AU2005203232B2

AU2005203232B2 - Topical formulations for the treatment of papillary tubercles, nail diseases and nail care

Info

Publication number: AU2005203232B2
Application number: AU2005203232A
Authority: AU
Inventors: Hans Meyer
Original assignee: BioEqual AG
Current assignee: BioEqual AG
Priority date: 2005-07-21
Filing date: 2005-07-21
Publication date: 2012-12-20
Anticipated expiration: 2025-07-21
Also published as: AU2005203232A1

Abstract

Topical Formulations for the Treatment of Papillary Tubercles, Nail Diseases and Nail Care Abstract The present invention relates to water-free, topical application products for removing 5 papillary tubercles (tissues) on the skin and for the treatment of nail diseases and nail care, containing one or more CI-C 4-alkyl esters of lactic acid, malic acid, tartaric acid, citric acid, undecanic acid or undecenic acid as carriers and optionally physiologically compatible adjuvants. The invention relates a method for manufacturing those formulations and the use 10 thereof.

Description

S&F Ref: 729237 AUSTRALIA PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT Name and Address BioEqual AG, of Hofackerstrasse 12, CH-4123, Muttenz of Applicant: BL, Switzerland Actual Inventor(s): Hans Meyer Address for Service: Spruson & Ferguson St Martins Tower Level 35 31 Market Street Sydney NSW 2000 (CCN 3710000177) Invention Title: Topical formulations for the treatment of papillary tubercles, nail diseases and nail care The following statement is a full description of this invention, including the best method of performing it known to me/us:- 1 Topical Formulations for the Treatment of Papillary Tubercles, Nail Diseases and Nail Care The present invention relates to water-free, topical application products for removing papillary tubercles (tissues) on the skin and for the treatment of nail diseases and nail care, 5 containing one or more Ci-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid, citric acid, undecanic acid or undecenic acid as carriers and optionally physiologically compatible adjuvants. The invention relates a method for manufacturing those formulations and the use thereof. 10 Papillary tubercles (Verruca) are mostly benign exuberances of papillary tissues under a congealed hornskin named kreatinine not easily to be penetrated caused by viruses, especially papoviruses. At least 50 different exuberances of papillary tissues are classified as papillary tubercles which may be caused by more than 100 papillary tubercles viruses, e.g. stems of papilloma-viruses. There are differentiated especially thread-like papillary 15 tubercles, long, narrow exuberances situated in faces, necks or eyelids. Flat papillary tubercles are to be found in faces, backs of hands, necks or breasts (chests). Those papillary tubercles may expand by scratching or by shaving. Furthermore there are so-called stalked papillary tubercles which are very similar looking to cauliflower and situated at the head or neck or periungual papillary tubercles on fingers and hands, often to be found situated around 20 nails. Furthermore annoying and troublesome papillary tubercles are to be found on the sole of the foot and are designated as thorn or spine papillary tubercles, which are very difficult to be treated. The topical treatment of papillary tubercles, nail diseases and nail care are free of side effects and may be executed at low costs. 25 The main problem of removing papillary tubercles and the use of the topical formulations for nail treatment and nail care is the possibility of having the active compounds, and adjuvants penetrated in adequate quantity through the horn layer or through the nail into the treated tissue, in order to remove viruses and mycotic infections below the horn layer. 30 Using common methods and common active ingredients the germs or spores may be reached and the mycotic infections reduced. In most cases after the stop of treatment, the symptoms may occur again. In cases of the treatment of papillary tubercles some natural methods are known which do not really guarantee success, the penetration of skin and hornlayers are defined as problematic. 35 It has already been proposed to improve the results of the treatment with the direct topical use of active substances in that the active substances were used together with a so called carrier, i.e. a substance which in addition to a good solubility for the active substance also possesses a good penetrability through hornskin- layers and the nail substance and the ability to transport the active substance through the nail tissue. As an example, EP-A-0 503 40 988 describes medicaments for the treatment of onychomycoses, which in addition to an 2 antimycotically active substance and an aqueous medium, in which the antimycotic is at least partly soluble, contains at least one hydrophilic substance promoting the penetration of the active ingredient, e.g. antimycotic through the nail. In addition to a large number of compounds also lactic acid ethyl ester is mentioned as penetration promoting substance. The formulation principle described in EP-A-0 503 988 is in view of the partial water-solubility postulated for the active substance only useful for a limited number of active substances. In addition, and in view of the water content of the formulation when using hydrolysable compounds as penetration promoting substances, such as lactic acid ethyl ester, no stable formulations can be prepared according to this principle, since such compounds decompose by hydrolysis during storage. Up to the present no satisfactory product for topical treatment papillary tubercles and of nail diseases and for topical nail care exists, which contains a carrier guaranteeing the transport of the amount of active substance through the hornskin layer and nail into the deeper situated tissue and nail bed and to the nail root (matrix) required for a long-term treatment result. It is therefore the task of the present invention to solve the problems connected with the topical treatment of papillary tubercles and of nail diseases and the topical nail care and to provide pharmaceutical and cosmetic products which enable a long-term treatment result. It is therefore the task of the present invention to solve the problems connected with the topical treatment of papillary tubercles and of nail diseases and the topical nail care and to provide pharmaceutical and cosmetic products which enable a long-term treatment result. According to the present invention water-free topical application products for removing papillary tubercles and for the treatment of nail diseases and nail care are proposed, which have the following composition: a) one or more active substances b) one or more CI-C- 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid, undecanic acid and undecenic acid as carrier and c) optionally physiologically compatible adjuvants. In a first aspect there is provided a water-free topical application composition when used for the treatment of papillary tubercles, of nail diseases and nail care consisting essentially of: a) one or more active substances; and b) one or more CI-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid, undecanic acid or undecenic acid as carrier, wherein the carrier is a penetration promoting substance and optionally physiologically compatible adjuvants.

2a In an embodiment, the topical application product is characterised in that it contains an ethyl ester of lactic acid, malic acid, tartaric acid, citric acid, undecanic acid or undecenic acid as carrier. In another embodiment, the topical application product is characterised in that it contains an isopropyl ester of lactic acid, malic acid, tartaric acid or citric acid, undecanic acid or undecenic acid as carrier. In an embodiment, the topical application product is characterised in that it contains lactic acid ethyl ester as carrier. For removing papillary tubercles formulations containing thuja- oil are of great importance.

3 In one embodiment, the topical application product is characterised by a content of one or more active substances selected from the group consisting of antimycotics of synthetic or natural origin, antibiotics, antiseptics, corticosteroids and nutrient and anabolic substances. In another embodiment, the topical application product is characterised by a content of one or 5 more antimycotic active substances selected from the group consisting of (+)-cis-2,6 dimethyl-4-[2-methyl-3-(p-tert-pentyl phenyl)propyl]morpholine (amorolfin), amphotericin, 6-cyclohexyl-1 -hydroxy-4-methyl-2(1H)pyridinone (ciclopirox), bis-phenyl-(2 chlorophenyl)- 1 -imidazolylmethane (clotrimazole), 1-[2-(2,4-dichlorophenyl)-2-(4 chlorobenzyloxy)ethyl-1-imidazole (econazole), 2,4-difluoro-a,a-bis(l H- 1,2,4-triazol- 1 10 ylmethyl)benzyl alcohol (fluconazole), 5-fluorocytosine (flucytosine), 7-chloro-trimethoxy methylspiro-[benzofuran-cyclohexene]dione-(griseofulvin), 1-[2,4-dichloro-p-(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]phenyl } -4,5-dihydro- 1,2,4-triazol-5-one (itraconazole), (+) 15 cis- 1 -acetyl-4- {4-([2-(2,4-dichlorophenyl)-2-(1 H-imidazol- 1 -ylmethyl)- 1,3 -dioxolan-4 yl]methoxy)phenyl}piperazine (ketoconazole), 1-[2,4-dichloro-$-(2,4-dichlorobenzyloxyl) phenethyl]-imidazole(miconazole), (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(2,4dichlorophenyl)ethyl]-1H-imidazole 20 (tioconazole), O-2-naphthyl-N-methyl-N(3-tolyl)-thiocarbamate (tolnaftat) and a-(2,4 difluorophenyl)-5-fluoro-p-methyl-a-(1H-1,2,4-tria zol- 1 -ylmethyl)-4-pyrimidinethanol (voriconazole). In one embodiment, the topical application product is characterised by a content of one or more antibacterially or antimycotically active substances selected from tea tree oil, 25 lavender oil, thuja oil and leaf extract of the neem tree and ABC-Oil. In one embodiment, the topical application product is characterised by a content of one or more antibiotic substances selected from a-amino-4-hydroxybenzylpenicillin (amoxicillin), D-(-)-a-aminobenzylpenicillin (ampicillin), 3,3-dimethyl-7-oxo-6 phenylacetamido-4-thia-1-azabicyclo-[3.2.0]-heptan-2-carboxylic acid (benzylpenicillin), 30 benzylpenicillin-benzathine, 3-chloro-7-D-(2-phenylglycinamido)-cephalosporanic acid (cefaclor), 7-p.-[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 fluoro-1,4-dihydro-4-oxo-7-(piperazinyl)3-quinolinecarboxylic acid (ciprofloxacin), (Z) 35 (2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptan-2-carboxylic acid (clavulanic acid), 7-chloro-7-desoxy- 1 -lincomycin (clindamycin), 6-desoxy-5 hydroxytetracycline (doxycycline), 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8 naphthyridin-3-carboxylic acid (enoxacin), erythromycin, 3-(2-chloro-6-fluorophenyl)5 methyl-4-isoxazolyl-penicillin (flucloxacillin), kanamycin, lincomycin, 7-dimethylamino-6 40 desoxy-desmethyltetracycline (minocycline), 6-(2-ethoxy- 1 -naphthamido)-penicillin 4 (nafcillin), 1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridin-3-carboxylic acid (nalidixic acid), neomycin, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (norfloxacin), (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo 7H-pyrido[1,2,3-de][1,4]benzoxazin-6-carboxylic acid (ofloxacin), 6-(5-methyl-3-phenyl-4 5 isoxazolcarboxamido)penicillanic acid (oxacillin), 6-phenoxyacetylamino-penicillanic acid (phenoxymethylpenicillin) and 4-dimethylamino-octahydro-pentahydroxy-1,11-dioxo-6 methyl-naphtacene-2-carbamide (tetracycline). In another embodiment, the topical application product is characterised by a content of one or more antiseptically active substances selected from alkylbenzyldimethylammonium 10 chloride (benzalkonium chloride), N-benzyl-N,N-dimethyl-2-{2-[p-(1,1,3,3 tetramethylbutyl)-phenoxy]ethoxy}ethylammonium hydroxide (benzethonium chloride), cetyltrimethylammonium hydroxide (cetrimonium bromide), 1,1'-hexamethylen-bis-[5-(p chlorophenyl)biguanide](chlorhexidine), N',Nl-decamethylen-bis-(4-aminoquinaldinium hydroxide) (dequalinium chloride), N-(4-chlorophenyl)-N'-(3,4dichlorophenyl)urea 15 (triclocarban) and 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan). In one embodiment, the topical application product is characterised by an active ingredient content of one or more corticosteroids selected from 9a-chloro-16p-methylprednisolone (beclomethasone), 9-fluoro- l1p,17,21-trihydroxy-16p-methyl-1,4-pregnadien-3,20-dione (betamethasone), 21-chloro-9-fluoro-1 I ,17-dihydroxy-16p-methyl-1,4-pregnadien-3,20 20 dione (clobetasol), 17,21-dihydroxy-pregn-4-en-3,11,20-trione (cortisone), lp,16a,17a,21 tetrahydroxy-1,4-pregnadien-3,20-dione-16 17-acetone acetal (desonide), 9-fluoro-11p 17,21-trihydroxy-16a-methylpregna-1,4-dien-3,20-dione (dexamethasone), 9a,11p-dichloro 6a-fluoro-21 -hydroxy- 1 6a,1 7a- (isopropylidenedioxy)-pregna-1,4-dien-3,20-dione (flucloronide), 6a,9a-difluoro- 1 6a, 1 7a-isopropylidenedioxy-corticosterone 25 (fluocinolonacetonide), 6a,9a-difluoro-16a,17a-isopropylidenedioxy-corticosterone-acetate (fluocinonide), 6a-fluoro- 11fP,21 -dihydroxy- 1 6a, 1 7-isopropylidenedioxy-4-pregnen- 3 ,20 dione (fludroxycortide), 3-(2-chloroethoxy)-9a-fluoro-6-formyl-11,21-dihydroxy-16a,17a isopropylidenedioxypregna-3,5-dien-20-one (formocortal), 21 -chloro-9a-fluoro- 11 p hydroxy- 1 6a,1 7a-isopropylidenedioxy-4-pregnen- 3 ,20-dione (halcinonide), 17a 30 hydroxycorticosterone (hydrocortisone), 11p,17,21-trihydroxy-6a-methyl-1,4-pregnadien 3,20-dione (methylprednisolone), 11 ,17,21-trihydroxy-pregna-1,4-dien-3,20-dione (prednisolone), 17a, 21-dihydroxypregna-1,4-dien-3,11,20-trione (prednisone), 9-fluoro-16a hydroxyprednisolone (triamcinolone) and triamcinolone-16a,17-acetonide (triamcinolone acetonide) 35 In another embodiment, the topical application product is characterised by a content of the nutrient and anabolic substance L-proline. In one embodiment, the topical application product is characterised by a content of L proline in combination with one or more further nutrient and anabolic substances selected from the group of the amino acids, the vitamins and the mineral substances.

5 In another embodiment, the topical application product is characterised by a content of L-proline in combination with one or more nutrient and anabolic substances selected from lysine, cysteine, gelatine, biotin, panthenol, dexpanthenol and inorganic or organic calcium, magnesium or zinc compounds. 5 In one embodiment, the topical application product is characterised by a content of one or more adjuvants from the group consisting of terpenes or terpene-containing oils, alcohols, ketones, fatty acid esters, polyglycols, tensides, urea, antioxidants and complexing agents. In another embodiment, the topical application product is characterised in that it contains 0.01 to 20 percent by weight of one or more active substances, 1 to 99.99 percent by weight 10 of CI-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid , undecanic acid or undecenic acid and 0 to 98.99 percent by weight of the adjuvants. In one embodiment, the process for the manufacture of topical application products is characterised in that one or more Ci-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid, undecanic acid or undecenic acid and, if desired, one or more adjuvants are 15 homogenously mixed, subsequently one or more active substances are dissolved in the mixture with stirring and optional heating, and stirring is continued until a homogenous solution is obtained. In another embodiment, the process for the manufacture of a topical application product is characterised in that the solution is further processed with the addition of physiologically 20 acceptable formulation adjuvants to topical application forms. The invention also relates to the use of a topical application product for the treatment, prevention, after-treatment and supporting treatment of papillary tubercles and of nail diseases and periungual diseases. The invention further relates to the use of a topical application product for nail care. 25 The invention still further relates to the non-human use of a topical application product for the treatment of mycotic infections of the hooves, paws and claws of pets and domestic animals It is therefore the task of the present invention to solve the problems connected with the topical treatment of papillary tubercles and of nail diseases and the topical nail care and to 30 provide pharmaceutical and cosmetic products which enable a long-term treatment result. According to the present invention water-free topical application products for the treatment of nail diseases and nail care are proposed, which have the following composition: a) one and more active substances b) one or more Ci-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid, 35 undecanic acid or undecenic acid as carrier and c) optionally physiologically compatible adjuvants. For the water-free topical application products of the invention principally all active substances of synthetic or natural origin are considered, which are active in the treatment of papillary tubercles and of nail and periungual diseases. In addition, nutrient and anabolic 40 substances, which are effective in the nail care, are considered as active substances.

6 Suitable active substances which can be contained in the products of the invention are antimycotics of synthetic and natural origin, antibiotics, antiseptics, corticosteroids, nutrient and anabolic substances as well as a combinations of the mentioned active substances. Specific examples of such active substances are: 5 s antimycotics and their physiologically acceptable salts, such as e.g. (±)-cis-2,6 dimethyl-4-[2-methyl-3-(p-tert-pentyl-phenyl)propylmorpholine (amorolfin), amphotericin, 6-cyclohexyl-1-hydroxy-4-methyl-2(lH)pyridinone (ciclopirox), bis phenyl-(2-chlorophenyl)- 1 -imidazolylmethane (clotrimazole), 1-[2-(2,4 dichlorophenyl)-2-(4-chlorobenzyloxy)-ethyl]imidazole (econazole), 2,4-difluoro 10 a,a-bis(1H-2,4-triazol-1-ylmethyl)benzyl alcohol (fluconazole), 5-fluorocytosine (flucytosine), 7-chloro-trimethoxy-methylspiro-[benzofuran-cyclohexen]-dione (griseofulvin), 1-[2,4-dichloro-p-(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 15 piperazinyl]phenyl} -4,5-dihydro- 1,2,4-triazol-5-one (itraconazole), (±)-cis-1-acetyl 4- {4-([2-(2,4-dichlorophenyl)-2-(l H-imidazol- 1 -ylmethy 1)-1,3-dioxolan-4 yl]methoxy)phenyl}piperazine (ketoconazole), 1-[2,4-dichloro-p-(2,4 dichlorobenzyloxyl)-phenethyl]-imidazole(miconazole), (E)-N-cinnamyl-N-methyl-1 naphthylmethylamine (naftifin), nystatin, (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N 20 methyl-1-naphthylmethylamine (terbinafin), 1[2-{(2-chloro-3-thienyl)methoxy}-2 (2,4-dichlorophenyl)ethyl]-1H-imidazole (tioconazole), O-2-naphthyl-N-methyl-N (3-tolyl)-thiocarbamate (tolnaftat) and a-(2,4-difluorophenyl)-5-fluoro-p-methyl-a (IH-1,2,4-triazol-1-ylmethyl)-4-pyrimidinethanol (voriconazole). e antimycotics of natural origin, such as e.g. etheric oils and plant extracts. 25 * antibiotics and their physiologically acceptable salts, such as e.g. a-amino-4 hydroxybenzylpenicillin (amoxicillin), D-(-)-a-aminobenzylpenicillin (ampicillin), 3,3-dimethyl-7-oxo-6-phenylacetamido-4-thia-1-azabicyclo-[3.2.0]-heptan-2 carboxylic acid (benzylpenicillin), benzylpenicillin-benzathine, 3-chloro-7-D-(2 phenylglycinamido)-cephalosporanic acid (cefaclor), 7p-[D-2-amino-(4 30 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-fluoro-1,4-dihydro-4-oxo-7-(piperazinyl)-3-quinolinecarboxylic acid (ciprofloxacin), (Z)-(2R, 5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2 35 0]heptan-2-carboxylic acid (clavulanic acid), 7-chloro-7-desoxy-lincomycin (clindamycin), 6-desoxy-5-hydroxytetracycline (doxycycline), 1-ethyl-6-fluoro-1,4 dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridin-3-carboxylic acid (enoxacin), erythromycin, 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl-penicillin (flucloxacillin), kanamycin, lincomycin, 7-dimethylamino-6-desoxy-6 40 desmethyltetracycline (minocycline), 6-(2-ethoxy- 1 -naphthamido)-penicillin 7 (nafcillin), 1-ethyl-1,4-dihydro-7-methyl-4-oxo- 1,8-naphthyridin-3-carboxylic acid (nalidixic acid), neomycin, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3 quinolinecarboxylic acid (norfloxacin), (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4 methyl-1-piperazinyl)-7-oxo-7H- pyrido[1,2,3-de][1,4]benzoxazin-6-carboxylic acid 5 (ofloxacin), 6-(5-methyl-3-phenyl-4-isoxazolcarboxamido)penicillanic acid (oxacillin), 6-phenoxyacetylamino-penicillanic acid (phenoxymethylpenicillin) and 4 dimethylamino-octahydro-pentahydroxy- 1,11 -dioxo-6-methyl-naphtacene-2 carbamide (tetracycline). * antiseptics such as e.g. alkylbenzyldimethylammonium chloride (benzalkonium 10 chloride), N-benzyl-N, N-dimethyl-2-{2-[p-(1,1,3,3-tetramethylbuthyl)-phenoxy] ethoxy}-ethylammonium hydroxide (benzethonium chloride), cetyltrimethylammonium hydroxide (cetrimonium bromide), 1,1'-hexamethylen-bis [5-(p-chlorophenyl)-biguanide](chlorohexidine), NI, N'-decamethylen-bis-(4 aminoquinaldinium hydroxide) (dequalinium chloride), N-(4-chlorophenyl)-N'a(3,4 15 dichlorophenyl)urea (triclocarban) and 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan). * corticosteroids and their physiologically acceptable salts, such as e.g. 9a-chloro-16p methylprednisolone (beclomethasone), 9-fluoro-1p,17,21-trihydroxy-16p-methyl 1,4-pregnadien-3,20-dione (betamethasone), 21-chloro-9-fluoro-111,17-dihydroxy 20 16-methyl-1,4-pregnadien-3,20-dione (clobetasol), 17,21-dihydroxy-pregn-4-en 3,11,20-trione (cortisone), 11p,16a,17a,21-tetrahydroxy-1,4-pregnadien-3,20-dione 16,17-acetone acetal (desonide), 9-fluoro-11p-17,21-trihydroxy-16a-methylpregna 1,4-dien-3,20-dione (dexamethasone), 9a, 11p -dichloro-6a-fluoro-2 I -hydroxy 16a,17a-(isopropylidenedioxy)-pregna-1,4-dien-3,20-dione (flucloronide), 6a,9a 25 difluoro-16a,17a-isopropylidenedioxy-corticosterone (fluocinolonacetonide), 6a,9a difluoro-16a,17a-isopropylidenedioxy-corticosterone-acetate (fluocinonide), 6a fluoro- 11p, 21-dihydroxy-16a,17-isopropylidenedioxy-4-pregnen-32,0-dione (fludroxycortide), 3-(2-chloroethoxy)-9a-fluoro-6-formyl-11p,21-dihydroxy-16a,17a isopropylidenedioxypregna-3,5-dien-20-one (formocortal), 21-chloro-9a-fluoro-11p 30 hydroxy- 1 6a,1 7a-isopropylidenedioxy-4-pregnen-3,20-dione (halcinonide), 17a hydroxycorticosterone (hydrocortisone), 11p,17,21 -trihydroxy-6a-methyl- 1,4 pregnadien-3,20-dione (methylprednisolone), 11p,17,21-trihydroxy-pregna-1,4-dien 3,20-dione (prednisolone), 17a,21-dihydroxypregna-1,4-dien-3,11,20-trione (prednisone), 9-fluoro-16a-hydroxyprednisolone (triamcinolone) and triamcinolone 35 16a,17-acetonide (triamcinolone acetonide) e nutrient and anabolic substances such as e.g. 2-pyrrolidinecarbolic acid (L-proline) Preferred antimycotics according to the present invention are bis-phenyl-(2 chlorophenyl)- I -imidazolylmethane (clotrimazole), 1-[2,4-dichloro-p-(2,6 dichlorobenzyloxy)-phenethyl]imidazole (isoconazole), 2,4-difluoro-a,a-bis(1 H- 1,2,4 40 triazol-1-ylmethyl)benzyl alcohol (fluconazole), (+)-1-sec-butyl-4-{4-[4-(4-{[2R*,4S*)-2- 8 (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 (2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4 yl]methoxy)phenyl}piperazine (ketoconazole), 1-[2,4-dichloro-p-(2,4-dichlorobenzyloxyl) 5 phenethyl]-imidazole (miconazole), (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl- 1 naphtylmethylamine (terbinafin), a-(2,4-difluorophenyl)-5-fluoro-p-methyl-a-(1 H- 1,2,4 triazol- 1 -ylmethyl)-4-pyrimid methanol (voriconazole). Particularly preferred antimycotics according to the present invention are bis-phenyl-(2 chlorophenyl)- 1 -imidazolylmethane (clotrimazole), 1-[2,4-dichloro-p-(2,6 10 dichlorobenzyloxy)-phenethylimidazole (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]phenyl} -4,5-dihydro- 1,2,4-triazol-5-one (itraconazole), (+)-cis-1-acetyl-4-{4-([2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4 yl]methoxy)phenyl}piperazine (ketoconazole). 15 Preferred antimycotics of natural origin are tea tree oil (Melaleuca alternifolia), lavender oil (Lavandula officinalis chaix) and leaf extract of the neem tree (Azadirachta indica). These natural antimycotics can be used as single active substances or as combinations of several such active substances. A preferred combination of active ingredients is a mixture of lavender oil, tea tree oil and leaf extract of the neem tree and especially thuja-oil for 20 removing papillary tubercles. Preferred antiseptics are e.g. 1,1 '-hexamethylene-bis-[5-(p-chlorophenyl) biguanide](chlorohexidine). Preferred corticosteroids are 11$,16a,1la,21-tetrahydroxy-1,4-pregnadien-3,20-dione 16,17-acetone acetal (desonide), 9a, 11 p-dichloro-6a-fluoro-21 -hydroxy- 1 6a, 1 7a 25 (isopropylidenedioxy)-pregna-1,4-dien-3,20-dione (flucloronide), 6a,9a-difluoro-16a,17a isopropylidenedioxy-corticosterone (fluocinolonacetonide), 6a,9a-difluoro-16a,17a isopropylidenedioxy-corticosterone-acetate (fluocinonide), 6a-fluoro- 111P,21 -dihydroxy 16a,17-isopropylidenedioxy-4-pregnen-3,20-dione (fludroxycortide), 3-(2-chloroethoxy)-9a fluoro-6-formyl-11p,21-dihydroxy-16a,17a-isopropylidenedioxypregna-3,5-dien-20-one 30 (formocortal), 21-chloro-9a-fluoro-11p-hydroxy-16pa,17a-isopropylidenedioxy-4-pregnen 3,20-dione (halcinonide), triamcinolone- 1 6a, 1 7a-acetonide (triamcinolone acetonide). Specific examples of combinations of active substances are: " combinations of corticosteroids with antimycotics, antibiotics or antiseptics. A preferred combination is e.g. (+)-cis-1-acetyl-4-{4-([2-(2,4-dichlorophenyl)-2-(1H 35 imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy)phenyl piperazine (ketoconazole) and 11p,16a,17a,21-tetrahydroxy-1,4-pregnadien-3,20-dione-16,17-acetone acetal (desonide). e combinations of antimycotics of synthetic origin with antimycotics of natural origin. A preferred combination is bis-phenyl-(2-chloro-phenyl)- 1 -imidazolylmethane 40 (clotrimazole) with tea tree oil.

9 " combinations of various antimycotics of natural origin. A preferred combination is lavender oil, tea tree oil and leaf extract of the neem tree and ABC-Oil and (Australian Blue Cypress Oil) and thuja oil. " combinations of 2-pyrrolidine carboxylic acid (L-proline) with one or more further 5 nutrient and anabolic substances selected from the group of the amino acids, the vitamins and the mineral substances. Preferred combinations of 2-pyrrolidine carboxylic acid (L-proline) with one or more nutrient and anabolic substances are combinations with (S)-2,6-diaminohexanoic acid (lysine), (R)-2-amino-3 mercaptopropionic acid (cysteine), gelatine, cis-2-(4-carboxybutyl)-3,4 10 ureidotetrahydrothiophene (biotin), (±)-2,4-dihydroxy-N-(3-hydroxypropyl)3,3 dimethylbutyric acid (panthenol), D(+)-2,4-dihydroxy-N-(3-hydroxypropyl)3,3 dimethylbutyric acid (dexpanthenol) and inorganic or organic calcium, magnesium or zinc compounds. With L-proline an anabolic substance was found, which has proven particularly suitable 15 for nail anabolism and for nail care. L-proline was up to the present only mentioned as optional component of cosmetic products for nail care which contain a sulfurised amino acid or a derivative thereof as active component (EP-A-0 534 810). The above-mentioned substances are in the following identified with the corresponding trivial name, entered in brackets in the above enumeration. 20 The C 1

-C

4 -alkyl esters used as carriers comprise the methyl, ethyl, n-propyl, isopropyl, n butyl, sec.-butyl, isobutyl and tert.-butyl esters. In the esters of the polybasic acids malic acid,.citric acid and tartaric acid the CI-C 4 -alkyl groups contained in the ester groups can be the same or different. In the aforementioned polybasic acids all carboxylic groups or only a part of the carboxylic groups can be esterified. In consequence, also the corresponding malic 25 acid and tartaric acid mono alkyl esters are considered in addition to malic acid and tartaric acid di-Ci-C 4 -alkyl esters. Of the Ci-C 4 -alkyl esters of citric acid the corresponding mono-, di- and tri-alkyl esters are suitable. Preferred esters are the ethyl esters. Further preferred esters are the isopropyl esters. A preferred single compound is lactic acid ethyl ester. Further preferred single compounds are malic acid diethylester and malic acid di 30 isopropylester. The topical application products according to the invention can in addition to one or more active substances and one or more Ci-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid as carriers also contain physiologically compatible adjuvants. Suitable adjuvants of this kind are e.g. terpenes or terpene containing oils, alcohols, ketones, fatty acid esters, 35 polyglycols, tensides, urea, antioxidants and complexing agents. Suitable terpenes are acyclic, monocyclic and bicyclic terpenes as well as oils containing these terpenes. Examples of acyclic terpenes are acyclic terpene hydrocarbons, such as e.g. myrcene, acyclic terpene alcohols, such as e.g. citronellol and geraniol, as well as acyclic terpene aldehydes and ketones, such as e.g. citral, a-ionone and p-ionone. Examples of 40 monocyclic terpenes are monocyclic terpene hydrocarbons, such as e.g. a-terpinene, y- 10 terpinene and limonene, monocyclic terpene alcohols such as e.g. thymol, menthol, cineol and carvacrol as well as monocyclic terpene ketones such as e.g. menthone and carvone. Examples of bicyclic terpenes are terpenes from the carane group such as e.g. carone, terpenes from the pinane group, such as e.g. a-pinene and p-pinene as well as terpenes from 5 the bornane group such as e.g. camphor and borneol. Particularly suitable terpenes are monocyclic terpene alcohols such as e.g. thymol and menthol. Examples for suitable oils containing terpenes are peppermint oil, cardamom oil, geranium oil, rose oil, thuja oil and thyme oil. Particularly suitable oils are peppermint oil, lavender oil and thyme oil. Especially suitable for removing papillary tubercles is as already said thuja-oil. 10 Suitable alcohols are branched or unbranched alcohols with 1 to 3 hydroxy groups and 2 to 6 carbon atoms, the hydroxy groups optionally being partly or completely etherified or esterified. Particularly suitable alcohols are ethanol, I -propanol, 2-propanol (isopropanol), 1,2-propanediol (propylene glycol), 2-phenylethanol (phenylethyl alcohol), 1-butanol (butyl alcohol), ethylene glycol monomethylether (methoxy ethanol), ethylene glycol 15 monophenylether (phenoxyethanol), 1,2,3-trihydroxypropane (glycerine), ethylacetate, butylacetate, glycerine diacetate (diacetin) and glycerine triacetate (triacetin). As suitable ketones e.g. acetone and methylethyl ketone (2-butanone) are considered. As fatty acid esters of saturated or unsaturated, branched or unbranched fatty acids with 8 to 21 carbon atoms are suitable, the alcohol component comprising branched and unbranched 20 alcohols with 1 to 6 carbon atoms. Particularly suitable fatty acid esters are tridecane carboxylic acid isopropylester, tetradecane carboxylic acid isopropyl ester (isopropylmyristate), pentadecane carboxylic acid methylester and 9-octadecenoic acid glycerine monoester (glycerine monooleate). A suitable polyglycol is e.g. polyglycol 400. 25 Suitable tensides are e.g. non-ionogenic surface active substances. Particularly suitable tensides are partial fatty acid esters of sorbitan (Span), partial fatty acid esters of polyoxyethylene sorbitan (Tween), fatty acid esters of polyoxyethylene (Myrj) and fatty alcohol ethers of polyoxyethylene (Brij). Suitable antioxidants are e.g. butylhydroxytoluene (BHT), butyl-4-methoxyphenol 30 (BHA), tocopherols and ascorbates As complexing agents e.g. ethylene diamine tetraacetic acid (EDTA) and disodium ethylene diamine tetraacetic acid (Na 2 -ETDA) are suitable. As topical application products according to the invention e.g. solutions, tinctures, emulsions, gels, salves, creams and pastes come into consideration. Preferred topical 35 application forms are solutions. The invention further concerns a process for the manufacture of the topical application products of the invention, which is characterised in that the lactic acid esters and one or more adjuvants are homogenously mixed, subsequently one or more active substances are dissolved in the mixture with stirring and optional heating (up to a maximum of 80*C.) and 40 stirring is continued until a homogenous solution is obtained. The solution obtained is 11 preferably used directly as such for topical application. However, the solution can also be converted into another topical application form by the addition of further physiologically acceptable formulation adjuvants with the aid of conventional solution, mixing and suspension procedures. 5 Preferably, the topical application products according to the invention are used in the form of solutions. Preferred topical application products according to the present invention contain * to 20% by weight one ore more active substances, * to 99.99% by weight one or more C-C 4 -alkyl esters of lactic acid, malic acid, tartaric 10 acid or citric acid or undecanic or undecenic acid and * 0 to 98.99% by weight one or more physiologically compatible adjuvants. The invention moreover concerns the use of the topical application products according to the invention for treatment, prevention, after-treatment and supporting treatment of papillary tubercles and of nail diseases and periungual diseases as well as for nail care. Furthermore, 15 the present invention concerns the use of the products of the invention for the treatment of mycotic infections of the hooves, paws and claws of pets and domestic animals. Topical application products containing antimycotics are e.g. suitable for the following indications: e treatment, prevention and after-treatment of onychomycoses, caused by dermatophytes, 20 yeasts or fungi or mixed infections " treatment, prevention and after-treatment of nail-fungus infections in patients with psoriasis, diabetes or AIDS * supporting treatment of periungual nail infections such as e.g. Candida paronychium. Topical application products containing antibiotics are suitable e.g. for the following 25 indications: * support of removing palliary tubercled and of the treatment and/or prevention of nail and periungual infections caused by bacteria. Topical application products containing antiseptics are suitable e.g. for the following indications: 30 e treatment and prevention of nail and periungual infections caused by unspecific or not identified pathogens. Topical application products containing corticosteroids or combinations of corticosteroids with antimycotics, antibiotics or antiseptics are suitable e.g. for the following indications: e treatment of papillary tubercles, prevention, after-treatment or supporting treatment of 35 nail psoriasis or other inflammatory nail and periungual conditions. The pharmaceutic topical application products according to the invention are suitable for the treatment of papillary tubercles and of nail diseases and periungual diseases on toenails and fingernails, as well as for the treatment of diseases of the hooves, paws and claws of pets and domestic animals. The frequency of application of the pharmaceutical products depends 40 on the degree and the localisation of the disease. In general, application once to three times a 12 day is sufficient. The solution is then directly applied onto the diseased papillary tissue or nail or to the hoof, paw or claw and if required, on the surrounding skin areas concerned. The therapy should be continued for about another two weeks after the symptoms have ceased, in order to prevent a relapse. 5 The cosmetic topical application products according to the invention containing one or more nutrient and anabolic substances are suitable for nail care such as e.g. in nail atrophies on toenails and fingernails. Nail atrophies include e.g. fragile, brittle and thin nails as well as dotted or streaky white spots. The preparation is applied upon the cosmetically unsightly nail(s) and if required also on the surrounding skin area. The frequency of application of the 10 preparation depends on the degree and the localization of the atrophy. In general, use once or twice a day is sufficient. The topical application products of the invention have the advantage that they penetrate the diseased nail together with the active substance within a few days and display their action in the nail bed and the nail root. Through the more rapid onset of the effect and the better 15 penetration, the treatment of nail diseases. is as a rule terminated after about two to three months. In this way patient-compliance is clearly improved, since the long duration of treatment required in other methods of treatment is substantially shortened. With diseased skin, in particular periungual skin areas, the healing process and the nursing effect set in faster, since the active substance penetrates sufficiently and rapidly into the skin. The nail 20 care should as a rule be carried out for one month. For maintenance of the healthy nail substance the nail care substance can also be used over a longer period of time. Example 1 Clotrimazole-solution 1% Lactic acid ethyl ester 20.OmL 25 Urea 2.Og Clotrimazole 1.Og Lactic acid ethyl ester ad 100,OmL Urea is dissolved in 20mL of lactic acid ethyl ester with stirring and heating (ca. 50*C.) in a 100mL flask. Clotrimazole is added with stirring to the above solution subsequently 30 lactic acid ethyl ester is added totalling 100mL. Stirring is continued until a homogenous solution is formed. Example 2 Thuja-oil 2.0% Lactic acid ethylester 98.0% 35 Example 3 Thuja oil 2.0% Tea-tree-oil 1.0% Lactic acid 2.0% Lactic acid ethylester 95.0% 13 Example 4 Thuja oil 2.0% Salicylic acid 2.0% Malic acid ethylester 96.0% 5 Example 5 Ciclopiroxolamin 8.0% Lactic acid ethylester 92.0% Example 6 Ethanol 5.0% 10 Undecenic acid 10.0% Citric acid methlester 85.0% Example 7 Lavender oil 2.0% Undecenic acid 10.0% 15 Lactic acid ethylester 88.0% Example 8 Clotrimazole-Tea Tree Oil Solution 1%+10% Lactic acid ethyl ester 20.0mL Urea 2.Og 20 Clotrimazole 1.0g Tea tree oil 1.og Lactic acid ethyl ester ad 100.OmL Urea is dissolved in 20mL of lactic acid ethyl ester with stirring and heating (ca. 50*C.) in a 1 OOmL flask. Subsequently clotrimazole and tea tree oil are added with stirring to the 25 above solution, and lactic acid ethyl ester is added totalling 100mL. Stirring is continued until a homogenous solution is formed. Example 9 Tea Tree Oil Solution 30% lactic acid ethyl ester 44.Og 30 Tea tree oil 30.Og Lavender oil 6.Og Propylene glycol 20.Og All substances are weighed in a beaker and stirred until a homogenous solution is formed. 35 Example 10 ABC-Oil solution 2% Propylene glycol 20.Og Lactic acid ethylester 72.Og Tea tree-oil 1.og 40 Lavender oil 5.Og 14 Stirring is continued until a homogenous solution is formed. Example 11 Proline-solution 1.5% L-proline 1.5g 5 Propylene glycol 65.Og lactic acid ethyl ester 33.5g L-proline is dissolved in propylene glycol with stirring and heating. Subsequently, lactic acid ethyl ester is added, and stirring is continued until a homogenous solution is formed. 10 Example 12 L-proline 2.Og Malic acid diethyl ester 93.Og Isopropyl alcohol 5.Og L-proline is added to malic acid diethyl ester with stirring, and stirring is continued 15 until complete dissolution. Example 13 In the following table further compositions of the invention are shown, which are obtained using each 50.Og of a hydroxy carboxylic acid Ci-C 4 -alkyl ester as carrier according to the invention and each 1.Og of active substance. For the manufacture of the compositions 20 the active substance was added to the hydroxy carboxylic ester with stirring at room temperature or slightly increased temperature (.about.30*C-50*C). Depending on the active ingredient a clear, immediately useful solution is formed after 1-5 hours of stirring. Active ingredient Hydroxy carboxylic acid ester Clotrimazole Lactic acid ethyl ester Isoconazole Lactic acid ethyl ester Ketoconazole Lactic acid ethyl ester Itraconazole Lactic acid ethyl ester Clotrimazole Citric acid triethyl ester Isoconazole Citric acid triethyl ester Ketoconazole Citric acid triethyl ester Itraconazole Citric acid triethyl ester Clotrimazole Malic acid diisopropyl ester Isoconazole Malic acid diisopropyl ester Ketoconazole Malic acid diisopropyl ester Itraconazole Malic acid diisopropyl ester Example 14 In the following table further compositions of the invention are shown, which are 25 obtained using each 88.Og of a hydroxy carboxylic acid CI-C 4 -alkyl ester used according to the invention as carrier and 12.Og of an active substance combination of 5g of lavender oil, 5g of tea tree oil and 2g of leaf extract of the neem tree. The compositions are prepared by stirring of the active substance combinations in the hydroxy carboxylic acid ester at room temperature. The compositions so obtained are immediately useful.

15 Active ingredient Hydroxy carboxylic acid ester Lavender oil/tea tree oil/leaf Lactic acid ethyl ester extract of neem tree ABC-OIL Lavender oil/tea tree oil/leaf Citric acid triethyl ester extract of neem tree ABC-Oil Lavender oil/tea tree oil/leaf Malic acid diisopropyl ester extract of neem tree ABC-Oil

Claims

2. The topical application composition according to claim 1, wherein the carrier is selected from the group consisting of ethyl ester of lactic acid, malic acid, tartaric acid, citric acid, undecanic acid or undecenic acid and mixtures thereof.
3. The topical application composition according to claim 1, wherein the carrier is selected from the group consisting of isopropyl esters of lactic acid, malic acid, tartaric acid, citric acid, undecanic acid or undecenic acid and mixtures thereof.
4. The topical application composition according to claim I or claim 2, wherein the carrier is lactic acid ethyl ester.
5. The topical application composition according to any one of claims I to 3, wherein the carrier is undecanic acid or undecenic acid methyl ester.
6. The topical application composition according to any one of claims I to 3, wherein the carrier is malic acid diethylester.
7. The topical application composition according to any one of claims 1 to 6, characterised by a content of one or more active substances selected from the group consisting of antimycotics of synthetic or natural origin, antibiotics, antiseptics, corticosteroids and nutrient and anabolic substances.
8. The topical application composition according to any one of claims I to 6, characterized by a content of one or more active substances selected from the group consisting of antimycotics active substances selected from the group consisting of (±)-cis-2,6-dimethyl-4-[2-methyl-3-(p-tert-penty phenyl)propyl]morpholine (amorolfin), amphotericin, 6-cyclohexyl-I -hydroxy-4-methyl-2(1 H)pyridinone (ciclopirox), bis-phenyl-(2-chlorophenyl)- I -imidazolylmethane (clotrimazole), 1-[2-(2,4-dichlorophenyl) 2-(4-chlorobenzyloxy)ethyl- 1 -imidazole (econazole), 2,4-difluoro-a,a-bis(1 H-1,2,4-triazol- I ylmethyl)benzyl alcohol (fluconazole), 5-fluorocytosine (flucytosine), 7-chloro-trimethoxymethylspiro [benzofuran-cyclohexene]dione-(griseofulvin), I-[2,4-dichloro-p-(2,6-dichlorobenzyloxy)phenethyl] imidazole (isoconazole), (±)-1-sec-butyl-4-{4-[4-(4-{{2R*,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-l ylmethyl)- I,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-(2,4-dichlorophenyl)-2-( IH-imidazol-1-ylmethyl)-1,3-dioxolan 4-yl]methoxy)phenyl}pi perazine (ketoconazole), 1-[2,4-d ichloro-p-(2,4-dichlorobenzyloxyl)-phenethyl] imidazole(miconazole), (E)-N-cinnamyl-N-methyl- I -naphthylmethylamine(naftifin), nystatin, (E)-N-(6,6 dimethyl-2-hepten-4-ynyl)-N-methyl-I-naphthylmethylamine(terbinafin), 1[2-{(2-chloro-3 thienyl)methoxy}-2-(2,4-dichlorophenyl)ethyl]-1 H-imidazole 17 (tioconazole), 0-2-naphthyl-N-methyl-N(3-tolyl)-thiocarbamate (tolnaftat) and a-(2,4 difluorophenyl)-5-fluoro-p-methyl-a-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidinethanol (voriconazole).
9. Topical application composition according to any one of claims 1 to 6, 5 characterised by a content of one or more active substances selected from the group consisting of one or more antibacterially or antimycotically active substances selected from tea tree oil, lavender oil, thuja oil and leaf extract of the neem tree and ABC-oil.
10. Topical application composition according to any one of claims 1 to 6 characterised by a content of one or more active substances selected from the group 10 consisting of one or more antibacterially or antimycotically active substances selected from thuja-oil and ABC-oil.
11. Topical application composition according to any one of claims 1 to 6, characterised by a content of one or more active substances selected from the group consisting of one or more antibacterially active substances selected from a-amino-4 15 hydroxybenzylpenicillin (amoxicillin), D-(-)-a-aminobenzylpenicillin (ampicillin), 3,3 dimethyl-7-oxo-6-phenylacetamido-4-thia-1-azabicyclo-[3.2.0]-heptan-2-carboxylic acid (benzylpenicillin), benzylpenicillin-benzathine, 3-chloro-7-D-(2-phenylglycinamido) cephalosporanic acid (cefaclor), 7p-[D-2-amino-(4-hydroxyphenyl)-acetylamino]-3-methyl cephalosporanic acid (cefadroxil), amino-phenylacetamido-methyl-cephalosporanic acid 20 (cephalexin), D(-)-threo-2-dichloroacetamido-1-(4-nitrophenyl)-1,3-propanediol (chloramphenicol), 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazinyl)3 quinolinecarboxylic acid (ciprofloxacin), (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa 1-azabicyclo[3.2.0]heptan-2-carboxylic acid (clavulanic acid), 7-chloro-7-desoxy-1 lincomycin (clindamycin), 6-desoxy-5-hydroxytetracycline (doxycycline), 1-ethyl-6-fluoro 25 1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridin-3-carboxylic acid (enoxacin), erythromycin, 3-(2-chloro-6-fluorophenyl)5-methyl-4-isoxazolyl-penicillin (flucloxacillin), kanamycin, lincomycin, 7-dimethylamino-6-desoxy-desmethyltetracycline (minocycline), 6 (2-ethoxy-1-naphthamido)-penicillin (nafcillin), 1-ethyl-1,4-dihydro-7-methyl-4-oxo- 1,8 naphthyridin-3-carboxylic acid (nalidixic acid), neomycin, 1-ethyl-6-fluoro-1,4-dihydro-4 30 oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (norfloxacin), (+)-9-fluoro-2,3-dihydro-3 methyl-1 0-(4-methyl- 1 -piperazinyl)-7-oxo-7H- pyrido[1,2,3-de][1,4]benzoxazin-6 carboxylic acid (ofloxacin), 6-(5-methyl-3-phenyl-4-isoxazolcarboxamido)penicillanic acid (oxacillin), 6-phenoxyacetylamino-penicillanic acid (phenoxymethylpenicillin) and 4 dimethylamino-octahydro-pentahydroxy- 1,11 -dioxo-6-methyl-naphtacene-2-carbamide 35 (tetracycline).
12. Topical application composition according to any one of claims 1 to 6, characterised by a content of one or more active substances selected from the group consisting of one or more antiseptic active substances selected from alkylbenzyldimethylammonium chloride (benzalkonium chloride), N-benzyl-N,N-dimethyl 40 2-{2-[p-(1,1,3,3-tetramethylbutyl)-phenoxy]ethoxy}ethylammonium hydroxide 18 (benzethonium chloride), cetyltrimethylammonium hydroxide (cetrimonium bromide), 1,1' hexamethylen-bis-[5-(p-chlorophenyl)biguanide](chlorohexidine), N',Nl-decamethylen-bis (4-aminoquinaldinium hydroxide) (dequalinium chloride), N-(4-chlorophenyl)-N' (3,4dichlorophenyl)urea (triclocarban) and 5-chloro-2-(2,4-dichlorophenoxy)phenol 5 (triclosan).
13. Topical application composition according to any one of claims 1 to 6, characterised by a content of one or more active substances selected from the group consisting of one or more corticosteroids selected from 9a-chloro-16p-methylprednisolone (beclomethasone), 9-fluoro-11 ,17,21 -trihydroxy- 1 6p-methyl- 1,4-pregnadien-3,20-dione 10 betamethasonee), 21 -chloro-9-fluoro- 11 P, 1 7-dihydroxy- 1 6p-methyl- 1,4-pregnadien-3,20 dione (clobetasol), 17,21-dihydroxy-pregn-4-en-3,11,20-trione (cortisone), 11p,16a,17a,21 tetrahydroxy-1,4-pregnadien-3,20-dione-16,17-acetone acetal (desonide), 9-fluoro-11p 17,21-trihydroxy-16a-methylpregna-1,4-dien-3,20-dione (dexamethasone), 9a,11p-dichloro 6ca-fluoro-21 -hydroxy- 1 6a, 1 7a-(isopropylidenedioxy)-pregna- 1,4-dien-3,20-dione 15 (flucloronide), 6a,9a-difluoro- 1 6a, 1 7a-isopropylidenedioxy-cortico sterone (fluocinolonacetonide), 6a,9a-difluoro-16a,17a-isopropylidenedioxy-cortico sterone-acetate (fluocinonide), 6a-fluoro-11p,21-dihydroxy-16a,17-isopropylidenedioxy-4-pregnen3,20 dione (fludroxycortide), 3-(2-chloroethoxy)-9a-fluoro-6-formyl-11,21-dihydroxy-16a,17a isopropylidenedioxypregna-3,5-dien-20-one (formocortal), 21 -chloro-9a-fluoro- 11P 20 hydroxy-16a,17a-isopropylidenedioxy-4-pregnen- 3 ,20-dione (halcinonide), 17a hydroxycorticosterone (hydrocortisone), 111,17,21-trihydroxy-6a-methyl-1,4-pregnadien 3,20-dione (methylprednisolone), 11p,17,21-trihydroxy-pregna-1,4-dien-3,20-dione (prednisolone), 17a,21-dihydroxypregna-1,4-dien-3,11,20-trione (prednisone), 9-fluoro-16a hydroxyprednisolone (triamcinolone) and triamcinolone-16a,17-acetonide (triamcinolone 25 acetonide).
14. Topical application composition according to any one of claims 1 to 6, characterised by a content of the nutrient and anabolic consisting of substance L-proline.
15. Topical application composition according to any one of claims 1 to 6, characterized by a content of L-proline in combination with one or more further nutrient and 30 anabolic substances selected from the group of the amino acids, the vitamins and the mineral substances.
16. Topical application composition according to any one of claims 1 to 6, characterised by a content of L-proline in combination with one or more of lysine, cysteine, gelatine, biotin, panthenol, dexpanthenol and inorganic or organic calcium, magnesium or 35 zinc compounds.
17. Topical application composition according to any one of claims 1 to 6, characterised by a content of one or more adjuvants from the group consisting of terpenes or terpene-containing oils, alcohols, ketones, fatty acid esters, polyglycols, tensides, urea, antioxidants and complexing agents. 19
18. Topical application composition according to any one of claims I to 6, characterized by a content that it contains 0.0 1 to 20 percent by weight of one or more active substances, 1 to 99.9 percent by weight of Ci-C 4 -alkyl esters of lactic acid, malic acid, tartaric acid or citric acid, undecanic or undecenic acid and 0 to 98.99 percent by weight of the adjuvants.
19. A water-free topical application composition when used for the treatment of papillary tubercles, said composition being substantially as hereinbefore described with reference to any one of the Examples.
20. A method for treating papillary tubercles comprising the step of: applying to papillary tubercles the topical composition of any one of claims I to 19. Dated 15 November 2012 BioEqual AG Patent Attorneys for the Applicant/Nominated Person SPRUSON & FERGUSON