OA11351A - Use of antifungal agents for the topical treatmentof fungus-induced mucositis. - Google Patents

Use of antifungal agents for the topical treatmentof fungus-induced mucositis. Download PDF

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Publication number
OA11351A
OA11351A OA1200000119A OA1200000119A OA11351A OA 11351 A OA11351 A OA 11351A OA 1200000119 A OA1200000119 A OA 1200000119A OA 1200000119 A OA1200000119 A OA 1200000119A OA 11351 A OA11351 A OA 11351A
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formulation
mammal
fungus
induced
antifungal
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OA1200000119A
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English (en)
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Jens Ponikau
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Jens Ponikau
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Publication of OA11351A publication Critical patent/OA11351A/en

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Claims (127)

  1. • 011351 - 73 - WHAT IS CLAIMED IS:
    1. A method for treating a mammal having non-invasive fungus-inducedrhinosinusitis, comprising mucoadministering to at least a portion of the nasal-paranasal anatomy of said mammal a formulation in an amount, at a frequency, and 5 for a duration effective to reduce or eliminate said non-invasive fungus-inducedrhinosinusitis, said formulation comprising an antifungal agent.
  2. 2. The method of claim 1, wherein said mammal is a human.
  3. 3. The method of claim 1, wherein said mammal is nonatopic.
  4. 4. The method of claim 1, wherein said mammal is immunocompétent.
  5. 5. The method of claim 1, wherein said non-invasive fungus-induced rhinosinusitis is characterized by polyp formation or polypoid change.
  6. 6. The method of claim 1, wherein said non-invasive fungus-induced rhinosinusitis is chronic.
    1. The method of claim 1, wherein said formulation is in a solid, liquid, or 15 aérosol form.
  7. 8. The method of claim 1, wherein said foAnulation 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, atomizedvapor, aérosol, and tincture.
  8. 9. The method of claim 1, wherein said mucoadministration is a direct muco administration. 011351 - 74 -
  9. 10. The.method of daim 9, wherein said direct mucoadministrationcomprises irrigating said nasal-paranasal anatomy with a liquid form of saidformulation.
  10. 11. The method of claim 9, wherein said direct mucoadministration 5 comprises applying an aérosol form of said formulation to said nasal-paranasalanatomy.
  11. 12. The method of claim 9, wherein said direct mucoadministrationcomprises applying a powder form of said formulation to said nasal-paranasalanatomy.
  12. 13. The method of claim 1, wherein said antifungal agent comprises a macrolide.
  13. 14.. The method of claim 1, wherein said antifungal agent comprises anazole.
  14. 15. The method of claim 1, wherein said antifungal agent interpolâtes fungal 15 cell wall components.
  15. 16. The method of claim 1, wherein said antifungal agent comprises a sterolinhibitor. Y*. \
  16. 17. The method of claim 1, wherein said antifungal agent comprises anantifungal agent selected from the group consisting of amphotericin B, 20 kétoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole,fluconazole, eriseofulvin, clotrimazole, econazole, terconazole, butoconazole,oxiconazole, sulconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine, 011351 -75 · terbinafine hydr'ochloride, morpholines, nystatin, natamycin, butenafine,undecylenic acid, Whitefield’s ointmenî, propionic acid, and caprylic acid.
  17. 18. The method of claim 17, wherein said antifungal agent comprises anantifungal agent selected from the group consisting of amphotericin B, 5 kétoconazole, itraconazole, saperconazole, and voriconazole.
  18. 19. The method of claim 17, wherein said antifungal agent comprisesamphotericin B.
  19. 20. The method of claim 17, wherein said antifungal agent comprisesitraconazole.
  20. 21. The method of claim 1, wherein said formulation comprises a pharmaceutically acceptable aqueous vehicle.
  21. 22. The method of claim 21, wherein said formulation comprises about 0.01ng to about 1000 mg of said antifungal agent per liter.
  22. 23. The method of claim 22. wherein said effective amount comprises about15 0.01 mL to about 1 L of said formulation per nostril of said mammal. ' 24. The method of claim 22, wherein said_effective amount comprises about Ÿ‘ 5 mL to about 100 mL of said formulation per nostril of said mammal.
  23. 25. The method of claim 22, wherein said effective amount comprises about 20 mL of said formulation per nostril of said mammal.
  24. 26. The method of claim 21, wherein said formulation comprises about 1 ng to about 500 mg of said antifungal agent per liter. 011351 - 76 -
  25. 27. The-method of claim 21, wherein said formulation comprises about 100mg of said antifungal agent per liter.
  26. 28. The method of claim 1, wherein said formulation comprises a pluralityof antifungal agents.
  27. 29. The method of claim 1, wherein said effective amount of said formulation comprises about 0.01 ng to about 1000 mg of said antifungal agent perkg of body weight of said mammal.
  28. 30. The method of claim 1, wherein said effective amount of saidformulation comprises about 1 ng to about 500 mg of said antifungal agent per kg 10 of body weight of said mammal.
  29. 31. The method of claim 1, wherein said effective amount of saidformulation remains constant during said effective duration.
  30. 32. The method of claim 1, wherein said effective frequency of saidmucoadministration is from about four times a day to about once every other week.
  31. 33. The method of claim 1, wherein said effective frequency of said mucoadministration is from about twice a day to about once a week.
  32. 34. The method of claim 1, wherein said effective frequency of saidmucoadministration is more frequent than once a day.
  33. 35. The method of claim 1, wherein said effective frequency of said 20 mucoadministration is more frequent than once a week. 011351 - 77 -
  34. 36. Themèthod of claim 1, wherein said effective duration is greater thanabout 7 daÿs.
  35. 37. The method of claim 1, wherein said effective duration is greater thanabout 14 days.
  36. 38. The method of claim 1, wherein said effective duration is greater thanabout 30 days.
  37. 39. The method of claim 1, wherein said effective duration is greater thanabout 60 days.
  38. 40. The method of claim 1, wherein said effective duration is greater than 10 about 90 days. 41. ·. The method of claim 1, wherein said formulation comprises a compound selected front the group consisting of pharmaceutically acceptable aqueous vehicles,pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents,anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, 15 and therapeutic compounds.
  39. 42. The method of claim 1, wherein said method comprises administering to - said mammal a second formulation. x__ y·
  40. 43. The method of claim 42, wherein said second formulation comprises acompound selected from the group consisting of antifungal agents, pharmaceutically 20 acceptable aqueous vehicles, pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents, anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, and therapeutic compounds. - 78 - 011Ξ51
  41. 44. The method of claim 1, said method comprising, after saidmucoadministration, prophylactically mucoadministering to said mammal aprophylactic formulation in an amount, at a frequency, and for a duration effectiveto prevent said non-invasive fungus-induced rhinosinusitis, said prophylactic 5 formulation comprising an antifungal agent.
  42. 45. The method of claim 44, wherein said prophylactic mucoadministrationcomprises direct mucoadministration.
  43. 46. A method for prophylactically treating a mammal at risk for developingnon-invasive fungus-induced rhinosinusitis, comprising mucoadministering to said 10 mammal a formulation in an amount, at a frequency, and for a duration effective toprevent said non-invasive fungus-induced rhinosinusitis, said formulationcomprising an antifungal agent.
  44. 47. A method for treating a mammal having a non-invasive fungus-inducedrhinosinusitis, comprising the steps of: 15 a) identifying said mammal, and b) directly mucoadministering to at least a portion of the nasal-paranasalanatomy of said mammal a formulation in an amount, at a frequency, and for aduration effective to reduce or eliminate said non-invasive fungus-inducedrhinosinusitis, said formulation comprising an antifungal agent. 2Q 48. The method of claim 47, wherein said identifying comprises diagnosing. λ '
  45. 49. A method for prophylactically treating a mammal at risk for developing non-invasive fungus-induced rhinosinusitis, comprising the steps of: a) identifying said mammal, and b) mucoadministering to at least a portion of the nasal-paranasal 25 anatomy of said mammal a formulation in an amount, at a frequency, and for a 011351 - 79 - duration effective’to prevent said non-invasive fungus-induced rhinosinusitis, saidformulation comprising an antifungal agent.
  46. 50. A method for treating a mammal having astnma, comprisingmucoadministering to at least a portion of the airways of said mammal a 5 formulation in an amount, at a frequency, and for a duration effective to reduce oreliminate symptoms of said asthma, said formulation comprising an antifungalagent..
  47. 51. The method of claim 50, wherein said mucoadministration comprises adirect mucoadministration.
  48. 52. The method of claim 51, wherein said direct mucoadministration comprises imgating the nasal-paranasal anatomy of said mammal with a liquidform of said formulation.
  49. 53. The method of claim 51, wherein said direct mucoadministration comprises inhaling said formulation through the mouth or nose of said mammal.
  50. 54. The method of claim 50, wherein said portion comprises nasal airways.
  51. 55. The method of claim 50, wherein said portion comprises lung airways.
  52. 56. The method of claim 50, said method comprising, after saidmucoadministration, prophylactically mucoadministering to said mammal aprophylactic formulation in an amount, at a frequency, and for a duration effective 20 to prevent symptoms of said asthma, said prophylactic formulation comprising an antifungal agent. - 80 -
  53. 57. A method for prophylactically treating a mammal at risk for developing asthma, comprising mucoadministering to at least a portion of the airways of saidmammal a formulation in an amount, at a frequency, and for a duration effective toprevent symptoms of said asthma, said formulation comprising an antifungal agent. 5 58. A method for treating a mammal having asthma, comprising the steps of: a) identifying said mammal, and b) directly mucoadministering to at least a portion of the airways of saidmammal a formulation in an amount, at a frequency, and for a duration effective to 10 reduce or eliminate symptoms of said asthma, said formulation comprising anantifungal agent.
  54. 59. A method for prophylactically treating a mammal at risk for developingasthma, comprising the steps of: a) identifying said mammal, and 15 b) mucoadministering to at least a portion of the airways of said mammal a formulation in an amount, at a frequency, and for a duration effective toprevent symptoms of said asthma, said formulation comprising an antifungal agent.
  55. 60. A method for treating a mammal having non-invasive fungus-inducedintestinal mucositis, comprising mucoadministering to said mammal a formulation 20 in an amount, at a frequency, and for a duration effective to reduce or eliminate- said non-invasive fungus-induced intestinal mucositis, said formulation comprising an antifungal agent.
  56. 61. A method for prophylactically treating a mammal at risk for developingnon-invasive fungus-induced intestinal mucositis, comprising mucoadministering to 25 said mammal a formulation in an amount, at a frequency, and for a duration . 011351 - 81 - effective to prevent said non-invasive fungus-induced intestinal mucositis, saidformulation comprising an antifungal agent.
  57. 62. À method for treating a mammal having a non-invasive fungus-induced intestinal mucositis, comprising the steps of: 5 a) identiîying said mammal, and b) mucoadministering to at least a portion of the digestive tract of saidmammal a formulation in an amount, at a frequency, and for a duration effective toreduce or eliminate said non-invasive fungus-induced intestinal mucositis, saidformulation comprising an antifungal agent.
  58. 63. The method of claim 62, wherein said identifying comprises diagnosing.
  59. 64. A method for prophylactically treating a mammal at risk for developingnon-invasive fungus-induced intestinal mucositis, comprising the steps of: a) identifying said mammal, and b) mucoadministering to at least a portion of the digestive tract of said 15 mammal a formulation in an amount, at a frequency, and for a duration effective toprevent said non-invasive fungus-induced intestinal mucositis, said formulationcomprising an antifungal agent.
  60. 65. A method for treating a mammal having non-invasive fungus-induced- otitis media, comprising mucoadministering to -said mammal a formulation in an Z , 20 amount, at a frequency, and for a duration effective"to reduce or eliminate said s non-invasive fungus-induced otitis media, said formulation comprising an antifungalagent.
  61. 66. A method for prophylactically treating a mammal at risk for developingnon-invasive fungus-induced otitis media, comprising mucoadministering to'said 25 mammal a formulation in an amount, at a frequency, and for a duration effective to 011 Γ < - 82 - prevent said non-invasive funsus-induced otitis media, said formulation comorisin^an antifungal agent.
  62. 67. A method for treating a mammal having a non-invasive fungus-induced otitis media, comprising the steps of: 5 a) identifying said mammal, and b) mucoadministering to at least a portion of the middle ear of said mammal a formulation in an amount, at a frequency, and for a duration effective toreduce or eliminate said non-invasive fungus-induced otitis media, said formulationcomprising an antifungal agent.
  63. 68. The method of ciaim 67, wherein said identifying comprises diagnosins.
  64. 69. A method for prophylactically treating a mammal at risk for developing non-invasive fungus-induced otitis media, comprising the steps of: a) identifying said mammal, and b) mucoadministering to at least a portion of the middle ear of said 15 mammal a formulation in an amount, at a frequency, and for a duration effective toprevent said non-invasive fungus-induced otitis media, said formulation comprisingan antifungal agent.
  65. 70. An article of manufacture, comprising packaging material and a formulation contained within said packaging material, wherein said formulationcomprises an antifungal agent and wherein said packaging material comorises a label or package insert indicating that said formulation can ce directiy mucoadministered to at least a portion of the nasal-paranasai anatomv of a mammal having non-invasive fungus-induced rhinosinusitis in an amount, at a ffequencv,and for a duration effective to reduce cr eliminate said non-invasive furisus-induced 25 rhinosinusitis. 011351 - 83 -
  66. 71. An article of manufacture, comprising packaging material and aformulation contained within said packaging material, wherein said formulationcomprises an antifungal agent and wherein said packaging material comprises alabel or package insert indicating that said formulation can be mucoadministered to 5 at least a portion of the nasal-paranasal anatomy of a mammal at risk fordeveloping non-invasive fungus-induced rhinosinusitis in an amount, at afrequency, and for a duration effective to prevent said non-invasive fungus-inducedrhinosinusitis.
  67. 72. An article of manufacture, comprising packaging material and a 10 formulation contained within said packaging material, wherein said formulationcomprises an antifungal agent and wherein said packaging material comprises alabel or package insert indicating that said formulation can be directlymucoadministered to at least a portion of the airways of a mammal having asthmain an amount, at a frequency, and for a duration effective to reduce or eliminate 15 symptoms of said asthma.
  68. 73. An article of manufacture, comprising packaging material and aformulation contained within said packaging material, wherein said formulationcomprises an antifungal agent and wherein said packaging material comprises alabel or package insert indicating that said formulation can be mucoadministered to 20 at least a portion of the airways of a mammal at risk for developing asthma in anamount, at a frequency, and for a duration effective to prevent symptoms of saidasthma. >''
  69. 74. An article of manufacture, comprising packaging material and aformulation contained within said packaging material, wherein said formulation 25 comprises an antifungal agent and wherein said packaging material comprises alabel or package insert indicating that said formulation can be mucoadministered toa mammal having non-invasive fungus-induced intestinal mucositis in an amount, at - 84 - a frequency, and for a duration effective to reduce or eiiminate said non-invasivefungus-induced intestinal mucositis.
  70. 75. An article of manufacture, comprising packaging material and a formulation contained within said packaging material, wherein said formulation5 comprises an antifungal agent and wherein said packaging material comprises alabel or package insert indicating thaï said formulation can be mucoadministered toa mammal at risk for developing non-invasive fungus-induced intestinal mucositisin an amount, at a frequency, and for a duration effective to prevent said non-invasive fungus-induced intestinal mucositis.
  71. 76. An article of manufacture, comprising packaging material and a formulation contained within said packaging material, wherein said formulationcomprises an antifungal agent and wherein said packaging material comprises alabel or package insert indicating that said formulation can be mucoadministered toa mammal having non-invasive fungus-induced otitis media in an amount, at a 15 frequency, and for a duration effective to reduce or eiiminate said non-invasivefungus-induced otitis media.
  72. 77. An article of manufacture, comprising packaging material and a formulation contained within said packaging material, wherein said formulationcomprises an antifungal agent and wherein said packaging material comprises a 20 label or package insert indicating that said formulation can be mucoadministered toa mammal ai risk for deveicping non-invasive fungps-induced otitis media in anamount. at a freouencv. and for a duration effective to nrevent said non-invasive fungus-induced otitis media.
  73. 78. The use of an antifungal agent in the manufacture of a médicament for 25 treating or preventing non-invasive fungus-induced rhinosinusitis. 011351 - 85 -
  74. 79. The "use as in claim 78, wherein said médicament is mucoadministered to at least a portion of the nasal-paranasal anatomy of a mammal in an amount, at a frequency, and for a duration effective to reduce, eliminate, or prevent said non- invasive fungus-induced rhinosinusitis.
  75. 80. The use as in claim 79, wherein said mucoadministration is a directmucoadministration.
  76. 81. The use as in claim 80, wherein said direct mucoadministrationcomprises irrigating said nasal-paranasal anatomy with a liquid form of saidmédicament.
  77. 82. The use as in claim 80, wherein said direct mucoadministrationcomprises applying an aérosol form of said médicament to said nasal-paranasalanatomy.
  78. 83. The use as in claim 80, wherein said direct mucoadministrationcomprises applying an powder form of said médicament to said nasal-paranasal 15 anatomy.
  79. 84. The use as in claim 79, wherein said effective amount comprises about0.01 mL to about 1 L of said médicament per nostril of said mammal.
  80. 85. The use as in claim 79, wherein said effective amount of saidmédicament remains constant during said effective duration.
  81. 86. The use as in claim 79, wherein said effective frequency of sâid mucoadministration is from about four times a day to about once every other week. 011351 - 86 -
  82. 87. The.use as in claim 79, wherein said effective duration is greater thanabout 7 days.
  83. 88. The use as in claim 78, wherein said non-invasive fungus-inducedrhinosinusitis is characterized by polyp formation or polypoid change.
  84. 89. The use as in claim 78, wherein said non-invasive fungus-induced rhinosinusitis is chronic.
  85. 90. The use as in claim 78, wherein said médicament is in a solid, liquid, oraérosol form.
  86. 91. The use as in claim 78, wherein said médicament is in a form selected10 from the group consisting of a powder, crystalline substance, gel, paste, ointment, salve, créant, solution, suspension, partial liquid, spray, nebulae, mist, atomizedvapor, aérosol, and tincture.
  87. 92. The use as in claim 78, wherein said antifungal agent comprises amacrolide.
  88. 93. The use as in claim 78, wherein said antifungal agent comprises an azole.
  89. 94. The use as in claim 78, wherein said antifungal agent comprises an antifungal agent selected front the group consisting of amphotericin B,kétoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole, 20 fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole,oxiconazole, sulconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine,terbinafme hydrochloride, morpholines, nystatin, natamycin, butenafine,undecylenic acid, Whitefield’s ointment, propionic acid, and caprylic acid. 01 1 - 87 -
  90. 95. Theuse as in claim 78, wherein said médicament comprises apharmaceutically acceptable aqueous vehicle.
  91. 96. The use as in claim 95, wherein said médicament comprises about 1 ngto about 500 mg of said antifungal agent per liter.
  92. 97. The use as in claim 95, wherein said médicament comprises about 100mg of said antifungal agent per . liter.
  93. 98. The use as in claim 78, wherein said médicament comprises about 0.01ng to about 1000 mg of said antifungal agent per liter.
  94. 99. The use as in claim 78, wherein said médicament comprises a plurality10 of antifungal agents.
  95. 100. The use as in claim 78, wherein said médicament comprises a compoundselected ffom the group consisting of pharmaceutically acceptable aqueous vehicles,pharmaceutically acceptable solid vehicles, mucolytic agents, antibacterial agents,anti-inflammatory agents, immunosuppressants, dilators, vaso-constrictors, steroids, 15 and therapeutic compounds.
  96. 101. . The use of an antifungal agent in the manufacture of a médicament for treating or preventing asthma. __ v
  97. 102. The use as in claim 101, wherein said médicament is mucoadministeredto at least a portion of the airways of a mammal in an amount, at a frequency, and 20 for a duration effective to reduce, eliminate, or prevent symptoms of said asthma.
  98. 103. The use of an antifungal agent in the manufacture of amedicament fortreating or preventing non-invasive fungus-induced intestinal mucositis. 011Z51 - 88 -
  99. 104. The.use as in claim 103, wherein said médicament is mucoadministeredto a mammal in an amount, at a frequency, and for a duration effective to reduce,eliminate, or prevent symptoms of said non-invasive fungus-induced intestinalmucositis.
  100. 105. The use of an antifungal agent in the manufacture of a médicament fortreating or preventing non-invasive fungus-induced otitis media.
  101. 106. The use as in claim 105, wherein said médicament is mucoadministeredto a mammal in an amount, at a frequency, and for a duration effective to reduce,eliminate, or prevent symptoms of said non-invasive fungus-induced otitis media.
  102. 107. An antifungal formulation comprising an antifungal agent, a flavoring,and water, wherein said water comprises at least about 50 percent of saidformulation.
  103. 108. The antifungal formulation of claim 107, wherein said water comprisesat least about 75 percent of said formulation.
  104. 109. The antifungal formulation of claim 107, wherein said water comprisesat least about 85 percent of said formulation.
  105. 110. An antifungal formulation comprising an antifungal agent, a flavoring,and water, wherein said water comprises at least abcut 50 percent of saidformulation, and wherein said antifungal agent comprises an antifungal agent20 selected from the group consisting of amphotericin B, kétoconazole, saperconazoie,voriconazole, flucytosine, miconazole. fiuconazole, griseofulvin, clotrimazole,econazole, terconazoie, butoconazole, oxiconazole, sulconazole, ciclopirox oinmlne.halccrozin. tclnafznte. nafriflns. terhinaflze hvcrcchlcride. mcmhcüne" rv^tatin 011351 - 89 - natamycin, butenafine, undecylenic acid, Whitefield’s ointment, propionic acid, andcaprylic acid.
  106. 111. An antifungal formulation comprising itraconazole and water, whereinsaid itraconazole is dissolved in said formulation at a concentration greater than 5 about 25 pg per mL and wherein said water comprises at least about 50 percent ofsaid formulation.
  107. 112. The antifungal formulation of ciaim 111, wherein said formulationcomprises polyethylene glycol.
  108. 113. The antifungal formulation of ciaim 111, wherein said formulation 10 comprises a flavoring.
  109. 114. An antifungal formulation comprising itraconazole and water, whereinsaid itraconazole is suspended in said formulation at a concentration greater thanabout 25 pg per mL and wherein said water comprises at least about 50 percent ofsaid formulation. 15 115. A method of making an antifungal formulation, said formulation comprising itraconazole and water, wherein said itraconazole is dissolved in saidformulation at a concentration greater than about 25 pg per mL and wherein saidwater comprises at least about 50 percent of said. formulation, said methodcomprising adding said water to a stock solution coritaining said itraconazole. 20 116. A method for culturing fungus from a mammaFs mucus, said methodcomprising: a) contactas said mucus with a mucolvtic agent to reduce the viscosityof said mucus, b) separating said fungus from said reduced-viscosity mucus, - 90- c) contacting said separated fungus with fungus growth medium to forma fungus culture, and d) incubating said fungus culture such that said separated fungus grows.
  110. 117. A method for obtaining a fungal antigen, said method comprising: 5 a) contacting a mammal’s mucus with a mucolytic agent to reduce the viscosity of said mucus, b) separating fungus from said reduced-viscosity mucus, c) contacting said separated fungus with fungus growth medium to forma fungus culture, 10 d) incubating said fungus culture such that said separated fungus grows, and e) isolating said antigen from said cultured fungus.
  111. 118. A method for producing a fungus-specific antibody, said methodcomprising: 15 a) contacting a mammal’s mucus with a mucolytic agent to reduce the viscosity of said mucus, b) separating fungus from said reduced-viscosity mucus, c) contacting said separated fungus with fungus growth medium to forma fungus culture, 20 d) incubating said fungus culture such that said separated fungus grows, e) isolating a fungal antigen from said cultured fungus, and f) immunizing an animal with said fungal'. antigen to produce said antibody.
  112. 119. A nasal mucus collecting apparatus, comprising:a) a collection retainer, said collection retainer being suitable for retaining mucus, 25 011351 - 91 - b) a'eollection tube extending from said collection retainer, wherein saidcollection tube defines a distal end and a;- lumen such that mucus can traverse saidlumen from said distal end of said collection tube to said collection retainer, saidcollection tube being generally flexible over at least a portion of the length of said5 collection tube such that said collection tube can be selectively manipulated into adesired configuration by a practitioner during a collection procedure, said collectiontube furiher being generally malléable such that said collection tube generallyretains said desired configuration until the practitioner manipulâtes said collectiontube to conform to a different configuration, and 10 c) a connecting portion extending from said collection retainer, wherein said connecting portion defines a second lumen that communicates with the interiorof said collection retainer, said connecting portion being adapted to receive avacuum source.
  113. 120. The apparatus of claim 119, wherein said apparatus comprises a valve 15 that adjusts the opening of said second lumen.
  114. 121. The apparatus of claim 119, wherein said collection retainer isremovable from said collection tube and said connection portion.
  115. 122. A pharmaceutical composition comprising an antifungal agent ·' 123. A pharmaceutical composition comprising an antifungal agent and a V*·' 20 mucolytic agent
  116. 124. A pharmaceutical composition comprising an antifungal agent and asteroid.
  117. 125. A pharmaceutical composition comprising an antifungal agent and adecongestant. 01135 ι - 92 -
  118. 126. A pharmaceutical composition comprising an antifungal agent and anantibiotic.
  119. 127. A pharmaceutical composition comprising an antifungal agent and ananti-inflammatory. 5 128. A composition for treating an immune response to fungus in a mammal, characterized by an agent configured for direct mucoadministration to the mucus ofthe mammal and having antifungal means for eliminating or reducing the fungusbelow a threshold level wherein the fungus ceases to activate éosinophile migrationto the affected area. 10 129. A pharmaceutical composition for treating a fungal related condition in the nasal-sinus anatomy, pulmonary anatomy, ear anatomy, or intestinal anatomy ofa mammalian patient, said composition comprising an effective dose of an anti-fungal as described herein.
  120. 130. A pharmaceutical composition for treating a fungal related condition in 15 the nasal-sinus anatomy, pulmonary anatomy, ear anatomy, or intestinal anatomy ofa mammalian patient, said composition comprising an effective dose of an anti-fungal and at least one other agent or inhibitor as described herein.
  121. 131. A pharmaceutical composition for treating a fungal related condition inthe nasal sinus anatomv, pulmonarv anatomv, ear anatomy, or intestinal anatomv of λ ' 20 a mammalian patient, said composition comprising an effective dose of an anti-fungal suitable for long term use within the nasal-sinus anatomy.
  122. 132. A médication for treating sinusitis, asthma, otitis media, or colitis of apatient, comprising a mucolytic agent; and an anti-fungal compound as describedherein. 011351 - 93 -
  123. 133. An-irrigation médication for treating an inflamed nasal area, lung area,ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area,or intestinal area being caused by the presence of a fungus, the médicationcomprising effective doses of an antifungal compound and a steroid as described 5 herein.
  124. 134. An irrigation médication for treating an inflamed nasal area, lung area,ear area, or intestinal area of a. patient, the inflamed nasal area, lung area, ear area,or intestinal area being causedby the presence of a fungus, the médicationcomprising effective doses of an antifungal compound and a mucolytic agent.
  125. 135. An irrigation médication for treating an inflamed nasal area, lung area, ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area,or intestinal area being caused by the presence of a fungus, the médicationcomprising effective doses of a steroid and a mucolytic agent as described herein.
  126. 136. .An irrigation médication for treating an inflamed nasal area, lung area. 15 ear area, or intestinal area of a patient, the inflamed nasal area, lung area, ear area, or intestinal area being caused by the presence of a fungus, the médicationcomprising effective doses of an antifungal compound, a steroid, and a mucolyticagent as described herein.
  127. 137. - An irrigation médication for treating_an inflamed nasal area, lung area, 20 ear area, or intestinal area of a patient, the inflame^· -nasal area, lung area, ear area. or intestinal area being caused by the presence of a fungus. the médicationcomprising .an effective dose of ai least one medicine selected èom the groupconsisting of an antifungal compound, a steroid, a mucciytic agent, and anycombination thereof as described herein.
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US6270997P 1997-10-22 1997-10-22
US6341897P 1997-10-28 1997-10-28
US6341497P 1997-10-28 1997-10-28
US8327298P 1998-04-28 1998-04-28
US8639798P 1998-05-22 1998-05-22

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