DE102011087316A1 - Cosmetic, non-therapeutic use of methimazole e.g. to influence, preferably stimulate and/or improve the natural production of components in the extracellular matrix of the dermis, where the components are e.g. collagen and elastin - Google Patents

Abstract

Cosmetic, non-therapeutic use of methimazole to influence the natural production of components in the dermis, is claimed. ACTIVITY : Dermatological. MECHANISM OF ACTION : None given.

Description

The invention is in the field of cosmetics and relates to the cosmetic, non-therapeutic use of methimazole for influencing the natural production of constituents in the dermis, as well as cosmetic, non-therapeutic methods for improving skin firmness and for improving dermal tissue shrinkage.

The beneficial effects of retinol and / or retinoids in cosmetic - especially topical - and / or pharmaceutical compositions are well known. For example, it has been demonstrated and described that retinoic acid and / or retinol in the dermis can stimulate new production of extracellular matrix components, such as collagen, and in the epidermis can regulate keratinocyte proliferation and differentiation. Macroscopically, the use of retinoic acid and / or retinol in topical compositions results in a refined skin appearance, a lightening of pigment and / or age spots, a normalization of the epidermis thickness and a tightening of the skin. In pharmaceutical compositions, retinol and retinoids are used because of their high efficacy in the treatment of keratinization disorders of the skin, such as fish scale disease (ichthyosis) and / or psoriasis, or in the treatment of severe acne.

The problem with the use of retinoids - especially in cosmetic compositions - are the strong side effects of retinoids (teratogenicity, hypertriglyceridaemia and / or retinoid dermatitis). These undesirable side effects virtually preclude the use of retinoids in the cosmetic mass market.

In the past, efforts have therefore been made to find effective alternatives for retinoids which have the same positive properties as retinoids, and which at the same time do not exhibit the aforementioned negative properties of the retinoids.

As a class of possible alternatives to retinoids, the so-called RAMBAs (Retinoic Acid Metabolism Blocking Agents) have been proposed. RAMBAs have so far been described for pharmaceutical applications ( Verfaille et al. (2008), JDDG 5: 355-364 ), in particular because of their action to block enzymes (predominantly those enzymes responsible for the degradation of cellular retinoic acid, especially cytochrome C enzyme Cyp26A1).

It is desirable to find other drugs and / or drug combinations that have a RAMBA activity to find the best possible alternative to the retinoids.

Methimazole (1,3-dihydro-methyl-2H-imidazole-2-thione) is a known drug used for the treatment of hyperthyroidism. In addition, methimazole has already been used for the treatment of hyperpigmentation (melasma) ( Kasree et al., Skin Pharm. Phys. 21: 300-305 (2008) ; Kasree et al., Dermatology 211: 360-362 (2005) ), for the treatment of psoriasis (proriasis) ( Elias et al. Int. J. Derm. 43: 889-892 (2004) ; Hasegawa et al., J. Derm. 31: 794-797 (2004). ; Elias, Medical Hypothesis, 62: 431-437 (2004) ), to lighten the skin ( Kasree, J. Invest. Dermat. 118: 205-207 (2002) ) and for the treatment of UV-induced skin damage ( Moseley et al., Photodermatology, 6: 32-36 (1989) ).

None of the aforementioned documents describe a RAMBA effect of methimazole.

It was an object of the present invention to find active substances and / or active ingredient combinations which have a RAMBA activity. In particular, the active substance or combination of active ingredients should have a positive influence on the collagen synthesis in the dermis.

These tasks could be fulfilled by the cosmetic use of methimazole.

The present invention accordingly provides the cosmetic, non-therapeutic use of methimazole (1,3-dihydro-methyl-2H-imidazole-2-thione) for influencing the natural production of constituents in the dermis.

The "dermis" is a complex system of filamentous connective tissue, which is traversed by a dense network of nerves and blood vessels. In addition to elastic fibers, it mainly comprises a tight mesh of (mostly) collagen fibers, which give the skin stability. The dermis includes Furthermore, the so-called extracellular matrix, which means substances and liquids in the intercellular spaces.

Fibroblasts are fixed connective tissue cells in the dermis, where the extracellular matrix substances are produced.

The extracellular matrix (ECM) consists of fibrous components as well as liquid in which various substances are dissolved. In addition to water, ECM mainly contains glycoproteins and polysaccharides (glycosaminoglycans) as well as amino acids, glucose, tissue hormones and electrolyte salts. Among the proteins, ECM contains mainly collagen and elastic fibers, which are formed from the proteins fibrillin and elastin. If the level of elastin and collagen in the ECM decreases, the skin becomes doughy, flabby and wrinkled. In addition, she loses her elasticity.

By "influencing the natural production of constituents in the dermis" is preferably understood the influencing of the natural production of components of the extracellular matrix in the dermis, wherein the influence can be both positive and negative, preferably positive. Especially preferred is the stimulation of the natural production of components of the extracellular matrix.

In a first preferred embodiment of the invention, the natural production-in particular the new production-of elastin, collagen and / or glycosaminoglycans in the extracellular matrix is influenced, preferably stimulated and / or improved, by the cosmetic use of methimazole.

Glycosaminoglycans are acidic polysaccharides that are built up linearly from repeating disaccharides. The disaccharide units usually consist of a uronic acid which is 1,3-glycosidically linked to an amino sugar (for example N-acetylglycosamine). The disaccharide units are 1,4-glycosidically linked together and may be partially esterified with acetic acid or sulfuric acid. Depending on the composition of the disaccharide units, a distinction is made between various subgroups of glycosaminoglycans such as hyaluronic acid, heparin, chondroitin sulfate and keratan sulfate. Hyaluronic acid improves the water-binding capacity in the skin. A reduced hyaluronic acid content in the skin is noticeable by loose, wrinkled and / or dry skin.

In a particularly preferred embodiment, natural collagen synthesis in the extracellular matrix is stimulated and / or improved by the cosmetic use of methimazole.

In a further particularly preferred embodiment, natural hyaluronic acid synthesis in the extracellular matrix is stimulated and / or improved by the cosmetic use of methimazole.

s, der Arme und/oder der Beine, insbesondere durch Auftragen auf die Gesichtshaut.According to a particular embodiment, the use according to the invention is topical, ie by application to the skin and / or skin appendages, preferably by application to the facial skin, the scalp and / or to the skin regions of the neck, the décolleté

s, the arms and / or the legs, in particular by applying to the facial skin.

Therefore, according to the invention, the cosmetic use is particularly preferred from 0.001 to 5 wt .-%, more preferably from 0.01 to 3 wt .-%, and in particular from 0.1 to 1 wt .-% methimazole in a cosmetic agent, in particular a cosmetic skin treatment agent, wherein the amounts are based on the total weight of the cosmetic product.

The cosmetic agents in which methimazole is preferably used (hereinafter referred to as "agents used in the invention") show, in addition to influencing the natural production of constituents in the dermis, improved care effects on the skin and / or the skin appendages. Especially on the skin, the positive effects are clearly pronounced, so that preferred cosmetic agents used in the invention are skin treatment agents.

Skin treatment agents according to the present invention can be formulated in various forms, for example as (optionally oil and fat-free) gel, as a cream, in stick form, as a liquid or gel roll-on application, as a soaked flexible substrate (pad), but also as powder or spray.

Skin treatment agents according to the present invention may be in solid, semi-solid, liquid, disperse, emulsified, suspended or gel form. Furthermore, they can be used as aerosol be prepared, that is, they are packaged in a pressure vessel, from which they can be sprayed using a propellant. Furthermore, the skin treatment agents can be sprayed as a propellant-free pump spray.

For the purposes of the present invention, preferred skin treatment agents may be, for example, cleansing compositions for the skin, such as shower and wash gels and / or soaps, skin care products, such as lotions, gels and / or creams for the body and / or face, face lotions, lip care compositions, but also decorative cosmetic products be like make-ups.

Particularly preferred skin treatment agents are characterized in that they are formulated as skin care agents, in particular as skin care compositions for facial skin, such as a face cream, a face gel and / or a tonic.

• – Harnstoff-Derivaten, ausgewählt aus Verbindungen gemäß Formel (I)
  
  worin die Reste R1, R2, R3 und R4 unabhängig voneinander für ein Wasserstoffatom, eine C₁-C₄-Alkylgruppe, eine C₂-C₆-Alkenylgruppe oder eine C₂-C₆-Hydroxyalkylgruppe mit mindestens einer Hydroxygruppe steht, mit der Maßgabe, dass mindestens einer der besagten Reste eine C₂-C₆Hydroxyalkylgruppe mit mindestens einer Hydroxygruppe bedeutet,
• – Vitaminen, Provitaminen und Vitaminvorstufen der Gruppen B, C, E, H und K und den Estern der vorgenannten Substanzen,
• – Monomeren, Oligomeren und Polymeren von Aminosäuren, N-C₂-C₂₄-Acylaminosäuren, den Estern und/oder den physiologisch verträglichen Metallsalzen dieser Substanzen,
• – DNA- oder RNA-Oligonucleotiden,
• – natürlichen Betainverbindungen,
• – α-Hydroxycarbonsäuren, α-Ketocarbonsäuren, β-Hydroxycarbonsäuren und deren Ester-, Lacton- oder Salzform, ausgenommen Zusammensetzungen mit 5 Gew.-% (2-Hydroxyethyl)harnstoff und 0,05 bzw. 5 Gew.-% Ammoniumlactat und Zusammensetzungen mit (2-Hydroxypropyl)harnstoff und α- und/oder β-Hydroxycarbonsäuren,
• – den Flavonoiden Naringin, α-Glucosylrutin, α-Glucosylmyricetin, α-Glucosylisoquercetin, α-Glucosylquercetin, Dihydroquercetin (Taxifolin), Hesperidin, Hesperitin, Neohesperidin, Rutin, Troxerutin, Monoxerutin, Diosmin, Eriodictin und Apigenin-7-glucosid,
• – Isoflavonoiden und Isoflavonoid-reichen Pflanzenextrakten,
• – Ubichinon und Ubichinol sowie deren Derivaten,
• – Silymarin,
• – natürlich vorkommenden Xanthin-Derivaten, ausgewählt aus Coffein, Theophyllin, Theobromin und Aminophyllin,
• – Ectoin,
• – Kreatin,
• – Olivenblattextrakten, Ursolsäure, Oleanol und/oder Oleanolsäure,
• – Mono- und Polyhydroxystilbenen und deren Estern,
• – Derivaten von methyliertem Silanol,
• – Phytinsäure,
• – Extrakten aus Maiskörnern (Zea Mays (Corn) Kernel Extract),
• – Extrakten aus Haferkörnern (Avena Sativa (Oat) Kernel Extract),
• – Saccharomyces/Xylinum/Black Tea Ferment,
• – Apfelkernextrakten (Pyrus Malus (Apple) Fruit Extract),
• – Lotuskeim-Extrakten (Nelumbo Nucifera Germ Extract),
• – Rotweinextrakten,
• – Traubenkernextrakten (Vitis Vinifera (Grape) Seed Extract), die bevorzugt aus der Chardonnay-Traube stammen,
• – Extrakten aus Schwarzen Holunderblüten (Sambucus Nigra Flower Extract),
• – Wirkstoffen, die die beta-Endorphinsynthese in Keratinozyten stimulieren,
• – anorganischen und organischen UV-Filtersubstanzen,
• – selbstbräunenden Wirkstoffen,
• – hautaufhellenden Wirkstoffen,
• – Wirkstoffen, die die Prostaglandinsynthese und/oder die Leukotrien-Synthese inhibieren,
• – sebumregulierenden Wirkstoffen,
• – sowie Desoxyzuckern oder Desoxyzucker-Bausteine enthaltenden Polysacchariden, enthält.

In a further preferred embodiment, agents used according to the invention for achieving improved care effects on the skin in addition to methimazole preferably contain a suitable cosmetic carrier, preferably a topical carrier, which furthermore contains at least one active ingredient selected from

• Urea derivatives selected from compounds of the formula (I)
  
  wherein the radicals R1, R2, R3 and R4 independently of one another represent a hydrogen atom, a C ₁ -C ₄ -alkyl group, a C ₂ -C ₆ -alkenyl group or a C ₂ -C ₆ -hydroxyalkyl group having at least one hydroxyl group, with In that at least one of said radicals is a C ₂ -C ₆ hydroxyalkyl group having at least one hydroxyl group,
• - vitamins, provitamins and vitamin precursors of groups B, C, E, H and K and the esters of the abovementioned substances,
• Monomers, oligomers and polymers of amino acids, NC ₂ -C ₂₄ -acylamino acids, the esters and / or the physiologically acceptable metal salts of these substances,
• - DNA or RNA oligonucleotides,
• - natural betaine compounds,
• Α-hydroxycarboxylic acids, α-ketocarboxylic acids, β-hydroxycarboxylic acids and their ester, lactone or salt form, except compositions containing 5% by weight of (2-hydroxyethyl) urea and 0.05 and 5% by weight of ammonium lactate and compositions with (2-hydroxypropyl) urea and α- and / or β-hydroxycarboxylic acids,
• The flavonoids naringin, α-glucosylrutin, α-glucosylmyricetin, α-glucosylisoquercetin, α-glucosylquercetin, dihydroquercetin (taxifolin), hesperidin, hesperitin, neohesperidin, rutin, troxerutin, monoxerutin, diosmin, eriodictin and apigenin-7-glucoside,
• Isoflavonoids and isoflavonoid-rich plant extracts,
• - ubiquinone and ubiquinol and their derivatives,
• - Silymarin,
• Naturally occurring xanthine derivatives selected from caffeine, theophylline, theobromine and aminophylline,
• - Ectoin,
• - Creatine,
• - Olive leaf extracts, ursolic acid, oleanol and / or oleanolic acid,
• Mono- and polyhydroxystilbenes and their esters,
• Derivatives of methylated silanol,
• - phytic acid,
• Corn kernel extracts (Zea mays (Corn) Kernel Extract),
• Oatmeal extracts (Avena sativa (Oat) kernel extract),
• - Saccharomyces / Xylinum / Black Tea Ferment,
• - apple seed extracts (Pyrus malus (Apple) Fruit Extract),
• - lotus germ extracts (Nelumbo nucifera germ extract),
• - red wine extracts,
• Grape seed extracts (Vitis vinifera (Grape) seed extract), which are preferably derived from the Chardonnay grape,
• Extracts of black elderflower (Sambucus Nigra Flower Extract),
• - agents that stimulate beta-endorphin synthesis in keratinocytes,
• Inorganic and organic UV filter substances,
• - self-tanning active ingredients,
• - skin lightening agents,
• - drugs that inhibit prostaglandin synthesis and / or leukotriene synthesis,
• - sebum-regulating active substances,
• - As well as deoxy sugars or deoxy sugar building blocks containing polysaccharides.

A suitable cosmetic carrier, preferably a topical carrier, is preferably understood as meaning an aqueous or aqueous-alcoholic carrier. Preferably, the support contains - based on its total weight - at least 30 wt .-%, more preferably at least 35 wt .-% particularly preferably at least 40 wt .-% and in particular at least 45 wt .-% water. Furthermore, the cosmetic carrier may contain from 0.01 to 40% by weight, preferably from 0.05 to 35% by weight and in particular from 0.1 to 30% by weight, of at least one alcohol which may be selected from ethanol. Propanol, 2-propanol, isopropanol, glycerol, diglycerol, triglycerol, 1-butanol, 2-butanol, 1,2-butanediol, 1,3-butanediol, 1-pentanol, 2-pentanol, 1,2-pentanediol, 1, 5-pentanediol, 1, hexanol, 2-hexanol, 1,2-hexanediol, 1,6-hexanediol, polyethylene glycols, sorbitol, sorbitan, benzyl alcohol, phenoxyethanol or mixtures of these alcohols. Preference is given to the water-soluble alcohols. Particularly preferred are ethanol, 1-propanol, 2-propanol, 1,2-propylene glycol, glycerol, and / or 1,6-hexanediol and mixtures of these alcohols. Particularly preferred are glycerol and / or 1,6-hexanediol.

Particularly preferred urea derivatives of the formula (I) are those which contain at least one C ₂ -C ₆ -hydroxyalkyl group having at least one hydroxyl group which is selected from at least one member selected from among 2-hydroxyethyl, 2-hydroxy-2-methylprop-2 yl, 1,3-dihydroxy-2-methylprop-2-yl, 1,3-dihydroxyprop-2-yl, tris (hydroxymethyl) methyl, 1,3-dihydroxy-2-hydroxymethylprop-2-yl, 2,3- Dihydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, 1-hydroxy-2-methylprop-2-yl, 2,3,4,5,6-pentahydroxyhexyl and 1,3,4,5,6-pentahydroxyhexane 2-yl is selected.

It is preferable to use those urea derivatives of the formula (I) which satisfy the preferred proviso of the formula (I) that at least one of R _{1 to} R _{4 represents} a C ₂ -C ₆ hydroxyalkyl group having at least one hydroxy group. With particular preference, in each case two radicals of R _1, R _2, R _{3 and} R _{4 represent} a C ₂ -C ₆ -hydroxyalkyl group having at least one hydroxyl group. Particularly preferably, the two radicals of R _1, R _2, R _{3 and} R _{4 are} a C ₂ -C ₆ -hydroxyalkyl group having at least one hydroxyl group, these two radicals being positioned at different nitrogen atoms of the urea (N, N 'position). Examples of C ₁ -C ₄ -alkyl groups which can be used in compounds of the formula (I) are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl. Examples of C ₂ -C ₆ -alkenyl groups which can be used in compounds of the formula (I) are vinyl, 2-propen-1-yl (allyl) or 3-buten-1-yl.

Particular preference is given to at least one compound from the group comprising the representatives N- (2-hydroxyethyl) urea, N, N-bis (2-hydroxyethyl) urea, N, N'-bis (2-hydroxyethyl) urea, N- (3-hydroxypropyl) urea, N, N-bis (3-hydroxypropyl) urea, N, N'-bis (3-hydroxypropyl) urea, N- (2-hydroxypropyl) urea, N, N-bis ( 2-hydroxypropyl) urea, N, N'-bis (2-hydroxypropyl) urea, N- (2-hydroxy-2-methyl-prop-2-yl) urea, N, N-bis (2-hydroxy) 2-methyl-prop-2-yl) urea, N, N'-bis (2-hydroxy-2-methyl-prop-2-yl) urea, N- (1,3-dihydroxy-2-methyl-prop Urea, N, N-bis (1,3-dihydroxy-2-methyl-prop-2-yl) urea, N, N'-bis (1,3-dihydroxy-2-methylpropyl) 2-yl) urea, N- (1,3-dihydroxy-2-hydroxymethyl-prop-2-yl) urea, N, N-bis- (1,3-dihydroxy-2-hydroxymethyl-prop-2-yl) urea and N, N'-bis (1,3-dihydroxy-2-hydroxymethyl-prop-2-yl) urea. Very particularly preferably, N- (2-hydroxyethyl) urea and N, N'-bis-urea (2-hydroxyethyl), for example, available as a commercial product Hydro Vance ^® by the company National Starch.

Cosmetic agents used according to the invention contain urea derivatives of the aforementioned formula (I) preferably in amounts of 0.75 to 4.5 wt .-%, more preferably from 1 to 4 wt .-%, particularly preferably from 2 to 3.5 Wt .-% and in particular from 2.5 to 3.2 wt .-%, wherein the amounts are based on the total weight of the composition.

• i) Vitamin B: Zur Vitamin B-Gruppe oder zu dem Vitamin B-Komplex gehören unter anderem – Vitamin B₁: Trivialname Thiamin, chemische Bezeichnung 3-[(4'-Amino-2'-methyl-5'-pyrimidinyl)-methyl]-5-(2-hydroxyethyl)-4-methylthiazoliumchlorid. Bevorzugt wird Thiaminhydrochlorid in den erfindungsgemäß verwendeten Mitteln in Mengen von 0,05 bis 1 Gew.-%, bezogen auf das gesamte Mittel, eingesetzt, – Vitamin B₂: Trivialname Riboflavin, chemische Bezeichnung 7,8-Dimethyl-10-(1-D-ribityl)-benzo[g]pteridin-2,4(3H,10H)-dion. Bevorzugt werden Riboflavin oder seine Derivate in den erfindungsgemäß verwendeten Mitteln in Mengen von 0,05 bis 1 Gew.-%, bezogen auf das gesamte Mittel, eingesetzt, – Vitamin B₃: Unter dieser Bezeichnung werden die Verbindungen Nicotinsäure und Nicotinsäureamid (Niacinamid) geführt. Bevorzugt ist das Nicotinsäureamid, das in den erfindungsgemäß verwendeten Mitteln bevorzugt in Mengen von 0,05 bis 1 Gew.-%, bezogen auf das gesamte Mittel, enthalten sein kann, – Vitamin B₅: Pantothensäure und Panthenol. Einsetzbare Derivate des Panthenols sind insbesondere die Ester und Ether des Panthenols sowie kationisch derivatisierte Panthenole. An Stelle von sowie zusätzlich zu Pantothensäure oder Panthenol können die erfindungsgemäß verwendeten Mittel auch Derivate des 2-Furanon mit der allgemeinen Strukturformel (II) enthalten,
  
  wobei 2-Furanon-Derivate bevorzugt sind, in denen die Substituenten R¹ bis R⁶ unabhängig voneinander ein Wasserstoffatom, einen Hydroxylrest, einen Methyl-, Methoxy-, Aminomethyl- oder Hydroxymethylrest, einen gesättigten oder ein- oder zweifach ungesättigten, linearen oder verzweigten C₂-C₄-Kohlenwasserstoffrest, einen gesättigten oder ein- oder zweifach ungesättigten, verzweigten oder linearen Mono-, Di- oder Trihydroxy-C₂-C₄-Kohlenwasser stoffrest oder einen gesättigten oder ein- oder zweifach ungesättigten, verzweig ten oder linearen Mono-, Di- oder Triamino-C₂-C₄-Kohlenwasserstoffrest dar stellen. Besonders bevorzugte Derivate sind die auch im Handel erhältlichen Substanzen Dihydro-3-hydroxy-4,4-dimethyl-2(3H)-furanon mit dem Trivialnamen Pantolacton (Merck), 4-Hydroxymethyl-γ-butyrolacton (Merck), 3,3-Dimethyl-2-hydroxy-γ-butyrolacton (Aldrich) und 2,5-Dihydro-5-methoxy-2-furanon (Merck), wobei ausdrücklich alle Stereoisomeren eingeschlossen sind. Ein außerordentlich bevorzugtes 2-Furanon-Derivat ist Pantolacton (Dihydro-3-hydroxy-4,4-dimethyl-2(3H)-furanon), wobei in Formel (II) R¹ für eine Hydroxylgruppe, R² für ein Wasserstoffatom, R³ und R⁴ für eine Methylgruppe und R⁵ und R⁶ für ein Wasserstoffatom stehen. Das Stereoisomer (R)-Pantolacton entsteht beim Abbau von Pantothensäure. Die genannten Verbindungen des Vitamin B₅-Typs sowie die 2-Furanonderivate können in den erfindungsgemäß verwendeten Mitteln in einer Gesamtmenge von 0,05 bis 5 Gew.-%, bevorzugt von 0,1 bis 3 Gew.-%, besonders bevorzugt von 0,5 bis 2 Gew.-%, jeweils bezogen auf das gesamte Mittel, enthalten sein, – Vitamin B₆: hierunter wird keine einheitliche Substanz, sondern die unter den Trivialnamen Pyridoxin, Pyridoxamin und Pyridoxal bekannten Derivate des 5-Hydroxymethyl-2-methylpyridin-3-ols verstanden. Vitamin B₆ kann in den erfindungsgemäß verwendeten Mitteln bevorzugt in Mengen von 0,0001 bis 1,0 Gew.-%, insbesondere in Mengen von 0,001 bis 0,01 Gew.-%, enthalten sein, wobei sich die Mengenangaben auf das Gesamtgewicht des Mittels beziehen, – Vitamin B₇: (Biotin), auch als Vitamin H oder ”Hautvitamin” bezeichnet. Bei Biotin handelt es sich um (3aS,4S,6aR)-2-Oxohexahydrothienol[3,4-d]-imidazol-4-valeriansäure. Biotin kann in den erfindungsgemäß verwendeten Mitteln bevorzugt in Mengen von 0,0001 bis 1,0 Gew.-%, insbesondere in Mengen von 0,001 bis 0,01 Gew.-% enthalten sein, wobei sich die Mengenangaben auf das Gesamtgewicht des Mittels beziehen,
• (ii) Vitamin C (Ascorbinsäure): kann in den erfindungsgemäß verwendeten Mitteln bevorzugt in Mengen von 0,1 bis 3 Gew.-%, bezogen auf das gesamte Mittel, eingesetzt werden. Die Verwendung der Derivate Ascorbylpalmitat, -stearat, -dipalmitat, -acetat, Mg-Ascorbylphosphat, Na-Ascorbylphosphat, Natrium- und Magnesiumascorbat, Dinatriumascorbylphosphat und -sulfat, Kaliumascorbyltocopherylphosphat, Chitosanascorbat oder Ascorbylglucosid kann bevorzugt sein. Die Verwendung in Kombination mit Tocopherolen kann ebenfalls bevorzugt sein,
• (iii) Vitamin E: Zur Vitamin E-Gruppe zählen Tocopherol, insbesondere α-Tocopherol, und seine Derivate. Bevorzugte Derivate sind insbesondere die Ester, wie Tocopherylacetat, -nicotinat, -phosphat, -succinat, -linoleat, -oleat, Tocophereth-5, Tocophereth-10, Tocophereth-12, Tocophereth-18, Tocophereth-50 und Tocophersolan. Tocopherol und seine Derivate können in den erfindungsgemäß verwendeten Mitteln bevorzugt in Mengen von 0,05–1 Gew.-%, bezogen auf das gesamte Mittel, enthalten sein,
• (iv) Vitamin F: Unter Vitamin F werden üblicherweise essentielle Fettsäuren, insbesondere Linolsäure, Linolensäure und Arachidonsäure, verstanden,
• (v) Vitamin H: Vitamin H ist eine andere Bezeichnung für Biotin oder Vitamin B₇ (siehe oben),
• (vi) Vitamin K: Zu den fettlöslichen Vitaminen der Vitamin K-Gruppe, denen das Grundgerüst des 2-Methyl-1,4-naphthochinons zugrunde liegt, gehören Phyllochinon (Vitamin K₁), Farnochinon oder Menachinon-7 (Vitamin K2) und Menadion (Vitamin K₃). Vitamin K kann in den erfindungsgemäß verwendeten Mitteln bevorzugt in Mengen von 0,0001 bis 1,0 Gew.-%, insbesondere 0,01 bis 0,5 Gew.-%, jeweils bezogen auf das gesamte Mittel, enthalten sein.

Suitable vitamins, provitamins or vitamin precursors of the vitamin groups B, C, E, H and K may for example be selected from:

• i) Vitamin B: The vitamin B group or the vitamin B complex includes, among others, vitamin B ₁ : common name thiamin, chemical name 3 - [(4'-amino-2'-methyl-5'-pyrimidinyl) - methyl] -5- (2-hydroxyethyl) -4-methylthiazolium chloride. Thiamine hydrochloride is preferably used in amounts of from 0.05 to 1% by weight, based on the total agent, of the agents used according to the invention. Vitamin B ₂ : Common name riboflavin, chemical name 7,8-dimethyl-10- (1- D-ribityl) benzo [g] pteridine-2,4 (3H, 10H) -dione. Riboflavin or its derivatives are preferably used in amounts of from 0.05 to 1% by weight, based on the total agent, of the agents used according to the invention. Vitamin B ₃ : Under this name, the compounds nicotinic acid and nicotinamide (niacinamide) are conducted , Preference is given to the nicotinic acid amide, which may preferably be present in the agents used according to the invention in amounts of from 0.05 to 1% by weight, based on the total agent, of vitamin B ₅ : pantothenic acid and panthenol. Useful derivatives of panthenol are, in particular, the esters and ethers of panthenol, as well as cationically derivatized panthenols. Instead of and in addition to pantothenic acid or panthenol, the agents used according to the invention may also contain derivatives of 2-furanone having the general structural formula (II),
  
  wherein 2-furanone derivatives are preferred in which the substituents R ¹ to R ⁶ independently of one another are a hydrogen atom, a hydroxyl radical, a methyl, methoxy, aminomethyl or hydroxymethyl radical, a saturated or mono- or diunsaturated, linear or branched C ₂ -C ₄ hydrocarbon radical, a saturated or mono- or diunsaturated, branched or linear mono-, di- or trihydroxy-C ₂ -C ₄ -hydrocarbon radical or a saturated or mono- or diunsaturated, branched th or linear Mono-, di- or triamino-C ₂ -C ₄ hydrocarbon radical represent. Particularly preferred derivatives are the commercially available substances dihydro-3-hydroxy-4,4-dimethyl-2 (3H) -furanone with the trivial name pantolactone (Merck), 4-hydroxymethyl-γ-butyrolactone (Merck), 3,3 Dimethyl 2-hydroxy-γ-butyrolactone (Aldrich) and 2,5-dihydro-5-methoxy-2-furanone (Merck), expressly including all stereoisomers. An exceptionally preferred 2-furanone derivative is pantolactone (dihydro-3-hydroxy-4,4-dimethyl-2 (3H) -furanone), wherein in formula (II) R ^{1 represents} a hydroxyl group, R ^{2 represents} a hydrogen atom, R ³ and R ^{4 represent} a methyl group and R ⁵ and R ^{6 represent} a hydrogen atom. The stereoisomer (R) -pantolactone is formed during the degradation of pantothenic acid. The said compounds of the vitamin B ₅ type and the 2-furanone derivatives can be used in the agents according to the invention in a total amount of from 0.05 to 5% by weight, preferably from 0.1 to 3% by weight, more preferably from 0 , 5 to 2 wt .-%, each based on the total agent, be contained, - Vitamin B ₆ : this is not a uniform substance, but the known under the common names pyridoxine, pyridoxamine and pyridoxal derivatives of 5-hydroxymethyl-2-methylpyridine -3-ols understood. Vitamin B ₆ may be contained in the compositions according to the invention preferably in amounts of from 0.0001 to 1.0 wt .-%, in particular in amounts of from 0.001 to 0.01 wt .-%, wherein the amounts are based on the total weight of Referred to by means of - Vitamin B ₇ : (biotin), also called vitamin H or "skin vitamin". Biotin is (3aS, 4S, 6aR) -2-oxohexahydrothienol [3,4-d] imidazole-4-valeric acid. Biotin may preferably be present in the agents used according to the invention in amounts of from 0.0001 to 1.0% by weight, in particular in amounts of from 0.001 to 0.01% by weight, the quantities being based on the total weight of the composition.
• (ii) Vitamin C (ascorbic acid): may be used in the compositions according to the invention preferably in amounts of 0.1 to 3 wt .-%, based on the total agent. The use of the derivatives ascorbyl palmitate, stearate, dipalmitate, acetate, Mg ascorbyl phosphate, Na ascorbyl phosphate, sodium and magnesium ascorbate, disodium ascorbyl phosphate and sulfate, potassium ascorbyl tocopheryl phosphate, chitosan ascorbate or ascorbyl glucoside may be preferred. The use in combination with tocopherols may also be preferred
• (iii) Vitamin E: The vitamin E group includes tocopherol, especially α-tocopherol, and its derivatives. Preferred derivatives are in particular the esters, such as tocopheryl acetate, nicotinate, phosphate, succinate, linoleate, oleate, tocophereth-5, tocophereth-10, tocophereth-12, tocophereth-18, tocophereth-50 and tocopherol. Tocopherol and its derivatives may be contained in the agents used in the invention preferably in amounts of 0.05-1 wt .-%, based on the total agent,
• (iv) Vitamin F: Vitamin F is usually understood as meaning essential fatty acids, in particular linoleic acid, linolenic acid and arachidonic acid.
• (v) Vitamin H: Vitamin H is another name for biotin or vitamin B ₇ (see above),
• (vi) Vitamin K: The fat-soluble vitamins of the vitamin K group underlying the backbone of 2-methyl-1,4-naphthoquinone include phylloquinone (vitamin K ₁ ), farnoquinone or menaquinone-7 (vitamin K2) and Menadione (Vitamin K ₃ ). Vitamin K may be contained in the agents used according to the invention preferably in amounts of 0.0001 to 1.0 wt .-%, in particular 0.01 to 0.5 wt .-%, each based on the total agent.

Panthenol, pantolactone, nicotinamide, pyridoxine, pyridoxamine, pyridoxal, biotin, ascorbyl palmitate, acetate, Mg ascorbyl phosphate, Na ascorbyl phosphate, sodium and magnesium ascorbate and the tocopherol esters, especially tocopheryl acetate, panthenol and pantolactone are particularly preferred.

Suitable monomers of amino acids and / or the NC ₂ -C ₂₄ acylamino acids may be selected from alanine, arginine, asparagine, aspartic acid, canavanine, citrulline, cysteine, cystine, desmosine, glutamine, glutamic acid, glycine, histidine, hydroxylysine, hydroxyproline, isodesmosine , Isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, pyroglutamic acid, sarcosine, serine, taurine, threonine, thyroxine, tryptophan, tyrosine and valine. Particularly preferred are taurine, arginine, hydroxyproline, proline and glutamic acid. The C ₂ -C ₂₄ acyl radical with which said amino acids are derivatized at the amino group is preferably selected from an acetyl, propanoyl, butanoyl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl -, undecanoyl, lauroyl, tridecanoyl, myristoyl, pentadecanoyl, cetoyl, palmitoyl, stearoyl, elaidoyl, arachidoyl or behenoyl radical. Mixtures of C ₈ -C ₁₈ acyl radicals are also referred to as cocoyl radical and are likewise preferred substituents. Preferred examples are zinc pyroglutamate, sodium octanoylglutamate, sodium decanoylglutamate, sodium lauroylglutamate, sodium myristoylglutamate, sodium cetoylglutamate and sodium stearoylglutamate. Particularly preferred are zinc pyroglutamate and sodium lauroylglutamate. Physiologically acceptable salts of the aforementioned active ingredients containing acid groups and capable of forming salts may be selected from the ammonium, alkali metal, magnesium, calcium, aluminum, zinc and manganese salts. Preferred are the sodium, potassium, magnesium, aluminum, zinc and manganese salts. Suitable oligomers of amino acids and / or the NC ₂ -C ₂₄ -acylamino acids may be selected from di-, tri-, tetra-, penta-, hexa-, hepta-, octa-, nona and decapeptides which acylates and / or can be esterified. Particularly preferred are the di-, tri-, tetra-, penta- and hexapeptides which may be acylated and / or esterified. Preferred, optionally acylated and / or esterified dipeptides are Tyr-Arg, Val-Trp, Asn-Phe, Asp-Phe, N-palmitoyl-β-Ala-His, N-acetyl-Tyr-Arg-hexyldecylester (e.g. Calmosensins from Sederma), carnosine (β-Ala-His) and N-palmitoyl-Pro-Arg. Preferred, optionally acylated and / or esterified tripeptides are Gly-His-Lys, N-palmitoyl-Gly-His-Lys, Gly-Lys-His, His-Ala-Orn, Lys-Phe-Lys, N-Elaidoyl-Lys- Phe-Lys and N-acetyl-Arg-Lys-Arg-NH ₂ . Preferred, optionally acylated and / or esterified tetrapeptides are Gly-Gln-Pro-Arg, Gly-Gln-Arg-Pro and N-palmitoyl-Gly-Gln-Pro-Arg. Preferred, optionally acylated and / or esterified pentapeptides are Lys-Thr-Thr-Lys-Ser, N-palmitoyl-Lys-Thr-Thr-Lys-Ser, N-palmitoyl-Tyr-Gly-Gly-Phe-Met and N- palmitoyl-Tyr-Gly-Gly-Phe-Leu. A preferred hexapeptide is palmitoyl-Val-Gly-Val-Ala-Pro-Gly (Biopeptide EL from Sederma). It may be particularly preferred that the agents used according to the invention comprise a mixture of at least two oligopeptides. A particularly preferred mixture is the combination of N-palmitoyl-Gly-His-Lys (eg, Biopeptide CL from Sederma) and N-palmitoyl-Gly-Gln-Pro-Arg (eg, in Eyeliss from Sederma). A preformed mixture of the tripeptide palmitoyl-Gly-His-Lys and the tetrapeptide N-palmitoyl-Gly-Gln-Pro-Arg is available under the tradename Matrixyl 3000, also from Sederma.

Suitable polymers of amino acids and / or the NC ₂ -C ₂₄ -acylamino acids can be selected from plant and animal protein hydrolysates and / or proteins. Among animal protein hydrolysates z. B. elastin, collagen, keratin, silk and milk protein protein hydrolysates to understand that may be present in the form of salts. Preference is given to vegetable protein hydrolysates, for. Soy, wheat, almonds, peas, potato and rice protein hydrolysates. Corresponding commercial products are z. B. Diahin ^® (Diamalt) Gluadin ^® (Cognis), Lexein ^® (Inolex) and Crotein ^® (Croda). Particularly preferred are soy protein hydrolysates, e.g. , The commercial products Phytokine ^® from Coletica or Ridulisse C ^® from Silab. Naturally, protein hydrolysates may also contain monomeric amino acids and oligopeptides; their composition is usually undefined. Also possible is the use of acyl derivatives of protein hydrolysates, z. In the form of their fatty acid condensation products. Corresponding commercial products are z. B. Lamepon ^® (Cognis), Gluadin ^® (Cognis), Lexein ^® (Inolex), Crolastin ^{® ®} or Crotein (Croda). Cationized protein hydrolysates can also be used according to the invention. In another preferred embodiment, the polymers of the amino acids may be selected from DNA repair enzymes. Preferred DNA repair enzymes are photolyase and T4 endonuclease V, the latter hereinafter abbreviated to "T4N5". These two enzymes are in the Prior art already known as so-called DNA repair enzymes. DNA repair is defined as the cleavage or removal of UV-induced pyrimidine dimers from the DNA.

Particularly preferred is the use of liposome-encapsulated DNA repair enzymes. Liposome-encapsulated photolyase is commercially available for. B. under the product name Photosome ^TM liposome-encapsulated T4N5 z. Available under the name Ultrasome ^™ from AGI Dermatics, USA. In the compositions used according to the invention, the Photosome ^™ or Ultrasome ^{™ may} preferably be used in amounts of 0.1-10% by weight, more preferably 0.5-5.0% by weight and particularly preferably 1.0-4, 0 wt .-%, based on the total agent to be included. In the agents used according to the invention, the monomers, oligomers or polymers of amino acids, NC ₂ -C ₂₄ -acylamino acids and / or the esters and / or the physiologically tolerable metal salts of these substances may preferably be used in amounts of 0.0001-10% by weight, more preferably from 0.01 to 5 wt .-% and particularly preferably from 0.1 to 3 wt .-%, in each case based on the total agent, be contained.

Suitable DNA or RNA oligonucleotides are preferably understood as meaning polymers of from 2 to 20, more preferably from 2 to 10, mononucleotides which, like polynucleotides and nucleic acids, are linked by phosphoric diester bridges. The nucleotides consist of nucleobases (usually pyrimidine or purine derivatives), pentoses (usually D-ribofuranose or 2-deoxy-D-ribofuranose in β-N-glycosidic bond to the nucleobase) and phosphoric acid. The mononucleotides are, for example, adenosine phosphates, cytidine phosphates, guanosine phosphates, uridine phosphates and thymidine phosphates, in particular CMP (cytidine 5'-monophosphate), UDP (uridine 5'-diphosphate), ATP (adenosine 5'-triphosphate) and GTP (guanosine). 5'-triphosphate). A particularly preferred oligonucleotide is the thymidine dinucleotide. In the agents used in the present invention, the DNA oligonucleotides or RNA oligonucleotides may preferably be used in amounts of 0.0001-5 wt%, preferably 0.001-1.0 wt%, and more preferably 0.01-0.5 Wt .-%, based on the total agent, be contained.

Suitable natural betaine compounds are preferably naturally occurring compounds having the atomic group R ₃ N ⁺ -CH ₂ -X-COO ^- according to IUPAC Rule C-816.1. So-called betaine surfactants (synthetic) are not among the suitable betaine compounds, nor are other zwitterionic compounds in which the positive charge on N or P and the negative charge are formally O, S, B or C, but not the IUPAC Comply with rule C-816.1. Preferred betaine compounds are betaine (Me ₃ N ⁺ -CH ₂ -COO ^- ) and carnitine (Me ₃ N ⁺ -CH ₂ -CHOH-CH ₂ -COO ^- ), each with Me = methyl and X = CC single bond (in the case of of betaine) or X = -CHOH-CH ₂ - (in the case of carnitine). The betaine compounds can be used in the compositions according to the invention preferably in a total amount of 0.05 to 5 wt .-%, preferably 0.1 to 3 wt .-%, particularly preferably 0.5 to 2 wt .-%, each based on the entire means, be included.

Among suitable α-hydroxycarboxylic acids, α-ketocarboxylic acids or β-hydroxycarboxylic acids or their ester, lactone or salt forms, preference is given to glycolic acid, lactic acid, tartaric acid, citric acid, 2-hydroxybutanoic acid, 2,3-dihydroxypropanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, 2-hydroxyheptanoic acid, 2-hydroxyoctanoic acid, 2-hydroxydecanoic acid, 2-hydroxydodecanoic acid, 2-hydroxytetradecanoic acid, 2-hydroxyhexadecanoic acid, 2-hydroxyoctadecanoic acid, mandelic acid, 4-hydroxymandelic acid, malic acid, erythraric acid, threaric acid, glucaric acid, galactaric acid, mannaric acid, gularic acid, 2- Hydroxy-2-methylsuccinic acid, gluconic acid, pyruvic acid, glucuronic acid and galacturonic understood. Particularly preferred α-hydroxycarboxylic acids are lactic acid, citric acid, glycolic acid and gluconic acid. A particularly preferred β-hydroxycarboxylic acid is salicylic acid. The esters of said acids may be selected from the methyl, ethyl, propyl, isopropyl, butyl, amyl, pentyl, hexyl, 2-ethylhexyl, octyl, decyl, dodecyl and hexadecyl esters. The .alpha.-hydroxycarboxylic acids, .alpha.-ketocarboxylic acids or .beta.-hydroxycarboxylic acids or their derivatives may be present in the agents used according to the invention preferably in amounts of from 0.1 to 10% by weight, preferably from 0.5 to 5% by weight the quantities are based on the total mean.

Preferred flavonoids include the glycosides of flavones, flavanones, 3-hydroxyflavones (flavonols), aurones and isoflavones. Particularly preferred flavonoids may be selected from naringin (aurantiine, naringenin-7-rhamnoglucoside), α-glucosylrutin, α-glucosylmyricetin, α-glucosylisoquercetin, α-glucosylquercetin, hesperidin (3 ', 5,7-trihydroxy-4'-methoxyflavanone- 7-rhamnoglucoside, hesperitin-7-O-rhamnoglucoside), neohesperidin, rutin (3,3 ', 4', 5,7-pentahydroxyflavone-3-rhamnoglucoside, quercetin-3-rhamnoglucoside), troxerutin (3,5-dihydroxy) 3 ', 4', 7-tris (2-hydroxyethoxy) flavone-3- (6-O- (6-deoxy-α-L-mannopyranosyl) -β-D-glucopyranoside)), monoxerutin (3,3 ' , 4 ', 5-Tetrahydroxy-7- (2-hydroxyethoxy) flavone-3- (6-O- (6-deoxy-α-L-mannopyranosyl) - (3-D-glucopyranoside)), diosmin (3' , 4 ', 7-trihydroxy-5-methoxyflavanon-7- rhamnoglucoside), eriodictin and apigenin-7-glucoside (4 ', 5,7-trihydroxyflavone-7-glucoside). Extremely preferred flavonoids are α-glucosylrutin, naringin and apigenin-7-glucoside. Also preferred are the constructed from two flavonoid biflavonoids, z. B. occur in gingko species. Other preferred flavonoids are the chalcones, especially phloricin, hesperidin methyl chalcone and neohesperidin dihydrochalcone. The flavonoids may be contained in the agents used in the invention preferably in amounts of from 0.0001 to 1 wt .-%, preferably from 0.0005 to 0.5 wt .-% and particularly preferably from 0.001 to 0.1 wt .-% , in each case based on the Flavonoidaktivsubstanz in the entire cosmetic agent. The isoflavones and the isoflavone glycosides are preferably counted among the suitable isoflavonoids. For the purposes of the present invention, isoflavones are to be understood as meaning substances which are hydrogenation, oxidation or substitution products of 3-phenyl-4H-1-benzopyran, hydrogenation of which may be in the 2,3-position of the carbon skeleton, oxidation under Formation of a carbonyl group in the 4-position may be present, and by substitution of the replacement of one or more hydrogen atoms by hydroxy or methoxy groups to understand. The preferred isoflavones include, for example, daidzein, genistein, prunetin, biochanin, orobol, santal, pratense, irigenin, glycitein, biochanin A and formononetin. Particularly preferred isoflavones are daidzein, genistein, glycitein and formononetin.

In preferred isoflavone glycosides, the isoflavones are glycosidically linked via at least one hydroxy group to at least one sugar. Suitable sugars are mono- or oligosaccharides, in particular D-glucose, D-galactose, D-glucuronic acid, D-galacturonic acid, D-xylose, D-apiose, L-rhamnose, L-arabinose and rutinose.

Particularly preferred isoflavone glycosides are daidzin and genistin.

It is further preferred if the isoflavones and / or their glycosides are contained in the preparations as constituents of a substance mixture obtained from a plant, in particular a plant extract. Such vegetable substance mixtures can be obtained in a manner familiar to the person skilled in the art, for example by squeezing or extracting from plants such as soya, red clover or chickpeas. Isoflavones or isoflavone glycosides in the form of extracts obtained from soybeans can be used with particular preference in the compositions according to the invention, as described, for example, under the product name Soy Protein Isolate SPI (Protein Technology International, St. Louis) or Soy Phytochemicals Concentrate SPC (Archer Daniels Midland, Decatur) are commercially available. Another particularly preferred isoflavonoid-rich plant extract is apple seed extract, in particular the commercial product Ederline from Seporga. Ederline contains phytohormones, isoflavonoids, phytosterols, triterpenoids, tocopherols and natural waxes. The isoflavonoids may be contained in the agents used in the invention preferably in amounts of 0.00001 to 1 wt .-%, preferably from 0.0005 to 0.5 wt .-% and particularly preferably from 0.001 to 0.1 wt .-% , in each case based on the Isoflavonoidaktivsubstanz in the entire cosmetic agent.

In a further preferred embodiment, the agents used according to the invention may additionally contain at least one polyphenol or a polyphenol-rich plant extract. Polyphenols are preferably aromatic compounds which contain at least two phenolic hydroxyl groups in the molecule. These include the three dihydroxybenzenes catechol, resorcinol and hydroquinone, phloroglucin, pyrogallol and hexahydroxybenzene. In nature, free and etherified polyphenols occur, for example, in floral dyes (anthocyanidins, flavones), in tannins (catechins, tannins), as lichen or fern ingredients (usnic acid, acylpolyphenols), in lignins and as gallic acid derivatives. Preferred polyphenols are flavones, catechins, usnic acid, and as tannins the derivatives of gallic acid, digallic acid and digalloylgallic acid. Particularly preferred polyphenols are the monomeric catechins, ie the derivatives of flavan-3-ols, and leucoanthocyanidins, ie the derivatives of leucoanthocyanidins which preferably carry phenolic hydroxyl groups in the 5,7,3 ', 4', 5 'position, preferably epicatechin and epigallocatechin, as well as the tannins resulting from self-condensation. Such tannins are preferably not used in isolated pure substance, but as extracts of tanning-rich plant parts, eg. Extracts of catechu, quebracho, oak bark and pine bark, as well as other tree bark, leaves of green tea (camellia sinensis) and mate. Also particularly preferred are the tannins. A particularly preferred polyphenol-rich cosmetic active ingredient is the commercial product Sepivinol R, an extract of red wine, available from Seppic. Another particularly preferred polyphenol-rich cosmetic active ingredient is the commercial product Crodarom Chardonnay L, an extract from the cores of the Chardonnay grape, available from Croda. The polyphenols may be used in the compositions according to the invention preferably in amounts of 0.001 to 10 wt .-%, preferably from 0.005 to 5 wt .-% and particularly preferably from 0.01 to 3 wt .-%, each based on the total cosmetic agent to be included.

mit n = 6, 7, 8, 9 oder 10. Besonders bevorzugt ist das Ubichinon der Formel (III) mit n = 10, auch bekannt als Coenzym Q10. Die Ubichinone, Ubichinole oder deren Derivate können in den erfindungsgemäß verwendeten Mitteln vorzugsweise in Mengen von 0,0001 bis 1 Gew.-%, bevorzugt von 0,001 bis 0,5 Gew.-% und besonders bevorzugt von 0,005 bis 0,1 Gew.-%, jeweils bezogen auf das gesamte Mitte, enthalten sein.In a further preferred embodiment, the agents used according to the invention may further comprise at least one ubiquinone or a ubiquinol or derivatives thereof. Ubiquinols are the reduced form of ubiquinones. Preferred ubiquinones have the formula (III):

with n = 6, 7, 8, 9 or 10. Particularly preferred is the ubiquinone of the formula (III) with n = 10, also known as coenzyme Q10. The ubiquinones, ubiquinols or their derivatives may be used in the compositions according to the invention preferably in amounts of from 0.0001 to 1% by weight, preferably from 0.001 to 0.5% by weight and more preferably from 0.005 to 0.1% by weight. %, in each case based on the entire center.

Silymarin is an active substance concentrate from the fruits of the milk thistle (Silybum marianum), previously considered to be a single substance. The main constituents of silymarin are silybin (silymarin I), silychristin (silymarin II) and silydianin, which belong to the group of flavanolignans.

Silymarin may be used in the compositions according to the invention preferably in amounts of from 0.0001 to 1 wt .-%, preferably from 0.001 to 1.0 wt .-% and particularly preferably from 0.005 to 0.5 wt .-%, each based on the entire means, be included.

In another preferred embodiment, the agents used in the invention may contain at least one naturally occurring xanthine derivative selected from caffeine, theophylline, theobromine and aminophylline. Particularly preferred is caffeine.

The naturally occurring xanthine derivatives can be used in the compositions according to the invention preferably in amounts of from 0.0001 to 5 wt .-%, preferably from 0.001 to 3 wt .-% and particularly preferably from 0.005 to 1 wt .-%, each based on the entire remedy to be included.

Ectoin is the common name for 2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylate. Ectoin may be used in the compositions according to the invention preferably in amounts of from 0.0001 to 1 wt .-%, preferably from 0.001 to 0.5 wt .-% and particularly preferably from 0.005 to 0.01 wt .-%, each based on the entire means, be included.

Suitable UV filter substances are preferably liquids which are liquid or crystalline at room temperature and which are capable of absorbing ultraviolet rays and which absorb the absorbed energy in the form of longer-wave radiation, eg. B. heat, again. One differentiates between UVA filters and UVB filters. The UVA and UVB filters can be used individually or in mixtures. The use of filter mixtures is preferred. Particularly suitable UV filters may be selected from the physiologically acceptable derivatives of dibenzoylmethane, cinnamic acid esters, diphenylacrylic acid esters, benzophenone, camphor, p-aminobenzoic acid esters, o-aminobenzoic acid esters, salicylic acid esters, benzimidazoles, symmetrically or asymmetrically substituted 1,3,5-triazines, monomeric and oligomeric 4,4-Diarylbutadiencarbonsäureestern and -carbonsäureamiden, Ketotricyclo (5.2.1.0) decane, Benzalmalonsäureestern, benzoxazole and any mixtures of the above components. The organic UV filters can be oil-soluble or water-soluble. Particularly preferred oil-soluble UV filters are 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione (Parsol ^® 1789), 1-phenyl-3- (4'-isopropylphenyl ) -propane-1,3-dione, 3- (4'-methylbenzylidene) -D, L-camphor, 4- (dimethylamino) benzoic acid 2-ethylhexyl ester, 4- (dimethylamino) benzoic acid 2-octyl ester, 4- (Dimethylamino) benzoate, 4-methoxycinnamic acid 2-ethylhexyl ester, propyl 4-methoxycinnamate, isopentyl 4-methoxycinnamate, 2-cyano-3,3-phenylcinnamic acid 2-ethylhexyl ester (octocrylene), 2-ethylhexyl salicylate, 4-isopropylbenzyl salicylate , Salicylic acid homomenthyl ester (3,3,5-trimethylcyclohexylsalicylate), 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 4-methoxybenzmalonic acid 2-ethylhexyl, 2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine (octyl Triazone, Uvinul ^® T150), Dimethicodiethylbenzal malonate (CAS no. 207574-74-1, Parsol ^® SLX), Dioctyl Butamido Triazone (Uvasorb HEB ^®), 2,4-bis- [5-1 (di-methylpropyl) benzoxazol-2-yl- (4 phenyl) imino] -6- (2-ethylhexyl) imino-1,3,5-triazine (CAS no. 288254-16-0, Uvasorb K2A ^®) and any desired mixtures of the stated components. Preferred water-soluble UV filters are 2-phenylbenzimidazole-5-sulfonic acid, phenylene-1,4-bis (2-benzimidazyl) -3,3'-5,5'-tetrasulfonic acid and their alkali metal, alkaline earth metal, ammonium, Alkylammonium-, Alkanolammonium- and Glucammoniumsalze, sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts, sulfonic acid derivatives of 3-Benzylidencamphers, such as. B. 4- (2-oxo-3-bomylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bomylidene) sulfonic acid and salts thereof. Some of the oil-soluble UV filters can themselves serve as solvents or solubilizers for other UV filters. Thus, solutions of the UV-A-filter 1 can be, for example, (4-tert-butylphenyl) -3- (4'methoxyphenyl) propane-1,3-dione (z. B. Parsol ^® 1789) in various UV-B Make filters. Therefore, in a further preferred embodiment, the compositions according to the invention contain 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione in combination with at least one UV-B filter selected from 4 2-ethylhexyl 2-ethoxycinnamate, 2-ethylhexyl 2-cyano-3,3-phenylcinnamate, 2-ethylhexyl salicylate and 3,3,5-trimethylcyclohexylsalicylate. In these combinations, the weight ratio of UV-B filter to 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione is between 1: 1 and 10: 1, preferably between 2 : 1 and 8: 1, the molar ratio is between 0.3 and 3.8, preferably between 0.7 and 3.0.

Preferred inorganic photoprotective pigments are finely dispersed or colloidally disperse metal oxides and metal salts, for example titanium dioxide, zinc oxide, iron oxide, aluminum oxide, cerium oxide, zirconium oxide, silicates (talc) and barium sulfate. The particles should have an average diameter of less than 100 nm, preferably between 5 and 50 nm and in particular between 15 and 30 nm, so-called nanopigments. They may have a spherical shape, but it is also possible to use those particles which have an ellipsoidal or otherwise deviating shape from the spherical shape. The pigments can also be surface-treated, ie hydrophilized or hydrophobized. Typical examples are coated titanium dioxides, such as. T805 as titanium dioxide (Degussa) or Eusolex ^® T2000 (Merck). Suitable hydrophobic coating agents are in particular silicones and in particular trialkoxyoctylsilanes or simethicones. Particularly preferred are titanium dioxide and zinc oxide. The organic UV filter substances can be used in the agents according to the invention preferably in amounts of 0.01-30% by weight, more preferably of 0.05-20% by weight, particularly preferably of 0.1-15% by weight. and most preferably from 0.25 to 10% by weight, based in each case on the total agent. The inorganic UV filter substances can be used in the compositions according to the invention preferably in amounts of 0.01-15 wt .-%, preferably from 0.05 to 10 wt .-%, particularly preferably from 0.1 to 5 wt .-% and most preferably from 0.25 to 4.0% by weight, based in each case on the total agent.

Suitable skin lightening agents may be selected from ascorbic acid, the esters of ascorbic acid with phosphoric acid and / or organic C ₂ -C ₂₀ carboxylic acids and their alkali and alkaline earth metal salts, kojic acid, hydroquinone, arbutin, mulberry extract and licorice extract, and mixtures thereof. Both as a single substance and as a mixture, the ascorbic acid derivatives and kojic acid are preferred. Particularly preferred are sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl monopalmitate, ascorbyl dipalmitate, ascorbyl monostearate, ascorbyl distearate, ascorbyl monoethyl hexanoate, ascorbyl diethylhexanoate, ascorbyl monooctanoate, ascorbyl dioctanoate, ascorbyl monoisostearate and ascorbyl diisostearate. The invention extraordinarily preferred ascorbic acid derivatives are sodium ascorbyl phosphate and magnesium ascorbyl phosphate. The skin-lightening active ingredients may preferably be present in the agents used according to the invention in an amount of 0.05 to 5% by weight, preferably 0.1-2% by weight, in each case based on the total agent.

Suitable skin-calming active ingredients are preferably selected from farnesol, allantoin, α-bisabolol and α-lipoic acid. The skin-soothing active ingredients may be contained in the compositions used according to the invention preferably in amounts of from 0.001 to 5% by weight, preferably from 0.005 to 1% by weight, in each case based on the total composition.

Suitable sebum-regulating agents may be selected from acnacidol, azelaic acid, azeloglycine and an extract of Spiraea ulmaria. The extract is z. B. included in the product Seburegul the company Silab. The sebum-regulating active ingredients may be used in the compositions according to the invention preferably in amounts of 0.001 to 5 wt .-%, preferably 0.01 to 2 wt .-% and particularly preferably 0.1 to 1 wt .-%, each based on the total agent to be included.

In a particularly preferred embodiment, methimazole is used in cosmetic skin treatment compositions which, in addition to the carrier described above, preferably at least two, more preferably contain at least three and more preferably at least four active ingredients from the aforementioned group. Particularly preferred is the use according to the invention in skin treatment compositions containing as further active ingredients at least two active ingredients from the group of vitamins (as described above), the urea derivatives according to formula (I), the natural betaine compounds, the xanthine derivatives and / or the hautberuhingenden Contain active ingredients.

Agents used according to the invention may also be present as pastes, ointments, lotions or creams. Solid funds can be present as a loose powder, pressed powder or as a pen.

Advantageously, the skin treatment compositions used in the invention are in the form of a liquid, flowable or solid oil-in-water emulsion, water-in-oil emulsion, multiple emulsion, in particular an oil-in-water-in-oil or water-in Oil-in-water emulsion, macroemulsion, miniemulsion, microemulsion, PIT emulsion, nanoemulsion, Pickering emulsion, hydrodispersion, a hydrogel, a lipogel, a mono- or multiphase solution, a foam, a powder or a mixture with at least a polymer suitable as a medical adhesive. The agents may also be presented in anhydrous form, such as an oil or a balm. Here, the carrier may be a vegetable or animal oil, a mineral oil, a synthetic oil or a mixture of such oils.

Particularly preferred agents used according to the invention are in the form of a flowable emulsion and preferably contain at least one further skin-conditioning active ingredient and at least one emulsifier.

Suitable conditioning active substances are preferably those substances which are absorbed on keratinic materials, in particular on the skin, and improve the physical and sensory properties of both the skin and of the product as such. Conditioners smooth the top layer of the skin and make it soft and supple. Through the choice of conditioning agents (greasy - less greasy, fast or slow spreading, quickly or slowly absorbed into the skin and so on), the skin feel of the entire product can be adjusted. Preferred conditioning agents may be selected from fatty substances, especially vegetable oils, such as sunflower oil, olive oil, soybean oil, rapeseed oil, almond oil, jojoba oil, orange oil, wheat germ oil, peach kernel oil and the liquid portions of coconut oil, lanolin and its derivatives, liquid paraffin oils, isoparaffin oils and synthetic hydrocarbons , Di-n-alkyl ethers having a total of 12 to 36 carbon atoms, z. B. di-n-octyl ether and n-hexyl-n-octyl ether, fatty acids, especially linear and / or branched, saturated and / or unsaturated C _8-30 fatty acids, fatty alcohols, particularly saturated, mono- or polyunsaturated, branched or unbranched fatty alcohols having 4-30 carbon atoms, which may be ethoxylated with 1-75, preferably 5-20 ethylene oxide units and / or propoxylated with 3-30, preferably 9-14 propylene oxide units, ester oils, ie esters of C _{6 30-} fatty acids with C _2-30 fatty alcohols, hydroxycarboxylic acid alkyl esters, dicarboxylic acid esters such as di-n-butyl adipate and diol esters such as ethylene glycol diol or propylene glycol di (2-ethylhexanoate), symmetrical, asymmetrical or cyclic esters of carbonic acid with fatty alcohols, eg. B. glycerol carbonate or dicaprylyl carbonate (Cetiol ^® CC), mono, - di- and tri fatty acid esters of saturated and / or unsaturated linear and / or branched fatty acids with glycerol, which, preferably 7-9 ethylene oxide units may be ethoxylated with 1-10, z. B. PEG-7 glyceryl cocoate, waxes, especially insect waxes, plant waxes, fruit waxes, ozokerite, microwaxes, ceresin, paraffin waxes, triglycerides gesaettigter and optionally hydroxylated C _16-30 fatty acids, eg. Hardened triglyceride fats, phospholipids, for example, soybean lecithin, egg lecithin and cephalins, shea butter, silicone compounds selected from decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, and silicone polymers, which may, if desired, be cross-linked, e.g. B. polydialkylsiloxanes, polyalkylarylsiloxanes, ethoxylated and / or propoxylated polydialkylsiloxanes having the earlier INCI name dimethicone copolyol, and polydialkylsiloxanes containing amine and / or hydroxyl groups, preferably substances with the INCI names Dimethiconol, Amodimethicone or Trimethylsilylamodimethicone. The amount of fatty substances used in the compositions according to the invention is preferably 0.1-99% by weight, more preferably 2-50% by weight and most preferably 5-20% by weight, based in each case on the total composition.

Suitable surface-active substances and / or emulsifiers are, for example, addition products of 4 to 30 mol of ethylene oxide and / or 0 to 5 mol of propylene oxide onto linear C ₈ -C ₂₂ -fatty alcohols, on C ₁₂ -C ₂₂ fatty acids and on C ₈ -C ₁₅ - Alkylphenols, C ₁₂ -C ₂₂ -Fettsaeuremono- and diesters of addition products of 1 to 30 moles of ethylene oxide to C ₃ -C ₆ polyols, in particular glycerol, ethylene oxide and polyglycerol addition products of methyl glucoside fatty acid esters, fatty acid alkanolamides and Fettsäureglucamide, C ₈ -C ₂₂ -alkylmono- and -oligoglycosides and their ethoxylated analogues, with degrees of oligomerization of 1.1 to 5, in particular 1.2 to 2.0, and glucose as sugar component being preferred, mixtures of alkyl (oligo) - glucosides and fatty alcohols, e.g. Example, the commercially available product Montanov ^® 68, addition products of 5 to 60 moles of ethylene oxide with castor oil and hydrogenated castor oil, partial esters of polyols having 3-6 carbon atoms with saturated C ₈ -C ₂₂ fatty acids, sterols (sterols), in particular cholesterol, lanosterol, beta-sitosterol, stigmasterol, campesterol and ergosterol, as well as mycosterols, phospholipids, especially glucose phospholipids, fatty acid ester of sugars and sugar alcohols such as sorbitol, polyglycerols and polyglycerol, preferably Polyglyceryl-2-dipolyhydroxystearate (commercial product Dehymuls ^® PGPH) and Polyglyceryl-3 -diisostearat (commercial product Lameform ^® TGI) as well as linear and branched C ₈ -C ₃₀ fatty acids and their Na, K, ammonium, Ca, Mg and Zn salts.

The agents used according to the invention may contain the emulsifiers preferably in amounts of from 0.1 to 25% by weight, particularly preferably 0.5-15% by weight, based on the total agent.

Other suitable additives of the emulsions are thickeners, eg. As anionic polymers of acrylic acid, methacrylic acid, crotonic acid, maleic anhydride and 2-acrylamido-2-methylpropansulfonsaeure, wherein the acidic groups may be wholly or partially present as sodium, potassium, ammonium, mono- or triethanolammonium salt and at least one may be included nonionic monomer. Preferred nonionic monomers are acrylamide, methacrylamide, acrylic esters, methacrylic esters, vinylpyrrolidone, vinyl ethers and vinyl esters. Preferred anionic copolymers are acrylic acid-acrylamide copolymers and in particular polyacrylamide copolymers with sulfonic acid-containing monomers. These copolymers can also be present in crosslinked form. Suitable commercial products are NS urchins ^® 305, Simulgel ^® 600, Simulgel ^® and Simulgel EPG ^® of the company SEPPIC. Further particularly preferred anionic homopolymers and copolymers are uncrosslinked and crosslinked polyacrylic acids. Such compounds are for example the commercial products Carbopol ^®. A particularly preferred anionic copolymer contains as monomer 80-98% of an unsaturated, optionally substituted C _3-6 carboxylic acid or its anhydride and 2-20% of optionally substituted acrylic acid esters of saturated C _10-30 carboxylic acids, the copolymer having the can be crosslinked aforementioned crosslinking agents. Corresponding commercial products are Pemulen ^® and Carbopol ^® grades 954, 980, 1342 and ETD 2020 (ex BF Goodrich).

• – Parfumöle,
• – Substanzen zur Einstellung des pH-Wertes,
• – Komplexbildner wie EDTA, NTA, β-Alanindiessigsaeure und Phosphonsaeuren,
• – Treibmittel wie Propan-Butan-Gemische, Pentan, Isopentan, Isobutan, N₂O, Dimethylether, CO₂ und Luft,
• – Wirkstoffe wie Hyaluronsäure und/oder Glycyrrhizinsäure bzw. deren physiologisch verträglich Salze und/oder Derivate,
• – Pigmente und/oder
• – Abrasivstoffe.

Further suitable additives are, for example:

• - perfume oils,
• - substances for adjusting the pH,
• Complexing agents such as EDTA, NTA, β-alaninediacetic acid and phosphonic acid,
• Propellants such as propane-butane mixtures, pentane, isopentane, isobutane, N ₂ O, dimethyl ether, CO ₂ and air,
• Active ingredients such as hyaluronic acid and / or glycyrrhizic acid or their physiologically tolerable salts and / or derivatives,
• - pigments and / or
• - Abrasives.

The use of methimazole in cosmetic products, especially in cosmetic skin treatment compositions, has the advantage of stimulating collagen neutron synthesis in the dermis. Methimazole is therefore suitable as a RAMBA. The skin has a more refined complexion after treatment with methimazole in a topical vehicle. Furthermore, the skin firmness can be improved by the use according to the invention - the skin is tightened overall. By stimulating collagen and / or hyaluronic acid synthesis in the dermis, the signs of dermal tissue shrinkage can be eliminated and / or diminished.

Accordingly, a second aspect of the invention is a cosmetic, non-therapeutic method for improving skin firmness and / or firming and / or reducing wrinkles in which methimazole is contacted with the skin in a suitable cosmetic carrier.

A third object of the invention is therefore a cosmetic, non-therapeutic method for improving dermal tissue shrinkage, in which methimazole is brought into contact with the skin in a suitable cosmetic carrier.

According to the invention, preference is given to a cosmetic process in which methimazole is preferably present in an amount of from 0.001 to 5% by weight, preferably from 0.01 to 3% by weight, and in particular from 0.1 to 1% by weight in the cosmetic Carrier is included, wherein the amounts are based on the total weight of the cosmetic carrier.

Also preferred according to the invention is a cosmetic method in which the use of methimazole influences, preferably stimulates and / or improves collagen and / or hyaluronic acid synthesis in the dermis.

With regard to the cosmetic carrier and the other optional ingredients of the cosmetic carrier, what has been said under the sections for use according to the invention applies.

Example:

Identification of 3-methyl-1-phenyl-5-pyrazolone as RAMBA

Various cosmetic agents that can be included in the azole class of compounds have been evaluated for possible RAMBA activity.

For this purpose, human keratinocytes were incubated for 16 hours with the corresponding substances in combination with retinoic acid and then followed by qPCR expression change of the marker CYP26A1. The enzyme CYP26A1 causes the metabolism of retinoic acid and is induced by the retinoic acid itself, whereby a feedbak regulation of the retinoic acid concentration in the cell is made possible. When a RAMBAS is administered at the same time, the extent of this incubation is markedly lower, and thus the retinoic acid degradation is inhibited. As a control, the known RAMBA ketoconazole was used. Table 1 Rel. Expression CYP26A1 HOURS Control 96% ethanol 1.0 0.3 Retinoic acid (RA) [10 nM] 37.6 0.3 RA + ketoconazole [10 μM] 11.1 0.1 RA + methimazole [0.1%] 12.7 0.1

Table 1 shows that methimazole (as well as ketoconazole) when combined with retinoic acid significantly reduces the induction of CYP26A1. Methimazole thus shows approximately the same RAMBA activity as ketoconazole.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited non-patent literature

• Verfaille et al. (2008), JDDG 5: 355-364 [0005]
• Kasree et al., Skin Pharm. Phys. 21: 300-305 (2008) [0007]
• Kasree et al., Dermatology 211: 360-362 (2005) [0007]
• Elias et al. Int. J. Derm. 43: 889-892 (2004) [0007]
• Hasegawa et al., J. Derm. 31: 794-797 (2004) [0007]
• Elias, Medical Hypothesis, 62: 431-437 (2004) [0007]
• Kasree, J. Invest. Dermat. 118: 205-207 (2002) [0007]
• Moseley et al., Photodermatology, 6: 32-36 (1989) [0007]

Claims (10)

Cosmetic, non-therapeutic use of 1,3-dihydro-methyl-2H-imidazole-2-thione (methimazole) to influence the natural production of components in the dermis. Use according to claim 1, characterized in that the natural production of components of the extracellular matrix in the dermis is influenced, in particular stimulated. Use according to claim 1 or 2, characterized in that the natural production of collagen, elastin and / or glycosaminoglycans in the extracellular matrix is influenced, preferably stimulated and / or improved. Use according to claim 3, characterized in that the collagen and / or hyaluronic acid synthesis is influenced, preferably stimulated and / or improved. Use according to one of claims 1 to 4, characterized in that the use is made topically. Use according to one of claims 1 to 5, characterized in that 0.001 to 5 wt .-%, preferably from 0.01 to 3 wt .-%, and in particular from 0.1 to 1 wt .-% methimazole in a cosmetic skin treatment agent the amounts are based on the total weight of the cosmetic skin treatment agent. Cosmetic process for improving skin firmness and / or for firming the skin and / or for reducing skin wrinkles, characterized in that methimazole is brought into contact with the skin in a suitable cosmetic carrier. Cosmetic, non-therapeutic method for improving dermal tissue shrinkage, which comprises contacting methimazole in a suitable cosmetic carrier with the skin. Cosmetic, non-therapeutic method according to one of claims 7 or 8, characterized in that methimazole in an amount of 0.001 to 5 wt .-%, preferably from 0.01 to 3 wt .-%, and in particular from 0.1 to 1 wt .-% is contained in the cosmetic carrier, wherein the amount refers to the total weight of the cosmetic carrier. Cosmetic method according to one of claims 7 to 9, characterized in that the collagen and / or hyaluronic acid synthesis in the dermis is influenced, preferably stimulated and / or improved.