Application of ozonized oils in human body and oral cavity systems

BRITO JÚNIOR, Anildo Alves de; CARNEIRO, Jaiza Kênsuly Moura Pinheiro; REIS, Júlia Vianna Neri Andrade; OLIVEIRA, Tiago José Silva; DANTAS, Juliana Borges de Lima

doi:10.1590/1981-86372022002720200152

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RGO - Revista Gaúcha de Odontologia

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REVISÃO • Rev Gaúch. Odontol. 70 • 2022 • https://doi.org/10.1590/1981-86372022002720200152 copy

Application of ozonized oils in human body and oral cavity systems

Aplicação dos óleos ozonizados nos sistemas do corpo humano e cavidade oral

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Wound healing consists of the coordinated cascade of molecular, cellular and biochemical events that interact for tissue recomposition to occur. The interruption or failure in this process can trigger the delay in closing the lesion and chronic wounds, in addition to infections. Ozonotherapy proves to be a promising alternative, capable of assisting in the tissue healing process, modulating the inflammatory response and preventing the development of infection. To present, analyze and discuss, through a literature review, the use of Ozonated Oils in the repair of the human body and oral cavity systems. SciELO, LILACS, MEDLINE and PubMed databases were consulted, using the following DeCS / MeSH descriptors: “ozonized oil”; “healing”; “ozone therapy”. After crossing, counting and analyzing, 13 studies were selected, according to the theme. Due to the complementary theoretical foundation, 44 articles were included, totaling 57 articles used for the present review. Ozonized Oil therapy has beneficial clinical effects, which include antimicrobial, immunostimulating, analgesic, antipoxic, immunoregulatory and antioxidant action. Topical management of ozone has proven effective for the treatment of foot-and-mouth disease, gingivitis, ulcers and dermatitis, contributing to pain relief and healing. Infectious skin diseases, abscesses, allergic skin diseases, scaly erythema, psoriasis and palmoplantar pustulosis are pathological conditions, the treatment of which benefits from the application of Ozonized Oils. Ozonized Oils have been shown to be effective in the treatment of local infections, when in appropriate formulations and in controlled cases, being a promising therapeutic alternative for tissue repair.

Indexing terms
Healing; Oil; Ozone

Data Base	Crossing	Simple Identified	Excluded	Final Sample
Total	–	51	38	13
SciELO	Óleo Ozonizado	2	1	1
MedLine	Oil AND ozone OR healing AND ozone therapy	19	17	2
LILACS	Oil AND ozone OR healing AND ozone therapy	6	6	0
BBO	Oil AND ozone OR healing AND ozone therapy	1	1	0
PubMed	Oil AND ozone OR healing AND ozone therapy	23	13	10

Authors / Year	Methodology	Results
Menéndez et al. [¹⁶16 Menéndez S, Falcón L, Simón DR, Landa N. Efficacy of ozonized sunflower oil in the treatment of tinea pedis. Mycoses. 2002;45(8):329-332. https://doi.org/10.1046/j.1439-0507.2002.00780.x https://doi.org/10.1046/j.1439-0507.2002... ]	Randomized controlled phase III clinical trial. The effectiveness of ozonized oil in the treatment of Tinea pedis was evaluated. Ozonized oil was compared with 2% ketoconazole cream (Nizora^l®, Janssen, São José dos Campos, SP, Brazil) in 200 people, with allocation of 100 patients in each group. Administration took place twice a day for 6 weeks.	All injuries regressed. From a clinical and mycological point of view, a success rate of 75 and 81% was achieved for ozonized oil and ketoconazole, respectively, with no statistically significant difference. None of the groups showed side effects. After 6 months of treatment, there was no recurrence in the ozone group. Ozonized oil proved to be an effective and low-cost medication.
Menéndez et al. [¹⁷17 Menéndez S, Falcón L, Maqueira Y. Therapeutic efficacy of topical OLEOZON® in patients suffering from onychomycosis. Mycoses. 2011;54(5):272-277. https://doi.org/10.1111/j.1439-0507.2010.01898.x https://doi.org/10.1111/j.1439-0507.2010... ]	Randomized phase III clinical trial for the treatment of onycosis. A total of 400 outpatients were randomly allocated to 2 groups: Experimental, treated with ozonized oil twice a day, and the control, treated twice a day with 2% cream ketoconazole (Nizoral^®, Janssen, São José dos Campos, SP, Brazil), for 3 months.	In the group that used ozonized oil, 90.5% of the patients exhibited complete remission. In the control group, 13.5% achieved complete regression and 59% maintained the initial clinical aspect. One year later, the experimental and control group had 2.8% and 44.4% of relapses, respectively. Topical ozone therapy has shown superior efficacy in the treatment of onycosis. No side effects were observed.
Campanati et al. [¹⁸18 Campanati A, De Blasio S, Giuliano A, et al. Topical ozonated oil versus hyaluronic gel for the treatment of partial- to full-thickness second-degree burns: A prospective, comparative, single-blind, non-randomised, controlled clinical trial. Burns. 2013;39(6):1178-1183.]	A total of 30 patients with 2nd degree skin burns in the reepithelialization phase were included. The burn was subdivided into 2 symmetrical parts: 1 st treated with exclusive application of ozonized oil and the 2nd part, used hyaluronic acid gel, daily, for 12 weeks. All patients underwent clinical evaluation and videocapillaroscopy at the beginning of the study, 6 and 12 weeks later.	Regardless of the treatment used, all injuries showed improvement. Ozonized oil was as effective as hyaluronic acid in improving tension, itching, erythema and burning sensation signaled by patients. However, ozonized oil appears to be more effective than hyaluronic acid in reducing hyperpigmentation after injury (p<0.05).
Solovăstru et al. [¹⁹19 Solovăstru LG, Stîncanu A, De Ascentii A, Capparé G, Mattana P, Vâţă D. Randomized, controlled study of innovative spray formulation containing ozonated oil and α-bisabolol in the topical treatment of chronic venous leg ulcers. Adv Skin Wound Care. 2015;28(9):406-409.]	Randomized controlled study with 29 patients who had chronic venous ulcers for less than 2 years. Ozonized Oil 9.6% O₃ and α-bisabolol (Azexin, Alfa Wassermann, Bologna, Italy) were administered in the Experimental group or cream of vitamin A and E, talc and zinc oxide, in the control group for 30 days. On days 0, 7, 14 and 30, ulcers were measured. The area of the wound and the speed of healing were calculated.	The group that received the formulation with ozonized oil and α-bisabolol showed complete healing of the ulcers (25% vs 0%). In addition, the ulcers in the Experimental group had a noticeable reduction in the wound, with 34%, 59% and 73% after 7, 14 and 30 days of ozone administration, respectively (p<0.05).
Laureti et al. [²⁰20 Laureti S, Aborajooh E, Mattioli B, Poggioli G. Treatment of minor dehiscence after endorectal advancement flap in perianal Crohn’s fistulas with ozonized oil NOVOX®. Tech Coloproctol. 2015;20(2):139-140. https://doi.org/10.1007/s10151-015-1404-4 https://doi.org/10.1007/s10151-015-1404-... ]	A total of 26 patients with Crohn’s disease and residual fistula with minimal drainage were included in the study. Patients were treated with ozonized oil. This agent was administered daily for a period of 1 to 6 months	Residual healing of the fistula occurred in 65.4% (17/26) of the patients, with an average follow-up time of 23.81 (range, 2 to 42) months.
Lu et al. [²¹21 Lu J, Guo M, Ligui H, Wu K, Xiang Y, Huang J, Gao L. Efficacy of combination of ozonated water with oil for treatment of tinea pedis. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018;43(2):147-151. Chinese. https://doi.org/10.11817/j.issn.1672-7347.2018.02.007 https://doi.org/10.11817/j.issn.1672-734... ]	Randomized blind study with 60 patients with Tinea pedis, who were allocated to 2 groups. In the control group, Naftinfin Hydrochloride (Chongqing Hua Bang Pharmaceutical Ltd., China) and ketoconazole cream (Chongqing Hua Bang Pharmaceutical Ltd., China) were applied once a day. The ozone group was treated with an ozonized water bath and subsequent topical application of ozonized oil, once a day. The treatments took place for 4 weeks. At the end of the 1st, 2nd and 4th week, clinical and laboratory information was collected.	Within 4 weeks of therapy, 6 patients in the control group were positive by mycological examination, while 1 patient using ozone was positive, with no statistical difference between the groups (p>0.05). Changes in signs and symptoms at the end of the 1st, 2nd and 4th week were noted and did not show any significant difference between the groups, in the 3 different moments (p>0.05). No observations regarding side effects were reported.
Quin et al. [²²22 Qin G, Huang J, Pan Y, Xiang Y, Ou C, Huang J, et al. Topical ozone application: An innovative therapy for infantile atopic dermatitis. Med Sci. 2018;43(2):163-167. https://doi.org/10.11817/j.issn.1672-7347.2018.02.010 https://doi.org/10.11817/j.issn.1672-734... ]	Randomized clinical study with 60 children with atopic dermatitis, who were allocated to the experimental group (n=30) and the control group (n=30). Hydrotherapy was performed 3-5 times a week and ozonized oil was applied twice a day. In the control group, washing was performed with warm running water and application of base oil (Nanhaizhi Medical Technoly Co., Ltd) and moisturizer, if necessary. The treatment lasted 2 weeks.	Inflammation in the skin reduced and erosions healed after 3-5 days of topical ozone application. The effective rates were 80% in the Experimental group and 20% in the control group in the respective treatments.

Authors / Year	Methodology	Results
Ripamonti et al. [²⁴24 Ripamonti CI, Cislaghi E, Mariani L, Maniezzo M. Efficacy and safety of medical ozone (O(3)) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: preliminary results of a phase I-II study. Oral Oncol. 2011;47(3):185-190. https://doi.org/10.1016/j.oraloncology.2011.01.002 https://doi.org/10.1016/j.oraloncology.2... ]	Preliminary prospective study of phase I-II in 10 subjects undergoing treatment with bisphosphonates diagnosed with osteonecrosis. Ozonized oil was applied to wounds ≤2.5cm. Each patient was treated with a maximum of 10 local applications of the oil, 1 time every 3 days, with each application lasting 10 minutes.	The lesions healed completely, between 3 and 10 applications. No surgical intervention was necessary. The radiographic examination found no residual bone lesions after therapy. It was also observed success and tolerability to ozone in the form of oil.
Hernández et al. [²⁷27 Hernández FM, Ibarra MDM, Valdés MRG. Evolución clínica de las pericoronaritis tratadas con OLEOZON® en urgencias estomatológicas. Rev Méd Electrônica. 2010;32(2):8-16.]	Phase III randomized clinical trial. The sample included 90 patients with pericoronitis. In the experimental group, ozonized oil was applied 3 times a day, for 48 or 72 hours. In the control group, trichloroacetic acid was applied, antibiotic therapy depending on the type of pericoronitis and relief of trauma in the region (extraction of the antagonist or reduction of cusps).	The effectiveness, with statistical significance (p=0.004) of the ozonized oil in the treatment of pericoronitis was verified in relation to the control group.
Patel et al. [²⁸28 Patel PV, Kumar V, Kumar S, GD V, Patel A. Therapeutic effect of topical ozonated oil on the epithelial healing of palatal wound sites: a planimetrical and cytological study. J Invest Clin Dent. 2011;2(4):248-258. https://doi.org/10.1111/j.2041-1626.2011.00072.x https://doi.org/10.1111/j.2041-1626.2011... ]	Randomized study with 18 individuals, who were divided into a control group (n=10) and an ozonized oil group at a concentration of 14 Ig/mL (n=8). A free gingival graft surgical procedure was performed, with the application of 2 mL of oil to the palatal wounds daily for 1 week. Clinical and cytological analysis was performed at 7 different times.	The group treated with ozonized oil, when compared to the control, showed significant improvements (p≤0.05) in wound size on days 5, 7, 14, 21 and 28 and higher cytological results (p≤0.001) on days 7, 14 and 21 and in the 2nd and 3rd month, after the surgical procedure.
Patel et al. [²⁹29 Patel PV, Kumar S, Vidya GD, Patel A, Holmes JC, Kumar V. Cytological assessment of healing palatal donor site wounds and grafted gingival wounds after application of ozonated oil: an eighteen-month randomized controlled clinical trial. Acta Cytol. 2012;56(3):277-284.]	Randomized triple-blind placebo controlled study with 24 subjects with localized gingival recession, who were treated surgically, and allocated to an ozonized oil group at a concentration of 14Ig/mL (n=12) and a control group (n=12). After 24 hours, from the 3rd, 7th, 14th and 21st day and 2, 3, 8 and 18 months after the operation, cytological parameters were recorded.	The results showed that there was a significant evolution (p<0.001) in epithelial repair on the 7th, 14th and 21st days and 2, 3 and 8 months after the operation in the ozonized oil group compared to the control group.
Huang et al. [³⁰30 Huang J, Huang J, Xiang Y, Gao L, Pan Y, Lu J. Topical ozone therapy: An innovative solution to patients with herpes zoster. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018;43(2):168-172.]	A total of 60 Herpes Zoster patients were allocated to two groups: control; oral use of valacyclovir, 0.3g per day, 3 times a day, associated with lowlevel laser and topical mupirocin ointment 2%, 2 times a day; ozone group followed the same treatment protocol, except replacing the mupirocin ointment with topical use of ozone, which included the daily hydrotherapy associated with ozonized oil, twice a day. Symptoms, adverse reactions and discoid cells were observed on days 0, 3, 7 and 14.	On the 7th day of treatment, the discoid cells in the ozone group regressed, with a statistically significant difference compared to the control group (p<0.05). The pain scores in each situation between the two groups was statistically significant (p<0.05). Clinical results showed 100% effectiveness in the Ozone group and 86.7% in the Control group, with statistical difference (p<0.05).

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[1] Correspondence to: JBL Dantas. E-mail: judyborges@gmail.com