COMPOSITIONS AND THEIR USE FOR REMOVING CHOLESTEROL
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.