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Preparation method of crosslinked sodium hyaluronate gel with ultralow crosslinking agent residual quantity and high viscosity

A cross-linked hyaluronic acid and cross-linking agent technology, applied in the field of preparation of cross-linked sodium hyaluronate gel, can solve the problems of large gap, poor viscosity, large specific surface area, etc., achieve low residual level, increase contact area effect

Active Publication Date: 2019-11-01
CHANGZHOU INST OF MATERIA MEDICA
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Problems solved by technology

After this type of gel is aggregated, the gap between the gel particles is large, resulting in a large specific surface area and poor viscosity

Method used

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  • Preparation method of crosslinked sodium hyaluronate gel with ultralow crosslinking agent residual quantity and high viscosity
  • Preparation method of crosslinked sodium hyaluronate gel with ultralow crosslinking agent residual quantity and high viscosity
  • Preparation method of crosslinked sodium hyaluronate gel with ultralow crosslinking agent residual quantity and high viscosity

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Embodiment Construction

[0020] The present invention will be further described in conjunction with specific embodiment now. These drawings are simplified schematic diagrams only to illustrate the basic structure of the present invention in a schematic way, so they only show the components relevant to the present invention.

[0021] A method for preparing an ultra-low residual amount of crosslinking agent and high viscosity crosslinked sodium hyaluronate gel, comprising the following steps;

[0022] S1. First configure 100ml of 0.5-2.5mol / L sodium hydroxide solution, add 5-30g sodium hyaluronate at room temperature, mix well and stir to dissolve until no white undissolved HA is visible to the naked eye. Adjust the temperature of the water bath to 35 -60°C, then add 2.5-15g of crosslinking agent, and crosslink for 30 minutes to 5 hours to obtain a gel;

[0023] S2. After the gel formed by cross-linking is swelled by buffer solution (i.e., purified water) for 1 hour, it is prepared into gel particles w...

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Abstract

The invention relates to a preparation method of crosslinked sodium hyaluronate gel with ultralow crosslinking agent residual quantity and high viscosity, which comprises the following steps: S1, swelling the gel formed by crosslinking with a buffer solution, and preparing gel particles with proper particle size by using a high-speed dispersion machine; S2, adding dimethyl sulfoxide for washing, so that the unreacted cross-linking agent is eluted from the interior of the gel; S3, removing the dimethyl sulfoxide by adopting ultrafiltration; and S4, collecting a sample, and filling the sample into a filling and sealing injector. The preparation method is simple, the contact area of the gel and the washing filtrate can be effectively increased, and the uncrosslinked crosslinking agent embedded in the gel can be effectively removed by using the dimethyl sulfoxide which is a special organic solvent, so that the residual level of the crosslinking agent is far lower than that of the crosslinking agent prepared by the conventional preparation method.

Description

technical field [0001] The invention relates to a preparation method of ultra-low residual amount of cross-linking agent and high viscosity cross-linked sodium hyaluronate gel. Background technique [0002] At present, the commonly used preparation method of cross-linked sodium hyaluronate is to stir and mix sodium hyaluronate and cross-linking agent under alkaline conditions, and make chemical bridging and bonding between the molecular chains of sodium hyaluronate through the cross-linking agent. of. Commonly used cross-linking agents are DVS and BDDE. Since BDDE is relatively less toxic and contains alkoxy bonds in the molecule, the alkoxy bonds can rotate freely after polymerization to make the material soft, especially suitable for soft tissue filling, so most of the products currently on the market use BDDE It is obtained by cross-linking as a cross-linking agent, such as foreign products: Restylane, Juvederm, Ai Liwei, etc.; domestic products: Shuyan, Moisturizing Be...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/00C08J3/24C08J3/12C08L5/08
CPCC08J3/00C08J3/12C08J3/24C08J2305/08
Inventor 管汉亮耿文鑫鲍远兵李立文
Owner CHANGZHOU INST OF MATERIA MEDICA
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