Methods for the cyto-protection of the trabecular meshwork

• US 5,599,535 A
• Filed: 06/07/1995
• Issued: 02/04/1997
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Bloom, Ernest, Fauss, Donald J., Polansky, Jon R.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/479,185
• Time in Patent Office: 608 Days
• Field of Search: 514/912, 514/913, 514/914, 514/915, 424/78.04, 424/423, 424/443, 424/450, 424/451, 424/464
• US Class Current: 424/78.04
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• 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 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• 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 produce cytoprotective effects on trabecular cells, and thus can be used to prevent injury to the cells and treat the loss of trabecular cells caused by oxidative or other forms of injury to the cells. Such treatment can ameliorate the severity, or prevent, glaucoma.

Claims

1. A method for cyto-protection of the trabecular meshwork 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 prevent the loss of 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 cyto-protection of the trabecular meshwork, comprising administering to a human a composition including (a) an ophthamologically effective amount of diclofenac, and (b) a pharmaceutically acceptable carrier, including a lightly cross-linkedcarboxy-containing polymer, in the form of an aqueous polymeric solution, suspension, ointment or gel for topical administration, to prevent the loss of trabecular cells.

12. The method according to claim 11, wherein said diclofenac is present in said formulation in an amount from about 0.001% to about 10% by weight of the composition.

13. The method according to claim 12, wherein said diclofenac is present in said formulation in an amount from about 0.001% to about 0.009% by weight of the composition.

14. The method according to claim 13, wherein said composition is administered in an amount sufficient to provide an ophthalmically effective amount of said diclofenac not exceeding 1×

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

15. A method for cyto-protection of the trabecular meshwork, comprising administering to a human in need of treatment or prevention of oxidative injury to its trabecular cells, or of damage to said trabecular cells from phagocytic or endocytic processes, a composition including (a) an ophthalmically effective amount of a non-steroidal anti-inflammatory cyclooxygenase inhibitor and (b) a pharmaceutically inert carrier, to prevent the loss of trabecular cells.

16. The method according to claim 15, wherein said nonsteroidal anti-inflammatory cyclooxygenase inhibitor is selected from the group consisting of salicylates, indoles, phenylalkanoic acids, phenylacetic acids and pyrazolons.

17. The method according to claim 15, wherein said non-steroidal anti-inflammatory cyclooxygenase inhibitor is selected from the group consisting of diclofenac, indomethacin and fenoprofen.

18. The method according to claim 15, wherein said non-steroidal anti-inflammatory cyclooxygenase inhibitor is diclofenac.

19. The method according to claim 15, wherein said composition is administered topically in an aqueous polymeric solution, aqueous suspension, ointment or gel vehicle.

20. The method according to claim 15, wherein said composition comprises between about 0.001 and about 10% by weight of said eicosanoid inhibitor.

21. The method according to claim 20, wherein said composition comprises between about0.001% and about 0.009% by weight of said inhibitor.

22. The method according to claim 21, 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.

23. The method according to claim 22, 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.

24. The method according to claim 15, wherein said composition is administered by a method selected from the group consisting of intraocular injection, oral administration and intravenous injection.

25. The method according to claim 24, wherein said composition is administered orally, and wherein the composition is an aqueous solution, aqueous suspension, elixir, tablet, caplet or capsule.

29. The method of claim 15, wherein said human is in need of treatment or prevention of oxidative injury to its trabecular cells.

30. The method of claim 29, wherein said oxidative injury is caused by hydrogen peroxide or lipidhydroperoxide.

31. The method of claim 15, wherein said human is in need of treatment or prevention of damage to its trabecular cells from phagocytic or endocytic processes.

26. A composition for cyto-protection of the trabecular meshwork, comprising (a) an opthalmically effective amount of between about 0.001 and about 0.009% by weight of a non-steroidal cyclooxygenase inhibitor of a type and in an amount to prevent trabecular cell damage or loss, and (b) a pharmaceutically acceptable carrier therefor.

27. The composition according to claim 26, wherein said cyclooxygenase inhibitor is diclofenac, indomethecin or fenoprofen.

28. The composition according to claim 27, wherein said cyclooxygenase inhibitor is diclofenac.