Process for preparing cross-linked sodium hyaluronate microspheres capable of being adopted as emboliaztion agent by adopting sodium hyaluronate as raw material

A cross-linked hyaluronic acid and sodium hyaluronate technology, which is applied in the field of interventional medicine, can solve the problems of cross-linked hyaluronic acid microbeads without effective oil phase residue, cross-linking agent residue control measures, and inapplicability. Good biocompatibility and degradability, good microsphere shape, and easy sieving effect

Active Publication Date: 2013-10-02
HANGZHOU SINGCLEAN MEDICAL PROD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The microbeads obtained by this method are uniform in shape, and the particle size distribution is between 1nm and 1μm. However, the finally obtained cross-linked hyaluronic acid microbeads have not been effectively controlled by oil phase residue and crosslinker residue, and are also not suitable for interventional procedures. Embolization

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  • Process for preparing cross-linked sodium hyaluronate microspheres capable of being adopted as emboliaztion agent by adopting sodium hyaluronate as raw material
  • Process for preparing cross-linked sodium hyaluronate microspheres capable of being adopted as emboliaztion agent by adopting sodium hyaluronate as raw material
  • Process for preparing cross-linked sodium hyaluronate microspheres capable of being adopted as emboliaztion agent by adopting sodium hyaluronate as raw material

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (1) Weigh 3.07 g of sodium hyaluronate dry powder with a molecular weight of 1.3 million Daltons, and prepare it with 1% NaOH solution to form a sodium hyaluronate lye gel with a mass percent concentration of 10% g / ml;

[0029] (2) Mix 100.05g of liquid paraffin and 2.03g of Span80 to obtain the oil phase, slowly add the sodium hyaluronate gel in step (1) into the oil phase, emulsify at high speed with a mixer, the emulsification speed is 1000rpm, and the time is 10min;

[0030] (3) After the emulsification in step (2) is completed, add 1ml of cross-linking agent (BDDE), stir at room temperature for 4 hours for cross-linking reaction, and let stand overnight after completion;

[0031] (4) Pour off the upper oil phase, and repeatedly wash the remaining oil phase on the surface of the microspheres with ethyl acetate, and then repeatedly wash the microspheres with absolute ethanol to remove ethyl acetate;

[0032] (5) Put the microspheres obtained in step (4) into a vacuu...

Embodiment 2

[0037] (1) Weigh 3.02 g of sodium hyaluronate dry powder with a molecular weight of 1.3 million Daltons, and mix it with 1% NaOH to prepare a sodium hyaluronate lye gel with a mass percent concentration of 15% g / ml;

[0038] (2) Mix 100.12g of liquid paraffin and 2.04g of Span80 to obtain an oil phase, slowly add the sodium hyaluronate gel in step (1) into the oil phase, and emulsify with high-speed shearing by an emulsifier at a shear rate of 1000rpm, the time is 10min;

[0039] (3) After the emulsification in step (2) is completed, add 1ml of cross-linking agent (BDDE), stir at room temperature for 4 hours for cross-linking reaction, and let stand overnight after completion;

[0040] (4) Pour off the upper oil phase, and repeatedly wash the remaining oil phase on the surface of the microspheres with ethyl acetate, and then repeatedly wash the microspheres with absolute ethanol to remove ethyl acetate;

[0041] (5) Put the microspheres obtained in step (4) into a vacuum dryi...

Embodiment 3

[0048] (1) Weigh 3.03 g of sodium hyaluronate dry powder with a molecular weight of 1.3 million Daltons, and mix it with 1% NaOH to prepare a sodium hyaluronate lye gel with a mass percent concentration of 10% g / ml;

[0049] (2) Mix 150.15g of liquid paraffin and 2.68g of Span80 to obtain an oil phase, slowly add the sodium hyaluronate gel in step (1) into the oil phase, and emulsify with high-speed shearing by an emulsifier at a shear rate of 1000rpm, the time is 10min;

[0050] (3) After the emulsification in step (2) is completed, add 1ml of cross-linking agent (BDDE), stir at room temperature for 4 hours for cross-linking reaction, and let stand overnight after completion;

[0051] (4) Pour off the upper oil phase, and repeatedly wash the remaining oil phase on the surface of the microspheres with ethyl acetate, and then repeatedly wash the microspheres with absolute ethanol to remove ethyl acetate;

[0052] (5) Put the microspheres obtained in step (4) into a vacuum dryi...

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Abstract

The present invention provides a process for preparing cross-linked sodium hyaluronate microspheres capable of being adopted as an emboliaztion agent by adopting sodium hyaluronate as a raw material. The process comprises the following steps: preparing a sodium hyaluronate alkaline solution gel with a concentration of 10-30% g/ml; adding the sodium hyaluronate alkaline solution gel to an emulsifier-containing oil phase, and carrying out high speed emulsification through a shearing machine, wherein an emulsification speed is 500-2000 rpm, and a time is 10-20 min; adding a certain amount of a cross-linking agent, stirring for 4-6 h at a room temperature, carrying out a cross-linking reaction, and standing overnight after completing the reaction, wherein a mass percentage of the cross-linking agent in the oil phase is 0.2-2%; and adopting a water-soluble organic solvent to wash to remove the oil phase remained on the surface of the microspheres, and finally drying to obtain the cross-linked sodium hyaluronate microspheres. According to the present invention, the preparation process is simple; and the size of the obtained microspheres is suitable for routine blood vessel emboliaztion, and the obtained microspheres have characteristics of controllable particle size, good microsphere shape, easy screening, elasticity, expandibility, no toxic-side effect on human body, good biocompatibility, good biodegradability, and ensured clinical safety.

Description

technical field [0001] The invention belongs to the field of interventional medicine, and specifically refers to a process for preparing a cross-linked sodium hyaluronate microsphere embolism agent using sodium hyaluronate as a raw material. Background technique [0002] At present, interventional therapy is widely used in the treatment of various diseases, involving the diagnosis and treatment of digestive, nervous, cardiovascular, respiratory, orthopedic, urological, gynecological and other systemic diseases, especially malignant tumors and other diseases that are difficult to treat by conventional medical methods . Interventional therapy can be divided into interventional chemotherapy, interventional hyperthermia, interventional cryotherapy, interventional endovascular isolation, and vascular embolization. Among them, vascular embolization to treat tumor diseases is a common method of interventional therapy. Its principle is to use a high-definition medical imager to gui...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08J3/16A61L31/04
Inventor 朱剑锋
Owner HANGZHOU SINGCLEAN MEDICAL PROD
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