Topical Application of Ozone in Medicine

To the best of our knowledge, the first application of gaseous O3 was performed during World War I for treating German soldiers affected by gaseous gangrene due to Clostridium anaerobic infections very sensitive to O3.
In 1936, Dr P. Aubourg, by using a metal cannula, was the first to propose the insufflations of gaseous O2/O3 in the rectum to treat chronic colitis, anal ragadis and fistulae. This approach is very empirical and unprecise and today it is mostly used by Cuban physicians. In 1937, a Swiss dentist, E. A. Fisch (1899– 1966) had the idea to use it in his practice and, by a twist of fate, he treated Dr. E. Payr (1871–1946) a surgeon who had a painful gangrenous pulpit. Payr was so enthusiastic of the O3 effect to use it in his surgical practice with great advantag. 
. Later on, Werkmeister mastered the use of gaseous O3 in several skin ulcers due to atherosclerosis, diabetes and radiotherapy by either enclosing a leg in a polythene-bag (the so-called bagging system) or using an ozone-resistant plastic cup applied in other areas. In the former application the gas was introduced to just inflate the bag containing some distilled water.
The system was static but after 20–25 minutes the gas was aspirated and destroyed. The O3 concentrations varied between a high 80 μg/mL in very purulent ulcers and progressively lower concentrations down to 10 μg/mL as the ulcers improved because excessive O3 would be deleterious for healing. As the cup system had an inlet and an outlet, Werkmeister could realize a continuous gas flow with a modest depression that enhanced the vasodilation of the ulcer’s area. With both systems he treated many extensive and otherwise incurable lesions within 50–200 days. It is noteworthy that gaseous O3 works well only in a water vapour-saturated bag because it must dissolve into superficial water or in the exudate to react proficiently. The normal skin does not undergo any damage during the treatment. Today these procedures are still in use but they are somewhat cumbersome and great care must be exercised to prevent air contamination.
How ozonated oils act remains an open question. Probably, when the stable triozonide comes into contact with the warm exudate of the wound, it slowly decomposes into different peroxides, which readily dissolves in water, probably generating hydrogen peroxide that can explain the prolonged disinfectant and stimulatory activity.
If it is correct, this reasoning implies that we should have titrated preparations with high, medium, or low ozonide concentrations to be used during the inflammatory septic phase I, regenerating phase II or remodelling phase III, respectively. These phases have been related to the rapidly changing cell types and to the release of cytokines and growth factors that modulate the complex healing process.
An alternative method for treating diabetic foot ulcers is the use of hyperbaric oxygen therapy (HOT) but in such a case one disadvantage is the use of only hyperbaric O2 and another is the need to close the patient in the chamber for two hours. Therapeutic results are far more modest than topical O3 application, particularly when it is contained in a close cabinet with thermostatically-controlled temperature. However this procedure requires considerable idle times and, if an aspirating pump is unavailable, it may contaminate the operating room.
For these reason today for cleaning and disinfecting cutaneous and mucosal infections and lesions due to many causes (like, e.g., trauma, ischemia, burns), it appears preferable to use at once freshly ozonated water and then ozonated oil, particularly during the night or at rest conditions. 
The process of water ozonation needs of double distilled water and O3 concentrations ranging from 20 up to 100 μg/mL of gas to have a final yield of 5 up to 25 μg/mL, respectively. O3 is directly bubbled into the water and the gas in excess is passed through a dehydrating device and finally through a destructor. Depending upon the water volume and the gas flow, a period of ozonation between 5– 20 minutes is sufficient to saturate the water with gaseous O3. In fact, if the water is ultrapure, O3 physically dissolves in the absence of chemical reactions and if kept in a glass bottle closed with a Teflon cap, the concentration halves only after 300 hours at 0◦C. However, at 20◦C the half-life is about 10 hours. It must be noted that monodistilled water allows a much faster O3 decomposition and it is not practical. It is adviced to maintain the bottle at 4◦C and to quickly close the bottle at any time, or better to have a valve system to prevent gas losses.
It would be useful to device a procedure for maintaining the O3 concentration for longer times and we are investigating a possible procedure. On the other hand, ozonation of either olive or sunflower oils requires a much longer time and the procedure needs to be well-standardized in terms of gas-flow, O3 concentration, oil volume, and temperature. As recently reviewed, at least twenty different vegetable oils have been patented but so far it remains impossible to define their relative cost/benefit. At this stage, after evaluating several physicochemical criteria, stability, efficacy, and cost, it seems that sesame oil has several advantages in comparison to other oils.

How and when ozonated water and oils are used?

Chronic wounds range from diabetic foot to putrid and deep ulcers due to limb atherosclerosis, or trauma and burns. Moreover, both immunosuppressive chemotherapy and/or malnutrition cause abscesses, anal fissures and fistulae, bed sores, furunculosis, and osteomyelitis which are difficult to treat and often fail after prolonged treatments. About 7 million patients in the United States are affected with a cost over US$ 25 billion annually.
Various types of disinfectants, antibiotics, antifungal, antiprotozoal, and growth factors are scarcely effective because the deranged metabolism and local hypoxia are not modified. Several other approaches such as vacuum therapy, maggot therapy and devices for providing topical oxygen therapy in a clinical setting have been proposed and variably used. This last approach has a rationale in the sense that enhanced oxygenation is useful for activating the metabolism and cell proliferation of ischemic tissues. However, it has also considerable limitations because it is a cumbersome therapy, with minimal disinfectant activity and modifications of the fundamental pathogenetic mechanisms.
Another topic of critical interest is the pathologies of the vaginal mucosa. Although rarely deadly (as the toxic shock syndrome due to a forgotten absorbent tampon), a majority of women physically and psychologically frequently suffer from a number of infections due to several pathogens such as Neisseria gonorrhoeae, Trichomonas vaginalis, Candida albicans, Chlamidia trachomatis, Herpes virus type-II (HVII), human papilloma viruses (HPV), human immunodeficiency virus (HIV), often due to unprotected sexual intercourses, stress, change in sexual partners and also physiological hormonal changes during menopausa. About 20 million Americans are affected by the distressing HV-II and as many 40 million have the genital HPV with warts and the impending risk of cervix cancer. Moreover, the further implantation of opportunistic infections complicates the treatment
It is unfortunate that orthodox medications are expensive and not so useful because of drug-resistant pathogens and side effects limiting the compliance. So far official medicine has not yet entertained the topical use of O3 and derivatives in therapy because they are not profitable and no extensive clinical trials have been published in peer-reviewed journals: the therapy has remained in practitioners’ hands and the results remain anecdotal. Moreover, the parenteral use of ozone, also known as ozone therapy, is very useful as adjuvant: it is reasonably ease to perform in terms of classical ozonated major and minor autohemotherapy. 
The latter modality has been successfully used for eliminating recurrences of HV-I and II infections. However, topical therapy is essential and it is carried out by using vaginal irrigation of fresh ozonated water and application of vaginal ozonated oil pessaries for the night. During prolonged treatment the ozonated compounds allows the elimination of any pathogens. So far no resistance to O3 has been demonstrated. Creams containing ozonated oils can be used 3-4 times daily for external genital areas and also for several anorectal affections.
As for the oral infections (aphthae, HV-I, opportunistic superinfections, or acne) the earliest as possible application of ozonated ointments, by minimizing pathogen diffusion and enhancing microcirculation, reduces the swelling, destroys the pathogen, and allows a rapid healing. Last but not least, clinical trials in tinea pedis as well as onychomycosis have been recently published and have shown the usefulness of ozonated sunflower oil.


At the present, especially in young people, venereal infections are increasingly frequent and therefore a suitable, effective medication with ozonated compounds will be a huge economical and social value. Also, elderly people are burdened with a variety of wounds and ulcers, some of which never heal, making life miserable. It is hoped that the the great number of research will inform official medicine for advance of ozone therapy and will incite to programme suitable clinical trials to show the full efficacy of ozone therapy by evidence-based medicine.

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