Treatment and prevention of abnormal cellular proliferation

Abstract

This invention provides a method for inhibiting or preventing the abnormal growth of cells, including transformed cells, by administering an effective amount of O-acylated heparin derivative. Abnormal growth of cells refers to cell growth independent of normal regulatory mechanism (e.g. loss of contact inhibition). This includes the abnormal growth of: (1) tumor cells (tumors); (2) benign and malignant cells of other proliferative disease in which aberrant cellular proliferation occurs; (3) aberrant smooth muscle cell proliferation, such as might occur following treatment for coronary atherosclerosis such as angioplasty or the insertion of a stent into an occluded vessel.

1 . A composition comprising a hexanoyl derivative of low molecular weight heparin with the chemical structure: 
     
       
         
         
             
             
         
       
       Wherein m=8 and 
       R═CH 3 (CH 2 ) 4 —. 
     
   
   
       2 . A composition comprising a butanoyl derivative of low molecular weight heparin with the chemical structure: 
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 2 —. 
     
   
   
       3 . A pharmaceutical composition comprising:
 a) a hexanoyl derivative of low molecular weight heparin with the chemical structure:   
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 4 —; and 
       b) a pharmaceutically acceptable carrier. 
     
   
   
       4 . A pharmaceutical composition comprising:
 a) a butanoyl derivative of low molecular weight heparin with the chemical structure:   
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 2 —; and 
       b) a pharmaceutically acceptable carrier. 
     
   
   
       5 . The pharmaceutical composition of  claim 3 , which is formulated for oral, rectal, topical or parenteral administration. 
   
   
       6 . A composition for intravascular implant coating comprising a hexanoyl derivative of low molecular weight heparin with the chemical structure: 
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 4 —. 
     
   
   
       7 . A composition for intravascular implant coating comprising a butanoyl derivative of low molecular weight heparin with the chemical structure: 
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 2 —. 
     
   
   
       8 . A polymer matrix which has incorporated therein, a hexanoyl derivative of low molecular weight heparin with the chemical structure: 
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 4 —. 
     
   
   
       9 . A polymer matrix which has incorporated therein, a butanoyl derivative of low molecular weight heparin with the chemical structure: 
     
       
         
         
             
             
         
       
       wherein m=8 and 
       R═CH 3 (CH 2 ) 2 —. 
     
   
   
       10 . The pharmaceutical composition of  claim 4 , which is formulated for oral, rectal, topical or parenteral administration.