Cosmetic preparation for protection from skin aging

Abstract

A cosmetic preparation that contains a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: Ubiquinone), b) vitamin C (INCI: Ascorbic Acid) and / or one of its esters, and c) luteolin or citrus reticulata peel extract, and the cosmetic use of this combination.

Description

[0001]Beiersdorf Aktiengesellschaft Hamburg Description Cosmetic preparation to protect against skin aging The present invention relates to a cosmetic preparation containing a combination of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), vitamin C (INCI: ascorbic acid) and / or one of its esters and luteolin or citrus reticulata peel extract as well as the cosmetic use of this combination for the treatment and / or prophylaxis of skin wrinkles and for the treatment and / or prophylaxis of the slackening of connective tissue. The skin is the largest organ in the human body. Of its many functions (for example for heat regulation and as a sensory organ), the barrier function, which prevents the skin (and thus ultimately the entire organism) from drying out, is arguably the most important. At the same time, the skin acts as a protective device against the penetration and absorption of external substances.This barrier function is achieved by the epidermis, which, as the outermost layer, forms the actual protective shell against the environment. At around one tenth of the total thickness, it is also the thinnest layer of the skin. Like all other organs in the body, the skin ages. Both intrinsic (irreversible) aging processes and extrinsic (exogenous) factors such as UV radiation play an important role. A central aspect of skin aging is the degradation of important components of the extracellular matrix in the dermis, which consists of numerous connective tissue fibers such as collagen and elastin. The accelerated degradation of connective tissue fibers with age by corresponding degrading enzymes, so-called matrix metalloproteinases (MMPs), plays a crucial role in this. More than 20 different MMPs have been described in humans, but only a few are responsible for collagen degradation, in particular MMP1.MMP1 is expressed in the skin and is capable of enzymatically degrading collagen. Furthermore, this enzyme is particularly strongly induced by UV radiation and is therefore considered the primary collagenolytic enzyme responsible for UV-induced collagen degradation. Age-related collagen fragmentation results in its accumulation, which irreversibly impairs the functional and structural integrity of the connective tissue in the dermis, thus leading to a loss of structure, elasticity, and firmness, even leading to the formation of wrinkles in the skin. (see for example Kohl et al. Skin aging, Hautarzt 2009, 60:917–934; Fisher et al. Collagen Fragmentation Promotes Oxidative Stress and Elevates Matrix Metalloproteinase-1 in Fibroblasts in Aged Human Skin, The American Journal of Pathology, 2009,174:101-114 or Brennan et al. Matrix metalloproteinase-1 is the collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin.Photochem Photobiol 2003, 78:43–48). People have long desired to effectively suppress this skin aging and wrinkle formation. Thus, those skilled in the art are familiar with a wide variety of cosmetic products offered for this purpose. However, the multitude of commercially available cosmetics should not obscure the fact that these prior art preparations still leave much to be desired in terms of their effectiveness. Therefore, the object of the present invention was to develop a novel combination of active ingredients that is effectively suitable for the prevention and / or treatment of skin wrinkles as well as for the prevention and / or treatment of slackening of connective tissue. Surprisingly, this object is achieved by a cosmetic preparation containing a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters, and c) luteolin.This object is further surprisingly achieved by a cosmetic preparation containing a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) citrus reticulata peel extract (INCI: citrus reticulata peel extract). This object is further surprisingly achieved by a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) luteolin, for use in cosmetic preparations for the treatment and / or prophylaxis of skin wrinkles.This problem is surprisingly solved by a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) citrus reticulata peel extract (INCI: citrus reticulata peel extract), for use in cosmetic preparations for the treatment and / or prophylaxis of skin wrinkles. This problem is surprisingly solved by a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) luteolin, for use in cosmetic preparations for the treatment and / or prophylaxis of connective tissue slackening.Last but not least, this task is surprisingly solved by a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters, and c) citrus reticulata peel extract (INCI: citrus reticulata peel extract), for use in cosmetic preparations for the treatment and / or prophylaxis of connective tissue slackening. The role of vitamin C and its derivatives, as well as coenzyme Q10, on collagen formation has already been the subject of scientific studies (see, for example, Pullar et al. The Roles of Vitamin C in Skin Health, Nutrients 2017, 9(8),866 or Mine et al. Stimulatory effects of collagen production induced by coenzyme Q). 10in cultured skin fibroblasts J. Clin Biochem Nutr 2022, 71(1):29-33), but these investigations could not point the way to the present invention. In the context of the present disclosure, the formulations “according to the invention”, “preparation according to the invention” etc. always refer to the preparations, combinations and uses according to the invention, ie also to preparations in which the uses according to the invention are realized. The Citrus Reticulata peel extract according to the invention can be obtained, for example, by maceration, reflux hydrodistillation by means of Soxhlet, ultrasound-assisted extraction, microwave-assisted extraction and in particular by means of supercritical fluid extraction (here extracted in particular by means of carbon dioxide). It can also be sold under the trade name “TEGO ®Natural Citrus” can be purchased from Evonik. This Citrus Reticulata peel extract is then extremely rich in luteolin. It is advantageous according to the invention if the cosmetic preparation or combination according to the invention is characterized in that sodium ascorbyl phosphate (INCI: Sodium Ascorbyl Phosphate) or ascorbyl palmitate (INCI: Ascorbyl Palmitate) is used as the vitamin C derivative. According to the invention, the sole use of sodium ascorbyl phosphate (INCI: Sodium Ascorbyl Phosphate) is particularly preferred. It is advantageous according to the invention if the cosmetic preparation or combination is characterized in that the cosmetic preparation contains coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: Ubiquinone) in an amount of 0.005 to 0.1% by weight, based on the total weight of the preparation.Advantageous embodiments of the present invention are also obtained in that the cosmetic preparation contains vitamin C (INCI: Ascorbic Acid) and / or one of its esters in a total amount of 0.01 to 1.0% by weight, based on the total weight of the preparation. Furthermore, it is advantageous according to the invention if the cosmetic preparation contains luteolin in a total amount of 0.00065 to 0.065% by weight, based on the total weight of the preparation. Advantageous embodiments of the cosmetic preparation or combination according to the invention are also characterized in that the cosmetic preparation contains Citrus Reticulata peel extract in a total amount of 0.001 to 0.1% by weight, based on the total weight of the preparation.According to the invention, cosmetic preparations or combinations are also advantageously characterized in that the weight ratio of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) to the total amount of vitamin C (INCI: ascorbic acid) and / or its esters in the cosmetic preparation is from 1:2 to 1:20. It is advantageous according to the invention if the weight ratio of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) to luteolin in the cosmetic preparation is from 1:4 to 5:1. Advantageous embodiments of the present invention are also characterized in that in the cosmetic preparation the weight ratio of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) to Citrus Reticulata peel extract is from 1:20 to 20:1.Also advantageous within the meaning of the present invention is a cosmetic preparation or combination which is characterized in that in the cosmetic preparation the weight ratio of luteolin to the total amount of vitamin C (INCI: ascorbic acid) and / or its esters is from 8:1 to 1:51. A cosmetic preparation or combination is also advantageous according to the invention in that in the cosmetic preparation the weight ratio of Citrus Reticulata peel extract to the total amount of vitamin C (INCI: ascorbic acid) and / or its esters is from 1:33 to 10:1. Furthermore, it is advantageous according to the invention if the cosmetic preparation is in the form of an emulsion and preferably in the form of an oil-in-water emulsion (O / W emulsion).In such a case, it is preferred according to the invention to use as emulsifier one or more compounds selected from the group glyceryl stearate citrate, glyceryl stearate (self-emulsifying), stearic acid, stearate salts, polyglyceryl-3 methylglycose distearate, sodium cetearyl sulfate, potassium cetyl phosphate, polyglyceryl-10 stearate, sodium stearoyl glutamate.Last but not least, a cosmetic preparation or combination is advantageous within the meaning of the present invention, which is characterized in that the preparation is free from propylparaben, butylparaben, methylisothiazolinone, chloromethylisothiazolinone, IPBC, DMDM ​​hydantoin, dimethylol glycol, dimethylol urea, sodium hydroxymethyl glycinate, BHT, 3-(4-methylbenzylidene)camphor and 2-hydroxy-4-methoxybenzophenone (INCI: oxybenzone) and ethylhexyl 2-cyano-3,3-diphenylacrylate (INCI: octocrylene), isoamyl 4-methoxycinnamate and ethylhexyl 4-methoxycinnamate, polyacrylates, cross-linked acrylate / C10-C30 alkyl acrylate polymers, polyethylene glycol ethers and polyethylene glycol esters. Furthermore, it is advantageous according to the invention if the preparation is free from methylparaben. Furthermore, the preparation according to the invention can be composed as usual and contain the usual cosmetic ingredients.Comparative Experiment / Proof of Efficacy: The most important cell type in the connective tissue of the dermis is the fibroblast. Fibroblasts are responsible for the formation of collagen. Therefore, primary dermal fibroblasts are very well suited as an in vitro model system for investigating the effects of active ingredients on collagen formation. This allows targeted conclusions to be drawn about the effects in the skin, particularly in the context of skin firmness and structure, which is primarily determined by the connective tissue fibers (see, for example: Lago et al.: The effect of aging in primary human dermal fibroblasts PLoS One 2019, 14(7): e0219165). 1. Experimental Assay Procedure: Human dermal fibroblasts (purchased from vetted external suppliers or self-isolated from human skin according to standard protocols) from 12 donors were cultured in Dulbecco's Modified Eagle Medium with appropriate supplements and seeded for the experiment in 96-well plates containing 100 µl of medium.After the cells had grown, the respective active ingredients to be tested were applied to the cells, either alone or in defined combinations. The active ingredients and concentrations used were 5 µg / mL bioflavonoid extract (Tego natural citrus, containing luteolin), 155 µM sodium ascorbyl phosphate (vitamin C derivative), and 5.79 µM Q10 (ubiquinone-10). Cells treated with the respective solvent of the active ingredients were used as controls. After 24 hours, the amount of matrix metalloproteinase-1 protein was determined from the supernatants using a commercially available assay (Human Pro-MMP-1Quantkine ELISA Kit from R&D Systems Inc. (cat# DMP 100) according to the manufacturer's instructions. The amounts were determined in ng / ml or normalized to the corresponding control, and the effects were then calculated as a percentage. 2. Calculation of the MMP1 protein amount The MMP1 protein amount was calculated in ng / ml (Fig 1).After normalization to the respective solvent control (100%), the values ​​were calculated as a percentage (Fig. 2). Significant p-values ​​were marked with * (p<0.05). 3. Result For the active ingredient combination of Citrus reticulata peel extract (luteolin), ascorbyl phosphate, and coenzyme Q10, a particularly good inhibition of the matrix metalloproteinase MMP1 protein level was demonstrated in vitro in skin fibroblasts. The biological inhibition of MMP1 by the combination of the three active ingredients was surprisingly high (80%), since the two-component combination of ascorbyl phosphate and coenzyme Q10 showed no positive effect on the MMP1 protein levels, but actually increased them (105%), and the effects of the bioflavonide extract (Tego natural citrus, containing luteolin) alone were also weaker (86%). Examples The following examples are intended to illustrate the present invention without limiting it.Unless otherwise stated, all quantities, proportions, and percentages are based on the weight and total quantity or the total weight of the preparations. Recipe I. NCI 1 2 3 4 5 wt.% wt.% wt.% wt.% wt.% Citrus Reticulata Peel Extract 0.010 0.010 0.050 0.010 0.008 Ubiquinone 0.010 0.020 0.010 0.010 0.020 Hydroxyacetophenone 0.200 0.200 0 0 0 Ethylhexylglycerol 0.100 0.100 0.100 0.100 0.100 Sodium Ascorbyl Phosphate 0.100 0.500 0.100 0.800 0.100 Cocoglycerides 1.000 1.000 0 0 0 Isopropyl Palmitate 4.000 4.000 4,500 2,000 2,000 Butyrospermum Parkii Butter 0 0 1,000 0 1,000 Hydrogenated Coco- G lycerides1.000 1.000 0 0 0Ethylhexyl Stearate 4.000 4.000 0 0 0 Isopropyl Stearate 4.000 4.000 0 0 0 Ethylhexyl Cocoate 0 0 0 3.400 3.400 Sodium Cetearyl Sulfate 0.150 0.150 0.100 0.100 0.100 Glyceryl Stearate SE 1.500 1.500 2.000 2.000 2.000 Glyceryl Stearate 0.500 0.500 0.500 0.500 0.500 Parfuem 0.350 0.350 0.350 0.350 0.350 Glycerin+Aqua 7.500 7.500 7.000 7.000 7.000 Citric Acid 0.040 0.040 0.060 0.040 0.060 Phenoxyethanol+Aqua 0.900 0.900 0.900 0.900 0.900 Alcohol Denat.+Aqua 5.000 5.000 5.000 5.000 5.000 Aqua+TrisodiumEthylenediamine Disuccinate0.100 0.100 0.150 0.100 0.150Myristyl Alcohol 1.000 1.000 0 0 0 Cetearyl Alcohol 2.000 2.000 3.500 4.000 3.000 Gellan Gum 0.060 0.060 0 0 0 Xanthan Gum 0.100 0.100 0.100 0.100 0.500 Hydroxypropyl Starch P hosphate 0.750 1.000 0.400 0.750 0.400Aqua ad 100 ad 100 ad 100 ad 100 ad 100

Claims

Patent claims 1. Cosmetic preparation containing a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) luteolin.

2. Cosmetic preparation containing a combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) citrus reticulata peel extract (INCI: citrus reticulata peel extract).

3. Combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters, and c) luteolin, for use in cosmetic preparations for the treatment and / or prophylaxis of skin wrinkles. 4.Combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) citrus reticulata peel extract (INCI: citrus reticulata peel extract), for use in cosmetic preparations for the treatment and / or prophylaxis of skin wrinkles.

5. Combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) luteolin, for use in cosmetic preparations for the treatment and / or prophylaxis of connective tissue relaxation. 6.Combination of a) coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone), b) vitamin C (INCI: ascorbic acid) and / or one of its esters and c) citrus reticulata peel extract (INCI: citrus reticulata peel extract), for use in cosmetic preparations for the treatment and / or prophylaxis of connective tissue relaxation.

7. Cosmetic preparation according to one of claims 1 or 2 or combination according to one of claims 3 to 6, characterized in that ascorbyl palmitate (INCI: Ascorbyl Palmitate) and / or sodium ascorbyl phosphate (INCI: Sodium Ascorbyl Phosphate) is used as the vitamin C derivative.

8. Cosmetic preparation according to one of claims 1 or 2 or combination according to one of claims 3 to 6, characterized in that sodium ascorbyl phosphate (INCI: Sodium Ascorbyl Phosphate) is used as the vitamin C derivative.

9. Cosmetic preparation or combination according to one of the preceding claims, characterized in that the cosmetic preparation contains coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) in an amount of 0.005 to 0.1% by weight, based on the total weight of the preparation. 10.Cosmetic preparation or combination according to one of the preceding claims, characterized in that the cosmetic preparation contains vitamin C (INCI: ascorbic acid) and / or one of its esters in a total amount of 0.01 to 1.0% by weight, based on the total weight of the preparation.

11. Cosmetic preparation or combination according to one of the preceding claims, characterized in that the cosmetic preparation contains luteolin in a total amount of 0.00065 to 0.065% by weight, based on the total weight of the preparation.

12. Cosmetic preparation or combination according to one of the preceding claims, characterized in that the cosmetic preparation contains citrus reticulata peel extract in a total amount of 0.001 to 0.1% by weight, based on the total weight of the preparation. 13.Cosmetic preparation or combination according to one of the preceding claims, characterized in that in the cosmetic preparation the weight ratio of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) to the total amount of vitamin C (INCI: ascorbic acid) and / or its esters is from 1:2 to 1:

20.

14. Cosmetic preparation or combination according to one of the preceding claims, characterized in that in the cosmetic preparation the weight ratio of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) to luteolin is from 1:4 to 5:

1.

15. Cosmetic preparation or combination according to one of the preceding claims, characterized in that in the cosmetic preparation the weight ratio of coenzyme Q10 (6-all-trans-decaprenyl-2,3-dimethoxy-5-methyl-1,4-benzoquinone, INCI: ubiquinone) to Citrus Reticulata peel extract is from 1:20 to 20:1.

16. Cosmetic preparation or combination according to one of the preceding claims, characterized in that in the cosmetic preparation, the weight ratio of luteolin to the total amount of vitamin C (INCI: ascorbic acid) and / or its esters is from 8:1 to 1:

51.

17. Cosmetic preparation or combination according to one of the preceding claims, characterized in that in the cosmetic preparation, the weight ratio of Citrus Reticulata peel extract to the total amount of vitamin C (INCI: ascorbic acid) and / or its esters is from 1:33 to 10:

1.

18. Cosmetic preparation or combination according to one of the preceding claims, characterized in that in the cosmetic preparation, the product is in the form of an emulsion, preferably in the form of an oil-in-water emulsion (O / W emulsion). 19.Cosmetic preparation or combination according to claim 18, characterized in that one or more compounds selected from the group consisting of glyceryl stearate citrate, glyceryl stearate (self-emulsifying), stearic acid, stearate salts, polyglyceryl-3 methylglycose distearate, sodium cetearyl sulfate, potassium cetyl phosphate, polyglyceryl-10 stearate, and sodium stearoyl glutamate are used as emulsifier. 20.Cosmetic preparation or combination according to one of the preceding claims, characterized in that the preparation is free from propylparaben, butylparaben, methylisothiazolinone, chloromethylisothiazolinone, IPBC, DMDM ​​hydantoin, dimethylol glycol, dimethylol urea, sodium hydroxymethyl glycinate, BHT, 3-(4-methylbenzylidene)camphor and 2-hydroxy-4-methoxybenzophenone (INCI: oxybenzone) and ethylhexyl 2-cyano-3,3-diphenylacrylate (INCI: octocrylene), 4-methoxycinnamic acid isoamyl ester and 4-methoxycinnamic acid ethylhexyl ester, polyacrylates, cross-linked acrylate / C10-C30 alkyl acrylate polymers, polyethylene glycol ethers and polyethylene glycol esters.

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