# US 12,005,143 B2 · Method for producing liposome and apparatus for producing liposome > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,143 B2 - Document ID: US12005143B2 - Status: Granted - Kind: B2 - Application number: 15/868,160 - Filed: 2018-01-11 - Published: 2018-05-17 - Granted: 2024-06-11 - Earliest claimed: 2014-12-19 - Assignees: FUJIFILM Corporation - Applicants: FUJIFILM Corporation - Inventors: Susumu Sugiyama; Naoki Yamada; Shigehisa Sugiyama; Yohei Okubo - Web page: https://patentgrep.com/patent/US12005143B2 ## CPC - A61K 9/1277: Preparation processes; Proliposomes - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - B01F 23/40: Mixing liquids with liquids; Emulsifying - B01F 23/41: Emulsifying - B01F 25/21: with submerged injectors, e.g. nozzles, for injecting high-pressure jets into a large volume or into mixing chambers - B01F 25/50: Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle - B01J 13/04: by physical processes, e.g. drying, spraying - B01J 13/08: Simple coacervation, i.e. addition of highly hydrophilic material {(combined with spraying B01J13/043; combined with mechanical division B01J13/04)} - B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery - B82Y 40/00: Manufacture or treatment of nanostructures - B01F 2101/22: Mixing of ingredients for pharmaceutical or medical compositions - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - B01F: MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING (mixing paints B44D3/06) - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES ## Abstract Disclosed herein are a method for producing a miniaturized liposome on a large production scale, and an apparatus for producing a liposome which is to be used in the above-mentioned method. Provided is a method for producing a liposome, including a step of stirring a mixture containing an oil phase in which at least one lipid is dissolved in an organic solvent and a water phase in a first tank of an apparatus having the first tank and a circulation path, in which the ratio of the capacity of the circulation path to the total capacity of the tank and the circulation path is 0.4 or less and/or the time required for the mixture to return to the first tank after being discharged therefrom is within 2.0 minutes. ## Claims ### Claim 1 An apparatus for producing a liposome, comprising: a first tank comprising an emulsifying apparatus; a circulation path; a second tank in the middle of the circulation path; and a pump in the middle of the circulation path, wherein the pump is configured to satisfy the formula “2X≥Y,” wherein X refers to the liquid feeding capacity (L/min) of the pump and Y refers to the capacity of circulation path (L), wherein the first tank and the emulsifying apparatus are configured to stir and emulsify a liquid, wherein the second tank is configured to separate and remove bubbles which are formed in the first tank, wherein the ratio of the capacity of the circulation path to the total capacity of the first tank comprising the emulsifying apparatus and the circulation path is 0.4 or less, and said capacity of the circulation path refers to the capacity of the entire circulation path including the second tank, wherein the pump is placed after the second tank and before the first tank. ### Claim 2 (depends on 1) The apparatus for producing a liposome according to claim 1, wherein the pump is a diaphragm pump or a rotary pump. ### Claim 3 (depends on 1) The apparatus for producing a liposome according to claim 1, wherein an intermittent jet flow generating type emulsifying apparatus is installed in the first tank. ### Claim 4 (depends on 1) The apparatus for producing a liposome according to claim 1, wherein the ratio of the capacity of the circulation path to the total capacity of the first tank and the circulation path is 0.2 or less. ### Claim 5 (depends on 1) The apparatus for producing a liposome according to claim 1, further comprising a mechanism for loading pressure in the first tank. ### Claim 6 (depends on 2) The apparatus for producing a liposome according to claim 2, further comprising a mechanism for loading pressure in the first tank. ### Claim 7 (depends on 3) The apparatus for producing a liposome according to claim 3, further comprising a mechanism for loading pressure in the first tank. ### Claim 8 (depends on 4) The apparatus for producing a liposome according to claim 4, further comprising a mechanism for loading pressure in the first tank. ### Claim 9 (depends on 1) The apparatus for producing a liposome according to claim 1, wherein the ratio of the capacity of the circulation path to the total capacity of the first tank comprising the emulsifying apparatus and the circulation path is 0.3 or less. ### Claim 10 (depends on 1) The apparatus for producing a liposome according to claim 1, wherein the pump is configured to satisfy the formula “X≥Y,” wherein X refers to the liquid feeding capacity (L/min) of the pump and Y refers to the capacity of circulation path (L). ### Claim 11 An apparatus for producing a liposome, comprising: a first tank comprising an emulsifying apparatus; a circulation path; a second tank in the middle of the circulation path; and a pump in the middle of the circulation path, wherein the first tank and the emulsifying apparatus are configured to stir and emulsify a liquid, wherein the second tank is configured to separate and remove bubbles which are formed in the first tank by communication of the circulation path with an outlet at the bottom of the second tank, wherein the ratio of the capacity of the circulation path to the total capacity of the first tank comprising the emulsifying apparatus and the circulation path is 0.4 or less, and said capacity of the circulation path refers to the capacity of the entire circulation path including the second tank, wherein the pump is placed after the second tank and before the first tank.