Compositions and their use for removing cholesterol

Abstract

The invention is directed to compositions that function to remove cholesterol from a mammal suffering from an elevated cholesterol level. The composition includes a polysaccharide having attached thereto at least one cyclic oligosaccharide. In a particular embodiment, the foregoing composition further includes at least one cell-targeting agent. The invention is also directed to methods that utilize these compositions for removing or reducing cholesterol and other lipids in a mammal suffering from an elevated level of cholesterol and/or other lipid.

1 . A composition comprising an active portion comprising a polysaccharide having attached thereto at least one cyclic oligosaccharide, and at least one cell-targeting agent attached to said active portion. 
     
     
         2 . The composition of  claim 1 , wherein said at least one cyclic oligosaccharide is attached as a pendant group from the polysaccharide. 
     
     
         3 . The composition of  claim 1 , wherein said cyclic oligosaccharide is a cyclodextrin. 
     
     
         4 . The composition of  claim 3 , wherein said cyclodextrin is an alkylated cyclodextrin by having at least one hydroxyl group of the cyclodextrin modified by substitution of a hydrogen atom of the hydroxyl group with a hydrocarbon group. 
     
     
         5 . The composition of  claim 4 , wherein said hydrocarbon group contains at least one and up to six carbon atoms. 
     
     
         6 . The composition of  claim 4 , wherein said alkylated cyclodextrin is a methylated cyclodextrin. 
     
     
         7 . The composition of  claim 6 , wherein said methylated cyclodextrin is a permethylated cyclodextrin. 
     
     
         8 . The composition of  claim 1 , wherein said cyclic oligosaccharide is attached to the polysaccharide via a linker. 
     
     
         9 . The composition of  claim 8 , wherein said linker is comprised of at least one ethyleneoxide moiety. 
     
     
         10 . The composition of  claim 1 , wherein said cell-targeting agent is attached to the polysaccharide. 
     
     
         11 . The composition of  claim 1 , wherein said cell-targeting agent is attached to the cyclic oligosaccharide. 
     
     
         12 . The composition of  claim 8 , wherein the cell-targeting agent is attached to the linker, 
     
     
         13 . The composition of  claim 1 , wherein said cell-targeting agent targets an entity residing on a surface of a cell. 
     
     
         14 . The composition of  claim 1 , wherein said cell-targeting agent targets a lysosome. 
     
     
         15 . The composition of  claim 14 , wherein said cell targeting agent is mannose-6-phosphate. 
     
     
         16 . The composition of  claim 1 , wherein said polysaccharide is a dextran. 
     
     
         17 . The composition of  claim 1 , wherein said polysaccharide has a molecular weight of at least 40,000 Da. 
     
     
         18 . The composition of  claim 1 , wherein said composition further comprises a fluorophore attached to said active portion. 
     
     
         19 . A pharmaceutical composition comprising the composition according to  claim 1 , in a pharmaceutically acceptable vehicle. 
     
     
         20 . A method for lowering a cholesterol level of a mammal, the method comprising administering to said mammal a polymer composition comprising a polysaccharide having attached thereto at least one cyclic oligosaccharide. 
     
     
         21 . The method of  claim 20 , wherein said polymer composition further comprises a cell-targeting agent. 
     
     
         22 . A method for treating a mammal suffering from a lysosomal storage disorder, the method comprising administering to said mammal a polymer composition comprising a polysaccharide having attached thereto at least one cyclic oligosaccharide. 
     
     
         23 . The method of  claim 22 , wherein said polymer composition further comprises a cell-targeting agent. 
     
     
         24 . The method of  claim 22 , wherein said lysosomal storage disorder is a Niemann-Pick disease. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . A method for lowering a cholesterol level of a mammal, the method comprising administering to said mammal a sphingomyelinase enzyme. 
     
     
         29 . A method for treating a mammal suffering from a lysosomal storage disorder, the method comprising administering to said mammal a sphingomyelinase enzyme. 
     
     
         30 . The method of  claim 29 , wherein said lysosomal storage disorder is a Niemann-Pick disease.