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 erythema or a symptom associated therewith, the method comprising administering topically to a subject in need thereof a composition comprising an agent selected from an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof, wherein the agent is effective to decrease the erythema. 
     
     
         26 . The method of  claim 25 , wherein the erythema is erythema associated with rosacea. 
     
     
         27 . The method of  claim 25 , wherein the composition comprises about 0.01% to about 20% of the agent. 
     
     
         28 . The method of  claim 25 , wherein the composition comprises about 0.05% to about 30% of the agent. 
     
     
         29 . The method of  claim 25 , wherein the composition comprises about 0.1% to about 10% of the agent. 
     
     
         30 . The method of  claim 25 , wherein the agent is administered in a therapeutically effective amount. 
     
     
         31 . The method of  claim 25 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         32 . The method of  claim 25 , wherein said composition comprises about 50% to about 99.999% of the carrier. 
     
     
         33 . The method of  claim 32 , wherein said composition comprises about 70% to about 99.99% of the carrier. 
     
     
         34 . The method of  claim 32 , wherein the carrier is a hydrophilic gelling agent or a lipophilic gelling agent. 
     
     
         35 . The method of  claim 32 , wherein the carrier is selected from a carboxyvinyl polymer, an acrylic copolymer, polyacrylamide, polysaccharide or a combination thereof. 
     
     
         36 . 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. 
     
     
         37 . 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, a sunscreen, a sun blocking agent, or an active agent which modifies at least one of cutaneous differentiation, proliferation, or pigmentation. 
     
     
         38 . 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. 
     
     
         39 . The method of  claim 25 , wherein the agent is co-administered with metronidazole, precipitated sulfur, sodium sulfacetamide, azelaic acid, or a combination thereof. 
     
     
         40 . A method of treating erythema or a symptom associated therewith, the method comprising administering topically to a skin area of the subject a topical gel composition comprising an agent selected from an alpha-2 adrenoreceptor agonist, a pharmaceutically acceptable salt thereof, or a combination thereof; and a pharmaceutically acceptable carrier, wherein the skin area is, or is prone to be, affected by the erythema or the symptom associated therewith. 
     
     
         41 . The method of  claim 40 , wherein the erythema is erythema associated with rosacea. 
     
     
         42 . The method of  claim 40 , wherein the gel composition is an aqueous gel composition. 
     
     
         43 . The method of  claim 40 , wherein the gel composition further comprises a gelling agent. 
     
     
         44 . The method of  claim 43 , wherein the gelling agent is hydrophilic or lipophilic. 
     
     
         45 . The method of  claim 43 , wherein the gelling agent is selected from a carboxyvinyl polymer, an acrylic polymer, a polyacrylamide, a polysaccharide or a combination thereof. 
     
     
         46 . The method of  claim 40 , wherein the composition comprises about 0.01% to about 20% of the agent. 
     
     
         47 . The method of  claim 40 , wherein the composition comprises about 0.05% to about 30% of the agent. 
     
     
         48 . The method of  claim 40 , wherein the composition comprises about 0.1% to about 10% of the agent. 
     
     
         49 . The method of  claim 40 , wherein the agent is administered in a therapeutically effective amount. 
     
     
         50 . The method of  claim 40 , wherein said composition comprises about 50% to about 99.999% of the carrier. 
     
     
         51 . The method of  claim 40 , wherein said composition comprises about 70% to about 99.99% of the carrier. 
     
     
         52 . The method of  claim 40 , 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 method of  claim 40 , 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, a sunscreen, a sun blocking agent, or an active agent which modifies at least one of cutaneous differentiation, proliferation, or pigmentation. 
     
     
         54 . The method of  claim 40 , further comprising administering to the subject at least one additional treatment for the erythema or the symptom associated therewith. 
     
     
         55 . The method of  claim 54 , wherein the at least one additional treatment is selected from metronidazole, precipitated sulfur, sodium sulfacetamide, azelaic acid, or a combination thereof. 
     
     
         56 . The method of  claim 25 , wherein the alpha-2 adrenoreceptor agonist is brimonidine. 
     
     
         57 . The method of  claim 25 , wherein the alpha-2 adrenoreceptor agonist is brimonidine tartrate. 
     
     
         58 . The method of  claim 40 , wherein the alpha-2 adrenoreceptor agonist is brimonidine. 
     
     
         59 . The method of  claim 40 , wherein the alpha-2 adrenoreceptor agonist is brimonidine tartrate.