WO2011028110A1

WO2011028110A1 - Composition for topical application, uses thereof, applicator device and kit of parts

Info

Publication number: WO2011028110A1
Application number: PCT/NL2010/050549
Authority: WO
Inventors: Miriam Clapposen
Original assignee: Zacco Netherlands B.V.
Priority date: 2009-09-01
Filing date: 2010-09-01
Publication date: 2011-03-10
Also published as: NL2003419C2

Abstract

The invention relates to a composition for topical application. The invention further relates to various uses for the treatment of skin conditions, including acne, warts, corns and calluses, psoriasis, keratosis pilaris and conditions in general involving keratinized skin. The invention further relates to an applicator device and kit of parts comprising such a composition. The composition comprises at least one physiologically acceptable C1 -C4 alkyl ester of a carboxylic acid as a carrier, and an effective amount of salicylic acid, and/or a physiologically acceptable ester of salt thereof.

Description

TITLE:

Composition for topical application, uses thereof, applicator device and kit of parts

FIELD OF THE INVENTION

The invention relates to a composition for topical application. The invention further relates to various uses for the treatment of skin conditions, including acne, warts, corns and calluses, psoriasis, keratosis pilaris and conditions in general involving keratinized skin. The invention further relates to an applicator device and kit of parts comprising such a composition.

BACKGROUND OF THE INVENTION

2-Hydroxybenzoic acid or salicylic acid, is known for its use in products aimed at the treatment of skin conditions, in particular warts, corns and calluses. Such products include creams and ointments.

The international patent application WO 92/13529 describes flexible collodion compositions, which form a film on the skin when dried. The described compositions use film-forming polymers and optionally also comprise salicylic acid as a therapeutic agent. P. 7, lines 1 -16 describes the problem of crystallization of salicylic acid in a flexible colluding applied to the skin, which is prevented by adding minor amounts of crystallization inhibitors such as lactic acid ethyl esters. As described on p. 9, lines 17- 27, the amount of inhibitor needed to suppress crystallization is minimized for economic reasons, and depends on the type of inhibitor used. OBJECT AND SUMMARY OF THE INVENTION

It is an object of the invention to provide an improved formulation for the treatment of skin conditions.

The invention provides a composition for topical application, comprising at least one physiologically acceptable C1 -C4 alkyl ester of a carboxylic acid as a carrier,

and an effective amount of salicylic acid, and/or a physiologically acceptable ester of salt thereof. The combination of salicylic acid or a derivative thereof and at least one physiologically acceptable C1 -C4 alkyl ester of a carboxylic acid as a carrier was shown to induce an improved effect in the treatment of skin conditions, in particular the treatment of acne, warts, corns and calluses, psoriasis, and keratosis pilaris. It is postulated that skin conditions benefit from the skin softening effect of salicylic acid, which is enhanced by presence of the C1 - C4 alkyl ester of a carboxylic acid as a carrier, which improves the penetration of salicylic acid or its derivatives into the skin.

The salicylic acid is preferably mixed homogeneously with the C1 -C4 alkyl ester of a carboxylic acid. Most preferably, the salicylic acid is dissolved in the C1 -C4 alkyl ester of a carboxylic acid. The C1 -C4 alkyl ester of a carboxylic acid is preferably present as a major component of the composition, in a quantity of at least 50% by weight of the composition, preferably at least 90%. In such amounts of carrier, the C1 -C4 alkyl ester of a carboxylic acid ensures that salicylic acid or a derivative salt or ester thereof is completely dissolved and is easily spread over a skin section to be treated for a more efficient use of the active ingredients.

Preferably, the composition is a liquid composition. In contrast to more viscous compositions such as gels and creams, liquid compositions are more easily applied, and easier penetrate irregular parts of the skin such as wrinkles.

It is advantageous if the composition is suitable for application using a pen applicator. Pen applicators allow for an easy a convenient application of the composition. Pen applicators depend on capillary action to deliver the composition to the skin surface to be treated, for instance through a felt tip. Liquids having a too high viscosity are unsuitable in practice. Also, liquids comprising polymerizing components are unsuitable, as the formed polymers will eventually clog the capillaries of the pen. Therefore, it is preferred if the composition is essentially free of film forming components. The composition may include additional suitable components, for instance fragrances, emulsifiers, detergents, antioxidants and preservatives, and other ingredients commonly used in pharmaceutical and cosmetic formulations. Preferably, the composition is essentially free of water, which increases the stability of the composition over time. Preferably, the composition is formulated as a fluid composition such as a cream, or more preferably as a liquid composition such as a tonic, which is relatively easy to apply to the human skin.

The C1 -C4 esters include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl esters. Ethyl esters are preferred. In case the carboxylic acid contains multiple carboxyl-groups, at least one of the carboxyl groups is a C1 -C4 ester. In case at least two carboxyl groups are esterified, the C1 -C4 esters of these groups may be the same or different. Preferably, the C1 -C4 alkyl ester is derived from a physiologically acceptable alpha-hydroxyl carboxylic acid.

Preferably, the C1 -C4 alkyl ester is derived from a physiologically acceptable carboxylic acid selected from the group consisting of lactic acid, malic acid, tartaric acid, citric acid, acetic acid, proprionic acid, isoproprionic acid, oxalic acid, glutaric acid, adipic acid, glycolic acid and mandelic acid. The C1 -C4 esters of these acids are particularly effective. The ethyl esters of these compounds are preferred. C1 -C4 alkyl esters of lactic acid was shown to be the most versatile of these compounds, and is therefore the most preferred.

In a preferred embodiment, the C1 -C4 alkyl ester is lactic acid ethyl ester. This compound showed the best results. Instead of salicylic acid as the free acid, also salicylic acid salt derivatives or esters may be used. Good results are obtained when the composition comprises at least one salicylic acid derivative selected from the group consisting of sodium salicylate, potassium salicylate, calcium salicylate, magnesium salicylate, bismuth subsalicylate, monoethylammonium (MEA) salicylate, triethylammonium (TEA) salicylate, sulfosalicylic acid, ethyl salicylate, butyloctyl salicylate, C12-15 Alkyl salicylate, capryolyl salicylic acid, hexyldecyl salicylate, isocetyl salicylate, isodecyl salicylate, ethylhexyl salicylate, methyl salicylate, myristyl salicylate, and tridecyl salicylate. Instead of salicylic acid, an equivalent dose of a derivative having the same effect may be used. For salicylate salts, this is usually an equimolar amount. A composition may comprise a mix of salicylic acid and/or one or more salicylic acid derivatives.

In a preferred embodiment, the composition comprises at least 0.1 % by weight of salicylic acid or a physiologically acceptable ester or salt thereof, preferably between 0.5 and 30% by weight. Such amounts have an advantageous effect on various skin conditions, in particular acne, warts, corns and calluses, psoriasis, keratosis pilaris and conditions in general involving keratinized skin. The amount may be optimized for a specific skin condition.

It is preferred if the composition also comprises the free acid or salt derived from the carboxylic acid used in the C1 -C4 alkyl ester in a molecular ratio of at least 1 :100 with respect to the C1 -C4 alkyl ester, preferably at least 1 :20, most preferably at least 1 :10. Thus, a more stable composition is achieved. The availability of the carboxylic acid prevents the reversal of the esterification reaction in the presence of water, resulting in the free carboxylic acid and alcohol. For instance, a composition according to the invention, based on lactic acid ethyl ester, could be stabilized by adding lactic acid in a ratio of at least 1 :100, preferably at least 1 :20, most preferably at least 1 : 10

In a preferred embodiment, the composition comprises at least 50% by weight C1 -C4 lactic acid ethyl ester, lactic acid in a ratio of at least 1 : 100 with respect to lactic acid ethyl ester, and at least 0.1 % by weight of salicylic acid, or a physiologically acceptable ester of salt thereof.

The invention relates to the use of a composition according to the invention for the preparation of a product, for instance a medicament, for the treatment of skin conditions. Such a product may be tailored for use against skin conditions that benefit from the skin softening effect of salicylic acid, enhanced by presence of the C1 -C4 ester of a carboxylic acid. Skin conditions the composition according to the invention may be used against include, but are not limited to, acne, warts, corns and calluses, psoriasis, keratosis pilaris and conditions in general involving keratinized skin. Typically, the amount of salicylic acid or derivatives thereof is within 0.1 -30% by weight. For use as an exfoliant an amount of 0.5-5% by weight of salicylic acid has a beneficial effect, for in stance on cornified skin.

The invention also relates to the use of a composition according to the invention for the preparation of a product, for instance a medicament, for the treatment of acne. For acne, a concentration of 0.5-5% by weight of salicylic acid (or an equivalent amount of a salicylic acid derivative having the same effect) is considered to be optimal when applied regularly, preferably using an applicator device.

The invention further relates to the use of a composition according to the invention for the preparation of a product, for instance a medicament, for the treatment of warts. In a preferred embodiment, the product against warts uses a composition having a concentration of 5-27% by weight of salicylic acid (or an equivalent amount of a salicylic acid derivative having the same effect). Such a composition is particularly effective against warts associated with human virus infections, in particular the human papilloma virus (HPV). Warts include various types, in particular the common wart (Verruca vulgaris), the flat wart (Verruca plana), filiform or digitate wart, and plantar wart (Verruca pedis). The invention also relates to the use of a composition according to the invention for the preparation of a product, for instance a medicament, for the treatment of corns and/or calluses. For such a purpose, optimal results are achieved using compositions having a concentration of 12-27% by weight of salicylic acid (or an equivalent amount of a salicylic acid derivative having the same effect).

The invention further relates to the use of a composition according to the invention for the preparation of a product, for instance a medicament, for the treatment of psoriasis. For psoriasis, a composition according to the invention having salicylic acid concentration of at least 10% by weight is preferred, more preferably a concentration in the range from 10% to 30% by weight.

The invention also relates to the use of a composition according to the invention for the preparation of a product for the treatment of keratosis pilaris. For keratosis pilaris, a composition according to the invention having salicylic acid concentration of at least 10% by weight is preferred, more preferably a concentration in the range from 10% to 30% by weight.

The invention also relates to the use of a composition according to the invention for the preparation of a product for the treatment of conditions in general involving keratinized skin. For such skin conditions, a composition according to the invention having salicylic acid concentration of at least 10% by weight is preferred, more preferably a concentration in the range from 10% to 30% by weight. The invention also relates to a device, comprising a container comprising a composition according to the invention, and an applicator connected to the container, wherein the applicator is adapted to apply the composition from the container to a part of human skin to be treated. Thus, the composition according to the invention is easy to apply and store.

The invention further relates to a kit of parts, comprising at least one container comprising a composition according to the invention and at least one scrub device for scrubbing a skin part treated with the composition, optionally also comprising a skin cream. Thus, skin conditions can be treated with a composition according to the invention and subsequently scrubbed mechanically by the scrub device. It is postulated that the pre-treatment with the composition according to the invention softens skin parts affected by skin conditions such as acne or warts, which may subsequently easily removed using the scrub device. Optionally, the skin cream may be used to treat the skin afterwards, in order to suppress possible skin irritations or treat skin lesions caused by scrubbing. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows an applicator for applying a composition according to the invention.

DESCRIPTION OF PREFERRED EMBODIMENTS

The invention will now be further elucidated by the following non-limiting examples.

Applicator device

Figure 1 shows a pen application device 1 , somewhat resembling a felt-tipped type marker. Fig. 1 a shows the outer appearance of the applicator 1 , whereas fig. 1 b shows the cross section. The device 1 comprises a reservoir 2 containing a liquid composition according to the invention. The device is pencil-shaped, and suitable to be hand-held. The reservoir is provided with an absorbing element 3 made of a liquid-absorbing material capable of capillary action. This absorbing element dips into the liquid composition and extends from the inner part reservoir to the outside of the reservoir. The liquid contained in the reservoir within the marker and would be applied via an applicator tip 4 connecting to or made out of the distal end of the absorbing element extending out of the reservoir. Due to capillary action, the tip 4 remains moist with the liquid product. For such an applicator device, the viscosity of the liquid composition will have to be sufficiently low. The device may be provided with a cap to prevent volatile solvents of the composition to evaporate and dry the tip out. The moist tip 4 is contacted with the skin part to be treated, preferably while applying some pressure, in order to apply the composition from the reservoir.

The reservoir may be filled with different preferred embodiments according to the invention, depending on the envisaged skin condition to be treated. For all of these applications it was shown that the combination of salicylic acid dissolved in or mixed with at least one physiologically acceptable C1 -C4 alkyl ester of a carboxylic acid as a carrier yielded a better absorbance of salicylic acid into the skin than a comparable aqueous composition with the same salicylic acid concentration. All components are commercially available; the compositions were prepared using well-known mixing and blending techniques. The compositions presented here are all liquid compositions, suitable for application using a commercially available pen applicator.

Example 1 : cornified skin

An effective composition for softening cornified skin was prepared by well know mixing techniques (percentages by weight): Salicylic acid 4%

Lactic acid 7%

Lactic acid ethyl ester 89%

The resulting liquid is applied as an ointment, and showed a softening of extra cornified skin, relieving the patient of discomforts and pain. At also became easier to remove some of the cornified skin using tools for skin treatment, for instance a skin scrub tool, skin cutting tool and/or a skin file.

An alternative formulation also yielding satisfactory results is the following:

Salicylic acid 8%

Citric acid 9%

Citric acid ester 83% Example 2: acne

An effective composition against acne was prepared by well know mixing techniques (percentages by weight):

Salicylic acid 5%

Lactic acid 19%

Lactic acid ethyl ester 76%

The resulting liquid was used in an applicator pen. A person suffering from reported an improved healing of acne after treatment with the liquid applied using the applicator pen.

An alternative composition is the following: Salicylic acid 2%

Malic acid 9%

Malic acid ester 89% Example 3: warts

An effective composition against warts was prepared by well know mixing techniques (percentages by weight):

Salicylic acid 2%

Lactic acid 20%

Lactic acid ethyl ester 78%

Various types of warts were successfully treated using this composition, resulting in complete or partial removal of the wart after multiple treatments.

An alternative composition is the following:

Sodium salicylate 20%

Lactic acid 7%

Lactic acid ethyl ester 73%

Example 4: corns and calluses

An effective composition for the treatment of corns and calluses was prepared by well know mixing techniques (percentages by weight):

Salicylic acid 18%

Lactic acid 16%

Lactic acid ethyl ester 66% The resulting liquid is applied the corns or calluses, and showed a softening of the affected skin parts, relieving the patient of discomforts and pain. At also became easier to remove some of the corns or calluses using tools for skin treatment, for instance a cutting tool and/or a file. An alternative composition contains the following components:

Salicylic acid 12% Glutaric acid 8%

Glutaric acid ester 80%

Example 5: psoriasis

An effective composition against psoriasis was prepared by well know mixing techniques (percentages by weight):

Salicylic acid 25%

Lactic acid 14%

Lactic acid ethyl ester 61 %

Multiple applications of the compositions to affected skin parts result in a decrease in red skin parts and development of scales on the skin.

An alternative composition is composed as follows:

Potassium salicylate 10%

Lactic acid 10%

Lactic acid ethyl ester 80%

Example 6: keratosis pilaris

An effective composition against keratosis pilaris was prepared by well know mixing techniques (percentages by weight): Salicylic acid 22%

Lactic acid 18%

Lactic acid ethyl ester 60%

After multiple treatments with this compositions, the bumps and roughness of the skin affected by keratosis pilaris improved and in some cases completely disappeared.

An alternative composition is as follows:

Capryolyl salicylic acid 12%

Glutaric acid 10%

Glutaric acid ester 78%

Claims

Claims:

1. Composition for the treatment of skin conditions, comprising

at least one physiologically acceptable C1 -C4 alkyl ester of a carboxylic acid as a carrier, and at least 0.1 % by weight of salicylic acid, and/or a physiologically acceptable ester of salt thereof, wherein the C1 -C4 alkyl ester of a carboxylic acid or mixture of carboxylic acid alkyl esters is present in a quantity of at least 50% by weight.

2. Composition according to claim 1 , wherein the composition is a liquid composition.

3. Composition according to claim 2, wherein the composition is suitable for application using a pen applicator.

4. Composition according to any of the preceding claims, wherein the composition is essentially free of film forming components.

5. Composition according to any of the preceding claims, wherein the composition is essentially free of water.

6. Composition according to any of the preceding claims, wherein the C1 -C4 alkyl ester is derived from a physiologically acceptable carboxylic acid selected from the group consisting of

lactic acid, malic acid, tartaric acid, citric acid, acetic acid, proprionic acid, isoproprionic acid, oxalic acid, glutaric acid, adipic acid, glycolic acid and mandelic acid.

7. Composition according to claim 6, wherein the C1 -C4 alkyl ester is lactic acid ethyl ester.

8. Composition according to any of the preceding claims, wherein the composition comprises at least 0.5% by weight of salicylic acid, and/or a physiologically acceptable ester of salt thereof.

9. Composition according to claim 8, wherein the composition comprises between 0.5 and 30% by weight of salicylic acid, and/or a physiologically acceptable ester of salt thereof.

10. Composition according to any of the preceding claims, wherein the composition also comprises the free acid or salt derived from the carboxylic acid used in the C1 -C4 alkyl ester in a molecular ratio of at least 1 :100 with respect to the C1 -C4 alkyl ester.

1 1 . Composition according to claim 10, wherein the composition comprises the free acid or salt derived from the carboxylic acid used in the C1 -C4 in a ration of at least 1 :20.

12. Composition according to any of the preceding claims, comprising

at least 50% by weight C1 -C4 lactic acid ethyl ester, lactic acid in a ratio of at least 1 :100 with respect to lactic acid ethyl ester, and at least 0.1 % by weight of salicylic acid, or a physiologically acceptable ester of salt thereof.

13. Pen applicator comprising a composition according to any of the preceding claims, wherein the composition is a liquid composition.

14. Use of a composition according to any of the preceding claims 1 -12 for the preparation of a product for the treatment of skin conditions.

15. Use of a composition according to claim 14 for the preparation of a product for the treatment of a skin condition selected from the group consisting of acne, warts, corns, calluses, psoriasis and keratosis pilaris.