METHODS AND COMPOSITIONS FOR TREATING MUCOSAL INFLAMMATION
Disclosed herein are methods for treating mucositis (e.g., Alternaria -activated mucositis) that involves the direct mucoadministration of an active agent that is antifungal and antibacterial in an amount and for a duration effective to treat mucositis.
1 . A method for treating Alternaria -activated mucositis, comprising directly mucoadministering to a subject in need thereof a composition comprising an active agent that is antifungal and antibacterial such that the Alternaria -activated mucositis is treated.
2 . The method of claim 1 , wherein the Alternaria -activated mucositis is rhinosinusitis.
3 . The method according to any of the preceding claims, wherein the Alternaria -activated mucositis is non-invasive rhinosinusitis.
4 . The method according to any of the preceding claims, wherein the Alternaria -activated mucositis is arrested, significantly reduced or eliminated.
5 . The method according to any of the preceding claims, wherein the Alternaria -activated mucositis is prevented from re-occurrence.
6 . A method for treating a subject with elevated levels of major basic protein in nasal mucin, comprising directly mucoadministering to the subject a composition comprising an active agent that is antifungal and antibacterial such that the levels of major basic protein in the subject are reduced.
7 . The method according to claim 6 , wherein the elevated levels of major basic protein are associated with exposure to an Alternaria species.
8 . A method for preventing or arresting fungus-induced inflammation or eosinophil degranulation in a subject, comprising directly mucoadministering to the subject a composition comprising an active agent that is antifungal and antibacterial such that the fungus-induced eosinophil degranulation is prevented.
9 . The method according to claim 8 , wherein the inflammation or eosinophil degranulation is associated with exposure to an Alternaria species.
10 . A method for reducing the load of Alternaria species in a subject, comprising directly mucoadministering to the subject a composition comprising an active agent that is antifungal and antibacterial such that the load of Alternaria species is reduced.
11 . A method for treating a symptom of Alternaria -activated mucositis, comprising directly mucoadministering to a subject in need thereof a composition comprising an active agent that is antifungal and antibacterial such that at least one symptom of the Alternaria -activated mucositis is treated.
12 . The method according to claim 11 , wherein symptoms of Alternaria -activated mucositis comprise head pressure, nasal pressure, difficulty breathing, nasal airway obstruction, nasal congestion, nasal discharge, head pain, face pain and decreased sense of smell.
13 . The method according to any of claims 1 - 5 , 7 or 9 - 12 , wherein the Alternaria species is Alternaria alternata.
14 . The method according to any of the preceding claims, wherein the active agent comprises at least one agent selected from the group consisting of: antiseptics, methyl and propyl parabens, sodium benzoate, benzyl alcohol, potassium sorbate, sodium metabisulfite, thimerasol, hydrogen peroxide, sodium perborate, polyquad, polyhexamethylene, sodium silver chloride, polyquaternium-1, chlorobutanol.
15 . The method according to any one of claims 1 - 14 , wherein the active agent is benzylalkonium chloride.
16 . The method according to any one of claims 1 - 14 , wherein the active agent is cetylpyridinium chloride.
17 . The method according to any one of claims 1 - 14 , wherein the active agent comprises a methyl paraben, a propyl paraben or combinations of both.
18 . The method according to any one of claims 1 - 14 , wherein the active agent comprises a quaternary ammonium salt.
19 . The method of any of claims 1 - 14 , wherein the active agent comprises at least one quaternary ammonium salt of formula (I):
wherein N has a valency of 5;
R 1 , R 2 , R 3 , R 4 are the same or different and are independently chosen from H, an alkyl group, an alkoxy group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, or a thioacyl group; or two or more of R 1 , R 2 , R 3 or R 4 are taken together with the nitrogen to which they are attached, to form a 5-7 membered heterocyclic ring, and
X is an anion.
20 . The method of claim 19 , wherein X is a halogen.
21 . The method of claim 19 or claim 20 , wherein three of R 1 , R 2 , R 3 or R 4 are taken together with the nitrogen to which they are attached to form a 5-7 membered heterocyclic ring.
22 . The method of any of claims claim 19 - 21 , wherein the compound of formula I is a compound of formula II:
wherein:
U, V, W, Y and Z are each independently selected from the group consisting of CR 5 , CHR 5 , N, NR 5 , O and S;
R 4 is selected from the group consisting of H, an alkyl group, an alkoxy group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, and a thioacyl group;
R 5 is selected from the group consisting of H, an alkyl group, an alkoxy group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an acyl group, and a thioacyl group;
and X is a halogen.
23 . The method of any of claims 19 - 22 , wherein all three occurrences of represent double bonds.
24 . The method of any of claims 19 - 23 , wherein U, V, W, Y and Z are each independently CH.
25 . The method of any of claims 19 - 24 , wherein R 4 is an alkyl group having 6-20 carbon atoms.
26 . The method of any of claims 19 - 25 , wherein the quaternary ammonium salt has the following structure:
wherein X is an anion.
27 . The method according to any of claims 19 - 26 , wherein X is chlorine.
28 . The method according to any of the preceding claims, further comprising co-administering a polysaccharide degrading enzyme.
29 . The method according to any of the preceding claims, further comprising co-administering hyaluronidase.
30 . The method of claim 29 , wherein the hyaluronidase is administered in an amount effective to reduce the viscosity of mucus.
31 . The method of any of claims 18 - 30 , wherein the amount of the quaternary ammonium salt is between about 0.01% and about 0.5% by weight or volume.
32 . The method of any of claims 18 - 30 , wherein the amount of the quaternary ammonium salt is about 0.05% by weight or volume.
33 . The method of any of claims 18 - 30 , wherein the amount of the quaternary ammonium salt is about 0.02% by weight or volume.
34 . The method of any of the preceding claims, comprising administering the formulation for at least two weeks.
35 . The method of any of the preceding claims, comprising administering the formulation for at least one month.
36 . The method of any of the preceding claims, wherein the formulation further comprises a masking agent.
37 . The method of any of the preceding claims, wherein the formulation administered comprises between about 10 μg/ml and about 500 μg/ml active agent.
38 . The method of any of the preceding claims, wherein said active agent is not benzalkonium chloride.
39 . The method of any of the preceding claims, wherein the composition comprises less than about 0.005% benzalkonium chloride.
40 . A pharmaceutical composition comprising an effective amount of an active agent that is antifungal and antibacterial, a polysaccharide degrading enzyme and a pharmaceutically acceptable carrier.
41 . The pharmaceutical composition of claim 40 , wherein the polysaccharide degrading enzyme is hyaluronidase.