Active ingredient combinations from alkylamidothiazoles and one or more biopolymers

Abstract

The invention relates to active ingredient combinations from one or more alkylamidothiazoles and one or more cosmetically or dermatologically acceptable biopolymers, which are suitable for increasing the viscosity of aqueous solutions, selected from the group of alcohols provided with one or more hydroxyl groups and / or from the group of polysaccharides esterified and / or etherified with carboxylic acids and of the non-esterified and non-etherified polysaccharides that are composed of interlinked glucose and / or mannose and / or galactose and / or glucuronic acid and / or rhamnose units, wherein, if xanthane or hydroxypropyl starch phosphate is selected as the biopolymer, at least one further biopolymer must be present.

Description

[0001] Beiersdorf Aktiengesellschaft Hamburg Description Active ingredient combinations of alkylamidothiazoles and one or more biopolymers The present invention relates to active ingredient combinations of one or more alkylamidothiazoles and one or more biopolymers. Furthermore, the present invention relates to cosmetic or dermatological preparations containing such an active ingredient combination and their use for lightening human skin. Melanocytes are responsible for the pigmentation of the skin. These pigment-forming cells are found in the lowest layer of the epidermis, the stratum basale, alongside the basal cells as pigment-forming cells - occurring either individually or in greater or lesser numbers depending on the skin type. Melanocytes contain melanosomes as characteristic cell organelles in which melanin is produced. Among other things, melanin production is increased when stimulated by UV radiation.This is ultimately transported through the living layers of the epidermis (keratinocytes) into the stratum corneum (corneocytes), producing a more or less pronounced brownish to brown-black skin color. Melanin is formed as the final stage of an oxidative process in which tyrosine, with the assistance of the enzyme tyrosinase, is converted via several intermediate stages into the brown to brown-black eumelanins (DHICA and DHI melanin) or, with the involvement of sulfur-containing compounds, into the reddish pheomelanin. DHICA and DHI melanin are formed via the common intermediates dopaquinone and dopachrome. The latter is converted, partly with the involvement of other enzymes, into either indole-5,6-quinonecarboxylic acid or indole-5,6-quinone, from which the two aforementioned eumelanins are formed. The formation of pheomelanin occurs, among other things, via the intermediate products dopaquinone and cysteinyldopa.The expression of the melanin-synthesizing enzymes is controlled by a specific transcription factor (microphthalmia-associated transcription factor, MITF). In addition to the described enzymatic processes of melanin synthesis, other proteins in the melanosomes are also important for melanogenesis. The so-called p-protein appears to play an important role here, although its exact function is still unclear. In addition to the previously described process of melanin synthesis in the melanocytes, the transfer of the melanosomes, their retention in the epidermis, as well as their degradation and the degradation of the melanin, are also crucial for skin pigmentation. It has been shown that the PAR-2 ​​receptor is important for the transport of melanosomes from the melanocytes to the keratinocytes (M. Seiberg et al., 2000, J. Cell. Sci., 113:3093-101).Furthermore, the size and shape of the melanosomes influence their light-scattering properties and thus the color appearance of the skin. For example, large, spheroidal, solitary melanosomes are more commonly found in Black Africans, while Caucasians tend to have smaller, grouped melanosomes. Problems with skin hyperpigmentation have diverse causes or are concomitant symptoms of many biological processes, e.g., UV radiation (e.g., freckles, ephelides), genetic predisposition, malpigmentation of the skin during wound healing or scarring (post-inflammatory hyperpigmentation), or skin aging (e.g., senile lentigines). After inflammatory reactions, the skin's pigmentation system reacts with partially opposite reactions. Post-inflammatory hyperpigmentation as well as hypopigmentation can occur. Post-inflammatory hypomelanosis occurs, among other things, inoften occurs in association with atopy, lupus erythematosus, and psoriasis. The various reactions of the pigmentation system of the human skin as a result of inflammatory phenomena are only very incompletely understood. Problems with post-inflammatory hyperpigmentation often occur in darker skin types. The problem of pseudofolliculitis barbae, which is associated with or results in cosmetically undesirable dyspigmentation, is particularly well known in black men. Forms of melasma, which occur particularly in the face and décolleté area in Asian women, as well as various forms of irregular skin pigmentation, are also counted as post-inflammatory hyperpigmentation. Dark circles under the eyes are also considered a form of post-inflammatory hyperpigmentation, although the underlying inflammation is usually subclinical.In many cases, such post-inflammatory dyspigmentation is further aggravated by exposure to sunlight (UV light) without resulting in UV-induced inflammation (sunburn). Active ingredients and preparations are known that counteract skin pigmentation. Hydroquinone-based preparations are primarily used in practice. However, some of these only become effective after several weeks of use, and excessively long-term use is questionable for toxicological reasons. Albert Kligman et al. developed a so-called "triformula" consisting of a combination of 0.1% tretinoin, 5.0% hydroquinone, and 0.1% dexamethasone (A. Kligman, 1975, Arch. Dermatol., 111:40-48). However, this formulation is also highly controversial due to potential irreversible changes in the skin's pigmentation system.Skin peeling methods (chemical and mechanical "peels") are also used, but these often result in inflammatory reactions and, due to subsequent post-inflammatory hyperpigmentation, can even lead to increased rather than reduced pigmentation. All of these common procedures, which are also used to treat post-inflammatory hyperpigmentation, are characterized by significant side effects. Furthermore, various other substances are known for which a skin-lightening effect has been described. These include hexadecene-1,16-dicarboxylic acid, kojic acid and derivatives, arbutin, ascorbic acid and derivatives, flavonoids, ellagic acid and derivatives, tranexamic acid, and various resorcinol derivatives, such as 4-n-butylresorcinol, 4-n-hexylresorcinol, and 4-(1-phenylethyl)benzene-1,3-diol. JM Ready describes in a publication (Bioorganic & Medicinal Chemistry Letter 17 (2007) 6871-6875 the effect of, among others,Substituted thiazole derivatives for the inhibition of fungal tyrosinase. In the patent application of Shiseido (WO 2009099195), substituted thiazolamines or hydrothiazolamines for skin lightening are described. The substances described in the above-mentioned prior art are characterized by moderate effectiveness. Dark circles under the eyes can also result from a pigmentation disorder, although they can also appear as a reaction to general stress, such as lack of sleep or simply due to eye strain. In younger people, the symptoms disappear after a sufficient night's rest; over longer periods, however, the condition can become chronic and very disturbing for those affected. There is also a lack of sufficiently promising active ingredients and treatment options for such skin conditions. Smell is one of the five human senses.Odorants, highly volatile substances, are bound by olfactory receptors in the nasal mucosa. The stimulus is transmitted to the nerve cells via a signaling cascade and forwarded to the brain. There, the actual perception of smell arises. Pleasant smells are distinguished from unpleasant smells. However, cosmetic products often have a somewhat unpleasant odor of their own, which is caused by the raw materials used. Alkylamidothiazoles can also, under certain circumstances, contribute to a deterioration in the fragrance experience of a cosmetic base. It was necessary to remedy this problem.This object is achieved by active ingredient combinations of one or more alkylamidothiazoles and one or more cosmetically or dermatologically acceptable biopolymers which are suitable for increasing the viscosity of an aqueous solution, selected from the group of polysaccharides esterified and / or etherified with one or more hydroxyl groups containing alcohols and / or carboxylic acids, as well as unesterified and unetherified polysaccharides which are composed of interconnected glucose and / or mannose and / or galactose and / or glucuronic acid and / or rhamnose units, wherein, if xanthan or hydroxypropyl starch phosphate is selected as the biopolymer, at least one further biopolymer must be present.The preparations according to the invention preferably contain 0.0001 - 10 wt% of one or more biopolymers, preferably 0.001 - 5 wt% of one or more biopolymers, particularly preferably 0.005 - 3 wt% of one or more biopolymers. Preparations or uses according to the invention are particularly advantageous, characterized in that the preparations contain 0.000001 to 10 wt%, in particular 0.0001 to 3 wt%, very particularly 0.001 to 1 wt% of one or more alkylamidothiazoles, based on the total weight of the preparation. Advantageous alkylamidothiazoles within the meaning of the present invention are substances of the general formula. at which R 1 , R 2, X and Y can be different, partially the same or completely the same and can independently mean: R1 = -C1–C24–alkyl (linear and branched), -C1–C24-alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C24 alkylhydroxy (linear and branched), -C1-C24 alkylamine (linear and branched), -C1–C24–alkylaryl (linear and branched), -C1–C24–alkylaryl-alkyl-hydroxy (linear and branched), -C1–C24–alkylheteroaryl (linear and branched), -C1-C24-alkyl-O-C1-C 24 -Alkyl (linear and branched), -C1-C 24 Alkyl-Morpholino, -C1-C 24 Alkyl-Piperidino, -C1-C 24 Alkyl-Piperazino, -C1-C 24 Alky-piperazino-N-alkyl means, R2 = H, -C1–C 24 –Alkyl (linear and branched), -C1–C 24 -Alkenyl (linear and branched), -C1-C8- cycloalkyl, -C1-C 24 -Hydroxyalkyl (linear and branched), -C1–C 24 –Alkylaryl (linear and branched), -C1–C 24–Alkylheteroaryl (linear and branched), means 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 polysubstituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1–C 24 -Heteroaryl (optionally mono- or polysubstituted 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 polysubstituted 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–C24–alkyl (linear and branched), -C1–C24-alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1–C24–aryl, -C1–C24-heteroaryl, -C1–C24–alkylaryl (linear and branched), -C1–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 can optionally also mean = condensed aromatic, where X and Y can form aromatic or aliphatic homo- or heterocyclic ring systems with up to n ring-forming atoms, and where the number n can assume values ​​from 5 to 8, and the respective ring systems 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. The thiazoles mentioned can exist both as free bases and as salts: e.g., as fluoride, chloride, bromide, iodide, sulfate, carbonate, ascorbate, acetate, or phosphate. Particularly as halogen salts, such as chloride and bromide.Furthermore, an advantageous implementation of the present invention consists in cosmetic or dermatological preparations with an effective content of one or more of the aforementioned alkylamidothiazoles. The invention further relates to the use of the aforementioned alkylamidothiazoles for the treatment and / or prophylaxis of unwanted skin pigmentation. The treatment and / or prophylaxis of unwanted skin pigmentation can take place both in a cosmetic and a pharmaceutical context. Pharmaceutical (or dermatological) treatment is understood primarily to refer to pathological skin conditions, whereas cosmetic treatment and / or prophylaxis of unwanted skin pigmentation primarily concerns healthy skin. Advantageously, X is selected from the group of substituted phenyls, where the substituents (Z) can be selected from the group consisting of -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl, and can be identical or different. Particularly advantageously, X is selected from the group of phenyl groups substituted with one or more hydroxy groups, where the substituent (Z) can be selected from the group -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl and the following generic structure is preferred, in which Y, R 1 and R 2 which may have the properties defined above. Particularly advantageous are those compounds in which Y = H R1= -C1–C 24 –Alkyl (linear and branched), -C1–C 24 -Alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C 24 Alkylhydroxy (linear and branched), -C1-C 24 Alkylamine (linear and branched), -C1–C 24 –Alkylaryl (linear and branched), -C1–C 24 –Alkylaryl- Alkyl-Hydroxy (linear and branched), -C1–C 24 –Alkylheteroaryl (linear and branched), -C1-C 24 - Alkyl-O-C1-C 24-Alkyl (linear and branched), -C1-C 24 Alkyl-Morpholino, -C1-C 24 Alkyl-Piperidino, -C1-C 24 Alkyl-Piperazino, -C1-C 24 Alky-piperazino-N-alkyl means, R2 = H, -C1–C 24 –Alkyl (linear and branched). Z = -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl. Particularly preferred compounds are those in which X = Y = H R1 = -C1-C24-alkyl (linear and branched), -C1-C24-alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C24 alkylhydroxy (linear and branched), -C1-C24 alkylamine (linear and branched), -C1-C24-alkylaryl (linear and branched), -C1-C24-alkylaryl-alkyl-hydroxy (linear and branched), -C1-C24-alkylheteroaryl (linear and branched), -C1-C24-alkyl-O-C1-C24-alkyl (linear and branched), -C1-C24 alkyl-morpholino, -C1-C24 alkyl-piperidino, -C1-C24 Alky-Piperazino, -C1-C24 Alky-Piperazino-N-Alkyl means, R2 = H. The compounds

[0002] are those preferred according to the invention. The The above alkylamidothiazoles, their synthesis, and application were described in EP2758381A1. Among the biopolymers preferred according to the invention are dehydroxanthan, gellan (INCI: Gellan Gum), xanthan, hydroxypropyl starch phosphate (INCI: Hydroxypropyl Starch Phosphate), and any mixtures thereof. Particularly advantageous within the meaning of the present invention are mixtures of a) dehydroxanthan, b) gellan, c) xanthan, d) hydroxypropyl starch phosphate, whose weight ratios a:b, a:c, a:d, b:c, b:d, and c:d each independently behave as rational numbers between 0 and 10. Particularly advantageous in the context of the present invention are mixtures of a) dehydroxanthan, b) gellan, c) xanthan, d) hydroxypropyl starch phosphate, whose weight ratios a : b : c : d are as follows: (0.1 to 5) : (0.1 to 5) : (0.1 to 5) : (0.1 to 5).It may be advantageous to dispense with other substances that increase the viscosity of aqueous solutions ("thickeners"). In particular, it is advantageous to dispense with polyacrylates that increase the viscosity of aqueous solutions. Cosmetic or dermatological preparations containing alkylamidothiazoles and biopolymers according to the invention or their use for the treatment and / or prophylaxis of unwanted skin pigmentation are likewise advantageous embodiments of the present invention. It is particularly advantageous if such preparations contain 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, very particularly 0.001 to 1% by weight, of one or more of the alkylamidothiazoles used according to the invention, based on the total weight of the preparation.It is of great advantage within the meaning of the present invention if the preparations have slightly basic pH values, i.e. values ​​between 7 and 9, preferably between 7 and 8, in particular between 7.4 and 7.6. Cosmetic and dermatological preparations according to the invention can be in various forms. For example, they can be a solution, an anhydrous preparation, an emulsion or microemulsion of the water-in-oil (W / O) or oil-in-water (O / W) type, a multiple emulsion, for example of the water-in-oil-in-water (W / O / W) type, a gel, a solid stick, an ointment or even an aerosol. It is also advantageous according to the invention to administer the substances used according to the invention and / or their derivatives in encapsulated form, e.g. in collagen matrices and other customary encapsulation materials, e.g. as cellulose encapsulations, in gelatin or liposomally encapsulated.It is also possible and advantageous within the meaning of the present invention to incorporate the substances used according to the invention and / or their derivatives into aqueous systems or surfactant preparations for cleansing the skin and hair. The cosmetic and dermatological preparations according to the invention can contain cosmetic auxiliaries as are customarily used in such preparations, e.g. preservatives, bactericides, perfumes, anti-foaming agents, dyes, pigments that have a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or humectant substances, fats, oils, waxes or other customary constituents of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.The lipid phase can advantageously be selected from the following group of substances: - mineral oils, mineral waxes - oils such as triglycerides of capric or caprylic acid, and also natural oils such as castor oil; - fats, waxes and other natural and synthetic fatty substances, preferably esters of fatty acids with low-carbon alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with low-carbon alkanoic acids or with fatty acids; - alkyl benzoates; - silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixtures thereof. The oil phase of the emulsions, oleogels orHydrodispersions or lipodispersions in the sense of the present invention are advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids with a chain length of 3 to 30 C atoms and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 C atoms, from the group of esters of aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 C atoms.Such ester oils can then advantageously be selected from the group of 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, oleyl oleate, dibutyl adipate, propylheptyl caprylate, diisopropyl adipate, cetearyl isononanoate, oleyl erucate, erucyl oleate, erucyl erucate as well as synthetic, semi-synthetic and natural mixtures of such esters, e.g. jojoba oil. The aqueous phase of the preparations according to the invention optionally advantageously contains humectants such as propylene glycol, panthenol, or hyaluronic acid, individually or in combination. In particular, mixtures of the above-mentioned solvents are used. In the case of alcoholic solvents, water can be a further component. Emulsions according to the invention are advantageous and contain, for example,the aforementioned fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as is usually used for this type of formulation. Gels according to the invention usually contain alcohols with a low carbon number, e.g. ethanol, propylene glycol, and water or an aforementioned oil in the presence of a thickener. Suitable propellants for preparations according to the invention that can be sprayed from aerosol containers are the customary, well-known, highly volatile, liquefied propellants, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in mixtures with one another. Compressed air can also be used advantageously. Preparations according to the invention can advantageously also contain substances that absorb UV radiation in the UVB range, the total amount of filter substances being, for example, 0.1% to 30% by weight, preferably 0.5 to 10% by weight, in particular 1.0 to 6.0% by weight.-%, based on the total weight of the preparations, in order to provide cosmetic preparations that protect the hair or skin from the entire range of ultraviolet radiation. They can also serve as sunscreens for the hair or skin. Furthermore, preparations according to the invention can advantageously additionally contain substances that mask unpleasant inherent odors of the remaining raw materials used, the total amount of perfume ingredients being, for example, 0.001% by weight to 30% by weight, preferably 0.05 to 10% by weight, in particular 0.1 to 5.0% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations.Test description: To determine the influence of the biopolymers used in the formula on odor development in combination with the active ingredient N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide compared to the synthetic polymer sodium polyacrylate (INCI: Sodium Polyacrylate), the samples were irradiated for 48 hours using an Atlas Suntester. All samples were contained in 30 ml sample vials. The irradiance of the device was 250 W / m2, which, after 48 hours of irradiation, corresponds to 8 months of storage of the samples in a light window. The samples were then assessed unopened by a panel of trained fragrance experts to evaluate odor development and odor intensity. To ensure comparability of the approaches, all other odor-influencing components of the formulation were removed or used at the same concentration.In this specific case, this means that all formulations are perfume-free and have the same ethanol concentration.

[0003] The following examples are intended to illustrate the present invention without limiting it. Unless otherwise stated, all quantities, proportions, and percentages are based on the weight and the total amount or the total weight of the preparations.

[0004]

Claims

Patent claims 1. Active ingredient combinations of one or more alkylamidothiazoles and one or more cosmetically or dermatologically acceptable biopolymers which are suitable for increasing the viscosity of an aqueous solution, selected from the group of polysaccharides esterified and / or etherified with one or more hydroxyl groups containing alcohols and / or carboxylic acids, as well as unesterified and unetherified polysaccharides composed of interconnected glucose and / or mannose and / or galactose and / or glucuronic acid and / or rhamnose units, wherein, if xanthan or hydroxypropyl starch phosphate is selected as the biopolymer, at least one further biopolymer must be present.

2. Active ingredient combinations according to claim 1, characterized in that the biopolymer(s) is / are selected from the group of dehydroxanthan, gellan gum, xanthan, hydroxypropyl starch phosphate and any mixtures thereof. 3.Active ingredient combinations according to claim 2, characterized in that mixtures of a) dehydroxanthan, b) gellan, c) xanthan, d) hydroxypropyl starch phosphate are selected, the weight ratios a : b, a : c, a : d, b : c, b : d and c : d of which, independently of one another, behave like rational numbers between 0 and 10.

4. Active ingredient combinations according to claim 2, characterized in that mixtures of a) dehydroxanthan, b) gellan, c) xanthan, d) hydroxypropyl starch phosphate are selected, the weight ratios a : b : c : d of which, in relation to one another, are as follows: (0.1 to 5) : (0.1 to 5) : (0.1 to 5) : (0.1 to 5).

5. Active ingredient combinations according to one of the preceding claims, characterized in that the alkylamidothiazole(s) are substances of the general formula. Is or are, at which R 1 , R 2, X and Y can be different, partially the same or completely the same and can independently mean: R1 = -C1–C24–alkyl (linear and branched), -C1–C24-alkenyl (linear and branched), -C1–C8-cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C24 alkylhydroxy (linear and branched), -C1-C24 alkylamine (linear and branched), -C1–C24–alkylaryl (linear and branched), -C1–C24–alkylaryl-alkyl-hydroxy (linear and branched), -C1–C24–alkylheteroaryl (linear and branched), -C1-C24-alkyl-O-C1-C24-alkyl (linear and branched), -C1-C24 alkyl-morpholino, -C1-C24 alkyl-piperidino, -C1-C24 alkyl-piperazino, -C1-C24 alkyl-piperazino-N-alkyl means, R2 = H, -C1–C24–alkyl (linear and branched), -C1–C24-alkenyl (linear and branched), - C1-C8-cycloalkyl, -C1-C24-hydroxyalkyl (linear and branched), -C1–C24–alkylaryl (linear and branched), -C1–C24–alkylheteroaryl (linear and branched), means, X = -H, -C1–C24–alkyl (linear and branched),-C1–C24-alkenyl (linear and branched), - C1-C8-cycloalkyl, -C1–C, 24 –Aryl (optionally mono- or polysubstituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1–C 24 -Heteroaryl (optionally mono- or polysubstituted 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 polysubstituted 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 (linear and branched), -C1–C 24 -Alkenyl (linear and branched), -C1-C8-cycloalkyl, -C1–C 24 –Aryl, -C1–C 24 -Heteroaryl, -C1–C 24 –Alkylaryl (linear and branched), -C1–C 24–Alkylheteroaryl (linear und verzweigt), -Aryl, -phenyl, -2,4-dihydroxy- phenyl, -2,3-dihydroxyphenyl, -2,4-Dimethoxyphenyl, -2,3-Dimethoxyphenyl, -COO- Alkyl, -COO-alkenyl, -COO-cycloalkyl, -COO-aryl, -COO-heteroaryl, and X, Y can optionally also denote condensed aromatic, where X and Y can form aromatic or aliphatic homo- or heterocyclic ring systems with up to n ring-forming atoms, and where the number n can assume values ​​from 5 to 8, and the respective ring systems 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 alkylamidothiazole(s) can be present both as a free base and as cosmetically and dermatologically usable salts.

6. Active ingredient combinations according to one of the preceding claims, characterized in that the alkylamidothiazole(s) have the following structure: A'-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)butyramide A r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-4-(hydroxymethyl)cyclohexanecarboxamide und 7. Active ingredient combinations according to one of the preceding claims, characterized in that the alkylamidothiazole(s) can be present as halide, carbonate, ascorbate, sulfate, acetate, and / or phosphate.

8. Cosmetic or dermatological preparations containing active ingredient combinations according to one of the preceding claims.

9. Preparations according to claim 8, characterized in that they contain 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, very particularly 0.001 to 1% by weight, of one or more alkylamidothiazoles, based on the total weight of the preparation.

10. Preparations according to one of the preceding claims, characterized in that the total amount of the preparations is 0.0001-10% by weight of one or more biopolymers, preferably 0.001-5% by weight of one or more biopolymers, particularly preferably 0.005-3% by weight of one or more biopolymers. 11.Preparations according to one of the preceding claims, characterized in that they have slightly basic pH values, i.e. values ​​between 7 and 9, preferably between 7 and 8, in particular between 7.4 and 7.

6.

12. Cosmetic, non-therapeutic use of preparations or active ingredient combinations according to one of the preceding claims for lightening human skin.

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