically homogenized to obtain a cross-linked sodium hyaluronate gel with a concentration of 20 mg / ml.

[0159] The cross-linked sodium ...

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Abstract

The invention relates to a cross-linked hyaluronic acid gel. The gel has an elastic modulus of from about 10 Pa to about 1000 Pa at 1 Hz, the viscous modulus of the gel is from about 10 Pa to about 500 Pa at 1 Hz, the ratio tandelta value of the viscous modulus to the elastic modulus of the gel is about 0.4 to about 1.5 at 1 Hz, and the cohesive force is from about 2N to about 10 N. The invention also relates to a preparation method and application of the cross-linked hyaluronic acid gel.

Description

technical field [0001] The invention relates to the field of medical biomaterials, in particular to cross-linked hyaluronic acid gel. The present invention also relates to a preparation method of the cross-linked hyaluronic acid gel of the present invention, a composition comprising the cross-linked hyaluronic acid gel of the present invention, and uses thereof. Background technique [0002] Hyaluronic acid is an important component of human skin, cartilage tissue and joint lubricating fluid. It is a chain polymer composed of (1-β-4) D-glucuronic acid and (1-β-3) N-acetylamino The disaccharide units of glucose are linked repeatedly. Thanks to its advantages of no species difference and no immunogenicity, natural hyaluronic acid is widely used in medical filling, osteoarthritis treatment and eye surgery. [0003] Natural hyaluronic acid has the disadvantages of short half-life, easy degradation and diffusion in tissues, which greatly limits its application in soft tissue fi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08L5/08A61L27/20A61L27/52A61L31/04A61L31/14
CPCC08J3/244A61L27/20A61L27/52A61L31/042A61L31/145A61L2400/06C08J2305/08C08L5/08
Inventor 黄兆辉张絮然解江冰
Owner 烟台德胜海洋生物科技有限公司
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