WO2008040451A1

WO2008040451A1 - Cosmetic or dermatological compositions with a content of 2-isopropyl-5- methyl-cyclohexancarbonyl-d-alanine ethyl ester and one or more antioxidants

Info

Publication number: WO2008040451A1
Application number: PCT/EP2007/008185
Authority: WO
Inventors: Julia Eckert; Ludger Kolbe; Gitta Neufang
Original assignee: Beiersdorf Ag
Priority date: 2006-09-29
Filing date: 2007-09-20
Publication date: 2008-04-10
Also published as: DE102006047155A1

Abstract

The invention relates to cosmetic or dermatological compositions with a content of 2-isopropyl-5- methyl-cyclohexanecarbonyl-D-alanine ethyl ester and one or more antioxidants.

Description

Beiersdorf Aktiengesellschaft Hamburg

description

Cosmetic or dermatological preparations containing 2-isopropyl-5-methyl-cyclohexanecarbonyl-D-alanine ethyl ester and one or more antioxidants

The present invention relates to cosmetic or dermatological preparations containing 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester and one or more antioxidants.

The present invention relates, in a particular embodiment, to cosmetic or pharmaceutical preparations with a reduced tack feeling, processes for their preparation and the use of active ingredients for reducing the stickiness of cosmetic preparations.

In a very particular embodiment, the present invention relates to cosmetic and dermatological preparations with a long-lasting cooling effect, in particular skin-care cosmetic and dermatological preparations.

In a very particular embodiment, the present invention relates to cosmetic and dermatological preparations with reduced skin irritation.

The cooling effect of cosmetic preparations is based on two basic principles:

Use of components that volatilize after topical application gaseous and the required amount of energy, the so-called evaporation enthalpy, to a large part of the skin surface. Therefore, suitable liquid components are used in corresponding non-occlusive cosmetics. Ethanol has proved to be particularly suitable here, in addition formulations with a high water content likewise show a clear cooling effect. Use of so-called "cooling agents", which interact with the heat receptors of the skin and thus trigger a sensation of cold without generating a measurable physical cooling, in particular menthol and various menthol derivatives (Frescolate, Physcool, Questice L, etc.) In particular high ethanol contents as well as menthol and its derivatives are not suitable for numerous applications under olfactory aspects in addition to the irritative potential, in particular because of their distinct inherent odor Frequently enough, such substances also simultaneously increase the circulation, which on the contrary causes a feeling of warmth.

In the literature, for example, ionic compounds, in particular ammonium salts, are described as cooling agents. As cooling preparations are also widely used isopropanolic gels with camphor and menthol additive.

The use of these substances, especially on irritated skin, is in any case problematic. In addition, many of these compounds are poorly water-soluble. Their use is therefore limited to a few cosmetics and dermatics.

It was therefore an object of the present invention to provide nourishing cosmetic and medical preparations which do not have the disadvantages of the prior art, in particular those which, applied to the skin or mucous membranes, have a moisturizing and / or cooling action.

DE 43 12 656 describes the use of cosmetically or pharmaceutically acceptable substances with positive enthalpy of solution in cosmetic or medical topical preparations, characterized in that the substance or substances in the preparations are present in a largely anhydrous medium and / or by a material barrier of one be shielded aqueous medium.

Although this procedure can in principle lead to cosmetically satisfactory preparations, they are galenically extremely expensive to produce.

It was therefore the object of the present invention to remedy the evils of the prior art and cooling cosmetic or dermatological preparations for To provide, which are easy to produce, no irritant effect on the skin or mucous membranes - for example, unpleasant tingling or itching - and donate pleasant cooling when used as intended.

A further object of the present invention was to provide preparations which markedly improve the condition of the skin, in particular reduce skin roughness.

Although it is known, by adding certain substances, for example a few selected powder raw materials, in particular talcum, to reduce a sticky feeling or also a feeling of smear. Apart from the fact that this rarely succeeds completely, such an addition also changes the viscosity of the product in question and reduces its stability.

The task was therefore to remedy all these disadvantages of the prior art. In particular, products with reduced tackiness should be provided. Products in the field of nourishing cosmetics, decorative cosmetics and pharmacological galenics should likewise be freed from the described disadvantages of the prior art.

Furthermore, it was an object of the invention to develop cosmetic bases for cosmetic preparations, which are characterized by good skin compatibility.

Furthermore, an object of the present invention to provide products with the widest possible variety of applications available. For example, principles should be created for preparation forms such as cleansing emulsions, face and body care preparations, but also pronounced medical-pharmaceutical dosage forms, for example preparations for acne and other skin conditions.

These objects are achieved according to the invention by cosmetic or dermatological preparations containing Z-isopropyl-δ-methylcyclohexanecarbonyl-D-alanine ethyl ester and one or more antioxidants. Preparations according to the invention are distinguished by outstanding, pleasant cooling effect and elegant cosmetic appearance. They are not unpleasantly sticky and stable against physical decomposition, such as up or down frame of their components.

2-Isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester is characterized by the following structure:

The synthesis of 2-isopropyl-δ-methylcyclohexanecarbonyl-D-alanine ethyl ester [synonom: (R) -2 - [((1R, 2S ₎ 5R) -2-isopropyl-5-methylcyclohexanecarbonyl) -amino ] Propionic acid ethyl ester can be made according to the following instructions:

1, 0 g of D-alanine ethyl ester hydrochloride (from Aldrich Chemical Co received) 1 ml of double distilled water, diethyl ether and in 28 ml and cooled to 0 ⁰ C. A spatula tip of the catalyst diaminopyrimidine was added. 1, 62 ml of p-menthyl chloride was added dropwise, followed by 2 ml of triethylamine. Flakes of a no-mist precipitate formed in the mixture, which was stirred overnight at room temperature. The precipitate was dissolved in ethyl acetate, washed with double-distilled water and dried over sodium sulfate. The organic phase was evaporated under reduced pressure to give 2 g of the final product, which crystallized at room temperature. The expected molecular mass and structure were confirmed by mass spectrometer or NMR spectrum.

Advantageously, the antioxidants are selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocaninic acid) and derivatives thereof, peptides such as D, L-carnosine, D-carnosine, L-carnosine. Carnosine and its derivatives (eg anserine), carotenoids, carotenes (eg α-carotene, β-carotene, lycopene) and their derivatives derivatives, (eg dihydroliproic acid), unsaturated fatty acids and their derivatives (eg .gamma.-linolenic acid, linoleic acid, oleic acid), ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (eg ascorbyl palmitate , Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), vitamin A and derivatives (vitamin A palmitate) and flavonoids such as rutinic acid and its derivatives, α-glycosylrutin, catechins (epicatechin), isoflavonoids, ferulic acid , furfuryl furylidenglucitol, butylhydroxytoluene, mannose and derivatives thereof, zinc and derivatives thereof (for example ZnO ₁ ZnSO ₄₎ selenium and derivatives thereof (for example selenomethionine), stilbenes and derivatives thereof (for example stilbene oxide, trans-stilbene oxide) and the present invention suitable derivatives ( Salts, esters, ethers) of these active substances.

It is advantageous according to the invention if the preparations are characterized in that they contain 0.001% by weight to 10% by weight, preferably 0.05% by weight to 5% by weight, in particular 0.1-2, 0 wt .-%, based on the total weight of the preparations, of one or more antioxidants.

Advantageously, the antioxidants used in the invention are selected from the group of flavonoids and isoflavones.

The active substance (s) selected from the group of flavones, flavanones and flavonoids in the narrower sense are also subsumed in the context of the present invention under the generic term "flavonoids".

Flavone and its derivatives (often collectively called "flavones") are characterized by the following basic structure (substitution positions given):

Some of the more important flavones found in living nature are listed in the table below:

In nature, flavones usually occur in glycosidated form.

Flavonoids in the narrower sense are glycosides of flavones, flavanones whose backbone is characterized by the following structure:

3-hydroxyflavones (flavonols) whose backbone is characterized by the following structure:

and the aurones whose skeleton is characterized by the following structure:

According to the invention, the flavonoids are preferably selected from the group of substances of the generic structural formula

wherein Z ₁ - Z _{7 are} independently selected from the group H, OH, alkoxy and hydroxyalkoxy, wherein the alkoxy or hydroxyalkoxy groups can be branched and unbranched and 1-18 have C atoms, and wherein GIy is selected from the group of mono- and oligoglycoside radicals.

According to the invention, however, the flavonoids can also be chosen advantageously from the group of substances of the generic structural formula

wherein Z ₁ - Z _{6 are} independently selected from the group H, OH, alkoxy and hydroxyalkoxy, where the alkoxy or hydroxyalkoxy groups can be branched and unbranched and 1-18 have C atoms, and wherein GIy is selected from the group of mono- and oligoglycoside radicals.

Preferably, such structures can be selected from the group of substances of the generic structural formula

wherein GIy ₁ , GIy ₂ and GIy _{3 are} independently monoglycoside or. GIy ₂ or GIy ₃ can also individually or together represent hydrogen atom saturation.

Preferably, GIy ₁ , GIy ₂ and GIy _{3 are} independently selected from the group of hexosyl radicals, in particular the rhamnosyl radicals and glucosyl radicals. However, other hexosyl radicals, for example allosyl, altrosyl, galactosyl, gulosyl, idosyl, mannosyl and talosyl, may also be advantageous to use. It may also be advantageous according to the invention to use pentosyl radicals.

Advantageously, Z ₁ - Z _{5 are} independently selected from the group H, OH, methoxy, ethoxy and 2-hydroxyethoxy, and the flavone glycosides have the structure

The flavone glycosides according to the invention are particularly advantageous from the group which are represented by the following structure:

where Glyi, Gly ₂ and Gly ₃ independently represent monoglycoside radicals or. GIy ₂ or GIy ₃ can also individually or together represent hydrogen atom saturation.

It is particularly advantageous for the purposes of the present invention to choose the flavone glycoside (s) from the group α-glucosylrutin, α-glucosylmyricetin, α-glucosylisoquercitrin, α-glucosylisoquercetin and α-glucosylquercitrin.

A particularly advantageous flavonoid according to the invention is α-glucosylrutin. It is characterized by the following structure:

Another flavonoid which is particularly advantageous according to the invention is naringin (aurantiine, naringenin-7-rhamnoglucoside). It is characterized by the following structure:

Another particularly advantageous flavonoid according to the invention is hesperidin (3 ', 5,7-trihydroxy-4'-methoxyflavanone-7-rutinoside, hesperidoside, hesperetin-7-O-rutinoside). It is characterized by the following structure:

Another particularly advantageous flavonoid according to the invention is rutin (3, 3 ', 4', 5, 7-pentahydroxyfly of 3-rutinoside, quercetin-3-rutinoside, sophorin, birutane, rutabion, taurutin, phytomelin, melin). It is characterized by the following structure:

Another havonoid particularly advantageous according to the invention is roxerutin (3,5-dihydroxy-3 ', 4', 7-tris (2-hydroxyethoxy) flavone-3- (6-O- (6-deoxy-α-L -mannopyranosyl) -β-D-glucopyranoside)). It is characterized by the following structure:

Another particularly advantageous flavonoid according to the invention is monoxerutin (3,3 ', 4', 5-tetrahydroxy-7- (2-hydroxyethoxy) flavone-3- (6-O- (6-deoxy-α-L-mannopyranosyl) - β-D-glucopyranoside)). It is characterized by the following structure:

Another particularly advantageous flavonoid according to the invention is dihydrorobinetine (3,3 ', 4', 5 ', 7-pentahydroxyflavanone). It is characterized by the following structure:

Another flavonoid particularly advantageous according to the invention is taxifolin (3, 3 ', 4', 5,7-pentahydroxyflavanone). It is characterized by the following structure:

Another flavonoid particularly advantageous according to the invention is eriodictyol-7-glucoside (3 ', 4', 5,7-tetrahydroxyflavanone-7-glucoside). It is characterized by the following structure:

Another particularly advantageous flavonoid according to the invention is flavanomareϊn (3 ', 4', 7, δ-Tetrahydroxyfιavanon-7-glucoside). It is characterized by the following structure:

Another flavonoid which is particularly advantageous according to the invention is isoquercetin (3, 3 ', 4', 5, 7-pentahydroxyflavanone-3- (β-D-glucopyranoside), which has the following structure:

The flavonoid or flavonoids are advantageously according to the invention in cosmetic or dermatological preparations preferably to 0.001 wt .-% to 10 wt .-%, preferably to 0.05 wt .-% to 5 wt .-%, particularly preferably to 0.1 - , 0 wt .-%, based on the total weight of the preparations.

Isoflavones are flavonoids, sometimes referred to as isoflavonoids, a group of mostly yellowish plant dyes derived from isoflavone. The unsubstituted body, the actual isoflavone (3-phenylchromone, 3-phenyl-4H-1-benzopyran-4-one) occurs in clover species. Some more well-known isoflavones are daidzeen (4 ', 7-dihydroxy-isoflavone), as 7-O-glucoside daidzin in soybean meal; Genistein (4 ', 5,7-trihydroxy-isoflavone) from soybeans and red clover; Prunetin (4 ', 5-dihydroxy-7-methoxy-isoflavone) from the bark of plum trees; Biocharin A (5,7-dihydroxy-4'-methoxy-isoflavone) from chick peas, red clover and other clover species; Orobol (3 ', 4', 5,7-tetrahydroxy isoflavone); Santal (3 ', 4', 5-trihydroxy-7-methoxy-isoflavone) from sandalwood, redwood and other woods; Pratenseϊn (3 ', 5,7-trihydroxy-4'-methoxyiso- flavone) from fresh red or meadow clover. Some of these isoflavones found in clover varieties and legumes such as alfalfa have estrogenic effects on grazing animals and may lead to reproductive disorders in these animals.

The following are substitution schemes of some naturally occurring isoflavones:

Suitable isoflavones to be used according to the invention are preferably the isoflavones listed in the table above.

Of these, in turn, the genistein is preferred. Genistein, 5,7-dihydroxy-3- (4-hydroxyphenyl) -4H-1-benzopyran-4-one, 4 ', 5,7-trihydroxyisoflate, also called differenol A, prunetol and sophoricol, has the following structure :

Genistein is a secondary metabolite of plants (legumes, papilionoids, rosaceae), but has also been found in cultures of microorganisms (Actinomycetes, Aspergillus, Mycobacteria). Low estrogens and antibacterial effects have been described.

Cosmetic or dermatological preparations according to the invention preferably contain 0.001-10% by weight, particularly preferably 0.01-1% by weight, of one or more isoflavonoids, based on the total composition of the preparations.

According to the invention, the cosmetic or dermatological preparations may be composed as usual and used for the treatment, care and cleansing of the skin and / or the hair and as a make-up product in decorative cosmetics.

They preferably contain from 0.001% by weight to 10% by weight, preferably from 0.05% by weight to 5% by weight, in particular from 0.1% to 2.0% by weight, based on the total weight of the preparations, 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester.

Cosmetic and dermatological preparations according to the invention can be present in various forms. For example, they may contain a solution, an anhydrous preparation, an emulsion or microemulsion of the water-in-oil (W / O) type or of the oil-in-water (O / W) type, a multiple emulsion, for example water-type. in-oil-in-water (W / O / W), a gel, a solid stick, an ointment or even an aerosol. It is also advantageous in accordance with the invention to administer folic acid and / or its derivatives in encapsulated form, for example in collagen matrices and other customary encapsulating materials, for example as encapsulated encapsulations, in gelatin, wax matrices or liposomally encapsulated. In particular wax matrices as described in DE-OS 43 08 282, have been found to be favorable. The cosmetic and dermatological preparations according to the invention may comprise cosmetic adjuvants conventionally used in such preparations, for example preservatives, bactericides, perfumes, foaming inhibitors, colorants, pigments having a coloring effect, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other customary constituents of a cosmetic or dermatological formulation, such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

The lipid phase can advantageously be selected from the following substance group: mineral oils, mineral waxes

Oils such as triglycerides of capric or caprylic acid, further natural oils such as e.g. 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; benzoates;

Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.

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 also synthetic, semisynthetic and natural mixtures of such esters, eg jojoba oil. The aqueous phase of the preparations according to the invention optionally advantageously contains alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or -mob nobutyl ether, propylene glycol monomethyl, -monoethyl- or monobutyl ether , Diethylene glycol monomethyl or monoethyl ether and analogous products, furthermore low-C alcohols, for example ethanol, isopropanol, 1,2-propanediol, glycerol and, in particular, one or more thickeners, which may advantageously be selected from the group silicon dioxide, Aluminum silicates, polysaccharides or their derivatives, for example hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly advantageously from the group of the polyacrylates, preferably a polyacrylic acid from the group of the so-called carbopols, for example Carbopols of the types 980, 981, 1382, 2984 , 5984, each alone or in combination.

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

Emulsions of the invention are advantageous and contain e.g. the said fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as commonly used for such a type of formulation.

Gels according to the 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 aluminosilicate in oily-alcoholic gels, in aqueous-alcoholic or alcoholic gels, preferably a polyacrylate.

Suitable propellants for preparations which can be sprayed from aerosol containers according to the invention are the customary known highly volatile, liquefied propellants, for example hydrocarbons (propane, butane, isobutane), which can be used alone or mixed with one another. Also, compressed air is advantageous to use.

Advantageously, preparations according to the invention may also contain substances which absorb UV radiation in the UVB range, the total amount of the filter substances For example, 0.1 wt .-% to 30 wt .-%, preferably 0.5 to 10 wt .-%, in particular 1, 0 to 6.0 wt .-%, based on the total weight of the preparations to cosmetic preparations to provide the hair or the skin against the entire range of ultraviolet radiation. They can also serve as a sunscreen for hair or skin.

The following examples are intended to illustrate the present invention without limiting it. All amounts, proportions and percentages are, unless otherwise stated, percentages by weight, based on the weight and the total amount or on the total weight of the preparations.

Claims

claims

1. Cosmetic or dermatological preparations containing 2-isopropyl-5-methyl-cyclohexanecarbonyl-D-alanine ethyl ester and one or more antioxidants.

2. Preparations according to claim 1, characterized in that the one or more antioxidants is or are selected from the group of flavonoids (especially α-glycosylrutin), catechins (especially epicatechin), butylated hydroxytoluene, vitamin C or vitamin E.

3. Preparations according to one of the preceding claims, characterized in that it contains from 0.001% by weight to 10% by weight, preferably from 0.01% by weight to 1.0% by weight, in particular 0.05-0, 5% by weight, based on the total weight of the preparations, of 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester.

4. Preparations according to one of the preceding claims, characterized in that they 0.001 wt .-% to 10 wt .-%, preferably 0.05 wt .-% to 5 wt .-%, in particular 0.1 - 2.0 wt .-%, based on the total weight of the preparations, of one or more antioxidants.