WO2012035478A2 - Composition de vernis antifongique - Google Patents

Composition de vernis antifongique Download PDF

Info

Publication number
WO2012035478A2
WO2012035478A2 PCT/IB2011/053964 IB2011053964W WO2012035478A2 WO 2012035478 A2 WO2012035478 A2 WO 2012035478A2 IB 2011053964 W IB2011053964 W IB 2011053964W WO 2012035478 A2 WO2012035478 A2 WO 2012035478A2
Authority
WO
WIPO (PCT)
Prior art keywords
composition
nail
varnish
concentration
extract
Prior art date
Application number
PCT/IB2011/053964
Other languages
English (en)
Other versions
WO2012035478A3 (fr
Inventor
Orna Levin
Yochanan Forman
Michael Friedman
Original Assignee
Pharmayeda Ltd
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
Application filed by Pharmayeda Ltd filed Critical Pharmayeda Ltd
Publication of WO2012035478A2 publication Critical patent/WO2012035478A2/fr
Publication of WO2012035478A3 publication Critical patent/WO2012035478A3/fr

Links

Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the present invention relates to the field of nail varnish compositions and more particularly, in some embodiments to antifungal nail varnish compositions for topical administration to the fingernails or toenails.
  • Fungal infections are probably the most common disorder of the fingernails or toenails. It has been estimated that 90% of elderly people have some degree of fungal infection of the toenails. Conditions of moisture and occlusion of the lower extremities favor fungal colonization. Pain may result from extreme deformity of the nail plate, but usually, the complaint is one of cosmetic appearance, particularly for infections of the fingernails.
  • the most common organisms involved in fungal infections of the nail include Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Candida albicans, Microsporum persiccolor, Cephalosporium species, Aspergillus species, and Fusarium oxysporum.
  • the teachings of the present invention relate to nail varnish compositions that, in some embodiments, are useful, for example, in the treatment of fungal infections of the fingernails or toenails.
  • a nail varnish composition comprising a liquid nail lacquer and at least four different plant extracts (such as essential oils and/or tinctures) selected from the group consisting of tea-tree oil, extract of Thymus, Propolis derivative, extract of calendula, extract of coneflower, extract of manuka, and extract of lemongrass.
  • plant extracts such as essential oils and/or tinctures
  • a method for the preparation of a nail varnish composition comprising mixing together a liquid nail lacquer and at least four different plant extracts (such as essential oils and/or tinctures) selected from the group consisting of tea-tree oil, extract of Thymus, Propolis derivative, extract of calendula, extract of coneflower, extract of manuka, and extract of lemongrass.
  • plant extracts such as essential oils and/or tinctures
  • the nail varnish composition is useful for the treatment of a fungal infection of a nail (a toenail, a fingernail, a claw) e.g., of a non-human animal, but especially of a human.
  • a fungal infection of a nail e.g., of a non-human animal, but especially of a human.
  • the nail varnish composition forms a solid film (a varnish layer) on the nail, the solid film together with other components of the nail varnish composition together treating a fungal infection of the nail.
  • the nail varnish composition is useful in the preparation of a composition useful for the treatment of a fungal infection of the nails.
  • the nail varnish composition is an intermediate and can be made into a composition useful for the treatment of a fungal infection of the nails by the addition of one or more plant extracts.
  • the at least four plant extracts of a composition or of a method comprise at least five different plant extracts selected from the group of plant extracts.
  • the at least four plant extracts of a composition or of a method comprise at least six different plant extracts selected from the group of plant extracts.
  • a first varnish composition comprising a liquid nail lacquer, an antifungal agent and substantially devoid (preferably devoid) of a keratolytic agent that is administered to skin in proximity of an infected nail;
  • a second varnish composition comprising a liquid nail lacquer, an antifungal agent and a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment that is administered to an infected nail concurrently with administration of the first varnish composition.
  • a method for the treatment of a fungal infection of the nails in a subject in need thereof comprising concurrently administering two compositions:
  • a first varnish composition comprising a liquid nail lacquer, an antifungal agent and substantially devoid (preferably devoid) of a keratolytic agent and is administered to skin in proximity of an infected nail;
  • a second varnish composition comprising a liquid nail lacquer, an antifungal agent and a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment administered to an infected nail concurrently with administration of the first varnish composition.
  • kits suitable for use in the treatment of a fungal infection of the nails in a human and/or non-human subject
  • a kit comprising two antifungal varnish compositions:
  • a first varnish composition comprising a liquid nail lacquer, an antifungal agent and substantially devoid (preferably devoid) of a keratolytic agent;
  • a second varnish composition comprising a liquid nail lacquer, an antifungal agent and a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment each of said two varnish compositions being individually administrable.
  • treating includes curing a condition, treating a condition, preventing a condition, treating symptoms of a condition, curing symptoms of a condition, ameliorating symptoms of a condition, treating effects of a condition, ameliorating effects of a condition, and preventing results of a condition.
  • the term "pharmaceutically acceptable” means approved by a regulatory agency of the US Federal or a US state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.
  • pharmaceutically acceptable carrier refers to an approved carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered conjugate.
  • carrier refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered.
  • excipient refers to an inert substance added to a pharmaceutical composition to further facilitate processes and administration of the active pharmaceutical ingredients.
  • the invention relates to nail varnish compositions that, in some embodiments, are useful, for example, in the treatment of fungal infections of the fingernails or toenails.
  • Some embodiments of the invention are related to the surprising and unexpected experimentally-proven result that an embodiment of a nail varnish composition described herein, substantially a mixture of plant extracts with a liquid nail lacquer, is effective in the treatment of fungal infections of the nails (fingernails, toenails, claws) and surrounding tissues.
  • Some embodiments of the invention are related to the surprising and unexpected experimentally-proven result that an embodiment of a nail varnish composition described herein, substantially a mixture of an essential oil and a keratolytic agent with a liquid nail lacquer damage the structural integrity of nails to an exceptional extent, allowing easy stripping thereof.
  • nail varnish composition that were formulated and experimentally-proven to be effective included extract of tea tree oil, extract of Thymus (specifically, thyme oil), a Propolis derivative (specifically, Propolis tincture), extract of calendula (specifically, calendula tincture), extract of conefiower (specifically, conefiower tincture), extract of lemongrass (specifically, lemongrass oil) and in some embodiments, also extract of manuka (specifically, manuka oil).
  • extract of tea tree oil extract of Thymus (specifically, thyme oil)
  • a Propolis derivative specifically, Propolis tincture
  • extract of calendula specifically, calendula tincture
  • extract of conefiower specifically, conefiower tincture
  • extract of lemongrass specifically, lemongrass oil
  • manuka specifically, manuka oil
  • the number of species of flowering plants on earth is estimated to be in the range of 250,000 to 400,000. In addition to flowering plants, at least 12,000 species of fern and 14,000 species of Bryophyta have been identified. From any given part of a plant (e.g., leaves, stems, fruit, flowers, roots, bark) different extracts may be extracted by different methods ⁇ inter alia, water extraction, infusion, alcoholic extraction, organic extraction, distillation, super critical fluid extraction). At least some extracts of at least some members of each of these groups have been found to, are rumored to have or are suspected as having some level of antifungal activity.
  • Active ingredients from plant origin are complex mixtures of tens or hundreds of individual chemicals, which may exhibit antifungal activity by a variety of different mechanism. Hence, interactions between any two or more particular plant extracts may result in the antifungal effect of one such extract being reduced or neutralized by the presence of the second extract.
  • the combination of any two or more of such active ingredients is therefore just as likely to have a lessened therapeutic effect, or even no additive therapeutic effect, as to have a simple additive effect. a priori, there is no reason to expect that any given combination of plant extracts, such as the nail varnish compositions described herein, would be safe for use, demonstrating no significant evidence of itching, burning, or other negative effect when administered in a course o f treatment .
  • a liquid nail lacquer to which a significant amount of different plant extracts are added retains suitable solid-film forming properties, for example, that the liquid nail lacquer remains spreadable and once administered, solidifies to form a solid film, and that a formed film has suitable properties such as a suitable thickness, sufficiently adheres to the administered surface and is not excessively frangible.
  • compositions and preparation of compositions are sufficiently mixable with the liquid nail lacquer, and apparently held in and released from the solid film formed by the liquid nail lacquer to the extent that in some embodiments the nail varnish composition is effective in the treatment of fungal infections of the nails.
  • a nail varnish composition comprising a liquid nail lacquer and at least four different plant extracts (such as essential oils and/or tinctures) selected from the group consisting of tea-tree oil, extract of Thymus, Propolis derivative, extract of calendula, extract of coneflower, extract of manuka and extract of lemongrass.
  • plant extracts such as essential oils and/or tinctures
  • a method for the preparation of a nail varnish composition comprising mixing together a liquid nail lacquer and at least four different plant extracts (such as essential oils and/or tinctures) selected from the group consisting of tea-tree oil, extract of Thymus, Propolis derivative, extract of calendula, extract of coneflower, extract of manuka and extract of lemongrass.
  • plant extracts such as essential oils and/or tinctures
  • the nail varnish composition is useful for the treatment of a fungal infection of a nail (a toenail, a fingernail, a claw) e.g., of a non-human animal, but especially of a human.
  • a fungal infection of a nail e.g., of a non-human animal, but especially of a human.
  • the nail varnish composition forms a solid film on the nail, the solid film together with other components of the nail varnish composition together treating a fungal infection of the nail.
  • the nail varnish composition is useful in the preparation of a composition useful for the treatment of a fungal infection of the nails.
  • the nail varnish composition is an intermediate and can be made into a composition useful for the treatment of a fungal infection of the nails by the addition of one or more plant extracts.
  • the at least four plant extracts of a composition or of a method comprise at least five different plant extracts selected from the group of plant extracts. In some embodiments, the at least four plant extracts of a composition or of a method comprise at least six different plant extracts selected from the group of plant extracts. In some embodiments, the at least four plant extracts of a composition or of a method comprise all seven different plant extracts selected from the group of plant extracts.
  • the plant extracts are essential oils, tinctures, or mixtures thereof.
  • An essential oil is a volatile mixture comprising, inter alia, esters, aldehydes, alcohols, ketones and terpenes, which can be prepared from botanical materials or plant cell biomass from cell culture.
  • essential oils are prepared by distillation from botanical materials (e.g., steam distillation, vacuum distillation), by solvent extraction (e.g., solvent extraction, alcohol extraction, oil extraction, super critical extraction, water extraction and hot water extraction) or by expression (e.g., in a press).
  • Tinctures of plants are typically prepared by solvent extraction, by contacting botanical materials with a solvent, usually ethanol, although in rare cases other solvents are used, for example, vinegar, glycerol, ether and propylene glycol or combinations thereof.
  • a tincture is prepared by macerating the plant while in contact with a solvent, allowing the solvent to remain in contact with the macerated plant material for an appropriate period of time and then filtering to remove solid or particulate material in order to form a filtered extract. If desired, additional solvent is added to the filtered extract to bring to a final volume or solvent is removed (e.g., evaporated) to increase the concentration of the extracted components in the tincture.
  • a tincture is prepared by percolating the plant with a solvent, in a percolation column.
  • the solvent is then allowed to flow through the column, contacting the plant materials, and is collected.
  • the collected solvent forms the extract.
  • Percolation has the advantage of allowing a minimal volume of solvent to be used during the extraction process.
  • the volume of solvent required can be partially controlled by the rate of fluid flow through the column, allowing for greater control over the final volume of extract.
  • the flow of solvent out of the column is stopped entirely during extraction, so that the efficiency of extraction is increased.
  • plant extracts used in implementing the teachings herein are commercially available and can be purchased from commercial sources.
  • Tea tree oil is commercially available and can be purchased from commercial sources.
  • Tea tree oil or melaleuca oil (CAS 68647-73-4) is obtained commercially from the leaves of the Melaleuca alternifolia, which is native to the northeast coast of New South Wales, Australia. Tea tree oil can also be extracted from Melaleuca dissitiflora and Melaleuca linariflora. Components of tea tree oil include terpinen-4-ol, ⁇ -terpinine, a- terpinine, 1,8-cineole, a -terpinolene, a-terpineol, a -pinene, and p-cymene. Tea tree oil is known to have beneficial antiseptic, antibacterial, antifungal and antiviral properties when administered topically.
  • Tea tree oil is one member of the group of seven plant extracts for implementing the teachings herein.
  • the tea tree oil is present at a concentration of between about 0.5% and about 10%> w/w, between about 0.5%> and about 6%> w/w and even between about 1% and about 4% w/w of a composition.
  • the tea tree oil is present at a concentration of about 2% w/w of a composition.
  • Thymus is a genus of about 350 species of herbaceous plants. Thymus vulgaris is considered to have medicinal uses. For example an infusion is considered to be an antiseptic useful for treating coughing, bronchitis and throat inflammation. Thyme oil, the essential oil of Thymus vulgaris, is considered useful for topical use as an antiseptic, antibacterial, and fungicide.
  • Thymus is one member of the group of seven plant extracts for implementing the teachings herein.
  • a preferred extract of Thymus for implementing the teachings herein is an extract of Thymus vulgaris, especially Thyme oil (CAS #8007-46-3), for example extracted from the leaves and flowers of Thymus vulgaris by steam distillation.
  • the extract of Thymus such as thyme oil
  • the extract of Thymus is present at a concentration of between about 0.5%> and about 10%> w/w, between about 0.5%> and about 6%> w/w and even between about 1%> and about 4%> w/w of a composition.
  • the extract of Thymus is present at a concentration of about 2% w/w of a composition.
  • Propolis is a wax-like substance gathered by honey bees and used to seal small gaps in the bee hive. Practitioners of natural medicine use Propolis for the relief of various conditions, including inflammations, viral diseases, ulcers, superficial burns or scalds.
  • Propolis derivatives (herein also termed “extracts of Propolis”) (including native
  • Propolis, partially purified Propolis, purified Propolis and extracts thereof are one member of the group of seven plant extracts for implementing the teachings herein.
  • a preferred Propolis derivative for implementing the teachings herein is Propolis tincture, for example extracted from native or purified Propolis by ethanolic extraction.
  • the Propolis derivative such as Propolis tincture, is present at a concentration of between about 0.5%> and about 10%> w/w, between about 0.5%> and about 6%) w/w and even between about 1%> and about 4%> w/w of a composition. In some embodiments, the Propolis derivative is present at a concentration of about 2% w/w of a composition. Extract of calendula
  • Calendula is a genus of about 12-20 species of annual or perennial herbaceous plants in the daisy family, Asteraceae, including Calendula arvensis, Calendula bicolor, Calendula echerleinii, Calendula lanzae, Calendula maderensis, Calendula maritime, Calendula maroccana, Calendula meuselii, Calendula officinalis, Calendula stellata, Calendula suffruticosa and Calendula tripterocarpa .
  • the flowers of Calendula officinalis comprise flavonol glycosides, triterpene oligoglycosides, oleanane-type triterpene glycosides, saponins, and a sesquiterpene glucoside.
  • Calendula extracts are considered to have anti-viral, anti-geno toxic and anti- inflammatory properties. Calendula in suspension or in tincture is used topically to treat acne, reducing inflammation, controlling bleeding and soothing irritated tissue.
  • Calendula extracts are one member of the group of seven plant extracts for implementing the teachings herein.
  • a preferred calendula extract for implementing the teachings herein is Calendula tincture, for example extracted from the leaves and flowers of Calendula officinalis by ethanolic extraction.
  • the Calendula extract such as Calendula tincture, is present at a concentration of between about 0.5% and about 10% w/w, between about 0.5%> and about 6%) w/w and even between about 1% and about 4% w/w of a composition. In some embodiments, the Calendula extract is present at a concentration of about 2% w/w of a composition.
  • Echinacea is a genus of herbaceous flowering plants in the daisy family, Asteraceae. Species of Echinacea include Echinacea angustifolia (Narrow-leaf Coneflower); Echinacea atrorubens (Topeka Purple Coneflower); Echinacea laevigata (Smooth Coneflower); Echinacea pallida (Pais Purple Coneflower); Echinacea paradoxa (Yellow Coneflower); Echinacea purpurea (Eastern Purple Coneflower); Echinacea sanguinea (Sanguine purple Coneflower); Echinacea simulata (Wavyleaf Purple Coneflower); and Echinacea tennesseensis (Tennessee Coneflower).
  • Coneflower is popularly believed to be an immuno stimulator and antimicrobial, has been suggested to have antitumor properties and to be effective against common colds. Use of coneflower has also been documented for treatment of snakebite, anthrax, coughs, sore throat, and relief of pain. Coneflower extracts comprise phenols, alkylamides and polysaccharides. The root is considered to contain a more efficacious mixture of active chemicals than the whole plant.
  • Coneflower extracts are one member of the group of seven plant extracts for implementing the teachings herein.
  • a preferred coneflower extract for implementing the teachings herein is Coneflower tincture, for example extracted from the roots of the plant by ethanolic extraction.
  • Lemongrass (cymbopogon) is a genus of about 55 species of grass, widely used as a herb in Asian cuisine. Lemongrass oil is used as a pesticide and preservative, and has been shown to have anti-fungal and anti-cancer properties. The grass is also considered a diuretic, tonic and stimulant. It promotes good digestion, and a preparation of lemon grass with pepper has been used for relief of menstrual troubles and nausea. It induces perspiration, to cool the body and reduce a fever.
  • Species include Cymbopogon ambiguus (Australian lemon-scented grass);
  • Cymbopogon citriodora West Indian lemon grass
  • Cymbopogon flexuosus East Indian lemon grass
  • Cymbopogon martinii (Palmarosa)
  • Cymbopogon nardus (Citronella Grass);
  • Cymbopogon obtectus (Silky-heads); Cymbopogon procerus; Cymbopogon proximus; Cymbopogon refractus (Barbed wire grass); Cymbopogon schoenanthus (camel grass); and
  • Cymbopogon winterianus (Citronella Grass).
  • Lemongrass extracts are one member of the group of seven plant extracts for implementing the teachings herein.
  • a preferred lemongrass extract for implementing the teachings herein is lemongrass oil (CAS #8007-02-1).
  • the lemongrass oil is present at a concentration of between about 0.5%) and about 10%> w/w, between about 0.5%> and about 6%> w/w and even between about 1% and about 4% w/w of a composition.
  • the lemongrass extract is present at a concentration of about 2% w/w of a composition. Extract of Manuka
  • Manuka (leptospermum scoparium) is a flowering plant that is typically found as a shrub (2-5 m tall) or moderately- sized tree (up to about 15 m) native to New Zealand and Southeast Australia. Kakariki parakeets chew the leaves and bark of manuka to extract materials which are then applied to the feathers during preening, apparently as an antiparasitic.
  • Manuka is known as a medicinal plant to Maori healers. A decoction of the leaves is allegedly useful for urinary-tract complaints as well as an antipyretic. Inhalation of the steam released during boiling of leaves is allegedly useful for relieving head colds. A decoction of the leaves and bark is topically administered to allegedly relieve muscle and joint pains. Chewing the bark is alleged to have a relaxing effect and to enhance sleep. The emollient gum is alleged to be useful in the treatment of scalds and burns. Manuka oil (CAS 219828- 87-2), is obtained by steam distillation of the biomass (especially leaves and branchlets). Folklore as well as Manuka oil sales representatives allege that the essential oil is useful for the treatment of skin and fungal infections, dandruff, cuts, scratches, acne, oily skin, rashes, body odor, insect bites and stings.
  • Manuka extracts are one member of the group of seven plant extracts for implementing the teachings herein.
  • a preferred manuka extract for implementing the teachings herein is manuka oil.
  • the manuka oil is present at a concentration of between about
  • the manuka extract is present at a concentration of about 2% w/w of a composition.
  • a composition as described herein comprises a kerato lytic agent.
  • keratolytic agent refers to an agent that reduces the structural integrity of a nail, especially by lysis of keratin, a fibrous structural protein present in nails, claws, hair and skin. Depending on the concentration, when administered to a nail, a keratolytic agent may dissolve or break down the outer layer of the nail or, at higher concentrations, may result in total loss of the nail.
  • the keratolytic agent, especially urea is present at a concentration of between about 0.5% and about 15% w/w, between about 0.5% and about 10%) w/w and even between about 3% and about 7% w/w of a composition. In some embodiments, the keratolytic agent, especially urea, is present at a concentration of about 5% w/w of a composition.
  • the concentration of a keratolytic agent is sufficient to lead to loss of the nail during a course of treatment, as discussed in greater detail hereinbelow.
  • concentration can be found for a specific keratolytic agent or combination of specific keratolytic agents by a person having ordinary skill in the art without undue experimentation.
  • the concentration of a keratolytic agent is insufficient to lead to loss of the nail during the course of treatment and functions, for example, as a penetration enhancer.
  • a composition as described herein is substantially devoid of a keratolytic agent.
  • substantially devoid is meant a concentration of keratolytic agent that is sufficiently low so as to not cause substantial damage to skin of a subject if administered thereto during the course of treatment. Such a concentration can be found for a specific keratolytic agent or combination of specific keratolytic agents by a person having ordinary skill in the art without undue experimentation.
  • a composition that is "substantially devoid of a keratolytic agent is devoid of a keratolytic agent.
  • a composition as described herein comprises an antioxidant to improve stability of the composition.
  • the antioxidant comprises an antioxidant selected from the group consisting of a form of vitamin E (for example, an ⁇ -, ⁇ -, ⁇ -, or ⁇ -tocopherol or tocotrienol, or a succinate, acetate, or nicotinate ester thereof), a carotene ( ⁇ -carotene or retinol), or ubiquinol (coenzyme Q), ascorbic acid, ascorbyl palmitate, butylated hydro xyanisole, butylated hydroxytoluene, ftimaric acid, malic acid, propyl gallate, sodium ascorbate, sodium metabisulfite, or mixtures thereof.
  • vitamin E for example, an ⁇ -, ⁇ -, ⁇ -, or ⁇ -tocopherol or tocotrienol, or a succinate, acetate, or nicotinate ester thereof
  • carotene ⁇ -
  • the antioxidant comprises a-tocopherol succinate.
  • the tocopherol succinate is present at a concentration of between about 0.1 % and 2% w/w, between about 0.2% and about 1.5%, and even between about 0.3% and about 1% w/w of a composition.
  • the tocopherol succinate is present at a concentration of about 0.5%) w/w of a composition.
  • the liquid nail lacquer comprises a film- forming polymer and a volatile solvent.
  • the film-forming polymer comprises a non- degradable film-forming polymer, such as polyethylene, polypropylene, poly(ethylene-co- vinyl acetate), or a non-degradable poly(meth)acrylate (including a poly(alkyl(meth)acrylate or poly(aromatic(meth)acrylate, such as poly(aryl(meth)acrylates), poly(aralkyl (meth)acrylates), and poly(aryloxyalkyl(meth)acrylates).
  • a non- degradable film-forming polymer such as polyethylene, polypropylene, poly(ethylene-co- vinyl acetate), or a non-degradable poly(meth)acrylate (including a poly(alkyl(meth)acrylate or poly(aromatic(meth)acrylate, such as poly(aryl(meth)acrylates), poly(aralkyl (meth)acrylates), and poly(aryloxyalkyl(meth)acrylates).
  • poly(aryl(meth)acrylates) examples include poly(9-anthracenyl methacrylate), poly(chlorophenylacrylate), poly(methacryloxy-2-hydroxybenzophenone), poly(methacryloxybenzotriazole), poly(naphthylacrylate) and -methacrylate), poly(4- nitrophenyl acrylate), poly(pentachloro(bromo, fluoro) acrylate) and -methacrylate), and poly(phenyl acrylate) and -methacrylate).
  • poly(aralkyl (meth)acrylates) examples include poly(benzyl acrylate) and -methacrylate), poly(2-phenethyl acrylate) and - methacrylate, and poly(l-pyrenylmethyl methacrylate).
  • poly(aryloxyalkyl (meth)acrylates) examples include poly(phenoxyethyl acrylate) and -methacrylate), and poly(polyethylene glycol phenyl ether acrylates) and -methacrylates with varying polyethylene glycol molecular weights.
  • the non-degradable film forming polymer comprises a poly(ethyl acrylate, methylmethacrylate, trimethylamino ethyl methacrylate chloride) copolymer, (sold commercially as Eudragit®RS or Eudragit®RL).
  • Eudragit®RS is present at a concentration of between about 1% and about 20% w/w, between about 2%> and about 10%> w/w and even between about 3% and about 5% w/w of a composition.
  • Eudragit®RS is present at a concentration of about 4% w/w of a composition.
  • the volatile solvent is selected from the group consisting of a ketone, an alcohol, or a mixture thereof. In some embodiments, the volatile solvent comprises a mixture of ethanol and acetone.
  • the composition further comprises an excipient selected from the group consisting of a plasticizer, a release enhancer, a stabilizer and a thickener, or mixtures thereof.
  • the plasticizer is selected from the group consisting of dibutyl sebacate, diethyl phthalate, lanolin alcohols, mineral oil, petrolatum, polyethylene glycol, propylene glycol, triacetin, triethyl citrate, or mixtures thereof.
  • the composition comprises a polyethylene glycol (PEG), such as PEG 100, PEG 150, PEG 200, PEG 300, PEG 400, PEG 600, PEG 800 and PEG 900 as a release enhancer and plasticizer
  • PEG polyethylene glycol
  • the polyethylene glycol comprises PEG-400.
  • the PEG-400 is present at a concentration of between about 0.1% and about 1% w/w, between about 0.1 % and about 0.8%> w/w and even between about 0.2%> and about 0.6%> w/w of a composition.
  • PEG-400 is present at a concentration of about 0.4% w/w of a composition.
  • the thickener and stabilizer comprises a non-ionic water-soluble cellulose ether.
  • the cellulose ether comprises hydro xypropylcellulose, such as that sold commercially as Klucel®HF.
  • the hydroxypropylcellulose is present at a concentration of between about 0.5% and about 5% w/w, between about 0.5%> and about 4% w/w and even between about 0.5% and about 2% w/w of a composition.
  • the hydroxypropylcellulose is present at a concentration of about 1.4% w/w of a composition.
  • the composition further comprises at least one additive selected from the group consisting of preservatives, surfactants and coloring agents which are well known in the art.
  • preservatives examples include benzoic acid, benzyl alcohol, bronopol, butyl paraben, chlorbutanol, chlorocresol, cresol, ethyl paraben, methyl paraben, phenol, propyl paraben, sodium benzoate, sodium propionate, sorbic acid, or mixtures thereof.
  • Suitable surfactants include cetrimide, sodium lauryl sulfate, docusate sodium, glyceryl monooleate, polysorbates, sorbitan esters, or mixtures thereof.
  • coloring agents include amaranth, brilliant blue, caratenoids, carmoisine, curcumin, eosine, erythrosine, fluorescein, rhodoxantin, tetrazine, or mixtures thereof.
  • the additional antifungal agent is selected from the group consisting of amphothericin B, butefanine, butoconazole, carbol-fuchsin, ciclopirox, clioquinol, clotrimazole, econazole, gentian violet, ketoconazole, miconazole, naftifme, nystatin, oxiconazole, sodium thiosulfate, terbinafme, terconazole, tolnaftate, undecylenic acid, therapeutically acceptable salts thereof, derivatives thereof, and mixtures thereof.
  • the antibacterial agent is selected from the group consisting of bacitracin, clindamycin, erythromycin, gentamicin, mupirocin, neomycin, tetracyclines, polymyxin B, benzalkonium chloride, boric acid, hexachlorophene, iodine, iodoquinol, mafenide, mercury ammoniated, metronidazole, nitrofurazone, selenium sulfide, silver sulfadiazine, salts thereof, derivatives thereof, and mixtures thereof.
  • the antiviral agent is selected from the group consisting of acyclovir, amantadine, cidofovir, famciclovir, foscarnet, ganciclovir, palivizumab, penciclovir, ribavirin, rimantadine, valcyclovir, salts thereof, derivatives thereof, and mixtures thereof.
  • the antipsoriatic agent is selected from the group consisting of alclometasone, ameinonide, betamethasone, clobetasol, clocortolone, desonide, desoximetasone, diflorasone, fluocinolone, fluocinonide, flurandrenolide, halcinonide, hydrocortisone, mometasone, prednicarbate and triamcinolone, salts thereof, derivatives thereof, and mixtures thereof.
  • the various components are mixed together in the appropriate amounts in an appropriate order to provide the desired nail varnish composition, formulated to form a solid film when topically administered (in the usual way) to a nail.
  • a nail varnish composition as described herein are useful in the preparation of a composition useful for the treatment of a fungal infection of the nails.
  • the nail varnish composition is an intermediate and can be made into a composition useful for the treatment of a fungal infection of the nails by the addition of one or more plant extracts.
  • a nail varnish composition as described herein are useful for the treatment of a fungal infection of a nail (a toenail, a fingernail, a claw) e.g., of a non-human animal, but especially of a human.
  • a nail varnish composition subsequent to administration of the nail varnish composition to a nail, the nail varnish composition forms a solid film on the nail, the solid film together with other components of the nail varnish composition together treating a fungal infection of the nail.
  • a use of a composition as described herein in the treatment of a fungal infection of the nails in a subject (human or non-human animal) in need thereof comprises topical administration of the composition in liquid form to the exposed surface of a nail.
  • the nail varnish composition forms a solid film (varnish layer) on the nail and the solid film together with other components of the nail varnish composition together treat the fungal infection of the nail.
  • the user when desired, strips the layer of varnish off of the infected nail, preferably after the layer has been soaked in water, for example, subsequent to a bath or shower.
  • stripping is performed by physical scraping, for example with a nail file or rasp. That said, it has been found that in some instances, the structural integrity of the nail is weakened to the extent that stripping can be performed with a mildly abrasive object such as cloth or a cotton ball together with a chemical varnish solvent such as acetone or ethyl acetate, as discussed below.
  • the nail varnish composition is administered repeatedly (e.g., at least once every two days, at least once daily) over a course of treatment (e.g., a period of at least 5 days, a period of at least 8 days), typically until the fungal infection is cured.
  • a healthy nail begins to grow, which is free of any recurring fungal infection, and the initially infected portion of the nail is periodically trimmed until only healthy nail remains.
  • a method for the treatment of a fungal infection of the nails in a subject comprising administering a composition as described herein.
  • administration of the nail varnish composition comprises administration of the composition in liquid form to the exposed surface of a nail.
  • the nail varnish composition forms a solid film on the nail and the solid film together with other components of the nail varnish composition together treat the fungal infection of the nail.
  • the need for which a composition is used or the method applied is related to infection with at least one of Trichophython rubrum, Trichophyton mentagrophytes, Epidermophyton floccusum, Candida albicans, Microsporum persiccolor, Cephalosporium species, Aspergillus species, and Fusarium oxysporum.
  • the composition is a topical composition and administering comprises topical administration to the nails, for example, at least once a week, at least twice a week and even at least three times a week. In some embodiments, the composition is administered between 1 and 4 times per day, for example once or twice a day.
  • Administration is for a period of from about 1 day to about 1 month, until infected nail has been trimmed away leaving only healthy nail.
  • the infected portion of the nail is dissolved (e.g., is no longer present, e.g., is stripped away or washed away during treatment). Once the infected nail is dissolved, a new nail, free of fungal infection, grows.
  • the nail varnish composition is suitable for self- administration by a patient. After administration, the volatile solvent evaporates, and a solid film is formed on the nail surface.
  • the method of treatment or use of the composition as described herein further comprises administration of an additional active ingredient, such as for example, an additional antifungal agent, an additional kerato lytic agent, or mixtures thereof.
  • an additional active ingredient such as for example, an additional antifungal agent, an additional kerato lytic agent, or mixtures thereof.
  • the additional active ingredient has an additive effect with the nail varnish composition.
  • the additional active ingredient has a synergistic effect with the nail varnish composition.
  • the additional active ingredient may be administered substantially simultaneously or sequentially, either before or after administration of the nail varnish composition.
  • compositions and methods of treatment useful for stripping nails Compositions and methods of treatment useful for stripping nails
  • kerato lytic agent to an antifungal composition in order to damage the structural integrity of the nail and ease stripping thereof.
  • Agispor® nail ointment Perrigo Israel Pharmaceuticals, Ltd.
  • a 1% Bifonazole ointment contains 40% by weight urea to allow nail stripping.
  • the ointment is topically administered to the nail and covered with a bandage for a period of time. The bandage is removed and the nail stripped with a rasp. It is important to note that even though such a high concentrations of urea noticeably damages the structural integrity of the nail, the nail remains sufficiently tough to make stripping a difficult task.
  • a nail varnish composition described herein includes no keratolytic agent.
  • a nail varnish composition described herein includes one or more keratolytic agents, such as urea, at a concentration sufficient to act as a penetration enhancer, that is to say, sufficient to damage the structural integrity of the nail (e.g., by damaging keratin) such that one or more active ingredients more easily than otherwise penetrate into the nail even though the nail remains tough.
  • keratolytic agents such as urea
  • a penetration enhancer sufficient to damage the structural integrity of the nail (e.g., by damaging keratin) such that one or more active ingredients more easily than otherwise penetrate into the nail even though the nail remains tough.
  • Some embodiments of the invention relate to the surprising and unexpected experimentally-proven result that some embodiments of a nail varnish composition described herein, substantially embodiments that include at least one essential oil and a keratolytic agent with a liquid nail lacquer damage the structural integrity of nails to an exceptional extent, allowing easy stripping thereof.
  • a nail varnish composition including at least one essential oil, at least one keratolytic agent, are used to treat a nail, the nail is quickly and easily stripped together with the varnish layer varnish , accelerating the course of treatment.
  • the structural integrity of the nail is observed to be significantly compromised (e.g., compared to equivalent use of a nail varnish composition as disclosed in US 7,074,392).
  • the nail appears soft and thin and is easily, even inadvertently, stripped away together with the varnish layer of composition, in some instances as a powdery residue.
  • stripping is typically performed using a hard abrasive object such as a rasp, nail file or emery board
  • the structural integrity of the nail is weakened to the extent that stripping can be performed with a mildly abrasive object such as cloth or a cotton ball together with a chemical varnish solvent such as acetone or ethyl acetate.
  • the keratolytic agent e.g., urea
  • an essential oil act together, in some embodiments, synergistically, to damage the structural integrity of the nail, rendering the nail easily strippable.
  • a nail varnish composition useful for stripping nails comprising a liquid nail lacquer, an essential oil and a keratolytic agent.
  • concentration of the keratolytic agent and the concentration of the essential oil is such that the composition is effective to weaken the structural integrity of a nail to which administered to an extent greater than with kerato lytic agent alone, in some embodiments to a synergistically greater extent.
  • the composition further comprises an antifungal agent.
  • at least one essential oil functions as the anti-fungal agent.
  • the composition comprises a nonessential oil anti-fungal agent, such as listed above.
  • the essential oil is a single essential oil. In some embodiments, the essential oil is a combination of different essential oils. In some embodiments, the essential oil is at least one essential oil selected from the group of four essential oils consisting of tea tree oil, thyme oil, lemongrass oil and manuka oil. In some embodiments, the essential oil is at least two different essential oils selected from the group of four oils. In some embodiments, the essential oil is at least three different essential oils selected from the group of four oils. In some embodiments, the essential oil is all four essential oils selected from the group of four oils.
  • the concentration of essential oils is not less than about 0.5%, not less than about 1%, not less than about 2%, not less than about 3%, and even not less than about 5% w/w of a composition. In some such embodiments, the concentration of essential oils is not more than about 35%, not more than about 30%, not more than about 25%o, and even not less than about 20%> w/w of a composition. In some such embodiments, the concentration of essential oils is between about 0.5%> and about 35% w/w, between about 1%) and about 30% w/w, between about 2% and about 25% w/w, and even between about 3% and about 20% w/w of a composition.
  • keratolytic agent including combination of specific keratolytic agents
  • Suitable keratolytic agents include, but are not limited to, the keratolytic agents listed hereinabove, for example, the keratolytic agent of the composition comprises urea or consists of urea.
  • the keratolytic agent may be of any suitable concentration (i.e., sufficient to cause a nail-weakening effect allowing stripping of the nail, in addition to a penetration-enhancing effect.
  • the concentration of keratolytic agent, especially urea is about 0.5%) and about 15% w/w, between about 0.5% and about 10% w/w and even between about 3% and about 7% w/w of a composition.
  • the keratolytic agent comprises urea, in some embodiments at a concentration of not more than about about 15% w/w.
  • Any liquid nail lacquer may be used in implementing a nail varnish composition useful for stripping nails.
  • the nail lacquer is as described herein or as described in US 7,074,392. Methods, uses and kits using two different compositions
  • a challenge in treating fungal infections of the nail and similar parts of the body is recurrence.
  • a fungal infection recurs, presumably due to the presence of the fungus in the skin surrounding the nail and nail bed. This problem is noted most often with long-term fungal infections.
  • an effective method to increase the efficacy of treatment and/or to reduce the incidence of recurrence of a fungal infection when using a composition as described herein is to administer an anti-fungal composition not only to the nail but also to skin and other tissue surrounding the nail, for example including one or more of the hyponychium (under the distal edge of the nail), the onychodermal band, the eponychium, the cuticle, the nail walls and paronychium
  • a nail varnish composition including a liquid nail lacquer and a keratolytic agent (especially including an essential oil) at a concentration sufficient to lead to loss of the nail during a course of treatment is effective in treating the nail, but may cause damage to a skin surface, apparently due to the combined action of the keratolytic agent and essential oil on the skin, especially keratin making up the skin.
  • a keratolytic agent especially including an essential oil
  • the first of the two varnish compositions is substantially devoid, preferably devoid, of a keratolytic agent, that is to say, is of a concentration of keratolytic agent that is sufficiently low so as to not cause substantial damage to skin of a subject if administered thereto during the course of treatment.
  • the second of the two varnish compositions further comprises a keratolytic agent, and in some embodiments also an essential oil, at a concentration sufficient to lead to loss of the nail during a course of treatment.
  • first varnish composition substantially devoid of keratolytic agent is administered to skin surrounding the nail
  • second varnish composition comprising a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment is concurrently administered to the nail.
  • first varnish composition substantially devoid of keratolytic agent is first administered to skin surrounding the nail, and subsequently (after a layer is formed on the administered areas) the second varnish composition comprising a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment is administered to the nail.
  • administration of the first varnish composition protects skin surrounding the nail from at least some of the negative effects of the keratolytic agent in the second varnish composition.
  • a first varnish composition comprising a liquid nail lacquer, an antifungal agent and substantially devoid (preferably devoid) of a keratolytic agent that is administered to skin in proximity of an infected nail (thereby forming a varnish layer covering the skin);
  • a second varnish composition comprising a liquid nail lacquer, an antifungal agent and a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment that is administered to an infected nail concurrently with administration of the first varnish composition, (thereby forming a varnish layer covering the nail).
  • the two varnish compositions are administered at least once daily for a sufficient number of days to treat the fungal infection. In some embodiments, the first varnish composition is administered prior to administration of the second varnish composition.
  • a method for the treatment of a fungal infection of the nails in a subject comprising concurrently administering two compositions: a first varnish composition comprising a liquid nail lacquer, an antifungal agent and substantially devoid (preferably devoid) of a keratolytic agent and is administered to skin in proximity of an infected nail (thereby forming a varnish layer covering the skin); and a second varnish composition comprising a liquid nail lacquer, an antifungal agent and a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment administered to an infected nail concurrently with administration of the first varnish composition (thereby forming a varnish layer covering the nail).
  • the two varnish compositions are administered at least once daily for a sufficient number of days to treat the fungal infection.
  • the first varnish composition is administered prior to administration of the second varnish composition.
  • one of the two varnish compositions is a varnish composition as described herein.
  • both of the two varnish compositions are a varnish composition as described herein.
  • kits suitable for use in the treatment of a fungal infection of the nails in a human and/or non-human subject
  • a kit comprising two antifungal varnish compositions:
  • a first varnish composition comprising a liquid nail lacquer, an antifungal agent and substantially devoid (preferably devoid) of a keratolytic agent;
  • a second varnish composition comprising a liquid nail lacquer, an antifungal agent and a keratolytic agent at a concentration sufficient to lead to loss of the nail during a course of treatment
  • each of said two varnish compositions being individually administrable.
  • the two varnish compositions of the kit as described above are each individually administrable, the first to a skin surface in proximity of a nail and the second to a (infected) nail, for example, each in an individual resealable bottle, each bottle provided with an appropriate applicator, such as a brush.
  • one of the two varnish compositions of the kit is a varnish composition as described herein.
  • both of the two varnish compositions of the kit are a varnish composition as described herein.
  • At least one of the first varnish composition and the second varnish composition (that is to say, only the first composition or only the second composition or both the first and second composition) comprises an essential oil.
  • at least one essential oil functions as the anti-fungal agent.
  • at least one of the first varnish composition and the second varnish composition comprises a non essential-oil anti-fungal agent in addition to the essential oil.
  • the second varnish composition comprises an essential oil at a concentration effective to assist (the keratolytic agent) in causing loss of the nail during the course of treatment.
  • one of the two varnish compositions is a varnish composition as described herein (i.e., including at least four of the seven plant extracts). In some embodiments, both of the two varnish compositions are a varnish composition as described herein (i.e., including at least four of the seven plant extracts).
  • the need for which the two compositions are used or the method is applied or the kit is suitable for is related to infection with at least one of Trichophython rubrum, Trichophyton mentagrophytes, Epidermophyton floccusum, Candida albicans, Microsporum persiccolor, Cephalosporium species, Aspergillus species, and Fusarium oxysporum.
  • the two compositions are topical compositions and administering comprises topical administration to the nails and skin surrounding the nails, for example, at least once a week, at least twice a week and even at least three times a week.
  • the composition is administered between 1 and 4 times per day, for example once or twice a day. Administration is for a period of from about 1 day to about 1 month, until infected nail has been trimmed away leaving only healthy nail.
  • the infected portion of the nail is dissolved (e.g., is no longer present, e.g., is stripped away or washed away during treatment). Once the infected nail is dissolved, a new nail, free of fungal infection, grows.
  • both nail varnish compositions are suitable for self- administration by a patient. After administration, the volatile solvent evaporates, and a solid film is formed on the nail surface.
  • Example 1 Exemplary embodiments of a composition
  • compositions 1 and 2 include the kerato lytic agent urea.
  • Composition 3 is substantially devoid (is devoid) of a kerato lytic agent.
  • Klucel EF hydroxypropylcellulose, CAS #9004- 64-2)
  • compositions 1, 2 and 3 were prepared as follows:
  • Ethanol, acetone and polyethylene glycol 400 (PEG 400) were mixed to a homogenous solution.
  • Eudragit RS® and/or Eudragit® L was then added, and mixed to a homogenous mixture 1 ;
  • Klucel HF and/or Klucel EF were added in small portions to mixture 1 and mixed until homogenous and viscous;
  • Example 2 Treatment of fungal infection of the nails with Composition 1
  • Example 1 Twelve otherwise healthy adult subjects, having nails of different thicknesses due to fungal infection, administered the composition of Example 1 to the nails up to twice a day, as shown in Table 2, and the number of days until the nail was dissolved was noted.
  • composition 1 topically administered (applied) Composition 1 to the infected nail at the listed frequency using an applicator brush such as used to apply nail polish, thereby forming a varnish layer on the nail. Every day, after a bath or shower, the subjects stripped away the varnish layer using an emery board or nail file (according to individual preference). During the stripping of the varnish layer, all subjects noted that the structural integrity of the underlying nail was damaged. Specifically, all the subjects noted that during stripping of the varnish layer, at least a portion of the underlying nail had become soft and weak, and was thereby easily stripped away with no special effort, in some cases as a powdery residue. After the listed number of days, the nail had completely dissolved (i.e., only a clean nail bed was observed with no tough nail present). Further administration of composition 1 was stopped and subsequently growth of new, healthy nails later occurred in all subjects.
  • Example 3 Treatment of fungal infection of the nails with Composition 2
  • Composition 2 was more effective than Composition 1 at treating the infection.
  • Example 4 Treatment of fungal infection of the nails with Composition 2 and 3
  • Composition 2 was applied and stripped together with infected portions of the nail, substantially as described above for Composition 1.
  • the subjects were instructed, subsequently to stripping of a previous varnish layer of Composition 2 but prior to application of a new varnish later of Composition 2, to apply a layer of Composition 3 to the skin surfaces around the nail, including one or more of the hyponychium (under the distal edge of the nail), the onychodermal band, the eponychium, the cuticle, the nail walls and paronychium.
  • the hyponychium under the distal edge of the nail
  • the onychodermal band the onychodermal band
  • the eponychium the cuticle
  • the nail walls the nail walls and paronychium

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Insects & Arthropods (AREA)
  • Zoology (AREA)
  • Animal Husbandry (AREA)
  • Dermatology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Les compositions et les procédés ci-décrits sont utiles dans certains modes de réalisation pour traiter les infections fongiques des ongles des doigts et des orteils.
PCT/IB2011/053964 2010-09-13 2011-09-11 Composition de vernis antifongique WO2012035478A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US38229310P 2010-09-13 2010-09-13
US61/382,293 2010-09-13

Publications (2)

Publication Number Publication Date
WO2012035478A2 true WO2012035478A2 (fr) 2012-03-22
WO2012035478A3 WO2012035478A3 (fr) 2012-06-07

Family

ID=44773102

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2011/053964 WO2012035478A2 (fr) 2010-09-13 2011-09-11 Composition de vernis antifongique

Country Status (1)

Country Link
WO (1) WO2012035478A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014055710A1 (fr) * 2012-10-02 2014-04-10 Amy Doan Composition de vernis à ongle
RU2536273C1 (ru) * 2013-12-03 2014-12-20 Государственное бюджетное учреждение Республики Башкортостан "Научно-исследовательский технологический институт гербицидов и регуляторов роста растений с опытно-экспериментальным производством Академии наук Республики Башкортостан" Средство ухода за кожей, обладающее антифунгальными свойствами
US9205042B1 (en) * 2012-12-31 2015-12-08 Robert Heiman Lip and skin care product, dispenser and methods
CN115836995A (zh) * 2022-08-15 2023-03-24 科丝美诗(上海)检测科技有限公司 一种麦卢卡树提取物的制备方法及在化妆品中的应用
US20230190621A1 (en) * 2021-12-17 2023-06-22 Ashley Ann Thomas Water-based nail polish

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7074392B1 (en) 2000-03-27 2006-07-11 Taro Pharmaceutical Industries Limited Controllled delivery system of antifungal and keratolytic agents for local treatment of fungal infections

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5696164A (en) * 1994-12-22 1997-12-09 Johnson & Johnson Consumer Products, Inc. Antifungal treatment of nails
US6027716A (en) * 1997-04-02 2000-02-22 Farmo-Nat Ltd. Synergistic herbal extracts
US6197305B1 (en) * 1998-01-05 2001-03-06 Farmo-Nat Ltd. Anti-fungal compositions with prolonged activity
US20100159035A1 (en) * 2006-04-04 2010-06-24 Avner Shemer Kit for treating skin infection
EP2207546A1 (fr) * 2007-10-09 2010-07-21 Humco Holding Group, Inc. Traitement des ongles contre les champignons

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7074392B1 (en) 2000-03-27 2006-07-11 Taro Pharmaceutical Industries Limited Controllled delivery system of antifungal and keratolytic agents for local treatment of fungal infections

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REMINGTON: "Remington's Pharmaceutical Sciences,latest edition,", MACK PUBLISHING CO.

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014055710A1 (fr) * 2012-10-02 2014-04-10 Amy Doan Composition de vernis à ongle
US9205042B1 (en) * 2012-12-31 2015-12-08 Robert Heiman Lip and skin care product, dispenser and methods
RU2536273C1 (ru) * 2013-12-03 2014-12-20 Государственное бюджетное учреждение Республики Башкортостан "Научно-исследовательский технологический институт гербицидов и регуляторов роста растений с опытно-экспериментальным производством Академии наук Республики Башкортостан" Средство ухода за кожей, обладающее антифунгальными свойствами
US20230190621A1 (en) * 2021-12-17 2023-06-22 Ashley Ann Thomas Water-based nail polish
CN115836995A (zh) * 2022-08-15 2023-03-24 科丝美诗(上海)检测科技有限公司 一种麦卢卡树提取物的制备方法及在化妆品中的应用

Also Published As

Publication number Publication date
WO2012035478A3 (fr) 2012-06-07

Similar Documents

Publication Publication Date Title
US9775872B2 (en) Topical pharmaceutical bases for preventing viral diseases
EP2207546A1 (fr) Traitement des ongles contre les champignons
JPH10298096A (ja) 相乗的草本抽出物
EP2112929B1 (fr) Préparation végétale cicatrisante
EP0621787A1 (fr) Melange therapeutique pour la peau, contenant un extrait d'aloes vera traite a froid dont la seve jaune et l'aloine ont ete enlevees
GB2459121A (en) A product for topical administration
JPH05506851A (ja) 育毛促進および皮膚の処理を行う方法および製品
WO2012035478A2 (fr) Composition de vernis antifongique
KR20200137526A (ko) 탈모 예방 및 발모 촉진용 조성물
Patil et al. Ethno-pharmacological review of a herbal drug: Anogeissus latifolia
US20200330543A1 (en) A topical herbal healing formulation
GB2518826A (en) Composition
CN107496792B (zh) 一种消炎抗菌治疗灰指甲的凝胶剂及其制备方法
CN100435801C (zh) 一种治疗皮肤病的外用药物及其制备方法
JP6590233B1 (ja) 皮膚疾患治療剤及びその製造方法
Ananthathavam et al. Treating periodontitis with the use of essential oil and herbs
EP1194136B1 (fr) Composition non solide pour application locale comprenant du glycerol et un extrait d'alchemille vulgaire
DE20109044U1 (de) Pharmazeutische Zubereitung
US20130052289A1 (en) Medicine containing extracts of Ficus microcarpa for healing wounds of a diabetic patient
CN114146051A (zh) 生肌愈疡中药凝胶剂及其制备方法
US11154583B2 (en) Composition and method of skin relief cream useful for eczema, psoriasis, lipoma, burn wounds, scars, keloids, shingles, dry skin disorders, and skin allergies
EP3108877A1 (fr) Composition topique comprenant des ingrédients naturels pour guérison d'ecchymoses ou hématomes sur la peau et son utilisation
CN104138499B (zh) 一种治疗手足癣和甲癣的中药组合物、其制备方法及其应用
JPH04253917A (ja) 茵▲ら▼蒿（カワラヨモギ）、枇杷葉の配合外用剤
CN111686189B (zh) 一种治疗红屁股的植物组合物及其应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11767298

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11767298

Country of ref document: EP

Kind code of ref document: A2