Lipid nano particles comprising cationic lipid for drug delivery system

Abstract

The present invention provides a lipid nano-particles, which allow nucleic acids to be easily introduced into cells, comprising a cationic lipid represented by formula (I) (wherein: R 1 and R 2 are, the same or different, alkenyl, etc, and X 3 is absent or is alkyl, etc, X 1 and X 2 are hydrogen atoms, or are combined together to form a single bond or alkylene, and Y 1 is absent or anion, L 1 is a single bond, etc, R 3 is alkyl, etc), and the like.

1 - 20 . (canceled) 
     
     
         21 . Lipid nano particles for drug delivery comprising;
 a cationic lipid represented by formula (I):   
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are, the same or different, each linear or branched alkyl, alkenyl or alkynyl having 10 to 24 carbon atoms, 
         X 1  and X 2  are hydrogen atoms, or are combined together to form a single bond or alkylene, 
         X 3  and Y 1  are absent
 L 1  is a single bond, R 3  is a hydrogen atom, alkyl having 1 to 6 carbon atoms, alkenyl having 3 to 6 carbon atoms, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, pyrrolidinyl, piperidyl or morpholinyl. 
 
       
     
     
         22 . The lipid nano particles for drug delivery according to  claim 21 , wherein R 1  and R 2  are dodecyl, tetradecyl, (Z)-dodec-7-enyl, (Z)-tetradec-7-enyl, (Z)-hexadec-4-enyl, (Z)-hexadec-7-enyl, (E)-hexadec-7-enyl, (Z)-hexadec-9-enyl, (7Z,10Z)-hexadec-7,10-dienyl, (7Z,10Z,13Z)-hexadec-7,10,13-trienyl, (Z)-octadec-9-enyl or (9Z,12Z)-octadec-9,12-dienyl. 
     
     
         23 . The lipid nano particles for drug delivery according to  claim 21 , wherein R 1  and R 2  are tetradecyl, hexadecyl, (Z)-tetradec-9-enyl, (Z)-hexadec-9-enyl, (Z)-octadec-6-enyl, (Z)-octadec-9-enyl, (E)-octadec-9-enyl, (Z)-octadec-11-enyl, (9Z,12Z)-octadeca-9,12-dienyl, (9Z,12Z,15Z)-octadeca-9,12,15-trienyl, (Z)-icos-11-enyl or (11Z,14Z)-icosa-11,14-dienyl. 
     
     
         24 . The lipid nano particles for drug delivery according to  claim 21 , wherein R 3  is a hydrogen atom, methyl, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, or alkyl having a carbon number of from 1 to 6 or alkenyl having a carbon number of from 3 to 6, each substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, monoalkylamino, dialkylamino, trialkylammonio, hydroxy, alkoxy, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, pyrrolidinyl, piperidyl or morpholinyl. 
     
     
         25 . The lipid nano particles for drug delivery according to  claim 21 , wherein X 1  and X 2  are combined together to form a single bond or alkylene. 
     
     
         26 . The lipid nano particles for drug delivery according to  claim 21 , wherein X 1  and X 2  are combined together to form a single bond or alkylene, and
 R 3  is a hydrogen atom, methyl or alkyl having a carbon number of from 1 to 6 or alkenyl having a carbon number of from 3 to 6, each substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, hydroxy or carbamoyl.   
     
     
         27 . The lipid nano particles for drug delivery according to  claim 21 , wherein X 1  and X 2  are hydrogen atoms, and
 R 3  is a hydrogen atom, methyl or alkyl having a carbon number of from 1 to 6 or alkenyl having a carbon number of from 3 to 6, each substituted with 1 to 3 substituent(s), which is(are), the same or different, amino, hydroxy or carbamoyl.   
     
     
         28 . The lipid nano particles for drug delivery according to  claim 21 , which comprise a nucleic acid as drug. 
     
     
         29 . The lipid nano particles for drug delivery according to  claim 28 , wherein the cationic lipid forms a complex together with the nucleic acid, or forms a complex between a combination of the cationic lipid with a neutral lipid and/or a polymer and the nucleic acid. 
     
     
         30 . The lipid nano particles for drug delivery according to  claim 28 , wherein the cationic lipid forms a complex together with the nucleic acid, or forms a complex between a combination of the cationic lipid with a neutral lipid and/or a polymer and the nucleic acid, and the composition comprises the complex and a lipid membrane for encapsulating the complex. 
     
     
         31 . The lipid nano particles for drug delivery according to  claim 29 , wherein the nucleic acid is a nucleic acid having an activity of suppressing the expression of the target gene by utilizing RNA interference (RNAi). 
     
     
         32 . The lipid nano particles for drug delivery according to  claim 31 , wherein the target gene is a gene associated with tumor or inflammation. 
     
     
         33 . A method for introducing the nucleic acid into a cell by using the lipid nano particles for drug delivery of  claim 28 . 
     
     
         34 . The method according to  claim 33 , wherein the cell is a cell at a tumor or inflammation site of a mammal. 
     
     
         35 . The method according to  claim 33 , wherein the cell is a cell in the liver, lungs, kidneys or spleen of a mammal. 
     
     
         36 . The method according to  claim 34 , wherein the method of the introduction into a cell is a method of introduction into a cell by intravenous administration. 
     
     
         37 . A method for treating cancer or inflammatory disease, the method including administering the lipid nano particles for drug delivery of  claim 21  to a mammal. 
     
     
         38 . The method according to  claim 37 , wherein the method of administration is intravenous administration.