Liposome composition and method for producing the same

Abstract

An object of the present invention is to provide a liposome composition containing a liposome having an excellent leakage rate of a nucleic acid analog anticancer agent, and a method for producing the same. According to the present invention, there are provided a liposome composition containing a liposome which (1) contains a nucleic acid analog anticancer agent and in which (2) a content ratio of a lysophospholipid contained in a lipid forming the liposome with respect to a total amount of phospholipids other than the lysophospholipid contained in the lipid forming the liposome is 0.01 mol % to 5 mol % and (3) a nucleic acid analog anticancer agent/lipid ratio is 2 mass % to 10 mass %, and a method for producing the same.

What is claimed is: 
     
         1 . A liposome composition comprising:
 a liposome which (1) contains a nucleic acid analog anticancer agent and in which (2) a content ratio of a lysophospholipid contained in a lipid forming the liposome with respect to a total amount of phospholipids other than the lysophospholipid contained in the lipid forming the liposome is 0.01 mol % to 5 mol % and (3) a nucleic acid analog anticancer agent/lipid ratio is 2 mass % to 10 mass %.   
     
     
         2 . The liposome composition according to  claim 1 ,
 wherein the nucleic acid analog anticancer agent is gemcitabine or a salt thereof.   
     
     
         3 . The liposome composition according to  claim 1 ,
 wherein an average particle diameter of the liposome is 10 nm to 150 nm.   
     
     
         4 . The liposome composition according to  claim 1 ,
 wherein the liposome having a particle diameter of greater than or equal to 200 nm is less than or equal to 1 mass %.   
     
     
         5 . The liposome composition according to  claim 1 ,
 wherein an osmotic pressure of an inner aqueous phase of the liposome is 2 to 8 times an osmotic pressure of an outer aqueous phase of the liposome.   
     
     
         6 . A method for producing a liposome composition containing a liposome which (1) contains a nucleic acid analog anticancer agent and in which (2) a content ratio of a lysophospholipid contained in a lipid forming the liposome with respect to a total amount of phospholipids other than the lysophospholipid contained in the lipid forming the liposome is 0.01 mol % to 5 mol % and (3) a nucleic acid analog anticancer agent/lipid ratio is 2 mass % to 10 mass %, the method comprising:
 a step (a) of mixing a nucleic acid analog anticancer agent solution with a solution in which an empty liposome is dispersed; and   a step (b) of heating the mixture to a temperature higher than or equal to 55° C.   
     
     
         7 . A method for producing a liposome composition containing a liposome which (1) contains a nucleic acid analog anticancer agent and in which (2) a content ratio of a lysophospholipid contained in a lipid forming the liposome with respect to a total amount of phospholipids other than the lysophospholipid contained in the lipid forming the liposome is 0.01 mol % to 5 mol % and (3) a nucleic acid analog anticancer agent/lipid ratio is 2 mass % to 10 mass %, the method comprising:
 a step (a) of mixing a nucleic acid analog anticancer agent solution with a solution in which an empty liposome is dispersed;   a step (b) of heating the mixture to a temperature higher than or equal to 55° C.; and   a step (c) of dissolving the nucleic acid analog anticancer agent solution at a pH of 1 to 5 before the step (a),   wherein the step (b) is a step of heating the mixture to a temperature higher than or equal to 55° C. at a pH 5.0 to 13.   
     
     
         8 . The method for producing a liposome composition according to  claim 6 , further comprising:
 a step (d) of lowering the temperature to 40° C. for longer than or equal to 5 minutes after the step (b) of heating the mixture to a temperature higher than or equal to 55° C.   
     
     
         9 . The method for producing a liposome composition according to  claim 7 , further comprising:
 a step (d) of lowering the temperature to 40° C. for longer than or equal to 5 minutes after the step (b) of heating the mixture to a temperature higher than or equal to 55° C.   
     
     
         10 . The method for producing a liposome composition according to  claim 6 , further comprising:
 a step (e) of adjusting an osmotic pressure of an inner aqueous phase of the liposome to be 2 to 8 times an osmotic pressure of an outer aqueous phase of the liposome.   
     
     
         11 . The method for producing a liposome composition according to  claim 7 , further comprising:
 a step (e) of adjusting an osmotic pressure of an inner aqueous phase of the liposome to be 2 to 8 times an osmotic pressure of an outer aqueous phase of the liposome.   
     
     
         12 . The method for producing a liposome composition according to  claim 6 ,
 wherein an empty liposome is prepared without being subjected to extrusion treatment.   
     
     
         13 . The method for producing a liposome composition according to  claim 7 ,
 wherein an empty liposome is prepared without being subjected to extrusion treatment.