MXPA06003354A - Pharmaceutical and cosmetic formulations for treating fingernails - Google Patents

Abstract

The invention relates to topical agents used for treating nail diseases and nail care containing besides one or several active substances and possibly adjuvants and solubilisation physiologically tolerable agents, one or several compounds of formula (I):R-O-R1, wherein R is a linear or branched alkyl group comprising 5-8 carbon atoms and R1 is hydrogen, a formula or acetyl group. The inventive agents are also appropriate for veterinary medicine for treating fungal infections of hooves and nails of domestic and working animals.

Description

PHARMACEUTICAL AND COSMETIC FORMULATIONS The present invention relates to products for topical application for the treatment of diseases of the nails and for the care of the nails, which have improved penetration properties through the substances of the nails and of the skin. Direct topical treatments of nail diseases and nail care are generally practically applied without any side effects; they are simple treatments to carry out and only generate minimum costs. However, the essential problem of the direct topical use of nail compositions is to transport active substances, including nutrients and anabolic substances in sufficient quantities, through the nails to the layers of tissue that are deeper and up to the root of the nail, in such a way that the pathogens that are present can be completely destroyed and the nutrients and anabolic substances supplied to the nail. Through the use of conventional products it is possible to alleviate the symptoms through a direct topical treatment; however, symptoms usually reappear after the treatment has ended. It has already been proposed to improve the results of the treatment with the direct topical use of active substances in which the active substances are used together with a so-called carrier, ie a substance which, in addition to having a good solubility for the active substance, also presents good penetrability through the substance of the nail and has the ability to transport the active substance through the nail tissue. For example, EP-A-0503988 describes medicaments for the treatment of onychomycosis, besides an active antimycotic substance at least water soluble portion and an alkanol C2-C8, straight or branched, contains a medium It consists of at least one third of water, a hydrophilic substance that promotes the penetration of the antifungal through the nail. The penetration-promoting substances are, for example, glycol, glycol monoether, glycol diether, dimethylsulfoxide, caprolactam, dimethylisosorbide, isopropylideneglycerol, dimethylimidazolidinone, N-metiIpirrolidona-2, pyrrolidone-2, ethyl acetate, polyoxyethylene glycerides C8- C10 and polyethylene glycol-glycerylurea and dimethylacetamide. The formulation principle described in EP-A-0503988 is, in view of the partial water solubility that is postulated for the active substance, only suitable for a limited amount of active substances, ie, that said formulation is not suitable for many active ingredients. In the application WO-A-9734644, topical formulations for the treatment of psoriasis of the nails containing n-octanol as a penetration-promoting substance are disclosed. Esters of formic acid and acetic acid are not mentioned as promoters of improved penetration. In published application WO-A-02-083084 for the treatment of nails containing fluconazole, carrier and promoter pentetración, especially caprylic alcohol, t-amyl or 3-pentanoI described. Formic acid esters and acetic acid esters are not mentioned as penetration promoting agents. In the publication by Mertin, Dirk et al. in "Journal of Pharmacy and Pharmacology ed" ( "Journal of Pharmacy and Pharmacology") 49 (3), 241 -245, a composition containing chloramphenicol and n-octanol and additives required for the production of enamel paints is disclosed, no formic acid or acetic acid esters are disclosed as penetration promoting agents. The application WO-A-03045339 discloses a lacquer as a topical agent for the treatment of mycosis and battery, whereby the lacquer containing the active agent does not penetrate the nail or in all layers containing keratin. Formic acid and acetic acid esters are not described as solubility promoting agents or penetration promoters. In DOS 1 0014673 an antifungal agent is described for the treatment of nails as a lacquer with vegetable agents, solubility promoters, based on lacquer-building agents, for example, nitrocellulose. DOS Application No. 101 26501 discloses keratin-dissolving compositions containing urea and lower alkanols. Acetic acid esters, respectively, are not described as penetration promoters. Added to this, the presence of water is essential. Other publications, such as for example Canadian Patent Number 1072009, are especially differentiated by the different solubility agents and penetration promoters, which mainly do not use formates or acetates of C5-C8 alkanols. In EP-A-0179675 respectively WO-A-0200176, the production of greasy lacquer from lacquers and ointments is described. The use of formic acid esters and acetic acid as penetration promoting agents is not mentioned. The publication of Derwent Number XP-002310735 discloses the production of a nail polish remover and its application talks.

All the formulations mentioned are different from the inventive formulation due to the absence of formic acid or acetic acid esters as a solubility or penetration promoting agent on the one hand, and in that they contain additives that form a lacquer or a film, such as nitrocellulose, on the other. The presence of additives that produce a lacquer changes the quality of the formulation drastically. The lacquer layer prevents the penetration of any component, such as, for example, any active ingredient of the formulation. So far, there is no satisfactory product for the topical treatment of nail diseases or for the care of the nails, which contains a carrier that allows the transport of the necessary amount of active substance through the nail to the root of the nail (matrix), which is necessary for a successful treatment. Therefore, it is one of the purposes of the present invention, to provide a solution to the problems that relate to the topical treatment of nail diseases and to the care of the nails, as well as to provide pharmaceutical and cosmetic products. that offer a successful treatment. It was discovered that the compounds of the formula (I) ROR-, (I) where R represents a straight or branched alkyl residue with 5-8 carbon atoms and Ri represents a formyl group or an acetyl group, not only have a excellent penetration through the substance of the keratinized nail and the surrounding skin, but can also transport, both therapeutic active substances, such as, for example, antifungals, antibiotics, antiseptics and corticosteroids, as well as other substances for the care of the nails, such as important nutrients through the keratinized nail and through the skin. Therefore, the object of the present invention is a topical application agent for the treatment of diseases of the nails and for the care of the nails which contains: (a) one or more active therapeutic or nutritive substances, (b) one or more of the compounds of the formula I R-0-Rt (I) wherein R represents a straight or branched alkyl residue with 5-8 carbon atoms and Ri represents a formyl group or an acetyl group, (c) if necessary, physiologically compatible adjuvants. Subject to the present invention, these compounds of the formula I, for the promotion of the penetration, include esters of formic acid and acetic acid of C5-C8 alkanols. The formula I anteiro includes both formates and acetates of C5-C8 straight and secondary straight alkanols, as well as the branched, alkanal isomers. Among the individual representatives of C5-C8 alkanols in formula I are 1-pentanol (amyl alcohol), 3-methyl-1-butanol (isoamyl alcohol), 1-hexanol, 2-hexanol, 4-methyl-1-pentanol, 4-methyl-2-pentanol, 1-heptanol, 2-heptanol, 5-methyl-1-hexanol, 5-methyl-2-hexanol, 1-octanol, 2-octanol, 6-methyl-1-heptanol, 6- methyl-2-heptanol. Of the C5-C8 primary and secondary alkanols mentioned, the C5-C6 alkanols are favored. In particular, pentanols are favored, especially 1-hexanol and 2-hexanol. The mixtures that are further favored are mixtures of two or more formic and / or ethyl acetates of Cs-Cs alkanols. Particularly a mixture of esters of hexanols and heptanols is favored, for example 1-hexanol and 1-heptanol, whereby the mixing ratio can vary from 0.5: 1.5 to 1.5: 0.5. Among the individual representatives of the C5-C8 alkanol formates and acetates of the formula I are amyl formates, amyl acetates, isoamyl formates, isoamyl acetate, 1-hexyl formate, 1-hexyl acetate, 2-hexyl formate, 2-hexyl acetate, 1-heptyl formate, 1-heptyl acetate, 2-heptyl formate, 2-heptyl lactate, 1-octyl formate, 1-octyl acetate, 2-octyl formate and 2-octyl acetate. Among the C5-C8 alkyl esters favored are the C5-C6 alkyl acetates. Particularly C5-C6 alkyls are favored. The mixtures of several C5-C6 alkyl acetates are further favored. Subject to the present invention for topically applicable agents basically all therapeutic active substances of synthetic and natural origin are considered, that are effective for diseases in the nails and periungueales. In addition, nutrients and anabolic substances that are effective for nail care are considered active substances. Among the appropriate therapeutic active substances, which can be present in the topical agents invented for the treatment of nail diseases, we find antimycotics of synthetic or natural origin, antibiotics, antiseptics and corticosteroids, as well as combinations of the active ingredients that are they mention. The particularly suitable active substances are the antifungals of synthetic and natural origin, and the nutrients and anabolic substances, which are effective for the care of the nails. Examples of active therapeutic substances include: -antimicotics and their physiologically acceptable salts, such as, for example, (±) -cis-2,6-dimethyl-4- [2-methyl-3- (p-rerí- pentyl-phenyl) propyl] morpholine (amorolfine), amphotericin, 6-cyclohexyl-1-h idroxy-4-methyl-2 (1 H) pyridone (cyclopirox), bis-phenyl- (2-chlorophenyl) -1-imidazolylmethane (clotrimazole), 1 - [2- (2,4-Dichlorophenyl) -2- (4-chlorobenzyloxy) -ethyl] -imidazole (econazole), 2,4-difluo-a, a-bis (1 H-1, 2,4-triazole) -1-methylmethyl) benzyl alcohol (fluconazole), 5-fluorocytosine (flucytosine), 7-chloro-trimethoxy-methylspiro- [benzofuran-cyclohexane] -dione (griseofulvin), 1 - [2,4-dichloro-β- (2, 6-dichlorobenzyloxy) -phenethyl] -imidazole (isoconazole), (±) -1 -sec-butyl-4-. { 4- [4- (4- { [(2R *, 4S *) - 2- (2,4-dichlorophenyl) -2- (1, 2,4-triazoI-1-methylmethyl) -1, 3-dioxolan-4-yl] methoxy.} - phenyl) -1-piperazinyl] phenyl} -4,5-dihydro-1, 2,4-triazol-5-one (itraconazole), (±) -cis-1-acetyl-4-. { 4 - ([2,4-dichlorof in yl) -2- (1 H -im idazol-1-ylmethyl) -1,3-d-oxolan-4-yl] methoxy) phenyl} piperazine (ketoconazole), 1 - [2,4-dichloro-β- (2,4-dichlorobenzyloxy) -phenethyl] -im idazole (miconazole), (£) -N-ci namil- / V-meti I- 1 - naphthylmethi lamina (naftifine), nistatin, (£) -N- (6,6-dimethyl-2-hepten-4-ynyl) -? / - methyl-1-naphthi-methylamine (terbinafine), 1 [2-. { (2-chloro-3-thienyl) methoxy} -2- (2,4-Dichlorophenyl) ethyl] -1H-imidazole (thioconazole), O-2-naphthyl-N-methyl-N- (3-tolyl) -thiocarbamate (tolnaftate). Among the preferred antifungals of the present invention are: (±) -cis-2,6-dimethyl-4- [2-methyl-3- (p-yerf-pentyl-phenyl) propyl] morpholine (amorolfine), bis- phenyl- (2-chlorophenyl) -1-imidazolylmethane (clotrimazole), 1 - [2,4-dichlor-β- (2,6-dichlorobenzyloxy) -phenethyl] -imidazole (isoconazole), 2,4-difluoro-a, a bis (1 H-1, 2,4-triazol-1-ylmethyl) benzylalcohol (fluconazole), (±) -1-sec-butyl-4-. { 4- [4- (4- { [(2R *, 4S *) - 2- (2,4-dichlorophenyl) -2- (1, 2,4-triazol-1-ylmethyl) -1, 3- dioxolan-4-yl] methoxy.}. phenyl) -1-piperazinyl] phenyl} -4,5-dihydro-1, 2,4-triazol-5-one (itraconazole), (±) -cis-1-acetyl-4-. { 4 - ([2,4-Dichlorophenyl) -2- (1 H -imidazol-1-ylmethyl) -1, 3-dioxolan-4-yl] methoxy) phenyl} piperazine (ketoconazole), 1- [2,4-dichlor-β- (2,4-dichlorobenzyloxy) -phenethyl-imidazole (miconazole), (£) -N- (6,6-dimethyl-2-hepten-4- inyl) -? / - methyl-1-naphthylmethylamine (terbinafine), a- (2,4-difluorophenyl) -5-fluoro-β-methyl-α- (1H-1, 2,4-triazole-1 - ilmethyl) -4-pyrimidinetanol (voriconazole). Among the particularly preferred antifungals according to the present invention are (±) -cis-2,6-dimethyl-4- [2-methyl-3- (p-ferf-pentyl-phenyl) propyl] -morpholine (amorolfine) , bis-phenyl- (2-chlorophenyl) -1-imidazolylmethane (clotrimazole), 1 - [2,4-dichlor-β- (2,6-dichlorobenzyloxy) -phenethyl] -imidazole (isoconazole), (+) - 1 -sec-butyl-4-. { 4- [4- (4-. {[[(2R *, 4S *) - 2- (2,4-dichlorophenyl) -2- (1, 2 > 4-triazol-1-ylmethyl) -1, 3 -dioxolan-4-yl] methoxy.}. - phenyl) -1-piperazinyl] phenol} -4,5-dihydro-1, 2,4-triazol-5-one (itraconazole), (±) -cis-1-acetyl-4-. { 4 - ([2- (2,4-Dichlorophenyl) -2- (1 H-imidazol-1-ylmethyl) -1, 3-dioxolan-4-yl] methoxy) phenyl} piperazine (ketoconazole). -antimicotics of natural origin, such as for example, essential oils and plant extracts. Among the preferred natural origan antifungals are tea tree oil (Melaleuca aternifolla), lavender oil (Lavandula officinalis chaix), Australian blue cypress oil (intratopic callitis) and leaf extract from the Nim tree (Azadirachta indica). These natural antifungals can be used as the sole active substance or in combinations of several such active substances. A preferred combination of active ingredients is the mixture of lavender oil, tea tree oil and Australian blue cypress oil (intratopic callitis). -antibiotics and their physiologically acceptable salts, such as, for example, α-amino-4-hydroxybenzylpenicillin (amoxicillin), D - (-) - α-aminobenzylpencycline (ampicillin), 3,3-dimethyl-7-oxo-6 acid -phenylacetamido-4-thia-1-azabicyclo- [3.2.0] -heptan-2-carboxylic acid (benzyl penicillin), benzylpenicillin-benzathine, 3-chloro-7-D- (2-phenylglycinamido) -cephalosporanic acid (cefaclor ), 7β- [D-2-amino- (4-hydroxyphenyl) -acetylamino] -3-methyl-cephalosporanic acid (cefadroxil), amino-phenylacetamido-methyl-cephalosporanic acid (cephalexin), D (-) - threo-2 -dichloroacetamido-1 - (4-nitrophenyl) -1, 3-propanediol (chloramphenicol), 1-cyclopropyl-6-f luoro-1,4-dihydro-4-oxo-7- (piperazinyl) -3-quinolinecarboxylic acid (ciprofloxacin), acid (Z) - (2R, 5R ) -3- (2-hydroxyethylidene) -7-oxo-4-oxa-1-azabicyclo [3.2.0] heptan-2-carboxylic acid (clavulanic acid), 7-chloro-7-deoxy-lincomycin (clindamycin), 6 -deoxy-5-hydroxytetracycline (doxycycline), 1-ethyl-6-fIuoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -1,8-naphthyridine-3-carboxylic acid (enoxacin), erythromycin, 3- (2-chloro-6-fluorophenyl) -5-methyl-4-isoxazolyl-penicillin (flucloxacillin), kanamycin, lincomycin, 7-dimethylamino-6-deoxy-6-demethyltetracycline (minocycline), 6- ( 2-ethoxy-1-naphthamido) -penicillin (nafcillin), 1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (nalidixic acid), neomycin, acid 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid (norfloxacin), acid (±) -9-fluoro-2,3-dihydro-3- methyl-10- (4-methyl-1-piperanzinyl) -7-oxo-7H-pyrido [1, 2,3-c / e] [1,4] -ben zoxacin-6-carboxylic acid (ofloxacin), 6- (5-methyl-3-phenyl-4-isoxazolecarboxamido) penicilinic acid (oxacillin), 6-phenoxyacetylamino-penicillanic acid (phenoxymethylpenicillin) and 4-dimethylamino-octahydropentahydroxy-1, 11-dioxo-6-methyl-naphtha-2-carbamide (tetracycline). Preferred antibiotics include doxycycline, minocycline, and neomycin. -antiseptics such as, for example, alkylbenzyl dimethyl ammonium chloride, (bezalkonium chloride), N-benzyl-N, N-dimethyl-2-hydroxide. { 2- [p- (1,1,3,3, -tetramethylbutyl) -phenoxy] -ethoxy} -ethyl ammonium (benzethonium chloride), cetyltrimethylammonium hydroxide (cetrimonium bromide), 1,1'-hexamethylene-bis- [5- (p-chlorophenyl) -biguanide] (chlorohexidine), N1 hydroxide, N1-decamethylene-bis - (4-aminoquinaldinio) (decquinio chloride), N- (4-chlorophenyl) -N '- (3,4-dichlorophenyl) urea (triclocarban) and 5-chloro-2- (2,4-dicyorophenoxy) phenol ( triclosan). Preferred antiseptics are, for example, 1,1'-hexamethylene-bis- [5- (p-chlorophenyl) -biguanide] (chlorohexidine). -corticosteroids and their physiologically acceptable salts, such as, for example, 9α-chloro-16β-methylprednisolone (beclomethasone), 9-fUuoro-11β, 17,21-trihydroxy-16β-methyl-1,4-pregnadiene-3.20 -dione (betamethasone), 21-cioro-9-fluoro-Hβ. ^ - dihydroxy-lβ-methyl-1 -pregnadiene-S-O-dione (clobetasol), 17,21-dihydroxy-pregn-4-en- 3,11,20-trione (cortisone), 11β acetal, 16a, 17a, 21-tetrahydroxy-1,4-pregnadiene-3, 20-dione-16,17-acetone (desonide), 9-fluoro-11β- 7,21-trihydroxy-16a-methylpregna-1,4-diene-3,20-dione (dexamethasone), 9a, 11β-dichloro-6a-f Ioro-21-hydroxy-16a, 17a- (isopropylidenedioxy) -pregna -1,4-diene-3,20-dione (flucloronide), 6a, 9a-difluoro-16a, 17a-isopropylidenedioxy-corticosterone (fluocinolonacetonide), 6a, 9a-difluoro-16a, 17a-isopropylidenedioxy-corticosterone acetate (fluocinonide) ), 6a-fluoro-11β, 21-dihydroxy-16a, 17-isopropylidenedioxy-4-pregnen-3,20-dione (fludroxicortide), 3- (2-chloroethoxy) -9a-fluoro-6-formyl-11β, 21 -dihydroxy-16a, 17a-isopropylidene xipregna-3,5-diene-20-one (formocortal), 21-chloro-9a-fluoro-11β-hydroxy-16a, 17a-isopropylidenedioxy-4-pregnen-3,20-dione (halcinonide), 17a-hydroxycorticosterone ( hydrocortisone), 11β, 17,21-trihydroxy-6α-methyl-1,4-pregnadiene-3,20-dione (methylprednisolone), 11β, 17,21-trihydroxy-pregna-1,4-diene-3,20- dione (prednisolone), 17a, 21-dihydroxypregna-1,4-dien-3,11, 20-trione (prednisone), 9-fluoro-16a-hydroxy-prednisolone (triamcinolone) and triamcinolone-16a, 17-acetonide (triamcinolone acetonide). Among the preferred corticosteroids are acetal of 11β, 16a, 17a, 21-tetrahydroxy-1,4-pregnadiene-3,20-dione-16,17-acetone (desonide), 9a, 11β-dichloro-6a-fluoro-21-hydroxy-16a, 17a- ( isopropylidenedioxy) -pregna-1,4-diene-3,20-dione (flucloronide), 6a, 9a-difluoro-16a, 17a-isopropylidenedioxy-corticosterone (fluocinolonacetonide), 6a, 9a-difluoro-16a, 17a-isopropylidenedioxy-corticosterone -acetate (fluocinonide), 6a-fluoro-11β, 21-dihydroxy-16a, 17-isopropylidenedioxy-4-pregnen-3,20-dione (fludroxicortide), 3- (2-chloroethoxy) -9a-fluoro-6-formyl -11β, 21-dihydroxy-16a, 17a-isopropylidenedioxypregna-3,5-dien-20-one (formocortal), 21-chloro-9a-fluoro-11β-hydroxy-16a, 17a-isopropylidenedioxy-4-pregneno-3, 20-dione (halcinonide), triamcinolone-16a, 17-acetonide (triamcinolone acetonide). The following are specific examples of combinations of active substances: combinations of corticosteroids with antifungals, antibiotics or antiseptics. For example, a preferred combination is (±) -cis-1-acetyl-4-. { 4 - ([2- (2,4-dichlorophenyl) -2- (1 H-imidazol-1-ylmethyl) -1, 3-dioxolan-4-yl] methoxy) phenyl} piperazine (ketoconazole) and 1 1β, 16a, 17a, 21 -tetrahydroxy-1,4-pregnadiene-3,20-dione-16,17 acetone (desonide) acetal. -combinations of antifungals of synthetic origin with antifungals of natural origin. A preferred combination is bis-phenyl- (2-chlorophenyl) -1-imidazolylmethane (clotrimazole) with tea tree oil. - combinations of several antifungals of natural origin. A preferred combination is lavender oil, with tea trea oil and Australian blue cypress oil (intratopic callitis). Among the nutritive active ingredients suitable according to the invention above all are the vital nutrients and the anabolic substances, preferably selected from the group of amino acids, vitamins and minerals. Preferred amino acids include (S) -2,6-diaminohexane acid (lysine), (R) -2-amino-3-mercaptopropionic acid (cysteine) and especially 2-pyrrolidinecarbonic acid (L-proline). An anabolic substance was found with L-proline, which proved to be suitable for the care and repair of nails. As previously, L-proline was only mentioned as an optional component in the cosmetic products for the care of the nails that come either sulfur amino acids or a derivative thereof as an active component (EP-A-0 534 810). Among the preferred vitamins are cis-2- (4-carboxybutyl) -3,4-ureido tetrahydrothiophene (biotin), (±) -2,4-dihydroxy-N- (3-hydroxypropyl) -3,3-dimethylbutyramide ( panthenol), D (+) - 2,4-dihydroxy-N- (3-hydroxypropyl) -3,3-dimethylbutyramide (dexpanthenol).

The preferred minerals are the inorganic and organic compounds of calcium, magnesium and zinc, particularly in the form of organic salts such as glycerophosphate or lactate. The specific combinations of vital nutrients and anabolic substances are the following: - combinations of 2-pyrrolidinecarboxylic acid (L-proline) with one or more other nutrient or anabolic substances selected from the group of amino acids, vitamins and mineral substances. Preferred combinations of 2-pyrrolidinecarboxylic acid (L-proline) with one or more nutrients or anabolic substances are combinations with (S) -2,6-diaminohexanoic acid (lysine), (R) -2-amino-3-mercaptopropionic acid (cysteine), gelatin, cis-2- (4-carboxybutyl) -3,4-ureido-tetrahydrothiophene (biotin), (±) -2,4-dihydroxy-N- (3-hydroxypropyl) -3,3- dimethylbutyric (panthenol), D (+) - 2,4-dihydroxy-N- (3-hydroxypropyl) -3,3-dimethylbutyric acid (dexpanthenol) and inorganic and organic compounds of calcium, magnesium or zinc. The topically applied products according to the invention in addition to one or more active substances and one or more of the compounds of the formula I may contain physiologically compatible adjuvants. Suitable adjuvants of this type include, for example, terpenes or oils, alcohols, ketones, fatty acid esters, polyglycols, tensides, ureas, antioxidants and complexing agents containing terpene.

Among the suitable terpenes are acyclic, monocyclic and bicyclic terpenes, as well as oils containing these terpenes. Examples of acyclic terpenes include acyclic hydrocarbon terpenes, such as, for example, myrcene, acyclic terpenes of alcohols, such as citronellol and geraniol, as well as acyclic terpenes, aldehydes and ketones, such as, for example, citral, α-ionone and β-ionone. Examples of monocyclic terpenes include monocyclic hydrocarbon terpenes, such as, for example, α-terpinene, α-terpinene and limonene, monocyclic terpenes alcohols, such as thymol, menthol, cineole and carvacrol, as well as monocyclic terpenes ketones, such as, for example, menthone and carvona. Examples of bicyclic terpenes include terpenes of the group of the carnes such as for example carone, terpenes of the pinene group, such as, for example, α-pinene and β-pinene, as well as pertenos of the "bornane" group such as for example, camphor and borneol. Particularly suitable terpenes are monocyclic terpenes alcohols such as for example thymol and menthol. Examples of suitable terpene-containing oils include peppermint oil, cardamom oil, geranium oil, rose oil, thuja oil and thymus oil. Especially suitable are the oils of mint, lavender and thymus. Suitable alcohols are branched or unbranched alcohols having from 1 to 3 hydroxy groups and from 2 to 6 carbon atoms, the hydroxy groups optionally may be fully or partially etherified or esterified. Among the especially suitable alcohols are ethanol, 1-propanol, 2-propanol (isopropanol), 1,2-propanediol (propylene glycol), 2-phenylethanol (phenylethyl alcohol), 1-butanol (butyl alcohol), monomethyl ether ethylene glycol (methoxyethanol), monophenylether of ethylene glycol (phenoxyethanol), 1,2,3-trihydroxypropane (glycerin), ethylacetate, butylacetate, glycerin diacetate (diacetin) and glycerin triacetate (triacetin).

Suitable ketones are, for example, acetone and methyl ethyl ketone (2-butanone). As esters of fatty acids, saturated or unsaturated fatty acids, branched or unbranched, having between 8 and 21 carbon atoms are suitable, the alcohol component comprises branched and unbranched alcohols with 1 to 6 carbon atoms . Particularly suitable fatty acid esters include tridecan carboxylic acid isopropylester, tetradecane carboxylic acid isopropylester (isopropylmyristate), pentadecanecarboxylic acid methyl ester and glycerin monoester of 9-octadecenoic acid (glycerin monooleate). A suitable polyglycol is for example a polyglycol 400. Suitable surfactants include, for example, the non-ionogenic surface active substances. Particularly suitable surfactants include sorbitan fatty acid partial esters (span), polyoxyethylene sorbitan fatty acid partial esters (tween), polyoxyethylene fatty acid esters (myrj) and polyoxyethylene fatty alcohol esters (brijs). ). Among the suitable antioxidants are, for example, butylhydroxytoluene (BHT), butyl-4-methoxyphene! (BHA), tocopherols and ascorbates. Suitable complexing agents include, for example, ethylene diamine tetraacetic acid (EDTA) and disodium-ethylene diamine tetraacetic acid (Na2-ETDA). As topical application products according to the invention are considered, for example, solutions, dyes, emulsions, gels, ointments, creams and pastes. The preferred topical application form are the solutions. For the development of solutions some active ingredients such as proline need traces of water together with a solution mediator as stabilizer (prevention of discoloration). Among the suitable mediators of solution are the low potency alkanols such as methanol, ethanol, propanol and isopropanol as well as acetone. The invention also relates to a process for the manufacture of the topical application products of the invention, characterized in that the individual components are mixed homogeneously and optionally heated (up to a maximum of 80 ° C) and Beat until a homogeneous solution is obtained. The solution that is obtained is preferably used directly as it is found for its topical application. However, the solution can also be converted into another form of topical application by adding other adjuvants of physiologically acceptable formulation with the aid of conventional solution, mixing and suspension procedures. Preferably, the topical application products according to the invention are used in the form of a solution. Preferred topical products according to the present invention contain 0.1 to 20% by weight of one or more active substances. 1 to 99, 90% by weight of one or more of the compounds of the formula I and 0 to 98, 90% by weight of one or more physiologically compatible adjuvants. Furthermore, the invention relates to the use of topical application products according to the invention for the treatment, prevention, post-treatment and to support the treatment of nail diseases and periungual diseases, as well as for the care of the nails. In addition, the present invention relates to the use of the products of the invention for the treatment of fungal infections of the hooves, claws and hooves of pets and domestic animals. Topical products containing antifungals are suitable, for example, for the following indications: - treatment, prevention and post-treatment of onychomycosis, caused by dermatophytes, yeasts or fungi or mixed infections. -treatment, prevention and post-treatment of fungal infections in the nails in patients suffering from psoriasis, diabetes or SI DA. - Back treatment of periungual nail infections such as for example candida paronychium. Topical products containing antibiotics are suitable, for example, for the following indications: support of the treatment and / or prevention of infections in the nails and periunguals caused by bacteria. The topical products containing antiseptics are suitable, for example, for the following indications: - the treatment and prevention of infections in the nails and periunguals caused by non-specific or unidentified pathogens. Topical products containing corticosteroids or combinations of corticosteroids with antifungals, antibiotics or antiseptics are suitable, for example, for the following indications: - the treatment, prevention, aftercare and supportive treatment of psoriasis or other conditions in the nails or inflammatory peringuales. The pharmaceutical topical application products according to the invention are suitable for the treatment of nail and periungual diseases in the nails of the feet and hands, as well as for the treatment of diseases of hooves, claws and hooves of pets and domestic animals. The frequency of application of pharmaceutical products depends on the degree and location of the disease. In general, one to three applications per day is enough. Then, the solution is applied directly on the nail or on the helmet, the claw or the diseased hoof and, if necessary, on the areas of skin surrounding the affected area. The therapy should be continued for approximately another two to four weeks after laboratory evaluations show that there are no traces of fungi, spores or other pathogens, in order to avoid relapse. Topical cosmetic products according to the invention containing one or more nutrients or anabolic substances are suitable for nail care such as for example, atrophies in the nails of the feet or hands. Nail atrophies include the following, for example, brittle, brittle and fine nails, as well as stippling or interspersed white spots. The preparation is applied on the cosmetically ugly part of the nail (s) and, if necessary, also on the skin surrounding the affected area. The frequency of application of the preparation depends on the degree and location of the atrophy. Generally, one or two applications a day is enough. The topical application products of the invention have the advantage that they penetrate into the diseased nail together with the active substance in a few days and display their action on the nail bed and on the nail root. Due to the Quicker on its effect and its better penetration, the treatment for nail diseases as a rule ends after approximately two to four months. In this way, compliance on the part of the patient is improved, since the long duration of treatment required by the other treatment methods is shortened substantially. With sick skin, especially the periungual skin areas, the curing process and the nourishing effect starts faster, since the active substance penetrates quickly and sufficiently into the skin. Nail care should, as a rule, be done for a month. For the maintenance of a healthy nail substance, the substance for the care of the nails can also be used for a longer period. The present invention can be visualized by the following examples: Oil of blue Australian cypress, tea tree oil and lavender oil solution 6% Australian blue cypress oil 2.0 g Tea tree oil 2.0 g Oil of lavender 2.0 g Isoamylacetate 94.0 g The mixture is stirred until a homogeneous solution is obtained.

Example 2: Proline solution 2.0% L-proline 2.0 g Water (deionized) up to 2.0 g Ethanol 48.0 g Amylacetate 48.0 g L-Proline is dissolved in ethanol and traces of water under stirring. Subsequently, amylacetate is added and stirred until a homogeneous solution is obtained. Example 3: amorolfine solution 1% Amorolfine 1, 0 g Ethanol 10.0 g 1 -hexylacetate 89.0 g Amorolfine is stirred in the mixture of ethanol and hexyl acetate until a homogeneous solution is obtained. Example 4: Terbinafine solution 1% Base terbinafine base 1.0 g Isoamylacetate 99.0 g The substances are weighed in a beaker and stirred until a homogeneous solution is obtained. Example 5: Cream with amylacetate. Ion-free H2O 720 g Carbopol Ultrez 10 9.6 g Glycerin 24.0 g Sunflower oil 216.0 g Emulgade 1000 N l 45.6 g Lanette N 9.6 g Amyl ether 36.0 g Fenonip 9.6 g Triethanolamine Under agitation, disperse the carbopol in H2O and let marinate. Add glycerin and heat to + 50 ° C. Under stirring and heated to 70 ° C, achieve a clear solution of sunflower oil, Emulgade and lanette. Add amyl ester to the fatty phase and homogenize with the aqueous phase under strong agitation. Mix the fenonip in the mixture. Cool the cream and adjust the pH to 5.5 with triethanolamine.

Claims (14)

1. CLAIMS 1. Topical application products for the treatment of diseases of the nails and for the care of the nails that contain: (a) one or more active therapeutic or nutritive substances. (b) one or more of the compounds of the formula I R-O-RT (I) wherein R represents a straight or branched alkyl residue with 5-8 carbon atoms and Ri represents a formyl group or an acetyl group. (c) if necessary, physiologically compatible adjuvants.
2. 2. A product for topical application according to claim 1, characterized in that it contains a C5-C7 alkyl residue as a compound of the formula I R.
3. 3. A product for topical application according to claim 1, caracerized because it contains a residue C6 alkyl as a compound of the formula I R.
4. 4. A product for topical application according to one of claims 1, 2 or 3, characterized in that it contains a 1-hexanol alkyl residue as a compound of the formula I.
5. 5. A product for topical application according to one of claims 1, 2 or 3, characterized in that it contains 2-hexanol as a compound of the formula I.
6. 6. A product for topical application according to one of claims 1 or 2 characterized in that it contains a mixture of two or more respectively acetic formic acids of C5-C7 alkanols.
7. 7. A product for topical application according to claim 1, characterized in that it contains one or more C5-C6 alkyl acetates as a compound of the formula I.
8. 8. A product for topical application according to one of claims 1 to 7, characterized in that it contains one or more active substances selected from the group of antimycotics, antibiotics or antiseptics and corticosteroids, synthetic or natural.
9. 9. A product for topical application according to one of claims 1 to 7, characterized in that it contains one or more nutritional and curative components of the group of nutritive and anabolic substances. 1 0.
10. A product for topical application according to one of claims 1 to 9, characterized in that it contains one or more adjuvants selected from the group of terpenes or oils, alcohols, ketones, esters of fatty acids, polyglycols, tensides, urea, antioxidants and complexing agents that contain terpenes, contained in gels, ointments, creams and pastes. eleven .
11. A product for topical application according to one of claims 1 to 10, characterized in that it contains between 0.1 and 20 weight percent of one or more active substances, 1 to 99.90 weight percent of one or more of the compounds of the formula I and 0 to 98.90 weight percent of adjuvants.
12. 12. A product for topical application according to one of claims 1 - 1 for the treatment, prevention, aftercare and support for a treatment for nail diseases and periungual diseases.
13. 13. Use of a topical application product according to one of claims 1 to 12 for the care of the nails.
14. 14. Use of a product for topical application according to one of claims 1 to 12 for the treatment of fungal infections of the hooves, legs and hooves of pets and domestic animals.