Ocular formulations for drug-delivery to the posterior segment of the eye

Abstract

for treating ocular neovascularization. The Compound-I is present in a solution or a suspension in about 0.005% to about 5.0% w/v, such that the solution or suspension delivers the compound at the posterior segment of the eye for inhibiting VEGF in the retina and/or the choroid.

What is claimed is: 
     
         1 . A topical ocular formulation, the formulation comprising:
 a. an active agent of Formula II:   
       
         
           
           
               
               
           
         
         b. or a pharmaceutically acceptable salt thereof, and 
         c. and pharmaceutically acceptable excipients; 
       
       wherein the active agent or the pharmaceutically acceptable salt is present in about 0.005% to about 5.0% w/v such that the formulation forms a solution or a suspension. 
     
     
         2 . The formulation of  claim 1 , comprising a solubilizing agent. 
     
     
         3 . The formulation of  claim 2 , wherein the solubilizing agent is cyclodextrin selected from the group consisting of 2-hydroxypropyl-β-cyclodextrin, methyl-β-cyclodextrin, randomly methylated-β-cyclodextrin, ethylated-β-cyclodextrin, triacetyl-β-cyclodextrin, peracetylated-β-cyclodextrin, carboxymethyl-β-cyclodextrin, hydroxyethyl-β-cyclodextrin, 2-hydroxy-3-(trimethylammonio)propyl-β-cyclodextrin, glucosyl-β-cyclodextrin, maltosyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, branched-β-cyclodextrin, hydroxypropyl-γ-cyclodextrin, randomly methylated-γ-cyclodextrin, trimethyl-γ-cyclodextrin, and combinations thereof. 
     
     
         4 . The formulation of  claim 3 , wherein the pharmaceutically acceptable salt is a hydrochloride salt provided by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The formulation of  claim 3 , wherein the solubilizing agent is 2-hydroxypropyl-β-cyclodextrin or β-cyclodextrin sulfobutyl ether. 
     
     
         6 . The formulation of  claim 3 , comprising about 0.005%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 2.0%, about 3.0%, about 4.0%, or about 5.0% w/v of the active agent or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The formulation of  claim 3 , comprising one or more of benzalkonium chloride (BAK), sodium chloride, and a pH adjusting agent. 
     
     
         8 . The formulation of  claim 1 , comprising about 0.005%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 2.0%, about 3.0%, about 4.0%, or about 5.0% w/v of the active agent or a pharmaceutically acceptable salt thereof, and about 0.3%-about 1% w/v tromethamine. 
     
     
         9 . The formulation of  claim 1 , comprising about 0.005%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 2.0%, about 3.0%, about 4.0%, or about 5.0% w/v of the active agent or a pharmaceutically acceptable salt thereof, about 0.3%-about 1% w/v tromethamine, and about 0.005% w/v benzalkonium chloride (BAK). 
     
     
         10 . The formulation of  claim 1 , having a pH value of about 4.5 to about 7.5 at or under about 40° C. 
     
     
         11 . The formulation of  claim 1 , having a pH value of about 6.0 at or under about 40° C. 
     
     
         12 . The formulation of  claim 1 , having a pH value of about 5.0 to about 7.0 at or under about 40° C. 
     
     
         13 . The formulation of  claim 1 , wherein the formulation is suitable for accessing posterior segment of the eye and/or for treating and/or ameliorating ocular neovascularization. 
     
     
         14 . Use of the formulation of  claim 1  in the manufacture of a medicament suitable for accessing posterior segment of the eye and/or for treating and/or ameliorating a posterior segment disease of the eye, selected from the group consisting of: diabetic retinopathy, age-related macular degeneration (AMD), pathologic choroidal neovascularization (CNV), pathologic retinal neovascularization, uveitis, retinal vein occlusion, ocular trauma, surgery induced edema, surgery induced neovascularization, cystoid macular edema, ocular ischemia, retinopathy of prematurity, Coat's disease, sickle cell retinopathy, and neovascular glaucoma. 
     
     
         15 . The use according to  claim 14 , wherein the diabetic retinopathy is background diabetic retinopathy, proliferative diabetic retinopathy, or diabetic macular edema. 
     
     
         16 . The use according to  claim 14 , wherein the AMD is neovascular AMD, dry AMD, or Geographic Atrophy. 
     
     
         17 . The use according to  claim 16 , wherein the neovascular AMD is wet or exudative AMD. 
     
     
         18 . The use according to  claim 14 , wherein the CNV is related to high myopia, trauma, sickle cell disease, ocular histoplasmosis, angioid streaks, traumatic choroidal rupture, drusen of the optic nerve, or some retinal dystrophies. 
     
     
         19 . The use according to  claim 14 , wherein the pathologic retinal neovascularization is related to sickle cell retinopathy, Eales disease, ocular ischemic syndrome, carotid cavernous fistula, familial exudative vitreoretinopathy, hyperviscosity syndrome, idiopathic occlusive arteriolitis; birdshot retinochoroidopathy, retinal vasculitis, sarcoidosis, or toxoplasmosis. 
     
     
         20 . The use according to  claim 14 , wherein retinal vein occlusion is central or branch occlusion.