US-12617875-B2 - Method for purifying a sodium alginate powder from endotoxins and endogenous pyrogens

US12617875B2US 12617875 B2US12617875 B2US 12617875B2US-12617875-B2

Abstract

A method for purifying a sodium alginate powder from endotoxins and endogenous pyrogens is provided. The sodium alginate powder is thermally treated at a temperature selected based on the viscosity of the sodium alginate powder. A suspension is prepared by adding an organic solvent to the sodium alginate powder, whereafter the suspension is mechanically stirred until homogeneous. The organic solvent comprises a mixture of hexane and isopropyl alcohol in a ratio of 0.5:1-2:1. When particles of the sodium alginate powder are sedimented, a liquid dispersed medium is removed from the suspension. The particles of the sodium alginate powder are dried, and a sodium alginate solution is prepared by dissolving the dried particles in pure water. A silver-impregnated activated carbon powder containing 0.01-0.4 wt % silver is added to the sodium alginate solution. The sodium alginate solution is purified by using ultrafiltration first and then lyophilization or spray drying.

Inventors

Iurii Uss
Sergey Yudin
Denis Turishchev

Assignees

Iurii Uss
Sergey Yudin
Denis Turishchev

Dates

Publication Date: 20260505
Application Date: 20230906

Claims (6)

1 . A method for purifying a sodium alginate powder from endotoxins and endogenous pyrogens, comprising: providing the sodium alginate powder comprising the endotoxins and the endogenous pyrogens, the sodium alginate powder having a viscosity; subjecting the sodium alginate powder to heat treatment, the heat treatment being performed at a temperature selected based on the viscosity of the sodium alginate powder; preparing a suspension by adding an organic solvent to the sodium alginate powder, the organic solvent comprising a mixture of hexane and isopropyl alcohol in a ratio of 0.5:1-2:1, the suspension comprising a solid dispersed phase in a liquid dispersed medium, the solid dispersed phase comprising particles of the sodium alginate powder; mechanically stirring the suspension to a homogeneous state; when the particles of the sodium alginate powder are sedimented in the suspension, removing the liquid dispersed medium; subjecting the particles of the sodium alginate powder to drying; preparing a sodium alginate solution by dissolving the dried particles of the sodium alginate powder in pure water; adding a silver-impregnated activated carbon powder to the sodium alginate solution, the silver-impregnated activated carbon powder containing 0.01-0.4 wt % silver; purifying the sodium alginate solution containing the silver-impregnated activated carbon powder by using ultrafiltration; and subjecting the purified sodium alginate solution to lyophilization or spray drying, thereby obtaining the sodium alginate powder purified from the endotoxins and endogenous pyrogens.
2 . The method of claim 1 , wherein the heat treatment is performed at a temperature of 60-80° C. for 30-60 minutes.
3 . The method of claim 1 , wherein the particles of the sodium alginate powder are dried using forced ventilation at a temperature less than 60° C. for 1-3 hours.
4 . The method of claim 1 , wherein the pure water is one of Type I water, Type II water, Type III water, and wherein the dried particles of the sodium alginate powder are dissolved in the pure water at a temperature of 35-80° C. to a final concentration of 0.1-2%.
5 . The method of claim 1 , wherein said adding of the silver-impregnated activated carbon to the sodium alginate solution comprises: pre-wetting the silver-impregnated activated carbon powder with purified water; adding the silver-impregnated activated carbon powder to the sodium alginate solution in a ratio of 0.1:1-1:1 at a temperature of 35-80° C.; and mechanically stirring the sodium alginate solution containing the silver-impregnated activated carbon powder until a uniform color of the sodium alginate solution is obtained.
6 . The method of claim 1 , wherein said ultrafiltration is performed by successively using a pre-filter and a sterilizing filter, the pre-filter comprising a dual cellulose acetate or polypropylene membrane having a pore size of 1-10 μm, and the sterilizing filter comprising a dual heterogeneous polyethersulfone membrane having a pore size of 0.2 μm.

Description

TECHNICAL FIELD The present disclosure relates generally to the field of cosmetology and medicine. In particular, the present disclosure relates to method for purifying a sodium alginate powder from endotoxins and endogenous pyrogens. BACKGROUND Polysaccharides are important components of brown algae, including alginate, fucoidan, laminaran, etc. Alginates, commonly referred to as sodium alginate, represent a linear copolymer having polysaccharide homopolymer blocks of (1-4)-linked β-D-mannuronate (M) and α-L-guluronate (G) residues. There are three types of structure of their segment chain: M blocks of continuous M units, G blocks of continuous G units, and an MG block formed by alternately connected G and M units. Alginates are also the most representative class of chemical products from algae. For ease of their storage and use, alginates are usually converted during their extraction from brown algae to sodium alginate as the final product. Being the sodium salt of an anionic polysaccharide (alginic acid), sodium alginate has a very wide range of industrial applications due to its inherent physical and chemical properties. Alginates are widely used due to their rheological properties as well as biocompatibility, biodegradability and lack of toxicity. The ratio of the three types of blocks, i.e., MM, GG and MG, determines the physical properties of alginates-high G alginates have higher gelling properties, while high M blocks have a higher viscosity. The evaluation of the M/G ratio is also fundamental—alginates having a high M/G ratio provide hard non-elastic gels, while alginates having a low M/G ratio provide soft elastic gels. Alginates having a high level of guluronic acid relative to mannuronic acid are most in demand. In cosmetology, alginates are used to create lines of medical cosmetics adapted to a specific consumer and combining cleansing, nourishing and protective functions. They can be used both as a component of an external agent, and as a separate hydrogel for subcutaneous use. Hydrogels for subcutaneous use maycontain biologically active substances (BAS), drugs and live cell cultures. In pharmacology, alginates are used as the basis for: a cellular material in 3D bioprinters (transplantology);passive and active systems for transdermal and buccal delivery of complex high-molecular drugs (e.g., insulin and other proteins, factors for transgenic therapy);immobilization of a cellular material (bacterial, yeast, plant and animal cell cultures) for use in the food, pharmaceutical and chemical industries;creation of biodegradable biopolymers for use in orthopedics;creation of a bioplatform for oral delivery of drugs sensitive to biotransformation (e.g., insulin) through the gastrointestinal system directly into the lymphatic and circulatory system, bypassing the liver and pancreas;creation of a bioplatform for encapsulation of biodegradable glucose microsensors and other biochemical markers (for continuous real-time monitoring) of transdermal and subcutaneous types;protection of cells/tissues during cryopreservation. However, the widespread use of sodium alginate in medical cosmetology and pharmacology is limited by the requirement of strict control over the content of endotoxin and endogenous pyrogens (peptides) in it. Typically, commercial alginates have endotoxin levels ranging from about 30000 EU/g to about 60000 EU/g. Pharmaceutical compositions for parenteral administration should generally contain no more than 100 EU/g. Therefore, before commercial alginates can be used parenterally, the endotoxin levels must be substantially reduced. Endotoxins are lipopolysaccharides that are an integral part of the outer membrane of gram-negative bacteria involved, among others, in stabilizing a bacterial cell wall. Although the endotoxins are strongly associated with the bacterial cell wall, they can be released into the environment not only during cell death, but also during their growth and division; in this case, one bacterial cell can contain approximately 2 million lipopolysaccharide molecules. Therefore, the endotoxins are found in all environments where gram-negative bacteria are found. Particularly high concentrations of the endotoxins are observed during the mass death of bacteria in the focus of infection and in the environments of biotechnological production. Even though the endotoxin itself is chemically inert, when it enters the bloodstream during a generalized bacterial infection, it binds to receptors and cells of the immune system that regulate an inflammatory response. In this case, an excessive release of inflammatory mediators (cytokines) occurs, and a too strong systemic inflammatory response develops, which is characterized by damage to the endothelium of blood vessels, coagulopathy, tissue hypoperfusion, cardiovascular failure, and multiple organ dysfunction. The general chemical structure of the endotoxins in most bacteria is similar—it contains a polar heteropolysaccharide fragmen