DE102009048976A1 - Cosmetic or dermatological preparation, useful to protect skin against UV radiation, and as sunscreen preparation, comprises a combination of 4-n-butylresorcinol and stearic acid esters e.g. glyceryl stearate and glyceryl stearate citrate - Google Patents

Abstract

Cosmetic or dermatological preparation comprises a combination of 4-n-butylresorcinol and one or more stearic acid esters.

Description

The present invention relates to cosmetic or dermatological preparations with combinations of 4-n-butylresorcinol and one or more stearic acid esters.

Responsible for the pigmentation of the skin are the melanocytes, which are found in the lowest layer of the epidermis, the stratum basale, in addition to the basal cells - depending on the skin type either isolated or more or less frequently occurring - pigment-forming cells.

Melanocytes contain as characteristic cell organelles melanosomes, in which the melanin is formed. Among other things, upon excitation by UV radiation melanin is increasingly formed. This is transported via the living layers of the epidermis (keratinocytes) ultimately in the horny layer (corneocytes) and causes a more or less pronounced brownish to brown-black skin color.

Melanin is formed as the final stage of an oxidative process in which tyrosine is converted with the participation of the enzyme tyrosinase via several intermediates to the brown to brown-black eumelanins (DHICA and DHI melanin) or with the participation of sulfur-containing compounds to the reddish phaeomelanin. DHICA and DHI melanin are produced via the common intermediates dopaquinone and dopachrome. The latter is reacted, sometimes with the participation of other enzymes, either in indole-5,6-quinone carboxylic acid or in indole-5,6-quinone, resulting in the two mentioned eumelanins.

The development of phaeomelanin occurs inter alia via the intermediates dopaquinone and cysteinyldopa. The expression of the melanin-synthesizing enzymes is controlled by a specific transcription factor (microphthalmia-associated transcription factor, MITF). In addition to the described enzymatic processes of melanin synthesis, further proteins are important for melanogenesis in the melanosomes. An important role here seems to be the so-called p-protein, the exact function is still unclear.

In addition to the process of melanin synthesis in the melanocytes described above, in the pigmentation of the skin and the transfer of melanosomes, their retention in the epidermis and their degradation and degradation of melanin is of crucial importance. It has been shown that the transport of melanosomes from the melanocytes into the keratinocytes, the PAR-2 receptor is significant ( Seiberg, M., et al., 2000, J. Cell. Sci., 113: 3093-101 ).

Furthermore, the size and shape of the melanosomes influence their light-scattering properties and thus the color appearance of the skin. For example, in black Africans, large spheroidal, isolated melanosomes are increasingly found, whereas in Caucasians, smaller, grouped melanosomes are found.

Problems with hyperpigmentation of the skin have many causes or are accompanying symptoms of many biological processes, eg. As UV radiation (eg freckles, ephelides), genetic disposition, Fehlpigmentierung the skin in wound healing or scarring (post-inflammatory hyperpigmentation) or skin aging (eg Lentigines seniles).

After inflammatory reactions, the pigmentation system of the skin reacts with partially opposite reactions. Both postinflammatory hyper- and hypopigmentation can occur. Postinflammatory Hypomelanosen occur u. a. often associated with atopy, lupus erythematosus and psoriasis. The different reaction forms of the pigmentation system of the human skin as a result of inflammatory phenomena are understood only very incompletely.

Problems with postinflammatory hyperpigmentation often occur in darker skin types. The problem of pseudofolliculitis barbae, which is associated with or results in cosmetically undesirable pigmentation of the pigmentation, is known, in particular for male colored individuals. Also forms of melasma, which in particular at. Women of Asian affiliation appear in the face and décolleté area, as well as various forms of irregular pigmentation of the skin are counted among the postinflammatory hyperpigmentations. In addition, dark circles are also considered to be a form of postinflammatory hyperpigmentation, with the underlying inflammation usually subclinical.

In many cases, such postinflammatory Fehlpigmentierung by the action of sunlight (UV light) is further enhanced, without causing a UV-induced inflammation (sunburn).

Active ingredients and preparations are known which counteract skin pigmentation. In practical use are essentially preparations based on hydroquinone, but on the one hand only after several weeks of application show their effect, the excessively long use on the other hand is of concern for toxicological reasons. By Albert Kligman et al. a so-called triformula was developed, which represents a combination of 0.1% tretinoin, 5.0% hydroquinone, 0.1% dexamethasone ( A. Kligman, 1975, Arch. Dermatol., 111: 40-48 ). However, this formulation is also very controversial because of possible irreversible changes in the pigmentation system of the skin.

In addition, peel-off methods (chemical and mechanical "peelings") are used, which, however, often lead to inflammatory reactions and can even lead to stronger rather than reduced pigmentation due to postinflammatory hyperpigmentation. All these common methods, which are also used to treat postinflammatory hypergigmentation, are characterized by significant side effects.

The aim of the invention below was therefore to remedy the disadvantageous state of the art.

Common cosmetic dosage forms are emulsions. This is generally understood to mean a heterogeneous system consisting of two liquids which are not miscible or have only limited miscibility, which are usually referred to as phases. One is in the form of droplets (dispere or inner phase), while the other liquid forms a continuous (coherent or inner phase). Rarer forms of administration are multiple emulsions, ie those which in turn contain droplets of a further dispersed phase in the droplets of the dispersed (or discontinuous) phase, eg. As W / O / W emulsions and O / W / O emulsions.

Recent findings have recently led to a better understanding of practice-relevant cosmetic emulsions. It is assumed that the emulsifier mixtures used in excess form lamellar liquid-crystalline phases or crystalline gel phases. In gel network theory, the stability and physicochemical properties of such emulsions are attributed to the formation of viscoelastic gel nets.

Cosmetic preparations with 4-n-butylresorcinol are known, for example from EP 1 490 017 ,

4-n-butylresorcinol is also called rucinol or lucinol. It inhibits melanin production by inhibiting the enzyme necessary for melanin synthesis (melanogenesis), tyrosinase. It inhibits first the production of melanin, then the production of the black. Melanins, which is responsible for the intense coloration of the pigment spots, blocked.

Although the use of 4-n-butylresorcinol would undoubtedly be dispersible cosmetically, cosmetic preparations containing 4-n-butylresorcinol are difficult to stabilize because it is sensitive to oxidation. This is manifested by various phenomena, including the fact that preparations with 4-n-butylresorcinol quickly turn brownish.

It was therefore an object of the present invention to remedy this situation.

It has been surprising and unforeseeable for a person skilled in the art that state-of-the-art remedies are eliminated by cosmetic or dermatological preparations with combinations of 4-n-butylresorcinol and one or more stearic acid esters.

gekennzeichnet.4-n-butylresorcinol, CAS [18979-61-8], is by chemical structure

characterized.

Cosmetic or dermatological preparations according to the invention preferably contain 0.001-10% by weight, particularly preferably 0.01-1% by weight, of 4-n-butylresorcinol, based on the total composition of the preparations.

A particularly preferred composition within the meaning of the present invention is embodied by preparations containing 0.001-10% by weight, particularly preferably 0.05-5% by weight, very particularly preferably 0.1-3% by weight of one or more several stearic acid esters.

Preferably, the stearic ester or esters are selected from the group of glyceryl stearate, glyceryl stearate citrate, sodium stearoyl glutamate and polysorbate 60.

For use, the cosmetic and dermatological preparations are applied according to the invention in the usual manner for cosmetics on the skin and / or hair in sufficient quantity.

Particularly preferred are those cosmetic and dermatological preparations which are in the form of a sunscreen. Advantageously, these may additionally comprise at least one further UVA filter and / or at least one further UVB filter and / or at least one inorganic pigment, preferably an inorganic micropigment.

The cosmetic and dermatological preparations according to the invention may contain cosmetic adjuvants, such as are commonly used in such preparations, for. Preservatives, bactericides, perfumes, foaming inhibitors, dyes, pigments having a coloring effect, thickeners, moisturizing and / or moisturizing substances, fats, oils, waxes or other common ingredients of a cosmetic or dermatological formulation such as alcohols, Polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

An additional level of conventional antioxidants is generally preferred. According to the invention, all antioxidants which are suitable or customary for cosmetic and / or dermatological applications can be used as favorable antioxidants.

The amount of the aforementioned antioxidants (one or more compounds) in the preparations is preferably 0.001 to 30 wt .-%, particularly preferably 0.05-20 wt .-%, in particular 1-10 wt .-%, based on the total weight of Preparation.

• – 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 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.

• – 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.
• – Erfindungsgemäß besonders bevorzugte Lipidkomponenten sind Isopropylstearat, Octylisostearat, Isopropyl stearat, Isopropyl isostearat, Ethylhexyl stearat, Isostearyl isostearat.

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 or as oil body:

• - water or aqueous solutions
• - Oils, such as triglycerides of capric or caprylic, 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 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.
• Lipid components which are particularly preferred according to the invention are isopropyl stearate, octyl isostearate, isopropyl stearate, isopropyl isostearate, ethylhexyl stearate, isostearyl isostearate.

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

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.

Of course, those skilled in the art will recognize that there are inherently nontoxic propellants which would be useful in the practice of the present invention in the form of aerosol preparations, but which should be avoided due to adverse environmental effects or other attendant circumstances, especially fluorocarbons and chlorofluorocarbons (US Pat. CFC).

Cosmetic preparations according to the present invention may also be present as gels, in addition to an effective content of the active ingredient according to the invention and solvents commonly used for this, preferably water, or organic thickening agents, for. Gum arabic, xanthan gum, sodium alginate, cellulose derivatives, preferably methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose or inorganic thickening agents, e.g. For example, aluminum silicates such as bentonites, or a mixture of polyethylene glycol and polyethylene glycol stearate or distearate. The thickener is in the gel z. B. in an amount between 0.1 and 30 wt .-%, preferably between 0.5 and 15 wt .-%.

It is advantageous according to the invention to use, in addition to the combinations according to the invention, further oil-soluble UVA filters and / or UVB filters in the lipid phase and / or further water-soluble UVA filters and / or UVB filters in the aqueous phase.

Advantageously, the sunscreen formulations according to the invention may contain other substances that absorb UV radiation in the UVB range, wherein the total amount of the filter substances z. B. 0.1 wt .-% to 30 wt .-%, preferably 0.5 to 10 wt .-%, in particular 1 to 6 wt .-%, based on the total weight of the preparations, to cosmetic preparations available which protect the skin from the entire range of ultraviolet radiation. They can also serve as sunscreen.

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.

Production instruction:

• 1. Add the emulsifier (1%) to 95.7% water → to dissolve, warm to 60 ° C
• 2. Addition of 0.3% 4-butyl-resorcinol in 3% butylene glycol → to release, warm to 40 ° C
• 3. Addition of the active ingredient solution to the emulsifier solution at 60.degree → stir cold

Approach overview: approaches Target amount (200 g batch) Actual amount (200 g batch) manufacturing Approach A - Glyceryl Stearate Citrate Active ingredient solution: 0.3% 4-butyl-resorcinol 0.6 g 0.61 g 4-butyl-resorcinol dissolved in butylene glycol at 40 ° C; 3% butylene glycol 6.0 g 6.07 g Emulsifier system: 1% glyceryl stearate citrate 2.0 g 2.02 g Glyceryl Stearate Citrate mixed with water and heated to 60 ° C. Then added warm drug solution; 95.7% water 191.4 g 192.31 g Batch B - stearic acid Active ingredient solution: 0.3% 4-butyl-resorcinol 0.6 g 0.60 g 4-butyl-resorcinol dissolved in butylene glycol at 40 ° C; 3% butylene glycol 6.0 g 6.01 g Emulsifier system: 1% stearic acid 2.0 g 2.02 g Stearic acid mixed with water and heated to 60 ° C. Then added warm drug solution; 95.7% water 191.4 g 192.12 g Batch C - polysorbate 60 Active ingredient solution: 0.3% 4-butyl-resorcinol 0.6 g 0.61 g 4-butyl-resorcinol dissolved in Natan at 40 ° C 3% butylene glycol 6.0 g 6.05 g Emulsifier system: 1% polysorbate 60 2.0 g 2.09 g Polysorbate 60 mixed with water and heated to 60 ° C. Then added warm drug solution; 95.7% water 191.4 g 192.02 g Result: Approach A: Glyceryl stearate citrate; pH = 5.09 Light: Clear, yellowish solution with sediment !; RT, 640, Sch-Test: No change; milky solution Approach B: stearic acid; pH = 6.72 Light, RT, 640, Sch-Test: Continuous yellowish discoloration + precipitations Approach C: Polysorbate 60; pH = 5.2 Light, RT, B40, Sch-Test: No changes, minimally discolored by light Light: light pattern RT: room temperature B40: Incubator (40 ° C) Sch test: Rocking test (+ 6 ° C <-> - 10 ° C) example 1 Wt .-% glyceryl stearate 2.00 behenyl 1.20 C12-15 alkyl benzoates 2.50 Caprylic / capric 2.50 Carbomer 0.10 cetyl alcohol 2.00 cyclomethicone 2.15 Dicaprylyfcarbonat 2.50 dimethicone 0.35 glycerin 8.60 methylparaben 0.20 4-butyl-resorcinol 0.30 phenoxyethanol 0.40 Propylparaben 0.10 water Ad 100 example 2 3 INCI name Wt .-% Wt .-% PEG-40 stearate 1.00 1.00 Caprylic / Capric Triglycerides 2.50 2.50 octyldodecanol 2.50 2.50 Cetearyl Alcohol 3.00 3.00 Polysorbate 60 2.00 3.00 glycerin 7.00 5.00 C12-15 alkyl benzoates 2.50 2.50 Dimethicone 0.25 0.35 Cyclomethicone 2.00 2.00 phenoxyethanol 0.20 0.30 Propylparaben 0.10 0.05 methylparaben 0.20 0.20 Trisodium EDTA + water 1.00 1.00 4-butylresorcinol 0.50 0.30 Diethylhexyl Syringylidenemalonate + Caprylic / Capric Triglyceride 0.10 0.10 Sodium Metabisulfite 0.15 0.15 Xanthan gum 0.10 0.10 Sodium polyacrylates 0.30 0.30 Distarch phosphate - 0.10 2-ethylhexyl-2-cyano-3-diphenylacrylate 1.0 - Phenylbenzimidazole sulfonic acid 1.0 - Bis-Ethylhexyloxyphenol Methoxyphenyl Triazines 1.0 - water Ad 100 Ad 100 example 4 5 6 INCI name Wt .-% Wt .-% Wt .-% Cetearyl Alcohol + PEG-40 Castor Oil + Sodium Cetearyl Sulfate 3 3 3 Cetearyl Alcohol - 0.5 - Glyceryl Stearate SE 0.50 0.25 0.50 Cyclomethicone 3 4 2 ethanol 2 3 2 Polysorbate 60 1.5 2 1.0 glycerin 5 7.5 5 Cyclomethicone + dimethiconol 2 1 4 Tapioca starch + water 1 2 1 Distarch phosphate 1 - 1 4-butylresorcinol 0.5 0.2 0.3 Diethylhexyl Syringylidenmalonate + Caprylic / Capric Triglyceride 0.1 0.1 0.1 methylparaben 0.3 0.2 0.3 Propylparaben 0.1 0.1 0.1 phenoxyethanol 0.2 0.3 0.2 ethylhexyl triazone 1 - - Phenylbenzimidazole sulfonic acid 1 - - Bis-Ethylhexyloxyphenol Methoxyphenyl Triazines - - 1 Butyl methoxydibenzoylmethane - - 1 Trisodium EDTA + water 1 1 1 Sodium Metabisulfite 0.15 0.15 0.15 Xanthan gum 0.3 0.15 0.3 Sodium polyacrylate - 0.25 - Perfume qs qs qs water Ad 100 ad 100 Ad 100 Note: Cetearyl Alcohol + PEG-40 Castor Oil + Sodium Cetearyl Sulfate - used was the Emulgade F ^™ blend from Cognis. example 7 8th 9 INCI name Wt .-% Wt .-% Wt .-% Glyceryl stearate citrate - - 2.00 PEG-40 stearate 1.00 1.00 Glyceryl stearate 2.60 2.60 - Dicaprylyl carbonate 2.50 2.50 2.50 Caprylic / Capric triglyceride 2.50 2.50 2.50 dimethicone 0.30 0.30 0.30 cyclomethicone 2.00 2.00 2.00 C12-15 alkyl benzoates 2.50 2.50 2.50 Behenyl alcohol - - 1.20 Cetearyl alcohol 3.00 3.00 - Cetyl alcohol - - 2.00 phenoxyethanol 0.40 0.40 0.40 methylparaben 0.20 0.20 0.20 Propylparaben 0.10 0.10 0.10 glycerin 7.00 5.00 7.00 4-butylresorcinol 0.30 0.30 0.20 Sodium Metabisulfite 0.15 0.15 0.15 Diethylhexyl Syringylidenmalonate + Caprylic / Capric Triglyceride - 0.10 - Xanthan gum - 0.15 - Sodium polyacrylate 0.20 - 0.20 Carbomer 0.10 0.20 0.10 Sodium hydroxide qs qs qs water ad 100 ad 100 ad 100 example 10 11 12 INCI name Wt .-% Wt .-% Wt .-% Sucrose polystearate + hydrogenated polyisobutene 1.00 2.00 3.00 Natriumstearoylglutamat 0.20 0.30 0.50 C12-15 alkyl benzoate 1.50 - 2.50 cetyl alcohol 0.50 - 1.00 cetearyl - - 2 cyclomethicone 7.00 5.00 2.00 dimethicone 3.00 2.50 0.50 glycerin 7.50 5.00 3.00 isopropyl 1.00 2.00 2.00 Caprylic / Capric Triglycerides - - 2.00 Dicaprylyl carbonates - - 2.00 octyldodecanol - - 1.00 Paraffin Liquidum 3.00 1.00 - methylparaben 0.10 0.10 0.20 Propylparaben 0.10 0.10 0.05 phenoxyethanol 0.20 0.50 0.30 4-butylresorcinol 0.10 0.05 0.05 ethylhexylmethoxycinnamate 2.00 3.00 1.00 butylmethoxydibenzoylmethane 2.00 1.00 1.00 Bis-Ethylhexyloxyphenol Methoxyphenyl Triazines 1.00 1.00 2.00 2-ethylhexyl-2-cyano-3-diphenylacrylate 1.00 - - Phenylbenzimidazole sulfonic acid - 1.00 1.00 Ammonium acryloyldimethyltaurate / VP copolymer 0.10 0.15 - Sodium polyacrylates - 0.10 0.20 Xanthan gum 0.10 - - Acrylates / C10-30 alkyl acrylate crosspolymer 0.25 - 0.10 Carbomer - - 0.10 Perfume qs qs qs sodium hydroxide qs qs qs water ad 100 ad 100 ad 100 Note: sucrose polystearate + hydrogenated polyisobutene - was used the mixture Emulgade Sucro ^™ Cognis

QUOTES INCLUDE IN THE DESCRIPTION

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Cited patent literature

• EP 1490017 [0017]

Cited non-patent literature

• Seiberg, M., et al., 2000, J. Cell. Sci., 113: 3093-101 [0006]
• A. Kligman, 1975, Arch. Dermatol., 111: 40-48 [0012]

Claims (5)

Cosmetic or dermatological preparations with combinations of 4-n-butylresorcinol and one or more stearic acid esters. Preparations according to Claim 1, characterized in that they are in the form of emulsions. A preparation according to claim 1 or 2, characterized in that the preparations contain 0.001-10% by weight, particularly preferably 0.01-1% by weight, of 4-n-butylresorcinol, based on the total composition of the preparations. A preparation according to any one of the preceding claims, characterized in that the preparations comprise 0.001-10% by weight, more preferably 0.05-5% by weight, most preferably 0.1-3% by weight of one or more stearic acid esters contained, based on the total composition of the preparations. Composition according to any one of the preceding claims, characterized in that the stearic ester or esters are or are selected from the group consisting of glyceryl distearate, glyceryl stearate citrate, sodium stearoyl glutamate and polysorbate 60.