Methods and materials for treating and preventing inflammation of mucosal tissue

Abstract

The invention involves methods and materials for treating and preventing non-invasive fungus-induced mucositis. Specifically, the invention involves administrating an antifungal agent such that it contact mucus in an amount, at a frequency, and for a duration effective to prevent, reduce, or eliminate non-invasive fungus-induced rhinosinusitis. This invention also provides methods and materials for diagnosing non-invasive fungus-induced rhinosinusitis and culturing non-invasive fungus from a mammalian mucus sample as well as specific antifungal formulations and medical devices for treating and preventing non-invasive fungus-induced rhinosinusitis. In addition, the invention provides methods and materials for treating and preventing other non-invasive fungus-induced mucositis conditions such as chronic otitis media, chronic colitis, and Crohn's disease. Further, the invention involves methods and materials for treating and preventing chronic asthma symptoms.

1 - 69 . (canceled)  
     
     
         70 . A method for treating a mammal having asthma and non-invasive fungus-induced rhinosinusitis, comprising effectively mucoadministering a formulation in an amount, at a frequency, and for a duration to said mammal, wherein said formulation comprises an antifungal agent.  
     
     
         71 . The method of  claim 70 , wherein said mammal is a human.  
     
     
         72 . The method of  claim 70 , wherein said mammal is nonatopic.  
     
     
         73 . The method of  claim 70 , wherein said mammal is immunocompetent.  
     
     
         74 . The method of  claim 70 , wherein said asthma is chronic.  
     
     
         75 . The method of  claim 70 , wherein said non-invasive fungus-induced rhinosinusitis is chronic.  
     
     
         76 . The method of  claim 70 , wherein said non-invasive fungus-induced rhinosinusitis is characterized by polyp formation or polypoid change.  
     
     
         77 . The method of  claim 70 , wherein said mucoadministration comprises direct mucoadministration.  
     
     
         78 . The method of  claim 70 , wherein said method comprises mucoadministering said formulation to at least a portion of the nasal-paranasal anatomy of said mammal.  
     
     
         79 . The method of  claim 70 , wherein said method comprises mucoadministering said formulation to at least a portion of the airways of said mammal.  
     
     
         80 . The method of  claim 70 , wherein said method comprises mucoadministering said formulation to at least a portion of the lung airways of said mammal.  
     
     
         81 . The method of  claim 70 , wherein said formulation is in a solid form.  
     
     
         82 . The method of  claim 70 , wherein said formulation is in a liquid form.  
     
     
         83 . The method of  claim 70 , wherein said formulation is in an aerosol form.  
     
     
         84 . The method of  claim 70 , wherein said formulation is in a form selected from the group consisting of a powder, crystalline substance, gel, paste, ointment, salve, cream, solution, suspension, partial liquid, spray, nebulae, mist, atomized vapor, aerosol, and tincture.  
     
     
         85 . The method of  claim 70 , wherein said mucoadministration comprises irrigating at least a portion of the nasal-paranasal anatomy of said mammal with a liquid form of said formulation.  
     
     
         86 . The method of  claim 70 , wherein said mucoadministration comprises applying an aerosol form of said formulation to at least a portion of the nasal-paranasal anatomy of said mammal.  
     
     
         87 . The method of  claim 70 , wherein said mucoadministration comprises applying a powder form of said formulation to at least a portion of the nasal-paranasal anatomy of said mammal.  
     
     
         88 . The method of  claim 70 , wherein said antifungal agent comprises a macrolide.  
     
     
         89 . The method of  claim 70 , wherein said antifungal agent comprises an azole.  
     
     
         90 . The method of  claim 70 , wherein said antifungal agent interpolates fungal cell wall components.  
     
     
         91 . The method of  claim 70 , wherein said antifungal agent comprises a sterol inhibitor.  
     
     
         92 . The method of  claim 70 , wherein said antifungal agent comprises an antifungal agent selected from the group consisting of amphotericin B, ketoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield's ointment, propionic acid, and caprylic acid.  
     
     
         93 . The method of  claim 70 , wherein said antifungal agent comprises an antifungal agent selected from the group consisting of amphotericin B, ketoconazole, itraconazole, saperconazole, and voriconazole.  
     
     
         94 . The method of  claim 70 , wherein said antifungal agent comprises amphotericin B.  
     
     
         95 . The method of  claim 70 , wherein said antifungal agent comprises itraconazole.  
     
     
         96 . The method of  claim 70 , wherein said formulation comprises a pharmaceutically acceptable aqueous vehicle.  
     
     
         97 . The method of  claim 96 , wherein said formulation comprises about 0.01 ng to about 1000 mg of said antifungal agent per liter.  
     
     
         98 . The method of  claim 96 , wherein said amount comprises about 0.01 mL to about 1 L of said formulation per nostril of said mammal.  
     
     
         99 . The method of  claim 96 , wherein said amount comprises about 5 mL to about 100 mL of said formulation per nostril of said mammal.  
     
     
         100 . The method of  claim 96 , wherein said amount comprises about 20 mL of said formulation per nostril of said mammal.  
     
     
         101 . The method of  claim 96 , wherein said formulation comprises about 1 ng to about 500 mg of said antifungal agent per liter.  
     
     
         102 . The method of  claim 96 , wherein said formulation comprises about 100 mg of said antifungal agent per liter.  
     
     
         103 . The method of  claim 70 , wherein said formulation comprises a plurality of antifungal agents.  
     
     
         104 . The method of  claim 70 , wherein said amount of said formulation comprises about 0.01 ng to about 1000 mg of said antifungal agent per kg of body weight of said mammal.  
     
     
         105 . The method of  claim 70 , wherein said amount of said formulation comprises about 1 ng to about 500 mg of said antifungal agent per kg of body weight of said mammal.  
     
     
         106 . The method of  claim 70 , wherein said amount of said formulation remains constant during said effective duration.  
     
     
         107 . The method of  claim 70 , wherein said frequency of said mucoadministration is from about four times a day to about once every other week.  
     
     
         108 . The method of  claim 70 , wherein said frequency of said mucoadministration is from about twice a day to about once a week.  
     
     
         109 . The method of  claim 70 , wherein said frequency of said mucoadministration is more frequent than once a day.  
     
     
         110 . The method of  claim 70 , wherein said frequency of said mucoadministration is more frequent than once a week.  
     
     
         111 . The method of  claim 70 , wherein said duration is greater than about 7 days.  
     
     
         112 . The method of  claim 70 , wherein said duration is greater than about 14 days.  
     
     
         113 . The method of  claim 70 , wherein said duration is greater than about 30 days.  
     
     
         114 . The method of  claim 70 , wherein said duration is greater than about 60 days.  
     
     
         115 . The method of  claim 70 , wherein said duration is greater than about 90 days.  
     
     
         116 . The method of  claim 70 , wherein said formulation comprises a compound selected from the group consisting of pharmaceutically acceptable aqueous vehicles, pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents, anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, and therapeutic compounds.  
     
     
         117 . The method of  claim 70 , wherein said method comprises administering to said mammal a second formulation.  
     
     
         118 . The method of  claim 117 , wherein said second formulation comprises a compound selected from the group consisting of antifungal agents, pharmaceutically acceptable aqueous vehicles, pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents, anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, and therapeutic compounds.  
     
     
         119 . The method of  claim 70 , said method comprising, after said mucoadministration, prophylactically mucoadministering to said mammal a prophylactic formulation in an amount, at a frequency, and for a duration, wherein said prophylactic formulation comprises an antifungal agent.  
     
     
         120 . The method of  claim 119 , wherein said prophylactic mucoadministration comprises direct mucoadministration.  
     
     
         121 . The method of  claim 70 , wherein said non-invasive fungus-induced rhinosinusitis comprises the presence of allergic mucus.  
     
     
         122 . The method of  claim 70 , wherein said non-invasive fungus-induced rhinosinusitis comprises the presence of a polyp.  
     
     
         123 . The method of  claim 70 , wherein said non-invasive fungus-induced rhinosinusitis comprises eosinophilia.  
     
     
         124 . The method of  claim 70 , wherein said mucoadministration begins during a period noncoincident with an intraoperative period, said intraoperative period being the time during a nasal surgery.  
     
     
         125 . The method of  claim 124 , wherein said mammal had a nasal surgery before said mucoadministration.  
     
     
         126 . The method of  claim 124 , wherein said mammal was nasal surgery-free before said mucoadministration.  
     
     
         127 . A method for treating a mammal having asthma and non-invasive fungus-induced rhinosinusitis, comprising the steps of: 
 a) identifying said mammal, and    b) effectively mucoadministering a formulation in an amount, at a frequency, and for a duration to said mammal, wherein said formulation comprises an antifungal agent.    
     
     
         128 . The method of  claim 127 , wherein said identifying comprises diagnosing.  
     
     
         129 . The method of  claim 127 , wherein said non-invasive fungus-induced rhinosinusitis comprises the presence of a polyp.  
     
     
         130 . The method of  claim 127 , wherein said non-invasive fungus-induced rhinosinusitis comprises the presence of allergic mucus.  
     
     
         131 . The method of  claim 127 , wherein said non-invasive fungus-induced rhinosinusitis comprises eosinophilia.  
     
     
         132 . The method of  claim 127 , wherein said mammal is a human.  
     
     
         133 . The method of  claim 127 , wherein said mammal is nonatopic.  
     
     
         134 . The method of  claim 127 , wherein said mammal is immunocompetent.  
     
     
         135 . The method of  claim 127 , wherein said mucoadministration comprises direct mucoadministration.  
     
     
         136 . The method of  claim 127 , wherein said method comprises mucoadministering said formulation to at least a portion of the nasal-paranasal anatomy of said mammal.  
     
     
         137 . The method of  claim 127 , wherein said method comprises mucoadministering said formulation to at least a portion of the airways of said mammal.  
     
     
         138 . The method of  claim 127 , wherein said method comprises mucoadministering said formulation to at least a portion of the lung airways of said mammal.  
     
     
         139 . The method of  claim 127 , wherein said formulation is in a solid form.  
     
     
         140 . The method of  claim 127 , wherein said formulation is in a liquid form.  
     
     
         141 . The method of  claim 127 , wherein said formulation is in an aerosol form.  
     
     
         142 . The method of  claim 127 , wherein said formulation is in a form selected from the group consisting of a powder, crystalline substance, gel, paste, ointment, salve, cream, solution, suspension, partial liquid, spray, nebulae, mist, atomized vapor, aerosol, and tincture.  
     
     
         143 . The method of  claim 127 , wherein said mucoadministration comprises irrigating at least a portion of the nasal-paranasal anatomy of said mammal with a liquid form of said formulation.  
     
     
         144 . The method of  claim 127 , wherein said mucoadministration comprises applying an aerosol form of said formulation to at least a portion of the nasal-paranasal anatomy of said mammal.  
     
     
         145 . The method of  claim 127 , wherein said mucoadministration comprises applying a powder form of said formulation to at least a portion of the nasal-paranasal anatomy of said mammal.  
     
     
         146 . The method of  claim 127 , wherein said antifungal agent comprises a macrolide.  
     
     
         147 . The method of  claim 127 , wherein said antifungal agent comprises an azole.  
     
     
         148 . The method of  claim 127 , wherein said antifungal agent interpolates fungal cell wall components.  
     
     
         149 . The method of  claim 127 , wherein said antifungal agent comprises a sterol inhibitor.  
     
     
         150 . The method of  claim 127 , wherein said antifungal agent comprises an antifungal agent selected from the group consisting of amphotericin B, ketoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield's ointment, propionic acid, and caprylic acid.  
     
     
         151 . The method of  claim 127 , wherein said antifungal agent comprises an antifungal agent selected from the group consisting of amphotericin B, ketoconazole, itraconazole, saperconazole, and voriconazole.  
     
     
         152 . The method of  claim 127 , wherein said antifungal agent comprises amphotericin B.  
     
     
         153 . The method of  claim 127 , wherein said antifungal agent comprises itraconazole.  
     
     
         154 . The method of  claim 127 , wherein said formulation comprises a pharmaceutically acceptable aqueous vehicle.  
     
     
         155 . The method of  claim 154 , wherein said formulation comprises about 0.01 ng to about 1000 mg of said antifungal agent per liter.  
     
     
         156 . The method of  claim 154 , wherein said amount comprises about 0.01 mL to about 1 L of said formulation per nostril of said mammal.  
     
     
         157 . The method of  claim 154 , wherein said amount comprises about 5 mL to about 100 mL of said formulation per nostril of said mammal.  
     
     
         158 . The method of  claim 154 , wherein said amount comprises about 20 mL of said formulation per nostril of said mammal.  
     
     
         159 . The method of  claim 154 , wherein said formulation comprises about 1 ng to about 500 mg of said antifungal agent per liter.  
     
     
         160 . The method of  claim 154 , wherein said formulation comprises about 100 mg of said antifungal agent per liter.  
     
     
         161 . The method of  claim 154 , wherein said formulation comprises a plurality of antifungal agents.  
     
     
         162 . The method of  claim 127 , wherein said amount of said formulation comprises about 0.01 ng to about 1000 mg of said antifungal agent per kg of body weight of said mammal.  
     
     
         163 . The method of  claim 127 , wherein said amount of said formulation comprises about 1 ng to about 500 mg of said antifungal agent per kg of body weight of said mammal.  
     
     
         164 . The method of  claim 127 , wherein said amount of said formulation remains constant during said effective duration.  
     
     
         165 . The method of  claim 127 , wherein said frequency of said mucoadministration is from about four times a day to about once every other week.  
     
     
         166 . The method of  claim 127 , wherein said frequency of said mucoadministration is from about twice a day to about once a week.  
     
     
         167 . The method of  claim 127 , wherein said frequency of said mucoadministration is more frequent than once a day.  
     
     
         168 . The method of  claim 127 , wherein said frequency of said mucoadministration is more frequent than once a week.  
     
     
         169 . The method of  claim 127 , wherein said duration is greater than about 7 days.  
     
     
         170 . The method of  claim 127 , wherein said duration is greater than about 14 days.  
     
     
         171 . The method of  claim 127 , wherein said duration is greater than about 30 days.  
     
     
         172 . The method of  claim 127 , wherein said duration is greater than about 60 days.  
     
     
         173 . The method of  claim 127 , wherein said duration is greater than about 90 days.  
     
     
         174 . The method of  claim 127 , wherein said formulation comprises a compound selected from the group consisting of pharmaceutically acceptable aqueous vehicles, pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents, anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, and therapeutic compounds.  
     
     
         175 . The method of  claim 127 , wherein said method comprises administering to said mammal a second formulation.  
     
     
         176 . The method of  claim 175 , wherein said second formulation comprises a compound selected from the group consisting of antifungal agents, pharmaceutically acceptable aqueous vehicles, pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents, anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, and therapeutic compounds.  
     
     
         177 . The method of  claim 127 , wherein said mucoadministration begins during a period noncoincident with an intraoperative period, said intraoperative period being the time during a nasal surgery.  
     
     
         178 . The method of  claim 177 , wherein said mammal had a nasal surgery before said mucoadministration.  
     
     
         179 . The method of  claim 177 , wherein said mammal was nasal surgery-free before said mucoadministration.  
     
     
         180 . The method of  claim 127 , said method comprising, after said mucoadministration, prophylactically mucoadministering a prophylactic formulation in an amount, at a frequency, and for a duration to said mammal, wherein said prophylactic formulation comprises an antifungal agent.  
     
     
         181 . The method of  claim 180 , wherein said prophylactic mucoadministration comprises direct mucoadministration.