WO2016034400A1

WO2016034400A1 - Use of gossypetin and/or gossypin against skin aging

Info

Publication number: WO2016034400A1
Application number: PCT/EP2015/068922
Authority: WO
Inventors: Marc Winnefeld; Sabine HAGEMANN; Jörn SÖHLE; Elke GRÖNNIGER; Torsten Schläger; Katrin Schmidt
Original assignee: Beiersdorf Ag
Priority date: 2014-09-02
Filing date: 2015-08-18
Publication date: 2016-03-10
Also published as: DE102014217490A1

Abstract

The invention relates to the use of gossypetin and/or gossypin in cosmetic or dermatological preparations for treating and preventing symptoms of intrinsic and/or extrinsic skin aging, and for treating and preventing the damaging effects of ultraviolet radiation on the skin.

Description

Beiersdorf Aktiengesellschaft

Hamburg

description

Use of Gossypetin and / or Gossypin against Skin Aging

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.

Chronic skin aging is e.g. caused by endogenous, genetically determined factors. In epidermis and dermis, age-related e. on the following structural damage and dysfunctions, which may also fall under the term "senile xerosis": a) dryness, roughness and formation of dryness lines,

b) itching and

c) diminished fatty tissue suppression through sebaceous glands (eg after washing). 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 associated with chronological aging: d) Visible vascular dilations (telangiectasias, cuperosis);

e) slackness and formation of wrinkles;

f) local hyper, hypo and false pigmentation (e.g., age spots) and

g) increased susceptibility to mechanical stress (e.g., 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 skin changes, such as skin aging, in particular the 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 having a wavelength smaller than 290 nm (the so-called UVC region) 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 region, 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-benzylidene camphor, 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 the 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 the 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 radical photoproducts, which form in the skin itself, can also be used because of their high reactivity. did uncontrolled subsequent reactions to the day. 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 article "Skin Diseases Associated with Oxidative Injury" in "Oxidative Stress in Dermatology", p. 323 et seq. (Marcel Decker Inc., New York, Basel, Hong Kong, publishers: Jürgen Fuchs, Frankfurt, and Lester Packer, Berkeley, California), oxidative damage to the skin and its nearer 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. For example, it has already been proposed in US Pat. Nos. 4,144,325 and 4,248,861, as well as numerous other documents, to use vitamin E, a substance with known antioxidant activity in sunscreen formulations, but the effect achieved remains far below the hoped-for effect.

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.

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

deficient or hypoactive skin conditions or deficient or hypoactive states of cutaneous structures

of premature aging of the skin (e.g., wrinkles, age spots, telangiectasias) and / or cutaneous 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. However, 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 also serves in a surprising manner

for the stimulation of collagen, hyaluronic acid, elastin synthesis

for stimulating 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 the pre- and post-treatment of 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 (eg 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.

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 acid, but preferably castor oil; Fats, waxes and other natural and synthetic fats, preferably esters of fatty acids with lower C-number alcohols, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids of low C number 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 advantageously be 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 advantageously be selected from the group of branched and unsaturated branched 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 having a chain length of 8 to 24, in particular 12 - 18 carbon atoms. The fatty acid triglycerides can be selected, for example, advantageously from the group of synthetic, semi-synthetic 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 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 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, eg Ethanol, isopropanol, 1, 2-propanediol, glycerol and in particular one or more thickening agents, which or which can be advantageously selected from the group of silica, aluminum silicates, polysaccharides or their derivatives, e.g. Hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageously from the group of polyacrylates, preferably a polyacrylate from the group of the so-called carbopols, for example carbopols of types 980, 981, 1382, 2984, 5984, in each case 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.

Usual base materials which are suitable for use as cosmetic sticks in the context of the present invention are liquid oils (eg paraffin oils, castor oil, isopropyl myristate), semi-solid constituents (eg petrolatum, lanolin), solid constituents (eg bees). wax, 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 weight% weight%

Stearic acid 3.00 2.00

Glyceryl stearate 1, 00 1, 00

C12-15 alkyl benzoates 5.00 5.00

Caprylic acid / capric acid triglycerides 2.50 2.50

Cetyl alcohol - 2.00

Stearyl alcohol 2.00 2.00

Cyclomethicone 1, 00 1, 00

Dicaprylyl carbonate 2.00 2.00

Dimethicone 1, 00 1, 00

Glycerine 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 q.s. q.s.

Perfume q.s. q.s.

Water ad 100 ad 100

Anti-Wrinkle Cream (Examples 3

3 4

INCI name weight% weight%

Glyceryl stearate citrate 2.00 3.00

Behenyl alcohol 2.00

Glyceryl stearate 2.00

C12-15 alkyl benzoates 3.00 3.00

Caprylic acid / capric triglycerides 5,00 5,00

Cetyl alcohol 2.00 2.00

Cyclomethicone - 2.00

Dicaprylyl carbonate 3.00

Dimethicone - 1.00

Glycerin 6.00 8.00

Methyl paraben 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

Ethylhexyl methoxycinnamate - 2.00

Octocrylene - 3.00

NaOH q.s. q.s.

Perfume q.s. q.s.

Water ad 100 ad 100

Claims

claims

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

- premature aging of the skin (e.g., wrinkles, age spots, telangiectasias) and / or cutaneous appendages,

- environmental factors (smoking, smog, reactive oxygen species, free radicals) and in particular light-induced negative changes in the skin and the appendages.

- light-induced skin damage

- pigmentation disorders,

- itching,

dry skin conditions and horny layer barrier disorders,

- Hair loss