Phospholipid derivatives and process for the production there

1. A phospholipid derivative represented by the following formula (1):

wherein [PG]k represents a residue of polyglycerin having a polymerization degree of k, wherein k is 2 to 50, R 1 CO and R 2 CO independently represent an acyl group having 8 to 22 carbon atoms, symbol “a” independently represents an integer of 0 to 5, symbol “b” independently represents 0 or 1, M represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium, and k1, k2, and k3 represent numbers satisfying the following conditions: 1≦k1≦(k+2)/2, 0≦k2, and k1+k2+k3=k+2.

2. The phospholipid derivative according to claim 1 , wherein k1 satisfies 1≦k1≦2.

3. The phospholipid derivative according to claim 1 , wherein k2 satisfies 0≦k2≦1.

4. The phospholipid derivative according to claim 1 , wherein k1, k2, and k3 satisfy 8≦k1+k2+k3≦52.

5. The phospholipid derivative according to claim 1 , wherein R 1 CO and R 2 CO independently represent an acyl group having 12 to 20 carbon atoms.

6. The phospholipid derivative according to claim 1 , wherein k2 is 0.

7. The phospholipid derivative according to claim 6 , wherein a and b represent 0.

8. The phospholipid derivative according to claim 1 , wherein k2 satisfies 0<k2.

9. A lipid membrane structure comprising the phospholipid derivative according to claim 1 .

10. The lipid membrane structure according to claim 9 , which is a liposome.

11. A surfactant comprising the phospholipid derivative according to claim 1 .

12. A solubilizer comprising the phospholipid derivative according to claim 1 .

13. A dispersing agent comprising the phospholipid derivative according to claim 1 .

14. A method for producing the phospholipid derivative according to claim 1 , which comprises reacting a compound represented by the following formula (2):

R 1 , R 2 , a, and M have the same meanings as defined above, and X represents hydrogen atom or N-hydroxysuccinimide, with a polyglycerin represented by the following formula (3):

wherein [PG]k represents a residue of polyglycerin having a polymerization degree of k, wherein k has the same meaning as defined above, and k4 is a number satisfying the following condition: k4=k+2.

15. A method for producing the phospholipid derivative according to claim 1 , which comprises:

(A) reacting a polyglycerin with a dibasic acid or a halogenated carboxylic acid to obtain a carboxylated polyglycerin; and

(B) reacting the carboxylated polyglycerin obtained in (A) with a phospholipid.

16. A method for producing the phospholipid derivative according to claim 1 , which comprises:

(A) reacting a polyglycerin with a halogenated carboxylic acid ester and hydrolyzing the resulting ester compound to obtain a carboxylated polyglycerin; and

(B) reacting the carboxylated polyglycerin obtained in (A) with a phospholipid.

17. A method for producing the phospholipid derivative according to claim 1 , which comprises reacting a polyglycerin derivative represented by the following formula (4):

wherein [PG]k represents a residue of polyglycerin having a polymerization degree of k, wherein k represent a number of 2 to 50, Y represents hydroxyl group or a leaving group, and k5 and k6 are numbers satisfying the following conditions: 1≦k5≦(k+2)/2, and k5+k6=k+2, with a phospholipid represented by the following formula (5):

wherein R 1 and R 2 have the same meanings as defined above, in an organic solvent in the presence of a basic catalyst.

18. A pharmaceutical composition containing the lipid membrane structure according to claim 9 retaining a medicament.

19. The pharmaceutical composition according to claim 18 , wherein the medicament is an antitumor agent.