# US 10,117,833 B2 · Method for producing liposome

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- Number: US 10,117,833 B2
- Document ID: US10117833B2
- Status: Granted
- Kind: B2
- Application number: 15/336,131
- Filed: 2016-10-27
- Published: 2017-02-16
- Granted: 2018-11-06
- Earliest claimed: 2014-04-30
- Assignees: FUJIFILM Corporation
- Applicants: FUJIFILM Corporation
- Inventors: Makoto Ono; Kohei Ono; Yuuko Igarasi
- Web page: https://patentgrep.com/patent/US10117833B2

## CPC

- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 8/14: Liposomes; Vesicles
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 9/1277: Preparation processes; Proliposomes
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61Q 19/00: Preparations for care of the skin
- B01J 13/125: {by evaporation of the solvent (apparatus therefor B01J13/043)}
- A61K 2800/10: General cosmetic use
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/906: Drug delivery
- Y10S 977/907: Liposome
- 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)
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Provided is a method for producing a liposome having safety and stability. According to the present invention, it is possible to provide a method for producing a liposome, including a step of mixing an oil phase with at least one lipid dissolved in an organic solvent and a water phase and stirring an aqueous solution containing the lipids, and a step of evaporating the organic solvent from the aqueous solution containing the liposomes obtained in the stirring step, in which the organic solvent is a mixed solvent of a water-soluble organic solvent and an ester-based organic solvent.

## Claims

### Claim 1

A method for producing liposomes, comprising:
a step of mixing an oil phase with at least one lipid dissolved in an organic solvent and a water phase and stirring an aqueous solution containing the lipids to thereby prepare an O/W emulsion in which oil phase and water phase are emulsified;
a step of evaporating the organic solvent from the aqueous solution containing the lipids obtained in the stirring step to form liposomes; and
a step of sterile filtration,
wherein the organic solvent comprises a mixture of a water-soluble organic solvent and an ester based organic solvent, wherein the water-soluble organic solvent comprises ethanol and wherein the ester-based organic solvent comprises ethyl acetate, and wherein the content of ethyl acetate is 20% to 30% by mass,
the particle size of the liposomes is 2 to 100 nm,
sizing processing is not carried out since the liposomes are miniaturized only by stirring step,
the concentration of the organic solvent contained in the aqueous solution containing the lipids is 15 mass % or less within 30 minutes from after the start of the step of evaporating the organic solvent,
the step of stirring imparts shearing at a circumferential speed of 20 m/sec or more to the aqueous solution containing lipids, and
the concentration of the lipid is 40 g/L to 200 g/L in terms of a solution where a mixed solution of a water-soluble organic solvent and an ester-based organic solvent serves as a solvent.

### Claim 2 (depends on 1)

The method for producing liposomes according to claim 1, wherein the ester-based organic solvent further includes at least one selected from methyl acetate, isopropyl acetate, t-butyl acetate, and methyl propionate.

### Claim 3 (depends on 1)

The method for producing liposomes according to claim 1, wherein the ester-based organic solvent consists of ethyl acetate.

### Claim 4 (depends on 1)

The method for producing liposomes according to claim 1, wherein the water-soluble organic solvent further includes one or more alcohols other than ethanol.

### Claim 5 (depends on 2)

The method for producing liposomes according to claim 2, wherein the water-soluble organic solvent further includes one or more alcohols other than ethanol.

### Claim 6 (depends on 3)

The method for producing liposomes according to claim 3, wherein the water-soluble organic solvent further includes one or more alcohols other than ethanol.

### Claim 7 (depends on 4)

The method for producing liposomes according to claim 4, wherein the alcohol other than ethanol is at least one selected from methanol, 2-propanol, and t-butanol.

### Claim 8 (depends on 5)

The method for producing liposomes according to claim 5, wherein the alcohol other than ethanol is at least one selected from methanol, 2-propanol, and t-butanol.

### Claim 9 (depends on 6)

The method for producing liposomes according to claim 6, wherein the alcohol other than ethanol is at least one selected from methanol, 2-propanol, and t-butanol.

### Claim 10 (depends on 1)

The method for producing liposomes according to claim 1, wherein the mass ratio of water-soluble organic solvent:ester-based organic solvent is 80:20 to 30:70.

### Claim 11 (depends on 2)

The method for producing liposomes according to claim 2, wherein the mass ratio of water-soluble organic solvent:ester-based organic solvent is 80:20 to 30:70.

### Claim 12 (depends on 4)

The method for producing liposomes according to claim 4, wherein the mass ratio of water-soluble organic solvent:ester-based organic solvent is 80:20 to 30:70.

### Claim 13 (depends on 1)

The method for producing liposomes according to claim 1, wherein the step of evaporating the organic solvent evaporates the organic solvent by heating.

### Claim 14 (depends on 2)

The method for producing liposomes according to claim 2, wherein the step of evaporating the organic solvent evaporates the organic solvent by heating.

### Claim 15 (depends on 4)

The method for producing liposomes according to claim 4, wherein the step of evaporating the organic solvent evaporates the organic solvent by heating.

### Claim 16 (depends on 10)

The method for producing liposomes according to claim 10, wherein the step of evaporating the organic solvent evaporates the organic solvent by heating.

### Claim 17 (depends on 1)

The method for producing liposomes according to claim 1, wherein the water-soluble organic solvent consists of ethanol.

### Claim 18 (depends on 1)

The method for producing liposomes according to claim 1, wherein the average particle size of the liposomes is 5 to 100 nm.