Claims
- 1. A quaternary salt of the formula
- 2. A salt according to claim 1, wherein the peptide is octreotide.
- 3. A salt according to claim 1, wherein the peptide is lanreotide.
- 4. A salt according to claim 1, wherein R1 is methyl.
- 5. A salt according to claim 1, wherein the depicted ring system is a pyridinium ion.
- 6. The salt according to claim 1, wherein
- 7. A salt according to claim 1, wherein R5 is t-butyl.
- 8. A salt according to claim 1, wherein “spacer” is an L-amino acid selected from the group consisting of alanine, proline, glycine and phenylalanine, or a dipeptide consisting of L-amino acid units selected from said group.
- 9. A salt according to claim 1, wherein:
(a) octreotide's C-terminal —CH2OH group has been replaced with a —CH2OCOR4 group, and the free amino group —NH2 of the Lys unit of octreotide has been replaced with a —NHCOOR5 group; (b) octreotide has its C-terminal —CH2OH group unchanged, wherein the free amino group —NH2 the Lys unit of octreotide has been replaced with a —NHCOOR4 group; (c) lanreotide's C-terminal —CONH2 group has been replaced with a -CO-Gly-OR4 group, and the free amino group —NH2 of the Lys unit of lanreotide has been replaced with a —NHCOOR5 group; or (d) lanreotide has its C-terminal —CONH2 group unchanged, the free amino group —NH2 of the Lys unit of lanreotide has been replaced with a —NHCOOR4 group.
- 10. A salt according to claim 1, wherein R4 is -CpH2p-steryl wherein p is 0.
- 11. A salt according to claim 10, wherein R4 is a radical of the formula
- 12. A salt according to claim 10, wherein R4 is a radical of the formula
- 13. A salt according to claim 11, wherein R6 is methyl.
- 14. A salt according to claim 1, wherein R4 is -CpH2p-adamantyl.
- 15. A salt according to claim 14, wherein R4 is
- 16. A quaternary salt of the formula
- 17. A salt according to claim 16, wherein R1 is methyl.
- 18. A salt according to claim 16, wherein the depicted ring system is a pyridinium ion.
- 19. A salt according to claim 16, wherein
- 20. A salt according to claim 16, wherein R5 is t-butyl.
- 21. A salt according to claim 16, wherein:
(a) octreotide's C-terminal —CH2OH group has been replaced with a —CH2OCOR4 group, wherein the free amino group —NH2 of the Lys unit of octreotide has been replaced with a —NHCOOR5 group; (b) octreotide has its C-terminal —CH2OH group unchanged, and the free amino group —NH2 of the Lys unit of octreotide has been replaced with a —NHCOOR4 group; (c) lanreotide's C-terminal —CONH2 group has been replaced with a -CO-Gly-OR4 group, and the free amino group —NH2 of the Lys unit of lanreotide has been replaced with a —NHCOOR5 group; or (d) lanreotide has its C-terminal —CONH2 group unchanged, and the free amino group —NH2 of the Lys unit of lanreotide has been replaced with a —NHCOOR4 group.
- 22. A salt according to claim 16, wherein R4 is -CpH2p-steryl wherein p is 0.
- 23. A salt according to claim 22, wherein R4 is a radical of the formula
- 24. A salt according to claim 22, wherein R4 is a radical of the formula
- 25. A salt according to claim 24, wherein R6 is methyl.
- 26. A salt according to claim 16, wherein R4 is -CpH2p-adamantyl.
- 27. A salt according to claim 26, wherein R4 is
- 28. A salt according to claim 16, wherein R4 is -CpH2p-steryl or -CpH2p-adamantyl.
- 29. A salt according to claim 21, wherein R4 is -CpH2p-steryl or -CpH2p-adamantyl.
- 30. The salt according to claim 21, wherein the cation has the formula
- 31. The salt according to claim 21, wherein the cation has the formula
- 32. The salt according to claim 21, wherein the cation has the formula
- 33. The salt according to claim 21, having the formula
- 34. A process for the preparation of a compound of the formula
- 35. A method for delivering to the retina of a patient in need of the prevention or treatment of diabetic retinopathy an amount effective to prevent or treat diabetic retinopathy of a peptide having 2 to 20 amino acid units having growth factor inhibiting activity, said method comprising administering to said patient, in an amount sufficient to deliver said effective amount of said peptide to said retina, a compound having the formula:
- 36. The method of claim 35, wherein the spacer is an L-amino acid selected from the group consisting of alanine or proline, or a dipeptide consisting of L-amino acid units selected from said group.
- 37. The method of claim 35, wherein the compound is administered in an amount sufficient to produce lessening of one or more of the effects of diabetic retinopathy.
- 38. The method of claim 35, wherein the compound is administered in an amount sufficient to produce regression of neovascularization.
- 39. The method of claim 35, wherein the compound is administered in an amount sufficient to produce improved visual acuity.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional of U.S. application Ser. No. 09/144,991, filed Sep. 1, 1998, now allowed, incorporated by reference herein in its entirety and relied upon, which claims the priority of U.S. Provisional Patent Application No. 60/058,423, filed Sep. 10, 1997.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60058423 |
Sep 1997 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09144991 |
Sep 1998 |
US |
Child |
10175833 |
Jun 2002 |
US |