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1. WO2013152227 - EMBELIN-BASED DELIVERY SYSTEM FOR WATER-INSOLUBLE ACTIVE AGENTS

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[ EN ]

What is claimed is:

1 . A composition comprising a structure of:

X - L - Y

wherein X comprises at least one embelin moiety;

L comprises a linker; and

Y comprises a hydrophilic moiety.

2. The composition of claim 1 , wherein the embelin moiety comprises embelin or an embelin analog.

3. The composition of claim 2, wherein the embelin moiety comprises a structure of:


wherein each of R1, R3, and R4 is individually hydroxyl, oxo, or methoxy; and R2 is a hydrophobic moiety selected from an optionally substituted alkyl having at least 6 carbon atoms, or an optionally substituted aryl, or a tautomer thereof.

4. The composition of any one of claims 1 to 3, wherein the linker is derived from an amino acid, a carbonyl-containing molecule, or an ether-containing molecule.

5. The composition of claim 4, wherein the linker comprises an aspartic acid structure.

6. The composition of any one of claims 1 to 5, wherein the hydrophilic moiety includes at least one of SO3-2, COO-1 , PO4 3 , (CH3)3N+1 , (CH3CH2)3N+1 , (HOCH2CH2)3N+1 , methyl pyridine+1 , multivalent cationic group, a polyalkylene glycol, polyglycerol, poly(vinyl alcohol), or a mono, oligo or polysaccharide.

7. The composition of claim 6, wherein the hydrophilic moiety comprises a polyethylene glycol.

8. The composition of claim 1, wherein:

the embelin moiety comprises a structure of:


wherein each of R1, R3, and R4 is individually hydroxyl; and R2 is an alkyl having at least 6 carbon atoms;

the linker comprises an aspartic acid structure; and

the hydrophilic moiety comprises a polyethylene glycol.

9. The composition of any one of claims 1 to 8, wherein the composition is formulated as a micelle.

10. The composition of any one of claims 1 to 9, further comprising a targeting moiety bonded to the embelin moiety, the linker, or the hydrophilic moiety.

11. The composition of claim 10, wherein the targeting moiety comprises a small molecule ligand for σ2 receptor.

12. The composition of any one of claims 1 to 11, wherein the composition is a conjugate.

13. A micelle comprising:

a core that includes at least one hydrophobic active agent and at least one embelin moiety; and

a hydrophilic zone surrounding the core and comprising at least one hydrophilic moiety.

14. The micelle of claim 13, wherein the active agent is a pharmaceutically active agent.

15. The micelle of claim 14, wherein the pharmaceutically active agent is selected from embelin, amphteracin B, doxurobicin, cyclosporine, FK506, a taxane (e.g. paclitaxel), or camptothecin.

16. The micelle of any one of claims 13 to 15, wherein the embelin moiety comprises a structure of:


wherein each of R1, R3, and R4 is individually hydroxyl, oxo, or methoxy; and R2 is a hydrophobic moiety selected from an optionally substituted alkyl having at least 6 carbon atoms, or an optionally substituted aryl, or a tautomer thereof.

17. The micelle of any one of claims 13 to 16, wherein the hydrophilic moiety includes at least one of SO3-2, COO-1, PO4-3, (CH3)3N+1, (CH3CH2)3N+1, (HOCH2CH2)3N+1, methyl pyridine+1, multivalent cationic group, a polyalkylene glycol, polyglycerol, poly( vinyl alcohol), or a mono, oligo or polysaccharide.

18. The micelle of any one of claims 13 to 17, wherein the embelin moiety and the hydrophilic moiety are conjugated to each other via a linker.

19. The micelle of claim 18, wherein the linker is derived from an amino acid, a carbonyl-containing molecule, or an ether-containing molecule.

20. The micelle of claim 19, wherein the linker comprises an aspartic acid structure.

21. The micelle of any one of claims 18 to 20, further comprising a targeting moiety bonded to the embelin moiety, the linker, or the hydrophilic moiety.

22. A composition comprising the micelle of any one of claims 13 to 21 and a continuous phase in which the micelle is solubilized.

23. The composition of claim 22, wherein the continuous phase comprises an aqueous phase.

24. The composition of claim 22, wherein the continuous phase is an aqueous phase.

25. A method for making a micelle-containing composition, comprising mixing the micelle of any one of claims 13 to 21 together with an aqueous phase.

26. The method of claim 24 or 25, wherein the aqueous phase is selected from water or saline.

27. A method comprising administering a therapeutically effective amount of the composition of any one of claims 1 to 12 to a subject in need thereof.

28. A method comprising administering a therapeutically effective amount of the micelle of any one of claims 13 to 21 to a subject in need thereof.

29. A method comprising administering a therapeutically effective amount of the composition of any one of claims 22 to 24 to a subject in need thereof.

30. The method of any one of claims 27 to 29, wherein the method comprises treating cancer in the subject.

31. The method of claim 30, wherein the pharmaceutically active agent is a taxane and the method comprises treating prostate cancer or breast cancer in the subject.

32. The method of claim 30 or 31 , wherein the cancer is a drug-resistant cancer.

33. The method of any one of claims 30 to 32, wherein the pharmaceutically active agent is doxurobicin.