Pharmaceutical angiostatic dipeptide compositions and methods of use thereof

Abstract

Disclosed are methods of inhibiting neovascularization in a subject by administering to the subject a pharmaceutical preparation of R'-Glu-Trp-R''.

1 . A method of treating a subject having a pathologic condition involving neovascularization comprising administering a pharmaceutical preparation comprising an R′-Glu-Trp-R″ dipeptide and a pharmaceutically acceptable carrier to the subject in an amount effective to inhibit neovascularization.  
     
     
         2 . The method of  claim 1  wherein the R′-Glu-Trp-R″ dipeptide is L-Glu-L-Trp.  
     
     
         3 . The method of  claim 2  wherein the condition is hemangioma.  
     
     
         4 . The method of  claim 2  wherein the condition is vascularized malignant tumor or vascularized benign tumor.  
     
     
         5 . The method of  claim 2  wherein the condition is neovascularization in post-recovery cerebrovascular accident; neovascularization due to head trauma; restenosis following angioplasty; or neovascularization due to heat or cold trauma.  
     
     
         6 . The method of  claim 2  wherein the condition is neovascularization associated with substance-induced neovascularization of the liver, anglogenic dysfunction related to an excess of hormone; neovascular sequelae of diabetes; neovascular sequelae to hypertension; or chronic liver infection.  
     
     
         7 . The method of  claim 2  comprising administering to the subject a dose of about 0.5 μg per 1 kilogram body weight to about 1 mg per 1 kg body weight.  
     
     
         8 . The method of  claim 7  wherein the effective amount is about 1 μg/kg to about 50 μg/kg body weight.  
     
     
         9 . The method of  claim 7  wherein the dose is administered daily over a period of 1 day to about 30 days.  
     
     
         10 . The method of  claim 7  wherein the pharmaceutical preparation is administered intramuscularly or intranasally.  
     
     
         11 . The method of  claim 2  comprising administering the pharmaceutical preparation in the form of an injectable solution containing 0.001% to 0.01% of L-Glu-L-Trp.  
     
     
         12 . The method of  claim 2  comprising administering the preparation in a unit dose form comprising a tablet, a suppository, a capsule, an eye film, an inhalant, a mucosal spray, a nose drop, an eye drop, a toothpaste, an ointment, or water soluble based cream.  
     
     
         13 . The method of  claim 12  wherein said unit dose form consists essentially of 0.01 mg of said R′-Glu-Trp-R″.  
     
     
         14 . The method of  claim 2  further comprising administering to the subject a vasoactive drug.  
     
     
         15 . The method of  claim 14  wherein the vasoactive drug is an angiotensin converting enzyme (ACE) inhibitor or a potassium channel opener (PCO).  
     
     
         16 . The method of  claim 2  wherein the subject suffers from a tumor wherein the method further comprises administering a chemotherapeutic agent.  
     
     
         17 . The method of  claim 2  wherein the subject is not immune compromised.