Use of Ozone Gel in Various Fields Including Atopic Dermatitis and Its Future Application in Dentistry

Background and Purpose:
In our country, it is estimated that approximately one in two people suffers from some form of allergy, with atopic dermatitis affecting about 10% of the population. Research into allergic diseases is gradually progressing, yet there are no complete preventive or curative treatments available. Current treatment primarily involves long-term symptomatic therapy through environmental management and pharmacotherapy with anti-inflammatory drugs. ¹⁾ Furthermore, it is also observed in the dentistry field with three-quarters of the population being said to be suffering from periodontal disease . The misuse of antibiotics, leading to multidrug-resistant bacteria, poses a significant social issue, and there are many cases where long-term antibiotic use is not feasible, especially in oral care. Both atopic dermatitis and periodontal disease are inflammatory diseases, and the long-term application of steroids as anti-inflammatory drugs has been problematic due to side effects like steroid-induced rosacea.

Against this backdrop, ozone has garnered attention as a bactericidal method that does not lead to resistance, unlike antibiotics, and also possesses wound healing and anti-inflammatory effects. Simultaneously, the correlation between dentistry and various systemic diseases has become clear, emphasizing the importance of cooperation between dentistry and other medical fields.
Here, we discuss the current and future applications of ozone in treating atopic dermatitis, primarily affecting the skin and eyes, and explore its potential in dentistry to improve the quality of life (QOL) through systemic disease approaches.

Use of Ozone in Dermatology:
According to the Atopic Dermatitis Treatment Guidelines by the Japanese Dermatological Association 2), atopic dermatitis is characterized by physiological dysfunction of the skin, inflammation caused by multiple specific stimuli or allergens, and tends to have a chronic progression. The consensus for treatment includes primarily using topical steroids for inflammation, incorporating skin care including moisturizers for physiological dysfunctions, using antihistamines and anti-allergy agents as adjunctive therapies for itching, and removing exacerbating factors as much as possible. Particularly, the non-steroidal anti-inflammatory drugs (NSAIDs) for topical application have very limited anti-inflammatory effect and can occasionally cause contact dermatitis. Thus their use is limited and steroid topical applications are the basis. However, long-term use of topical steroids can lead to skin thinning and the development of steroid-induced rosacea, necessitating caution with prolonged use. Normal wound healing involves three phases: inflammatory, proliferative, and remodeling, typically requiring 3 to 14 days. Inflammation is a biological defense response against infections by bacteria or viruses, characterized by redness, swelling, fever, pain, and functional impairment. However, when this inflammatory state becomes chronic rather than a transient acute inflammation, it can lead to various complications. At this point, there is a need for antibiotics and anti-inflammatory drugs that do not cause side effects even with long-term administration. Specifically for atopic dermatitis, Staphylococcus aureus has been identified as an exacerbating factor 3). There are reports indicating the effectiveness of ozonated water, mainly for its bactericidal effects 4), suggesting the possibility of ozone application in cases that conventional guidelines would not work. Additionally, mites are often implicated as specific allergens, and ozone has been shown to inactivate both allergens and proteases, suggesting similar effects in house dust containing many substances other than allergens 5). Furthermore, under pharmaceutical law, while applicable to cosmetics, ozonated glycerin gel—a moisturizer—has been confirmed for its safety 6), bactericidal effects 7), and wound healing properties 8), and is being used for chronic inflammations and ulcers, including intractable atopic dermatitis that are difficult to heal with conventional methods. 9)

Angular Cheilitis Recovery Case

Use of Ozone in Ophthalmology:
The use of ozonated water is increasing in ophthalmology, one of the most delicate organs. This is because it causes significantly less corneal epithelial damage compared to commonly used povidone-iodine formulations, does not contribute to resistant bacteria formation 10), and is effective against a broad spectrum of bacteria and viruses.11) Additionally, it has been noted that wound healing after cataract surgery is cleaner and faster, and eyesight recovery is quicker.
Ozonated water, a highly non-irritating solvent with a neutral pH that quickly reverts to oxygen, does not exhibit cytotoxic residuals on cells, contributing instead to wound healing. This distinguishes it from traditional disinfectants and chlorinated agents, making it an ideal low-irritant antimicrobial and wound healing agent in ophthalmology.

Use of Ozone in Dentistry:
The oral cavity, which harbors the same level of bacteria as the gastrointestinal tract (around 1011), is susceptible to bacterial infections even from minor injuries. However, due to its mucosal sensitivity and issues such as anaphylactic shock with chlorhexidine gluconate, there is a high demand for safe and effective antimicrobial and anti-inflammatory agents for mucosal application. The rise of an aging society has also gradually unveiled the correlation between oral health and systemic diseases, increasing the need for safe and effective oral care.
Against this background, ozonated water has garnered attention and various dental applications are being explored, though clinical reports are still few. Reasons include the impact of ozone gas on respiratory pathways and the instability of ozone in the organically rich environment of the mouth, which has hindered its widespread adoption. High concentrations of ozone gas are toxic to the respiratory system, but reports suggest that using a vacuum during oral application can reduce ozone gas levels to below detectable limits 12), indicating the. potential for safe use of ozonated water in the mouth. Also, the instability of ozone in an organic-rich environment has been addressed by using water as a solvent, which has a short half-life(30~40 minutes) and high fluidity, making retention at the affected part challenging.
The developed ozone gel, a moisturizer widely used in food and pharmaceutical products, contains ozonated glycerin, which significantly extends its half-life. The viscous nature of glycerin improves retention, making it more suitable for use in the mouth. Moreover, while ozonated water can only dissolve about 20 ppm of ozone under normal temperature and pressure, ozone gel can dissolve up to 1000 ppm, greatly increasing the total amount of ozone involved in reactions, which can be effective even in the presence of organic material. Importantly, even at 1000 ppm high, the gel promotes wound healing. The slow release of ozone from glycerin, despite the high concentration, ensures it is extremely low-irritating. Moreover, the moisturizing properties of glycerin, combined with the bactericidal and anti-inflammatory effects of ozone, provide an ideal moist wound healing environment. Furthermore, the ozone gel does not release any ozone gas, eliminating concerns about respiratory impacts and making it ideal for oral use.
This suggests that ozone gel, which does not lead to resistant bacteria and has bactericidal and anti-inflammatory effects, could be widely applied for treating periodontal disease and other inflammatory oral diseases.

Future Guidelines for the Use of Ozone in Dentistry:
Traditionally, dental allergies were mostly associated with metal allergies. However, with the national issue of increasing allergic diseases and the importance of oral care in an aging society impacting systemic diseases, a more focused approach to allergies and inflammatory diseases in dentistry is required. Additionally, there are increasing cases where patients with atopic dermatitis, due to misunderstandings including myths about steroid formulations, avoid dermatologists and worsen their condition with home remedies, becoming a social issue. Dentists frequently encounter oral manifestations of various diseases, such as stomatitis and angular cheilitis, and are well-positioned to provide appropriate guidance, playing a crucial role in addressing these issues.13) Skin is often described as the mirror of the organs, and the mouth as the mirror of the body. Using ozone to contribute centrally to the healing of various refractory diseases is considered a critically important mission for the future of dentistry.

References:
1)”Direction for Allergy Disease Control,” Notification by the Director of the Disease Control Division, Health Bureau, Ministry of Health, Labour and Welfare, Japan, August 31, 2011.
2)”Atopic Dermatitis Clinical Guidelines,” Journal of the Japanese Dermatological Association, Vol. 119.8, 2009.
3)Kei Iwatsuki, “Staphylococcus aureus Colonization and Infection in Chronic Atopic Dermatitis,” Journal of Dermatological Science, Vol. 5.7, November 2006.
4)Takuzo Nagano, “Treatment Outcomes of Facial Erythrodermic Atopic Dermatitis with Ozonated Water,” The Gate of Medicine, Vol. 38.6, 1998.
5)Yoshiyuki Murakami, “Study on the Inactivation of Mite Allergens Using Ozone,” Clinical Environmental Medicine, Vol. 19.2, 2010.
6)Houre Oh, “Safety Evaluation of Ozone Gel on Skin and Eyes in Animal Experiments,” J. Hard Tissue Biology, Vol. 20.4, 2012.
7)Kazuhito Aratame, “Bactericidal Effects of Ozone Gel,” Journal of the Showa Dental Society, Vol. 24, 2004.
8)Miyako Terakado, “Histopathological Study on the Wound Healing Effects of Ozone Gel,” Journal of the Japanese Society of Oral Function and Water, Vol. 5, 2004.
9)Takeo Watai, “Presentation of Cases with Refractory Lower Leg Ulcers and Contact Dermatitis Treated with Ozone Gel,” 3rd Japanese Oxidation Therapy Research Association Seminar.
10) Hiroshi Takahashi, “The Usefulness of Ozonated Water as an Eye Wash Disinfectant,” Journal of Medical Equipment, September 2011.
11) Hidetoshi Hanasaki, “Eye Wash Surgery and Postoperative Progress of Cataract Surgery with Ozonated Water,” Ophthalmic Surgery Journal, Vol. 13.3, March 2000.
12)Daisuke Kato, “Measurement of Volatile Gas Concentrations during the Use of Ozonated Water in the Oral Cavity,” Proceedings of the 17th Conference of the Japanese Medical Environmental Ozone Society.
13)Shunichi Okabe, “Angular Cheilitis and Effective Oral Supplements Guidebook,” 2010.