Combination of brimonidine and timolol for topical ophthalmic use

Abstract

Disclosed are pharmaceutical compositions comprising brimondine and timolol for topical ophthalmic delivery and a method of treatment comprising administering said composition when indicated for glaucoma and associated conditions such as elevated intraocular pressure in the eyes of humans.

1 . A pharmaceutical composition for use in lowering intraocular pressure in patients suffering from elevated intraocular pressure or glaucoma, the composition comprising: brimonidine tartrate at a concentration of 0.2% w/v and timolol at a concentration of 0.5% w/v in a single composition, wherein the composition is sterile and is suitable for topical ophthalmic use and is administered twice a day. 
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein the timolol is timolol maleate and is present in the amount of 0.68% w/v. 
     
     
         4 . (canceled) 
     
     
         5 . The composition of  claim 1 , having a pH of about 6.9. 
     
     
         6 . The composition of  claim 1 , wherein the composition is superior in lowering intraocular pressure in patients as compared to the administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         7 . The composition of  claim 1 , wherein the composition is superior in lowering intraocular pressure in patients and results in fewer side effects than the administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         8 . The composition of  claim 1 , wherein the composition results in a lower incidence of allergic conjunctivitis as compared to administration of a 0.02% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the composition results in a lower incidence of conjunctival hyperemia as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the composition results in a lower incidence of somnolence as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the composition results in a lower incidence of visual disturbance as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the composition results in a lower incidence of oral dryness as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         13 . An ophthalmic composition for use in lowering intraocular comprising: brimonidine tartrate at a concentration of 0.2% w/v and timolol at a concentration of 0.5% w/v, a phosphate buffer, water and having a pH of about 4.5-8. 
     
     
         14 . The ophthalmic composition of  claim 13 , wherein timolol is timolol maleate and is present at a concentration of about 0.68% w/v. 
     
     
         15 . The ophthalmic composition of  claim 13 , further comprising benzalkonium chloride. 
     
     
         16 . The ophthalmic composition of  claim 13 , wherein the composition is at a pH of about 6.9. 
     
     
         17 . The composition of  claim 13 , wherein the composition results in a lower incidence of allergic conjunctivitis as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         18 . The composition of  claim 13 , wherein the composition results in a lower incidence of conjunctival hyperemia as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         19 . The pharmaceutical composition of  claim 13 , wherein the composition results in a lower incidence of somnolence as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol. 
     
     
         20 . An ophthalmic composition for use in lowering intraocular in patients suffering from elevated intraocular pressure or glaucoma comprising brimonidine tartrate at a concentration of 0.2% w/v and timolol at a concentration of 0.5% w/v, further comprising benzalkonium chloride and having a pH of about 6.9. 
     
     
         21 . The composition of  claim 20 , further comprising sodium phosphate. 
     
     
         22 . The composition of  claim 20 , further comprising a mixture of sodium phosphate, monobasic monohydrate and sodium phosphate, dibasic heptahydrate. 
     
     
         23 . The composition of  claim 20 , wherein the composition results in a lower incidence of allergic conjunctivitis as compared to administration of a 0.2% w/v brimonidine tartrate composition administered three times a day without the concurrent administration of timolol.