Claims
- 1. A modified brain-derived neurotrophic factor comprising:a first moiety of a brain-derived neurotrophic factor, from which a number average of 1 to 10 hydroxyl group(s) and/or hydrogen atom(s) have been removed from the carboxyl groups and/or amino groups of amino acids of the brain-derived neurotrophic factor, and a second moiety that is a 1-acyl-glycerol derivative selected from the group consisting of 1-acyl-glycero-3-phosphoryl choline, 1-acyl-glycero-3-phosphoryl serine and 1-acyl-glycero-3-phosphoryl ethylamine; wherein said first and second moieties are chemically cross-linked.
- 2. A modified brain-derived neurotrophic factor, wherein said modified brain-derived neurotrophic factor is a compound of formula (1):A(X—B)m (1) wherein A is a residue of a brain-derived neurotrophic factor, B is a residue of a 1-acyl-glycerol derivative having an oxygen atom at the 2-position of the glycerol moiety, which is prepared by removing a hydrogen atom from the hydroxyl group at the 2-position of the glycerol moiety, X is a chemical cross-linker, and m is number average of groups modifying the brain-derived neurotrophic factor and ranges from 1 to about 10.
- 3. The modified brain-derived neurotrophic factor according to claim 2, wherein X of the modified brain-derived neurotrophic factor is a group of the formula (2): wherein R1 is an alkylene group, or a group of the formula (3): wherein R2 and R3 are independently an alkylene group.
- 4. The modified brain-derived neurotrophic factor according to claim 2, wherein the 1-acyl-glycerol derivative is 1-acyl-glycero-3-phosphoryl choline, 1-acyl-glycero-3-phosphoryl serine, or 1-acyl-glycero-3-phosphoryl ethylamine.
- 5. The modified brain-derived neurotrophic factor according to claim 2 or claim 3, wherein B of the modified brain-derived neurotrophic factor is a group of the formula (4): wherein R4 is an acyl group.
- 6. The modified brain-derived neurotrophic factor according to claim 4, wherein the acyl group of formula (4) is an alkanoyl group having 8 to 30 carbon atoms.
- 7. A pharmaceutical composition comprising:a) a modified brain-derived neurotrophic factor of the formula (1): A(X—B)m (1) wherein A is a residue of a brain-derived neurotrophic factor, B is a residue of a 1-acyl-glycerol derivative having an oxygen atom at the 2-position of the glycerol moiety, which is prepared by removing a hydrogen atom from the hydroxyl group at the 2-position of the glycerol moiety, X is a chemical cross-linker, and m is number average of groups modifying the brain-derived neurotrophic factor and ranges from 1 to about 10; and b) a pharmaceutically acceptable carrier.
- 8. The pharmaceutical composition according to claim 7, wherein X of the modified brain-derived neurotrophic factor is a group of the formula (2): wherein R1 is an alkylene group, or a group of the formula (3): wherein R2 and R3 are independently an alkylene group.
- 9. The pharmaceutical composition according to claim 7, wherein the 1-acyl-glycerol derivative is 1-acyl-glycero-3-phosphoryl choline, 1-acyl-glycero-3-phosphoryl serine, or 1-acyl glycero-3-phosphoryl ethylamine.
- 10. The pharmaceutical composition according to claim 7 or claim 8, wherein B of the modified brain-derived neurotrophic factor is a group of the formula (4): wherein R4 is an acyl group.
- 11. The pharmaceutical composition according to claim 10, wherein the acyl group of formula (4) is an alkanoyl group having 8 to 30 carbon atoms.
- 12. A pharmaceutically acceptable salt of the modified brain-derived neurotrophic factor of claim 2.
- 13. The modified brain-derived neurotrophic factor according to claim 2, wherein the 1-acyl-glycerol derivative is lecithin.
Priority Claims (1)
Number |
Date |
Country |
Kind |
2000-053581 |
Feb 2000 |
JP |
|
Parent Case Info
This application is the national phase under 35 U.S.C. § 371 of PCT International Application No. PCT/JP01/01422 which has an International filing date of Feb. 26, 2001, which designated the United States of America.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/JP01/01422 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO01/64742 |
9/7/2001 |
WO |
A |
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
6391312 |
Kishino et al. |
May 2002 |
B1 |
Foreign Referenced Citations (4)
Number |
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Country |
3-163100 |
Jul 1991 |
JP |
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JP |
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JP |
9832458 |
Jul 1998 |
WO |
Non-Patent Literature Citations (2)
Entry |
Taiji M. et al., BDNF: A Novel Hypoglycemic Agent Acting Central Nervous System, Cell vol. 31, pp. 488-491, No. 12 (1999). |
Sakane et al., Reduction of the Plasma Clearance of Brain-Derived Neurotrophic Factor (BDNF) : Carboxyl-Directed Pegylation, Drug Delivery System, vol. 13, pp. 173-178, No. 3 (1998). |