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WO2016015094A1 - Composition topique - Google Patents

Composition topique Download PDF

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Publication number
WO2016015094A1
WO2016015094A1 PCT/AU2015/000457 AU2015000457W WO2016015094A1 WO 2016015094 A1 WO2016015094 A1 WO 2016015094A1 AU 2015000457 W AU2015000457 W AU 2015000457W WO 2016015094 A1 WO2016015094 A1 WO 2016015094A1
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WO
WIPO (PCT)
Prior art keywords
composition
topical composition
group
active agent
topical
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.)
Ceased
Application number
PCT/AU2015/000457
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English (en)
Inventor
Felicia Maria COLAGRANDE
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.)
Acrux DDS Pty Ltd
Original Assignee
Acrux DDS Pty 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
Priority claimed from AU2014902967A external-priority patent/AU2014902967A0/en
Application filed by Acrux DDS Pty Ltd filed Critical Acrux DDS Pty Ltd
Publication of WO2016015094A1 publication Critical patent/WO2016015094A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to topical compositions and to the use of the
  • topical compositions for the transdermal or topical delivery of an active agent to treat conditions such as bacterial, fungal, yeast and/or mould infections, inflammation and joint pain are intended to be used to aid in transdermal, transmucosal, subdermal, transmembrane, local and musculoskeletal deliveries of a therapeutically effective amount of an active ingredient to a subject.
  • the invention is
  • Topical compositions have been used to deliver a range of active agents for achieving treatment of the skin and/or localised delivery to underlying tissues tissue such as muscles, bones, ligaments and internal organs covered by the skin. Topical compositions have been used in the delivery of antifungals to the skin and mucosal membranes and anti-inflammatory agents to relieve joint pain.
  • DMSO Dimethyl sulfoxide
  • Topical compositions with DMSO for administration of a range of actives including Diclofenac are known but generally speaking require a content of at least 60% DMSO for good efficacy. However at these levels DMSO can cause erythema and wheals in the stratum corneum and may denature some proteins. Other side effects associated with the use of high concentration of DMSO include scaling, contact uticaria, stinging and burning sensations. DMSO also is associated with the metabolite dimethyl sulphide which produces a foul odour on the breath and body odour.
  • the invention provides topical composition comprising: from 0.01 to 15% w/v of at least one active agent;
  • polar aprotic solvent selected from the group consisting of DMSO, acetone and ethyl acetate;
  • polyol selected from glycerol, propylene glycol, sorbitol and mixtures thereof;
  • the active agent is generally for treatment of conditions selected from
  • active agents include those selected from the group consisting of antifungal agents, antibiotics, anti-bacterial agents, anti-cancer agents, anti- rheumatic agents, anti-inflammatory agents, anti-histamine agents, anti- psoriatic agents or combinations thereof. More preferably the active agent is selected from antifungal agents and anti-inflammatory agents.
  • the polar aprotic solvent is selected from ethyl acetate, acetone or dimethylsufloxide. Most preferably the polar aprotic solvent is
  • DMSO dimethylsulphoxide
  • the polyol is selected from linear and branched chain alkyl polyhydroxyl compounds such as, propylene glycol, sorbitol and glycerol. Most preferably the polyol is glycerol.
  • the topical composition is selected from linear and branched chain alkyl polyhydroxyl compounds such as, propylene glycol, sorbitol and glycerol. Most preferably the polyol is glycerol.
  • polar aprotic solvent selected from the group consisting of DMSO, acetone and ethyl acetate, preferably DMSO;
  • polyol selected from glycerol, propylene glycol, sorbitol and mixtures thereof;
  • the polar aprotic solvent selected from DMSO, acetone and ethyl acetate, preferably DMSO is preferably present in an amount of from 1 % to 15.0% w/v of the composition, more preferably from 1 % to 10% w/v of the composition.
  • the weight ratio of polar aprotic solvent to polyol is
  • the weight ratio of DMSO to glycerol is between 10:1 to 1 :10, preferably 1 :5 to 5:1 or about 1 :2 to 2:1 such as about 1 :1 .
  • the active agent is present in an amount of from 0.1 % to 10% w/v of the composition, and preferably between 0.1 % to 5%, w/v of the composition.
  • the ratio of polar aprotic solvent to polyol is used to manipulate the permeation of the active. By altering the ratio of polar aprotic solvent to polyol, the rate of delivery of the active agent can be modified.
  • the composition comprises a lower alkanol selected from ethanol, isopropanol or a mixture thereof.
  • mixture thereof is generally in the range of from 40% to 90%, preferably from 45% to 90% v/v of the composition and still more preferably from 50% to 90% v/v of the composition and most preferably from 55% to 90% v/v of the composition.
  • 60% to 90% v/v of the composition is ethanol, isopropanol or a mixture thereof.
  • the composition comprises water.
  • water is present in an amount of up to 55% v/v of the composition, preferably 1 % to 55% v/v of the composition, more preferably from 5% to 55% and in some embodiments from 10% to 55% v/v of the composition.
  • composition further comprises
  • the physiologically acceptable surfactant comprises a physiologically acceptable surfactant.
  • the physiologically acceptable surfactant comprises an anionic surfactant, a cationic surfactant, a non-ionic surfactant, an amphoteric surfactant or combinations thereof.
  • the physiologically acceptable surfactant is an amphoteric surfactant comprising a quaternary ammonium group.
  • the composition further comprises a physiologically acceptable acid.
  • the acid is selected from the group consisting of citric acid, succinic acid, salicylic acid, salicylates (for example the methyl, ethyl and propyl glycol derivatives), tartaric acid, lactic acid, glycolic acid, phosphoric acid, hyaluronic acid, undecylenic acid, ascorbic acid, formic acid, alpha Hydroxy acid (AHA), beta hydroxy acid (BHA), trichloracetic acid (TCA) or retinoic acid, and mixtures thereof.
  • composition further comprises
  • the preservative is selected from the group consisting of sepicide, tween 80, methylparaben, benzalkonium chloride or other surfactants, benzoic acid, benzyl alcohol, bithional, butyl p- hydroxy benzoate, p-chloro- m-xylenol, dehydro acetia acid, ethyl paraben, methyl-p- hydroxybenzoate, propyl-p- hydroxybenzoate and sorbic acid and mixtures thereof.
  • composition further comprises
  • the emollient is an ester, a fatty acid, an alcohol, a polyol, a triglyceride, a hydrocarbon or mixtures thereof.
  • the emollient fatty alcohol is do to C20 fatty alcohol such as cetyl, myristyl, palmitic and stearyl alcohols or mixtures thereof.
  • the emollient polyol is polyethylene glycol and propylene glycol or mixtures thereof.
  • the emollient hydrocarbon is C12 to C30 hydrocarbon such as mineral oil, petroleum jelly, squalene, isoparaffins or mixtures thereof
  • composition further comprises
  • the physiologically acceptable cosolvent is selected from the group consisting of acetone, N-Methyl-2-pyrrolidone, oleyl alcohol, phenylethyl alcohol, propylene glycol, pentylene glycol, polyethylene glycol, liquid paraffin, triglyceride oils, lanolin alcohols, ecamsule, drometrizole trisiloxane, octyldodecanol, octisalate, acetylated lanolin alcohols, benzyl alcohol, cerostearyl alcohol, C10 to C26 fatty alcohols and salts thereof, liquid mono- or diglycerides and mixtures thereof.
  • the total amount of solvent other than the polar aprotic solvent selected from DMSO, acetone and ethyl acetate, polyol selected from glycerol, propylene glycol and mixtures thereof, lower alkanol selected from ethanol, isopropanol and mixtures thereof and water constitutes no more than 5% w/v of the topical composition, preferably no more than 2% w/v, more preferably no more than 1 % and most preferably no more than 0.5% w/v of the topical composition.
  • the active agent is an antifungal agent.
  • classes of antifungals include ciclopirox and salts thereof, imidazole
  • the antifungal agent comprises one or more selected from the group consisting of azoles, echinocandins, polyenes, allylamines, imidazoles, triazoles, thiazoles, allylamines, and others.
  • the active agent is an antibiotic.
  • the active agent is an antibiotic.
  • antibiotic comprises carbocephems, ansamycins, aminoglycosides,
  • carbapenems cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, penicillins, flouroquinolones,
  • the active agent is an anti-bacterial agent.
  • the anti-bacterial agent comprises quinolones, fluoroquinolones,
  • the active agent is an anti-cancer agent.
  • the anti-cancer agent comprises bleomycin, hydroxyurea, doxorubicin, cisplatin, tretinoin, hydroxyurea, 5-fluorouracil, 5-aminolevulinic acid (5-ALA) and its derivatives, imiquimod, resiquimod , ubidecarenone, cis-urocanic acid, indomethacin, disitertide, alitretinoin, ingenol mebutate,
  • the active agent is an anti-rheumatic agent.
  • the anti-rheumatic agent comprises symptom modifying anti-rheumatics, corticosteroids, non-steroidal anti-inflammatory agents, disease modifying antirheumatic agents, slow-acting anti-rheumatic agents and immunosuppressive cytotoxic drugs or combinations thereof.
  • the active agent is an anti-inflammatory agent.
  • the anti-inflammatory agent comprises inhibitors of COX-1 , inhibitors of COX-2, naproxen, ibuprofen, ketoprofen, diclofenac, sulindac, etodolac, flubiprofen, piroxicam, ketorolac, indomethacin, meloxicam, mefenamic acid, nabumetone, oxaprozin, meclofenamate, tolmetin or combinations thereof.
  • the active agent is an anti-histamine agent.
  • the anti-histamine agent comprises fexofenadine, loratadine, phenindamine, dexchlorpheniramine, terfenadine, cetirizine, tripolidine, promethazine, brompheniramine, chlorpheniramine, diphenhydramine, carbinoxamine, cyproheptadine, promethazine, levocetirizine, hydroxyzine, desloratadine, clemastine or combinations thereof.
  • the preferred active agents are antifungals, anti-inflammatory agents and
  • the active agent is an anti-psoriatic agent.
  • the anti-psoriatic agent comprises acitretin, methotrexate or combinations thereof.
  • the composition is in the form of a liquid or semisolid solution, gel, spray, emulsion, suspension, cream, microemulsion or patch.
  • the present invention provides a method of treating or
  • the present invention provides a method of treating skin diseases comprising applying to the skin a therapeutically affective amount of the composition as described herein.
  • the composition will preferably be applied in a dose sufficient to provide an effective amount of the active agent on the skin of the human and other mammal.
  • the present invention provides use of the composition as described herein for the manufacture of a medicament for the treatment of diseases and conditions affecting the skin of humans and other mammals. In some embodiments, the present invention provides use of the composition as described herein for the manufacture of a medicament for the treatment or prevention of skin disease.
  • topical composition is used to refer to a composition for application to body surfaces such as the skin or mucous membranes to treat ailments.
  • the composition may be in any of a range of forms including but not limited to creams, foams, gels, lotions, patches and ointments.
  • the topical composition may be epicutaneous, meaning that it is applied directly to the skin or mucosa.
  • the effect of the topical composition in the pharmacodynamics sense may be local and primarily address condition of the skin including either or both of the epidermis and underlying dermal layers and/or tissue such as muscles, bones, ligaments and internal organs covered by the skin rather than systemic, or be systemic or provide both local and systemic effects.
  • Topical compositions can be used for both topical and transdermal administration of substances.
  • active agent is used herein to refer to a broad class of useful
  • physiologically active agent includes prodrugs of the agent which in vivo exerts the physiological effect.
  • a “prodrug” is an active agent which is administered in an inactive or less
  • a pharmaceutically active agent used in the transdermal delivery system of the invention include agents which are prodrugs which on administration form a more active agent in vivo during or after the process of transdermal administration.
  • physiologically acceptable in relation to a component means a
  • a component which may be topically applied to a host, particularly to the skin of a host, and is compatible with the skin and preferably suitable for coming into contact with the skin without causing a toxic reaction.
  • alcohol is used herein in the broadest sense to refer to compounds in which a hydroxy group, -OH, is attached to a saturated carbon atom.
  • polypeptide means a polymer made up of amino acids
  • polypeptide may constitute a portion of a full length protein.
  • antifungal agent includes agents that are effective against fungi that cause infections of the skin and/or mucous membranes.
  • the "antifungal” agent is effective against the fungi that cause fungal infections of the skin such as one or both of the dermal and epidermal layers of the skin.
  • a listing of antifungal agents, without limitation thereto, may be found, for example, in the Fifteenth Edition of The Merck Index (2013) under the classification "Antifungal”.
  • % w/v refers to the percent by weight in the total volume of
  • composition Generally %w/v refers to the number of grams in 100 ml_ of composition.
  • the preferred antifungals are non-plant derived polypeptide
  • antifungal agents that is, they are preferably not polypeptides which have been both derived from plants and contain antifungal activity.
  • polar aprotic solvent includes solvents with a
  • polar aprotic solvent and dipolar aprotic solvent are used
  • polyol as used herein includes alcohols which contain two or more hydroxyl groups.
  • the polar aprotic solvent is selected from ethyl acetate, acetone or
  • DMSO dimethylsulphoxide
  • the polyol is selected from linear and branched chain alkyl
  • polyhydroxyl compounds such as, propylene glycol, glycerol, sorbitol and mixtures thereof. Most preferably the polyol is glycerol.
  • the invention provides topical composition
  • topical composition comprising: from 0.01 to 15% w/v of at least one active agent; from 0.1 % to 20% w/v of polar aprotic solvent selected from the group consisting of DMSO, acetone and ethyl acetate; from 0.1 % to 20% w/v of polyol selected from glycerol, propylene glycol, sorbitol and mixtures thereof; and from 40% to 90% v/v of lower alkanol selected from the group consisting of ethanol, isopropanol and mixtures thereof.
  • polar aprotic solvent selected from the group consisting of DMSO, acetone and ethyl acetate
  • polyol selected from glycerol, propylene glycol, sorbitol and mixtures thereof
  • lower alkanol selected from the group consisting of ethanol, isopropanol and mixtures thereof.
  • the topical composition comprises: from 0.01 to 15% w/v of at least one active agent selected from the group consisting of antifungals and anti-inflammatory agents; from 0.1 % to 20% w/v of polar aprotic solvent selected from the group consisting of DMSO, acetone and ethyl acetate, preferably DMSO; from 0.1 % to 20% w/v of polyol selected from glycerol, propylene glycol, sorbitol and mixtures thereof; and from 40% to 90% v/v of lower alkanol selected from the group consisting of ethanol, isopropanol and mixtures thereof; and optionally water in an amount of from 5% to 55% v/v of the composition, preferably 10% to 55%v/v of the composition and still more preferably from 20% to 55% v/v of the composition.
  • active agent selected from the group consisting of antifungals and anti-inflammatory agents
  • polar aprotic solvent selected from the group consisting of DMSO, ace
  • composition of the present invention is useful for topical delivery of an
  • topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having the topical composition having
  • topical composition of the present invention can shorten the treatment period, avoid or eliminate at least some of the disadvantages associated with systemic drugs and improve clinical efficacy as it is applied to the site of the disease.
  • topical composition of the present invention is suitable for use for the
  • the active agent may be a pharmacologically active compound.
  • pharmaceutically active compound is a compound that has a therapeutic effect on the human or animal body in the treatment or prevention of a condition.
  • the active agent is selected from the group consisting of antifungal agents, antibiotics, anti-bacterial agents, anti-cancer agents, antirheumatic agents, anti-inflammatory agents, anti-histamine agents, anti- psoriatic agents or combinations thereof.
  • the active agent is an antibiotic.
  • the active agent is an antibiotic.
  • antibiotic comprises at least one selected from the group consisting of carbocephems, ansamycins, aminoglycosides, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, penicillins, flouroquinolones, sulfonamides, tetracyclines, oxazolidonones, penicillins or combinations thereof.
  • the active agent is an antifungal such as selected from the group consisting of ciclopirox and pharmaceutically acceptable salts thereof, imidazole antifungals, triazole antifungals, thiazole antifungals, allylamine antifungals and echinocandin antifungals.
  • imidazole antifungals may be selected from the group consisting of bifonazole,
  • ketoconazole luliconazole, miconazole, omoconazole, oxiconazole,
  • Triazole antifungals may be selected from the group consisting of
  • Thiazole antifungals include abafungin and salts thereof.
  • allylamine antifungals examples include amorolfine, butenafine, naftifine, terbinafine and salts thereof.
  • echinocandin antifungals examples include anidulafungin, caspofungin, micafungin, and salts or mixtures of these.
  • Preferred antifungals comprise at least one selected from the group consisting of ciclopirox or its olamine, amorolfine or its salt, amorolafine, bifonazole, tavarole (AN2690), flucytosine, griseofulvin, haloprogin, tolnaftate, terbinafine, intraconazole, fluconazole, clotrimazole, griseofulvin, flucytosine, ketoconazole, voriconazole, naftifine, nystatin, undecylenic acid, econaxzole, miconazole, miconozole nitrate, mycostatin, tolnaftate, oxiconazole, oxiconazole nitrate, sertacanazole, sulconazole, sulconazole nitrate, luliconazole, efinaconazole , butoconazole, fenticonazole, is
  • posaconazole 17-AAG, E1210, D75-4590, isavuconazonium sulfate, and micafungin.
  • the active agent comprises ciclopirox, luliconazole or efinaconazole.
  • the antifungal agent is a lytic peptide, mammalian peptide, insect-derived antimicrobial peptide, amphibian-derived peptide, antifungal peptides produced by bacteria and fungi, chitin synthase inhibitors, peptides affecting glucan synthesis and synthetic peptides.
  • the composition comprises an antibiotic.
  • an antibiotic any antibiotic known to a person skilled in the art may be used. Suitable antibiotics comprise, but are not limited to, carbocephems, ansamycins, aminoglycosides, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, oxazolidonones, penicillins and the like or combinations thereof.
  • antibiotics may include, for example, chloramphenicol,
  • the composition comprises an anti-bacterial agent.
  • any anti-bacterial agent known to a person skilled in the art may be used.
  • Suitable anti-bacterial agents comprise, but are not limited to, quinolones, fluoroquinolones, sulphonamides, tetracyclines, actives against mycobacterial and the like or combinations thereof.
  • the composition comprises an anti-cancer agent.
  • any anti-cancer agent known to a person skilled in the art may be used.
  • Suitable anti-cancer agents comprise, but are not limited to, bleomycin, hydroxyurea, 5-fluorouracil and others or combinations thereof.
  • the active agent comprises an anti-inflammatory agent.
  • the anti-inflammatory agent may be selected from the group consisting of steroidal anti-inflammatory agents, particularly corticosteroids, non-steroidal anti-inflammatory agents (NSAIDS) and mixtures thereof.
  • non-steroidal anti-inflammatory agents for use in the composition of the present invention include their racemic mixtures or individual
  • enantiomers where applicable, such as ibuprofen, flurbiprofen, ketoprofen, aclofenac, diclofenac, aloxiprin, aproxen, aspirin, diflunisal, fenoprofen, indomethacin, mefenamic acid, naproxen, phenylbutazone,
  • non-steroidal anti-inflammatory agents which can be present in the composition of the present invention include salicylamide, salicylic acid, flufenisal, salsalate, triethanolamine salicylate, aminopyrine, antipyrine, oxyphenbutazone, apazone, cintazone, flufenamic acid, clonixeril, clonixin, meclofenamic acid, flunixin, colchicine, demecolcine, allopurinol, oxypurinol, benzydamine hydrochloride, dimefadane, indoxole, intrazole, mimbane hydrochloride, paranylene
  • NSAIDS may be present in the form of salts including metal salts such as the sodium salt and organic salts such as the lysine salt.
  • diclofenac is used in a form selected from the acid form, sodium salt form or lysine salt form.
  • anti-inflammatory agents include corticosteroids which may be corticosteroids.
  • betamethasone comprise at least one selected from the group consisting of betamethasone, betamethasone valerate, betamethasone dipropionate, diflucortolone valerate, cortisone, methylprednisolone aceponate, Clobetasone butyrate,
  • dexamethasone dexamethasone 21 -phosphate, fludrocortisone,
  • symptom modifying anti-rheumatics for use in the composition of the present invention include aspirin, non-steroidal anti-inflammatory drugs, steroids and the like.
  • compositions of the present invention include cyclosporine, cyclophosphamide, hydroxychloroquine, leflunomide, methotrexate, mycophenolate, sulfasalazine and the like.
  • Additional examples include biological therapies such as abatacept, rituximab, tocilizumab, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and the like.
  • Examples of slow-acting anti-rheumatic agents for use in the present invention include hydroxychloroquine, aurothioglucose and the like.
  • methotrexate mechlorethamine, cyclophosphamide, chlorambucil, azathioprine and the like.
  • the composition comprises an anti-inflammatory agent.
  • any anti-inflammatory agent known to a person skilled in the art may be used.
  • Suitable anti-inflammatory agents comprise, but are not limited to, inhibitors of COX-1 , inhibitors of COX-2, naproxen, ibuprofen, ketoprofen, diclofenac, sulindac, etodolac, flubiprofen, piroxicam, ketorolac, indomethacin, meloxicam, mefenamic acid, nabumetone, oxaprozin, meclofenamate, tolmetin and the like or combinations thereof.
  • the composition comprises an anti-histamine agent.
  • any anti-histamine agent known to a person skilled in the art may be used.
  • Suitable anti-histamine agents comprise, but are not limited to, fexofenadine, loratadine, phenindamine, dexchlorpheniramine, terfenadine, cetirizine, tripolidine, promethazine, brompheniramine, chlorpheniramine, diphenhydramine, carbinoxamine, cyproheptadine, promethazine,
  • the composition comprises anti-psoriatic agents.
  • any anti-psoriatic agent known to a person skilled in the art may be used.
  • Suitable anti-psoriatic agents comprise, but are not limited to, acitretin, methotrexate and others or mixtures thereof.
  • the more preferred active agents are antifungals, anti-inflammatory agents and a combination of antifungal and anti-inflammatory agent.
  • the use of a combination is particularly useful in treating fungal infection of the skin and general provides more effective treatment by reducing inflammation to provide improved efficacy in controlling the fungal infection.
  • the amount of active agent in the composition will differ depending on the
  • the amount will be an amount required to achieve an effective concentration of the active at the required treatment site.
  • the amount of physiologically active agent is in the range between about 0.1 to about 15% by weight of the composition, or in the range between about 0.5 to about 15% by weight of the composition, or in the range between about 0.5 to about 10% by weight of the composition, such as 0.5%, 1 .0%, 1 .5% 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, by weight, or in the range between about 0.5 to about 5% by weight of the composition.
  • the topical composition according to the invention also comprises a combination of from about 0.1 % to 20% w/v of a polar aprotic solvent; and from about 0.1 % to 20% w/v of a polyol.
  • the polar aprotic solvent is selected from the group consisting of ethyl acetate, acetone and dimethylsufloxide.
  • DMSO and mixtures thereof is particularly preferred. Of the polar aprotic solvents DMSO alone is the most preferred.
  • the polyol is selected from the group consisting of propylene glycol, glycerol, sorbitol and mixtures thereof.
  • the polyol is preferably selected from glycerol, propylene glycol and mixtures thereof. Glycerol alone is the most preferred.
  • the polar aprotic solvent is present in an amount sufficient to enhance the
  • topical delivery of the active agent can vary depending on the amount of polyol present in the composition and the desired delivery rate.
  • the composition comprises from about 0.1 % to 20% w/v of polar aprotic solvent.
  • the composition comprises polar aprotic solvent in an amount in the range of from 1 % to 15%, preferably between about 2% to 15.0% w/v, such as from 2% to 10% w/v, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 1 1 %, 12%, 13%, 14% and 15% w/v of the composition..
  • Polyol is present in an amount sufficient to enhance the topical delivery of the active agent.
  • the amount can vary depending on the amount of polar aprotic solvent present in the composition and the desired delivery rate.
  • the composition comprises from about 0.1 % to 20.0% w/v, and preferably between about 1 % to 15.0% w/v such as from 2% to 15% w/v, 2% to 10% w/v, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 1 1 %, 12%, 13%, 14%, 15% w/v.
  • the polar aprotic solvent is DMSO and polyol is
  • DMSO polar aprotic solvent
  • polyol particularly glycerol
  • DMSO is preferably present in an amount sufficient to enhance the topical delivery of the active agent. The amount can vary depending on the amount of glycerol present in the composition and the desired delivery rate.
  • the composition comprises DMSO in an amount in the range between about 0.1 % to 20.0% w/v, and preferably between about 1 % to 15.0% w/v, such as 2% to 15% w/v, 2% to 10% w/v, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 1 1 %, 12%, 13%, 14%, 15% w/v.
  • Glycerol is preferably present in an amount sufficient to enhance the topical delivery of the active agent.
  • the amount can vary depending on the amount of DMSO present in the composition and the desired delivery rate.
  • the composition comprises glycerol in an amount in the range between about 0.1 % to 20.0% w/v, and preferably between about 1 % to 15.0% w/v such as 2% to 15% w/v, 2% to 10% w/v, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 1 1 %, 12%, 13%, 14%, 15% w/v.
  • the ratio of DMSO to glycerol can vary and depends on the desired topical delivery rate of the active agent.
  • the optimal ratio may vary depending on the nature and concentration of the non-plant derived polypeptide antifungal agent and the concentration of polar aprotic solvents, particularly DMSO, and polyol, particularly glycerol, in the composition.
  • the weight ratio is in the range of from 100:1 to 1 :100.
  • the weight ratio of polar aprotic solvent, particularly DMSO, to polyol, particularly glycerol is in the range of from 1 :10 to 10:1 , preferably from 1 :5 to 5:1 such as 1 :10, 1 :9, 1 :8, 1 :7, 1 :6, 1 :5, 1 :4, 1 :3, 1 :2, 1 :1 , 2:1 , 3:1 , 4:1 , 5:1 , 6:1 , 7:1 , 8:1 , 9:1 and 10:1
  • the weight ratio of DMSO to glycerol is from 2:1 to 1 :2 such as about 1 :1 .
  • the ratio of DMSO to glycerol is used to manipulate the permeation of the active. By altering the ratio polar aprotic solvent to polyol, the rate of topical delivery of the active agent can be modified.
  • the topical composition comprises lower alkanol selected from the group
  • the topical composition according to the invention further comprises water.
  • Water is preferably present in an amount of from 1 % to 55% v/v, preferably 5% to 55% v/v of the composition, more preferably 10% to 55%v/v of the composition.
  • water is present in from 15% to 55% such as 15% to 50%v/v, 15% to 40% v/v or 15% to 30% v/v of the composition.
  • Water may have several functions. Water may solubilise the active agent and may also function in combination with the polar aprotic solvent and polyol to enhance transdermal delivery of the active agent.
  • glycerol, polyols and the like contain a certain amount of water.
  • composition according to the present invention may, and preferably will also comprise additional water, that is water that is in addition to the water present in the alcohols, DMSO and glycerol.
  • the topical composition according to the invention comprises
  • a thickener further comprises a thickener.
  • a thickener any thickener known to a person skilled in the art may be used. Suitable thickeners include, but are not limited to, polyacrylic acids; and acrylic acid copolymers, agar, acacia, carrageenan, food starch, gelatins, germ Arabic, guorgem, hydroxyethyl cellulose
  • hydroxypropymethyl cellulose protein, polyvinyl pyrrolidone; guargum, xanthan gum, gelatin, methylcellulose, methylhydroxypropylcellulose,
  • the preferred thickener is polyvinyl pyrrolidone.
  • the thickener may also serve other functions, such as enhancing topical delivery of the active agent.
  • the thickener is present in an amount to provide a viscosity of 15 - 1000 cp. In some embodiments, the amount of thickener present in the topical composition is sufficient to enhance the topical delivery of the active agent. In some embodiments, the thickener is present in an amount of from 0.1 to 10%, by weight of the composition.
  • the thickener may be present in an amount of 0.1 , 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1.2, 1 .5, 1 .7, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5 and 10% by weight of the composition.
  • composition according to the invention further comprises
  • the preservative comprises a preservative.
  • the preservative may be selected from the group consisting of sepicide, tween 80, methylparaben, benzalkonium chloride or other surfactants, benzoic acid, Bithional, butyl p-hydroxy benzoate, p- chloro- m-xylenol, dehydro acetia acid, ethyl paraben, methyl-p- hydroxybenzoate, propyl-p- hydroxybenzoate, sorbic acid and combinations thereof.
  • the preservative is present in an amount from 0.01 to 20%.
  • the preservative may be present in an amount of 0.01 , 0.02, 0.03, 0.04, 0.05, 0.06, 007, 0.05, 0.08, 0.09, 0.1 , 0.12, 0.15, 0.017, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 and 20% by weight of the composition
  • the topical composition according to the invention comprises
  • physiologically acceptable cosolvent any physiologically acceptable cosolvent known to a person skilled in the art may be used.
  • the physiologically acceptable cosolvent is selected from the group consisting of acetone, ethyl acetate, butyl acetate or other acetates, oleyl alcohol, phenylethyl alcohol, pentylene glycol, polyethylene glycol, liquid paraffin, triglyceride oils, lanolin alcohols, octyldodecanol, octisalate, acetylated lanolin alcohols, benzyl alcohol, cerostearyl alcohol, C6 to C26 fatty alcohols and salts thereof such as C-io to C 2 6 fatty alcohols, and liquid mono- or diglyceride and the like and combinations thereof.
  • the cosolvent is present in an amount from 2% to 40%.
  • the preservative may be present in an amount of 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 36, 37, 38, 39 and 40% by weight of the composition
  • pH stabilisers including acidifying compounds and their use to lower the pH of a formulation are well known to a practitioner in the art.
  • acidifying stabilizers include, but are not limited to compounds selected from the group consisting of hydrochloric acid, citric acid, lactic acid, ascorbic acid, malic acid, isoascorbic acid, cysteine hydrochloride, cysteine dihydrochloride, citric acid fumaric acid, acetic acid, sorbic acid, glycine hydrochloride, arginine hydrochloride, succinic hydrochloride, succinic acid, tartaric acid, phosphoric acid, hydrochloric acid, glucono-delta-lactone, salicylic acid, salicylates (for example the methyl, ethyl and propyl glycol derivatives), glycolic acid, hyaluronic acid, undecylenic acid, formic acid, alpha hydroxy acid (AHA), beta hydroxy acid (BHA), trichlorace
  • pH stabilising agent may be present in an amount of from
  • 0.01 % to 10% w/v of the composition such as , 0.02, 0.03, 0.04, 0.05, 0.06, 007, 0.05, 0.08, 0.09, 0.1 , 0.12, 0.15, 0.17, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10% w/v of the composition.
  • the topical composition may comprise an antioxidant which may, for example, comprise one or more selected from the group consisting of alpha tocopheral, ascorbic acid, ascobyl palmitate, fumeric acid, malic acid, citric acid, sodium ascorbate, sodium metabisulfate, n-propyl gallate, BHA (butylated
  • topical composition according to the invention further comprises a physiologically acceptable emollient.
  • a physiologically acceptable emollient in some embodiments
  • the emollient is an ester, a fatty acid, an alcohol, a polyol, a hydrocarbon or mixtures thereof.
  • the emollient fatty alcohol is C10 to C20 fatty alcohol such as cetyl, myristyl, palmitic and stearyl alcohols or mixtures thereof.
  • the emollient polyol is polyethylene glycol and propylene glycol or mixtures thereof.
  • the emollient hydrocarbon is C12 to C30 hydrocarbon such as mineral oil, petroleum jelly, squalene, isoparaffins or mixtures thereof.
  • the composition comprises emollient in an amount in the range between about 0.1 % to 20.0% w/v, and preferably between about 2% to 15.0% w/v such as 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 6%, 7%, 8%, 9%, 10%, 1 1 %, 12%, 13%, 14%, 15% w/v of the composition.
  • the topical composition according to the invention comprises
  • physiologically acceptable surfactant any physiologically acceptable surfactant known to a person skilled in the art may be used.
  • the physiologically acceptable surfactant is selected from the group consisting of an anionic surfactant, a cationic surfactant, a non-ionic surfactant, an amphoteric surfactant and combinations thereof.
  • Suitable anionic surfactants may include one or more of sodium laurate,
  • Suitable cationic surfactants may include one or more of
  • etyltrimethylammonium bromide tetradecyltrimethylammonium bromide
  • benzalkonium chloride octadecyltrimethylammonium chloride, cetylpyridinium chloride, dodecyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, and mixtures thereof.
  • Suitable non-ionic surfactants include one or more of a-hydro- ⁇ - hydroxypoly(oxyethylene)-poly(oxypropyl) poly(oxyethylene) block copolymers, polyoxyethylene ethers, polyoxyethylene sorbitan esters, polyethylene glycol esters of fatty alcohols, and mixtures thereof.
  • amphoteric surfactant we mean to include any surfactants having the ability to exhibit both positive and negative functional groups.
  • Suitable amphoteric surfactants may include one or more surfactants referred to as betaines (including sultaines), for example alkyl betaines, alkylamidopropyl betaines, alkyl sulphobetaines, alkylamidopropyl hydroxy sultaines, alkylampho acetates, alkylamphodiacetates, alkylamphopropionates, alkylamphodipropionates, alkyliminodipropionates and alkyliminodiacetates (sulphobetaines) and the like wherein preferably the alkyl and acyl groups have from 8 to 18 carbon atoms.
  • betaines including sultaines
  • Suitable amphoteric surfactants may also comprise alkyl glycinates, alkyl carboxyglycinates, alkyl amphopropionates, acyl taurates and acyl glutamates and the like wherein preferably the alkyl and acyl groups have from 8 to 18 carbon atoms or other zwitterionic or amphoteric surfactant.
  • alkyl glycinates alkyl carboxyglycinates, alkyl amphopropionates, acyl taurates and acyl glutamates and the like wherein preferably the alkyl and acyl groups have from 8 to 18 carbon atoms or other zwitterionic or amphoteric surfactant.
  • amphoteric surfactants may comprise lauramidopropyl betaine,
  • cocoamphoprqpionate disodium lauroamphodipropionate, disodium
  • cocoamphodipropionate sodium lauriminodipropionate, disodium
  • cocoamphocarboxymethylhydroxypropylsulfate and the like.
  • the surfactant is an amphoteric surfactant comprising a quaternary ammonium group.
  • the topical composition according to the invention further comprises a colour pigment. Any colour pigment known to a person skilled in the art may be used.
  • the composition according to the present invention comprises at least one excipient such as, but not limited to, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous and water.
  • excipient such as, but not limited to, sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous and water.
  • the compositions encompassed herein will be understood to optionally include one or more other excipients as known to those skilled in the art. A person skilled in the art will know how to identify such an excipient as useful in the present compositions and methods, for example, when such an excipient enhances the therapeutic effectiveness, stability, or potency of a composition or method.
  • a preferred topical composition according to the invention comprises: from about 0.01 to 10% w/w active agent (preferably 0.1 % to 10% w/v), wherein the active agent is selected from the group consisting of antifungal agents, antibiotics, anti-bacterial agents, anti-cancer agents, anti-rheumatic agents, anti-inflammatory agents, anti-histamine agents, anti-psoriatic agents or combinations thereof, preferably antifungals, anti-inflammatory agents and mixtures thereof; from about 1 % to 10% w/v DMSO; from about 1 % to 15% w/v glycerol; from about 45% to 90% v/v lower alcohol selected from the group consisting of ethanol, isopropanol and mixtures thereof; and optionally from about 5% to 55% v/v water.
  • active agent is selected from the group consisting of antifungal agents, antibiotics, anti-bacterial agents, anti-cancer agents, anti-rheumatic agents, anti-inflammatory agents, anti-histamine agents, anti-psoriatic agents or
  • the topical composition according to the invention consists of: from about 0.01 to 10% w/w active agent (preferably 0.1 % to 10% w/v), wherein the active agent is selected from the group consisting of antifungal agents, antibiotics, anti-bacterial agents, anti-cancer agents, anti-rheumatic agents, anti-inflammatory agents, anti-histamine agents, anti-psoriatic agents or combinations thereof, preferably antifungals, anti-inflammatory agents and mixtures thereof; from about 1 % to 10% w/v DMSO; from about 1 % to 10% w/v glycerol; from about 45% to 90% v/v lower alcohol selected from the group consisting of ethanol, isopropanol and mixtures thereof; and optionally from about 5% to 50% v/v water.
  • active agent is selected from the group consisting of antifungal agents, antibiotics, anti-bacterial agents, anti-cancer agents, anti-rheumatic agents, anti-inflammatory agents, anti-histamine agents, anti-psoriatic agents or
  • a method of treatment of fungal infection of the skin or mucous membrane comprising topically applying the surface of the skin or mucous membrane a topical composition comprising: from 0.1 % to 10% w/v of active agent component comprising at least one antifungal active and optionally and anti-inflammatory in the range of from 0.1 % to 10% w/v;
  • a method of treatment of joint pain comprising topically applying to the joint a topical composition comprising: from 0.1 % to 10% w/v of at least one anti-inflammatory active agent;
  • the composition is in the form of a liquid or semisolid solution, gel, spray, emulsion, suspension, microemulsion or patch.
  • the composition may be suitable for application at least once a day, twice daily or as needed.
  • the composition may be re-applied with or without an intervening water rinse.
  • the composition will preferably be applied to the affected area of skin in a dose and for a period of time sufficient to achieve efficacy.
  • substantially dry to the touch within a period in the range between 0.5 to 10 minutes, preferably within the range of about 1 to 5 minutes.
  • the person skilled in the art will appreciate the period before the skin is substantially dry to the touch may depend on the specific composition. We have found in this regard that a high proportion of lower alcohol provides rapid drying and also more reliable skin penetration by providing a reservoir of the active agent within the skin layer.
  • the topical compositions containing antiinflammatory drugs are particularly useful in treatment of joint pain.
  • Joint pains include: shoulder pain, such as AC arthrosis (bursitis, rotator cuff tendonitis); elbow pain, such as medial and lateral Epicondylitis (tennis elbow, golfer's elbow); wrist pain, such as extension and flexor tendonitis; De Quervain's Tenosynovitis (tendonitis); finger problems; hip pain, caused by a "snapping hip;” Trochanteric Bursitis; knee pain; Patellar Athrosis; Post-traumatic patellofemoral pain; Patellar Tendonitis (runner's knee, jumper's knee); Plica; Apophysitis (Osgood-Schlatter) (growing pains); leg pain, such as Gastrocnemius Strain (calf strain); Achilles Tendonitis; ankle pain, such as acute or chronic ankle sprain; foot pain, such as
  • Dysfunction back pain, such as Lumbar Strain; SI pain (sciatica pain); cervical pain and strain; and Trapezius Trigger Points (pinched nerve).
  • the topical composition is useful in treatment of arthritis. Pain, particularly of the joints throughout the body, characterizes arthritis. Psoriasis, primarily a skin disorder, can progress to psoriatic arthritis if left untreated. Rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis are all examples of degenerative arthritic diseases which may be treated using the topical composition comprising an anti-inflammatory active agent.
  • arthritic causes, normal function of a joint and its movement, and other portions of the body, can be severely impaired as a result of trauma or following orthopaedic and other surgical procedures. This may result in tenderness, aching, pain, and lengthy recovery times, as well as loss of joint mobility or reduced range of motion, tonicity, or elasticity of the joint/articular structures, such as for example, muscle, tendon, capsule, bone, or ligament. Reduced joint mobility may also involve permanently altered or shortened joint or tissue architecture.
  • Altered or abnormal joint mobility or joint architecture may also be associated with or caused by a variety of injuries and conditions such as, for example, metabolic disorders, ischemia, injury to joint, capsule, bone, cartilage, tendon, ligament or muscle, fractures, subluxation, dislocation, crush injuries, prolonged immobilization (e.g., immobilization of a joint in a cast or splint), and paralysis.
  • injuries and conditions such as, for example, metabolic disorders, ischemia, injury to joint, capsule, bone, cartilage, tendon, ligament or muscle, fractures, subluxation, dislocation, crush injuries, prolonged immobilization (e.g., immobilization of a joint in a cast or splint), and paralysis.
  • the topical composition for treatment of joint pain may comprise one or more additional active agent selected from the group consisting of glutamine, hyaluronic acid, methylsulfonylmethane and glucosamine.
  • the topical composition comprising antifungal active agent may be used in treatment of a range of fungal diseases, or mycoses, in both humans and animals.
  • the relevant fungal diseases affecting humans can be divided into four groups based on the level of penetration into the body tissues.
  • Cutaneous mycoses or dermatomycoses include such infections as athlete's foot and ringworm, where growth occurs only in the superficial layers of skin or hair;
  • mentagrophytes are responsible for fungal infections of the skin or
  • Dermatophytosis Dermatophytosis (dermatophytose).
  • Dermatophytosis (tinea or ringworm) of the scalp and glabrous skin is caused by a by one of the three genera of fungi collectively called dermatophytes— Epidermophyton, Microsporum, and Trichophyton which have the ability to utilise keratin as a nutrient source, i.e. they have a unique enzymatic capacity [keratinase].
  • the type and severity of the host response is often related to the species and strain of dermatophyte causing the infection.
  • the topical composition may be used in treatment of Tinea Pedis, also known as athletes foot, which is a common and contagious dermatophytic fungal infection of the skin that causes scaling, flaking, and itching of the affected areas. Symptoms are caused by fungi such as Epidermophyton floccosum or fungi of the Trichophyton genus such as T. rubrum or T. mentagrophytes.
  • the disease is typically transmitted in moist communal areas where people walk barefoot, such as showers or bathhouses, and requires a warm moist environment, (e.g., the inside of a shoe) to incubate.
  • the condition typically affects the feet, but may infect or spread to other areas of the body such as the groin and tends to spread to areas of skin that are kept hot and moist, such as with insulation, body heat, and sweat.
  • the topical composition is used in treatment of one or more selected from the group consisting of Tinea Corporis, also known as ringworm, tinea circinata, and tinea glabrosa, is a superficial fungal infection (dermatophytosis) of the arms and legs, especially on glabrous skin; however, it may occur on any part of the body.
  • Tinea Corporis also known as ringworm, tinea circinata, and tinea glabrosa
  • the topical composition may be used in treatment of Tinea Cruris, also known as jock itch or ringworm of the groin, which is a dermatophyte fungal infection of the groin region in either sex, though more often seen in males.
  • Tinea which may be treated using the topical composition include Tinea barbae, tinea capitis, Tinea manuum, Tinea imbricate, Tinea Nigra , Tinea blanca and Tinea versicolor.
  • the topical composition may be used in treatment of Candida,
  • Candida albicans is the most commonly isolated species, and can cause infections (candidiasis or thrush) in humans and other animals.
  • the common sites for Candida to cause infection are the vagina (vaginal thrush), the mouth (oral thrush), and the skin.
  • Candida skin infections can occur on almost any area of the body, but are more commonly found in intertriginous regions— where two skin areas may touch or rub together— such as armpits, the groin, skin folds, and the area between the fingers and toes.
  • the fungus thrives in warm, moist, and sweaty conditions.
  • compositions of the present invention are useful for treatment of diseases of the skin, diseases of diseases of the skin and/or joint pain.
  • compositions of the present invention may be useful for the treatment of fungal infections of the skin such as psoriasis, paronychia, Tinea pedis, Tinea corporis, Tinea cruris, Tinea capitis, Tinea manuum, Tinea barbae, Tinea facilae, Tinea versicolor, candidiasis, fungal keratitis, or any combination thereof.
  • composition of the present invention is useful for the treatment of psoriasis.
  • the topical composition is administered on a schedule once a day. In some embodiments, the topical composition is administered twice a day. In some embodiments, the topical composition is administered three times a day, four times a day, five times a day, or more. In some embodiments the topical composition is administered less frequently than once a day. In some embodiments the topical composition is administered once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days. In some embodiments the topical composition is administered less frequently than once a week. In some embodiments the topical composition is administered once a month. In some embodiments the topical composition is administered twice a month. In some embodiments the topical composition is administered as needed.
  • the composition may be re-applied with or without an intervening water rinse. In some embodiments, one application off the composition is used. In other embodiments, at least two applications of the composition are used depending on the severity and persistence of the condition.
  • the topical composition is applied in a daily regimen for a period sufficient to achieve efficacy.
  • the method according to the invention is practiced daily until the area of skin is visibly free of the disease. Preferably, the method according to the invention is practiced daily until the condition to be treated is relieved.
  • a therapeutic dosing regimen is continued for at least one day, at least two days, at least three days, at least four days, at least five days, at least six days, or at least seven days. In some embodiments, a therapeutic dosing regimen is continued for at least one week, at least two weeks, at least three weeks, at least four weeks, at least six weeks, at least eight weeks, at least ten weeks, at least twelve weeks, at least fourteen weeks, or at least sixteen weeks. In some embodiments, a
  • the present invention provides use of the composition as described herein for the manufacture of a medicament for the treatment of at least one of skin diseases and joint pain.
  • the composition as described herein for the manufacture of a medicament for the treatment of at least one of skin diseases and joint pain.
  • the medicament is for administration on a schedule once a day. In some embodiments, the medicament is for administration twice a day. In some embodiments, the medicament is for administration three times a day, four times a day, five times a day, or more. In some embodiments, the medicament is for administration less frequently than once a day. In some embodiments, the medicament is for administration once every two days, once every three days, once every four days, once every five days, once every six days, or once every seven days. In some embodiments, the medicament is for administration less frequently than once a week. In some embodiments, the medicament is for administration once a month. In some embodiments, the medicament is for administration twice a month. In some embodiments, the medicament is for administration as needed. [135] In some embodiments, the medicament may be re-applied with or without an intervening water rinse. In some embodiments, one coat of the topical composition comprising an antifungal is applied to the skin. In other
  • At least two applications of the medicament are applied. Where more than one application is applied, the first application is substantially touch dry before the subsequent application is applied.
  • the medicament is for administration in a daily regimen for a period sufficient to achieve efficacy.
  • the use according to the invention is practiced daily until the skin is visibly free of disease.
  • compositions encompassed herein may be determined empirically through clinical and/or pharmacokinetic experimentation, and that such dosages may be adjusted according to prespecified effectiveness and/or toxicity criteria. It will also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity and concentration of the specific compounds employed, the characteristics of the patient, drug combination, the judgment of the treating physician and the nature and severity of the particular disease or condition being treated.
  • compositions, methods and uses of the present invention provide a
  • compositions, methods and uses of the present invention are desired to improve the delivery of the active agent and improve the topical bioavailability of the active agent.
  • the compositions, methods and uses of the present invention will allow for more rapid treatment and control of infection relative to conventional topical treatment compositions.
  • Figure 1 is a column chart relating to Example 3 comparing the diffusion (IBU Q24h mean ⁇ g/cm2)) of a composition of the invention containing DMSO and glycerol ("DMSO/GLY”) with corresponding compositions containing only DMSO or only glycerol.
  • compositions 1 to 6 and a comparison composition were prepared by
  • Composition (Comp) 1 1 .0 to 8.0% ciclopirox olamine, 5.0% DMSO, 5% Glycerol, 5%, water, 45% ethyl acetate in aqueous ethanol (95%)
  • Composition (Comp) 1 1 .0 to 8.0% ciclopirox olamine, 5.0% DMSO, 5% Glycerol, 5%, water, 45% ethyl acetate in aqueous ethanol (95%)
  • o Comp 2 1 .0 to 8.0% Ciclopirox, 5.0% DMSO, 5% Glycerol, 2% polyvinyl pyrrolidone in 70% aqueous ethanol (95%)
  • o Comp 3 0.5 to 5% Ibuprofen, 5.0% DMSO, 1 % Glycerol, 50% water, 10% oleyl alcohol in isopropyl alcohol
  • o Comp 4 0.1 to 5% Diclofenac, 5.0% DMSO, 1 % Glycerol, 50% water, 10% oleyl alcohol in isopropyl alcohol
  • o Comp 5 0.5 to 5% Naproxen, 5.0% DMSO, 1 % Glycerol, 50% water, 10% oleyl alcohol in isopropyl alcohol
  • o Comp 6 0.1 to 5% Ketoprofen, 5.0% DMSO, 1 % Glycerol, 50% water, 10% oleyl alcohol in isopropyl alcohol.
  • compositions 1 and 2 may be used to treat skin fungal infections by topical to mycoses such as tinea versicolor.
  • compositions 3 to 6 may be used in treatment of joint pain by topical
  • Diclofenac can be in acid or salt form including diclofenac, diclofenac sodium, diclofenac potassium and diclofenac diethylamine.
  • compositions of Example 2 may be used in treatment of joint pain by
  • the diffusion cells were maintained at a flow rate of approximately 0.5 mL/hr by a microcassette peristaltic pump (Watson Marlow 505S UK). The cells were kept at 32 ⁇ 1 °C by a heater bar and the samples were collected into appropriately sized glass vials for a period of 24 hr.
  • the receptor solutions Phosphate Buffered Saline pH7.4 maintained sink conditions below the skin.
  • Composition B may be used in treatment of joint pain by topical application to the joint in which pain if suffered.
  • compositions 1 , 2, 3 and 6 may be used to treat joint pain by topical
  • compositions 4 and 5 may be used to treat skin fungal infections by topical to mycoses such as tinea versicolor.

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Abstract

La présente invention concerne une composition topique comprenant : de 0,01 à 15 % en p/v d'au moins un principe actif choisi dans le groupe constitué par des agents antifongiques et des agents actifs anti-inflammatoires ; de 0,1 % à 20 % en p/v de solvant aprotique polaire choisi dans le groupe constitué par du DMSO, de l'acétone et de l'acétate d'éthyle ; de 0,1 % à 20 % en p/v de polyol choisi parmi le glycérol, le propylène glycol, le sorbitol et leurs mélanges ; et de 40 % à 90 % en v/v d'alcanol inférieur choisi dans le groupe constitué par l'éthanol, l'isopropanol et leurs mélanges.
PCT/AU2015/000457 2014-07-31 2015-07-31 Composition topique Ceased WO2016015094A1 (fr)

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AU2014902967A AU2014902967A0 (en) 2014-07-31 Topical composition

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020077106A1 (fr) * 2018-10-11 2020-04-16 Imbria Pharmaceuticals, Inc. Compositions et procédés de traitement et de prévention de la neuropathie optique héréditaire de leber
CN111329834A (zh) * 2020-04-27 2020-06-26 重庆华邦制药有限公司 一种含有二丙酸阿氯米松的乳膏制剂及其制备方法
US10765117B2 (en) 2013-01-30 2020-09-08 Agrofresh Inc. Volatile applications against pathogens
US10966429B2 (en) 2016-03-07 2021-04-06 Agrofresh Inc. Synergistic methods of using benzoxaborole compounds and preservative gases as an antimicrobial for crops
CN112957314A (zh) * 2016-08-16 2021-06-15 湖南中威制药有限公司 一种硝酸奥昔康唑乳膏制剂及其生产方法
US11039617B2 (en) 2013-01-30 2021-06-22 Agrofresh Inc. Large scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness
WO2022059027A1 (fr) * 2020-09-18 2022-03-24 Alkem Laboratories Limited Composition topique de luliconazole
US20220296513A1 (en) * 2021-03-19 2022-09-22 Cathay General Hospital Microemulsion mixture and method of using the same, and pharmaceutical microemulsion mixture and method of using the same
US12490742B2 (en) 2024-03-01 2025-12-09 Agrofresh Inc. Volatile applications against pathogens

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB872893A (en) * 1958-04-19 1961-07-12 Smith & Nephew Improvements in antifungal compositions
WO2001052897A2 (fr) * 2000-01-21 2001-07-26 Panacea Biotec Limited Composition therapeutique anti-inflammatoire et analgesique contenant des medicaments selectifs inhibiteurs cox-2 a utiliser transdermiquement, et procede de fabrication de la composition
US20010046526A1 (en) * 2000-04-19 2001-11-29 C-Quest Treatment of fungal infections
US6455592B1 (en) * 1991-03-08 2002-09-24 Novartis Ag Use of hydrophilic penetration agents in dermatological compositions for the treatment of onychomycoses, and corresponding compositions
US20070134232A1 (en) * 2005-12-14 2007-06-14 Joel Studin Topical bite care composition
WO2010125470A2 (fr) * 2009-04-28 2010-11-04 Foamix Ltd. Véhicule moussant et compositions pharmaceutiques comportant des solvants polaires aprotiques et leurs utilisations

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB872893A (en) * 1958-04-19 1961-07-12 Smith & Nephew Improvements in antifungal compositions
US6455592B1 (en) * 1991-03-08 2002-09-24 Novartis Ag Use of hydrophilic penetration agents in dermatological compositions for the treatment of onychomycoses, and corresponding compositions
WO2001052897A2 (fr) * 2000-01-21 2001-07-26 Panacea Biotec Limited Composition therapeutique anti-inflammatoire et analgesique contenant des medicaments selectifs inhibiteurs cox-2 a utiliser transdermiquement, et procede de fabrication de la composition
US20010046526A1 (en) * 2000-04-19 2001-11-29 C-Quest Treatment of fungal infections
US20070134232A1 (en) * 2005-12-14 2007-06-14 Joel Studin Topical bite care composition
WO2010125470A2 (fr) * 2009-04-28 2010-11-04 Foamix Ltd. Véhicule moussant et compositions pharmaceutiques comportant des solvants polaires aprotiques et leurs utilisations

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11917997B2 (en) 2013-01-30 2024-03-05 Agrofresh Inc. Volatile applications against pathogens
US10765117B2 (en) 2013-01-30 2020-09-08 Agrofresh Inc. Volatile applications against pathogens
US11039617B2 (en) 2013-01-30 2021-06-22 Agrofresh Inc. Large scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness
US11202448B2 (en) 2013-01-30 2021-12-21 Agrofresh Inc. Volatile applications against pathogens
US12329158B2 (en) 2013-01-30 2025-06-17 Agrofresh Inc. Large-scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness
US11771089B2 (en) 2013-01-30 2023-10-03 Agrofresh Inc. Large-scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness
US10966429B2 (en) 2016-03-07 2021-04-06 Agrofresh Inc. Synergistic methods of using benzoxaborole compounds and preservative gases as an antimicrobial for crops
CN112957314A (zh) * 2016-08-16 2021-06-15 湖南中威制药有限公司 一种硝酸奥昔康唑乳膏制剂及其生产方法
CN112888419A (zh) * 2018-10-11 2021-06-01 安布里亚制药公司 用于治疗和预防Leber遗传性视神经病变的组合物和方法
WO2020077106A1 (fr) * 2018-10-11 2020-04-16 Imbria Pharmaceuticals, Inc. Compositions et procédés de traitement et de prévention de la neuropathie optique héréditaire de leber
CN111329834A (zh) * 2020-04-27 2020-06-26 重庆华邦制药有限公司 一种含有二丙酸阿氯米松的乳膏制剂及其制备方法
CN111329834B (zh) * 2020-04-27 2023-01-31 重庆华邦制药有限公司 一种含有二丙酸阿氯米松的乳膏制剂及其制备方法
WO2022059027A1 (fr) * 2020-09-18 2022-03-24 Alkem Laboratories Limited Composition topique de luliconazole
US11786465B2 (en) * 2021-03-19 2023-10-17 Cathay General Hospital Microemulsion mixture and method of using the same, and pharmaceutical microemulsion mixture and method of using the same
US20220296513A1 (en) * 2021-03-19 2022-09-22 Cathay General Hospital Microemulsion mixture and method of using the same, and pharmaceutical microemulsion mixture and method of using the same
US12490742B2 (en) 2024-03-01 2025-12-09 Agrofresh Inc. Volatile applications against pathogens

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