Liposome including taxane compound

Patent metadata

Field	Value
Publication number	US-2018280300-A1
Application number	US-201615766641-A
Country	US
Kind code	A1
Filing date	Oct 6, 2016
Priority date	Oct 7, 2015
Publication date	Oct 4, 2018
Grant date	—

Abstract

An object of the present invention is to provide a method for encapsulating a poorly water-soluble pharmacologically active substance in a liposome with high efficiency.
The present invention provides a composition comprising a lipid having a phosphatidylcholine group, a cholesterol compound, a lipid having a phosphatidylethanolamine group, and a poorly water-soluble pharmacologically active substance, wherein the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and the poorly water-soluble pharmacologically active substance is 3 to 8:2 to 7:0.1 to 3:0.001 to 5, respectively.

First claim

1 . A composition comprising a lipid having a phosphatidylcholine group, a cholesterol compound, a lipid having a phosphatidylethanolamine group, and paclitaxel or a glycoside thereof, docetaxel, or bafilomycin, wherein:
the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and paclitaxel is 3 to 8:2 to 7:0.1 to 3:0.5 to 2, respectively, the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and the paclitaxel glycoside is 3 to 8:2 to 7:0.1 to 3:1 to 3, respectively, the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and docetaxel is 3 to 8:2 to 7:0.1 to 3:1 to 3, respectively, and the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and bafilomycin is 3 to 8:2 to 7:0.1 to 3:0.1 to 0.2, respectively.

2 . The composition according to claim 1 , wherein the lipid having a phosphatidylcholine group is at least one member selected from the group consisting of hydrogenated soy lecithin, egg yolk phospholipid, distearoyl phosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, and dioleoyl phosphatidylcholine.

3 . The composition according to claim 1 , wherein the cholesterol compound is at least one member selected from the group consisting of cholesterol, cholestanol, 7-dehydrocholesterol, and phytosterol.

4 . The composition according to claim 1 , wherein the lipid having a phosphatidylethanolamine group is at least one member selected from the group consisting of distearoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, and dioleoyl phosphatidylethanolamine.

5 . The composition according to claim 1 , wherein any one of the lipid having a phosphatidylethanolamine group, the cholesterol compound, and the lipid having a phosphatidylcholine group is modified by polyalkylene glycol.

6 - 8 . (canceled)

9 . The composition according to claim 1 , wherein the composition is used to form a lipid film.

10 . A lipid film comprising a lipid having a phosphatidylcholine group, a cholesterol compound, a lipid having a phosphatidylethanolamine group, and paclitaxel or a glycoside thereof, docetaxel or bafilomycin, wherein:
the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and the paclitaxel is 3 to 8:2 to 7:0.1 to 3:0.5 to 2, respectively, the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and the paclitaxel glycoside is 3 to 8:2 to 7:0.1 to 3:1 to 3, respectively. the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and docetaxel is 3 to 8:2 to 7:0.1 to 3:1 to 3, respectively, and the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and bafilomycin is 3 to 8:2 to 7:0.1 to 3:0.1 to 0.2, respectively.

11 . A method for producing a liposome encapsulating paclitaxel or a glycoside thereof, docetaxel, or bafilomycin, comprising the step of bringing the lipid film of claim 10 into contact with a polyoxyethylene ester compound in an aqueous solvent.

12 . The method according to claim 11 , wherein lower alcohol is further contained as an aqueous solvent.

13 . The method according to claim 11 , wherein a buffer is further contained as an aqueous solvent.

14 . The method according to claim 11 , further comprising the step of loading an antibody recognizing a cancer cell.

15 . A liposome formulation comprising a liposome encapsulating a lipid having a phosphatidylcholine group, a cholesterol compound, a lipid having a phosphatidylethanolamine group, paclitaxel or a glycoside thereof, docetaxel, or bafilomycin, and a polyoxyethylene ester compound, wherein;
the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and paclitaxel is 3 to 8:2 to 7:0.1 to 3:0.5 to 2, respectively, the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and the paclitaxel glycoside is 3 to 8:2 to 7:0.1 to 3:1 to 3, respectively, the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and docetaxel is 3 to 8:2 to 7:0.1 to 3:1 to 3, respectively, and the molar ratio of the lipid having a phosphatidylcholine group, the cholesterol compound, the lipid having a phosphatidylethanolamine group, and bafilomycin is 3 to 8:2 to 7:0.1 to 3:0.1 to 0.2, respectively.

Assignees

• Hamada Hiroki
• Shimizu Yoshio
• Ensuiko Sugar Refining
• Nat Univ Corporation Okayama Univ

Inventors

• Hamada Hiroki
• Seno Masaharu
• Kasai Tomonari
• Shigehiro Tsukasa
• Hara Koji
• Ito Tetsuya
• Fujiwara Ichiro

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• A61K9/1278 Primary

  Post-loading, e.g. by ion or pH gradient · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title