口腔ケア製品におけるヒアルロン酸の使用は何ですか?

ヒアルロン酸 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ヒアルロン酸と口腔の関係

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 ヒアルロン酸の研究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ヒアルロン酸の口腔ケアの利点

2.1口腔に潤いを与え、口渇を緩和する

通常の成人は1日1000 ~ 1500 mlの唾液を生産する。唾液の分泌率が、口腔粘膜による唾液の吸収率と唾液の蒸発率の合計よりも低いと、身体は口渇状態または感覚[11]を経験する。口腔乾燥症の有病率は5.5%から46%であり、加齢とともに増加し、65歳以上の人では約30 ~ 40%である[12]。さらに、口腔乾燥症は、特定の疾患またはその治療によって引き起こされる唾液腺への損傷と関連している可能性があります。口腔乾燥は、口腔粘膜や歯肉組織などの口腔軟組織を物理的、化学的、生物学的損傷の影響を受けやすくする。長期の口渇は口臭、口腔の炎症につながる、口腔環境を変化させることができ、重症例では、スピーチに影響を与え、嚥下困難を引き起こす可能性があります。

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ら[14]使用hyaluronic 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 . pielkeらは、口腔の乾燥を治療するための歯磨き粉の成分について特許を出願した[15]。歯磨き粉と口腔のリンスにヒアルロン酸を加えて水分を維持し、口の乾燥を防ぎ、改善する。

2.2歯垢を抑制し、歯肉の健康を改善する

プラーク誘発歯肉炎は、病原微生物によって引き起こされる歯肉組織の慢性感染症であり、歯周炎の前駆体である。速やかに治療しないと、内外の要因の影響を受けて歯茎の炎症が歯周炎に進行し、口腔全体の健康に重大なリスクをもたらします。

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細胞増殖を促進し、口腔損傷を修復する

口腔粘膜は、上皮の機能的完全性を維持しながら、外部の有害な刺激に対して遮蔽する、人体の重要な保護システムです。悪い食生活、病気、その他の要因は、口腔粘膜を損傷する可能性があります。さらに、不適切なブラッシング技術は歯肉組織に機械的損傷を与える可能性があります。

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市販のヒアルロン酸を含む口腔ケア製品

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吉田Company'の「オーラルウェットマウスウォッシュ」- 2002年まで発売されていませんでした;2007年、最初のヒアルロン酸含有歯磨き粉「サファイア感受性歯磨き粉」がオランダで発売されました。今日、ヒアルロン酸を含む口腔ケア製品は100種類近くあります。Sunstar'sガムとora2は、世界中の複数の地域でヒアルロン酸を含む経口保湿製品シリーズを発売した。lacalutとoral-o-septは、ヒアルロン酸を有効成分とするガムケア製品を導入した。2020年以降、中国市場では、歯磨き粉、マウスウォッシュ、口腔スプレーなど、ヒアルロン酸を含む複数の口腔ケア製品が様々な形で発売されています(表1参照)。

4口腔ケア製品におけるヒアルロン酸の応用動向

4.1ヒアルロン酸の処方

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. High-molecular-weightヒアルロン酸 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ら[29]は、aを含む多機能オーラルケア成分を明らかにしたヒアルロン酸混合さまざまな分子量のヒアルロン酸を主成分とし、クエン酸亜鉛との併用により相乗効果を発揮し、毎日の口腔の健康維持に有益な効果をもたらします。feng ningらは、異なる分子量のヒアルロン酸のオーラルケア効果について詳細な研究を行い、ヒアルロン酸オーラルケア処方を開発しました。この制定は以下の要素から構成されています30%-40% hydrolysedヒアルロン酸や、2 ~ 5 kDaの分子量との塩35%-45%ヒアルロン酸またはその塩の分子重量200-600 kDa、との20 ~ 30%ヒアルロン酸分子重量1,300-1,500 kDaまたはその塩である。有効性評価の結果、口腔保湿効果が高く、歯肉細胞からの炎症因子の放出を抑制し、損傷した口腔細胞を修復することが確認されました。歯磨き粉、マウスウォッシュ、スプレーなど、さまざまなオーラルケア製品に適用できます。xu haiyanら[31]は、この配合をさまざまな配合の歯磨き粉に加え、歯磨き粉の物理的および化学的性質とヒアルロン酸含有量を調べた。その結果、歯磨き粉の物理的・化学的性質は安定しており、ヒアルロン酸含有量は有意に低下せず、他の原料や補助材料との親和性が良好であることが示された。

4.2オーラルケア製品の革新的なアプリケーション

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.

2014年6月29日、中国・上海#39;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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