Method for preparing cross-linked hyaluronic acid

A technology for cross-linking hyaluronic acid and hyaluronic acid, which is applied in the field of manufacturing cross-linking hyaluronic acid, can solve the problems of inability to remove the cross-linking agent, cannot effectively remove the cross-linking agent, and reduce the content of the cross-linking agent, so as to achieve a low content of the cross-linking agent. , high biocompatibility, overcoming the effect of purification steps

Active Publication Date: 2010-06-09
SCIVISION BIOTECH
View PDF5 Cites 20 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of the colloids obtained under these reactions have purification steps to remove the cross-linking agent or have no purification procedures, but still have a considerable amount or a large amount of cross-linking agent
[0013] The methods for removing the cross-linking agent known in the cu

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing cross-linked hyaluronic acid
  • Method for preparing cross-linked hyaluronic acid
  • Method for preparing cross-linked hyaluronic acid

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0037] Example 1: Sodium hyaluronate concentration=20w / v%HHA, alkali concentration=0.5N, reaction temperature=30℃, crosslinking agent concentration=1v / v% 1,2,7,8-diepoxyoctane

[0038] Take 8.9mL of deionized water, add 1mL of 5N sodium hydroxide aqueous solution and 0.1mL of cross-linking agent 1,2,7,8-diepoxyoctane, and add 2 grams (dry weight) with magnetic stirring, the average molecular weight is 135 Sodium hyaluronate (high molecular weight hyaluronic acid, HHA) was stirred at room temperature for 5 minutes, and then placed in a thermostat at 30°C for the reaction time shown in Table 1. After the reaction, 79.2mL of 0.073M phosphate buffer solution with a pH of 7.0±0.2 and 0.8mL of 6N hydrogen chloride aqueous solution were added to the resulting reaction to homogenize to physiologically acceptable pH and osmotic pressure. After homogenizing the colloidal solution, the cross-linked hyaluronic acid product can be obtained.

[0039] The homogenized cross-linked hyaluronic acid...

Example Embodiment

[0040] Example 2: 1,3-Diepoxybutane with sodium hyaluronate concentration=20w / v%HHA, alkali concentration=0.5N, reaction temperature=30℃, crosslinking agent concentration=1v / v%

[0041] Except that the crosslinking agent is changed to 1,3-diepoxybutane, the rest of the reaction conditions and the content determination method are the same as in Example 1. The content of crosslinked hyaluronic acid and the content of crosslinking agent with free functional groups of the products obtained under different reaction times are shown in Table 1.

Example Embodiment

[0042] Example 3: 1,4-Butanediol diglycidyl ether with sodium hyaluronate concentration=20w / v%HHA, alkali concentration=0.25N, reaction temperature=10℃, crosslinking agent concentration=1v / v%

[0043] Take 9.4mL of deionized water, add 0.5mL of 5N sodium hydroxide aqueous solution and 0.1mL of cross-linking agent 1,4-butanediol diglycidyl ether, add 2 grams (dry weight) with magnetic stirring, the average molecular weight is 1.35 million Sodium hyaluronate (HHA) was stirred at room temperature for 5 minutes, and then placed in a thermostat at 10°C for reaction. After the reaction, 79.6mL of a 0.1M phosphate buffer solution with a pH of 7.0±0.2 and 0.4mL of a 6N hydrogen chloride aqueous solution were added to the resulting reaction to homogenize to physiologically acceptable pH and osmotic pressure. After homogenizing the colloidal solution, a cross-linked hyaluronic acid product can be obtained. The method for determining the content of the crosslinked hyaluronic acid and the c...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a method for preparing cross-linked hyaluronic acid, which comprises the step of ensuring that a cross-linking reaction of solution containing hyaluronic acid is performed for more than about 48 hours at the low temperature of between about 10 and about 30 DEG C. The method can reduce the content of a cross-linking agent without a purification step.

Description

technical field [0001] The present invention relates to a technology for producing cross-linked hyaluronic acid (cross-linked HA). Specifically, the present invention relates to a method for producing cross-linked hyaluronic acid that reduces the content of cross-linking agents in products. Background technique [0002] Hyaluronic acid is a polysaccharide whose structure consists of β-1,3-glucoseacetamide (β-1,3-N-acetyl glucosamine) and β-1,4-glucuronic acid (β-1,4-glucuronic acid ) with β-1-4 bonds to form a disaccharide repeating unit with a molecular weight of about 400D, which is then repeatedly linked with β-1-3 bonds to form a linear polymer. Its commercial sources can be obtained from the acid fermentation of strains such as Streptococcus and from animal tissues such as cockscombs. [0003] Hyaluronic acid, its salts or its derivatives are widely used in cosmetics, biomedicine, medical equipment and pharmaceutical. [0004] Straight-chain hyaluronic acid is easil...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C08J3/24C08L5/08C08K5/1515
Inventor 陈拓成陈丽夙
Owner SCIVISION BIOTECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products