¿Cuál es el uso del ácido hialurónico en productos de cuidado Oral?

Ácido hialurónico is a linear polysaccharide composed of D-glucuronic acid and N-acetylglucosamine units linked by glycosidic bonds. Its commercial form is primarily its sodium salt, known as ‘sodium hyaluronate.’ Hyaluronic acid is a major component of the intercellular matrix and extracellular matrix, widely distributed throughout human tissues. It is most abundant in the dermis layer of human skin and in joint synovial fluid. Due to its excellent moisturising properties, viscoelasticity, and biocompatibility, hyaluronic acid has been widely applied in the fields of medicine, cosmetics, and functional foods. In the cosmetics industry, it primarily serves functions such as moisturisation, repair, and delaying skin ageing. Currently, hyaluronic acid is being used as a new functional ingredient in oral care products such as toothpaste and mouthwash.

1 relación entre el ácido hialurónico y la cavidad Oral

In oral tissues, the hyaluronic acid content in periodontal soft tissues, gingiva, and periodontal ligaments is higher than in hard tissues such as alveolar bone and cementum. The tissue structure of oral mucosa is similar to that of skin, consisting of epithelium and a lamina propria, with hyaluronic acid primarily present in the lamina propria [1-3]. Xing Roudong et al. [4] used an enzyme-linked immunosorbent assay (ELISA) to measure hyaluronic acid levels in saliva from healthy individuals, finding that total saliva hyaluronic acid levels ranged approximately from 136 to 587 ng/mL, while the concentration in parotid gland fluid was approximately 63–158 ng/mL. The high concentration of hyaluronic acid in saliva may facilitate rapid wound healing without scarring, as well as lubricate and protect the oral mucosa. Yang Guofeng et al. [5] found that hyaluronic acid exhibits time- and space-specific expression during tooth germ development, first appearing in the thickened tooth plate epithelium, then in the intercellular spaces of epithelial cells in the central region of tooth buds during the budding stage, followed by expression in the intercellular spaces of cells in the stellate network layer of the tooth germ and in the intercellular spaces of odontoblastic mesenchymal cells, suggesting that hyaluronic acid may be closely associated with tooth germ morphogenesis.

In recent years, with the deepening of basic Research on hyalurronic acid (en inglés)and the accumulation of clinical experience, its anti-inflammatory, antibacterial, osteogenic, anti-edema, and wound-healing properties have been increasingly discovered and applied in the treatment of oral diseases. Numerous studies both domestically and internationally have shown that hyaluronic acid has a good auxiliary effect in the treatment of periodontal diseases, oral mucosal diseases, and dental pulp diseases [6]. and it has also found relatively widespread application in the field of oral and maxillofacial surgery [7]. However, there are few reports on the use of hyaluronic acid in oral care.

Oral care is an important means of maintaining oral hygiene, preventing or alleviating oral diseases, and improving oral health [8]. Oral care products primarily include toothpaste, toothbrushes, mouthwash, and other oral care items, with toothpaste accounting for approximately 65% of the market share, toothbrushes for approximately 25%, and mouthwash for approximately 5% [9]. Oral health is an important component of overall human health. With the continuous improvement of living standards and the upgrading of consumption awareness, the quality and functionality of oral care products have become a growing focus for consumers. Traditional products primarily emphasise the prevention of dental issues, with functions such as cleaning teeth, preventing cavities, alleviating tooth sensitivity, and inhibiting plaque formation. In recent years, products targeting oral issues such as alleviating gum problems, repairing oral mucosa, reducing oral odour, and maintaining oral health have gained greater market acceptance [10]. Hyaluronic acid, a natural active ingredient with moisturising, anti-inflammatory, and repairing properties, offers new possibilities for upgrading oral care products.

2 beneficios del ácido hialurónico para el cuidado Oral

2.1 hidratar la cavidad bucal y aliviar la sequedad bucal

Los adultos normales producen entre 1.000 y 1.500 mL de saliva al día. Cuando la tasa de secreción de saliva es menor que la suma de la tasa de absorción de saliva por la mucosa oral y la tasa de evaporde saliva, el cuerpo experimenta una condición o sensación de sequedad en la boca [11]. La prevalencia de xerostomía varía de 5,5% a 46%, aumentando con la edad, y en individuos mayores de 65 años, la tasa de incidencia es de aproximadamente 30% a 40% [12]. Además, la xerostomía puede estar asociada con el daño a las glándulas salicausadas por ciertas enfermedades o sus tratamientos. La sequedad Oral puede hacer que los tejidos blanorales como la mucosa Oral y el tejido gingival sean más susceptibles al daño físico, químico o biológico. La boca seca prolongada puede alterar el ambiente oral, lo que conduce a la halitosis, inflamación oral, y en casos graves, puede afectar el habla y causar dificultad para tragar.

Hyaluronic acid molecules are linear single chains, with each disaccharide unit containing a carboxyl group. Under physiological conditions, they dissociate into negative ions, which repel each other at equal distances, causing the molecules to highly extend in aqueous solutions, resembling ‘molecular sponges.’ Water molecules bind to hyaluronic acid molecules through polar bonds and hydrogen bonds within this space, enabling hyaluronic acid to absorb and retain water equivalent to 1,000 times its own weight. Wang Bing et al. [13] utilised the excellent moisture-retaining properties of hyaluronic acid for the treatment and relief of oral dryness. By comparing saliva volumes before and after use, they demonstrated that formulations containing hyaluronic acid exhibit sustained oral moisturising effects, while being non-toxic, odourless, and having a pleasant taste.

Meng Xiangjing et al. [14] usadohyaluronic acid as one of the active ingredients in a formulation to alleviate dry mouth symptoms, effectively reducing chronic and temporary dry mouth caused by diseases, medication use, chemotherapy, and aging, while lubricating the oral cavity and maintaining oral moisture. Colgate-Palmolive Company's S. Pielke et al. [15] solicitaron una patente para una composición de pasta de dientes para tratar la sequedad oral, añadiendo ácido hialurónico a la pasta de dientes y enjuagues orales para mantener la humedad, prevenir y mejorar la sequedad bucal.

2.2 inhibir la placa dental y mejorar la salud de las enc.

La gingivitis indupor placas es una enfermedad infecciosa crónica del tejido de las enccausada por microorganismos patógenos, que actúa como un precursor de la periodontitis. Si no se trata a tiempo y a fondo, la inflamación de las encpuede progresar a periodontitis bajo la influencia de factores internos y externos, lo que representa riesgos significativos para la salud oral y general.

Huang Jiao [16] used the paper disc diffusion method to study the antibacterial activity of hyaluronic acid against four of the most common periodontal pathogens. The results showed that at a concentration of 2 mg/mL, hyaluronic acid exhibited inhibitory effects against Porphyromonas gingivalis (P. gingivalis, P.g), Actinomyces actinomysetum (A. actinomycetemcomitans, A.a), Prevotella intermedia (P.i), and Fusobacterium nucleatum (F.n), with inhibition zones of 2 mm in diameter. At a concentration of 1 mg/mL, hyaluronic acid still inhibited P.g and P.i, but the inhibitory effect on P.i was weaker, forming only a 1 mm inhibition zone.

Munerah Bins et al. [17] conducted an in vitro antibacterial test to compare the inhibitory effects of 0.2% chlorhexidine and 0.8% hyaluronic acid on P.g. The results showed that the 0.8% hyaluronic acid group exhibited a significant decrease in P.g colony counts at 24 h, 48 h, and 72 h; the 0.2% chlorhexidine group showed a significant decrease in P.g colony counts only at 72 h, and the colony counts at 48 and 72 hours were higher than those in the 0.8% hyaluronic acid group, indicating that 0.8% hyaluronic acid has superior in vitro inhibitory activity against P.g compared to 0.2% chlorhexidine.

Chlorhexidine is the most commonly used antimicrobial component in mouthwashes, but it also has side effects such as mucosal irritation, dryness, and staining. How to use hyaluronic acid as an alternative component or reduce its dosage has attracted increasing attention from researchers. Begum Gizligoz et al. [18] selected 33 healthy participants and employed a randomised, double-blind, crossover clinical study design, using plaque index (PI), gingival index (MGI), and gingival crevicular fluid volume (GCF) as evaluation criteria to assess the oral hygiene efficacy of 0.025% hyaluronic acid mouthwash, 0.2% chlorhexidine mouthwash, and pure water. The results showed that hyaluronic acid had a slightly lower plaque-inhibiting effect than chlorhexidine; the improvement effects of hyaluronic acid on MGI and GCF were similar to those of chlorhexidine; compared with pure water and chlorhexidine mouthwash, hyaluronic acid mouthwash had a better taste and could alleviate irritation, burning sensation, dry mouth, and numbness.

Ali A. Abdulkareem et al. [19] selected 75 dental students with plaque gingivitis and evaluated three commercially available products—0.12% chlorhexidine mouthwash, 0.025% hyaluronic acid mouthwash, and an antioxidant mouthwash—and obtained similar results. All three mouthwashes significantly improved gingival bleeding. Although chlorhexidine mouthwash had the strongest inhibitory effect on plaque, participants preferred the hyaluronic acid mouthwash. Some researchers have also combined hyaluronic acid with chlorhexidine to enhance their effects. Genovesi et al. [20] added 0.12% hyaluronic acid to 0.12% chlorhexidine mouthwash and found that adding hyaluronic acid to the mouthwash significantly inhibited plaque formation compared to using chlorhexidine alone.

In the field of oral medicine, hyaluronic acid also plays an important regulatory role in the inflammatory process: inhibiting the levels of prostaglandin E2; suppressing the chemotaxis and migration of inflammatory cells; inhibiting the phagocytic activity of phagocytes; and scavenging prostaglandins, metalloproteinases, and reactive oxygen species produced by inflammatory cells [21]. Additionally, Chen et al. [22] found that hyaluronic acid with a molecular weight of 1,300 kDa at a concentration of 5 mg/mL significantly reduced the production of inflammatory factors IL-6, IL-8, IL-1β, IL-4, IL-10, with inhibition rates of 80.17%, 69.07%, 88.61%, 84.56%, and 84.66%, respectively. Zhang Huwei et al. [23] investigated the efficacy of a toothpaste containing bioactive hyaluronic acid in improving gingivitis. The results showed that a toothpaste containing 2% bioactive hyaluronic acid could significantly alleviate common symptoms of gingivitis, such as gum discomfort, swelling, and bad breath, and improve clinical signs such as gum bleeding and gum colour within a short period. Lei Xiquan et al. [24] disclosed a patent for a toothpaste containing hyaluronic acid and trehalose, with hyaluronic acid content ranging from 0.05% to 0.5%, providing a moist environment for the oral cavity and exhibiting moisturising and gum-protective effects.

2.3 promover la proliferación celular y reparar lesiones orales

La mucosa Oral es un importante sistema de protección del cuerpo humano, que protege contra los estímulos nocivos externos mientras mantiene la integridad funcional del epitelio. Los malos hábitos alimenticios, las enfermedades y otros factores pueden causar daño a la mucosa oral. Además, las técnicas de cepillado inadecuado puede conducir a daños mecánicos en el tejido gingival.

Hyaluronic acid, as an endogenous component of the body, plays a crucial role in wound healing. During tissue repair, hyaluronic acid collaborates with collagen, fibrin, and other matrix molecules to form a temporary scaffold that supports cell migration and adhesion, regulating cell adhesion, migration, and differentiation. Additionally, hyaluronic acid can reduce the activity of serum proteases, slowing down the degradation rate of the extracellular matrix, thereby promoting wound healing [25]. Furthermore, hyaluronic acid has the function of promoting granulation tissue formation.

Chen Minshan et al. [22] used a human gingival cell mechanical injury repair model and found that the cell proliferation rates in the 300 kDa hyaluronic acid group and the 1,300 kDa hyaluronic acid group were significantly higher than those in the control group, indicating that hyaluronic acid can promote cell proliferation and repair gingival tissue damage. Hyaluronic acid [26] was found by Mmad H.M. et al. to significantly increase the content of hyaluronic acid and type III collagen in damaged tissues and maintain their stable presence for a certain period of time when applied to rat oral wound sites, thereby promoting wound healing and reducing scar tissue formation. Zhang Zhen [27] used a circular full-thickness defect model on the oral mucosa of the palate (φ3 mm) in SD rats to study the effects of exogenous hyaluronic acid on oral wound healing. The results indicated that hyaluronic acid promotes wound healing in the early stage, reduces inflammatory responses during the healing process, and promotes mucosal epithelial regeneration.

3 productos de cuidado oral disponibles comercialmente que contienen ácido hialurónico

In 1998, Japanese company LION [28] disclosed a hyaluronic acid-containing oral care compound designed to inhibit bacteria causing periodontal issues, which could be formulated into toothpaste, tooth powder, mouthwash, and other oral care products. However, according to data from Mintel, the first hyaluronic acid-containing mouthwash—Japan's Yoshida Company's «enjuague bucal Oral y húmedo», no se puso en marcha hasta 2002; En 2007, se introdujo en los países bajos la primera pasta de dientes con ácido hialurónico, 'pasta de dientes sensible al zafir'. Hoy en día, hay cerca de 100 productos de cuidado oral que contienen ácido hialurónico. Sunstar's GUM y Ora2 han lanzado una serie de productos hidratantes orales que contienen ácido hialurónico en múltiples regiones del mundo; LACALUT y ORAL-O-SEPT han introducido productos para el cuidado de las encías con ácido hialurónico como ingrediente activo; Desde 2020, el mercado chino también ha visto el lanzamiento de múltiples productos de cuidado oral que contienen ácido hialurónico, incluyendo pasta de dientes, enjuague bucal y aerosoles orales en varias formul(ver tabla 1).

4 tendencias de aplicación del ácido hialurónico en productos para el cuidado bucal

4.1 formulación de ácido hialurónico

Hyaluronic acid is a high-molecular-weight polysaccharide with a wide molecular weight range, from several thousand to several million. Different molecular weights

hyaluronic acid exhibit distinct characteristics and functions. Ácido hialurónico de alto peso molecular has strong film-forming properties, forming a physical barrier on the oral mucosa surface to prevent moisture evaporation, moisturise the oral mucosa, isolate bacterial or foreign stimuli, and protect cells; low-molecular-weight hyaluronic acid can be absorbed through the skin, supplementing endogenous hyaluronic acid, and possesses deep moisturisation, free radical scavenging, oral mucosa repair, and beneficial effects on gum health.

Chen Minshan et al. [29] revelaron una composición multifuncional del cuidado oral que contiene aMezcla de ácido hialurónicoCombinando ácido hialurónico de diferentes rangde peso molecular como principal ingrediente activo y coformulado con citrato de zinc para lograr un efecto sinérgico, proporcionando efectos beneficiosos para el mantenimiento diario de la salud bucal. Feng Ning et al. [30] realizaron un estudio en profundidad sobre los efectos del ácido hialurónico en el cuidado oral con diferentes pesos moleculares y formulde ácido hialurónico para el cuidado oral. Esta formulación consta de los siguientes componentes: 30%-40% de ácido hialurónico hidrolizado o sus sales con un peso molecular de 2-5 kDa, 35%-45% de ácido hialurónico o sus sales con un peso molecular de 200-600 kDa, y 20-30% de ácido hialurónico con un peso molecular de 1.300-1.500 kDa o sus sales. Los resultados de la evaluación de la eficacia indicaron que esta formulación presenta importantes efectos hidratantes orales, reduce la liberación de factores inflamatorios de las células gingivales y repara las células orales dañadas, proporcionando un cuidado integral para la salud oral. Se puede aplicar a varios productos de cuidado bucal como pasta de dientes, enjuague bucal y aerosoles. Xu Haiyan et al. [31] añadiesta formulación a la pasta de dientes con diferentes formuly examinó las propiedades físicas y químicas de la pasta de dientes, así como el contenido de ácido hialurónico. Los resultados mostraron que las propiedades físicas y químicas de la pasta de dientes eran estables, que el contenido de ácido hialurónico no disminuía significativamente y que era bien compatible con otras materias primas y auxiliares.

4.2 aplicaciones innovadoras de productos para el cuidado bucal

Mintel's February 2020 Oral Hygiene Product Innovation Report noted that incorporating oral health into the beauty category is one of the key trends in product innovation, drawing inspiration from the cosmetics market to develop fashionable packaging designs and introduce innovative product concepts. As a star ingredient in the cosmetics industry, hyaluronic acid has garnered increasing attention from oral care product developers. According to data from Mintel GNPD (Mintel Global New Product Database), hyaluronic acid-containing oral care products have seen significant growth since 2018.

El 29 de junio de 2020, China's ‘Regulations on the Supervision and Administration of Cosmetics’ were officially implemented, stipulating for the first time that ‘toothpaste shall be managed in accordance with the relevant provisions of these regulations for ordinary cosmetics.’ This policy adjustment will also promote cross-industry integration between beauty and skincare and oral care in the Chinese market, and hyaluronic acid, as a natural, multi-functional ingredient, will have greater application opportunities.

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