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Preparation method of subcutaneous filling hyaluronic acid gel

A technology of hyaluronic acid and sodium hyaluronate, which is used in the preparation of subcutaneous fillers and the preparation of hyaluronic acid gel for subcutaneous fillings. It can solve the problems of poor adhesion and troublesome clinical use, and improve the bonding strength. , to overcome the effect of wandering shift

Active Publication Date: 2019-06-14
WUHAN TEXTILE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the adhesion between the in-situ cross-linked polysaccharide gel formed at the injection site and the tissue at the injection site is still poor, and it is difficult to solve the problem of fillers moving downstream of external force extrusion. cause trouble

Method used

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preparation example Construction

[0035] A preparation method for subcutaneous filling hyaluronic acid gel, said preparation method is carried out according to the following steps:

[0036] a. Preparation of aldehyde sodium hyaluronate

[0037] Put sodium hyaluronate in deionized water, the mass volume ratio of sodium hyaluronate to deionized water is 1g: 20-100mL, stir at room temperature for 10 hours to form a sodium hyaluronate aqueous solution, add Sodium periodate, the molar ratio of hydroxyl groups on the molecular chain of sodium hyaluronate to sodium periodate is 1:0.05~10, stir evenly at room temperature, react at 25~60°C, and the reaction time is 1~24 hours. Dialyze the mixed solution of sodium hyaluronate and sodium periodate after the reaction, and the dialysis time is 2 days to form a sodium aldehyde hyaluronate solution. Under the condition of a pressure of 1-20 Pa, freeze-dry for 48 hours to obtain sodium aldehyde hyaluronate with a molar substitution degree of aldehyde group of 0.1-0.9.

[00...

Embodiment 1

[0064] Weigh 1g of hyaluronic acid, add it to 20mL of deionized water, stir at room temperature for 10 hours, add 22.6g of sodium periodate, stir well at room temperature, react at 60°C for 24 hours, and dialyze the mixed solution for two days after the reaction , freeze-dried at -50°C and 20 Pa for 48 hours to obtain aldehyde sodium hyaluronate with a molar substitution of aldehyde groups of 0.9.

[0065] Weigh 1g of aldehyde-based sodium hyaluronate and 5.2g of maleic anhydride, add them to 5mL of dimethyl sulfoxide, stir well at room temperature, and react at 80°C for 48 hours. After the reaction, add 1mol / L NaHCO 3 Solution, adjust the pH of the mixed solution to 7-8, dialyze the mixed solution, the dialysis time is 2 days, freeze-dry the dialysate at a temperature of -50°C and a pressure of 1Pa for 24 hours, and obtain the maleoyl mole Sodium maleylated aldehyde hyaluronate with a degree of substitution of 2.0.

[0066] Weigh 1 g of hyaluronic acid, add it to 20 mL of deio...

Embodiment 2

[0069] Weigh 1g of hyaluronic acid, add it to 100mL of deionized water, stir at room temperature for 10 hours, add 0.11g of sodium periodate, stir well at room temperature, react at 25°C for 1 hour, and dialyze the mixed solution for two days after the reaction , freeze-dried at -50°C and 1Pa for 48 hours to obtain aldehyde sodium hyaluronate with a molar substitution of aldehyde groups of 0.1.

[0070] Weigh 1g of sodium aldehyde hyaluronate and 0.52g of maleic anhydride, add them into 100mL of acetonitrile, stir well at room temperature, and react at 25°C for 12 hours. After the reaction, add 1mol / L of KHCO 3 solution, adjust the pH of the mixed solution to 7-8, dialyze the mixed solution for 2 days, freeze-dry the dialysate for 72 hours at a temperature of -50°C and a pressure of 20 Pa to obtain the maleoyl mole Sodium maleylated aldehyde hyaluronate with a degree of substitution of 1.0.

[0071] Weigh 1 g of hyaluronic acid, add it to 100 mL of deionized water, stir at ro...

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Abstract

The invention relates to a preparation method of a subcutaneous filling material, in particular to a preparation method of a subcutaneous filling hyaluronic acid gel, and belongs to the technical field of preparation of biological materials. According to the preparation method disclosed by the invention, an aldehyde group and an hydrazide group are introduced to a high molecular chain, so that theeffect of fine-needle injection and rapid in-situ forming is realized, and the problem of needle burst caused for the fact that a pre-formed hydrogel is high in viscosity and fine needle injection isnot easy to perform and biological safety caused by residue of a small-molecular cross-linking agent are avoided. In addition, the preparation method disclosed by the invention adopts a process of modifying aldehyde-based sodium hyaluronate by a maleic acyl group after freeze-drying, and the high-substitution-degree grafting of the maleic acyl group on a hyaluronic acid molecular chain is realized, so that hyaluronic acid can be further polymerized under the irradiation of ultraviolet light in the subsequent in-situ molding process, the bonding strength of the gel on tissues of an injection part is greatly improved, and the problem that a gel filler is displaced when being extruded by external force is completely overcome.

Description

technical field [0001] The invention relates to a method for preparing a subcutaneous filling, in particular to a method for preparing a hyaluronic acid gel for subcutaneous filling, and belongs to the technical field of biological material preparation. Background technique [0002] Hyaluronic acid is a natural, non-immunogenic glycosaminoglycan composed of D-glucuronic acid and N-acetyl-D-glucosamine disaccharide units linked by glycosidic bonds. Due to its high water retention capacity and unique viscoelasticity, hyaluronic acid is increasingly used in the field of medical aesthetics, especially as a dermal filler to enhance facial features and reduce wrinkles and folds. [0003] However, hyaluronic acid without structural modification has a short retention time in the body, and it is easy to be completely degraded and absorbed within a few weeks under the action of enzymes in the body, which brings difficulties to long-term shaping. For this reason, hyaluronic acid needs...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08B37/08A61L27/20A61L27/50A61L27/52C08L5/08
Inventor 周应山李尚志刘欣杨红军柏自奎顾绍金徐卫林
Owner WUHAN TEXTILE UNIV
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