¿Cuáles son los usos del polvo de ácido hialurónico?

Ácido hialurónico, also known as hyaluronic acid, is an acidic mucopolysaccharide that forms a viscoelastic substance when combined with water molecules [1]. Hyaluronic acid is mainly found in the skin and connective tissues of the human body, where it acts as an extracellular matrix for cellular insertion. In addition to providing a certain volume of extracellular matrix for the cells in the body, hyaluronic acid also influences the stability, binding and viscoelasticity of the tissues. elmolecular structure of all natural hyaluronic acids is the same, with virtually no species- or tissue-specific differences, so pure hyaluronic acid is not immunogenic [2].

Hyaluronic acid was first isolated from the vitreous body of the bovine eye by Meyer et al, Professor of Ophthalmology at Columbia University, USA, in 1934 [3]. Since Kendall et al. discovered that Streptococcus haemolyticus could produce hyaluronic acid in 1937, many scientists and scholars have been engaged in the study of hyaluronic acid production by microbial fermentation. In 1985, Shiseido of Japan first reported the production of hyaluronic acid by streptococcal fermentation. In 2003, the United States also approved a patent for the production of hyaluronic acid by fermentation [4].

Since then, there have been many studies on the selection and breeding of hyaluronic acid fermentation strains. For example, Fong et al. [5] obtained non-hemolytic and non-hyaluronidase-producing strains of Streptococcus zooepidemicus by mutagenicity with nitrosoguanidine. Up to now, the technology of hyaluronic acid production by microbial fermentation has been matured in foreign countries and has entered the industrialisation stage. In China, the production of hyaluronic acid by fermentation of Streptococcus faecalis has also become a research hotspot and has gradually entered into the industrialisation stage, and the development, production and application of hyaluronic acid has a very attractive prospect.

1 propiedades físicas y químicas y funciones fisiológicas del ácido hialurónico

1.1 propiedades físicas y químicas

El ácido hialurónico es soluble en agua, y su solución es ácida con cierta carga negativa. La molécula de ácido hialurónico es un polisacárido de alto contenido molecular formado por la polimeride las unidades disacáride de ácido − -d-glucurónico y − -d-n-acetilglucosaminoglucosa.

Hyaluronic acid is a major component of some bacterial pods such as Streptococcus and Pseudomonas aeruginosa. Unlike other mucopolysaccharides, hyaluronic acid is an acidic mucopolysaccharide and does not contain sulphur in its molecular structure. elspecific intermolecular configuration of hyaluronic acid gives it a high viscosity and moisturising effect. Hyaluronic acid molecules can carry about 500 times as much water as themselves, which is recognised as the best moisturising substance, and is therefore mass-produced and widely used in functional foods and cosmetics [6].

1.2 funciones fisiológicas

1.2.1 función de retención de agua:

Hyaluronic acid has strong water absorption and water retention. In higher concentration solution, hyaluronic acid has strong hydrophilicity, and its long molecular chains are interwoven in a grid shape, which are combined with water molecules through hydrogen bonding.

1.2.2 protección de la piel:

The effect of hyaluronic acid on the skin depends on its molecular weight. Hyaluronic acid with large molecular weight is mainly used for skin moisturising. Hyaluronic acid coated on the skin surface can quickly form a breathable hydration film wrapped around the skin surface, which softens the skin's estrato córneo y mejora aún más la absorción y utilización de sustancias activas por el estrato córneo de la piel, haciendo que la piel delicada y suave [7].

1.2.3 función antienvejecimiento:

El ácido hialurónico tiene la función de eliminar los radicales libres, por lo que puede retrasar el envejecimiento de la piel y proteger la piel de daños.

Otras funciones:

Hyaluronic acid has the function of drug-carrying, which can be used as a carrier to embed drugs, not only slow release but also promote drug absorption. Hyaluronic acid also has antibacterial and anti-inflammatory effects [8].

2 aplicación de ácido hialurónico

2.1 aplicación del ácido hialurónico en alimentos saludables

Los productos de salud oral a base de ácido hialurónico se hicieron populares en Japón en la década de 1980 [8]. Como alimento funcional, el ácido hialurónico no ejerce directamente funciones de salud después del consumo, pero aumenta los precursores para la síntesis de ácido hialurónico en el cuerpo y promueve la síntesis de ácido hialurónico en la piel y otros tejidos [9].

2.2 aplicación del ácido hialurónico en cosméticos

As mentioned earlier, hyaluronic acid has strong moisturising properties and is a naturally occurring substance found in a wide range of skin and other tissues. This property has led to its popularity in the cosmetic industry worldwide [9]. Currently, there are many cosmetic products containing hyaluronic acid in their formulations, such as toners, lotions, serum capsules, masks, body lotions, powders, lipsticks, shampoos, sunscreens, conditioners, mousses, and so on [10].

2.2.1 hidratante:

La hidratante es la principal función deÁcido hialurónico en cosmética. Comparado con glicer, propilenglicol y otros humectantes de uso común, el ácido hialurónico tiene la higroscopicidad más fuerte a una humedad relativa más baja (menos del 33%), y la higroscopicidad más débil a una humedad relativa más alta (más del 75%), que es adecuado para la protección de la piel en diferentes estaciones, así como para los diferentes requisitos para el efecto hidratante de los cosméticos en diferentes ambientes húmedos (por ejemplo, invierno seco y verano húmedo). En otras palabras, las propiedades hidratantes del ácido hialurónico no se ven afectadas por la humedad relativa del entorno [10].

Of course, the moisturising property of hyaluronic acid is also related to its relative molecular weight, the larger the molecular weight, the stronger the moisturising property; the smaller the molecular weight, the weaker the moisturising property [10]. Hyaluronic acid as a moisturising agent is seldom used alone, but is often used in conjunction with other moisturising agents, so as to complement each other's y lograr un mejor efecto blanqueador e hidratante.

2.2.2 suplementos para la nutrición de la piel:

Exogenous supplementation of hyaluronic acid can be used as a supplement to the skin's ácido hialurónico endógeno. El uso Regular de cosméticos relevantes conduce a la transferencia de nutrientes dela piel y la descarga metabólica de residuos, manteniendo un cierto nivel de contenido de agua en la piel, con el fin de lograr el efecto de retrasar el envejecimiento dela piel, la belleza y el cuidado dela piel.

2.2.3 protección solar y reparación de la piel dañada:

Hyaluronic acid has a certain effect on sun protection, but its mechanism of action is different from that of ordinary sunscreen. Sunscreens often include ultraviolet absorbers to achieve the purpose of sun protection; hyaluronic acid can largely reduce the transmittance of ultraviolet rays and repair skin damage caused by the small amount of ultraviolet rays that pass through. When the skin is exposed to sunlight, resulting in redness, burning pain, peeling, etc., cosmetics containing hyaluronic acid can be used to promote the proliferation and differentiation of epidermal cells, and hyaluronic acid can be used to remove the effect of oxygen free radicals to help the injured part of the skin to recover [10].

2.2.4 propiedades lubricantes y de formación de película:

Hyaluronic acid has certain lubricating and film-forming properties, which can be used in cosmetics to enhance lubrication, increase the feel of skin care, and make the face feel good, and its film can be formed on the surface of the skin, which can improve the cosmetic effect of the skin, and make the skin have a good feeling of smoothness and moistness. When using shampoo and hair care products containing hyaluronic acid, it is equivalent to coating the surface of the hair with a protective film that lubricates and removes static electricity, which has the effect of making the hair easy to take care of and preventing it from falling off.

2.2.5 engrosamiento:

Hyaluronic acid has a certain viscosity after absorbing water, and the 1% concentration of aqueous solution is in the form of a gel, which can be added to water, creams and other cosmetics to increase the viscosity and stability.

2.3 aplicación de ácido hialurónico en inyección cosmética

Ya sea en países extranjeros o grandes ciudades nacionales, la tecnología cosmética de inyección es una tecnología cosmética popular hoy en día. A través de la inyección subcutánea de rellen, las arrude la piel se pueden eliminar rápidamente, tales como aumento de labios, aumento de barbilla, rinoplastia y otras cirugcosméuna vez que se utiliza la solución de colágeno como un relleno.

Although natural collagen, like hyaluronic acid, is the main component of the extracellular matrix of animal connective tissues, the commercial collagen used in the cosmetic market is generally a protein extracted from animal tissues, and its structure and amino acid composition are not exactly the same as that of collagen in human tissues, so it has a certain degree of immunogenicity, and once injected subcutaneously, it will most likely cause immune response, leading to serious consequences and physical harm and economic losses to consumers. This can lead to serious consequences, causing bodily harm and economic loss to the consumer. Therefore, when using natural collagen as a cosmetic filler, it is necessary to conduct a ‘skin test’ [10].

Hyaluronic acid soft-tissue fillers can be injected or used surgically to eliminate crow' pies, pliegues nasolabiales, y otras arrugas facihasta cierto punto. Los rellende aumento de labios pueden reducir el colapso local causado por la atrofia facial y algunas cicatrices faci, como el acné y cicatrices cicatri. Los rellende ácido hialurónico reticulno pueden usarse para el aumento de mamas ya que no son permanentes y serán degradados y absorbidos por los tejidos después de unos meses.

2.4 aplicaciones ortopédicas del ácido hialurónico

2.4.1 aplicación en el tratamiento de enfermedades articulares:

Hyaluronic acid is the main component of cartilage and synovial fluid, and its physiological properties play an irreplaceable role in the function of joints [10]. Abnormalities in the production and metabolism of hyaluronic acid in the joints can lead to the deterioration of osteoarthritis, rheumatoid arthritis, and other infectious and non-infectious joint diseases, as well as to the degradation and destruction of cartilage.

En el tratamiento de las enfermedades articulares, el ácido hialurónico puede ser inyectado para reponer y reemplazar el líquido sinovial, principalmente a través de la suplementación de ácido hialurónico exógeno, para promover la reparación del cartílago y restaurar la capacidad lubricdel líquido sinovial, a fin de mejorar la función de las articulaciones [11].

2.4.2 aplicación en la prevención de adherencias postoper:

Hyaluronic acid has been widely used to prevent postoperative tissue adhesions. As early as 1980, hyaluronic acid was first successfully used in the treatment of tendon repair in order to reduce postoperative adhesions. Numerous animal studies and clinical trials have shown that hyaluronic acid is a safe and effective substance for the prevention and reduction of post-surgical tissue adhesions [12].

Ácido hialurónico 2.5 en tratamiento oftálmico

Distribución y función del ácido hialurónico en el ojo animal:

As an acidic mucopolysaccharide, hyaluronic acid is distributed in the intercellular matrix of various tissues in animals, and has the important physiological functions of maintaining a stable osmotic pressure in cells and bonding adjacent cells [13]. The content of hyaluronic acid in the vitreous humor of animal eyes is high, and the content of hyaluronic acid in the vitreous humor of adult animals is higher than that of juvenile animals. Of course, the distribution of hyaluronic acid in the vitreous body of the eye is not uniform, with a low level of hyaluronic acid in the middle of the vitreous body of the eye and a high level of hyaluronic acid in the vicinity of the ciliary body.

2.5.2 el hialuronato de sodio se utiliza en la cirugía oftálmica:

El ácido hialurónico tiene una amplia gama de aplicaciones en cirugía oftálmica, principalmente por sus propiedades de visco, pseudoplasticidad, elas, adhesión y adherencia, que lo hacen tener importantes funciones como amortiguviscoelástico, desprendimiento intratisular, oclusión visco, hemostasis visco, amortiguviscoelástico, fijación elástica y así sucesivamente [14].

Currently, hyaluronic acid is used as a viscoelastic agent in many ophthalmic surgeries, such as retina-related surgeries, cataract-related surgeries, and artificial lens-related surgeries.

The Sal de sodio de ácido hialurónico plays a very important role in IOL implantation and cataract surgery. For example, hyaluronic acid-Na can be injected into the anterior chamber of the cornea in order to form a protective layer in the cornea's endotelio, que no sólo reduce la tasa de pérdida de células endoteli, sino que también reduce los efectos perjudiciales sobre las células endotelidebido al corte mecánico y la implantación de las lio; Además, con el fin de implantar una lente en la córnea, el ácido hialurónico puede ser inyectado en la cámara anterior. Además, se puede utilizar para profundizar la cámara anterior y abrir la cápsula del cristalpara que el lio de la cámara anterior pueda deslizarse fácilmente en la cámara anterior para la implantación del cristalliso [15].

By injecting hyaluronic acid into the anterior chamber, the normal depth of the anterior chamber can be maintained, the complications of insufficient aqueous secretion and choroidal detachment after glaucoma surgery can be reduced, the occurrence of shallow anterior chamber can be prevented, and the injection of hyaluronic acid-Na in the anterior chamber and subconjunctival valve can reduce the rate of haemorrhage, post-surgical scarring and post-surgical adhesion, and increase the rate of functional follicle formation. Therefore, the use of hyaluronan-Na in ophthalmic surgery can better prevent the formation of postoperative scarring, reduce intraocular pressure and the incidence of shallow anterior chamber and choroidal detachment, and is a safe, reliable, and effective treatment for glaucoma [16].

Hyaluronic acid-Na also plays an important role in corneal surgery, mainly in its protective effects on tissues, such as avoiding damage to intraocular tissues by surgical instruments, reducing astigmatism in the postoperative period, reducing the sudden loss of aqueous humor, avoiding postoperative adhesions, and facilitating postoperative recovery of epithelial tissues. The use of hyaluronic acid-Na in corneal transplantation can effectively protect the corneal tissue and promote the recovery of the transparency of the corneal implant [16].

2.5.3 el papel del hialuronato de sodio en la lubricocular:

Dry eye disease is a common comprehensive ophthalmic disease, which is mainly caused by the dysfunction of certain ocular gland cells, including various types of conjunctivitis. Hyaluronic acid-Na has a prolonged residence time in the eye due to its non-Newtonian fluid properties. Hyaluronic acid-Na also has more hydrophilic groups, which can combine with water molecules to achieve hydrophilicity and lubrication, so it can alleviate the symptoms of dry eyes to a certain extent. This is because when blinking, hyaluronic acid-Na has a certain degree of viscoelasticity like tear mucin, so it can replace the role of tear mucin and alleviate the discomfort of dry eyes [17].

2.5.4 el papel del ácido hialurónico en los preparados oftálmicos:

The properties of dilute solution of hyaluronic acid are close to those of tear fluid, which belongs to non-Newtonian fluid, and its viscosity and elasticity are the same as those of animal tear fluid, with good biotolerance. Therefore, hyaluronic acid solution can be used as a pharmaceutical medium to thicken ophthalmic preparations, and its effect is better than the general chemical thickeners.

Currently, hyaluronic acid-Na is also widely used as an ophthalmic agent to treat intraocular inflammation by intraocular injection of highly concentrated hyaluronic acid mixed with anti-inflammatory drugs in a gel. This method is different from systemic medications such as oral medications or intravenous injections, and it has the characteristics of quick effect and less frequent administration, which can reduce the pain of patients [17].

2.5.5 otras aplicaciones del ácido hialurónico en oftalmología:

Además de las aplicaciones anteriores, el ácido hialurónico también juega un papel en muchas otras aplicaciones clínicas en oftalmología, tales como trauma ocular, extracción de hemorragia de la cámara anterior, cirugía del músculo extraocular y cirugía oculoplástica.

2.5.6 efectos adversos:

Increased intraocular pressure is a common complication following ophthalmic surgery due to blockage of ocular outflow pathways, e.g., tissue debris, tissue oedema, and tissue residue [17]. This complication occurs mainly a few hours after injection and peaks when the postoperative intraocular pressure normalises, and the peak intraocular pressure is related to the concentration of hyaluronan-Na. In order to reduce the postoperative increase in intraocular pressure and in patients with glaucoma, it is generally recommended that hyaluronan be aspirated or flushed out of the anterior chamber after surgery.

Cuando el ácido hialurónico se utiliza en cirugía ocular, de vez en cuando pueden ocurrir reacciones inflamatorias y opacamiento acuoso dentro de las 24 horas, y algunas reacciones inflamatorias pueden persistir durante varias semanas, principalmente debido a impurezas como residuos de proteínas o ácidos nucleen la formulación de ácido hialurónico, así como daño a los instrumentos quirúr, restos de tejido residual, y la falta de eliminación oportuna de la sangre [17].

2.6 otras aplicaciones del ácido hialurónico

2.6.1 aplicación en urología:

Hyaluronic acid can be injected directly into the bladder as a temporary replacement for the lack of a protective layer of bladder epithelial glycosaminoglycans, thus achieving the purpose of treating interstitial cystitis [18]. Currently, hyaluronic acid is being used for a wider range of indications than just interstitial cystitis, which provides a broader market opportunity for hyaluronic acid products [19].

2.6.2 aplicación en el diagnóstico de enfermedades:

Dado que el nivel de ácido hialurónico en el cuerpo muestra un aumento significativo en la aparición de muchas enfermedades, es posible reflejar los cambios de diversas enfermedades a través de la medición de ácido hialurónico en el suero sanguíneo.

3 métodos de producción de ácido hialurónico

El ácido hialurónico puede ser producido por dos métodos: extracción de tejido animal y fermentación microbiana. Entre ellos, la fermentación microbiana es el principal método de producción de ácido hialurónico en la actualidad.

3.1 extracción de tejido Animal

El ácido hialurónico existe en casi todos los tejidos animales y está ampliamente distribuido. Los materiales animales que pueden ser utilizados para la extracción de ácido hialurónico incluyen principalmente el cuerpo vítrede de la corona de pollo y la vaca#39, y el cordón umbilical humano y así sucesivamente. Los principales procedimientos operativos son:

Raw materials → acetone or ethanol to raw materials degreasing, dehydration, air drying → soaked in distilled water, filtration → aqueous sodium chloride and chloroform solution treatment → add trypsin insulation → ion exchange agent treatment, purification → refined hyaluronic acid.

El método de extracción de tejido Animal tiene mayores requerimientos para las materias primas, que deben ser frescas y seguras. Las materias primas de los tejidos animales son caras, y es difícil obtener algunas de ellas, lo que se ve muy afectado por el ciclo de crecimiento de los animales y las estaciones, por lo que la pureza de ácido hialurónico en las materias primas de los tejidos animales no es alta, y el rendimiento de extracción es bajo.

The extraction of hyaluronic acid is complicated by the consumption of large amounts of organic solvents and hydrolytic enzymes, and the number of operating units increases the cost of hyaluronic acid extraction. In addition, due to the low purity of hyaluronic acid extracted from animal tissues, further refinement and purification of the product is more complicated, which limits the application of the product. The extraction method can no longer meet the current market needs, so fermentation has basically replaced the extraction method for the production of hyaluronic acid [20].

3.2 fermentación microbiana

The production of hyaluronic acid by microbial fermentation has been studied since the 1930s. Since hyaluronic acid in the fermentation broth exists in a free state, it is easy to isolate and purify hyaluronic acid. Therefore, the production of hyaluronic acid by microbial fermentation method has more advantages than that by animal tissue extraction method, such as low production cost and unlimited scale of raw materials.

There are two types of streptococci that can produce hyaluronic acid: group A and group C. Group A mainly includes Streptococcus pyogenes, which is generally not used as a production strain because of its strong pathogenicity; group C includes Streptococcus zooepidemicus, Streptococcus equi, and Streptococcus equi, etc., which are all used in the production of hyaluronic acid, and are also used in the production of hyaluronic acid. Group C includes S. zooepidemicus, S. equi, S. equisimilis, etc., all of which are non-pathogenic bacteria, so they can be used as hyaluronic acid production strains [21]. Luo Ruiming et al. [22] isolated Streptococcus zooepidemicus strain NUF-035 from the lung fluid of sheep with pneumonia, and the yield of hyaluronic acid obtained by optimising the medium was 1.88 g/L. Feng Jiansheng et al.

Feng Jianjian et al. [23] usaron Streptococcus equi SH0 como la cepa inicial y seleccionuna cepa genéticamente estable, no hemolíy con deficiencia de hialuronida SH0201 por mutagénesis física y química, y obtuvieron ácido hialurónico con un peso molecular relativo de 2,06 ×106 Da por fermentación en matraz agit. Li Zigang et al[24] aislaron una cepa de Streptococcus faecalis de la mucosa nasal de vacas lech, y el rendimiento de ácido hialurónico podría alcanzar 6,94 g/L después de mutagenesis UV y mutagenesis nitrosoguanidina.

The quality and yield of hyaluronic acid produced by microbial fermentation are mainly affected by the following aspects: the selection of strains, the optimisation of medium and fermentation conditions, and the downstream technology of biotechnology, i.e., the extraction of hyaluronic acid [25-27]. So far, many scholars at home and abroad have conducted research on the production of hyaluronic acid by microbial fermentation.

Guo Xueping et al. [28] carried out research on the fermentation production process of hyaluronic acid, and carried out laboratory pilot and production workshop pilot studies; Chen Yonghao et al. [29] used γ-rays and ultraviolet rays in combination with irradiation for mutation breeding, and obtained non-haemolytic strains, so that the yield of hyaluronic acid and relative molecular mass has been further improved; Yang Li et al. Yang Li et al. [30] explored the factors affecting the molecular weight of hyaluronic acid, and obtained the relationship between the dissolved oxygen level and stirring speed and the molecular weight of hyaluronic acid; Fu Li et al. [31] screened a hyaluronic acid-producing bacterium from the natural world; Ye Hua et al. [32] studied the process of adding hyaluronic acid to the fermentation medium; Shi Peng [33] researched on the process of hyaluronic acid production and extraction by the fermentation method; Hao Ning et al. Hao Ning et al. [34] carried out genetic modification of hyaluronic acid producing bacteria, and the yield of hyaluronic acid produced by recombinant bacteria was greatly improved.

Holmstrm [35] and Johns [36] optimized the fermentation nutrient conditions of hyaluronic acid by shaking flasks and then fermenting in small fermentation tanks; Kim et al [37] selected Streptococcus zooepidemicus and optimized the cultivation conditions; Armstrong [38] and Chong [39] studied the fermentation conditions of hyaluronic acid. 38] and Chong [39] obtained the relationship between the culture conditions of hyaluronic acid-producing bacteria on the yield and molecular weight of hyaluronic acid.

The main process of hyaluronic acid fermentation production is as follows: slant seed → shake bottle seed → inoculation → fermentation culture → replenishment → tank placement → fermentation broth (crude extraction with ethanol) → crude extraction (add filter aid, activated carbon, adjust pH value) → filtration (remove impurities) → filtrate (ethanol precipitation) → precipitate (dehydration and drying) → product hyaluronic acid [40-41].

4 perspectivas

The market demand and sales of hyaluronic acid are increasing every year. The research and development of hyaluronic acid mainly focuses on the molecular modification of hyaluronic acid and the application of its derivatives in various industries. The selection of strains, optimisation of fermentation conditions, improvement of the extraction process and analytical modifications can expand the range of applications of hyaluronic acid and increase its economic value.

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