METHOD OF INHIBITING LEAKAGE OF DRUG ENCAPSULATED IN LIPOSOMES

• US 20090041835A1
• Filed: 06/16/2008
• Published: 02/12/2009
• Est. Priority Date: 06/24/1999
• Status: Abandoned Application

• Current Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited)
• Inventors: Kato, Yusuki, Kusano, Hiroko, Yamauchi, Masahiro, Ishihara, Atsushi
• Application Number:
  US12/139,702
• Publication Number:
  US 20090041835A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 9/127 Liposomes

Abstract

The present invention provides a method of inhibiting the leakage of a drug encapsulated in liposomes, which comprises satisfying at least two requirements selected from the group consisting of the following three requirements: using at least two lipid bilayers of the liposomes, controlling the average particle size of the liposomes to 120 nm or more, and using lipid having a phase transition temperature higher than in vivo temperature as lipid constituting the liposomes. Also, the present invention provides a liposome preparation which is stable in vivo and satisfies at least two requirements selected from the group consisting of the following three requirements: the number of lipid bilayers of the liposomes is at least two, the liposomes have an average particle size of 120 nm or more, and lipid constituting the liposomes has a phase transition temperature higher than in vivo temperature.

Claims

1-2. -2. (canceled)

3. A method of preparing a drug encapsulated in liposomes, which comprises selecting a drug and encapsulating said drug satisfying at least two requirements selected from the group consisting of:

using at least two lipid bilayers of the liposomes, controlling the average particle size of the liposomes to 120 nm or more, and using lipid having a phase transition temperature higher than in vivo temperature as lipid constituting the liposomes.

4. The method according to claim 3, wherein the lipid comprises at least one component selected from the group consisting of hydrogenated soybean phosphatidylcholine, polyethylene glycol-modified phospholipid, and cholesterol.

5. The method according to claim 3, wherein the lipid comprises at least one component selected from the group consisting of distearoyl phosphatidylcholine, polyethylene glycol-modified phospholipid, and cholesterol.

8. The method according to any one of claims 3-5, wherein the encapsulated drug exhibits reduced leakage in blood.

9. The method according to claims 3-5, wherein the drug encapsulated is an indolocarbazole derivative.

10. The method according to claims 3-5, wherein the drug encapsulated is an antitumor agent.

11. The method according to claims 3-5, wherein the drug encapsulated is an antibiotic.

12. The method according to claims 3-5, wherein the drug encapsulated is a pharmaceutically active substance.

26. The method of inhibiting the leakage according to claim 8, wherein the drug encapsulated is an indolocarbazole derivative.

27. The method of inhibiting the leakage according to claim 8, wherein the drug encapsulated is an antitumor agent.

28. The method of inhibiting the leakage according to claim 8, wherein the drug encapsulated is an antibiotic.

29. The method of inhibiting the leakage according to claim 8, wherein the drug encapsulated is a pharmaceutically active substance.

30. The method of inhibiting the leakage according to any one of claims 3 to 5, wherein said liposome comprises at least two bilayers of said lipid.

31. The method of inhibiting the leakage according to claim 26, wherein said liposome comprises at least two bilayers of said lipid.

32. The method of inhibiting the leakage according to claim 27, wherein said liposome comprises at least two bilayers of said lipid.

33. The method of inhibiting the leakage according to claim 28, wherein said liposome comprises at least two bilayers of said lipid.

34. The method of inhibiting the leakage according to claim 29, wherein said liposome comprises at least two bilayers of said lipid.

6-7. -7. (canceled)

13-25. -25. (canceled)

35. A method of inhibiting the leakage of an encapsulated drug in the presence of a biological component, which comprises the steps of:

selecting a lipid with a phase transition temperature higher than in vivo temperature; and

encapsulating said drug within liposomes comprising said lipid, wherein said liposomes do not comprise cholesterol and said liposomes have an average particle size of 120 to 500 nm.