US20140303249A1 - Topical fungicidal agents for treating nail disorders - Google Patents

Topical fungicidal agents for treating nail disorders Download PDF

Info

Publication number
US20140303249A1
US20140303249A1 US14/301,368 US201414301368A US2014303249A1 US 20140303249 A1 US20140303249 A1 US 20140303249A1 US 201414301368 A US201414301368 A US 201414301368A US 2014303249 A1 US2014303249 A1 US 2014303249A1
Authority
US
United States
Prior art keywords
acid
alkyl esters
composition according
esters
lactic acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US14/301,368
Inventor
Hans Meyer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BioEqual AG
Original Assignee
BioEqual AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39768241&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20140303249(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by BioEqual AG filed Critical BioEqual AG
Priority to US14/301,368 priority Critical patent/US20140303249A1/en
Publication of US20140303249A1 publication Critical patent/US20140303249A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01L—SHOEING OF ANIMALS
    • A01L15/00—Apparatus or use of substances for the care of hoofs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00—Manicure or pedicure preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A61K2800/31—Anhydrous

Definitions

  • This invention relates to anhydrous, topical agents which are intended for the treatment of nail disorders caused by mycoses and for nail care and which contain a C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid or citric acid and, where applicable, physiologically acceptable excipients.
  • the invention also relates to use of the fungicidal agent in any form of administration.
  • the application PCT CH99 0049 describes topical agents comprising one or more active substances in addition to carriers, including acid esters and, where applicable, physiologically acceptable excipients.
  • agents comprising only one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid or citric acid or mixtures thereof without further additives are outstandingly suitable for the treatment of nail disorders caused by a mycotic infection (fungal infection).
  • topical antimycotic agents can be used extremely effectively without the addition of further active substances and without the addition of further carriers.
  • GBP 1234297 for example, the fungicidal effect of low-alkyl esters lactic acid, malic acid, tartaric acid and citric acid is neither described nor mentioned in combination with other active substances.
  • the various lactic acid esters are also not mentioned as bactericidal agents.
  • lactic acid esters with low alkanols as carriers are described as effective for the treatment of acne, pityriasis and oleosa capitis.
  • the fungicidal or antimycotic effect is not mentioned, only the bactericidal effect.
  • the esters are used in combination with alcohols in alcoholic solution as carriers.
  • GBP 156 1475 the manufacture of bacteriostatic solutions is described as capable of being used as a deodorant, the free lactic acid being in alcoholic solution. Lactic acid esters are not mentioned, but the hydrolysation of these esters is. It has to be concluded that there is an equilibrium. A fungicidal effect of the solutions is not described. The suspicion is expressed that part of the bactericidal effect is attributable to the alcohol used.
  • compositions that reduce bacteria on the hand comprise esters of lactic acid and are bacteriostatically effective in particular.
  • the esters of lactic acid are dissolved in various solvents.
  • a fungicidal effect is by no means described or even claimed.
  • WO 2004032886 describes the use of lactic and citric acid salts as bactericidal agents. In particular, it describes the use of these agents on the skin and in particular for the hair to combat bacteria. Fungicidal effects are neither mentioned nor claimed.
  • surfactants surface active agents
  • a second acid is described as advantageous.
  • the C1-C4 alkyl esters can be used as fungicidal active substances and at the same time also as carriers, if needed, which make any further additive unnecessary.
  • the C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid and also citric acid show surprisingly good antimycotic effects and at the same, time good properties as carriers themselves, which guarantee the required quantity of active substance for a lasting therapeutic effect as cosmetic agents for topical treatment of nail disorders, i.e. the transport of a C1-C4 alkyl ester of the corresponding acids through the nail into the underlying nail bed and root (matrix).
  • the C1-C4 alkyl esters to be used as active substance and carrier at the same time comprise the methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl esters.
  • the esters of the polybasic acids malic acid, citric acid and tartaric acid
  • the C1-C4 alkyl groups contained in the ester groups may be the same or different.
  • all carboxy groups or part of the carboxy groups may be esterified.
  • malic and tartaric acid C1-C4 alkyl esters Apart from malic and tartaric acid C1-C4 alkyl esters, therefore, the corresponding malic and tartaric acid C1-C4 dialkyl esters and the corresponding malic and tartaric acid monoalkyl esters may also be considered.
  • C1-C4 alkyl esters of citric acid the corresponding monoalkyl, dialkyl and trialkyl esters are suitable.
  • esters are the ethyl esters. Further preferred esters are the isopropyl esters.
  • a preferred single compound is ethyl lactate. Further preferred single compounds are diethyl malate and disopropyl malate. Likewise monoethyl tartrate and monoethyl citrate are described as preferred compounds.
  • agents for topical application according to the invention may comprise customary physiologically acceptable excipients.
  • Suitable excipients of this type are, for example, terpenes or oils containing terpenes, alcohols, ketones, fatty acid esters, polyglycols, tensides, urea, antioxidants and complexing agents.
  • Suitable terpenes are acyclic, monocyclic and bicyclic terpenes and also oils which contain these terpenes.
  • 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, ⁇ -ionone and ⁇ -ionone.
  • monocyclic terpenes are monocyclic terpene hydrocarbons, such as e.g.
  • ⁇ -terpenes ⁇ -terpenes and limonenes
  • monocyclic terpene alcohols such as e.g. thymol, menthol, cineol and carvacrol
  • monocyclic terpene ketones such as e.g. menthone and carvone.
  • bicyclic terpenes are terpenes from the carane group, such as e.g. carone, terpenes from the pinane group, such as e. g. ⁇ -pinene and ⁇ -pinene, and also terpenes from the bornane group, such as e.g. campher and borneol.
  • terpenes are monocyclic terpene alcohols, such as e.g. thymol and menthol.
  • suitable oils containing terpenes are peppermint oil, cardamom oil, geranium oil, rose oil, thuja oil and thyme oil.
  • Especially suitable oils are peppermint oil, lavender oil, tea tree oil. ABC oil (callitris intra tropic a wood oil) and thyme oil.
  • Suitable alcohols are branched or unbranched alcohols with 1 to 3 hydroxy groups and 2 to 6 carbon atoms, wherein the hydroxyl groups may be partially or fully etherified and esterified.
  • Especially suitable alcohols are ethanol, 1-propanol, 2-propanol (isopropanol), 1,2-propandiol (propylene glycol), 2-phenylethanol (phenyl ethyl alcohol), 1-butanol (butyl alcohol), ethylene glycol monomethyl ether (methoxyethanol), ethylene glycol monophenyl ether (phenoxyethanol), 1,2,3-trihydroxypropane (glycerol), ethyl acetate, butyl acetate, glycerol diacetate (diacetine) and glycerol triacetate (triacetin).
  • Suitable ketones that may be considered are, for example, acetone and methyl ethyl ketone (2-butanone).
  • Esters of saturated and unsaturated, branched and unbranched fatty acids with 8 to 21 carbon atoms, wherein the alcohol component comprises branched and unbranched alcohols with 1 to 6 carbon atoms are suitable as fatty acid esters.
  • suitable fatty acid esters are tridecanecarboxylic acid isopropyl ester, tetradecanecarboxylic acid isopropyl ester (isopropyl myristate), pentadecanecarboxylic acid methyl ester and 9-octadecenoic acid glycerol monoester (glycerol monooleate).
  • a suitable polyglycol for example, is polyglycol 400.
  • Suitable tensides are non-ionogenic surfactants.
  • Especially 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 butyl hydroxyl toluene (BHT), butyl-4-methoxy-phenol (BHA), tocopherols and ascorbates.
  • Suitable complexing agents are ethylenediaminetetraacetic acid (EDTA) and disodium ethylenediaminetetraacetic acid (Na 2 -ETDA).
  • EDTA ethylenediaminetetraacetic acid
  • Na 2 -ETDA disodium ethylenediaminetetraacetic acid
  • Formulations for topical application according to the invention which could be considered suitable are, for example, anhydrous solutions, tinctures, emulsions, gels, ointments, creams and pastes.
  • Preferred topical dosage forms are anhydrous solutions.
  • the solution obtained is preferably used directly as such for topical application.
  • anhydrous solution obtained may also be produced in another topical dosage form with the addition of further physiologically acceptable formulation aids using conventional methods of dissolution, blending and suspension.
  • the agents for topical use according to the invention are preferably used in the form of anhydrous solutions.
  • Preferred agents for topical use comprise according to this invention 1 to 99.9% by weight of one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid and 0 to 98.99% by weight of one or more physiologically acceptable excipients.
  • the invention relates to the use of agents for topical use according to the invention for the treatment, prevention, follow-up or supportive treatment of nail disorders and periungual diseases and for nail care.
  • the invention relates to the treatment of fungal infections, for example finger or toe-nails infected with Candida albicans or Trichophyton mentagroph.
  • agents according to the invention may also be used for the treatment of fungal infections of hooves, claws and talons of pets and farm animals and wild animals living in captivity.
  • Agents which are typically intended for topical use and comprise a C1-C4 alkyl ester of said acids are suitable as antimycotic agents, for example, for
  • pharmaceutical agents according to the invention are suitable for the treatment of nail disorders and periungual diseases of toe and finger nails, and also for the treatment of hooves, claws and talons of pets and farm animals and wild animals in captivity (zoo).
  • the frequency of application of the agent according to the invention depends on the extent and localization of the disorders.
  • the anhydrous solution in this case is applied directly to the diseased nail, or hoof, claw or talon, and if necessary also to the likewise infected surrounding areas of skin using a pipette or applicator.
  • the agents for topical use according to the invention have the advantage that they penetrate the diseased nail and can exert the full effect in the nail bed or nail root within a few days.
  • Lactic acid ethyl ester pure without additives.
  • Citric acid triethyl ester 50% Isopropanol 50%, No further additives.

Abstract

Anhydrous agents for topical application, comprising one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid and physiologically acceptable excipients, are described for the treatment of nail disorders caused by mycoses and for nail care. The agents according to the invention are also suitable in veterinary medicine for treating fungal infections of the hooves, claws and talons of pets and farm animals and wild animals living in captivity.

Description

  • This invention relates to anhydrous, topical agents which are intended for the treatment of nail disorders caused by mycoses and for nail care and which contain a C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid or citric acid and, where applicable, physiologically acceptable excipients.
  • The invention also relates to use of the fungicidal agent in any form of administration.
  • The application PCT CH99 0049 describes topical agents comprising one or more active substances in addition to carriers, including acid esters and, where applicable, physiologically acceptable excipients.
  • Surprisingly, it was found that agents comprising only one C1-C4 alkyl ester of lactic acid, malic acid, tartaric acid or citric acid or mixtures thereof without further additives are outstandingly suitable for the treatment of nail disorders caused by a mycotic infection (fungal infection).
  • Surprisingly, these topical antimycotic agents can be used extremely effectively without the addition of further active substances and without the addition of further carriers.
  • The bactericidal effect of C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid and citric acid is sufficiently known in the prior art.
  • In GBP 1234297, for example, the fungicidal effect of low-alkyl esters lactic acid, malic acid, tartaric acid and citric acid is neither described nor mentioned in combination with other active substances. The various lactic acid esters are also not mentioned as bactericidal agents.
  • In U.S. Pat. No. 3,806,513, lactic acid esters with low alkanols as carriers are described as effective for the treatment of acne, pityriasis and oleosa capitis. The fungicidal or antimycotic effect is not mentioned, only the bactericidal effect. The esters are used in combination with alcohols in alcoholic solution as carriers.
  • In GBP 156 1475, the manufacture of bacteriostatic solutions is described as capable of being used as a deodorant, the free lactic acid being in alcoholic solution. Lactic acid esters are not mentioned, but the hydrolysation of these esters is. It has to be concluded that there is an equilibrium. A fungicidal effect of the solutions is not described. The suspicion is expressed that part of the bactericidal effect is attributable to the alcohol used.
  • USP-2005019355 describes compositions that reduce bacteria on the hand, comprise esters of lactic acid and are bacteriostatically effective in particular. The esters of lactic acid are dissolved in various solvents. A fungicidal effect is by no means described or even claimed.
  • WO 2004032886 describes the use of lactic and citric acid salts as bactericidal agents. In particular, it describes the use of these agents on the skin and in particular for the hair to combat bacteria. Fungicidal effects are neither mentioned nor claimed. The use of surfactants (surface active agents) and in particular the use of a second acid is described as advantageous.
  • In none of the patent specifications mentioned is reference made to the fungicidal effect of the esters of lactic, malic, tartaric or citric acid, which are suitable for the treatment of diseases of the nail bed resulting from fungal infection.
  • Surprisingly, the C1-C4 alkyl esters can be used as fungicidal active substances and at the same time also as carriers, if needed, which make any further additive unnecessary.
  • There is not yet a satisfactory agent for topical treatment of nail disorders caused by mycoses (fungi), which is used either without an additional carrier or without an additional active substance. The C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid and also citric acid show surprisingly good antimycotic effects and at the same, time good properties as carriers themselves, which guarantee the required quantity of active substance for a lasting therapeutic effect as cosmetic agents for topical treatment of nail disorders, i.e. the transport of a C1-C4 alkyl ester of the corresponding acids through the nail into the underlying nail bed and root (matrix).
  • The C1-C4 alkyl esters to be used as active substance and carrier at the same time comprise the methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl esters. Among the esters of the polybasic acids malic acid, citric acid and tartaric acid, the C1-C4 alkyl groups contained in the ester groups may be the same or different. In the aforementioned polybasic acids, all carboxy groups or part of the carboxy groups may be esterified. Apart from malic and tartaric acid C1-C4 alkyl esters, therefore, the corresponding malic and tartaric acid C1-C4 dialkyl esters and the corresponding malic and tartaric acid monoalkyl esters may also be considered.
  • Of the C1-C4 alkyl esters of citric acid, the corresponding monoalkyl, dialkyl and trialkyl esters are suitable.
  • Preferred esters are the ethyl esters. Further preferred esters are the isopropyl esters.
  • A preferred single compound is ethyl lactate. Further preferred single compounds are diethyl malate and disopropyl malate. Likewise monoethyl tartrate and monoethyl citrate are described as preferred compounds.
  • Besides one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid, agents for topical application according to the invention may comprise customary physiologically acceptable excipients.
  • Suitable excipients of this type are, for example, terpenes or oils containing terpenes, alcohols, ketones, fatty acid esters, polyglycols, tensides, urea, antioxidants and complexing agents.
  • Suitable terpenes are acyclic, monocyclic and bicyclic terpenes and also oils which contain 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, α-ionone and β-ionone. Examples of monocyclic terpenes are monocyclic terpene hydrocarbons, such as e.g. α-terpenes, γ-terpenes and limonenes, 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. α-pinene and β-pinene, and also terpenes from the bornane group, such as e.g. campher and borneol. Especially suitable terpenes are monocyclic terpene alcohols, such as e.g. thymol and menthol. Examples of suitable oils containing terpenes are peppermint oil, cardamom oil, geranium oil, rose oil, thuja oil and thyme oil. Especially suitable oils are peppermint oil, lavender oil, tea tree oil. ABC oil (callitris intra tropic a wood oil) and thyme oil.
  • Suitable alcohols are branched or unbranched alcohols with 1 to 3 hydroxy groups and 2 to 6 carbon atoms, wherein the hydroxyl groups may be partially or fully etherified and esterified. Especially suitable alcohols are ethanol, 1-propanol, 2-propanol (isopropanol), 1,2-propandiol (propylene glycol), 2-phenylethanol (phenyl ethyl alcohol), 1-butanol (butyl alcohol), ethylene glycol monomethyl ether (methoxyethanol), ethylene glycol monophenyl ether (phenoxyethanol), 1,2,3-trihydroxypropane (glycerol), ethyl acetate, butyl acetate, glycerol diacetate (diacetine) and glycerol triacetate (triacetin).
  • Suitable ketones that may be considered are, for example, acetone and methyl ethyl ketone (2-butanone).
  • Esters of saturated and unsaturated, branched and unbranched fatty acids with 8 to 21 carbon atoms, wherein the alcohol component comprises branched and unbranched alcohols with 1 to 6 carbon atoms, are suitable as fatty acid esters. Especially suitable fatty acid esters are tridecanecarboxylic acid isopropyl ester, tetradecanecarboxylic acid isopropyl ester (isopropyl myristate), pentadecanecarboxylic acid methyl ester and 9-octadecenoic acid glycerol monoester (glycerol monooleate).
  • A suitable polyglycol, for example, is polyglycol 400.
  • Suitable tensides, for example, are non-ionogenic surfactants. Especially 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, for example, are butyl hydroxyl toluene (BHT), butyl-4-methoxy-phenol (BHA), tocopherols and ascorbates.
  • Suitable complexing agents, for example, are ethylenediaminetetraacetic acid (EDTA) and disodium ethylenediaminetetraacetic acid (Na2-ETDA).
  • Formulations for topical application according to the invention which could be considered suitable are, for example, anhydrous solutions, tinctures, emulsions, gels, ointments, creams and pastes. Preferred topical dosage forms are anhydrous solutions. The solution obtained is preferably used directly as such for topical application.
  • However, the anhydrous solution obtained may also be produced in another topical dosage form with the addition of further physiologically acceptable formulation aids using conventional methods of dissolution, blending and suspension.
  • The agents for topical use according to the invention are preferably used in the form of anhydrous solutions.
  • Preferred agents for topical use comprise according to this invention 1 to 99.9% by weight of one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid and 0 to 98.99% by weight of one or more physiologically acceptable excipients.
  • As mentioned in the introduction, the invention relates to the use of agents for topical use according to the invention for the treatment, prevention, follow-up or supportive treatment of nail disorders and periungual diseases and for nail care. In particular, the invention relates to the treatment of fungal infections, for example finger or toe-nails infected with Candida albicans or Trichophyton mentagroph. Furthermore, agents according to the invention may also be used for the treatment of fungal infections of hooves, claws and talons of pets and farm animals and wild animals living in captivity.
  • Agents which are typically intended for topical use and comprise a C1-C4 alkyl ester of said acids are suitable as antimycotic agents, for example, for
      • treatment, prevention and follow-up treatment of onychomycosis caused by dermatophytes, yeasts or moulds or mixed infections,
      • treatment, prevention and follow-up treatment of fungal infections of the nails in patients with psoriasis, diabetes or also AIDS,
      • supportive therapy for periungual nail infections such as e.g. Candida paronychium, Candida albicans or Trychophyton mentagroph.
  • As already mentioned, pharmaceutical agents according to the invention are suitable for the treatment of nail disorders and periungual diseases of toe and finger nails, and also for the treatment of hooves, claws and talons of pets and farm animals and wild animals in captivity (zoo). The frequency of application of the agent according to the invention depends on the extent and localization of the disorders.
  • Generally, one to three applications daily are sufficient.
  • The anhydrous solution in this case is applied directly to the diseased nail, or hoof, claw or talon, and if necessary also to the likewise infected surrounding areas of skin using a pipette or applicator.
  • The agents for topical use according to the invention have the advantage that they penetrate the diseased nail and can exert the full effect in the nail bed or nail root within a few days.
    • EXAMPLE 1
  • Nail applicator comprising
  • Lactic acid ethyl ester, pure without additives.
    • EXAMPLE 2
  • Nail applicator comprising
  •
    Malic acid diethyl ester 70%
    Ethanol 30%,
    No further additives.
    • EXAMPLE 3
  • Nail applicator comprising
  •
    Citric acid triethyl ester 50%
    Isopropanol 50%,
    No further additives.
    • EXAMPLE 4
  • Nail applicator comprising
  •
    Tartaric acid diethyl ester 40%
    Ethanol 30%
    Propylene glycol 30%
    No further additives.
  • The following, for example, may be used as possible applicators:
    • 1) Applicators based on a capillary system, comparable with textile liners, which are made of suitably resistant materials such as e.g. polypropylene, described in DE 3202435C1 and U.S. Pat. No. 4,973,181.
    • 2) Swab bottles with automatic spring or roll closure such as e.g. Dab-O-Matic from Dab-O-Matic Corp. in Mount Vernon, N.Y. (USA), or
    • 3) Customary tincture bottles of glass or plastic with a brush or pipette built into the cap.

Claims (11)

1-11. (canceled)
12. A water-free topical application composition consisting essentially of
one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid as the sole active ingredient and
one or more physiologically acceptable excipients,
wherein the water-free topical application composition is effective to treat nail diseases caused by mycoses under the nail plate.
13. The composition according to claim 12, wherein the one or more C1-C4 alkyl esters is an ethyl ester of lactic acid, malic acid, tartaric acid or citric acid.
14. The composition according to claim 12, wherein the one or more C1-C4 alkyl esters is an isopropyl ester of lactic acid, malic acid, tartaric acid or citric acid.
15. The composition according to claim 12, wherein the one or more C1-C4 alkyl esters is lactic acid ethyl ester.
16. The composition according to claim 12, wherein the one or more C1-C4 alkyl esters is malic acid diisopropyl ester.
17. The composition according to claim 12, consisting essentially of 1 to 99.99% by weight of C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid.
18. The composition according to claim 12, wherein the one or more physiologically acceptable excipients are selected from the group consisting of terpenes or oils containing terpenes, alcohols, ketones, fatty acid esters, polyglycols, tensides, urea, antioxidants and complexing agents.
19. The composition according to claim 12, consisting essentially of 30 to 98.99% by weight of the one or more physiologically acceptable excipients.
20. The composition according to claim 12, wherein the one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid is/are present in the composition in an amount effective to kill Candida albicans and/or Trichophyton mentagroph.
21. A water-free topical application composition consisting of
one or more C1-C4 alkyl esters of lactic acid, malic acid, tartaric acid or citric acid as the sole active ingredient and
one or more physiologically acceptable excipients,
wherein the water-free topical application composition is effective to treat nail diseases caused by mycoses under the nail plate.
US14/301,368 2007-04-20 2014-06-11 Topical fungicidal agents for treating nail disorders Abandoned US20140303249A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/301,368 US20140303249A1 (en) 2007-04-20 2014-06-11 Topical fungicidal agents for treating nail disorders

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CH656/07 2007-04-20
CH6562007 2007-04-20
PCT/EP2008/002642 WO2008128627A2 (en) 2007-04-20 2008-04-03 Topically applicable fungicide agents for treating nails
US45055209A 2009-10-30 2009-10-30
US14/301,368 US20140303249A1 (en) 2007-04-20 2014-06-11 Topical fungicidal agents for treating nail disorders

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/EP2008/002642 Continuation WO2008128627A2 (en) 2007-04-20 2008-04-03 Topically applicable fungicide agents for treating nails
US12/450,552 Continuation US8790671B2 (en) 2007-04-20 2008-04-03 Topical fungicidal agents for treating nail disorders

Publications (1)

Publication Number Publication Date
US20140303249A1 true US20140303249A1 (en) 2014-10-09

Family

ID=39768241

Family Applications (2)

Application Number Title Priority Date Filing Date
US12/450,552 Active 2028-04-28 US8790671B2 (en) 2007-04-20 2008-04-03 Topical fungicidal agents for treating nail disorders
US14/301,368 Abandoned US20140303249A1 (en) 2007-04-20 2014-06-11 Topical fungicidal agents for treating nail disorders

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US12/450,552 Active 2028-04-28 US8790671B2 (en) 2007-04-20 2008-04-03 Topical fungicidal agents for treating nail disorders

Country Status (20)

Country Link
US (2) US8790671B2 (en)
EP (1) EP2190425B1 (en)
JP (1) JP5824739B2 (en)
KR (1) KR20100015708A (en)
CN (1) CN101686958B (en)
AU (1) AU2008241071B2 (en)
BR (1) BRPI0810091A2 (en)
CA (1) CA2683958C (en)
DK (1) DK2190425T3 (en)
ES (1) ES2556944T3 (en)
HU (1) HUE027381T2 (en)
IL (1) IL201322A (en)
MX (1) MX337732B (en)
MY (1) MY162090A (en)
NZ (1) NZ580111A (en)
PL (1) PL2190425T3 (en)
PT (1) PT2190425E (en)
RU (2) RU2573025C2 (en)
WO (1) WO2008128627A2 (en)
ZA (1) ZA200906961B (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2556944T3 (en) 2007-04-20 2016-01-21 Bioequal Ag Topical application fungicide products for nail treatment
NL2003711C2 (en) 2009-10-27 2011-04-28 Shield Mark B V Aqueous composition for topical application, method of preparation, uses and device.
NL2003786C2 (en) 2009-11-11 2010-07-30 Medner B V COMPOSITION FOR TOPICAL APPLICATION, USES THEREOF, APPLICATOR DEVICE AND KIT OF PARTS.
US8518941B2 (en) * 2010-08-19 2013-08-27 American Sterilizer Company Extreme temperature aqueous decontamination composition
BE1018742A3 (en) * 2010-09-02 2011-07-05 Oystershell Nv COMPOSITION FOR TREATMENT OF NAIL MEL DISEASES AND USE THEREOF.
PT2460509T (en) * 2010-12-06 2018-02-13 Abbex Ab Composition for the treatment of warts
EP2462991A1 (en) 2010-12-13 2012-06-13 PQS Group B.V. Composition and use of a fermented olive leaf product for the treatment of nail infections
JP5934437B2 (en) 2012-05-28 2016-06-15 アベックス アクティエボラーグ Wart treatment composition
KR102367092B1 (en) 2021-07-14 2022-02-25 주식회사 이엔플러스 AIR STERILIZER INCLUDING PHOTOCATALYTIC LAMP OF TiO2 BY VUV ULTRAVIOLET PHOTOPLASMA
KR102329494B1 (en) 2021-07-14 2021-11-22 주식회사 이엔플러스 AIR STERILIZER INCLUDING PHOTOCATALYTIC FILER OF TiO2 BY VUV ULTRAVIOLET PHOTOPLASMA

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3806593A (en) * 1971-06-01 1974-04-23 Medisan Ab Hygienic-cosmetic compositions
US5189200A (en) * 1990-12-21 1993-02-23 Sepracor, Inc. Process for the stereoselective transformation of a diol to an alcohol
US5372742A (en) * 1993-01-22 1994-12-13 Dotolo Research Corporation Nail polish remover
US6797684B2 (en) * 2002-03-11 2004-09-28 Vertec Biosolvents, Inc. Biosolvent composition of lactate ester and D-limonene with improved cleaning and solvating properties

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR93907E (en) * 1963-12-07 1969-06-06 Philippe Serviere New use in cosmetology of a cell activator.
US3806513A (en) * 1969-10-04 1974-04-23 Beecham Group Ltd Alpha-substituted indolizine propionic acid and its salts
CA1085299A (en) * 1976-03-05 1980-09-09 Joseph D. Mandell Lactic acid composition and method of use
DE3202435C1 (en) 1982-01-26 1983-11-03 Fa. A.W. Faber-Castell, 8504 Stein Cosmetic cleaning device
FR2673537B1 (en) * 1991-03-08 1993-06-11 Oreal USE OF HYDROPHILIC PENETRATION AGENTS IN DERMATOLOGICAL COMPOSITIONS FOR THE TREATMENT OF ONYCHOMYCOSES, AND CORRESPONDING COMPOSITIONS.
SE9403541L (en) * 1994-10-14 1996-04-15 Sven Moberg Antimicrobial composition
CN1073845C (en) * 1997-12-16 2001-10-31 苏州医学院附属第一医院 Liniment film for onychomycosis and its preparation technology
DK0983037T3 (en) * 1998-02-09 2003-09-01 Macrochem Corp Fungicide nail polish
JP5170486B2 (en) * 1998-09-10 2013-03-27 バイオイコール ア−ゲー Topically applicable product
US6344190B1 (en) 1999-02-08 2002-02-05 Board Of Trustees Of Michigan State University Method and compositions for treatment of fungal nail disease
US20020039513A1 (en) * 2000-09-29 2002-04-04 Jeff Pink Nail polish container and applicator cap
WO2004021964A2 (en) * 2002-09-05 2004-03-18 Michal Broshi Ben-Levi Container
PL373235A1 (en) 2002-09-05 2005-08-22 Galderma S.A. Solution for ungual application
US7135194B2 (en) * 2002-09-27 2006-11-14 Birnbaum Jay E Subunguicide, and method for treating onychomycosis
GB2393967A (en) * 2002-10-11 2004-04-14 Reckitt Benckiser Surface treatment composition
US20050020678A1 (en) * 2003-07-23 2005-01-27 Denton Robert Michael Environmentally safe fungicides
US20050019355A1 (en) 2003-07-23 2005-01-27 Denton Robert Michael Skin antiseptic and disinfectant
DE102004028018A1 (en) 2004-06-08 2006-06-08 Henkel Kgaa Use of substances that release terpenes and / or perfume alcohols, to inhibit the adhesion of microorganisms
CN1939539A (en) 2005-09-29 2007-04-04 瑞士商拜欧伊果公司 Local prescription for wart, nail-disease treatment and nail care
ES2556944T3 (en) 2007-04-20 2016-01-21 Bioequal Ag Topical application fungicide products for nail treatment

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3806593A (en) * 1971-06-01 1974-04-23 Medisan Ab Hygienic-cosmetic compositions
US5189200A (en) * 1990-12-21 1993-02-23 Sepracor, Inc. Process for the stereoselective transformation of a diol to an alcohol
US5372742A (en) * 1993-01-22 1994-12-13 Dotolo Research Corporation Nail polish remover
US6797684B2 (en) * 2002-03-11 2004-09-28 Vertec Biosolvents, Inc. Biosolvent composition of lactate ester and D-limonene with improved cleaning and solvating properties

Also Published As

Publication number Publication date
ZA200906961B (en) 2010-07-28
CA2683958C (en) 2014-01-28
CA2683958A1 (en) 2008-10-30
WO2008128627A2 (en) 2008-10-30
US8790671B2 (en) 2014-07-29
AU2008241071B2 (en) 2013-11-14
RU2013129676A (en) 2015-01-10
NZ580111A (en) 2011-12-22
EP2190425A2 (en) 2010-06-02
HUE027381T2 (en) 2016-10-28
MX2009011221A (en) 2009-11-02
BRPI0810091A2 (en) 2014-10-21
PL2190425T3 (en) 2016-04-29
IL201322A (en) 2015-06-30
CN101686958A (en) 2010-03-31
US20100113593A1 (en) 2010-05-06
JP2010524866A (en) 2010-07-22
KR20100015708A (en) 2010-02-12
EP2190425B1 (en) 2015-10-07
ES2556944T3 (en) 2016-01-21
IL201322A0 (en) 2010-05-31
RU2573025C2 (en) 2016-01-20
RU2009142688A (en) 2011-05-27
JP5824739B2 (en) 2015-11-25
AU2008241071A1 (en) 2008-10-30
MX337732B (en) 2016-03-16
DK2190425T3 (en) 2016-01-25
CN101686958B (en) 2017-02-08
MY162090A (en) 2017-05-31
WO2008128627A3 (en) 2009-09-24
PT2190425E (en) 2016-02-04

Similar Documents

Publication Publication Date Title
US8790671B2 (en) Topical fungicidal agents for treating nail disorders
CA2343284C (en) Topical application products
CN107708665B (en) Pharmaceutical tetracycline compositions for dermatological use
KR101647545B1 (en) Novel antifungal composition
KR101582448B1 (en) New pharmaceutical composition for the treatment of fungal infections
US10335442B1 (en) Method for topical treatment of nail conditions
WO2020004202A1 (en) COMPOSITION INCLUDING D-chiro-INOSITOL
AU2005203232B2 (en) Topical formulations for the treatment of papillary tubercles, nail diseases and nail care
JP2000212090A (en) Skin-modifying agent
US20200129495A1 (en) Ebastine topical composition
JP2020002106A (en) Composition containing d-chiro-inositol
KR20060104011A (en) Topical formulation to be applied to wart removal, nail-disease treatment and nail care
KR20140048908A (en) Topical formulation to be applied to wart removal, nail-disease treatment and nail care
CA2536567C (en) Pharmaceutical and cosmetic formulations for treating fingernails
KR20130001197A (en) Topical formulation to be applied to wart removal, nail-disease treatment and nail care
BE1021016B1 (en) COMPOSITION FOR TREATMENT OF NAIL DISEASES AND USE
TWI520729B (en) Topische formulierungen fuer anwendung bei warzen, nagelerkrankungen und zur nagelpflege
MXPA05005429A (en) Topical formulations for treating warts, finger nail diseases, and nail care
TW201622710A (en) Topical formulation for the treatment of papillary tubercles, nail diseases and nail care
JPH0565483B2 (en)
BG1574U1 (en) Composition of therapeutic shampoo

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION