TW201622710A - Topical formulation for the treatment of papillary tubercles, nail diseases and nail care - Google Patents

Abstract

Disclosed is an anhydrous topical formulation for the treatment of papillary tubercles, nail diseases and nail care, including one or more active ingredients, at least one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid, citric acid, undecanoic acid, or undecenoic acid as carrier and optional physiologically compatible auxiliary substances. The product according to the invention can be used as human medicine and also be used in veterinary medicine for treating fungal infections of hooves, claws and talons of pets, domestic animals and wild animals in captivity as well as human skin and nail.

Description

Topical formula for sputum, nail disease, and nail care

The present invention relates to an anhydrous topical product for treating cockroaches, nail diseases and nail care, comprising one or more active ingredients, one or more lactic acid, malic acid, tartaric acid, citric acid, undecane as a carrier A C ₁ -C ₄ -alkyl ester of an acid or undecylenic acid, and a physiologically compatible adjuvant as desired.

The invention also relates to a method of making such formulations and to uses thereof.

Verruca is caused by a virus, specifically papillomavirus (Papovaviren), which is a benign hyperproliferative substance in the skin papillary tissue called agglomerated keratinized skin. Easy to penetrate. At least 50 different hyperproliferative substances of the skin are classified as sputum and are caused by more than 100 prions, namely papillomavirus. It is especially divided into linear tendons, which appear as long strips of hyperproliferative substances on the face, neck or face. A flat sputum appears on the face, back of the hand, neck or chest. These defects may spread due to scratching or shaving. In addition, there is a so-called rod-shaped scorpion, which has a shape similar to that of cauliflower, which may appear on the head or neck, or a type of nail that appears on the fingers and hands, and often appears around the nail. In addition, the more troublesome and troublesome cockroaches appear on the soles of the feet, called thorns, which are extremely difficult to handle. The local treatment of sputum, nail disease and nail maintenance has no side effects and low processing cost. The main problem in the application of exfoliation and topical formulations in nail treatment and nail care is how to get enough active ingredients, nourishment - and anabolic substances through the stratum corneum Or nails that penetrate into the deep tissue to be treated to exclude pathogens under the stratum corneum, such as viral and fungal infections. Existing pathogens can be treated in a conventional manner and their symptoms can be eliminated by direct topical treatment. However, in most cases, the symptoms may recur after stopping treatment. It is known that some natural methods can be used to treat warts, but it does not really guarantee success because penetration of the skin and stratum corneum remains a problem.

It has been proposed to directly apply the active ingredient locally to improve the treatment result, wherein the active ingredient is used together with a so-called carrier, that is, in addition to improving the solubility of the active ingredient, the substance is well permeable to the stratum corneum and nails. Sexual and capable of transporting active ingredients through nail tissue. For example, in the medicine for treating mesomycin as described in EP-A-0 503 988, in addition to the antifungal active ingredient and the aqueous medium (which at least partially dissolves the antifungal agent), at least one species is promoted to promote the penetration of the antifungal agent. A hydrophilic substance of nails. In addition to a wide variety of compounds, ethyl lactate is also mentioned as a substance that promotes penetration. The formulation described in EP-A-0 503 988 is only suitable for a limited amount of active ingredient since it only partially dissolves the active ingredient. Further, from the viewpoint of the water content in the formulation, when a hydrolyzable compound (e.g., ethyl lactate) is used as the permeation-promoting substance, a stable formulation cannot be prepared because these compounds are hydrolyzed during storage. degradation.

There are currently no satisfactory products for topical treatment of nail diseases or local maintenance of nails, which contain a carrier that ensures long-term delivery of the required amount of active ingredient through the stratum corneum and nails into the nail bed and the methyl portion.

Accordingly, the object of the present invention is to solve the problems associated with the elimination of sputum, the local treatment of nail diseases and the local maintenance of nails, and to provide a medical and beauty care product which can be treated for a long period of time.

According to the present invention, there is an anhydrous topical product which can treat cockroaches, treat nail diseases and maintain nails, and has the following composition: a) one or more active ingredients, b) one or more lactic acid, malic acid, tartaric acid as a carrier a C ₁ -C ₄ alkyl ester of citric acid, undecanoic acid or undecylenic acid, and c) a physiologically compatible adjuvant which may optionally be used.

The anhydrous topical product of the present invention can basically employ all synthetic and natural substances which can treat nails and periungual diseases of sputum (super hyperproliferative substances). It can also be used to effectively maintain the nourishment and anabolic substances of nails.

A particularly important substance that eliminates cockroaches is a preparation containing tar.

Suitable active ingredients which may be included in the products according to the invention are anti-fungal agents (including synthetic and natural sources), antibiotics, antibacterial agents, corticosteroids, nourishing and anabolic substances, and combinations thereof. Specific examples of such active ingredients are:

- an antifungal agent and a physiologically compatible salt thereof, such as, for example, (±)-cis-2,6-dimethyl-4-[2-methyl-3-(p-tripentyl) -Phenyl)propyl]morpholine (Amorolfin), Amphotericin, 6-Cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridinone (Hick Ciclopirox, bis-phenyl-(2-chlorophenyl)-1-imidazolylmethane (Clotrimazol), 1-[2-(2,4-dichlorophenyl)-2 -(4-chlorobenzyloxy)-ethyl]-imidazole (Econazol), 2,4-difluoro-α,α-bis(1H-1,2,4-triazole-1 -ylmethyl)benzyl alcohol (Fluconazol), 5-fluorocytosine (Flucytosin), 7-chloro-trimethoxy-methylspiro-[benzofuran-ring Hexene]-dione (Griseofulvin), 1-[2,4-dichloro-β-(2,6-dichlorobenzyloxy)-phenethyl]-imidazole (Isoconazol)), (±)-1-second-butyl-4-{4-[4-(4-{[(2R*,4S*)-2-(2,4-dichlorophenyl)) -2-(1,2,4-triazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy}phenyl)-1-hexahydropyridyl Phenyl]-4,5-dihydro-1,2,4-triazol-5-one (Itraconazol), (±) cis-1-ethenyl-4-{ 4-([2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy)phenyl}hexahydropyridyl (Ketoconazol), 1-[2,4-dichloro-β-(2,4-dichlorobenzyloxy)-phenethyl]-imidazole (Miconazol), ( E)-N-cinnamyl-N-methyl-1-naphthylmethylamine (Naftifin), Nystatin, (E)-N-(6,6-dimethyl -2-hepten-4-ynyl)-N-methyl-1-naphthylmethylamine (Terbinafin), 1[2-{(2-chloro-3-thienyl)methoxy }}-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole (Tioconazol), O-2-naphthyl-N-methyl-N-(3-toluene Base)-thiocarbamate (Tolnaftat), α-(2,4-difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4- Triazol-1-ylmethyl)-4-pyrimidinemethanol (Voriconazol).

- Natural anti-fungal agents such as, for example, aromatic essential oils and plant extracts.

Antibiotics and their physiologically compatible salts, such as, for example, α-amino-4-hydroxybenzylpenicillin (Amoxicillin), D-(-)-α-aminobenzylmethyl Penicillin (Ampicillin), 3,3-dimethyl-7-oxo-6-phenylacetamido-4-thia-1-azabicyclo-[3.2.0]-g Alkane-2-carboxylic acid (benzylpenicillin), benzylpenicillin-bisbenzylethylenediamine, 3-chloro-7-D(2-phenylglycinenonylamino)-cephalosporic acid (Sefek) (Cefaclor)), 7β-[D-2-Amino-(4-hydroxy-phenyl)-ethinylamino]-3-methyl-cephalosporic acid (Cefadroxil), Aminobenzene -Ethylamino-methyl-cephalosporic acid (Cefalexin), D(-)-threo-2-dichloroacetamido-1-(4-nitrophenyl)-1 , 3-propanediol (Chloramphenicol, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-hexahydropyridyl) Benzyl-3-carboxylic acid (Ciprofloxacin), (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1 - azabicyclo[3.2.0]heptane-2-carboxylic acid (Clavulansaure), 7-chloro-7-deoxy-lincomycin (Clindamycin), 6- Deoxy-5-hydroxytetracycline (Doxycyclin), 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-hexahydropyridyl) 1,1,8-naphthyridine-3-carboxylic acid (Enoxacin), erythromycin, 3-(2-chloro-6-fluorophenyl)-5-methyl-4-iso Zozolyl-penicillin (Flucloxacillin), Kanamycin, Lincomycin, 7-dimethylamino-6-deoxy-6-desmethyltetracycline (II) Minocyclin, 6-(2-ethoxy-1-naphthylamino)-penicillin (Nafcillin), 1-ethyl-1,4-dihydro-7-A 4-Oxo-1,8-naphthyridine-3-carboxylic acid (Nalidixinsaure), neomycin, 1-ethyl-6-fluoro-1,4-dihydrogen -4-oxo-7-(1-hexahydropyridyl) Benzyl-3-carboxylic acid (Norfloxacin), (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-hexa) Hydrogen pyridyl -7-oxo-7H-pyrido[1,2,3-de][1,4]benzo -6-carboxylic acid (Ofloxacin), 6-(5-methyl-3-phenyl-4-iso Oxazol carboxamide) penicillin (Oxacillin), 6-phenoxyethylamino-penicillanic acid (phenoxymethyl penicillin), 4-dimethylamino-octane Hydrogen-pentahydroxy-1,11-dioxo-6-methyl-naphthylnaphthalene-2-carboxamide (tetracycline).

- an antibacterial agent such as, for example, alkylbenzyldimethylammonium chloride (benzylbenzylamine), N-benzyl-N,N-dimethyl-2-{2-[p-(1) ,1,3,3-tetramethylbutyl)-phenoxy]-ethoxy}-ethylammonium hydroxide (benzyloxychloride), cetyltrimethylammonium hydroxide (bromination Cetrimonium bromid, 1,1'-hexamethylene-bis-[5-(p-chlorophenyl)-bi-indole] (Chlorhexidin), N ¹ , N ¹ -10 Methylene-bis-(4-aminomethylquinolinium hydroxide) (Dequaliniumchlorid), N-(4-chlorophenyl)-N'-(3,4-dichlorobenzene Urea (Triclocarban), 5-chloro-2-(2,4-dichlorophenoxy)phenol (Triclosan).

a corticosteroid with a physiologically compatible salt thereof, for example, 9α-chloro-16β-methylhydropondenis (Beclomethason), 9-fluoro-11β, 17,21-trihydroxyl -16β-methyl-1,4-pregnane-3,20-dione (Betamethason), 21-chloro-9-fluoro-11β, 17-dihydroxy-16β-methyl-1 , 4-pregnane-3,20-dione (Clobetasol), 17,21-dihydroxy-pregn-4-ene-3,11,20-trione (Cortison) ), 11β, 16α, 17α, 21-tetrahydroxy-1,4-pregnane-3,20-dione-16,17-acetone acetal (Desonid), 9-fluoro- 11β-17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione (dexamethasone), 9α,11β-dichloro-6α-fluoro-21- Hydroxy-16α,17α-(isopropylidene dioxide)-pregnant-1,4-diene-3,20-dione (Flucloronid), 6α, 9α-difluoro-16α, 17α- Isopropyldioxy-corticosterone (Fluocinolonacetonid), 6α, 9α- Difluoro-16α,17α-isopropylidene dioxy-corticosterone-acetate (Fluocinonind), 6α-fluoro-11β, 21-dihydroxy-6α, 17-isopropylidene dioxide -4-pregnene-3,20-dione (Fludroxycortid), 3-(2-chloroethoxy)-9α-fluoro-6-methylindolyl-11β,21-dihydroxy- 16α,17α-isopropylidenedione-3,5-dien-20-one (Formocortal), 21-chloro-9α-fluoro-11β-hydroxy-16α, 17α-iso Propyldioxy-4-pregnene-3,20-dione (Halcinonid), 17α-hydroxycorticosterone (Hydrocortison), 11β,17,21-trihydroxy- 6α-methyl-1,4-pregnane-3,20-dione (Methylprednisolon), 11β,17,21-trihydroxy-pregnant-1,4-diene-3 , 20-diketone (Prednisolon), 17α, 21-dihydroxy-pregnant-1,4-diene-3,11,20-trione (Prednison), 9- Fluorine-16α-hydroxyhydroprednisolone (Triamcinolon), Hydroxyprednisolone-16α, 17α-acetonide (Triamcinolonacetonid).

A preferred antifungal agent according to the invention is bis-phenyl-(2-chlorophenyl)-1-imidazolylmethane (Clotrimazol), 1-[2,4-dichloro-β-(2) ,6-dichlorobenzyloxy)-phenethyl]-imidazole (Isoconazol), 2,4-difluoro-α,α-bis(1H-1,2,4-triazole- 1-ylmethyl)benzyl alcohol (Fluconazol), (±)-1-t-butyl-4-{4-[4-(4-{[(2R*,4S*)) -2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy}phenyl)-1-hexahydropyridyl Phenyl]-4,5-dihydro-1,2,4-triazol-5-one (Itraconazol), (±)cis-1-ethinyl-4-{ 4-([2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy)phenyl}hexahydropyridyl (Ketoconazol), 1-[2,4-dichloro-β-(2,4-dichlorobenzyloxy)-phenethyl]-imidazole (Miconazol), ( E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthylmethylamine (Terbinafin), α-(2 ,4-difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidinemethanol (Voriconazol )).

A preferred antifungal agent according to the invention is bis-phenyl-(2-chlorophenyl)-1-imidazolylmethane (Clotrimazol), 1-[2,4-dichloro-β-(2) ,6-dichlorobenzyloxy)-phenethyl]-imidazole (Isoconazol), (±)-1-t-butyl-4-{4-[4-(4-{[ (2R*,4S*)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy}phenyl)-1-hexahydropyridyl Phenyl]-4,5-dihydro-1,2,4-triazol-5-one (Itraconazol), (±)cis-1-ethinyl-4-{ 4-([2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy)phenyl}hexahydropyridyl (Ketoconazol).

Preferred natural antifungal agents are Melaleuca alternifolia, Lavandula officinalis chaix and ABC-oil (Australien Blue Cypress Oel-Callitris Intratropica). These natural antifungal agents can be used alone as active ingredients or in combination with other various such active ingredients. A preferred combination of active ingredients is a mixture of lavender oil, tea tree oil, rock oil and ABC oil.

Preferred antibacterial agents are, for example, 1,1'-hexamethylene-bis-[5-(p-chlorophenyl)-bi-indole] (Chlorhexidin).

Preferred corticosteroids are 11β, 16α, 17α, 21-tetrahydroxy-1,4-pregnane-3,20-dione-16,17-acetone acetal (Desonid), 9α , 11β-dichloro-6α-fluoro-21-hydroxy-16α, 17α-(isopropylidene dioxide)-pregnant-1,4-diene-3,20-dione (Flucloronid) , 6α, 9α-difluoro-16α, 17α-isopropylidene dioxy-corticosterone (Fluocinolonacetonid), 6α, 9α-difluoro-16α, 17α-isopropylidene dioxy-corticosterone- Acetate (Fluocinonind), 6α-fluoro-11β, 21-dihydroxy-6α, 17-isopropylidenedioxo-4-pregnene-3,20-dione (fluorohydrogen) (Fludroxycortid)), 3-(2-chloroethoxy)-9α-fluoro-6-methylindolyl-11β,21-dihydroxy-16α,17α-isopropylidenedioxypregnant-3,5-di Ace-20-one (Formocortal), 21-chloro-9α-fluoro-11β-hydroxy-16α, 17α-isopropylidenedioxo-4-pregnene-3,20-dione ( Halcinonid), Hydroxyprednisolone-16α, 17α-acetonide (Triamcinolonacetonid).

Examples of specific combinations of active ingredients are:

A combination of a corticosteroid and an antifungal, antibiotic or antibacterial agent. A preferred combination is, for example: (±)cis-1-ethylindolyl-4-{4-([2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl) )-1,3-two Pultane-4-yl]methoxy)phenyl}-hexahydropyridyl (Ketoconazol) with 11β,16α,17α,21-tetrahydroxy-1,4-pregnane-3,20-dione-16,17-acetone acetal (Desonid) )) combination.

A combination of a synthetic antifungal agent and a natural antifungal agent. A preferred combination is a combination of bis-phenyl-(2-chloro-phenyl)-1-imidazolylmethane (Clotrimazol) and tea tree oil.

A combination of various natural antifungal agents. A preferred combination is a combination of lavender oil, tea tree oil and ABC oil (Australian Blue Cypress Oel).

2-pyrrolidinecarboxylic acid (L-proline) is combined with one or more other nourishing-and metabolites selected from the group consisting of amino acids, vitamins and minerals.

A preferred combination of 2-pyrrolidinecarboxylic acid (L-proline) with one or more nourishing-and metabolites is (S)-2,6-diaminohexanoic acid (isoamine), (R )-2-amino-3-hydrothiopropionic acid (cysteine), gelatin, cis-2-(4-carboxybutyl)-3,4-ureidotetrahydrothiophene (biotin), (±) 2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutylimamine (ubiquinol), D(+)-2,4-dihydroxy-N- Combination of (3-hydroxypropyl)-3,3-dimethylbutyramine (panthenol) with an inorganic or organic calcium, magnesium or zinc compound.

L-proline is an anabolic substance that is particularly suitable for nail anabolism and nail care. L-proline is currently only a component of the nail care product as an active ingredient comprising a thiol-containing acid or a thiol-containing acid derivative (EP-A-0 534 810).

The above substances are represented below by the corresponding names indicated by the names in parentheses above.

The C ₁ -C ₄ -alkyl ester used as a carrier includes a methyl ester, an ethyl ester, a n-propyl ester, an isopropyl ester, a n-butyl ester, a second butyl ester, an isobutyl ester, and a third butyl ester. The polybasic acid: an ester of malic acid, citric acid and tartaric acid, the C ₁ -C ₄ -alkyl group of the ester group may be the same or different. The polybasic acid as described above may be esterified from all carboxylates or partial carboxylates. In addition to malic acid and di-C ₁ -C ₄ -alkyl tartaric acid, the corresponding malic acid and monoalkyl tartrate can also be used. Suitable C ₁ -C ₄ -alkyl citrates are the corresponding mono-, di- and trialkyl esters. Preferred esters are ethyl esters. Other preferred esters are isopropyl esters. A preferred single compound is ethyl lactate. Other preferred single compounds are diethyl malate and diisopropyl malate.

The topical product of the present invention comprises one or more active ingredients and one or more C ₁ -C ₄ -alkyl esters of lactic acid, malic acid, tartaric acid, citric acid, undecanoic acid or undecylenic acid as a carrier In addition, physiologically compatible adjuvants may also be included. Suitable adjuvants are, for example, terpenes or terpene-containing oils, alcohols, ketones, fatty acid esters, polyethylene glycols, surfactants, ureas, antioxidants and error correcting agents.

Suitable terpenes are acyclic, monocyclic and bicyclic terpenes and oils containing such terpenes. Examples of acyclic terpenes are acyclic azepines such as, for example, geranyl, acyclic terpene alcohols such as, for example, citronellol and geraniol, and acyclic alkene aldehydes and Ketones such as, for example, citral, alpha-ionone and beta-ionone. Examples of the monocyclic terpene are monocyclic decenes such as, for example, α-萜, γ-萜 and decene, monocyclic decenol, such as, for example, thymol, menthol, eucalyptus and incense Celery, and monocyclic terpene ketones such as, for example, menthone and carvone. Examples of the bicyclic terpene are decane terpenes such as, for example, anthrone, decane terpenes such as, for example, α-pinene and β-pinene, and borneane-based terpenes such as, for example, hydrazine Alkene and borneol. Particularly suitable terpenes are monocyclic terpene alcohols such as, for example, thymol and menthol. Examples of suitable terpene-containing oils are peppermint oil, cardamom oil, yak oil, rose oil, rock oil and thyme oil. Particularly suitable oils are peppermint oil, lavender oil and thyme oil. As mentioned above, rock tar is particularly suitable for eliminating cockroaches.

Suitable alcohols are branched or unbranched alcohols having from 1 to 3 hydroxyl groups and from 2 to 6 carbon atoms, wherein the hydroxyl groups may be partially or fully etherified or esterified. Particularly suitable alcohols are ethanol, 1-propanol, 2-propanol (isopropanol), 1,2-propanediol (propylene glycol), 2-phenylethanol (phenylethanol), 1-butanol (butanol) ), ethylene glycol monomethyl ether (methoxyethanol), ethylene glycol monophenyl ether (phenoxyethanol), 1,2,3-trihydroxypropane (glycerol), ethyl acetate, butyl acetate , diacetin (diacetin) and triacetin (triacetin).

Examples of suitable ketones are acetone and methyl ethyl ketone (2-butanone).

Fatty acid esters are saturated and unsaturated, branched and unbranched fats of 8 to 21 carbon atoms An acid ester having an alcohol component comprising branches of 1 to 6 carbon atoms and unbranched alcohols. Particularly suitable fatty acid esters are isopropyl tridecyl carboxylic acid, isopropyl myristate (isopropyl myristate), methyl pentadecylcarboxylate and 9-octadecenoic acid glycerol. Monoester (glycerol monooleate).

A suitable polyethylene glycol is, for example, polyethylene glycol 400.

Suitable surfactants are, for example, nonionic surfactants. Particularly suitable surfactants are partial fatty acid esters of sorbitan (Span), partial fatty acid esters of polyoxyethylene sorbitan (Tween), fatty acid esters of polyoxyethylene (Myrj) and poly A fatty alcohol ether of oxyethylene (Brij).

Suitable antioxidants are, for example, butylhydroxytoluene (BHT), butyl-4-methoxyphenol (BHA), tocopherol and ascorbic acid.

Suitable, for example, the wrong agent: ethylenediaminetetraacetic acid (EDTA) and disodium ethylenediaminetetraacetic acid (Na ₂ -ETDA).

The topical product according to the present invention may be, for example, a solution, an elixir, an emulsion, a gel, an ointment, a cream, and a paste. A preferred topical application form is a solution.

The invention also relates to a method for producing a topical product of the invention, characterized in that uniformly mixing ethyl lactate with one or more auxiliary agents, and then adding one or more active ingredients to the mixture by stirring, if necessary, heating (up to 80 ° C), Stirring is continued until a homogeneous solution is obtained. The resulting solution is preferably used directly for topical application. However, the solution may also be supplemented with other physiologically compatible formulation adjuvants, converted to another topical application form using conventional dissolution, mixing and suspension methods.

The topical product of the present invention is preferably used in a solution form. Preferred topical products according to the invention comprise: 0.01 to 20% by weight of one or more active ingredients, 1 to 99.99% by weight of one or more C ₁ -C ₄ -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid and 0 Up to 98.99% by weight of one or more physiologically compatible adjuvants.

The invention also relates to the use of the topical product of the invention for treatment, prevention, post-treatment or supportive treatment of sputum, nail disease and periungual disease, and nail maintenance. Furthermore, the present invention relates to the use of the product of the present invention for the treatment of fungal infections of domestic animals and pets, hooves, claws and claws.

Topical products containing anti-fungal agents are suitable for the following diseases: - treatment, prevention and post-treatment of onychomycosis caused by dermatophytes, yeasts or molds or mixed infections - treatment, prevention and post-treatment of dryness, diabetes or Nail mold infection in AIDS patients, - supportive treatment of nail infections in the week, such as, for example, Candida paronychium.

The topical product containing antibiotics is suitable for, for example, the following diseases: - supportive treatment and/or prevention of nail-to-peri-infection caused by bacteria.

The topical product containing the antibacterial agent is suitable for, for example, the following diseases: - treatment and prevention of nail-to-peri-infection caused by non-specific or unidentified pathogenic bacteria.

Topical products containing corticosteroids or a combination of corticosteroids and antifungal agents, antibiotics or antibacterial agents are suitable, for example, for the following diseases: treatment, prophylaxis, post-treatment or supportive treatment, nails, cognac or other inflamed nails - With a week of disease.

The topical medicinal product of the invention is suitable for treating nail diseases and nail disease of sputum, fingers and toes, and can treat diseases of hooves, claws and claws of pets and livestock. The frequency of application of pharmaceutical products depends on the extent and location of the disease. It is usually sufficient to apply 1 to 3 times a day. The solution can be applied directly to the affected area of the nail, or to the hoof, claw or claw, and if desired, to the skin surrounding the affected area. The therapy should continue to be administered for about 2 weeks after the symptoms are removed to prevent recurrence.

Containing one or more nourishing-and topical cosmetic uses of anabolic substances in accordance with the present invention The product is suitable for the maintenance of nails, such as, for example, the toes of the toes and fingers are atrophied. Nail atrophy includes, for example, fragility, cracking and thin nails, as well as the appearance of spots or line-like white spots. The formulation is applied to unsightly nails and can be applied to the surrounding skin as needed. The frequency of application of the formulation varies depending on the degree of shrinkage and location. Usually, it is sufficient to apply 1-2 times a day.

An advantage of the topical product of the present invention is that it allows the active ingredient to enter the affected part of the nail within a few days and function at the nail bed and nail base. The treatment of nail disease usually ends after about 2 to 3 months by the effect of a quick start and its improved penetration. In this way, it is clear that the patient's adaptability can be improved because it substantially shortens the long-term treatment required by other methods. In the affected part of the skin, in particular, the skin part of the nail is cured, and the healing process is quick and fast, because the active ingredient can penetrate into the skin sufficiently and rapidly. Nail maintenance is usually carried out for one month. To maintain healthy nails, you can also use nail care products for a long time.

The following examples illustrate the invention:

Example 1:

Clotrimazol-solution 1%

The urea was added with stirring to 20 ml of ethyl lactate, and dissolved in a 100 ml flask by heating (about 50 ° C). Clotrimazol was added to the above solution with stirring, and then ethyl lactate was added to 100 ml. Stirring is continued until a homogeneous solution is formed.

Example 2:

Example 3:

Rock oil 2.0%

Example 4:

Example 5:

Example 6:

Example 7:

Example 8:

Clotrimazol - Tea Tree Essential Oil - Solution 1% + 10%

The urea was added with stirring to 20 ml of ethyl lactate, and dissolved in a 100 ml flask by heating (about 50 ° C). Clotrimazol and tea tree essential oil were added to the above solution with stirring, and then ethyl lactate was added to 100 ml. Stirring is continued until a homogeneous solution is formed.

Example 9:

Tea Tree Oil - Lavender Oil - Solution 1.0%

Measure all the ingredients and add to the beaker and stir until a homogeneous solution is formed.

Example 10:

ABC oil - solution 2%

The mixture was stirred until a homogeneous solution was formed.

Example 11:

Proline-solution 1.5%

L-proline was added to propylene glycol with stirring and dissolved by heating. Finally, ethyl lactate was added and stirring was continued until a homogeneous solution was formed.

Example 12:

L-Proline was added to the diethyl malate with stirring and stirring was continued until complete dissolution.

Example 13:

The compositions of the invention are shown in the table below using 50.0 grams of each of the hydroxycarboxylic acid-C ₁ -C ₄ -alkyl esters according to the invention as carrier and each 1.0 gram of active ingredient. The composition is prepared by adding the active ingredient to the hydroxycarboxylate under stirring at room temperature or slightly (about 30 ° C to 50 ° C). Depending on the active ingredient, after stirring for 1-5 hours, a solution which can be used immediately is formed, wherein 2-5% of the lower alcohol is added as a solvent depending on the solubility of the active ingredient.

Example 14:

Other compositions of the invention are shown in the table below using 92.0 grams of each of the hydroxycarboxylic acid-C ₁ -C ₄ -alkyl esters according to the invention as carrier and 8.0 grams of 5 grams of lavender oil, 1.0 grams of tea tree oil and 2 grams of ABC oil consists of a combination of active ingredients. The composition is prepared by adding the active ingredient to the respective hydroxycarboxylic acid esters used at room temperature with stirring. The resulting composition can be used.

Claims (20)

A topical composition for treating bismuth comprising a) one or more active ingredients, b) one or more lactic acid, malic acid, tartaric acid, citric acid, undecanoic acid or undecene as a carrier The C ₁ -C ₄ -alkyl acid of the acid and c) may be selected as physiologically compatible adjuvants. A topical composition according to claim 1 which is characterized in that it comprises ethyl esters of lactic acid, malic acid, tartaric acid, citric acid, undecanoic acid or undecylenic acid as a carrier. A topical composition according to claim 1, characterized in that it comprises isopropyl ester of lactic acid, malic acid, tartaric acid, citric acid, undecanoic acid or undecylenic acid as a carrier. A topical composition according to claim 1 or 2, characterized in that it contains ethyl lactate as a carrier. A topical composition according to claim 1 which is characterized in that it contains methyl undecanoate or methyl undecylenate. A topical composition according to claim 1 or 2, characterized in that it comprises diethyl malate as a carrier. The topical composition according to any one of claims 1 to 3, characterized in that it contains one or more substances selected from the group consisting of: synthetic or natural antifungal agents, antibiotics, antibacterial agents Agents, corticosteroids and nourishment - and anabolic substances. The topical composition according to any one of claims 1 to 3, characterized in that it comprises one or more anti-fungal active ingredients selected from the group consisting of: (±)-cis-2,6- Dimethyl-4-[2-methyl-3-(p-tripentyl-phenyl)propyl]morpholine (Amorolfin), Amhotericin, 6-ring Hexyl-1-hydroxy-4-methyl-2(1H)-pyridone (Ciclopirox), bis-phenyl-(2-chlorophenyl)-1-imidazolylmethane (clotrimazole) Clotrimazol)), 1-[2-(2,4-dichlorophenyl)-2-(4-chlorobenzyloxy)-ethyl]-imidazole (Econazol), 2,4- Difluoro-α,α-bis(1H-1,2,4-triazol-1-ylmethyl)benzyl alcohol (Fluconazol), 5-fluorocytosine (Flucytosin) )), 7-chloro-trimethoxy-methylspiro-[benzofuran-cyclohexene]-dione (Griseofulvin), 1-[2,4-dichloro-β-(2 ,6-dichlorobenzyloxy)-phenethyl]-imidazole (Isoconazol), (±)-1-second-butyl-4-{4-[4-(4-{ [(2R*,4S*)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy}phenyl)-1-hexahydropyridyl Phenyl]-4,5-dihydro-1,2,4-triazol-5-one (Itraconazol), (±) cis-1-ethenyl-4-{ 4-([2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-di Pultane-4-yl]methoxy)phenyl}hexahydropyridyl (Ketoconazol), 1-[2,4-dichloro-β-(2,4-dichlorobenzyloxy)-phenethyl]-imidazole (Miconazol), ( E)-N-cinnamyl-N-methyl-1-naphthylmethylamine (Naftifin), Nystatin, (E)-(6,6-dimethyl-2 -hepten-4-ynyl)-N-methyl-1-naphthylmethylamine (Terbinafin), 1-[2-{(2-chloro-3-thienyl)methoxy }-2-(2,4-Dichlorophenyl)ethyl]-1H-imidazole (Tioconazol), O-2-naphthyl-N-methyl-N-(3-methylphenyl) )-thiocarbamate (Tolnaftat), α-(2,4-difluorophenyl)-5-fluoro-β-methyl-α-(1H-1,2,4-three Zin-1-ylmethyl)-4-pyrimidinemethanol (Voriconazol). A topical composition according to any one of claims 1 to 3, characterized in that it comprises one or more antibacterial or antifungal active ingredients selected from the group consisting of: tea tree oil, lavender oil, rock oil and ABC oil. A topical composition according to any one of claims 1 to 3, characterized in that it comprises one or more antibacterial or antifungal active ingredients selected from the group consisting of rock oil and ABC oil. The topical composition according to any one of claims 1 to 3, characterized in that it comprises one or more antibiotic active ingredients selected from the group consisting of α-amino-4-hydroxybenzylthamycin (Amoxicillin), D-(-)-α-aminobenzylpenicillin (Ampicillin), 3,3-dimethyl-7-oxo-6-phenyl Amidino-4-thia-1-azabicyclo-[3.2.0]-heptane-2-carboxylic acid (benzylpenicillin), benzylpenicillin-bisbenzylethylenediamine, 3-chloro -7-D (2-phenylglycine amide)-cephalosporic acid (Cefaclor), 7β-[D-2-amino-(4-hydroxy-phenyl)-ethinylamine 3-methyl-cephalosporic acid (Cefadroxil), aminophenyl-acetamido-methyl-cephalosporic acid (Cefalexin), D(-)-threo -2-Dichloroacetamido-1-(4-nitrophenyl)-1,3-propanediol (Chloramphenicol, 1-cyclopropyl-6-fluoro-1,4-dihydrogen) -4-oxo-7-(1-hexahydropyridyl) Benzyl-3-carboxylic acid (Ciprofloxacin), (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1 - azabicyclo[3.2.0]heptane-2-carboxylic acid (Clavulan-saure), 7-chloro-7-deoxy-lincomycin (Clindamycin), 6-deoxy-5-hydroxytetracycline (Doxycyclin), 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-hexahydropyridyl) 1,1,8-naphthyridine-3-carboxylic acid (Enoxacin), erythromycin, 3-(2-chloro-6-fluorophenyl)-5-methyl-4-iso Zozolyl-penicillin (Flucloxacillin), Kanamycin, Lincomycin, 7-dimethylamino-6-deoxy-6-desmethyltetracycline (II) Minocyc-lin), 6-(2-ethoxy-1-naphthylamino)-penicillin (Nafcilin), 1-ethyl-1,4-dihydro-7 -Methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (Nalidixinsaure), neomycin, 1-ethyl-6-fluoro-1,4- Dihydro-4-oxo-7-(1-hexahydropyridyl Benzyl-3-carboxylic acid (Norfloxacin), (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-hexa) Hydrogen pyridyl -7-oxo-7H-pyrido[1,2,3-de][1,4]benzo -6-carboxylic acid (Ofloxacin), 6-(5-methyl-3-phenyl-4-iso Oxazol carbamoyl) penicillin (Oxacillin), 6-phenoxyethylaminol-penicillanic acid (phenoxymethyl penicillin) and 4-dimethylamino-octane Hydrogen-pentahydroxy-1,11-dioxo-6-methyl-naphthylnaphthalene-2-carboxamide (tetracycline). The topical composition according to any one of claims 1 to 3, characterized in that it comprises one or more antibacterial active ingredients selected from the group consisting of alkylbenzyldimethylammonium chloride ( Chlorobenzylamine), N-benzyl-N,N-dimethyl-2-{2-[p-(1,1,3,3-tetramethylbutyl)-phenoxy]-B Oxy}-ethylammonium hydroxide (benzyloxyethylamine chloride), cetyltrimethylammonium hydroxide (Cetrimonium bromid), 1,1'-hexamethylene-bis- [5-(p-chlorophenyl)-bi-indole] (Chlorhexidin), N ¹ , N ¹ - decamethylene-bis-(4-aminomethylquinolinium hydroxide) (Dequaliniumchlorid), N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)urea (Triclocarban), 5-chloro-2- (2,4-Dichlorophenoxy)phenol (Triclosan). The topical composition according to any one of claims 1 to 3, characterized in that it comprises one or more corticosteroid active ingredients selected from the group consisting of 9α-chloro-16β-methylhydropononi Pine (Beclomethason), 9-fluoro-11β, 17,21-trihydroxy-16β-methyl-1,4-pregnane-3,20-dione (Betamethason) , 21-chloro-9-fluoro-11β, 17-dihydroxy-16β-methyl-1,4-pregnane-3,20-dione (Clobetasol), 17,21-dihydroxy -pregn-4-ene-3,11,20-trione (Cortison), 11β,16α,17α,21-tetrahydroxy-1,4-pregnane-3,20-dione- 16,17-acetone acetal (Desonid), 9-fluoro-11β-17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione (Dexa-methason), 9α, 11β-dichloro-6α-fluoro-21-hydroxy-16α, 17α-(isopropylidene dioxide)-pregnant-1,4-diene-3, 20-diketone (Flucloronid), 6α, 9α-difluoro-16α, 17α-isopropylidene dioxy-corticosterone (Fluocinolonacetonid), 6α, 9α-difluoro-16α, 17α-isopropylidene dioxy-corticosterone-acetate (Fluocinonid), 6α-fluoro-11β, 21-two Base-6α,17-isopropylidenedioxo-4-pregnene-3,20-dione (Fludroxycortid), 3-(2-chloroethoxy)-9α-fluoro-6 -Methylmercapto-11β,21-dihydroxy-16α,17α-isopropylidenedioxos-3,5-dien-20-one (Fluoromethine) (Formocortal)), 21-chloro-9α-fluoro-11β-hydroxy-16α, 17α-isopropylidenedioxo-4-pregnene-3,20-dione (Halcinonid), 17α - Hydroxycorticosterone (Hydrocortison), 11β, 17, 21-trihydroxy-6α-methyl-1,4-pregnane-3,20-dione (methylhydropondenol) Methylprednisolon)), 11β,17,21-trihydroxy-pregnant-1,4-diene-3,20-dione (Prednisolon), 17α,21-dihydroxy-pregnant-1,4 -diene-3,11,20-trione (Prednison), 9-fluoro-16α-hydroxyhydroprednisolone (Triamcinolon), Hydroxyprednisolone -16α, 17α-acetonide (Triamcinolonacetonid). A topical composition according to any one of claims 1 to 3, characterized in that it comprises a nourishing-and anabolic substance L-proline. The topical composition according to any one of claims 1 to 3, wherein the composition comprises L-proline and one or more nourishment- and anabolisms selected from the group consisting of amino acids, vitamins and minerals. a combination of substances. The topical composition according to any one of claims 1 to 3, characterized in that it comprises L-proline and one or more selected from the group consisting of: lysine, cysteine, gelatin, biotin, ubiquinol , a combination of panthenol and inorganic or organic calcium, magnesium or zinc compounds - a combination of anabolic substances. The topical composition according to any one of claims 1 to 3, characterized in that it contains one or more adjuvants selected from the group consisting of terpenes or terpene-containing oils, alcohols, ketones, Fatty acid esters, polyethylene glycols, surfactants, urea, antioxidants and modifiers. The topical composition according to any one of claims 1 to 3, characterized in that it contains 0.01 to 20% by weight of one or more active ingredients, 1 to 99.99% by weight of lactic acid, malic acid, tartaric acid, citric acid, ten a C ₁ -C ₄ -alkyl ester of monoalkanoic acid or undecylenic acid, and 0 to 98.99% by weight of an adjuvant. A method of producing a topical composition according to any one of claims 1 to 18, characterized by uniformly mixing one or more of lactic acid, malic acid, tartaric acid, citric acid, undecanoic acid or undecylenic acid The C ₁ -C ₄ -alkyl ester can be optionally added with one or more adjuvants, and then one or more active ingredients are added to the mixture with stirring, and if necessary, heated to dissolve, and stirring is continued until a homogeneous solution is formed. A method of producing a topical composition according to any one of claims 1 to 18, characterized in that other physiologically compatible compounding agents are added to the solution of claim 18, and converted into the same by conventional methods. Topical application pattern.