Compositions, formulations and methods for treating ocular diseases

Abstract

Disclosed herein are compounds effective for activation of Tie-2 and inhibition of HPTP-beta. The compounds can provide effective therapy for conditions associated with angiogenesis, for example, ocular conditions. Formulations for increased solubility are disclosed. Combination therapy with antibodies and PK/PD data are also disclosed.

1 - 54 . (canceled) 
     
     
         55 . A pharmaceutical composition comprising:
 a) a therapeutically-effective amount of a Tie-2 activator; and   b) an effective amount of a solubilizing agent,   
       wherein the solubilizing agent improves aqueous solubility of the Tie-2 activator by at least 10% at each of 5° C., ambient temperature, and 50° C. 
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein the Tie-2 activator binds HPTP-β. 
     
     
         57 . The pharmaceutical composition of  claim 55 , wherein the Tie-2 activator inhibits HPTP-β. 
     
     
         58 . The pharmaceutical composition of  claim 55 , wherein the solubilizing agent improves the aqueous solubility of the Tie-2 activator by at least 25%. 
     
     
         59 . The pharmaceutical composition of  claim 55 , wherein the solubilizing agent improves the aqueous solubility of the Tie-2 activator by at least 50%. 
     
     
         60 . The pharmaceutical composition of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is from about 0.1 mg to about 100 mg. 
     
     
         61 . The pharmaceutical composition of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 15 mg. 
     
     
         62 . The pharmaceutical composition of  claim 55 , wherein the therapeutically-effective amount of the Tie-2 activator is about 40 mg. 
     
     
         63 . The pharmaceutical composition of  claim 55 , wherein the Tie-2 activator is present in the pharmaceutical composition at a concentration of from about 0.1 mg/mL to about 100 mg/mL. 
     
     
         64 . The pharmaceutical composition of  claim 55 , wherein the Tie-2 activator is present in the pharmaceutical composition at a concentration of about 15 mg/mL. 
     
     
         65 . The pharmaceutical composition of  claim 55 , wherein the Tie-2 activator is present in the pharmaceutical composition at a concentration of about 20 mg/mL. 
     
     
         66 . The pharmaceutical composition of  claim 55 , wherein the Tie-2 activator is present in the pharmaceutical composition at a concentration of about 40 mg/mL. 
     
     
         67 . The pharmaceutical composition of  claim 55 , wherein the solubilizing agent is present in the pharmaceutical composition at a concentration of about 40 mg/mL. 
     
     
         68 . The pharmaceutical composition of  claim 55 , wherein the solubilizing agent is present in the pharmaceutical composition at a concentration of about 10% weight by volume. 
     
     
         69 . The pharmaceutical composition of  claim 55 , wherein the solubilizing agent is present in the pharmaceutical composition at a concentration of about 15% weight by volume. 
     
     
         70 . The pharmaceutical composition of  claim 55 , formulated for topical administration. 
     
     
         71 . The pharmaceutical composition of  claim 55 , formulated for subcutaneous administration. 
     
     
         72 . The pharmaceutical composition of  claim 55 , formulated for intravenous administration. 
     
     
         73 . The pharmaceutical composition of  claim 55 , formulated for administration to an eye. 
     
     
         74 . The pharmaceutical composition of  claim 55 , formulated for intravitreal administration. 
     
     
         75 . The pharmaceutical composition of  claim 55 , formulated as a drop. 
     
     
         76 . The pharmaceutical composition of  claim 55 , formulated as an eye drop. 
     
     
         77 . The pharmaceutical composition of  claim 55 , formulated as a unit dosage form.