A kind of preparation method of cross-linked sodium hyaluronate gel with asymmetric structure
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A cross-linked hyaluronic acid, asymmetric technology, used in medical biomaterials, medical field, can solve the problems of low utilization rate of cross-linking agent, difficulty in cross-linking agent removal, etc., to achieve long residual time in the body and improve resistance to enzyme degradation , the effect of improving the utilization rate
Active Publication Date: 2017-12-01
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD +1
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[0005] Usually the preparation of cross-linked sodium hyaluronate gel is carried out with a fixed concentration of reactants. In such a reaction, the utilization rate of the cross-linking agent is low. In order to achieve a better cross-linking effect, more cross-linking agents are usually added. Reaction of the cross-linking agent, so that the removal of the cross-linking agent is more difficult
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Embodiment 1
[0020] Prepare 20ml of 1% sodium hydroxide aqueous solution, add 0.02g of cross-linking agent BDDE, mix well, add 2.0g sodium hyaluronate, stir well, put it in a 10°C reaction box, set the dehydration rate to 3% / day , after reacting for 10 days, put it into a 40°C water bath, heat for 2 hours, take out the gel cut into about 0.5g in mass, put it in PBS buffer solution, and perform swelling dialysis to obtain cross-linked sodium hyaluronate gel. 20mg / ml.
Embodiment 2
[0022] Prepare 20ml of 1% sodium hydroxide aqueous solution, add 0.01g of cross-linking agent BDDE, mix well, add 2.0g of sodium hyaluronate, stir well, put it in a 10°C reaction box, set the dehydration rate to 4% / day , after reacting for 10 days, put it into a 40°C water bath, heat for 2 hours, take out the gel cut into about 0.5g in mass, put it in PBS buffer solution, and perform swelling dialysis to obtain cross-linked sodium hyaluronate gel. 20mg / ml.
Embodiment 3
[0024] Prepare 20ml of 1.5% sodium hydroxide aqueous solution, add 0.007g of cross-linking agent BDDE, mix well, add 2.0g of sodium hyaluronate, stir well, put it in a 10°C reaction box, set the dehydration rate to 5% / day , after reacting for 10 days, put it into a 40°C water bath, heat for 2 hours, take out the gel cut into about 0.5g in mass, put it in PBS buffer solution, and perform swelling dialysis to obtain cross-linked sodium hyaluronate gel. 20mg / ml.
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Abstract
The invention relates to a preparation method for a cross-linked sodium hyaluronate gel with an asymmetric structure. The method comprises the steps: adopting a sodium hyaluronate solution containing a cross-linking agent as a starting material, adding a precious small amount of the cross-linking agent, under conditions of constant temperature and constant humidity, carrying out gradient concentration dehydration, then dialyzing the cross-linked sodium hyaluronate gel in a buffer solution, dialyzing until the gel is no longer expanded, and finally, granulating to obtain the cross-linked sodium hyaluronate gel with the asymmetric structure. The cross-linked sodium hyaluronate obtained by the preparation method provided by the invention has the gradient asymmetric structure in microcosmic scale and shows the characteristics of dense exterior and loose interior; the structure ensures that the cross-linked sodium hyaluronate gel can effectively buffer attacking action of sodium hyaluronate enzymes, the survival time in bodies is greatly extended, and at the same time, excellent biological safety is also showed with precious small addition amount of the cross-linking agent.
Description
technical field [0001] The invention relates to the technical field of medical biomaterials, and relates to a preparation method of a novel cross-linked sodium hyaluronate. The cross-linked sodium hyaluronate is used for medical filling and cosmetology, and belongs to the medical field. Background technique [0002] Sodium hyaluronate is an important component of human and animal skin, vitreous body, joint lubricating fluid and cartilage tissue, which consists of (1-β-4) D - Glucuronic acid and (1-β-3) N -Acetyl- D -Glucosamine disaccharide units are repeatedly connected, and are widely used in repair surgery, eye surgery or as a cosmetic filling material. Sodium hyaluronate has good physical and chemical properties and biocompatibility, but it is rapidly degraded by specific hyaluronidase in vivo, with a half-life of only 2-3 days and a short retention time, which cannot meet the needs of clinical application . Cross-linked sodium hyaluronate is a polymer gel modified b...
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