Liposome

Abstract

This invention provides a liposome having a drug included therein, which has active targeting property and ensured stability in blood and can be used effectively in the diagnosis and/or treatment of diseases, particularly renal diseases, that accompany production of proteoglycan, comprising (1) a basic compound which takes positive charge within a physiological pH range, (2) a lipid derivative of a hydrophilic polymer and (3) a lipid which constitutes the liposome, as its membrane constituting components, wherein their constituting ratios are from 1 to 20 mol % of (1) based on (3) and from 0.2 to 5 mol % of (2) based on the total of (1) and (3).

1 . A liposome in which a drug is included, which comprises (1) a basic compound which takes positive charge within a physiological pH range, (2) a lipid derivative of a hydrophilic polymer and (3) a lipid which constitutes the liposome, as its membrane constituting components, wherein their constituting ratios are from 1 to 20 mol % of (1) based on (3) and from 0.2 to 5 mol % of (2) based on the total of (1) and (3).  
     
     
         2 . A liposome in which a drug is included, which comprises (1) a basic compound which takes positive charge within a physiological pH range, (2) a lipid derivative of a hydrophilic polymer and (3) a lipid which constitutes the liposome, as its membrane constituting components, wherein their constituting ratios are from 5 to 15 mol % of (1) based on (3) and from 0.2 to 5 mol % of (2) based on the total of (1) and (3).  
     
     
         3 . The liposome according to  claim 1  or  2 , wherein the basic compound which takes positive charge within a physiological pH range is a basic compound which has an amidino group, a basic compound which has two or more amino groups, a basic compound which has a piperidine ring or a basic compound which has a quaternary amine.  
     
     
         4 . The liposome according to  claim 3 , wherein the basic compound which takes positive charge within a physiological pH range is any one of those represented by the following formulae 1 to 4;  
       
         
           
           
               
               
           
         
         (in the formula 1, A represents an aromatic ring, each of R 1  and R 2  represents an alkyl or alkenyl group having from 10 to 25 carbon atoms, wherein R 1  and R 2  may be the same or different from each other, each of X 1  and X 2  represents —O—, —S—, —COO—, —OCO—, —CONH— or —NHCO—, wherein X 1  and X 2  may be the same or different from each other, m is 0 or 1 and n is 0 or an integer of from 1 to 6),  
         
           
             
             
                 
                 
             
           
         
         (in the formula 2, R 3  represents hydrogen or an alkyl or alkenyl group having from 1 to 8 carbon atoms, R 4  represents hydrogen or an alkyl or alkenyl group having from 1 to 8 carbon atoms, each of R 5  and R 6  represents hydrogen or an alkyl or alkenyl group having from 1 to 25 carbon atoms (excluding a case in which R 5  and R 6  are both hydrogen), wherein R 5  and R 6  may be the same or different from each other, X 3  represents —O— or —S—, p is 0 or 1 and q is 0 or an integer of from 1 to 10),  
         
           
             
             
                 
                 
             
           
         
         (in the formula 3, each of R 7  and R 8  represents an alkyl or alkenyl group having from 1 to 8 carbon atoms, wherein R 7  and R 8  may be the same or different from each other, R 9  represents hydrogen or an alkyl or alkenyl group having from 1 to 8 carbon atoms, each of R 10  and R 11  represents hydrogen or an alkyl or alkenyl group having from 1 to 25 carbon atoms (excluding a case in which R 10  and R 11  are both hydrogen), wherein R 10  and R 11  may be the same or different from each other, X 4  represents —O— or —S—, r is 0 or 1 and s is 0 or an integer of from 1 to 10), and  
         
           
             
             
                 
                 
             
           
         
       
     
     
         5 . The liposome according to any one of  claims 1  to  4 , wherein the lipid derivative of a hydrophilic polymer is a lipid derivative of polyethylene glycol.  
     
     
         6 . The liposome according to  claim 5 , wherein the aforementioned lipid derivative of polyethylene glycol is a compound which contains a polyethylene glycol chain and a diacyl glycerol in one molecule.  
     
     
         7 . The liposome according to any one of  claims 1  to  6 , wherein the lipid derivative of a hydrophilic polymer has a molecular weight of from 1,000 to 7,000.  
     
     
         8 . The liposome according to any one of  claims 1  to  7 , wherein the aforementioned drug to be included in the liposome is a drug for use in diagnosing and/or treating renal diseases.  
     
     
         9 . The liposome according to  claim 8 , wherein the aforementioned drug for use in diagnosing and/or treating renal diseases is an adrenocortical steroid and/or a derivative thereof.  
     
     
         10 . The liposome according to any one of  claims 1  to  9 , wherein the aforementioned drug to be included in the liposome is a drug for use in diagnosing and/or treating diseases which accompany production of proteoglycan in injured portions of tissues and/or organs.  
     
     
         11 . The liposome according to any one of  claims 1  to  10 , wherein the major particle size range of the aforementioned liposome is from 90 to 200 nm.  
     
     
         12 . The liposome according to any one of  claims 1  to  11 , wherein the lipid which constitutes the aforementioned liposome is a phospholipid or a hydrogenated product of a phospholipid.  
     
     
         13 . The liposome according to any one of  claims 1  to  12 , wherein it further contains a stabilizing agent or an antioxidant.  
     
     
         14 . Use of the liposome of  claim 1  or  2  as a drug for treating inflamed kidney.  
     
     
         15 . Use of the liposome of  claim 1  or  2  in the production of a therapeutic drug for inflamed kidney.  
     
     
         16 . A method for treating inflamed kidney, which comprises administering the liposome of  claim 1  or  2  to mammals including human.