Sustained release intraocular implants and methods for preventing retinal dysfunction

Abstract

Biocompatible intraocular microspheres and implants include an alpha-2 adrenergic receptor agonist and a polymer associated with the alpha-2 adrenergic receptor agonist to facilitate release of the alpha-2 adrenergic receptor agonist into an eye for an extended period of time. The alpha-2 adrenergic receptor agonist may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. The implants may be placed in an eye to treat or to prevent the occurrence of one or more ocular conditions, to reduce one or more symptoms of an ocular condition, such as an ocular neurosensory disorder and the like, to enhance normal retinal function and/or to lower intraocular pressure.

1 . An ophthalmic composition comprising microspheres of an alpha-2 adrenergic receptor agonist associated with a biodegradable polymer matrix, the microspheres capable of releasing the alpha-2 adrenergic receptor agonist upon intravitreal injection of the microspheres.  
     
     
         2 . The ophthalmic composition of  claim 1 , wherein the composition is effective upon intravitreal injection of enhancing normal retinal neuronal function.  
     
     
         3 . The ophthalmic composition of  claim 1 , wherein the composition is effective upon intravitreal injection of lowering intraocular pressure.  
     
     
         4 . The ophthalmic composition of  claim 1 , wherein the alpha-2 adrenergic agonist is selected from the group consisting of quinoxalines, (2-imidozolin-2-ylamino) quinoxalines, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxalines, derivatives thereof and mixtures thereof.  
     
     
         5 . The ophthalmic composition of  claim 1 , wherein the alpha-2 adrenergic agonist is brimonidine.  
     
     
         6 . The ophthalmic composition of  claim 1 , wherein the polymer matrix comprises a polylactide polyglycolide copolymer.  
     
     
         7 . An ophthalmic composition comprising microspheres of a brimonidine associated with a biodegradable polylactide polyglycolide copolymer, the microspheres capable of releasing the brimonidine upon intravitreal injection of the microspheres.  
     
     
         8 . The ophthalmic composition of  claim 7 , wherein the composition is effective upon intravitreal injection of enhancing normal retinal neuronal function.  
     
     
         9 . The ophthalmic composition of  claim 7 , wherein the composition is effective upon intravitreal injection of lowering intraocular pressure.  
     
     
         10 . A method of making an ophthalmic composition comprising the steps of: 
 (a) combining an organic mixture comprising an alpha-2 adrenergic receptor agonist and a biodegradable polymer, and an aqueous phase, and;    (b) stirring to form biodegradable microspheres capable of releasing the alpha-2 adrenergic receptor agonist upon intravitreal injection of the microspheres.    
     
     
         11 . The method of  claim 10 , wherein the alpha-2 adrenergic agonist is selected from the group consisting of quinoxalines, (2-imidozolin-2-ylamino) quinoxalines, 5-bromo-6-(2-imidozolin-2-ylamino) quinoxalines, derivatives thereof and mixtures thereof.  
     
     
         12 . The method of  claim 10 , wherein the alpha-2 adrenergic agonist is selected from the group consisting of brimonidine, salts thereof, and mixtures thereof.  
     
     
         13 . The method of  claim 10 , wherein both the organic phase and the aqueous phase are liquids.  
     
     
         14 . A method of making an ophthalmic composition comprising the steps of: 
 (a) combining an organic mixture comprising a brimonidine and a biodegradable polylactide polyglycolide copolymer, and an aqueous phase comprising an aliphatic alcohol, and;    (b) stirring the combination to form biodegradable microspheres capable of releasing the brimonidine upon intravitreal injection of the microspheres.    
     
     
         15 . A method for enhancing normal retinal neuronal function comprising the step of intravitreal administration of an ophthalmic composition comprising microspheres of an alpha-2 adrenergic receptor agonist associated with a biodegradable polymer matrix.  
     
     
         16 . A method for reducing intraocular pressure comprising the step of intravitreal administration of an ophthalmic composition comprising microspheres of an alpha-2 adrenergic receptor agonist associated with a biodegradable polymer matrix.  
     
     
         17 . A method of treating a retinal dysfunction in an eye of a patient, comprising the step of intravitreal administration of biodegradable intraocular microspheres, the microspheres comprising an alpha-2 adrenergic receptor agonist associated with a biodegradable polymer matrix that releases alpha-2 adrenergic receptor effective to prevent or reduce a symptom of a retinal dysfunction.  
     
     
         18 . The method of  claim 17 , wherein the method is effective to treat a retinal neurosensory dysfunction.  
     
     
         19 . The method of  claim 17 , wherein the method is effective to treat an ocular condition selected from the group consisting of: retinitis pigmentosa, Leber's congenital amaurosis, retinal degeneration, Usher syndrome, Bardet-Biedl syndrome, rod-cone dystrophy, choroideremia, gyrate-atrophy, macular degeneration, and Stargardt's disease.  
     
     
         20 . The method of  claim 17 , wherein the alpha-2 adrenergic receptor agonist is selected from the group consisting of brimonidine, salts thereof, and mixtures thereof.  
     
     
         21 . A method for enhancing normal retinal neuronal function and reducing intraocular pressure without significantly obscuring vision, the method comprising the step of intravitreal administration of an ophthalmic composition comprising microspheres of a brimonidine associated with a biodegradable polylactide polyglycolide copolymer polymer matrix.