Topical treatment or prevention of ocular infections
View Patent ↗The topical application of an azalide antibiotic such as azithromycin to the eye is useful in treating or preventing ocular infections. In one embodiment, the azalide antibiotic is supplied to the eye in a depot for sustained release. A more convenient dosing regimen can also be provided by the use of an appropriate depot. Furthermore, a composition containing a combination of medicaments is also provided.
1. An aqueous topical ophthalmic composition comprising azithromycin, an anti-inflammatory agent and an ophthalmically acceptable carrier, wherein said topical ophthalmic composition has a pH of 6 to 7.
2. The topical ophthalmic composition according to claim 1 , wherein said anti-inflammatory agent is a steroidal anti-inflammatory agent.
3. The topical ophthalmic composition according to claim 2 , wherein said steroidal anti-inflammatory agent is selected from the group consisting of Prednisolone acetate, Fluorometholone, Dexamethasone and a pharmaceutically acceptable salt thereof.
4. The topical ophthalmic composition according to claim 2 , wherein said steroidal anti-inflammatory agent is Dexamethasone.
5. The topical ophthalmic composition according to claim 1 , wherein said anti-inflammatory agent is a non-steroidal anti-inflammatory agent.
6. The process for treating an eye of claim 5 , wherein said non-steroidal anti-inflammatory agent is selected from the group consisting of diclofenac, flurbiprofen, ketorolac, and suprofen.
7. The topical ophthalmic composition according to claim 1 , wherein said topical ophthalmic composition comprises an additional medicament.
8. The topical ophthalmic composition according to claim 7 , wherein said additional medicament is selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents.
9. The topical ophthalmic composition according to claim 7 , wherein said additional medicament is selected from the group consisting of amikacin, gentamycin, tobramycin, streptomycin, netilmycin, kanamycin, ciprofloxacin, norfloxacin, ofloxacin, trovafloxacin, lomefloxacin, levofloxacin, enoxacin, sulfonamides, polymyxin, chloramphenicol, neomycin, paramomomycin, colistimethate, bacitracin, vancomycin, tetracyclines, rifampins, cycloserine, beta-lactams, cephalosporins, amphotericins, fluconazole, flucytosine, natamycin, miconazole, ketoconazole, corticosteroids, diclofenac, flurbiprofen, ketorolac, suprofen, comolyn, lodoxamide, levocabastin, naphazoling, antazoline, and pheniramimane.
10. The topical ophthalmic composition according to claim 1 , wherein said azithromycin is azithromycin dihydrate.
11. The topical ophthalmic composition according to claim 1 , wherein the amount of said azithromycin is at least about 5.0%.
12. The topical ophthalmic composition according to claim 1 , wherein the amount of said azithromycin is from about 0.01% to about 2%.
13. The topical ophthalmic composition according to claim 1 , wherein the amount of said azithromycin is from about 0.1% to about 1%.
14. The topical ophthalmic composition according to claim 1 , wherein said topical ophthalmic composition is in the form of a depot.
15. The topical ophthalmic composition according to claim 1 , wherein said topical ophthalmic composition is in the form of an aqueous solution or aqueous suspension.
16. The topical ophthalmic composition according to claim 14 , wherein said topical ophthalmic composition is an aqueous solution and has an osmotic pressure of from 10 to 400 mOsM.
17. The topical ophthalmic composition according to claim 1 , wherein said topical ophthalmic composition does not contain constituents that are physiologically or ophthalmically harmful to the eye.
18. The composition according to claim 7 , wherein said additional medicament is contained in the amount of from about 0.01% to about 5%.
19. The topical ophthalmic composition according to claim 1 , wherein said anti-inflammatory agent is contained in an amount of from about 0.01% to about 5%.
20. The topical ophthalmic composition according to claim 1 , wherein said anti-inflammatory agent is contained in an amount of from about 0.01% to about 2%.
21. A process for treating infection in a tissue of an eye, which comprises: topically applying an aqueous ophthalmic composition to an eye, wherein said ophthalmic composition comprises azithromycin in an amount effective to treat infection in the tissue of the eye, an anti-inflammatory agent and an ophthalmically acceptable carrier and said ophthalmic composition has a pH of 6 to 7.
22. The process for treating an eye of claim 21 , wherein said anti-inflammatory agent is a steroidal anti-inflammatory agent.
23. The process for treating an eye of claim 22 , wherein said steroidal anti-inflammatory agent is selected from the group consisting of Prednisolone acetate, Fluorometholone and Dexamethasone.
24. The process for treating an eye of claim 22 , wherein said steroidal anti-inflammatory agent is Dexamethasone.
25. The process for treating an eye of claim 21 , wherein said anti-inflammatory agent is a non-steroidal anti-inflammatory agent.
26. The process for treating an eye of claim 25 , wherein said non-steroidal anti-inflammatory agent is selected from the group consisting of diclofenac, flurbiprofen, ketorolac, and suprofen.
27. The process for treating an eye of claim 21 , wherein said topical ophthalmic composition comprises an additional medicament.
28. The process for treating an eye of claim 27 , wherein said additional medicament is selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents.
29. The process for treating an eye of claim 27 , wherein said additional medicament is selected from the group consisting of amikacin, gentamycin, tobramycin, streptomycin, netilmycin, kanamycin, ciprofloxacin, norfloxacin, ofloxacin, trovafloxacin, lomefloxacin, levofloxacin, enoxacin, sulfonamides, polymyxin, chloramphenicol, neomycin, paramomomycin, colistimethate, bacitracin, vancomycin, tetracyclines, rifampins, cycloserine, beta-lactams, cephalosporins, amphotericins, fluconazole, flucytosine, natamycin, miconazole, ketoconazole, corticosteroids, comolyn, lodoxamide, levocabastin, naphazoling, antazoline, and pheniramimane.
30. The process for treating an eye of claim 21 , wherein said azithromycin is azithromycin dihydrate.
31. The process for treating an eye of claim 21 , wherein the amount of said azithromycin is at least about 5.0%.
32. The process for treating an eye of claim 21 , wherein the amount of said azithromycin is from about 0.01% to about 2%.
33. The process for treating an eye of claim 21 , wherein the amount of said azithromycin is from about 0.01% to about 1%.
34. The process for treating an eye of claim 21 , wherein said topical ophthalmic composition is in the form of a depot.
35. The process for treating an eye of claim 21 , wherein said topical ophthalmic composition is in the form of an aqueous solution or aqueous suspension.
36. The process for treating an eye of claim 21 , wherein said topical ophthalmic composition is an aqueous solution and has an osmotic pressure of from 10 to 400 mOsM.
37. The process for treating an eye of claim 21 , wherein said topical ophthalmic composition does not contain constituents that are physiologically or ophthalmically harmful to the eye.
38. The process for treating an eye of claim 27 , wherein said additional medicament is contained in the amount of from about 0.01% to about 5%.
39. The process for treating an eye of claim 22 , wherein said steroidal anti-inflammatory agent is contained in an amount of from about 0.01% to about 5%.
40. The process for treating an eye of claim 22 , wherein said steroidal anti-inflammatory agent is contained in an amount of from about 0.01% to about 2%.
41. The process for treating an eye of claim 21 , wherein said applying provides a therapeutically effective concentration of azithromycin within a tissue of the eye for at least 8 hours.
42. The process for treating an eye of claim 21 , wherein said applying provides a therapeutically effective concentration azithromycin within a tissue of the eye for at least 12 hours.
43. The process for treating an eye of claim 21 , wherein said applying provides a therapeutically effective concentration of azithromycin within a tissue of the eye for at least 18 hours.
44. The process for treating an eye of claim 34 , wherein said depot remains for at least 30 minutes after administration.
45. The process for treating an eye of claim 34 , wherein said depot remains for at least 4 hours after administration.
46. The process for treating an eye of claim 21 , wherein said eye is selected from the group consisting of an eye of a human, cow, sheep, horse, pig, goat, rabbit, and dog.
47. The process for treating an eye of claim 21 , wherein said eye is suffering from at least one condition selected from the group consisting of blepharitis, conjunctivitis, ophthalmic neonatorum, trachoma, corneal ulcers, keratitis, keratoconjunctivitis, endophthalmitis, infectious uveitis end combinations thereof, and said amount of said azithromycin is therapeutically effective to treat said condition.
48. The topical ophthalmic composition according to claim 1 , wherein said topical ophthalmic composition comprises a polyacrylic acid-type polymer and has a pH of less than about 6.7.
49. The process for treating an eye of claim 21 , wherein said topical ophthalmic composition retains substantially the same viscosity in the eye as it had prior to administration to the eye or has increased viscosity after application to the eye.
50. The topical ophthalmic composition according to claim 1 , wherein the composition retains substantially the same viscosity in the eye as it had prior to administration to the eye or has increased viscosity after application to the eye.
51. The process according to claim 21 , wherein the ophthalmically acceptable carrier comprises a polyacrylic acid-type polymer and has a pH of less than about 6.7.
52. An aqueous topical ophthalmic composition comprising azithromycin, an anti-inflammatory agent and an ophthalmically acceptable carrier, wherein said topical ophthalmic composition has a pH of 6 to 7, and wherein said composition is in drop form.
53. The aqueous topical ophthalmic composition according to claim 52 , wherein said anti-inflammatory agent is Prednisolone acetate.
54. The aqueous topical ophthalmic composition according to claim 52 , wherein said anti-inflammatory agent is Fluorometholone.
55. The aqueous topical ophthalmic composition according to claim 53 , wherein said anti-inflammatory agent is Dexamethasone.
56. The aqueous topical ophthalmic composition according to claim 52 , wherein said topical ophthalmic composition comprises an additional medicament.
57. A process for treating infection in a tissue of an eye, which comprises: topically applying an aqueous ophthalmic composition to an eye, wherein said ophthalmic composition comprises azithromycin in an amount effective to treat infection in the tissue of the eye, an anti-inflammatory agent and an ophthalmically acceptable carrier and said ophthalmic composition has a pH of 6 to 7 and wherein said composition is in drop form.
58. The process for treating an eye of claim 57 , wherein said anti-inflammatory agent is a steroidal anti-inflammatory agent.
59. The process for treating an eye of claim 58 , wherein said steroidal anti-inflammatory agent is Prednisolone acetate.
60. The process for treating an eye of claim 58 , wherein said steroidal anti-inflammatory agent is Fluorometholone.
61. The process for treating an eye of claim 58 , wherein said steroidal anti-inflammatory agent is Dexamethasone.
62. The process according to claim 57 , wherein said topical ophthalmic composition comprises an additional medicament.