DE4341000A1 - Use of L-arginine, L-ornithine or L-citrulline and topical preparations with these substances - Google Patents

Description

The present invention relates to the use of L-arginine, L-ornithine and / or L-citrulline and the Use of cosmetic and dermatological topical Preparations containing these active substances.

The epidermis is rich with nerves and Nerve end apparatus such as Father Pacini lamellar bodies, Merkel cell neurite complexes and free Nerve endings for pain, cold, heat sensation and itching equipped.

In people with sensitive, sensitive or vulnerable skin can therefore be a "stinging" (English "sting" hurt, burn, hurt) observed neurosensory phenomenon observed become. This "sensitive skin" is different basically of "dry skin" with thickened and hardened horny layers.  

Typical reactions of "stinging" in sensitive skin are redness, tightness and burning of the skin as well Itching.

Another neurosensory phenomenon is the Itching in atopic skin, as well as itching in skin diseases.

The object of the invention was therefore, active ingredients and topical preparations with such active ingredients To provide what neurosensory phenomena Prevent upper relief after occurrence or fast bring to a subside, so for prophylaxis and / or Treatment are suitable.

"Stinging" phenomena can be considered cosmetically too treating disorders are considered. Stronger Itching on the other hand, especially in atopy severe itching, can also be more severe dermatological disorder.

These tasks are solved by the use of one or more compounds selected from the Group of L-arginine, L-ornithine and L-citrulline or their salts, acid addition salts, esters or amides, optionally with the addition of folic acid or its Salts and / or one or more compounds, selected from the group of flavins, for prophylaxis and / or treatment of neurosensory phenomena.

They are preferably used for prophylaxis and / or treatment of neurosensory phenomena of the skin, in particular "stinging" or atopy (atopic dermatitis).

The invention is also the use cosmetic and dermatological topical Preparations containing the active compounds according to the invention  contain, for the prophylaxis and / or treatment of neurosensory phenomena.

It was not foreseeable for the expert that the Active ingredients of the invention and that cosmetic or dermatological preparations with effective levels of arginine, citrulline, ornithine, folic acid and flavins according to the invention is excellent for prophylaxis and treatment of neurosensory phenomena.

Preferred salts of L-arginine, L-ornithine and L-citrulline are water-soluble salts, e.g. For example, sodium, Potassium and ammonium salts. This also applies to the Acid addition salts. Suitable acid addition salts be with inorganic and organic acids receive. Preference is given to the hydrochlorides, sulfates, Acetates, caprylates or citrates.

Suitable esters of these compounds are, for. For example, those with short-chain and medium-chain alcohols be formed, preferably mono-alcohols, but especially methanol, ethanol or propanol. Preference is given to the ethyl esters.

Preferred amides are short and medium chain mono- and di-alkylamides.

Alkyls of the above substituents contain, for. B. up to 12, preferably up to 6 carbon atoms.

Particularly preferred are drug combinations and topical preparations containing L-arginine and / or its contain derivatives of the invention.

L-arginine and its derivatives are also known a particularly good skin penetration capacity.  

The amino acids according to the invention and / or their Derivatives are preferably in amounts of from 0.01 to 30 Wt .-%, particularly preferably 0.01 to 10 wt .-%, in particular 0.1-7.5 wt .-%, each based on the entire preparation, in the inventive cosmetic and dermatological preparations contain. L-arginine, ornithine and citrulline and the Derivatives may be used singly or in combination However, preparations contain special ingredients preferably L-arginine in amounts of from 1 to 10% by weight, based on the entire preparation.

Particularly suitable salts of folic acid are water-soluble salts, in particular sodium, potassium and ammonium salts.

Preferred compounds from the group of flavins are Flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN).

Folic acid or its salts and / or flavins are preferably in the preparations according to the invention each preferably in amounts of from 0.0001 to 5 Wt .-%, in particular 0.01 to 1.5 wt .-%, respectively based on the total weight of the preparations.

The cosmetic or cosmetic according to the invention dermatological topical preparations may be on customary formulation bases are based and Treatment of the skin in terms of a dermatological Treatment or treatment in the sense of nourishing cosmetics.

Particularly advantageous preparations are further obtained when the active compounds according to the invention Antioxidants are combined.  

It had not been foreseen that the active ingredients and combinations with an effective content Arginine, ornithine or citrulline and the mentioned Cofactors or the combination with Antioxidants neurosensory and hypersensitivity Reduce itching. Furthermore, it was not predictable been that they lead to skin-friendly products or increase their tolerability and healthy Skin does not interfere with the skin's microflora.

This will solve the tasks.

Typical, with the terms "stinging" or "sensitive skin", disturbing Neurosensory phenomena are skin reddening, tingling, Tingling, tightening and burning of the skin and itching. They can be stimulated by stimulating environmental conditions z. B. massage, surfactant action, weather influence such Sun, cold, dryness, but also damp heat, Heat radiation and UV radiation, z. The sun, be caused.

Surprisingly, the invention Symptoms of sensitive skin and itching Skin diseases, such. B. atopy, mitigated or avoided.

The antioxidants of the invention may be advantageous from the group of the usual cosmetic and dermatological antioxidants are chosen in particular from the group consisting of tocopherols and their derivatives, especially α-tocopherol or α-tocopheryl esters, in particular α-tocopheryl acetate, sesamol, bile acid derivatives such as methyl, Ethyl, propyl, amyl, butyl and lauryl gallate, the Konyferylbenzoat of Benzoeharzes, Nordihydroguajakharzsäure, Nordihydroguajaretsäure,  Butylhydroxyanisole, butylhydroxytoluene, ascorbic acid, Citric acid, phosphoric acid, lecithin, Trihydroxybutyrophenone, carotenes, vitamin A and its Derivatives, in particular retinyl palmitate, ascorbic acid, Ascorbyl palmitate, dilauryl thiodipropionate, Distearyl thiodipropionate, monoisopropyl citrate, Thiodipropionic acid, EDTA and EDTA derivatives, cysteine, Glutathione and esters, uric acid, lipoic acid and Esters, carotenes, heavy metal complexing agents such as delta-aminolevulinic acid and phytic acid.

The cosmetic or cosmetic according to the invention Dermatological preparations preferably contain 0.01 up to 10% by weight, but in particular 0.1 to 6% by weight, based on the total weight of the preparations one or more substances from the group of Antioxidants.

Preferably, the antioxidants of the invention the group of tocopherols and their derivatives choose.

Furthermore, the preparations contain advantageously also urea. The urea content is for example 0.01-30% by weight, in particular 0.1-10 wt .-%, each based on the total weight the preparations.

For use, the preparations in the for Cosmetics or dermatological usual way to the skin in applied sufficient amount.

Particularly preferred are skin and Hand care preparations, sunscreen and After-sun preparations, washing and shower preparations with skin care function.  

Dermatological and cosmetic preparations according to the The invention may be in various forms. So can z. As aqueous, alcoholic or aqueous-alcoholic solutions, emulsions of the type Oil-in-water (O / W), emulsions of the water-in-oil type (W / o), multiple emulsions e.g. B. of the type water-in Oil-in-water (W / O / W), gels, hydrodispersions, solid Pens or aerosols the o.g. drug combinations contain.

The topical preparations according to the invention can the usual auxiliaries such as emulsifiers and Preservative included.

Also preferred are such cosmetic and dermatological preparations in the form of a Sunscreen available. Advantageously included this additionally at least one UVA filter and / or at least one UVB filter and / or at least one inorganic pigment.

But are also very advantageous Preparations which after exposure to light on Skin are applied, so Apr's-Soleil products. It is at the discretion of the Professional, whether additional UV filter substances should be used or not.

Cosmetic preparations according to the invention for Protecting the skin from UV rays can be in different forms exist as z. B. usually for this type of preparations be used. So they can z. B. an aqueous, alcoholic or aqueous-alcoholic solution, a Emulsion of the water-in-oil (W / O) or oil-type in-water (O / W), or a multiple emulsions, for example of the water-in-oil-in-water (W / O / W) type,  a gel, a hydrodispersion, a solid stick or also constitute an aerosol.

The topical preparations according to the invention can contain cosmetic excipients, as they commonly used in such preparations be, for. B. preservatives, bactericides, Perfumes, antifoaming agents, Dyes, pigments that have a coloring effect, Thickeners, surface-active substances, Emulsifiers, softening substances, moisturizing and / or moisturizing substances, fats, oils, waxes or other common ingredients of a cosmetic Formulation such as alcohols, polyols, polymers, Foam stabilizers, electrolytes, organic Solvent or silicone derivatives.

If the cosmetic or dermatological preparation a solution or lotion can be considered as Solvents are used:

• - water or aqueous solutions;
• - Oils, such as triglycerides of caprine or Caprylic acid, but preferably castor oil;
• - fats, waxes and other natural and synthetic fat bodies, preferably esters of Fatty acids with low C-number alcohols, e.g. B. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanoic acids 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 analogues Products.

In particular, mixtures of the above Solvent used. For alcoholic Solvents can be another component of water his.

Emulsions according to the invention z. B. in the form of a Sunscreen cream, a sunscreen lotion or a Sunscreen milk are beneficial and contain z. B. the said fats, oils, waxes and others Fat body, as well as water and an emulsifier, like him usually for such a type of formulation is used.

Cosmetic and dermatological preparations for Treatment and care of the skin can be used as gels present, in addition to the active ingredients and for that commonly used solvents yet organic thickeners, e.g. Gum arabic, Xanthan gum, sodium alginate, cellulose derivatives, preferably methylcellulose, hydroxymethylcellulose, Hydroxyethyl cellulose, hydroxypropyl cellulose, Hydroxypropylmethylcellulose or inorganic Thickener, z. B. aluminum silicates such for example, 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% by weight.

Gels according to the invention usually contain alcohols low C number, z. For example, ethanol, isopropanol, 1,2-propanediol, glycerol and water or one above called oil in the presence of a thickener, the  in oily-alcoholic gels preferably Silica or an aluminum silicate, at aqueous-alcoholic or alcoholic gels preferably a polyacrylate.

Hydrodispersions make dispersions of a liquid, semi-solid or solid inner (discontinuous) Lipid phase in an external aqueous (continuous) Phase dar.

In contrast to O / W emulsions, which are characterized by a are distinguished similar phase arrangement, are Hydrodispersions but essentially free of Emulsifiers. Hydrodispersions provide, as otherwise also emulsions, metastable systems and are inclined, into a state of two in itself to pass on coherent discrete phases. In Emulsions prevents the choice of a suitable one Emulsifier the phase separation.

For hydrodispersions of a liquid lipid phase in an external aqueous phase can be the stability of such a system, for example be ensured that in the aqueous phase Gel skeleton is built, in which the lipid droplets are stably suspended.

Solid pins according to the invention can, for. Natural or synthetic waxes, fatty alcohols or fatty acid ester included. Preference is given to lip balms.

As propellant for the invention, from Aerosolbehäl tern sprayable cosmetic or dermatological Preparations are the usual known volatile, liquefied propellants, For example, hydrocarbons (propane, butane, Isobutane), alone or in admixture  can be used together. Also compressed air is advantageous to use.

Of course, the expert knows that it is not in itself toxic propellants, which are basically for the present invention would be suitable, however nonetheless because of its harmful effect on the environment or other accompanying circumstances should be waived, in particular fluorohydrocarbons and Chlorofluorocarbons (CFCs).

Preference is given to the preparations according to the invention In addition, substances containing UV radiation in the Absorb UVB area, the total amount of Filter substances z. From 0.1% to 30% by weight, preferably 0.5 to 10 wt .-%, in particular 1 to 6 % By weight, based on the total weight of the Preparation to make cosmetic preparations available to put the skin in front of the entire area of the skin Protect ultraviolet radiation. You can also as To use sunscreen.

The UVB filters can be oil-soluble or water-soluble his. As oil-soluble substances z. To name, for example:

• 3-benzylidene camphor derivatives, preferably 3- (4-methylbenzylidene) camphor, 3-benzylidene camphor;
• 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoesäureamylester;
• - esters of cinnamic acid, preferably 4-methoxycinnamate (2-ethylhexyl) ester, 4-methoxycinnamate;
• - esters of salicylic acid, preferably  Salicylic acid (2-ethylhexyl) ester, Salicylic acid (4-isopropylbenzyl) ester, salicylate;
• - Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;
• Esters of benzalmalonic acid, preferably 4-methoxybenzalmalonate (2-ethylhexyl) ester;
• 2,4,6-trianilino (p-carbo-2'-ethyl-1'-hexyloxy) 1,3,5-triazine.

As water-soluble substances z. To name, for example:

• - Salts of 2-phenylbenzimidazole-5-sulfonic acid like her Sodium, potassium or their triethanolammonium salt, as well as the sulfonic acid itself;
• Sulfonic acid derivatives of benzophenones, preferably 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;
• Sulfonic acid derivatives of the 3-benzylidene camphor, such as z. B. 4- (2-oxo-3-bomylidenemethyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bomylidenemethyl) sulfonic acid and their salts.

The invention is also the combination of active compounds according to the invention with one or more UVB filters or inventive cosmetic or dermatological preparations, which also include one or several UVB filters included.  

It may also be advantageous to use the active ingredients with UVA To combine filters that were previously customary in cosmetic and / or dermatological are included. These substances are preferably Derivatives of dibenzoylmethane, in particular to 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3- dione and 1-phenyl-3- (4'-isopropylphenyl) propane 1,3-dione. Also these combinations or preparations, which contain these combinations are the subject of Invention. It may be the one for the UVB combination used quantities.

There are also obtained advantageous preparations when the active compounds according to the invention with UVA and UVB filters are combined.

Also combinations of the invention Active ingredients with one or more antioxidants and one or more UVA filters and / or one or more Several UVB filters are particular according to the invention advantageous.

Cosmetic or dermatological preparations may also contain inorganic pigments that Usually used in cosmetics to protect the skin UV rays are used. It refers to Oxides of titanium, zinc, iron, zirconium, silicon, Manganese, aluminum, cerium and mixtures thereof, as well as Variations in which the oxides are the active agents are. Particularly preferred are pigments based on titanium dioxide.

The invention also provides the process for Preparation of the topical according to the invention Preparations characterized in that in known manner, the active ingredients in  cosmetic or dermatological formulations incorporated.

All quantities, proportions and percentages are, Unless otherwise indicated, on the weight and the Total or on the total weight of Preparations related.

The following examples are intended to illustrate the present Illustrate the invention without limiting it.

example 1 Sonnengel LF 4 (transparent) Wt .-% L-arginine hydrochloride 10 Benzophenone-4 0.5 phenylbenzimidazolesulfonic 1.3 Acrylamide / sodium acrylate copolymer 1.6 ethanol 5.0 glycerin 15.0 NaOH (15%) q.s. Perfume, preservative q.s. Water, VES (desalted) ad 100.0

Example 2 Hydro dispersion Wt .-% L-ornithine hydrochloride 5.0 Phenyl 1.0 Carbomer (Carbopol 981) 1.0 hydroxypropyl methylcellulose 0.2 butylene 3.0 tromethamine q.s.   EDTA solution (14%) 0.5 ethanol 5.0 Perfume, preservative q.s. Water, VES ad 100.0

Example 3 Sun Milk O / W Wt .-% L-arginine hydrochloride 5.0 octyl 5.0 butylmethoxydibenzoylmethane 1.0 Cetearyl Alcohol + PEG-40 Castor Oil + Sodium Cetearyl Sulfate 2.5 glyceryl 1.0 Laurylmethicone copolyol 0.5 Mineral oil (DAB 9) 5.0 Caprylic / capric triglycerides 5.0 Acrylamide / sodium acrylate copolymer 0.3 cyclomethicone 2.0 TiO₂ 1.0 glycerin 3.0 EDTA solution (14%) 0.5 ethanol 5.0 Perfume, preservative q.s. Water, VES ad 100.0

Example 4 Care lotion W / O Wt .-% L-arginine hydrochloride 2.5 folic acid 0.1 cyclomethicone 3.0 PEG-1-Glycerol Sorbitan Oleostearate 1.7   PEG-7 Hydrogenated castor oil 6.3 Mineral oil (DAB 9) 13.0 Caprylic / capric triglycerides 13.0 glycerin 4.0 MgSO₄ 0.7 Perfume, preservative q.s. Water, VES ad 100.0

Example 5 Nourishing daily creams O / W Wt .-% L-arginine hydrochloride 5.0 L-ornithine 1.0 PEG-5 glyceryl stearate 2.00 glyceryl stearate 3.00 cyclomethicone 3.00 Caprylic / capric triglycerides 3.00 cetyl alcohol 3.00 octyl 2.50 ethanol 1.00 hyaluronic acid 0.05 tocopheryl acetate 0.50 glycerin 4.00 Perfume, preservative q.s. Water, VES ad 100.00

Example 6 W / O Cream Wt .-% L-citrulline 2.5 L-arginine hydrochloride 2.5 FAD 0.1 FMN 0.05   PEG-22 dodecyl glycol copolymer 3.0 Cetyl dimethicone copolyol 2.0 cyclomethicone 4.0 Mineral oil (DAB 9) 4.0 Caprylic / capric triglycerides 4.0 glycerin 4.00 Perfume, preservative q.s. Water, VES ad 100.00

Example 7 W / O Cream Wt .-% L-ornithine hydrochloride 2.5 L-citrulline 2.5 L-arginine hydrochloride 2.5 FAD 0.1 FMN 0.05 PEG-22 dodecyl glycol copolymer 3.0 Cetyl dimethicone copolyol 2.0 cyclomethicone 4.0 Mineral oil (DAB 9) 4.0 Caprylic / capric triglycerides 4.0 glycerin 4.00 Perfume, preservative q.s. Water, VES ad 100.00

Example 8 After Sun Lotion Wt .-% L-arginine hydrochloride 5.0 folic acid 0.1 urea 2.5   Cetearyl Alcohol + PEG-40 Castor Oil + Sodium Cetearyl Sulfate 2.50 Glyceryl stearate SE 0.60 Mineral oil (DAB 9) 4.00 Caprylic / capric triglycerides 2.00 shea butter 2.00 avocado oil 2.00 tocopheryl acetate 3.00 Acrylamide / sodium acrylate copolymer 0.30 glycerin 4.00 hyaluronic acid 0.05 bisabolol 0.05 Perfume, preservative q.s. Water, VES ad 100.00

Example 9 shower milk Wt .-% L-arginine hydrochloride 10.0 folic acid 1.0 Sodum Laureth Sulfate 12 Cocamidopropyl betaines 5 Cocamide DEA 1 PEG-8 1 Soybean oil 1 Citric Acid 0.1 Sodium Chloride 0.2 Fragrance 0.1 Water, demin. ad 100.00

Example 10 W / O Cream Wt .-% L-ornithine hydrochloride 2.5 L-citrulline 2.5 L-arginine hydrochloride 2.5 FAD 0.1 FMN 0.05 folic acid 0.1 tocopheryl acetate 1.0 urea 2.5 PEG-22 dodecyl glycol copolymer 3.0 Cetyl dimethicone copolyol 2.0 cyclomethicone 4.0 Mineral oil (DAB 9) 4.0 Caprylic / capric triglycerides 4.0 glycerin 4.00 Perfume, preservative q.s. Water, VES ad 100.00

test report

With the following test report the excellent effect of the active compounds according to the invention demonstrated. For this purpose, the lotion of Example 4, but with an active ingredient content of 5 wt .-% L-arginine and without folic acid and perfume in a "Stingingtest" with 5 wt .-% lactic acid in water as a "stinger" analog Frog and Kligman used (Peter J. frog and Albert M. Kligman: "A method for appraising the stinging capacity of topically applied substances ", J. Soc. Cosmet. Chem. 28, 197-209, 1977).

After a one-week contralateral product application (twice daily) the stinging potential of 5% Lactic acid after a single application on the cheeks determined. First on one cheek and about 1 hour later, after the decay of the stimulus, at the other Cheek. The stinging potential of 5% lactic acid is on the cheeks previously treated with 5% L-arginine significantly reduced.

Claims (8)

1. use of one or more compounds, selected from the group of L-arginine, L-ornithine and L-citrulline or their salts, Acid addition salts, esters or amides, optionally with the addition of folic acid or their salts and / or one or more Compounds selected from the group of Flavins, for the prophylaxis and / or treatment of neurosensory phenomena. 2. Use of cosmetic and dermatological topical preparations containing one or more compounds selected from the group of L-arginine, L-ornithine and L-citrulline or its salts, Acid addition salts, esters or amides, optionally with the addition of folic acid or their salts and / or one or more Compounds selected from the group of Flavins, for the prophylaxis and / or treatment of neurosensory phenomena. 3. Use according to claim 2, characterized characterized in that the preparations L-arginine contain. 4. Use according to claim 2, characterized in that the preparations are folic acid and / or one or more compounds, selected from the group of flavins.   5. Use according to claim 2, characterized characterized in that the preparations at least contain an antioxidant. 6. Use according to claim 2, characterized characterized in that the preparations urea contain. 7. Use according to claim 2, characterized characterized in that the preparations at least a UVA filter and / or at least one UVB filter and / or at least one inorganic Pigment included. 8. Use according to claim 2, characterized characterized in that the preparations L-arginine, folic acid, one or more Compounds selected from the group of Flavins, at least one antioxidant, urea and optionally at least one UVA filter and / or at least one UVB filter and / or contain at least one inorganic pigment.