Combinations for the treatment of diseases involving angiogenesis

Abstract

Compositions for the inhibition of the formation of new vasculature by angiogenesis are provided comprising the combination of a vasculature damaging agent and an inhibitor of the formation or action of nitric oxide in mammalian systems. There are also provided the use of said combinations in medicaments and kits of said compounds and treatment employing said materials.

1 - 15 . (canceled)  
     
     
         16 . A pharmaceutical composition for the treatment of a disease involving active angiogenesis which comprises (a) a tubulin binding agent in an amount sufficient to cause damage to neovaasculature, (b) an inhibitor of the formation of nitric oxide in a mammalian system and (c) a pharmaceutically acceptable excipient.  
     
     
         17 . A pharmaceutical composition for the damage of the formation of new vasculature by angiogenesis comprising a combination of (a) a tubulin binding agent in an amount sufficient to cause damage to neovasculature, (b) an inhibitor of nitric oxide synthase in an amount sufficient to augment the effect of the tubulin binding agent and (c) a pharmaceutically acceptable excipient.  
     
     
         18 . A composition according to claim  2  wherein the inhibitor of nitric oxide synthase is selected from a derivative of arginine, ornithine, lysine, citrulline, S-alkylthioureas and aminoguanidine.  
     
     
         19 . A composition according to claim  4  wherein the nitric oxide synthase inhibitor is an N G -substituted L-arginine selected from N-nitro-L-arginine and alkyl esters thereof, N G -methyl-L-arginine and N G -amino-L-arginine.  
     
     
         20 . A composition according to claim  4  wherein the derivative of ornithine is L-N6-(1iminoethyl)-ornithine.  
     
     
         21 . A composition according to claim  4  wherein the derivative of lysine is L-N6-(1-iminoethyl)-lysine.  
     
     
         22 . A composition according to claim  4  wherein the derivative of citrulline is selected from L-thiocitrulline, L-homothiocitrulline or an S-alkylthiocitrulline.  
     
     
         23 . A composition according to claim  1  wherein the composition is in the form of a kit, one part of the kit containing the tubulin binding agent and the second part of the kit the inhibitor of the formation of nitric oxide.