Quelles sont les utilisations de la poudre d’acide hyaluronique?

Acide hyaluronique, 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. Le conseil des ministresmolecular 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 propriétés physiques et chimiques et fonctions physiologiques de l’acide hyaluronique

1.1 propriétés physiques et chimiques

L’acide hyaluronique est soluble dans l’eau, et sa solution est acide avec une certaine charge négative. La molécule d’acide hyaluronique est un polysaccharide moléculaire élevé formé par la polymérisation des unités disaccharidiques de l’acide β-d-glucuronique et du β-d-n-acétylglucosaminoglucose.

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. Le conseil des ministresspecific 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 fonctions physiologiques

1.2.1 fonction de rétention d’eau:

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 protection de la peau:

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 stratum corneum et améliore encore l’absorption et l’utilisation des substances actives par le stratum corneum de la peau, rendant ainsi la peau délicate et lisse [7].

1.2.3 fonction anti-âge:

L’acide hyaluronique a pour fonction de récupérer les radicaux libres, de sorte qu’il peut ralentir le vieillissement de la peau et protéger la peau contre les dommages.

1.2.4 autres fonctions:

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 Application d’acide hyaluronique

2.1 Application de l’acide hyaluronique dans les aliments diététiques

Les produits buccodentaires à base d’acide hyaluronique sont devenus populaires au Japon dans les années 1980 [8]. En tant qu’aliment fonctionnel, l’acide hyaluronique n’exerce pas directement de fonctions de santé après consommation, mais augmente les précurseurs de la synthèse de l’acide hyaluronique dans le corps et favorise la synthèse de l’acide hyaluronique dans la peau et d’autres tissus [9].

2.2 Application de l’acide hyaluronique dans les cosmétiques

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 hydratation:

L’hydratation est la fonction principale deAcide hyaluronique dans les cosmétiques....... Comparé au glycérol, au propylène glycol et à d’autres humectants couramment utilisés, l’acide hyaluronique présente l’hygroscopicité la plus forte à une humidité relative inférieure (moins de 33%), et l’hygroscopicité la plus faible à une humidité relative plus élevée (plus de 75%), ce qui convient à la protection de la peau en différentes saisons, ainsi qu’aux différentes exigences pour l’effet hydratant des cosmétiques dans différents environnements humides (par exemple, hiver sec et été humide). En d’autres termes, les propriétés hydratantes de l’acide hyaluronique ne sont pas affectées par l’humidité relative du milieu environnant [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 et obtenir de meilleurs effets blanchissants et hydratants.

2.2.2 supplémentation de la nutrition de la peau:

Exogenous supplementation of hyaluronic acid can be used as a supplement to the skin' S acide hyaluronique endogène. L’utilisation régulière de produits cosmétiques appropriés est propice au transfert des nutriments dela peau et à la décharge de déchets métaboliques, en maintenant un certain niveau de teneur en eau dans la peau, afin d’obtenir l’effet de retarder le vieillissement dela peau, la beauté et les soins dela peau.

2.2.3 protection solaire et réparation de la peau endommagée:

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 propriétés lubrifiantes et pelliculaires:

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 épaississement:

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 Application de l’acide hyaluronique en injection cosmétique

Que ce soit dans les pays étrangers ou les grandes villes nationales, la technologie cosmétique d’injection est une technologie cosmétique populaire aujourd’hui. Grâce à l’injection sous-cutanée de produits de comblement, les rides de la peau peuvent être éliminées rapidement, telles que l’augmentation des lèvres, l’augmentation du menton, la rhinoplastie et d’autres chirurgies cosmétiques une fois utilisé solution de collagène comme remplisseur.

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' S pieds, plis nasolabiaux et autres rides faciales dans une certaine mesure. Les produits de comblement d’augmentation des lèvres peuvent réduire l’effondrement local causé par l’atrophie faciale et certaines cicatrices faciales, telles que l’acné et cicatrices curatives. Les produits de comblement à l’acide hyaluronique récroisé ne peuvent pas être utilisés pour l’augmentation mammaire car ils ne sont pas permanents et seront dégradés et absorbés par les tissus après quelques mois.

2.4 applications orthopédiques de l’acide hyaluronique

2.4.1 Application dans le traitement des maladies articulaires:

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.

Dans le traitement de maladies articulaires, l’acide hyaluronique peut être injecté pour reconstituer et remplacer le liquide synovial, principalement par la supplémentation d’acide hyaluronique exogène, pour favoriser la réparation du cartilage et restaurer la capacité lubrifiante du liquide synovial, de manière à améliorer la fonction des articulations [11].

2.4.2 Application dans la prévention des adhésions postopératoires:

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].

2.5 acide hyaluronique dans le traitement ophtalmique

2.5.1 Distribution et rôle de l’acide hyaluronique dans l’œil des animaux:

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 l’hyaluronate de Sodium est utilisé en chirurgie ophtalmique:

L’acide hyaluronique a un large éventail d’applications en chirurgie ophtalmique, principalement en raison de ses propriétés de viscosité, de pseudoplasticité, d’élasticité, d’adhésion et de enduit, qui lui font avoir des fonctions importantes telles que l’amortissement viscoélastique, le décollement intra-tissu, l’occlusion visqueuse, l’hémostase visqueuse, l’amortissement viscoélastique, la fixation élastique et ainsi de suite [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 Sel de sodium de l’acide hyaluronique 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 l’endothélium, qui non seulement réduit le taux de perte des cellules endothéliales, mais réduit également les effets nocifs sur les cellules endothéliales dus au cisaillement mécanique et à l’implantation des iol; De plus, pour implanter une lentille dans la cornée, on peut injecter de l’acide hyaluronique dans la chambre antérieure. En outre, il peut être utilisé pour approfondir la chambre antérieure et ouvrir la capsule de la lentille de sorte que le IOL de la chambre antérieure puisse être facilement glissé dans la chambre antérieure pour une implantation lisse de la lentille [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 le rôle de l’hyaluronate de sodium dans la lubrification des yeux:

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 le rôle de l’acide hyaluronique dans les préparations ophtalmiques

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 autres applications de l’acide hyaluronique en ophtalmologie:

En plus des applications ci-dessus, l’acide hyaluronique joue également un rôle dans de nombreuses autres applications cliniques en ophtalmologie, telles que les traumatismes oculaires, l’ablation d’hémorragie de la chambre antérieure, la chirurgie du muscle extraoculaire et la chirurgie oculoplastique.

2.5.6 effets néfastes:

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.

Lorsque l’acide hyaluronique est utilisé en chirurgie oculaire, des réactions inflammatoires et un trouble aqueux peuvent occasionnellement se produire dans les 24 heures, et certaines réactions inflammatoires peuvent perdurer pendant plusieurs semaines, principalement en raison d’impuretés comme des résidus de protéines ou d’acides nucléiques dans la formulation d’acide hyaluronique, ainsi que des dommages aux instruments chirurgicaux, des débris de tissus résiduels et l’absence de prélèvement rapide du sang [17].

2.6 autres Applications de l’acide hyaluronique

2.6.1 Application en urologie:

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 Application dans le diagnostic des maladies:

Étant donné que le niveau d’acide hyaluronique dans le corps montre une augmentation significative de l’apparition de nombreuses maladies, il est possible de refléter les changements de diverses maladies par la mesure de l’acide hyaluronique dans le sérum sanguin.

3 méthodes de Production de l’acide hyaluronique

L’acide hyaluronique peut être produit par deux méthodes: l’extraction de tissus animaux et la fermentation microbienne. Parmi eux, la fermentation microbienne est actuellement la principale méthode de production d’acide hyaluronique.

3.1 Extraction de tissus animaux

L’acide hyaluronique existe dans presque tous les tissus animaux et est largement répandu. Les matières animales qui peuvent être utilisées pour l’extraction de l’acide hyaluronique comprennent principalement le corps vitreux de la couronne de poulet et de la vache et#39; S oeil, et le cordon ombilical humain et ainsi de suite. Les principales procédures de fonctionnement sont:

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.

La méthode d’extraction de tissus animaux a des exigences plus élevées pour les matières premières, qui doivent être fraîches et sûres. Les matières premières des tissus animaux sont chères, et il est difficile d’obtenir certains d’entre eux, qui est grandement affecté par le cycle de croissance des animaux et les saisons, de sorte que la pureté de l’acide hyaluronique dans les matières premières des tissus animaux n’est pas élevée, et le rendement d’extraction est faible.

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 fermentation microbienne

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] ont utilisé Streptococcus equi SH0 comme souche de début et ont choisi une souche SH0201 génétiquement stable, non hémolytique et déficiente en hyaluronidase par mutagénèse physique et chimique, et ont obtenu de l’acide hyaluronique avec un poids moléculaire relatif de 2,06emon 106 Da par fermentation en fiole agité. Li Zigang et al. [24] ont isolé une souche de Streptococcus faecalis à partir de la muqueuse nasale de vaches laitières, et le rendement en acide hyaluronique pourrait atteindre 6,94 g/L après une mutagénèse aux UV et une mutagénèse à la nitrosoguanidine.

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 perspectives

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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