Topical treatment or prevention of ocular infections

• US 20040266702A1
• Filed: 07/26/2004
• Published: 12/30/2004
• Est. Priority Date: 03/31/1999
• Status: Active Grant

• 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.
• Granted Patent: US 7,732,415 B2
• Time in Patent Office: Days
• US Class Current: 514/28
• 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

1-44. -44. cancelled

45. A topical ophthalmic composition comprising an azalide antibiotic, an anti-inflammatory agent and an ophthalmically acceptable carrier.

46. The topical ophthalmic composition according to claim 45, wherein said anti-inflammatory agent is a steroidal anti-inflammatory agent.

47. The topical ophthalmic composition according to claim 45, wherein said steroidal anti-inflammatory agent is selected from the group consisting of Prednisolone acetate, Fluorometholone, Dexamethasone and a pharmaceutically acceptable salt thereof.

48. The topical ophthalmic composition according to claim 45, wherein said steroidal anti-inflammatory agent is Dexamethasone.

49. The topical ophthalmic composition according to claim 45, wherein said anti-inflammatory agent is a non-steroidal anti-inflammatory agent.

50. The process for treating an eye of claim 49, wherein said non-steroidal anti-inflammatory agent is selected from the group consisting of diclofenac, flurbiprofen, ketorolac, and suprofen.

51. The topical ophthalmic composition according to claim 45, wherein said topical ophthalmic composition comprises an additional medicament.

52. The topical ophthalmic composition according to claim 50, wherein said additional medicament is selected from the group consisting of antibiotics, antivirals, antifungals, anesthetics, anti-inflammatory agents, and anti-allergic agents.

53. The topical ophthalmic composition according to claim 50, 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.

54. The topical ophthalmic composition according to claim 45, wherein said azalide antibiotic is a compound of formula (I):

55. The topical ophthalmic composition according to claim 45, wherein said azalide antibiotic is azithromycin.

56. The topical ophthalmic composition according to claim 45, wherein said azalide antibiotic is azithromycin dihydrate.

57. The topical ophthalmic composition according to claim 45, wherein the amount of said azalide antibiotic is at least about 5.0%.

58. The topical ophthalmic composition according to claim 45, wherein the amount of said azalide antibiotic is from about 0.01% to about 2%.

59. The topical ophthalmic composition according to claim 45, wherein the amount of said azalide antibiotic is from about 0.1% to about 1%.

60. The topical ophthalmic composition according to claim 45, wherein said topical ophthalmic composition is in the form of a depot.

61. The topical ophthalmic composition according to claim 45, wherein said topical ophthalmic composition is in the form of an aqueous solution, aqueous suspension, an ointment, or an insert.

62. The topical ophthalmic composition according to claim 60, wherein said topical ophthalmic composition is an aqueous solution and has an osmotic pressure of from 10 to 400 mOsM.

63. The topical ophthalmic composition according to claim 45, wherein said topical ophthalmic composition does not contain constituents that are physiologically or ophthalmically harmful to the eye.

64. The composition according to claim 62, wherein said additional medicament is contained in the amount of from about 0.01 to about 5%.

65. The topical ophthalmic composition according to claim 45, wherein said anti-inflammatory agent is contained in an amount of from about 0.01 to about 5%.

66. The topical ophthalmic composition according to claim 45, wherein said anti-inflammatory agent is contained in an amount of from about 0.1 to about 2%.

67. A process for treating an eye, which comprises:

topically applying an ophthalmic composition to an eye, wherein said ophthalmic composition comprises an azalide antibiotic in an amount effective to treat infection in a tissue of the eye, an anti-inflammatory agent and an ophthalmically acceptable carrier.

68. The process for treating an eye of claim 67, wherein said anti-inflammatory agent is a steroidal anti-inflammatory agent.

69. The process for treating an eye of claim 67, wherein said steroidal anti-inflammatory agent is selected from the group consisting of Prednisolone acetate, Fluorometholone and Dexamethasone.

70. The process for treating an eye of claim 67, wherein said steroidal anti-inflammatory agent is Dexamethasone.

71. The process for treating an eye of claim 67, wherein said anti-inflammatory agent is a non-steroidal anti-inflammatory agent.

72. The process for treating an eye of claim 71, wherein said non-steroidal anti-inflammatory agent is selected from the group consisting of diclofenac, flurbiprofen, ketorolac, and suprofen.

73. The process for treating an eye of claim 67, wherein said topical ophthalmic composition comprises an additional medicament.

74. The process for treating an eye of claim 73, wherein said additional medicament is selected from the group consisting of antibiotics, antivirals, antifingals, anesthetics, anti-inflammatory agents, and anti-allergic agents.

75. The process for treating an eye of claim 73, 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.

76. The process for treating an eye of claim 67, wherein said azalide antibiotic is a compound of formula (I):

77. The process for treating an eye of claim 67, wherein said azalide antibiotic is azithromycin.

78. The process for treating an eye of claim 67, wherein said azalide antibiotic is azithromycin dihydrate.

79. The process for treating an eye of claim 67, wherein the amount of said azalide antibiotic is at least about 5.0%.

80. The process for treating an eye of claim 67, wherein the amount of said azalide antibiotic is from about 0.01% to about 2%.

81. The process for treating an eye of claim 67, wherein the amount of said azalide antibiotic is from about 0.1% to about 1%.

82. The process for treating an eye of claim 67, wherein said topical ophthalmic composition is in the form of a depot.

83. The process for treating an eye of claim 67, wherein said topical ophthalmic composition is in the form of an aqueous solution, aqueous suspension, an ointment, or an insert.

84. The process for treating an eye of claim 67, wherein said topical ophthalmic composition is an aqueous solution and has an osmotic pressure of from 10 to 400 mOsM.

85. The process for treating an eye of claim 67, wherein said topical ophthalmic composition does not contain constituents that are physiologically or ophthalmically harmful to the eye.

86. The process for treating an eye of claim 73, wherein said additional medicament is contained in the amount of from about 0.01 to about 5%.

87. The process for treating an eye of claim 67, wherein said steroidal anti-inflammatory agent is contained in an amount of from about 0.01 to about 5%.

88. The process for treating an eye of claim 67, wherein said steroidal anti-inflammatory agent is contained in an amount of from about 0.1 to about 2%.

89. The process for treating an eye of claim 67, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 8 hours.

90. The process for treating an eye of claim 67, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 12 hours.

91. The process for treating an eye of claim 67, wherein said applying provides a therapeutically effective concentration of azalide antibiotic within a tissue of the eye for at least 18 hours.

92. The process for treating an eye of claim 83, wherein said depot remains for at least 30 minutes after administration.

93. The process for treating an eye of claim 83, wherein said depot remains for at least 4 hours after administration.

94. The process for treating an eye of claim 67, wherein said eye is selected from the group consisting of an eye of a human, cow, sheep, horse, pig, goat, rabbit, and dog.

95. The process for treating an eye of claim 67, 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 and combinations thereof, and said amount of said azalide antibiotic is therapeutically effective to treat said condition.