Ocular solutions

Abstract

Ocular solutions containing at least one macrolide antibiotic and/or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial, and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions. The solution may contain a supratherapeutic concentration of agent(s) so that a therapeutic concentration of a topically administered solution accumulates in a diseased ocular structure sufficient to treat the disease. The agent(s) may be formulated with polymers or other components for extended or slow release to provide a substantially constant concentration over the course of treatment.

1 . A non-invasive method to treat a diseased eye in a patient: comprising topically administering to the patient a composition comprising a concentration ranging between 0.5% w/v  to about 10% w/v  of a macrolide antibiotic and/or mycophenolic acid in a pharmaceutically acceptable topical formulation for a duration to achieve a concentration of the macrolide antibiotic and/or mycophenolic in a diseased ocular structure sufficient to treat the diseased eye.  
     
     
         2 . The method of  claim 1  wherein the diseased ocular structure is at least one of the choroid, retina, or uvea.  
     
     
         3 . The method of  claim 1  wherein the macrolide antibiotic is selected from at least one of tacrolimus, Cyclosporin A, sirolimus, ascomycin, and everolimus.  
     
     
         4 . The method of  claim 1  wherein the macrolide antibiotic is selected from at least one of erythromycin, azithromycin, clarithromycin, lincomycin, dirithromycin, josamycin, spiramycin, diacetyl-midecamycin, tylosin, troleandomycin, roxithromycin, ABT-773, telithromycin, macrolides derived from leucomycins, and lincosamides.  
     
     
         5 . The method of  claim 1  wherein the composition is an extended-release formulation.  
     
     
         6 . The method of  claim 5  wherein the composition is provided on a contact lens or intraocular lens.  
     
     
         7 . The method of  claim 1  wherein the composition is formulated as at least one of a polymer, a microcapsule, a microsphere, a microvesicle, and a liposome.  
     
     
         8 . The method of  claim 1  for treating at least one of retinopathy, retinitis pigmentosa, age related macular degeneration, scleritis, uveitis, vasculitis, retinoblastoma, choroidal melanoma, and pre-malignant and malignant melanoma of the conjunctiva.  
     
     
         9 . The method of  claim 1  for administration to at least one of an ocular mucosal surface or the conjunctiva.  
     
     
         10 . The method of  claim 1  wherein the concentration of the macrolide antibiotic and/or mycophenolic acid is from at least one of about 0.5% w/v  to about 3% w/v , about 3% w/v  to about 5% w/v , about 5% w/v  to about 10%w w/v , or about 3% w/v  to about 10% w/v ,  
     
     
         11 . The method of  claim 1  for treating age related macular degeneration wherein the composition further comprises a cyclooxygenase inhibitor.  
     
     
         12 . A non-invasive method to treat a diseased eye in a patient comprising topically administering to the eye a composition consisting essentially of tacrolimus at a concentration from 0.5% w/v  to about 10% w/v  in a pharmaceutically acceptable formulation for a duration to achieve a concentration in an internal ocular structure sufficient to treat the structure.  
     
     
         13 . The method of  claim 12  for treating at least one of retinopathy, retinitis pigmentosa, age related macular degeneration, uveitis, vasculitis, retinoblastoma, choroidal melanoma, and pre-malignant and malignant melanoma of the conjunctiva.  
     
     
         14 . A non-invasive method to treat a diseased eye in a patient comprising topically administering to the eye a composition consisting essentially of Cyclosporin A at a concentration from 0.5% w/v  to about 10% w/v  in a pharmaceutically acceptable formulation for a duration to achieve a concentration in an internal ocular structure sufficient to treat the structure.  
     
     
         15 . The method of  claim 14  for treating at least one of retinopathy, retinitis pigmentosa, age related macular degeneration, uveitis, vasculitis, retinoblastoma, choroidal melanoma, pre-malignant and malignant melanoma of the conjunctiva.  
     
     
         16 . A non-invasive method to treat a diseased eye in a patient comprising topically administering to the eye a composition consisting essentially of sirolimus at a concentration from 0.5% w/v  to about 10% w/v  in a pharmaceutically acceptable formulation for a duration to achieve a concentration in an internal ocular structure sufficient to treat the structure.  
     
     
         17 . The method of  claim 16  for treating at least one of retinopathy, retinitis pigmentosa, age related macular degeneration, uveitis, vasculitis, retinoblastoma, choroidal melanoma, pre-malignant and malignant melanoma of the conjunctiva.  
     
     
         18 . A non-invasive method to treat a diseased eye in a patient comprising topically administering to the eye a composition consisting essentially of ascomycin at a concentration from 0.5% w/v  to about 10% w/v  in a pharmaceutically acceptable formulation for a duration sufficient to achieve a concentration in an internal ocular structure sufficient to treat the structure.  
     
     
         19 . The method of  claim 18  for treating at least one of retinopathy, retinitis pigmentosa, age related macular degeneration, uveitis, vasculitis, retinoblastoma, choroidal melanoma, and pre-malignant and malignant melanoma of the conjunctiva.  
     
     
         20 . A non-invasive method to treat a diseased eye in a patient comprising topically administering to the eye a composition consisting essentially everolimus of at a concentration from 0.5% w/v  to about 10% w/v  in a pharmaceutically acceptable formulation for a duration to achieve a concentration in an internal ocular structure sufficient to treat the structure.  
     
     
         21 . The method of  claim 20  for treating at least one of retinopathy, retinitis pigmentosa, age related macular degeneration, uveitis, vasculitis, retinoblastoma, choroidal melanoma, and pre-malignant and malignant melanoma of the conjunctiva.  
     
     
         22 . A topical ocular composition comprising at least one macrolide antibiotic and/or mycophenolic acid a concentration ranging from about 0.5% w/v  to about 10% w/v  and at least one of a polymer, a liposome, a microcapsule, and a microsphere in a pharmaceutically acceptable extended release topical ocular formulation.  
     
     
         23 . The composition of  claim 22  wherein the macrolide antibiotic is at least one of tacrolimus, cyclosporine, sirolimus, everolimus, ascomycin, erythromycin, azithromycin, clarithromycin, clindamycin, lincomycin, dirithromycin, josamycin, spiramycin, diacetyl-midecamycin, tylosin, roxithromycin, ABT-773, telithromycin, leucomycins, and lincosamide.  
     
     
         24 . The composition of  claim 22  provided with a contact lens or an intraocular lens.  
     
     
         25 . The composition of  claim 24  wherein the composition is on a lens surface.  
     
     
         26 . The composition of  claim 24  wherein the composition is contained in pores of a porous lens.  
     
     
         27 . The composition of  claim 22  further comprising at least one of a cyclooxygenase inhibitor or a chemotherapeutic agent.  
     
     
         28 . An article comprising an ocular lens containing a concentration of at least one macrolide antibiotic and/or mycophenolic acid in a formulation to slowly release from the lens an intraocular concentration of the macrolide antibiotic and/or mycophenolic acid that does not exceed about 40 μg/ml.  
     
     
         29 . The article of  claim 28  wherein the intraocular concentration of macrolide antibiotic and/or mycophenolic acid ranges from about 10 μg/ml to about 30 μg/ml.  
     
     
         30 . The article of  claim 28  wherein the lens is a contact lens or an intraocular lens.  
     
     
         31 . A non-invasive method to treat a diseased eye in a patient having diabetic retinopathy, age related macular degeneration, or retinitis pigmentosa, the method comprising topically administering to the patient a composition comprising a concentration ranging between 0.1% w/v  to about 10% w/v  of a macrolide antibiotic and/or mycophenolic acid in a pharmaceutically acceptable topical formulation for a duration to achieve a concentration of the macrolide antibiotic and/or mycophenolic in a diseased ocular structure sufficient to treat the diseased eye.  
     
     
         32 . The method of  claim 31  wherein the macrolide antibiotic and/or mycophenolic acid is formulated for extended release.  
     
     
         33 . The method of  claim 31  wherein the macrolide antibiotic and/or mycophenolic acid is provided with a contact lens or intraocular lens.  
     
     
         34 . The method of  claim 31  wherein the composition further comprises at least one cyclooxygenase inhibitor.