Method and therapeutic/cosmetic topical compositions for the treatment of rosacea and skin erythema using a1-adrenoceptor agonists

Abstract

The present invention is directed to the treatment of skin erythema as exhibited in rosacea and other conditions characterized by increased erythema (redness) of the skin. These conditions exhibit dilation of blood vessels due to a cutaneous vascular hyper-reactivity. In particular, the present invention is directed to a novel composition and method for the treatment of skin erythema using α 1 -adrenergic receptor (α 1 -adrenoceptor) agonists incorporated into cosmetic, pharmacological or dermatological compositions for topical application to the skin.

1 - 24 . (canceled) 
     
     
         25 . A method of treating or preventing rosacea and the symptoms associated therewith, the method comprising topically administering to the skin of a patient in need of such treatment or prevention, a composition comprising an agent selected from an alpha-1 adrenoreceptor agonist, an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof. 
     
     
         26 . The method of  claim 25 , wherein the alpha-1 adrenoreceptor agonist is oxymetazoline. 
     
     
         27 . The method of  claim 25 , wherein the alpha-1 adrenoreceptor agonist is oxymetazoline hydrochloride. 
     
     
         28 . The method of  claim 25 , wherein the composition comprises about 0.01% to about 20% of the agent. 
     
     
         29 . The method of  claim 25 , wherein the composition comprises about 0.05% to about 30% of the agent. 
     
     
         30 . The method of  claim 25 , wherein the composition comprises about 0.1% to about 10% of the agent. 
     
     
         31 . The method of  claim 25 , wherein the agent is administered in a therapeutically effective amount. 
     
     
         32 . The method of  claim 25 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         33 . The method of  claim 32 , wherein the composition comprises about 50% to about 99.999% of the carrier. 
     
     
         34 . The method of  claim 32 , wherein the composition comprises about 70% to about 99.99% of the carrier. 
     
     
         35 . The method of  claim 32 , wherein the carrier is a hydrophilic gelling agent. 
     
     
         36 . The method of  claim 32 , wherein the carrier is selected from a carboxyvinyl polymer, an acrylic copolymer, polyacrylamide, polysaccharide or a combination thereof. 
     
     
         37 . The method of  claim 25 , wherein the composition further comprises a vitamin, a hormone, an amino acid, a surfactant, a colorant, a dye, a pigment, a fragrance, an odor absorber, an antiseptic, a preservative, a bactericide, a humectant, a thickener, a solvent, a filler, an antioxidant, a sequestering agent, a sunscreen, an additive or a combination thereof. 
     
     
         38 . The method of  claim 25 , wherein the agent is co-administered with at least one other active agent selected from an antibacterial agent, an antiparasitic agent, an antifungal agent, an anti-inflammatory agent, an antihistamine, an anti-pruriginous agent, an anesthetic, an antiviral agent, a keratolytic agent, an anti free-radical agent, an antiseborrheic agent, an antidandruff agent, an antiacne agent, an sunscreen, an sun blocking agent, or an active agent which modifies at least one of cutaneous differentiation, proliferation, or pigmentation. 
     
     
         39 . The method of  claim 25 , wherein the agent is administered in a pharmacologically or cosmetically acceptable form selected from a solution, a gel, a lotion a cream, an ointment, a foam, an emulsion, a microemulsion, a milk, a serum, an aerosol, a spray, a dispersion, a microcapsule, a vesicle or a microparticle thereof. 
     
     
         40 . The method of  claim 25 , wherein the agent is co-administered with metronidazole, precipitated sulfur, sodium sulfacetamide, azelaic acid, or a combination thereof. 
     
     
         41 . A topical composition suitable for treating or preventing at least one symptom of rosacea comprising an agent selected from an alpha-1 adrenoreceptor agonist, an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof; and a pharmaceutically acceptable carrier. 
     
     
         42 . The composition of  claim 41 , wherein the alpha-1 adrenoreceptor agonist is oxymetazoline. 
     
     
         43 . The composition of  claim 41 , wherein the alpha-1 adrenoreceptor agonist is oxymetazoline hydrochloride. 
     
     
         44 . The composition of  claim 41 , wherein the composition comprises about 0.01% to about 20% of the agent. 
     
     
         45 . The composition of  claim 41 , wherein the composition comprises about 0.05% to about 30% of the agent. 
     
     
         46 . The composition of  claim 41 , wherein the composition comprises about 0.1% to about 10% of the agent. 
     
     
         47 . The composition of  claim 41 , wherein the agent is administered in a therapeutically effective amount. 
     
     
         48 . The composition of  claim 41 , wherein the composition comprises about 50% to about 99.999% of the carrier. 
     
     
         49 . The composition of  claim 41 , wherein the composition comprises about 70% to about 99.99% of the carrier. 
     
     
         50 . The composition of  claim 41 , wherein the carrier is a hydrophilic gelling agent. 
     
     
         51 . The composition of  claim 41 , wherein the carrier is selected from a carboxyvinyl polymer, an acrylic copolymer, polyacrylamide, polysaccharide or a combination thereof. 
     
     
         52 . The composition of  claim 41 , wherein the composition further comprises a vitamin, a hormone, an amino acid, a surfactant, a colorant, a dye, a pigment, a fragrance, an odor absorber, an antiseptic, a preservative, a bactericide, a humectant, a thickener, a solvent, a filler, an antioxidant, a sequestering agent, a sunscreen, an additive or a combination thereof. 
     
     
         53 . The composition of  claim 41 , wherein the composition further comprises at least one other active agent selected from an antibacterial agent, an antiparasitic agent, an antifungal agent, an anti-inflammatory agent, an antihistamine, an anti-pruriginous agent, an anesthetic, an antiviral agent, a keratolytic agent, an anti free-radical agent, an antiseborrheic agent, an antidandruff agent, an antiacne agent, an sunscreen, an sun blocking agent, or an active agent which modifies at least one of cutaneous differentiation, proliferation, or pigmentation. 
     
     
         54 . The composition of  claim 41 , wherein the composition is in a pharmacologically or cosmetically acceptable form selected from a solution, a gel, a lotion a cream, an ointment, a foam, an emulsion, a microemulsion, a milk, a serum, an aerosol, a spray, a dispersion, a microcapsule, a vesicle or a microparticle thereof. 
     
     
         55 . The composition of  claim 41 , wherein the composition further comprises metronidazole, precipitated sulfur, sodium sulfacetamide, azelaic acid, or a combination thereof. 
     
     
         56 . A method of treating acute erythema, the method comprising topically administering to a subject in need thereof a composition comprising an effective amount of an agent selected from an alpha-1 adrenoreceptor agonist, an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof; and a pharmaceutically acceptable carrier. 
     
     
         57 . The method of  claim 56 , wherein the acute erythema is associated with rosacea. 
     
     
         58 . The method of  claim 56 , wherein the acute erythema is emotionally or physiologically induced. 
     
     
         59 . The method of  claim 56 , wherein the alpha-1 adrenoreceptor agonist is oxymetazoline. 
     
     
         60 . The method of  claim 56 , wherein the alpha-1 adrenoreceptor agonist is oxymetazoline hydrochloride. 
     
     
         61 . The method of  claim 56 , wherein the composition comprises about 0.01% to about 20% of the agent. 
     
     
         62 . The method of  claim 56 , wherein the composition comprises about 0.05% to about 30% of the agent. 
     
     
         63 . The method of  claim 56 , wherein the composition comprises about 0.1% to about 10% of the agent. 
     
     
         64 . The method of  claim 56 , wherein the agent is administered in a therapeutically effective amount. 
     
     
         65 . The method of  claim 56 , wherein the composition comprises about 50% to about 99.999% of the carrier. 
     
     
         66 . The method of  claim 56 , wherein the composition comprises about 70% to about 99.99% of the carrier. 
     
     
         67 . The method of  claim 56 , wherein the carrier is a hydrophilic gelling agent. 
     
     
         68 . The method of  claim 56 , wherein the carrier is selected from a carboxyvinyl polymer, an acrylic copolymer, polyacrylamide, polysaccharide or a combination thereof. 
     
     
         69 . The method of  claim 56 , wherein the composition further comprises a vitamin, a hormone, an amino acid, a surfactant, a colorant, a dye, a pigment, a fragrance, an odor absorber, an antiseptic, a preservative, a bactericide, a humectant, a thickener, a solvent, a filler, an antioxidant, a sequestering agent, a sunscreen, an additive or a combination thereof. 
     
     
         70 . The method of  claim 56 , wherein the composition further comprises at least one other active agent selected from an antibacterial agent, an antiparasitic agent, an antifungal agent, an anti-inflammatory agent, an antihistamine, an anti-pruriginous agent, an anesthetic, an antiviral agent, a keratolytic agent, an anti free-radical agent, an antiseborrheic agent, an antidandruff agent, an antiacne agent, an sunscreen, an sun blocking agent, or an active agent which modifies at least one of cutaneous differentiation, proliferation, or pigmentation. 
     
     
         71 . The method of  claim 56 , wherein the composition is administered in a pharmacologically or cosmetically acceptable form selected from a solution, a gel, a lotion a cream, an ointment, a foam, an emulsion, a microemulsion, a milk, a serum, an aerosol, a spray, a dispersion, a microcapsule, a vesicle or a microparticle thereof. 
     
     
         72 . The method of  claim 56 , wherein the composition further comprises metronidazole, precipitated sulfur, sodium sulfacetamide, azelaic acid, or a combination thereof. 
     
     
         73 . A topical gel composition comprising an agent selected from an alpha-1 adrenoreceptor agonist, an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof; and a pharmaceutically acceptable carrier. 
     
     
         74 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing redness associated with rosacea. 
     
     
         75 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing erythema. 
     
     
         76 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing erythema associated with rosacea. 
     
     
         77 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing telangiectasias. 
     
     
         78 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing telangiectasias associated with rosacea. 
     
     
         79 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing acute erythema. 
     
     
         80 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing acute erythema associated with rosacea. 
     
     
         81 . The gel composition of  claim 73 , wherein the gel composition is suitable for treating or preventing rosacea. 
     
     
         82 . The gel composition of  claim 73 , wherein the gel composition is suitable for administration by spreading the gel onto an affected area. 
     
     
         83 . The gel composition of  claim 73 , wherein the composition further comprises excipients, binders, lubricants, disintegrants, fats, oils, waxes, hydrocarbons, fatty acids, higher alcohols, ester oils, metallic soaps, animal or vegetable extracts, hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, vitamins, hormones, amino acids, surfactants, colorants, dyes, pigments, fragrances, odor absorbers, antiseptics, preservatives, bactericides, humectants, thickeners, solvents, fillers, antioxidants, sequestering agents, sunscreens, or a combination thereof. 
     
     
         84 . A topical aqueous gel composition comprising an agent selected from an alpha-1 adrenoreceptor agonist, an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof; and a pharmaceutically acceptable carrier. 
     
     
         85 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing redness associated with rosacea. 
     
     
         86 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing erythema. 
     
     
         87 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing erythema associated with rosacea. 
     
     
         88 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing telangiectasias. 
     
     
         89 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing telangiectasias associated with rosacea. 
     
     
         90 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing acute erythema. 
     
     
         91 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing acute erythema associated with rosacea. 
     
     
         92 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for treating or preventing rosacea. 
     
     
         93 . The aqueous gel composition of  claim 84 , wherein the gel composition is suitable for administration by spreading the gel onto an affected area. 
     
     
         94 . The aqueous gel composition of  claim 84 , wherein the composition further comprises excipients, binders, lubricants, disintegrants, fats, oils, waxes, hydrocarbons, fatty acids, higher alcohols, ester oils, metallic soaps, animal or vegetable extracts, hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, vitamins, hormones, amino acids, surfactants, colorants, dyes, pigments, fragrances, odor absorbers, antiseptics, preservatives, bactericides, humectants, thickeners, solvents, fillers, antioxidants, sequestering agents, sunscreens, or a combination thereof.