Method for removing endotoxin in oligomeric sodium hyaluronate

Abstract

The invention discloses a method for removing endotoxin in oligomeric sodium hyaluronate, and the method comprises the following steps in sequence: (1) performing raw material endotoxin limit detection; (2) dissolving the oligomeric sodium hyaluronate in water; (3) respectively adding a sodium hydroxide solid and a sodium chloride solid, and stirring; (4) adjusting the pH of the solution to neutrality; and (5) adding ethanol for precipitation, dewatering and drying to obtain oligomeric sodium hyaluronate powder. The method has the advantages of thorough treatment, simple steps and low cost, and the endotoxin content of the treated oligomeric sodium hyaluronate reaches the medical standard (less than 0.05 EU / mg).

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for removing endotoxin in oligomeric sodium hyaluronate. Background technique [0002] Oligomeric sodium hyaluronate is a molecular fragment of sodium hyaluronate with a very low molecular weight prepared by the degradation of hyaluronic acid, and is an inherent component in the human body. It has strong skin permeability and can penetrate into the cutin of the skin. At the same time, it has all-round moisturizing and anti-aging properties, and has a wide range of applications in the field of cosmetics. The injection oligomeric sodium hyaluronate is more easily absorbed than sodium hyaluronate, and can be used for injection repair of bone and joint trauma and wrinkle removal. [0003] Endotoxin is a substance released by Gram-negative bacteria, and the human body is extremely sensitive to endotoxin. Endotoxin can cause fever, microcirculation disturbance...

AI Technical Summary

Problems solved by technology

Existing endotoxin removal methods mainly include liquid phase separation, activated carbon adsorption, quaternary ammonium salts drug removal, and ultrafiltration, but these endotoxin removal methods have problems such as incomplete treatment, long time and high cost.

[0004] The liquid phase separation method uses some detergents, such as Triton-114. Sodium deoxycholate can combine with the lipid part of endotoxin to remove endotoxin by extraction, but there will be detergent residue in the removed product, which is not Conform to medical grade quality requirements of oligomeric sodium hyaluronate

Activated carbon uses the gaps to absorb impurities and remove endotoxins at the same time. However, due to the limitation of pore size, the endotoxin removal effect in general oligomeric hyaluronic acid is 0.5 EU / mg, which is ten times greater than the medical grade standard of 0.05 EU / mg, and cannot reach the medical grade. Quality requirements

Quaternary ammonium salts such as cetylpyridinium chloride (CPC) combine with oligomeric sodium hyaluronate to form a chelate, remove impurities by washing the chelate, and then dissociate CPC and oligomeric sodium hyaluronate , remove CPC by alcohol precipitation and washing, and obtain oligomeric hyaluronate sodium. The quality of this method is reliable and stable, but the steps are cumbersome, the amount of sodium chloride and alcohol is relatively large, and the cost is high

Ultrafiltration is a commonly used method for removing endotoxin, but both endotoxin and oligomeric hyaluronate are lipopolysaccharides with similar molecular weights, so ultrafiltration cannot remove impurities in oligomeric hyaluronic acid, including toxin