Method for producing liposome and apparatus for producing liposome

Patent metadata

Field	Value
Publication number	US-11325091-B2
Application number	US-201715625020-A
Country	US
Kind code	B2
Filing date	Jun 16, 2017
Priority date	Dec 19, 2014
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

Disclosed herein are a method for producing a liposome which is capable of reducing the facility costs and also capable of rapid desolvation, and an apparatus for producing a liposome which is for use in the above-mentioned method. Provided is a method for producing a liposome, including a stirring step of stirring a mixed liquid containing an oil phase in which at least one lipid is dissolved in an organic solvent and a water phase, and an evaporating step of evaporating an organic solvent from the mixed liquid, in which the condensed organic solvent is removed by passing a gas having a temperature not higher than the dew point of the solvent in the evaporating step.

First claim

What is claimed is:

1. A method for producing a liposome, comprising:
stirring a mixed liquid containing an oil phase in which at least one lipid is dissolved in an organic solvent and a water phase;
evaporating the organic solvent from the mixed liquid in a container;
introducing a gas having a temperature not higher than the dew point of the solvent into the container;
condensing evaporated organic solvent with introduced gas in a gas space in the container; and
discharging the gas from the container together with condensed organic solvent.

2. The method for producing a liposome according to claim 1 , wherein the capacity of the container is within a range of 10 L or more and 100 L or less.

3. The method for producing a liposome according to claim 1 , wherein the evaporating step is carried out in the container, and the ratio A/B of length A of the widest portion of the liquid horizontal plane of the mixed liquid in the container at the start of the evaporating step to length B of the deepest portion of the liquid depth is 2 or more.

4. The method for producing a liposome according to claim 1 , wherein the evaporating step is carried out in the container, and the ratio C/D of length C of the widest portion of the horizontal plane of the gas space in the container at the start of the evaporating step to length D of the longest portion of the height of the gas space is 3 or more, where the gas space refers to a space occupied by the gas flowing in a horizontal direction on the liquid surface.

5. The method for producing a liposome according to claim 3 , wherein the evaporating step is carried out in the container, and the ratio C/D of length C of the widest portion of the horizontal plane of the gas space in the container at the start of the evaporating step to length D of the longest portion of the height of the gas space is 3 or more, where the gas space refers to a space occupied by the gas flowing in a horizontal direction on the liquid surface.

6. The method for producing a liposome according to claim 3 , wherein the capacity of the container is within a range of 10 L or more and 100 L or less.

7. The method for producing a liposome according to claim 4 , wherein the capacity of the container is within a range of 10 L or more and 100 L or less.

8. The method for producing a liposome according to claim 5 , wherein the capacity of the container is within a range of 10 L or more and 100 L or less.

9. The method for producing a liposome according to claim 1 , wherein the evaporating step is carried out by stirring using a centrifugal stirrer.

10. The method for producing a liposome according to claim 9 , wherein the centrifugal stirrer has 2 to 10 discharge ports, the discharge rate coefficient indicated by total opening area of the discharge ports×circumferential length of a rotor of the centrifugal stirrer is 60 cm 3 to 6,000 cm 3 , and the rotation speed of the centrifugal stirrer is 100 to 1,500 rpm.

11. The method for producing a liposome according to claim 3 , wherein the evaporating step is carried out by stirring using a centrifugal stirrer.

12. The method for producing a liposome according to claim 4 , wherein the evaporating step is carried out by stirring using a centrifugal stirrer.

13. The method for producing a liposome according to claim 5 , wherein the evaporating step is carried out by stirring using a centrifugal stirrer.

14. The method for producing a liposome according to claim 1 , wherein in the evaporating step, the gas is introduced or sucked into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

15. The method for producing a liposome according to claim 3 , wherein in the evaporating step, the gas is introduced or sucked into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

16. The method for producing a liposome according to claim 4 , wherein in the evaporating step, the gas is introduced or sucked into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

17. The method for producing a liposome according to claim 5 , wherein in the evaporating step, the gas is introduced or sucked into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

18. The method for producing a liposome according to claim 1 , wherein the gas is saturated with organic solvent gas after being introduced into the container.

19. The method for producing a liposome according to claim 1 , wherein in the evaporating step, the gas is introduced into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

20. The method for producing a liposome according to claim 3 , wherein in the evaporating step, the gas is introduced into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

21. The method for producing a liposome according to claim 4 , wherein in the evaporating step, the gas is introduced into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

22. The method for producing a liposome according to claim 5 , wherein in the evaporating step, the gas is introduced into the container from a central portion of an upper portion of the container, and the gas and the condensed organic solvent are discharged from a peripheral portion of the upper portion of the container.

Assignees

• Fujifilm Corp

Inventors

• Sugiyama Susumu
• Yamada Naoki
• Sugiyama Shigehisa
• Okubo Yohei
• Sasaki Takashi
• Ishiguro Tetsu

Classifications

• A61K9/127 Primary

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

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• B01J13/04 Primary

  by physical processes, e.g. drying, spraying · CPC title

• A61K9/1277

  Preparation processes; Proliposomes · CPC title

• B01D5/006

  with evaporation or distillation · CPC title