US 12,220,482 B2
Liposome composition and method for producing the same
Takahiro Sekiguchi, Ashigarakami-gun (JP); Mikinaga Mori, Ashigarakami-gun (JP); Kentaro Numajiri, Ashigarakami-gun (JP); and Hiroyuki Kitaoka, Ashigarakami-gun (JP)
Assigned to FUJIFILM Corporation, Tokyo (JP)
Filed by FUJIFILM Corporation, Tokyo (JP)
Filed on Jan. 4, 2021, as Appl. No. 17/140,502.
Application 17/140,502 is a continuation of application No. 15/968,110, filed on May 1, 2018, abandoned.
Application 15/968,110 is a continuation of application No. PCT/JP2016/082417, filed on Nov. 1, 2016.
Claims priority of application No. 2015-215767 (JP), filed on Nov. 2, 2015.
Prior Publication US 2021/0128471 A1, May 6, 2021
Int. Cl. A61K 9/127 (2006.01); A61K 31/7068 (2006.01)
CPC A61K 9/127 (2013.01) [A61K 9/1271 (2013.01); A61K 9/1278 (2013.01); A61K 31/7068 (2013.01)] 6 Claims
OG exemplary drawing
 
1. A method of producing a liposome composition, the method comprising the following steps:
(a) preparing empty liposomes by an O/W type emulsification of an oil phase, wherein said oil phase comprises hydrogenated soybean phosphatidylcholine, cholesterol, and 1,2-distearoyl-3-phosphatidylethanolamine-polyethlene glycol dissolved in an organic solvent, and an aqueous phase having pH 5-9, and removing the organic solvent after forming the empty liposomes;
(b) preparing a drug solution by dissolving gemcitabine or a salt thereof at pH 1-5;
(c) mixing the empty liposomes and the drug solution;
(d) adjusting pH with a pH adjuster; and
(e) heating to 55° C. or higher at pH 5.0 to 13,
wherein the liposome composition comprises liposomes which encapsulate gemcitabine or a salt thereof, wherein a lipid forming the liposomes comprises hydrogenated soybean phosphatidylcholine, cholesterol, 1,2-distearoyl-3-phosphatidylethanolamine-polyethlene glycol and a lysophospholipid produced by hydrolysis of hydrogenated soybean phosphatidylcholine,
a content ratio of gemcitabine or a salt thereof to the lipid is 2 mass % to 10 mass %, and
a content ratio of the lysophospholipid contained in the lipid forming the liposomes with respect to a total amount of hydrogenated soybean phosphatidylcholine contained in the liposomes is 0.01 mol % to 3 mol %.