Non-steroidal anti-inflammatory ophthalmic compositions

Abstract

The disclosure provides compositions and systems for topical ophthalmic application, which include an aqueous mixture of bromfenac and flowable mucoadhesive polymer, for treating inflammation and inflammatory conditions of the eye.

We claim: 
     
       1. A topical ophthalmic composition formulated for application to the eye, said composition comprising a therapeutically effective amount of bromfenac and a flowable crosslinked carboxy-containing polycarbophil mucoadhesive polymer, wherein the composition has a viscosity in the range of about 1,000 to about 3,400 cps and a pH of about 7.4 to about 8.5,
 wherein the viscosity is measured with a Brookfield cone and plate viscosity DV-II+ with the spindle No. CP-52 at 6 rpm. 
 
     
     
       2. The ophthalmic composition according to  claim 1 , wherein the composition further comprises a therapeutically effective amount of ketorolac. 
     
     
       3. The ophthalmic composition according to  claim 1 , wherein the flowable mucoadhesive polymer is in an amount of about 0.5% to about 1.5% by weight of the composition. 
     
     
       4. The ophthalmic composition according to  claim 1 , wherein bromfenac is in an amount of about 0.005% to about 0.5% by weight of the composition. 
     
     
       5. The ophthalmic composition according to  claim 1 , wherein the composition further comprises an additional therapeutically active agent selected from the group consisting of antibacterial antibiotic agent, synthetic antibacterial agent, antifungal antibiotic agent, synthetic antifungal agent, antineoplastic agent, steroidal anti-inflammatory agent, non-steroidal anti-inflammatory agent, anti-allergic agent, glaucoma-treating agent, antiviral agent and anti-mycotic agent. 
     
     
       6. The ophthalmic composition according to  claim 5 , wherein the additional therapeutic active agent is a non-steroidal anti-inflammatory agent selected from the group consisting of aspirin, benoxaprofen, benzofenac, bucloxic acid, butibufen, carprofen, cicloprofen, cinmetacin, clidanac, clopirac, diclofenac, diflupredinate, etodolac, fenbufen, fenclofenac, fenclorac, fenoprofen, fentiazac, flunoxaprofen, furaprofen, flurbiprofen, furobufen, furofenac, ibuprofen, ibufenac, indomethacin, indoprofen, isoxepac, ketorolac, ketroprofen, lactorolac, lonazolac, metiazinic, miroprofen, naproxen, oxaprozin, oxepinac, phenacetin, pirprofen, pirazolac, protizinic acid, sulindac, suprofen, tiaprofenic acid, tolmetin, and zomepirac. 
     
     
       7. The ophthalmic composition according to  claim 6 , wherein the additional non-steroidal anti-inflammatory agent is ketorolac. 
     
     
       8. The ophthalmic composition according to  claim 5 , wherein the additional therapeutic active agent is a steroidal anti-inflammatory agent selected from the group consisting of 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone 25-diethylamine-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide, and triamcinolone hexacetonide. 
     
     
       9. The topical ophthalmic composition of  claim 1 , wherein the viscosity of the composition is in the range of about 1,000 to about 2,000 cps. 
     
     
       10. The ophthalmic composition of  claim 1 , wherein the composition comprises from about 0.01 to 0.09 bromfenac by weight of the composition. 
     
     
       11. The ophthalmic composition of  claim 10  wherein the composition has a pH of about 8.3. 
     
     
       12. An ophthalmic composition comprising a therapeutically effective amount of bromfenac, a therapeutically effective amount of ketorolac and a flowable crosslinked carboxy-containing polycarbophil mucoadhesive polymer, wherein
 the composition has a viscosity in the range of about 1,000 to about 3,400 cps and is formulated for administration to the eye of a mammal in drop form, and 
 the composition has a pH of about 7.4 to about 8.5, 
 wherein the viscosity is measured with a Brookfield cone and plate viscosity DV-II+ with the spindle No. CP-52 at 6 rpm. 
 
     
     
       13. An ophthalmic composition comprising a therapeutically effective amount of bromfenac and a flowable mucoadhesive polymer, wherein:
 the composition has a viscosity in the range of about 1,000 to about 3,400 cps and is formulated for administration to the eye of a mammal in drop form, 
 the composition further comprises at least one additional non-steroidal anti-inflammatory agent, 
 the flowable mucoadhesive polymer is a crosslinked carboxy-containing polycarbophil, and 
 the composition has a pH of about 7.4 to about 8.5, 
 wherein the viscosity is measured with a Brookfield cone and plate viscosity DV-II+ with the spindle No. CP-52 at 6 rpm. 
 
     
     
       14. An ophthalmic composition comprising a therapeutically effective amount of bromfenac and a flowable mucoadhesive polymer, wherein:
 the composition has a viscosity in the range of about 1,000 to about 3,400 cps and is formulated for administration to the eye of a mammal in drop form, 
 the composition further comprises at least one steroidal anti-inflammatory agent, 
 the flowable mucoadhesive polymer is a crosslinked carboxy-containing polycarbophil, and 
 the composition has a pH of about 7.4 to about 8.5, 
 wherein the viscosity is measured with a Brookfield cone and plate viscosity DV-II+ with the spindle No. CP-52 at 6 rpm. 
 
     
     
       15. An ophthalmic composition comprising a therapeutically effective amount of bromfenac and a flowable mucoadhesive polymer, wherein:
 the composition has a viscosity in the range of about 1,000 to about 3,400 cps and is formulated for administration to the eye of a mammal in drop form, 
 the composition further comprises at least one antibacterial agent, 
 the flowable mucoadhesive polymer is a crosslinked carboxy-containing polycarbophil, and 
 the composition has a pH of about 7.4 to about 8.5, 
 wherein the viscosity is measured with a Brookfield cone and plate viscosity DV-II+ with the spindle No. CP-52 at 6 rpm. 
 
     
     
       16. A method for therapeutic treatment of an inflammatory condition of the eye in a mammal comprising
 administering the composition of  claim 1  to the eye of a mammal in need thereof to treat inflammation or inflammatory conditions of the eye. 
 
     
     
       17. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 16 , wherein the ophthalmic composition further comprises a therapeutically active agent selected from the group consisting of antibacterial antibiotic agent, synthetic antibacterial agent, antifungal antibiotic, synthetic antifungal agent, antineoplastic agent, steroidal anti-inflammatory agent, non-steroidal anti-inflammatory agent, anti-allergic agent, glaucoma-treating agent, antiviral agent and anti-mycotic agent. 
     
     
       18. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 17 , wherein the therapeutically active agent is ketorolac. 
     
     
       19. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 16 , wherein the inflammatory condition is selected from the group consisting of inflammatory conditions associated with surgical trauma; dry eye; allergic conjunctivitis; viral conjunctivitis; bacterial conjunctivitis; blepharitis; anterior uveitis; injury from a chemical; radiation or thermal burn; injury from penetration of a foreign body; pain in or around the eye; redness and pain in the eye; light sensitivity; seeing colored circles or halos around lights; protrusion of the eye; swelling of eye tissues; discharge, crusting or excessive tearing; eyelids stuck together; blood on the colored part or white of the eye; cataracts; wearing contact lenses; corneal-associated condition; conjunctival tumor excision; conjunctivitis; corneal edema associated with cataract surgery; corneal clouding; corneal transplantation; corneal ulcer; dry eye syndrome; dystrophies; excimer laser phototherapeutic keratectomy; herpes simplex keratitis; keratoconus; pterygium; recurrent erosion syndrome; eye movement disorder; glaucoma; ocular tumor; ocuplastic surgery; enucleation; eyelid or orbit injuries; ectropion; entropion; graves' disease; involuntary eyelid blinking; refractive surgery; and retinal condition. 
     
     
       20. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 16 , wherein the inflammatory condition is associated with a retinal condition. 
     
     
       21. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 20 , wherein the retinal condition is selected from the group consisting of age related macular degeneration, AIDS-related ocular disease, CMV retinitis, birdshot retinochoroidopathy (BR), choroidal melanoma, coats disease, cotton wool spots, diabetic retinopathy diabetic macular edema, cystoid macular edema, lattice degeneration, macular disease, macular degeneration, hereditary macular dystrophy, macular edema, macular hole, macular pucker, central serous chorioretinopathy, ocular histoplasmosis syndrome (OHS), posterior vitreous detachment, retinal detachment, retinal artery obstruction, retinal vein occlusion, retinoblastoma, retinopathy of prematurity (ROP), retinitis pigmentosa, acquired or x-linked retinoschisis, stargardt's disease, toxoplasmosis of retina and uveitis. 
     
     
       22. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 19 , wherein the inflammatory condition is selected from the group consisting of inflammatory conditions associated with surgical trauma; cataracts; and corneal edema associated with cataract surgery. 
     
     
       23. The ophthalmic composition of  claim 1 , wherein the composition has an osmolality from about 10 mOsm/kg to 400 mOsm/kg. 
     
     
       24. The ophthalmic composition of  claim 1 , wherein the composition has an osmolality of about 290 mOsm/kg and a pH of about 8.3. 
     
     
       25. The ophthalmic composition of  claim 10 , wherein the composition comprises from about 0.045% to 0.09% bromfenac by weight of the composition. 
     
     
       26. The ophthalmic composition according to  claim 12 , wherein the flowable mucoadhesive polymer is in an amount of about 0.5% to about 1.5% by weight of the composition. 
     
     
       27. The ophthalmic composition of  claim 12 , wherein the composition has a viscosity in the range of about 1,000 to about 2,000 cps. 
     
     
       28. The ophthalmic composition of  claim 12 , wherein the composition has a pH of about 8.3. 
     
     
       29. The ophthalmic composition of  claim 12 , wherein the composition has an osmolality from about 10 mOsm/kg to 400 mOsm/kg. 
     
     
       30. The ophthalmic composition of  claim 12 , wherein the composition has an osmolality of about 290 mOsm/kg and a pH of about 8.3. 
     
     
       31. The ophthalmic composition of  claim 12 , wherein the composition comprises from about 0.045% to 0.09% bromfenac by weight of the composition. 
     
     
       32. The ophthalmic composition according to  claim 13 , wherein the flowable mucoadhesive polymer is in an amount of about 0.5% to about 1.5% by weight of the composition. 
     
     
       33. The ophthalmic composition of  claim 13 , wherein the composition has a viscosity in the range of about 1,000 to about 2,000 cps. 
     
     
       34. The ophthalmic composition of  claim 13 , wherein the composition has a pH of about 8.3. 
     
     
       35. The ophthalmic composition of  claim 13 , wherein the composition has an osmolality from about 10 mOsm/kg to 400 mOsm/kg. 
     
     
       36. The ophthalmic composition of  claim 13 , wherein the composition has an osmolality of about 290 mOsm/kg and a pH of about 8.3. 
     
     
       37. The ophthalmic composition of  claim 13 , wherein the composition comprises from about 0.045% to 0.09% bromfenac by weight of the composition. 
     
     
       38. The ophthalmic composition according to  claim 14 , wherein the flowable mucoadhesive polymer is in an amount of about 0.5% to about 1.5% by weight of the composition. 
     
     
       39. The ophthalmic composition of  claim 14 , wherein the composition has a viscosity in the range of about 1,000 to about 2,000 cps. 
     
     
       40. The ophthalmic composition of  claim 14 , wherein the composition has a pH of about 8.3. 
     
     
       41. The ophthalmic composition of  claim 14 , wherein the composition has an osmolality from about 10 mOsm/kg to 400 mOsm/kg. 
     
     
       42. The ophthalmic composition of  claim 14 , wherein the composition has an osmolality of about 290 mOsm/kg and a pH of about 8.3. 
     
     
       43. The ophthalmic composition of  claim 14 , wherein the composition comprises from about 0.045% to 0.09% bromfenac by weight of the composition. 
     
     
       44. The ophthalmic composition according to  claim 15 , wherein the flowable mucoadhesive polymer is in an amount of about 0.5% to about 1.5% by weight of the composition. 
     
     
       45. The ophthalmic composition of  claim 15 , wherein the composition has a viscosity in the range of about 1,000 to about 2,000 cps. 
     
     
       46. The ophthalmic composition of  claim 15 , wherein the composition has a pH of about 8.3. 
     
     
       47. The ophthalmic composition of  claim 15 , wherein the composition has an osmolality from about 10 mOsm/kg to 400 mOsm/kg. 
     
     
       48. The ophthalmic composition of  claim 15 , wherein the composition has an osmolality of about 290 mOsm/kg and a pH of about 8.3. 
     
     
       49. The ophthalmic composition of  claim 15 , wherein the composition comprises from about 0.045% to 0.09% bromfenac by weight of the composition. 
     
     
       50. A topical ophthalmic composition formulated for application to the eye, said composition comprising a therapeutically effective amount of bromfenac and a flowable crosslinked carboxy-containing polycarbophil mucoadhesive polymer,
 wherein the composition has a viscosity in the range of about 1,000 to about 3,400 cps and a pH of about 7.4 to about 8.5; the flowable mucoadhesive polymer is in an amount of about 0.5% to about 1.5% by weight of the composition; the composition comprises from about 0.045% to 0.09% bromfenac by weight of the composition, and   wherein the viscosity is measured with a Brookfield cone and plate viscosity DV-II+ with the spindle No. CP-52 at 6 rpm.   
     
     
       51. The ophthalmic composition of  claim 50 , wherein the composition has an osmolality from about 10 mOsm/kg to 400 mOsm/kg. 
     
     
       52. The ophthalmic composition of  claim 50 , wherein the composition has an osmolality of about 290 mOsm/kg and a pH of about 8.3. 
     
     
       53. The ophthalmic composition of  claim 50 , wherein the composition has a viscosity in the range of about 1,000 to about 2,000 cps. 
     
     
       54. The ophthalmic composition of  claim 50 , wherein the composition has a pH of about 8.3. 
     
     
       55. A method for therapeutic treatment of an inflammatory condition of the eye in a mammal comprising administering the composition of  claim 50  to the eye of a mammal in need thereof to treat inflammation or inflammatory conditions of the eye. 
     
     
       56. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 55 , wherein the ophthalmic composition further comprises a therapeutically active agent selected from the group consisting of antibacterial antibiotic agent, synthetic antibacterial agent, antifungal antibiotic, synthetic antifungal agent, antineoplastic agent, steroidal anti-inflammatory agent, non-steroidal anti-inflammatory agent, anti-allergic agent, glaucoma-treating agent, antiviral agent and anti-mycotic agent. 
     
     
       57. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 56 , wherein the therapeutically active agent is ketorolac. 
     
     
       58. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 55 , wherein the inflammatory condition is selected from the group consisting of inflammatory conditions associated with surgical trauma; dry eye; allergic conjunctivitis; viral conjunctivitis; bacterial conjunctivitis; blepharitis; anterior uveitis; injury from a chemical; radiation or thermal burn; injury from penetration of a foreign body; pain in or around the eye; redness and pain in the eye; light sensitivity; seeing colored circles or halos around lights; protrusion of the eye; swelling of eye tissues; discharge, crusting or excessive tearing; eyelids stuck together; blood on the colored part or white of the eye; cataracts; wearing contact lenses; corneal-associated condition; conjunctival tumor excision; conjunctivitis; corneal edema associated with cataract surgery; corneal clouding; corneal transplantation; corneal ulcer; dry eye syndrome; dystrophies; excimer laser phototherapeutic keratectomy; herpes simplex keratitis; keratoconus; pterygium; recurrent erosion syndrome; eye movement disorder; glaucoma; ocular tumor; ocuplastic surgery; enucleation; eyelid or orbit injuries; ectropion; entropion; graves' disease; involuntary eyelid blinking; refractive surgery; and retinal condition. 
     
     
       59. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 55 , wherein the inflammatory condition is associated with a retinal condition. 
     
     
       60. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 59 , wherein the retinal condition is selected from the group consisting of age related macular degeneration, AIDS-related ocular disease, CMV retinitis, birdshot retinochoroidopathy (BR), choroidal melanoma, coats disease, cotton wool spots, diabetic retinopathy diabetic macular edema, cystoid macular edema, lattice degeneration, macular disease, macular degeneration, hereditary macular dystrophy, macular edema, macular hole, macular pucker, central serous chorioretinopathy, ocular histoplasmosis syndrome (OHS), posterior vitreous detachment, retinal detachment, retinal artery obstruction, retinal vein occlusion, retinoblastoma, retinopathy of prematurity (ROP), retinitis pigmentosa, acquired or x-linked retinoschisis, stargardt's disease, toxoplasmosis of retina and uveitis. 
     
     
       61. The method for therapeutic treatment of an inflammatory condition of the eye in a mammal according to  claim 55 , wherein the inflammatory condition is selected from the group consisting of inflammatory conditions associated with surgical trauma; cataracts; and corneal edema associated with cataract surgery.