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 method for lowering a cholesterol level in a patient, the method comprising administering to said patient a composition consisting essentially of a therapeutically effective amount of a polysaccharide having attached thereto at least one cyclodextrin and a cell-targeting agent, wherein said cyclodextrin is an alkylated cyclodextrin having at least one hydroxyl group of the cyclodextrin modified by substitution of a hydrogen atom of the hydroxyl group with a hydrocarbon group.
2. A method for treating a mammal suffering from a lysosomal storage disorder resulting in an accumulation of lipids, the method comprising administering to said mammal a polymer composition comprising an active portion comprising a polysaccharide having attached thereto at least one cyclodextrin.
3. The method of claim 2 , wherein said polymer composition further comprises a cell-targeting agent attached to said active portion.
4. The method of claim 2 , wherein said lysosomal storage disorder is a Niemann-Pick disease.
5. The method of claim 1 , wherein said at least one cyclodextrin is attached as a pendant group from the polysaccharide.
6. The method of claim 1 , wherein said alkylated cyclodextrin is a permethylated cyclodextrin.
7. The method of claim 1 , wherein said alkylated cyclodextrin is a hydroxypropyl cyclodextrin.
8. The method of claim 1 , wherein said cell-targeting agent targets an entity residing on a surface of a cell.
9. The method of claim 1 , wherein said cell-targeting agent targets a lysosome.
10. The method of claim 9 , wherein said cell-targeting agent is mannose-6-phosphate.
11. The method of claim 1 , wherein said polysaccharide is a dextran.
12. The method of claim 1 , wherein said polysaccharide has a molecular weight of at least 40,000 Da.
13. The method of claim 2 , wherein said at least one cyclodextrin is attached as a pendant group from the polysaccharide.
14. The method of claim 2 , 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.
15. The method of claim 14 , wherein said alkylated cyclodextrin is a permethylated cyclodextrin.
16. The method of claim 14 , wherein said alkylated cyclodextrin is a hydroxypropyl cyclodextrin.
17. The method of claim 3 , wherein said cell-targeting agent targets an entity residing on a surface of a cell.
18. The method of claim 3 , wherein said cell-targeting agent targets a lysosome.
19. The method of claim 18 , wherein said cell-targeting agent is mannose-6-phosphate.
20. The method of claim 2 , wherein said polysaccharide is a dextran.
21. The method of claim 2 , wherein said polysaccharide has a molecular weight of at least 40,000 Da.
22. The method of claim 1 , wherein said cyclodextrin is unloaded when administered to the patient.