EP3393464A1

EP3393464A1 - Composition for the treatment of keratosis

Info

Publication number: EP3393464A1
Application number: EP16825586.7A
Authority: EP
Inventors: Robert Stal; Johannes Witte
Original assignee: YouMedical BV
Current assignee: YouMedical BV
Priority date: 2015-12-22
Filing date: 2016-12-21
Publication date: 2018-10-31
Also published as: WO2017111587A1; NL2016000B1

Abstract

The invention pertains to a composition for the topical treatment of a keratosis, preferably a wart, comprising a halogenated acetic acid and an alpha-hydroxy acid. The invention further pertains to a dermal patch comprising this composition, and to kits comprising this composition and a patch, as well as to liquid plasters comprising the composition. Also, the invention pertains to the treatment of keratosis by contacting the keratosis with the composition.

Description

Title: Composition for the treatment of keratosis

Introduction

The invention pertains to the treatment of keratosis, preferably warts.

Keratosis is a horn-like skin condition, which includes benign skin lesions, and includes for example warts. Warts are small, benign growths caused by a viral infection of the skin or mucous membrane. The virus infects the surface layer. The viruses that cause warts are members of the human papilloma virus (HPV) family. Warts are not likely to cause harm, but are generally considered of unattractive appearance, for which reason wart removal has been a subject of considerable interest.

Wart removal may be achieved in various ways. Warts may be treated by cryotherapy, such as by the use of liquid nitrogen, or a mixture of propane with e.g. dimethylether, isobutane and/or aceton.

An alternative treatment comprises application of an acid.

Although the acid does not kill the virus, the acid softens the skin, which gradually loosens, with the virus in it. Thus, infected skin is removed, and thereby the wart is removed. Suitable acids which have been applied for this use are, among others, salicylic acid, hydrochloric acid and formic acid.

A drawback of such treatments is that current treatments require daily application, and/or use strong acids that often damage the skin.

The present invention provides a composition which eliminates the need to apply the product every day and still provide a safe and effective treatment.

Description of figures

Figure 1: the combination of an alpha-hydroxy acid with an halogenated acid is more effective (A) and leads to less adverse events (B) in the treatment of warts than the application of a composition comprising an alpha-hydroxy acid alone.

Figure 2: an occlusive patch prefilled with a composition according to the invention (X).

Figure 3: A method for treating a wart using a composition according to the invention in conjunction with an occlusive patch. A) place the bottle firmly on a flat surface and unscrew the cap; B) Carefully lift the applicator from the bottle; C) Apply the liquid on a wart and allow to dry approximately 30 seconds; D) Place a patch over the wart and leave for minimum 4 hours.

Summary of the invention

The invention pertains to a composition for the topical treatment of keratosis, preferably a wart, comprising a halogenated acetic acid and an alpha-hydroxy acid. The invention further pertains to a dermal patch comprising this composition, and to kits comprising this composition and a patch. Also, the invention pertains to the treatment of keratosis by contacting the keratosis with the composition. Detailed description

The present invention pertains to a composition for use in the topical treatment of keratosis, comprising 1 - 50 wt.% of one or more halogenated acetic acids and one or more alpha-hydroxy acids.

Keratosis is a horn -like skin condition, and includes, in the context of the present invention, benign skin lesions. Two types exist, congenital keratosis and acquired keratosis.

A congenital keratosis is a horn-like skin condition caused by an endogenous factor. An acquired keratosis is a horn-like skin condition which is caused by an external factor, such as a virus or excessive UV-radiation. Congenital keratoses include simple and complex keratosesdermas, which may for instance be palmoplantar keratoses, such as diffuse, focal or punctuate palmoplantar keratoses.

Acquired keratoses include for instance

• Arsenical keratoses

• Climacteric keratoses

• Clavi (Corns)

• Human papillomavirus infections

• Keratoderma blenorrhagicum

• Lichen planus

• Paraneoplastic keratoses

• Tinea pedis

• Acrochordons

• Actinic keratoses

• Seborrheic keratoses

• Scars

Preferred types of keratosis in the present context are actinic keratosis, scars, and human papillomavirus infections. More preferably, a keratosis in the present context is a human papilloma virus infection, most preferably a wart.

Warts, in this context, are small, benign growths caused by a viral infection of the skin or mucous membrane. The virus infects the surface layer. Several different types of warts exist, among which:

• Common wart (Verruca vulgaris), a raised wart with

roughened surface, most common on hands, but can grow anywhere on the body.

• Flat wart (Verruca plana), a small, smooth flattened wart, flesh-coloured, which can occur in large numbers; most common on the face, neck, hands, wrists and knees. • Filiform or digitate wart, a thread- or finger-like wart, most common on the face, especially near the eyelids and lips.

• Genital wart (venereal wart, Condyloma acuminatum,

Verruca acuminata), a wart that occurs on the genitalia.

• Mosaic wart, a group of tightly clustered plantar-type warts, commonly on the hands or soles of the feet.

• Periungual wart, a cauliflower-like cluster of warts that

occurs around the nails.

• Plantar wart (Verruca plantaris), a hard sometimes painful lump, often with multiple black specks in the center; usually only found on pressure points on the soles of the feet.

Among warts, preferred types of warts are common wart, flat wart, mosaic wart, periungal wart or plantar wart, more preferably common warts or plantar warts.

Treatment of a keratosis in the present context is a topical treatment, which means treatment by application of the composition to the affected skin. Preferably, the composition is applied only to the area of the skin affected by the keratosis to avoid healthy skin being exposed to the composition.

The composition can be applied by any means, such as by finger, pipette, brush, sponge or stick, preferably by pipette, brush, sponge or stick. Further preferably, the composition is allowed to contact the keratosis for at least 4 hours, preferably at least 8 hours, more preferably at least 12 hours, even more preferably at least 24 hours, even more preferably at least 2 days, such as more preferably 3 or 4 days.

Treatment comprises repeated application, such as for example application 1 - 7 times a week, preferably 1 - 6 times a week, more

preferably 1 - 4 times a week, more preferably 2 or 3 times a week, most preferably about twice a week. Preferably, treatment is continued for at least 4 weeks, and continued until the keratosis has vanished, which may take up to 6 months or even longer. Preferably however, this can for example be 4 to at most 16 weeks, preferably 4 to at most 12 weeks.

The composition of the invention comprises a halogenated acetic acid, or a mixture of various halogenated acetic acids. The composition comprises 1 - 50 wt.%, based on the total weight of the composition, of a halogenated acetic acid or of the mixture of halogenated acetic acids.

Preferably, the composition comprises 2 - 25 wt.%, more preferably 5 - 20 wt.%, of the halogenated acetic acid(s), even more preferably 8- 15 wt.%.

The halogenated acetic acid can for example be a mono-, di- or trihalogenated acetic acid. Preferably, the halogenated acetic acid is a chloro, bromo- or fluoroacetic acid, more preferably a chloro- or fluoroacetic acid, even more preferably a chloroacetic acid, such as mono-, di or trichloroacetic acid. Most preferably, the invention comprises trichloroacetic acid ([CAS 76-03-9], abbreviated as "TCA").

In addition to a halogenated acetic acid, the composition comprises an alpha-hydroxy acid. Preferred alpha-hydroxy acids are lactic acid, glycolic acid, malic acid, citric acid and tartaric acid, more preferably lactic acid, glycolic acid and citric acid. Combinations of alpha-hydroxy acids may also be comprised in the composition.

Preferably, the quantity of alpha-hydroxy acid, (or in case of multiple alpha-hydroxy acids, the total quantity of alpha-hydroxy acids) is 1 - 50 wt.%, based on the total weight of the composition, preferably 10 - 40 wt.%, more preferably 15 - 35 wt.%, even more preferably 20-34 wt.% or 25- 32 wt.%.

It is an advantage of the present composition that by introducing a combination of one or more alpha-hydroxy acids and one or more halogenated acetic acids, the quantity of halogenated acetic acid(s) in the composition can be reduced while retaining a functional treatment. This has the advantage that there is less risk of damaging healthy skin by the presence of a large quantity of the corrosive halogenated acetic acid(s).

Alternatively, the advantage of the present combination of one or more alpha-hydroxy acids and one or more halogenated acetic acids is that the total quantity of acid may be reduced. It has been found this

combination is particularly effective, such that an effective treatment using less corrosive acids is possible. This has the added advantage of decreasing the number of side effects.

Generally, the present combination results in increased skin corrosion associated with less adverse events, such as itching, redness and other irritation of skin around the location where the keratosis is located.

The combination comprising one or more halogenated acetic acids and one or more alpha-hydroxy acids in the composition of the invention has the effect of weakening the bonds of the upper layers of the skin that hold the dead cells together, allowing the removal of dead skin (exfoliation). The addition of one or more alpha-hydroxy acids furthermore helps to guide the halogenated acetic acid into the deeper layers of the skin which has the beneficial effect of being able to use lower concentrations of the halogenated acetic acid with the same effect. While the alpha-hydroxy acid and the halogenated acetic acid have an effect on peeling the skin independently, there appears to be a synergy between the acids that allows a better performance of the combined acids than the acids used separately. This allows a reduced concentration of acid to remove skin allowing continued efficacy with significantly improved safety.

Also, the combination allows for reducing the number of applications per week, compared to known compositions.

The composition will typically further comprise a solvent. It is preferred that a Cl - C3 alcohol is used as a solvent, or any mixture of Cl- C3 alcohols. Preferred solvents include C1-C3 alcohols with one or more alcohol groups, preferably methanol, ethanol, n-propanol and isopropanol, more preferably ethanol. These alcohols are preferred because they evaporate quickly.

In a preferred embodiment, the composition further comprises one or more gel-forming polymers. A gel-forming polymer in this context is a polymer which dissolves or suspends in a C1-C3 alcohol as defined above. A composition which is based on a solution or suspension of the gel -forming polymer in the solvent has the advantage of more easily staying in place on the skin. These so-called "liquid plasters" are a highly viscous layer comprising the composition of the invention, which is present on the skin. This can be achieved by application of a composition in a form which is already a gel on the skin, or by application of a liquid composition which upon evaporation of solvent will form a gel by increasing the relative quantity of the gel -forming polymer in the composition.

A composition in which gel-forming polymer is already present in sufficient concentration can itself be a gel, also prior to application to the skin. A gel, in this context, is a viscous composition, and may in this context be referred to as a paste, suspension or cream. The advantage of using a gelled composition is that the higher viscosity will allow the product to be applied more accurately to the keratosis.

The concentration of gel -forming polymer to result in gel- formation depends on the type of polymer and the type of solvent chosen, and is well-known. For example, concentrations of 0.1 - 60 wt.%, such as 10 - 50 wt.% or 20 - 40 wt.%, based on the weight of the composition, may be usable, in order to obtain a composition according to the invention in the form of a gel. This formulation, after application to a keratosis, results in a liquid plaster. Evaporation of solvent after application may result in a strengthening of the gel, as compared to the initially gelled composition.

A composition according to the invention may also be in liquid form while further comprising a suitable concentration of gel forming polymer, such that upon evaporation of solvent after application to the skin, the composition forms a gel. Generally, the quantity of gel -forming polymer in a liquid, gel-forming composition is between 0.1% - 15% wt.%, based on the total weight of the composition, preferably 0.1% - 9% wt.%. Such concentrations have the effect that after application of the composition to a keratosis, part of the solvent evaporates such that the concentration of gel- forming polymer increases to a concentration where gelling occurs. This results in the liquid plaster.

In both forms of liquid plaster (compositions including a gel- forming polymer, one liquid, the other one gelled), the composition of the invention is present, and the plaster ensures contact of the composition of the invention with the skin at the location of an keratosis.

An advantage of liquid plaster formulations is that no additional covering with a patch is required. Instead, the formulation remains on the skin, protected from the surrounding, by the liquid plaster. This has the beneficial effect of being able to reduce the number of applications per week.

A further advantage of liquid plasters is that application is easier, as there is no need to position a patch on the same area as where the liquid plaster has been applied. Also, in skin areas which are subject to heavy motion, such as locations where limbs join the body, the gelled layer comprising the composition retains its position more readily than a patch.

Suitable gel -forming polymers to obtain liquid plaster

formulations are gel-forming polymers which are suitable for topical application to human skin, i.e. they are pharmaceutically acceptable for topical application. Such polymers are well-known, and include for instance polyvinylalcohol (PVA), polyvinylpyrrolidone (PVP), cellulose ether, pyroxylin, nitrocellulose, methylacrylate, acrylate, isobutene,

isopropylmaleate and/or siloxane polymers. Preferably, the gel -forming polymer is PVA or PVP. Mixtures comprising multiple suitable gel-forming polymers, or copolymers (or mixtures thereof) comprising chain segments based on suitable gel-forming polymers may also be used as gel -forming polymer in the present context.

The viscosity of the liquid plaster is generally such that the gel can be readily applied, but is difficult to remove. This viscosity is preferably 1 - 50000 centipoise, preferably 0 - 5000 centipoise. The viscosity of the gel may be determined by viscosimetry at 33 °C, using known procedures for gels for topical pharmaceutical applications.

Thus, the invention further pertains to a liquid plaster, comprising one or more halogenated acetic acids, one or more alpha-hydroxy acids, one or more solvents and one or more gel-forming polymers in a concentration sufficient to form a liquid plaster. The appropriate quantities of these components for a liquid plaster formulation comprising the composition of the invention have been described above. Also, the viscosity of a liquid plaster is as defined above.

A liquid plaster may also be covered by a patch, as described below. This has the advantage of providing even more protection of the composition while being in contact with the skin, such that the application frequency may be reduced relative to known compositions.

The composition of the invention, whether in the form of a liquid without gel-forming polymer or of a liquid plaster (i.e. comprising a gel- forming polymer in a quantity sufficient to result in gel -formation) may additionally include other suitable additives. Such additives may include colorants, dispersants, stabilizers, salts, buffers, fragrances, emulsifiers, humectants and/or preservatives. Also, the composition may comprise inorganic matter, such as micro- or nanoparticles, such as for instance silver nanoparticles for an antimicrobial effect, or silicates to alter the physical appearance.

Furthermore, the composition may additionally comprise pharmaceutical compounds, such as pharmaceutical compounds which help in treating human papillomavirus infections. Suitable examples of such compounds include salicylic acid, zinc, imoquimod, squaric acid dibutyl ester, diphencyclopropenone, podophyllin , cantharidine, Cidofovir, 5- fluorouracil, tretinoin, vitamin A and Carica papaya extract. Preferably however, the composition comprises no pharmaceutical compounds.

The pH of the composition is preferably between 0 and 3, more preferably between 0.5 and 2, more preferably between 1 and 1.5. In a preferred embodiment, the composition comprises a buffer to effect the desired pH.

Optionally, the composition may comprise up to 60 wt.% water, based on the total weight of the composition, preferably up to 30 wt.%, even more preferably up to 10 wt.%. Most preferably, the composition comprises less than 5 wt.% water.

The composition of the invention can be prepared by mixing the separate components as defined above in any order. Mixing may be achieved by any conventional method, such as stirring and shaking. All components may be mixed at once, or two components may be mixed first, to

subsequently add other components, either at once or separately. Mixing is preferably continued until the composition is homogenous, which may take from 1 min up to 5 hours. Optionally, the composition may be heated during preparation, such as to a temperature of between 20 - 100 °C. When the composition is homogenous, the composition is preferably cooled to room temperature, at least prior to application to a keratosis.

As has already been mentioned, the composition will generally be applied topically to the affected skin. Preferably, only the affected skin is brought into contact with the composition.

In a preferred embodiment, in advertent removal of the composition from the keratosis during regular activities, e.g. by wiping or friction when the skin comes into contact with the surface of other materials such as clothing, can be avoided by covering the keratosis to which the composition has been applied by a patch. This has the beneficial effect of providing protection to the applied composition, so that it remains effective at the proper location. This may result in decreasing the frequency of application, relative to formulations which are not covered by a patch.

Two ways of treating keratoses with a composition according to the invention using a patch can be envisioned, and both are encompassed by the invention. In both cases, the composition may comprise a gel-forming polymer, but may also not comprise a gel -forming polymer.

a) the composition is applied to the keratosis, and subsequently covered by a dermal patch, and

b) the composition is applied to a dermal patch, and applied to the keratosis such that the composition contacts the keratosis.

A dermal patch, (which is also called patch in the context of the present invention), is preferably an occlusive patch. An occlusive patch is a patch which connects to the skin such that the composition is essentially contained under the patch, and does not leak or spill from under the patch.

It furthermore assures that the acid remains in place of application without being washed off. This can be achieved by a patch system comprising at least two layers, wherein the composition is comprised in, or is applied to or under, the bottom layer.

Suitable materials for making the bottom (skin -touching) layer of the patch include acrylic, polyethylene or polypropylene polymer systems.

Preferably, the bottom layer comprises an acrylic polymer.

Suitable materials for making the top layer include cellulose, polyester, cotton, viscose, polyamide, polyether, polyurethane, polyethylene terephthalate or mixtures thereof, preferably cellulose, polyether, polyurethane or cotton. A highly preferred polymer for the top layer is a mixture of p oly ether/p oly ur eth ane .

Preferably, the top layer has a surface area which is larger than the surface area of the bottom (skin-touching) layer, such that the top layer completely covers the bottom layer. In this embodiment, the top layer can be used to attach the patch to the skin, such that the bottom layer is in direct contact with the skin.

Optionally, the patch may comprise a reservoir for taking up, holding and/or releasing the composition. The reservoir may for example comprise polyethylene foam, polyester, cotton, polyamide or a mixture of polyethylene, viscose, and a polyethylene/polypropylene copolymer.

The patch generally has a size sufficient to cover the keratosis, such as a surface area of 0.1-50 cm², preferably 0.2-12 cm², more preferably 4-12 cm².

The patch may have any shape, such as square, round or oval, and may have any color. Preferably, the patch has various skin-tone colors or is transparent, in order to render the patch more or less invisible.

Alternatively, the patch may have various bright colors, and is optionally provided with figures or drawings.

The patch is preferably applied to the skin by the use of a suitable glue, such as hot melt glue or acrylic adhesive. In case the top layer has a larger surface area than the bottom layer, this glue may be preferably present on the whole, or parts of the, freely accessible part the skin-facing side of the top layer.

Application of the composition to either the patch or to the keratosis can be achieved by any known means, such as by finger, pipette, brush, sponge or stick. Preferably, to avoid irritation of healthy skin, the composition is applied by brush, sponge or stick. Alternatively, patches comprising the composition may be produced in large quantities and provided in single or multiple units to subjects in order to treat a keratosis with the composition of the invention.

Consequently, the invention further pertains to a dermal patch, comprising any composition defined above.

The quantity of composition applied to either the patch or directly to the keratosis is variable, and depends on the seize of the keratosis. Preferably, the quantity is such that the composition contacts the keratosis, but contacts as little as possible healthy skin around the keratosis.

Generally, a suitable quantity is between 1-100 ml, preferably 20-50 ml.

Also, the invention pertains to a kit of parts, comprising a composition as defined above, as well as a dermal patch. Preferably, the kit of the invention may further comprise suitable means to apply the composition to the keratosis or the patch, such as a pipette, brush, sponge or stick. Further preferably, the kit may comprise means to measure the volume of the composition to be applied.

In addition to the two treatments using a patch, the invention further discloses a composition which can be applied to a keratosis without a patch, in the form of a liquid plaster. In this embodiment, it is highly preferred if the composition comprises a gel-forming polymer.

The invention further provides a method, which may be medical but is preferably a cosmetic method, for the topical treatment of keratosis, comprising a procedure of application of a composition as defined above to a keratosis or to a dermal patch and allowing the composition to contact the keratosis for at least 4 hours, and repeating this procedure for at least 4 weeks, preferably 4 to at most 16 weeks, with a frequency of application of 1 - 4 times per week, preferably twice a week. In a much preferred

embodiment, the composition is applied to the keratosis, and subsequently covered by a dermal patch as defined above. The method of the invention is defined in line with the treatment of keratosis, defined above.

Also, the invention pertains to medical use of the composition defined above, in particular use of the composition defined above for the manufacture of a medicament for the treatment of a keratosis, preferably a wart. Alternatively, the present invention pertains to use of the composition in the treatment of keratosis, defined above.

For the purpose of clarity and a concise description features are described herein as part of the same or separate embodiments, however, it will be appreciated that the scope of the invention may include

embodiments having combinations of all or some of the features described.

The invention will now be illustrated by the following, non- limiting examples.

Example 1

The following compositions were prepared.

Composition 1

Aqua 30.08 g

Xanthan Gum 1.00 g

Ethyl alcohol (96%) 31.25 g

Polyvinyl alcohol Sigma 1.00 g

TCA (Trichloroacetic acid) 16.67 g

Citric acid 20.00 g

TOTAL 100.00 s

Composition 2

Aqua 10.00 g

Carbopol 940 0.20 g

Carboxymethylcellulose sodium 0.20 g

Ethyl alcohol (96%) 50.93 g

MCA (Monochloroacetic acid) 11.67 g

Glycolic acid 25.00 g

Aminomethylpropanolol (90%) 2.00 g

TOTAL 100.00 s Composition 3

Aqua 11.00 g

Carbopol 940 1.00 g

Selvol Ultalux FA 1.00 g

Ethyl alcohol (96%) 36.00 g

TCA (Trichloroacetic acid) 20.00 g

Citric Acid 30,00 g TOTAL 100.00 g

Composition 4

Aqua 21.00 g

Selvol Ultalux FA 9.00 g

Ethyl alcohol (96%) 30.00 g

TCA (Trichloroacetic acid) 10.00 g

Tartaric Acid 30.00 g TOTAL 100.00 g

Composition 5

Aqua 10.00 g

Polyvinyl alcohol Sigma 0.2 g

Ethyl alcohol (96%) 49.80 g

TCA (Trichloroacetic acid) 10.00 g

Malic Acid 30.00 g TOTAL 100.00 g Composition 6

Aqua 10.00 g

Polyvinyl alcohol Sigma 0.2 g

Ethyl alcohol (96%) 49.80 g

TCA (Trichloroacetic acic 1) 10.00 g

Lactic Acid 30.00 g TOTAL 100.00 g

Composition 7

Aqua 10.00 g

Polyvinyl alcohol Sigma 0.2 g

Ethyl alcohol (96%) 49.80 g

BCA (Bichloroacetic Acic ) 8.00 g

Glycolic acid 32.00 g TOTAL 100.00 g

Composition 8

Composition 9

The compositions were applied to keratoses on human skin. It was found that a combination of an alpha-hydroxy acid (AHA) with a

halogenated acetic acid allowed for decreasing the concentration of halogenated acetic acid while maintaining effectiveness. Presence of gel- forming polymers did not affect the skin peeling capacity of the composition, but did increase the time with which the composition was retained on the skin.

Example 2

This study included 7 subjects each applying 2 different products to at least two keratoses twice per day for 14 days. While this application is more frequent than clinically needed it will expedite results of the study and present a worst case basis for the safety of the products. The first product was a composition containing a high concentration of a keratinolytic acid (50%). The second composition contained a lower concentration of 2 acids (10% each of TCA and glycolic acid). The solvent in both cases was ethyl alcohol (ethanol), and no further ingredients were present. After application of the composition to the skin, the site of application was covered with an occlusive patch. The occlusive patch consisted of a acrylic bottom layer and a polyether/polyurethane top layer.

At the end of 14 days of application the users were asked to judge the rate of peeling of their skin and the amount of adverse events of the products. The results of the study clearly showed that the combination of 2 acids at lower concentrations can have a significant increase of efficacy and decrease in adverse reactions than a high concentration of a single acid. The combination of TCA with glycolic acid at low concentrations caused a high peeling effect more than 3x as high while having half of the adverse event of the high concentration of a single keratinolytic acid (Figure 1).

Example 3

A liquid formulation comprising 10% each of TCA and glycolic acid was prefilled into a an occlusive patch comprising an acrylic bottom layer and a polyether/polyurethane top layer, and a reservoir for holding the liquid composition. The reservoir may comprise for example polyethylene foam, polyester, cotton, polyamide or a mixture of polyethylene, viscose, and a polyethylene/polypropylene copolymer.

The patch was applied to a kerotosis on human skin, and left in position for 3.5 days until a fresh but otherwise equal patch was applied to the same position. This treatment was continued for 12 weeks. After this time, the keratosis was gone.

Claims

1. A composition for use in the topical treatment of a keratosis, comprising 1 - 50 wt.% of a halogenated acetic acid, and an alpha-hydroxy acid.

2. A composition for use according to claim 1, wherein the alpha- hydroxy acid is lactic acid, glycolic acid, malic acid, citric acid and tartaric acid.

3. A composition for use according to claim 1 or 2, wherein the total quantity of alpha-hydroxy acid is 1 - 50 wt.%.

4. A composition for use according to any of claims 1 - 3, wherein the composition comprises a Cl - C3 alcohol as a solvent, preferably ethanol.

5. A composition for use according to any of claims 1 - 4, wherein the keratosis is a wart.

6. A composition for use according to any of claims 1 - 5, wherein the composition comprises a gel -forming polymer.

7. A composition for use according to claim 6, wherein the gel- forming polymer comprises a polyvinylalcohol (PVA), polyvinylpyrrolidone (PVP), cellulose ether, pyroxylin, nitrocellulose, methylacrylate, acrylate, isobutene, isopropylmaleate and/or siloxane polymer.

8. A dermal patch comprising a composition according to any of claims 1 - 7 for topical administration.

9. A dermal patch according to claim 8, wherein the patch is occlusive.

10. A kit of parts, comprising a composition according to any of claims

1 - 7, and a dermal patch.

11. A kit according to claim 10, further comprising means to apply the composition to a keratosis, preferably a pipette, brush, sponge or stick.

12. A method for the topical treatment of keratosis, comprising a procedure of application of a composition according to any of claims 1 - 7 to a keratosis or to a dermal patch, and allowing the composition to contact the keratosis for at least 4 hours, and repeating this procedure for at least 4 weeks with a frequency of application of 1 - 4 times per week.

13. A method according to claim 12, wherein the method is a cosmetic method.

14. A method according to claim 12 or 13, wherein the frequency of application is twice a week.

15. A method according to any of claims 12 - 14, wherein the procedure is repeated for 4 to at most 16 weeks.

16. A method according to any of claims 12 - 15, wherein after application of the composition to the keratosis, the keratosis is covered with a dermal patch.

17. A liquid plaster, comprising 1 - 50 wt.% of a halogenated acetic acid, an alpha-hydroxy acid, a solvent and a gel-forming polymer.