Administration of eritoran or pharmaceutically acceptable salts thereof to treat orthomyxovirus infections

Abstract

The present invention is directed to methods for treating orthomyxovirus infections comprising administering to a subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

1 - 37 . (canceled) 
     
     
         38 . A method for treating a patient infected with an H1N1 influenza virus comprising:
 administering to the infected patient in need of said treatment a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof.   
     
     
         39 . The method of claim  1  further comprising administering to the infected patient a therapeutically effective amount of an antiviral compound. 
     
     
         40 . The method of claim  1 , wherein the infected patient is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof following testing positive for the presence of the H1N1 influenza infection. 
     
     
         41 . The method of claim  3 , wherein the infected patient tested for the presence of the H1N1 influenza infection using PCR, rt-PCR direct antigen detection tests, virus isolation in cell culture, or combinations thereof. 
     
     
         42 . The method of claim  1 , further comprising causing a decrease in influenza-induced cytokine mRNA levels in the infected patient. 
     
     
         43 . The method of claim  5 , further comprising causing a decrease in influenza-induced cytokine mRNA levels in the infected patient wherein the cytokines comprise TNF-α, IL-1β, IL-6, COX-2, IL-12 p40, KC, IL-10, IL-5, TGF-β or combinations thereof. 
     
     
         44 . The method of claim  1 , further comprising causing a decrease in influenza-induced interferon-beta or interferon gamma mRNA levels in the infected patient. 
     
     
         45 . The method of claim  1 , wherein the infected patient is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof following the onset of clinical symptoms, wherein the clinical symptoms comprise cough, fever, pneumonia or combinations thereof. 
     
     
         46 . The method of claim  1 , wherein eritoran or a pharmaceutically acceptable salt thereof is administered by one of the routes comprising intravenous administration, intraperitoneal administration, intramuscular administration, intracoronary administration, intraarterial administration, intradermal administration, subcutaneous administration, transdermal delivery, intratracheal administration, intraarticular administration, intraventricular administration, inhalation, intracerebral, nasal, naval, oral, intraocular, pulmonary administration, impregnation of a catheter, by suppository and direct injection into a tissue, or systemically absorbed topical or mucosal administration. 
     
     
         47 . The method of claim  9 , wherein eritoran or a pharmaceutically acceptable salt thereof is administered intravenously. 
     
     
         48 . The method of claim  1 , wherein the effects of administering eritoran or pharmaceutically acceptable salts thereof cause a decrease in viral titers in the infected patient. 
     
     
         49 . The method of claim  1 , wherein the infected patient is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof in a range of from between about 1 μg to about 240 mg, per dose. 
     
     
         50 . A method for treating a patient infected with an H1N1 influenza virus comprising:
 administering to the infected patient in need of said treatment a composition comprising an active ingredient and a pharmaceutically acceptable carrier wherein the active ingredient comprises eritoran or a pharmaceutically acceptable salt thereof.   
     
     
         51 . The method of claim  13 , further comprising administering to the infected patient a therapeutically effective amount of an antiviral compound. 
     
     
         52 . The method of claim  13 , wherein the infected patient is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof following testing positive for the presence of the H1N1 influenza infection. 
     
     
         53 . The method of claim  15 , wherein the infected patient tested for the presence of the H1N1 influenza infection using PCR, rt-PCR direct antigen detection tests, virus isolation in cell culture, or combinations thereof. 
     
     
         54 . The method of claim  13 , further comprising causing a decrease in influenza-induced cytokine mRNA levels in the infected patient. 
     
     
         55 . The method of claim  17 , further comprising causing a decrease in influenza-induced cytokine mRNA levels in the infected patient wherein the cytokines comprise TNF-α, IL-1β, IL-6, COX-2, IL-12 p40, KC, IL-10, IL-5, TGF-β or combinations thereof. 
     
     
         56 . The method of claim  13 , further comprising causing a decrease in influenza-induced interferon-beta or interferon gamma mRNA levels in the infected patient. 
     
     
         57 . The method of claim  13 , wherein the infected patient is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof following the onset of clinical symptoms, wherein the clinical symptoms comprise cough, fever, pneumonia or combinations thereof. 
     
     
         58 . The method of claim  13 , wherein eritoran or a pharmaceutically acceptable salt thereof is administered by one of the routes comprising intravenous administration, intraperitoneal administration, intramuscular administration, intracoronary administration, intraarterial administration, intradermal administration, subcutaneous administration, transdermal delivery, intratracheal administration, intraarticular administration, intraventricular administration, inhalation, intracerebral, nasal, naval, oral, intraocular, pulmonary administration, impregnation of a catheter, by suppository and direct injection into a tissue, or systemically absorbed topical or mucosal administration. 
     
     
         59 . The method of claim  21 , wherein eritoran or a pharmaceutically acceptable salt thereof is administered intravenously. 
     
     
         60 . The method of claim  13 , wherein the effects of administering eritoran or pharmaceutically acceptable salts thereof cause a decrease in viral titers in the infected patient. 
     
     
         61 . The method of claim  13 , wherein the infected patient is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof in a range of from between about 1 μg to about 240 mg, per dose. 
     
     
         62 . A method for mitigating influenza-induced lung pathology, cytokine production, liver enzyme levels, and/or oxidized host phospholipids in an animal infected with an H1N1 influenza virus comprising: administering to the infected animal in need of said mitigation a therapeutically effective amount of a TLR4 antagonist, wherein the TLR4 antagonist comprises eritoran or a pharmaceutically acceptable salt thereof. 
     
     
         63 . The method of claim  25 , further comprising administering to the infected animal a therapeutically effective amount of an antiviral compound. 
     
     
         64 . The method of claim  25 , wherein the infected animal is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof following testing positive for the presence of the H1N1 influenza infection. 
     
     
         65 . The method of claim  27 , wherein the infected animal tested for the presence of the H1N1 influenza infection using PCR, rt-PCR direct antigen detection tests, virus isolation in cell culture, or combinations thereof. 
     
     
         66 . The method of claim  25 , further comprising causing a decrease in influenza-induced cytokine mRNA levels in the infected animal. 
     
     
         67 . The method of claim  29 , further comprising causing a decrease in influenza-induced cytokine mRNA levels in the infected animal wherein the cytokines comprise TNF-α, IL-18, IL-6, COX-2, IL-12 p40, KC, IL-10, IL-5, TGF-8 or combinations thereof. 
     
     
         68 . The method of claim  25 , further comprising causing a decrease in influenza-induced interferon-beta or interferon gamma mRNA levels in the infected animal. 
     
     
         69 . The method of claim  25 , wherein the infected animal is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof following the onset of clinical symptoms, wherein the clinical symptoms comprise cough, fever, pneumonia or combinations thereof. 
     
     
         70 . The method of claim  25 , wherein eritoran or a pharmaceutically acceptable salt thereof is administered by one of the routes comprising intravenous administration, intraperitoneal administration, intramuscular administration, intracoronary administration, intraarterial administration, intradermal administration, subcutaneous administration, transdermal delivery, intratracheal administration, intraarticular administration, intraventricular administration, inhalation, intracerebral, nasal, naval, oral, intraocular, pulmonary administration, impregnation of a catheter, by suppository and direct injection into a tissue, or systemically absorbed topical or mucosal administration. 
     
     
         71 . The method of claim  33 , wherein eritoran or a pharmaceutically acceptable salt thereof is administered intravenously. 
     
     
         72 . The method of claim  25 , wherein the effects of administering eritoran or pharmaceutically acceptable salts thereof cause a decrease in viral titers in the infected animal. 
     
     
         73 . The method of claim  25 , wherein the infected animal is administered a therapeutically effective amount of eritoran or a pharmaceutically acceptable salt thereof in a range of from between about 1 μg to about 240 mg, per dose.