Method of producing liposome

• US 4,877,561 A
• Filed: 04/02/1987
• Issued: 10/31/1989
• Est. Priority Date: 04/02/1986
• Status: Expired due to Term

• Current Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Hamaguchi, Naoru, Ogawa, Yasuaki, Iga, Katsumi
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US07/033,498
• Time in Patent Office: 943 Days
• Field of Search: 264/4.3, 264/4.6, 424/450, 436/829
• US Class Current: 264/4.3
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: Y10S 436/829 Liposomes, e.g. encapsulation
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

Liposomes with an increased drug trap can be prepared by adding a readily volatile organic solvent to a drug-containing liquid with liposomes dispersed therein to cause gel formation and then removing said organic solvent by evaporation.

Claims

1. A method of producing liposomes with increased drug trap ratio, which comprises (1) providing a dispersion containing a drug and liposomes prepared from a phospholipid, (2) adding an organic solvent having a boiling point not higher than 100°

C. to the dispersion to cause gel formation, and then (3) removing said organic solvent by evaporation to reconstitute liposomes.

2. The method according to claim 1, wherein the dispersion contains multilamellar vesicles (MLV).

3. The method according to claim 1, wherein the dispersion contains small unilamellar vesicles (SUV).

4. The method according to claim 1, wherein the drug is a hydrophilic drug having an octyl alcohol/water-distribution ratio lower than 10 as the logarithmic value.

5. The method according to claim 1, wherein the drug is selected from the group consisting of antiinflammatory analgesics, lymphokines, anticancer agents, immunopotentiators, phsyiologically active peptides, antibiotics, antiprotozoa agents, enzymes and antiallergics.

6. The method according to claim 5, wherein the lymphokine is interleukin 2.

7. The method according to claim 5, wherein the anticancer agent is cisplatin.

8. The method according to claim 5, wherein the antiinflammatory analgesic is manganese superoxide dismutase or superoxide dismutase-PEG.

9. The method according to claim 1, wherein the organic solvent is ethyl ether.

10. The method according to claim 1, wherein the organic solvent is acetone.

11. The method according to claim 1, wherein the organic solvent is ethyl alcohol.

12. The method according to claim 1, wherein the organic solvent is added in amount of about 1 to 30 parts by volume per 10 parts by volume of the dispersion containing a drug and liposomeses.

13. The method according to claim 12, wherein the amount of the organic solvent is 2 to 10 parts by volume on the same basis described in claim 12.