Liposome Preparation Containing Slightly Water-Soluble Camptothecin

• US 20080193509A1
• Filed: 06/17/2005
• Published: 08/14/2008
• Est. Priority Date: 06/18/2004
• Status: Abandoned Application

• Current Assignee: Kabushiki Kaisha Yakult Honsha, Terumo Kabushiki Kaisha (Terumo Corporation)
• Original Assignee: Kabushiki Kaisha Yakult Honsha, Terumo Kabushiki Kaisha (Terumo Corporation)
• Inventors: Kurosaki, Yasuo, Kato, Ikuo, Matsuzaki, Takeshi, Nozawa, Shigenori, Yoshino, Keisuke, Ogata, Yoshitaka, Sawda, Seigo
• Application Number:
  US11/629,869
• Publication Number:
  US 20080193509A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention aims at providing a slightly water-soluble camptothecin liposome preparation with an excellent retention in blood for a drug, which can stably hold a slightly water-soluble camptothecin compound for a long period of time, whereby hydrolysis of an α-hydroxylactone ring in blood is suppressed and the slightly water-soluble camptothecin compound is kept in a structure in which the ring is not opened and which makes the compound effective as an antitumor-active drug, and, moreover, the liability of the drug to leave a liposome is advantageously reduced, so that it is possible to maintain the drug concentration in plasma for a long period of time after administration. This object is achieved by the liposome preparation as described in the specification. The liposome preparation according to the present invention includes a liposome preparation including as lipid components for forming a membrane a phospholipid and a fatty acid, and containing as a drug a lightly water-soluble camptothecin compound.

Claims

1. A liposome preparation, including as lipid components for forming a membrane a phospholipid and a fatty acid, and containing as a drug a slightly water-soluble camptothecin compound.

2. The liposome preparation according to claim 1, wherein said slightly water-soluble camptothecin compound comprises 20(S)-camptothecin, 7-ethyl-10-hydroxycamptothecin (SN-38), 7-(β

-trimethylsilyl)ethylcamptothecin, or 7-(t-butoxy)iminomethylcamptothecin.

3. The liposome preparation according to claim 1, wherein said fatty acid comprises a saturated fatty acid.

4. The liposome preparation according to claim 3, wherein said saturated fatty acid has an alkyl chain length of 14 to 18.

5. The liposome preparation according to claim 1, wherein said phospholipid comprises a hydrogenated phospholipid.

6. The liposome preparation according to claim 3, wherein said phospholipid comprises a hydrogenated phospholipid.

7. The liposome preparation according to claim 1, further comprising as said lipid components at least one other lipid in addition to the phospholipid and the fatty acid.

8. The liposome preparation according to claim 3, further comprising as said lipid components at least one other lipid in addition to the phospholipid and the fatty acid.

9. The liposome preparation according to claim 7, in which the other lipid comprises cholesterol.

10. The liposome preparation according to claim 8, in which the other lipid comprises cholesterol.

11. The liposome preparation according to claim 1, wherein said membrane has a modification moiety.

12. The liposome preparation according to claim 3, wherein said membrane has a modification moiety.

13. The liposome preparation according to claim 11, wherein the modification moiety comprises a hydrophilic polymer chain.

14. The liposome preparation according to claim 12, wherein the modification moiety comprises a hydrophilic polymer chain.

15. The lipsome preparation according to claim 13, wherein the hydrophilic polymer chain comprises a polyethylene glycol chain.

16. The liposome preparation according to claim 14, wherein the hydrophilic polymer chain comprises a polyethylene glycol chain.

17. The liposome preparation according to claim 1, wherein the liposome preparation has a drug/lipid molar ratio of 0.001 to 0.1 or less.

18. The liposome preparation according to claim 3, wherein the liposome preparation has a drug/lipid molar ratio of 0.001 to 0.1 or less.

19. The liposome preparation according to claim 1, wherein said fatty acid is included in a ratio of 1 to 30 mol % of the total mol of the lipid components.

20. The liposome preparation according to claim 3, wherein said fatty acid is included in a ratio of 1 to 30 mol % of the total mol of the lipid components.

21. The liposome preparation according to claim 1, wherein said liposome preparation has an average particle diameter of 50 to 300 nm.

22. The liposome preparation according to claim 3, wherein said liposome preparation has an average particle diameter of 50 to 300 nm.

23. The liposome preparation according to claim 1, wherein said liposome preparation includes a liposome preparation which is producible by stirring the lipid components and the slightly water-soluble camptothecin compound to prepare a liposome dispersion, and subjecting the liposome dispersion to a particle sizing treatment by causing high-pressure streams of the liposome dispersion to collide with each other.

24. The liposome preparation according to claim 3, wherein said liposome preparation includes a liposome preparation which is producible by stirring the lipid components and the slightly water-soluble camptothecin compound to prepare a liposome dispersion, and subjecting the liposome dispersion to a particle sizing treatment by causing high-pressure streams of the liposome dispersion to collide with each other.

25. A pharmaceutical composition, including the liposome preparation according to claim 1.

26. A pharmaceutical composition, including the liposome preparation according to claim 3.