DE102014217490A1 - Use of Gossypetin and / or Gossypin against Skin Aging - Google Patents

Abstract

Use of gossypetin and / or gossypin in cosmetic or dermatological 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.

Description

The present invention relates to cosmetic or dermatological preparations containing active ingredients for the care and protection of the skin, in particular the skin aged or aging by intrinsic and / or extrinsic factors and the use of such active ingredients and combinations of such active ingredients in the field of cosmetic and dermatological skin care ,

Cosmetic skincare is primarily understood as strengthening or restoring the skin's natural function as a barrier against environmental influences (e.g., dirt, chemicals, microorganisms) and against the loss of endogenous substances (e.g., water, natural fats, electrolytes).

If this function is disturbed, it may lead to increased absorption of toxic or allergenic substances or the infestation of microorganisms and as a result to toxic or allergic skin reactions.

The aim of skin care is also to compensate for the daily loss of fat and water loss of the skin. This is especially important when the natural regeneration capacity is insufficient. In addition, skin care products to protect against environmental influences, especially from the sun and wind, and delay the aging of the skin.

• a) Trockenheit, Rauhigkeit und Ausbildung von Trockenheitsfältchen,
• b) Juckreiz und
• c) verminderte Rückfettung durch Talgdrüsen (z.B. nach Waschen).

The chronological skin aging is caused eg by endogenous, genetically determined factors. In the epidermis and dermis, aging causes, for example, the following structural damage and dysfunctions, which may also fall under the term "senile xerosis":

• a) dryness, roughness and formation of dryness wrinkles,
• b) itching and
• c) diminished fatty tissue suppression through sebaceous glands (eg after washing).

• 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). Verminderte Regenerationsfähigkeit durch Schädigung von Hautzellen

Exogenous factors, such as UV light and chemical noxae, can be cumulatively effective and, for example, accelerate or supplement endogenous aging processes. In the epidermis and dermis, the following structural and functional disorders in the skin occur, in particular due to exogenous factors, which go beyond the extent and quality of the damage caused by chronological aging:

• d) Visible vascular dilations (telangiectasias, cuperosis);
• e) slackness and formation of wrinkles;
• f) local hyper-, hypo- and false pigmentation (eg age spots) and
• g) increased susceptibility to mechanical stress (eg cracking). Reduced ability to regenerate due to damage to skin cells

The present invention relates in particular to products for the care of naturally aged skin, as well as for the treatment of the consequential damages of photoageing, in particular of 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 derivatives thereof) or vitamin A and / or its derivatives. Their effect on the structural damage, however, is limited in scope. In addition, there are significant difficulties in product development in stabilizing the active ingredients sufficiently against oxidative degradation. In addition, the use of vitamin A acid-containing products often causes severe erythematous skin irritation. Retinoids can therefore only be used in low concentrations.

In particular, the present invention relates to cosmetic preparations with effective protection against harmful oxidation processes in the skin, but also for the protection of cosmetic preparations themselves or for the protection of the components of cosmetic preparations from harmful oxidation processes.

The present invention further relates to antioxidants, preferably those which are used in skin-care cosmetic or dermatological preparations. In particular, the invention also relates to cosmetic and dermatological preparations containing such antioxidants. In a preferred embodiment, the present invention relates to cosmetic and dermatological preparations for the prophylaxis and treatment of cosmetic or dermatological lesions, e.g. Skin aging, especially skin aging caused by oxidative processes.

In a further advantageous embodiment, the present invention relates to combinations of active substances and preparations which serve for the prophylaxis and treatment of photosensitive skin, in particular photodermatoses.

The damaging effect of the ultraviolet part of solar radiation on the skin is well known. While rays with a wavelength less 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.

As a maximum of the erythema efficiency of sunlight, the narrower range around 308 nm is given.

For protection against UVB radiation, numerous compounds are known, which are derivatives of 3-Benzylidencamphers, 4-aminobenzoic acid, cinnamic acid, salicylic acid, benzophenone and also of 2-phenylbenzimidazole.

Also for the range between about 320 nm and about 400 nm, the so-called UVA range, it is important to have available filter substances, since its rays can cause reactions in photosensitive skin. It has been proven that UVA radiation leads to damage to the elastic and collagenous fibers of connective tissue, causing the skin to age prematurely, and that it is the cause of numerous phototoxic and photoallergic reactions. The damaging influence of UVB radiation can be amplified by UVA radiation.

For protection against the rays of the UVA range, therefore, certain derivatives of dibenzoylmethane are used whose photostability (Int. J. Cosm. Science 10, 53 (1988) ), is not given sufficiently.

However, the UV radiation can also lead to photochemical reactions, in which case the photochemical reaction products intervene in the skin metabolism.

Predominantly, such photochemical reaction products are free-radical compounds, for example hydroxy radicals. Undefined free radical photoproducts that form in the skin itself may show uncontrolled sequelae due to their high reactivity. But also singlet oxygen, a non-radical excited state of the oxygen molecule can occur on UV irradiation, as well as short-lived epoxides and many others. Singlet oxygen, for example, is distinguished from the normally present triplet oxygen (radical ground state) by increased reactivity. However, there are also excited, reactive (radical) triplet states of the oxygen molecule.

Furthermore, UV radiation counts as ionizing radiation. Thus, there is a risk that ionic species may also be formed upon UV exposure, which in turn may oxidatively interfere with the biochemical processes.

Mainly antioxidants are used as protective substances against spoilage of 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.

In the tower "Skin Diseases Associated with Oxidative Injury" in "Oxidative Stress in Dermatology", p. 323 et seq. (Marcel Decker Inc., New York, Basel, Hong Kong, publisher: Jürgen Fuchs, Frankfurt, and Lester Packer, Berkeley, California) , oxidative damage to the skin and its causes are listed.

Also, for the purpose of preventing such reactions, antioxidants and / or radical scavengers may additionally be incorporated into cosmetic or dermatological formulations.

Although some antioxidants and radical scavengers are known. So is already in the U.S. Patents 4,144,325 and 4,248,861 and numerous other documents have been proposed to use vitamin E, a substance with known antioxidant effect in sunscreen formulations, yet here again, the effect achieved remains far behind the hoped for.

The object of the present invention was therefore to find ways that avoid the disadvantages of the prior art. In particular, the effect of repairing the damage associated with endogenous, chronological and exogenous skin aging and the prophylaxis should be permanent, sustainable and without the risk of side effects.

To remedy these evils was the object of the present invention.

It has surprisingly been found that the use of gossypetin in cosmetic or dermatological formulations for the treatment and prophylaxis of the symptoms of intrinsic and / or extrinsic skin aging as well as for the treatment and prophylaxis of the harmful effects of ultraviolet radiation on the skin remedies the drawbacks of the prior art.

• – von defizitären, oder hypoaktiven Hautzuständen oder defizitären, oder hypoaktiven Zuständen von Hautanhangsgebilden
• – von Erscheinungen vorzeitiger Alterung der Haut (z.B. Falten, Altersflecken, Teleangiektasien) 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 Juckreiz,
• – von trockenen Hautzuständen und Hornschichtbarrierestörungen,
• – von entzündlichen Hautzuständen wie dem seborrhoischem Ekzem, polymorpher Lichtdermatose und Vitiligo möglich. Der erfindungsgemäße Wirkstoffes bzw. kosmetischer oder topischer dermatologischer Zubereitungen mit einem wirksamen Gehalt an erfindungsgemäßem Wirkstoff dient aber auch in überraschender Weise
• – zur Stimulation der Kollagen-, Hyaluronsäure-, Elastinsynthese
• – zur Stimulation der intrazellulären Zellteilung, 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.

When using the active ingredient according to the invention or cosmetic or topical dermatological preparations having an effective content of the active ingredient used according to the invention, surprisingly an effective treatment, but also a prophylaxis

• - of deficient or hypoactive skin conditions or deficient or hypoactive states of skin appendages
• - signs of premature aging of the skin (eg wrinkles, age spots, telangiectasias) and / or skin appendages,
• - of environmental factors (smoking, smog, reactive oxygen species, free radicals) and in particular light-induced negative changes in the skin and the appendages.
• - of light-induced skin damage,
• - from itching,
• Dry skin conditions and corneal barrier disorders,
• - of inflammatory skin conditions such as seborrheic dermatitis, polymorphic photodermatosis and vitiligo possible. The active ingredient according to the invention or cosmetic or topical dermatological preparations with an effective content of the active ingredient according to the invention, however, also serves in a surprising manner
• - To stimulate collagen, hyaluronic acid, elastin synthesis
• - To stimulate intracellular cell division, especially in deficient or hypoactive skin conditions.
• - to increase the cell renewal and regeneration of the skin
• - to increase the skin's own protective and repair mechanisms (eg for dysfunctional enzymes, DNA, lipids, proteins)
• - For pre- and post-treatment in topical application of laser and Abschleifbehandlungen z. As the reduction of skin wrinkles and scars serve to counteract the resulting skin irritation and promote the regeneration processes in the injured skin.

It is particularly advantageous according to the invention to use gossypetin and / or gossypin or cosmetic or topical dermatological preparations with an effective content of gossypetin and / or gossypin for the cosmetic or dermatological treatment or prophylaxis of undesired skin conditions.

A use according to the invention is particularly advantageous, characterized in that the preparations contain 0.0001 to 5 wt.%, In particular 0.001 to 1 wt.%, Very particularly 0.005 to 0.15 wt.% Of gossypetin and / or gossypin, based on the total weight of the preparation.

Gossypetine (3,3 ', 4', 5,7,8-hexahydroxyflavone) is a flavanol isolated from the calyx of the Sudan marshmallow (Hibiscus sabdariffa) and other plants, such as the eponymous Gossypium hirsutum. In nature, gossypetin usually occurs as 8-O-glucoside (gossypine).

The chemical structure of gossypetine is characterized as follows:

The chemical structure of the gossypin is characterized as follows:

The use of gossypetin / gossypin as antimicrobial agent is known per se. Nevertheless, this could not point the way to the present invention.

Advantageously, this use is realized in topical preparations, in particular cosmetic or dermatological preparations.

Cosmetic or dermatological preparations according to the invention preferably contain 0.001-10% by weight, particularly preferably 0.01-1% by weight of gossypetin and / or gossypin, based on the total composition of the preparations.

Emulsions are advantageous dosage forms 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 fatty substances, as well as water and one or more emulsifiers, as they are commonly used for such a type of formulation.

Medicinal topical compositions according to the present invention usually contain one or more drugs in effective concentration. For the sake of simplicity, reference is made to the clear distinction between cosmetic and medical use and corresponding products to the statutory provisions of the Federal Republic of Germany (for example, Cosmetics Regulation, Food and Medicines Act).

It is also advantageous to add the active ingredient used according to the invention as an additive to preparations which already contain other active ingredients for other purposes.

• – Wasser oder wässrige Lösungen
• – Öle, wie Triglyceride der Caprin- oder der Caprylsäure, vorzugsweise aber Rizinusöl;
• – Fette, Wachse und andere natürliche und synthetische Fettkörper, vorzugsweise Ester von Fettsäuren mit Alkoholen niedriger C-Zahl, z.B. mit Isopropanol, Propylenglykol oder Glycerin, oder Ester von Fettalkoholen mit Alkansäuren niedriger C-Zahl oder mit Fettsäuren;
• – Alkohole, Diole oder Polyole niedriger C-Zahl, sowie deren Ether, vorzugsweise Ethanol, Isopropanol, Propylenglykol, Glycerin, Ethylenglykol, Ethylenglykolmonoethyl- oder -monobutylether, Propylenglykolmonomethyl, -monoethyl- oder -monobutylether, Diethylenglykolmonomethyl- oder -monoethylether und analoge Produkte.

If the cosmetic or dermatological preparation in the sense of the present invention is a solution or emulsion or dispersion, it is possible to use as solvent:

• - water or aqueous solutions
• - Oils, such as triglycerides of capric or caprylic, but preferably castor oil;
• Fats, waxes and other natural and synthetic fatty substances, preferably esters of fatty acids with lower C-number alcohols, for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with lower C-number alkanoic acids or with fatty acids;
• Alcohols, diols or polyols of low C number, and 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 analogous products.

In particular, mixtures of the abovementioned solvents are used. For alcoholic solvents, water can be another ingredient.

The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms. Such ester oils can then be advantageously selected from the group isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2 Octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of such esters, eg Jojoba oil.

Furthermore, the oil phase can be advantageously 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 the fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12-18 C-atoms. For example, the fatty acid triglycerides can be advantageously selected from the group of synthetic, semi-synthetic and natural oils, e.g. Olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil, and the like.

• – Alkohole, Diole oder Polyole niedriger C-Zahl, sowie deren Ether, vorzugsweise Ethanol, Isopropanol, Propylenglykol, Glycerin, Ethylenglykol, Ethylenglykolmonoethyl- oder -monobutylether, Propylenglykolmonomethyl, -monoethyl- oder -monobutylether, Diethylenglykolmonomethyl- oder -monoethylether und analoge Produkte, ferner Alkohole niedriger 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.

Any desired mixtures of such oil and wax components are advantageous in The aqueous phase of the preparations according to the invention optionally contains advantageous

• 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 analogous products, furthermore low C-number alcohols, for example ethanol, isopropanol, 1,2-propanediol, glycerol and in particular one or more thickening agents, which can be advantageously selected from the group of silicon dioxide, aluminum silicates, polysaccharides or their derivatives, for example hyaluronic acid, xanthan gum , Hydroxypropylmethylcellulose, particularly advantageous from the group of polyacrylates, preferably a polyacrylate from the group of so-called Carbopols, for example Carbopols types 980, 981, 1382, 2984, 5984, each individually or in combination.

Gels used in the present invention usually contain low C number alcohols, e.g. Ethanol, isopropanol, 1,2-propanediol, glycerol and water or an above-mentioned oil in the presence of a thickener which is preferably silica or an aluminum silicate in oily-alcoholic gels, preferably a polyacrylate in aqueous-alcoholic or alcoholic gels.

Fixed pins contain e.g. natural or synthetic waxes, fatty alcohols or fatty acid esters.

Conventional base materials which are suitable for use as cosmetic sticks in the context of the present invention are liquid oils (for example paraffin oils, castor oil, isopropyl myristate), semi-solid constituents (eg petrolatum, lanolin), solid constituents (eg beeswax, ceresin and microcrystalline waxes or Ozokerite) and high-melting waxes (eg carnauba wax, candelilla wax)

Suitable propellants for sprayable from aerosol containers cosmetic and / or dermatological preparations in the context of the present invention, the usual known volatile, liquefied propellants, such as hydrocarbons (propane, butane, isobutane) are suitable, which can be used alone or in mixture with each other. Also, compressed air is advantageous to use.

The following examples are intended to illustrate the present invention without limiting it. Unless indicated otherwise, all amounts, proportions and percentages are based on the weight and the total amount or on the total weight of the preparations. Wrinkle cream (examples 1-2) 1 2 INCI name Wt .-% Wt .-% stearic acid 3.00 2.00 glyceryl stearate 1.00 1.00 C12-15 alkyl benzoates 5.00 5.00 Caprylic / capric 2.50 2.50 cetyl alcohol - 2.00 Stearylalcohol 2.00 2.00 cyclomethicone 1.00 1.00 dicaprylyl 2.00 2.00 dimethicone 1.00 1.00 glycerin 5.00 10.00 methylparaben 0.20 - phenoxyethanol 0.40 0.10 ethanol 3.00 - ascorbic acid 0.10 - Carbomer 0.20 0.10 Acrylates / C10-30 Alkyl Acrylate Crosspolymer - 0.20 Trisodium EDTA - 0.20 tapioca starch 1.50 - Gossypine - 0.5 gossypetin 0.2 - NaOH qs qs Perfume qs qs water ad 100 ad 100 Anti-Wrinkle Cream (Examples 3-4) 3 4 INCI name Wt .-% Wt .-% glyceryl stearate 2.00 3.00 Behenylalcohol 2.00 - glyceryl stearate - 2.00 C12-15 alkyl benzoates 3.00 3.00 Caprylic / capric 5.00 5.00 cetyl alcohol 2.00 2.00 cyclomethicone - 2.00 dicaprylyl 3.00 - dimethicone - 1.00 glycerin 6.00 8.00 methylparaben 0.10 0.20 phenoxyethanol 0.40 0.60 hexanediol 0.40 - Carbomer 0.10 0.20 Carbomer 0.30 - xanthan gum - 0.15 gossypetin 0.10 - Gossypine - 1.00 butylmethoxydibenzoylmethane - 2.00 Ethylhexylmethoxycinnamate - 2.00 octocrylene - 3.00 NaOH qs qs Perfume qs qs water ad 100 ad 100

QUOTES INCLUDE IN THE DESCRIPTION

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

Cited patent literature

• US 4144325 [0023]
• US 424861 [0023]

Cited non-patent literature

• J. Cosm. Science 10, 53 (1988) [0016]
• "Skin Diseases Associated with Oxidative Injury" in "Oxidative Stress in Dermatology", p. 323 et seq. (Marcel Decker Inc., New York, Basel, Hong Kong, publisher: Jürgen Fuchs, Frankfurt, and Lester Packer, Berkeley, California) [0021]

Claims (3)

 Use of gossypetin and / or gossypin in cosmetic or dermatological 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. Use according to Claim 1, characterized in that the preparations contain from 0.0001 to 5% by weight, in particular from 0.001 to 1% by weight, very particularly from 0.005 to 0.5% by weight, of gossypetin and / or gossypin, based on the total weight of the preparation. Use according to claim 1, characterized in that the following aging processes or conditions of the skin are treated or prevented: - deficient or hypoactive skin conditions or deficient or hypoactive states of skin appendages - phenomena of premature aging of the skin (eg wrinkles, age spots, telangiectasias) and / or the skin appendages, - environmental (smoking, smog, reactive oxygen species, free radicals) and in particular light-induced negative changes in the skin and the appendages. - photodamaged skin damage - pigmentation disorders, - itching, - dry skin conditions and horny layer barrier disorders, - hair loss