METHOD OF INHIBITING LEAKAGE OF DRUG ENCAPSULATED IN LIPOSOMES
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.
1 - 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.
6 - 7 . (canceled)
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.
13 - 25 . (canceled)
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.
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.