WO2004089326A1 - Cosmetic or dermatological preparations containing a combination of creatinine, creatine and bioquinones - Google Patents

Cosmetic or dermatological preparations containing a combination of creatinine, creatine and bioquinones Download PDF

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Publication number
WO2004089326A1
WO2004089326A1 PCT/EP2004/050482 EP2004050482W WO2004089326A1 WO 2004089326 A1 WO2004089326 A1 WO 2004089326A1 EP 2004050482 W EP2004050482 W EP 2004050482W WO 2004089326 A1 WO2004089326 A1 WO 2004089326A1
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WIPO (PCT)
Prior art keywords
skin
preparations
cosmetic
derivatives
prophylaxis
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PCT/EP2004/050482
Other languages
German (de)
French (fr)
Inventor
Uwe Schoenrock
Volker Schreiner
Franz Staeb
Inge Kruse
Helga Biergiesser
Holger Lenz
Claudia Mundt
Melanie Schmidt
Thomas Blatt
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Beiersdorf Ag
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Publication of WO2004089326A1 publication Critical patent/WO2004089326A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • A61K8/355Quinones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/02Preparations containing skin colorants, e.g. pigments
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/004Aftersun preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/005Preparations for sensitive skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth

Definitions

  • the present invention relates to the use of combinations of creatinine and / or creatinine derivatives with creatine and / or its derivatives with bioquinones in cosmetic or dermatological preparations for the treatment and prophylaxis of the symptoms of UV and or ozone-induced skin damage and of inflammatory and degenerative skin conditions.
  • Cosmetic skin care is primarily understood to mean that the natural function of the skin as a barrier against environmental influences (e.g. dirt, chemicals, microorganisms) and against the loss of the body's own substances (e.g. water, natural fats, electrolytes) is strengthened or restored.
  • environmental influences e.g. dirt, chemicals, microorganisms
  • loss of the body's own substances e.g. water, natural fats, electrolytes
  • the aim of skin care is also to compensate for the loss of fat and water in the skin caused by daily washing. This is especially important when the natural regeneration ability is insufficient.
  • skin care products are intended to protect against environmental influences, especially sun and wind, and to delay skin aging.
  • Chronological skin aging is caused, for example, by endogenous, genetically determined factors.
  • the following structural damage and functional disorders occur in the epidermis and dermis due to aging, which can also fall under the term "senile xerosis”: a) dryness, roughness and the formation of wrinkles due to dryness, b) itching and c) reduced regreasing due to sebum glands (eg after washing).
  • Exogenous factors such as UV light and chemical pollutants can be cumulative and e.g. accelerate or complement the endogenous aging processes.
  • exogenous factors e.g. to the following structural damage and functional disorders in the skin that go beyond the extent and quality of the damage caused by chronological aging: d) visible vasodilation (telangiectasias, cuperosis); e) flaccidity and wrinkling; f) local hyper-, hypo- and incorrect pigmentations (e.g. age spots) and g) increased susceptibility to mechanical stress (e.g. cracking).
  • the present invention relates in particular to products for the care of naturally aged skin and for the treatment of the consequential damage caused by light aging, in particular the phenomena listed under a) to g).
  • Products for the care of aged skin are known per se. They contain e.g. Retinoids (vitamin A acid and / or its derivatives) or vitamin A and / or its derivatives.
  • Retinoids vitamin A acid and / or its derivatives
  • their effect on structural damage is limited in scope.
  • the use of products containing vitamin A acid often causes severe erythematous skin irritation. Retinoids can therefore only be used in low concentrations.
  • the present invention relates to cosmetic preparations with effective protection against harmful oxidation processes in the skin, but also for protecting cosmetic preparations themselves or for protecting the constituents of cosmetic preparations against harmful oxidation processes.
  • UVC range rays with a wavelength shorter than 290 nm
  • UVB range rays in the range between 290 nm and 320 nm
  • the narrower range around 308 nm is given as a maximum of the erythema effectiveness of sunlight.
  • Numerous compounds are known for protection against UVB radiation, which are derivatives of 3-benzylidene camphor, 4-aminobenzoic acid, cinnamic acid, salicylic acid, benzophenone and also 2-phenylbenzimidazole.
  • UVA range It is also important to have filter substances available for the range between about 320 nm and about 400 nm, the so-called UVA range, since their rays can cause reactions in light-sensitive skin. It has been proven that UVA radiation leads to damage to the elastic and collagen fibers of the connective tissue, which causes the skin to age prematurely, and that it is to be seen as the cause of numerous phototoxic and photoallergic reactions. The damaging influence of UVB radiation can be intensified by UVA radiation.
  • UV radiation can also lead to photochemical reactions, in which case the photochemical reaction products interfere with the skin's metabolism.
  • Such photochemical reaction products are predominantly free radical compounds, for example hydroxy radicals.
  • Undefined radical photo products which are created in the skin itself, can also display uncontrolled subsequent reactions due to their high reactivity.
  • singlet oxygen a non-radical excited state of the oxygen molecule can occur with UV radiation, just as short-lived epoxies and many others.
  • Singlet oxygen for example, is characterized by increased reactivity compared to the triplet oxygen that is normally present (radical ground state). However, there are also excited, reactive (radical) triplet states of the oxygen molecule.
  • UV radiation also belongs to ionizing radiation. There is therefore a risk that ionic species also develop when exposed to UV, which in turn can then oxidatively intervene in the biochemical processes. In order to prevent these reactions, additional antioxidants and / or free radical scavengers can be incorporated into the cosmetic or dermatological formulations.
  • vitamin E a substance with a known antioxidant effect, in light protection formulations, but the effect achieved here also falls far short of the hoped-for effect.
  • the object of the invention was therefore also to provide cosmetic, dermatological and pharmaceutical active substances and preparations and light protection formulations which are used for the prophylaxis and treatment of light-sensitive skin, in particular photodermatoses, preferably PLD.
  • Antioxidants are mainly used as protective substances against the spoilage of the preparations containing them. Nevertheless, it is known that undesirable oxidation processes can also occur in human and animal skin. Such processes play an essential role in skin aging.
  • antioxidants and / or free radical scavengers can be incorporated into cosmetic or dermatological formulations.
  • antioxidants and radical scavengers are known. It has already been proposed in US Pat. Nos. 4,144,325 and 4,248,861 and from numerous other documents to use vitamin E, a substance with a known antioxidant activity in light protection formulations, but the effect achieved here also falls far short of the hoped-for effect.
  • the object of the present invention was therefore to find ways which avoid the disadvantages of the prior art. In particular, the effect of remedying the damage associated with endogenous, chronological and exogenous skin aging and the prophylaxis should be permanent, sustainable and without the risk of side effects. The object of the present invention was to remedy these shortcomings.
  • the invention also includes the use of such preparations for the prophylaxis and / or treatment of inflammatory skin conditions and / or for skin protection in the case of sensitive and dry skin (such as, for example, atopic eczema, seborrheic eczema, polymorphic light dermatosis, psoriasis, vitiligo, Wound healing disorders, itching, sensitive or irritated skin, light-induced skin damage and UV-induced immunosuppression, changes in desquamation, changes in normal fibroblast and keratinocyte proliferation, changes in normal fibroblast and keratinocyte differentiation, deficient, sensitive or hypoactive skin conditions, sensitive or hypoactive skin conditions, sensitive, or hypoactive skin conditions, sensitive, or hypoactive skin conditions, sensitive, or hypoactive skin conditions and to reduce skin thickness).
  • sensitive and dry skin such as, for example, atopic eczema, seborrheic eczema, polymorphic light dermatosis, psori
  • the invention comprises the use of such preparations for the treatment and prophylaxis of the symptoms of intrinsic and / or extrinsic skin aging and for the treatment and prophylaxis of the harmful effects of ultraviolet radiation on the skin, for.
  • degenerative symptoms of the skin such as age spots, wrinkles, telangiectasias, sagging skin, loss of elasticity, as well as loss of the epidermal and dermal cell layers, the components of the connective tissue, the rete cones and capillary vessels), so-called skin luster and fatigue (skin sagging and / or skin fatigue), increased activation of proteolytic enzymes in the skin such as B.
  • Metalloproteinases disorders of normal collagen, hyaluronic acid, elastin and glycosaminoglycan homeostasis and normal skin regeneration, changes in normal fibroblast and keratinocyte proliferation. Changes in normal fibroblast and keratinocyte differentiation, deficiency symptoms of the intracellular DNA synthesis (especially in deficient or hypoactive skin conditions), environmental (caused by smoking, smog, reactive oxygen species, free radicals and the like) negative changes in the skin and / or the appendages of the skin.
  • Also according to the invention is the use of such preparations for the treatment and / or prophylaxis of pigmentation disorders, for increasing ceramide biosynthesis (such as changes in the ceramide, lipid and energy metabolism of healthy skin), for strengthening the barrier function of the skin (such as. B. Horn layer barrier disorders, changes in normal lipid peroxidation, changes in transepidermal water loss and normal moisture content of the skin), for the treatment and / or prophylaxis of disorders of the normal skin pH and the osmolytic balance, for the treatment and / or prophylaxis of deviations from normal cell-cell communication in the skin (e.g. intercellular communication via mediators and / or via mechanical / physiological connections).
  • ceramide biosynthesis such as changes in the ceramide, lipid and energy metabolism of healthy skin
  • barrier function of the skin such as. B. Horn layer barrier disorders, changes in normal lipid peroxidation, changes in transepidermal water loss and normal moisture content of the skin
  • compositions for the treatment and / or prophylaxis of functional disorders of the skin appendages for example hair loss, improved hair growth, improved hair gloss, improved hair structure, seborrheic symptoms, oily skin, oily hair, comedones, but also dandruff.
  • Preparations and uses according to the invention are preferably characterized in that coenzyme Q10 is contained as bioquinone.
  • Preparations and uses according to the invention are particularly preferably characterized in that coenzyme Q10 and vegetable and animal extracts containing the same are contained in cosmetic or topical dermatological preparations in concentrations of 0.001-30% by weight, particularly preferably 0.01-1% by weight based on the total weight of the preparations and the content of creatinine and / or its derivatives 0.001-50% by weight, preferably 0.1-10% by weight and the content of creatine and its derivatives 0.001-50% by weight , preferably 0.1-10% by weight, based on the total weight of the preparations.
  • Creatinine is contained in meat extract and bouillon cubes.
  • Creatinine is formed in aqueous solution. It arises in the organism through transamidation of L-arginine on glycine to guanidinoacetic acid and its subsequent methylation using S-adenosylmethionine (through guanidinoacetate methyltransferase). Creatine is thought to be an appetite-enhancing component of beef and meat extract. Adding creatine to food increases physical performance.
  • the weight ratio of creatinine to creatine in the range from 50: 1 to 1:50, preferably from 10: 1 to 1:10, particularly preferably from 2: 1 to 1: 2.
  • the preferred derivative is creatine phosphate, which has the following structure:
  • Creatine phosphate is present in the working muscle Adenosine 5'-diphosphate under the influence of the enzyme creatine kinase adenosine 5'-triphosphate (ATP) and creatine; the reverse reaction takes place in the resting muscle. But also creatine sulfate, creatine acetate, creatine ascorbate and the derivatives esterified on the carboxyl group with mono- or polyfunctional alcohols lead to advantageous embodiments of the invention.
  • Coenzyme Q-10 for example, is characterized by the following structural formula:
  • Ubiquinones serve the organisms as electron carriers in the respiratory chain. They are located in the mitochondria where they enable the cyclic oxidation and reduction of the substrates of the citric acid cycle. Plastoquinones have the general structural formula
  • Cosmetic preparations with coenzyme Q-10 from DE-A-33 09 850 are known which are used for the treatment of skin diseases, for the prophylaxis of dystrophic and dysmabolic conditions of the skin and for use in the case of chemical and physical respiratory damage or in the case of delayed respiration Age and wear are suitable.
  • coenzyme Q-10 for cosmetics is described in Japanese laid-open publication 58, 180, 410. It is said to activate skin cell metabolism and suppress oxidation. As a result, coenzyme Q10 has an important function in the prevention of skin damage from UV rays and the prevention of skin aging.
  • JP2000 / 247866 describes skin cosmetics with a content of creatine and / or creatinine, which can be used as a cream or as a milky lotion, the preparations in question being attributed excellent skin-care properties.
  • this document could not pave the way for the present invention.
  • WO00 / 33787 describes the use of creatinine as an effective component of deodorants. This document also could not pave the way to the present invention.
  • EP-A 565 010 describes hair growth and hair dye preparations containing creatine phosphate. This document also could not pave the way to the present invention.
  • the combination of active substances according to the invention or cosmetic or topical dermatological preparations with an effective content of active substance combination according to the invention also serves, surprisingly, to calm sensitive or irritated skin to stimulate collagen, hyaluronic acid, elastin synthesis to stimulate intracellular DNA synthesis, in particular with deficient or hypoactive skin conditions.
  • to increase cell renewal and regeneration of the skin to increase the skin's own protection and repair mechanisms (for example for dysfunctional enzymes, DNA, lipids, proteins) for pre-treatment and post-treatment with topical application of laser and abrasive treatments, e.g. B. serve the reduction of skin folds and scars to counteract the resulting skin irritation and to promote the regeneration processes in the injured skin.
  • Effects according to the invention lie in the stabilization of the energy metabolism in the sense of a synergism between the components creatine, creatinine and coenzyme Q10 according to the invention in comparison to creatine and creatinine alone.
  • the improved energy level of the skin cells can have a significantly better effect for prophylaxis and Treatment of degenerative skin and hair symptoms (wrinkles, sagging, degeneration, age spots, circulatory disorders, itching, sensitivity to stress, brittleness) can be achieved.
  • the antioxidants are advantageously selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L- Carnosine and its derivatives (e.g. anserine), carotenoids, carotenes (e.g. ⁇ -carotene, ß-carotene, lycopene) and their derivatives, lipoic acid and their derivatives (e.g. dihydroliponic acid), arthioglucose, propylthiouracil and other thiols (e.g.
  • amino acids eg glycine, histidine, tyrosine, tryptophan
  • imidazoles eg urocanic acid
  • peptides such as D, L-carnosine, D-carnosine, L-
  • thioredoxin glutathione , Cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, ⁇ -linoleyl, cholesteryl and glyceryl esters) as well as their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g.
  • buthioninsulfoximines homocysteine sulfoximine, buthioninsulfones, pentathione, hexa-, imine
  • low tolerable doses e.g. pmol to ⁇ mol / kg
  • metal chelators e.g. -hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin
  • -hydroxy acids e.g.
  • citric acid lactic acid, malic acid
  • humic acid bile acid, bile extracts, bilirubin, biliverdin , EDTA, EGTA and their derivatives
  • unsaturated fatty acids and their derivatives eg ⁇ -linolenic acid, linoleic acid, oleic acid
  • folic acid and their derivatives alanine diacetic acid, flavonoids, taurine and derivatives, polyphenols, catechins, vitamin C and derivatives (eg ascorbyl palmitate , Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, ferulic acid and its derivatives, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguajakharzenic acid, noredihydroxychloric acid
  • stilbenes and their derivatives e.g. stilbene oxide, trans-stilbene oxide
  • derivatives suitable according to the invention salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids
  • the amount of the antioxidants (one or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05 to 20% by weight, in particular 1 to 10% by weight, based on the total weight of the preparation ,
  • the prophylaxis or the cosmetic or dermatological treatment with the active substance combinations used according to the invention or with the cosmetic or topical dermatological preparations with an effective content of active substance combination used according to the invention is carried out in the usual way, in such a way that the active substance used according to the invention or the cosmetic ones or topical dermatological preparations with an effective content of active ingredient used according to the invention is applied to the affected skin areas.
  • the active ingredient combination used according to the invention can advantageously be incorporated into customary cosmetic and dermatological preparations, which can be in various forms. So you can e.g. a solution, an emulsion of the type water-in-oil (W / O) or of the type oil-in-water (O / W), or a multiple emulsions, for example of the type water-in-oil-in-water (W / O / W) or oil-in-water-in-oil (O / W / O), a hydrodispersion or lipodispersion, a gel, a solid stick or an aerosol.
  • Emulsions according to the invention in the sense of the present invention are advantageous and contain e.g. Fats, oils, waxes and / or other fat bodies, as well as water and one or more emulsifiers, as are usually used for such a type of formulation.
  • the active ingredient combination used according to the invention into aqueous systems or surfactant preparations for cleaning and also care of the skin and hair.
  • Medical topical compositions in the sense of the present invention generally contain one or more medicaments in an effective concentration.
  • medicaments in an effective concentration.
  • cosmetic or topical dermatological compositions within the meaning of the present invention, depending on their structure, can be used, for example, as skin protection cream, cleansing milk, sunscreen lotion, nutritional cream, day or night cream, etc. It is possibly possible and advantageous to add the compositions according to the invention as the basis for pharmaceutical formulations use.
  • cosmetic and dermatological preparations which are in the form of a sunscreen are also favorable.
  • these preferably additionally contain at least one UVA filter substance and / or at least one UVB filter substance and / or at least one inorganic pigment.
  • Preparations according to the invention can advantageously contain substances which absorb UV radiation in the UVB range, the total amount of filter substances e.g. 0.1% by weight to 30% by weight, preferably 0.5 to 10% by weight, in particular 1 to 6% by weight, based on the total weight of the preparations.
  • the UVB filters can be oil-soluble or water-soluble.
  • oil-soluble substances e.g. to call:
  • 4-aminobenzoic acid derivatives preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester;
  • Esters of cinnamic acid preferably 4-methoxycinnamic acid (2-ethylhexyl) ester, 4-methoxycinnamic acid isopentyl ester;
  • esters of salicylic acid preferably salicylic acid (2-ethylhexyl) ester, salicylic acid (4-isopropylbenzyl) ester, salicylic acid homomethyl ester;
  • Esters of benzalmalonic acid preferably 4-methoxybenzalmalonic acid di (2-ethylhexyl) ester;
  • 2-phenylbenzimidazole-5-sulfonic acid and its salts e.g. Sodium, potassium or triethanolammonium salts
  • Sulfonic acid derivatives of benzophenones preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;
  • Sulfonic acid derivatives of 3-benzylidene camphor e.g. 4- (2-oxo-3-bornylidene-methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidene-methyl) sulfonic acid and their salts.
  • UVB filters which can be used according to the invention, is of course not intended to be limiting.
  • the invention also relates to the combination of a UVA film according to the invention. ters with a UVB filter or a cosmetic or dermatological preparation according to the invention, which also contains a UVB filter.
  • UVA filters in preparations according to the invention, which are usually contained in cosmetic and / or dermatological preparations.
  • Such filter substances are preferably derivatives of dibenzoylmethane, in particular 1 - (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione and 1-phenyl-3- (4 '-isopropylphenyl) propane-1,3-dione. Preparations containing these combinations are also the subject of the invention.
  • the same amounts of UVA filter substances that were mentioned for UVB filter substances can be used.
  • Cosmetic and / or dermatological preparations in the sense of the present invention can also contain inorganic pigments which are usually used in cosmetics to protect the skin from UV rays. These are oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum, cerium and mixtures thereof, as well as modifications in which the oxides are the active agents. Pigments based on titanium dioxide are particularly preferred. The amounts mentioned for the above combinations can be used.
  • the cosmetic and dermatological preparations according to the invention can contain cosmetic active ingredients, auxiliaries and / or additives as are usually used in such preparations, e.g. Antioxidants, preservatives, bactericides, perfumes, anti-foaming substances, dyes, pigments that have a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other common ingredients a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.
  • cosmetic active ingredients e.g. Antioxidants, preservatives, bactericides, perfumes, anti-foaming substances, dyes, pigments that have a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other common ingredients
  • the cosmetic or dermatological preparation in the sense of the present invention is a solution or emulsion or dispersion, the following can be used as solvents:
  • Oils such as triglycerides of capric or caprylic acid, but preferably Ri- zinusöl;
  • Fats, waxes and other natural and synthetic fat bodies preferably
  • Esters of fatty acids with low C alcohols e.g. with isopropanol, propylene glycol or glycerin, or esters of fatty alcohols with lower C- alkanoic acids
  • the oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the sense of the present invention is advantageously selected from the group of esters from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms, from the group of esters from aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms.
  • ester oils can then advantageously be selected from the group of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononylisononanoate, 2-ethylhexyluryl, 2-ethylhexyl palylate, Octyldodecyl palmitate, olefin oleate, olefin erucate, erucyl oleate, erucyl erucate as well as synthetic, semi-synthetic and natural mixtures of such esters, for example Jojoba oil.
  • the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and also the fatty acid triglycerides, especially the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12 - 18 carbon atoms.
  • the fatty acid triglycerides can, for example, advantageously be selected from the group of synthetic, semisynthetic and natural oils, for example olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, Palm oil, coconut oil, palm kernel oil and the like.
  • any mixtures of such oil and wax components can also be used advantageously for the purposes of the present invention. It may also be advantageous to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.
  • the oil phase is selected from the group 2-ethylhexyl advantageous Octyldo- decanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C 12 ⁇ 5 -alkyl, Ca Pryl-capric acid triglyceride, dicaprylyl ether.
  • the oil phase can also advantageously have a content of cyclic or linear silicon oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or the silicone oils.
  • Cyclomethicone (octamethylcyclotetrasiloxane) is advantageously used as the silicone oil to be used according to the invention.
  • other silicone oils can also be used advantageously for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).
  • Mixtures of cyclomethicone and isotridecyl isononanoate, of cyclomethicone and 2-ethylhexyl isostearate are also particularly advantageous.
  • the aqueous phase of the preparations according to the invention optionally advantageously contains alcohols, diols or polyols of low C number, and also their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or - monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether , Diethylene glycol monomethyl or monoethyl ether and analog products, furthermore alcohols low Riger C number, for example ethanol, isopropanol, 1, 2-propanediol, glycerol and in particular one or more thickeners, which or which can advantageously be selected from the group silicon dioxide, aluminum silicates, polysaccharides or their derivatives, for example hyaluronic acid, xanthan gum, hydroxypropylmethyl cellulose , particularly advantageously from the group of polyacrylates, preferably a polyacrylate from the group
  • Gels used in the present invention usually contain low C number alcohols, e.g. Ethanol, isopropanol, 1, 2-propanediol, glycerol and water or an oil mentioned above in the presence of a thickener which is preferably silicon dioxide or an aluminum silicate in the case of oily-alcoholic gels, and is preferably a polyacrylate in the case of aqueous-alcoholic or alcoholic gels.
  • low C number alcohols e.g. Ethanol, isopropanol, 1, 2-propanediol, glycerol and water or an oil mentioned above in the presence of a thickener which is preferably silicon dioxide or an aluminum silicate in the case of oily-alcoholic gels, and is preferably a polyacrylate in the case of aqueous-alcoholic or alcoholic gels.
  • Fixed pens contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters.
  • Usual base materials which are suitable for use as cosmetic sticks in the sense of the present invention are liquid oils (for example paraffin oils, castor oil, isopropyl myristate), semi-solid components (for example petroleum jelly, lanolin), solid components (for example beeswax, ceresin and microcrystallines) Waxes or ozokerite) and high-melting waxes (e.g. carnauba wax, candelilla wax)
  • liquid oils for example paraffin oils, castor oil, isopropyl myristate
  • semi-solid components for example petroleum jelly, lanolin
  • solid components for example beeswax, ceresin and microcrystallines
  • Waxes or ozokerite for example beeswax, ceresin and microcrystallines
  • high-melting waxes e.g. carnauba wax, candelilla wax
  • Suitable blowing agents for cosmetic and / or dermatological preparations which can be sprayed from aerosol containers for the purposes of the present invention are the customary known volatile, liquefied blowing agents, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in a mixture with one another. Compressed air can also be used advantageously.
  • hydrocarbons propane, butane, isobutane
  • Cosmetic preparations in the sense of the present invention can also be in the form of gels which, in addition to an effective content of the active ingredient according to the invention and solvents usually used therefor, preferably water, and also organic thickeners, for example gum arabic, xanthan gum, sodium alginate, cellulose derivatives, preferably methyl cellulose, Hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose or inorganic thickeners, e.g. B. aluminum silicates such as bentonite, or a mixture of polyethylene glycol and polyethylene glycol stearate or distearate.
  • the thickener is contained in the gel, for example, in an amount between 0.1 and 30% by weight, preferably between 0.5 and 15% by weight.
  • Cosmetic preparations according to the invention are listed below by way of example, all of which generate the described advantages of high and long-lasting skin moisture retention.

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Abstract

The invention relates to cosmetic or dermatological preparations containing a combination of active ingredients made from creatinine and/or derivatives thereof containing creatine and/or derivatives thereof and bioquinones, in addition to plant and animal extracts containing the latter.

Description

Beschreibung description
KOSMETISCHE ODER DERMATOLOGISCHE ZUBEREITUNGEN MIT EINER KOMBINATION VON KREATININ MIT KREATIN UND BIOCHINONENCOSMETIC OR DERMATOLOGICAL PREPARATIONS WITH A COMBINATION OF CREATININE WITH CREATINE AND BIOCHINONES
Die vorliegende Erfindung betrifft die Verwendung von Kombinationen von Kreatinin und/oder Kreatininderivaten mit Kreatin und/oder seinen Derivaten mit Biochinonen in kosmetischen oder dermatologischen Zubereitungen zur Behandlung und Prophylaxe der Symptome von UV- und oder Ozon- induzierten Hautschäden sowie von entzündlichen und degenerativen Hautzuständen.The present invention relates to the use of combinations of creatinine and / or creatinine derivatives with creatine and / or its derivatives with bioquinones in cosmetic or dermatological preparations for the treatment and prophylaxis of the symptoms of UV and or ozone-induced skin damage and of inflammatory and degenerative skin conditions.
Unter kosmetischer Hautpflege ist in erster Linie zu verstehen, daß die natürliche Funktion der Haut als Barriere gegen Umwelteinflüsse (z.B. Schmutz, Chemikalien, Mikroorganismen) und gegen den Verlust von körpereigenen Stoffen (z.B. Wasser, natürliche Fette, Elektrolyte) gestärkt oder wiederhergestellt wird.Cosmetic skin care is primarily understood to mean that the natural function of the skin as a barrier against environmental influences (e.g. dirt, chemicals, microorganisms) and against the loss of the body's own substances (e.g. water, natural fats, electrolytes) is strengthened or restored.
Wird diese Funktion gestört, kann es zu verstärkter Resorption toxischer oder aiiergener Stoffe oder zum Befall von Mikroorganismen und als Folge zu toxischen oder allergischen Hautreaktionen kommen.If this function is disturbed, there may be an increased absorption of toxic or allergic substances or an infestation of microorganisms and, as a result, toxic or allergic skin reactions.
Ziel der Hautpflege ist es ferner, den durch tägliche Waschen verursachten Fett- und Wasserverlust der Haut auszugleichen. Dies ist gerade dann wichtig, wenn das natürliche Regenerationsvermögen nicht ausreicht. Außerdem sollen Hautpflegeprodukte vor Umwelteinflüssen, insbesondere vor Sonne und Wind, schützen und die Hautalterung verzögern.The aim of skin care is also to compensate for the loss of fat and water in the skin caused by daily washing. This is especially important when the natural regeneration ability is insufficient. In addition, skin care products are intended to protect against environmental influences, especially sun and wind, and to delay skin aging.
Die chronologische Hautalterung wird z.B. durch endogene, genetisch determinierte Faktoren verursacht. In Epidermis und Dermis kommt es alterungsbedingt z.B. zu folgenden Strukturschäden und Funktionsstörungen, die auch unter den Begriff „Senile Xerosis" fallen können: a) Trockenheit, Rauhigkeit und Ausbildung von Trockenheitsfältchen, b) Juckreiz und c) verminderte Rückfettung durch Talgdrüsen (z.B. nach Waschen).Chronological skin aging is caused, for example, by endogenous, genetically determined factors. The following structural damage and functional disorders occur in the epidermis and dermis due to aging, which can also fall under the term "senile xerosis": a) dryness, roughness and the formation of wrinkles due to dryness, b) itching and c) reduced regreasing due to sebum glands (eg after washing).
Exogene Faktoren, wie UV-Licht und chemische Noxen, können kumulativ wirksam sein und z.B. die endogenen Alterungsprozesse beschleunigen bzw. sie ergänzen. In Epidermis und Dermis kommt es insbesondere durch exogene Faktoren z.B. zu folgenden Strukturschäden- und Funktionsstörungen in der Haut, die über Maß und Qualität der Schäden bei chronologischer Alterung hinausgehen: d) Sichtbare Gefäßerweiterungen (Teleangiektasien, Cuperosis); e) Schlaffheit und Ausbildung von Falten; f) lokale Hyper-, Hypo- und Fehlpigmentierungen (z.B. Altersflecken) und g) vergrößerte Anfälligkeit gegenüber mechanischem Stress (z.B. Rissigkeit).Exogenous factors such as UV light and chemical pollutants can be cumulative and e.g. accelerate or complement the endogenous aging processes. In the epidermis and dermis, it is particularly caused by exogenous factors, e.g. to the following structural damage and functional disorders in the skin that go beyond the extent and quality of the damage caused by chronological aging: d) visible vasodilation (telangiectasias, cuperosis); e) flaccidity and wrinkling; f) local hyper-, hypo- and incorrect pigmentations (e.g. age spots) and g) increased susceptibility to mechanical stress (e.g. cracking).
Die vorliegende Erfindung betrifft insbesondere Produkte zur Pflege der auf natürliche Weise gealterten Haut, sowie zur Behandlung der Folgeschäden der Lichtalterung, insbesondere der unter a) bis g) aufgeführten Phänomene.The present invention relates in particular to products for the care of naturally aged skin and for the treatment of the consequential damage caused by light aging, in particular the phenomena listed under a) to g).
Produkte zur Pflege gealterter Haut sind an sich bekannt. Sie enthalten z.B. Retinoide (Vitamin A-Säure und/oder deren Derivate) bzw. Vitamin A und/oder dessen Derivate. Ihre Wirkung auf die Strukturschäden ist allerdings umfangsmäßig begrenzt. Daüber hinaus gibt es bei der Produktentwicklung erhebliche Schwierigkeiten, die Wirkstoffe in ausreichendem Maße gegen oxidativen Zerfall zu stabilisieren. Die Verwendung Vitamin A- Säure-haltiger Produkte bedingt darüber hinaus oft starke erythematöse Hautreizungen. Retinoide sind daher nur in geringen Konzentrationen einsetzbar.Products for the care of aged skin are known per se. They contain e.g. Retinoids (vitamin A acid and / or its derivatives) or vitamin A and / or its derivatives. However, their effect on structural damage is limited in scope. In addition, there are considerable difficulties in product development to sufficiently stabilize the active ingredients against oxidative decay. The use of products containing vitamin A acid often causes severe erythematous skin irritation. Retinoids can therefore only be used in low concentrations.
Insbesondere betrifft die vorliegende Erfindung kosmetische Zubereitungen mit einem wirksamen Schutz vor schädlichen Oxidationsprozessen in der Haut, aber auch zum Schütze kosmetischer Zubereitungen selbst bzw. zum Schütze der Bestandteile kosmetischer Zubereitungen vor schädlichen Oxidationsprozessen.In particular, the present invention relates to cosmetic preparations with effective protection against harmful oxidation processes in the skin, but also for protecting cosmetic preparations themselves or for protecting the constituents of cosmetic preparations against harmful oxidation processes.
Die schädigende Wirkung des ultravioletten Teils der Sonnenstrahlung auf die Haut ist allgemein bekannt. Während Strahlen mit einer Wellenlänge, die kleiner als 290 nm ist (der sogenannte UVC-Bereich), von der Ozonschicht in der Erdatmosphäre absorbiert werden, verursachen Strahlen im Bereich zwischen 290 nm und 320 nm, dem sogenannten UVB-Bereich, ein Erythem, einen einfachen Sonnenbrand oder sogar mehr oder weniger starke Verbrennungen. Als ein Maximum der Erythemwirksamkeit des Sonnenlichtes wird der engere Bereich um 308 nm angegeben.The damaging effect of the ultraviolet part of solar radiation on the skin is well known. While rays with a wavelength shorter than 290 nm (the so-called UVC range) are absorbed by the ozone layer in the earth's atmosphere, rays in the range between 290 nm and 320 nm, the so-called UVB range, cause erythema simple sunburn or even more or less severe burns. The narrower range around 308 nm is given as a maximum of the erythema effectiveness of sunlight.
Zum Schutz gegen UVB-Strahlung sind zahlreiche Verbindungen bekannt, bei denen es sich um Derivate des 3-Benzylidencamphers, der 4-Aminobenzoesäure, der Zimtsäure, der Salicylsäure, des Benzophenons sowie auch des 2-Phenylbenzimidazols handelt.Numerous compounds are known for protection against UVB radiation, which are derivatives of 3-benzylidene camphor, 4-aminobenzoic acid, cinnamic acid, salicylic acid, benzophenone and also 2-phenylbenzimidazole.
Auch für den Bereich zwischen etwa 320 nm und etwa 400 nm, des sogenannten UVA- Bereich, ist es wichtig, Filtersubstanzen zur Verfügung zu haben, da dessen Strahlen Reaktionen bei lichtempfindlicher Haut hervorrufen können. Es ist erwiesen, daß UVA- Strahlung zu einer Schädigung der elastischen und kollagenen Fasern des Bindegewebes führt, was die Haut vorzeitig altern läßt, und daß sie als Ursache zahlreicher phototoxischer und photoallergischer Reaktionen zu sehen ist. Der schädigende Einfluß der UVB- Strahlung kann durch UVA-Strahlung verstärkt werden.It is also important to have filter substances available for the range between about 320 nm and about 400 nm, the so-called UVA range, since their rays can cause reactions in light-sensitive skin. It has been proven that UVA radiation leads to damage to the elastic and collagen fibers of the connective tissue, which causes the skin to age prematurely, and that it is to be seen as the cause of numerous phototoxic and photoallergic reactions. The damaging influence of UVB radiation can be intensified by UVA radiation.
Zum Schutz gegen die Strahlen des UVA-Bereichs werden daher gewisse Derivate des Dibenzoylmethans verwendet, deren Photostabilität (Int. J. Cosm. Science 10, 53 (1988)), nicht in ausreichendem Maße gegeben ist.To protect against the rays of the UVA range, certain derivatives of dibenzoylmethane are therefore used, the photostability (Int. J. Cosm. Science 10, 53 (1988)) of which is insufficient.
Die UV-Strahlung kann aber auch zu photochemischen Reaktionen führen, wobei dann die photochemischen Reaktionsprodukte in den Hautmetabolismus eingreifen.However, UV radiation can also lead to photochemical reactions, in which case the photochemical reaction products interfere with the skin's metabolism.
Vorwiegend handelt es sich bei solchen photochemischen Reaktionsprodukten um radikalische Verbindungen, beispielsweise Hydroxyradikale. Auch Undefinierte radikalische Photoprodukte, welche in der Haut selbst entstehen, können aufgrund ihrer hohen Reaktivität unkontrollierte Folgereaktionen an den Tag legen. Aber auch Singulettsauerstoff, ein nichtradikalischer angeregter Zustand des Sauerstoffmoleküls kann bei UV- Bestrahlung auftreten, ebenso kurzlebige Epoxide und viele andere. Singulettsauerstoff beispielsweise zeichnet sich gegenüber dem normalerweise vorliegenden Triplettsauerstoff (radikalischer Grundzustand) durch gesteigerte Reaktivität aus. Allerdings existieren auch angeregte, reaktive (radikalische) Triplettzustände des Sauerstoffmoleküls.Such photochemical reaction products are predominantly free radical compounds, for example hydroxy radicals. Undefined radical photo products, which are created in the skin itself, can also display uncontrolled subsequent reactions due to their high reactivity. But also singlet oxygen, a non-radical excited state of the oxygen molecule can occur with UV radiation, just as short-lived epoxies and many others. Singlet oxygen, for example, is characterized by increased reactivity compared to the triplet oxygen that is normally present (radical ground state). However, there are also excited, reactive (radical) triplet states of the oxygen molecule.
Ferner zählt UV-Strahlung zur ionisierenden Strahlung. Es besteht also das Risiko, daß auch ionische Spezies bei UV-Exposition entstehen, welche dann ihrerseits oxidativ in die biochemischen Prozesse einzugreifen vermögen. Um diesen Reaktionen vorzubeugen, können den kosmetischen bzw. dermatologischen Formulierungen zusätzliche Antioxidantien und/oder Radikalfänger einverleibt werden.UV radiation also belongs to ionizing radiation. There is therefore a risk that ionic species also develop when exposed to UV, which in turn can then oxidatively intervene in the biochemical processes. In order to prevent these reactions, additional antioxidants and / or free radical scavengers can be incorporated into the cosmetic or dermatological formulations.
Es ist bereits vorgeschlagen worden, Vitamin E, eine Substanz mit bekannter antioxida- tiver Wirkung in Lichtschutzformulierungen einzusetzen, dennoch bleibt auch hier die erzielte Wirkung weit hinter der erhofften zurück.It has already been proposed to use vitamin E, a substance with a known antioxidant effect, in light protection formulations, but the effect achieved here also falls far short of the hoped-for effect.
Aufgabe der Erfindung war es daher auch, kosmetische, dermatologische und pharmazeutische Wirkstoffe und Zubereitungen sowie Lichtschutzformulierungen zu schaffen, die zur Prophylaxe und Behandlung lichtempfindlicher Haut, insbesondere Photodermatosen, bevorzugt PLD dienen.The object of the invention was therefore also to provide cosmetic, dermatological and pharmaceutical active substances and preparations and light protection formulations which are used for the prophylaxis and treatment of light-sensitive skin, in particular photodermatoses, preferably PLD.
Weitere Bezeichnungen für die polymorphe Lichtdermatose sind PLD, PLE, Mallorca- Akne und eine Vielzahl von weiteren Bezeichnungen, wie sie in der Literatur (z.B. A. Voelckel et al, Zentralblatt Haut- und Geschlechtskrankheiten (1989), 156, S.2), angegeben sind.Other names for polymorphic light dermatosis are PLD, PLE, Mallorca acne and a variety of other names, such as those used in the literature (e.g. A. Voelckel et al, Zentralblatt Haut- und Sexually Diseases (1989), 156, p.2), are specified.
Hauptsächlich werden Antioxidantien als Schutzsubstanzen gegen den Verderb der sie enthaltenden Zubereitungen verwendet. Dennoch ist bekannt, daß auch in der menschlichen und tierischen Haut unerwünschte Oxidationsprozesse auftreten können. Solche Prozesse spielen eine wesentliche Rolle bei der Hautalterung.Antioxidants are mainly used as protective substances against the spoilage of the preparations containing them. Nevertheless, it is known that undesirable oxidation processes can also occur in human and animal skin. Such processes play an essential role in skin aging.
Im Aufsatz "Skin Diseases Associated with Oxidative Injury" in "Oxidative Stress in Der- matology", S. 323 ff. (Marcel Decker Inc., New York, Basel, Hong Kong, Herausgeber: Jürgen Fuchs, Frankfurt, und Lester Packer, Berkeley/Californien), werden oxidative Schäden der Haut und ihre näheren Ursachen aufgeführt.In the article "Skin Diseases Associated with Oxidative Injury" in "Oxidative Stress in Dermatology", p. 323 ff. (Marcel Decker Inc., New York, Basel, Hong Kong, publisher: Jürgen Fuchs, Frankfurt, and Lester Packer, Berkeley / California), oxidative damage to the skin and its closer causes are listed.
Auch aus dem Grunde, solchen Reaktionen vorzubeugen, können kosmetischen oder dermatologischen Formulierungen zusätzlich Antioxidantien und/oder Radikalfänger einverleibt werden.Also for the reason of preventing such reactions, additional antioxidants and / or free radical scavengers can be incorporated into cosmetic or dermatological formulations.
Zwar sind einige Antioxidantien und Radikalfänger bekannt. So ist bereits in den US-Patentschriften 4,144,325 und 4,248,861 sowie aus zahlreichen anderen Dokumenten vorgeschlagen worden, Vitamin E, eine Substanz mit bekannter antioxidativer Wirkung in Lichtschutzformulierungen einzusetzen, dennoch bleibt auch hier die erzielte Wirkung weit hinter der erhofften zurück. Aufgabe der vorliegenden Erfindung war es somit, Wege zu finden, die die Nachteile des Standes der Technik vermeiden. Insbesondere soll die Wirkung der Behebung der mit der endogenen, chronologischen und exogenen Hautalterung verbundenen Schäden und die Prophylaxe dauerhaft, nachhaltig und ohne das Risiko von Nebenwirkungen sein. Diesen Übelständen abzuhelfen, war Aufgabe der vorliegenden Erfindung.Some antioxidants and radical scavengers are known. It has already been proposed in US Pat. Nos. 4,144,325 and 4,248,861 and from numerous other documents to use vitamin E, a substance with a known antioxidant activity in light protection formulations, but the effect achieved here also falls far short of the hoped-for effect. The object of the present invention was therefore to find ways which avoid the disadvantages of the prior art. In particular, the effect of remedying the damage associated with endogenous, chronological and exogenous skin aging and the prophylaxis should be permanent, sustainable and without the risk of side effects. The object of the present invention was to remedy these shortcomings.
Es hat sich überraschenderweise herausgestellt, daß kosmetische oder dermatologische Zubereitungen mit einem Gehalt an einer Wirkstoffkombination aus Kreatinin und /oder dessen Derivaten mit Kreatin und/oder dessen Derivaten und Biochinonen sowie pflanzlicher und tierischer Extrakte dieselben enthaltend, den Nachteilen des Standes der Technik abhelfen und gleichzeitig der Gehalt an Kreatinin die Stabilität von Kreatin in kosmetischen oder dermatologischen Zubereitungen erhöht.It has surprisingly been found that cosmetic or dermatological preparations containing an active ingredient combination of creatinine and / or its derivatives with creatine and / or its derivatives and bioquinones and vegetable and animal extracts containing the same, alleviate the disadvantages of the prior art and at the same time the creatinine content increases the stability of creatine in cosmetic or dermatological preparations.
Die Erfindung umfasst auch die Verwendung von derartigen Zubereitungen zur Prophylaxe und/oder Behandlung von entzündlichen Hautzuständen und/oder zum Hautschutz bei empfindlich determinierter und trockener Haut (wie z. B. atopisches Ekzem, seborrhoi- sches Ekzem, polymorphe Lichtdermatose, Psoriasis, Vitiligo, Wundheilungsstörungen, Juckreiz, empfindliche oder gereizte Haut, lichtbedingte Hautschäden und UV-induzierte Immunsuppression, Veränderungen der Desquamation, Veränderungen der normalen Fibroblasten- und KeratinozytenproliferationNeränderungen der normalen Fibroblasten- und Keratinozytendifferenzierung, defizitäre, sensitive oder hypoaktive Hautzustände oder defizitäre, sensitive oder hypoaktive Zustände von Hautanhangsgebilde und zur Verringerung der Hautdicke).The invention also includes the use of such preparations for the prophylaxis and / or treatment of inflammatory skin conditions and / or for skin protection in the case of sensitive and dry skin (such as, for example, atopic eczema, seborrheic eczema, polymorphic light dermatosis, psoriasis, vitiligo, Wound healing disorders, itching, sensitive or irritated skin, light-induced skin damage and UV-induced immunosuppression, changes in desquamation, changes in normal fibroblast and keratinocyte proliferation, changes in normal fibroblast and keratinocyte differentiation, deficient, sensitive or hypoactive skin conditions, sensitive or hypoactive skin conditions, sensitive, or hypoactive skin conditions, sensitive, or hypoactive skin conditions, sensitive, or hypoactive skin conditions and to reduce skin thickness).
Weiterhin umfasst die Erfindung die Verwendung von derartigen Zubereitungen zur Behandlung und Prophylaxe der Symptome der intrinsischen und/oder extrinsischen Hautalterung sowie zur Behandlung und Prophylaxe der schädlichen Auswirkungen ultravioletter Strahlung auf die Haut z. B. degenerative Erscheinungen der Haut (wie Altersflecken, Falten, Teleangiektasien, Hautschlaffheit, Elastizitätsverlust, sowie Schwund der epidermalen und dermalen Zellschichten, der Bestandteile des Bindegewebes, der Retezapfen und Kapillargefässe), sogenannte Skin luster und fatigue (Hauterschlaffung und/oder Hautermüdung), gesteigerte Aktivierung proteolytischer Enzyme in der Haut wie z. B. Me- talloproteinasen, Störungen der normalen Kollagen-, Hyaluronsäure-, Elastin- und Glyko- saminoglycan-Homeostase und der normalen Hautregeneration, Veränderungen der normalen Fibroblasten- und Keratinozytenproliferation.Veränderungen der normalen Fibroblasten- und Keratinozytendifferenzierung, Mangelerscheinungen der intrazellulären DNS-Synthese (insbesondere bei defizitären oder hypoaktiven Hautzuständen), umweltbedingte (durch Rauchen, Smog, reaktive Sauerstoffspecies, freie Radikale und dergleichen verursachte) negative Veränderungen der Haut und/oder der Hautanhangsgebilde. Ebenfalls erfindungsgemäß ist die Verwendung von solchen Zubereitungen zur Behandlung und/oder Prophylaxe von Pigmentierungsstörungen, zur Steigerung der Ceramidbio- synthese (wie z.B. Veränderungen des Ceramid-, Lipid- und Energiestoffwechsels der gesunden Haut), zur Stärkung der Barrierefunktion der Haut (wie z. B. Hornschicht- barrierestörungen, Veränderungen der normalen Lipidperoxidationen, Veränderungen des transepidermalen Wasserverlustes und des normalen Feuchtigkeitsgehaltes der Haut), zur Behandlung und/oder Prophylaxe von Störungen des normalen Haut-pH-Werts und der Osmolytbalance, zur Behandlung und/oder Prophylaxe von Abweichungen von der normalen Zell-Zell-Kommunikation in der Haut (z.B. interzelluläre Kommunikationen über Mediatoren und/ oder über mechanische/ physiologische Verbindungen). Ebenfalls erfindungsgemäß ist die Verwendung von solchen Zubereitungen zur Behandlung und/oder Prophylaxe von funktioneilen Störungen der Hautanhangsgebilde (z.B. Haarausfall, verbessertes Haarwachstum, verbesserter Haarglanz, verbesserte Haarstruktur, seborrhoischer Erscheinungen, fettige Haut, fettiges Haar, Komedonen, aber auch Kopfschuppen).Furthermore, the invention comprises the use of such preparations for the treatment and prophylaxis of the symptoms of intrinsic and / or extrinsic skin aging and for the treatment and prophylaxis of the harmful effects of ultraviolet radiation on the skin, for. B. degenerative symptoms of the skin (such as age spots, wrinkles, telangiectasias, sagging skin, loss of elasticity, as well as loss of the epidermal and dermal cell layers, the components of the connective tissue, the rete cones and capillary vessels), so-called skin luster and fatigue (skin sagging and / or skin fatigue), increased activation of proteolytic enzymes in the skin such as B. Metalloproteinases, disorders of normal collagen, hyaluronic acid, elastin and glycosaminoglycan homeostasis and normal skin regeneration, changes in normal fibroblast and keratinocyte proliferation. Changes in normal fibroblast and keratinocyte differentiation, deficiency symptoms of the intracellular DNA synthesis (especially in deficient or hypoactive skin conditions), environmental (caused by smoking, smog, reactive oxygen species, free radicals and the like) negative changes in the skin and / or the appendages of the skin. Also according to the invention is the use of such preparations for the treatment and / or prophylaxis of pigmentation disorders, for increasing ceramide biosynthesis (such as changes in the ceramide, lipid and energy metabolism of healthy skin), for strengthening the barrier function of the skin (such as. B. Horn layer barrier disorders, changes in normal lipid peroxidation, changes in transepidermal water loss and normal moisture content of the skin), for the treatment and / or prophylaxis of disorders of the normal skin pH and the osmolytic balance, for the treatment and / or prophylaxis of deviations from normal cell-cell communication in the skin (e.g. intercellular communication via mediators and / or via mechanical / physiological connections). Also according to the invention is the use of such preparations for the treatment and / or prophylaxis of functional disorders of the skin appendages (for example hair loss, improved hair growth, improved hair gloss, improved hair structure, seborrheic symptoms, oily skin, oily hair, comedones, but also dandruff).
Bevorzugt sind erfindungsgemäße Zubereitungen und Verwendungen dadurch gekennzeichnet, dass als Biochinon Coenzym Q10 enthalten ist.Preparations and uses according to the invention are preferably characterized in that coenzyme Q10 is contained as bioquinone.
Besonders bevorzugt sind erfindungsgemäße Zubereitungen und Verwendungen dadurch gekennzeichnet, daß Coenzym Q10 sowie pflanzliche und tierische Extrakte dieselbe enthaltend in kosmetischen oder topischen dermatologischen Zubereitungen in Konzentrationen von 0,001 - 30 Gew.-%, besonders bevorzugt 0,01 - 1 Gew.-%, bezogen auf das Gesamtgewicht der Zubereitungen, vorliegen und der Gehalt an Kreatinin und/oder dessen Derivaten 0,001 - 50 Gew.-% , vorzugsweise 0,1 - 10 Gew.-% sowie der Gehalt an Kreatin und dessen Derivaten 0,001 - 50 Gew.-% , vorzugsweise 0,1 - 10 Gew.-%, bezogen auf das Gesamtgewicht der Zubereitungen, beträgt.Preparations and uses according to the invention are particularly preferably characterized in that coenzyme Q10 and vegetable and animal extracts containing the same are contained in cosmetic or topical dermatological preparations in concentrations of 0.001-30% by weight, particularly preferably 0.01-1% by weight based on the total weight of the preparations and the content of creatinine and / or its derivatives 0.001-50% by weight, preferably 0.1-10% by weight and the content of creatine and its derivatives 0.001-50% by weight , preferably 0.1-10% by weight, based on the total weight of the preparations.
Kreatinin (von grch.: τo Kpε ς = „das Fleisch") ist durch folgende Struktur gekennzeichnetCreatinine (from Greek: τo Kpε ς = "the meat") is characterized by the following structure
Figure imgf000007_0001
und entsteht im Organismus durch nichtenzymatische Umwandlung aus Kreatin oder
Figure imgf000007_0001
and arises in the organism from non-enzymatic conversion from creatine or
Kreatinphosphat gemäßCreatine phosphate according to
Figure imgf000008_0001
und wird über die Niere ausgeschieden. Die Menge der Kreatininausscheidung ist der Muskelmasse proportional und für das jeweilige Individuum annähernd konstant. Kreatinin ist in Fleischextrakt und Fleischbrühwürfeln enthalten.
Figure imgf000008_0001
and is excreted via the kidney. The amount of creatinine excretion is proportional to the muscle mass and almost constant for the individual. Creatinine is contained in meat extract and bouillon cubes.
Kreatin (ebenfalls von grch.: τo Kpεας = „das Fleisch") zeichnet sich durch folgende Struktur aus:Creatine (also from Greek: τo Kpεας = "the meat") is characterized by the following structure:
Figure imgf000008_0002
Figure imgf000008_0002
Es findet sich im Muskelsaft der Wirbeltiere zu 0,05-0,4%, in geringen Mengen auch im Gehirn und Blut. Als Monohydrat stellt es ein farbloses, kristallines Pulver dar. In wäßriger Lösung wird Kreatinin gebildet. Im Organismus entsteht es durch Transamidinierung von L-Arginin auf Glycin zu Guanidinoessigsäure und deren anschließende Methylierung mittels S-Adenosylmethionin (durch Guanidinoacetat-Methyltransferase). Man hält Kreatin für einen appetitfördernden Bestandteil von Rindfleisch und Fleisch extrakt. Kreatinzusatz zur Nahrung verstärkt die körperliche Leistungsfähigkeit .It is found in the vertebrate muscle juice to 0.05-0.4%, in small amounts also in the brain and blood. As a monohydrate, it is a colorless, crystalline powder. Creatinine is formed in aqueous solution. It arises in the organism through transamidation of L-arginine on glycine to guanidinoacetic acid and its subsequent methylation using S-adenosylmethionine (through guanidinoacetate methyltransferase). Creatine is thought to be an appetite-enhancing component of beef and meat extract. Adding creatine to food increases physical performance.
Bevorzugt ist es von Vorteil, das Gewichtsverhältnis von Kreatinin zu Kreatin aus dem Bereich von 50 : 1 bis 1 : 50, bevorzugt von 10 : 1 bis 1 : 10, insbesondere bevorzugt von 2 : 1 bis 1 : 2 zu wählen.It is preferably advantageous to choose the weight ratio of creatinine to creatine in the range from 50: 1 to 1:50, preferably from 10: 1 to 1:10, particularly preferably from 2: 1 to 1: 2.
Bevorzugtes Derivat ist das Kreatinphosphat, welches folgende Struktur aufweist:The preferred derivative is creatine phosphate, which has the following structure:
Figure imgf000008_0003
und welches im frischen Muskel verbreitet ist und dort als energiespeicherndes Phosphat (Phosphagen) eine wichtige Rolle spielt. Im arbeitenden Muskel gibt Kreatinphosphat mit Adenosin-5'-diphosphat unter dem Einfluß des Enzyms Kreatin-Kinase Adenosin-5'- triphosphat (ATP) und Kreatin; im ruhenden Muskel läuft die umgekehrte Reaktion ab. Aber auch Kreatinsulfat, Kreatinacetat, Kreatinascorbat und die an der Carboxylgruppe mit mono- oder polyfunktionalen Alkoholen veresterten Derivate führen zu vorteilhaften Ausführungsformen der Erfindung.
Figure imgf000008_0003
and which is widespread in fresh muscle and plays an important role there as energy-storing phosphate (phosphagen). Creatine phosphate is present in the working muscle Adenosine 5'-diphosphate under the influence of the enzyme creatine kinase adenosine 5'-triphosphate (ATP) and creatine; the reverse reaction takes place in the resting muscle. But also creatine sulfate, creatine acetate, creatine ascorbate and the derivatives esterified on the carboxyl group with mono- or polyfunctional alcohols lead to advantageous embodiments of the invention.
Ubichinone zeichnen sich durch die StrukturformelUbiquinones are characterized by the structural formula
Figure imgf000009_0001
aus und stellen die am weitesten verbreiteten u. damit am besten untersuchten Bio- chinone dar. Ubichinone werden je nach Zahl der in der Seitenkette verknüpften Isopren-Einheiten als Q-1 , Q-2, Q-3 usw. oder nach Anzahl der C-Atome als U-5, U-10, U-15 usw. bezeichnet. Sie treten bevorzugt mit bestimmten Kettenlängen auf, z. B. in einigen Mikroorganismen u. Hefen mit n=6. Bei den meisten Säugetieren einschließlich des Menschen überwiegt Q-10.
Figure imgf000009_0001
and make the most widespread u. thus the best studied bio-quinones. Depending on the number of isoprene units linked in the side chain, ubiquinones are classified as Q-1, Q-2, Q-3 etc. or according to the number of C atoms as U-5, U- 10, U-15 and so on. They preferably occur with certain chain lengths, e.g. B. in some microorganisms u. Yeast with n = 6. Q-10 predominates in most mammals, including humans.
Coenzym Q-10 beispielsweise ist durch folgende Strukturformel gekennzeichnet:Coenzyme Q-10, for example, is characterized by the following structural formula:
Figure imgf000009_0002
Figure imgf000009_0002
Ubichinone dienen den Organismen als Elektronenüberträger in der Atmungskette. Sie befinden sich in den Mitochondrien wo sie die cyclische Oxidation und Reduktion der Substrate des Citronensäure-Cyclus ermöglichen. Plastochinone weisen die allgemeine StrukturformelUbiquinones serve the organisms as electron carriers in the respiratory chain. They are located in the mitochondria where they enable the cyclic oxidation and reduction of the substrates of the citric acid cycle. Plastoquinones have the general structural formula
Figure imgf000009_0003
auf. Sie können aus Chloroplasten isoliert werden und spielen als Redoxsubstrate in der Photosynthese beim cyclischen und nichtcyclischen Elektronentransport eine Rolle, wobei sie reversibel in die entsprechenden Hydrochinone (Plastochinol) übergehen. Plasto- schinone unterscheiden sich in der Anzahl n der Isopren-Reste und werden entsprechend bezeichnet, z. B. PQ-9 (n=9). Ferner existieren andere Plastochinone mit unterschiedlichen Substituenten am Chinon-Ring.
Figure imgf000009_0003
on. They can be isolated from chloroplasts and play a role as redox substrates in photosynthesis in the cyclic and noncyclic electron transport, whereby they reversibly change into the corresponding hydroquinones (plastoquinol). Plastoquinones differ in the number n of isoprene residues and are designated accordingly, e.g. B. PQ-9 (n = 9). There are also other plastoquinones with different substituents on the quinone ring.
Kosmetische Zubereitungen mit Coenzym Q-10 aus der DE-A-33 09 850 sind bekannt, die zur Behandlung von Hautkrankheiten, zur Prophylaxe von dystrophischen und dysme- tabolischen Zuständen der Haut und zur Anwendung bei chemischen und physikalischen Respirationsschäden oder bei verzögerter Respiration verbunden mit Alter und Abnutzung geeignet sind.Cosmetic preparations with coenzyme Q-10 from DE-A-33 09 850 are known which are used for the treatment of skin diseases, for the prophylaxis of dystrophic and dysmabolic conditions of the skin and for use in the case of chemical and physical respiratory damage or in the case of delayed respiration Age and wear are suitable.
In der japanischen Offenlegungsschrift 58,180,410 ist die Eignung von Coenzym Q-10 für Kosmetika beschrieben. Es soll den Hautzellmetabolismus aktivieren und die Oxidation unterdrücken. Coenzym Q10 hat im Resultat eine wichtige Funktion bei der Prävention von Hautschäden durch UV-Strahlen und der Prävention von Hautalterung.The suitability of coenzyme Q-10 for cosmetics is described in Japanese laid-open publication 58, 180, 410. It is said to activate skin cell metabolism and suppress oxidation. As a result, coenzyme Q10 has an important function in the prevention of skin damage from UV rays and the prevention of skin aging.
Zwar beschreibt die JP2000/247866 Hautkosmetika mit einem Gehalt an Kreatin und/oder Kreatinin, welche als Creme oder als milchige Lotion verwendet werden können, wobei den betreffenden Zubereitungen vorzügliche hautpflegende Eigenschaften zugeschrieben werden. Diese Schrift konnte jedoch nicht den Weg zur vorliegenden Erfindung ebnen.JP2000 / 247866 describes skin cosmetics with a content of creatine and / or creatinine, which can be used as a cream or as a milky lotion, the preparations in question being attributed excellent skin-care properties. However, this document could not pave the way for the present invention.
Ferner beschreibt die WO00/33787 die Verwendung von Kreatinin als wirksamen Bestandteil von Desodorantien. Auch diese Schrift konnte nicht den Weg zur vorliegenden Erfindung ebnen.Furthermore, WO00 / 33787 describes the use of creatinine as an effective component of deodorants. This document also could not pave the way to the present invention.
Weiterhin beschreibt die EP-A 565 010 Haarwuchs- und Haarfärbezubereitungen mit einem Gehalt an Kreatinphosphat. Auch diese Schrift konnte nicht den Weg zur vorliegenden Erfindung ebnen.Furthermore, EP-A 565 010 describes hair growth and hair dye preparations containing creatine phosphate. This document also could not pave the way to the present invention.
Schließlich werden in der US-A 4,590,067 und der EP-A-178 602 die Verwendung von Kreatin bzw. Kreatinin zur Herstellung von Zubereitungen mit antiinflammatorischer Wirksamkeit beschrieben. Auch diese Schriften konnten nicht den Weg zur vorliegenden Erfindung ebnen.Finally, US-A 4,590,067 and EP-A-178 602 describe the use of creatine and creatinine for the preparation of preparations with anti-inflammatory activity. These writings were also unable to pave the way to the present invention.
Bei Anwendung der erfindungsgemäß verwendeten Wirkstoffkombination bzw. kosmeti- scher oder topischer dermatologischer Zubereitungen mit einem wirksamen Gehalt an erfindungsgemäßer Wirkstoffkombination ist in überraschender Weise eine wirksame Behandlung, aber auch eine Prophylaxe von defizitären, sensitiven oder hypoaktiven Hautzuständen oder defizitären, sensitiven oder hypoaktiven Zustände von Hautanhangsgebilden von Erscheinungen vorzeitiger Alterung der Haut (z.B. Falten, Altersflecken, Telean- giektasien) und/oder der Hautanhangsgebilde, von umweltbedingten (Rauchen, Smog, reaktive Sauerstoffspecies, freie Radikale) und insbesondere lichtbedingten negativen Veränderungen der Haut und der Hautanhangsgebilde, von lichtbedingten Hautschäden von Pigmentierungsstörungen, von Juckreiz, von trockenen Hautzuständen und Hornschichtbarrierestörungen, von Haarausfall und für verbessertes Haarwachstum von entzündlichen Hautzuständen sowie atopischem Ekzem, seborrhoischem Ekzem, polymorpher Lichtdermatose, Psoriasis, Vitiligo möglich. Die erfindungsgemäße Wirkstoffkombination bzw. kosmetische oder topische dermatologische Zubereitungen mit einem wirksamen Gehalt an erfindungsgemäßer Wirkstoffkombination dient aber auch in überraschender weise zur Beruhigung von empfindlicher oder gereizter Haut zur Stimulation der Kollagen-, Hyaluronsäure-, Elastinsynthese zur Stimulation der intrazellulären DNA-Synthese, insbesondere bei defizitären oder hypoaktiven Hautzuständen. zur Steigerung der Zellerneuerung und Regeneration der Haut zur Steigerung der hauteigenen Schutz- und Reparaturmechanismen (beispielsweise für dysfunktionelle Enzyme, DNA, Lipide, Proteine) zur Vor- und Nachbehandlung bei topischer Anwendung von Laser- und Abschleifbehandlungen, die z. B. der Reduzierung von Hautfalten und Narben dienen, um den resultierenden Hautreizungen entgegenzuwirken und die Regenerationsprozesse in der verletzten Haut zu fördern. Erfindungsgemäße Effekte liegen in der Stabilisierung des Energiestoffwechsels im Sinne eines Synergismus zwischen den erfindungsgemäßen Komponenten Kreatin, Kreatinin und Coenzym Q10 im Vergleich zu Kreatin und Kreatinin allein. Durch die verbesserte Energielage der Hautzellen kann eine wesentliche bessere Wirkung zur Prophylaxe und Behandlung von degenerativen Haut- und Haarerscheinungen (Falten, Erschlaffung, Degeneration, Altersflecken, Durchblutungsstörungen, Juckreiz, Stressempfindlichkeit, Sprö- digkeit) erzielt werden.When using the active ingredient combination or cosmetic Shear or topical dermatological preparations with an effective content of the active ingredient combination according to the invention is surprisingly an effective treatment, but also a prophylaxis of deficient, sensitive or hypoactive skin conditions or deficient, sensitive or hypoactive conditions of skin appendages from signs of premature aging of the skin (e.g. wrinkles, Age spots, telangiectasia) and / or the appendages of the skin, of environmental ones (smoking, smog, reactive oxygen species, free radicals) and in particular light-related negative changes of the skin and appendages, of light-related skin damage from pigmentation disorders, itching, dry skin conditions and horny layer barrier disorders , of hair loss and for improved hair growth of inflammatory skin conditions as well as atopic eczema, seborrheic eczema, polymorphic light dermatosis, psoriasis, vitiligo possible. The combination of active substances according to the invention or cosmetic or topical dermatological preparations with an effective content of active substance combination according to the invention also serves, surprisingly, to calm sensitive or irritated skin to stimulate collagen, hyaluronic acid, elastin synthesis to stimulate intracellular DNA synthesis, in particular with deficient or hypoactive skin conditions. to increase cell renewal and regeneration of the skin to increase the skin's own protection and repair mechanisms (for example for dysfunctional enzymes, DNA, lipids, proteins) for pre-treatment and post-treatment with topical application of laser and abrasive treatments, e.g. B. serve the reduction of skin folds and scars to counteract the resulting skin irritation and to promote the regeneration processes in the injured skin. Effects according to the invention lie in the stabilization of the energy metabolism in the sense of a synergism between the components creatine, creatinine and coenzyme Q10 according to the invention in comparison to creatine and creatinine alone. The improved energy level of the skin cells can have a significantly better effect for prophylaxis and Treatment of degenerative skin and hair symptoms (wrinkles, sagging, degeneration, age spots, circulatory disorders, itching, sensitivity to stress, brittleness) can be achieved.
Es ist erfindungsgemäß insbesondere äußerst vorteilhaft, die erfindungsgemäß verwendete Wirkstoffkombination bzw. kosmetische oder topische dermatologische Zubereitungen mit einem wirksamen Gehalt an erfindungsgemäß verwendeter Wirkstoffkombination zur kosmetischen oder dermatologischen Behandlung oder Prophylaxe unerwünschter Hautzustände zu verwenden.It is particularly advantageous according to the invention to use the active ingredient combination or cosmetic or topical dermatological preparations with an effective content of active ingredient combination used according to the invention for cosmetic or dermatological treatment or prophylaxis of undesirable skin conditions.
Erfindungsgemäß können Zubereitungen, welche die erfindungsgemäßen Wirkstoffkombinationen enthalten, übliche Antioxidantien eingesetzt werden.Preparations which contain the active compound combinations according to the invention and customary antioxidants can be used according to the invention.
Vorteilhaft werden die Antioxidantien gewählt aus der Gruppe bestehend aus Aminosäuren (z.B. Glycin, Histidin, Tyrosin, Tryptophan) und deren Derivate, Imidazole (z.B. Uro- caninsäure) und deren Derivate, Peptide wie D,L-Carnosin, D-Carnosin, L-Carnosin und deren Derivate (z.B. Anserin), Carotinoide, Carotine (z.B. α-Carotin, ß-Carotin, Lycopin) und deren Derivate, Liponsäure und deren Derivate (z.B. Dihydroliponsäure), Au- rothioglucose, Propylthiouracil und andere Thiole (z.B. Thioredoxin, Glutathion, Cystein, Cystin, Cystamin und deren Glycosyl-, N-Acetyl-, Methyl-, Ethyl-, Propyl-, Amyl-, Butyl- und Lauryl-, Palmitoyl-, Oleyl-, γ-Linoleyl-, Cholesteryl- und Glycerylester) sowie deren Salze, Dilaurylthiodipropionat, Distearylthiodipropionat, Thiodipropionsäure und deren Derivate (Ester, Ether, Peptide, Lipide, Nukleotide, Nukleoside und Salze) sowie Sulf- oximinverbindungen (z.B. Buthioninsulfoximine, Homocysteinsulfoximin, Buthioninsulfone, Penta-, Hexa-, Heptathioninsulfoximin) in sehr geringen verträglichen Dosierungen (z.B. pmol bis μmol/kg), ferner (Metall)-Chelatoren (z.B. -Hydroxyfettsäuren, Palmitinsäure, Phytinsäure, Lactoferrin), -Hydroxysäuren (z.B. Citronensäure, Milchsäure, Apfelsäure), Huminsäure, Gallensäure, Gallenextrakte, Bilirubin, Biliverdin, EDTA, EGTA und deren Derivate, ungesättigte Fettsäuren und deren Derivate (z.B. γ-Linolensäure, Linolsäure, Öl- säure), Folsäure und deren Derivate, Alanindiessigsäure, Flavonoide, Taurin und Derivate, Polyphenole, Catechine, Vitamin C und Derivate (z.B. Ascorbylpalmitat, Mg-Ascor- bylphosphat, Ascorbylacetat), Tocopherole und Derivate (z.B. Vitamin-E-acetat), sowie Koniferylbenzoat des Benzoeharzes, Rutinsäure und deren Derivate, Ferulasäure und deren Derivate, Butylhydroxytoluol, Butylhydroxyanisol, Nordihydroguajakharzsäure, Nor- dihydroguajaretsäure, Trihydroxybutyrophenon, Harnsäure und deren Derivate, Mannose und deren Derivate, Zink und dessen Derivate (z.B. ZnO, ZnS04) Selen und dessen Derivate (z.B. Selenmethionin), Stilbene und deren Derivate (z.B. Stilbenoxid, Trans-Stilben- oxid) und die erfindungsgemäß geeigneten Derivate (Salze, Ester, Ether, Zucker, Nukleo- tide, Nukleoside, Peptide und Lipide) dieser genannten Wirkstoffe.The antioxidants are advantageously selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, L- Carnosine and its derivatives (e.g. anserine), carotenoids, carotenes (e.g. α-carotene, ß-carotene, lycopene) and their derivatives, lipoic acid and their derivatives (e.g. dihydroliponic acid), arthioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathione , Cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) as well as their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g. buthioninsulfoximines, homocysteine sulfoximine, buthioninsulfones, pentathione, hexa-, imine) low tolerable doses (e.g. pmol to μmol / kg), also (metal) chelators (e.g. -hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), -hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin , EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (eg γ-linolenic acid, linoleic acid, oleic acid), folic acid and their derivatives, alanine diacetic acid, flavonoids, taurine and derivatives, polyphenols, catechins, vitamin C and derivatives (eg ascorbyl palmitate , Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), as well as coniferyl benzoate of benzoin, rutinic acid and its derivatives, ferulic acid and its derivatives, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguajakharzenic acid, noredihydroxychloric acid, nor- dihydric acid, trihydroxyhydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrohydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrochloric acid, nor- dihydrohydrochloric acid, nor- dihydrochloric acid tri- and their derivatives, mannose and their derivatives, zinc and its derivatives (eg ZnO, ZnS0 4 ) selenium and its derivatives (e.g. selenium methionine), stilbenes and their derivatives (e.g. stilbene oxide, trans-stilbene oxide) and the derivatives suitable according to the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these active substances.
Die Menge der Antioxidantien (eine oder mehrere Verbindungen) in den Zubereitungen beträgt vorzugsweise 0,001 bis 30 Gew.-%, besonders bevorzugt 0,05 - 20 Gew.-%, insbesondere 1 - 10 Gew.-%, bezogen auf das Gesamtgewicht der Zubereitung.The amount of the antioxidants (one or more compounds) in the preparations is preferably 0.001 to 30% by weight, particularly preferably 0.05 to 20% by weight, in particular 1 to 10% by weight, based on the total weight of the preparation ,
Die Prophylaxe bzw. die kosmetische oder dermatologische Behandlung mit dem erfindungsgemäß verwendeten Wirkstoffkombinationen bzw. mit den kosmetischen oder topischen dermatologischen Zubereitungen mit einem wirksamen Gehalt an erfindungsgemäß verwendeter Wirkstoffkombination erfolgt in der üblichen Weise, und zwar dergestalt, daß der erfindungsgemäß verwendete Wirkstoff bzw. die kosmetischen oder topischen dermatologischen Zubereitungen mit einem wirksamen Gehalt an erfindungsgemäß verwendetem Wirkstoff auf die betroffenen Hautstellen aufgetragen wird.The prophylaxis or the cosmetic or dermatological treatment with the active substance combinations used according to the invention or with the cosmetic or topical dermatological preparations with an effective content of active substance combination used according to the invention is carried out in the usual way, in such a way that the active substance used according to the invention or the cosmetic ones or topical dermatological preparations with an effective content of active ingredient used according to the invention is applied to the affected skin areas.
Vorteilhaft kann die erfindungsgemäß verwendete Wirkstoffkombination eingearbeitet werden in übliche kosmetische und dermatologische Zubereitungen, welche in verschiedenen Formen vorliegen können. So können sie z.B. eine Lösung, eine Emulsion vom Typ Wasser-in-ÖI (W/O) oder vom Typ Öl-in-Wasser (O/W), oder eine multiple Emulsionen, beispielsweise vom Typ Wasser-in-ÖI-in-Wasser (W/O/W) oder Öl-in-Wasser-in- Öl (O/W/O), eine Hydrodispersion oder Lipodispersion, ein Gel, einen festen Stift oder auch ein Aerosol darstellen.The active ingredient combination used according to the invention can advantageously be incorporated into customary cosmetic and dermatological preparations, which can be in various forms. So you can e.g. a solution, an emulsion of the type water-in-oil (W / O) or of the type oil-in-water (O / W), or a multiple emulsions, for example of the type water-in-oil-in-water (W / O / W) or oil-in-water-in-oil (O / W / O), a hydrodispersion or lipodispersion, a gel, a solid stick or an aerosol.
Erfindungsgemäße Emulsionen im Sinne der vorliegenden Erfindung, z.B. in Form einer Creme, einer Lotion, einer kosmetischen Milch sind vorteilhaft und enthalten z.B. Fette, Öle, Wachse und/oder andere Fettkörper, sowie Wasser und einen oder mehrere Emul- gatoren, wie sie üblicherweise für einen solchen Typ der Formulierung verwendet werden.Emulsions according to the invention in the sense of the present invention, e.g. in the form of a cream, a lotion, a cosmetic milk are advantageous and contain e.g. Fats, oils, waxes and / or other fat bodies, as well as water and one or more emulsifiers, as are usually used for such a type of formulation.
Es ist auch möglich und vorteilhaft im Sinne der vorliegenden Erfindung, die erfindungsgemäß verwendete Wirkstoffkombination in wäßrige Systeme bzw. Tensidzubereitungen' zur Reinigung und auch Pflege der Haut und der Haare einzufügen.For the purposes of the present invention, it is also possible and advantageous to insert the active ingredient combination used according to the invention into aqueous systems or surfactant preparations for cleaning and also care of the skin and hair.
Es ist dem Fachmanne natürlich bekannt, daß anspruchsvolle kosmetische Zusammensetzungen zumeist nicht ohne die üblichen Hilfs- und Zusatzstoffe denkbar sind. Darunter zählen beispielsweise Konsistenzgeber, Füllstoffe, Parfüm, Farbstoffe, Emulgatoren, zu- sätzliche Wirkstoffe wie Vitamine oder Proteine, Lichtschutzmittel, Stabilisatoren, Insek- tenrepellentien, Alkohol, Wasser, Salze, antimikrobiell, proteolytisch oder keratolytisch wirksame Substanzen usw.It is of course known to the person skilled in the art that sophisticated cosmetic compositions are usually inconceivable without the customary auxiliaries and additives. These include, for example, consistency agents, fillers, perfume, dyes, emulsifiers, additional active ingredients such as vitamins or proteins, light stabilizers, stabilizers, insect repellents, alcohol, water, salts, antimicrobial, proteolytic or keratolytically active substances etc.
Mutatis mutandis gelten entsprechende Anforderungen an die Formulierung medizinischer Zubereitungen.Mutatis mutandis, corresponding requirements apply to the formulation of medical preparations.
Medizinische topische Zusammensetzungen im Sinne der vorliegenden Erfindung enthalten in der Regel ein oder mehrere Medikamente in wirksamer Konzentration. Der Einfachheit halber wird zur sauberen Unterscheidung zwischen kosmetischer und medizinischer Anwendung und entsprechenden Produkten auf die gesetzlichen Bestimmungen der Bundesrepublik Deutschland verwiesen (z.B. Kosmetikverordnung, Lebensmittel- und Arznei mittelgesetz).Medical topical compositions in the sense of the present invention generally contain one or more medicaments in an effective concentration. For the sake of simplicity, reference is made to the legal provisions of the Federal Republic of Germany for a clear distinction between cosmetic and medical use and corresponding products (e.g. cosmetics ordinance, food and drug law).
Es ist dabei ebenfalls von Vorteil, die erfindungsgemäß verwendete Wirkstoffkombination als Zusatzstoff zu Zubereitungen zu geben, die bereits andere Wirkstoffe für andere Zwecke enthalten.It is also advantageous to add the active ingredient combination used according to the invention as an additive to preparations which already contain other active ingredients for other purposes.
Entsprechend können kosmetische oder topische dermatologische Zusammensetzungen im Sinne der vorliegenden Erfindung, je nach ihrem Aufbau, beispielsweise verwendet werden als Hautschutzcreme, Reinigungsmilch, Sonnenschutzlotion, Nährcreme, Tagesoder Nachtcreme usw. Es ist gegebenenfalls möglich und vorteilhaft, die erfindungsgemäßen Zusammensetzungen als Grundlage für pharmazeutische Formulierungen zu verwenden.Accordingly, cosmetic or topical dermatological compositions within the meaning of the present invention, depending on their structure, can be used, for example, as skin protection cream, cleansing milk, sunscreen lotion, nutritional cream, day or night cream, etc. It is possibly possible and advantageous to add the compositions according to the invention as the basis for pharmaceutical formulations use.
Günstig sind gegebenenfalls auch solche kosmetischen und dermatologischen Zubereitungen, die in der Form eines Sonnenschutzmittels vorliegen. Vorzugsweise enthalten diese neben der erfindungsgemäß verwendeten Wirkstoffkombination zusätzlich mindestens eine UVA-Filtersubstanz und/oder mindestens eine UVB-Filtersubstanz und/oder mindestens ein anorganisches Pigment.If appropriate, cosmetic and dermatological preparations which are in the form of a sunscreen are also favorable. In addition to the active ingredient combination used according to the invention, these preferably additionally contain at least one UVA filter substance and / or at least one UVB filter substance and / or at least one inorganic pigment.
Es ist aber auch vorteilhaft im Sinne der vorliegenden Erfindungen, solche kosmetischen und dermatologischen Zubereitungen zu erstellen, deren hauptsächlicher Zweck nicht der Schutz vor Sonnenlicht ist, die aber dennoch einen Gehalt an UV-Schutzsubstanzen enthalten. So werden beispielsweise in Tagescremes gewöhnlich UV-A- bzw. UV-B- Filtersubstanzen eingearbeitet.However, it is also advantageous in the sense of the present inventions to produce cosmetic and dermatological preparations whose main purpose is not protection against sunlight, but which nevertheless contain UV protection substances. For example, day creams are usually UV-A or UV-B Filter substances incorporated.
Vorteilhaft können erfindungsgemäße Zubereitungen Substanzen enthalten, die UV- Strahlung im UVB-Bereich absorbieren, wobei die Gesamtmenge der Filtersubstanzen z.B. 0,1 Gew.-% bis 30 Gew.-%, vorzugsweise 0,5 bis 10 Gew.-%, insbesondere 1 bis 6 Gew.-% beträgt, bezogen auf das Gesamtgewicht der Zubereitungen.Preparations according to the invention can advantageously contain substances which absorb UV radiation in the UVB range, the total amount of filter substances e.g. 0.1% by weight to 30% by weight, preferably 0.5 to 10% by weight, in particular 1 to 6% by weight, based on the total weight of the preparations.
Die UVB-Filter können öllöslich oder wasserlöslich sein. Als öllösliche Substanzen sind z.B. zu nennen:The UVB filters can be oil-soluble or water-soluble. As oil-soluble substances e.g. to call:
3-Benzylidencampher und dessen Derivate, z.B. 3-(4-Methylbenzyliden)campher,3-benzylidene camphor and its derivatives, e.g. 3- (4-methylbenzylidene) camphor,
4-Aminobenzoesäure-Derivate, vorzugsweise 4-(Dimethylamino)-benzoesäure(2- ethylhexyl)ester, 4-(Dimethylamino)benzoesäureamylester;4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester;
Ester der Zimtsäure, vorzugsweise 4-Methoxyzimtsäure(2-ethylhexyl)ester, 4-Meth- oxyzimtsäureisopentylester;Esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester, 4-methoxycinnamic acid isopentyl ester;
Ester der Salicylsäure, vorzugsweise Salicylsäure(2-ethylhexyl)ester, Salicylsäure(4- isopropylbenzyl)ester, Salicylsäurehomomenthylester;Esters of salicylic acid, preferably salicylic acid (2-ethylhexyl) ester, salicylic acid (4-isopropylbenzyl) ester, salicylic acid homomethyl ester;
Derivate des Benzophenons, vorzugsweise 2-Hydroxy-4-methoxybenzophenon, 2-Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-
Hydroxy-4-methoxy-4'-methylbenzophenon, 2,2'-Dihydroxy-4-methoxybenzophenon;Hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;
Ester der Benzalmalonsäure, vorzugsweise 4-Methoxybenzalmalonsäuredi(2-ethyl- hexyl)ester;Esters of benzalmalonic acid, preferably 4-methoxybenzalmalonic acid di (2-ethylhexyl) ester;
2,4,6-Trianilino-(p-carbo-2'-ethyl-1 '-hexyloxy)-1 ,3,5-triazin.2,4,6-trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1, 3,5-triazine.
Als wasserlösliche Substanzen sind vorteilhaft:The following are advantageous as water-soluble substances:
2-Phenylbenzimidazol-5-sulfonsäure und deren Salze, z.B. Natrium-, Kalium- oder Triethanolammonium-Salze,2-phenylbenzimidazole-5-sulfonic acid and its salts, e.g. Sodium, potassium or triethanolammonium salts,
Sulfonsäure-Derivate von Benzophenonen, vorzugsweise 2-Hydroxy-4-methoxyben- zophenon-5-sulfonsäure und ihre Salze;Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;
Sulfonsäure-Derivate des 3-Benzylidencamphers, wie z.B. 4-(2-Oxo-3-bornyliden- methyl)benzolsulfonsäure, 2-Methyl-5-(2-oxo-3-bornylidenmethyl)sulfonsäure und ihre Salze.Sulfonic acid derivatives of 3-benzylidene camphor, e.g. 4- (2-oxo-3-bornylidene-methyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidene-methyl) sulfonic acid and their salts.
Die Liste der genannten UVB-Filter, die erfindungsgemäß Verwendung finden können, soll selbstverständlich nicht limitierend sein.The list of UVB filters mentioned, which can be used according to the invention, is of course not intended to be limiting.
Gegenstand der Erfindung ist auch die Kombination eines erfindungsgemäßen UVA-Fil- ters mit einem UVB-Filter bzw. eine erfindungsgemäßes kosmetische oder dermatologische Zubereitung, welche auch einen UVB-Filter enthält.The invention also relates to the combination of a UVA film according to the invention. ters with a UVB filter or a cosmetic or dermatological preparation according to the invention, which also contains a UVB filter.
Es kann auch von Vorteil sein, in erfindungsgemäßen Zubereitungen UVA-Filter einzusetzen, die üblicherweise in kosmetischen und/oder dermatologischen Zubereitungen enthalten sind. Bei solchen Filtersubstanzen handelt es sich vorzugsweise um Derivate des Dibenzoylmethans, insbesondere um 1 -(4'-tert.Butylphenyl)-3-(4'-methoxyphenyl)propan- 1,3-dion und um 1-Phenyl-3-(4'-isopropylphenyl)propan-1 ,3-dion. Auch Zubereitungen, die diese Kombinationen enthalten, sind Gegenstand der Erfindung. Es können die gleichen Mengen an UVA-Filtersubstanzen verwendet werden, welche für UVB-Filtersubstanzen genannt wurden.It can also be advantageous to use UVA filters in preparations according to the invention, which are usually contained in cosmetic and / or dermatological preparations. Such filter substances are preferably derivatives of dibenzoylmethane, in particular 1 - (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione and 1-phenyl-3- (4 '-isopropylphenyl) propane-1,3-dione. Preparations containing these combinations are also the subject of the invention. The same amounts of UVA filter substances that were mentioned for UVB filter substances can be used.
Kosmetische und/oder dermatologische Zubereitungen im Sinne der vorliegenden Erfindung können auch anorganische Pigmente enthalten, die üblicherweise in der Kosmetik zum Schütze der Haut vor UV-Strahlen verwendet werden. Dabei handelt es sich um Oxide des Titans, Zinks, Eisens, Zirkoniums, Siliciums, Mangans, Aluminiums, Cers und Mischungen davon, sowie Abwandlungen, bei denen die Oxide die aktiven Agentien sind. Besonders bevorzugt handelt es sich um Pigmente auf der Basis von Titandioxid. Es können die für die vorstehenden Kombinationen genannten Mengen verwendet werden.Cosmetic and / or dermatological preparations in the sense of the present invention can also contain inorganic pigments which are usually used in cosmetics to protect the skin from UV rays. These are oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum, cerium and mixtures thereof, as well as modifications in which the oxides are the active agents. Pigments based on titanium dioxide are particularly preferred. The amounts mentioned for the above combinations can be used.
Die erfindungsgemäßen kosmetischen und dermatologischen Zubereitungen können kosmetische Wirk-, Hilfs- und/oder Zusatzstoffe enthalten, wie sie üblicherweise in solchen Zubereitungen verwendet werden, z.B. Antioxidationsmittel, Konservierungsmittel, Bakterizide, Parfüme, Substanzen zum Verhindern des Schäumens, Farbstoffe, Pigmente, die färbende Wirkung haben, Verdickungsmittel, oberflächenaktive Substanzen, Emul- gatoren, weichmachende, anfeuchtende und/oder feuchthaltende Substanzen, Fette, Öle, Wachse oder andere übliche Bestandteile einer kosmetischen oder dermatologischen Formulierung wie Alkohole, Polyole, Polymere, Schaumstabilisatoren, Elektrolyte, organische Lösungsmittel oder Silikonderivate.The cosmetic and dermatological preparations according to the invention can contain cosmetic active ingredients, auxiliaries and / or additives as are usually used in such preparations, e.g. Antioxidants, preservatives, bactericides, perfumes, anti-foaming substances, dyes, pigments that have a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other common ingredients a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.
Sofern die kosmetische oder dermatologische Zubereitung im Sinne der vorliegenden Erfindung eine Lösung oder Emulsion oder Dispersion darstellt, können als Lösungsmittel verwendet werden:If the cosmetic or dermatological preparation in the sense of the present invention is a solution or emulsion or dispersion, the following can be used as solvents:
Wasser oder wäßrige LösungenWater or aqueous solutions
Öle, wie Triglyceride der Caprin- oder der Caprylsäure, vorzugsweise aber Ri- zinusöl;Oils, such as triglycerides of capric or caprylic acid, but preferably Ri- zinusöl;
Fette, Wachse und andere natürliche und synthetische Fettkörper, vorzugsweiseFats, waxes and other natural and synthetic fat bodies, preferably
Ester von Fettsäuren mit Alkoholen niedriger C-Zahl, z.B. mit Isopropanol, Propy- lenglykol oder Glycerin, oder Ester von Fettalkoholen mit Alkansäuren niedriger C-Esters of fatty acids with low C alcohols, e.g. with isopropanol, propylene glycol or glycerin, or esters of fatty alcohols with lower C- alkanoic acids
Zahl oder mit Fettsäuren;Number or with fatty acids;
Alkohole, Diole oder Polyole niedriger C-Zahl, sowie deren Ether, vorzugsweiseAlcohols, diols or polyols of low C number, and their ethers, preferably
Ethanol, Isopropanol, Propylenglykol, Glycerin, Ethylenglykol, Ethylenglykol- monoethyl- oder -monobutylether, Propylenglykolmonomethyl, -monoethyl- oder - monobutylether, Diethylenglykolmonomethyl- oder -monoethylether und analogeEthanol, isopropanol, propylene glycol, glycerin, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and similar
Produkte.Products.
Insbesondere werden Gemische der vorstehend genannten Lösungsmittel verwendet. Bei alkoholischen Lösungsmitteln kann Wasser ein weiterer Bestandteil sein. Die Ölphase der Emulsionen, Oleogele bzw. Hydrodispersionen oder Lipodispersionen im Sinne der vorliegenden Erfindung wird vorteilhaft gewählt aus der Gruppe der Ester aus gesättigten und/oder ungesättigten, verzweigten und/oder unverzweigten Alkancarbon- säuren einer Kettenlänge von 3 bis 30 C-Atomen und gesättigten und/oder ungesättigten, verzweigten und/oder unverzweigten Alkoholen einer Kettenlänge von 3 bis 30 C-Atomen, aus der Gruppe der Ester aus aromatischen Carbonsäuren und gesättigten und/oder ungesättigten, verzweigten und/oder unverzweigten Alkoholen einer Ketteniänge von 3 bis 30 C-Atomen. Solche Esteröle können dann vorteilhaft gewählt werden aus der Gruppe Isopropylmyristat, Isopropylpalmitat, Isopropylstearat, Isopropyloleat, n-Butylstearat, n- Hexyllaurat, n-Decyloleat, Isooctylstearat, Isononylstearat, Isononylisononanoat, 2- Ethylhexylpalmitat, 2-Ethylhexyllaurat, 2-Hexyldecylstearat, 2-Octyldodecylpalmitat, Oley- loleat, Oleylerucat, Erucyloleat, Erucylerucat sowie synthetische, halbsynthetische und natürliche Gemische solcher Ester, z.B. Jojobaöl.Mixtures of the abovementioned solvents are used in particular. Water can also be a component of alcoholic solvents. The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the sense of the present invention is advantageously selected from the group of esters from saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms, from the group of esters from aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols with a chain length of 3 to 30 carbon atoms. atoms. Such ester oils can then advantageously be selected from the group of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononylisononanoate, 2-ethylhexyluryl, 2-ethylhexyl palylate, Octyldodecyl palmitate, olefin oleate, olefin erucate, erucyl oleate, erucyl erucate as well as synthetic, semi-synthetic and natural mixtures of such esters, for example Jojoba oil.
Ferner kann die Ölphase vorteilhaft gewählt werden aus der Gruppe der verzweigten und unverzweigten Kohlenwasserstoffe und -wachse, der Silkonöle, der Dialkylether, der Gruppe der gesättigten oder ungesättigten, verzweigten oder unverzweigten Alkohole, sowie der Fettsäuretriglyceride, namentlich der Triglycerinester gesättigter und/oder ungesättigter, verzweigter und/oder unverzweigter Alkancarbonsäuren einer Kettenlänge von 8 bis 24, insbesondere 12 - 18 C-Atomen. Die Fettsäuretriglyceride können beispielsweise vorteilhaft gewählt werden aus der Gruppe der synthetischen, halbsynthetischen und natürlichen Öle, z.B. Olivenöl, Sonnenblumenöl, Sojaöl, Erdnußöl, Rapsöl, Mandelöl, Palmöl, Kokosöl, Palmkernöl und dergleichen mehr.Furthermore, the oil phase can advantageously be selected from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and also the fatty acid triglycerides, especially the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids with a chain length of 8 to 24, in particular 12 - 18 carbon atoms. The fatty acid triglycerides can, for example, advantageously be selected from the group of synthetic, semisynthetic and natural oils, for example olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, Palm oil, coconut oil, palm kernel oil and the like.
Auch beliebige Abmischungen solcher Öl- und Wachskomponenten sind vorteilhaft im Sinne der vorliegenden Erfindung einzusetzen. Es kann auch gegebenenfalls vorteilhaft sein, Wachse, beispielsweise Cetylpalmitat, als alleinige Lipidkomponente der Ölphase einzusetzen.Any mixtures of such oil and wax components can also be used advantageously for the purposes of the present invention. It may also be advantageous to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.
Vorteilhaft wird die Ölphase gewählt aus der Gruppe 2-Ethylhexylisostearat, Octyldo- decanol, Isotridecylisononanoat, Isoeicosan, 2-Ethylhexylcocoat, C12-ι5-Alkylbenzoat, Ca- pryl-Caprinsäure-triglycerid, Dicaprylylether.The oil phase is selected from the group 2-ethylhexyl advantageous Octyldo- decanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C 12 ι 5 -alkyl, Ca Pryl-capric acid triglyceride, dicaprylyl ether.
Besonders vorteilhaft sind Mischungen aus Cι2-i5-Alkybenzoat und 2-Ethylhexylisostearat, Mischungen aus Cι2-15-Alkybenzoat und Isotridecylisononanoat sowie Mischungen aus Cι2-i5-Alkybenzoat, 2-Ethylhexylisostearat und Isotridecylisononanoat. Von den Kohlenwasserstoffen sind Paraffinöl, Squalan und Squalen vorteilhaft im Sinne der vorliegenden Erfindung zu verwenden.Mixtures of Cι 2- i5 alkylbenzoate and 2-ethylhexyl isostearate, mixtures of Cι 2-15 alkylbenzoate and isotridecyl isononanoate and mixtures of Cι 2- i5 alkylbenzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate are particularly advantageous. Of the hydrocarbons, paraffin oil, squalane and squalene can be used advantageously for the purposes of the present invention.
Vorteilhaft kann die Ölphase femer einen Gehalt an cyclischen oder linearen Siiikonölen aufweisen oder vollständig aus solchen Ölen bestehen, wobei allerdings bevorzugt wird, außer dem Silikonöl oder den Silikonölen einen zusätzlichen Gehalt an anderen Ölpha- senkomponenten zu verwenden.The oil phase can also advantageously have a content of cyclic or linear silicon oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or the silicone oils.
Vorteilhaft wird Cyclomethicon (Octamethylcyclotetrasiloxan) als erfindungsgemäß zu verwendendes Silikonöl eingesetzt. Aber auch andere Silikonöle sind vorteilhaft im Sinne der vorliegenden Erfindung zu verwenden, beispielsweise Hexamethylcyclotrisiloxan, Polydi- methylsiloxan, Poly(methylphenylsiloxan).Cyclomethicone (octamethylcyclotetrasiloxane) is advantageously used as the silicone oil to be used according to the invention. However, other silicone oils can also be used advantageously for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).
Besonders vorteilhaft sind ferner Mischungen aus Cyclomethicon und Isotridecylisononanoat, aus Cyclomethicon und 2-Ethylhexyiisostearat.Mixtures of cyclomethicone and isotridecyl isononanoate, of cyclomethicone and 2-ethylhexyl isostearate are also particularly advantageous.
Die wäßrige Phase der erfindungsgemäßen Zubereitungen enthält gegebenenfalls vorteilhaft Alkohole, Diole oder Polyole niedriger C-Zahl, sowie deren Ether, vorzugsweise Etha- nol, Isopropanol, Propylenglykol, Glycerin, Ethylenglykol, Ethylenglykolmonoethyl- oder - monobutylether, Propylenglykolmonomethyl, -monoethyl- oder -monobutylether, Diethy- lenglykolmonomethyl- oder -monoethylether und analoge Produkte, ferner Alkohole nied- riger C-Zahl, z.B. Ethanol, Isopropanol, 1 ,2-Propandiol, Glycerin sowie insbesondere ein oder mehrere Verdickungsmittel, welches oder welche vorteilhaft gewählt werden können aus der Gruppe Siliciumdioxid, Aluminiumsilikate, Polysaccharide bzw. deren Derivate, z.B. Hyaluronsäure, Xanthangummi, Hydroxypropylmethylcellulose, besonders vorteilhaft aus der Gruppe der Polyacrylate, bevorzugt ein Polyacrylat aus der Gruppe der sogenannten Carbopole, beispielsweise Carbopole der Typen 980, 981 , 1382, 2984, 5984, jeweils einzeln oder in Kombination.The aqueous phase of the preparations according to the invention optionally advantageously contains alcohols, diols or polyols of low C number, and also their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or - monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether , Diethylene glycol monomethyl or monoethyl ether and analog products, furthermore alcohols low Riger C number, for example ethanol, isopropanol, 1, 2-propanediol, glycerol and in particular one or more thickeners, which or which can advantageously be selected from the group silicon dioxide, aluminum silicates, polysaccharides or their derivatives, for example hyaluronic acid, xanthan gum, hydroxypropylmethyl cellulose , particularly advantageously from the group of polyacrylates, preferably a polyacrylate from the group of so-called carbopoles, for example carbopoles of types 980, 981, 1382, 2984, 5984, each individually or in combination.
Erfindungsgemäß verwendete Gele enthalten üblicherweise Alkohole niedriger C-Zahl, z.B. Ethanol, Isopropanol, 1 ,2-Propandiol, Glycerin und Wasser bzw. ein vorstehend genanntes Öl in Gegenwart eines Verdickungsmittels, das bei ölig-alkoholischen Gelen vorzugsweise Siliciumdioxid oder ein Aluminiumsilikat, bei wäßrig-alkoholischen oder alkoholischen Gelen vorzugweise ein Polyacrylat ist.Gels used in the present invention usually contain low C number alcohols, e.g. Ethanol, isopropanol, 1, 2-propanediol, glycerol and water or an oil mentioned above in the presence of a thickener which is preferably silicon dioxide or an aluminum silicate in the case of oily-alcoholic gels, and is preferably a polyacrylate in the case of aqueous-alcoholic or alcoholic gels.
Feste Stifte enthalten z.B. natürliche oder synthetische Wachse, Fettalkohole oder Fettsäureester.Fixed pens contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters.
Übliche Grundstoffe, welche für die Verwendung als kosmetische Stifte im Sinne der vorliegenden Erfindung geeignet sind, sind flüssige Öle (z.B. Paraffinöle, Ricinusöl, Iso- propylmyristat), halbfeste Bestandteile (z.B. Vaseline, Lanolin), feste Bestandteile (z.B. Bienenwachs, Ceresin und Mikrokristalline Wachse bzw. Ozokerit) sowie hochschmelzende Wachse (z.B. Carnaubawachs, Candelillawachs)Usual base materials which are suitable for use as cosmetic sticks in the sense of the present invention are liquid oils (for example paraffin oils, castor oil, isopropyl myristate), semi-solid components (for example petroleum jelly, lanolin), solid components (for example beeswax, ceresin and microcrystallines) Waxes or ozokerite) and high-melting waxes (e.g. carnauba wax, candelilla wax)
Als Treibmittel für aus Aerosolbehältern versprühbare kosmetische und/oder dermatologische Zubereitungen im Sinne der vorliegenden Erfindung sind die üblichen bekannten leichtflüchtigen, verflüssigten Treibmittel, beispielsweise Kohlenwasserstoffe (Propan, Butan, Isobutan) geeignet, die allein oder in Mischung miteinander eingesetzt werden können. Auch Druckluft ist vorteilhaft zu verwenden.Suitable blowing agents for cosmetic and / or dermatological preparations which can be sprayed from aerosol containers for the purposes of the present invention are the customary known volatile, liquefied blowing agents, for example hydrocarbons (propane, butane, isobutane), which can be used alone or in a mixture with one another. Compressed air can also be used advantageously.
Natürlich weiß der Fachmann, daß es an sich nichttoxische Treibgase gibt, die grundsätzlich für die Verwirklichung der vorliegenden Erfindung in Form von Aerosolpräparaten geeignet wären, auf die aber dennoch wegen bedenklicher Wirkung auf die Umwelt oder sonstiger Begleitumstände verzichtet werden sollte, insbesondere Fluorkohlenwasserstoffe und Fluorchlorkohlenwasserstoffe (FCKW). Kosmetische Zubereitungen im Sinne der vorliegenden Erfindung können auch als Gele vorliegen, die neben einem wirksamen Gehalt am erfindungsgemäßen Wirkstoff und dafür üblicherweise verwendeten Lösungsmitteln, bevorzugt Wasser, noch organische Verdi- ckungsmittel, z.B. Gummiarabikum, Xanthangummi, Natriumalginat, Cellulose-Derivate, vorzugsweise Methylcellulose, Hydroxymethylcellulose, Hydroxyethylcellulose, Hydro- xypropylcellulose, Hydroxypropylmethylcellulose oder anorganische Verdickungsmittel, z. B. Aluminiumsilikate wie beispielsweise Bentonite, oder ein Gemisch aus Polyethylengly- kol und Polyethylenglykolstearat oder -distearat, enthalten. Das Verdickungsmittel ist in dem Gel z.B. in einer Menge zwischen 0,1 und 30 Gew.-%, bevorzugt zwischen 0,5 und 15 Gew.-%, enthalten.Of course, the person skilled in the art knows that there are non-toxic propellant gases per se which would in principle be suitable for the implementation of the present invention in the form of aerosol preparations, but which should nevertheless be dispensed with because of their harmful effects on the environment or other accompanying circumstances, in particular fluorocarbons and chlorofluorocarbons ( CFC). Cosmetic preparations in the sense of the present invention can also be in the form of gels which, in addition to an effective content of the active ingredient according to the invention and solvents usually used therefor, preferably water, and also organic thickeners, for example gum arabic, xanthan gum, sodium alginate, cellulose derivatives, preferably methyl cellulose, Hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose or inorganic thickeners, e.g. B. aluminum silicates such as bentonite, or a mixture of polyethylene glycol and polyethylene glycol stearate or distearate. The thickener is contained in the gel, for example, in an amount between 0.1 and 30% by weight, preferably between 0.5 and 15% by weight.
Im Folgenden sind erfindungsgemäße kosmetische Zubereitungen beispielhaft aufgeführt, die alle die beschriebenen Vorzüge einer hohen und langanhaltenden Hautfeuchtigkeits- speicherung generieren. Cosmetic preparations according to the invention are listed below by way of example, all of which generate the described advantages of high and long-lasting skin moisture retention.
1. PIT- Emulsionen1. PIT emulsions
Figure imgf000021_0001
Figure imgf000022_0001
2. Beispiele O/W-Creme
Figure imgf000021_0001
Figure imgf000022_0001
2. Examples of O / W cream
Figure imgf000023_0001
Figure imgf000024_0001
Figure imgf000023_0001
Figure imgf000024_0001
3. Beispiele O/W-Creme3. Examples of O / W cream
Figure imgf000025_0001
Figure imgf000025_0001
Figure imgf000026_0001
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000028_0001
Figure imgf000029_0001
4. Beispiele W/O-Emulsionen
Figure imgf000029_0001
4. Examples of W / O emulsions
Figure imgf000030_0001
Figure imgf000031_0001
5. Beispiele W/O Emulsionen
Figure imgf000030_0001
Figure imgf000031_0001
5. Examples of W / O emulsions
Figure imgf000032_0001
Figure imgf000032_0001
Figure imgf000033_0001
Figure imgf000033_0001
6. Beispiele Hydrodispersionen6. Examples of hydrodispersions
Figure imgf000034_0001
Figure imgf000035_0001
7. Beispiel (Gelcreme)
Figure imgf000034_0001
Figure imgf000035_0001
7th example (gel cream)
Figure imgf000036_0001
Figure imgf000036_0001
8. Beispiel (W/O-Creme )Example 8 (W / O cream)
Figure imgf000037_0001
Figure imgf000037_0001
9. Beispiel (W/O/W-Creme)Example 9 (W / O / W cream)
Figure imgf000038_0001
Figure imgf000038_0001

Claims

Patentansprüche: claims:
1. Kosmetische oder dermatologische Zubereitungen mit einem Gehalt an einer Wirkstoffkombination aus Kreatinin und /oder dessen Derivaten mit Kreatin und/oder dessen Derivaten und Biochinonen sowie pflanzlicher und tierischer Extrakte dieselben enthaltend.1. Cosmetic or dermatological preparations containing an active ingredient combination of creatinine and / or its derivatives with creatine and / or its derivatives and bioquinones as well as vegetable and animal extracts containing the same.
2. Verwendung von Zubereitungen nach Anspruch 1 zur Prophylaxe und/oder Behandlung von entzündlichen Hautzuständen und/oder zum Hautschutz bei empfindlich determinierter und trockener Haut insbesondere atopisches Ekzem, seborrhoisches Ekzem, polymorphe Lichtdermatose, Psoriasis, Vitiligo, Wundheilungsstörungen, Juckreiz, empfindliche oder gereizte Haut, lichtbedingte Hautschäden und UV-induzierte Immunsuppression, Veränderungen der Desquamation, Veränderungen der normalen Fibroblasten- und Keratinozytenproliferation.Veränderungen der normalen Fibroblasten- und Keratinozytendifferenzierung defizitäre, sensitive oder hypoaktive Hautzustände oder defizitäre, sensitive oder hypoaktive Zustände von Hautanhangsgebilden und zur Verringerung der Hautdicke.2. Use of preparations according to claim 1 for the prophylaxis and / or treatment of inflammatory skin conditions and / or for skin protection in the case of sensitive, determined and dry skin, in particular atopic eczema, seborrheic eczema, polymorphic light dermatosis, psoriasis, vitiligo, wound healing disorders, itching, sensitive or irritated skin , light-related skin damage and UV-induced immunosuppression, changes in desquamation, changes in normal fibroblast and keratinocyte proliferation, changes in normal fibroblast and keratinocyte differentiation deficit, sensitive or hypoactive skin conditions or deficient, sensitive or hypoactive conditions of the skin appendages to reduce skin attachments.
3. Verwendung von Zubereitungen nach Anspruch 1 zur Behandlung und Prophylaxe der Symptome der intrinsischen und/oder extrinsischen Hautalterung sowie zur Behandlung und Prophylaxe der schädlichen Auswirkungen ultravioletter Strahlung auf die Haut z. B. degenerative Erscheinungen der Haut insbesondere Altersflecken, Falten, Teleangiektasien, Hautschlaffheit, Elastizitätsverlust, sowie Schwund der epidermalen und dermalen Zellschichten, der Bestandteile des Bindegewebes, der Retezapfen und Kapillargefässe), sogenannte Skin luster und fatigue (Hauterschlaffung und/oder Hautermüdung), gesteigerte Aktivierung proteolytischer Enzyme in der Haut (wie z. B. Metalloproteinasen), Störungen der normalen Kollagen-, Hyaluronsäure-, Elastin- und Glykosaminoglycan-Homeostase und der normalen Hautregeneration, Veränderungen der normalen Fibroblasten- und Keratinozytenproliferation.Veränderungen der normalen Fibroblasten- und Keratinozytendifferenzierung, Mangelerscheinungen der intrazellulären DNS-Synthese (insbesondere bei defizitären oder hypoaktiven Hautzustä n- den), umweltbedingte (durch Rauchen, Smog, reaktive Sauerstoffspecies, freie Radikale und dergleichen verursachte) negative Veränderungen der Haut und/oder der Hautanhangsgebilde). 3. Use of preparations according to claim 1 for the treatment and prophylaxis of the symptoms of intrinsic and / or extrinsic skin aging and for the treatment and prophylaxis of the harmful effects of ultraviolet radiation on the skin, for. B. degenerative symptoms of the skin, in particular age spots, wrinkles, telangiectasias, sagging skin, loss of elasticity, as well as loss of the epidermal and dermal cell layers, the components of the connective tissue, the rete cones and capillary vessels), so-called skin luster and fatigue (skin sagging and / or skin fatigue), increased Activation of proteolytic enzymes in the skin (such as metalloproteinases), disorders of normal collagen, hyaluronic acid, elastin and glycosaminoglycan homeostasis and normal skin regeneration, changes in normal fibroblast and keratinocyte proliferation, changes in normal fibroblast and keratinocyte differentiation , Deficiency symptoms of intracellular DNA synthesis (especially in deficient or hypoactive skin conditions), environmental (caused by smoking, smog, reactive oxygen species, free radicals and the like) negative changes in the skin and / or the skin appendages image).
4. Verwendung von Zubereitungen nach Anspruch 1 zur Behandlung und/oder Prophylaxe von Pigmentierungsstörungen, zur Steigerung der Ceramidbiosynthese (wie z.B. Veränderungen des Ceramid-, Lipid- und Energiestoffwechsels der gesunden Haut), zur Stärkung der Barrierefunktion der Haut (wie z. B. Hornschichtbarrierestörungen, Veränderungen der normalen Lipidperoxidationen, Veränderungen des transepider- malen Wasserverlustes und des normalen Feuchtigkeitsgehaltes der Haut), zur Behandlung und/oder Prophylaxe von Störungen des normalen Haut-pH-Werts und der Osmolytbalance, zur Behandlung und/oder Prophylaxe von Abweichungen von der normalen Zell-Zell-Kommunikation in der Haut (z.B. interzelluläre Kommunikationen über Mediatoren und/ oder über mechanische/ physiologische Verbindungen).4. Use of preparations according to claim 1 for the treatment and / or prophylaxis of pigmentation disorders, for increasing ceramide biosynthesis (such as changes in the ceramide, lipid and energy metabolism of healthy skin), for strengthening the barrier function of the skin (such as Horny layer barrier disorders, changes in normal lipid peroxidation, changes in transepider- mal water loss and the normal moisture content of the skin), for the treatment and / or prophylaxis of disorders of the normal skin pH value and the osmolyte balance, for the treatment and / or prophylaxis of deviations from the normal cell-cell communication in the skin (e.g. intercellular communication via mediators and / or via mechanical / physiological connections).
5. Verwendung von Zubereitungen nach Anspruch 1 zur Behandlung und/oder Prophylaxe von funktionellen Störungen der Hautanhangsgebilde insbesondere von Haarausfall, zur Verbesserung des Haarwachstums, zur Verbesserung des Haarglanzes, zur Verbesserung der Haarstruktur, gegen seborrhoische Erscheinungen, gegen fettige Haut, gegen fettiges Haar, gegen Komedonen, gegen Kopfschuppen.5. Use of preparations according to claim 1 for the treatment and / or prophylaxis of functional disorders of the skin appendages, in particular hair loss, for improving hair growth, for improving hair shine, for improving hair structure, against seborrheic phenomena, against oily skin, against oily hair, against comedones, against dandruff.
6. Zubereitungen nach Anspruch 1 und Verwendung nach Anspruch 2 bis 5, dadurch gekennzeichnet, dass als Biochinon Coenzym Q10 enthalten ist.6. Preparations according to claim 1 and use according to claims 2 to 5, characterized in that coenzyme Q10 is contained as bioquinone.
7. Kosmetische oder dermatologische Zubereitungen nach Anspruch 1 und Verwendung nach Anspruch 2 bis 6, dadurch gekennzeichnet, daß Coenzym Q10 sowie pflanzliche und tierische Extrakte dieselbe enthaltend in kosmetischen oder topischen dermatologischen Zubereitungen in Konzentrationen von 0,001 - 30Gew.-%, besonders bevorzugt 0,01 - 1 Gew.-%, bezogen auf das Gesamtgewicht der Zubereitungen, vorliegen und der Gehalt an Kreatinin und/oder dessen Derivaten 0,001 - 50 Gew.-% , vorzugsweise 0,1 - 10 Gew.-% sowie der Gehalt an Kreatin und dessen Derivaten 0,001 - 50 Gew.-% , vorzugsweise 0,1 - 10 Gew.-%, bezogen auf das Gesamtgewicht der Zubereitungen, beträgt. 7. Cosmetic or dermatological preparations according to claim 1 and use according to claims 2 to 6, characterized in that coenzyme Q10 and plant and animal extracts containing the same in cosmetic or topical dermatological preparations in concentrations of 0.001-30% by weight, particularly preferably 0, 01-1% by weight, based on the total weight of the preparations, and the content of creatinine and / or its derivatives 0.001-50% by weight, preferably 0.1-10% by weight and the content of creatine and whose derivatives is 0.001-50% by weight, preferably 0.1-10% by weight, based on the total weight of the preparations.
PCT/EP2004/050482 2003-04-10 2004-04-07 Cosmetic or dermatological preparations containing a combination of creatinine, creatine and bioquinones WO2004089326A1 (en)

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