Cytoskeletal active agents for glaucoma therapy

• US 6,110,912 A
• Filed: 02/11/1998
• Issued: 08/29/2000
• Est. Priority Date: 02/21/1996
• Status: Expired due to Term

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System), Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System), Yeda Research and Development Co. Ltd. (Weizmann Institute of Science)
• Inventors: Kaufman, Paul L., Geiger, Benjamin
• Primary Examiner(s): FAY, ZOHREH A
• Application Number:
  US09/022,228
• Time in Patent Office: 930 Days
• Field of Search: 514/218, 514/912, 514/913
• US Class Current: 514/218
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

Methods for the treatment of glaucoma are described. The compounds described cause a perturbation of cell adhesions in the trabecular meshwork, mainly via disruption of the associated cytoskeletal structures or the modulation of their interactions with the underlying membrane. Perturbation of these adhesions reduces the resistance of the trabecular meshwork to fluid flow and thereby reduces intraocular pressure.

Claims

1. A method of enhancing aqueous humor outflow in the eye of a subject to treat glaucoma, comprising:

a) providing a subject with glaucoma; and

b) administering to said subject an ophthalmic preparation comprising an effective amount of a non-corneotoxic serine-threonine kinase inhibitor, thereby enhancing aqueous humor outflow in the eye and treating the glaucoma.

2. The method of claim 1, wherein said serine-threonine kinase inhibitor is selected from the group consisting of H-7, ML-7, staurosporine, and KT-5926.

3. The method of claim 1, wherein said administration is topical.

4. The method of claim 1, wherein said administration is intracameral.

5. The method of claim 1, wherein said administration is intracanalicular.

6. A method of enhancing aqueous humor outflow in the eye of a subject to treat glaucoma, comprising:

a) providing a subject with glaucoma; and

b) administering to said subject an ophthalmic preparation comprising an effective amount of H-7 or a pharmaceutically acceptable salt thereof, thereby enhancing aqueous humor outflow in the eye and treating the glaucoma.

7. The method of claim 6, wherein said administration is topical.

8. The method of claim 6, wherein said administration is intracameral.

9. The method of claim 6, wherein said administration is intracanalicular.

10. A method of enhancing aqueous humor outflow in the eye of a subject to treat glaucoma, comprising:

a) providing a subject with glaucoma; and

b) administering to said subject an ophthalmic preparation comprising an effective amount of staurosporine or a pharmaceutically acceptable salt thereof, thereby enhancing aqueous humor outflow in the eye and treating the glaucoma.

11. The method of claim 10, wherein said administration is topical.

12. The method of claim 10, wherein said administration is intracameral.

13. The method of claim 10, wherein said administration is intracanalicular.