Combinations of ileal bile acid transport inhibitors and bile acid sequestering agents for cardiovascular indications

Abstract

The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an ileal bile acid transport inhibitor combined with a bile acid sequestrant.

What is claimed is:  
     
         1 . A therapeutic combination comprising a first amount of an ileal bile acid transport inhibiting compound and a second amount of a bile acid sequestering compound wherein the first amount and the second amount together comprise an anti-hyperlipidemic condition effective amount, an anti-atherosclerotic condition effective amount, or an anti-hypercholesterolemic condition effective amount of the compounds.  
     
     
         2 . The therapeutic combination of  claim 1  wherein the ileal bile acid transport inhibiting compound has the structure of formula B-2:  
       
         
           
           
               
               
           
         
       
       or an enantiomer or racemate thereof.  
     
     
         3 . The therapeutic combination of  claim 1  wherein the ileal bile acid transport inhibiting compound has the structure of formula E-12:  
       
         
           
           
               
               
           
         
       
       or an enantiomer or racemate thereof.  
     
     
         4 . The therapeutic combination of  claim 1  wherein the ileal bile acid transport inhibiting compound has the structure of formula B-29:  
       
         
           
           
               
               
           
         
       
       or an enantiomer or racemate thereof, wherein PEG is an about 3000 to about 4000 molecular weight polyethylene glycol polymer chain.  
     
     
         5 . The therapeutic combination of  claim 1  wherein the ileal bile acid transport inhibiting compound has the structure of formula B-7:  
       
         
           
           
               
               
           
         
       
       or an enantiomer or racemate thereof.  
     
     
         6 . The therapeutic combination of  claim 1  wherein the bile acid sequestering compound comprises cholestyramine.  
     
     
         7 . The therapeutic combination of  claim 1  wherein the bile acid sequestering compound comprises colestipol.  
     
     
         8 . The therapeutic combination of  claim 1  wherein the bile acid sequestering compound comprises an amphiphilic copolymer having a crosslinked shell domain and an interior core domain.  
     
     
         9 . The therapeutic combination of  claim 1  wherein the bile acid sequestering compound comprises a polyallylamine polymer.  
     
     
         10 . The therapeutic combination of  claim 9  wherein the polyallylamine polymer comprises CholestaGel.  
     
     
         11 . The therapeutic combination of  claim 9  wherein the polyallylamine polymer comprises OmegaGel.  
     
     
         12 . The therapeutic combination of  claim 1  wherein the combination comprises a composition comprising an ileal bile acid transport inhibiting compound and a bile acid sequestering compound.  
     
     
         13 . A method for the prophylaxis or treatment of a hyperlipidemic condition comprising administering to a patient in need thereof a combination in unit dosage form wherein the combination comprises a first amount of an ileal bile acid transport inhibiting compound and a second amount of a bile acid sequestering compound wherein the first amount and the second amount together comprise an anti-hyperlipidemic condition effective amount of the compounds.  
     
     
         14 . A method for the prophylaxis or treatment of an atherosclerotic condition comprising administering to a patient in need thereof a combination in unit dosage form wherein the combination comprises a first amount of an ileal bile acid transport inhibiting compound and a second amount of a bile acid sequestering compound wherein the first amount and the second amount together comprise an anti-atherosclerotic condition effective amount of the compounds.  
     
     
         15 . A method for the prophylaxis or treatment of hypercholesterolemia comprising administering to a patient in need thereof a combination in unit dosage form wherein the combination comprises a first amount of an ileal bile acid transport inhibiting compound and a second amount or a bile acid sequestering compound wherein the first amount and the second amount together comprise an anti-hypercholesterolemic condition effective amount of the compounds.