EP4687824A1

EP4687824A1 - Combinations of one or more alkylamidothiazoles, tocopherol and 3-o-ethyl ascorbic acid and cosmetic preparations containing such combinations

Info

Publication number: EP4687824A1
Application number: EP24712016.5A
Authority: EP
Inventors: Donglin XIE; Xiao Zhu; Hanjun CHEN; Luan LUAN; Lu Wang
Original assignee: Beiersdorf AG
Current assignee: Beiersdorf AG
Priority date: 2023-04-04
Filing date: 2024-03-13
Publication date: 2026-02-11
Also published as: AU2024243403A1; WO2024208548A1; MX2025011809A; CN118766785A; KR20250163986A; CN121001701A; WO2024207204A1

Abstract

The present invention belongs to the cosmetic field, and relates to active ingredient combinations of a) one or more alkylamidothiazoles, b) tocopherol, and c) 3-O-ethyl ascorbic acid, and cosmetic preparations containing such combinations. It is found that the active ingredient combinations of the present invention may prevent or reduce the deterioration of alkylamidothiazoles caused by oxidative processes and/or heat and/or UV-light in cosmetic preparations containing one or more alkylamidothiazoles.

Description

Combinations of one or more alkylamidothiazoles, tocopherol and 3-O-ethyl ascorbic acid and cosmetic preparations containing such combinations Technical field The present invention belongs to the cosmetic field, and specifically relates to combinations of one or more alkylamidothiazoles, tocopherol and 3-O-ethyl ascorbic acid and cosmetic preparations containing such combinations. Background art In general, cosmetic products not only serve to look beautiful and attractive, but with their effect they make a decisive contribution to increased self-esteem and the well-being of people. Accordingly, a wide variety of cosmetic products are used for the daily cleaning and care of human skin. For example, cosmetic preparations for the care of human skin are known from DE 102011083259 A1, which contain alkylamidothiazoles. The alkylamidothiazoles used are used in the cosmetic preparations to combat and prevent undesired pigmentation of the skin. In this way, the user's complexion can be decisively improved. It is also known from DE 102013226711 A1 that alkylamidothiazoles can be used in cosmetic or dermatological preparations for the prophylaxis and treatment of sensitive skin, itching, dry skin and inflammatory symptoms of human skin. The document discloses various cosmetic O/W emulsions for application to human skin. Furthermore, DE 102013204110 A1 discloses a large number of cosmetic preparations for the care of human skin containing alkylamidothiazoles. A particularly effective lightening of human skin is achieved by the combined use of alkylamidothiazoles with one or more cyclodextrins. However, the fact that the person skilled in the art knows a large number of cosmetic preparations containing alkylamidothiazoles must not obscure the fact that a large number of problems can arise when formulating cosmetic or dermatological preparations. A disadvantage, for example, is the fact that the color of newly produced cosmetic or dermatological preparations changes during storage. This occurs more intensely when the preparation is exposed to light. This circumstance creates considerable difficulties for manufacturers of cosmetic preparations, since it is necessary to carry out studies on the color stability of cosmetic preparations. This often requires a large number of approaches, which significantly increases the development costs of cosmetic products. It is therefore desirable to provide systems and methods which effectively prevent or minimize degradation processes in cosmetic or dermatological preparations, so that the development costs can be minimized. The problem of degradation processes in cosmetic or dermatological preparations is also relevant for the consumer. Products are often selected based on their optical appearance or their skin. However, if the white appearance of a product deteriorates over the storage period, the consumer is usually annoyed because the decisive purchase criterion is no longer met. The color stability of cosmetic or dermatological preparations can in principle be assessed by specially trained personnel who compare the color of a freshly prepared preparation (within 24 hours of preparation) and after a corresponding storage time. However, the color change of the products is always very difficult to judge. It is, therefore, advantageous using a special instrument called Digi-Eye on the color change. Summary of the invention One object of the present invention was therefore to provide a way of preventing or minimizing degradation processes in cosmetic products in a particularly effective manner, so that color stability is ensured. This object is achieved by active ingredient combinations of a) one or more alkylamidothiazoles, b) tocopherol, and c) 3-O-ethyl ascorbic acid. Astonishingly the combination of tocopherol and 3-O-ethyl ascorbic acid acts in a synergistic way in comparison to the single substances to prevent or reduce the deterioration of alkylamido- thiazoles caused by oxidative processes and/or heat and/or UV-light. Another embodiment of the present invention is cosmetic preparations containing such combinations. Yet another embodiment of the present invention is use of active ingredient combinations of b) tocopherol, and c) 3-O-ethyl ascorbic acid to prevent or reduce the deterioration of alkylamidothiazoles caused by oxidative processes and/or heat and/or UV-light in cosmetic preparations containing one or more alkylamidothiazoles. 3-O-ethyl ascorbic acid is a well-known antioxidant and free radical scavenger. It not only protects against skin damage caused by sun exposure, but is also able to repair existing skin damage. It ensures improved collagen synthesis, helps to reduce wrinkles and also has a skin- lightening effect. Advantageous embodiments of the present invention are also cosmetic or dermatological preparations with a content of such active ingredient combination, and the use thereof for lightening human skin. Advantageously, preparations according to the invention comprise formulations, where the total amount of the one or more alkylamidothiazoles is e.g. 0.00001% by weight to 10% by weight, preferably 0.001% by weight to 5% by weight, in particular 0.005% by weight to 3% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations. Advantageously, preparations according to the invention comprise formulations, where the total amount of the tocopherol is e.g. 0.00001% by weight to 10% by weight, preferably 0.001% by weight to 5% by weight, in particular 0.005% by weight to 3% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations. Advantageously, preparations according to the invention comprise formulations, where the total amount of the 3-O-ethyl ascorbic acid is e.g. 0.00001% by weight to 10% by weight, preferably 0.001% by weight to 5% by weight, in particular 0.005% by weight to 3% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations. Advantageous alkylamidothiazoles in the context of the present invention are substances of the general formula in which R1, R2, X and Y can be different, partly identical or completely identical and, independently of one another, can mean: R1= -C1-C24-alkyl (linear and branched), -C1-C24-alkenyl (linear and branched), -C1-C8- cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C24-alkylhydroxy (linear and branched), -C1-C24 alkylamine (linear and branched), -C1-C24-alkylaryl (linear and branched), -C1-C24-alkylaryl- alkyl-hydroxy (linear and branched), -C1-C24-alkylheteroaryl (linear and branched), -C1-C24- alkyl-O-C1-C24-alkyl (linear and branched), -C1-C24 alky-morpholino, -C1-C24 alky-piperidino, - C1-C24 alky-piperazino, -C1-C24 alky-piperazino-N-alkyl, 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), X= -H, -C1-C24-alkyl (linear and branched), -C1-C24-alkenyl (linear and branched), -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, 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=condensed aromatic, where X and Y can form with one another 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. Said thiazoles can either be in the form of the free base or the salt: e.g. fluoride, chloride, bromide, iodide, sulfate, carbonate, ascorbate, acetate or phosphate. In particular in the form of halogen salts, such as e.g., chloride and bromide. Furthermore, there is an advantageous realization of the present invention in cosmetic or dermatological preparations with an effective content of one or more aforementioned alkylamidothiazoles. Also in accordance with the invention is the use of the aforementioned alkylamidothiazoles for the treatment and/or prophylaxis of undesired skin pigmentation. Here, treatment and/or prophylaxis of undesired skin pigmentation can be both in the cosmetic sphere and in the pharmaceutical sphere. In this connection, the pharmaceutical (or dermatological) treatment is primarily understood for diseased skin conditions, whereas the cosmetic treatment and/or prophylaxis of undesired skin pigmentation primarily relates to healthy skin. Advantageously, X is selected from the group of substituted phenyls, in which case the substituents (Z) can be selected from the group of -H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl and can be identical or different. Particularly advantageously, X is selected from the group of phenyl groups substituted with one or more hydroxy groups, in which case the substituent (Z) can be selected from the group of -H, - OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl, and preference is given to the following generic structure in which Y, R1 and R2 can have the same definitions above. [0034] Particularly advantageous compounds are those in which R1= -C1-C24-alkyl (linear and branched), -C1-C24-alkenyl (linear and branched), -C1-C8- cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C24 alkylhydroxy (linear and branched), -C1-C24 alkylamine (linear and branched), -C1-C24-alkylaryl (linear and branched), -C1-C24-alkylaryl- alkyl-hydroxy (linear and branched), -C1-C24-alkylheteroaryl (linear and branched), -C1-C24- alkyl-O-C1-C24-alkyl (linear and branched), -C1-C24-alky-morpholino, -C1-C24 alky-piperidino, - C1-C24 alky-piperazino, -C1-C24 alky-piperazino-N-alkyl, R2= H, -C1-C24-alkyl (linear and branched), Z=-H, -OH, -F, -Cl, -Br, -I, -OMe, -NH2, -CN, acetyl. Particular preference is given to those compounds in which Image available on "Original document". R1= -C1-C24-alkyl (linear and branched), -C1-C24-alkenyl (linear and branched), -C1-C8- cycloalkyl, -C1-C8-cycloalkyl-alkylhydroxy, -C1-C24-alkylhydroxy (linear and branched), -C1-C24 alkylamine (linear and branched), -C1-C24-alkylaryl (linear and branched), -C1-C24-alkyl-aryl- alkyl-hydroxy (linear and branched), -C1-C24-alkylheteroaryl (linear and branched), -C1-C24- alkyl-O-C1-C24-alkyl (linear and branched), -C1-C24 alky-morpholino, -C1-C24 alky-piperidino, - C1-C24 alky-piperazino, -C1-C24 alky-piperazino-N-alkyl, R2= H The following compounds are most preferred ones within the scope of the present invention: 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)-4-(hydroxymethyl)cyclohexanecarboxamide} . Cosmetic or dermatological preparations with a content of alkylamidothiazoles and their use for the treatment and/or prophylaxis of undesired skin pigmentation are likewise advantageous embodiments of the present invention. It is particularly advantageous if such preparations comprise 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. Cosmetic and dermatological preparations according to the invention can be in various forms. Thus, they can be e.g., a solution, an anhydrous preparation, an emulsion or micro-emulsion of the water-in-oil (W/O) type or of the oil-in-water (O/W) type, a multiple emulsions, for example of the water-in-oil-in-water (W/O/W) type, a gel, a solid stick, a balm or else an aerosol. It is also advantageous according to the invention to administer the substances used according to the invention and/or their derivatives in encapsulated form, e.g. in collagen matrices and other customary encapsulation materials, e.g. as cellulose encapsulations, in gelatin or liposomally encapsulated. It is also possible and advantageous in the context of the present invention to add the substances used according to the invention and/or their derivatives in aqueous systems or surfactant preparations for cleaning the skin and the hair. The cosmetic and dermatological preparations according to the invention can comprise 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 constituents of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives. The lipid phase can advantageously be selected from the following substance group: mineral oils, mineral waxes oils, such as triglycerides of capric acid or of caprylic acid, also natural oils such as e.g. castor oil; fats, waxes and other natural and synthetic fatty bodies, preferably esters of fatty acids with alcohols of low carbon number, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids of low carbon number or with fatty acids; alkyl benzoates; silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixtures thereof. The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions within the context of the present invention is advantageously selected from the group of esters of saturated and/or unsaturated, branched and/or unbranched alkanecarboxylic acids of chain length from 3 to 30 C atoms and saturated and/or unsaturated, branched and/or unbranched alcohols of chain length from 3 to 30 C atoms, from the group of esters of aromatic carboxylic acids and saturated and/or unsaturated, branched and/or unbranched alcohols of chain length from 3 to 30 C atoms. Such ester oils can then advantageously be selected from the group of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate, and synthetic, semisynthetic and natural mixtures of such esters, e.g. jojoba oil. The aqueous phase of the preparations according to the invention optionally advantageously comprises humectants such as e.g. propylene glycol, panthenol or hyaluronic acid, and in particular one or more thickeners which can advantageously be selected from the group of silicon dioxide, aluminum silicates, hydroxypropylmethylcellulose, particularly advantageously a polyacrylate such as, for example, carbopol grade 980, in each case individually or in combination. In particular, mixtures of the aforementioned solvents are used. In the case of alcoholic solvents, water can be a further constituent. Emulsions according to the invention are advantageous and comprise e.g. the specified fats, oils, waxes and other fatty bodies, as well as water and an emulsifier, as is customarily used for such a type of formulation. Gels according to the invention usually comprise alcohols of low carbon number, e.g. ethanol, propylene glycol, and water or an aforementioned oil in the presence of a thickener which, in the case of oily-alcoholic gels, is preferably silicon dioxide or an aluminum silicate, and in the case of aqueous-alcoholic or alcoholic gels is preferably a polyacrylate. Suitable propellants for preparations according to the invention that can be sprayed from aerosol containers are the customary known readily volatile, liquefied propellants, for example hydrocarbons (propane, butane, isobutane), which can be used on their own or in a mixture with one another. Compressed air is also to be used advantageously. Advantageously, preparations according to the invention can furthermore advantageously comprise substances which absorb UV radiation in the UVB region, the total amount of the filter substances being e.g. 0.1% by weight 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 which protect the hair and/or the skin from the entire range of ultraviolet radiation. They can also serve as sunscreens for the hair or the skin. Furthermore, preparations according to the invention can advantageously additionally comprise substances which conceal the troublesome intrinsic odor of the remaining raw materials used, the total amount of the perfume ingredients being e.g., 0.001% by weight to 30% by weight, preferably 0.05 to 10% by weight, in particular 0.1 to 5.0% by weight, based on the total weight of the preparations, in order to provide cosmetic preparations. Examples The examples below are intended to illustrate the present invention without limiting it. Unless stated otherwise, all of the quantities, fractions and percentages stated are based on the weight and the total amount or on the total weight of the preparations. FORMULATION EXAMPLES Example One in Toner EU INCI Control EX-1 EX-2 RE-1 RE-2 RE-3 Isobutylamido Thiazolyl Resorcinol 0.3 0.3 0.3 0.3 0.3 0.3 Tocopherol 0 0.1 0 0.1 0 0 Tocopherol + Helianthus Annuus Seed Oil 0 0 0.1 0 0.1 0 3-o-Ethyl Ascorbic Acid 0 0.11 0.11 0 0 0.2 Sodium Hyaluronate + Aqua 0.15 0.15 0.15 0.15 0.15 0.15 Niacinamide 3 3 3 3 3 3 Isopropyl Palmitate 0.25 0.25 0.25 0.25 0.25 0.25 Glycerin+Aqua 10 10 10 10 10 10 1,2-Hexanediol 0.3 0.3 0.3 0.3 0.3 0.3 Citric Acid 0.2 0.2 0.2 0.2 0.2 0.2 Aqua+Sodium Hydroxide 0.01675 0.01675 0.01675 0.01675 0.01675 0.01675 Phenoxyethanol + Aqua 0.8 0.8 0.8 0.8 0.8 0.8 Alcohol Denat. + Aqua 7.5 7.5 7.5 7.5 7.5 7.5 PEG-40 Hydrogenated Castor Oil 2 2 2 2 2 2 Xanthan Gum 0.2 0.2 0.2 0.2 0.2 0.2 Aqua Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 ΔE_cmc for SILI at 2 months 18.75 0.54 1.5 1.67 2.06 6.33 Note: EX --> experiments mentioned within this application; and RE --> reference experiments within only Tocopherol or Ethyl Ascorbic Acid. Example Two in Emulsion EU INCI Control EX-1 EX-2 RE-1 RE-2 RE-3 Isobutylamido Thiazolyl Resorcinol 0.275 0.275 0.275 0.275 0.275 0.275 Tocopherol 0 0.2 0 0.2 0 0 Tocopherol + Helianthus Annuus Seed Oil 0 0 0.2 0 0.2 0 3-o-Ethyl Ascorbic Acid 0 0.11 0.11 0 0 0.11 Hydrogenated Lecithin 0.2 0.2 0.2 0.2 0.2 0.2 Sodium Hyaluronate+Aqua 0.11 0.11 0.11 0.11 0.11 0.11 Panthenol+Aqua+Pantolactone+Citric Acid 7.5 7.5 7.5 7.5 7.5 7.5 Ethylhexylglycerin 0.5 0.5 0.5 0.5 0.5 0.5 Dibutyl Adipate 2.5 2.5 2.5 2.5 2.5 2.5 Pentaerythrityl Tetraisostearate 1 1 1 1 1 1 Octyldodecanol 1 1 1 1 1 1 Caprylic/Capric Triglyceride 2 2 2 2 2 2 Propylheptyl Caprylate 1.5 1.5 1.5 1.5 1.5 1.5 Hydrogenated Vegetable Oil 0.5 0.5 0.5 0.5 0.5 0.5 Dicaprylyl Carbonate 1.5 1.5 1.5 1.5 1.5 1.5 Sodium Stearoyl Glutamate+Sodium Chloride 0.2 0.2 0.2 0.2 0.2 0.2 Silica 0.5 0.5 0.5 0.5 0.5 0.5 Methylpropanediol 3 3 3 3 3 3 Butylene Glycol+Aqua 4.5 4.5 4.5 4.5 4.5 4.5 Citric Acid 0.06 0.06 0.06 0.06 0.06 0.06 Aqua+Sodium Hydroxide 0.05 0.05 0.05 0.05 0.05 0.05 Phenoxyethanol+Aqua 0.5 0.5 0.5 0.5 0.5 0.5 Alcohol Denat.+Aqua 6 6 6 6 6 6 Aqua+Trisodium Ethylenediamine Disuccinate 0.5 0.5 0.5 0.5 0.5 0.5 Cetyl Alcohol 1.3 1.3 1.3 1.3 1.3 1.3 Xanthan Gum 0.3 0.3 0.3 0.3 0.3 0.3 Hydroxypropyl Starch Phosphate 0.7 0.7 0.7 0.7 0.7 0.7 Aqua Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 Ad 100 ΔE_cmc for SILI at 2 months 9.4 6.77 5.53 11.69 10.03 7.32 Note: EX --> experiments mentioned within this application; and RE --> reference experiments within only Tocopherol or Ethyl Ascorbic Acid.

Claims

Claims 1. Active ingredient combinations of a) one or more alkylamidothiazoles, b) tocopherol, and c) 3-O-ethyl ascorbic acid. 2 Cosmetic preparations containing combinations according to claim 1. 3 Use of active ingredient combinations of b tocopherol and c 3-O-ethyl ascorbic acid to prevent or reduce the deterioration of alkylamidothiazoles caused by oxidative processes and/or heat and/or UV-light in cosmetic preparations containing one or more alkylamidothiazoles. 4 Cosmetic preparations according to claim 2 or use according to claim 3, characterised in that the total amount of the one or more alkylamidothiazoles is 0.00001% by weight to 10% by weight, preferably 0.001% by weight to 5% by weight, in particular 0.005% by weight to 3% by weight, based on the total weight of the preparations. 5 Cosmetic preparations according to one of the preceding claims, characterized in that the total amount of the tocopherol is 0.00001% by weight to 10% by weight, preferably 0.001% by weight to 5% by weight, in particular 0.005% by weight to 3% by weight, based on the total weight of the preparations. 6 Cosmetic preparations according to one of the preceding claims, characterized in that the total amount of the 3-O-ethyl ascorbic acid is e.g. 0.00001% by weight to 10% by weight, preferably 0001% by weight to 5% by weight, in particular 0.005% by weight to 3% by weight, based on the total weight of the preparations. 7 Active ingredient combination or cosmetic preparations according to one of the preceding claims, characterized in that the alkylamidothiazole or the alkylamidothiazoles is or are selected from the group consisting of the following substances: 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-(24-dihydroxyphenylthiazol-2-yl-4-(hydroxymethyl)cyclohexanecarboxamide} .