Ophthalmic composition for treatment of dry eye disease

Abstract

The invention provides pharmaceutical compositions comprising about 0.05 to 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane for use in the topical treatment of dry eye disease and provides for dosing and treatment methods thereof. The invention further provides kits comprising such compositions.

1 - 15 . (canceled) 
     
     
         16 . A method of treating dry eye disease, the method comprising topically administering twice daily to an eye of a human with dry eye disease a composition comprising about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane, wherein said composition is substantially free of water and is substantially free of a preservative, wherein the amount of cyclosporine administered in a single dose per eye is about 10 μg cyclosporine. 
     
     
         17 . The method according to  claim 16 , wherein the composition comprises up to about 1% (w/w) ethanol. 
     
     
         18 . The method according to  claim 16 , wherein the composition comprises about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         19 . The method according to  claim 18 , wherein the composition consists of about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         20 . The method according to  claim 18 , wherein
 i. a reduction in corneal staining,   ii. an early onset of action,   iii. a reduction of visual impairment associated with dry eye disease, or   iv. a reduction of ocular surface damage associated with dry eye disease is achieved.   
     
     
         21 . The method according to  claim 16 , wherein the dry eye disease is moderate to severe dry eye disease, and optionally wherein the subject is not responsive to treatment with artificial tears. 
     
     
         22 . The method according to  claim 16 , wherein the subject suffering from dry eye disease experiences symptoms such as blurring, pain, irritation or corneal surface damage. 
     
     
         23 . The method according to  claim 16 , wherein the composition further comprises up to about 2% (w/w) 2-perfluorobutyl-pentane. 
     
     
         24 . A method of reducing reading impairment associated with dry eye disease, the method comprising topically administering twice daily to an eye of a human with dry eye disease a composition comprising about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane, wherein said composition is substantially free of water and is substantially free of a preservative, wherein the amount of cyclosporine administered in a single dose per eye is about 10 μg cyclosporine. 
     
     
         25 . The method according to any of the  claim 24 , wherein the composition further comprises up to about 1% (w/w) ethanol. 
     
     
         26 . The method according to  claim 24 , wherein the composition comprises about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         27 . The method according to  claim 26  wherein the composition consists about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         28 . The method according to  claim 26 , wherein
 i. a reduction in corneal staining,   ii. an early onset of action, or   iii. a reduction of ocular surface damage associated with dry eye disease is achieved.   
     
     
         29 . The method according to  claim 24 , wherein the composition further comprises up to about 2% (w/w) 2-perfluorobutyl-pentane. 
     
     
         30 . A method of reducing ocular surface damage associated with dry eye disease, the method comprising topically administering twice daily to an eye of a human with dry eye disease a composition comprising about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane, wherein said composition is substantially free of water and is substantially free of a preservative, wherein the amount of cyclosporine administered in a single dose per eye is about 10 μg cyclosporine. 
     
     
         31 . The method according to any of the  claim 30 , wherein the composition comprises up to about 1% (w/w) ethanol. 
     
     
         32 . The method according to  claim 30 , wherein the composition comprises about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         33 . The method according to  claim 32 , wherein the composition consists of about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         34 . The method according to  claim 32 , wherein
 i. a reduction in corneal staining,   ii. an early onset of action, or   iii. a reduction of visual impairment associated with dry eye disease is achieved.   
     
     
         35 . The method according to  claim 30 , wherein the composition further comprises up to about 2% (w/w) 2-perfluorobutyl-pentane. 
     
     
         36 . A pharmaceutical composition for (a) treating dry eye disease or (b) reducing ocular surface damage associated with dry eye disease, the composition comprising about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane, wherein said composition is substantially free of water and is substantially free of a preservative, and wherein said composition is topically administered twice daily in a single dose per eye of about 10 μg cyclosporine. 
     
     
         37 . The composition according to  claim 36 , wherein the composition comprises up to about 1% (w/w) ethanol. 
     
     
         38 . The composition according to  claim 36 , wherein the composition comprises about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         39 . The composition according to  claim 38 , wherein the composition consists about 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane and about 1.0% (w/w) of ethanol. 
     
     
         40 . The composition according to  claim 36 , wherein said composition is safe, well tolerated and comfortable to the eye of the human. 
     
     
         41 . The composition according to  claim 36 , wherein the composition further comprises up to about 2% (w/w) 2-perfluorobutyl-pentane. 
     
     
         42 . The composition according to  claim 36 , wherein the composition is essentially free of ethanol. 
     
     
         43 . A kit comprising the pharmaceutical composition according to  claim 36 , wherein the kit comprises a container for holding the composition and a drop dispenser adapted for administering about 10 μL volume of the composition per drop. 
     
     
         44 . The kit according to  claim 43 , wherein the ratio of the volume of the pharmaceutical composition in the container to the total volume of the container is between 0.4 to 0.7, or wherein the ratio of the volume of the head space of the container to the volume of the pharmaceutical composition is between 0.5 to 1.5. 
     
     
         45 . The kit according to  claim 43 , wherein the container and/or drop dispenser is manufactured from a thermoplastic material, optionally selected from polyethylene or polypropylene.