Preparation method and application of cross-linked hyaluronic acid gel microspheres

A technology of cross-linked hyaluronic acid and gel microspheres, applied in the medical field, can solve the problems of residual oil phase, residual surfactant, inability to clean the cross-linked hyaluronic acid microbeads, etc., and achieve controllable particle size distribution. , good shape, easy to remove clean effect

Active Publication Date: 2018-09-04
ZHEJIANG UNIVERSITY OF SCIENCE AND TECHNOLOGY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the present invention also uses the oil phase and the active agent, and the crosslinked hyaluronic acid microbeads obtained in the final product fail to carry out effective oil phase residue, surfactant residue and crosslinking agent residue control measures, and there are many impurities in the product. , the transparency is not enough, the problem that cannot be cleaned

Method used

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  • Preparation method and application of cross-linked hyaluronic acid gel microspheres

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] (1) Prepare a hyaluronic acid alkaline solution with a concentration of 5% g / ml. The hyaluronic acid used is the hyaluronic acid produced by bacterial fermentation with a molecular weight of 2 million Daltons.

[0035] (2) In the organic phase cyclohexane, add the inorganic dispersant basic magnesium carbonate under stirring, and stir fully to make it evenly dispersed. The particle size of the inorganic dispersant basic magnesium carbonate is less than 15 microns. The weight ratio of the hyaluronic acid alkaline solution and cyclohexane in this embodiment is 1:1; the mass percentage of the inorganic dispersant in n-hexane is 0.5%.

[0036] (3) Add the hyaluronic acid alkaline solution prepared in step (1) into the organic phase prepared in step (2) under stirring, so that the hyaluronic acid alkaline solution can be fully dispersed to form a suspension.

[0037](4) Slowly add a certain amount of cross-linking agent divinyl sulfone dropwise under stirring, and stir at r...

Embodiment 2

[0041] (1) Prepare a hyaluronic acid alkaline solution with a concentration of 30% g / ml. The hyaluronic acid used is the hyaluronic acid produced by bacterial fermentation with a molecular weight of 500,000 Daltons.

[0042] (2) In the organic phase cyclohexane, add the inorganic dispersant calcium hydroxyphosphate under stirring, and stir well to make it disperse evenly. The particle size of the inorganic dispersant calcium hydroxyphosphate is less than 15 microns. The weight ratio of the hyaluronic acid alkaline solution and cyclohexane in this embodiment is 1:10; the mass percentage of the inorganic dispersant in n-hexane is 5%.

[0043] (3) Add the hyaluronic acid alkaline solution prepared in step (1) into the organic phase prepared in step (2) under stirring, so that the hyaluronic acid alkaline solution can be fully dispersed to form a suspension.

[0044] (4) Slowly add a certain amount of cross-linking agent 1,4-butanediol diglycidyl ether dropwise under stirring, an...

Embodiment 3

[0048] (1) Prepare a hyaluronic acid alkaline solution with a concentration of 10% g / ml. The hyaluronic acid used is the hyaluronic acid produced by bacterial fermentation with a molecular weight of 1.5 million Daltons.

[0049] (2) In the organic phase cyclohexane, add the inorganic dispersant calcium carbonate under stirring, stir well to make it disperse evenly. The particle size of the inorganic dispersant calcium carbonate is less than 15 microns. The weight ratio of the hyaluronic acid alkaline solution and cyclohexane in this embodiment is 1:5; the mass percentage of the inorganic dispersant in n-hexane is 1.5%.

[0050] (3) Add the hyaluronic acid alkaline solution prepared in step (1) into the organic phase prepared in step (2) under stirring, so that the hyaluronic acid alkaline solution can be fully dispersed to form a suspension.

[0051] (4) Slowly add a certain amount of cross-linking agent ethylene glycol diglycidyl ether dropwise under stirring, and stir at ro...

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Abstract

The invention discloses a preparation method and application of cross-linked hyaluronic acid gel microspheres. The preparation method comprises the steps that a hyaluronic acid alkaline solution withthe concentration being 5-30% g / ml is prepared, inorganic dispersants are added into organic phase cyclohexane under stirring, full stirring is conducted, and thus the inorganic dispersants are uniformly dispersed. By adopting the technical scheme, the preparation method is simple, products are controllable in particle size, intact in form, low in impurity content, high in purity and highly transparent, and meanwhile, the degradation period can also be controlled within the range of 30-300 days. In the preparation method and the application of the cross-linked hyaluronic acid gel microspheres,the cross-linked hyaluronic acid gel microspheres prepared through the preparation method can be used for producing medical or prevention products and used for injection, tissue repair and tissue strength in animals and especially in humans; and because of the extremely-low impurity content, the products have good biocompatibility and degradability, and clinical safety is ensured.

Description

technical field [0001] The invention relates to the medical field, in particular to a preparation method and application of cross-linked hyaluronic acid gel microspheres. Background technique [0002] Hyaluronic acid is an acidic mucopolysaccharide, which was first isolated from bovine vitreous by Meyer et al. in the United States in 1934. It has high viscoelasticity, unique moisture retention, biocompatibility and degradability, and has been widely used in ophthalmology, orthopedics, cosmetics, health food, pharmaceutical excipients and other fields. With the in-depth understanding of the structure, it was found that it has multiple sites that can be cross-linked and modified, thus developing cross-linked hyaluronic acid. [0003] Hyaluronic acid (HA) is a chain-like polyanionic mucopolysaccharide composed of repeated links of glucuronic acid and N-acetylglucosamine disaccharide units, the specific structure and its modification site (see formula 1). There are three sites...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/50A61L27/20A61L27/02A61L27/12
CPCA61L27/025A61L27/12A61L27/20A61L27/50A61L2400/06C08L5/08
Inventor 张治国索艳格黄伟孙伟庆
Owner ZHEJIANG UNIVERSITY OF SCIENCE AND TECHNOLOGY
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