Method for the treatment of a trabecular meshwork whose cells are subject to inhibition of cell division

• US 5,674,888 A
• Filed: 06/07/1995
• Issued: 10/07/1997
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: University of California
• Inventors: Bloom, Ernest, Polansky, Jon R., Fauss, Donald J.
• Primary Examiner(s): FAY, ZOHREH A
• Application Number:
  US08/486,255
• Time in Patent Office: 853 Days
• Field of Search: 514/418, 514/420, 514/912
• US Class Current: 514/418
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The invention concerns the recognition that certain non-steroidal anti-inflammatory agents can overcome or ameliorate limitations on trabecular meshwork cell division produced by environmental stresses (e.g., oxidative or phagocytic injury, or glucocorticoid exposure), and thus can be used to prevent or treat loss of trabecular cells found in certain forms of glaucoma and in normal aging. The use of such non-steroidal anti-inflammatory agents can ameliorate the severity, or prevent glaucoma.

Claims

1. A method for treatment of a trabecular meshwork whose cells are subject to inhibition of cell division, comprising administering to a human a composition including (a) an ophthalmologically effective amount of a non-steroidal cyclooxygenase inhibitor, and (b) a pharmaceutically acceptable carrier, to enhance the mitotic rate of said trabecular cells.

2. The method according to claim 1, wherein said cyclooxygenase inhibitor is selected from the group consisting of salicylates, indoles, phenylalkanoic acids, phenylacetic acids and pyrazolons.

3. The method according to claim 1, wherein said non-steroidal cyclooxygenase inhibitor is selected from the group consisting of diclofenac, indomethacin and fenoprofen.

4. The method according to claim 1, wherein said composition is administered topically in an aqueous polymeric solution, aqueous suspension, ointment or gel vehicle.

5. The method according to claim 1, wherein said composition comprises between about 0.001 and about 10% by weight of said cyclooxygenase inhibitor.

6. The method according to claim 5, wherein said composition comprises between about 0.001 and about 0.009% by weight of said inhibitor.

7. The method according to claim 1, wherein said composition is administered to provide a concentration of said inhibitor of less than about 1×

10^-5 M in the aqueous humor of the eye.

8. The method according to claim 7, wherein said composition is administered to provide a concentration of said inhibitor of between about 1×

10^-9 M and about 1×

10^-5 M in the aqueous humor of the eye.

9. The method according to claim 1, wherein said composition is administered by a method selected from the group consisting of intraocular injection, oral administration and intravenous injection.

10. The method according to claim 9, wherein said composition is administered orally, and wherein the composition is an aqueous solution, aqueous suspension, elixir, tablet, caplet or capsule.

11. A method for treatment of a trabecular meshwork whose cells are subject to inhibition of cell division, comprising administering to a human a composition including (a) an ophthamologically effective amount of diclofenac, and (b)a pharmaceutically acceptable carrier, to enhance the mitotic rate of said trabecular cells.

12. The method according to claim 11, wherein said pharmaceutically acceptable carrier is a topical formulation of an aqueous polymeric solution, suspension, ointment or gel.

13. The method according to claim 12, wherein said pharmaceutically acceptable carrier includes a lightly cross-linked carboxy-containing polymer.

14. The method according to claim 13, wherein said diclofenac is present in said formulation in an amount from about 0.001% to about 10% by weight of the composition.

15. The method according to claim 14, wherein said diclofenac is present in said formulation in an amount from about 0.001% to about 0.009% by weight of the composition.

16. The method according to claim 15, wherein said composition is administered in an amount sufficient to provide an opthalmically effective amount of said diclofenac not exceeding 1×

10^-5 M in the aqueous humor of the eye.

17. A method for treatment of a trabecular meshwork whose cells are subject to inhibition of cell division from aging, glucocorticoid exposure or exposure to toxic substances, comprising administering to a human a composition including (a) an ophthalmically effective amount of a non-steroidal anti-inflammatory cyclooxygenase inhibitor and (b) a pharmaceutically acceptable inert carrier, to enhance the mitotic rate of said trabecular cells.

18. The method according to claim 17, wherein said non-steroidal anti-inflammatory cyclooxygenase inhibitor is selected from the group consisting of salicylates, indoles, phenylalkanoic acids, phenylacetic acids and pyrazolons.

19. The method according to claim 17, wherein said non-steroidal anti-inflammatory cyclooxygenase inhibitor is selected from the group consisting of diclofenac, indomethacin and fenoprofen.

20. The method according to claim 17, wherein said non-steroidal anti-inflammatory cyclooxygenase inhibitor is diclofenac.

21. The method according to claim 17, wherein said composition is administered topically in an aqueous polymeric solution, aqueous suspension, ointment or gel vehicle.

22. The method according to claim 17, wherein said composition comprises between about 0.001% and about 10% by weight of said eicosanoid inhibitor.

23. The method according to claim 22, wherein said composition comprises between about 0.001% and about 0.009% by weight of said inhibitor.

24. The method according to claim 23, wherein said composition is administered to provide a concentration of said inhibitor of less than about 1×

10^-5 M in the aqueous humor of the eye.

25. The method according to claim 24, wherein said composition is administered to provide a concentration of said inhibitor of between about 1×

10^-9 M and about 1×

10^-5 M in the aqueous humor of the eye.

26. The method according to claim 25, wherein said composition is administered by a method selected from the group consisting of intraocular injection, oral administration and intravenous injection.

27. The method according to claim 26, wherein said composition is administered orally, and wherein the composition is an aqueous solution, aqueous suspension, elixir, tablet, caplet or capsule.

28. The method of claim 17, wherein said inhibition of cell division is caused by aging.

29. The method of claim 17, wherein said inhibition of cell division is caused by glucocorticoid exposure or exposure to a toxic substance.