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Preparation method of polysialic acid-hyaluronic acid composite gel, obtained product and application

A technology of polysialic acid and hyaluronic acid, which is applied in the direction of medical preparations of non-active ingredients, liquid delivery, and pharmaceutical formulations, and can solve problems such as reducing user acceptance, lack of a good solution, and increasing user pain , to achieve the effect of easy operation, excellent biocompatibility, and less side effects

Active Publication Date: 2016-07-27
BLOOMAGE BIOTECHNOLOGY CORP LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, cross-linked hyaluronic acid has been widely used in the fields of micro-plastic surgery, breast augmentation, and drug release. However, it is found that cross-linked hyaluronic acid has certain defects during use. Linking agents such as 1,4-butanediol diglycidyl (BDDE), divinyl sulfone (DVS), carbodiimide (EDC), etc. are cross-linked, and the cross-linked hyaluronic acid may also contain The terminal unreacted group is exposed on the surface of the gel particles, which will cause some users to experience redness and swelling after surgery, and this defect reduces the user's acceptance and increases the pain of the user
Currently, there is no good solution

Method used

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  • Preparation method of polysialic acid-hyaluronic acid composite gel, obtained product and application
  • Preparation method of polysialic acid-hyaluronic acid composite gel, obtained product and application
  • Preparation method of polysialic acid-hyaluronic acid composite gel, obtained product and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Take 1.5g PSA (molecular weight 50KDa), dissolve it in 10ml sodium carbonate-sodium bicarbonate buffer solution (pH10), add 0.6ml epichlorohydrin and 1ml sodium hydroxide solution (0.5% mass volume concentration), then stir at 35°C React for 4 hours. After the reaction, the excess epichlorohydrin is removed in vacuum, and then the mixture of water: ethanol (volume ratio 1:4) is precipitated. The precipitate obtained is centrifuged and mixed with water: ethanol (volume ratio 1:4). The solution was repeatedly purified to obtain activated PSA.

[0058] With the ratio of PSA:HA mass ratio of 2:1, the activated PSA was added to 20ml of HA solution with a concentration of 1.5% (g / ml) (HA molecular weight was 1500KDa. The HA solution was prepared with pH6.0 phosphate buffer as the solvent), stirred and reacted at 30°C for 56 hours, after the reaction, the reaction solution was concentrated under reduced pressure to 1 / 4 of the original volume, and the concentrated solution was ...

Embodiment 2

[0061] Take 1.5g polysialic acid (molecular weight 10kDa) and dissolve it in 10ml sodium carbonate-sodium bicarbonate buffer solution (pH8.5~11), then add 0.8ml epichlorohydrin and 2ml sodium hydroxide solution (0.2% mass volume concentration ), magnetically stirred at 35°C for 4 hours, then removed excess epichlorohydrin in vacuum, concentrated the solution to 1 / 4 of its original volume under reduced pressure, and precipitated with a mixture of water:ethanol (volume ratio 1:4) , the resulting precipitate was purified by repeated precipitation and purification with ethanol aqueous solution to obtain activated polysialic acid.

[0062] With the ratio of PSA:HA mass ratio of 2:1, the activated PSA was added to 20ml of HA solution with a concentration of 1.5% (g / ml) (HA molecular weight was 1000KDa. The HA solution was prepared with pH6.0 phosphate buffer as the solvent), stirred and reacted at 30°C for 56 hours, after the reaction, the reaction solution was concentrated under re...

Embodiment 3

[0064] Take 0.5g polysialic acid (molecular weight 100kDa) dissolved in 9ml sodium carbonate-sodium bicarbonate buffer (pH10), then add 0.3ml epichlorohydrin and 1ml sodium hydroxide solution (2% mass volume concentration), at 45 Stir magnetically at ℃ for 3 hours, then remove excess epichlorohydrin in vacuum, concentrate the solution to 1 / 3 of the original volume under reduced pressure, and conduct precipitation with a mixture of water: ethanol (volume ratio 1:4), and the obtained precipitate is used The ethanol aqueous solution was repeatedly precipitated and purified to obtain activated polysialic acid.

[0065] With the ratio of PSA:HA mass ratio of 1:1, add activated PSA to 30ml of HA solution with a concentration of 1% (g / ml) (HA molecular weight is 3000KDa. The HA solution is citric acid-lemon at pH 4.0 Sodium acid buffer solution as the solvent), stirred and reacted at 25°C for 96 hours, after the reaction, the reaction solution was concentrated under reduced pressure ...

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Abstract

The invention discloses a preparation method of polysialic acid-hyaluronic acid composite gel, an obtained product and an application. The preparation method comprises steps as follows: in an alkaline aqueous solution environment, polysialic acid is linked with a crosslinking agent, and activated polysialic acid is obtained; the activated polysialic acid is added to a hyaluronic acid solution, so that the polysialic acid is grafted on the hyaluronic acid in an acid environment, and the product is obtained. The reaction process is controllable, few side reactions exist, the obtained product has excellent biocompatibility of the hyaluronic acid and non-immunogenicity of the polysialic acid, can be applied to embedded slow-release of polypeptide or protein drugs and can also applied to coating of crosslinked hyaluronic acid gel particles for injection, the postoperative inflammatory reaction is reduced, skin redness and swelling are relieved, pain of users is relieved, besides, the product stability can be improved, the degradation time can be prolonged, and the half-life period can be prolonged.

Description

technical field [0001] The invention relates to a preparation method of polysialic acid-hyaluronic acid composite gel, the obtained polysialic acid-hyaluronic acid composite gel and the application of the composite gel, belonging to the technical field of polymer materials. Background technique [0002] With the development of biomedical engineering, many new biosynthetic materials have been widely studied and applied in the fields of induced tissue regeneration, skin filling, and drug sustained release due to their diverse properties and ease of processing. The grafting and cross-linking modification of biocompatible polysaccharides as biomaterials has become a current research hotspot. [0003] Polysialic acid (PSA) is an electronegative, homotype polymer linked by N-acetylneuraminic acid (a type of sialic acid) with α-2,8 glycosidic bonds; in the human body, polysialic acid exists in On the nerve adhesion molecule (NCAM), it acts as a cell interaction regulator, and PSA ...

Claims

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Application Information

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IPC IPC(8): C08G81/00C08B37/08C08B37/00A61K47/36A61K9/06A61K9/00A61L27/20A61L27/50A61L27/52
CPCA61K9/0019A61K9/06A61K47/36A61L27/20A61L27/50A61L27/52A61L2400/06C08B37/00C08B37/0072C08G81/00C08L5/08
Inventor 吴剑荣辛瑜金雪坤张春莉
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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