DE102006047154A1 - Cosmetic or dermatological composition comprises 2-isopropyl-5-methylcyclohexylcarbonyl-D-alanine ethyl ester and an antiinflammatory agent - Google Patents

Abstract

Cosmetic or dermatological composition comprises 2-isopropyl-5-methylcyclohexylcarbonyl-D-alanine ethyl ester (I) and an antiinflammatory agent. ACTIVITY : Dermatological; Antiinflammatory; Antiallergic; Immunosuppressive; Vulnerary. No biological data given. MECHANISM OF ACTION : None given.

Description

The The present invention relates to cosmetic or dermatological Preparations containing 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester and one or more anti-inflammatory drugs.

The The present invention relates in a very particular embodiment Cosmetic and dermatological preparations with long-lasting cooling Effect, in particular skin care cosmetic and dermatological Preparations.

The The present invention relates in a very particular embodiment 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.

commitment from so-called "cooling Agents "with the heat receptors the skin interact and thus a feeling of cold trigger, without a measurable one physical cooling to generate. Therefor Menthol and various menthol derivatives (Frescolate, Physcool, Questice L, etc.). In particular, high ethanol contents menthol and its derivatives are, in addition to the irritative potential, especially because of their distinct inherent odor for numerous Uses from olfactory viewpoint not suitable. Often In addition, such substances simultaneously cause one Circulation increase, on the contrary causes a feeling of warmth.

task The object of the present invention was to overcome the disadvantages of the prior art Technique remedy and active ingredients and preparations, such agents containing, for cosmetic and dermatological treatment and / or Prophylaxis erythematous, inflammatory, allergic or autoimmune-reactive phenomena, in particular Dermatoses, but also the appearance of "stinging" available put.

Further should such agents or preparations, such agents containing, available be placed, which for immune stimulation of the skin, while beneficial also for immune stimulation in the sense of promoting wound healing Effect, can be used.

Of the Term "inflammation" is a relative broad and old term. Even before the turn of the century Aulus led Celsus four of the five Cardinal sign of inflammation a: rubor, tumor, calor and dolor (redness, swelling, heat and Pain). In the 2nd century Galen of Pergamon defined the 5th Character functio laesa (restricted Function). Total includes the inflammatory research 2000 years, of which 200 years at the cellular level and 20 years up molecular level. It became increasingly obvious that the term inconsistent is.

inflammatory Diseases are characterized by infiltrates of inflammatory cells however, they can be composed very differently. Psoriasis, an inflammatory Dermal insult, is e.g. characterized by an infiltrate of oligoclonal T cells and polymorphonuclear granulocytes in sharply circumscribed inflammatory Plaques. The involved skin of atopic eczema, however, is characterized by infiltrating T-cells against environmental antigens and eosinophilic granulocytes. As diverse as the inflammatory Manifestations are also the therapies with anti-inflammatory Substances.

under no circumstances It can be assumed that one substance is inflammatory in one Disease has a very good effect also with other inflammations will work in the same way. That's why intensive research is being done in this field, many of these mostly chronic diseases are not satisfactorily treatable. The next is one corticosteroids, but because of the partial effect Serious side effects come for a continuous and longer Application out of the question. For Cosmetic applications are even corticosteroids for this reason completely forbidden, here other substances must be used.

Skin-soothing cosmetics are used in acute skin irritations, these are from the top delineate described (chronic) inflammations. Causes of irritation can be eg physical stimuli such as UV radiation or shaving. In particular, in the early stage and at low stimulus level, there is no infiltrate of inflammatory cells (T cells, macrophages, granulocytes, ...), but the affected skin cells (mainly keratinocytes and fibroblasts) produce themselves a wealth of pro-inflammatory mediators. These mediators activate the cells, induce defense and repair mechanisms and then attract inflammatory cells. The aim of the skin-soothing effect of cosmetics must therefore be to prevent the negative effects of irritation, without blocking the necessary repair mechanisms. The known anti-inflammatory substances, which are mainly to act on the infiltrating cells are therefore only partially useful as model substances.

Also these evils were true to remedy it.

In The literature, for example, ionic compounds, in particular Ammonium salts, as cooling Agents described. As a cooling Preparations are also widely used isopropanolic gels with camphor and menthol additive applied.

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

task So it was the present invention, nourishing cosmetic and to provide medical preparations that are not the disadvantages of the prior art, in particular those which, on the skin or mucous membranes applied, moisturizing and / or cooling effect.

The 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 are present in the preparations in a substantially anhydrous medium and / or shielded by a material barrier of an aqueous medium.

Even though this procedure basically can lead to cosmetically satisfactory preparations, however, these are Galenically extremely expensive manufacture.

It So was the task of the present invention, the evils of the State of the art remedy and cooling cosmetic or dermatological Preparations available to provide, which are easy to produce, no irritating effect on skin or mucous membranes exercise - for example unpleasant tingling or itching - as well as under normal use pleasant cooling donate.

Of the Use of skin moisturizer - like to be used multivalent Alcohols such as glycerin - is generally desirable. A disadvantage of preparations of the prior art, however, is that these - provided Polyol quantities are used, which in terms of skin moisturization show a certain effectiveness - a noticeable stickiness and spread poorly on the skin.

Around reduce the stickiness of polyol-containing O / W emulsions and a light skin feeling reachable (easily dispersible, hardly any residue, quickly absorbed), becomes common worked with very thin oils (ie with oils with a viscosity from 1 to 15 mPa.s), Furthermore, a very high spreading capacity (800 to 1200 mm 2/10 min).

It So it was an object of the invention to achieve good skin moisturization, without that cosmetic appearance of the preparations suffers.

Further An object of the present invention was to provide preparations which significantly improve the condition of the skin, in particular reduce the skin roughness.

task was, therefore, all these disadvantages of the prior art remedy to accomplish. In particular, should products with reduced stickiness or greasiness available be put. Products in the field of nourishing cosmetics, of decorative cosmetics and pharmacological galenics should equally freed from the disadvantages of the prior art become.

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

Further It was an object of the present invention to provide products with a preferably to provide a wide variety of applications. For example should be the basics for Forms of preparation such as cleansing emulsions, face and body care preparations, but also pronounced medical-pharmaceutical dosage forms be created, for example, preparations for acne and other skin conditions.

To be solved according to the invention these tasks by cosmetic or dermatological preparations containing 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester and one or more anti-inflammatory drugs.

Preparations according to the invention are characterized by excellent, pleasant cooling effect and elegant cosmetic Appearance. They are not unpleasantly sticky and stable against physical decomposition such as framing or framing their Ingredients. They are characterized by an extremely low irritation potential out.

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

Synthesis of 2-isopropyl-5-methyl-cyclohexanecarbonyl-D-alanine ethyl ester [(R) (syn: R (R) -2 - [((1R, 2S, 5R) -2-isopropyl-5-methyl-cyclohexanecarbonyl) -amino] -propionic acid may be made in accordance with the following rule:
1.0 g of D-alanine ethyl ester hydrochloride (obtained from Aldrich Chemical Co.) was dissolved in 28 ml of diethyl ether and 1 ml of double-distilled water and cooled to 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.

advantageous anti-inflammatory Active substances in the context of the present invention are, for example Licochalcone A, lignan, pentacyclic triterpenes (e.g., ursolic acid, glycyrrhetinic acid), witch hazel or flavonoids, isoflavonoids, chamomile extracts or bisabolol, Allantoin, calendula extracts and / or panthenol.

Licochalcone A, is characterized by the following structural formula:

It is in the form of aqueous extracts obtained from the root of the plant Glycyrrhiza inflata, which like in Europe, officinal licorice Glycyrrhiza glabra belongs to the genus Glycyrrhiza, which in turn belongs to the plant family the Fabaceae (pea plants) belongs. The drug Radix Glycyrrhizae inflatae, d. h., the root of the plant, is, for example, in the Far East Medicine, in use. The use of the drug as an anti-inflammatory is also known.

Prefers contain cosmetic or dermatological preparations according to the invention 0.001-10 wt .-%, particularly preferably 0.01-1 Wt .-%, based on one or more anti-inflammatory agents on the total composition of the preparations.

The Cosmetic or dermatological preparations according to the invention can be composed as usual and for the treatment, care and cleansing of the skin and / or hair and as a make-up product in decorative cosmetics.

she contain preferably 0.001% by weight to 10% by weight, preferably 0.05% by weight to 5 wt .-%, in particular 0.1-2.0 Wt .-%, based on the total weight of the preparations, of 2-isopropyl-5-methyl-cyclohexanecarbonyl-D-Alaninethylester.

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 present folic acid and / or derivatives thereof in encapsulated form, for example in collagen matrices and other customary encapsulating materials, for example as cellulose encapsulates, in gelatin, wax matrices or liposomally encapsulated. In particular wax matrices like those in the DE-OS 43 08 282 have been described, have turned out to be favorable.

It is possible, too and advantageous for the purposes of the present invention, folic acid and / or their derivatives in aqueous systems or to add surfactant preparations for cleansing the skin and hair.

The cosmetic according to the invention and dermatological preparations may be cosmetic adjuncts contain as they usually do used in such preparations, e.g. Preservatives, Bactericides, perfumes, Substances for preventing foaming, dyes, pigments, the one coloring Have thickening agents, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other usual ones Components of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

• – Mineralöle, Mineralwachse
• – Öle, wie Triglyceride der Caprin- oder der Caprylsäure, ferner natürliche Öle wie z.B. 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;
• – Alkylbenzoate;
• – Siliconöle wie Dimethylpolysiloxane, Diethylpolysiloxane, Diphenylpolysiloxane sowie Mischformen daraus.

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 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;
• - alkyl benzoates;
• - Silicone oils such as dimethylpolysiloxanes, diethylpolysiloxanes, diphenylpolysiloxanes and mixed forms thereof.

The oil phase of Emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected the group of esters from saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols of 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 of a chain length of 3 to 30 carbon atoms. Such ester oils can then chosen advantageous are 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 dipalmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyl dodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate as well as synthetic, semi-synthetic and natural mixtures of such esters, e.g. Jojoba oil.

The aqueous phase the preparations according to the invention contains optionally advantageous alcohols, diols or polyols lower 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 lower alcohols C number, e.g. Ethanol, isopropanol, 1,2-propanediol, glycerin as well in particular one or more thickening agents, which or which chosen favorably can be from the group silicon dioxide, aluminum silicates, polysaccharides or their derivatives, e.g. Hyaluronic acid, xanthan gum, hydroxypropyl methylcellulose, 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.

Especially Mixtures of the abovementioned solvents are used. For alcoholic solvents Water can be another ingredient.

Inventive emulsions are advantageous and contain e.g. the said fats, oils, waxes and other fat bodies, as well as water and an emulsifier, as usually for one such type of formulation is used.

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 a thickening agent, preferably in oily-alcoholic gels Silica or an aluminum silicate, in aqueous-alcoholic or alcoholic Gels is preferably a polyacrylate.

When Propellant for according to the invention aerosol containers sprayable Preparations are the usual known volatile, liquefied Propellants, for example hydrocarbons (propane, butane, isobutane) suitable, which are used alone or in mixture with each other can. Also, compressed air is advantageous to use.

Advantageous can preparations according to the invention Furthermore Contain substances that absorb UV radiation in the UVB range, the total amount of filter substances being e.g. 0.1% by weight to 30% by weight, preferably 0.5 to 10% by weight, in particular 1.0 to 6.0% by weight is, based on the total weight of the preparations to cosmetic Preparations available to put the hair or the skin in front of the entire area of the Protect ultraviolet radiation. You can also as a sunscreen for Hair or the skin serve.

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. example 1 Wt .-% vanishing cream glyceryl stearate 2.5 stearyl 2 PEG-40 Stearate 1 cetyl alcohol 2 shea butter 2 Fillers (SiO ₂ , nylon) 1 tapioca starch 1 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (Tinosorb S ^®) 2 Ethlyhexylmethoxycinnamat 2 phenoxyethanol 0.4 C _12-15 alkyl benzoate 3 p-Hydroxybenzoic acid alkyl ester (paraben) 0.4 Aristoflex AVC (ammonium polyacryldimethyltauride / vinylformamide copolymer) 0.2 Licochalcone A 0.05 2-isopropyl-5-ethyl-cyclohexanecarbonyl-D-alanine ethyl ester 0.5 glycerin 8th EDTA 0.2 Perfume 0.3 Sodium hydroxide solution (pH 7 adjusted) qs Water 100% ad 100 Example 2 Wt .-% Protective cream (day cream) glyceryl stearate 3 stearyl 2 PEG-40 Stearate 1 shea butter 2 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (Tinosorb S ^®) 2 Ethlyhexylmethoxycinnamat 5 phenoxyethanol 0.4 dimethicone 2 cyclomethicone 4 Titanium dioxide 0.5 Powder raw materials (tapioca starch, nylon) 3 tocopheryl acetate 1 retinyl palmitate 0.3 panthenol 2 carrageenan 0.1 polyacrylic acid 0.1 2-isopropyl-5-ethyl-cyclohexanecarbonyl-D-alanine ethyl ester 0.2 folic acid 0.05 glycerin 8th lignans 0.2 Perfume 0.3 Caustic soda (pH 6.5 adjusted) qs water ad 100 Example 3 Wt .-% O / W emulsion glyceryl stearate 2 cetyl alcohol 3 shea butter 3 butylhydroxytoluene 0.05 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (Tinosorb S ^®) 2 ethylhexyl triazone 2 squalane 2 cyclomethicone 5 dimethicone 2 lauroyllysine 2 carrageenan 0.15 Carbomer 0.1 creatine 0.2 licorice extract 0.03 glycerin 8th 2-isopropyl-5-ethyl-cyclohexanecarbonyl-D-alanine ethyl ester 0.2 Perfume 0.3 Caustic soda (pH 6.5 adjusted) qs water ad 100 Example 4 Wt .-% care cream Hydrogenated Coconut Glycerides (Hydrogenated Coco Glycerides) 2 stearyl 2 cetyl alcohol 2 cetearylglucoside 2 Ethlyhexylmethoxycinnamat 3 2,4-bis - {[4- (2-ethyl-hexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (Tinosorb S ^®) 2 butylhydroxytoluene 0.04 myristate 1 macadamia 0.5 shea butter 2 cyclomethicone 2 polyacrylic acid 0.1 creatine 0.4 Chamomile extract (bisabolol) 0.04 glycerin 9 EDTA 0.1 Perfume 0.3 tocopheryl acetate 0.5 2-isopropyl-5-ethyl-cyclohexanecarbonyl-D-alanine ethyl ester 0.5 methyl propanediol 2 Sodium hydroxide solution (pH 6.8) qs water ad 100 Example 5 Wt .-% O / W emulsion Caprylic / capric 3 sorbitan 1 stearyl 1 Polyglyceryl-3 methyl glucose distearate: 3 cyclomethicone 4 2,4-bis- [5-1 (dimethylpropyl) benzoxazol-2-yl- (4-phenyl) -imino] -6- (2-ethylhexyl) -imino-1,3,5-triazine (CAS No. 288254 -16-0) 1 Butyl methoxydibenzoylmethane 1 Ethlyhexylmethoxycinnamat 3 ethylhexyl triazone 1 dimethicone 2 C _12-15 alkyl benzoate 2 dicaprylyl 2 carrageenan 0.1 Crosslinked Alkyl Acrylate (Alkyl Acrylic Crosspolymer) 0.1 creatine 0.4 bisabolol 0.05 glycerin 8th EDTA 0.2 Licochalcone A 0.02 2-isopropyl-S-ethyl-cyclohexanecarbonyl-D-alanine ethyl ester 0.4 Citric acid, sodium salt (pH 6.5) qs water ad 100 Example 6 Wt .-% lotion Glyceryistearat 2.5 PEG-40 Stearate 1 cetyl alcohol 2.5 C _12-15 alkyl benzoate 2 Hydrogenated Coconut Glycerides (Hydrogenated Coco Glycerides) 2 octyldodecanol 2 cyclomethicone 2 beeswax 1 ethylhexylmethoxycinnamate 6 phenylbenzimidazolesulfonic 2 sodium ascorbyl 0.1 methyl propanediol 2 diazolidinyl 0.1 carrageenan 0.1 Carbomer 0.1 glycerin 7 panthenol EDTA 0.2 2-isopropyl-5-ethyl-cyclohexanecarbonyl-D-alanine ethyl ester 0.5 Sodium hydroxide solution (pH 6.8) qs water ad 100

Claims (4)

Cosmetic or dermatological preparations containing 2-isopropyl-5-methylcyclohexanecarbonyl-D-alanine ethyl ester and one or more anti-inflammatory Agents. Preparations according to Claim 1, characterized that this or the anti-inflammatory Active ingredients selected is or are from the group licochalcone A (licorice extract), lignan, or Isoflavonoids, flavonoids, bisabolol and panthenol. Preparations according to one of the preceding claims, characterized characterized in that they 0.001% by weight to 10% by weight, preferably 0.01% by weight to 1.0% by weight, in particular 0.05-0.5 Wt .-%, based on the total weight of the preparations, of 2-isopropyl-5-methyl-cyclohexanecarbonyl-D-Alaninethylester contain. Preparations according to one of the preceding claims, characterized characterized in that they 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, on a or more antioxidants.