Methods of treating intraocular pressure with activators of Tie-2
Disclosed herein are compounds effective for activation of Tie-2 and inhibition of HPTP-beta. The compounds can provide effective therapy for eye conditions associated with angiogenesis, for example, intraocular pressure, ocular hypertension, and glaucoma.
1. A method for reducing intraocular pressure in an eye of a subject in need thereof, the method comprising topically administering to the eye of the subject a therapeutically-effective amount of a Tie-2 activator, wherein:
the administration reduces the intraocular pressure by about 0.1 mmHg to about 9 mmHg compared to absence of administration;
the subject expresses Ang-1 and Ang-2;
the subject is a human; and
the Tie-2 activator is a compound of the formula:
or
a pharmaceutically-acceptable salt or zwitterion thereof.
2. The method of claim 1 , wherein the Tie-2 activator binds a phosphatase.
3. The method of claim 1 , wherein the Tie-2 activator inhibits a phosphatase.
4. The method of claim 1 , wherein the Tie-2 activator binds HPTP-β.
5. The method of claim 1 , wherein the Tie-2 activator inhibits HPTP-β.
6. The method of claim 1 , wherein the therapeutically-effective amount is from about 1 mg to about 100 mg.
7. The method of claim 1 , wherein the therapeutically-effective amount is from about 0.5 mg to about 30 mg.
8. The method of claim 1 , wherein the therapeutically-effective amount is about 1 mg to about 5 mg.
9. The method of claim 1 , wherein the therapeutically-effective amount is about 1 mg.
10. The method of claim 1 , wherein the therapeutically-effective amount is about 2 mg.
11. The method of claim 1 , wherein the Tie-2 activator is formulated as a drop.
12. The method of claim 1 , wherein the intraocular pressure is reduced by at least about 2 mmHg.
13. The method of claim 1 , wherein the subject has glaucoma, wherein the intraocular pressure is associated with glaucoma.
14. The method of claim 1 , wherein the intraocular pressure is ocular hypertension.
15. The method of claim 14 , wherein the subject has glaucoma, wherein the ocular hypertension is associated with glaucoma.
16. The method of claim 1 , wherein the Tie-2 activator is presented in a composition at a concentration of from about 0.1 mg/mL to about 100 mg/mL.
17. The method of claim 1 , wherein the Tie-2 activator is presented in a composition at a concentration of about 25 mg/mL.
18. The method of claim 1 , wherein the Tie-2 activator is presented in a composition at a concentration of about 40 mg/mL.
19. The method of claim 1 , wherein the Tie-2 activator reduces intraocular pressure by stabilizing vasculature associated with a trabecular meshwork in the subject.
20. The method of claim 1 , wherein the Tie-2 activator is formulated with hydroxypropyl-3-cyclodextrin.
21. The method of claim 1 , wherein the Tie-2 activator is formulated with hydroxypropyl-β-cyclodextrin.
22. A method for treating glaucoma in a subject in need thereof, the method comprising topically administering to an eye of the subject a therapeutically-effective amount of a Tie-2 activator, wherein:
the administration reduces intraocular pressure by about 0.1 mmHg to about 9 mmHg compared to absence of administration;
the subject expresses Ang-1 and Ang-2;
the subject is a human; and
the Tie-2 activator is a compound of the formula:
or
a pharmaceutically-acceptable salt, tautomer, or zwitterion thereof.
23. The method of claim 22 , wherein the therapeutically-effective amount is from about 1 mg to about 100 mg.
24. The method of claim 22 , wherein the therapeutically-effective amount is from about 0.5 mg to about 30 mg.
25. The method of claim 22 , wherein the therapeutically-effective amount is about 1 mg to about 5 mg.
26. The method of claim 22 , wherein the therapeutically-effective amount is about 1 mg.
27. The method of claim 22 , wherein the therapeutically-effective amount is about 2 mg.
28. The method of claim 22 , wherein the Tie-2 activator is formulated as a drop.
29. The method of claim 22 , wherein the Tie-2 activator is presented in a composition at a concentration of from about 0.1 mg/mL to about 100 mg/mL.
30. The method of claim 22 , wherein the Tie-2 activator is presented in a composition at a concentration of about 25 mg/mL.
31. The method of claim 22 , wherein the Tie-2 activator is presented in a composition at a concentration of about 40 mg/mL.
32. The method of claim 22 , wherein the Tie-2 activator reduces intraocular pressure by stabilizing vasculature associated with a trabecular meshwork in the subject.