Poly(diallylamine)-based bile acid sequestrants

Abstract

The present invention relates to a method for removing bile acids from a patient and certain polymers of use in the method. The method comprises the step of administering to the patient a therapeutically effective amount of a polymer composition which includes a a poly(diallylamine)polymer which is substituted with hydrophobic groups. The hydrophobic groups can be a substituted or unsubstituted, straight chain or branched C 3 -C 24 -alkyl group, an aralkyl group or an aryl group.

1 . A method for removing bile acids from a patient comprising the step of orally administering to the patient a therapeutically effective amount of a poly(diallylamine)polymer wherein more than 10% of the amino nitrogen atoms are substituted by a hydrophobic substituent.  
   
   
       2 . The method of  claim 1  wherein the polymer is a homopolymer.  
   
   
       3 . The method of  claim 1  wherein the polymer is a copolymer.  
   
   
       4 . The method of  claim 1  wherein the hydrophobic substituent is a normal or branched C 2 -C 24 -alkyl group.  
   
   
       5 . The method of  claim 1  wherein the polymer comprises a repeat unit of the general formula  
     
       
         
         
             
             
         
       
     
     wherein R 2  is hydrogen, a substituted or unsubstituted C 1 -C 24 -alkyl group, a substituted or unsubstituted arylalkyl group or a substituted or unsubstituted aryl group; R 1  is a substituted or unsubstituted C 3 -C 24 -alkyl group, a substituted or unsubstituted arylalkyl group or a substituted or unsubstituted aryl group; and X −  is a pharmaceutically acceptable anion.  
   
   
       6 . The method of  claim 5  wherein X −  is a conjugate base of an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, citric acid, tartaric acid, lactic acid, phosphoric acid, methanesulfonic acid, acetic acid, formic acid, maleic acid, fumaric acid, malic acid, succinic acid, malonic acid, sulfuric acid, L-glutamic acid, L-aspartic acid, pyruvic acid, mucic acid, benzoic acid, glucuronic acid, oxalic acid, ascorbic acid and acetylglycine.  
   
   
       7 . The method of  claim 5  wherein R 1  is a normal or branched C 3 -C 24 -alkyl group which is substituted by an amino group, an ammonium group, an amido group, a hydroxyl group, a sulfone group, a sulfoxide group or an alkoxy group.  
   
   
       8 . The method of  claim 5  wherein R 1  is an alkyl group selected from the group consisting of hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl and tetradecyl.  
   
   
       9 . The method of  claim 8  wherein R 2  is methyl and R 1  is selected from the group consisting of octyl, decyl and dodecyl.  
   
   
       10 . The method of  claim 1  wherein the polymer is characterized by a repeat unit of the general formula  
     
       
         
         
             
             
         
       
     
     wherein R is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group.  
   
   
       11 . The method of  claim 10  wherein R is a C 3 -C 24 -alkyl group.  
   
   
       12 . The method of  claim 11  wherein the alkyl group is selected from the group consisting of hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl and tetradecyl.  
   
   
       13 . The method of  claim 11  wherein the alkyl group is substituted by an amino group, an ammonium group, an amido group, a hydroxyl group, a sulfoxide group, a sulfone group or an alkoxy group.  
   
   
       14 . The method of  claim 1  wherein the polymer comprises a first monomer of the general formula  
     
       
         
         
             
             
         
       
     
     wherein R 1  is hydrogen, a substituted or unsubstituted C 1 -C 24 -alkyl group or a substituted or unsubstituted aryl group; R 2  is a substituted or unsubstituted C 3 -C 24 -alkyl group or a substituted or unsubstituted aryl group; and X −  is a pharmaceutically acceptable anion; and a second monomer of the general formula  
     
       
         
         
             
             
         
       
     
     wherein R is hydrogen, a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group.  
   
   
       15 . The method of  claim 1  wherein the polymer is a crosslinked polymer.  
   
   
       16 . The method of  claim 15  wherein the polymer is crosslinked by a multifunctional co-monomer.  
   
   
       17 . The method of  claim 16  wherein the multifunctional co-monomer is selected from the group consisting of diacrylates, triacrylates, tetraacrylates, dimethacrylates, diacrylamides, dimethacrylamides, diallylacrylamides and polyvinylarenes.  
   
   
       18 . (canceled)  
   
   
       19 . The method of  claim 16  wherein the multifunctional comonomer is a multifunctional diallylamine.  
   
   
       20 . (canceled)  
   
   
       21 . (canceled)  
   
   
       22 . The method of  claim 15  wherein the polymer is crosslinked by a bridging unit selected from the group consisting of straight chain or branched, substituted or unsubstituted alkylene groups, diacylalkylene groups, diacylarene groups and alkylene bis(carbamoyl) groups.  
   
   
       23 - 55 . (canceled)