Compound modified with glycerol derivative

• US 20060280784A1
• Filed: 09/03/2004
• Published: 12/14/2006
• Est. Priority Date: 09/03/2003
• Status: Active Grant

• Current Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited), Techno Network Shikoku, Co., Ltd.
• Inventors: Kusano, Hiroko, Yamasaki, Motoo, Yamauchi, Masahiro, Kato, Yasuki, Nemoto, Hisao, Suzawa, Toshiyuki
• Granted Patent: US 7,696,359 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 47/00 Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• CPC Class Codes: C07D 207/452 with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
• CPC Class Codes: C07F 9/10 Phosphatides, e.g. lecithin
• CPC Class Codes: C07K 5/0202 containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids

Abstract

Objects of the present invention are to provide a compound which is useful as a surface modifier for producing a drug carrier or the like, or a salt thereof; a fine particle comprising the same; and the like. The present invention provides a compound in which a substance to be modified, which is selected from the group consisting of an amphiphilic substance and a hydrophobic substance, is modified with a glycerol derivative represented by the following formula (1):
wherein R represents a residue comprising a reactive group for the substance to be modified, which is selected from the group consisting of an amphiphilic substance and a hydrophobic substance or for a spacer capable of binding the substance to be modified, which is selected from the group consisting of an amphiphilic substance and a hydrophobic substance, to R-X, or a group capable of being transformed into the reactive group; n represents an integer of 3 or more; and X represents a residue capable of having the following structure by n in number: directly or via the spacer, or a salt thereof; a fine particle comprising the same; and the like.

Claims

1. A compound comprising a glycerol derivative represented by formula (1):

2. The compound according to claim 1, wherein n is 2^m, in which m is an integer of 2 or more, or a salt thereof.

4. The compound according to any one of claims 1 or 2, wherein X comprises one to (n−

1) structure(s) represented by

5. The compound according to claim 4, wherein at least one X comprises

6. The compound according to claim 4, wherein at least one X comprises

7. The compound according to claim 4, wherein at least one X comprises

8. The compound according to claim 4, wherein at least one X comprises

9. The compound according to claim 4, wherein R comprises a member selected from the group consisting of carboxy, amino, a hydroxyl group, mercapto, formyl, a sulfuric acid residue, a phosphoric acid residue and a phosphonic acid residue.

10. The compound according to claim 4, wherein R comprises a member selected from the group consisting of a carboxylic acid active ester residue, carbonate, maleimido, mercapto, formyl, tresyl, isocyanato, an acid anhydride residue, an acid halide residue, vinylsulfonyl, hydrazido, amino, a hydroxyl group, halogen, carboxy, vinyl and phosphono, or a salt thereof.

11. A composition comprising a mixture of at least two different compounds or salts according to claim 4.

12. The compound according to claim 4, wherein modified moiety is a lipid or a derivative thereof, or a salt thereof.

23. A fine particle comprising a compound

of claim 4,

or a salt thereof.

25. The fine particle according to claim 23, wherein the fine particle is selected from the group consisting of a liposome, a fat emulsion, an emulsion, a micell and a fine particle crystal.

3. (canceled)

13. A compound represented by formula (2):

22. The compound according to any one of claims 13 to 21, wherein R³ and R⁴ are ethylene.

24. A fine particle comprising the compound according to any one of claims 13-21, or a salt thereof.

29. The fine particle according to claim 24, wherein the fine particle is selected from the group consisting of a liposome, a fat emulsion, an emulsion, a micell and a fine particle crystal.

14. A compound represented by formula (3):

15. A compound represented by formula (4):

16. A compound represented by formula (5):

17. A compound represented by formula (6):

18. A compound represented by formula (7):

19. A compound represented by formula (8):

20. A compound represented by formula (9):

21. A compound represented by formula (10):

26-28. -28. (canceled)