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Preparation method of linear cross-linked hyaluronic acid

A technology of cross-linking hyaluronic acid and hyaluronic acid, which is applied in medical science, surgery, etc., and can solve problems such as unusable surgical wounds

Inactive Publication Date: 2019-06-18
HANGZHOU TECHDERM BIOLOGICAL PROD CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It also cannot be used for surgical wounds that require no particles, anti-adhesion and improvement of joint function

Method used

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  • Preparation method of linear cross-linked hyaluronic acid
  • Preparation method of linear cross-linked hyaluronic acid

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preparation example Construction

[0020] The preparation method of linear cross-linked hyaluronic acid provided by the present invention comprises the following steps:

[0021] A. The hyaluronic acid raw material is treated to reduce its molecular weight; preferably, the hyaluronic acid raw material with a molecular weight of 100kDa-300kDa is treated to reduce its molecular weight to 30kDa-80kDa. For example: put the hyaluronic acid raw material into an airtight container, put it into a humid heat sterilization cabinet for heat treatment, the temperature is 114°C-121°C, and the time is 10min-45min. The method for reducing the molecular weight of hyaluronic acid can be methods such as heat treatment and acid treatment.

[0022] B. Mix the alkaline solution and the cross-linking agent to form a mixed solution, add the hyaluronic acid raw material into the mixed solution, stir and dissolve completely, and perform a low-temperature cross-linking reaction to form a hyaluronic acid gel; wherein, the cross-linking ag...

Embodiment 1

[0029] A method for preparing linearly cross-linked hyaluronic acid, comprising the following steps:

[0030] 1) Heat treatment of the most commonly used hyaluronic acid raw material to reduce the molecular weight to 30kDa, the heating temperature is 121°C, and the time is 40min.

[0031] 2) Mix the alkaline solution and the cross-linking agent to form a mixed solution, the cross-linking agent is 1,4-butanediol diglycidyl ether, add the processed hyaluronic acid raw material into the mixed solution, stir and dissolve, and carry out low-temperature exchange Cross-linking reaction to form hyaluronic acid gel, the low-temperature cross-linking reaction temperature is 2°C, and the reaction time is 36h; wherein, the pH of the alkaline solution is > 13, and the concentration of the alkaline solution is 3.5%, and the cross-linking agent and hyaluronic acid The weight ratio of raw materials is 1:33.

[0032] 3) Carrying out thermal alkali-activated cross-linking reaction on the hyalu...

Embodiment 2

[0035] A method for preparing linearly cross-linked hyaluronic acid, comprising the following steps:

[0036] 1) The most commonly used raw material of hyaluronic acid is heat-treated to reduce the molecular weight to 80kDa at a heating temperature of 114°C for 15 minutes.

[0037] 2) Mix the alkaline solution and the cross-linking agent to form a mixed solution, the cross-linking agent is 1,4-butanediol diglycidyl ether, add the processed hyaluronic acid raw material into the mixed solution, stir and dissolve, and carry out low-temperature exchange Cross-linking reaction to form hyaluronic acid gel, the low-temperature cross-linking reaction temperature is 20°C, and the reaction time is 12 hours; wherein, the pH of the alkaline solution is > 13, and the concentration of the alkaline solution is 0.5%, and the cross-linking agent and hyaluronic acid The weight ratio of raw materials is 1:20.

[0038]3) Carrying out thermal alkali-activated cross-linking reaction on the hyaluro...

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Abstract

Belonging to the field of material preparation, the invention discloses a preparation method of a linear cross-linked hyaluronic acid. The method includes: firstly treating a hyaluronic acid raw material to reduce the molecular weight; then mixing an alkaline solution with a cross-linking agent into a mixed solution, adding the hyaluronic acid raw material into the mixed solution and performing stirring till complete dissolution, and then carrying out low temperature cross-linking reaction at 2DEG C-20DEG C for 12h-36h to form a hyaluronic acid gel; then carrying out hot alkali activation cross-linking reaction on the hyaluronic acid gel at 25DEG C-65DEG C for 1h-6.5h to form a gel; and then using PBS dialysate for dialysis treatment on the gel so as to obtain a gel paste.

Description

【Technical field】 [0001] The invention relates to a preparation method of linear cross-linked hyaluronic acid. 【Background technique】 [0002] In the process of making hyaluronic acid gel, a prior art is: the cross-linking of hyaluronic acid is carried out under hot alkaline conditions, and the cross-linking agent and hyaluronic acid are mixed unevenly, resulting in uneven cross-linking reactions. The subcutaneous injection of the gel will cause local redness and swelling of the skin or fail to achieve the subcutaneous repair effect. [0003] Another existing technology is: low-temperature secondary cross-linking hyaluronic acid technology, which can make the mixing of hyaluronic acid and cross-linking agent more uniform, but the removal of cross-linking agent residue in the gel is not very thorough, and the desired effect cannot be achieved. It will lead to redness and swelling of the local skin, and subcutaneous injection of incompletely cross-linked gel particles will no...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08J3/075C08B37/08A61L31/04C08L5/08
Inventor 金家铸黎斌江淑云江云东程小杰
Owner HANGZHOU TECHDERM BIOLOGICAL PROD CO LTD
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