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A kind of hyaluronic acid molecular weight classification method

A classification method and technology of sodium hyaluronate, applied in the field of hyaluronic acid molecular weight classification, can solve the problems of high cost, high equipment requirements, and unsuitability for large-scale production.

Active Publication Date: 2021-12-03
HEC PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is difficult to obtain high molecular weight sodium hyaluronate with high economic value and medical grade requirements
[0004] Ultrafiltration membrane separation technology such as CN103319627A has high requirements for equipment and high cost, and is not suitable for large-scale production and only two specifications of hyaluronic acid finished products can be obtained

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Take 1.0 g of a sodium hyaluronate sample with a molecular weight of 747,000 Da, dissolve it in 600 mL of purified water to obtain a sodium hyaluronate solution with a concentration of 1.67 g / L, adjust the concentration of the sodium hyaluronate solution with 1 mol / L NaOH or HCl After the pH value was 6.5, 40.0 g of strong base anion exchange resin was added, stirred and adsorbed for 8 hours. Filter the solution to obtain the resin. The desorption process is divided into 3 stages: first add 2M NaCl 600mL solution and let it stand for 3h for analysis, during this period stir once every 1h, and then filter to obtain the first analysis solution; then add 2M NaCl 600mL solution for 3h and stir for 3h, the stirring speed is 100rpm Then filter to obtain the second analytical solution; finally add 2M NaCl+0.1M NaOH 600mL solution and stir for regeneration for 3 hours, then filter to obtain the regeneration solution. The first analysis solution, the second analysis solution an...

Embodiment 2

[0079] Take 1.0 g of a sodium hyaluronate sample with a molecular weight of 747,000 Da, dissolve it in 600 mL of purified water to obtain a sodium hyaluronate solution with a concentration of 1.67 g / L, adjust the concentration of the sodium hyaluronate solution with 1 mol / L NaOH or HCl After the pH value was 6.5, 40.0 g of strong base anion exchange resin was added, stirred and adsorbed for 8 hours. Filter the solution to obtain the resin. The desorption process is divided into 3 stages: first add 0.1M NaCl 600mL solution and let it stand for analysis for 3 hours, during this period stir once every 1 hour, and then filter to obtain the first analysis solution; then add 2M NaCl 600mL solution and stir for 3 hours, the stirring speed After 100 rpm, filter to obtain the second analysis solution; finally add 2M NaCl+0.1M NaOH 600mL solution and stir for regeneration for 3 hours, then filter to obtain the regeneration solution. The first analysis solution, the second analysis solu...

Embodiment 3

[0082] Take 1.0 g of a sodium hyaluronate sample with a molecular weight of 925,000 Da and dissolve it in 600 mL of purified water to obtain a sodium hyaluronate solution with a concentration of 1.67 g / L and a pH value of 5.65. Add 40.0 g of strong base anion exchange resin therein and stir for adsorption for 8 hours. Filter the solution to obtain the resin. The desorption process is divided into 3 stages: first add 2M NaCl 600mL solution and let it stand for analysis for 3 hours, stir once every 1 hour during this period, and then filter to obtain the first analysis solution; then add 2M NaCl 600mL solution and stir for 3 hours, after the stirring speed is 100rpm Filter to obtain the second analytical solution; finally add 2M NaCl+0.1M NaOH 600mL solution and stir for regeneration for 3 hours, then filter to obtain the regeneration solution. The first analysis solution, the second analysis solution and the regeneration solution were respectively precipitated with 2 times the...

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Abstract

The invention provides a method for grading the molecular weight of sodium hyaluronate, which is characterized in that it comprises the following steps: (1) preparing a sodium hyaluronate solution; (2) adding 4% to the sodium hyaluronate solution in step (1) 40% (w / v) strong base anion exchange resin, stirring and adsorbing; (3) adding the first strong electrolyte salt solution, standing to analyze the resin, and collecting the first analysis solution; (4) adding the second strong electrolyte salt solution, Stir and analyze the resin, collect the second analysis solution; (5) add the third strong electrolyte salt solution and inorganic alkali solution to regenerate the resin, collect the regeneration solution; (6) ethanol the first analysis solution, the second analysis solution and the regeneration solution respectively Precipitation; (7) drying. The method uses a resin separation technology with low cost and simple operation, and adopts static adsorption, which is suitable for large-scale production.

Description

technical field [0001] The invention relates to a method for grading the molecular weight of hyaluronic acid. Background technique [0002] Hyaluronic acid (HA for short), also known as hyaluronic acid, is a linear macromolecular acidic mucopolysaccharide formed by repeated alternation of D-glucuronic acid and N-acetylglucosamine disaccharide units. Charge, its weight-average molecular weight is generally 100,000 to 10 million Da, and sodium hyaluronate is the sodium salt form of hyaluronic acid. The current commercialized HA is generally in the form of Na salt, which is a white fibrous or powdery solid with strong hygroscopicity, soluble in water, and insoluble in organic solvents. More than 2 million Da is high molecular weight HA; 1 million Da-2 million Da is medium molecular weight HA; 10,000 Da-1 million Da is low molecular weight HA; less than 10,000 is oligomeric HA. Its molecular weight is closely related to its physiological functions, and sodium hyaluronate with ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/08
CPCC08B37/0072
Inventor 罗明明石江水林小鹊王海刚屈代鑫郭振权赵裕栋张鸿李文佳
Owner HEC PHARM CO LTD