JP2006510738A - Use of alkyl stilbene alkyl ethers for the treatment of dry skin - Google Patents

Abstract

The present invention relates to a composition comprising at least one alkyl ether of hydroxystilbene having a saturated or unsaturated linear or branched C ₁ -C ₆ alcohol in a physiologically acceptable medium. The present invention relates to a method for cosmetic treatment of dry skin or dry scalp, which comprises topically applying to the skin or scalp. The composition is used in cosmetic applications, especially to treat dryness after menopause, or in dermatological applications, particularly to treat diseases associated with seborrheic dry skin in the form of dermatitis be able to.

Description

The present invention relates to a composition comprising at least one alkyl ether of hydroxystilbene having a saturated or unsaturated linear or branched C ₁ -C ₆ alcohol in a physiologically acceptable medium. The present invention relates to a method for cosmetic treatment of dry skin or dry scalp, which comprises topically applying to the skin or scalp.

  From the age of 35, and especially after menopause, many women have dry skin and unpleasant or unsatisfactory effects due to age and menopause (exfoliation of the epidermis, no skin color, skin sagging, facial Often complains about This dryness of the skin is due to a decrease in sebum production with age, as is now known.

  In addition, children with inactive sebum function often have signs of dry skin that can progress to atopic dermatitis.

  Sebum is naturally produced in the sebaceous glands and is produced with sweat by the eccrine or apocrine glands, making it a natural moisturizer for the epidermis. In essence, sebum consists mostly of a complex mixture of lipids.

  Traditionally, sebaceous glands produce squalene, triglycerides, aliphatic waxes, cholesterol waxes and, in some cases, free cholesterol (Stewart, M. E., Semin. Dermatol. 11, 100-105 (1992)). The action of bacterial lipase converts the variable part of triglycerides into free fatty acids.

  Sebocytes are competent cells of the sebaceous glands. Sebum production is associated with this cell terminal differentiation program. During this differentiation, the metabolic activity of sevosite is essentially focused on lipogenesis (lipogenesis) and more precisely on neosynthesis of fatty acids and squalene.

Therefore, the compound that stimulates the production of lipids constituting sebum by sebaceous gland cells (sebocite) is a treatment for skin with seborrheic dry skin, that is, a skin whose sebum content in the forehead is less than 100 μg / cm ^2. Obviously beneficial to.

For this reason, the US-4496556 patent suggests the use of DHEA (dehydroepiandrosterone) or its ester, a locally administered steroid secreted from the adrenal gland, to increase sebum production. It was.
US-4496556 EP-0953345 WO01 / 43705 WO03 / 055444 FR-2816843 FR-2368708 Stewart, ME, Semin. Dermatol. 11, 100-105 (1992)

  However, due to regulations, the use of this type of compound in the cosmetic industry is not always possible. Furthermore, this compound does not have sufficient efficacy for seborrheic skin. Thus, there is still a need for cosmetically acceptable compounds for effectively stimulating sebum function to treat seborrheic dry skin.

  Applicants have surprisingly found that certain hydroxystilbene ethers can satisfy this requirement.

  Hydroxystilbenes such as resveratrol and pinosylvin are produced in particular from plants such as grape vines (leaves, stems and fruits) and especially from plants of the genus Polygonum such as Polygonum cuspidatum Stilbene. These compounds can reduce microbial adherence to the skin, and in particular to cosmetic or dermatological products intended for the treatment of acne, dandruff or unpleasant odors, and even more It is described as being useful especially for products for physical hygiene (EP-0953345). In order to increase the latter's medicinal effect synergistically, in order to brighten the skin in particular, it has been proposed to use these in combination with a retinoid (WO01 / 43705).

  Finally, the specification of WO03 / 055444 describes a great variety of lessons, including alkyl ethers, that can be used to treat signs of skin aging, especially by stimulating collagen synthesis and fibroblast proliferation. Veratrol analogs are disclosed.

  However, to the best of Applicants' knowledge, it has not yet been proposed that hydroxystilbene alkyl ethers are beneficial for the treatment of dry skin, particularly hypolipidemic skin.

  Resveratrol, on the other hand, has been described as an inhibitor of 5α-reductase, and of course can be found to apply to the treatment of fatty skin (FR-2816843). In fact, Applicants have demonstrated that resveratrol reduces the ability of sevosite to produce sebum.

  And contrary to all expectations, Applicants have found that hydroxystilbene alkyl ethers increase the ability of sevosite to produce sebum.

［上式中、Ｒ_１とＲ_２は独立に、飽和または不飽和の直鎖状または分枝状のＣ_１〜Ｃ_６アルキル基を表し、
ｍとｎは独立に、０〜３の整数で、ｍとｎは同時に零にならないと理解される。］
のヒドロキシスチルベンのアルキルエーテルまたはそのシス異性体の少なくとも一種以上を含有する組成物を、肌または頭皮に局所的に適用することを含む、乾燥肌または乾燥頭皮の美容処置方法である。 The subject of the present invention is therefore the formula (I):

[Wherein R ₁ and R ₂ independently represent a saturated or unsaturated linear or branched C ₁ -C ₆ alkyl group,
It is understood that m and n are independently integers of 0 to 3, and m and n are not zero at the same time. ]
A method for cosmetic treatment of dry skin or dry scalp, comprising topically applying to the skin or scalp a composition containing at least one alkyl stilbene alkyl ether or cis isomer thereof.

  The subject of the present invention is also the cosmetic use of at least one alkyl ether of hydroxystilbene of the above formula (I) as a treatment for dry skin or dry scalp.

The composition used according to the present invention is particularly suitable for the treatment of seborrheic skin and seborrheic scalp and is therefore measured, for example, by the method described in FR-2368708. It is beneficial to apply to individuals showing sebum content of less than 100 μg / cm ² .

  The composition according to the invention makes it possible to restore sebum production by sevosite and to improve the comfort of dry skin and dry scalp with similar indications.

  The composition also makes it possible to counter the appearance of lack of skin and / or even hair and / or hair due to dryness and / or dryness of the skin.

  The subject of the invention is also the above-mentioned hydroxystilbene for the preparation of compositions, in particular dermatological compositions, intended to treat diseases associated with seborrheic dry skin, in particular dermatitis forms. Of alkyl ethers.

Preferred compounds of formula (I) for use in the present invention are those where n = 2 and m = 0 or 1, ie resveratrol or pinosylvin alkyl ethers, in particular the methyl ethers of these hydroxystilbenes, ie All of R ₁ groups and R ₂ groups are compounds representing a methyl group.

  Alkyl ethers of hydroxystilbene according to the present invention can be synthesized by various synthetic methods, for example, Mc Murry (NA Ali, K. Kondo, Y. Tsuda, Chem. Pharm. Bull., 40 (5), 1130. -1136, (1992)), Wittig (NA Ali, K. Kondo, Y. Tsuda, Chem. Pharm. Bull., 40 (5), 1130-1136, (1992)), Perkin (Spath E., Kromp K , Chem. Ber., 1941, 74, 189-192) and Heck (Synlett, 1998, 792) according to a synthetic method known as the reaction.

  The trimethyl ether of resveratrol is obtained synthetically, in particular according to the production method described in Phytochemistry, 24 (7), 2309-12 (1998) and FIG.

  According to this process, commercially available dimethoxybenzyl alcohol is converted to the corresponding bromide, which is itself converted to diethyl phosphonate. The yield is 84% after purification and distillation. The key step in the synthesis is the Wittig-Horner reaction. The desired olefin is formed from diethyl phosphonate and p-methoxybenzaldehyde in the presence of sodium methoxide in THF, in 88% yield after purification by filtration on silica.

  Furthermore, the dimethyl ether of pinosylvin can use what is marketed from APIN CHEMICALS.

  The amount of hydroxystilbene alkyl ether used in the present invention is, of course, dependent on the desired effect and can therefore be in a wide range. If indicated, the alkyl ether of hydroxystilbene can be used in an amount that is 0.001-5% of the total weight of the composition, preferably 0.05-1% of the total weight of the composition. .

  The compositions according to the invention are generally suitable for topical application to the skin and / or scalp. Therefore, it includes a physiologically acceptable medium, ie a medium that is compatible with the skin, its outer skin (eyelashes, nails and hair) and / or mucous membranes.

  The composition can take any form of presentation normally used in cosmetics and dermatology. In particular, any gel-like oily solvent, dispersion, any two-phase, lotions, emulsion obtained by dispersing the fatty phase in the aqueous phase (O / W) or vice versa (W / O), or three It may be in the form of a phase emulsion (W / O / W or O / W / O) or an ionic and / or non-ionic vesicle dispersion. These compositions are prepared according to the general methods. Compositions in the form of oil-in-water emulsions are preferably used according to the present invention.

  The composition may be somewhat fluid and may have the appearance of a white or colored cream, ointment, emulsion, lotion, serum, paste or mousse. It may optionally be applied in the form of an aerosol. Further, it may be in a solid state, and particularly in a bar shape. It can be used as a skin care product and / or cleansing / makeup remover and / or makeup product. Moreover, you may use as a shampoo and a conditioner.

  Also, as is well known, compositions used in accordance with the present invention include hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillings. Adjuvants commonly used in the cosmetics industry such as agents, screening agents, pigments, deodorants and colorants can be included. The amount of these various adjuvants is conventionally used in the cosmetic industry, for example, 0.01-20% of the total weight of the composition. Depending on their nature, these adjuvants can be introduced into the fatty phase, aqueous phase or lipid vesicles. In any event, these adjuvants and their proportions are selected so as not to disturb the desirable properties of the alkyl ethers of hydroxystilbenes according to the present invention.

  When the composition used according to the invention is an emulsion, the proportion of the fatty phase is 5 to 80% by weight, preferably 5 to 50% by weight, based on the total weight of the composition. The oils, emulsifiers and auxiliary emulsifiers used in the emulsion-type composition are selected from those conventionally used in the cosmetic industry. The emulsifier and the auxiliary emulsifier are present in the composition in a proportion of 0.3 to 30% by weight, preferably 0.5 to 20% by weight, based on the total weight of the composition.

  As oils used in the present invention, mineral oil (liquid petrolatum), vegetable oil (avocado oil, soybean oil), animal oil (lanolin), synthetic oil (perhydrosqualene), silicone oil (cyclomethicone) And fluorine-based oil (perfluoropolyether). In addition, fatty alcohols (cetyl alcohol), fatty acids and waxes (carnauba wax, ground wax) can also be used as fatty substances.

  Examples of the emulsifier and auxiliary emulsifier used in the present invention include polyethylene glycol fatty acid esters such as PEG-100 stearate and glycerol fatty acid esters such as glyceryl stearate.

  Particularly mentioned hydrophilic gelling agents include carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylic ester / alkyl acrylate copolymers, polyacrylamides, polysaccharides, natural rubbers and clays. Lipophilic gelling agents that may be mentioned include modified clays such as benton, metal salts of fatty acids, hydrophobic silica and polyethylene.

  As the active agent, at least one compound selected from an epidermis stripping agent; an antibacterial agent; a humectant; a sedative; and a keratinocyte proliferation and / or differentiation stimulant is introduced into the composition used according to the present invention. It is beneficial.

  Indeed, stimulation of seborrhea with hydroxystilbene alkyl ethers according to the present invention provides, in a given individual, a growth area for the resident flora of the follicular orifice (especially acne propion bacteria). Along with that, it results in significant hydrolysis of sebum triglycerides to free fatty acids and a reduction in the degree of unsaturation of polyunsaturated fatty acids (particularly linoleic acid). These two phenomena contribute to fungal organ keratinization and microcomedone formation. This denatures into comedones, causing unpleasant occlusion and pore expansion. In a more advanced stage, this obstruction degenerates into inflammatory acne trauma.

  Addition of an epidermal exfoliant or a keratinocyte growth or differentiation regulator to the composition according to the present invention can inhibit the formation of these comedones. Similarly, antibacterial or bacteriostatic agents can achieve similar effects by altering the growth of the resident microbiota.

  Furthermore, the humectant can supplement the effect obtained by using the alkyl ether of hydroxystilbene according to the present invention. Sedatives are also beneficial in improving the degree of seborrheic dry skin comfort.

  Examples of such additive activators are described below.

[Skin remover]
The term “skin peeling agent” means any compound capable of the following actions.
Β-hydroxy acids, in particular salicylic acid and its derivatives (including 5-n-octanoylsalicylic acid); α-hydroxy acids such as glycolic acid, citric acid, lactic acid, tartaric acid, malic acid or mandelic acid; urea; gentisic acid Oligofucose; Cinnamic acid; Extract of Saphora japonica; Resveratrol and other substances that act directly on exfoliation by promoting exfoliation.
-Alternatively, it acts on enzymes, glycosidases, stratum corneum chymotrypsin enzyme (SCCE), or entirely different proteases (trypsin, chymotrypsin analogues) involved in epidermal exfoliation and degradation of keratinous adhesion spots. N-acyl-N, N ′, N′-ethylenediaminetriacetic acid; aminosulfone compounds and especially (N-2-hydroxyethylpiperazine-N-2-ethane) sulfonic acid (HEPES); 2-oxothiazolidine-4 Carboxylic acid (procysteine) derivatives; α-amino acid derivatives of the glycine type (as described in EP-0852949) and sodium methylglycine diacetate sold by BASF under the trade name Trilon M; honey and O-octanoyl Examples include chelating inorganic salts such as -6-D-maltose and saccharide derivatives such as N-acetylglucosamine.

[Humectant]
The term “humectant” is
-A compound that acts on the barrier function to maintain the moisture retention of the stratum corneum or an occlusive compound. Ceramide, sphingoid-based compound, lecithin, glycosphingolipid, phospholipid, cholesterol and its derivatives, plant sterol (stigmasterol, β-sitosterol or campesterol), essential fatty acid, 1,2-diacylglycerol, 4 -Triterpene five-membered rings such as chromanone and ursolic acid, petrolatum and lanolin.
-Alternatively, threalose and its derivatives, hyaluronic acid and its derivatives, glycerol, pentanediol, sodium pidolate, serine, xylitol, sodium lactate, polyglyceryl acrylate, ectoine and its derivatives, chitosan, oligosaccharides and polysaccharides, cyclic carbonates , N-lauroylpyrrolidone carboxylic acid, N-α-benzoyl-L-arginine and the like compounds that directly increase the water content of the stratum corneum.
Or alternatively, a compound that activates sebaceous glands such as DHEA and its derivatives and vitamin D and its derivatives.

[Keratinocyte proliferation and / or differentiation stimulating agent]
The keratinocyte growth stimulator used in the composition according to the invention contains in particular phloroglucinol; a walnut cake extract sold by Gattefosse; and a potato extract sold by Sederma. To do.

  Keratinocyte differentiation stimulating agents include, for example, minerals such as calcium; an extract of lupine sold by Silab under the trade name Photopreventine; sodium β-sitosterol sulfate sold by Seporga under the trade name Phytocohesine; and Phytovityl Contains a corn extract sold under the trade name of Solabia.

[Sedative]
Among the raw materials that are effective as sedatives, the following active agents can be mentioned, but are not limited to: Triterpene five-membered rings such as β-glycyrrhetinic acid and salts and / or derivatives thereof (glycyrrhetinic acid monoglucuronide, Stearyl glycyrrhetinate, 3-stearoyloxyglycyrrhetinic acid), ursolic acid and salts thereof, oleanolic acid and salts thereof, betulinic acid and salts thereof; extracts of buttons (Paeonia suffruticosa) and / or peonies (lactiflora), rosemary (Rosmarinus officinalis extract, Epilobium extract, Pygeum extract, Boswellia serrata extract, Centipeda cunnighami extract, sunflower (Helianthus annuus) Extract, Cola nitida extract, clove Extracts and extracts of Bacopa moniera; salicylates and in particular zinc salicylate; extracts of algae, especially extracts of Laminaria saccharina; omega-3 such as canola oil, musk rose oil Unsaturated oil, Blackcurrant oil, Ethium oil, Fish oil; Extract of α-bisabolol and chamomile; Allantoin; Phosphate diester of vitamin E and vitamin C; Capryloylglycine; Tocotrienol; Piperonal; Aloe vera; Plant sterol; Salt; springs and especially springs of the Vichy basin and springs of La Roche Posay; bacterial extracts and in particular non-photosynthetic filamentous fungi described in the patent application of EP-0761204 Extract, preferably Beggia Torre iatoales) and more particularly extracts of Vitreoscilla filiformis; cells of at least one Iridacea family plant obtained in vitro culture ( Preferably extract of undifferentiated cells), preferably a water-soluble extract of Iris pallid as specifically described in the patent application of EP-0765668; preferably of the Rosaceae family grown in vivo An extract, advantageously a Rosa gallic species, more preferably a water-glycol extract of Rosa Galica petals as specifically described in the patent application EP-0909556.

[Antimicrobial agent]
Antibacterial agents used in the present invention include 2,4,4′-trichloro-2′-hydroxydiphenyl ether (or triclosan), 3,4,4′-trichlorovanylide, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, Undecylenic acid and its salt, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, phytic acid, N-acetyl-L-cysteic acid, lipoic acid, azelaic acid and its salt, arachidonic acid, 2,4,4'-trichloro -2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, octopirox, octoxyglycerin, octanoylglycine, caprylyl glycol, 10-hydroxy-2-decanoic acid, in WO93 / 18743 patent Described dichlorophenylimidazole dioxolane And derivatives thereof, farnesol and phytosphingosine, and mixtures thereof.

  The composition used according to the invention preferably does not contain any retinoids.

  The invention is illustrated using the following non-limiting examples. In these examples, the amount is expressed in weight percent.

Example 1 Demonstration of Hydroxystilbene Alkyl Ether Activity in Lipogenesis Resveratrol trimethyl ether was converted to immortalized human sevosite in culture, namely Zouboulis, CC, Seltmann, H., Neitzel, H. And Orfanos, CE, “Establishment and Characterization of an Immortalized Human Sebaceous Gland Cell Line”, J. Invest. Dermatol., 113, 1011-1020 (1999). Were tested in a model derived from the SZ95 strain described in.

The final amount of DMSO in the culture medium is 0.1% and resveratrol trimethyl ether is 0.01% (4 × 10 ⁻⁴ M) and 0.001% (4 × 10 ⁻⁵ M), respectively. A test to measure the amount of lipid produced in sevosite of SZ95 strain (in confluence) in the presence or absence of an active agent diluted with DMSO at two different concentration conditions Went. After treatment for 24 hours, adherent cells are treated with Nile Red (1 μg / ml). Lipid concentration is then quantified by measuring dye fluorescence (two excitation / emission pairs: 485-540 nm fluorescence for neutral lipids and 540-620 nm fluorescence for non-neutral lipids). The total amount of lipid is obtained (by a combination of two measurements).

  The experiment is repeated 4 times in 96 plates, 6 fold (assay and control product).

  The following table shows the results.

  As can be seen from this table, resveratrol trimethyl ether induces a significant increase in lipogenesis in sevosite. In contrast, resveratrol tested at the same concentration and under the same conditions significantly inhibits lipogenesis by 20% and 67%, respectively.

Example 2 Cosmetic Composition This composition is prepared by methods well known to those skilled in the art. The amounts given in these examples are expressed in weight percent.

Resveratrol trimethyl ether 0.5%
5-n-octanoylsalicylic acid 1%
Methylparaben 0.1%
Propylparaben 0.1%
Lanolin 5%
Liquid petrolatum 4%
Sesame oil 4%
Cetyl alcohol 5%
2% glyceryl monostearate
Triethanolamine 1%
Propylene glycol 5%
Carbomer 940 0.1%
Water proper amount 100%

  This cream makes it possible to restore the bright shine of dry skin with twice a day application.

It is the figure which showed the synthesis | combining method of the trimethyl ether of resveratrol.

Claims (20)

In a physiologically acceptable medium, formula (I):

[Wherein R ₁ and R ₂ independently represent a saturated or unsaturated linear or branched C ₁ -C ₆ alkyl group,
It is understood that m and n are independently integers of 0 to 3, and m and n are not zero at the same time. ]
A method for cosmetic treatment of dry skin or dry scalp, comprising topically applying a composition containing at least one alkyl ether of hydroxystilbene or a cis isomer thereof to the skin or scalp.   The method of claim 1, wherein n = 2 and m = 0 or 1. The method according to claim 1, wherein all of the R ₁ group and the R ₂ group represent a methyl group.   The process according to any one of claims 1 to 3, characterized in that the alkyl ether of hydroxystilbene is 0.05 to 1% of the total weight of the composition.   The method according to any one of claims 1 to 4, wherein the composition does not contain any retinoid.   Furthermore, the said composition contains at least 1 or more types of skin peeling agents, The method as described in any one of Claims 1-5 characterized by the above-mentioned.   The skin peeling agent is salicylic acid and its derivatives (including 5-n-octanoylsalicylic acid); α-hydroxy acids such as glycolic acid, citric acid, lactic acid, tartaric acid, malic acid, or mandelic acid; urea; gentisic acid; Oligofucose; cinnamic acid; extract of enju; resveratrol; EDTA; N-acyl-N, N ′, N′-ethylenediaminetriacetic acid; aminosulfone compounds and in particular (N-2-hydroxyethylpiperazine-N-2 -Ethane) sulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine) derivatives; glycine-type α-amino acid derivatives (such as sodium methylglycine diacetate); honey; and O-octanoyl-6- Selected from saccharide derivatives such as D-maltose and N-acetylglucosamine The method according to claim 6.   Furthermore, the said composition contains a moisturizer, The method as described in any one of Claims 1-7 characterized by the above-mentioned.   The humectant is ceramide, a sphingoid-based compound, lecithin, glycosphingolipid, phospholipid, cholesterol and its derivatives, plant sterol (stigmasterol, β-sitosterol or campesterol), essential fatty acid, 1,2 -Triterpene 5-membered rings such as diacylglycerol, 4-chromanone, ursolic acid, petrolatum and lanolin; trealose and its derivatives, hyaluronic acid and its derivatives, glycerol, pentanediol, sodium pidolate, serine, xylitol, sodium lactate, acrylic acid Polyglyceryl, ectoine and its derivatives, chitosan, oligosaccharides and polysaccharides, cyclic carbonates, N-lauroylpyrrolidone carboxylic acid, N-α-benzoyl-L-arginine; DHEA and 9. The method of claim 8, wherein the method is selected from: vitamin D and derivatives thereof.   Furthermore, the said composition contains at least 1 or more types of sedative, The method as described in any one of Claims 1-9 characterized by the above-mentioned.   The sedative agent is a triterpene five-membered ring such as β-glycyrrhetinic acid and salts thereof, and / or derivatives thereof, ursolic acid and salts thereof, oleanolic acid and salts thereof, betulinic acid and salts thereof; , Rosemary extract, red plant extract, pidium extract, decoction extract, centipeda kaningami extract, sunflower extract, koranoki extract, clove extract and bacopa Extracts of Moniera; salicylates and in particular zinc salicylates; extracts of algae, especially extracts of carafcomb; omega-3-unsaturated oils such as canola oil, musk rose oil, black currant oil, etium oil, fish oil; α-bisabolol and chamomile extract; Vitamin E and vitamin C phosphate diesters; capryloylglycine; tocotrienol; piperonal; aloe vera; plant sterols; extract of Vitreosilla filiformis, water-soluble extract of Iris and petals of Rosa Galica The process according to claim 10, characterized in that it is selected from water-glycol extracts of   The method according to any one of claims 1 to 11, wherein the composition further comprises at least one antibacterial agent.   13. The method of claim 12, wherein the antibacterial agent is selected from triclosan, phenoxyethanol, octoxyglycerin, octanoylglycine, 10-hydroxy-2-decanoic acid, caprylyl glycol, farnesol and azelaic acid. .   The method according to any one of claims 1 to 11, wherein the composition further contains at least one or more keratinocyte proliferation and / or differentiation stimulating agents.   15. A method according to any one of the preceding claims, wherein the composition is in the form of an oil-in-water emulsion. The method according to claim 1, wherein the composition is applied to an individual having a sebum content of the forehead of less than 100 μg / cm ² .   17. A method according to any one of the preceding claims, characterized in that it is intended to combat skin tightness and / or skin and / or hairless and / or animate appearance.   Cosmetic use of at least one alkyl ether of hydroxystilbene of formula (I) according to any one of claims 1 to 3 as a treatment for dry skin or dry scalp.   To prepare a composition intended to treat diseases associated with seborrheic dry skin, a hydroxystilbene alkyl ether of the formula (I) according to any one of claims 1-3. At least one or more uses. 20. Use according to claim 19, characterized in that the disease is in the form of dermatitis.

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