Active ingredient combinations consisting of alkylamidothiazoles and oil components

Abstract

The invention relates to cosmetic or dermatological preparations containing a) one or more alkylamidothiazoles and b) one or more substances selected from the group of the ba) C5 - C25 triglycerides bb) the isopropylesters of the branched or unbranched C14 - C26 alkanoic acids bc) the esters of the branched C6 - C16 alkanols and the branched or unbranched C14 - C26 alkanoic acids c) and / or any mixtures thereof d) in cosmetic or dermatological preparations which contain no more than 10 wt.% water, preferably no more than 5 wt.% water, particularly preferably no more than 1 wt.% and ideally are completely free of water.

Description

[0001] Beiersdorf Aktiengesellschaft

[0002] Hamburg

[0003] Description

[0004] Active ingredient combinations of alkylamidothiazoles and oil components

[0005] The present invention relates to active ingredient combinations comprising one or more alkylamidothiazoles and oil components. Furthermore, the present invention relates to cosmetic or dermatological preparations containing such active ingredient combinations and their use for lightening human skin.

[0006] 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 - depending on the skin type, they occur either individually or in greater or lesser numbers.

[0007] Melanocytes contain melanosomes, characteristic cell organelles in which melanin is produced. Stimulated by UV radiation, among other things, melanin production increases. This melanin is 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.

[0008] 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 steps 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-quinone carboxylic acid or indole-5,6-quinone, from which the two aforementioned eumelanins are formed.

[0009] The formation of pheomelanin occurs, among other things, via the intermediates 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.

[0010] In addition to the previously described process of melanin synthesis in melanocytes, the transfer of melanosomes, their retention in the epidermis, and their degradation and the degradation of 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).

[0011] Furthermore, the size and shape of melanosomes influence their light-scattering properties and thus the color appearance of the skin. For example, black Africans tend to have larger, solitary spheroidal melanosomes, while Caucasians tend to have smaller, clustered melanosomes.

[0012] Problems with hyperpigmentation of the skin have a variety of causes or are side effects of many biological processes, e.g. UV radiation (e.g. freckles, ephelides), genetic predisposition, incorrect pigmentation of the skin during wound healing or scarring (post-inflammatory hyperpigmentation) or skin aging (e.g. lentigines seniles).

[0013] Following inflammatory reactions, the skin's pigmentation system reacts with partially opposite reactions. Both post-inflammatory hyperpigmentation and hypopigmentation can occur. Post-inflammatory hypomelanosis frequently occurs in association with atopy, lupus erythematosus, and psoriasis, among other conditions. The various reactions of the human skin's pigmentation system following inflammatory phenomena are only very incompletely understood.

[0014] Problems with post-inflammatory hyperpigmentation often occur in darker skin types. Pseudofolliculitis barbae, which is associated with or results in cosmetically undesirable dyspigmentation, is particularly common in black men. Forms of melasma, which occur particularly in Asian women on the face and décolleté area, as well as various forms of irregular skin pigmentation, are also considered 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, this type of post-inflammatory dyspigmentation is further aggravated by exposure to sunlight (UV light), without UV-induced inflammation (sunburn) occurring.

[0015] Active ingredients and preparations that counteract skin pigmentation are known. 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.

[0016] 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.

[0017] Furthermore, various other substances are known for which a skin-lightening effect has been described. These include, among others, 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.

[0018] JM Ready describes in a publication (Bioorganic & Medicinal Chemistry Letter 17 (2007) 6871-6875) the effect of substituted thiazole derivatives on the inhibition of mushroom tyrosinase.

[0019] The patent application of Shiseido (WO 2009099195) describes substituted thiazolamines or hydrothiazolamines for skin lightening.

[0020] The substances described in the above-mentioned prior art demonstrate moderate efficacy. 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; however, over longer periods, the condition can become chronic and very bothersome for those affected. There is also a lack of sufficiently promising active ingredients and treatment options for such skin conditions. The stable incorporation of alkylthiazoles into anhydrous bases is a major challenge due to the poor solubility of the active ingredients.Accordingly, common methods for incorporating alkylthiazoles into emulsion bases by using water-soluble solvents such as methylpropanediol or ethanol cannot be used in anhydrous systems. This object is achieved by cosmetic or dermatological preparations containing a) one or more alkylamidothiazoles and b) one or more substances selected from the group of ba) C5 - C25 triglycerides bb) the isopropyl esters of branched or unbranched C14 - C26 alkanoic acids bc) the esters of branched C6 - C16 alkanols and of branched or unbranched C14 - C26 alkanoic acids c) and / or any mixtures thereof d) in cosmetic or dermatological preparations which contain not more than 10% by weight of water, preferably not more than 5% by weight of water, particularly preferably not more than 1% by weight and ideally are completely anhydrous.Within the disclosure of the present invention, "anhydrous" means that water is introduced into the preparations according to the invention at most unintentionally, but not deliberately incorporated therein. The preparations according to the invention preferably contain 0.1-70% by weight of one or more of the substances listed under point ba) above, preferably 5-40% by weight, particularly preferably 10-25% by weight. The preparations according to the invention preferably contain 0.1-70% by weight of one or more of the substances listed under point bb) above, preferably 5-40% by weight, particularly preferably 10-25% by weight.

[0021] The preparations according to the invention preferably contain 0.1 - 70 wt% of one or more of the substances listed under point bc) above, preferably 5 - 40 wt%, particularly preferably 10 - 25 wt%.

[0022] Compositions according to the invention advantageously contain mixtures of the substances mentioned under the above points ba) : bb) : bc) in weight ratios of (10 to 100) : (10 to 100) : (10 to 100), preferably of (30 to 100) : (15 to 80) : (5 to 80).

[0023] Particularly preferred weight ratios are ba) : bb) : bc) of (60 to 70) : (25 to 35) : (3 to 8).

[0024] Preferred substances of the substances referred to under point ba) are

[0025] Caprylic Capric T riglycerides

[0026] Coco Caprylate Caprate

[0027] Glyceryl Caprylate Caprate

[0028] Glyceryl Stearate

[0029] Glyceryl Oleate

[0030] Particularly preferred is.

[0031] Caprylic Capric T riglycerides

[0032] Preferred substances of the substances referred to under point bb) are isopropyl stearate,

[0033] Isopropyl isostearate,

[0034] Isopropyl palmitate,

[0035] Isopropyl myristate

[0036] Isopropyl lanolate

[0037] Isopropyl palmitate is particularly preferred.

[0038] Preferred substances of the substances referred to under point bc) are

[0039] Ethylhexyl cocoate

[0040] Ethylhexyl myristate Ethylhexyl stearate Ethylhexyl palmitate Ethylhexyl behenate Ethylhexyl stearate is particularly preferred. 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.%, 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-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 24Alkyl-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–C24–alkylaryl (linear and branched), -C1–C24–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–C24–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 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. In particular, as halogen salts,such as chloride and bromide. Furthermore, an advantageous realization 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 be for 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 the same 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 = HR1 = -C1–C24–alkyl (linear and branched), -C1–C24-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-C24-alkyl (linear and branched), -C1-C24 alkyl-morpholino, -C1-C24 alkyl-piperidino, -C1-C24 alkyl-piperazino, -C1-C24 alkyl-piperazino-N-alkyl, R2 = H, -C1–C24–alkyl (linear and branched). Z = -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl. Particularly preferred are those compounds in which Y = HR1 = -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. The connections

[0041] A'-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide

[0042] A r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)butyramide

[0043] A r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-4-(hydroxymethyl)cyclohexanecarboxamide are the preferred ones according to the invention.

[0044] The most preferred option is

[0045] A' r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide The above alkylamidothiazoles, their synthesis and application were described in EP2758381A1.

[0046] Cosmetic or dermatological preparations containing alkylamidothiazoles and biopolymers according to the invention or their use for the treatment and / or prophylaxis of undesired skin pigmentation are also advantageous embodiments of the present invention.

[0047] 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.

[0048] 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, substances for preventing foaming, dyes, pigments which have a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or humectant substances, fats, oils, waxes or other customary components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

[0049] The lipid phase can advantageously be chosen from the following group of substances:

[0050] Mineral oils, mineral waxes

[0051] Oils such as triglycerides of capric or caprylic acid, and natural oils such as castor oil;

[0052] 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;

[0053] alkyl benzoates;

[0054] Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixtures thereof.

[0055] The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions within the meaning of 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 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 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, oleyl erucate, erucyl oleate, erucyl erucate as well as synthetic, semi-synthetic and natural mixtures of such esters, e.g. jojoba oil.

[0056] Suitable propellants for preparations according to the invention that can be sprayed from aerosol containers are the usual, readily 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.

[0057] 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.

[0058] Furthermore, preparations according to the invention can advantageously additionally contain substances which mask the unpleasant inherent odor of the remaining raw materials used, the total amount of the perfume ingredients being, for example, 0.001% by weight to 5% by weight, preferably 0.05 to 3% by weight, in particular 0.1 to 1% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations.

[0059] The following examples are intended to illustrate the present invention. Unless otherwise stated, the numerical values ​​refer to percentages by weight.

Claims

Claims 1. Cosmetic or dermatological preparations containing a) one or more alkylamidothiazoles and b) one or more substances selected from the group of b a) C5 – C25- Triglyceride bb) der Isopropylester der verzweigten oder unverzweigten C14 – C26-Alkansäu- ren b c) der Ester der verzweigten C6 – C16-Alkanole und der verzweigten oder un- verzweigten C14 – C26-Alkansäuren c) und / oder beliebige Gemische daraus d) in kosmetischen oder dermatologischen Zubereitungen, welche nicht mehr als 10 Gew. % Wasser enthalten, bevorzugt nicht mehr als 5 Gew.-% an Wasser, particularly preferably not more than 1 wt.% and ideally completely anhydrous.

2. Zubereitungen nach Anspruch 1, dadurch gekennzeichnet, dass das oder die Al- kylamidothiazole 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 mean independently of each other: R 1 = -C1–C24–Alkyl (linear und verzweigt), -C1–C24-Alkenyl (linear und verzweigt), -C1- C 8 -Cycloalkyl, -C 1 -C 8 -Cycloalkyl-alkylhydroxy, -C 1 -C 24 Alkylhydroxy (linear and branched), -C 1 -C 24 Alkylamine (linear and branched), -C 1 –C 24 –Alkylaryl (linear and branched), -C 1 –C 24–Alkylaryl-alkyl-hydroxy (linear and branched), -C 1 –C 24 –Alkylhetero- aryl (linear and branched), -C 1 -C 24 -Alkyl-OC 1 -C 24 -Alkyl (linear and branched), -C 1 -C 24 Alkyl-Morpholino, -C 1 -C 24 Alkyl-Piperidino, -C 1 -C 24 Alkyl-Piperazino, -C 1 -C 24 Alky-piperazino-N-alkyl means, R 2 = H, -C1–C24–Alkyl (linear und verzweigt), -C1–C24-Alkenyl (linear und verzweigt), - C1-C8-cycloalkyl, -C1-C24-hydroxyalkyl (linear and branched), -C1–C24–alkylaryl (linear and branched), -C 1 –C 24 –Alkylheteroaryl (linear and branched), X = -H, -C1–C24–Alkyl (linear und verzweigt), -C1–C24-Alkenyl (linear und verzweigt), -C1-C8-cycloalkyl, -C1–C24–aryl (optionally mono- or polysubstituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1–C24-heteroaryl (optionally mono- or polysubstituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN), -C1–C24–alkylaryl (linear and branched), -C1–C24–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 means, Y = H, -C1–C24–Alkyl (linear und verzweigt), -C1–C24-Alkenyl (linear und verzweigt), -C1- C8-cycloalkyl, -C1-C24-aryl, -C1-C24-heteroaryl, -C1-C24-alkylaryl (linear and branched), -C1-C24-alkylheteroaryl (linear and branched), -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, means, among others nd X, Y gegebenenfalls auch = kondensierter Aromat bedeuten können, wobei X und Y untereinander aromatische oder aliphatische homo- oder heterozykli-cal ring systems with up to n ring-forming atoms, and where the number n can take values ​​from 5 to 8, and the respective ring systems in turn m it bis zu n – 1 Alkylgruppen, Hydroxylgruppen, Carboxylgruppen, Aminogruppen, Nit- ril functions, sulfur-containing substituents, ester groups and / or ether groups, w obei das oder die Alkylamidothiazole sowohl als freie Base wie auch als kosmetisch and dermatologically usable salts may be present.

3. Active ingredient combinations according to one of the preceding claims, characterized in that eichnet, dass das oder die Alkylamidothiazole folgende Struktur aufweisen: A r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)pival amide A r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide A'-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)butyramide A r -(4-(2,4-dihydroxyphenyl)thiazol-2-yl)-4-(hydroxymethyl)cyclohexanecarboxamide 4. Preparations according to one of the preceding claims, 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.

5. Preparations according to one of the preceding claims, characterized in that they contain 0.1 - 70 wt.% of one or more of the substances listed under point ba) above, preferably 5 - 40 wt.%, particularly preferably 10 - 25 wt.%.

6. Preparations according to one of the preceding claims, characterized in that they contain 0.1 - 70 wt.% of one or more of the substances listed under point bb) above, preferably 5 - 40 wt.%, particularly preferably 10 - 25 wt.% 7. Preparations according to one of the preceding claims, characterized in that they contain 0.1 - 70 wt.% of one or more of the substances listed under point bc) above, preferably 5 - 40 wt.%, particularly preferably 10 - 25 wt.%.

8. Preparations according to one of the preceding claims, characterized in that they contain mixtures of the substances mentioned under the above points ba) : bb) : bc) in weight ratios of (10 to 100) : (10 to 100) : (10 to 100), preferably of (30 to 100) : (15 to 80) : (5 to 80).

9. Preparations according to one of the preceding claims, characterized in that the weight ratios ba) : bb) : bc) are (60 to 70) : (25 to 35) : (3 to 8).

10. Preparations according to one of the preceding claims, characterized in that the substances of the substances referred to under point ba) are selected from the group Caprylic Capric Triglycerides Coco Caprylate Caprate Glyceryl Caprylate Caprate Glyceryl Stearate Glyceryl Oleate 11. Preparations according to one of the preceding claims, characterized in that the substance referred to under ba) is caprylic capric triglycerides 12. Preparations according to one of the preceding claims, characterized in that the substances of the substances referred to under point bb) are selected from the group Isopropyl stearate, isopropyl isostearate, isopropyl palmitate, Isopropyl myristate Isopropyl lanolate 13. Preparations according to one of the preceding claims, characterized in that isopropyl palmitate is chosen as the substance referred to under bb).

14. Preparations according to one of the preceding claims, characterized in that the substances of the substances referred to under point bc) are selected from the group Ethylhexyl cocoate Ethyl hexyl myristate Ethylhexyl stearate Ethylhexyl palmitate Ethylhexyl behenate 15. Preparations according to one of the preceding claims, characterized in that ethylhexyl stearate is selected as the substance referred to under bc) 16. Cosmetic, non-therapeutic use of preparations according to one of the preceding claims for lightening human skin.

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