Method for producing liposome encapsulating paclitaxel monoglycoside and/or docetaxel monoglycoside

Patent metadata

Field	Value
Publication number	US-10682330-B2
Application number	US-201314386855-A
Country	US
Kind code	B2
Filing date	Mar 22, 2013
Priority date	Mar 22, 2012
Publication date	Jun 16, 2020
Grant date	Jun 16, 2020

Abstract

In order to reduce the side effects of paclitaxel derivatives having excellent anti-cancer effects, an attempt was made to produce a liposome encapsulating paclitaxel derivatives such as paclitaxel monoglycosides and docetaxel monoglycosides. However, the introduction efficiency of paclitaxel derivatives, etc., into a liposome was poor, and this technique was not developed to a practical level. The present invention provides a method for producing a liposome encapsulating a paclitaxel monoglycoside and/or a docetaxel monoglycoside, and having an antibody specifically recognizing a cancer cell, the method comprising a step of bringing a liposome encapsulating a polyoxyethylene ester derivative, a lower alcohol, and a buffer or water into contact with a solution in which a paclitaxel monoglycoside and/or a docetaxel monoglycoside is dissolved in an alkylene glycol-containing buffer or water.

First claim

The invention claimed is:

1. A method for producing a liposome encapsulating a paclitaxel monoglucoside and/or a docetaxel monoglucoside, and having an antibody specifically recognizing a cancer cell,
the method comprising a step of bringing a liposome encapsulating a polyoxyethylene ester derivative, a lower alcohol, and a buffer or water into contact with a solution in which a paclitaxel monoglucoside and/or a docetaxel monoglucoside is dissolved in an alkylene glycol-containing buffer or water, wherein the liposome contains 3 parts by weight dipalmitoylphosphatidylcholine (DPPC) to 0.5-3 parts by weight cholesterol.

2. The method according to claim 1 , wherein the polyoxyethylene ester derivative is polyoxyethylene castor oil ester.

3. The method according to claim 1 , wherein the contact time is 10 to 40 minutes.

4. The method according to claim 1 , wherein the cancer cell is a breast cancer cell.

5. The method according to claim 1 , wherein the antibody specifically binds to HER2 protein.

6. A liposome formulation comprising liposomes encapsulating a liquid solution of paclitaxel monoglucoside and/or docetaxel monoglucoside, and an antibody specifically recognizing a cancer cell bound thereto, wherein the liquid solution is a mixed solvent consisting of polyoxyethylene castor oil ester, C 1-4 alcohol, and a buffer or water, in which paclitaxel monoglucoside and/or docetaxel monoglucoside is dissolved, and wherein the liposomes contain 3 parts by weight DPPC to 0.5-3 parts by weight cholesterol.

7. The liposome formulation according to claim 6 , wherein the mol of the paclitaxel of monoglucoside of total lipids of the liposome is 1.0 to 15.0×10 −2 .

8. The liposome formulation according to claim 6 , wherein the cancer cell is a breast cancer cell.

9. The liposome formulation according to claim 6 , wherein the antibody specifically binds to HER2 protein.

Assignees

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

Inventors

• Hamada Hiroki
• Fujiwara Ichiro
• Seno Masaharu
• Kasai Tomonari
• Shigehiro Tsukasa
• Murakami Masaharu
• Mikuni Katsuhiko

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K31/337 Primary

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