구강 관리 제품에 히알루론산의 용도는?

루 론 산 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.

히알루론산과 구강의 관계 1

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 [화학공학] 히알루론산에 대한 자료입니다and 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.

히알루론산의 구강 관리 이점 2

2.1 구강을 촉촉하게하고 구강건조증을 완화시킨다

정상적인 성인은 매일 1,000~1,500 mL의 타액을 분비한다.타액 분비율이 구강 점막에 의한 타액 흡수율과 타액 증발율의 합보다 낮아지면 신체는 구강건조증이나 감각을 경험하게 된다 [11].제로스토미아의 유병률은 5.5%에서 46%에 이르며, 나이가 들수록 증가하며, 65세 이상의 개체에서 발병률은 약 30%에서 40% 정도이다 [12].게다가, 제로스토미아 (xerostomia)는 특정 질병이나 그 치료법으로 인한 침샘의 손상과 관련이 있을 수 있다.구강 건조증은 구강 점막 및 치은조직과 같은 구강 연부조직을 물리적, 화학적 또는 생물학적 손상에 더 쉽게 만들 수 있습니다.구강건조증이 오래 지속되면 구강 환경을 변화시켜 구취, 구강 염증을 유발할 수 있으며 심한 경우, 언어에도 영향을 미쳐 삼키는데 어려움을 초래할 수 있다.

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.

맹상징 외 [14] 가 사용했다hyaluronic 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 등 15)은 구강 건조증 치료용 치약 조성물에 대한 특허를 출원하였으며, 치약과 구강 린스에 히알루론산을 첨가하여 수분 유지, 구강건조증 예방 및 개선효과를 나타내었다.

2.2치태 억제 및 잇몸 건강 개선

Plaque-induced gingivitis)는 병원성 미생물에 의해 발생하는 잇몸 조직의 만성 감염성 질환으로 치주염의 전구체 역할을 한다.신속하고 철저하게 치료하지 않으면 잇몸 염증이 내 · 외부적 요인의 영향으로 치주염으로 진행되어 구강 및 전반적인 건강에 중대한 위험을 초래할 수 있다.

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.

2.3세포 증식 촉진 및 구강 손상 회복

구강 점막은 상피의 기능적 온전성을 유지하면서 외부의 유해 자극으로부터 차폐하는 인체의 중요한 보호체계이다.잘못된 식습관, 질병 등의 요인으로 구강 점막이 손상될 수 있다.또한 잘못된 칫솔질 기술은 치은 조직의 기계적 손상을 초래할 수 있습니다.

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.

시중에서 판매되고 있는 히알루론산을 함유한 구강 케어 제품 3

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 요시다 컴패니 's'구강 습식 구강청결제'-2002년까지 출시되지 않았다;2007년 네덜란드에서 최초로 히알루론산 함유 치약인'사파이어 감성 치약'을 선보였다.현재 히알루론산을 함유한 구강 관리 제품은 100여 종에 이른다.Sunstar's GUM과 Ora2는 전세계 여러 지역에서 히알루론산 함유 경구 보습제 제품 시리즈를 출시했다;LACALUT와 ORAL-O-SEPT는 히알루론산을 활성 성분으로 한 껌 관리 제품을 선보였다;2020년 이후 중국 시장에도 다양한 제형의 치약, 구강청결제, 구강 스프레이 등 히알루론산을 함유한 여러 구강관리 제품들이 출시되고 있다 (표 1 참조).

구강관리제품의 히알루론산 적용 동향 4

4.1 히알루론산의 제조

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. 고분자 히알루론산 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.

천민산 등 [29]은 a 가 함유된 다기능 구강관리 조성물을 공개했다히알루론산 혼합물, 다양한 분자량 범위의 히알루론산을 주요 활성 성분으로 결합하고 구연산아연과 공생하여 시너지 효과를 얻음으로써 매일 구강 건강 유지에 유익한 효과를 제공합니다.펑닝 등 30명은 분자량에 따른 히알루론산의 구강 케어 효과에 대해 심도 있는 연구를 진행해 히알루론산 구강 케어 제형을 개발했다.이 제조물은 분자량이 2-5 kDa인 가수분해 된 히알루론산 또는 그 염의 30%-40%, 분자량이 200-600 kDa인 히알루론산 또는 그 염의 35%-45%, 분자량이 1,300~1,500 kDa인 히알루론산 또는 그 염의 20~30%의 성분으로 구성된다.효능 평가 결과,이 조성물은 현저한 구강 보습 효과를 나타내며, 치은세포로부터 염증인자의 방출을 감소시키고, 손상된 구강 세포를 복구하여 구강 건강에 대한 종합적인 관리를 제공하는 것으로 나타났다.치약, 구강청결제, 스프레이 등 다양한 구강 관리 용품에 적용할 수 있다.쑤하이옌 등 [31]은 제형이 다른 치약에이 제형을 첨가하고 히알루론산 함량과 치약의 물리적, 화학적 특성을 조사하였다.그 결과 치약의 물리적 · 화학적 특성이 안정적이며, 히알루론산 함량이 크게 감소하지 않았고, 다른 원료 및 보조원료와도 잘 호환되는 것으로 나타났다.

구강 관리 제품의 혁신적인 응용 4.2

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.

2020년 6월 29일 차이나'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.

참조

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[4] 싱러둥, 장시궈, 장시민.건강한 인간 살리브 [J]의 히알루론산 수치 검출.현대기공학회지 2001, 15(3):176-178.

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[6] 장이딩, 청싱퀸, 우홍근.구강 질환 치료에 히알루론산의 응용 [J.대한노인치과학회지, 2019, 17(2):108-112.

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[11] 장잉, 최단.xerostomia의 임상적 평가와 대책.중국실용기공학회지 2017, 10(9):530-534.

[12] NARHI T O. 노인에서 구강건조증의 주관적 감정 유병률 (J.대한치과연구회지, 1994, 73(1):20-25.

[13] 왕빈, 싱양핑, 판수 등이 있다.히알루론산 및 히알루론산의 제로스토미아 치료 및 완화용 조성물 제조용 응용:CN103405470A [P].2013-11-27다.

[14] 맹상징, 류소잉, 중공리 등.제로스토미아 완화용 조성물 및 이의 제조 방법:CN105267234A [P].2016-01-27다.

[15] MASTERS J G, SHIRA P. Dentifrice composition for treating xerostomia:CN101795686A [P].2010-08-04다.

[16] 황자오.세균 유발 치은염 치료에서 Gengigel gel의 효과에 대한 연구 (The study of Gengigel gel in The treatment of plague-induced gingivitis)청두:쓰촨 대학교, 2004.

[17] MUN ERA H B, KAW THER A, FITOON A 외.Porphyromonas gingivalis 균주에 대한 0.8% hyaluronic acid와 0.2% chlorhexidine의 항균효능:in vitro 연구 [J].파키스탄 의학 저널, 2020, 36(2):111-114.

[18] BEGUM G, GIZEM I K, OGUL L T, 그 외.히알루로난 함유 구강청결제4일 무양치 모델에서의 플라크 억제 효과 [J.구강 건강 &예방치의학, 2020, 18(1):61-69.

[19] 알리 AA, 자이드 A M, 헤이더 R A 외.클로르헥시딘, 항산화제, 히알루론산 구강청정제의 생체세포유발 치은염 관리에 대한 효능을 평가하기 위한 무작위 이중맹검 임상시험.국제치위생학회지 2020 (1):1-10.

[20] 제노베시아, 바로네아, 토티 P 외.0.12% 클로르헥시딘 대 0.12% 클로르헥시딘 플러스 히알루로니산 구강청정제의 침수 단일 임플란트 삽입 부위 치유에 대한 효능:단기 무작위 대조 임상시험 [J].국제치위생학회지 2017, 15(1):65-72.

[21] 손춘옌, 천수, 린리.히알루론산의 경구약 [J] 에의 적용.중국실천기공학회지 2013, 6(1):56-59.

[22] 천민산, 리린, 왕젠시 등.고 분자량 히알루론산은 MAPK와 NF-kappaB 신호전달 경로 [J]를 통해 P. gingivalis-유발된 염증과 인간 치은섬섬유세포에서의 이동을 조절한다.Oral Biology Archives, 2019(98):75-80.

[23] 장화웨이, 위왕룽, 청스팡 등.치은염의 히알루론산 양치처리의 생물학적 활성 효과를 조사하기 위한 연구 (J.임상의학문헌학회지, 2015, 23(2):4808-4809.

[24] 레이시캉, 관우유, 펑슈칭.히알루론산과 트레할로스를 함유한 치약 및 이의 제조방법:CN110123702A [P].2019-08-16다.

[25] 보철미 M, 베빌라콰 C.외인성 히알루론산과 상처 치유:갱신된 시력 [J].판 미네르바 메디아, 2012, 54(2):129-135.

[26] 무함마드 H M, 무함마드 M, 압델하디이엔 외.쥐 모델에서 국소 적용 약제가 구강 내 상처 치유에 미치는 영향:임상적 및 조직학적 연구.국제치위생학회지 2011, 9(1):9-16.

[27] 장선.히알루론산이 쥐의 경구 상처 치유에 미치는 영향에 관한 조직학적 연구 (D.타이위안:산시의과대학, 2019.

[28] 모리시마 세이지, 오카다 토시모치, 요시카와 마사루.구강용 조성:JPH10182390A [P].1998-07-07다.

[29] 천민산, 왕젠시, 리린 등.히알루론산 혼합물을 포함하는 다중효과 구강 내 조성물 및 이의 적용:CN107536725A [P].2018-01-05다.

[30] 펑닝, 종원빈, 마오화이 외.히알루론산 구강 케어 조성물 및 준비 방법 및 그 응용:CN110585062A [P].2019-12-20다.

[31] 쑤하이옌, 왕하이잉, 샤오샤오홍 외.치약의 히알루론산 응용 [J.구강관리산업, 2019, 29(2):6-10.