Active substance combinations consisting of alkylamidothiazoles and indoles

Abstract

The present invention relates to active substance combinations consisting of one or more alkylamidothiazoles and indoles.

Description

TECHNICAL FIELD

[0001] The present application relates to an active substance combination consisting of one or more alkylamidothiazoles and indoles. 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 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 melanosomes affect their light scattering properties, thus influencing the appearance of skin color. Therefore, large, spherical, solitary melanosomes are more commonly found in African populations, while smaller, grouped melanosomes are more prevalent in Caucasian populations.

[0008] Hyperpigmentation of the skin has a variety of causes or is a symptom of many biological processes, such as: ultraviolet radiation (e.g., freckles, moles), genetic predisposition, abnormal pigmentation of the skin during wound healing or scar formation (post-inflammatory hyperpigmentation) or skin aging (e.g., age spots, senile lentigines).

[0009] Following an inflammatory response, the skin's pigmentary system may exhibit a partially opposite reaction. Post-inflammatory hyperpigmentation or hypopigmentation may occur. Post-inflammatory hypopigmentation is particularly often associated with atopic dermatitis, lupus erythematosus, and psoriasis. Our understanding of the different response patterns of the human skin's pigmentary system following inflammation is still very incomplete.

[0010] Post-inflammatory hyperpigmentation is a common problem in darker skin types. Particularly in men of color, pseudofolliculitis barbae is known, a condition that is accompanied by or causes cosmetically undesirable pigmentation abnormalities. Melasma, particularly in the facial and chest areas of Asian women, as well as various forms of irregular pigmentation, is also classified as post-inflammatory hyperpigmentation. Furthermore, dark circles under the eyes are also considered a form of post-inflammatory hyperpigmentation, where the underlying inflammation often occurs in a subclinical manner.

[0011] In many cases, such post-inflammatory hyperpigmentation abnormalities are exacerbated by sunlight (ultraviolet radiation) without causing UV-induced inflammation (sunburn).

[0012] Active substances and formulations for combating skin pigmentation are known. In practical use, hydroquinone-based formulations are mainly used, but these formulations only show their effects after several weeks of application, and prolonged use is problematic for toxicological reasons. Albert Kligman et al. have developed a so-called "triple formulation," which is a combination of 0.1% retinoic acid, 5.0% hydroquinone, and 0.1% dexamethasone (A. Kligman, 1975, Arch. Dermatol., 111:40-48). Of course, this formulation is also highly controversial due to the potentially irreversible alteration of the skin pigmentation system.

[0013] In addition, skin peeling methods (chemical and mechanical "resurfacing") are used, but these methods often trigger inflammatory responses and can even worsen rather than alleviate hyperpigmentation due to subsequent post-inflammatory hyperpigmentation. All of these commonly used methods for treating post-inflammatory hyperpigmentation have significant side effects.

[0014] In addition, many other substances are known to have skin-brightening effects. These include, but are not limited to, hexadecyl-1,16-dicarboxylic acid, kojic acid and its derivatives, arbutin, ascorbic acid and its derivatives, flavonoids, ellagic acid and its derivatives, tranexamic acid, and various resorcinol derivatives, such as 4-n-butylresorcinol, 4-n-hexylresorcinol, and 4-(1-phenylethyl)benzene-1,3-diol.

[0015] JM Ready described, in a publication (Bioorganic & Medicinal Chemistry Letter 17(2007) 6871-6875), the inhibitory effects of substituted thiazole derivatives on mushroom tyrosinase.

[0016] In Shiseido's patent application (WO 2009099195), substituted thiazolidinedioides or hydrogenated thiazolidinedioides are described for use in skin brightening.

[0017] The substance described in the prior art is characterized by moderate efficacy.

[0018] Dark circles can also result from pigmentation disorders, including those caused by general stress, such as lack of sleep, or simply eye strain. In young people, the symptoms may disappear after a good night's rest, but in the long term, the condition can become chronic and significantly bothersome. There are also a lack of sufficiently promising active ingredients and treatment options for this type of skin condition.

[0019] Smell is one of the five human senses. Here, odorous substances, or volatile substances, are bound by olfactory receptors in the nasal mucosa. Through a signal cascade, the stimulus is transmitted to nerve cells and then to the brain. There, the actual olfactory perception occurs. Pleasant odors are distinguished from unpleasant odors.

[0020] However, cosmetic products often have a slightly unpleasant inherent odor caused by the raw materials used. In some cases, alkylamidothiazoles can also contribute to a worsened odor experience in cosmetic bases. This drawback needs to be eliminated. Summary of the Invention

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

[0022] Indole is characterized by the following structural formula:

[0023] Indole includes, but is not limited to, naturally occurring in jasmine flowers, and is also characteristic of the jasmine aroma at low concentrations. At higher concentrations, indole is more easily perceived as unpleasant.

[0024] Preferably, the formulation according to the invention contains 0.00001 to 1% by weight of indole, more preferably 0.0001 to 0.5% by weight of indole, and particularly preferably 0.0005 to 0.3% by weight of indole.

[0025] 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.

[0026] The advantageous alkylamidothiazole for the purposes of this invention is of the general formula:

[0027] The substance in which

[0028] 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-chain), -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.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] 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.

[0034]

[0035] 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.

[0036]

[0037] Advantageous, especially, are the following compounds, among which

[0038] X=

[0039] Y=H

[0040] R1=-C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched-chain), -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).

[0041] Z=-H, -OH, -F, -Cl, -Br, -I, -OMe, -NH 2、 -CN, acetyl group.

[0042] The following compounds are particularly preferred, wherein

[0043] X=

[0044] Y=H

[0045] R1 represents -C1-C 24 -alkyl (straight-chain and branched-chain), -C1-C 24 -Alkenyl (straight-chain and branched-chain), -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-C24 alkyl-piperidinyl, -C1-C 24 alkyl-piperazinyl, -C1-C 24 alkyl-piperazinyl-N-alkyl, R2=H.

[0046] According to the present invention, the following compounds are preferred:

[0047] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)neopentamide,

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

[0049] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)butyramide,

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

[0051] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)-6-hydroxyhexamamide,

[0052] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)-3-hydroxypropionamide,

[0053] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)-2-methoxyacetamide,

[0054] 3-Amino-N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)propionamide,

[0055] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)acetamide,

[0056] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)-4-(hydroxymethyl)cyclohexaneformamide,

[0057] N-(4-(2,4-dihydroxyphenyl)thiazo-2-yl)cyclohexaneformamide, and

[0058] N-(4-(2,4-dihydroxyphenyl)thiazolyl)-2-(4-(hydroxymethyl)phenyl)acetamide.

[0059] Especially preferred is

[0060] N-(4-(2,4-dihydroxyphenyl)thiazolyl-2-yl)isobutyramide.

[0061] The above-mentioned alkylamidothiazoles, their synthesis and applications have been described in EP2758381A1.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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 encapsulating materials, such as encapsulated as cellulose, encapsulated in gelatin, or encapsulated in liposomes.

[0066] 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.

[0067] 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.

[0068] 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.

[0069] 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 alkylcarboxylic 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.

[0070] 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.

[0071] In particular, mixtures of the solvents described above are used. In the case of alcohol solvents, water can be another component.

[0072] 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.

[0073] 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.

[0074] 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.

[0075] 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.

[0076] 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

[0077] The following examples are intended to illustrate the invention. Unless otherwise stated, all values ​​are weight percentages.

[0078]

Claims

1. Active substance combination consisting of one or more alkylamidothiazoles and indoles.

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. 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 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 indole, preferably 0.0001 to 0.5% by weight of indole, particularly preferably 0.0005 to 0.3% by weight of indole.

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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