Use of radical-scavenging compounds for treatment and prevention of NO-dependent microcirculation disorders

Abstract

A method of treatment of the human or non-human animal body for treating NO-dependent microcirculation disorders is disclosed, for example microcirculation disorders caused by metabolic diseases, such as elevated levels of homocystin-homocystein inflammatory reactions or autoimmune diseases, furthermore peripheral microcirculation disorders or microcirculation disorders associated with increased cell fragmentation, which method comprises administering to a human or non-human animal body in need of such treatment an effective amount of a pharmaceutical composition containing a substance which scavenges free radicals, e.g. a pyrimido-pyrimidine selected from Dipyridamole, Mopidamol and the pharmaceutically acceptable salts thereof, and the use such substance for the manufacture of a corresponding pharmaceutical composition, optionally in combination with an agent capable of increasing NO procution.

1 . A pharmaceutical composition for treating NO-dependent microcirculation disorders comprising dipyridamole or a pharmaceutically acceptable salt thereof in combination with one or more HMG CoA reductase inhibitors.  
   
   
       2 . The pharmaceutical composition of  claim 1 , wherein administration of the composition to an animal results in a maintained plasma level of about 0.2 to 5 μmol/L of dipyridamole.  
   
   
       3 . The pharmaceutical composition of  claim 1 , wherein the composition is administered orally in a sustained or controlled release formulation.  
   
   
       4 . The pharmaceutical composition of  claim 1 , wherein the composition is administered parenterally.  
   
   
       5 . The pharmaceutical composition of  claim 1 , wherein the dipyridamole is administered orally in a daily dosage of 25 to 450 mg or parenterally in a dosage of 0.5 to 5 mg/kg body weight over 24 hours.  
   
   
       6 . The pharmaceutical composition of  claim 1  wherein the HMG CoA reductase inhibitor may be one or more selected from the group consisting of: 
 lovastatin,    pravastatin,    simvastatin,    fluvastatin,    dalvastatin,    compactin, mevastatin,    HR 780,    BMY 22,089,    BMY 22,566,    SQ 33,600,    GR 95,030 and    CI 981.    
   
   
       7 . The pharmaceutical composition of  claim 1  wherein the HMG CoA reductase inhibitor is selected from the group consisting of: 
 lovastatin,    pravastatin,    simvastatin,    fluvastatin,    dalvastatin, and    mevastatin.    
   
   
       8 . The pharmaceutical composition of  claim 1  wherein the HMG CoA reductase inhibitor is pravastatin.