Compositions and Methods for Modulating Inflammation Using Fluoroquinolones
Compositions for modulating an inflammation comprise a fluoroquinolone having one of Formulae I-VIII. Methods for modulating an inflammation comprise administering such compositions to a subject in need thereof. The compositions and methods are suitable for modulating an ocular or ophthalmic inflammation, including uveitis, vernal keratoconjunctivitis, or inflammation associated with contact lens-associated corneal infiltrates.
1 . A method for modulating an inflammation in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fluoroquinolone having Formula I, II, III, IV, V, VI, VII, or VIII, or a salt thereof
wherein R 1 is selected from the group consisting of hydrogen, unsubstituted lower alkyl groups, substituted lower alkyl groups, cycloalkyl groups, unsubstituted C 5 -C 24 aryl groups, substituted C 5 -C 24 aryl groups, unsubstituted C 5 -C 24 heteroaryl groups, substituted C 5 -C 24 heteroaryl groups, and groups that can be hydrolyzed in living bodies;
R 2 is selected from the group consisting of hydrogen, unsubstituted amino group, and amino groups substituted with one or two lower alkyl groups;
R 3 is selected from the group consisting of hydrogen, unsubstituted lower alkyl groups, substituted lower alkyl groups, cycloalkyl groups, unsubstituted lower alkoxy groups, substituted lower alkoxy groups, unsubstituted C 5 -C 24 aryl groups, substituted C 5 -C 24 aryl groups, unsubstituted C 5 -C 24 heteroaryl groups, substituted C 5 -C 24 heteroaryl groups, unsubstituted C 5 -C 24 aryloxy groups, substituted C 5 -C 24 aryloxy groups, unsubstituted C 5 -C 24 heteroaryloxy groups, substituted C 5 -C 24 heteroaryloxy groups, and groups that can be hydrolyzed in living bodies;
X is selected from the group consisting of halogen atoms;
Y is selected from the group consisting of CH 2 , O, S, SO, SO 2 , and NR 4 , wherein R 4 is selected from the group consisting of hydrogen, unsubstituted lower alkyl groups, substituted lower alkyl groups, and cycloalkyl groups; and
Z is selected from the group consisting of oxygen and two hydrogen atoms.
2 . The method of claim 1 , wherein said inflammation is selected from the group consisting of uveitis, vernal keratoconjunctivitis, or inflammation associated with contact lens-associated corneal infiltrates.
3 . The method of claim 1 , wherein said inflammation comprises a sequela of an infection.
4 . The method of claim 3 , wherein said infection comprises an ocular or ophthalmic infection.
5 . The method of claim 1 , wherein R 1 is selected from the group consisting of hydrogen, C 1 -C 5 substituted and unsubstituted alkyl groups, C 3 -C 10 cycloalkyl groups, C 5 -C 14 substituted and unsubstituted aryl groups, C 5 -C 14 substituted and unsubstituted heteroaryl groups, and groups that can be hydrolyzed in living bodies. In one embodiment, R 1 is selected from the group consisting of C 1 -C 5 substituted and unsubstituted alkyl groups.
6 . The method of claim 1 , wherein R 2 is selected from the group consisting of unsubstituted amino group and amino groups substituted with one or two C 1 -C 5 alkyl groups.
7 . The method of claim 1 , wherein R 3 is selected from the group consisting of hydrogen, C 1 -C 5 substituted and unsubstituted alkyl groups, C 3 -C 10 cycloalkyl groups, C 1 -C 5 substituted and unsubstituted alkoxy groups, C 5 -C 14 substituted and unsubstituted aryl groups, C 5 -C 14 substituted and unsubstituted heteroaryl groups, and C 5 -C 14 substituted and unsubstituted aryloxy groups.
8 . The method of claim 1 , wherein R 3 is selected from the group consisting of C 3 -C 10 cycloalkyl groups.
9 . The method of claim 1 , wherein X is selected from the group consisting of Cl, F, and Br.
10 . The method of claim 1 , wherein X is Cl.
11 . The method of claim 5 , wherein X is F.
12 . The method of claim 10 , wherein Y is CH 2 .
13 . The method of claim 10 , wherein Z comprises two hydrogen atoms.
14 . The method of claim 1 , wherein Y is NH, Z is O, and X is Cl.
15 . The method of claim 1 , wherein the composition is administered into the subject topically, orally, subcutaneously, or systemically.
16 . The method of claim 1 , wherein the composition comprises a solution, emulsion, dispersion, suspension, ointment, or gel.
17 . The method of claim 16 , wherein the fluoroquinolone or salt thereof is present in an amount from about 0.0001% to 10% by weight of the composition.
18 . The method of claim 17 , wherein the composition further comprises a carrier and a material selected from the group consisting of preservatives, surfactants, adjuvants, antioxidants, tonicity adjusters, viscosity modifiers, solubility enhancers, and combinations thereof.
19 . The method of claim 17 , wherein the composition further comprises a non-steroidal anti-inflammatory drug.
20 . A method for modulating an inflammation in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fluoroquinolone having Formula IV or a salt thereof
21 . The method of claim 20 , wherein the inflammation comprises an ocular or ophthalmic inflammation.
22 . The method of claim 21 , wherein said administering comprises a topical or intraocular administration.
23 . The method of claim 21 , wherein said inflammation comprises a sequela of an infection.
24 . A method for treating, controlling, reducing, or ameliorating an ocular or ophthalmic infection and an inflammatory sequela thereof in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fluoroquinolone having Formula IV or a salt thereof
25 . A method for modulating an inflammation in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fluoroquinolone having Formula VI or a salt thereof
26 . A method for treating, controlling, reducing, or ameliorating an ocular or ophthalmic infection and an inflammatory sequela thereof in a subject, the method comprising administering to the subject a composition comprising an effective amount of a fluoroquinolone having Formula VI or a salt thereof
27 . Use of a fluoroquinolone having Formula I, II, III, IV, V, VI, VII, or VIII for a preparation of a medicament for modulating an inflammation in a subject.
28 . A pharmaceutical composition comprising a fluoroquinolone having Formula I, II, III, IV, V, VI, VII, or VIII, wherein said fluoroquinolone is present in an amount effective to modulate an inflammation.
29 . The pharmaceutical composition of claim 28 , wherein said inflammation comprises a sequela of an infection.
30 . The pharmaceutical composition of claim 29 , wherein said infection comprises an ocular or ophthalmic infection.