Active ingredient combination of alkylamidothiazoles with one or more biopolymers

Abstract

1. An active ingredient combination of one or more alkylamidothiazoles with one or more cosmetically or dermatologically unproblematic biopolymers suitable for increasing the viscosity of aqueous solutions, selected from the group of polysaccharides esterified and / or etherified with alcohols and / or carboxylic acids having one or more hydroxyl groups, and non-esterified and non-etherified polysaccharides composed of glucose units, mannose units, galactose units, glucuronic acid units and / or rhamnose units linked to one another, wherein if xanthan 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 ingredient combination of one or more alkylamidothiazoles and one or more biopolymers. Furthermore, the present invention relates to cosmetic or dermatological preparations containing such active ingredient combinations and their use for whitening human skin.

[0002] Melanocytes are responsible for skin pigmentation and are present in the stratum basale, the lowest layer of the epidermis, as pigment-producing cells that occur sporadically or in more or less layers alongside basal cells, depending on the skin type.

[0003] Melanocytes contain melanosomes as characteristic organelles where melanin is formed. In particular, when stimulated by UV rays, more melanin is produced. Melanin is eventually transported through the living layers of the epidermis (keratinocytes) to the stratum corneum (corneocytes), where it gives rise to the skin's color, which can range from a more or less pronounced brownish to brownish-black.

[0004] Melanin is formed as the final step in an oxidation process in which tyrosine is converted through several intermediate steps, with the cooperation of the enzyme tyrosinase, into brown to brownish-black eumelanins (DHICA and DHI melanins), or into reddish pheomelanins with the involvement of sulfur-containing compounds. DHICA and DHI melanins are generated via the common intermediate steps dopaquinone and dopachrome. The latter is converted, in part with the cooperation of additional enzymes, into indole-5,6-quinonecarboxylic acid or indole-5,6-quinone, from which the two eumelanins mentioned are generated.

[0005] Pheomelanin production occurs primarily through the intermediates dopaquinone and cysteinyldopa. The expression of melanin synthesis enzymes is controlled by a specific transcription factor (microphthalmia-associated transcription factor, MITF). In addition to the enzymatic process of melanin synthesis described above, additional proteins within melanosomes are also important for melanogenesis. Here, the so-called p protein appears to play a key role, although its exact function remains unclear.

[0006] In addition to the above-mentioned process of melanin synthesis in melanocytes, the transport of melanosomes, their retention in the epidermis, and their degradation and degradation of melanamine are also very important in skin pigmentation. It has been found 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 affect their light scattering properties and therefore the appearance of skin color. Thus, in African-Americans, significantly larger, spheroidal, individual melanosomes are found, whereas in Caucasians, smaller, clustered melanosomes are found.

[0008] Skin hyperpigmentation problems can have various causes or are a side effect of many biological processes, such as UV radiation (e.g., freckles, ebony), genetic predisposition, abnormal pigmentation of the skin during wound healing or scarring (post-inflammatory hyperpigmentation) or skin aging (e.g., age spots).

[0009] After an inflammatory reaction, the skin pigmentation system undergoes partially opposing reactions. Both post-inflammatory hyperpigmentation and hypopigmentation can occur. In particular, post-inflammatory hypomelanosis often occurs in association with atopy, lupus erythematosus, and psoriasis. The various forms of reaction of the human skin pigmentation system as a result of inflammatory manifestations are very poorly understood.

[0010] Post-inflammatory hyperpigmentation problems often occur in darker skin types. Pseudofolliculitis barbae, which is associated with or accompanies cosmetically undesirable abnormal pigmentation, is a known problem, particularly in men of color. Melasma, which occurs on the face and décolleté area, especially in Asian women, as well as various forms of irregular skin pigmentation, are also considered post-inflammatory hyperpigmentation. Furthermore, dark circles under the eyes are also seen as a form of post-inflammatory hyperpigmentation, and the underlying inflammation often progresses asymptomatically.

[0011] In many cases, such post-inflammatory hyperpigmentation is further intensified by the action of sunlight (UV light) without causing UV-induced inflammation (sunburn).

[0012] Active ingredients and preparations that suppress skin pigmentation are known. In practical use, most preparations are based on hydroquinone, which, on the one hand, only shows its effect after several weeks of application, and on the other hand, its excessively long application is questionable for toxicological reasons. Albert Kligman et al. proposed the so-called "Triformula," which is 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 possibility of irreversible changes in the skin pigmentation system.

[0013] Furthermore, dermabrasion methods (chemical and mechanical "peeling") are applied, which are often accompanied by an inflammatory response and may even increase rather than decrease pigmentation due to the subsequent post-inflammatory hyperpigmentation. All of these common methods, which are also applied to treat post-inflammatory hyperpigmentation, are characterized by significant side effects.

[0014] Furthermore, a variety of other substances are known that have been described for their skin-lightening effect, including, inter alia, 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 in a publication (Bioorganic & Medicinal Chemistry Letter 17 (2007) 6871-6875) describes inter alia the effectiveness of substituted thiazole derivatives for inhibiting mushroom tyrosinase.

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

[0017] The substances described in the prior art mentioned above show moderate effectiveness.

[0018] Dark circles under the eyes can also be the result of pigmentation disorders, and they also appear as a reaction to general stress, such as lack of sleep or simply overuse of the eyes.In relatively young people, these symptoms disappear after a night of adequate rest, but this condition can become chronic over a long period of time and become very troublesome for the affected person.In addition, there is a lack of sufficiently promising active ingredients and treatment options for such skin symptoms.

[0019] The sense of smell is one of the five human senses. Here, odorants, which are easily volatile substances, are bound by odor receptors in the nasal mucosa. The impulse is transmitted to neurons via a signal cascade and then to the brain, where the actual perception of odor occurs. Pleasant odors are distinguished from unpleasant odors.

[0020] However, in many cases, cosmetics also have some unpleasant inherent odors caused by the raw materials used.Alkylamidothiazoles may also be involved in the deterioration of the fragrance experience of cosmetic foundations in some cases.It is necessary to address this problem.

[0021] This problem is solved by an active ingredient combination of one or more alkylamidothiazoles with one or more cosmetically or dermatologically unproblematic biopolymers suitable for increasing the viscosity of aqueous solutions, selected from the group of polysaccharides esterified and / or etherified with alcohols and / or carboxylic acids having one or more hydroxyl groups, and non-esterified and non-etherified polysaccharides composed of glucose units, mannose units, galactose units, glucuronic acid units and / or rhamnose units linked to one another, in which at least one further biopolymer must be present if xanthan or hydroxypropyl starch phosphate is selected as the biopolymer.

[0022] Preferably, the formulation according to the invention contains 0.0001 to 10% by weight of one or more biopolymers, preferably 0.001 to 5% by weight of one or more biopolymers, particularly preferably 0.005 to 3% by weight of one or more biopolymers.

[0023] Advantageously, in particular the formulation or use according to the invention is characterized in that the formulation contains 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, very in particular 0.001 to 1% by weight, of one or more alkylamidothiazoles, based on the total weight of the formulation.

[0024] Advantageous alkylamidothiazoles within the meaning of the present invention have the general formula: [ka] [In the formula, R 1 , R 2, X and Y may be different, partially identical, or completely identical, and 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 to C 24 Alkylamines (linear and branched), -C1 to 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 alkyl-piperazino-N-alkyl, 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), 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 to -C 24-heteroaryl (optionally mono- or polysubstituted with -OH, -F, -Cl, -Br, -I, -OMe, -NH, -CN), -C1-C 24 -Alkylaryl (linear and branched), -C1-C 24 means -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 means -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, X and Y may also represent fused aromatic rings, X and Y may together form an aromatic or aliphatic homocyclic or heterocyclic ring system having up to n ring-forming atoms, the number n having a value from 5 to 8, and each ring system may also be substituted with up to n-1 alkyl, hydroxyl, carboxyl, amino, nitrile functional groups, sulfur-containing substituents, ester and / or ether groups. It is a substance.

[0025] The thiazoles mentioned can be present both as free bases and as salts, for example as fluorides, chlorides, bromides, iodides, sulfates, carbonates, ascorbates, acetates or phosphates, in particular as halogen salts, such as chlorides and bromides.

[0026] Furthermore, an advantageous realization of the invention is a cosmetic or dermatological preparation having an effective content of one or more of the above-mentioned alkylamidothiazoles.

[0027] Furthermore, according to the present invention, there is provided the use of the aforementioned alkylamidothiazoles for the treatment and / or prevention of unwanted skin pigmentation, wherein the treatment and / or prevention of unwanted skin pigmentation can be carried out both in the cosmetic field and in the pharmaceutical field.

[0028] Here, pharmaceutical (or dermatological) treatment is understood to be primarily in diseased skin conditions, whereas cosmetic treatment and / or prevention of unwanted skin pigmentation primarily concerns healthy skin.

[0029] Advantageously, X is selected from the group of substituted phenyl and the substituents (Z) can be selected from the group -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl and can be the same or different.

[0030] [ka]

[0031] Particularly advantageously, X is selected from the group of phenyl groups substituted with one or more hydroxy groups, the substituents (Z) can be selected from the group -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl, and the following general structure is preferred, in which Y, R 1 and R 2 may have the properties defined above.

[0032] [ka]

[0033] especially, X= [ka] 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 to C 24 Alkylamines (linear and branched), -C1 to 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 alkyl-piperazino-N-alkyl, R2=H, -C1~C 24 - alkyl (linear and branched), Z = -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl Advantageously, the compound is

[0034] X= [ka] 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 to C 24 Alkylamines (linear and branched), -C1 to 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 alkyl-piperazino-N-alkyl, R2=H Particularly preferred is a compound wherein:

[0035] These compounds: [ka] [ka] [ka] is preferred according to the invention.

[0036] [ka] is very particularly preferred.

[0037] Previous alkylamidothiazoles, their synthesis and applications are described in EP-A-2758381.

[0038] Preferred biopolymers according to the present invention include dehydroxanthan, gellan (INCI: Gellan Gum), xanthan, hydroxypropyl starch phosphate (INCI: Hydroxypropyl Starch Phosphate) and any mixtures thereof.

[0039] In the sense of the present invention, a) Dehydroxanthan b) gellan, c) xanthan, d) hydroxypropyl starch phosphate; and wherein the weight ratios a:b, a:c, a:d, b:c, b:d and c:d each have a ratio independently of one another such that they are rational numbers from 0 to 10.

[0040] In the sense of the present invention, a) Dehydroxanthan b) gellan, c) xanthan, d) hydroxypropyl starch phosphate; and a mixture of the following in weight ratios a:b:c:d relative to one another: (0.1~5):(0.1~5):(0.1~5):(0.1~5) Very particularly preferred are mixtures which have the formula:

[0041] It may be advantageous to avoid other substances that increase the viscosity of aqueous solutions ("thickeners"), in particular polyacrylates, which have the effect of increasing the viscosity of aqueous solutions.

[0042] Cosmetic or dermatological preparations containing alkylamidothiazoles and biopolymers according to the invention, or their use for the treatment and / or prevention of unwanted skin pigmentation, are likewise advantageous realizations of the invention.

[0043] It is particularly advantageous if such formulations contain 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, and very particularly 0.001 to 1% by weight, of one or more alkylamidothiazoles used according to the invention, based on the total weight of the formulation.

[0044] Within the meaning of the present invention, it is highly advantageous if the formulation has a slightly basic pH value, ie a value between 7 and 9, preferably between 7 and 8, in particular between 7.4 and 7.6.

[0045] The cosmetic and dermatological preparations according to the invention can be in various forms. They can thus be, for example, solutions, anhydrous preparations, water-in-oil (W / O) or oil-in-water (O / W) emulsions or microemulsions, multiple emulsions, for example water-in-oil-in-water (W / O / W) multiple emulsions, gels, solid sticks, ointments or aerosols. 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 common encapsulating materials, for example in gelatin as cellulose encapsulation or in liposomes.

[0046] It is also possible, and advantageous within the context 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.

[0047] The cosmetic and dermatological preparations according to the invention may contain cosmetic auxiliaries such as preservatives, bactericides, fragrances, substances for preventing foaming, dyes, pigments with a coloring effect, thickeners, surface-active substances, emulsifiers, emollients, moisturizing and / or hydrating substances, fats, oils, waxes, or other typical constituents of cosmetic or dermatological formulations, such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives, as are commonly used in such preparations.

[0048] The lipid phase can advantageously be chosen from the following group of substances: - Mineral oil, mineral wax, oils such as capric or caprylic triglycerides, as well as natural oils, for example castor oil; fats, waxes and other natural and synthetic fatty bodies, preferably esters of fatty acids with alcohols of low C number, such as isopropanol, propylene glycol or glycerin, or esters of fatty alcohols with alkanoic acids of low C number or with fatty acids, alkyl benzoates, - Silicone oils such as dimethylpolysiloxane, diethylpolysiloxane, diphenylpolysiloxane, and mixtures thereof.

[0049] The oil phase of the emulsions, oleogels or aqueous or lipid dispersions 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 carbon 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 with saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 C atoms. Such ester oils may 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, and synthetic, semi-synthetic and natural mixtures of such esters, for example jojoba oil.

[0050] The aqueous phase of the preparation according to the invention optionally and advantageously contains moisturizing agents, such as, for example, propylene glycol, panthenol or hyaluronic acid, either individually or in combination.

[0051] In particular, mixtures of the aforementioned solvents are used. In the case of alcoholic solvents, water may be a further constituent.

[0052] The emulsions according to the invention are advantageous and contain, for example, the fats, oils, waxes and other fatty bodies mentioned, as well as water and emulsifiers as are commonly used in formulations of this type.

[0053] Gels according to the invention generally contain a low C number alcohol, such as ethanol, propylene glycol, and water or an oil as mentioned above, in the presence of a thickener.

[0054] Suitable propellants for the formulations according to the invention that can be sprayed from aerosol containers are the commonly known readily volatile liquefied propellants, such as hydrocarbons (propane, butane, isobutane), which can be used alone or in admixture with one another. Advantageously, compressed air is also used.

[0055] Advantageously, the formulations according to the invention may further contain substances that absorb UV rays 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 formulation, in order to provide cosmetic formulations that protect hair or skin from the entire UV range, which can also serve as sunscreens for hair or skin.

[0056] Furthermore, advantageously, the formulation according to the invention may further contain substances that mask the unpleasant inherent odor of the remaining raw materials used, the total amount of perfume ingredients being, for example, 0.001% 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 formulation, in order to provide a formulation suitable for cosmetic use.

[0057] Test Description: To determine the effect of the biopolymers used in the formulations on odor development in combination with the active ingredient N-(4-(2,4-dihydroxyphenyl)thiazol-2-yl)isobutyramide, in comparison with the synthetic polymer Sodium Polyacrylate (INCI), samples were irradiated for 48 hours using so-called Atlas Suntesters. All samples were contained in 30 ml sample vials. The irradiance of the device was 250 W / m², which corresponds to 8 months of sample storage in a light window after 48 hours of irradiation. The samples were then evaluated unopened by a panel of trained odor experts to assess odor development and odor intensity. To compare batches, all other components of the formulations that affect odor were removed or used at the same concentration. In certain cases, this means that all formulations were fragrance-free and had the same ethanol concentration.

[0058] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4]

[0059] The following examples are intended to clarify, but not limit, the invention. Unless otherwise specified, all amounts, parts and percentages are by weight and total amount or weight of the formulation.

[0060] [Table 2-1]

Table 2-2

Table 2-3

Claims

1. 1. An active ingredient combination of one or more alkylamidothiazoles with one or more cosmetically or dermatologically unproblematic biopolymers suitable for increasing the viscosity of aqueous solutions, selected from the group of polysaccharides esterified and / or etherified with alcohols and / or carboxylic acids having one or more hydroxyl groups, and non-esterified and non-etherified polysaccharides composed of glucose units, mannose units, galactose units, glucuronic acid units and / or rhamnose units linked to one another, wherein if xanthan or hydroxypropyl starch phosphate is selected as the biopolymer, at least one further biopolymer must be present.

2. 2. The active ingredient combination according to claim 1, characterized in that the biopolymer is selected from the group consisting of dehydroxanthan, gellan gum, xanthan, hydroxypropyl starch phosphate and any mixture thereof.

3. a) dehydroxanthan, b) gellan, c) xanthan, d) Hydroxypropyl starch phosphate 3. The active ingredient combination according to claim 2, wherein the weight ratios a:b, a:c, a:d, b:c, b:d and c:d are each independently a rational number between 0 and 10.

4. a) dehydroxanthan, b) gellan, c) xanthan, d) Hydroxypropyl starch phosphate and a mixture of a:b:c:d in the following weight ratios relative to each other: （０．１～５）：（０．１～５）：（０．１～５）：（０．１～５） 3. The active ingredient combination according to claim 2, characterized in that it comprises:

5. The alkylamidothiazole has the general formula: 【Chemical 1】 [In the formula, R １ , R ２ , X and Y may be different, partially identical, or completely identical, and independently of each other, 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-alkylhydroxy, -C １ ~C ２４ Alkylhydroxy (linear and branched), -C １ ~C ２４ Alkylamines (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 -alkylheteroaryl (linear and branched), -C １ ~C ２４ -Alkyl-O-C 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 alkyl-piperazino-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 -OH, -F, -Cl, -Br, -I, -OMe, -NH ２ , mono- or polysubstituted with —CN), —C １ ~C ２４ -heteroaryl (optionally -OH, -F, -Cl, -Br, -I, -OMe, -NH ２ , mono- or polysubstituted with —CN), —C １ ~C ２４ - alkylaryl (linear and branched), -C １ ~C ２４ -alkylheteroaryl (linear and branched), -aryl (optionally -OH, -F, -Cl, -Br, -I, -OMe, -NH ２ , mono- or polysubstituted by —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 means -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, X and Y may also represent fused aromatic groups, X and Y together can form an aromatic or aliphatic homo- or heterocyclic ring system having up to n ring-forming atoms, the number n can have a value from 5 to 8, and each ring system can also be substituted with up to n-1 alkyl, hydroxyl, carboxyl, amino, nitrile functional groups, sulfur-containing substituents, ester and / or ether groups; The alkylamidothiazoles can exist as free bases or as cosmetically and dermatologically acceptable salts.

5. The active ingredient combination according to claim 1, wherein the active ingredient combination is a substance of formula (I).

6. The alkylamidothiazole has the following structure: 【Chemistry 2-1】 【Chemistry 2-2】 【Chemistry 2-3】 【Chemistry 2-4】 6. The active ingredient combination according to claim 1, wherein the active ingredient combination comprises:

7. 7. The active ingredient combination according to claim 1, wherein the alkylamidothiazoles can be present as halides, carbonates, ascorbates, sulfates, acetates and / or phosphates.

8. 8. Cosmetic or dermatological preparations containing an active ingredient combination according to any one of claims 1 to 7.

9. 9. Formulation according to claim 8, characterized in that the formulation contains 0.000001 to 10% by weight, in particular 0.0001 to 3% by weight, and very particularly 0.001 to 1% by weight of one or more alkylamidothiazoles, based on the total weight of the formulation.

10. 10. Formulation according to claim 8 or 9, characterized in that the total amount of the formulation is 0.0001 to 10% by weight of one or more biopolymers, preferably 0.001 to 5% by weight of one or more biopolymers, particularly preferably 0.005 to 3% by weight of one or more biopolymers.

11. 11. Formulation according to any one of claims 8 to 10, characterized in that the formulation has a slightly basic pH value, i.e. a value between 7 and 9, preferably between 7 and 8, in particular between 7.4 and 7.

6.

12. 12. Cosmetic, non-therapeutic use of a formulation or active ingredient combination according to any one of claims 1 to 11 for whitening human skin.

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