Claims
- 1. A pharmaceutical compound, comprising: a therapeutic agent, a spacer and a galactose, the spacer being covalently linked to the therapeutic agent at a first site on the spacer and at a second site on the spacer, being covalently linked via an ether linkage with the galactose.
- 2. A pharmaceutical compound according to claim 1, wherein the spacer is polyhydroxylated.
- 3. A pharmaceutical compound according to claim 2, wherein the spacer is a selected from an aldose and a ketose.
- 4. A pharmaceutical compound according to claim 1, further comprising the agent linked to —CH2—(CHOH)n—CH2—O— (Galactose) where n=≧0 and <20.
- 5. A pharmaceutical compound according to claim 1, further comprising the agent linked to
- 6. A pharmaceutical compound according to claim 3, wherein the spacer is an open chain saccharide selected from a triose, a tetrose, a pentose, a hexose and a septose.
- 7. A pharmaceutical compound according to claim 1, wherein the first site is separated from the second site by at least two carbon atoms.
- 8. A pharmaceutical compound according to claim 3, wherein the spacer is an open chain hexose.
- 9. A pharmaceutical compound according to claim 1, wherein a covalent linkage is formed with a reactive group on the therapeutic agent, the reactive group being selected from an amino group, a alkoxy group, a hydroxy group, a carbonyl group, a carboxylic group, a halogen and a thiol group.
- 10. A pharmaceutical compound according to claim 1, wherein the therapeutic agent is Adriamycin.
- 11. A pharmaceutical compound according to claim 10, wherein the spacer is covalently linked to an amine group on the daunosamine.
- 12. A pharmaceutical compound according to claim 8, wherein the galactose is linked to the spacer by means of a glycosidic linkage
- 13. A pharmaceutical compound according to claim 1, further comprising N-[β-D-galactopyranosyl-(1→4)-β-O-D-sorbityl]doxorubicin.
- 14. A pharmaceutical compound according to claim 1, further comprising N-[α-D-galactopyranosyl-(1→6)-β-O-D-sorbityl]doxorubicin.
- 15. A pharmaceutical preparation, comprising: an effective dose of a compound according to claim 1 and a pharmaceutically acceptable excipient.
- 16. A method for synthesizing a pharmaceutical compound, comprising:
(a) providing (i) a therapeutic agent; and (ii) a spacer linked to galactose; (b) protecting reactive groups on the therapeutic agent other than at a reactive site for linking to the spacer; (c) reacting the protected therapeutic agent with the spacer linked to galactose; and (d) deprotecting the therapeutic agent to form the pharmaceutical compound.
- 17. A method according to claim 16, wherein the spacer linked to galactose has a formula:
- 18. A method according to claim 16, wherein the spacer linked to galactose has a formula:
- 19. A method according to claim 16, wherein the spacer is an aldose or ketose.
- 20. A method according to claim 19, wherein the spacer is a hexose.
- 21. A method of treating a chronic disease in a subject, comprising: administering to a subject, an effective dose of a pharmaceutical compound linked via a spacer to a galactose.
- 22. A method of treating a subject suffering from a medical condition, so as to reduce side effects associated with a therapeutic agent selected for treating the condition without substantially reducing efficacy of the agent, comprising:
(a) providing as a conjugate, the therapeutic agent covalently linked to a spacer at a first site and the spacer being covalently linked to galactose at a second site; and (b) administering an effective dose of the conjugate to the subject so that the side effects in the subject are less then they would have been with the unconjugated therapeutic agent.
- 23. A method according to claim 22, wherein the medical condition is selected from a proliferative disease, high cholesterol, depression, asthma, hypertension and bacterial infections.
- 24. A method according to claim 22, wherein the proliferative disease is a tumor.
- 25. A method according to claim 22, wherein the proliferative disease is lymphocytic leukemia.
- 26. A method according to claim 22, wherein the therapeutic agent is Adriamycin.
- 27. A method according to claim 22, wherein the spacer is selected from a ketose and an aldose.
- 28. A method according to claim 22, wherein the galactose is linked via an ether linkage to the galactose.
- 29. A method according to claim 22, wherein the spacer is selected from
(agent) —CH2—(CHOH)n—CH2-O— (Galactose) where n=≧0 and <20, or 10where n=≧0 and <20 and m=≧0 and <20.
- 30. A method according to claim 22, wherein the conjugate is selected from N-[β-D-galactopyranosyl-(1→4)-β-O-D-sorbityl]doxorubicin and N-[α-D-galactopyranosyl-(1→6)-β-O-D-sorbityl]doxorubicin.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application gains priority from parent U.S. patent application Ser. No. 09/961,681, filed Sep. 24, 2001, which in turn claims priority from provisional patent application serial No. 60/235,141 filed Sep. 25, 2000, both of which are hereby incorporated herein by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60235141 |
Sep 2000 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09961681 |
Sep 2001 |
US |
Child |
10354750 |
Jun 2003 |
US |