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US 10,894,110 B2Granted
Developable hyaluronic acid microspherical embolic agent, preparation method and use thereof
AssigneeHangzhou Singclean Medical Products Co., Ltd
InventorJianfeng Zhu
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Abstract
A developable hyaluronic acid microspherical embolic agent includes a hyaluronic acid and an X-ray opaque contrast material; wherein the hyaluronic acid is a modified hyaluronic acid, wherein a modifying method for preparing the modified hyaluronic acid is cross-linking, grafting, esterification, or recombination, and is preferably cross-linking.
Claims10
A method of preparing a developable hyaluronic acid microspherical embolic agent, wherein the method comprises the following steps:
- 1) preparing a hyaluronic acid solution having a concentration ranging from 0.1 g/mL to 0.3 g/mL, wherein the solution contains an iodine compound;
- 2) adding the hyaluronic acid solution resulted from step 1) to a liquid paraffin containing an emulsifying agent, and emulsifying with a shearing machine at a speed ranging from 500 rpm to 2000 rmp, to produce a water-in-oil emulsion comprising hyaluronic acid microspheres embedded with the iodine compound;
- 3) adding 0.2-2 vol% of a cross-linking agent to the emulsion resulted from step 2), stirring the emulsion at room temperature for 4-6 hours for cross-linking reaction, keeping the emulsion still after the reaction is finished to form an oil phase layer and an aqueous phase layer, removing the oil phase layer, then washing the aqueous phase layer orderly with an acid solvent and a water soluble organic solvent, and vacuum drying the aqueous phase layer to obtain hyaluronic acid microspheres containing the iodine compound, wherein the microspheres are the hyaluronic acid microspherical embolic agents developable under an X-ray machine.
A method of preparing a developable hyaluronic acid microspherical embolic agent, wherein the method comprises the following steps:
- 1) preparing a hyaluronic acid in sodium hydroxide solution having a concentration of about 0.1 g/mL, wherein the solution contains 0.07 g/mL of iohexol;
- 2) adding the hyaluronic acid solution resulted from step 1) to a liquid paraffin containing about 200-205g of liquid paraffin and about 3.0 to 4.0g sorbitan oleate, and emulsifying with a shearing machine at a speed ranging from 500 rpm to 2000 rmp, to produce a water-in-oil emulsion comprising hyaluronic acid microspheres embedded with iohexol;
- 3) adding about 1% of 1,4-butanediol diglycidyl ether to the emulsion resulted from step 2), stirring the emulsion at room temperature for 4-6 hours for cross-linking reaction, keeping the emulsion still after the reaction is finished to form an oil phase layer and an aqueous phase layer, removing the oil phase layer, then washing the aqueous phase layer orderly with an acetic acid and in turn with ethyl acetate and absolute ethanol, and vacuum drying the aqueous phase layer to obtain hyaluronic acid microspheres containing iohexol, wherein the microspheres are hyaluronic acid microspherical embolic agents developable under an X-ray machine.
Dependencies are inferred from the claim text.