The ability to precisely identify and measure the Ozoile® content in each formulation allows for high-definition dosing. It has thus been possible to develop products in which the concentration of the technology is not random, but is defined based on the specific intended use.
Each Erbagil® product therefore contains a defined quantity of Ozoile®, designed to express the activity required for the specific therapeutic application. This rational approach to formulation development forms the foundation of the patented therapeutic applications of Ozoile® Technology.

For many years, oxidative stress was considered exclusively a harmful phenomenon. Today, it is known that the biological response does not depend simply on the presence of oxidizing molecules, but above all on the quality, intensity, and duration of the oxidative signal that reaches the cells.

When this signal is intense, uncontrolled, and persistent, a condition defined as oxidative distress is established, characterized by an excess of reactive oxygen species (ROS) that exceeds the capacity of the body's antioxidant defenses. The result is an alteration of the redox balance that promotes inflammation, cellular damage, and loss of normal physiological function.

However, there is a completely different condition.

When the oxidative signal is moderate, controlled, and transient, it represents a physiological stimulus capable of activating the cell's natural adaptive responses. This condition is called oxidative eustress.

This is precisely the principle behind Ozoile® technology.

The stable Ozonides of Ozoile® do not act as simple direct oxidizing molecules, but as oxidative lipid messengers. Thanks to their stability, they release a controlled oxidative signal that modulates the redox balance without causing the damage typical of distress. The mild and transient perturbation of the redox balance derived from the interaction of stable Ozonides with the extracellular environment (Extracellular Matrix) contributes to a physiological stimulus capable of modulating the body's adaptive responses and its natural antioxidant defenses.

This mechanism of action was described for the first time in the study published in Current Issues in Molecular Biology (Saija et al., 2024). It has been demonstrated, for the first time, that the stable Ozonides of Ozoile activate the NRF2 transcription factor and increase the expression of Superoxide Dismutase 2 (SOD2), two of the main cellular defense systems against
oxidative stress.

These findings identify the modulation of the redox balance as the biological foundation of Ozoile® Technology, from which the main physiological responses induced by stable Ozonides derive.

The Eustress induced by stable Ozonides represents the biological signal that triggers a cascade of adaptive responses responsible for the main biological activities of Ozoile®:

· Activation of endogenous antioxidant defenses
· Anti-inflammatory activity
· Regenerative and restorative activity
· Support for tissue oxygenation
· Anti-proliferative activity

Taken together, these activities constitute the biological cascade induced by eustress and represent the expression of a single mechanism of action, now confirmed by numerous experimental, clinical, and scientific findings.

The mild and transient disturbance of the redox balance (eustress) resulting from the interaction of stable Ozoile® Ozonides with the extracellular environment triggers the activation of antioxidant defenses.

The study published in Current Issues in Molecular Biology (Saija et al., 2024) demonstrated that eustress activates the transcription factor NRF2, one of the main regulators of the cellular response to oxidative stress. NRF2 activation leads to a significant increase in the expression of Superoxide Dismutase 2 (SOD2), one of the most important endogenous antioxidant enzymes responsible for neutralizing reactive oxygen species at the mitochondrial level. Unlike corticosteroid treatment, Ozoile® induced marked activation of the NRF2/SOD2 pathway, confirming that Ozoile® Technology enhances physiological antioxidant defenses through a biological mechanism distinct from that of corticosteroids.

The study published in Antioxidants (Bravoco et al., 2026), conducted on three-dimensional human intestinal epithelial models (organoids), demonstrated that Ozoile® significantly reduces the intracellular accumulation of reactive oxygen species (ROS), measured using a specific fluorometric assay for the evaluation of cellular oxidative stress (DCFDA). The reduction in ROS confirms that the activation of antioxidant defenses translates into a concrete rebalancing of the cellular redox state, contributing to the maintenance of the epithelial barrier integrity and the tissue microenvironment.

The activation of antioxidant defenses constitutes an important step in the biological cascade resulting from the interaction of stable Ozonides with the cellular environment. The action of stable Ozoile® Ozonides on the redox balance, in fact, creates favorable conditions for the modulation of the inflammatory response, the control of the tissue microenvironment, the protection of the epithelial barrier, and the repair and regeneration processes.

The modulation of the inflammatory response is one of the main biological consequences of eustress induced by stable Ozonides. The activation of endogenous antioxidant defenses must be framed within the broader concept of the recovery of cellular homeostasis, the cell's natural state: the subsequent restoration of this status creates the conditions for physiological control of inflammation.

Unlike treatments that act through the direct suppression of inflammatory mediators, Ozoile® promotes a physiological modulation of the cellular response. The reduction of inflammation is therefore the consequence of the rebalancing of biological processes that regulate tissue homeostasis, rather than a pharmacological inhibition of the inflammatory response.

The anti-inflammatory effect is today documented by a research path that includes experimental studies, clinical trials, and advanced human epithelial models. Taken together, this evidence demonstrates a significant reduction in the expression of the main pro-inflammatory cytokines, including TNF-α, IL-1β, IFN-γ, IL-8 and IL-23, which are key mediators involved in the amplification and maintenance of chronic inflammation.

The first evidence was published in Molecules (Currò et al., 2018), where the topical application of Ozoile® led to a significant reduction in the main mediators of inflammation, associated with an improvement in tissue repair processes. The study demonstrated for the first time that the modulation of inflammation is closely related to the ability of stable Ozonides to re-establish a biological microenvironment favorable to physiological healing processes.

These results were subsequently confirmed in the clinical study published in Urologia Internationalis (Russo et al., 2019), conducted in patients suffering from Lichen sclerosus. The analysis of tissue biomarkers showed a marked reduction in the expression of TNF-α and IL-1β in patients treated with Ozoile®, with levels comparable to, and for some biomarkers, lower than those observed in patients undergoing corticosteroid therapy. This result demonstrates that Ozoile® is able to effectively modulate the inflammatory response through a biological mechanism different from that of steroids, favoring the rebalancing of the tissue microenvironment rather than the pharmacological suppression of inflammation.

Further confirmation has come from the study published in Current Issues in Molecular Biology (Bertuccio et al., 2023), in which Ozoile® was evaluated in human colon epithelial cells (HT 29) and THP-1 monocytes subjected to inflammatory stimulus with lipopolysaccharide (LPS). Treatment with Ozoile® dose-dependently reduced the expression and release of the main pro-inflammatory cytokines, including TNF-α and IL-1β, confirming that stable Ozonides are capable of early modulation of the inflammatory response during the initial phases of cellular activation.

The most recent evidence comes from the study published in Antioxidants (Bravoco et al., 2026), in which Ozoile® was evaluated in three-dimensional intestinal epithelial models derived from patients with inflammatory bowel disease. In this model, among the most representative of human intestinal physiology available today, Ozoile® significantly reduced the expression of the cytokines IL-8, IL-23 and TNF-α, confirming that the modulation of the inflammatory response observed in previous studies is reproducible even in experimental systems of high biological complexity.

The study also demonstrated that Ozoile® helps preserve the integrity of the epithelial barrier and restore a favorable tissue microenvironment, creating the biological conditions necessary for the recovery of physiological tissue function.

Tissue repair represents the natural evolution of the biological cascade resulting from the interaction of stable Ozoile® Ozonides with the extracellular environment.

Tissue regeneration depends on the reactivation of the “biological programs” that regulate cellular survival, adaptation to stress, the reconstruction of tissue architecture, and the recovery of normal tissue functionality.

A further element that characterizes the action of Ozoile® in chronically damaged tissues is the ability to favor the reactivation of the physiological healing process. The study by Zagolin et al. (2022) describes, during treatment, a temporary exacerbation of the lesion, observable on average starting from the third week of application. This phenomenon is interpreted as the transient transition from a chronic condition, in which normal repair mechanisms are blocked, to a biologically active acute phase, capable of restarting the cicatrization process.

The evolution of the repair process has also been documented through histological evaluations performed on tissue biopsies, which allowed for direct observation of the changes associated with the progression of healing. The analyses highlighted the formation of granulation tissue, the proliferation and migration of fibroblasts, and the development of new blood vessels, confirming at the tissue level the reactivation of physiological repair mechanisms.

The temporary transformation of the lesion from a chronic condition to a biologically active phase therefore creates the favorable conditions for the start of re-epithelialization and the formation of neovascularized epithelium. Ozoile® thus contributes to bringing the tissue back within a physiological repair dynamic, allowing the chronic lesion to resume its normal progression toward
healing.

One of the main regulators of this response is HIF-1α (Hypoxia-Inducible Factor-1α), a transcription factor that coordinates the cellular response to hypoxia and promotes the expression of numerous genes involved in tissue repair. Among
these, VEGF (Vascular Endothelial Growth Factor), PDGF (Platelet-Derived Growth Factor), FGF (Fibroblast Growth Factor), and TGF-β (Transforming Growth Factor-β) play a fundamental role; these factors regulate neoangiogenesis, cell proliferation, extracellular matrix deposition, and the remodeling of the injured tissue.

The first experimental evidence was published in Molecules (Currò et al., 2018), where Ozoile® determined a significant increase in the expression of HIF-1α, demonstrating the ability of stable Ozonides to activate the main
molecular programs involved in the adaptive response to hypoxia and tissue repair.

The activation of HIF-1α represents the link between the rebalancing of the biological microenvironment and the initiation of regenerative processes. Through the regulation of growth factors and cellular adaptation mechanisms, Ozoile® prepares the tissue for the reconstruction phase, favoring the progressive recovery of structure and functionality.

The molecular and histological evidence is also confirmed in clinical practice. In the study published in Medicina (Ronsini et al., 2024), treatment with Ozoile® led to a rapid improvement in symptoms related to genitourinary syndrome, with a reduction in pain, burning, dryness, itching, and dyspareunia, accompanied by the recovery of mucosal functionality. These results confirm that the modulation of the tissue microenvironment induced by stable Ozoile® Ozonides also promotes the restoration of tissue integrity and functionality.

The activation of HIF-1α induces the expression of numerous genes involved in tissue regeneration. Among these, VEGF and E-cadherin play a central role in coordinating the formation of new blood vessels and the restoration of epithelial barrier integrity.

VEGF promotes neoangiogenesis, increasing the supply of oxygen and nutrients essential to the healing tissue. E-cadherin, on the other hand, promotes epithelial reorganization and the recovery of cell-to-cell junctions, contributing to the restoration of normal tissue architecture.

The study published in Molecules (Currò et al., 2018) demonstrated that Ozoile® leads to a significant increase in the expression of VEGF and E-cadherin, confirming the ability of stable Ozonides to simultaneously activate the main biological programs involved in regeneration.

The molecular evidence was subsequently confirmed in the randomized clinical trial published by Zagolin et al. (Biomedical Journal of Scientific & Technical Research, 2022), conducted on patients suffering from chronic venous ulcers of the lower limbs. Compared to standard treatment, Ozoile® resulted in a significant reduction in re-epithelialization time, better exudate control, and a lower need for analgesic therapy. Histological analysis of the biopsies also showed an increase in granulation tissue, fibroblast proliferation, and neoangiogenesis, demonstrating that the activation of regenerative programs observed at the molecular level translates into an effective acceleration of healing processes.

These findings are further confirmed in the study published in International Wound Journal (De Angelis et al., 2025), conducted on 200 patients suffering from chronic diabetic ulcers. The therapeutic protocol based on Ozoile® led to a significant acceleration of healing, associated with pain reduction, control of biofilm and local infection, and an improvement in the quality of the newly formed tissue. Histological analyses also documented faster granulation tissue formation, greater fibroblast proliferation, an increase in neoangiogenesis, and more effective collagen remodeling, confirming that the activation of regenerative programs translates into a concrete clinical benefit.

Taken together, this evidence demonstrates that Ozoile® does not merely promote wound closure, but fosters a physiological regeneration of the tissue. Through the coordinated activation of HIF-1α, VEGF, and E-cadherin, the stable Ozonides of Ozoile® promote neoangiogenesis, the restoration of epithelial barrier integrity, and the reconstruction of the tissue microenvironment, creating the biological conditions for faster, more stable, and higher-quality healing.

The antiproliferative activity represents one of the consequences of the progressive rebalancing of the tissue microenvironment resulting from the interaction of stable Ozoile® ozonides with the cellular environment.

In addition to promoting tissue repair, Ozoile® contributes to the restoration of normal cellular homeostasis through the modulation of proliferative processes. In a condition of chronic inflammation, continuous tissue stimulation can lead to excessive cell proliferation, accompanied by the alteration of specific biological markers involved in cell cycle control.

Among these, Ki-67, an index of cell proliferative activity, and p53, a protein involved in cell cycle regulation and DNA damage response, are of particular importance. Increased expression of these markers is frequently associated with pathological proliferation conditions and persistent inflammatory states.

The study published in Pediatric Surgery International (Cassaro et al., 2025), conducted on pediatric patients affected by penile Lichen Sclerosus, demonstrated that treatment with Ozoile® leads to a significant reduction in the expression of Ki-67 and p53, accompanied by a marked decrease in the cell density of the basal epithelial layer.

Particularly relevant is the comparison with corticosteroid therapy. While both showed a favorable effect on proliferative markers, Ozoile® resulted in a more pronounced reduction of Ki-67 and p53 compared to the corticosteroid, suggesting a greater ability to return the tissue toward physiological proliferative activity.

These results indicate that Ozoile® not only helps to reduce inflammation but also contributes to restoring normal cell proliferation control mechanisms. The modulation of Ki-67 and p53 represents, in fact, an additional element of the biological cascade induced by stable Ozoile® ozonides, through which the tissue microenvironment is progressively returned to conditions favorable to the recovery of normal tissue architecture and function

The creation of an oxidative microenvironment ensured by stable Ozoile Ozonides promotes a direct action on microorganisms, which guarantees the control of microbial load and the protection of tissues.

Unlike traditional antibiotics, which act on specific metabolic and structural targets of the microorganism, Ozoile® exerts a physical-oxidative action.

The antimicrobial activity of Ozoile® has been confirmed by microbiological tests conducted on numerous strains of clinical interest, in which a reduction in bacterial and fungal load of up to 99.9% was observed. The microorganisms evaluated include Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis, Acinetobacter baumannii, and various dermatophytes, documenting effective activity against Gram-positive bacteria, Gram-negative bacteria, and fungal species.

Stable Ozonides interact with the lipid components of the cell membranes and envelopes of microorganisms, altering their structural integrity and compromising their viability.

Because this mechanism affects fundamental structures common to numerous microorganisms, Ozoile® exhibits broad-spectrum activity against Gram-positive bacteria, Gram-negative bacteria, yeasts, and fungi. In enveloped viruses, the oxidative modification of the glycoproteins and lipids of the envelope can also hinder recognition and entry into target cells,
helping to limit their spread.

Experimental evidence is also confirmed in clinical practice. In the study published by Di Maria et al. (Journal of Otolaryngology-ENT Research, 2020), the treatment of patients with chronic eczema of the external auditory canal resulted in a reduction of itching by 62.5%, scaling by 72%, and secretions by 80%, with no adverse effects. The results also highlighted the usefulness of Ozoile® in recurrent forms of external bacterial otitis and otomycosis, confirming the technology's contribution to controlling the local microenvironment.

Further clinical confirmation comes from the study published in Medicina (Ronsini et al., 2024), in which treatment with Ozoile® in women suffering from genitourinary syndrome led to the complete clearance of vaginal swabs that had tested positive at enrollment, associated with a significant reduction in burning, itching, dryness, dyspareunia, and other local symptoms. These results demonstrate that Ozoile® contributes to the control of the microbiological microenvironment, favoring the restoration of the physiological conditions of the vaginal mucosa.

Additional confirmation comes from the observational study published by Ricci et al. (Italian Journal of Wound Care, 2022), in which the use of Ozoile® in the treatment of chronic skin lesions was associated with a significant reduction in the incidence of infections, accompanied by an improvement in lesion area and pain symptoms. These results indicate that the control of microbial load helps create a biological microenvironment favorable to physiological tissue repair processes.

The role of antimicrobial activity was further confirmed by Marinova et al. (Trakia Journal of Sciences, 2023), who evaluated the use of Ozoile® in combination with negative pressure wound therapy (NPWT) in the treatment of deep soft tissue infections. The association with Ozoile® resulted in a significant reduction in the time required for wound sterilization, faster re-epithelialization, and a reduction in hospital stay compared to conventional treatments, demonstrating the contribution of Ozoile® Technology to infection control and wound bed preparation.

The microbiological evidence was further consolidated by the study published in the International Wound Journal (De Angelis et al., 2025), conducted on 200 patients suffering from chronic diabetic ulcers. The therapeutic protocol based on Ozoile® favored the control of local infection and bacterial biofilm, helping to restore a tissue microenvironment favorable to healing. This effect was accompanied by a significant acceleration of the healing process, a reduction in pain, and an improvement in the quality of the regenerated tissue. These results confirm that the control of biofilm and microbial load represents one of the first steps in the biological cascade induced by the stable Ozonides of Ozoile® and constitutes a fundamental prerequisite for subsequent tissue repair processes.

The innovation of a healthcare technology is not measured exclusively by demonstrating its biological or clinical efficacy, but also by its ability to improve the organization of care and optimize the use of healthcare resources. In this context, pharmacoeconomics serves as the tool that allows for the evaluation of a technology's overall value, considering not only clinical outcomes but also its impact on the direct and indirect costs of care.

The gathered evidence demonstrates that Ozoile® Technology modulates the primary biological mechanisms involved in tissue healing: it modulates the redox balance and inflammatory response, contributes to controlling the microbiological microenvironment, promotes tissue regeneration, and restores physiological cellular homeostasis. The clinical translation of these effects results in more favorable lesion progression, with a reduction in complications and a more rapid recovery of tissue functionality.

These benefits are also directly reflected in the use of healthcare resources. Faster healing, in fact, leads to a reduction in the number of dressings, follow-up visits, the need for additional treatments, and the risk of infectious complications. At the same time, better pain control helps reduce reliance on analgesic drugs and improves the patient's quality of life throughout the care pathway.

Important confirmation of these aspects comes from the study published by Perrone et al. in the Italian Journal of Wound Care (2025), which evaluated an integrated home-based protocol for the management of chronic skin lesions based on the use of medical devices containing Ozoile®. The study documented complete healing in 31.6% of patients and a reduction in lesion stage in the majority of treated cases, demonstrating how Ozoile® Technology can be effectively integrated into local care pathways.

Particularly significant was the reduced reliance on systemic antibiotics and the reduced need for microbiological testing, results that reflect improved control of the lesion microenvironment and contribute to a more appropriate use of healthcare resources. The ability to limit the use of antibiotics also holds strategic value in the context of antimicrobial stewardship policies, which aim to combat the emergence and spread of antibiotic resistance.

The study also highlights the organizational value of Ozoile® Technology. The efficacy of the protocol in a home setting demonstrates that treatment can be managed safely and effectively outside the hospital, promoting continuity of care, reducing visits to healthcare facilities, and improving the management of chronic patients.

Taken together, this evidence shows that Ozoile® Technology is not only a biologically innovative platform, but also a solution capable of generating value for the healthcare system. The integration of clinical efficacy, safety, reduction of complications, resource optimization, and improvement in care organization forms the foundation of its pharmacoeconomic value and supports its use in care models oriented toward sustainability and quality of care.

The effectiveness of a technology intended for therapeutic use cannot be separated from the demonstration of its biological safety. For this reason, Ozoile® has undergone an extensive toxicological evaluation program, aimed at verifying that the biological activity induced by stable Ozonides was not associated with harmful effects on cells or genetic material.

The safety of the technology was evaluated according to international OECD guidelines, through specific genotoxicity, mutagenicity, and cytotoxicity tests, which are considered the reference standards for the toxicological characterization of new substances intended for use in humans.

One of the most important aspects concerns the ability to exclude any effects on genetic material.

Genotoxicity identifies the ability of a substance to cause damage to DNA or chromosomes, alterations that could compromise normal cellular function. Mutagenicity, on the other hand, evaluates whether such damage can turn into permanent mutations transmissible to daughter cells.

To exclude these risks, Ozoile® has undergone the two main tests required by the OECD guidelines:

• In vitro micronucleus test (OECD 487), performed on HuH-7 human cells, to evaluate the possible appearance of
  chromosomal alterations.
• Ames test (OECD 471), conducted on various strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537) and the Escherichia coli WP2 uvrA strain, to verify any potential to induce genetic mutations.

In both tests, Ozoile® showed no genotoxic or mutagenic activity, confirming that stable Ozonides do not cause alterations to the genetic makeup and can be considered biologically safe in this respect.

Safety was also assessed through cytotoxicity tests performed according to the OECD 249 guideline on human fibroblasts (HFF1) using an MTT assay.

Cytotoxicity measures a substance's ability to impair cell viability. Unlike genotoxicity, which concerns DNA, cytotoxicity evaluates potential harmful effects on cell survival and functionality.

In this case as well, Ozoile® showed no cytotoxic effects at the tested concentrations, demonstrating high biological compatibility with human cells.

A safety profile consistent with the mechanism of action.

The results obtained confirm that the moderate oxidative stress induced by the stable Ozonides in Ozoile® remains within the limits of eustress and does not evolve into biological damage.

The absence of genotoxicity, mutagenicity, and cytotoxicity is therefore natural confirmation of the
mechanism of action of Ozoile® technology: stable Ozonides do
not exert uncontrolled oxidative aggression on cells, but rather generate a transient
and modulable biological signal, sufficient to activate the body's adaptive responses
without compromising cellular or genetic integrity.

This safety profile
completes the scientific rationale for Ozoile® technology: a biological
platform capable of activating physiological processes of defense, inflammation modulation,
and tissue regeneration while maintaining high biocompatibility
with tissues.

✅ A

· Acnozoil® Cream: 1.35g/40ml

✅ B

· Banival® Cream: 0.13g/3ml

✅ D

· Dermozoil® Cream: 2.8g/100ml

· Dermozoil® Rinse-Off Cleanser: 0.3g/150ml

· Dermozoil® Fluid Cleanser: 0.45g/250ml

· Dermozoil® Hydro: 4.5g/250ml

· Dermozoil® Plus: 4g/100ml

· Dermozoil® Shampoo: 0.28g/150ml

· Dermozoil® Spray: 2g/20ml

· Dolaren® Emulgel: 2g/100ml

· Dolaren® Refillable Tape: 0.04g/pc

✅ I

· Idrozoil® Rinse-Off Cleanser: 0.33g/150ml

✅ N

· Neurofisiodol® Emulgel: 2g/100ml

✅ O

· Otorig® Drops: 2g/10ml

· Otorig® Nasal Spray: 0.2g/20ml

· Otorig® Oral Spray: 0.2g/20ml

· Ozocidina® Germ: 0.3g/80ml ~ 1.9g/500ml - 3.8g/1L - 9.5g/5L

· Ozogea® Booster: 42g/250ml — 84g/500ml — 168g/1L

· Ozogea® Ready-to-Use Booster: 2g/750ml

· Ozogea® Professional Booster: 840g/5L — 3360g/20L

· Ozomar® Dolor Emulgel: 2g/100ml — 4g/200ml

· Ozomar® Legs Gel: 0.5g/100ml ~ 1g/200ml

· Ozomar® New Skin: 4g/100ml

· Ozomar® Body Skin Regeneration: 2g/100ml

· Ozomar® Facial Skin Regeneration: 1g/50ml

✅ P

· Podoped® Cream: 5g/100ml

· Podoped® Barrier Cream: 8g/100ml

· Podoped® Cleanser: 0.5g/150ml

· Podoped® Fresh: 1g/100ml

· Podoped® Hydrogel: 5g/100ml

· Podoped® Nerv: 3.3g/100ml

· Podoped® Tape: 0.06g/pc

· Podoped® Spray: 4g/20ml

· Procten® Cream: 2g/40ml

· Psozoil® Cream: 3g/100ml

✅ R

· Rigenoma® Alginate: 0.5g/pc

· Rigenoma® Cream: 4g/100ml

· Rigenoma® Barrier Cream: 6g/100ml

· Rigenoma® Rinse-Off Cleanser: 0.4g/150ml

· Rigenoma® No-Rinse Cleanser: 2g/750ml — 2.6g/1L

· Rigenoma® Gauze: 0.2g/pc 10"10 —
0.6g/pc 10"30

· Rigenoma® Hydrogel: 4g/100ml

· Rigenoma® Refillable Tape: 0.05g/pc

· Rigenoma® Spray: 3g/20ml

✅ V

· Vulvovagi® Cream: 0.14g/3ml

· Vulvovagi® Spray: 2.6g/20ml