Composition for blocking angiogenesis

Abstract

Compositions including the combination of cremastranone analogs and anti-angiogenic agents and the use of the compositions for targeting ocular angiogenesis such as seen in neovascular eye diseases are disclosed.

1 . A composition comprising a synthetic compound comprising formula (I) 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of hydrogen, hydroxyl, alkoxy, substituted alkoxy, alkyl carbonyloxy, substituted alkyl carbonyloxy, alkyl carbonyl, substituted alkyl carbonyl, aryl carbonyloxy, substituted aryl carbonyloxy, halogen, amino, nitro, hydrocarbyl and substituted hydrocarbyl; and X, Y, and Z are independently selected from the group consisting of carbon, nitrogen, and oxygen, and
 an anti-angiogenic agent. 
 
     
     
         2 . The composition as set forth in  claim 1  wherein the synthetic compound comprises the formula 
       
         
           
           
               
               
           
         
       
     
     
         3 . The composition as set forth in  claim 1  wherein the anti-angiogenic agent is an anti-vascular endothelial growth factor agent selected from the group consisting of pegaptanib, ranibizumab, aflibercept, bevacizumab, and combinations thereof. 
     
     
         4 . The composition as set forth in  claim 1  further comprising a pharmaceutically acceptable carrier. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . A method of treating a neovascular eye disease in a subject in need thereof, the method comprising administering an effective amount of the composition of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . A method of treating a neovascular eye disease in a subject in need thereof, the method comprising administering an effective amount of the composition of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A method of treating an angiogenesis-mediated disease in a subject in need thereof, the method comprising administering an effective amount of the composition of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         17 . A method of treating an angiogenesis-mediated disease in a subject in need thereof, the method comprising administering an effective amount of the composition of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . The composition as set forth in  claim 1  wherein the anti-angiogenic agent is aflibercept. 
     
     
         21 . The composition as set forth in  claim 1  wherein the synthetic compound comprises the formula 
       
         
           
           
               
               
           
         
       
     
     
         22 . The composition as set forth in  claim 1  wherein the synthetic compound comprises the formula selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and mixtures thereof. 
     
     
         23 . The method as set forth in  claim 12  wherein the neovascular eye disease is selected from the group consisting of retinopathy of prematurity, diabetic retinopathy, wet age-related macular degeneration, pathological myopia, hypertensive retinopathy, occlusive vasculitis, polypoidal choroidal vasculopathy, uveitic macular edema, central retinal vein occlusion, branch retinal vein occlusion, coreneal neovascularization, retinal neovascularization, ocular histoplasmosis, and neovascular glaucoma. 
     
     
         24 . The method as set forth in  claim 12  wherein the neovascular eye disease is selected from the group consisting of coreneal neovascularization, retinal neovascularization, and wherein the synthetic compound comprises the formula 
       
         
           
           
               
               
           
         
       
     
     
         25 . The method as set forth in  claim 24  wherein the anti-angiogenic agent is aflibercept. 
     
     
         26 . The method as set forth in  claim 16  wherein the angiogenesis-mediated disease is selected from the group consisting of non-ocular hemorrhage, myocardial infarction, stroke, cancer, atherosclerosis, ischaemic heart disease, coronary heart disease, peripheral arterial disease, wound healing disorder and combinations thereof.