Topical treatment or prevention of ocular infections

• US 6,569,443 B1
• Filed: 01/24/2001
• Issued: 05/27/2003
• Est. Priority Date: 03/31/1999
• Status: Expired due to Term

• Current Assignee: Insite Vision Incorporated (Daiichi Sankyo Company Limited)
• Original Assignee: Insite Vision Incorporated (Daiichi Sankyo Company Limited)
• Inventors: Bowman, Lyle M., Dawson, Chandler R.
• Primary Examiner(s): Peselev; Elli
• Application Number:
  US09/767,943
• Time in Patent Office: 853 Days
• Field of Search: 514/29 424/427,433
• US Class Current: 424/433
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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.

Claims

1. A process for treating an eye, comprising:

topically applying an azalide antibiotic to an eye in an amount effective to treat infection in a tissue of the eye, wherein said topically applying comprises supplying a depot of a composition containing said azalide antibiotic on the eye.

2. The process according to claim 1, wherein said eye is suffering from at least one condition selected from the group consisting of conjunctivitis, ophthalmia neonatorum, trachoma, corneal ulcers, keratitis, keratoconjunctivitis, endophthalmitis, infectious uveitis and combinations thereof, and said amount of said azalide antibiotic is therapeutically effective to treat said condition.

3. The process according to claim 1, wherein said azalide antibiotic is a compound of formula (I):

wherein R¹ and R² each independently represent a hydrogen atom or methyl group.

4. The process according to claim 3, wherein said azalide antibiotic is azithromycin.

5. The process according to claim 3, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 8 hours.

6. The process according to claim 5, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 12 hours.

7. The process according to claim 6, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 18 hours.

8. The process according to claim 1, wherein said depot is an aqueous polymeric suspension of said azalide antibiotic.

9. The process according to claim 8, wherein said aqueous polymeric suspension further comprises an additional medicament.

10. The process according to claim 9, 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.

11. The process according to claim 1, wherein said depot is a composition selected from the group consisting of an aqueous suspensions, ointments, and inserts.

12. The process according to claim 11, wherein said composition further comprises an additional medicament.

13. The process according to claim 12, wherein said additional medicament is selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents.

14. The process according to claim 1, wherein said depot remains for at least 30 minutes after administration.

15. The process according to claim 14, wherein said depot remains for at least 4 hours after administration.

40. The process according to claim 1, wherein the amount of said azalide antibiotic is at least about 5.0%.

41. The process according to claim 1, wherein the amount of said azalide antibiotic is from about 0.1 to about 5.0%.

16. A topical ophthalmic composition comprising an aqueous polymeric suspension comprising water, 0.01% to 1.0% of an azalide antibiotic and 0.1 to 10% of a polymeric suspending agent, wherein said topical ophthalmic composition has an osmotic pressure of from 10 to 400 mOsM and wherein said composition does not contain constituents that are physiologically or ophthalmically harmful to the eye.

17. The composition according to claim 16, wherein said suspension further comprises an additional medicament selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents.

18. The composition according to claim 17, wherein said additional medicament is contained in the amount of from 0.01 to 5.0%.

19. The composition according to claim 17, 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, bacitran, vancomycin, tetracyclines, rifampins, cycloserine, beta-lactams, cephalosporins, amphotericins, fluconazole, flucytosine, matamycin, miconazole, ketoconazole, corticosteroids, diclofenac, flurbiprofen, ketorolac, suprofen, comolyn, lodoxamide, levocabastin, naphazoling, antazoline, and pheniramimane.

20. A topical ophthalmic composition comprising about 0.01 to about 5% of an azalide antibiotic, an ophthalmically acceptable carrier, and an additional medicament selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents, wherein said topical ophthalmic composition has an osmotic pressure of from 10 to 400 mOsM and wherein said composition does not contain constituents that are physiologically or ophthalmically harmful to the eye.

21. The composition according to claim 20, wherein said composition is fluid;

said azalide antibiotic is contained in an amount of from about 0.01 to 2.0%; and

said additional medicament is contained in an amount of from about 0.01 to 5.0%.

22. The composition according to claim 21, wherein said ophthalmically acceptable carrier is water or an aqueous solution and 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.

42. The composition according to claim 20, wherein said composition is fluid;

said azalide antibiotic is contained in an amount from at least about 5.0%, and said additional medicament is contained in an amount of from about 0.01 to 5.0%.

43. The composition according to claim 20, wherein said composition is fluid;

said azalide antibiotic is contained in an amount from about 0.1 to about 5.0%, and said additional medicament is contained in an amount of from about 0.001 to 5.0%.

45. The composition according to claim 20, wherein said azalide antibiotic is azithromycin.

23. A process for treating an eye, comprising:

topically applying an azalide antibiotic to an eye of a non-human animal in an amount effective to treat infection in a tissue of the eye, wherein said topically applying comprises supplying a depot of a composition containing said azalide antibiotic on the eye.

24. The process according to claim 23, wherein said non-human animal is a mammal.

25. The process according to claim 23, wherein said mammal is selected from the group consisting of cows, sheep, horses, pigs, goats, rabbits, dogs, and cats.

26. The process according to claim 23, wherein said depot is an aqueous polymeric suspension of said azalide antibiotic.

27. The process according to claim 26, wherein said aqueous polymeric suspension further comprises an additional medicament.

28. The process according to 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, diclofenac, flurbiprofen, ketorolac, suprofen, comolyn, lodoxamide, levocabastin, naphazoling, antazoline, and pheniramimane.

29. The process according to claim 23, wherein said depot is a composition selected from the group consisting of an aqueous suspensions, ointments, and inserts.

30. The process according to claim 29, wherein said depot remains for at least 30 minutes after administration.

31. The process according to claim 30, therein said depot remains for at least 4 hours after administration.

32. The process according to claim 23, wherein said composition further comprises an additional medicament.

33. The process according to claim 32, wherein said additional medicament is selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents.

34. The process according to claim 23, wherein said eye is suffering from at least one condition selected from the group consisting of conjunctivitis, ophthalmic neonatorum, trachoma, corneal ulcers, keratitis, keratoconjunctivitis, endophthalmitis, infectious uveitis and combinations thereof, and said amount of said azalide antibiotic is therapeutically effective to treat said condition.

35. The process according to claim 23, wherein said azalide antibiotic is a compound of formula (I):

wherein R¹ and R² each independently represent a hydrogen atom or methyl group.

36. The process according to claim 35, wherein said azalide antibiotic is azithromycin.

37. The process according to claim 23, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 8 hours.

38. The process according to claim 37, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 12 hours.

39. The process according to claim 38, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 18 hours.

44. A topical ophthalmic composition comprising an aqueous polymeric suspension comprising water, from about 0.1 to about 5.0% of an azalide antibiotic, and 0.1 to 10% of a polymeric suspending agent, wherein said topical ophthalmic composition has an osmotic pressure of from 10 to 400 mOsM and wherein said composition does not contain constituents that are physiologically or ophthalmically harmful to the eye and said topical ophthalmic composition is in the form of a depot which is capable of sustained release of said azalide antibiotic.