Emulsified cross-linked sodium hyaluronate gel microspheres for injection and preparation method thereof

A technology of sodium hyaluronate and gel microspheres, which is applied in the field of medical materials and can solve problems such as product instability, uneven cross-linking degree, and irregular particle shape

Active Publication Date: 2020-09-22
HANGZHOU SINGCLEAN MEDICAL PROD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are many methods for preparing cross-linked hyaluronic acid at home and abroad. Usually, hyaluronic acid and cross-linking agent are stirred and mixed in an aqueous solution, and the cross-linking agent is added to form chemical bonds between hyaluronic acid polymer chains. Block gels are generally crushed mechanically or passed through a sieve under pressure to obtain different particle sizes, but the prepared cross-linked hyaluronic acid gels have uneven cross-linking degrees, irregular particle shapes, and uneven particle sizes. question
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Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] (1) Weigh 6.39 g of sodium hyaluronate with a molecular weight of 1.1 million to 1.3 million Daltons, and configure it with 1% NaOH solution to form a sodium hyaluronate lye gel with a mass percent concentration of 8% g / ml;

[0025] (2) Mix 300.05g of liquid paraffin and 18.03g of Span 80 to obtain an oil phase, slowly add the sodium hyaluronate gel obtained in step (1) into the oil phase, emulsify at high speed with a mixer, and the emulsification speed is 4000rpm, The time is 30 minutes;

[0026] (3) After the emulsification in step (2) is completed, add 1.06 g of the cross-linking agent divinyl sulfone, stir in an ice bath for 1 hour, stir in a room temperature for 1.5 hours, stir in a water bath at 40°C for 1 hour, and adjust the pH value to 5.0 with glacial acetic acid after cooling down;

[0027] (4) Pour the upper oil phase, add n-hexane to stir and clean for the first 8 minutes, pour off the upper oil phase after standing for stratification, add n-hexane and sti...

Embodiment 2

[0036] (1) Weigh 6.45 g of sodium hyaluronate with a molecular weight of 1.1 million to 1.3 million Daltons, and configure it with 1% NaOH solution to form a sodium hyaluronate lye gel with a mass percent concentration of 8% g / ml;

[0037] (2) Take 300.05g of liquid paraffin and mix 18.03g of Span 80 to obtain an oil phase, slowly add the sodium hyaluronate gel obtained in step (1) into the oil phase, emulsify at high speed with a mixer, and the emulsification speed is 4500rpm, The time is 30 minutes;

[0038] (3) After the emulsification in step (2) is completed, add 1.07 g of the cross-linking agent divinyl sulfone, stir in an ice bath for 1 hour, stir in a room temperature for 1.5 hours, and stir in a water bath at 40°C for 1 hour. After cooling down, adjust the pH value to 5.0 with glacial acetic acid;

[0039] (4) Pour the upper oil phase, add n-hexane to stir and clean for the first 8 minutes, pour off the upper oil phase after standing for stratification, add n-hexane a...

Embodiment 3

[0049] (1) Weigh 6.40 g of sodium hyaluronate with a molecular weight of 1.1 million to 1.3 million Daltons, and configure it with 1% NaOH solution to form a sodium hyaluronate lye gel with a mass percent concentration of 16% g / ml;

[0050] (2) Take 300.07g of liquid paraffin and mix 18.02g of Span 80 to obtain an oil phase, slowly add the sodium hyaluronate gel obtained in step (1) into the oil phase, emulsify at high speed with a mixer, and the emulsification speed is 4000rpm, The time is 30 minutes;

[0051] (3) After the emulsification in step (2) is completed, add 1.06 g of the cross-linking agent divinyl sulfone, stir in an ice bath for 1 hour, stir in a room temperature for 1.5 hours, stir in a water bath at 40°C for 1 hour, and adjust the pH value to 5.0 with glacial acetic acid after cooling down;

[0052] (4) Pour the upper oil phase, add n-hexane to stir and clean for the first 8 minutes, pour off the upper oil phase after standing for stratification, add n-hexane a...

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Abstract

The invention provides a preparation method of emulsified cross-linked sodium hyaluronate gel microspheres for injection. The preparation method comprises the following steps: firstly, preparing an emulsion of sodium hyaluronate microsphere particles; adding a cross-linking agent into the emulsion according to a certain mass ratio of the cross-linking agent to the sodium hyaluronate;, stirring anduniformly mixing the components in an ice bath, then stirring the mixture at room temperature to carry out primary reaction; and finally stirring the reactant in a water bath at 35-42 DEG C to reactto obtain a microsphere emulsion; cleaning the reaction product with n-hexane, ethyl acetate and absolute ethyl alcohol in sequence. According to the preparation method, uniform and ordered cross-linking reaction in a single sodium hyaluronate colloidal particle is ensured, so that proper viscous modulus, elastic modulus and pushing force are obtained, cross-linking reaction among the particles isavoided, and the yield of qualified gel microspheres is increased. The gel microsphere is suitable for injection and has a wide application prospect.

Description

technical field [0001] The invention relates to the technical field of medical materials, in particular to an emulsified cross-linked sodium hyaluronate gel microsphere for injection and a preparation method thereof. Background technique [0002] Sodium hyaluronate (SH) is an acidic mucopolysaccharide. As early as 1930-1940, Meyer extracted sodium hyaluronate from animal synovial fluid, skin, rooster comb, and human umbilical cord. Kendell et al. extracted SH from bacteria in 1937. Although SH obtained from different sources and different refining methods has different molecular weights, there is no species difference. Hyaluronic acid preparations have a long history of medical use, usually in ophthalmology and orthopedics. In 1962, sodium hyaluronate preparations (Healon Xilang) were approved by the FDA for use as substitutes for aqueous humor and vitreous in ophthalmic surgery and Substrates for ophthalmic topical drugs. Since then, it has also been used for joint cavit...

Claims

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Application Information

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IPC IPC(8): B01J13/14B01J13/02A61L27/20A61L27/50A61L27/52
CPCB01J13/14B01J13/02A61L27/20A61L27/50A61L27/52C08L5/08
Inventor 邓连霞周奎孙伟庆
Owner HANGZHOU SINGCLEAN MEDICAL PROD
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