Claims for Patent: 5,811,446

Summary for Patent: 5,811,446

Title:	Prophylactic and therapeutic methods for ocular degenerative diseases and inflammations and histidine compositions therefor
Abstract:	The present invention relates to methods for protecting the eye from degenerative eye conditions by administering prophylactic histidine compositions. The invention also relates to methods for treating ocular inflammation resulting from various causative agents, by administering therapeutic histidine compositions. The invention relates further still to novel histidine compositions for carrying out the present methods.
Inventor(s):	Thomas; Peter G. (Charlottesville, VA)
Assignee:	Cytos Pharmaceuticals LLC (Durham, NC)
Application Number:	08/839,805
Patent Claims:	1. A method for protecting a mammal from a degenerative eye condition comprising administering to a mammal suseptible to a degenerative eye condition a prophylactically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof. 2. The method according to claim 1 wherein said degenerative eye condition comprises glaucoma, diabetic retinopathy, disease-based posterior vitreous detachment (PVD), age-based posterior vitreous detachment (PVD), corneal amyloidosis, age-related macular degeneration, retinal photic injury, retinal ischemia-induced eye injury, age-related macular degeneration, or a free-radical-mediated ocular disease. 3. The method according to claim 1 wherein said prophylactically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered intravenously, orally, topically to at least one eye, or a combination thereof. 4. The method according to claim 3 wherein said prophylactically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered as an eye drop, an eye ointment, an intraocular injection or as an ocular insert. 5. A method for treating ocular inflammation associated with at least one of degenerative eye conditions, chronic eye conditions, a secondary sequela of primary disease, an infectious agent, an ophthalmic procedure, and unintentional eye trauma in a mammal comprising administering to said mammal a therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof. 6. The method according to claim 5 wherein said degenerative eye condition comprises glaucoma, diabetic retinopathy, disease-based posterior vitreous detachment (PVD), age-based posterior vitreous detachment (PVD), Dellen, Terrein's Marginal Degeneration, or calcific band keratopathy. 7. The method according to claim 5 wherein the secondary sequela of primary disease comprises at least one of corneal ulceration, corneal infiltration and corneal thinning caused by a primary autoimmune or non-autoimmune disease. 8. The method according to claim 7 wherein said primary autoimmune disease comprises ulcerative colitis, Mooren's ulcer, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, Wegener's granulomatosis, polyarteritis nodosa, or myasthenia gravis. 9. The method according to claim 7 wherein said non-autoimmune disease comprises syphilis, gonorrhea, bacillary dysentery, leukemia, food allergy, ocular or dystrophies. 10. The method according to claim 5 wherein said infectious agent comprises a bacterium, a virus, a fungus, or a parasite. 11. The method according to claim 10 wherein the infectious agent is a bacterium comprising Pseudomonas, Staphylococcus sp., Serratia marcescens, Streptococcus sp., Haemophilus sp., N. gonorrhoeae, N. meningitidis, Moroxella, B. burgdorferi, Corynebacterium diphtheriae, or a combination thereof. 12. The method according to claim 11 wherein said Staphylococcus sp. is selected from the group consisting of S. aureus and S. epidermidis. 13. The method according to claim 7 wherein said infectious agent is a DNA virus selected from the group consisting of Herpes simplex (HSV-1 and HSV-2), Varicella-zoster, Epstein-Barr, Adenovirus, Cytomegalovirus, and Papilloma. 14. The method according to claim 7 wherein said infectious agent is an RNA virus selected from the group consisting of Poliovirus, Enterovirus 70, Rhinovirus, Arbovirus, Influenza, Mumps, Measles, Rabies, and HIV. 15. The method according to claim 5 wherein said eye inflammation is caused by an ophthalmic procedure involving a cutting implement or clinical or surgical use of a laser. 16. The method according to claim 15 wherein said eye inflammation is caused by photoreactive keratectomy, or laser in-situ keratomileusis, laser peripheral iridectomies, laser posterior capsulotomies, and laser-treated retinal/subretinal neovascularization. 17. The method according to claim 15 wherein said ophthalmic procedure is radial keratotomy or cataract surgery. 18. The method according to claim 5 wherein said eye inflammation is caused by an unintentional eye trauma. 19. The method according to claim 18 wherein said unintentional eye trauma comprises an acid chemical burn or an alkaline chemical burn. 20. The method according to claim 15 wherein said therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered at a time comprising at least one of before, during, and after said ophthalmic procedure. 21. The method according to claim 15 wherein said therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered intravenously, orally, topically, or a combination thereof. 22. The method according to claim 21 wherein said therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered as an eye drop or an eye ointment. 23. The method according to claim 5 wherein said therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered as an eye drop or an eye ointment. 24. A method for enhancing wound healing following a corneal excimer laser procedure comprising administering to a patient at a time comprising at least one of before, during, and after the corneal excimer laser procedure an amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof effective to prevent a regrowth of non-planar keratocytes. 25. The method according to claim 24 wherein said therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered intravenously, orally, topically to at least one eye, or a combination thereof. 26. The method according to claim 25 wherein said therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof is administered as an eye drop or an eye ointment. 27. The method according to claim 5 further comprising coadministering said therapeutically effective amount of histidine in combination with a therapeutically effective amount of at least one of an antibiotic, an antibacterial agent, an antioxidant, an antiviral agent, a corticosteroid, an hydroxyacid, a ketoacid, a non-steroidal antiinflammatory agent, a cycloplegic, a miotic, a collagenase inhibitor, an anti-glaucoma agent, a carbonic anhydrase inhibitor, a glycoprotein, and silver nitrate. 28. The method according to claim 27 wherein said therapeutically effective amount of histidine is coadministered with a therapeutically effective amount of at least one of ciprofloxacin, ofloxacin, norfloxacin, cefazolin, tobramycin, gentamycin, an aminoglycoside, a penicillin, a semisynthetic penicillin, amoxicillin, ampicillin, carbenicillin, ticarcillin, mezlocillin, a cephalosporin, vancomycin, chloramphenicol, erythromycin, clindamycin, rifampin, bacitracin, polymyxin, spectinomycin, a sulfonamide, trimethoprim, super oxide dismutase, astaxanthin, canthazanthin, .beta.-carotene, zeaxanthin, lutein, .alpha.-tocopherol, ascorbic acid, glutathione, selenous acid, sodium selenate, acyclovir, ganciclovir, idoxuridine, vidarabine, trifluridine, bromovinyldeoxyuridine, azidothymidine, amantadine, rimantadine, dexamethasone, prednisolone, prednisone, fluorometholone, betamethasone, hydrocortisone, ketorolac, indomethacin, flurbiprofen, ketoprofen, loxoprofen, diclofenac, atropine, pilocarpine, carbachol, physostigmine, phenylephrine, acetazolamide, timolol maleate, fibronectin and vitronectin as well as analogs or fragments thereof, and acetyl cysteine. 29. The method according to claim 25 further comprising coadministering said therapeutically effective amount of histidine in combination with a therapeutically effective amount of at least one of an antibiotic, an antibacterial, an antioxidant, an antiviral, a corticosteroid, an hydroxyacid, a ketoacid, a non-steroidal antiinflammatory, a cycloplegic, a miotic, a collagenase inhibitor, an anti-glaucoma agent, a carbonic anhydrase inhibitor, a glycoprotein, and silver nitrate. 30. The method according to claim 29 wherein said therapeutically effective amount of histidine is coadministered with a therapeutically effective amount of at least one of ciprofloxacin, ofloxacin, norfloxacin, cefazolin, tobramycin, gentamycin, an aminoglycoside, a penicillin, a semisynthetic penicillin, amoxicillin, ampicillin, carbenicillin, ticarcillin, mezlocillin, a cephalosporin, vancomycin, chloramphenicol, erythromycin, clindamycin, rifampin, bacitracin, polymyxin, spectinomycin, a sulfonamide, trimethoprim, super oxide dismutase, astaxanthin, canthazanthin, .beta.-carotene, zeaxanthin, lutein, .alpha.-tocopherol, ascorbic acid, glutathione, selenous acid, sodium selenate, acyclovir, ganciclovir, idoxuridine, vidarabine, trifluridine, bromovinyldeoxyuridine, azidothymidine, amantadine, rimantadine, dexamethasone, prednisolone, prednisone, fluorometholone, betamethasone, hydrocortisone, ketorolac, indomethacin, flurbiprofen, ketoprofen, loxoprofen, diclofenac, atropine, pilocarpine, carbachol, physostigmine, phenylephrine, acetazolamide, timolol maleate, fibronectin and vitronectin as well as analogs or fragments thereof, and acetyl cysteine. 31. The method according to claim 5 wherein said ocular inflammation is associated with a condition comprising allergic conjunctivitis, adenoviral keratoconjuctivitis, bacterial conjunctivitis, blepharitis, cytomegalovirus retinitis, edema, H. simplex epithelial keratitis, H. zoster keratitis, H. zoster iridocyclitis, interstitial keratitis, nummular keratitis, scleritis, trachoma, uveitis, or viral necrotizing keratitis. 32. The method according to claim 4 wherein said prophylactically effective amount of histidine is co-administered with at least one of an absorption promoter and an ophthalmic preservative. 33. The method according to claim 23 wherein said therapeutically effective amount of histidine is co-administered with at least one of an absorption promoter and an ophthalmic preservative. 34. The method according to claim 26 wherein said therapeutically effective amount of histidine is co-administered with at least one of an absorption promoter and an ophthalmic preservative. 35. A composition for administration to an eye to treat ocular inflammatory conditions, comprising a therapeutically effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof, an ophthalomological carrier therefor, and optionally, formulation adjuvants. 36. The composition according to claim 35 wherein said ophthalmological carrier comprises a liquid, suspension, or emulsion. 37. The composition according to claim 35 wherein said formulation adjuvants comprise an absorption promoter, a tonicity agent, a pH-adjusting agent, a buffer, a viscosity/lubricating agent, a nonionic surfactant, a sequestering agent, a wetting agent, a preservative, or mixtures thereof. 38. The composition according to claim 35 further comprising a therapeutically effective amount of an additional therapeutically active material. 39. The composition according to claim 38 wherein said additional therapeutically active material comprises ciprofloxacin, ofloxacin, norfloxacin, cefazolin, tobramycin, gentamycin, an aminoglycoside, a penicillin, a semisynthetic penicillin, amoxicillin, ampicillin, carbenicillin, ticarcillin, mezlocillin, a cephalosporin, vancomycin, chloramphenicol, erythromycin, clindamycin, rifampin, bacitracin, polymyxin, spectinomycin, a sulfonamide, trimethoprim, super oxide dismutase, astaxanthin, canthazanthin, .beta.-carotene, zeaxanthin, lutein, .alpha.-tocopherol, ascorbic acid, glutathione, selenous acid, sodium selenate, acyclovir, ganciclovir, idoxuridine, vidarabine, trifluridine, bromovinyldeoxyuridine, azidothymidine, amantadine, rimantadine, dexamethasone, prednisolone, prednisone, fluorometholone, betamethasone, hydrocortisone, an .alpha.-hydroxyacid, a .beta.-hydroxyacid, an .alpha.-ketoacid, a .beta.-ketoacid, ketorolac, indomethacin, flurbiprofen, loxoprofen, diclofenac, atropine, pilocarpine, carbachol, physostigmine, phenylephrine, acetazolamide, timolol maleate, fibronectin and vitronectin as well as analogs or fragments thereof, acetyl cysteine, or mixtures thereof. 40. The composition according to claim 35 wherein said therapeutically effective amount of histidine is formulated with bicarbonate in a liquid carrier to form an artificial tear solution. 41. The composition according to claim 36 wherein said ophthalmologic carrier is an emulsion to provide a histidine ointment. 42. An eye cosmetic composition comprising a mascara, a liquid eyeliner, or an eye creme and an antiinflammation effective amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof. 43. A method of preventing or treating corneal haze formation in an eye of a patient to undergo or having undergone laser-assisted photoablative surgical procedure causing a removal of corneal tissue, comprising administering to said patient at a time comprising before, during, or after said photoablative procedure an amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof, effective to prevent or treat corneal haze formation. 44. The method according to claim 43 wherein said amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof, effective to prevent or treat corneal haze formation is administered topically or by intraocular injection to said eye of said patient. 45. The method according to claim 44 further comprising coadministering a therapeutic amount of an additional ocular therapeutic agent in combination with said amount of D-histidine, L-histidine, racemic or non-racemic mixtures of histidine, or pharmaceutically acceptable salts thereof.

Details for Patent 5,811,446

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2039-02-26