Pharmaceutical cream compositions of oxymetazoline and methods of use

Abstract

The present invention is directed to: a) a method of treating telangiectasia; b) a method of treating inflammatory lesions; and c) a method of treating two or more symptoms of rosacea selected from erythema, telangiectasia, or inflammatory lesions comprising topical administration of a pharmaceutical composition comprising oxymetazoline and a pharmaceutically acceptable excipient.

1 .- 20 . (canceled) 
     
     
         21 . A method of treating erythema, telangiectasia or inflammatory lesions associated with rosacea comprising topically administering a pharmaceutical composition comprising a therapeutically effective amount of oxymetazoline or a pharmaceutically acceptable salt thereof, and about 1% to about 50% by weight of an emollient comprising medium chain triglycerides, diisopropyl adipate, oleyl alcohol, and lanolin. 
     
     
         22 . The method of  claim 21 , wherein the inflammatory lesions are selected from the group consisting of papules, pustules, cysts and phymas. 
     
     
         23 . The method of claim  2   1 , wherein the pharmaceutically acceptable salt of oxymetazoline is oxymetazoline hydrochloride. 
     
     
         24 . The method of claim  2   1  , wherein the composition further comprises an additive selected from the group consisting of emulsifiers, preservatives, emulsion stabilizers, pH adjusters, chelating agents, viscosity modifiers, anti-oxidants, surfactants, emollients, opacifying agents, skin conditioners, buffers, and combinations thereof. 
     
     
         25 . The method of  claim 21 , wherein the composition further comprises a topically active pharmaceutical or cosmetic agent. 
     
     
         26 . The method of claim  2   5 , wherein the topically active pharmaceutical or cosmetic agent is selected from a group consisting of an anti-rosacea agent, an antibacterial agent, an antimycobacterial agent, an anti-acne agent, an anti-parasitic agent, an antifungal agent, an steroidal anti-inflammatory agent, an non-steroidal anti-inflammatory agent, an anesthetic agent, an anti-pruriginous agent, an anti-free radical agent, an anti-seborrheic agent, an antipsoriatic agent, a tricyclic anti-depressant, an antihistamine, and a chemotherapeutic agent. 
     
     
         27 . The method of  claim 21 , wherein the oxymetazoline or the pharmaceutically acceptable salt thereof is in an amount of from about 0.0075% to about 5% by weight. 
     
     
         28 . The method of  claim 21 , wherein the oxymetazoline or the pharmaceutically acceptable salt thereof is in an amount of from about 0.0075% to about 3% by weight. 
     
     
         29 . The method of  claim 21 , wherein the oxymetazoline or the pharmaceutically acceptable salt thereof is in an amount from about 0.01% to about 2.5% by weight. 
     
     
         30 . The method of  claim 21 , wherein the oxymetazoline or the pharmaceutically acceptable salt thereof is in an amount from about 0.01% to about 2% by weight. 
     
     
         31 . The method of  claim 21 , wherein the oxymetazoline or the pharmaceutically acceptable salt thereof is in an amount from about 0.01% to about 1% by weight. 
     
     
         32 . The method of  claim 21 , wherein the oxymetazoline or the pharmaceutically acceptable salt thereof is in an amount of about 1% by weight. 
     
     
         33 . The method of  claim 21 , wherein the composition further comprises an additional therapeutic agent for the treatment of non-inflammatory manifestation of rosacea such as telangiectasias, erythema, epidermal barrier dysfunction, or other manifestation of rosacea. 
     
     
         34 . The method of  claim 33 , wherein the additional therapeutic is selected from the group consisting of a selective alpha-1 adrenoreceptor agonist, a selective alpha-2 adrenoreceptor agonist, a non-selective alpha-1 adrenoreceptor agonist, a non-selective alpha-2 adrenoreceptor agonist, and a combination thereof. 
     
     
         35 . The method of  claim 21 , wherein administration of the composition is in combination with another therapy directed toward the treatment of inflammatory lesions. 
     
     
         36 . The method of  claim 21 , wherein the pharmaceutical composition comprises:
 about 1.0% by weight oxymetazoline HCl; and   wherein a pH of the pharmaceutical composition is about 4.5 at room temperature.   
     
     
         37 . The method of  claim 21 , wherein the pharmaceutical composition of further comprises an emulsifier including at least one of the following: polyethylene glycol stearate (PEG-6 stearate), polyethylene glycol 32 stearate (PEG-32 stearate), glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, and ceteareth-25. 
     
     
         38 . The method of  claim 37 , wherein the ratio of the emulsifier to the emollient is about 0.87:1. 
     
     
         39 . The method of  claim 37 , wherein the emulsifier further comprises about 2% by weight of macrogol (6) cetostearyl ether, and about 2% by weight of macrogol (25) cetostearyl ether. 
     
     
         40 . The method of  claim 37 , comprising PEG-6 stearate, PEG-32 stearate, and glycol stearate in a mixture comprising about 7% to about 8% by weight of the composition. 
     
     
         41 . The method of  claim 37 , wherein the cetostearyl alcohol comprises about 4% to about 8% by weight. 
     
     
         42 . The method of  claim 37 , wherein the ratio of the PEG-6 stearate, PEG-32 stearate and glycol stearate to the cetostearyl alcohol is about 1:1. 
     
     
         43 . The method of  claim 21 , wherein the pharmaceutical composition further comprises a pH regulator selected from the group consisting of sodium citrate dihydrate, anhydrous citric acid, and a combination thereof. 
     
     
         44 . The method of  claim 21 , wherein the pharmaceutical composition further comprises a preservative selected from the group consisting of methylparaben, propylparaben, phenoxyethanol, and a combination thereof. 
     
     
         45 . The method of  claim 21 , wherein the pharmaceutical composition further comprises an antioxidant selected from the group consisting of vitamin B, nordihydroguaiaretic acid, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, erythorbate acid, sodium erythorbate, ascorbir palmitate, and ascorbir stearate, and a combination thereof. 
     
     
         46 . The method of  claim 21 , wherein the pharmaceutical composition of further comprises a chelating agent selected from the group consisting of alanine, sodium polyphosphate, sodium methaphosphate, citric acid, phosphoric acid, tartaric acid, disodium edetate (EDTA), dihydroxyethyl glycine, derivatives thereof, salts thereof, and a combination thereof. 
     
     
         47 . The method of  claim 21 , wherein the pharmaceutical composition further comprises a solvent selected from the group consisting of polyethylene glycol 300, water, and a combination thereof. 
     
     
         48 . The method of  claim 21 , wherein the pH of the pharmaceutical composition is about 4.5 at room temperature. 
     
     
         49 . The method of  claim 21 , wherein the emollient comprises about 7% by weight of medium chain triglycerides, about 7% by weight of diisopropyl adipate, about 7% by weight of oleyl alcohol, and about 2% by weight of lanolin. 
     
     
         50 . The method of  claim 21 , wherein the pharmaceutical composition further comprises about 0.01% to about 5% by weight of a preservative comprising methylparaben, propylparaben, and phenoxyethanol. 
     
     
         51 . The method of  claim 21 , wherein the composition is a cream. 
     
     
         52 . The method of  claim 21 , wherein the pharmaceutical composition comprises, oxymetazoline HCI in an amount of about 1.0% by weight. 
     
     
         53 . A method of treating erythema, telangiectasia or inflammatory lesions associated with rosacea comprising topically administering a pharmaceutical composition comprising
 about 1.0% by weight oxymetazoline HCl;   about 20% by weight of an emulsifier, wherein the emulsifier comprises polyethylene glycol stearate (PEG-6 stearate), polyethylene glycol 32 stearate (PEG-32 stearate), glycol stearate, cetostearyl alcohol, ceteareth-6, and ceteareth-25; and   about 23% of an emollient comprising anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, and oleyl alcohol;   about 4% of a solvent;   about 0.05% of butylated hydroxytoluene;   about 0.01% of a disodium edetate;   about 0.52% of a buffer comprising sodium citrate dihyrate and anhydrous citric acid;   about 1.05% of a preservative comprising methylparaben, propylparaben, and phenoxyethanol;   wherein the composition is a cream;   wherein the ratio of the PEG-6 stearate, PEG-32 stearate and glycol stearate to the cetostearyl alcohol is about 1:1;   wherein the ratio of the emulsifier to the emollient is about 0.87:1; and   wherein the pH of the composition is about 4.5.