Combination of retinol, alkylamidothiazoles and flavonoids for improving active substance stabilization

Abstract

A substance combination of retinol and / or derivatives thereof with alkylamidothiazoles and flavonoids allows a topically applicable preparation, in particular a cosmetic or dermatological preparation, to be provided.

Description

[0001] Beiersdorf AG

[0002] Combination of retinol, alkylamidothiazoles and flavonoids to improve drug stabilization

[0003] The present invention relates to topically applicable, in particular cosmetic or dermatological, preparations comprising a combination of substances consisting of retinol, alkylamidothia zoles and flavonoids.

[0004] The desire to look beautiful and attractive is rooted in human nature. Even though the ideal of beauty has changed over time, the pursuit of a flawless appearance has always been a human goal, as a pleasing appearance boosts self-esteem and attractiveness to others. The condition and appearance of the skin plays a significant role in a beautiful and attractive appearance.

[0005] One problem with skin condition and appearance is hyperpigmentation of the skin, which arises due to a variety of causes or accompanying symptoms of many biological processes, e.g. UV radiation (e.g. freckles, ephelides), genetic predisposition, malpigmentation of the skin during wound healing or scarring (post-inflammatory hyperpigmentation) or skin aging (e.g. lentigines seniles).

[0006] For example, alkyl-amido-thiazole derivatives are known for the cosmetic or dermatological treatment and / or prophylaxis of unwanted skin pigmentation, as described in WO 2013041526 A1.

[0007] Flavonoids are natural substances belonging to the group of polyphenols. They are formally derived from the basic structure flavan (2-phenylchroman). Around 8,000 compounds exist in nature. Flavonoids are universally present in plants as secondary plant compounds, and thus also in the human diet. They are attributed with particularly strong antioxidant properties and are therefore used in cosmetic products, both as plant extracts (e.g., Glycyrrhiza inflata root extract) and as pure substances, such as licochalcone A. For example, EP 1839645 A1 describes licochalcone A in cosmetic preparations.

[0008] Retinol, also known as vitamin A, is known for its anti-aging effects and is therefore frequently used in cosmetic skincare products. It stimulates cell renewal and supports the body's own collagen production.

[0009] However, retinol is also a light- and oxidation-sensitive active ingredient that is difficult to stabilize. Furthermore, it is known that retinol, especially at higher concentrations and sometimes in combination with light, tends to cause intolerances.

[0010] The state of the art EP 4076680 A1 comprehensively describes cosmetic preparations containing retinol, di-t-butylpentaerythrityltetrahydroxycinnamic acid ester and ethylenediamine disuccinic acid salt (EDDS).

[0011] For example, WO 96 / 07396 A1 proposes stabilizing retinol in a cosmetic composition in the form of an oil-in-water emulsion by using at least one fat-soluble antioxidant and / or at least one masking agent. Butylated hydroxytoluene (BHT) is given as an example of an antioxidant. Ethylenediaminetetraacetic acid (EDTA) and its derivatives are also mentioned as sequestering agents.

[0012] There are various cosmetic products on the market that contain retinol in combination with different substances and active ingredients, such as Typology Lab 1026, which contains retinol and backuchiol, or Hollywood Skin Instant Plumping & Smoothing Lip Mask with retinol and hyaluronic acid. The Brighten & Co night cream from Derma E contains sodium hyaluronate in addition to vitamin C, backuchiol, and retinol.

[0013] In addition to the problems associated with stabilizing active ingredients in cosmetic preparations and the related side effects, such as changes in odor and color, it is important to improve the skin compatibility of these preparations. Ideally, a preparation should be available that offers a balanced combination of stability, efficacy, skin care, and skin compatibility.

[0014] It was therefore the object of the present invention to eliminate the disadvantages of the prior art. Consequently, it was the object of the present invention to provide a topically applicable preparation base which stabilizes active ingredients that are prone to light instability, particularly in the visible wavelength range (400 nm to 800 nm).

[0015] Another object of the present invention was to provide topically applicable, in particular cosmetic or dermatological, preparations containing retinol and / or its derivatives, so that the active ingredients are stabilized with regard to light stability, in particular in the visible wavelength range (400 nm to 800 nm).

[0016] Another object of the present invention was to provide topically applicable, in particular cosmetic or dermatological, preparations which lead to an increased efficacy of alkylamidothiazoles at the same active ingredient concentration.

[0017] Surprisingly for those skilled in the art, it has now been found that the problems of light stability of retinol and / or derivatives in the visible wavelength range could be solved by the present invention.

[0018] The present invention relates to a topically applicable, in particular cosmetic or dermatological, preparation comprising a combination of substances consisting of a) retinol

[0019] b) One or more alkylamidothiazoles, and

[0020] c) Advantageously containing at least one flavonoid, in particular Licochalcone A and / or Glycyr- rhiza inflata root extract.

[0021] Another aspect of the invention is the use of the topically applicable, in particular cosmetic or dermatological, preparations according to the invention for improving skin condition. Surprisingly, the preparations according to the invention lead to...

[0022] • To improve the stability of the individual substances, especially retinol and / or their derivatives

[0023] • To improved skin tolerance

[0024] • Increased efficacy of alkylamidothiazoles at a constant drug concentration

[0025] Where values ​​for the light stability of retinol and / or its derivatives are given in this disclosure, all values ​​refer to measurements of the recovery of retinol after irradiation. The samples were irradiated in the Suntester (Atlas Suntester (“back glass”), BDF 121283) with a fixed filter combination (coated quartz glass 56052388, FG 56052372 and ID6556077769) at 25 °C. For this purpose, samples (Qe 15 mL) were each placed in a 20 mL glass vial (bottle: 20 mL EPA screw-top bottle, 57 x 27.5 mm, clear glass, 1st hydrolytic class (article number VWR 548-0154); cap: screw cap PP, closed top, 24 mm, butyl / PTFE, 55°, 2.5 mm (article number VWR 548-0642)) and irradiated horizontally. Irradiation was carried out at an irradiance of 500 W / m². Unless otherwise specified, the samples were irradiated for a duration of 6 h, 12 h, or 18 h. As a temperature control, one of the glass vials was wrapped in aluminum foil and irradiated for 18 h.The retinol content was then determined by HPLC-DAD after extraction with acetone. Quantification was performed via external calibration using the reference substance "Retinol 10 SU" (90% Glycine Soja Oil + 10% Retinol, Lot 22462004, BASF AG), and therefore the retinol recovery values ​​refer to the reference substance used for calibration.

[0026] Where weight percentages (wt%) are subsequently given without reference to a specific composition or mixture, these percentages always refer to the total weight of the cosmetic preparation. Where ratios of components / substances / groups of substances are disclosed below, these ratios refer to weight ratios of the components / substances / groups of substances mentioned. Within the scope of this disclosure, the phrases "according to the invention," "advantageous according to the invention," "advantageous in the sense of the present invention," etc., always refer to both the preparation according to the invention and its use according to the invention.

[0027] Unless otherwise stated, all tests were conducted under standard conditions. "Standard conditions" means 20°C, 1013 hPa, and a relative humidity of 50%.

[0028] Emulsifiers are defined as all substances listed as "emulsifying agents" in the International Cosmetic Ingredient Dictionary and Handbook, Thirteenth Edition 2010 (ISBN 1-882621-47-6). Surfactants are defined as all substances listed as "surfactants" in the International Cosmetic Ingredient Dictionary and Handbook, Thirteenth Edition 2010 (ISBN 1-882621-47-6).

[0029] Where weight percentage ranges for the components of the preparation are specified below, the disclosure of the present application also includes all individual values ​​in steps of 0.1 wt.% within these weight percentage ranges.

[0030] When the term skin is used, it preferably refers to human skin.

[0031] According to the invention, retinol and its derivatives are selected as the substance group a.) . In addition to or instead of retinol, its derivatives can also be used according to the invention. Retinol derivatives are in particular retinol esters, such as retinyl palmitate, retinyl acetate, retinyl propionate and / or retinyl linoleate (vitamin A acetate, vitamin A palmitate, vitamin A linoleate, vitamin A propionate).

[0032] Another object of the present invention is a topically applicable, in particular cosmetic or dermatological, preparation comprising a combination of substances consisting of

[0033] a) Retinol and / or its derivatives, selected from the group of retinol esters, such as retinyl palmitate, retinyl acetate, retinyl propionate and / or retinyl linoleate (vitamin A acetate, vitamin A palmitate, vitamin A linoleate, vitamin A propionate) b) One or more alkylamidothiazoles, and

[0034] c) Advantageously containing at least one flavonoid, in particular Licochalcone A and / or Glycyrrhiza inflata root extract.

[0035] It is advantageous for retinol and / or its derivatives to also be encapsulated.

[0036] The Phyto Vec process allows sensitive active ingredients to be encapsulated using chlorophyll, including retinol (Phyt Vec Vitamin A).

[0037] Retinol and / or its derivatives are advantageously used in a proportion of up to a maximum of 3 wt.%, preferably from 0.05 to 2 wt.%, in particular between 0.2 and 1 wt.%, advantageously between 0.1 and 0.5 wt.%, based on the total mass of the preparation.

[0038] Advantageously chosen flavonoids include licochalcone A, licochalcone C, licochalcone E, and / or glabrol, especially licochalcone A. Instead of the flavonoids themselves, extracts, solutions, and mixtures containing these flavonoids can also be used, such as the plant extract Glycyrrhiza inflata Root Extract. Licochalcone A has the following structure:

[0039]

[0040] The topical preparation according to the invention therefore preferably contains flavonoids, flavonoid-containing extracts, flavonoid-containing solutions and / or flavonoid-containing mixtures, wherein the flavonoids are in particular licochalcones, and preferably licochalcone A, licochalcone C, licochalcone E and / or glabrol.

[0041] One or more flavonoids are advantageously used in a proportion in the range of 0.0001 wt% to 5 wt%, preferably in the range of 0.001 wt%, based on the total mass of the preparation. Advantageous alkylamidothiazoles within the meaning of the present invention are substances of general formula I:

[0042] X

[0043] i

[0044]

[0045] R 2

[0046] at which

[0047] R 1 , R 2 , X and Y can be different, partially the same, or completely the same and can mean independently of each other:

[0048] Ri = -Ci-C24-Alkyl (linear and branched), -Ci-C24-Alkenyl (linear and branched), -Ci-Cs-Cycloalkyl, -Ci-Cs-Cycloalkyl-Alkylhydroxy, -C1-C24 Alkylhydroxy (linear and branched), -C1-C24 Alkylamine (linear and branched), -Ci-C24-Alkylaryl (linear and branched), -Ci-C24-Alkylaryl-Alkyl-Hydroxy (linear and branched), -Ci-C24-Alkylheteroaryl (linear and branched), -C1-C24-Alkyl-O-Ci-C24-Alkyl (linear and branched), -C1-C24 Alky-Morpholino, -C1-C24 Alky-Piperidino, -C1-C24 Alky-Piperazino, -C1-C24 Alkyl-piperazino-N-alkyl means,

[0049] R2 = H, -Ci-C24-Alkyl (linear and branched), -Ci-C24-Alkenyl (linear and branched), -Ci-Cs-Cycloalkyl, -Ci-C24-Hydroxyalkyl (linear and branched), -Ci-C24-Alkylaryl (linear and branched), -Ci-C24-Alkylheteroaryl (linear and branched), means,

[0050] X = -H, -Ci-C24-alkyl (linear and branched), -Ci-C24-alkenyl (linear and branched), -Ci-Cs-cycloalkyl, -Ci-C24-aryl (possibly singly or multiply substituted with -OH, -F, -CI, -Br, -I, -OMe, -NH2, -CN), -Ci-C24-heteroaryl (possibly singly or multiply substituted with -OH, -F, -CI, -Br, -I, -OMe, -NH2, -CN), -Ci-C24-alkylaryl (linear and branched), -Ci-C24-alkylheteroaryl (linear and branched), -aryl (possibly singly or multiply substituted with -OH, -F, -CI, -Br, -I, -OMe, -NH2, -CN), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl means,

[0051] Y = H, -Ci-C24-Alkyl (linear and branched), -Ci-C24-Alkenyl (linear and branched), -Ci-Cs-Cycloalkyl, -Ci-C24-Aryl, -Ci-C24-Heteroaryl, -Ci-C24-Alkylaryl (linear and branched), -C1-C24-Alkylheteroaryl (linear and branched), -Aryl, -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydrohydroxyphenyl, -2,4-Dimethoxyphenyl, -2,3-Dimethoxyphenyl, -COO-Alkyl, -COO-Alkenyl, -COO-Cycloalkyl, -COO-Aryl, -COO-Heteroaryl, means,

[0052] and X, Y may also mean = condensed aromatic compound, where X and Y can form aromatic or aliphatic homo- or heterocyclic ring systems with up to n ring-forming atoms, and where the number n can take values ​​from 5 to 8, and the respective ring systems in turn may 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.

[0053] The aforementioned thiazoles can exist both as free bases and as salts: e.g., as fluoride, chloride, bromide, iodide, sulfate, carbonate, ascorbate, acetate, or phosphate. In particular, they exist as halogen salts, such as chloride and bromide.

[0054] Furthermore, an advantageous realization of the present invention consists in cosmetic or dermatological preparations containing an effective amount of one or more of the aforementioned alkylamidothiazoles.

[0055] The / V-[4-(2,4-Dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpro-panamide of the structure is particularly preferred.

[0056] HO.

[0057]

[0058] S

[0059] The above alkylamidothiazoles, their synthesis and their use were described in EP2758381A1.

[0060] It is particularly advantageous if the preparations contain 0.000001 to 10 wt.%, in particular 0.0001 to 3 wt.%, and most especially 0.001 to 1 wt.% of one or more of the alkylamidothiazoles used according to the invention, based on the total weight of the preparation.

[0061] An advantageous combination according to the invention is obtained by using the three material groups in a specific weight ratio to one another. Preferably in the weight ratios as shown in Table 1. Table 1 - Weight ratios

[0062] Retinol / Derivatives Alkylamidothiazoles Flavonoids

[0063] 50 100 1

[0064] 5 10 1

[0065] 1 2 1

[0066] 100 100 1

[0067] 50 150 1

[0068] 5 15 1

[0069] 2 3 1

[0070] 100 200 1

[0071] 10 20 1

[0072] 2 4 1

[0073] 50 300 1

[0074] 5 30 1

[0075] 2 6 1

[0076] 1 3 0

[0077]

[0078] In a preferred embodiment of the invention, the weight ratio of retinol and / or its derivatives to alkylamidothiazoles, in particular compounds according to structure I, to flavonoids, in particular licochalcone A and / or Glycyrrhiza inflata root extract, is 1:2:1, preferably 50:300:1 and particularly preferably 10:20:1.

[0079] The preparation according to the invention advantageously comprises, in addition to the three substances, further cosmetic and dermatological substances selected from the groups

[0080] i. one or more thickeners of natural, especially plant, origin, ii. one or more lipids,

[0081] iii. one or more skin-conditioning substances,

[0082] iv. Hyaluronic acid or its salts and / or

[0083] v. Bakuchiol.

[0084] As additional skin-conditioning agents, one or more substances are advantageously selected from the group consisting of panthenol, evening primrose oil, witch hazel, aloe vera, echinacea, chamomile, linoleic acid, vitamin K, urea, pentylene glycol, 4-t-butylcyclohexanol (Symsitive), Calendula officinalis extract, allantoin, glycyrrhetinic acid, glycine soja germ extract, creatine, Magnolia officinalis bark extract, Origanum majorana leaf extract powder, ceramides, N-acetylhydroxyproline (NaHP), hydroxypinacolone retinoate, retinal, niacinamide, dehydromyricetin, tocopherol, hydroxyacetophenone, ascorbic acid, as well as vitamin C derivatives: 3-0-ethyl ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesium ascorbyl phosphate and / or Q10.

[0085] Preferably, the proportion of skin-conditioning substances in the preparation is in the range of 1 to 20 wt.%, preferably between 2 and 15 wt.%, in particular between 3 and 12 wt.%, based on the total mass of the preparation.

[0086] Bakuchiol is a meroterpene belonging to the terpenophenol class. Bakuchiol has antioxidant, anti-inflammatory, and antibacterial properties.

[0087] Although it has no structural similarity to retinol, bakuchiol shows a functional analogy to retinol through similar regulation of gene expression between retinol and bakuchiol. In 2018, a randomized, double-blind study with 44 volunteers showed that bakuchiol was comparable to retinol in its efficacy against photoaging (wrinkles, hyperpigmentation), but bakuchiol exhibited better skin tolerance.

[0088] Bakuchiol is advantageously used in a proportion of 0.01 to 5 wt.%, in particular between 0.2 and 1 wt.%, advantageously between 0.01 and 0.5 wt.%, based on the total mass of the preparation.

[0089] Als Lipide werden vorteilhaft ein oder mehrere Lipide aus der Gruppe gebildet aus Dibutyl Adipate, Isopropyl Myristate, Isodecyl Neopentanoate, Octyldodecanol, Caprylic / Capric Triglyceride, Propylene Glycol Dicaprylate / Dicaprate, Dicaprylyl Ether, Paraffinum Liquidum, C13-16 Isoparaffin, Isohexadecane, Cyclomethicone, Hydrogenated Polydecene, Octyldodecyl Myristate, Decyl Oleate, Butylene Glycol Dicaprylate / Dicaprate, Dicaprylyl Carbonate, Hydrogenated Polyisobutene, Isopropyl Isostearate, Cetearyl Isononanoate, Isopropyl Stearate, Phenyl Trimethicone, C12-15 Alkyl Benzoate, Ethylhexyl Cocoate, Squalane, Ethylhexyl Stearate, Cetearyl Ethylhexanoate / lsopropyl Myristate, C12-13 Alkyl Lactate, Coco-Caprylate / Caprate, Persea Gratissima Oil, Simmondsia Chinensis Seed Oil, Jojobaöl, Kokosöl, Isopropylpalmitat, Isododekan, Mandelöl (Prunus Amygdalus Dulcis Oil), Sonnenblumenöl (Helianthus Annuus Seed Oil), Coco-Caprylate / Caprate und Butyrosper-mum Parkii Butter gewählt.

[0090] The proportion of one or more lipids is advantageously selected in the range of 5 wt.% to 30 wt.%, preferably in the range of 8 wt.% to 25 wt.%, particularly preferably in the range of 10 wt.% to 15 wt.%, based on the total mass of the preparation.

[0091] Hyaluronic acid (also known as hyaluronan, abbreviation HA, CAS: 9004-61-9) is a glycosaminoglycan that is an important component of connective tissue. HA is characterized by a disaccharide repeat unit according to the structure shown below.

[0092]

[0093] HA is a linear, acidic polysaccharide composed of numerous alternating disaccharide units made up of 1,3-glycosidically linked N-acetyl-β-D-glucosamine (GIcNAc) and β-D-glucuronic acid (GIcA) molecules. Each of the disaccharide units is linked to the next by a β(1-4) bond. The number of units can exceed 10,000, with a molar mass of 4 million Daltons. Due to its hydrophilic acid groups and hydroxyl groups, HA is capable of forming numerous hydrogen bonds, allowing for the addition of hydration ions and thus making it homogeneously miscible with water. In aqueous solution, HA is able to bind increasing amounts of water, thereby increasing the average chain distance, as the negative charges cause repulsion between closely spaced chain segments.Under physiological conditions, the carboxyl groups of hyaluronic acid (HA) are practically completely dissociated and represent a polyanionic compound. The term "hyaluronic acid" is generally used, regardless of whether HA itself or its salts are meant. Due to its viscoelastic properties and biocompatibility, HA has therapeutic significance as an injectable solution in ophthalmology, orthopedics, and cosmetic surgery. Hyaluronic acid is a natural component of the skin. Two forms of hyaluronic acid are used in cosmetic products: a short-chain and a long-chain form. Short-chain hyaluronic acid penetrates the upper layer of the skin and influences its internal moisture balance. Long-chain hyaluronic acid, on the other hand, is intended to have a plumping effect on the skin. It effectively binds moisture in the upper layer of the skin.Its moisture-binding effect results from the fact that it releases its hydration layer gradually, thus providing long-lasting protection for the skin. Other functions of hyaluronic acid (HA) include supplying connective tissue and skin with moisture and nutrients.

[0094] The sodium salt of hyaluronic acid is also used, among other things, as a moisturizer for the production of cosmetic products (Römpp online lexicon version 2.5, 2004).

[0095] Hyaluronic acid is commercially available in a cross-linked state (e.g., Hylaform®, a cross-linked hyaluronic acid from Biomatrix, NJ, USA; for manufacturing see also US-A-4713 448, US-A-4605691, APC® from Fidia, Incert® from Anika Therapeutics, interge) from LifeCore or Restylane® from Q-Med).

[0096] Hyaluronic acid and / or hyaluronic acid salt is preferably used in a proportion in the range of 0.01 to 3 wt.%, in particular in the range of 0.05 to 1.5 wt.%, preferably in the range of 0.1 to 1 wt.%, advantageously 0.15 to 0.5 wt.%, based on the total mass of the preparation.

[0097] The preparation according to the invention advantageously comprises one or more thickeners of natural, in particular plant, origin. According to the invention, acrylate compounds are advantageously not used as thickeners.

[0098] Thickeners increase the viscosity and thus reduce the flowability of liquids, making them more viscous. The natural cosmetics industry already uses natural or modified natural thickeners such as xanthan gum, guar gum, or cellulose derivatives, which are preferred according to the invention.

[0099] According to the invention, one or more thickeners are selected from the group consisting of starch, gelatin, casein, konjac root flour, cellulose, xanthan gum, xanthan gum, algin, scleroglucan, gellan gum, gellan gum, high acylated gellan gum, dehydroxanthan gum, hydroxypropyl starch phosphate, pectin, acacia senegal gum, carrageenan and / or guarana.

[0100] Thickeners from the group of thickeners of plant origin are particularly advantageous.

[0101] Thickeners from the group consisting of xanthan gum, gellan, gellan gum, high acylated gellan gum, dehydroxanthan gum, acacia senegal gum and / or hydroxypropyl starch phosphate are particularly advantageous.

[0102] Organic natural thickeners, such as starch, gelatin, casein or konjac root flour (glucomannan), as well as natural substances, especially celluloses, such as hydroxyethylcellulose, carboxymethylcellulose (CMC, E 466), hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylhydroxyethylcellulose, are advantageous to choose.

[0103] These natural thickeners offer a more skin-friendly alternative to synthetic thickeners, thus fulfilling the desire for balanced skin compatibility.

[0104] The proportion of one or more thickeners is advantageously chosen in the range of 0.1 to 5 wt.%, in particular 0.4 to 2 wt.%, advantageously in the range of 0.3 to 1.7 wt.%, based on the total mass of the preparation.

[0105] Further preferred additives are stabilizing agents. These substances serve to stabilize the preparation. Preferably used for stabilization are di-t-butyl-pentaerythrityl-tetrahydro-xycinnamate compounds, such as those marketed by BASF under the name Tinogard TT, ethylenediamine disuccinic acid salt trisodium ethylenediamine disuccinate, such as Natrlquest® E30 from Innospec Active Chemicals, tocopherol, or sodium phytate.

[0106] Preferably, di-t-butyl-pentaerythrityl tetrahydroxycinnamate (pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, Tinogard TT) and / or sodium phytate are used. The preparation according to the invention may also contain other ingredients commonly used in cosmetics, provided that these are not excluded according to the invention.

[0107] Preparations according to the invention can be in various forms:

[0108] For example, they can be a solution, an anhydrous preparation, an emulsion or microemulsion of the water-in-oil (W / O) or oil-in-water (O / W) type, a multiple emulsion, for example of the water-in-oil-in-water (W / O / W) type, a gel, a solid stick, an ointment, or even an aerosol. It is also advantageous according to the invention to provide the substances used according to the invention and / or their derivatives in encapsulated form, e.g., in collagen matrices and other conventional encapsulation materials, e.g., as cellulose encapsulations, in gelatin, or liposomally encapsulated.

[0109] According to the invention, the preparations are used for the care, treatment, or prevention of skin aging, for improving skin elasticity and / or firmness, for tightening the skin, and / or for skin regeneration / strengthening. Comparative tests and examples

[0110] The following examples are intended to illustrate the present invention without limiting it. Unless otherwise stated, all quantities, proportions, and percentages are based on weight and total quantity or total weight of the preparation.

[0111] The following formulations were prepared for the comparative tests. Formulation #1 is not according to the invention, while formulations #2 and #3 are according to the invention.

[0112] 1 2 3

[0113] INCI Declaration wt.% wt.% wt.% Retinol 0.10 0.10 0.10 Glycine Soja Oil 0.90 0.90 0.90 Isobutylamido Thiazolyl Resorcinol — 0.15 0.15 Glycyrrhiza Infl ata Root Extract — — 0.05 Isoamyl Laurate 29.75 29.71 29.70 Capryl ic / Capric Triglyceride 19.75 19.71 19.70 Dicaprylyl Ether 39.75 39.71 39.70 Propylheptyl Caprylate Ad 100 Ad 100 Ad 100

[0114]

[0115] The preparations listed above were manufactured and their properties were tested for active ingredient stability under light in a comparative experiment. For this purpose, the light stability of retinol in the respective preparations was determined by the recovery of retinol after irradiation for 6 h, 12 h, and 18 h, as previously described. Retinol [wt.%]

[0116] Preparation (recovery in %)*

[0117] TO 6 h 12 h 18 h TK 0.075 0.006 0.074 #1 nn ** nn *

[0118] (100%) (8%) (99%) 0.087 0.011 0.005 0.002 0.086 #2

[0119] (100%) (13%) (6%) (2%) (99%) 0.086 0.019 0.01 0.006 0.084 #3

[0120] (100%) (22%) (12%) (7%) (98%)

[0121]

[0122] * Recovery based on the respective retinol content at 1 ro

[0123] not detectable (detection limit: 0.002%)

[0124] Surprisingly, light stabilization of retinol was observed when combined with isobutylamido thiazolyl resorcinol and licochalcone A (the lead compound in Glycyrrhiza inflata root extract) under the described irradiation conditions, even after a measurement time of 18 hours. Retinol recovery was higher when combined with isobutylamido thiazolyl resorcinol (preparation #2) or isobutylamido thiazolyl resorcinol and licochalcone A (the lead compound in Glycyrrhiza inflata root extract) (preparation #3). In contrast, preparation #1 showed a significant degradation of the active ingredient retinol after irradiation under the described conditions.

[0125] Furthermore, the combination of retinol with isobutylamido thiazolyl resorcinol and licochalcone A (key substance in Glycyrrhiza Inflata Root Extract) showed better skin tolerance than retinol alone.

[0126] Furthermore, the combination of retinol with isobutylamido thiazolyl resorcinol and licochalcone A (the key compound in Glycyrrhiza inflata root extract) showed better efficacy of the individual active ingredients than isobutylamido thiazolyl resorcinol alone. The following examples are intended to further illustrate the invention without limiting it:

[0127] 4 5 6

[0128] INCI Declaration wt.% wt.% wt.%

[0129] Dibutyl Adipate 2.50 — 1.50

[0130] Capryl ic / Capric Triglyceride 2.50 1.50 4.00 Propylheptyl Caprylate 1.25 — —

[0131] Isopropyl Palmitate 2.00 3.00 — Pentaerythrityl Tetraisostearate — 2.00 1.00 Butyrospermum Parkii Butter — 0.50 —

[0132] Butylene Glycol Dicaprylate / Di- — —

[0133] caprate 0.50

[0134] Glyceryl Stearate Citrate 1.30 1.25 1.00

[0135] Glyceryl Stearate SE — 0.50 —

[0136] Glycerin 7,50 4,00 5,00 Methylpropanediol 2,00 3,00 —

[0137] Butylene Glycol 3,00 — —

[0138] Sodium Citrate 0,15 — — Phenoxyethanol 0,60 0,60 —

[0139] Silica 1,00 0,50

[0140] Alcohol Denat. 5,00 — — Tocopherol 0,10 — —

[0141] Trisodium Ethylenediamine — Disuccinate 0,20 0,25

[0142] Cetearyl Alcohol 0,75 — 1,00

[0143] Xanthan Gum 0,30 0,20 — Succinoglycan 0,20 — —

[0144] Sclerotium Gum — 0,20 —

[0145] Coco-Caprylate / Caprate — — 1,50

[0146] Glyceryl Stearate — — 0,50 Ethylhexylglycerin — — 0,25 Hydroxypropyl Starch Phosphate — — 0,50

[0147] Gellan Gum — — 0,10

[0148] Behenyl Alcohol — — 1,00

[0149] Sodium Hyaluronate 0,12 — —

[0150]

[0151] Isobutylamido Thiazolyl Resorcinol 0,10 0,15 0,18 Glycyrrhiza Inflata Root Extract 0,03 — — Licochalcone A — 0,03 0,01 Retinol 0,10 0,05 0,05 Retinyl Palmitate — 0,10 0,10 Aqua ad 100 ad 100 ad 100

[0152]

[0153] 7 8 9 10 INCI Declaration Gew.% Gew.% Gew.% Gew.% Ethylhexylglycerin 0,20 0,20 — — Pentaerythrityl Tetraisostearate 1,00 — 1,00 1,00 Capryl ic / Capric Triglyceride 2,00 — 4,00 4,00 Isopropyl Palmitate 5,00 — — — Isopropyl Lauroyl Sarcosinate — 2,50 — — Cocoglycerides — 1,00 — — Diisopropyl Adipate 1,00 — — — Polyglyceryl-6 Stearate+Polyglyceryl-6

[0154] 2,20 0,60 1,00 1,00 Behenate

[0155] Glyceryl Stearate — — 0,50 0,50 Lauroyl Lysine 1,00 — — — Glycerin 7,00 3,00 7,00 7,00 Methylpropanediol 2,00 — — — Butylene Glycol 3,00 3,00 — — Phenoxyethanol 0,75 0,60 — — Diethylhexyl Syringylidenemalo- nate+Caprylic / Capric Triglyceride (Ox- 0,25

[0156] ynex ST Liquid™)

[0157] Trisodium Ethylenediamine Disuccinate 0,20 0,10 — — Cetearyl Alcohol 0,50 — 1,50 1,50 Xanthan Gum 0,60 0,20 — — Sclerotium Gum — 0,40 — — Succinoglycan+Aqua — 0,05 — — Citric Acid — 0,03 — — Tocopherol 0,20 0,10 0,15 0,15 Hydroxypropyl Starch Phosphate — — 0,50 0,50 Gellan Gum — — 0,05 0,05 Caesalpinia Spinosa Gum / — —

[0158] 0,10 0,10 Ammonium AMPS Crosspolymer

[0159] Butylene Glycol Dicaprylate / Dicaprate — — 0,50 0,50 Dibutyl Adipate — — 1,50 1,50 Coco-Caprylate / Caprate — — 1,50 1,50 Dicaprylyl Ether — — 1,50 1,50

[0160]

[0161] Glyceryl Stearate Citrate — — 1,00 1,00 Isobutylamido Thiazolyl Resorcinol 0,15 0,10 0,20 0,20 Retinol 0,10 0,05 0,10 0,10 Retinyl Palmitate 0,10 — 0,05 0,05 Bakuchiol 0,01 — — — Glycyrrhiza Inflata Root Extract 0,03 0,05 — — Licochalcone A — 0,01 — Pentaerythrityl Tetra-di-t-butyl — — —

[0162] 0,20

[0163] Hydroxyhydrocinnamate

[0164] Aqua ad 100 ad 100 ad 100 ad 100

[0165]

[0166] 11 12 13 14 INCI Declaration Gew.% Gew.% Gew.% Gew.% Sodium Hyaluronate 0,1 0,25 0,1 0,1 Panthenol 4 3,00 — — Octyldodecanol 1,5 — — — Glyceryl Stearate SE 0,2 — — — Sodium Stearoyl Glutamate 0,1 0,50 0,50 0,50 Glycerin 11 9,00 9,00 9,00 Citric Acid 0,046 — — — Phenoxyethanol+Aqua 0,6 0,90 0,90 0,90 Alcohol Denat.+Aqua 5 — — — Xanthan Gum 0,6 0,30 0,30 0,30 Sodium Phytate — 0,20 0,20 0,20 Pentylene Glycol — 1,00 1,00 1,00 Pentaerythrityl Tetra-di-t-butyl —

[0167] Hydroxyhydrocinnamate 0,20 0,20 0,20 Isoamyl Laurate — 3,00 3,00 3,00 Dicaprylyl Ether — 4,00 4,00 4,00 Caprylic / Capric Glycerides — 2,00 2,00 2,00 Propylheptyl Caprylate — 1,00 1,00 1,00 Glyceryl Stearate — 1,00 1,00 1,00 Cetearyl Alcohol — 0,50 0,50 0,50 Retinol 0,05 0,10 0,10 0,10 Retinyl Palmitate — 0,25 0,10 0,10 Bakuchiol — 0,01 — — Isobutylamido Thiazolyl Resorcinol 0,20 0,10 0,15 0,15 Glycyrrhiza Inflata Root Extract 0,03 — — — Licochalcone A — 0,01 0,02 — Aqua ad 100 ad 100 ad 100 ad 100

[0168]

[0169] 15 16 17 18 INCI Declaration Gew.% Gew.% Gew.% Gew.% Propylheptyl Caprylate 2,00 2,00 2,00 2,00 Isopropyl Palmitate 2,50 2,50 2,50 2,50 Cetearyl Isononanoate 2,00 2,00 2,00 2,00 Diisopropyl Adipate 2,50 2,50 2,50 2,50 Sodium Stearoyl Glutamate 0,20 0,20 0,20 0,20 Glyceryl Stearate 0,70 0,70 0,70 0,70 Distarch Phosphate 1,50 1,50 1,50 1,50 Glycerin + Aqua 5,00 5,00 5,00 5,00 Citric Acid 0,04 0,04 0,04 0,04 Phenoxyethanol 0,60 0,60 0,60 0,60 Butylene Glycol + Aqua 3,00 3,00 3,00 3,00 Alcohol Denat. + Aqua 5,00 5,00 5,00 5,00 Trisodium EDTA 0,15 0,15 0,15 0,15 Cetearyl Alcohol 1,50 1,50 1,50 1,50 Dehydroxanthan Gum 0,20 0,20 0,20 0,20 Gellan Gum 0,05 0,05 0,05 0,05 Hydroxypropyl Starch Phosphate 0,75 0,75 0,75 0,75 Xanthan Gum 0,10 0,10 0,10 0,10 Isobutylamido Thiazolyl Resorcinol 0,15 0,10 0,20 0,10 Retinol 0,10 0,10 0,05 0,10 Licochalcone A 0,05 0,03 — — Glycyrrhiza Inflata Root Extract — — 0,05 — Retinyl Palmitate — 0,10 0,20 0,10 Pentaerythrityl Tetra-di-t-butyl

[0170] Hydroxyhydrocinnamate 0,10 0,20 0,20 0,20 Bakuchiol 0,10 — — — Aqua ad 100 ad 100 ad 100 ad 100

[0171]

Claims

Patent claims 1. Cosmetic or dermatological preparation comprising a combination of substances consisting of a) retinol and / or its derivatives b) One or more alkylamidothiazoles, and c) Advantageously containing at least one flavonoid, in particular Licochalcone A and / or Gly-cyrrhiza inflata root extract.

2. Preparation according to claim 1 characterized in that the proportion of retinol and / or its derivatives, preferably retinyl palmitate, retinyl acetate, retinyl propionate and / or retinyl linoleate, is selected in the range of up to a maximum of 3 wt.%, preferably from 0.05 to 2 wt.%, in particular between 0.2 and 1 wt.%, advantageously between 0.1 and 0.5 wt.%, based on the total mass of the preparation.

3. Preparation according to one of the preceding claims characterized in that the total proportion of one or more alkylamidothiazoles is selected to be 0.000001 to 10 wt. %, in particular 0.0001 to 3 wt. %, and most particularly 0.001 to 1 wt. %, based on the total weight of the preparation.

4. Preparation according to one of the preceding claims characterized in that the alkylamidothiazole(s) are substances of the general formula x i R 2 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 things independently of each other: R 1= -Ci-C24-Alkyl (linear and branched), -Ci-C24-Alkenyl (linear and branched), -Ci-Cs- Cycloalkyl, -Ci-Cs-Cycloalkyl-Alkylhydroxy, -C1-C24 Alkylhydroxy (linear and branched), -C1-C24 Alkylamine (linear and branched), -Ci-C24-Alkylaryl (linear and branched), -C1-C24-Alkylaryl-Alkyl-Hydroxy (linear and branched), -Ci-C24-Alkylheteroaryl (linear and branched), -Ci-C24-Alkyl-O-Ci-C24-Alkyl (linear and branched), -C1-C24 Alky-Morpholino, -C1-C24 Alky-Piperidino, -C1-C24 Alky-Piperazino, -C1-C24 Alkyl-piperazino-N-alkyl means, R 2 = H, -Ci-C24-Alkyl (linear and branched), -Ci-C24-Alkenyl (linear and branched), - Ci-Cs-cycloalkyl, -Ci-C24-hydroxyalkyl (linear and branched), -Ci-C24-alkylaryl (linear and branched), -Ci-C24-alkylheteroaryl (linear and branched), means, X = -H, -Ci-C24-alkyl (linear and branched), -Ci-C24-alkenyl (linear and branched), -Ci-Cs-cycloalkyl, -Ci-C24-aryl (possibly singly or multiply substituted with -OH, -F, -CI, -Br, -I, -OMe, -NH2, -CN), -Ci-C24-heteroaryl (possibly singly or multiply substituted with -OH, -F, -CI, -Br, -I, -OMe, -NH2, -CN), -Ci-C24-alkylaryl (linear and branched), -Ci-C24-alkylheteroaryl (linear and branched), -aryl (possibly singly or multiply substituted with -OH, -F, -CI, -Br, -I, -OMe, -NH2, -CN), -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-dimethoxyphenyl, -2,3-dimethoxyphenyl means, Y = H, -Ci-C24-Alkyl (linear and branched), -Ci-C24-Alkenyl (linear and branched), -Ci-Cs-Cycloalkyl, -Ci-C24-Aryl, -Ci-C24-Heteroaryl, -Ci-C24-Alkylaryl (linear and branched), -Ci-C24-Alkylheteroaryl (linear and branched), -Aryl, -phenyl, -2,4-dihydroxyphenyl, -2,3-dihydroxyphenyl, -2,4-Dimethoxyphenyl, -2,3-Dimethoxyphenyl, -COO-Al-kyl, -COO-Alkenyl, -COO-CylcIoalkyl, -COO-Aryl, -COO-Heteroaryl, means, The alkylamidothiazoles can exist both as a free base and as salts that can be used cosmetically and / or dermatologically.

5. Preparation according to one of the preceding claims characterized in that the alkylamidothiazole(s) have the following structure:

6. Preparation according to one of the preceding claims characterized in that the proportion of one or more flavonoids is selected in the range of 0.0001 wt.% to 5 wt.%, preferably in the range of 0.001 to 2 wt.%, based on the total mass of the preparation.

7. Preparation according to one of the preceding claims characterized in that the weight ratio of retinol and / or its derivatives to alkylamidothiazoles, in particular compounds according to structure I, to flavonoids, in particular licochalcone A and / or Glycyrrhiza inflata root extract, is 1:2:1, preferably 50:300:1 and in particular preferably 10:20:

1.

8. Preparation according to any one of the preceding claims comprising i. one or more thickeners of natural, especially plant, origin, ii. one or more lipids, iii. one or more skin-conditioning substances, iv. Hyaluronic acid or its salts and / or v. Bakuchiol.

9. Preparation according to one of the preceding claims characterized in that one or more substances from the group consisting of starch, gelatin, casein, konjac root flour, cellulose, xanthan, xanthan gum, algin, scleroglucan, gellan, gellan gum, high acylated gelan gum, dehydroxanthan gum, acacia senegal gum, hydroxypropyl starch phosphate, pectin, carrageenan, guarana are selected as thickeners.

10. Preparation according to one of the preceding claims, characterized in that the lipids are one or more substances from the group consisting of dibutyl adipate, isopropyl myristate, isodecyl neopentanoate, octyldodecanol, caprylic / capric triglyceride, propylene glycol dicaprylate / dicaprate, dicaprylyl ether, paraffinum liquidum, C13-16 isoparaffin, isohexadecane, cyclomethicone, hydrogenated polydecene, octyldodecyl myristate, decyl oleate, butylene glycol dicaprylate / dicaprate, dicaprylyl carbonate, hydrogenated polyisobutene, isopropyl isostearate, cetearyl isononanoate, isopropyl stearate, phenyl trimethicone, C12-15 alkyl benzoate, ethylhexyl cocoate, squalane, ethylhexyl stearate, cetearyl Ethylhexanoate + Isopropyl Myristate, C12-13 Alkyl Lactate, Coco-Caprylate / Caprate, Persea Gratissima Oil, Simmondsia Chinensis Seed Oil, Jojoba Oil, Coconut Oil, Isopropyl Palmitate, Isododecane, Almond Oil (Prunus Amygdalus Dulcis Oil), Sunflower Oil (Helianthus Annuus Seed Oil)Coco-caprylate / caprate and Butyrospermum parkii butter are selected.

11. Preparation according to one of the preceding claims, characterized in that one or more substances from the group consisting of panthenol, evening primrose oil, witch hazel, aloe vera, echinacea, chamomile, linoleic acid, vitamin K, urea, pentylene glycol, 4-t-butylcyclohexanol (Symsitive), Calendula officinalis extract, allantoin, glycyrrhetinic acid, glycine soja germ extract, creatine, Magnolia officinalis bark extract, Origanum majorana leaf extract powder, ceramides, N-acetylhydroxyproline (NaHP), hydroxypinacolone retinoate, retinal, niacinamide, dehydromyricetin, tocopherol, hydroxyacetophenone, ascorbic acid, and vitamin C are used as skin-conditioning agents. Derivatives, in particular 3-0-Ethyl Ascorbic Acid, Ascorbyl Glucoside, Ascorbyl Palmitate, Magnesium Ascorbyl Phosphate and / or Q10, may be selected.

12. Preparation according to one of the preceding claims characterized in that it contains hyaluronic acid and / or hyaluronic acid salts, wherein it is advantageous if the total proportion of this hyaluronic acid and / or hyaluronic acid salts is in the range of 0.01 to 3 wt.%, in particular in the range of 0.05 to 1.5 wt.%, preferably in the range of 0.1 to 1 wt.%, advantageously 0.15 to 0.5 wt.%, based on the total mass of the preparation.

13. Preparation according to one of the preceding claims characterized in that it contains bakuchiol, wherein it is advantageous if the total proportion of bakuchiol is in the range of 0.01 to 5 wt.%, in particular between 0.2 and 1 wt.%, advantageously between 0.01 and 0.5 wt.%, based on the total mass of the preparation.

14. Use of the preparation according to any of the preceding claims to improve the light stability of retinol and / or derivatives.

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