Claims
- 1. A pharmaceutical composition suitable for topical administration to an eye, comprising:
(a) an antibiotic drug in an antibiotic concentration effective for treatment and/or prophylaxis of a gram-positive bacterial infection of at least one tissue of the eye; (b) a pharmaceutically acceptable cyclodextrin compound in a cyclodextrin concentration sufficient to maintain the drug in solution; and (c) cetyl pyridinium chloride.
- 2. The composition of claim 1, wherein the antibiotic drug is an oxazolidinone antibiotic drug and the bacterial infection is a gram-positive bacterial infection.
- 3. The composition of claim 2 wherein the oxazolidinone antibiotic drug is a compound of formula (I)
- 4. The composition of claim 3 wherein, is CH3; R2 and R3 are independently selected from H and F but at least one of R2 and R3 is F; R4 and R5 are each H; n is 1; and X is selected from O, S and SO2.
- 5. The composition of claim 2 wherein the oxazolidinone antibiotic drug is selected from the group consisting of: linezolid, eperezolid, N-((5S)-3-(3-fluoro-4-(4-(2-fluoroethyl)-3-oxopiperazin-1-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide, (S)-N-[[3-[5-(3-pyridyl)thiophen-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide, (S)-N-[[3-[5-(4-pyridyl)pyrid-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride and N-[[(5S)-3-[4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide.
- 6. The composition of claim 2 wherein the oxazolidinone antibiotic drug is linezolid.
- 7. The composition of claim 2, wherein the oxazolidinone antibiotic drug is present at a concentration is about 0.1 mg/ml to about 100 mg/ml.
- 8. The composition of claim 1 wherein the cyclodextrin compound is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, an alkylcyclodextrin, a hydroxyalkylcyclodextrin, a carboxyalkylcyclodextrin, and sulfoalkylether cyclodextrin.
- 9. The composition of claim 1 wherein the cyclodextrin compound is selected from the group consisting of hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin.
- 10. The composition of claim 1 wherein the cyclodextrin compound is present at a concentration of about 1 to about 500 mg/ml.
- 11. The composition of claim 1, wherein the cetyl pyridinium chloride is present at a concentration of about 0.001 to about 10 mg/ml.
- 12. The composition of claim 1, further comprising an antioxidant.
- 13. The composition of claim 12, wherein the antioxidant is selected from the group consisting of sodium thiosulfate, acetyl cysteine, and thioglycerol.
- 14. The composition of claim 12, wherein the antioxidant is selected from the group consisting of sodium sulfite, acetone sodium bisulfite, dithioerythreitol, dithiothreitol, thiourea, and erythorbic acid.
- 15. The composition of claim 12, wherein the antioxidant is sodium bisulfite.
- 16. The composition of claim 1, further comprising at least one ophthalmically acceptable excipient that reduces a rate of removal of the composition from the eye by lacrimation, such that the composition has an effective residence time in the eye of about 2 to about 24 hours.
- 17. The composition of claim 1, further comprising an in situ gellable material in a form selected from a solution, a suspension and a solution/suspension, wherein the in situ gellable material has an ophthalmically compatible pH and osmolality.
- 18. The composition of claim 1, further comprising a buffering agent and/or an agent for adjusting osmolality in amounts whereby the solution is substantially isotonic and has an ophthalmically acceptable pH.
- 19. A method of treating an eye infection in a subject, comprising administering to the subject a therapeutically effective dose of a pharmaceutical composition suitable for topical administration to an eye, comprising:
an antibiotic drug in an antibiotic concentration effective for treatment and/or prophylaxis of a gram-positive bacterial infection of at least one tissue of the eye; a pharmaceutically acceptable cyclodextrin compound in a cyclodextrin concentration sufficient to maintain the drug in solution; and cetyl pyridinium chloride.
- 20. The method of claim 19, wherein the subject is a mammal.
- 21. The method of claim 19, wherein the subject is a human being.
- 22. The method of claim 19, wherein the antibiotic drug is an oxazolidinone antibiotic drug.
- 23. The method of claim 22 wherein the oxazolidinone antibiotic drug is a compound of formula
- 24. The method of claim 23 wherein, in said formula, R1 is CH3; R2 and R3 are independently selected from H and F but at least one of R2 and R3 is F; R4 and R5 are each H; n is 1; and X is selected from O, S and SO2.
- 25. The method of claim 22 wherein the oxazolidinone antibiotic drug is selected from the group consisting of: linezolid, eperezolid, N-((5S)-3-(3-fluoro-4-(4-(2-fluoroethyl)-3-oxopiperazin-1-yl)phenyl)-2-oxooxazolidin-5-ylmethyl)acetamide, (S)-N-[[3-[5-(3-pyridyl)thiophen-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide, (S)-N-[[3-[5-(4-pyridyl)pyrid-2-yl]-2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride and N-[[(5S)-3-[4-(1,1-dioxido-4-thiomorpholinyl)-3 ,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide.
- 26. The method of claim 22 wherein the oxazolidinone antibiotic drug is linezolid.
- 27. The method of claim 26, wherein the pharmaceutical composition is administered in a dose of about 1 to about 100 mg of linezolid at least once per day.
- 28. A pharmaceutical composition suitable for topical administration to an eye, comprising:
(a) linezolid in a concentration effective for treatment and/or prophylaxis of a gram-positive bacterial infection of at least one tissue of the eye; (b) a pharmaceutically acceptable cyclodextrin compound in a cyclodextrin concentration sufficient to maintain the linezolid in solution; and (c) cetyl pyridinium chloride.
- 29. The composition of claim 28 wherein the linezolid concentration is about 0.1 mg/ml to about 100 mg/ml.
- 30. The composition of claim 28 wherein the cyclodextrin compound is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, an alkylcyclodextrin, a hydroxyalkylcyclodextrin, a carboxyalkylcyclodextrin, and sulfoalkylether cyclodextrin.
- 31. The composition of claim 28 wherein the cyclodextrin compound is selected from the group consisting of hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin.
- 32. The composition of claim 28 wherein the cyclodextrin compound is present at a concentration of about 1 mg/ml to about 500 mg/ml.
- 33. The composition of claim 28 wherein the cetyl pyridinium chloride is present at a concentration of about 0.001 to about 10 mg/ml.
- 34. The composition of claim 28 further comprising an antioxidant.
- 35. The composition of claim 34 wherein the antioxidant is selected from the group consisting of sodium thiosulfate, acetyl cysteine, cysteine, thioglycerol, sodium sulfite, acetone sodium bisulfite, dithioerythreitol, thiourea, and erytherythorbic acid.
- 36. The composition of claim 34, wherein the antioxidant is sodium bisulfite.
- 37. The composition of claim 36, wherein the sodium bisulfite is present at a concentration of about 0.1 to about 5 mg/ml.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application No. 60/358,760, filed Feb. 22, 2002.
Provisional Applications (1)
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Number |
Date |
Country |
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60358760 |
Feb 2002 |
US |