KR20140071956A - Composition for topical use based on ozonized oil - Google Patents

Abstract

The present invention relates to a medical device for sanitary treatment having improved local activity during the regeneration of ulcers and wounds and in the resolution of inflammatory conditions. This composition comprises an effective amount of an ozonized oil and an essential oil extracted from an effective amount of chamomile, and the present invention also relates to its use in the cosmetic and pharmaceutical field. The compositions of the present invention have applicability to disinfection and scarring of skin lesions such as wound and abrasion, acute or chronic ulcers, and pressure sores of various origins and properties.

Description

Technical Field [0001] The present invention relates to a composition for topical use based on ozonized oils,

The present invention relates to compositions for topical use based on ozonated oils.

In particular, the present invention relates to a sanitary medical device having local activity for improving the regeneration process of ulcers and wounds, including ozonated oil for topical use.

According to some aspects, the present invention relates to compositions based on ozonated oils and their use in pharmaceutical and / or cosmetic sectors.

The present invention relates in particular to synergistic compositions based on ozonated oils and selected ingredients suitable for disinfecting epithelial-tissue lesions and restoring the physiological state of damaged skin and / or subcutaneous structures.

Skin is the most widespread tissue in human organisms and is known to perform a number of functions, including the function of defense against external agonists.

The skin of a human organism may be damaged not only due to external causes such as in the case of trauma, trauma, abrasions, skin burns, but also due to endogenous causes such as in the case of peripheral type metabolic or ischemic diseases, There is a decrease in the supply of oxygen and nutrients. These pathological conditions result in the formation of ulcers, sores and wounds and their chronicity.

In general, the area of the epidermis invaded by wound or ulceration constitutes a fertile area for the development of bacterial infections. In fact, in wounds and pressure sores, in particular Pseudomonas (Pseudomonas), β- hemolytic Streptococcus (Streptococcus), Staphylococcus (Staphylococcus), keulrep when Ella (Klebsiella) and other colonization of other pathogens, bacterial strain are frequently I will meet you.

It is also not uncommon for anaerobic microorganisms to form colonies in tissues beneath the epidermis, such as the dermis and subcutaneous tissue. Including these subcutaneous infections as well as the risk of causing systemic infection is often difficult to detect by microbiological studies using standard diagnostic tools or by sore-analysis protocols.

Currently, conventional protocols for the treatment of skin ulcers provide for the removal of dead tissue using mechanical or enzymatic exfoliation and the application of disinfectants and / or cicatrising products, which generally contain cell growth factors. Instead, there is also a possibility of dependence on transplantation of a suitable cell line.

Nonetheless, in most cases it has been found that standard protocols for treating wounds and ulcers do not provide satisfactory results. For this reason, the scientific literature demonstrates the existence of alternative disinfectants and scarring treatments. For example, the use of ozonated oils in the treatment of skin ulcers has been known. Ozonated oils are products of the reaction of unsaturated fatty acids with ozone (O ₃ ), a three-atom form of oxygen.

The preparation of ozonated oils by saturating olefinic double bonds with ozone under suitable reaction conditions has been extensively documented in the literature.

For example, International Patent Application Publication No. WO 2006/021924 describes a method for preparing ozonated oils provided by high concentrations of long chain fatty acids compared to short chain fatty acids, and its use in the treatment of skin infections.

U.S. Patent Application Publication No. 2009/1291122 describes compositions for treating wounds containing fresh honey and ozonated vegetable oil in an amount of 5 to 50% by weight. The described compositions have, for example, bacteriostatic activity against Pseudomonas and can be formulated as a spray.

U.S. Patent No. 5,183,911 describes a method for producing stable ozonated oils.

U.S. Patent Application Publication No. 2006/0074129 discloses ozonated oils and vegetable oils containing various types of peroxides of various degrees of peroxidation, generally expressed in peroxide index (PI, milliequivalents of O ₂ per kg), generally in the range of 1000-1200 units Describes how to produce fat. After being treated with ozone, the oils and fats described acquire sterilizing, viral, parasitic and fungicidal properties and, as such, are applied in the cosmetic and pharmaceutical fields, especially in ophthalmology, dermatology, gynecology and gastroenterology There is a castle.

United States Patent Application Publication No. 2005/0113441 discloses a process for the preparation of ozonated oils and certain natural or synthetic products similar to ozonated, such as fatty acids having a double bond in the Ω-3, Ω-6 position, in the vehicle of the pharmaceutical excipient Compositions have been described which have utility in cosmetic or pharmaceutical applications, particularly dermatological applications.

European Patent EP 2,149,598 also discloses the use of topical treatment of skin infections, including secondary-types limited by phlebitis, necrosis, thrombotic phlebitis, viral causes, and also the treatment of inflammatory-infectious diseases of the mouth, A method and apparatus for producing a vehicle or a substrate for obtaining an ozone derivative or ozone having applicability as a bactericidal drug product for promoting vascular tissue regeneration by the method of the present invention has been described.

United States Patent Application Publication No. 2009/0291122 defines ozonated vegetable oil as an oil applied to treatment with ozone gas until a variable ozone concentration in the oil of 15 to 53 mg of ozone per gram of oil is reached.

U.S. Patent Application Publication No. 2009/02901122 describes a composition for medical use containing ozone at a concentration in the range of 5% to 50% (w / w) with respect to the other constituents of the composition.

European patent 1,626,767 describes a device suitable for providing a spray of ozonated material useful for disinfection and treatment of infected wounds and describes the natural mechanism of the organism in the removal of the infection from the "cascade" - and the production and efficacy of relative oxygen species (ROS) that inhibit the survival of anaerobic bacterial strains.

Despite the use of ozonated oils in medicine to some extent, the medical-scientific literature has similarly demonstrated a number of serious drawbacks associated with their use, linked to the formation of potentially toxic free radicals.

Thus, the mechanism of action of ozonated oils has been the subject of experiments in an attempt to reduce the formation of toxic radicals.

Indeed, the literature has shown that ozonated oils in the initial phase yield defined ROS (reactive oxygen species), and the ozone ion radicals in contact with water in a modular manner in plasma produce active oxygen and molecular species [Halliwell B. Annu Rev Nutr 1996; 16: 33-50].

This initial phase (ROS) leads to lipid peroxidation (LOP), where one mole of ozone ion radical (or ozone) provides two moles of aldehyde and one mole of hydrogen peroxide [Pryor et al., Free Rad Biol Med 1995; 19: 935-941, reported in Velio Bocci, Ozone a New Medical Drug, Springer, Dordrecht, The Netherlands, 2005, p. 20]. On the ROS, potentially cytotoxic free radicals such as hydroxide (OH ^- ), superoxide (O ₂ ^- ), peroxynitrite (O = NOO ^- ) are produced while active and therapeutic effects Responsible "ozone messengers" only occur in the second slower phase (LOP) [Velio Bocci, Ozone a New Medical Drug, Springer, Dordrecht, The Netherlands, 2005, p. 26]. However, at present, there has been no success in improving the formation of toxic radicals, and as a result, the use of ozonated oils is limited by the occurrence of these disadvantages.

There is therefore a perceived need to take into account the prior art and to have available means of internal and external overcurrent protection, in particular for disinfecting chronic wounds and ulcers and facilitating their healing. In contrast to this background, there is also a perceived need for ozonated oils that can be used for the treatment of lesions of the skin, with an improved safety profile compared to that currently available.

In particular, once applied to frequently infected skin lesions, it is desirable to be able to measure significant reductions in the release of free radicals harmful to organisms and to make available ozonated oils that exhibit greater antimicrobial activity.

SUMMARY OF THE INVENTION

The Applicant has now found that by combining ozonated oils with essential oils extracted from chamomile, synergistic sterilization and scarring effects are obtained in association with the reduced formation of free radicals.

Thus, according to a first aspect of the present invention there is provided a composition for topical use characterized in that it comprises an effective amount of at least one ozonized oil and an effective amount of essential oil extracted from chamomile.

Essential oils that can be used within the scope of the present invention can be extracted from flowers of a plant of the order Chamomaria (Matricaria chamomilla) according to conventional techniques, for example, as reported in the Italian Pharmacopoeia.

For example, the essential oil of chamomile can be obtained from the head of a plant using steam distillation. The product obtained is typically a viscous consistency blue oil.

According to one embodiment, the essential oil extracted from chamomile comprises or essentially consists of? -Bisabolol.

In particular, Applicants have also unexpectedly discovered that the combination of ozonated oil and alpha-bisabolol determines a significant reduction in the generation of free radicals normally observed for the ozonated oil on the ROS of the release of ozone ion radicals Respectively.

Alpha-bisabolol has a molecular weight of 222.37 and has the formula C ₁₅ (R) -6-methyl-2 - ((R) -4-methylcyclohex- It is a natural sesquiterpene alcohol, also called levomenol [23089-26-1] of H ₂₆ O.

Ozonated oils used in the formulation of the compositions of the present invention are the reaction or adducts of ozone with one or more unsaturated fatty acids, such as those present in vegetable or animal fats or oils.

In some embodiments, an oil of plant origin is used to obtain an ozonized oil. Examples of suitable vegetable oils include, but are not limited to, olive oil, sunflower oil, corn oil, mixed seed oil, and mixtures thereof.

Ozonated oils that can be used within the scope of the present invention can be obtained using conventional procedures and techniques. For example, suitable ozonated oils can be obtained by the procedure described in German patent DE 12 55 660 (Gabelein) or by one of the methods described in this patent.

According to one embodiment, the ozonated oils used in the compositions of the present invention are based on vegetable oils having an unsaturated fatty acid content of at least 80%.

By way of example, ozonated oils used within the scope of the present invention are oils rich in oleic acid and linoleic acid. These two fatty acids applied to ozonation can typically provide addition by ozone up to a degree of peroxidation of at least 60% of the unsaturation.

Applicants have found that the combination of ozonated oil and alpha -bispherulol in compositions for topical application comprises the following additional advantages:

This manifests a synergistic action of antimicrobial activity against, among other things, bacterial strains of Pseudomonas, β-hemolytic Streptococcus, Staphylococcus, Klebsiella and other pathogens;

This prevents ozonated oil from degrading, modulates its rapid reaction with plasma (ROS) and inhibits its potential toxic effects;

This accelerates the healing process of wounds and ulcers due to the anti-inflammatory action of biomolecules, "ozone messengers" produced and derived from low-level LOPs;

This maintains the sensory qualities of the composition, its tolerability and, together with the resultant advantage of delaying the appearance of odors mainly due to aldehyde hexane in the decomposition products of the ozone with other aldehydes, Slow down the decomposition process.

DETAILED DESCRIPTION OF THE INVENTION

The invention derives from the discovery that the essential oil extracted from chamomile, in particular the combination of o-bisabolol and ozonated oil, determines the synergistic action of the antibacterial and / or scarring action on the damaged skin.

Certain embodiments of the invention are reported in dependent claims 2-14.

Indeed, the combination of alpha -bispherulol and ozonated oils is a particularly common bacterial strain found in the wound, for example, Pseudomonas aeruginosa , Klebsiella pneumoniae , and Streptococcus agalactiae , which have been shown to enhance the antimicrobial activity of ozonated oils.

Thus, in a general aspect of the present invention there is provided a composition for topical use comprising an effective amount of an ozonized oil in combination with an effective amount of an essential oil extracted from chamomile.

According to one embodiment, the ozonated oil present in the composition of the present invention is obtained by ozonation of sunflower oil.

According to one embodiment, the essential oil or alpha-bisabolol extracted from chamomile is present in an amount ranging from 1 to 20%, preferably from 5 to 10% by weight, based on the ozonated oil.

According to another embodiment, the ozonated oil present in the composition of the present invention has a degree of peroxidation of up to 60% of the double bond.

According to another embodiment, the ozonated oil of the composition of the present invention has a peroxide index (PI) in the range of 3400 to 4600.

In some embodiments, the oil ozonation is carried out under specific operating conditions in a closed reactor. During this reaction with O ₃ , a linear correlation was found between the peroxide index of the peroxidized oil and the density of the reaction medium. The above linear correlation has proven to be very useful in controlling the reaction itself.

In some embodiments of the invention, the ozonated oil is derived from the ozonation of vegetable oils, or from a mixture of various types of oils. For example, one formulation of the composition of the present invention includes the ozonated sunflower oil listed in Table I below, along with the characteristics of the sunflower oil starting material.

Table 1 Ozonated oils with a peroxide index (PI) of about 4000 and their precursors Characteristics of sunflower oil

PI = peroxide index

From the ¹ H-NMR spectrum of the sunflower oil and its ozonated derivatives, the percentage and structure of various levels of peroxidation in the mixture can be confirmed.

According to one embodiment, the ozonated oil of the composition has a peroxide index of about 4000 corresponding to 96 g of O ₃ per kg of product (as a function of ozone ion radical) and 64 g of O ₂ (with peroxide function) (PI).

In the compositions of the present invention, alpha -bispherulol and ozonated oils may be present at specific quantitative ratios. According to one embodiment, the composition of the present invention comprises a-bisabolol and ozonated oil in a ratio of 1: 5 to 1:20. One embodiment provides a 1: 5 to 1:10 a-bisabolol and an ozonated oil ratio.

According to one embodiment, the compositions of the present invention comprise alpha-bisabolol and ozonated oils in proportions of 1 to 10 parts each.

The compositions of the present invention may typically contain one or more additives and / or vehicles and / or excipients which are suitable for topical application for human and veterinary use, in particular in the pharmaceutical or cosmetic field.

In one embodiment, the compositions of the present invention may be formulated as emollients, soothers, humectants, pH adjusting agents, stabilizers, antimicrobial agents, protective skin forming agents, and one or more of a variety of properties And may contain one or more substances selected from active ingredients.

For example, the composition of the present invention may contain one or more micro-elements or trace elements, such as zinc, magnesium, selenium, manganese, of any form (salt, ester, For example, from 0.001% by weight to 10% by weight with respect to the weight.

According to another embodiment, the composition comprises, for example, 0.001 to 25% by weight of vitamins such as vitamins of group A, B, C, E, F and / or their derivatives and / Can be included in the concentration.

According to another embodiment, the composition of the present invention is administered in an amount varying from 0.001 to 10%, for example, a substance that plays a role in scarring of the wound, ulcer and skin pressure ulcer, for example, cysteine, arginine, glycine And derivatives thereof; For example, an acid, linoleic acid or linolenic acid of the type? -3 and / or? -6 in an amount that can vary from 0.001 to 30% by weight.

According to another embodiment, the composition of the present invention further comprises one or more substances which form protective coversings on the skin, such as perfluorocarbons, for example, Fombolin (R) In an amount varying from 0.001 to 10% by weight.

According to one embodiment of the present invention, the two components of the composition, ozonated oil and alpha-bisabolol, are present in an amount of 10% to 90%, based on the total weight of the formulation, For example, excipients of the type described above or other materials.

According to some embodiments, the compositions of the present invention are provided in a liquid or semi-liquid form suitable for topical application, for example, a gel or solution that can be applied to a skin area requiring treatment. According to another embodiment, the composition is provided in the form of a spray. According to another embodiment, the composition of the present invention is provided in solid form, for example, as a paste, a pomade or a cream.

According to another embodiment, the composition of the present invention is provided in the form of a device suitable for transdermal or dermal release of the active ingredient, for example in the form of a transdermal patch.

The compositions of the present invention are applicable in both cosmetic and pharmaceutical fields. In general, the composition of the present invention is applicable in all cases where damage to epidermal tissue occurs and sanitizing treatment is required to restore the structure of the skin and / or the physiological condition of the damaged subcutaneous structure.

According to an aspect of the present invention there is provided a cosmetic use of a composition comprising ozonated oil, a-bisabolol in a cosmetically beneficial amount, and a cosmetically beneficial vehicle for skin regeneration.

In certain embodiments, compositions for cosmetic use include one or more vehicles or excipients conventionally used in the formulation of cosmetic preparations.

In certain embodiments, the compositions of the present invention may be formulated as, for example, puckering, especially as a cosmetic of non-aesthetic features of the skin, such as skin discolorations due to aging of the skin, It is used for treatment.

According to another aspect, the present invention relates to a composition comprising a pharmaceutically beneficial amount of ozonated oil and alpha -bispherulol for use in the treatment of skin lesions.

The term skin lesion is used to mean all lesions of the epidermis where the epidermis is no longer intact, torn or cut, or even merely superficial, where there may simply be abrasions of the epidermis.

Lesions of the epidermis are, for example, wounds, skin bedsore, bedsores, ulcers and ulcers, abrasions, burns.

According to one embodiment, the composition of the present invention is applicable to disinfection and / or scarring of wound, ulcer or skin bedsore.

According to another embodiment, the compositions of the present invention are used for the treatment and / or prophylaxis of the wound healing process when it is necessary to reduce or otherwise maintain the bacterial load present on the wound, It is applicable in case of.

According to another embodiment, the composition of the present invention is applicable to the sanitization and regeneration of skin invaded by bedsore and / or ulcer. For example, the compositions of the present invention are applicable to the treatment of bedsore ulcers, infected ulcers, and chronic ulcers.

Moreover, Applicants have surprisingly found the presence of a direct linear correlation between the peroxide index PI expressed as O ₂ equivalents / kg of oil / kg, or the amount of ozone absorbed by the oil during the ozonation reaction and the density of the reaction mass Respectively.

The presence of this correlation advantageously allows the ozonation reaction to run substantially continuously until the desired ozonation concentration is reached, without stopping the reaction to perform an analytical sample collection.

Thus, in one aspect, the present invention extends to a method for determining the peroxide index PI (milli-equivalent of O ₂ per kg of oil) of ozonated oil by measuring the density of the reaction mixture expressed in g / l.

This analytical method can generally be used as an alternative to the method reported in the Pharmacopoeia to obtain a reliable reaction only to a lower ozone cargo ion radical concentration than can be achieved in the ozonation method of the present invention.

According to one embodiment, the ozonated oil of the present invention is a vegetable oil from which it is derived, for example, O ₂ at 7000 m-equivalent or more per kilogram of oil compared to sunflower oil, typically at about 5500 m-equivalent per kilogram of oil O _2, advantageously undergoes a mean increase of the oxygen O ₂ in the kilogram to 4000 equivalents per m- of the oil to the.

Many aspects of the present invention are also described in detail below with reference to attached Figure 1 which illustrates the linear correlation present between the peroxide index (PI) and the density (d) of the ozonated mixture.
Specifically, the graph in FIG. 1 represents the peroxide index value expressed in terms of O ₂ equivalents per kilogram of oil on the Y-axis, and the value for the density of the mixture during the ozonation reaction expressed in g / ml on the X- . This graph demonstrates the existence of a direct linear correlation between the two values.

The present invention is described below by way of example only with reference to the following examples which are provided for illustrative purposes only and should not be construed as limiting the present invention.

Example

Example  One

A method for producing an ozonized oil as shown in Table 1.

Supplying pure medical-grade oxygen to a suitable 30-L generator at a flow rate of 140 L / h; An electric charge of 6000 volts is applied to the generator and ozone is formed in this manner to reach an O ₃ concentration of 90 mg / L. Ozone now bubbles in a suitable reactor containing sunflower oil. The amount of ozone absorbed is monitored by both conventional titration and by measuring the density of the reaction mixture. A linear correlation was found between the density of the reaction medium expressed in g / L and the measured peroxide index (PI) expressed in equivalents of O ₂ / kg. This correlation represents a direct and reliable means of control of the process of the reaction. An example of the correlation applied in the industrial production method of ozonized oil is shown in Fig.

Example  2

Experiments comparing compositions 2a) containing ozone oil and alpha-bisabolol, both formulated as a spray oil for the treatment of skin ulcers, and formulation 2b containing ozonated oils as the sole active substance.

2a) A suitable reactor is filled with 67 parts of caprylic / capric triglyceride and 30 parts of ozonated oil. After proper mixing, 3 parts of? -Bisaborolol are added.

An analysis of the Peroxide Index (PI) of the homogeneous mixture is performed.

2b) A preparation similar to 2a above is carried out using 70 parts of triglyceride and 30 parts of ozonated oil. The? -bisbolol component was excluded from this preparation.

Agents 2a and 2b were compared in the treatment of skin ulcers with an average diameter of about 2 cm. After 15 days, the ulcer treated with formulation 2a proved to be significantly smaller in size compared to the control consisting of ulcer treated with formulation 2b. In addition, patients who were treated alternately and continuously (crossover) with formulation 2a were more likely to have a greater likelihood of having more resistance, premature sensation of increased sensitivity, and reduced pruritus and burning sensation, He said that he had gained a great advantage.

Example  3

Description of the preparation of a composition based on ozone oil and alpha-bisabolol, in the form of an emulsion, for the treatment of skin redness, and comparative efficacy with an ozonated oil-free formulation without alpha-bisabolol exam.

3a) 65.38 parts of water were placed in a smelting vessel and heated to 80 ° C. At the same time, the turboemulsifier was mixed with 6 parts of C12-20 fatty acid esterified with polyethylene glycol (s) (PEG), 2.5 parts of C13-C15 alkane, 3 parts of variously hydrogenated alkenes, 1.5 parts of cetyl alcohol, Caprylic / capric triglyceride, 8 parts of other emulsifiers and conventional thickeners. The whole is heated to 80 DEG C with stirring, and previously heated water is transferred to the emulsifier. The mass is emulsified until a homogeneous and consistent mass is obtained. Cool it to 40 ° C, add aromas and fragrances, and continue stirring while the temperature continues to fall. 10 parts of ozonized oil and 1 part of? -Bisabolol are placed in a separate mixer and mixed. The mixture is then transferred to a turbo-emulsifier, where a homogeneous and uniform emulsion is obtained and its pH is adjusted to the specified value by possible addition of sodium hydroxide solution. All specifications including peroxide index (PI) are identified in the final product.

3b) The preparation is carried out as in Example 3a without the addition of alpha -bispherulol.

Formulation 3a showed a larger and faster antioxidant activity and greater anti-inflammatory activity than 3b due to the presence of alpha -bispherulol.

Example  4

Demonstration of increased antimicrobial activity of the combination as compared to the efficacy of ozonated oil alone.

Comparisons were made for strains Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 27736) and Streptococcus agalactiae (ATCC 12368)

a) 9 parts of an ozonated oil of the type shown in table 1 and 1 part of an < RTI ID = 0.0 > a-

b) again on the sterilizing activity of the ozonated oil of the type shown in Table 1.

Conventional culture media were used and methods well known in the art such as diffusion in agar and serial dilution in vitro also apply. The comparison was made with the constituent ozonized oils shown in Table 1 under the same experimental conditions. The following table shows the percent reduction in the number of colony-forming units (cfu) at the initial concentration of the microbial inoculum and the duration of exposure to the antimicrobial agent.

Evaluation of bactericidal or bactericidal activity of the product for comparison of pathogenic organisms was performed by applying in vitro linear regression method and calculating the% reduction (R%) in the survival rate of the microorganisms. R% is defined as the ratio of final and initial number of microorganisms multiplied by 100. Microbiological analyzes were performed at the University of Ferrara Department of Diagnostic and Experimental Medicine.

[Table 2a] Composition: α-Bisabolol in a ratio of 1: 9: ozonated oil

[Table 2b] 100% ozonized oil

From the results, it can be seen that the composition of 1 part alpha -bisabolol-9 part ozonated oil is comparable to that of the microorganism used, i. E., Streptococcus agalactiae, Klebsiella nymonyi and Pseudomonas aeruginosa, Compared to the control group.

Example  5

Using the techniques and methods described in Example 4, the synergistic effects of a 1: 15 ratio of a-bisabolol and ozonated oil (Table 1) were evaluated for the antimicrobial activity against the strain indicated above. Table 3 shows the survival percentage of the inoculum concentration up to 24 hours over time as an effect of the o-bisonolol: ozonized oil composition at a ratio of 1:15.

[Table 3]

Composition 1: 15 a-Bisabolol: Percent survival of inoculum concentration of ozonated oil (PI 4000)

Comparison with Table 2b (Example 4) showed that there was a significant reduction in the survival of the strain as rapidly as 4 hours, even at a 1:15 ratio of? -Bisabolol: ozonated oil 4000.

Claims (14)

A composition for topical use comprising an effective amount of an ozonated oil and an essential oil extracted from an effective amount of chamomile. 3. The composition of claim 1, wherein the essential oil extracted from chamomile comprises alpha -bispherulol or consists essentially of alpha -bispherulol. The composition according to claim 1 or 2, wherein said ozonated oil is a vegetable oil, preferably a sunflower oil. 4. The oil according to any one of claims 1 to 3, wherein the essential oil or a-bisabolol extracted from chamomile is present in an amount ranging from 1 to 20% by weight, preferably from 5 to 10% by weight, based on the ozonated oil And wherein the ozonated oil is present in the composition or medical device in an amount of from 5 to 50% by weight. 5. Composition according to any one of claims 1 to 4, characterized in that the ozonized oil has a degree of peroxidation of up to 60% of the double bonds. The process according to any one of claims 1 to 5, wherein the ozonated oil is peroxidized to 14% to 39% by weight of peroxidized up to 60% of its double bonds and up to 40% is peroxidized to single-ozone and up to 20% Characterized in that it comprises 47 to 74% linoleic acid peroxidized with ozone. 7. The composition according to any one of claims 1 to 6, characterized in that the ozonized oil has a peroxide index (PI) in the range of 3400 to 4600. 8. The composition according to any one of claims 1 to 7, wherein the production of the ozonized oil is controlled by the density in the reaction medium by applying a direct correlation between the density and the peroxide index. 9. A pharmaceutical composition according to any one of claims 1 to 8, characterized in that it comprises at least one pharmaceutically or cosmetically advantageous excipient, preferably a form suitable for topical application selected from emulsions, gels or spray solutions Composition. Use of a composition according to any one of claims 1 to 9 in the cosmetic treatment of skin. 10. A composition according to any one of claims 1 to 9 for use in the treatment of diseases of the skin. 12. The composition of claim 11, wherein the skin disease is wound, pressure sores, ulcers, burns, sunburns or abrasions. 13. The composition of claim 12, wherein the disease of the skin is wounded by one or more microorganisms. 14. The composition of claim 13, wherein the microorganism is Streptococcus agalactiae, Klebsiella annumi or Pseudomonas eruginosine.

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