Liposome composition and pharmaceutical composition

Abstract

An object of the present invention is to provide a liposome composition and a pharmaceutical composition, which exhibit a high AUC. Provided are a liposome composition including a hydrophilic polymer-modified diacylphosphatidylethanolamine, a dihydrosphingomyelin, and cholesterols as components of a liposome membrane, in which the liposome composition encapsulates a drug, an inner water phase thereof contains ammonium sulfate, and a molar ratio of sulfate ions in the inner water phase to the drug in an entire water phase is 0.36 or more; and a pharmaceutical composition including the liposome composition.

What is claimed is: 
     
         1 . A liposome composition comprising: liposomes each of which has an inner water phase and an aqueous solution which constitutes an outer water phase and in which the liposomes are dispersed,
 wherein the liposomes comprise   a hydrophilic polymer-modified diacylphosphatidylethanolamine;   a dihydrosphingomyelin, and cholesterols;   wherein each of the liposomes encapsulates a drug;   the inner water phase thereof contains ammonium sulfate,   and the dihydrosphingomyelin is a dihydrosphingomyelin containing a long-chain alkyl group having 16 carbon atoms and a long-chain alkyl group having 18 carbon atoms.   
     
     
         2 . The liposome composition according to  claim 1 ,
 wherein the drug is an anticancer drug.   
     
     
         3 . The liposome composition according to  claim 1 ,
 wherein the drug is an anthracycline-based anticancer agent, a cisplatin-based anticancer agent, a taxane-based anticancer agent, a  vinca  alkaloid-based anticancer agent, a bleomycin based anticancer agent, a sirolimus-based anticancer agent, a camptothecin-based anticancer agent, a metabolic antagonists, or a molecularly targeted drug.   
     
     
         4 . The liposome composition according to  claim 1 ,
 wherein the drug is topotecan or a salt thereof, doxorubicin or a salt thereof, irinotecan or a salt thereof, or sunitinib or a salt thereof.   
     
     
         5 . The liposome composition according to  claim 1 ,
 wherein the hydrophilic polymer-modified diacylphosphatidylethanolamine is a polyethylene glycol- or methoxy polyethylene glycol-modified diacylphosphatidylethanolamine.   
     
     
         6 . The liposome composition according to  claim 1 ,
 wherein the percentage of the hydrophilic polymer-modified diacylphosphatidylethanolamine in the liposome is 2 to 10 mol %.   
     
     
         7 . The liposome composition according to  claim 1 ,
 wherein the percentage of cholesterols in the liposome is 35 to 43 mol %.   
     
     
         8 . The liposome composition according to  claim 1 , wherein the liposomes have a particle size of 30 nm to 150 nm. 
     
     
         9 . The liposome composition according to  claim 1 ,
 wherein the outer water phase has a pH of 5.5 to 8.5.   
     
     
         10 . The liposome composition according to  claim 1 ,
 wherein the percentage of the dihydrosphingomyelin in the liposome is 40 to 70 mol %.   
     
     
         11 . A pharmaceutical composition comprising the liposome composition according to  claim 1 . 
     
     
         12 . A method for treating an anticancer disease, comprising to the pharmaceutical composition according to  claim 11 .