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Cross-linked hyaluronic acid derivatives preparation and the preparing technique

A technology of cross-linking hyaluronic acid and hyaluronic acid, which is applied in medical science, surgery, etc., can solve the problem of short residence time and achieve the effect of increasing viscoelasticity and enhancing stability

Active Publication Date: 2012-10-17
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the highest molecular weight of natural exogenous HA is about 1.7 million, and the residence time in the body is very short, which limits its application in some fields, such as soft tissue filling, because these applications require HA in the There is a long retention time in the body, the half-life of natural hyaluronic acid in the body is generally several days, and natural hyaluronic acid is degraded under acidic or alkaline or high temperature conditions

Method used

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  • Cross-linked hyaluronic acid derivatives preparation and the preparing technique
  • Cross-linked hyaluronic acid derivatives preparation and the preparing technique
  • Cross-linked hyaluronic acid derivatives preparation and the preparing technique

Examples

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Effect test

Embodiment 1

[0026] Dissolve 3 g of hyaluronic acid dry powder (molecular weight: 1,500,000 Daltons) in 200 ml of 1M NaOH solution, stir to dissolve completely. Add 2 g of divinyl sulfone and stir well. Place in a thermostat at 25°C for 24 hours to form cross-linked hyaluronic acid. Glucose solution was added to the cross-linked hyaluronic acid, and the reaction concentration of the glucose solution was 4%, and placed in a 25° C. incubator for 24 hours. The pH value of the cross-linked hyaluronic acid gel was adjusted to neutral with HCl solution. Take out the cross-linked hyaluronic acid gel block and put it into an electric mixer, stir, and the cross-linked hyaluronic acid block gel becomes a particulate gel. Sterilize by autoclaving at 121°C for 30 minutes.

Embodiment 2

[0028] Dissolve 5g of hyaluronic acid dry powder (molecular weight: 1,500,000 Daltons) in 200ml of 1M KOH solution, stir to dissolve completely. Add 5 g of divinyl sulfone and stir well. Place in a thermostat at 25°C for 24-48 hours to form cross-linked hyaluronic acid. Glucose solution was added to the cross-linked hyaluronic acid curd, and the reaction concentration of the glucose solution was 8%, and placed in a 25°C thermostat for 36 hours. The pH value of the cross-linked hyaluronic acid gel was adjusted to neutral with HCl solution. Take out the cross-linked hyaluronic acid gel block and put it into an electric mixer, stir, and the cross-linked hyaluronic acid block gel becomes a particulate gel. Sterilize by autoclaving at 121°C for 15 minutes.

Embodiment 3

[0030] Dissolve 4.5g of hyaluronic acid dry powder (molecular weight: 1,500,000 Daltons) in 200ml of 2M Na 2 CO 3 solution, stir to dissolve completely. Add 3.5 g of divinyl sulfone and stir well. Place in a thermostat at 25°C for 36 hours to form cross-linked hyaluronic acid. Glucose solution was added to the cross-linked hyaluronic acid curd, and the reaction concentration of the glucose solution was 6%, and placed in a 25° C. incubator for 32 hours. The pH value of the cross-linked hyaluronic acid gel was adjusted to neutral with HCl solution. Take out the cross-linked hyaluronic acid gel block and put it into an electric mixer, stir, and the cross-linked hyaluronic acid block gel becomes a particulate gel. Sterilize by autoclaving at 121°C for 20 minutes.

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Abstract

The invention relates to a preparation technique of crosslinked hyaluronic acid gel preparation, characterized in that divinylsulphone reacts with hydroxyl group of hyaluronic acid to form ether linkage. The steps are that the raw material of hyaluronic acid being put into container and dissolving in alkali reagent; stirring to make it thoroughly dissolve; mixing the alkaline hyaluronic acid solution and divinylsulphone in container to form crosslinked hyaluronic acid gel clot; adding substance riched in hydroxyl groups into the reaction solution; extracting the crosslinked hyaluronic acid gel clot and putting it into agitator to stir; and then crosslinked hyaluronic acid gel becoming micro grained. The advantages thereof are that the gel preparation is suitable for injection in vivo, with long residence timen in humans and good filling effect.

Description

technical field [0001] The invention relates to a cross-linked hyaluronic acid gel preparation and a preparation process thereof, which can be used for surgical anti-adhesion, subcutaneous injection filling for wrinkle removal, defect repair, intra-articular injection lubrication and shock absorption, and a carrier for drug delivery systems, etc. It belongs to the technical field of medical supplies. Background technique [0002] Hyaluronate acid (HA for short) is a linear polysaccharide composed of disaccharides of (1→4)-D glucuronic acid-β(1→3)-N-acetylglucose, widely present in human and animal cells In many soft connective tissues such as interstitium, vitreous body, umbilical cord, skin, joint synovial fluid and rooster comb. HA is a physiological substance with high viscoelasticity, unique rheological properties, good biocompatibility and non-immunogenicity, and is a widely used bioabsorbable material. Clinically, HA is often used in the treatment of osteoarthritis, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L31/04
Inventor 顾其胜奚珊珊
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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