SE1550068A1

SE1550068A1 - Prevention and treatment of skin mycosis

Info

Publication number: SE1550068A1
Application number: SE1550068A
Authority: SE
Inventors: Stefan Pierzynowski; Pawel Michalowski
Priority date: 2014-03-10
Filing date: 2015-01-23
Publication date: 2015-09-11
Also published as: WO2015135876A1

Description

25 30 2 ln young and middle age persons the effectiveness of a proper treatment can by around 70% and up to 100%. ln elderly the treatment of foot mycosis is less effective due to e.g. the wrong spectrum of the drug, irregularity of administration, side effects, early termination of treatment and lack of shoe disinfection. For prophylaxis and treatment shoe disinfection is essen?aL The proper blood circulation ensures proper effects of the treatment.

This is an important factor in the treatment of mycoses in the elderly, when blood circulation is impaired. Thus in such a situation the simultaneous administration of a drug which improves the blood circulation is necessary to introduce in order to achieve full effect of the treatment.

A problem with current local and systemic therapies forfungal skin infections is the risk of the development of resistance to the drugs. Another problem during systemic (i.v., i.m., i.p) therapy is the need for a proper blood circulation in the patient to ensure full effects of the systemic treatments.

Sweat fermentation is caused by bacteria. Due to its composition, sweat is a good substrate for bacterial growth. ln addition, the temperature of the sweat is optimal for bacterial growth. The products of sweat fermentation are mercaptans and ammonium and their derivatives which give rise to the specific sweat malodour. The specific malodour of sweat is also influenced by the food intake.

One of the simplest ways to stop sweat fermentation is its removal from the skin. The most effective method to stop sweat fermentation is using bactericidal drugs. Antibiotics are not recommended because of the risk of the bacteria developing resistance against the antibiotic used.

The most recommended way of limiting sweat fermentation is the use of preparations to which the bacteria cannot develop resistance. However, bacteria have the ability to develop resistance to all known compounds used in the treatment of skin mycosis today.

Summarv of the invention 10 15 20 25 30 3 According to a first aspect of the invention, the above and other objects of the invention are achieved, in full or at least in part, by a use according to ciaim 1.

According to this claim, the above object is achieved by a composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use as a medicament. The highly dispersed silica may have a specific surface area of 200 to 400 m2/g, and the at least one highly dispersed titanium acid may be in the form of a powder comprising particles having a diameter of 10 to 70 nm. The composition may be activated by an aqueous solution of hydrogen peroxide.

According to a second aspect of the invention, the above and other objects of the invention are achieved, in full or at least in part, by a composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use in the prevention or treatment of skin mycosis.

The skin mycosis may be epidermophytosis of the feet.

According to a third aspect of the invention, the above and other objects of the invention are achieved, in full or at least in part, by a composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use in the prevention of fermentation of sweat.

An advantage of a composition according to the present invention is that it is not selective, but has effect on a wide range of different fungi and bacteria. Thus, the composition may be used to treat any fungal or bacterial skin infection having different ethiology and intensity. This is especially advantageous, since, in contrast, the preparations used today have selective action on the selected strains, which in combination with their narrow- spectrum effect, results in that a mixture of several antibiotics often is used to obtain the desired effect.

Another advantage of a composition according to the present invention is the very low likelihood of the development of resistance against the composition in the microorganisms, since the microorganism cannot switch on defence mechanisms. The composition is acting via free radicals and via electrostatic surface load of the highly dispersed silica (SiOg) on cell 10 15 20 25 30 4 membrane or wall, having a destructive effect on the cell membrane or the cell wall of the microorganisms.

A third advantage of a composition according to the present invention is that the combination of two high-dispersed components allows for simple, quick, effective and close coverage to skin surface regardless of its shape.

A fourth advantage of a composition according to the present invention is that the mixture also has a sorption capacity of sweat and exudations from the skin surface altered by fungal infection. Since the mixture has also bacteriostatic and bactericidal effect, it prevents fermentation of sweat which is important for people with hyperhidrosis (heavily sweating) and for people who wear the same shoes for many hours (e.g. uniformed services). Bacteria on the skin which ferment sweat cause microabrasions of the skin which in turn facilitates the invasion of fungi causing mycosis. Thus, by limiting the development of microorganisms which are responsible for the fermentation of sweat and of the subsequent destruction of the epithelium, a composition according to the present invention protects the skin from invasion of fungi.

For all aspects of the invention, the highly dispersed silica may be alimentary or pharmaceutical grade highly dispersed silica.

According to an embodiment of the invention, the highly dispersed silica may have a specific surface area of 250 to 350 mz/g, preferably 300 mZ/g.

According to an embodiment of the invention, the at least one highly dispersed titanium acid (titanic acid) may be highly dispersed orthotitanium acid (orthotitanic acid) or highly dispersed polytitanium acid (polytitanic acid). ln this application, the wording “titanium acid” is to be understood as being the same as “titanic acid”, “orthotitanium acid” is to be understood as being the same as “orthotitanic acid” and “polytitanium acid” is to be understood as being the same as “polytitanic acid".

The proportion of the at least one titanium acid may range from 0.2 to 5 % (weight/weight), preferably 0.5 to 3 % (weight/weight), more preferably 1 % (weight/weight) in relation to the weight of highly dispersed silica. 10 15 20 25 30 5 According to an embodiment of the invention, the at least one highly dispersed titanium acid may be in the form of a powder comprising particles having a diameter of 20 to 60 nm, preferably 30 to 50 nm.

According to one embodiment of the invention, the aqueous solution of hydrogen peroxide may be a solution of 0.1 to 10 % (vol/vol), preferably 1 to 8 % (vol/vol), more preferably 2 to 5 % (vol/vol), most preferably 3 % (vol/vol).

The aqueous solution of hydrogen peroxide may be comprised in an aerosol. The activation with small amount of hydrogen peroxide in aerosol is simple in use, requires a small amount of fluid, and allows the activation of titanium acids on each, even corrugated, surface, without the necessity of wetting it.

According to a fourth aspect of the invention, the above and other objects of the invention are achieved, in full or at least in part, by a method of activating a composition comprising highly dispersed silica and at least one highly dispersed titanium acid by subjecting the composition to activation by an aqueous solution of hydrogen peroxide. The highly dispersed silica may have a specific surface area of 200 to 400 mZ/g, and the at least one highly dispersed titanium acid may be in the form of a powder comprising particles having a diameter of 10 to 70 nm. The aqueous solution of hydrogen peroxide may be a solution of 0.1 to 10 % (vol/vol), preferably 3 % (vol/vol).

According to a fifth aspect of the invention, the above and other objects of the invention are achieved, in full or at least in part, by a kit comprising a) a composition comprising highly dispersed silica and at least one highly dispersed titanium acid, wherein the highly dispersed silica has a specific surface area of 200 to 400 mZ/g, and the at least one highly dispersed titanium acid is in the form of a powder comprising particles having a diameter of 10 to 70 nm, and b) an aqueous solution of hydrogen peroxide, wherein the aqueous solution of hydrogen peroxide may be a solution of0.1 to 10 % (vol/vol), preferably 3 % (vol/vol), and c) optionally, instructions for use.

Detailed description of the invention 10 15 20 25 30 6 An essential feature of the present invention is the synergism between highly dispersed SiOz and highly dispersed polytitanic and orthotitanic acid in antibacterial and antifungal (antimycotic) action both in therapy and in prophylaxis.

The inventors have unexpectedly found that a composition according to the present invention has a strong, non-selective antifungal and bactericidal activity providing for an effective prevention and reduction of skin mycosis, especially when the skin mycosis is epidermophytosis of the feet.

The effect is not dependent on the kind of fungi or bacteria causing the skin Iesions. The invention provides for a composition for use in the general treatment and/or protection against mycosis of different ethiology. The present invention also provides a method of production of the composition and a method of use of the composition.

The composition comprises highly dispersed silica (SiOg) and at least one highly dispersed titanium acid. The titanium acid may be polytitanic acid TiO(OH)2 or orthotitanic acid H4TiO4, but other kinds of titanic acids or the corresponding salts of the titanic acids may also be present.

The composition may be used in powder form.

The composition may be used as it is or activated by applying an aqueous solution of 3 % (vol/vol) hydrogen peroxide. The hydrogen peroxide may be in the form of an aerosol, but other modes of application such as swabbing, dabbing or application with a sponge, may also be used.

The activation of highly dispersed TiO(OH)2 by H2O2 one can follow reaction of H4TiO4. On the surface a particle the active centre >Ti3*OH is created. ln the presence of H2O2 very active free radicals are created. >Ti3*oH + Hzoz s >Ti4*oH + oH1'+ oHï >Ti3*oH + H2o2 s >Ti4*o2H1' + H20 >Ti3*oH + Hzog s >Tr**oH + o31-+ 2H¥ Dependent on particle size and the characteristics of agglomerates, highly dispersed particles of SiOg are given a high electrostatic load, which can be both hydrophobic and hydrophilic, dependent of the materials used. 10 15 20 25 30 7 The proposed mechanism of action of a composition according to the present invention is that the highly dispersed particies surround the fungi/bacteria and destroy the cell membranes/cell walls of the microorganisms. Hence, it is important to use hydrophilic highly dispersed SiOg in order for the particies to be able to surround the bacteria/fungi. ln contrast to other antibiotics/antifungal compositions, the composition is not acting as liquid phase but only as a suspension.

Free radicals act effectively on all fungi that cause fungal infections of the skin.

Since the composition exhibits its mode of action through contact features, it is recommended to use the composition on skin without strong/lot of hair. lmportantly, the mechanism of action of the product eliminates the possibility of the development of resistance by the microorganisms.

A composition according to the present invention may be used in the treatment and/or the prophylaxis of skin mycosis. lt may also be used in the treatment and/or the prophylaxis of bacterial infections and/or in the treatment and/or the prophylaxis of inflammation caused by fungi and/or bacteria.

Further, the composition may be used in the treatment and/or the prophylaxis of infections/inflammations having a mixture of different ethiology.

Examples of fungal infections which may be treated and/or prevented by a composition according to the present invention are infections caused by e.g. Candida albicans, Candida spp., Trichophyton rubrum, Trichophyton spp.

Microsporum or Epidermophyton fungi or other epidemic fungi.

Examples of bacterial infections which may be treated and/or prevented by a composition according to the present invention are infections caused by e.g. Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, and Enterobacteriaceae such as Citrobacter freundi and, Proteus mirabilis or other infectious bacteria.

The location of the infection and/or inflammation may be the nail or the skin, such as the foot, the groin, an arm or a leg (e.g. tinea corporis), the back or chest (e.g. tinea versicolor) or any other part of the body. 10 15 20 25 30 8 The infection and/or inflammation may also be located on mucosa, such as in the mouth or the vagina.

The composition may be used in the treatment and/or the prophylaxis of the above mentioned conditions in individuals of any age.

None of the components of the composition according to the present invention is absorbed by the skin. Furthermore, none of the components exhibit cytotoxic effects. Hence the likelihood that a patient using the composition will develop allergy towards the composition is very low. ln addition, the composition according to the present invention does not show any interaction with other drugs taken by the patient per os or as injections.

Because of the strong antifungal and bactericidal effect of a composition according to the present invention, it is suitable for the treatment of difficult skin mycosis which coincides with skin destruction and bacterial infection. Using highly dispersed SiOg allows the skin to be covered with a micro layer having drying capacity.

The likelihood of the development of resistance against a composition according to the present invention is very low, which makes it suitable for the use in the prevention of fermentation of sweat.

A composition according to the present invention acts against bacteria and fungi via the generation of free radicals and via electrostatic loads. Most importantly, a composition based on free radicals and electrostatic loads is safe for the host to use.

A composition according to the present invention may be recommended for prevention of mycosis, in particular in the case of prolonged use of shoes in different conditions such as the uniformed services. The composition according to the present invention will reduce existing skin fungal infection, in particular when the skin mycosis is epidermophytosis of the feet, irrespective of the kind of fungal strain causing the infection.

Method of administration and dosages of a composition according to the present invention may be determined separately for prevention, active disease and post diseases states. Preferably, the dosis is in relation to the status of the skin such that a higher dosis is used for the treatment of infected 10 15 20 25 9 skin and a lower dosis is used for prophylactic treatment. The composition according to the present invention may be administered e.g. once or twice a day, but a less or more frequent administration is also possible.

Experiments De?nition of McFarland Turbiditv Standards: The McFarland Scale is well known in the field and represents specific concentrations of CFU/mL (colony forming units/mL) and is designed to be used for estimating concentrations of bacteria. McFarland standards are used as a reference to adjust the turbidity of bacterial suspensions so that the number of bacteria will be within a given range. The McFarland scale is based on the density principle: 0.5; 1.0; 2.0; 3.0; 4.0. 0.5 in McFarland scale is used as standard when testing sensitivity of microorganisms to antibiotics and sulphonamides in order to judge effectiveness of composition or preparations. Specific standards are used when preparing bacterial suspensions. Original McFarland standards were mixing specified amounts of barium chloride and sulphuric acid together.

Mixing the two compounds forms a barium sulphate precipitate, which causes turbidity in the solution. A 0.5 McFarland standard is prepared by mixing 0.05 mL of 1 .175% barium chloride dihydrate (BaCl2-2H2O), with 9.95 mL of 1% sulphuric acid (H2SO4).

McFarland Standard No. 0.5 1 2 3 4 1.0% BaCI ml 0.05 0.1 0.2 0.3 0.4 1.0% H2SO4 ml 9.95 9.9 9.8 9.7 9.6 cell density (1x10“ cfu/mi) 1.5 3.0 6.0 9.0 12.0 Transmittance % (at 600 nm) 74.3 55.6 35.6 26.4 21.5 Absorbance 0.132 0.257 0.451 0.582 0.669 Test of the antifunqal/antibacteria/ effect of a composition according to the present invention: The antifungal/antibacterial effect of the composition according to the present invention was tested against fungi which are responsible for 70% skin mycosis e.g. Trichophyton rubrum and against fungi which always join skin abrasion e.g. Candida albicans. Very often wounds are 10 15 20 25 30 10 at the same time infected with e.g. Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli and Enterobacteriaceae such as Citrobacter freundi and Proteus mirabilis. The presence of these bacteria in wounds disturbs essentially the whole healing process. The antibacterial effect of the composition was also tested against these bacteria.

To confirm the effectiveness of a composition according to the present invention, experiments were performed which explore the decrease of density of the bacterial strains and fungi discussed above, in the presence of the composition comprising highly dispersed silica and highly dispersed polytitanium acid and activated with 3% (vol/vol) hydrogen peroxide.

The composition according to the present invention was sterilized with gamma radiation.

The antibacterial/antifungal activity of the composition was tested both in broth and on plate.

Studies in broth: The study was performed for a suspension of 0.5 in McFarland scale and for a suspension of 0.1 in McFarland scale. To exclude the effect of hydrogen peroxide it was added alone to the broth in the amount, form and concentration identical to the experiment using the composition according to the present invention. Studies on plate: After preparation of suspensions of selected microorganisms they were seeded with a moistened swab with a 3-fold plating on prepared Mueller-Hinton agar base. On the prepared and infected plates rings having a diameter of 30 mm were placed and inside each ring the composition was placed in a manner not to contaminate the surface outside the rings. Using a container with a mechanical spray head containing 3% (vol/vol) aqueous hydrogen peroxide solution allowing for one dose of 0.14 ml, a single dose (0.14 ml) of hydrogen peroxide was applied over the entire inner surface of the ring in a manner to avoid the contact of the solution mist of hydrogen peroxide with the plate surface outside the ring.

To confirm that the composition activated with hydrogen peroxide solution has activity against microorganisms, and not the hydrogen peroxide solution alone, a single dose of 0.14 ml of 3% aqueous hydrogen peroxide 10 11 solution was applied into the ring in the absence of the composition on a prepared and infected plate, in the manner described above.

The prepared plates were incubated in 37°C for 24 hours and then assessed for the presence of growth inhibition zones.

Results - Studies in broth: The results are shown in the table below. “+” (plus) means antibacterial/antifungal effect and (minus) means no effect. 3% aqueous hydrogen Preparation activated with peroxide No. Microorganism hydrogen peroxide solution Suspension Suspension 0.5 Suspension 1.0 0.5 in in McFarland in McFarland McFarland scale scale scale Candida albicans + + + + + + + + + + + + - 2 Trichophyton rubrum + + + + + + + + + + + + - Staphylococcus 3 aureug + + + + + + + Pseudomonas 4 aeruginosa + + + + + + + 5 Citrobacter freundii + + + + + + + 6 Proteus mirabilis + + + + + + 7 Escherichia coli + + + + +/- lt was found that highly dispersed titanium acids, including highly dispersed polytitanium acid and highly dispersed orthotitanium acid, together with highly dispersed silica and activated with hydrogen peroxide, have potent antifungal properties against all standard strains tested and strains collected from the skin surface. lmportantly, the preparation, comprising highly dispersed silica and highly dispersed polytitanium acid and activated ex tempore with hydrogen ”IO 15 20 25 30 12 peroxide, has a strong non-selective antifungal activity against the tested fungi. ln three bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa and Citrobacter freundii), the inhibition zone was achieved by the treatment of hydrogen peroxide alone, but of less intensity than by the treatment with the composition activated with hydrogen peroxide. The effect of hydrogen peroxide alone against fungi was not achieved.

The number of the “+” in the table shows that the effect of the composition according to the present invention on Candida albicans or Trichophyton rubrum is twice as high as on tested test bacteria.

The use of two different densities of microorganisms shows that the antimicrobial/antifungal activity does not depend on the inoculum turbidity on the site of bacterial contamination.

Additional experiments test with suspensions 1.0 in McFarland scale were performed. Very similar results were obtained as with suspensions 0.5 in McFarland scale. This demonstrates that the composition has the same activity (effectiveness) independent of bacterial density. This is very important in the treatment and prophylaxis of mycosis.

Results - Studies on plate: The inventors observed the zones of inhibition. The results correspond to the results for the studies in broth. ln the presence of complete contact on the surface, similar to that of the powder on the skin, the preparation showed the effect of decreasing density of the used bacterial strains, and the effect intensity was different in different strains, but strong, non-selective fungicidal activity was observed.

The change in the zone of inhibition was significantly greater for the tested fungi than to the tested bacteria, which demonstrates that the composition according to the invention has more potent fungicidal than bactericidal activity.

Examples Example I -The preparation of a composition for use in the pronh vlaxis and treatment of skin funqa/ Infections in particular when the skin mvcosis is 10 15 20 25 30 13 eDidermoDhvtos/s of the feet of anv ethio/oqv: The weighed amount of highly dispersed silica with pharmaceutical quality and weighed amount of highly dispersed orthototitanium acid were placed in a homogenizer and homogenized. The proportion of the titanium acid was 1 % (weight/weight) in relation to the weight of highly dispersed silica. After a prescribed time, the mixture is put to temporary packages and samples are taken for the analysis of compliance with the corporation requirements (company standards). After obtaining the approval of the Quality Control Department, the powder is put into a packaging machine packing it into packages for powder, the packages are labelled in accordance with the relevant rules valid in the country of destination. On a separate production line, an aqueous solution of 3 % (vol/vol) hydrogen peroxide is packaged in packages with a spray head allowing for a specific dosage. The package is labelled and analyzed. After analyzing for compliance with company standards, the packages may be used in the next phase of production. An alternative to the own production is ordering of packages from a licensed manufacturer of aerosols. One package with powder and one package with hydrogen peroxide with relevant lea?et are placed in one carton. One package is placed in packs and undergoes a final quality control.

Examole I/ - The oreparation of a comnosition for use in the oroDhv/axis and treatment of skin fur/dal Infections in particular when the skin mvcosis is eøidermonhvtosis of the feet of anv ethio/oqv: The weighed amount of highly dispersed silica with pharmaceutical quality and weighed amount of highly dispersed orthotitanium acid were placed in a the homogenizer and homogenized. The proportion of the titanium acid was 1 % (weight/weight) in relation to the weight of highly dispersed silica. After a prescribed time, the mixture is put to temporary packages and samples are taken for the analysis of compliance with the corporation requirements (company standards). After obtaining the approval of the Quality Control Department the powder is put into a packaging machine packing it into packages for powder, the packages are labelled in accordance with the relevant rules valid in the country of 10 15 20 25 30 14 destination. On a separate production line, an aqueous solution of 3% (vol/vol) hydrogen peroxide is packaged in packages with a spray head allowing for a specific dosage. The package is Iabelled and analyzed. After analyzing for compliance with company standards, the packages may be used in the next phase of production. An alternative to the own production is ordering packages from a licensed manufacturer of aerosols. One package with powder and one package with hydrogen peroxide with relevant lea?et are placed in one carton. One package is placed in packs and undergoes a final quality control.

Embodiments 1. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use as a medicament. 2. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use in the prevention or treatment of skin mycosis. 3. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to embodiment 2, wherein the skin mycosis is epidermophytosis of the feet. 4. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use in the prevention of fermentation of sweat. 5. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of embodiments 1 to 4, wherein the highly dispersed silica is alimentary or pharmaceutical grade highly dispersed silica. 6. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of embodiments 1 to 5, 10 15 20 25 30 15 wherein the highly dispersed silica has a specific surface area of 200 to 400 mZ/g, preferably 250 to 350 m2/g, more preferably 300 m2/g. 7. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of embodiments 1 to 6, wherein the at least one highly dispersed titanium acid is highly dispersed orthotitanium acid or highly dispersed polytitanium acid. 8. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of embodiments 1 to 7, wherein the proportion of the at least one titanium acid ranges from 0.2 to 5 % (weight/weight), preferably 0.5 to 3 % (weight/weight), more preferably 1 % (weight/weight) in relation to the weight of highly dispersed silica. 9. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of embodiments 1 to 8, wherein the at least one highly dispersed titanium acid is in the form of a powder comprising particles having a diameter of 10 to 70 nm. 10. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of embodiments 1 to 9, wherein the composition is activated by an aqueous solution of hydrogen peroxide, wherein the aqueous solution of hydrogen peroxide preferably is a solution of preferably 0.1 to 10 % (vol/vol), more preferably 3 % (vol/vol). 11. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to embodiment 10, wherein the aqueous solution of hydrogen peroxide is comprised in an aerosol. 12. Method of treating epidermophytosis of the feet, wherein a composition comprising highly dispersed silica and at least one highly dispersed titanium 10 15 16 acid according to anyone of embodiments 3 to 10 is applied to at least one foot and subsequently activated by hydrogen peroxide. 13. Method of treating epidermophytosis of the feet according to embodiment 12, wherein the composition is applied as a single dosis and subsequently activated by hydrogen peroxide before putting on footwear and/or after removal of the footvvear. 14. Method of treating epidermophytosis of the feet according to embodiment 12, wherein the composition is applied and subsequently activated by hydrogen peroxide after awakening and/or before sleeping and before putting on footwear and/or after removal of the footvvear. 15. Method of preventing fermentation of sweat, wherein a composition comprising highly dispersed silica and at least one highly dispersed titanium acid according to embodiment 12 or 14, wherein the composition is applied as a single dosis.

Claims

10 15 20 25 30 17 CLAIMS

1. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use as a medicament, wherein the highly dispersed silica has a specific surface area of 200 to 400 mZ/g, and the at least one highly dispersed titanium acid is in the form of a powder comprising particles having a diameter of 10 to 70 nm, and wherein the composition is activated by an aqueous solution of hydrogen peroxide.

2. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use in the prevention or treatment of skin mycosis.

3. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to claim 2, wherein the skin mycosis is epidermophytosis of the feet.

4. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use in the prevention of fermentation of sweat.

5. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of claims 1 to 4, wherein the highly dispersed silica is alimentary or pharmaceutical grade highly dispersed silica.

6. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of claims 1 to 5, wherein the highly dispersed silica has a specific surface area of 250 to 350 mZ/g, preferably 300 mZ/g.

7. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of claims 1 to 6, wherein 10 15 20 25 30 18 the at least one highly dispersed titanium acid is highly dispersed orthotitanium acid or highly dispersed polytitanium acid.

8. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of claims 1 to 7, wherein the proportion of the at least one titanium acid ranges from 0.2 to 5 % (weight/weight), preferably 0.5 to 3 % (weight/weight), more preferably 1 % (weight/weight) in relation to the weight of highly dispersed silica.

9. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of claims 1 to 8, wherein the at least one highly dispersed titanium acid is in the form of a powder comprising particles having a diameter of 20 to 60 nm, preferably 30 to 50 Hm.

10. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to anyone of claims 1 to 9, wherein the aqueous solution of hydrogen peroxide is a solution of0.1 to 10 % (vol/vol), preferably 3 % (vol/vol).

11. A composition comprising highly dispersed silica and at least one highly dispersed titanium acid for use according to claim 10, wherein the aqueous solution of hydrogen peroxide is comprised in an aerosol.

12. Method of activating a composition comprising highly dispersed silica and at least one highly dispersed titanium acid according to anyone of claims 1 to 9, wherein the composition is subjected to activation by an aqueous solution of hydrogen peroxide, wherein the aqueous solution of hydrogen peroxide is a solution of preferably 0.1 to 10 % (vol/vol), preferably 3 % (vol/vol).

13. A kit comprising a) a composition according to anyone of claims 1-11, and 19 b) an aqueous solution of hydrogen peroxide, wherein the aqueous solution of hydrogen peroxide preferably is a solution of 0.1 to 10 % (vol/vol), preferably 3 % (vol/vol), and c) optionaiiy, instructions for use.