IP Library Granted Patent US 11,266,680
Granted Patent B2
US 11,266,680 · App. 15/903,738 · Granted Mar 8, 2022

Compositions based on methyl cyclodextrins for the treatment and/or prevention of diseases by increasing the HDL cholesterol level

Inventors: Marc Salome (Mervilla, FR); Daniel Wils (Morbecque, FR); Xavier Parissaux (Saint Omer, FR); Francois Mach (Geneva, CH); Fabrizio Montecucco (Geneva, CH)
Assignee: Roquette Freres
A61K31/724A61K45/06
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Quick Facts
Patent No.
US 11,266,680
App. No.
15/903,738
Granted
Mar 8, 2022
Kind
B2
Abstract

Pharmaceutical composition and their uses are disclosed, the composition comprising at least one methyl cyclodextrin having a molar substitution (MS) degree of between 0.05 and 1.5 in the treatment and/or prevention of diseases that can be treated and/or prevented by an increase in the HDL cholesterol level.

Claims (20)

1. A method of treating diseases of the central nervous system, comprising increasing the HDL without modifying the LDL-cholesterol level of a subject by administrating a pharmaceutical composition comprising at least one methyl-β-cyclodextrin having a degree of molar substitution between 0.2 and 1.5, to a subject having diseases of the central nervous system, wherein the diseases of the central nervous system are selected from the group consisting of Alzheimer's disease, Parkinson's disease, and lysosomal diseases affecting the central nervous system.

2. The method of claim 1 , wherein the methyl-β-cyclodextrin has a degree of molar substitution between 0.2 and 1.2.

3. The method of claim 2 , wherein the methyl-β-cyclodextrin has a degree of molar substitution between 0.6 and 0.8.

4. The method of claim 3 , wherein the methyl-β-cyclodextrins comprises one or more methyl-β-cyclodextrins selected from the group consisting of methyl-β-cyclodextrins substituted on the hydroxyl borne by the C 2 carbon of the glucopyranose units, methyl-β-cyclodextrins substituted on the hydroxyl borne by the C 3 and/or C 6 carbons of the glucopyranose units, and methyl-β-cyclodextrins substituted on the hydroxyl borne by the C 2 , C 3 and/or C 6 carbons of the glucopyranose units.

5. The method of claim 1 , wherein the methyl-β- cyclodextrin is substituted on the hydroxyl borne by the C 2 carbon of the glucopyranose units, or by the C 3 and/or C 6 carbons of the glucopyranose units, or by a combination of the C 2 , C 3 and/or C 6 carbons of the glucopyranose units.

6. The method of claim 1 , wherein the lysosomal diseases affecting the central nervous are selected from Niemann-Pick disease, Niemann-Pick disease type A, Niemann-Pick disease type B, or Niemann-Pick disease type C.

7. The method of claim 1 , wherein the composition of methyl-β-cyclodextrins comprises at least 50% of methyls substituted on the hydroxyl borne by the C 2 carbon of the glucopyranose units.

8. The method of claim 1 , wherein the composition comprising at least one methyl-β-cyclodextrin also comprises at least one of cyclodextrin which is unsubstituted and cyclodextrin substituted with sulfobutyl ether (SBE) or hydroxypropyl (HP) groups.

9. The method of claim 1 , wherein said composition is free of phospholipid vesicles.

10. The method of claim 1 , wherein said methyl-β-cyclodextrin is the sole active ingredient of said pharmaceutical composition.

11. A method of treating diseases of the central nervous system, comprising administrating a pharmaceutical composition comprising at least one methyl-β-cyclodextrin having a degree of molar substitution between 0.2 and 1.5 to a subject having diseases of the central nervous, increasing the level of HDL without modifying the LDL-cholesterol level in the subject and thereby reducing at least one of overload, storage and accumulation of cholesterol in the tissues of the central nervous system, wherein the diseases of the central nervous system are selected from the group consisting of Alzheimer's disease, Parkinson's disease, and lysosomal diseases affecting the central nervous system.

12. The method of claim 11 , wherein said pharmaceutical composition further comprises at least one additional active agent.

13. The method of claim 12 , wherein the active ingredient is tocopherol.

14. The method of claim 11 , wherein diseases are selected Alzheimer's disease, Parkinson's disease or Niemann Pick disease type C.

15. The method of claim 11 , wherein said pharmaceutical composition is administered without the addition of phospholipid.

16. The method of claim 11 , wherein said methyl-β-cyclodextrin is the sole active ingredient of said pharmaceutical composition.

17. A method of treating diseases of the central nervous system, comprising administering a pharmaceutical composition comprising at least one methyl-β-cyclodextrin having a degree of molar substitution between 0.2 and 1.5 to a subject having diseases of the central nervous, and increasing expression of the HDL receptor SR-B1, thereby promoting transport of cytoplasmic cholesterol to blood of the subject and increasing plasma HDL cholesterol without modifying the LDL-cholesterol level, wherein the diseases of the central nervous system are selected from the group consisting of Alzheimer's disease, Parkinson's disease, and lysosomal diseases affecting the central nervous system.

18. The method of claim 17 , wherein said pharmaceutical composition is administered without the addition of phospholipid.

19. The method of treating diseases of the central nervous system according to claim 17 , wherein the composition is administered orally, parenterally, mucosally, cutaneously, intrathecal or spinally.

20. The method of claim 17 , wherein said methyl-β-cyclodextrin is the sole active ingredient of said pharmaceutical composition.

Priority Claims (1)
FR 1362633 · Dec 13, 2013 · national
Continuity (2)
Division 15039864
Related Publication 20180207198A1 · Jul 26, 2018