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Method for preparing crosslinked hyaluronic acid microgel for tissue filling

A technology of cross-linked hyaluronic acid and microgel, which is applied in the fields of medical cosmetology and biomedicine, can solve problems not described, and achieve good biocompatibility, good stability, and long-term effects

Inactive Publication Date: 2008-08-20
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned patents only describe the preparation process of cross-linked hyaluronic acid gel blocks, the removal of impurities in the gel, that is, unreacted cross-linking agents, the process of preparing injectable gels, and the biocompatibility of gels. etc., not described

Method used

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  • Method for preparing crosslinked hyaluronic acid microgel for tissue filling

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029]1.0g of sodium hyaluronate dry powder (molecular weight: 1,000,000 Daltons) derived from bacterial fermentation, whose structure is shown in Figure 1, was dissolved in 10ml of 0.2M NaOH solution, stirred to make it completely dissolved, and prepared into 10.0 % (w / v) hyaluronic acid alkaline solution, the reaction formula is shown in Figure 2, add 1.3g of butanediol diglycidyl ether, and stir well. Pour it into a 24-well plate for cell culture with a volume of about 2.9ml per well, and place it in a 35°C incubator for 6 hours to form cross-linked hyaluronic acid gel blocks of uniform size and regular shape. Take out the gel block, add it to 50ml of hydrochloric acid solution with a concentration of 0.1M, and place it at room temperature for 14 hours. The physiological balance solution was replaced 10 times, and the physiological balance solution used for dialysis was 500ml each time. Remove the physiological balance liquid, put the cross-linked hyaluronic acid gel block...

Embodiment 2

[0031] Dissolve 1.0g of sodium hyaluronate dry powder (molecular weight: 1,000,000 Daltons) derived from bacterial fermentation in 10ml of 0.5M NaOH solution, stir to dissolve completely, and prepare 10.0% (w / v) hyaluronic acid Alkaline solution, add 1.0 g of butanediol diglycidyl ether, and stir well. Pour it into a 24-well plate for cell culture with a volume of about 2.9ml per well, and place it in a 35°C incubator for 6 hours to form cross-linked hyaluronic acid gel blocks of uniform size and regular shape. Take out the gel block and add into 50ml of hydrochloric acid solution with a concentration of 0.1M, and stand at room temperature for 14 hours. Then pour off the hydrochloric acid solution, wash and dialyze with the physiological balance solution, and in the following 5 days, change the physiological balance solution 10 times, and the physiological balance solution used for dialysis is 500ml each time. Remove the physiological balance liquid, put the cross-linked hyal...

Embodiment 3

[0033] Dissolve 1.0g of sodium hyaluronate dry powder (molecular weight: 1.2 million Daltons) derived from bacterial fermentation in 10ml of 0.2M NaOH solution, stir to dissolve completely, and prepare 10.0% (w / v) hyaluronic acid Alkaline solution, add 1.2 g of ethylene glycol diglycidyl ether, and stir well. Pour it into a 24-well plate for cell culture with a volume of about 2.9ml per well, and place it in a 37°C incubator for 4 hours to form cross-linked hyaluronic acid gel blocks of uniform size and regular shape. The gel block was taken out, added to 50ml of hydrochloric acid solution with a concentration of 0.1M, and left at room temperature for 16 hours. Then pour off the hydrochloric acid solution, wash and dialyze with the physiological balance solution, and in the following 5 days, change the physiological balance solution 10 times, and the physiological balance solution used for dialysis is 500ml each time. Remove the physiological balance liquid, put the cross-lin...

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Abstract

The invention relates to a preparation method of cross-linking hyaluronic acid microgel for tissue filler; wherein, the monolithic gel is generated by the cross-linking reaction of the hyaluronic acid and the di-epoxide in the certain mold and processed by acid solution; the purification and dialysis by physiological balanced solution are processed; the microgel is made by extrusion of mechanical equipment. The cross-linking hyaluronic acid microgel has the advantages of (1) specific physical properties that the storage modulus (G') is 500-2000Pa, the loss modulus (G'') is 50-200Pa, the phase angle (Delta) is below 20 and the complex viscosity (Eta*) is 10-3500Pa x s as described by the dynamic viscoelasticity at frequency of 0.05-10Hz, (2) good stability that the performance of gel is independent of high pressure-high temperature treatment and the enzymolysis-resistant performance is excellent, (3) injectable property that the size of fine particle is 50-1000Mum, (4) good biocompatibility of no cytotoxicity, (5) biodegradability of being fully degraded by hyaluronidase, and (6) being suitable for tissue filler and bio-medical treatment.

Description

technical field [0001] The present invention relates to a preparation method of a cross-linked hyaluronic acid microgel for tissue filling, in particular to a preparation method of a water-insoluble cross-linked hyaluronic acid microgel, which can be implanted through an injection needle Into the soft tissue, it plays the role of filling wrinkle removal, filling depression and lip augmentation, etc., and belongs to the field of medical cosmetology and biomedical technology. Background technique [0002] Hyaluronic acid is a linear polymer polysaccharide composed of glucuronic acid and acetylglucosamine disaccharides combined with each other. It is widely present in the connective tissue of mammals, cockscomb and the capsule of streptococci. Hyaluronic acid is a physiological substance with high viscoelasticity, good biocompatibility, non-immunogenicity, no species specificity, and does not cause allogeneic rejection and allergic reactions when implanted into the human body ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/20A61L31/04
Inventor 葛翠兰顾其胜朱彬刘秀杰
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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