Active substance combinations of alkylaminothiazoles and one or more biopolymers

Abstract

The invention relates to a combination of active substances consisting of one or more alkylaminothiazoles and one or more cosmetically or dermatologically safe biopolymers suitable for increasing the viscosity of an aqueous solution, the biopolymer is selected from the group consisting of alcohols having one or more hydroxyl groups and / or carboxylic acid esterified and / or etherified polysaccharides, and unesterified and unetherified polysaccharides consisting of interconnected glucose and / or mannose and / or galactose and / or glucuronic acid and / or rhamnose units, wherein if xanthan gum or hydroxypropyl starch phosphate is selected as the biopolymer, at least one further biopolymer must be present.

Description

Technical Field

[0001] The present invention relates to an active substance combination of one or more alkylaminothiazoles and one or more biopolymers. In addition, the present invention relates to a cosmetic or dermatological preparation containing such an active substance combination and its use for brightening human skin. Background Art

[0002] Melanocytes are responsible for skin pigmentation and can be found next to basal cells in the deepest layer of the epidermis, i.e., the basal layer. Depending on the skin type, they can be pigment-forming cells that occur sporadically or more or less frequently.

[0003] Melanocytes contain melanosomes as characteristic organelles in which melanin is formed. In addition, when stimulated by ultraviolet radiation, melanin is strongly formed. This is ultimately transported through the living layer of the epidermis (keratinocytes) to the stratum corneum (corneocytes), resulting in a more or less distinct brown to brown-black skin color.

[0004] Melanin is formed as the final stage of an oxidation process in which tyrosine is converted into brown to brown-black eumelanin (DHICA and DHI melanin) through multiple intermediate stages under the action of tyrosinase, or is converted into light red pheomelanin with the participation of sulfur-containing compounds. DHICA and DHI melanin are produced through the general intermediate stages dopaquinone and dopachrome. The latter is partially converted into indole-5,6-quinone carboxylic acid or indole-5,6-quinone with the participation of other enzymes, from which the two aforementioned eumelanins are formed.

[0005] The production of pheomelanin occurs especially through the intermediates dopaquinone and cysteinyldopa. The expression of melanogenic enzymes is controlled by specific transcription factors (microphthalmia-associated transcription factor, MITF). In addition to the described enzymatic process of melanin synthesis, other proteins are also important for melanogenesis in melanosomes. The so-called p protein seems to play an important role here, the exact function of which is still unclear.

[0006] In addition to the process of melanin synthesis in melanocytes described above, the transfer of melanosomes, their retention in the epidermis, their degradation, and the degradation of melanin are crucial in 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] In addition, the size and shape of melanosomes affect their light-scattering properties, thus influencing the color appearance of the skin. For example, in some populations, large spherical single melanosomes are increasingly found, while in other populations, smaller melanosomes occur in groups.

[0008] The problem of hyperpigmentation of the skin has many causes or is a concomitant symptom of many biological processes, such as ultraviolet radiation (e.g., summer sunburn, freckles), genetic predisposition, abnormal pigmentation of the skin during the wound healing process or scar formation (post-inflammatory hyperpigmentation) or skin aging (e.g., senile freckles).

[0009] After an inflammatory reaction, the pigmentation system of the skin reacts in part in the opposite way. Post-inflammatory hyperpigmentation and hypopigmentation can occur. Post-inflammatory hypomelanosis is usually associated with atopic dermatitis, systemic lupus erythematosus and psoriasis. The different reaction forms of the human skin pigmentation system due to inflammatory phenomena are only very incompletely understood.

[0010] The problem of post-inflammatory hyperpigmentation usually occurs in dark skin types. The problem of pseudofolliculitis is especially known among men of color, which is accompanied by or leads to undesired abnormal pigmentation in terms of cosmetics. In addition, forms of melasma, especially occurring on the face and shoulder area of women of Asian descent, as well as various forms of irregular skin pigmentation, also belong to post-inflammatory hyperpigmentation. In addition, dark circles under the eyes are also considered a form of post-inflammatory hyperpigmentation, where the underlying inflammation is usually subclinical.

[0011] In many cases, this post-inflammatory abnormal pigmentation is enhanced by the action of sunlight (ultraviolet rays) without causing inflammation (sunburn) caused by ultraviolet rays.

[0012] Active ingredients and preparations are known that can counteract skin pigmentation. In practical use, preparations based essentially on hydroquinone are used. However, on the one hand, hydroquinone shows its effect only after several weeks of use, and on the other hand, its excessive long-term use is doubtful due to toxicological reasons. Albert Kligman et al. developed a so-called "Triformula", which represents a combination of 0.1% tretinoin, 5.0% hydroquinone, 0.1% dexamethasone (A. Kligman, 1975, Arch. Dermatol., 111:40 - 48). However, this formula is also very controversial because irreversible changes may occur in the skin pigmentation system.

[0013] In addition, skin peeling methods (chemical and mechanical "peeling") are used, but this usually leads to an inflammatory reaction and may even result in an exacerbation of post-inflammatory hyperpigmentation rather than a reduction in pigmentation. All these commonly used methods are also used to treat post-inflammatory hyperpigmentation, which is characterized by significant side effects.

[0014] In addition, various other substances are known that are described as having a skin brightening effect. Among these, 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 will be mentioned here.

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

[0016] In a patent application of the Shiseido Company (WO 2009099195), substituted thiazolamines or hydrothiazolamines for skin whitening are described.

[0017] The substances described in the above prior art are characterized by medium effectiveness.

[0018] Dark circles under the eyes can also be the result of a pigmentation disorder, which can also be a reaction to general stress, such as lack of sleep or simply due to overexertion of the eyes. In young people, the symptoms disappear after sufficient sleep, but over a longer period, the situation can become chronic and very bothersome for the affected person. Even for this skin symptom, there is a lack of sufficiently promising active ingredients and treatment options.

[0019] Smell is one of the five human senses. Odorants are volatile substances that bind to odor receptors in the nasal mucosa in olfaction. Through a series of signals, the stimulus is transmitted to nerve cells and forwarded to the brain. True odor perception is generated here. Pleasant odors are distinguished from unpleasant odors.

[0020] However, cosmetics usually have a slightly unpleasant inherent odor due to the raw materials used. Alkylaminothiazoles can also contribute to the deterioration of the fragrance experience of the cosmetic matrix. This drawback must be overcome. Summary of the Invention

[0021] This object is achieved by an active substance combination consisting of one or more alkylaminothiazoles and one or more cosmetically or dermatologically safe biopolymers capable of increasing the viscosity of an aqueous solution, said biopolymers being selected from polysaccharides esterified and / or etherified with alcohols and / or carboxylic acids having one or more hydroxyl groups, and unesterified and unetherified polysaccharides consisting of interconnected glucose units and / or mannose units and / or galactose units and / or glucuronic acid units and / or rhamnose units, where if xanthan gum or hydroxypropyl starch phosphate is selected as the biopolymer, at least one other biopolymer must be present.

[0022] Preferably, the preparation according to the invention contains 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.

[0023] Particularly advantageous is the preparation or use according to the invention, characterized in that the preparation contains 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, especially 0.001 to 1% by weight of one or more alkylaminothiazoles, relative to the total weight of the preparation.

[0024] Advantageous alkylaminothiazoles in the sense of the present invention are substances of the following general formula

[0025]

[0026] where

[0027] R 1 、R 2 、X and Y can be different, partially the same or completely the same, and can each independently represent:

[0028] R 1 =-C 1 -C 24 alkyl (straight-chain and branched), -C 1 -C 24 alkenyl (straight-chain and branched), -C 1 -C 8 cycloalkyl, -C1-C8 cycloalkyl-alkyl hydroxy, -C 1 -C 24 alkyl hydroxy (straight-chain and branched), -C 1 -C 24 alkylamine (straight-chain and branched), -C 1 -C 24 -alkylaryl (straight-chain and branched), -C1-C24-alkyl-aryl-alkyl hydroxy (straight-chain and branched), -C 1 -C 24-alkyl heteroaryl (linear and branched), -C 1 -C 24 -alkyl - O - C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkyl morpholinyl, -C 1 -C 24 -alkyl piperidinyl, -C 1 -C 24 -alkyl piperazinyl, -C 1 -C 24 -alkyl piperazinyl - N - alkyl.

[0029] R 2 = H, -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 24 -hydroxyalkyl (linear and branched), -C 1 -C 24 -alkyl aryl (linear and branched), -C 1 -C 24 -alkyl heteroaryl (linear and branched),

[0030] X = -H, -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 24 -aryl (optionally mono - or multi - substituted by -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN), -C 1 -C 24 -heteroaryl (optionally mono - or multi - substituted by -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN), -C 1 -C 24 -alkyl aryl (linear and branched), -C 1 -C 24 -alkyl heteroaryl (linear and branched), -aryl (optionally mono - or multi - substituted by -OH, -F, -Cl, -Br, -I, -OMe, -NH 2, -CN (monosubstituted or polysubstituted), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl,

[0031] Y = H, -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 24 -aryl, -C 1 -C 24 -heteroaryl, -C 1 -C 24 -alkylaryl (linear and branched), -C 1 -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,

[0032] and X, Y may optionally also represent a fused aromatic group;

[0033] wherein X and Y may form an aromatic or aliphatic homocyclic or heterocyclic system having at most n ring atoms with each other, and wherein the number n may take values from 5 to 8, and each ring system may in turn be substituted by at most n - 1 alkyl, hydroxy, carboxy, amino, nitrile functional groups, sulfur-containing substituents, ester groups and / or ether groups.

[0034] The thiazole may exist in the form of a free base as well as salts: for example, fluoride, chloride, bromide, iodide, sulfate, carbonate, ascorbate, acetate or phosphate. Especially halogen salts such as chloride and bromide.

[0035] Furthermore, an advantageous implementation of the present invention lies in a cosmetic or dermatological preparation having an effective content of one or more of the above alkylaminothiazoles.

[0036] According to the present invention, there is also the use of the above alkylaminothiazoles for the treatment and / or prevention of undesired skin pigmentation. Here, the treatment and / or prevention of undesired skin pigmentation can be carried out in the cosmetic and pharmaceutical aspects.

[0037] Here, pharmaceutical (or dermatological) treatment mainly refers to pathological skin diseases, while cosmetic treatment and / or prevention of undesired skin pigmentation mainly relate to healthy skin.

[0038] Advantageously, X is selected from substituted phenyl, wherein the substituent (Z) may be selected from -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN, acetyl, and may be the same or different.

[0039]

[0040] Particularly advantageously, X is selected from phenyl substituted by one or more hydroxyl groups, wherein the substituent (Z) may be selected from -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN, acetyl, and preferably has the following general structure, wherein Y, R 1 and R 2 may have the properties defined above.

[0041]

[0042] Particularly advantageous are compounds wherein

[0043]

[0044] Y = H

[0045] R 1 = -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 8 -cycloalkyl-alkyl-hydroxy, -C 1 -C 24 -alkyl-hydroxy (linear and branched), -C 1 -C 24 -alkyl-amine (linear and branched), -C 1 -C 24 -alkyl-aryl (linear and branched), -C1-C24-alkyl-aryl-alkyl-hydroxy (linear and branched), -C 1 -C 24 -alkyl-heteroaryl (linear and branched), -C 1 -C 24 -alkyl-O-C 1 -C 24 alkyl (linear and branched), -C 1 -C 24 -alkyl-morpholinyl, -C 1 -C24 -alkylpiperidinyl, -C 1 -C 24 -alkylpiperazinyl, -C 1 -C 24 -alkylpiperazinyl-N-alkyl,

[0046] R 2 = H, -C 1 -C 24 alkyl (linear and branched).

[0047] Z = -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN, acetyl.

[0048] Particularly preferred are compounds in which

[0049]

[0050] Y = H

[0051] R 1 = -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 8 -cycloalkyl-alkyl-hydroxy, -C 1 -C 24 -alkyl-hydroxy (linear and branched), -C 1 -C 24 -alkyl-amine (linear and branched), -C 1 -C 24 -alkyl-aryl (linear and branched), -C1-C24-alkyl-aryl-alkyl-hydroxy (linear and branched), -C 1 -C 24 -alkyl-heteroaryl (linear and branched), -C 1 -C 24 -alkyl-O-C 1 -C 24 alkyl (linear and branched), -C 1 -C 24 -alkyl-morpholinyl, -C 1 -C 24 -alkylpiperidinyl, -C 1 -C 24 -alkylpiperazinyl, -C 1 -C 24 -alkylpiperazinyl-N-alkyl,

[0052] R 2 = H.

[0053] Compound

[0054]

[0055]

[0056]

[0057] is a compound preferred according to the present invention.

[0058] Particularly preferred is

[0059]

[0060] The above alkylaminothiazoles and their synthesis and applications are described in EP2758381A1.

[0061] Biopolymers preferred according to the present invention include dehydroxanthan gum, gellan gum (INCI: Gellan Gum), xanthan gum, hydroxypropyl starch phosphate (INCI: Hydroxypropyl Starch Phosphate), and any mixture thereof.

[0062] Particularly advantageous in the sense of the present invention is a mixture of the following substances:

[0063] (a) Dehydroxanthan gum;

[0064] (b) Gellan gum;

[0065] (c) Xanthan gum;

[0066] (d) Hydroxypropyl starch phosphate;

[0067] The weight ratios a:b, a:c, a:d, b:c, b:d, and c:d are independent of each other and take rational numbers between 0 and 10.

[0068] Particularly advantageous in the sense of the present invention is a mixture of the following substances:

[0069] (a) Dehydroxanthan gum;

[0070] (b) Gellan gum;

[0071] (c) Xanthan gum;

[0072] (d) Hydroxypropyl starch phosphate;

[0073] The relationship between the weight ratios a:b:c:d is as follows:

[0074] (0.1 to 5):(0.1 to 5):(0.1 to 5):(0.1 to 5).

[0075] It can be advantageous not to use other substances that increase the viscosity of the aqueous solution ("thickeners"). Particularly advantageously, polyacrylates that have an effect of increasing the viscosity of the aqueous solution are dispensed with.

[0076] Cosmetic or dermatological preparations containing alkylaminothiazoles and the biopolymers according to the invention, and their use for treating and / or preventing undesired skin pigmentation are likewise advantageous embodiments of the invention.

[0077] Particularly advantageously, these preparations contain 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, especially 0.001 to 1% by weight of one or more alkylaminothiazoles used according to the invention, relative to the total weight of the preparation.

[0078] Particularly advantageously in the sense of the present invention, the preparation has a slightly alkaline pH value, i.e., a value between 7 and 9, preferably between 7 and 8, especially between 7.4 and 7.6.

[0079] The cosmetic and dermatological preparations according to the invention can exist in various forms. For example, they can be solutions, anhydrous preparations, emulsions or microemulsions of the water-in-oil (W / O) or oil-in-water (O / W) type, multiple emulsions such as water-in-oil-in-water (W / O / W) type, gels, solid sticks, ointments or aerosols. It is also advantageous according to the invention that the substances used according to the invention and / or their derivatives are present in encapsulated form, for example in a collagen matrix and other common encapsulating materials, such as in cellulose encapsulation, encapsulated in gelatin or liposomes.

[0080] It is also possible and advantageous in the sense of the present invention to add the substances used according to the invention and / or their derivatives to an aqueous system or a surfactant preparation for cleaning the skin and hair.

[0081] The cosmetic and dermatological preparations according to the invention can contain cosmetic adjuvants commonly used in such preparations, such as preservatives, bactericides, fragrances, anti-foaming substances, dyes, pigments with a coloring effect, thickeners, surface-active substances, emulsifiers, softening substances, wetting substances 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.

[0082] The lipid phase can advantageously be selected from the following groups of substances:

[0083] - Mineral oils, mineral waxes;

[0084] - Oils, such as triglycerides of capric or caprylic acid, and natural oils such as castor oil;

[0085] - fats, waxes and other natural and synthetic fatty substances, preferably esters of fatty acids with lower alcohols, such as esters with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with lower chain alkanoic acids or fatty acids;

[0086] - alkyl benzoates;

[0087] - silicone oils, such as dimethylpolysiloxane, diethylpolysiloxane, diphenylpolysiloxane and their mixed forms.

[0088] The oil phase of the emulsion, oil gel or aqueous dispersion or lipid dispersion in the sense of the present invention is advantageously selected from esters obtained from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with 3 to 30 carbon atoms in the chain length and saturated and / or unsaturated, branched and / or unbranched alcohols with 3 to 30 carbon atoms in the chain length, and esters obtained from aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols with 3 to 30 carbon atoms in the chain length. These ester oils can thus advantageously be selected from the following 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-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, dibutyl adipate, propylheptyl octanoate, diisopropyl adipate, cetearyl isononanoate, erucyl oleate, oleyl erucate, erucyl erucate, and synthetic, semi-synthetic and natural mixtures of such esters, such as jojoba oil.

[0089] The aqueous phase of the preparation according to the invention advantageously contains, if necessary, humectants such as propylene glycol, panthenol or hyaluronic acid, used individually or in combination.

[0090] In particular, mixtures of the above solvents are used. In the case of alcoholic solvents, water can be another component.

[0091] The emulsion according to the invention is advantageous and contains, for example, the fats, oils, waxes and other fatty substances described, as well as water and an emulsifier, which are commonly used in this type of formulation.

[0092] The gel according to the invention generally contains lower alcohols, such as ethanol, propylene glycol, and water, or the above oils are used in the presence of a thickening agent.

[0093] Volatile liquefied propellants commonly known, such as hydrocarbons (propane, butane, isobutane) are suitable as propellants for the preparations according to the invention that can be sprayed from an aerosol container, which can be used alone or mixed with each other. It is also advantageous to use compressed air.

[0094] Advantageously, the preparation according to the invention may also contain substances that absorb UV radiation in the UVB range, wherein the total amount of the filtering substances is, for example, from 0.1% to 30% by weight, preferably from 0.5 to 10% by weight, in particular from 1.0 to 6.0% by weight, relative to the total weight of the preparation, to provide a cosmetic preparation for protecting hair or skin from various ultraviolet radiations. They can also be used as sunscreens for hair or skin.

[0095] Furthermore, the preparation according to the invention may also contain substances that mask the disturbing inherent odors of the remaining raw materials used, wherein the total amount of the perfume ingredients is, for example, from 0.001% to 30% by weight, preferably from 0.05 to 10% by weight, in particular from 0.1 to 5.0% by weight, relative to the total weight of the preparation, to provide a cosmetic preparation. Detailed Description

[0096] Test Description:

[0097] To determine the influence of the biopolymer used in the formulation in combination with the active substance N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide on odor development and to compare it with the synthetic polymer sodium polyacrylate (INCI: Sodium Polyacrylate), the samples were irradiated for 48 hours with the so-called Atlas Suntester. All samples were placed in 30 ml test bottles. The irradiance of the device was 250 W / m 2 , which is equivalent to storing the samples in the light window for 8 months after irradiating them for 48 hours. Subsequently, the unopened samples were evaluated by a team of trained fragrance experts to assess the odor development and odor intensity. To establish the comparability of the methods, all other odor-influencing ingredients of the formulations were removed or used at the same concentration. In particular, this means that all formulations were free of fragrances and had the same ethanol concentration.

[0098]

[0099]

[0100]

[0101] The following examples are intended to illustrate the invention without limiting it. Unless otherwise stated, all quantities, shares, and percentages are based on weight and total amounts or on the total weight of the preparation.

[0102]

[0103]

[0104]

Claims

1. An active substance combination, which is composed of one or more alkylaminothiazoles and one or more cosmetically or dermatologically safe biopolymers suitable for increasing the viscosity of an aqueous solution, and the biopolymers are selected from polysaccharides esterified and / or etherified with alcohols and / or carboxylic acids having one or more hydroxyl groups, and unesterified and unetherified polysaccharides composed of interconnected glucose units and / or mannose units and / or galactose units and / or glucuronic acid units and / or rhamnose units, wherein if xanthan gum or hydroxypropyl starch phosphate is selected as the biopolymer, at least one other biopolymer must be present.

2. The active substance combination according to claim 1, characterized in that, the one or more biopolymers are selected from dehydroxanthan gum, gellan gum, xanthan gum, hydroxypropyl starch phosphate and any mixture thereof.

3. The active substance combination according to claim 2, characterized in that, the mixture is selected from (a) dehydroxanthan gum, (b) gellan gum, (c) xanthan gum, (d) hydroxypropyl starch phosphate, and the weight ratios a:b, a:c, a:d, b:c, b:d and c:d each independently take rational numbers between 0 and 10.

4. The active substance combination according to claim 2, characterized in that, the mixture is selected from (a) dehydroxanthan gum, (b) gellan gum, (c) xanthan gum, (d) hydroxypropyl starch phosphate, and the weight ratio a:b:c:d is related as follows: (0.1 to 5):(0.1 to 5):(0.1 to 5):(0.1 to 5).

5. The active substance combination according to any one of the preceding claims, characterized in that, the one or more alkylaminothiazoles are substances of the following general formula: wherein R 1 、R 2 、X, and Y can be different, partially the same, or completely the same, and can each independently represent: R 1 = -C 1 -C 24 alkyl (linear and branched), -C 1 -C 24 alkenyl (linear and branched), -C 1 -C 8 cycloalkyl, -C1-C8 cycloalkyl-alkyl hydroxy, -C 1 -C 24 alkyl hydroxy (linear and branched), -C 1 -C 24 alkyl amine (linear and branched), -C 1 -C 24 -alkyl aryl (linear and branched), -C1-C24-alkyl-aryl-alkyl hydroxy (linear and branched), -C 1 -C 24 -alkyl heteroaryl (linear and branched), -C 1 -C 24 -alkyl-O-C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkyl morpholinyl, -C 1 -C 24 -alkyl piperidinyl, -C 1 -C 24 -alkyl piperazinyl, -C 1 -C 24 -alkyl piperazinyl-N-alkyl, R 2 = H, -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 24 -hydroxyalkyl (linear and branched), -C 1 -C 24 -alkylaryl (linear and branched), -C 1 -C 24 -alkylheteroaryl (linear and branched), X = -H, -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 24 -aryl (optionally mono- or polysubstituted by -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN), -C 1 -C 24 -heteroaryl (optionally mono- or polysubstituted by -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN), -C 1 -C 24 -alkylaryl (linear and branched), -C 1 -C 24 -alkylheteroaryl (linear and branched), -aryl (optionally mono- or polysubstituted by -OH, -F, -Cl, -Br, -I, -OMe, -NH 2 , -CN), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl Y = H, -C 1 -C 24 -alkyl (linear and branched), -C 1 -C 24 -alkenyl (linear and branched), -C 1 -C 8 -cycloalkyl, -C 1 -C 24 -aryl, -C 1 -C 24 -heteroaryl, -C 1 -C 24 -alkylaryl (linear and branched), -C 1 -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 and Y may optionally also represent fused aromatic groups; wherein X and Y may form an aromatic or aliphatic homocyclic or heterocyclic system having at most n ring atoms with each other, and the number n may take a value of 5 to 8, and each ring system may in turn be substituted by at most n - 1 alkyl, hydroxyl, carboxyl, amino, nitrile functional groups, sulfur-containing substituents, ester groups and / or ether groups, wherein the one or more alkylaminothiazoles may exist either in the form of the free base or in the form of cosmetically and dermatologically acceptable salts.

6. The active substance combination according to any one of the preceding claims, characterized in that, the one or more alkylaminothiazoles have the following structures: N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)pivalamide 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)heptamide 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.

7. The combination of active substances according to any one of the preceding claims, characterized in that the one or more alkylaminothiazoles may be present in the form of halides, carbonates, ascorbates, sulfates, acetates and / or phosphates.

8. A cosmetic or dermatological preparation containing the combination of active substances according to any one of the preceding claims.

9. The preparation according to claim 8, characterized in that it contains 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, in particular 0.001 to 1% by weight of one or more alkylaminothiazoles, relative to the total weight of the preparation.

10. The preparation according to any one of the preceding claims, characterized in that the total amount of one or more biopolymers in the preparation is 0.0001 - 10% by weight, preferably 0.001 - 5% by weight, particularly preferably 0.005 - 3% by weight.

11. The preparation according to any one of the preceding claims, characterized in that it has a slightly alkaline pH value, i.e. a value between 7 and 9, preferably between 7 and 8, in particular between 7.4 and 7.

6.

12. Non-therapeutic cosmetic use of the preparation or combination of active substances according to any one of the preceding claims for lightening human skin.

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