WO2012120454A1

WO2012120454A1 - Composition for topical use based on ozonized oil

Info

Publication number: WO2012120454A1
Application number: PCT/IB2012/051057
Authority: WO
Inventors: Primo TORTINI; Alessia DE ASCENTIIS
Original assignee: Neovalis S.R.L.
Priority date: 2011-03-07
Filing date: 2012-03-07
Publication date: 2012-09-13
Also published as: KR20140071956A; ITMI20110354A1; MX2013010275A; EP2683356A1; MA35021B1; BR112013022891A2

Abstract

The present invention relates to a sanitising medical device having topical activity improved in the process of regeneration of ulcers and wounds, and in the resolution of inflammatory states. This composition comprises an effective amount of an ozonized oil and an effective amount of an essential oil extracted from chamomile and the uses thereof in the cosmetic and pharmaceutical sector. The composition of the invention finds specific application in the disinfection and cicatrisation of skin lesions such as wounds, abrasions, acute or chronic ulcers, and sores of varying origin and nature.

Description

COMPOSITION FOR TOPICAL USE BASED ON OZONIZED OIL

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DESCRIPTION

FIELD OF THE INVENTION

The present invention relates to a composition for topical use based on ozonized oil.

In particular, the invention relates to a sanitising medical device having topical activity that improves the process of regeneration of ulcers and of wounds, comprising ozonized oil for topical use.

According to some aspects, the invention relates to a composition based on ozonized oil and its uses in the pharmaceutical and/or cosmetic sector.

The present invention specifically relates to a synergistic composition based on ozonized vegetable oil and a selected constituent, which composition is suitable for disinfecting epithelial-tissue lesions and restoring the physiological conditions of the damaged cutaneous and/or sub-cutaneous structures.

THE PRIOR ART

The skin is the most widespread tissue in the human organism and is known to perform numerous functions including that of protection from external agents.

The skin of the human organism can be damaged due both to external causes, such as in the case of lacerations, trauma, abrasions, skin burns, but also due to endogenous causes such as in the case of metabolic or ischemic diseases of peripheral type, wherein there is a reduction in the supply of oxygen and of nutrient substances. These pathological conditions lead to the formation of ulcers, sores and wounds, and to their becoming chronic.

In general, the areas of the epidermis affected by wounds or ulcerations constitute a fertile terrain for the development of bacterial infections. Indeed, colonization by bacterial strains, in particular of Pseudomonas, β-hemolytic Streptococcus, Staphylococcus, Klebsiella and other pathogens in wounds and sores is frequently encountered.

It is also not uncommon for anaerobic microorganisms to be able to form colonies within the tissues underlying the epidermis, such as the dermis and the subcutaneous tissue. These subcutaneous infections, as well as involving the risk of causing systemic infections, are frequently difficult to detect using the normal diagnostic means or with the microbiological investigations provided for by sore- analysis protocols.

Currently, the conventional protocols for the treatment of skin ulcers provide for the removal of dead tissue by means of mechanical or enzymatic exfoliation and the application of disinfectant and/or cicatrising products generally containing cellular growth factors. Alternatively, recourse to the transplantation of suitable cell lines is also a possibility.

Nevertheless, it has been found that in many cases the standard protocols for treating wounds and ulcers do not produce satisfactory results. For this reason, the scientific literature documents the existence of alternative disinfectant and cicatrising treatments. For example, the use of ozonized oils in the treatment of skin ulcerations is known. Ozonized oils are the products of reacting unsaturated fatty acids with ozone (O₃), the triatomic form of oxygen.

The preparation of ozonized oils by means of saturating olefinic double bonds with ozone under appropriate reaction conditions is widely documented in the literature. For example, international patent application WO2006/021924 describes a process for preparing an ozonized oil provided with a high concentration of long- chain fatty acids relative to short-chain fatty acids, and the use thereof in the treatment of skin infections.

American patent application US2009/1291 122 describes a composition for the treatment of wounds, containing raw honey and ozonized vegetable oil in an amount from 5 to 50% by weight. The composition described possesses bacteriostatic activity, for example against Pseudomonas, and can be formulated as a spray.

American patent US 5.183.911 describes a method for preparing stable ozonized oil.

American patent application US2006/0074 29 describes a method for producing ozonized oils and vegetable fats comprising different types of peroxides of varying degrees of peroxidation, generally within the range from 1000-1200 units expressed as the peroxide index (PI, milli-equivalents of O₂ per kg). After being treated with ozone, the oils and fats described acquire bactericidal, virucidal, parasiticidal and fungicidal properties and, as such, find applications in the cosmetic and the pharmaceutical sector, in particular in ophthalmology, dermatology, gynecology and gastroenterology.

American patent application US2005/0113441 describes compositions comprising combinations of ozonized oils with specific, likewise ozonized, natural or synthetic products, such as: vitamins, fatty acids having double bonds in position Ω-3, Ω-6, in a vehicle of pharmaceutical excipients and intended for cosmetic or pharmaceutical use, in particular for dermatological applications.

European patent application EP 2.149.598 further describes a method and a device for producing a vehicle or substrate for yielding ozone derivatives or ozonides that find applications as bactericidal medicinal products for the topical treatment of phlebitis, gangrene, thrombophlebitis, skin infections, including secondary-type determined by viral causes, and also for the treatment of inflammatory-infective diseases of the oral cavity, for promoting angioneogenesis, with the effect of regenerative action on the tissues.

US patent application US2009/0291122 defines ozonized vegetable oil as an oil that has been subjected to treatment with ozone gas until a variable ozone concentration in the oil from 15 to 53 mg of ozone per gram of oil is reached.

American patent application US2009/02901122 describes a composition for medical use containing ozonides in a concentration within the range from 5% to 50% (w/w) relative to the other constituents of the composition.

European patent application EP 1626767 describes a device adapted to providing a spray of ozonized water, usable for disinfecting and treating infected wounds, and illustrates the production and efficacy of relative oxygen species (ROS) which, in their "cascade" of rearrangement and transformation, co-assist the natural mechanisms of the organism in the removal of infections and inhibit the^' survival of anaerobic bacterial strains.

Notwithstanding that the use of ozonized oils in medicine has spread to a certain degree, the medico-scientific literature has similarly documented a number of serious disadvantages associated with their use, principally linked to the formation of potentially toxic free radicals.

The action mechanism of ozonized oils has therefore been the subject of experimentation in the attempt to reduce the formation of toxic radicals.

Indeed, the literature has documented (Halliwell B. Annu Rev Nutr 1996; 16:33-50) that, in an initial phase, defined ROS (Reactive Oxygen Species), the ozonized oil yields - in a modular manner - ozonide ion radicals which, in contact with the water in plasma, generate molecular species with active oxygen.

This initial phase (ROS) is followed by lipid peroxidation (LOPs) wherein one mole of ozonide ion radical (or ozonide) results in two moles of aldehydes 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). In the ROS phase potentially cytotoxic free radicals are generated, such as hydroxide (OH^"), superoxide (O₂ ^~), peroxynitrite (O=NOO^"), while "ozone messengers", responsible for the activity and therapeutic effects, arise only in the second, slower, phase (LOPs) (Velio Bocci, Ozone a New Medical Drug, Springer, Dordrecht, The Netherlands, 2005, p. 26). Currently, however, there has been no success in remedying the formation of toxic radicals, as a result of which the use of ozonized oils is limited by the occurrence of this disadvantage.

In the light of the prior art, there is therefore a perceived need to have available medico-surgical protective measures capable of adequately disinfecting, particularly chronic, wounds and ulcers, and promoting the healing thereof. Against this background, there is also a perceived need to have available ozonized oils for the treatment of lesions of the skin, which oils have an improved safety profile by comparison with those currently available.

In particular, it is desirable to be able to make available ozonized oils which, once applied to a - frequently infected - skin lesion, determine a substantial reduction in the release of free radicals harmful to the organism and express greater antibacterial activity.

SUMMARY OF THE INVENTION

The Applicant has now found that by combining an ozonized oil with an essential oil extracted from chamomile, a synergistic bactericidal and cicatrising effect is obtained which is accompanied by a reduced formation of free radicals.

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

The essential oil usable within the scope of the invention may be extracted from flowers of the chamomile plant (Matricaria chamomilla) in accordance with conventional techniques, for example those reported in the Italian Pharmacopoeia. For example, the essential oil of chamomile may be obtained from heads of the plant by means of steam distillation. The product obtained is typically a blue oil of viscous consistency.

In accordance with one embodiment, said essential oil extracted from chamomile comprises or essentially consists of a-bisabolol.

In particular, the Applicant has furthermore unexpectedly found that combination of an ozonized oil with alpha-bisabolol determines a substantial reduction in the development of free radicals that is commonly observed for the ozonized oils in the ROS phase of release of ozonide ion radicals.

Alpha-bisabolol is a natural sesquiterpenic alcohol, also called levomenol, [23089-

26-1] of empirical formula Ci₅H₂₆0, which has a molecular weight of 222.37 and is designated (R)-6-methyl-2-((R)-4-methylcyclohex-3-enyl)ept-5-en-2-ol.

The ozonized oil used in the formulation of the composition of the invention is a reaction or addition product of ozone with one or more unsaturated fatty acids, for example those present in vegetable or synthetic fats or oils.

In some embodiments, an oil of vegetable origin is used to obtain the 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.

The ozonized oils used within the scope of the invention may be obtained by means of conventional procedures and techniques. For example, suitable ozonized oils may be obtained with the procedure described in German patent

DE 12 55 660 in the name of Gabelein or with one of the methods described therein.

According to one embodiment, the ozonized oil used in the composition of the invention is based on a vegetable oil having an unsaturated fatty acid content of at least 80%.

By way of example, the ozonized oils utilized within the scope of the invention are oils particularly rich in oleic and linoleic acid. These two fatty acids, subjected to ozonization, can typically produce addition with ozone up to a degree of peroxidation of at least 60% of unsaturations.

The Applicant has found that combination of ozonized oil and a-bisabolol in a composition for topical application comprises the following further advantages:

- it expresses synergy of antibacterial activity, above all against the bacterial strains of Pseudomonas, β-hemolytic Streptococcus, Staphylococcus, Klebsiella and other pathogens.

- it protects the ozonized oil from degradation, modulates its rapid reaction with plasma (ROS) and opposes its potential toxic effects;

- it accelerates the healing process of wounds and ulcers, thanks to the antiinflammatory action of the biomolecules, "ozone messengers" produced and derived from the slow phase LOPs;

- it slows the natural process of degradation of ozonides, with the consequent advantage of maintaining the organoleptic qualities of the composition, its tolerability, and the delayed appearance of the odour due primarily to the aldehyde hexanal, which, with other aldehydes, are among the degradation products of ozonides.

DETAILED DESCRIPTION OF THE INVENTION

The present invention originates from the discovery that combination of an essential oil extracted from chamomile, in particular a-bisabolol, with an ozonized oil determines a synergy of antibacterial and/or cicatrising action on the damaged epidermis.

Specific embodiments of the invention are reported in the dependent claims 2-14. Indeed, it has been observed that combination of α-bisabolol with an ozonized oil determines a potentiation of the antibacterial activity of the ozonized oil that is especially marked against the bacterial strains most commonly found in wounds, for example, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus agalactiae.

In a general aspect of the present invention, a composition for topical use is therefore provided, comprising an effective amount of an ozonized oil in combination with an effective amount of an essential oil extracted from chamomile. In accordance with one embodiment, the ozonized oil present in the composition of the invention is obtained by ozonization of sunflower oil.

According to one embodiment, said essential oil extracted from chamomile or alpha-bisabolol is present in an amount within the range from 1 to 20%, preferably from 5 to 10% by weight, relative to said ozonized oil.

In accordance with another embodiment, the ozonized oil present in the composition of the invention has a degree of peroxidation of up to 60% of the double bonds.

According to another embodiment, the ozonized oil of the composition of the invention has a peroxide index (PI) within the range from 3400 to 4600.

In some embodiments, the oil ozonization is performed in a sealed reactor and under particular operating conditions. During said reaction with 0₃, a linear correlation was found between the peroxide index of the peroxidated oil and the density of the reaction medium. Said linear correlation proved exceedingly useful for controlling the reaction itself.

In some embodiments of the invention, the ozonized oil derives from ozonization of a vegetable oil or from mixtures of various types of oil. By way of example, one formulation of the composition of the invention incorporates an ozonized sunflower oil the characteristics of which are listed, together with the characteristics of the sunflower oil starting substance, in Table I below.

Table I: Characteristics of the ozonized oil having a peroxide index (PI) of approx. 4000 and its precursor sunflower oil.

PI = peroxide index

From the ¹H-NMR spectra of sunflower oil and its ozonized derivatives, it is possible to confirm the structure and the percentages of the various peroxidation levels in the mixture.

In accordance with one embodiment, the ozonized oil of the composition has a peroxide index (P I) equal to approximately 4000, corresponding to 96g of O3 (as a function of ozonide ion radical), and 64g of O₂ (as peroxide functions) per kg of product.

In the composition of the invention, the a-bisabolol and the ozonized oil may be present in specific quantitative ratios. In accordance with one embodiment, the composition of the invention comprises α-bisabolol and ozonized oil in a ratio from 1 :5 to 1 :20. One embodiment provides for an α-bisabolol and ozonized oil ratio of 1 :5 to 1 :10.

In accordance with one embodiment, the composition of the invention comprises α-bisabolol and ozonized oil, respectively in a ratio of 1 to 10 parts.

The composition of the invention may typically contain one or more additives and/or vehicles and/or excipients suitable for topical application in particular in the pharmaceutical or cosmetics sector, for human or veterinary use.

In one embodiment, the composition of the invention may contain one or more substances selected from emollients, soothers, humectants, pH regulators, stabilizers, antimicrobials, substances that generate a protective skin, and one or more active principles of varied nature.

By way of example, the composition of the invention may comprise, as active principles, one or more micro-elements or trace elements, such as zinc, magnesium, selenium, manganese, in whatever form (salts, esters, hydroxides etc.) and a concentration that may vary, for example from 0.001 % to 10% by weight, relative to the weight of the total composition.

In accordance with another embodiment, the composition may comprise vitamins, and/or their derivatives and/or precursors such as e.g. vitamins of group A, B, C, E, F, for example in a concentration that may vary from 0.001 to 25% by weight. According to another embodiment, the composition of the invention may comprise substances, which play a role in the cicatrisation process of wounds, ulcers, skin sores, such as amino acids and derivatives thereof, such as cysteine, arginine, glycine, for example in quantities varying from 0.001 to 10%; fatty acids such as acids of type Ω-3 and/or Ω-6, linoleic or linolenic acid, in quantities which may vary for example from 0.001 to 30% by weight.

In accordance with another embodiment, the composition of the invention may further include one or more substances, which form protective coverings on the skin, such as perfluorocarbons, for example Fombolin®, in quantities varying from 0.001 to 10% by weight.

In accordance with one embodiment of the invention, the two constituents of the composition, ozonized oil and alpha- bisabolol are present in an amount from 10% to 90% relative to the total weight of the formulation, the remainder to make up to 100% being composed of excipients or other substances, for example of the type previously described.

In accordance with some embodiments, the composition of the invention is provided in liquid or semi-liquid form suitable for local application, for example as a gel or solution to be applied in the cutaneous zone in need of treatment. In accordance with another embodiment, the composition is provided in spray form. In accordance with another embodiment, the composition of the invention is provided in solid form, for example as a paste, pomade or cream.

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

The composition of the invention finds applications in both the cosmetic and the pharmaceutical field. In general, the composition of the invention finds applications in all cases wherein damage to the epidermal tissues occurs and wherein a sanitising treatment is required to restore the physiological conditions of the structures of the skin, and/or the damaged subcutaneous structures.

In accordance with an aspect of the present invention, the cosmetic use of a composition is provided for, which composition comprises ozonized oil, a-bisabolol in cosmetically advantageous quantities and a vehicle cosmetically advantageous for regeneration of the skin.

In certain embodiments, the composition for cosmetic use comprises one or more vehicles or excipients commonly used in the formulation of cosmetic preparations. In certain embodiments, the composition of the invention is used for the cosmetic treatment of an non-aesthetic features of the skin, such as, for example, puckering, skin blemishes forming, in particular, with aging of the skin, vitiligo, wrinkles, stretch marks, or adiposity.

According to another aspect, the present invention relates to a composition comprising ozonized oil and a-bisabolol in pharmaceutical advantageous quantities, for use in the treatment of a skin lesion.

The term skin lesion is used to mean any lesion of the epidermis wherein the epidermis is no longer intact or is lacerated or cut, or wherein there simply exists abrasion of the epidermis, even if only superficial.

Legions of the epidermis are, for example, wounds, skin sores, bed sores, ulcers and ulcerations, abrasions, burns.

In accordance with one embodiment, the composition of the invention finds applications in the disinfection and/or cicatrisation of wounds, ulcers or skin sores. In accordance with another embodiment, the composition of the invention finds applications in cases wherein it is necessary to reduce or at any rate maintain unchanged the bacterial load present in a wound, and in certain cases wherein it is necessary to increase the rate of the natural process of regeneration and healing of the wound.

In accordance with another embodiment, the composition of the invention finds applications in the sanitisation and regeneration of skin affected by sores and/or ulcers. By way of example, the composition of the invention finds applications in the treatment of decubital ulcers, infected ulcers, chronic ulcers.

The Applicant has, moreover, surprisingly discovered the existence of a direct linear correlation between the peroxide index PI expressed in equivalents of O₂/kg of oil, or the amount of ozone absorbed by an oil during the ozonization reaction, and the density of the reaction mass.

The existence of this correlation allows the ozonization reaction to be run substantially continuously until the desired ozonide concentration is reached, advantageously without interrupting the reaction to perform analytical sampling. According to one aspect, the invention therefore extends to a method for determining the peroxide index PI (milli-equivalents of O₂ per kg of oil) of an ozonized oil by measuring the density, expressed in g/l, of the reaction mixture. This method of analysis may be used as an alternative to the method reported in the Pharmacopoeia, which generally yields reliable responses only up to ozonide ion radical concentrations lower than those achievable in the present ozonization process.

In accordance with One embodiment, the ozonized oils of the invention are subjected to a mean increase in oxygen, relative to a vegetable oil, for example, sunflower oil, from which is derived, of more than 7000 m-equivalents of O2 per kilogram of oil, typically up to approximately 5500 m-equivalents of O₂ per kilogram and advantageously up to 4000 m-equivalents of O₂ per kilogram of oil.

BRIEF DESCRIPTION OF THE DRAWINGS

A number of aspects of the present invention are described in detail below, also with reference to the attached Figure 1 , which illustrates the linear correlation existing between the peroxide index (PI) and the density (d) of the ozonization mixture.

Specifically, the graph in Fig. 1 shows the peroxide index values, expressed as equivalents of O2 per kilogram of oil, on the Y-axis, and the values for the density of the mixture during the ozonization reaction, expressed as g/ml, on the X-axis. The graph illustrated demonstrates the existence of a direct linear correlation between the two values.

The present invention is described below with reference to the following examples, which are provided solely for illustrative purposes and should not be understood in the sense of limiting the invention.

EXAMPLES EXAMPLE 1

Process of preparation of the ozonized oil identified in Table 1.

Pure medical-grade oxygen is fed into a suitable 30-L generator at a flow rate of 140 L/h; an electrical charge of 6000 volts is applied to the generator, in this way ozone is formed, reaching a concentration of 90 mg/L of 0₃. The ozone is in turn bubbled into a suitable reactor containing sunflower oil. The amount of ozone absorbed is monitored both by means of conventional titration, and by measuring the density of the reaction mixture. The linear correlation existing between the density of the reaction medium, expressed in g/L, and the measured peroxide index (PI), expressed in equivalents of 0₂/kg, was discovered. This correlation represents a means of direct and reliable control of the course of the reaction. An example correlation, applied in the process of industrial production of ozonized oil, is shown in Fig. 1.

EXAMPLE 2

Experiment comparing a composition 2a), containing ozonized oil and alpha- bisabolol, and a formulation 2b), containing ozonized oil as the only active principle, both formulated as a spray oil intended for treating cutaneous ulcers. 2a) A suitable reactor is charged with 67 parts of caprylic/capric acid triglycerides and 30 parts of ozonized oil. Following adequate mixing, 3 parts of a-bisabolol are added.

Analysis of the peroxide index (PI) of the homogenous mixture is performed.

2b) A preparation analogous to 2a above is carried out with 70 parts of triglycerides and 30 parts of ozonized oils. The a-bisabolol constituent was omitted from this preparation.

Preparations 2a and 2b were compared in the treatment of cutaneous ulcers of mean diameter approximately 2 cm. After 15 days, the ulcers treated with preparation 2a proved to have significantly smaller dimensions by comparison with the control, consisting of ulcers treated with preparation 2b. Moreover, the patients treated alternately and successively (crossover) with preparation 2a stated that they had obtained greater benefit, as compared with preparation 2b, due to the greater tolerability, the early sensation of increased sensitivity, and reduced pruritus and burning.

EXAMPLE 3

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

3a. 65.38 parts of water are placed in a smelting vessel and heated to 80°C. Simultaneously, a turboemulsifier is charged with 6 parts of C12-20 fatty acids esterified with polyethylene glycol(s) (PEG), 2.5 parts of C13-C15 alkanes, 3 parts of variously hydrogenated alkenes, 1.5 parts of cetyl alcohol, 2 parts of caprylic/capric acid triglycerides, 8 parts of other emulsifiers and conventional thickeners. The whole is heated, with stirring, to 80°C and the water, previously heated separately, is transferred to the emulsifier. The mass is emulsified until a homogenous and consistent mass is obtained. It is cooled to 40°C, aromas and fragrances are added, and stirring is continued while the temperature continues to fall. 10 parts of ozonized oil and 1 part of a-bisabolol are placed into a separate mixer, and mixed. This mixture is then transferred to the turboemulsifier, wherein a homogenous and constant emulsion is obtained, the pH of which is regulated at the specified value with possible addition of sodium hydroxide solutions. All the specifications, including the peroxide index (PI), are verified in the finished product.

3b. The preparation is performed as in example 3a, but without addition of a-bisabolol. Preparation 3a showed greater and earlier antipruriginous and anti-inflammatory activity than 3b, thanks to the presence of a-bisabolol.

EXAMPLE 4

Demonstration of the increased antibacterial activity of the combination, as compared with the efficacy of the ozonized oil alone.

A comparison was made between the bactericidal activity of

a) a preparation containing 9 parts of ozonized oil of the type indicated in Table 1 and 1 part of a-bisabolol, with

b) an ozonized oil again of the type shown in Table 1 ,

against the strains Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (ATCC 27736) and Streptococcus agalactiae (ATCC 12368).

The conventional culture media were used, and the methods well-known in the art were applied, diffusion in agar and also serial dilution in a test tubes. The comparisons were made with the constituent ozonized oil referred to in Table 1 , under identical experimental conditions. The tables below show the initial concentrations of the microorganism inoculum and the percentage reductions in the number of colony-forming units (cfu) in the period of exposure to the antibacterial agent.

The evaluation of the bactericidal or bacteriostatic capacity of the products for comparison of pathogenic organisms, was performed by applying the linear regression method in-vitro and calculating the % reduction (R%) in the viability of the microorganisms. R% is defined by the ratio of the final and initial microorganism counts, multiplied by 100. The microbiological analyses were performed at the University of Ferrara Department of Diagnostic and Experimental Medicine. Table 2a: Composition: α-bisabolol : ozonized oil in a ratio of 1 : 9

Table 2b: 100% Ozonized oil

From the results, it emerged that the composition 1 part a-bisabolol - 9 parts ozonized oil showed a more elevated bactericidal activity than ozonized oil alone in comparisons of the microorganisms used: Streptococcus agalactae, Klebsiella pneumoniae and Pseudomonas aeruginosa.

EXAMPLE 5

Using the technology and the methods described in Example 4, the synergistic effect of a-bisabolol and ozonized oil (of Table 1 ) in a ratio of 1 :15 was evaluated in respect of the antibacterial activity against the strains indicated above. Table 3 shows the percentage survival of the inoculum concentrations over time and up to 24 h, as the effect of the α-bisabolol : ozonized oil composition in a ratio of 1 :15. Table 3: Percentage survival of the concentrations of inoculum of composition 1 :15 α-bisabolol : ozonized oil (PI 4000)

Comparison with Table 2b (in Example 4) showed that, even in the ratio 1 :15 α-bisabolol : ozonized oil 4000, there is a significant drop in survival of the strains as early as from the fourth hour.

Claims

1. Composition for topical use, comprising an effective amount of an ozonized oil and an effective amount of an essential oil extracted from chamomile.

2. Composition according to claim 1 , characterized in that said essential oil extracted from chamomile comprises or essentially consists of a-bisabolol.

3. Composition according to claim 1 or claim 2, characterized in that said ozonized oil is a vegetable oil, and is preferably sunflower oil.

4. Composition according to any one of claims 1-3, characterized in that said essential oil extracted from chamomile or a-bisabolol is present in an amount within the range from 1 to 20%, preferably from 5 to 10% by weight, relative to the ozonized oil, and said ozonized oil is present from 5 to 50% by weight in the composition or medical device.

5. Composition according to any one of the preceding claims 1-4, characterized in that the ozonized oil has a degree of peroxidation of up to 60% of the double bonds.

6. Composition according to any one of claims 1-5, characterized in that the ozonized oil comprises oleic acid from 14 to 39% by weight, peroxidised up to 60% of the double bond thereof, and linoleic acid from 47 to 74% peroxidised into mono-ozonide up to 40% and into bi-ozonide up to 20%.

7. Composition according to any one of claims 1-6, characterized in that the ozonized oil has a peroxide index (PI) within the range from 3400 to 4600.

8. Composition according to any one of claims 1-7, wherein the production of the ozonized oil is controlled by means of the density in the reaction medium, by applying the direct correlation between density and peroxide index.

9. Composition according to any one of claims 1-8, characterized in that it comprises at least one pharmaceutically or cosmetically advantageous excipient and in that it is in a form suitable for topical application, preferably selected from emulsion, gel, or spray solution.

10. Use of a composition according to any one of claims 1-9 in a method for cosmetically treating the skin.

11. Composition according to any one of claims 1-9 for use in treating affections of the skin.

12. Composition for the use according to claim 1 1 , wherein said affections of the skin are wounds, sores, ulcers, burns, sunburns or abrasions.

13. Composition for the use according to claim 12, wherein the affections of the skin are wounds infected with one or more of the microorganisms.

14. Composition according to claim 13, wherein said microorganisms are Streptococcus agalactae, Klebsiella pneumoniae or Pseudomonas aeruginosa.