Active substance combination consisting of alkylamidothiazoles and delta-decalactone

Abstract

The present invention relates to an active substance combination consisting of one or more alkylamidothiazoles and a delta-decalactone.

Description

TECHNICAL FIELD

[0001] The present application relates to an active substance combination consisting of one or more alkylamidothiazoles and delta-decalactone. The present application also relates to a cosmetic or dermatological preparation having a share of this active substance combination and to the use thereof for lightening human skin. BACKGROUND

[0002] The cells responsible for skin pigmentation are the melanocytes, which occur as pigment-forming cells, i.e. pigment-forming cells which either separate or more or less aggregate depending on the skin type, in the basal layer, the deepest layer of the epidermis, next to the basal cells.

[0003] The melanocytes contain melanosomes as characteristic organelles, in which melanin is formed. The formation of melanin is enhanced, including but not limited to upon stimulation by ultraviolet radiation. The melanin is ultimately transported via the living cell layer of the epidermis (keratinocytes) into the horny layer (horny cells) and causes a skin color which exhibits varying degrees of brown to black-brown.

[0004] Melanin is formed as the end product of an oxidation process in which tyrosine is converted, via a plurality of intermediates, to brown to black-brown eumelanin (DHICA-melanin and DHI-melanin) or, with the involvement of sulfur-containing compounds, to reddish-brown pheomelanin under the action of tyrosinase. DHICA-melanin and DHI-melanin are formed via the common intermediates dopaquinone and dopachrome. The latter is partly converted, with the involvement of further enzymes, to indole-5,6-quinone carboxylic acid or to indole-5,6-quinone, thereby forming the two aforementioned eumelanins.

[0005] The formation of pheomelanin includes, but is not limited to, the pathway intermediates dopaquinone and cysteinyl dopa. The expression of the enzymes which synthesize melanin is controlled by specific transcription factors (microphthalmia-associated transcription factor, MITF). In addition to the described enzymatic processes of melanin synthesis, other proteins in the melanosome are also important for melanogenesis. Here, the so-called p protein appears to play an important role, but the exact function is not yet known.

[0006] In addition to the previously described processes of melanin synthesis in the melanocytes, the transport of the melanosomes, their residence in the epidermis and their degradation and the degradation of the melanin are also of great importance for skin pigmentation. It can be shown that the PAR-2 receptor is important for the transport of the melanosomes from the melanocytes into the keratinocytes (M. Seiberg et al., 2000, J. Cell. Sci., 113:3093-101).

[0007] Furthermore, the size and shape of the melanin bodies affect their light scattering properties and thus the color appearance of the skin. Thus, in the African black race, more large, spherical, solitary melanin bodies are found, while in the Caucasian race, smaller, grouped melanin bodies are more common.

[0008] The problem of hyperpigmentation of the skin has various causes or is a concomitant phenomenon of many biological processes, such as, for example, UV radiation (e.g. freckles, lentigo), genetic predisposition, abnormal pigmentation of the skin in wound healing or scar formation (postinflammatory hyperpigmentation) or skin aging (e.g. age spots, senile lentigo).

[0009] After an inflammatory reaction, the pigmentation system of the skin reacts in part oppositely. Postinflammatory hyperpigmentation can occur, but also hypopigmentation. Postinflammatory hypopigmentation is particularly often associated with atopic dermatitis, lupus erythematosus and psoriasis. The understanding of the different reaction patterns of the pigmentation system of human skin after inflammatory phenomena is still very incomplete.

[0010] The problem of postinflammatory hyperpigmentation often occurs in darker skin types. In particular, the problem of pseudofolliculitis barbae in men of color is known, which is accompanied or leads to cosmetically undesirable abnormal pigmentation. Forms of melasma, which occur in particular in the facial and chest area of Asian women, as well as various forms of irregular pigmentation of the skin, are also classified as postinflammatory hyperpigmentation. In addition, dark circles under the eyes are also considered a form of postinflammatory hyperpigmentation, wherein the underlying inflammation is usually carried out in a subclinical manner.

[0011] In many cases, such postinflammatory pigmentation abnormalities are exacerbated by the action of sunlight (UV), without causing UV-induced inflammation (sunburn).

[0012] Active substances and preparations are known which counteract the pigmentation of the skin. In practical use, preparations based primarily on hydroquinone are used, but these preparations, on the one hand, only show their effect after several weeks of application and, on the other hand, the application over a long period of time is problematic for toxicological reasons. Albert Kligman et al. have developed a so-called "triple formulation", which is a combination of 0.1% tretinoin, 5.0% hydroquinone, 0.1% dexamethasone (A. Kligman, 1975, Arch. Dermatol., 111 :40-48). Of course, this formulation is also highly controversial due to the possible irreversible changes to the pigmentation system of the skin.

[0013] Furthermore, exfoliation methods (chemical and mechanical "peeling") are applied, but these methods often induce an inflammatory reaction and, due to the subsequent postinflammatory hyperpigmentation, even lead to an intensification of the pigmentation instead of a reduction. All of these conventional methods, which are also used to treat postinflammatory hyperpigmentation, have significant side effects.

[0014] Furthermore, a number of other substances are known which are reported to have skin lightening efficacy. Here, mention can be made, without limitation, of hexadecane-1, 16-dicarboxylic acid, kojic acid and derivatives thereof, arbutin, ascorbic acid and derivatives thereof, flavonoids, ellagic acid and derivatives thereof, tranexamic acid and various resorcinol derivatives, such as 4-n-butylresorcinol, 4-n-hexylresorcinol and 4-(1-phenylethyl)benzene-1,3-diol.

[0015] J. M. Ready describes in a publication (Bioorganic & Medicinal Chemistry Letter 17 (2007) 6871-6875) the inhibition of mushroom tyrosinase by, inter alia, substituted thiazole derivatives.

[0016] In a patent application of the company Shiseido (WO 2009099195), substituted thiazole amines or hydrogenated thiazole amines are described for skin lightening.

[0017] The substances described in the above-mentioned prior art are characterized by a moderate degree of efficacy.

[0018] Dark circles under the eyes can likewise form as a consequence of a pigmentation disorder, wherein dark circles under the eyes also occur as a reaction to general stress, for example lack of sleep or simply due to excessive eye strain. In young people, the symptoms disappear again after sufficient night's rest, but in the long term the condition becomes chronic and causes great disturbance to the affected person. There is also a lack of sufficiently promising active substances and treatment options for such skin phenomena.

[0019] The sense of smell is one of the five senses of humans. Here, odorants, i.e. volatile substances, are bound by the olfactory receptors in the nasal mucosa. Via a signal cascade, the stimulus is transmitted to the nerve cells and conducted to the brain. There the actual perception of the smell takes place. Pleasant smells are distinguished from unpleasant smells.

[0020] However, cosmetic products also often have a slightly unpleasant intrinsic odor caused by the raw materials used. In certain cases, alkylamidothiazoles can also contribute to a worsening of the odor experience of the cosmetic base. There is a need to eliminate this disadvantage. SUMMARY

[0021] This task is accomplished through a combination of active substances consisting of one or more alkylamidothiazoles and Δ-decanolide.

[0022] Δ-decanolide is characterized by the following structural formula:

[0023] Δ-Decanolactone is present as a flavoring agent in a variety of foods. It is one of the most important components of butter flavor and also contributes to the flavor of other dairy products, such as UHT milk and various cheeses. In addition, it is also found in many fruits, such as peaches, apricots, coconuts, and raspberries.

[0024] Δ-decanolide can exist in two different enantiomers, namely the R-type and the S-type. According to the invention, both enantiomers, as well as racemic mixtures having the same or different enantiomer contents, are equally advantageous.

[0025] Preferably, the formulation according to the invention comprises 0.00001 to 1% by weight of Δ-decylactin, more preferably 0.0001 to 0.5% by weight of Δ-decylactin, and particularly preferably 0.0005 to 0.3% by weight of Δ-decylactin.

[0026] In particular, an advantageous feature of the formulations and / or uses according to the invention is that the formulation contains 0.000001 to 10% by weight, particularly 0.0001 to 3% by weight, and especially particularly 0.001 to 1% by weight of one or more alkylamidothiazoles based on the total weight of the formulation.

[0027] The advantageous alkylamidothiazole for the purposes of this invention is of the general formula:

[0028] The substance in which

[0029] Where R 1 R 2 X and Y can be different, partially the same, or completely identical, and can be represented independently of each other: R1 = -C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C 24 Alkyl hydroxyl groups (straight and branched), -C1-C 24 Alkylamino (straight-chain and branched), -C1-C 24 -alkylaryl (straight-chain and branched-chain), -C1-C 24 -alkylaryl-alkyl-hydroxy (straight chain and branched chain), -C1-C 24-alkylheteroaryl (straight-chain and branched-chain), -C1-C 24 -alkyl-O-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 Alkyl-morpholino, -C1-C 24 alkyl-piperidinyl, -C1-C 24 alkyl-piperazinyl, -C1-C 24 alkyl-piperazinyl-N-alkyl, R2=H、-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched), -C1-C8-cycloalkyl, -C1-C 24 -Hydroxyalkyl (straight-chain and branched-chain), -C1-C 24 -alkylaryl (straight-chain and branched-chain), -C1-C 24 -alkyl heteroaryl (straight chain and branched chain). X=-H、-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched), -C1-C8-cycloalkyl, -C1-C 24 -aryl (optionally mono- or poly-substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1-C 24 - Heteroaryl (optionally mono- or poly-substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1-C 24 -alkylaryl (straight-chain and branched-chain), -C1-C 24 -alkylheteroaryl (straight-chain and branched), -aryl (optionally mono- or poly-substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl Y=H、-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched), -C1-C8-cycloalkyl, -C1-C 24 -Aryl, -C1-C 24 -Heteroaryl, -C1-C 24 -alkylaryl (straight-chain and branched-chain), -C1-C 24-alkyl heteroaryl (straight-chain and branched), -aryl, -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl, -COO-alkyl, -COO-alkenyl, -COO-cycloalkyl, -COO-aryl, -COO-heteroaryl, Furthermore, X and Y can optionally represent fused aromatic compounds. X and Y can form an aromatic or aliphatic homocyclic or heterocyclic ring system with a maximum of n ring-forming atoms, where n can take values ​​from 5 to 8, and the corresponding ring system can be substituted with a maximum of n-1 alkyl groups, hydroxyl groups, carboxyl groups, amino groups, nitrile functional groups, sulfur-containing substituents, ester groups and / or ether groups.

[0030] The thiazoles mentioned can exist both as free bases and as salts: for example, as fluorides, chlorides, bromides, iodides, sulfates, carbonates, ascorbic acid salts, acetates, or phosphates. They are particularly effective as halogen salts, such as chlorides and bromides.

[0031] Furthermore, an advantageous implementation of the invention lies in a cosmetic or dermatological preparation having an effective proportion of one or more of the aforementioned alkylamidothiazoles.

[0032] According to the present invention, the use of the aforementioned alkylamidothiazole for the treatment and / or prevention of undesirable skin pigmentation is also relevant. Here, the treatment and / or prevention of undesirable skin pigmentation can be carried out in both the cosmetic and pharmaceutical fields.

[0033] Here, drug (or dermatological) treatment is understood primarily in the context of pathological skin conditions, while cosmetic treatment and / or prevention of undesirable skin pigmentation primarily involve healthy skin.

[0034] Advantageously, X is selected from substituted phenyl groups, wherein the substituent (Z) can be selected from the following: -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl, and can be the same or different.

[0035]

[0036] Particularly advantageously, X is selected from a phenyl group substituted with one or more hydroxyl groups, wherein the substituent (Z) can be selected from: -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl group, and preferably the following general formula, wherein Y, R 1 and R 2 It can possess the properties defined above.

[0037]

[0038] Advantageous, especially, are the following compounds, among which

[0039] X=

[0040] Y=H

[0041] R1=-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C 24 Alkyl hydroxyl groups (straight and branched), -C1-C 24 Alkylamino (straight-chain and branched), -C1-C 24 -alkylaryl (straight-chain and branched-chain), -C1-C 24 -alkylaryl-alkyl-hydroxy (straight chain and branched chain), -C1-C 24 -alkylheteroaryl (straight-chain and branched-chain), -C1-C 24 -alkyl-O-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 Alkyl-morpholino, -C1-C 24 alkyl-piperidinyl, -C1-C 24 alkyl-piperazinyl, -C1-C 24 alkyl-piperazinyl-N-alkyl, R2=H、-C1-C 24 -Alkyl groups (straight-chain and branched-chain).

[0042] Z=-H, -OH, -F, -Cl, -Br, -I, -OMe, -NH 2、 -CN, acetyl group.

[0043] The following compounds are particularly preferred, wherein

[0044] X=

[0045] Y=H

[0046] R1 represents -C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C 24 Alkyl hydroxyl groups (straight and branched), -C1-C 24 Alkylamino (straight-chain and branched), -C1-C 24-alkylaryl (straight-chain and branched-chain), -C1-C 24 -alkylaryl-alkyl-hydroxy (straight chain and branched chain), -C1-C 24 -alkylheteroaryl (straight-chain and branched-chain), -C1-C 24 -alkyl-O-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 Alkyl-morpholino, -C1-C 24 alkyl-piperidinyl, -C1-C 24 alkyl-piperazinyl, -C1-C 24 alkyl-piperazinyl-N-alkyl, R2=H.

[0047] According to the present invention, the following compounds are preferred:

[0048] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)neopentamide,

[0049] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)isobutyramide,

[0050] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)butyramide,

[0051] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)heptanamide,

[0052] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)-6-hydroxyhexamamide,

[0053] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)-3-hydroxypropionamide,

[0054] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)-2-methoxyacetamide,

[0055] 3-Amino-N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)propionamide,

[0056] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)acetamide,

[0057] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)-4-(hydroxymethyl)cyclohexaneformamide,

[0058] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)cyclohexaneformamide, and

[0059] N-(4-(2,4-dihydroxyphenyl)thiazolyl)-2-(4-(hydroxymethyl)phenyl)acetamide.

[0060] Especially preferred is

[0061] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)isobutyramide.

[0062] The above-mentioned alkylamidothiazoles, their synthesis and applications have been described in EP2758381A1.

[0063] Cosmetic or dermatological preparations having an alkylamide thiazole and a biopolymer fraction according to the invention and / or their use for the treatment and / or prevention of undesirable skin pigmentation are also advantageous embodiments of the invention.

[0064] It is particularly advantageous that the formulation contains, by weight of the total formulation, 0.000001 to 10% by weight, particularly 0.0001 to 3% by weight, especially particularly 0.001 to 1% by weight of one or more alkylamidothiazoles used according to the invention.

[0065] The major advantage of this invention is that the formulation has a weakly alkaline pH value, i.e., a value between 7 and 9, preferably between 7 and 8, and particularly between 7.4 and 7.6.

[0066] Cosmetic and dermatological preparations according to the invention can exist in various forms. For example, the preparations can therefore be solutions, anhydrous formulations, oil-in-water (W / O) or water-in-oil (O / W) emulsions or microemulsions, multiple emulsions (e.g., water-in-oil-in-water (W / O / W)), gels, solid rods, ointments, or even aerosols. According to the invention, it is also advantageous to provide the substances and / or their derivatives used according to the invention in encapsulated form, for example, encapsulated in a collagen matrix and other conventional encapsulation materials, such as cellulose encapsulation, encapsulation in gelatin, or liposomes.

[0067] It is also feasible and advantageous, in the context of this invention, to add the substances used according to the invention and / or their derivatives to aqueous systems and / or surfactant formulations used for cleaning skin and hair.

[0068] Cosmetic and dermatological preparations according to the present invention can contain cosmetic adjuvants commonly used in such preparations, such as preservatives, bactericides, fragrances, defoaming substances, dyes, pigments with coloring properties, thickeners, surfactants, emulsifiers, emollients, humectants and / or moisturizing substances, fats, oils, waxes, or other common components of cosmetic or dermatological formulations, such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents, or silicone derivatives.

[0069] The lipid phase can be advantageously selected from the following group of substances: -Mineral oil, mineral wax - Oils, such as triglycerides of capric or caprylic acid, and natural oils, such as castor oil; - Fats, waxes and other natural and synthetic lipids, preferably esters of fatty acids having low C-number alcohols, such as isopropanol, propylene glycol or glycerol, or esters of fatty alcohols having low C-number alkanes or fatty acids. -alkyl benzoate; -Silicone oils, such as dimethylpolysiloxane, diethylpolysiloxane, diphenylpolysiloxane, and mixtures thereof.

[0070] For the purposes of this invention, the oil phase of the emulsion, oleogel, aqueous dispersion, or lipid dispersion is advantageously selected from: esters consisting of saturated and / or unsaturated, branched and / or straight-chain alkyl carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or straight-chain alcohols with a chain length of 3 to 30 carbon atoms, and esters consisting of aromatic carboxylic acids and esters consisting of saturated and / or unsaturated, branched and / or straight-chain alcohols with a chain length of 3 to 30 carbon atoms. This ester oil can be advantageously selected from: isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleate, dibutyl adipate, propylheptyl octanoate, diisopropyl adipate, cetearyl isononanoate, oleate, mustard oleate, mustard oleate, and synthetic, semi-synthetic and natural mixtures of such esters, such as jojoba oil.

[0071] The aqueous phase of the formulation according to the invention optionally and advantageously contains a humectant, either alone or in combination, such as propylene glycol, panthenol, or hyaluronic acid.

[0072] In particular, mixtures of the solvents described above are used. In the case of alcohol solvents, water can be another component.

[0073] The emulsions according to the invention are advantageous and, for example, contain the aforementioned fats, oils, waxes and other fatty bodies, as well as water and emulsifiers as commonly used in this type of formulation.

[0074] The gels according to the invention typically contain low-C alcohols, such as ethanol, propylene glycol, and water or the aforementioned oils, in the presence of a thickener.

[0075] Commonly known volatile, liquefied propellants, such as hydrocarbons (propane, butane, isobutane), are suitable as propellants for formulations according to the invention that can be ejected from an aerosol container, said propellants being used alone or in mixtures with each other. Compressed air can also be used advantageously.

[0076] The formulations according to the invention can also advantageously contain substances that absorb ultraviolet radiation in the UVB range, wherein the total amount of the filtering substance, based on the total weight of the formulation, is, for example, 0.1% to 30% by weight, preferably 0.5% to 10% by weight, particularly 1.0% to 6.0% by weight, to provide a cosmetic formulation that protects hair or skin from the entire range of ultraviolet radiation. The substance can also be used as a sunscreen for hair or skin.

[0077] Furthermore, the formulations according to the invention can also advantageously include substances that mask the interfering inherent odors of the other raw materials used, wherein the total amount of fragrance contents is, for example, 0.001% to 5% by weight, preferably 0.05% to 3% by weight, particularly 0.1% to 1% by weight, based on the total weight of the cosmetic formulation, to provide a cosmetic formulation. Detailed Implementation

[0078] The following examples are intended to illustrate the invention. Unless otherwise stated, all values ​​are weight percentages.

[0079]

Claims

1. An active substance combination consisting of one or more alkylamidothiazoles and delta-decalactone.

2. The active substance combination according to claim 1, characterized in that The one or more alkylamidothiazoles are of the general formula substances, wherein R 1 , R 2 , X and Y can be different, partially identical or completely identical and can independently of one another represent: R1= -C1-C 24 -alkyl (linear and branched), -C1-C 24 -alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkyl-hydroxy, -C1-C 24 -alkyl-hydroxy (linear and branched), -C1-C 24 -alkyl-amino (linear and branched), -C1-C 24 -alkyl-aryl (linear and branched), -C1-C 24 -alkyl-aryl-alkyl-hydroxy (linear and branched), -C1-C 24 -alkyl-heteroaryl (linear and branched), -C1-C 24 -alkyl-O-C1-C 24 -alkyl (linear and branched), -C1-C 24 -alkyl-morpholinyl, -C1-C 24 -alkyl-piperidinyl, -C1-C 24 -alkyl-piperazinyl, -C1-C 24 -alkyl-piperazinyl-N-alkyl, R2= H, -Ci-C 24 -alkyl (linear and branched), -Ci-C 24 -alkenyl (linear and branched), -Ci-C8-cycloalkyl, -Ci-C 24 -hydroxyalkyl (linear and branched), -Ci-C 24 -alkylaryl (linear and branched), -Ci-C 24 -alkylheteroaryl (linear and branched), X = -H, -C1-C 24 -alkyl (linear and branched), -C1-C 24 -alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1-C 24 -aryl (optionally mono- or poly-substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1-C 24 -heteroaryl (optionally mono- or poly-substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1-C 24 -alkylaryl (linear and branched), -C1-C 24 -alkylheteroaryl (linear and branched), -aryl (optionally mono- or poly-substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl, Y = H, -Ci-C 24 -alkyl (linear and branched), -Ci-C 24 -alkenyl (linear and branched), -Ci-C8-cycloalkyl, -Ci-C 24 -aryl, -Ci-C 24 -heteroaryl, -Ci-C 24 -alkylaryl (linear and branched), -Ci-C 24 -alkylheteroaryl (linear and branched), -aryl, -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl, -COO-alkyl, -COO-alkenyl, -COO-cycloalkyl, -COO-aryl, -COO-heteroaryl, and X, Y optionally can also be able to represent fused aromatic compounds, where X and Y can form with each other an aromatic or aliphatic homocyclic or heterocyclic ring system having up to n ring-forming atoms, and where the number n can take values from 5 to 8, and the respective ring system can in turn be substituted with up to n-1 alkyl groups, hydroxyl groups, carboxyl groups, amino groups, nitrile functions, sulfur-containing substituents, ester groups and / or ether groups, where the one or more alkylamidothiazoles can exist both as free bases and as cosmetically and dermatologically acceptable salts.

3. Active substance combination according to any of the preceding claims, characterized in that The one or more alkylamidothiazoles have the following structures: N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)neopentanamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)butyramide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)heptanamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-6-hydroxyhexanamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-3-hydroxypropanamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-methoxyacetamide, 3-amino-N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)propanamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)acetamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-4-(hydroxymethyl)cyclohexanecarboxamide, N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)cyclohexanecarboxamide, and N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-2-(4-(hydroxymethyl)phenyl)acetamide.

4. Active substance combination according to any of the preceding claims, characterized in that The one or more alkylamidothiazoles can exist as halides, carbonates, ascorbates, sulfates, acetates and / or phosphates.

5. A cosmetic or dermatological preparation having a share of the active substance combination according to any of the preceding claims.

6. The preparation according to claim 5, characterized in that, The preparation comprises 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, especially particularly preferably 0.001 to 1% by weight, of the one or more alkylamidothiazoles, based on the total weight of the preparation.

7. Formulation according to any of the preceding claims, characterized in that The total amount of the preparation is 0.00001 to 1% by weight of delta-decalactone, preferably 0.0001 to 0.5% by weight of delta-decalactone, particularly preferably 0.0005 to 0.3% by weight of delta-decalactone.

8. Non-therapeutic cosmetic use of a preparation or active substance combination according to any of the preceding claims for lightening human skin.

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