Active ingredient combinations of alkylamidothiazoles and gamma-undecalactone

Abstract

Drug combinations consisting of one or more alkylamidothiazoles and gamma-undecalactone.

Description

[0001] The present invention relates to combinations of active ingredients consisting of one or more alkylamidothiazoles and gamma-undecalactone. Furthermore, the present invention relates to cosmetic or dermatological preparations containing such combinations of active ingredients and their use for lightening human skin.

[0002] The pigmentation of the skin is caused by melanocytes, which are found in the lowest layer of the epidermis, the stratum basale, alongside the basal cells as pigment-forming cells – either individually or in greater or lesser numbers, depending on the skin type.

[0003] Melanocytes contain melanosomes as characteristic cell organelles, in which melanin is produced. Melanin production increases, for example, when stimulated by UV radiation. This melanin is transported via the living layers of the epidermis (keratinocytes) ultimately to the stratum corneum (corneocytes), resulting in a more or less pronounced brownish to brownish-black skin color.

[0004] Melanin is formed as the final stage of an oxidative process in which tyrosine, with the involvement of the enzyme tyrosinase, is converted via several intermediate steps to the brown to brownish-black eumelanins (DHICA and DHI melanin) or, with the involvement of sulfur-containing compounds, to the reddish pheomelanin. DHICA and DHI melanin are formed via the common intermediates dopaquinone and dopachrome. The latter is converted, sometimes with the involvement of other enzymes, either to indole-5,6-quinone carboxylic acid or to indole-5,6-quinone, from which the two aforementioned eumelanins are formed.

[0005] Pheomelanin production involves, among other things, the intermediates dopaquinone and cysteinyldopa. The expression of 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 melanosomes are also important for melanogenesis. The so-called p-protein appears to play a key role, although its exact function remains unclear.

[0006] In addition to the previously described process of melanin synthesis in melanocytes, the transfer of melanosomes, their retention in the epidermis, and their degradation, as well as the breakdown 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 melanocytes to keratinocytes (M. Seiberg et al., 2000, J. Cell. Sci., 113:3093-101).

[0007] Furthermore, the size and shape of melanosomes influence their light-scattering properties and thus the skin's color appearance. For example, large, spheroidal, solitary melanosomes are more common in Black Africans, while smaller melanosomes occurring in groups are more typical in Caucasians.

[0008] Problems with hyperpigmentation of the skin have diverse causes or are accompanying 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. lentigines seniles).

[0009] Following inflammatory reactions, the skin's pigmentation system reacts with partially opposing responses. Both post-inflammatory hyperpigmentation and hypopigmentation can occur. Post-inflammatory hypomelanosis is frequently associated with atopy, lupus erythematosus, and psoriasis, among other conditions. The various reaction patterns of the human skin's pigmentation system to inflammatory processes are only very poorly understood.

[0010] Problems with post-inflammatory hyperpigmentation are common in darker skin types. Pseudofolliculitis barbae, a cosmetically undesirable condition, is particularly well-known in Black men. Forms of melasma, which occur especially in Asian women on the face and décolletage, as well as various forms of irregular skin pigmentation, are also classified as post-inflammatory hyperpigmentation. Furthermore, dark circles under the eyes are considered a form of post-inflammatory hyperpigmentation, although the underlying inflammation is usually subclinical.

[0011] In many cases, such post-inflammatory hyperpigmentation is further intensified by exposure to sunlight (UV light), without resulting in UV-induced inflammation (sunburn).

[0012] Several active ingredients and preparations are known to counteract skin pigmentation. In practical use, preparations based on hydroquinone are primarily employed. However, these often only show their effect after several weeks of use, while excessively long use is problematic 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 the potential for irreversible changes in the skin's pigmentation system.

[0013] Furthermore, skin-peeling methods (chemical and mechanical "peels") are used, but these often lead to inflammatory reactions and, due to subsequent post-inflammatory hyperpigmentation, can even result in increased rather than reduced pigmentation. All these common procedures, which are also used to treat post-inflammatory hyperpigmentation, are characterized by significant side effects.

[0014] Furthermore, various other substances are known for their skin-lightening effects. 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.

[0015] JM Ready describes in a publication (Bioorganic & Medicinal Chemistry Letter 17 (2007) 6871-6875) the effect of, among others, substituted thiazole derivatives on the inhibition of mushroom tyrosinase.

[0016] Shiseido's patent application (WO 2009099195) describes substituted thiazolamines or hydrothiazolamines for skin lightening.

[0017] The substances described in the above-mentioned state of the art are characterized by moderate effectiveness.

[0018] Dark circles under the eyes can also result from a pigmentation disorder, and can also appear as a reaction to general stress, such as lack of sleep or simply eye strain. In younger people, the symptoms disappear after sufficient sleep, but over longer periods the condition can become chronic and very bothersome for those affected. There is also a lack of sufficiently effective active ingredients and treatment options for such skin conditions.

[0019] Smell is one of the five human senses. Odor molecules, volatile substances, are bound by olfactory receptors in the nasal mucosa. A signaling cascade transmits the stimulus to nerve cells and then to the brain, where the actual perception of smell arises. Pleasant smells are distinguished from unpleasant ones.

[0020] However, cosmetic products often have a somewhat unpleasant inherent odor caused by the raw materials used. Alkylamidothiazoles can also, under certain circumstances, contribute to a deterioration in the fragrance experience of a cosmetic base. This problem needed to be remedied.

[0021] This task is solved by combinations of active ingredients consisting of one or more alkylamidothiazoles and gamma-undecalactone.

[0022] Gamma-undecalactone (undecano-1,4)-lactone) is characterized by the following structural formula:

[0023] Gamma-undecalactone is a well-known perfume ingredient with a fruity scent.

[0024] The preparations according to the invention preferably contain 0.00001 - 1 wt% of gamma-undecalactone, preferably 0.0001 - 0.5 wt% of gamma-undecalactone, and in particular preferably 0.0005 - 0.3 wt% of gamma-undecalactone.

[0025] Particularly advantageous are preparations or uses according to the invention, characterized in that the preparations contain 0.000001 to 10 wt.%, in particular 0.0001 to 3 wt.%, most especially 0.001 to 1 wt.% of one or more alkylamidothiazoles, based on the total weight of the preparation.

[0026] Advantageous alkylamidothiazoles according to the present invention are substances of the general formula in which R 1 , R 2 X and Y can be different, partially the same, or completely the same, and can mean things independently of each other: 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 Alky-Morpholino, -C1-C 24 Alky-Piperidino, - C1-C 24 Alky-Piperazino, -C1-C 24 Alkyl-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 (possibly simply or multiplely substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1-C 24-Heteroaryl (possibly simply or multiplely 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 (possibly simply or multiplely substituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl means, 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 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, means, and X, Y may also mean = condensed aromatic compound, wherein X and Y can form aromatic or aliphatic homo- or heterocyclic ring systems with up to n ring-forming atoms, and wherein the number n can take 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.

[0027] The aforementioned thiazoles can exist both as free bases and as salts: e.g., as fluoride, chloride, bromide, iodide, sulfate, carbonate, ascorbate, acetate, or phosphate. In particular, they exist as halogen salts, such as chloride and bromide.

[0028] Furthermore, an advantageous realization of the present invention consists in cosmetic or dermatological preparations containing an effective amount of one or more of the aforementioned alkylamidothiazoles.

[0029] According to the invention, the aforementioned alkylamidothiazoles are also used for the treatment and / or prophylaxis of unwanted skin pigmentation. This treatment and / or prophylaxis of unwanted skin pigmentation can be carried out in both cosmetic and pharmaceutical contexts.

[0030] Pharmaceutical (or dermatological) treatment is primarily understood to refer to pathological skin conditions, whereas cosmetic treatment and / or prophylaxis of unwanted skin pigmentation primarily concerns healthy skin.

[0031] Advantageously, X is chosen from the group of substituted phenyls, where the substituents (Z) can be chosen from the group -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, Acetyl and can be the same or different.

[0032] Particularly advantageous is X chosen from the group of phenyl groups substituted with one or more hydroxyl groups, wherein the substituent (Z) can be chosen 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.

[0033] Connections are particularly advantageous 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 Alky-Morpholino, -C1-C 24 Alky-Piperidino, - C1-C 24 Alky-Piperazino, -C1-C 24 Alkyl-piperazino-N-alkyl means, R2= H, -C1-C 24 -Alkyl (linear and branched). Z = -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl.

[0034] Particularly preferred are those connections 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 Alky-Morpholino, -C1-C24 Alky-Piperidino, - C1-C 24 Alky-Piperazino, -C1-C 24 Alkyl-piperazino-N-alkyl means, R2=H.

[0035] The compounds are the preferred ones according to the invention.

[0036] The most preferred thing is the

[0037] The above alkylamidothiazoles, their synthesis and application were described in EP2758381A1.

[0038] 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 also advantageous embodiments of the present invention.

[0039] It is particularly advantageous if such preparations contain 0.000001 to 10 wt.%, in particular 0.0001 to 3 wt.%, and most especially 0.001 to 1 wt.% of one or more of the alkylamidothiazoles used according to the invention, based on the total weight of the preparation.

[0040] It is a great advantage in the sense 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.

[0041] 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 provide the substances used according to the invention and / or their derivatives in encapsulated form, for example, in collagen matrices and other conventional encapsulation materials, such as cellulose encapsulations, gelatin, or liposomal encapsulation.

[0042] It is also possible and advantageous in the sense of the present invention to incorporate the substances used according to the invention and / or their derivatives into aqueous systems or surfactant preparations for cleaning the skin and hair.

[0043] The cosmetic and dermatological preparations according to the invention may contain cosmetic excipients such as are commonly used in such preparations, e.g. preservatives, bactericides, perfumes, antifoaming agents, dyes, pigments with a coloring effect, thickeners, surfactants, emulsifiers, softening, moisturizing and / or humectant substances, fats, oils, waxes or other usual components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

[0044] The lipid phase can be advantageously 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.

[0045] The oil phase of the emulsions, oleogels, hydrodispersions, or lipodispersions according to the present invention is 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 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon 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 carbon atoms.Such ester oils can then be advantageously selected from the group consisting 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-hexyl decyl stearate, 2-octyldodecyl palmitate, oleyl oleate, dibutyl adipate, propylheptyl caprylate, diisopropyl adipate, cetearyl isononanoate, oleylerucate, erucyl oleate, erucylerucate, as well as synthetic, semi-synthetic and natural mixtures of such esters, e.g. jojoba oil.

[0046] The aqueous phase of the preparations according to the invention may advantageously contain humectants such as propylene glycol, panthenol or hyaluronic acid, either individually or in combination.

[0047] In particular, mixtures of the aforementioned solvents are used. Water may be an additional component of alcoholic solvents.

[0048] 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 such as is commonly used for this type of formulation.

[0049] Gels according to the invention typically contain alcohols with a low carbon number, e.g. ethanol, propylene glycol, and water or one of the aforementioned oils in the presence of a thickening agent.

[0050] Suitable propellants for the preparations according to the invention, which can be sprayed from aerosol containers, are the usual known volatile, liquefied propellants, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in mixtures. Compressed air can also be used advantageously.

[0051] Advantageously, preparations according to the invention can also contain substances that absorb UV radiation in the UVB range, wherein the total amount of the filter substances is, for example, 0.1 wt.% to 30 wt.%, preferably 0.5 wt.%, and in particular 1.0 wt.% to 6.0 wt.%, 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 hair or skin.

[0052] Furthermore, preparations according to the invention can advantageously contain additional substances that mask the disturbing inherent odor of the remaining raw materials used, wherein the total amount of perfume ingredients is, for example, 0.001 wt.% to 5 wt.%, preferably 0.05 to 3 wt.%, in particular 0.1 to 1 wt.% based on the total weight of the preparations, in order to provide cosmetic preparations.

[0053] The following examples are intended to illustrate the present invention. Unless otherwise stated, the numerical values ​​refer to percentages by weight. Anti-Pigment Sunscreen extra high SPF Anti Pigment Daycare SPF 30 Anti Pigment Nightcare Anti Pigment Intense Serum Anti Pigment Serum EU INCI Declaration Concentration(%) Concentration(%) Concentration(%) Concentration(%) Concentration(%) Sodium Hyaluronate 0 0 0 0 0,1 Panthenol+Aqua+Pantolactone+Citric Acid 0 0 4.0 0 0 Isobutylamido Thiazolyl Resorcinol 0,1 0,25 0,3 0,5 0,15 Glucosylrutin+lsoquercitrin 0 0,05 0,3 0,1 0 Tocopheryl Acetate 1.00000 0,5 1 0,5 0 Hydroxyacetophenone 0.4 0 0 0 0 Ethylhexylglycerin 0,3 0 0 0 0 Glycyrrhetinic Acid 0,2 0,2 0 0 0 Ascorbyl Glucoside 0,5 0,1 Dibutyl Adipate 2 0 1 0 2,5 Cocoglycerides 0 1 0 0 2 Propylheptyl Caprylate+Tocopherol 0 1 0 0 2 Isopropyl Palmitate 0 0 5 0 0 Butyrospermum Parkii Butter 0,5 0 2 0 0 Hydrogenated CocoGlycerides 0 0 2.0 0 0 Butylene Glycol Dicaprylate / Dicaprate 3,5 2 0 0 1 Copernicia Cerifera Cera 1 0 0 0 0 Cetearyl Isononanoate 0 0 3 0 0 Dimethicone 0 2 0 0 1 C12-15 Alkyl Benzoate 6 2 1 0 0 Glyceryl Stearate Citrate 2.0 0 2 0 0 Sodium Stearoyl Glutamate+Sodium Chloride 2.0 0.4 0 0 0.1 Glyceryl Stearate 0 0.8 0 0 0 Lauroyl Lysine 0 0 1.0 0 0 Distarch Phosphate 0 1 0 0 0 Silica Dimethyl Silylate 1.0 1 2 0 0 Tapioca Starch+Aqua 3 2 0 0 0 Glycerin+Aqua 5 2 10 5 10 Methylpropanediol 0 0 2.0 0 2 Aqua+Sodium Hydroxide 0.9 0.75 0.15 0 0.1 Phenoxyethanol+Aqua 1 0.9 0.5 0 0.6 Alcohol Denat. 6 5 5 50 8 Aqua+Trisodium EDTA 0,5 1.0 0 1 Aqua+Trisodium Ethylenediamine Disuccinate 0 0 0,5 0 0 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine 4 3 0 0 0 Diethylamino Hydroxybenzoyl Hexyl Benzoate 2 0 0 0 0 Butyl Methoxydibenzoylmethane 5 5 0 0 0 Homosalate 0 5 0 0 0 Ethylhexyl Salicylate 0 5 0 0 0 Ethylhexyl Triazone 4,5 3 0 0 0 Phenylbenzimidazole Sulfonic Acid 1,5 2 0 0 0 Behenyl Alcohol 0,75 0 0 0 0 Carrageenan 0.2 0 0,2 0,2 0 Cetearyl Alcohol 1.0 0 3 0 0 Cetyl Alcohol 1.0 1 0 0 3.0 Stearyl Alcohol 0 0,75 0 0 0 Hydroxypropyl Methylcellulose 0,05 0 0 0 0 Carbomer 0 0,2 0.2 0 0,2 Xanthan Gum 0,1 0.2 0 0 0 gamma Undecalactone 0,005 0,1 0,0001 0.02 0,3 Aqua ad 100 ad 100 ad 100 ad 100 ad 100 QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] WO 2009099195

[0016] Cited non-patent literature

[0000] M. Seiberg et al., 2000, J. Cell. Sci., 113:3093-101

[0006] A. Kligman, 1975, Arch. Dermatol., 111:40-48

[0012] JM Ready describes in a publication (Bioorganic & Medicinal Chemistry Letter 17 (2007) 6871-6875

[0015]

Claims

[1] Active ingredient combinations of one or more alkylamidothiazoles and gamma-undecalactone. [2] Active ingredient combinations according to claim 1, characterized by that the alkylamidothiazole(s) is / are a substance of the general formula in which R 1 , R 2 , X and Y can be different, partially the same or completely the same and can mean independently of each other: 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-C24 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-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 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, means, and X, Y may 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, wherein the alkylamidothiazole(s) may be present both as a free base and as cosmetically and dermatologically usable salts. [3] Active ingredient combinations according to one of the preceding claims, characterized by that the alkylamidothiazole(s) has(have) the following structure:and [4] Active ingredient combinations according to one of the preceding claims, characterized by that the alkylamidothiazole(s) may be present as halide, carbonate, ascorbate, sulfate, acetate and / or phosphate. [5] Cosmetic or dermatological preparations containing active ingredient combinations according to one of the preceding claims. [6] Preparations according to claim 5, characterized by 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. [7] Preparations according to any one of the preceding claims, characterized by that the total amount of the preparations is 0.00001 - 1 wt% of gamma-undecalactone, preferably 0.0001 - 0.5 wt% of gamma-undecalactone, particularly preferably 0.0005 - 0.3 wt% of gamma-undecalactone. [8] Cosmetic, non-therapeutic use of preparations or combinations of active ingredients according to one of the preceding claims for lightening human skin.