WO2015185979A1 - Compositions ano-rectales comprenant un anesthésique sous forme de base libre et un vasoconstricteur sous forme de sel - Google Patents

Compositions ano-rectales comprenant un anesthésique sous forme de base libre et un vasoconstricteur sous forme de sel Download PDF

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WO2015185979A1
WO2015185979A1 PCT/IB2015/000827 IB2015000827W WO2015185979A1 WO 2015185979 A1 WO2015185979 A1 WO 2015185979A1 IB 2015000827 W IB2015000827 W IB 2015000827W WO 2015185979 A1 WO2015185979 A1 WO 2015185979A1
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composition
anorectal
surfactant
group
water
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PCT/IB2015/000827
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English (en)
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Evgenia LOZINSKY
Eran Eilat
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Peritech Pharma Ltd.
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Publication of WO2015185979A1 publication Critical patent/WO2015185979A1/fr

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    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
    • 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
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/0031—Rectum, anus
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Definitions

  • Anorectal disorders are widespread and include a number of different conditions, such as hemorrhoids, anal fissures, anal pruritus and other local anorectal lesions.
  • topically applied formulations for the treatment of anorectal conditions including ointments, creams, gels, jellies and pastes, foams, sprays and medicated pads.
  • Topical compositions and methods of treatment of anorectal disorders are disclosed herein.
  • a topical anorectal composition that includes trimethylsiloxysilicate (TMSS), at least one surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, a polysorbate (also known as Tween), a silicone surfactant, and a combination thereof; a reducing agent, a thickener, a non-polar volatile siloxane solvent; phenylephrine hydrochloride, lidocaine (as free base) and water or a buffer, wherein the composition is sufficiently designed to dry within 60 seconds after application to the anorectal mucosa to form a dried composition, and wherein the dried composition forms: a flexible film, wherein the flexible film closely follows irregularities of the body surface as well as movement of the body surface, and (ii) a durable film, wherein the durable film does not crack or flake off and remains intact for more than 12 hours giving release of the TMSS), at least one surfact
  • a topical anorectal composition that includes from about 10.0% (w/w) to about 30.0% (w/w) of trimethylsiloxysilicate; from about 1.0% (w/w) to about 8.0% (w/w) of at least one surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, a polysorbate (also known as Tween), 2-6% of a silicone surfactant, and a combination thereof; from about 30.0% (w/w) to about 50.0% (w/w) of a non-polar volatile siloxane solvent; 0.05-0.5% w/w of a reducing agent, 0.1 -1% w/w of a thickener, about 0.25% w/w phenylephrine hydrochloride, about 1% w/w lidocaine (as free base), and 15-40% w/w of water or
  • a topical anorectal composition that includes from about 10.0% (w/w) to about 30.0% (w/w) of trimethylsiloxysilicate; from about 1.0% (w/w) to about 7.0% (w/w) of at least one surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, silicone surfactant, polysorbate and a combination thereof; from about 1 % (w/w) to about 40% (w/w) of water; from about 0.1% (w/w) to about 1% (w/w) of a reducing agent; from about 30.0% (w/w) to about 70.0% (w/w) of a non-polar volatile siloxane solvent; and from about 1% (w/w) to about 10% (w/w) lidocaine free base and from about 0.1% (w/w) to about 1% (w/w) phenylephrine
  • the composition is substantially non-stinging. In an embodiment, the composition is in the form of a gel. In an embodiment, the composition is in the form of an oil-in-water emulsion. In an embodiment, the at least one surfactant is polysorbate. In an embodiment, the polysorbate is polyoxyethylene sorbitan monooleate. In an embodiment, the composition further comprises an additive selected from the group consisting of a dimethicone/vinyl dimethicone crosspolymer, a silicone gum blend, a gelling agent, and a combination thereof. In an embodiment, the composition further comprises a buffer to adjust the pH of the composition to a pH of about 4.2 to about 4.4. In an embodiment, the composition further comprises an organosilicone surfactant. In an embodiment, the organosilicone surfactant is a cetyl dimethicone copolyol. In an embodiment, the composition further comprises a viscosity modifier.
  • a topical anorectal composition that includes about 25.0% (w/w) of trimethylsiloxysilicate; about 1.5% of Tween® 80; from about 30.0% (w/w) to about 40.0% (w/w) of a non-polar volatile siloxane solvent; from about 15% (w/w) to about 40% (w/w) of water; about 1% (w/w) lidocaine free base; about 0.25% (w/w) phenylephrine HCi; and about 0.1% to about 0.2% sodium metabisulfite, wherein the lidocaine free base is dissolved in the organic phase and wherein the composition is sufficiently designed to dry within 60 seconds after application to the anorectal mucosa to form a dried composition, and wherein the dried composition forms: a flexible film, wherein the flexible film closely follows irregularities of the body surface as well as movement of the body surface, and (ii) a durable film, wherein the durable film does not crack or fla
  • topical anorectal compositions that include at least one flexible film forming ingredient, at least one surfactant, at least one reducing agent, at least one non-polar volatile solvent, and a therapeutically effective concentrations of lidocaine free base and phenylephrine hydrochloride, wherein the composition is sufficiently designed to dry within 60 seconds after application to the anorectal mucosa to form a dried composition, and wherein the dried composition forms: (i) a flexible film, wherein the flexible film closely follows irregularities of the body surface as well as movement of the body surface, and (ii) a durable film, wherein the durable film does not crack or flake off and remains intact for more than 12 hours giving release of the pharmaceutical agent for an extended period of time.
  • a method of preventing or treating an anorectal disorder that includes topically applying once daily to the mucosal surface of an anorectal region of a subject in need of such treatment, a therapeutically effective amount of a topical composition of the present invention.
  • a similar or better therapeutic effect is observable than a commercially available composition comprising the same active ingredient(s) in the same concentrations wherein applied several times daily.
  • the anorectal disorder is hemorrhoids.
  • a method of preventing or treating an anorectal disorder that includes topically applying, once every other day or twice weekly to the mucosal surface of an anorectal region of a subject in need of such treatment, a therapeutically effective concentration of a topical composition of the present invention.
  • a similar or better therapeutic effect is observable than a commercially available composition comprising the same active ingredient(s) in the same concentrations wherein applied several times daily.
  • the anorectal disorder is hemorrhoids.
  • a stable anorectal composition that includes an anesthetic in the form of free base selected from the group consisting of lidocaine, dibucaine, tetracaine, benzocaine and a vasoconstrictor in the form of a salt selected from the group consisting of phenylephrine hydrochloride, ephedrine sulfate, epinephrine hydrochloride.
  • compositions comprising an anesthetic in the form of free base and a vasoconstrictor in the form of salt, wherein the anesthetic free base is dissolved in an organic phase, the vasoconstrictor in the form of salt is dissolved in an aqueous phase, and wherein the composition comprises from about 0.1% (w/w) to about 1% (w/w) of a reducing agent, from about 1% (w/w) to about 7% (w/w) of a surfactant, and from about 25% (w/w) to about 40% (w/w) of water.
  • a topical anorectal composition that includes from about 10.0% (w/w) to about 30.0% (w/w) of trimethylsiloxysilicate (TMSS); from about 1.0% (w/w) to about 5.0% (w/w) at least one surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, a polysorbate (also known as Tween), a silicone surfactant, polyalkyl & polyether modified silicone oil (also known as PEMS-33) and a combination thereof; from about 30.0% (w/w) to about 75.0% (w/w) of a non-polar volatile siloxane solvent; from about 0.1% (w/w) to about 1% (w/w) of Natrosol thickener; from about 0.05% (w/w) to about 0.5% (w/w) sodium metabisulfite; from about 0.25% (w/w)
  • TMSS trimethylsil
  • kits that includes a topical anorectal composition of the present invention and a container-applicator device suitable for storage and application of the composition to the anorectal region.
  • the container-applicator device is selected from the group consisting of a single use wipe, a syringe, a dropper, a spray dispenser, a compressible bottle or tube, a spatula, a suppository insertion tube, an extrusion tube, and an inflatable member.
  • the anorectal disorders treated with the compositions of the present invention include, but are not limited to, hemorrhoids, anal fissures, anal cracks, anal fistulas, anal abscesses, anal pruritus and other local anorectal lesions.
  • the present invention provides topical compositions comprising active pharmaceutical agents and uses thereof for treating anorectal disorders, including hemorrhoids, anal fissures, anal cracks, anal fistulas, anal abscesses, anal pruritus and other local anorectal lesions.
  • anorectal disorders including hemorrhoids, anal fissures, anal cracks, anal fistulas, anal abscesses, anal pruritus and other local anorectal lesions.
  • Topical compositions of the present invention are applied to the anorectal mucosa for the treatment of anorectal disorders.
  • Topical formulations currently available for use in the treatment of anorectal disorders typically comprise polar solvents which enable the incorporation of the medicaments into the formulation.
  • polar solvents e.g. ethanol
  • the topical compositions of the present invention comprise an aqueous phase which allows reducing or avoiding the use of polar solvents.
  • addition of water to the topical composition reduces or avoids the need to use of stinging polar solvents and hence improves the compliancy of the subject to be treated.
  • the topical compositions of the present invention upon drying, form a film on the anorectal mucosal surfaces and thus provide a protective coating on irritated hemorrhoids and open fissures, resulting in protection of the laceration during defecation.
  • topical compositions of the present invention when dried, form a durable film which does not crack or flake off and remains intact for more than 12 hours giving release of the pharmaceutical agent for an extended period of time, thus leading to enhanced healing of the affected areas.
  • sustained or extended release of the pharmaceutical agent(s) from the compositions of the present invention enables methods of treatment including less frequent administration (such as once daily, once every other day or twice weekly) than existing commercially available products, while achieving similar or better therapeutic results.
  • topical compositions of the present invention when dried, form a flexible film, closely following irregularities of the body surface as well as movement of the body surface.
  • non-soiling anorectal compositions affording convenience for the patient, improving patient compliance and avoiding embarrassment.
  • the present invention provides a topical anorectal composition that includes:
  • TMSS trimethylsiloxysilicate
  • surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and aikoxy- dimethicone copolyol, a polysorbate (also known as Tween), a silicone surfactant, polyalkyl & polyether modified silicone oil (also known as PEMS-33) and a combination thereof;
  • composition is sufficiently designed to dry within 60 seconds after application to the anorectal mucosa to form a dried composition, and wherein the dried composition forms:
  • the present invention provides a topical composition that includes:
  • composition is sufficiently designed to dry within 60 seconds after application to a mucosal surface of an anorectal region to form a dried composition, wherein the dried composition forms: (i) a flexible film, wherein the flexible film closely follows irregularities of the mucosal surface as well as movement of the mucosal surface, and (ii) a durable film, wherein the durable film does not crack or flake off and remains intact for more than 12 hours giving release of the pharmaceutical agent for an extended period of time.
  • compositions comprising an anesthetic in the form of free base selected from the group consisting of lidocaine, dibucaine, tetracaine, benzocaine and a vasoconstrictor in the form of a salt selected from the group consisting of phenylephrine hydrochloride, ephedrine sulfate, epinephrine hydrochloride.
  • compositions comprising an anesthetic in the form of free base and a vasoconstrictor in the form of salt, whereby the anesthetic free base is dissolved in the organic phase, the vasoconstrictor in the form of salt is dissolved in the aqueous phase, wherein the composition comprises from about 0.1% w/w to about 1% w/w of a reducing agent, from about 1% w/w to about 7% w/w of a surfactant and from about 25% w/w to about 40% w/w of water.
  • the present invention provides a topical anorectal composition that includes:
  • TMSS trimethylsiloxysilicate
  • surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, a polysorbate (also known as Tween), a silicone surfactant, polyalkyl & polyether modified silicone oil (also known as PEMS-33) and a combination thereof;
  • vasoconstrictor in the form of a salt selected from the group comprising phenylephrine hydrochloride, ephedrine sulfate and epinephrine hydrochloride;
  • an anesthetic in the form of free base selected from the group comprising lidocaine, dibucaine, tetracaine and benzocaine; and from about 15% to about 40% w/w of water or of a buffer of pH 4-7,
  • composition is sufficiently designed to dry within 60 seconds after application to the anorectal mucosa to form a dried composition, and wherein the dried composition forms:
  • a topical composition of the present invention is in the form of an emulsion.
  • the emulsion is an oil-in-water emulsion.
  • the emulsion may be in the form of a viscous gel (25000-45000 cP) or a liquid whose viscosity ranges from 1-1.2 cP, close to the viscosity of water. While the gel is applied to the anorectal mucosal surface as such, the liquid emulsion is mainly used for the preparation of the wipes.
  • compositions of the present invention can be administered as a gel, a wipe, a towellete, a water-based solution, a spray or a foam.
  • the at least one film forming ingredient is selected from the group consisting of a siloxysilicate, silsesquioxane or other silicone polymers.
  • the siloxysilicate is trimethylsiloxysilicate.
  • the silsesquioxane is polymethylsilsesquioxane.
  • the at least one surfactant is an anionic surfactant.
  • the anionic surfactant can be selected from the group consisting of sodium alkyl sulfate, sodium alkyl sulfonate, sodium alkyl aryl sulfonate, sodium stearate, dioctyl sodium sulfosuccinate, sodium cholate, and any combination thereof.
  • the sodium alkyl sulfate is sodium lauryl sulfate.
  • the at least one surfactant is a nonionic surfactant.
  • the nonionic surfactant can be selected from the group consisting of organosilicone surfactants, nonionic organic surfactants and a combination thereof.
  • the organosilicone surfactant comprises alkyl- and alkoxy- dimethicone copolyol.
  • the alkyl- and alkoxy- dimethicone copolyol is cetyl dimethicone copolyol.
  • the cetyl dimethicone copolyol is Cetyl PEG/PPG- 10/1 Dimethicone.
  • the nonionic organic surfactant is selected from the group consisting of polysorbate, glyceryl stearate, polyoxyethylene (POE) fatty acid ester, poly(oxyethylene) alkylyl ether, polyethoxylene castor oil derivative, PEG-6 octanoic/decanoic glycerides, polyoxyethylene glycerol trioleate, decaglycerol mono/dioleate, and any combination thereof.
  • the polysorbate can be selected from the group consisting of polyoxyethylene sorbitan monolaurate (Tween 20), polyoxyethylene sorbitan monopalmitate (Tween 40), polyoxyethylene sorbitan monostearate (Tween 60) and polyoxyethylene sorbitan monooleate (Tween 80).
  • the at least one surfactant is a cationic surfactant, an amphoteric surfactant, or a combination thereof.
  • the volatile solvent is a non-polar volatile siloxane, such as methylsiloxane or a polydimethylsiloxane.
  • the volatile polydimethylsiloxane is a linear polydimethylsiloxane or a cyclic polydimethylsiloxane.
  • the volatile polydimethylsiloxane is selected from the group consisting of hexamethyldisiloxane, heptamethyloctyftrisiloxane octamethylcyclotetrasiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, dodecamethylcyclohexasiloxane, and a combination thereof.
  • the volatile polydimethylsiloxane is hexamethyldisiloxane.
  • the non-polar volatile siloxane is dimethyl silicone oil SF 1000N (0.65).
  • the volatile solvent is a volatile aliphatic hydrocarbon selected from the group consisting of alkanes, alkenes, alkynes, and mixtures thereof.
  • the alkane is selected from the group consisting of pentane, isooctane, isododecane, isohexadecane and a combination thereof.
  • the volatile aliphatic hydrocarbon is isooctane.
  • the volatile solvent is a combination of a siloxane and isooctane.
  • the pharmaceutical agent is selected from the group consisting of anesthetic agents, vasoconstrictors, and a combination thereof.
  • anesthetic agents vasoconstrictors, and a combination thereof.
  • the anesthetic agent is lidocaine (as free base). According to some embodiments, the anesthetic agent is present in the topical composition in an amount ranging from about 1% (w/w) to about 10% (w/w), 5% w/w.
  • the vasoconstrictor is phenylephrine hydrochloride. According to some embodiments, the vasoconstrictor is present in the topical composition in an amount ranging from about 0.1% (w/w) to about 1% (w/w), 0.25% w/w.
  • the pharmaceutical topical composition comprises a combination of lidocaine and phenylephrine hydrochloride.
  • a topical composition of the present invention can further comprise an astringent, a keratolytic agent, an antibiotic agent, an antiseptic agent, an antioxidant, a keratolytic, a protectant, an astringent or a combination thereof.
  • an astringent a keratolytic agent, an antibiotic agent, an antiseptic agent, an antioxidant, a keratolytic, a protectant, an astringent or a combination thereof.
  • pharmaceutical topical composition of the present invention can further comprise an additive/excipient selected from the group consisting of a dimethicone/vinyl dimethicone crosspolymer, a silicone gum blend, a gelling agent and a combination thereof.
  • an additive/excipient selected from the group consisting of a dimethicone/vinyl dimethicone crosspolymer, a silicone gum blend, a gelling agent and a combination thereof.
  • the dimethicone/vinyl dimethicone crosspolymer comprises bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone.
  • the silicone gum blend comprises a blend of high and low molecular weight silicones.
  • the silicone gum blend comprises cyclopentasiloxane and dimethiconol.
  • the gelling agent is a cellulose derivative.
  • the cellulose derivative is hydroxypropyl methyl cellulose.
  • the gelling agent is selected from the group consisting of carbomer, carbomer copolymers, gelatin, aluminum monostearat, dextrin, sodium alginate, alginic acid, pectin, acacia, alginic acid, carrageenan, xanthan, tragacanth, magnesium aluminum silicate, bentonite, poloxamers, polyvinyl alcohol, and a combination thereof.
  • a topical composition comprises: (i) trimethylsiloxysilicate; (ii) a surfactant selected from the group consisting of an anionic surfactant, a nonionic surfactant and a combination thereof; (iii) a volatile solvent selected from the group consisting of a siloxane such as methylsiloxane or a polydimethylsiloxane, an aliphatic hydrocarbon, and a combination thereof, (iv) water or buffer; (v) a thickener, (vi) a reducing agent and (vii) at least one pharmaceutical agent selected from the group consisting of an anesthetic agent, a vasoconstrictor, and a combination thereof.
  • the surfactant is an anionic surfactant.
  • the topical composition fiirther comprises an additive selected from the group consisting of a dimethicone/vinyl dimethicone crosspolymer, a silicone gum blend, a gelling agent and a combination thereof.
  • the at least one surfactant is sodium lauryl sulfate.
  • the surfactant is a combination of silicone surfactant and Tween 80.
  • the surfactant is a combination of polysorbate and cetyl dimethicone copolyol.
  • cetyl dimethicone copolyol is Cetyl PEG/PPG- 10/1 Dimethicone.
  • polydimethylsiloxane is hexamethyldisiloxane.
  • volatile aliphatic hydrocarbon is isooctane.
  • the topical composition further comprises about 0.2% (w/w) to about 15% (w/w) of an additive selected from the group consisting of bis- vinyldimethicone, vinyldimethicone and hydrogen dimethicone; cyclopentasiloxane and dimethiconol; hydroxypropyl methyl cellulose; and a combination thereof.
  • bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone can be present in the topical composition in an amount ranging from about 5.0% (w/w) to about 15% (w/w).
  • cyclopentasiloxane and dimethiconol can be present in the topical composition in an amount ranging from about 0.5% (w/w) to about 2.5% (w/w).
  • hydroxypropyl methyl cellulose can be present in the topical composition in an amount ranging from about 0.05% (w/w) to about 5% (w/w).
  • a topical composition comprises: (i) about 20% w/w trimethylsiloxysilicate; (ii) about 3% (w/w) sodium lauryl sulfate; (iii) about 27% (w/w) hexamethyldisiloxane and 20% w/w isooctane; (iv) about 30% w/w water; and (v) about 0.25% w/w phenylephrine HC1 in an amount of about 0.25% w/w as the pharmaceutical agent.
  • the pH of a topical composition of the present invention is from about 3.5 to about 5. According to other embodiments, the pH of a topical composition of the present invention is from about 4.0 to about 4.6. According to additional embodiments, the pH of a topical composition of the present invention is from about 4.2 to about 4.4. According to some embodiments, the pH is maintained using citrate buffer.
  • the present invention provides a method of treating or preventing an anorectal disorder, the method comprising the step of topically applying to a mucosal surface of the anorectal region of a subject in need of such treatment a therapeutically effective amount of a topical composition of the present invention.
  • the anorectal disorder is selected from the group consisting of hemorrhoids, anal fissures, anal cracks, anal fistulas, anal abscesses and anal pruritus.
  • the anorectal disorder is hemorrhoids.
  • the pharmaceutical agent is an anesthetic agent, a vasoconstrictor, or a combination thereof.
  • the topical composition for use in treating or preventing hemorrhoids comprises a combination of about 5% (w/w) lidocaine and about 0.25% (w/w) phenylephrine hydrochloride.
  • the topical composition for use in treating or preventing anal pruritus comprises an antipruritic agent.
  • the antipruritic agent is hydrocortisone in an amount of about 1% (w/w) hydrocortisone.
  • the subject to be treated is a human being. According to another embodiment, the subject to be treated is an animal.
  • the present invention provides a kit comprising a topical composition of the present invention, a container-applicator device suitable for storage and application of the composition to the anorectal region, and instructions for administering the topical composition to a subject in need thereof.
  • the container-applicator device is selected from the group consisting of a single use wipe, a syringe, a dropper, a spray dispenser, a swab, a compressible bottle or tube, a spatula, a suppository insertion tube, an extrusion tube, a pump dispenser, a pressurized dispenser and an inflatable member.
  • the present invention provides a topical composition for use in treating or preventing an anorectal disorder.
  • a topical composition of the present invention comprises at least one film forming agent, at least one surfactant, at least one non-polar volatile solvent, water and at least one pharmaceutically active agent.
  • One such film forming agent may be a silicone resin.
  • the topical composition can further comprise additives, such as dimethicone/vinyl dimethicone crosspolymers, silicone gum blends and gelling agents.
  • film forming agent or “film forming ingredient” or “film former”, as used herein, means an inactive ingredient such as a silicone resin that after dissolution in at least one solvent and application on a substrate leaves a film on the substrate to which it is applied, for example once the at least one solvent evaporates, absorbs and/or dissipates on the substrate.
  • the anorectal disorders have a unique feature which is only shared with topical use on skin and joints.
  • Anal fissure a tear in the anus
  • hemorrhoids both extend significantly during defecation, which causes reopening of the anal fissure, bleeding, itching and pain. Therefore, flexible films possess a distinct advantage for the treatment of anorectal disorders such as anal fissure and hemorrhoids, providing reduction of bleeding, itching and pain during extension that occurs during defecation.
  • Silicone resins such as polydimethylsiloxane and polymethylsilsesquioxane have a unique semi-organic structure and are flexible. While using film forming agents in the instant invention, it is desirable to use such flexible film forming agents and formulate them in such compositions which produce flexible and durable films. In an embodiment, there are provided flexible and durable film forming compositions, providing beneficial therapeutic effects like reduced bleeding, pain, and itching.
  • the film formed on the substrate allows the tissues to "breathe", which is beneficial because of the extended period of time the film stays on the tissues.
  • compositions of the instant invention dry relatively fast after application on the substrate (anus, rectum), between 5 seconds and 1 minute to form a durable and elastic film.
  • the film formed on the substrate is substantially dry, which means it contains less than 10% volatiles, typically less than 5% and less than 2% volatiles.
  • the important aspect of the substantially dry films of this invention, whatever the percentage of volatiles left, is that they feel dry to touch and do not soil, stain or otherwise absorb into the underwear.
  • compositions of the instant invention may be administered less often than commercial products containing the same pharmaceutically active agents in the same concentrations.
  • the inclusion of the active pharmaceutical in the flexible film seems to have a long-acting or sustained release effect, achieving comparable or superior results compared to similar commercial products, while exposing the patient to smaller amounts of the active pharmaceutical ingredient(s).
  • anorectal compositions achieving a similar or better therapeutic effect than a commercially available composition comprising the same active pharmaceutical agent(s) in the same concentrations wherein applied several times daily.
  • once daily anorectal topical compositions comprising:
  • composition is sufficiently designed to dry within 60 seconds after application to a mucosal surface of an anorectal region to form a dried composition, wherein the dried composition forms: (i) a flexible film, wherein the flexible film closely follows irregularities of the mucosal surface as well as movement of the mucosal surface, and (ii) a durable film, wherein the durable film does not crack or flake off and remains intact for more than 12 hours giving release of the pharmaceutical agent for an extended period of time.
  • the dried film is non-soiling.
  • compositions may be topically administered even less often than once daily, such as once every other day or twice weekly.
  • once daily anorectal topical compositions comprising:
  • composition is sufficiently designed to dry within 60 seconds after application to a mucosal surface of an anorectal region to form a dried composition, wherein the dried composition forms: (i) a flexible film, wherein the flexible film closely follows irregularities of the mucosal surface as well as movement of the mucosal surface, and (ii) a durable film, wherein the durable film does not crack or flake off and remains intact for more than 12 hours giving Telease of the pharmaceutical agent for an extended period of time.
  • the dried film is non-soiling.
  • a method of treatment of anorectal compositions comprising the step of topically applying once daily, or once every other day or twice weekly to the mucosal surface of an anorectal region of a subject in need of such treatment, a therapeutically effective concentration of a topical composition of the present invention.
  • the film forming agents used in the compositions of the present invention are non-polymerizable and therefore, unlike the polymerizable agents are less sensitive to moisture, more stable and more suitable for repeated use.
  • volatile solvent means that the solvent has a measurable vapor pressure.
  • volatile solvents used in this Invention can be non-polar solvents.
  • silicone resins Some of the film forming agents according to the present invention are silicone resins.
  • silicone resins useful in the compositions of the invention are siloxysilicates, silsesquioxanes (usually denoted as T-resins) and a combination thereof.
  • siloxysilicates silsesquioxanes (usually denoted as T-resins) and a combination thereof.
  • T-resins siloxysilicates
  • T-resins siloxysilicates
  • T-resins siloxysilicates
  • trimethylsiloxysilicate which may be represented by the following formula:
  • x and y may, for example, range from 50 to 80 (e.g., but not limited to, 50-
  • siloxysilicates are commercially available from General Electric and Dow Corning under the trade name Resin Q®.
  • One non- limiting example of silsesquioxane is polymethylsilsesquioxane.
  • the present invention discloses for the first time the use of trimethylsiloxysilicate for therapeutic applications, inter alia, for treatment of anorectal disorders.
  • Trimethylsiloxysilicate is soluble in the volatile solvent of a topical composition of the present invention.
  • the amount of the silicone resin film forming agent in the composition is determined based on the desired adhesion properties of the dried film to the target surface.
  • the amount depends, inter alia, on the target surface, the condition to be treated, and the amount of composition ingredients.
  • the amount of the silicone resin film forming agent further defines the viscosity of the topical composition.
  • the amount of the silicone resin film forming agent in the composition typically ranges from about 10% (w/w) to about 40% ( /w).
  • the term "about” as used herein denotes ⁇ 10 % of the value indicated.
  • the volatile solvent useful for dissolving the silicone resin is chosen from volatile silicone or volatile aliphatic hydrocarbon. Water solubility of the volatile solvent is less than about 0.1 %.
  • the volatile silicone solvent is a linear or cyclic polydimethylsiloxane, having from 2 to 9 silicon atoms, these silicones being optionally substituted with alky! or alkoxy groups of 1 to 10 carbon atoms.
  • the polydimethylsiloxane used in the compositions is hexamethyldisiloxane.
  • the volatile solvent can further comprise a volatile aliphatic hydrocarbon.
  • the aliphatic hydrocarbon in accordance with the present invention may be any aliphatic hydrocarbon, including an alkane, a mixture of alkanes, an alkene, a mixture of aikenes, an alkyne, a mixture of alkynes, an ester or a mixture thereof.
  • the aliphatic hydrocarbon is an alkane such as pentane, isooctane, isododecane, isohexadecane or a mixture thereof.
  • the aliphatic hydrocarbon is isooctane.
  • the volatile ester useful for dissolving the film former may be a branched ester, such as isohexyl or isodecyl neopentanoate and mixture thereof.
  • the volatile solvent may comprise a volatile silicone, a volatile aliphatic hydrocarbon or a mixture thereof.
  • the volatile solvent comprises methylsiloxane or a hexamethyldisiloxane and isooctane.
  • the presence of water in a topical composition of the present invention allows reducing or avoiding the need to use polar solvents.
  • the pharmaceutically active agents are completely dissolved in the compositions of the present invention and do not precipitate or crystallize on drying, the resulting essentially dry films comprising the active(s) are clear, transparent and not "white films".
  • the emulsion can be a water-in-oil or oil-in-water emulsion.
  • a topical composition of the present invention is an oil-in-water emulsion.
  • the stable emulsion provides fine dispersion of the emulsion ingredients in the topical composition, in the container-applicator device and upon the application to the target surface, such that once the volatile solvent and water evaporate both the film former and the pharmaceutical active ingredients remain finely dispersed on the target surface.
  • the stable emulsion prevents clamping, floating and/or precipitation of the polar active ingredients in the non-polar volatile solvents.
  • the presence of the aqueous phase in the topical composition further obviates the use of polar solvents, formerly required to dissolve and disperse pharmaceutical active ingredients in silicone based liquid bandages.
  • the amount of the volatile solvent and water affects the viscosity and evaporation time of the topical composition when applied to a target surface.
  • the amount of the volatile solvent and water is determined so as to adjust the viscosity and evaporation time to desired values.
  • the amount of volatile solvent and water further affects the morphology of the silicone/water emulsion.
  • the amount of the volatile solvent can be adjusted to obtain the desired emulsion type.
  • the amount of the volatile solvent in the composition typically ranges from about 30% (w/w) to about 70% (w/w).
  • the amount of water can be adjusted to obtain the desired emulsion type.
  • the amount of water in the composition typically ranges from about 15% (w/w) to about 40% (w/w).
  • the topical compositions of the present invention further comprise at least one surfactant.
  • Addition of the surfactant allows mixing of the silicone and the aqueous phases, producing a silicone/water emulsion.
  • Addition of the surfactant further allows the emulsion stabilization.
  • the obtained emulsion may be an oil- in-water emulsion, wherein the aqueous phase includes dissolved pharmaceutical ingredients and finely dispersed volatile solvent phase, containing the dissolved film former.
  • the surfactant is selected from the group consisting of an anionic surfactant, a non- ionic surfactant, selected from organosilicone surfactant or nonionic organic surfactant, a cationic surfactant, an amphoteric surfactant and a combination thereof.
  • an anionic surfactant a non- ionic surfactant, selected from organosilicone surfactant or nonionic organic surfactant, a cationic surfactant, an amphoteric surfactant and a combination thereof.
  • the anionic surfactants usable in the compositions of the present invention include sodium alkyl sulfates, such as, but not limited to sodium lauryl sulfate; sodium alkyl sulfonates; sodium alkyl aryl sulfonates, such as sodium dodecyl benzene sulfonate and the like; sodium stearate; dioctyl sodium sulfosuccinate; sodium cholate; and a combination thereof.
  • suitable organosilicone surfactants include, but are not limited to dimethicone copolyols such as: alkoxy dimethicone copolyols, alkyl and alkoxy- dimethicone copolyols, silicones having pendant hydrophilic moieties such as linear silicones having pendant polyether groups, branched polyether and alkyl modified silicones, branched polyglycerin and alkyl modified silicones.
  • the dimethicone copolyol is cetyl dimethicone copolyol, such as Cetyl PEG/PPG- 10/1 Dimethicone sold under the name Abil EM-90.
  • dimethicone copolyols include branched polyether and alkyl modified silicones such as Lauryl PEG-9 Polydimethylsi!oxyethyl Dimethicone sold under the name F-6038, and branched polyglycerin and alkyl modified silicones such as Lauryl Polyglyceryl-3 Polydimethylsiloxyethyl Dimethicone sold under the name KF-6105.
  • dimethicone copolyols useful in the compositions of the present invention include bis-PEG/PPG-14/dimethicone copolyol sold under the name Abil EM- 97 and the polyglyceryl-4 isostearate/cetyl dimethicone copolyol/hexyl laurate mixture sold under the name Abil WE 09.
  • Another suitable dimethicone copolyol is PEG-9 Polydimethylsiloxyethyl Dimethicone sold under the name KF-6028.
  • Abil EM-90, Abil EM-97 and Abil WE 09 are available from Evonik Goldschmidt GmbH of Essen, Germany.
  • KF-6038 are KF-6105 are available from Shin-Etsu Silicones of Akron, Ohio.
  • Non-limiting examples of possible non-ionic organic surfactants include polysorbates, such as polyoxyethylene sorbitan monolaurate (Tween 20), polyoxyethylene sorbitan monopalmitate (Tween 40), polyoxyethylene sorbitan monostearate (Tween 60) and polyoxyethylene sorbitan monooleate (Tween 80); glyceryl stearate; polyoxyethylene (POE) fatty acid esters, such as Myrj 45, Myrj 49, Myrj 52 and Myrj 59; poly(oxyethylene) alkylyl ethers, such as poly(oxyethylene) cetyl ether (Brij 52, Brij 56, Brij 58), poly(oxyethylene) palmityl ether, polyethylene oxide hexadecyl ether, polyethylene glycol cetyl ether, and the like; polyethoxylene castor oil derivatives, such as Cremophor EL, ELP and RH 40; PEG-6 octanoic/decan
  • the nonionic organic surfactants may further comprise sorbitan fatty acid esters, such as sorbitan monolaurate (Span 20), sorbitan monopalmitate (Span 40), sorbitan monooleate (Span SO), sorbitan monostearate (Span 60); mono/diglycerides of octanoic/dectanoic acids, such as but not limited to Imwitor-742, Imwitor-308, and a combination thereof.
  • sorbitan fatty acid esters such as sorbitan monolaurate (Span 20), sorbitan monopalmitate (Span 40), sorbitan monooleate (Span SO), sorbitan monostearate (Span 60); mono/diglycerides of octanoic/dectanoic acids, such as but not limited to Imwitor-742, Imwitor-308, and a combination thereof.
  • Non-limiting examples of possible cationic surfactants include phosphatides, such as phosphatidyl choline and the like; quaternary ammonium cationic surfactants, such as hexadecyltrimethyl ammonium bromide and the like; pyrimidinium cationic surfactants, such as, but not limited to dodecyl pyridinium chloride; and a combination thereof.
  • the amphoteric surfactant may include lecithine, N-dodecyl alanine, cocamidopropyl amino betaine or a combination thereof.
  • the type and the amount of surfactant may be determined by a person skilled in art so as to obtain the Hydrophile-Liphophile Balance (HLB) of the surfactant or the surfactant mixture suitable for the oil-in-water systems.
  • HLB Hydrophile-Liphophile Balance
  • the surfactant used in the compositions of the present invention is an anionic surfactant
  • the surfactant may further comprise nonionic surfactant.
  • the nonionic surfactant may be selected from the group consisting of nonionic organic surfactant, organosilicone surfactant and a combination thereof.
  • the surfactant in the compositions of the present invention is a nonionic surfactant.
  • the surfactant is sodium alkyl sulfate, such as sodium lauryl sulfate.
  • the surfactant is a combination of sodium alkyl sulfate and alkyl and alkoxy- dimethicone copolyol, for example, sodium lauryl sulfate and Cetyl PEG PPG- 10/1 Dimethicone.
  • the surfactant is selected from polyoxyethylene sorbitan monolaurate (Tween 20), polyoxyethylene sorbitan monopalmitate (Tween 40), polyoxyethylene sorbitan monostearate (Tween 60), polyoxyethylene sorbitan monooleate (Tween 80) or any mixture thereof.
  • the silicone surfactant is a combination of polysorbate alkyl and alkoxy- dimethicone copolyol, for example, polyoxyethylene sorbitan monooleate (Tween 80) and Cetyl PEG/PPG- 10/1 Dimethicone.
  • a topical composition of the present invention may further comprise an additive selected from the group consisting of dimethicone/vinyldimethicone crosspolymers, silicone gum blends, gelling agents, and a combination thereof.
  • the dimethicone/vinyldimethicone crosspolymer is available, for example, from Dow Corning as Dow Corning 9506 Cosmetic Powder. According to other embodiments, the dimethicone/vinyldimethicone crosspolymer can be present in the compositions of the present invention in a form of two-part silicone elastomer. Without being bound to any mechanism of action, the addition of two-part silicone elastomers to the topical composition can provide enhanced film adhesion onto the target surface and can allow reduction of skin strain, which may be caused by the silicone resin. The two- part silicone elastomers form a crosspolymer network by addition reaction, upon mixing the two parts, enhancing the composition adhesive properties.
  • One part of the two-part silicone elastomer usually contains vinyl endblocked silicone polymer and a catalyst suitable for promoting the addition reaction and another part contains vinyl endblocked silicone polymer and silicone polymer carrying SiH groups. These two parts are stored separately before use and the crosslinking reaction starts upon mixing the two parts in a defined ratio. The ratio of the two parts is usually 50:50 and the crosslinking reaction may proceed at room temperature (25 ⁇ 5°C).
  • the two-part silicone elastomers may comprise dimethicone, hydrogen dimethicone, vinyldimethicone, bis-vinyldimethicon and phenyltrimethicone.
  • the topical composition of the present invention comprises bis-vinyldimethicone as the first part of the two-part silicone elastomers and vinyldimethicone and hydrogen dimethicone as the second part.
  • the first part can further contain a platinum catalyst.
  • the bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone are available, for example, from KCC as SM9010TM or SM9020TM.
  • the amount of the dimethicone/vinyldimethicone in the composition may be in a range from about 5% (w/w) to about 15% (w/w).
  • the topical compositions of the present invention may further comprise a silicone gum blend.
  • silicone gum blend may be a blend of a high molecular weight and a low molecular weight silicone.
  • the average molecular weight of the high molecular weight silicone is 100,000 or greater.
  • the average molecular weight of the low molecular weight silicone is 10,000 or less.
  • High molecular and low molecular weight silicones may comprise dimethicone and/or dimethiconol.
  • the non-limiting examples of a silicone gum blend are cyclopentasiloxane and dimethiconol, and cyclotetrasiloxane and cyclopentasiloxane and dimethiconol.
  • the cyclopentasiloxane and dimethiconol blends are available, for example, from KCC as SF9902ETM or from Momentive as Silsoft 1215 dimethiconeTM.
  • the amount of the silicone gum blend in the composition may be in a range from about 0.5% (w/w) to about 2.5% (w/w).
  • the topical composition in form of a gel comprises pharmaceutical agents primordially dissolved in the aqueous phase of the emulsion, finely dispersed in the continuous jelly phase and the silicone resin, primordially dissolved in the volatile solvent and finely dispersed in the aqueous phase of the emulsion, dispersed in the continuous jelly phase of the topical composition.
  • the gelling agent useful in a topical composition of the present invention may comprise hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, carbomer, carbomer copolymers, gelatin, aluminum monostearate, dextrin, sodium alginate, alginic acid, pectin, acacia, alginic acid, carrageenan, xanthan, tragacanth, magnesium aluminum silicate (Veegum®), bentonite, poloxamers (Pluronics®), polyvinyl alcohol, or mixtures thereof.
  • hydroxypropyl cellulose hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, carbomer, carbomer copolymers
  • gelatin aluminum monostearate, dextrin, sodium alginate, alginic
  • the gelling agents are cellulose derivatives. According to one embodiment, the gelling agent is hydroxypropyl methylce!lulose. According to some embodiments, the gelling agent is not soluble is the volatile solvent and/or in the silicone oil phase of the emulsion.
  • the amount of the gelling agent in the composition may be in a range from about 0.05% (w/w) to about 5.0% (w/w).
  • the pH is maintained in the range from about 3.5 to about 5, or from about 4.0 to about 4:6 ⁇ or from about 4.2 to about 4.4 using an appropriate buffering system.
  • the non-limiting examples of the weak acids suitable for buffering the compositions of the present invention include citric acid, citric acid monohydrate, boric acid, and phosphoric acid.
  • Some acid salts which can be used in the buffering systems of the compositions of the present invention include, but are not limited to, sodium citrate, sodium citrate dihydrate, monopotassium phosphate, and di sodium phosphate.
  • compositions of the present invention are devoid of polar solvents required for dissolving active ingredients, thus providing non-stinging topical compositions that have a comfortable feel when applying on the mucosal anal/genital surface.
  • the emulsions of the instant invention possess the advantage of reduced stinging effect in comparison with non-aqueous or polar compositions.
  • compositions of the instant invention are essentially non- stinging.
  • compositions of the present invention are devoid of acrylates.
  • the adhesiveness of the compositions does not require acrylates.
  • compositions of the present invention further comprise at least one pharmaceutically active agent, such as an anesthetic agent, a vasoconstrictor, an antipruritic agent, an anti-inflammatory agent, a muscle relaxant, an astringent, a keratolytic agent, an antibiotic agent, an antiseptic agent, or a combination thereof.
  • pharmaceutically active agents include for example, analgesics, antimicrobial agents and botanical products or extracts.
  • Additional pharmaceutical active agents include for example, analgesics, antimicrobial agents and botanical products or extracts.
  • the compositions of the present invention may further comprise antioxidants.
  • the compositions may further contain one or more protectant active ingredients, excipients and carriers.
  • compositions may be included in the composition, in particular for maintaining the stability and sterility of the composition, and for promoting delivery, release and/or application of the active agent(s) to the body surface to which the composition is applied.
  • the compositions may contain more than one active agent, and/or may be suitable for use in treating different anorectal disorders.
  • the pharmaceutically active agent and the dosage thereof is dependent upon the particular condition to be treated, the age of the subject and other factors evident to those skilled in the art.
  • the composition comprises an anesthetic agent and a vasoconstrictor.
  • the anesthetic agent is lidocaine in its free base form. Suitable amounts of such anesthetic agents in the composition may be readily ascertained by one of ordinary skill in the art, and may range, for example, between 0.15% (w/w) and 25% (w/w).
  • the anesthetic agent is lidocaine.
  • the composition of the invention comprises lidocaine free base at a concentration of 5% w/w based on the total weight of the composition.
  • the vasoconstrictor agent is phenylephrine HCI.
  • the composition of the invention comprises phenylephrine HCI at a concentration of about 0.25% (w/w) based on the total weight of the composition.
  • Antipruritic agents which are suitable for use in the invention include corticosteroids, camphor, juniper tar and menthol.
  • corticosteroids include hydrocortisone, fluocinolone, flurandrenolide, triamcinolone, fluticasone, and desonide.
  • Antipruritic agents may further comprise corticosteroids such as tetrahydrocortisol, prednisone; prednisolone, fludrocortisone, 1 1-desoxycortisol, cortisone, corticosterone, paramethasone, betamethasone, dexamethasone, desoxycorticosterone acetate, desoxycorticosterone pivalate, fludrocortisone acetate, Cortisol acetate, Cortisol cypionate, Cortisol sodium phosphate, Cortisol sodium succinate, beclomethasone dipropionate, betamethasone, betamethasone sodium phosphate and acetate, betamethasone dipropionate, betamethasone valerate, betamethasone benzoate, cortisone acetate, dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate, fluprednisolone, meprednis
  • Anti-inflammatory agents include salicylic acid, indomethacin, sodium indomethacin trihydrate, salicylamide, naproxen, colchicine, fenoprofen, sulindac, diflunisal, diclofenac, indoprofen and sodium salicylamide.
  • Muscle relaxants which are suitable for use in the invention include nitroglycerin, nifedipine, amlodopine, sildenafil, tizanidine, and baclofen, or salts thereof including, but not limited to, sildenafil citrate. Suitable amounts of such muscle relaxants in the composition may be readily ascertained by one of ordinary skill in the art, and may range, for example, between about 0.1% (w/w) and about 15% (w/w).
  • a topical composition of the present invention may further include an astringent.
  • an "astringent” refers to a substance that causes tissue (e.g., a hemorrhoidal) to contract and can optionally arrest secretion or control bleeding from tissue.
  • tissue e.g., a hemorrhoidal
  • Astringents which are suitable for use in the invention include, e.g., alum, tannic acid, calamine, witch hazel, zinc oxide, or a combination thereof. Suitable amounts of such astringents in the composition may be readily ascertained by one of ordinary skill in the art, and may range, for example, between about 2% (w/w) and about 50% (w/w).
  • a topical composition of the present invention may further include a keratolytic agent.
  • a "keratolytic agent” refers to a substance that causes desquamation (loosening) and debridement or sloughing of the surface cells of the epidermis.
  • the keratolytic agent used in the compositions of the present invention is pharmaceutically acceptable for topical use in humans.
  • Suitable keratolytic agents include, but are not limited to, alcloxa, resorcinol, or a combination thereof. Suitable amounts of such keratolytic agents in the composition may be readily ascertained by one of ordinary skill in the art, and may range, for example, between about 0.1% (w/w) and about 5% (w/w).
  • Antibiotics for use in the invention are those suitable for topical application.
  • the antibiotic(s) may be classified in one or more of the following groups: penicillins, cephalosporins, carbepenems, beta-lactam antibiotics, aminoglycosides, amphenicols, ansamycines, macroHdes, lincosamides, glycopeptides, polypeptides, tetracylines, chloramphenicol, quinolones, fiicidines, sulfonamides, sulfones, nitrofiirans, diaminopyrimidines, trimethoprim, rifamycins, oxalines, streptogramins, lipopeptides, ketolides, polyenes, azoles, and echinocandines.
  • antibiotics which are suitable for use in the invention include: amikacin, aminosidine, paromomycin, chloramphenicol, ciprofloxacin, clindamycin, colistimethate-sodium, colistin, enfuvirtid, enoxacin, erythromycin, flucloxacillin, fosfomycin, fusafungin, gentamicin, levofloxacin, linezolid, mefloquin, metronidazol, mezlocillin, moxifloxacin, mupirocin, norfloxacin, ofloxacin, oxacillin, penicillin G, penicillin V, phenoxymethylpenicillin, phenoxymethylpenicillin-benzathin, pipemidinic acid, piperacillin, piperacillin+tazobactam, proguanil, propicillin, pyrimethamine, rumblemulin, rifaximin, roxithromycin, sodium s
  • Antiseptics which are suitable for use in the invention include, e.g., triclosan, phenoxy isopropanol, chlorhexidine gluconate, povidone iodine, and any combination thereof.
  • Antioxidative compounds may also be included in the composition, in particular the antioxidative compounds collectively termed catechins. These include for example, epicatechin, epicatechin gallate, epigallocatechin gallate, and gallocatechin, as well as stereoisomers and enantiomers of these compounds and combinations thereof. Such compounds may be provided as synthetic compounds or in the forms of mixtures as components of plant extracts, in particular green tea extracts. Botanical products and extracts include those derived from peppermint, ginger horseradish, yarrow, chamomile, rosemary, capsicum, aloe vera, tea tree oil (melaleuca oil), among many others.
  • a topical composition of the present invention may further include protectant active ingredients.
  • the protectant active ingredients can be selected from the group consisting of aluminum hydroxide gel, cocoa butter, aqueous solution of glycerin, hard fat, kaolin, lanolin, mineral oil, petrolatum, topical starch, white petrolatum, cod liver, shark liver oil, and a combination thereof.
  • the protectant active ingredient and the dosage thereof is dependent upon the particular condition to be treated, the pharmaceutical active agents present in the composition and other factors evident to those skilled in the art.
  • a topical composition of the present invention may include one or more of the following additional ingredients: emulsifiers (e.g.
  • anionic, cationic or nonionic chelating agents, colorants, emollients, fragrances, humectants, lubricants, moisturizers, preservatives, skin penetration enhancers, stabilizers, thickeners, and viscosity modifiers.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) at least one surfactant selected from the group consisting of sodium lauryl sulfate, silicone surfactant, alkyl- and alkoxy- dimethicone copolyol, polysorbate and a combination thereof; (iii) a non-polar volatile siloxane solvent, and (iv) phenylephrine HC1, lidocaine and combinations thereof.
  • the composition further comprises from about 15% (w/w) to about 40% (w/w) of water.
  • the composition further comprises a buffer to adjust the pH of the composition to a pH of about 4.2-4.4.
  • the composition further comprises a viscosity modifier.
  • a topical composition of the present invention comprises: (i) from about 10.0% (w/w) to about 30.0% (w/w) of trimethylsiloxysilicate; (ii) from about 1.0% (w/w) to about 7.0% (w/w) of at least one surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, polysorbate and a combination thereof; (iii) from about 30.0% (w/w) to about 75.0% (w/w) of a non-polar volatile siloxane solvent, and (iv) from about 1% (w/w) to about 10.0% (w/w) of lidocaine and from about 0.1% to about 1% phenylephrine HC1 and combinations thereof.
  • the composition further comprises from about 15% (w/w) to about 40% (w/w) of water.
  • the composition further comprises a buffer to adjust the pH of the composition to a pH of about 4.2-4.4.
  • the composition further comprises a viscosity modifier.
  • the composition further comprises a reducing agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) an anionic surfactant; (iii) a volatile solvent, (iv) water; and (v) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent selected from the group comprising trimethylsiloxysilicate, a siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) an anionic surfactant; (iii) a nonionic surfactant, (iv) at least one volatile solvent, (v) water; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising a siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) a nonionic surfactant; (iii) a volatile solvent, (iv) water; and (v) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) an anionic surfactant; (iii) a volatile solvent, (iv) water; (v) gelling agent; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) an anionic surfactant; (iii) a nonionic surfactant, (iv) a volatile solvent, (v) water; (vi) gelling agent; and (vii) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) a nonionic surfactant; (iii) a volatile solvent, (iv) water; (v) gelling agent; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium Iauryl sulfate; (iii) a volatile solvent, selected from the group consisting of methylsiloxane, hexamethy!disHoxane, isooctane and a combination thereof; (iv) water; and (v) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium alkyl sulfate; (iii) alkyl- and alkoxy- dimethicone copolyol; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) water; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium lauryl sulfate; (iii) Cetyl PEG/PPG- 10/1 Dimethicone; (tv) a volatile solvent, selected from the group consisting of methylsiloxane, hexamethyldisiloxane, isooctane and a combination thereof; (v) water; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) polysorbate; (iii) alkyl- and alkoxy- dimethicone copolyol; (iv) a volatile solvent, selected from the group consisting of polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) water; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) Tween 80; (iii) Cety] PEG/PPG- 10/1 Dimethicone; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, hexamethyldisiloxane, isooctane and a combination thereof; (v) water; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium alkyl sulfate; (iii) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (iv) water; (v) cellulose derivatives at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium lauryl sulfate; (iii) a volatile solvent, selected from the group consisting of methylsiloxane, hexamethyldisiloxane, isooctane and a combination thereof; (iv) water; (v) hydroxypropyl methyl cellulose; and (vi) at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) a surfactant; (iii) a volatile solvent, (iv) water; (v) at least one pharmaceutical agent; (vi) a dimethicone/vinyldimethicone crosspolymer; and (vii) a silicone gum blend.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) a surfactant; (iii) a volatile solvent, (iv) water; (v) at least one pharmaceutical agent; (vi) a dimethicone/vinyldimethicone crosspolymer; (vii) a silicone gum blend; and (ix) a gelling agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) anionic surfactant; (iii) a volatile solvent, (iv) water; (v) at least one pharmaceutical agent; (vi) a dimethicone/vinyldimethicone crosspolymer; and (vii) a silicone gum blend.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) anionic surfactant; (iii) a volatile solvent, (iv) water; (v) at least one pharmaceutical agent; (vi) a dimethicone/vinyldimethicone crosspolymer; (vii) a silicone gum blend; and (ix) a gelling agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent; (ii) anionic surfactant; (iii) nonionic surfactant; (iv) a volatile solvent, (v) water; (vi) at least one pharmaceutical agent; (vii) a dimethicone/vinyldimethicone crosspolymer; and (viii) a silicone gum blend.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) anionic surfactant; (Iii) nonionic surfactant; (iv) a volatile solvent, (v) water; (vi) at least one pharmaceutical agent; (vii) a dimethicone/vinyldimethicone crosspolymer; (viii) a silicone gum blend; and (ix) a gelling agent.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) nonionic surfactant; (iii) a volatile solvent, (iv) water; (v) at least one pharmaceutical agent; (vi) a dimethicone/vinyldimethicone crosspolymer; and (vii) a silicone gum blend.
  • a topical composition of the present invention comprises: (i) a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) nonionic surfactant; (iii) a volatile solvent, (iv) water; (v) at least one pharmaceutical agent; (vi) a dimethicone/vinyldimethicone crosspolymer; (vii) a silicone gum blend; and (ix) a gelling agent.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium alkyl sulfate; (iii) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (iv) water; (v) at least one pharmaceutical agent; (vi) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; and (vii) dimethiconol and silicone oil blend.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium alkyl sulfate; (iii) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (iv) water; (v) at least one pharmaceutical agent; (vi) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; (vii) dimethiconol and silicone oil blend; and (iv) cellulose derivative.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium alkyl sulfate; (iii) alkyl- and alkoxy- dimethicone copolyol; (iv) a volatile solvent, selected from the group consisting of a methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) water; (vi) at least one pharmaceutical agent; (vii) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; and (viii) dimethiconol and silicone oil blend.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) sodium alkyl sulfate; (iii) alkyl- and alkoxy- dimethicone copolyol; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) water; (vi) at least one pharmaceutical agent; (vii) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; (viii) dimethiconol and silicone oil blend; and (ix) cellulose derivative.
  • a topical composition of the present invention comprises: ( ⁇ ) trimethylsiloxysilicate; (ii) polysorbate; (iii) alkyl- and alkoxy- dimethicone copolyol; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) water; (vi) at least one pharmaceutical agent; (vii) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; and (viii) dimethiconol and silicone oil blend.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) polysorbate; (iii) alkyl- and alkoxy- dimethicone copolyol; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) water; (vi) at least one pharmaceutical agent; (vii) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; (viii) dimethiconol and silicone oil blend; and (ix) cellulose derivative.
  • a topical composition of the present invention comprises: ( ⁇ ) trimethylsiloxysilicate; (ii) silicone surfactant; (iii) Cetyl PEG PPG-10/l Dimethicone; (iv) a volatile solvent, selected from the group consisting of hexamethyldisiloxane, dimethyl silicone oil, isooctane and a combination thereof; (v) water or a buffer; (vi) at least one pharmaceutical agent selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic agent, an antiinflammatory agent, a muscle relaxant, or a combination thereof; (vii) bis- vinyldimethicone, vinyldimethicone and hydrogen dimethicone; (viii) cyclopentasiloxane and dimethiconol; and (ix) hydroxypropyl methyl cellulose.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) Tween 80; (iii) Cetyl PEG/PPG- 10/1 Dimethicone; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, hexamethyldisiloxane, isooctane and a combination thereof; (v) water; (vi) at least one pharmaceutical agent selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic agent, an anti-inflammatory agent, a muscle relaxant, or a combination thereof; (vii) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; and (viii) cyclopentasiloxane and dimethiconol.
  • a topical composition of the present invention comprises: (i) trimethylsiloxysilicate; (ii) Tween 80; (iii) Cetyl PEG/PPG- 10/1 Dimethicone; (iv) a volatile solvent, selected from the group consisting of methylsiloxane, hexamethyldisiloxane, isooctane and a combination thereof; (v) water; (vi) at least one pharmaceutical agent selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic agent, an anti-inflammatory agent, a muscle relaxant, or a combination thereof; (vii) bis-vinyldimethicone, vinyldimethicone and hydrogen dimethicone; (viii) cyclopentasi xane and dimethiconol; and (ix) hydroxypropyl methyl cellulose.
  • a topical composition of the present invention comprises: (i) about 10-40% (w/w) of a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 7% (w/w) of a surfactant; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent; (iv) about 20% (w/w) to about 40% (w/w) of water; and (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 2.5% (w/w) of an anionic surfactant; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent; (iv) about 15$ (w/w) to about 40% (w/w) of water; and (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of a silicone resin film forming agent comprising a siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 2.5% (w/w) of an anionic surfactant; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent; (iv) about 20% (w/w) to about 40% (w/w) of water; (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent; and (vi) about 0.05% (w/w) to about 5.0% (w/w) gelling agent.
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 2.5% (w/w) of an anionic surfactant; (iii) about 2% (w/w) to about 7% (w/w) of a nonionic surfactant; (iv) about 30% (w/w) to about 50% (w/w) of a volatile solvent; (v) about 25% (w/w) to about 40% (w/w) of water; and (vi) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent.
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of a silicone resin film forming agent comprising a siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 2.5% (w/w) of an anionic surfactant; (iii) about 2% (w/w) to about 7% (w/w) of a nonionic surfactant; (iv) about 30% (w/w) to about 80% (w/w) of a volatile solvent; (v) about 20% (w/w) to about 40% (w/w) of water; (vi) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent and (vii) about 0.05% (w/w) to about 5.0% (w/w) gelling agent.
  • a silicone resin film forming agent comprising a siloxysilicate, silsesquio
  • a topical composition of the present invention comprises: (i) about 10$ (w/w) to about 40% (w/w) of a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 7.0% (w/w) of a nonionic surfactant; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent; (iv) about 20% (w/w) to about 40% (w/w) of water; and (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of a silicone resin film forming agent comprising siloxysilicate, silsesquioxane, or a derivative or a combination thereof; (ii) about 0.5% (w/w) to about 7.0% (w/w) of a nonionic surfactant; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent; (iv) about 20% (w/w) to about 40% (w/w) of water; (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent; and (vi) about 0.05% (w/w) to about 5% (w/w) gelling agent.
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of trimethylsHoxysilicate; (ii) about 0.5% (w/w) to about 2.5% (w/w) of silicone surfactant; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent, selected from the group consisting of a methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (iv) about 15% (w/w) to about 40% (w/w) of water; (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent, selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic agent, an anti-inflammatory agent, a muscle relaxant, or a combination thereof; (vi) about 5.0% (w/w) to about 15% (w/w)
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of trimethylsiloxysilicate; (ii) about 0.5% (w/w) to about 2.5% (w w) of sodium alkyl sulfate; (iii) about 30% (w/w) to about 80% (w/w) of a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (iv) about 15% (w/w) to about 40% (w/w) of water; (v) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent, selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic agent, an anti-inflammatory agent, a muscle relaxant, or a combination thereof; (vi) about 5.0% (w/w) to about 15% (w/w) to
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of trimethylsiloxysilicate; (ii) about 0.5% (w/w) to about 2.5% (w/w) of sodium alkyl sulfate; (iii) about 2.0% (w/w) to about 7% (w/w) of alkyl- and alkoxy- dimethicone copolyol; (iv) about 30% (w/w) to about 80% (w/w) of a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) about 15% (w/w) to about 40% (w/w) of water; (vi) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent, selected from the group consisting of an anesthetic agent, a vasoconstrictor,
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of trimethylsiloxysilicate; (ii) about 0.5% (w/w) to about 2.5% (w/w) of sodium alkyl sulfate; (iii) about 2.0% (w/w) to about 7% (w/w) of alkyl- and alkoxy- dimethicone copolyol; (iv) about 30% (w/w) to about 80% (w/w) of a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) about 15% (w/w) to about 40% (w/w) of water; (vi) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent, selected from the group consisting of an anesthetic agent, a vasoconstrictor,
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of trimethylsiloxysilicate; (ii) about 0.5% (w/w) to about 2.5% (w/w) of polysorbate; (iii) about 2.0% (w/w) to about 7% (w/w) of alkyl- and alkoxy- dimethicone copolyol; (iv) about 30% (w/w) to about 80% (w/w) of a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) about 15% (w/w) to about 40% (w/w) of water; (vi) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent, selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic agent
  • a topical composition of the present invention comprises: (i) about 10% (w/w) to about 40% (w/w) of trimethylsiloxysilicate; (ii) about 0.5% (w/w) to about 2.5% (w/w) of polysorbate; (iii) about 2.0% (w/w) to about 7.0% (w/w) of alkyl- and alkoxy- dimethicone copolyol; (iv) about 30% (w/w) to about 80% (w/w) of a volatile solvent, selected from the group consisting of methylsiloxane, a polydimethylsiloxane, aliphatic hydrocarbon and a combination thereof; (v) about 15.0% (w/w) to about 40% (w/w) of water; (vi) about 0.005% (w/w) to about 25% (w/w) of at least one pharmaceutical agent, selected from the group consisting of an anesthetic agent, a vasoconstrictor, an antipruritic
  • a topical composition of the present invention comprises: (i) about 15% (w/w) trimethylsiloxysilicate; (ii) about 3% (w/w) sodium lauryl sulfate; (iii) about 22% (w/w) hexamethyldisiloxane and 21% (w/w) isooctane; (iv) about 27% (w/w) water or citrate buffer or a combination thereof; (v) about 1% (w/w) pramoxine; (vi) about 0.25% (w/w) phenylephrine; (vii) about 5% (w/w) bis- vinyldimethicone and 5% (w/w) vinyldimethicone and hydrogen dimethicone; and (viii) about 1% (w/w) cyclopentasiloxane and dimethiconol.
  • a topical composition of the present invention comprises: ( ⁇ ) about 15% (w/w) trimethylsiloxysilicate; (ii) about 6% (w/w) silicone surfactant; (iii) about 22% (w/w) hexamethyldisiloxane and 21% (w/w) isooctane; (iv) about 27% (w/w) water or citrate buffer or a combination thereof; (v) about 5% (w/w) lidocaine; (vi) about 0.25% (w/w) phenylephrine HC1; (vii) about 5% (w/w) bis- vinyldimethicone and 5% (w/w) vinyldimethicone and hydrogen dimethicone; (viii) about 1% (w/w) cyclopentasiloxane and dimethiconol; and (ix) about 0.5% (w/w) hydroxypropyl methyl cellulose
  • a topical composition of the present invention comprises: (i) about 15% (w/w) trimethylsiloxysilicate; (ii) about 1.5% (w/w) sodium lauryl sulfate; (iii) about 4% (w/w) Cetyl PEG/PPG-10/1 Dimethicone; (iv) about 22% (w/w) hexamethyldisiloxane and 21% (w/w) isooctane; (v) about 25% (w/w) water; (vi) about 5% (w/w) lidocaine; (vii) about 0.25% (w/w) phenylephrine HC1; (viii) about 5% (w/w) bis-vinyldimethicone and 5% (w/w) vinyldimethicone and hydrogen dimethicone; and (ix) about 1% (w/w) cyclopentasiloxane and dimethiconol.
  • a topical composition of the present invention comprises: (i) about 15% (w/w) trimethylsiloxysilicate; (ii) about 1.5% (w/w) sodium lauryl sulfate; (iii) about 4% (w/w) Cetyl PEG/PPG- 10/1 Dimethicone; (iv) about 18% (w/w) hexamethyldisiloxane and 19% (w/w) isooctane; (v) about 30% (w/w) water; (vi) about 5% (w/w) lidocaine; (vii) about 0.25% (w/w) phenylephrine HCl; (viii) about 5% (w/w) bis-vinyldimethicone and 5% (w/w) vinyldimethicone and hydrogen dimethicone; (ix) about 1% (w/w) cyclopentasiloxane and dimethiconol; and (x) about
  • a topical composition of the present invention comprises: (i) about 15% (w/w) trimethylsiloxysilicate; (ii) about 1.5% (w/w) Tween 80; (iii) about 4% (w/w) Cetyl PEG PPG- 10/1 Dimethicone; (iv) about 22% (w/w) hexamethyldisiloxane and 21% (w/w) isooctane; (v) about 25% (w/w) water; (vi) about 5% (w/w) lidocaine; (vii) about 0.25% (w/w) phenylephrine HCl; (viii) about 5% (w/w) bis-vinyldimethicone and 5% (w/w) vinyldimethicone and hydrogen dimethicone; and (ix) about 1% (w/w) cyclopentasiloxane and dimethiconol.
  • a topical composition of the present invention comprises: (i) about 15% (w/w) trimethylsiloxysilicate; (ii) about 1.5% (w/w) Tween 80; (iii) about 4% (w/w) Cetyl PEG/PPG-10/1 Dimethicone; (iv) about 18% (w/w) hexamethyldisiloxane and 19% (w/w) isooctane; (v) about 30% (w/w) water; (vi) about 5% (w/w) lidocaine; (vii) about 0.25% (w/w) phenylephrine HCl; (viii) about 5% (w/w) bis-vinyldimethicone and 5% (w/w) vinyldimethicone and hydrogen dimethicone; (ix) about 1% (w/w) cyclopentasiloxane and dimethiconol; and (x) about 0.5% (w/w/w) tri
  • compositions for use in the present invention are generally stored in a container-applicator device for use in a single dose application (e.g., a wipe or a swab in a disposable container) or for use in repeated applications to the anus and rectum.
  • Single dose applicators include those having breakable or removable seals that prevent moisture, including atmospheric moisture, from contacting the formulation.
  • a topical water-based composition is in the form of a pre-packaged towelette/wipe.
  • the wipe substrate is typically uniformly impregnated with the topical water-based composition.
  • the topical water-based composition is in a liquid form, when applied to the wipe.
  • the topical water-based composition is in a gel form, when applied to a wipe.
  • the wipe provides the user with a single dose of sterile medication.
  • the topical composition is transferred to the body surface upon contacting the wipe with the target surface.
  • Each wipe is generally packaged as a single-use sealed unit.
  • the wipe is formed of woven or non- woven fabric, cloth or tissue substrate and the impregnated wipe is sealed into an enveloping sachet or pocket.
  • the sachet or pocket is formed by sandwiching a folded and impregnated wipe between two sheets of an aluminum foil/polyethylene film laminate.
  • the sheets of laminate may comprise folded over portions of a single sheet of such material.
  • a container-applicator may further comprise two parts: (1) a storage area or reservoir which holds the composition and protects it from air, water and contaminants; and (2) the applicator which generally comprises a specially shaped tip designed to aid in application of the composition to the anal and/or rectal mucosa.
  • the applicator is an element integral to the container, for example, an elongated insertion tube extending from a reservoir.
  • the storage area and the applicator may be separate components, such as a tube reservoir and a separately supplied dropper.
  • the container and the applicator may be supplied as separate elements which are connected during use, for example via compatible male and female connectors respectively provided on the container and the applicator or vice versa.
  • Still another container-applicator device comprises a brush or solid paddle applicator wherein the topical composition is "painted" onto the surface requiring treatment.
  • the container-applicator device for repeated and intermittent usage may comprise a container suitable for non-sterile storage of the composition, and an applicator suitable for metered dispensing of the composition after opening of the applicator.
  • the applicator is characterized as having a resealable opening of no more than about 0.05 square inch (0.323 square centimeters) so as to permit the metered dispensement of the composition from the applicator and which is capable of multiple administrations of the composition, and is further characterized as having resealing means such as a cap which either tightly mates with the applicator or which screws onto the applicator.
  • the opening may be at the terminus of an elongated and tapered tube-like member suitable for insertion into the anal canal and accessing internal hemorrhoids.
  • the opening of the applicator is about 0.001 to about 0.01 square inch (about 0.00645 to about 0.0645 square centimeters).
  • the walls of the container-applicator device are made of a pliable material, so that upon application of pressure onto the walls, the walls depress sufficiently to force the composition in the container into the applicator and through the opening.
  • the composition is released from the applicator by gravity feed methods well known in the art. Such methods do not require application of pressure to the walls of the container.
  • the applicator is manufactured with its opening covered by a metal foil or other similar construction which closes this opening until the device is ready for use. The opening is then reinstated by use of a pin or similar device which punctures the covering.
  • Such devices for intermittent use enable multiple uses of the topical composition at different points in time by the same individual.
  • the selected composition is bacteriostatic, prolonged storage at ambient conditions can be achieved without regard to the sterility of the formulation because there is no adverse buildup of bacteria during storage.
  • the reservoir of the container-applicator device may be both air-tight and watertight, and keeps the media within free from contaminants.
  • the reservoir may contain a desiccant material to keep the media free of water.
  • Reservoirs may be of any shape, including shapes which provide for a smooth internal flow of media, such as cylindrical or conical shapes.
  • the size of the reservoir may vary within a wide range, but is slightly larger than the volume of composition which will be placed inside the reservoir to minimize the amount of gas within the reservoir.
  • the reservoir may be made from any of a variety of medical grade materials, such as plastics, excluding glass. Pharmaceutical agents of the topical composition suffer from caking when stored in glass reservoir.
  • the reservoir may be rigid, collapsible, or compressible.
  • a compressible or collapsible reservoir allows the user to have greater control over the rate at which the composition is expressed, as exertion of pressure on a compressible or collapsible reservoir would place a force on the on the composition causing it to flow at a faster rate than it would in the absence of such pressure.
  • the compressible or collapsible reservoir design for the topical composition in the form of gel can be used, for which the force of gravity may not be strong enough to cause a flow through an applicator sufficient to treat hemorrhoids or fissures.
  • Collapsible reservoirs which retain their collapsed shape have the additional advantage of reducing the amount of air which enters the reservoir following use. This advantage of collapsible containers is of greater importance in multiple-use (reusable) devices, wherein media is kept relatively free of potential contaminants between uses.
  • Applicator tips can be of any of a number of shapes, sizes, and configurations. They may be fairly rigid and may be made out of any material which is compatible with the media formulation, e.g., but not limited to, plastic, excluding glass. The choice of a proper applicator tip for a given application will depend on factors such as the viscosity of the composition, the desired application rate of the composition, the nature of the anal disorder, and its severity.
  • the container-applicators of the present invention may be either single-use or multiple-use devices.
  • a container or reservoir containing enough topical composition for multiple applications may be configured to accommodate replaceable tips.
  • the reservoir would typically have a means such as a valve, septum or sealing gasket which allows the reservoir to be sealed in the absence of an applicator tip. Placing an applicator tip on the reservoir would cause the valve to open, allowing composition to flow out from the reservoir. In this manner, one reservoir containing enough composition for several applications could be used over a period of hours, days or weeks.
  • This embodiment would also allow the user to use one reservoir with applicator tips of varying shapes and sizes chosen to best accommodate the anal disorder during the healing process. Uses
  • disorders of the anorectal region are commonly encountered among the general population, but are often inadequately unaddressed, since many patients delay or fail to seek medical attention due to embarrassment. Furthermore, many medications for such conditions fail to provide adequate relief and healing. In addition, many medications which are intended for treatment of conditions such as hemorrhoids and anal warts may be difficult to self-administer, and are unsatisfactory due to their uncomfortable sensation after application.
  • the present invention provides compositions which are useful for effectively treating a variety of anorectal disorders including hemorrhoids, anal fissures, anal cracks, anal fistulas, anal abscesses, and anal pruritus, wherein the compositions provide enhanced therapeutic efficacy and are associated with improved patient compliance, as compared to prior art Compositions.
  • the provided compositions may be useful for simultaneously treating a number of anorectal disorders.
  • Hemorrhoids also known as piles
  • form part of the normal human anatomy of the anal canal but may become pathological when swollen or inflamed. In their physiological state they act as cushions composed of arterio-venous channels and connective tissue that aid the passage of stool.
  • the symptoms of pathological hemorrhoids include rectal bleeding, tenderness and pain in the anal area.
  • Pathological hemorrhoids are typically classified as external or internal, which are differentiated via their position with respect to the dentate line. External hemorrhoids occur outside the anal verge (the distal end of the anal canal) as varicosities of the veins draining the territory of the inferior rectal arteries, which are branches of the internal pudendal artery. External hemorrhoids are frequently painful, and are often accompanied by swelling, skin irritation and itching. External hemorrhoids are prone to thrombosis, which may occur if the vein ruptures and/or a blood clot develops.
  • Internal hemorrhoids occur within the rectum as varicosities of veins draining the territory of branches of the superior rectal arteries. As this area lacks pain receptors, internal hemorrhoids are often painless and affected individuals may be unaware of their occurrence. Internal hemorrhoids may however, bleed when irritated. Untreated internal hemorrhoids can lead to the more sever conditions of prolapsed or strangulated hemorrhoids. Prolapsed hemorrhoids are severely distended such that they are extruded outside the anus.
  • anal sphincter muscle goes into spasm and traps a prolapsed hemorrhoid outside the anal opening, the supply of blood is cut off, and the hemorrhoid becomes a strangulated hemorrhoid.
  • Internal hemorrhoids can be further graded by the degree of prolapse, in which
  • Grade I is characterized by the absence of prolapse; Grade II is characterized by prolapse upon defecation but which reduce spontaneously; Grade III is characterized by prolapse upon defecation, which may be manually reduced; and Grade IV is characterized by prolapse which cannot be manually reduced.
  • An anal fissure is a crack or tear in the skin of the anal canal. Acute cases may be associated with severe periodic pain after defecation, while chronic cases are associated with less intense pain.
  • Anal fissures usually extend from the anal opening and are usually located posteriorly in the midline. Fissure depth may be superficial or extend down to the underlying sphincter muscle. Most anal fissures are due to stretching of the anal mucosa beyond their capability.
  • a common cause of non-healing chronic fissures is spasm of the internal anal sphincter muscle, resulting in impaired blood supply to the anal mucosa. The result is a non-healing ulcer, which may become infected by fecal bacteria.
  • Non-surgical conventional treatments for acute and chronic anal fissures are generally those used for hemorrhoids.
  • Topically applied medications used for relaxation of the sphincter muscle include nitroglycerine, nifedipine, diltiazem, sildenafil citrate, and/or lidocaine.
  • Surgical treatment procedures such as anal stretch (Lord's operation) or lateral sphincterotomy are aimed to decrease sphincter spasm.
  • Another approach involves injection of botulinum toxin into the anal sphincter.
  • Anorectal or perianal abscess is an abscess occurring adjacent to the anus, due to infection at one of the anal crypts of Morgagni. Most cases are sporadic, although individuals with diabetes mellitus or Crohn's disease, or those undergoing chronic steroid treatment have increased risk and incidence. The condition is generally treated by surgery to drain the infection, followed by oral administration of antibiotics and possibly topical treatments. Anal abscess often leads to an anal fistula, which is the development of an infected channel within a gland between the anal canal and external skin near the anus or rectum. This condition also requires surgical treatment generally followed by administration of antibiotics.
  • Anal pruritus (also known as pruritus ani or anusitis) is an irritation of the skin at the anus, associated with intensive urge to scratch the affected area.
  • the condition may be idiopathic, or associated with various factors or co-existing conditions, including occult or overt fecal soiling, ingestion of certain foods, bacterial or fungal infection, hemorrhoids or additional co-existing anorectal disorders, and dermatological conditions, in particular allergic contact dermatitis or psoriasis.
  • Treatment measures include enhanced hygiene, antibiotics or antifungal medications when infections are present, various creams and ointments, generally containing local anesthetics, vasoconstrictors, protectants or combinations thereof, and topical steroids.
  • composition is applied to areas of the anal canal or rectum affected by hemorrhoids, fissures, fistulae, cracks, warts or pruritus, under conditions suitable for film formation of the composition so as to form a protective coating and typically under non-sterile conditions.
  • sufficient amounts of topical composition are employed to cover the entire affected mucosal surface area.
  • the coating is extended by at least about 1 centimeter and by at least about 5 centimeters beyond the affected surface area.
  • terapéuticaally effective amount means an amount of the pharmaceutical agent which is sufficient to provide a beneficial effect to the subject to which the pharmaceutical agent is administered. More specifically, a therapeutically effective amount means an amount of the pharmaceutical agent effective to alleviate or ameliorate the symptoms of an anorectal disorder of the subject being treated.
  • compositions of certain fixed concentrations As the anorectal disorders are treated with compositions of certain fixed concentrations, reference is made herein to "therapeutically effective concentration".
  • a second layer may be applied over the initial film. Additional amounts of topical composition can be applied as needed.
  • a topical composition is employed to form a coating of less than about 0.5 mm thick and of at least about 0.1 mm thick.
  • Such coatings can be formed by applying, for example, about 0.02 ml of topical composition per square centimeter of affected surface area.
  • film formation is generally complete within about 10 to about 60 seconds. During this period, the person to whom application of the topical composition has been made minimizes actions and body movements thus allowing the composition to form a dried film coating.
  • the topical compositions of the present invention typically act at temperatures between room temperature (20° C) and body temperature (37° C).
  • the dried films are conformable and comfortable and may be elastic and flexible, and do not irritate the skin and mucous membrane during the application and in use after drying.
  • the dried films are substantially painless and easily removable substantially without pain.
  • the dried films formed from the topical compositions are also substantially non- water sensitive and waterproof.
  • the dried films formed from the topical compositions comprise finely- dispersed pharmaceutical ingredients, which can be gradually released to the adhesion area.
  • compositions of the present invention are applicable to both human patients and to non-human mammalian subjects such as in veterinary use, for example for treatment of canine, feline, equine, bovine, porcine and primate species.
  • Table 1 summarizes Examples 1-8 and various embodiments of topical compositions of the present invention in the form of an oil-in-water emulsion gel prepared for use in treating anorectal disorders.
  • composition comprising lidocaine HCl and phenylephrine HCl
  • Phenylephrine HCl (0.25 g) was dissolved in 25 g water - solution A
  • Lidocaine HCl (5 g) was dissolved in solution A (aqueous phase) - solution B Tween 80 (1.5 g) was dissolved in solution B - solution C
  • silicone surfactant PEMS-33 (4 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (38,7 g) - solution
  • Trimethylsiloxysilicate 25 g was dissolved in solution F - solution G.
  • composition comprising lidocaine free base and phenylephrine HC1
  • Phenylephrine HCI (0.25 g) was dissolved in 25 g water - solution A
  • Lidocaine free base (5 g) was suspended in solution A (aqueous phase) - suspension B
  • silicone surfactant PEMS-33 (4 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (38,7 g) - solution F
  • Trimethylsiloxysilicate 25 g was dissolved in solution F - solution G.
  • composition comprising lidocaine free base in the organic phase and phenylephrine HCI
  • Phenylephrine HCI (0.25 g) was dissolved in 25 g water - solution A
  • silicone surfactant PEMS-33 (4 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (38,7 g) - solution F
  • Lidocaine free base (5g) was dissolved in solution F (organic phase)-solution
  • Trimethylsiloxysilicate 25 g was dissolved in solution
  • G - solution H Trimethylsiloxysilicate
  • composition comprising Iidocaine free base in the organic phase and phenylephrine HCI in buffer pH 4
  • Phenylephrine HCI (0.25 g) was dissolved in 25 g buffer pH 4 - solution A
  • silicone surfactant PEMS-33 (4 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (38,7 g) - solution F
  • Lidocaine free base (5g) was dissolved in solution F (organic phase)-solution G
  • Trimethylsiloxysilicate 25 g was dissolved in solution G - solution H.
  • composition comprising lidocaine free base in the organic phase and phenylephrine HCI in buffer pH 7
  • Phenylephrine HCI (0.25 g) was dissolved in 25 g buffer pH 7 - solution A
  • silicone surfactant PEMS-33 (4 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (38,7 g) - solution
  • Lidocaine free base (5g) was dissolved in solution
  • Trimethylsiloxysilicate 25 g was dissolved in solution
  • G - solution H Trimethylsiloxysilicate
  • composition comprising lidocaine free base in the organic phase and phenylephrine HCl with addition of sodium metabisulfite, increased amount of silicone surfactant Phenylephrine HCl (0.25 g) was dissolved in 25 g water - solution A
  • silicone surfactant PEMS-33 (6 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (36.26 g) - solution G
  • Lidocaine free base (5g) was dissolved in solution G (organic phase)-solution H
  • Trimethylsiloxysilicate 25 g was dissolved in solution H - solution I.
  • composition comprising lidocaine free base in the organic phase and phenylephrine HCl with addition of sodium metabisulfite and increased amount of silicone surfactant
  • Phenylephrine HCl (0.25 g) was dissolved in 30 g water - solution A
  • silicone surfactant PEMS-33 (6 g) was dissolved in hexamethyldisiloxane SF 10OON (0.65) (31.55g) - solution G
  • Lidocaine free base (5g) was dissolved in solution G (organic phase)-solution H
  • TrimethylsUoxysilicate 25 g was dissolved in solution H - solution I.
  • composition comprising lidocaine free base in the organic phase and phenylephrine HCl with addition of sodiam metabisulfite and increased amounts of silicone surfactant, of water, of silicone surfactant and of sodium metabisulfite
  • Phenylephrine HCl (0.25 g) was dissolved in 30 g water - solution A
  • silicone surfactant PEMS-33 (6 g) was dissolved in hexamethyldisiloxane SF1000N (0.65) (31.55g) - solution G
  • Lidocaine free base (5g) was dissolved in solution G (organic phase)-solution H
  • Trimethylsiloxysilicate 25 g was dissolved in solution H - solution I.
  • a test will be conducted to assess durability of dried films of the present disclosure.
  • the model will be based on the principle that efficacious films provide a physical barrier between the skin and the external environment. Therefore, the film should also prevent wash-off and wear-off of a harmless inert marker substance.
  • Activated carbon powder (ACP) is one such marker.
  • Film performance will be assessed by randomly applying films of the present disclosure over uniformly made ACP prepared sites on the backs of healthy adult subjects, and measuring the amount of ACP remaining on those sites over a wear period (e.g., one-day period, two-day period, three-day period or more). Subjects will go about normal daily activities and will be asked to shower once per day and avoid excessive physical activity or prolonged water exposure. On a daily basis, standardized digital photographs will be taken of the test sites and used to monitor the amount of ACP remaining using computer-assisted image analysis. The amount of marker stain (ACP) remaining after 1, 2, and 3 days of wear will be used as a measure of film effectiveness. The more stain remaining, the more effective the film at protecting the test site. The results can be presented as a chart of mean ⁇ SEM durability expresses as a percentage of the original ACP marker on Day 0.
  • ACP marker stain
  • a test will be conducted to assess flexibility of dried films of the present disclosure.
  • the films will be prepared on synthetic skin and bent over three sized mandrel bend rods (1/2", 1 ⁇ 4", 1/8") based on ASTM method D4338-97. Multiple data points will be collected for each film. Whether or not the film cracked during the bending process will be recorded.
  • a tattoo practice skin (synthetic skin) coated with a film of the present disclosure.
  • the skin will be folded to form an inverted U-shaped angle over the mandrel maintaining intimate contact with the upper surface of the film.
  • the test will be repeated with progressively smaller diameter mandrels.
  • test films and the test apparatus will be stored at the test conditions for 24 hours.
  • test film will be grasped between the thumb and forefinger of one hand, with the longest dimensions between the fingers.
  • a cotton work glove can be used to insulate the test film from the warm fingers.
  • test film A flat steel (or other support structure) of the test film will be laid tangentially at right angles to the longitudinal axis of the test mandrel.
  • test film will be folded with the lower surface opposite to the mandrel to form an inverted U-shaped angle over the mandrel maintaining intimate contact with the mandrel.
  • test will be repeated a number of times, using fresh films, on three mandrels with different diameters.
  • Flexibility of the films will be determined by the ability of the films to not crack when subjected to bending.
  • a topical anorectal composition of the present invention includes from about 10.0% (w/w) to about 30.0% (w/w) of trimethylsiloxysilicate (TMSS); from about 1.0% (w/w) to about 5.0% (w/w) at least one surfactant selected from the group consisting of sodium lauryl sulfate, alkyl- and alkoxy- dimethicone copolyol, a polysorbate (also known as Tween), a silicone surfactant, polyalkyl & polyether modified silicone oil (also known as PEMS-33) and a combination thereof; from about 30.0% (w/w) to about 75.0% (w/w) of a non-polar volatile siloxane solvent; from about 0.1% (w/w) to about 1% (w/w) of Natrosol thickener; from about 0.05% (w/w) to about 0.5% (w/w) sodium metabisulfite; from about 0.25% (w/w) to about

Abstract

La présente invention concerne une composition ano-rectale topique, comprenant de 10,0 % (p/p) à 30,0 % (p/p) de triméthylsiloxysilicate ; de 1,0 % (p/p) à 5,0 % (p/p) d'au moins un tensioactif choisi dans le groupe constitué par le laurylsulfate de sodium, un copolyol d'alkyl- et d'alcoxy-diméthicone, un polysorbate, un tensio-actif de silicone, une huile de silicone à modification polyéther et polyalkyle et une combinaison de ceux-ci ; de 30,0 % (p/p) à 75,0 % (p/p) d'un solvant siloxane volatil non polaire ; de 0,1 % (p/p) à 1 % (p/p) de l'épaississant Natrosol ; de 0,05 % (p/p) à 0,5 % (p/p) de métabisulfite de sodium ; de 0,25 % (p/p) à 10 % (p/p) d'un vasoconstricteur sous la forme d'un sel choisi dans le groupe constitué par le chlorhydrate de phényléphrine, le sulfate d'éphédrine et le chlorhydrate d'épinéphrine ; de 0,1 % (p/p) à 5 % (p/p) d'un anesthésique choisi dans le groupe constitué par la lidocaine, la dibucaïne, la tétracaïne et la benzocaïne ; et de 15 % (p/p) à 40 % (p/p) d'eau ou d'un tampon de pH 4 à 7.
PCT/IB2015/000827 2014-06-04 2015-06-03 Compositions ano-rectales comprenant un anesthésique sous forme de base libre et un vasoconstricteur sous forme de sel WO2015185979A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021152575A1 (fr) * 2020-01-30 2021-08-05 Innocan Pharma Ltd. Compositions pour le traitement des hémorroïdes
US20220287862A1 (en) * 2019-01-24 2022-09-15 Robert S. Cutler Topical treatment for anorectal disorders with and without seat cushion
WO2023154047A1 (fr) * 2022-02-10 2023-08-17 Glaxosmithkline Consumer Healthcare Holdings (Us) Llc Pulvérisation à décharge rapide

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020192273A1 (en) * 2001-06-15 2002-12-19 Teri Buseman Therapeutic patch useful for the treatment of hemorrhoids
US20060110415A1 (en) * 2004-11-22 2006-05-25 Bioderm Research Topical Delivery System for Cosmetic and Pharmaceutical Agents
US20090035354A1 (en) * 2005-12-30 2009-02-05 Mor Research Applications Ltd. Device and Method for Treating the Anal Sphincter
US20130178433A1 (en) * 2010-10-20 2013-07-11 Galderma S.A. Method of treating hemorrhoids using macrocyclic lactone compound
WO2014064703A1 (fr) * 2012-10-28 2014-05-01 Peritech Pharma Ltd. Compositions adhésives liquides pharmaceutiques pour le traitement de troubles anorectaux

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020192273A1 (en) * 2001-06-15 2002-12-19 Teri Buseman Therapeutic patch useful for the treatment of hemorrhoids
US20060110415A1 (en) * 2004-11-22 2006-05-25 Bioderm Research Topical Delivery System for Cosmetic and Pharmaceutical Agents
US20090035354A1 (en) * 2005-12-30 2009-02-05 Mor Research Applications Ltd. Device and Method for Treating the Anal Sphincter
US20130178433A1 (en) * 2010-10-20 2013-07-11 Galderma S.A. Method of treating hemorrhoids using macrocyclic lactone compound
WO2014064703A1 (fr) * 2012-10-28 2014-05-01 Peritech Pharma Ltd. Compositions adhésives liquides pharmaceutiques pour le traitement de troubles anorectaux

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220287862A1 (en) * 2019-01-24 2022-09-15 Robert S. Cutler Topical treatment for anorectal disorders with and without seat cushion
WO2021152575A1 (fr) * 2020-01-30 2021-08-05 Innocan Pharma Ltd. Compositions pour le traitement des hémorroïdes
WO2023154047A1 (fr) * 2022-02-10 2023-08-17 Glaxosmithkline Consumer Healthcare Holdings (Us) Llc Pulvérisation à décharge rapide

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