Modulation of inflammation by hops fractions and derivatives

Abstract

A natural formulation of compounds that would to modulate inflammation is disclosed. The formulation would also inhibit expression of COX-2, inhibit synthesis of prostaglandins selectively in target cells, and inhibit inflammatory response selectively in target cells. The compositions containing at least one fraction isolated or derived from hops.

What is claimed is:  
     
         1 . A method of modulating the inflammatory response in cells, the method comprising contacting the cells with a composition comprising a fraction isolated or derived from hops.  
     
     
         2 . A method of treating or inhibiting a pathological condition in a mammal associated with tissue-specific activation of inflammation, the method comprising administering to the mammal a composition comprising a fraction derived from hops.  
     
     
         3 . The method of  claim 2 , wherein the fraction derived from hops is selected from the group consisting of isoalpha acids, reduced isoalpha acids, tetra-hydroisoalpha acids, hexa-hydroisoalpha acids, beta acids, and spent hops.  
     
     
         4 . The method of  claim 2 , wherein the fraction derived from hops comprises a compound of a supragenus having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl;  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 ; and  
         wherein R, T, X, and Z are independently selected from the group consisting of H, F, Cl, Br, I, and π orbital, with the proviso that if one of R, T, X, or Z is a π orbital, then the adjacent R, T, X, or Z is also a π orbital, thereby forming a double bond.  
       
     
     
         5 . The method of  claim 2 , wherein the fraction derived from hops comprises a compound of Genus A having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .  
       
     
     
         6 . The method of  claim 2 , wherein the fraction derived from hops comprises a compound of Genus B having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .  
       
     
     
         7 . The method of  claim 2 , wherein the fraction derived from hops comprises a compound selected from the group consisting of cohumulone, adhumulone, isohumulone, isocohumulone, isoadhumulone, dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.  
     
     
         8 . The method of  claim 2 , wherein the composition comprises about 0.5 to 10000 mg of the fraction derived from hops.  
     
     
         9 . The method of  claim 8 , wherein the composition comprises about 50 to 7500 mg of the fraction derived from hops.  
     
     
         10 . The method of  claim 2 , wherein the composition comprises about 0.001 to 10 weight percent of the fraction derived from hops.  
     
     
         11 . The method of  claim 10 , wherein the composition comprises about 0.1 to 1 weight percent of the fraction derived from hops.  
     
     
         12 . The method of  claim 2 , wherein the pathological condition is selected from the group consisting of autoimmune diseases, inflammatory diseases, neurological diseases, and cancer.  
     
     
         13 . The method of  claim 2 , wherein the pathological condition is selected from the group consisting of inflammation, inflammation-associated disorders, arthritis, asthma, bronchitis, menstrual cramps, tendonitis, bursitis, skin-related conditions, gastrointestinal conditions, cancer, ophthalmic diseases, pulmonary inflammation, nervous system disorders, allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, atherosclerosis, and central nervous damage.  
     
     
         14 . The method of  claim 2 , wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         15 . The method of  claim 2 , wherein the composition is administered orally, topically, parenterally, or rectally.  
     
     
         16 . A method of modulating the amount of cyclooxygenase-2 (COX-2) activity in target cells without substantially modulating COX-2 activity in non-target cells, the method comprising contacting the cells with a fraction derived from hops.  
     
     
         17 . The method of  claim 16 , wherein the non-target cells are also contacted with said fraction derived from hops.  
     
     
         18 . The method of  claim 16 , wherein the contacting step is in vivo.  
     
     
         19 . The method of  claim 16 , wherein the COX-2 activity is modulated by inhibition of COX-2 gene.  
     
     
         20 . A method of treating or inhibiting a pathological condition in a mammal involving inhibiting inducibility or activity of cyclooxygenase-2 (COX-2), the method comprising administering to the mammal a composition comprising a fraction derived from hops.  
     
     
         21 . The method of  claim 20 , wherein the fraction derived from hops is selected from the group consisting of isoalpha acids, reduced isoalpha acids, tetra-hydroisoalpha acids, hexa-hydroisoalpha acids, beta acids, and spent hops.  
     
     
         22 . The method of  claim 20 , wherein the fraction derived from hops comprises a compound of a supragenus having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl;  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 ; and  
         wherein R, T, X, and Z are independently selected from the group consisting of H, F, Cl, Br, I, and π orbital, with the proviso that if one of R, T, X, or Z is a π orbital, then the adjacent R, T, X, or Z is also a π orbital, thereby forming a double bond.  
       
     
     
         23 . The method of  claim 20 , wherein the fraction derived from hops comprises a compound of Genus A having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .  
       
     
     
         24 . The method of  claim 20 , wherein the fraction derived from hops comprises a compound of Genus B having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .  
       
     
     
         25 . The method of  claim 20 , wherein the fraction derived from hops comprises a compound selected from the group consisting of cohumulone, adhumulone, isohumulone, isocohumulone, isoadhumulone, dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.  
     
     
         26 . The method of  claim 20 , wherein the pathological condition is selected from the group consisting of wherein the pathological condition is selected from the group consisting of inflammation, inflammation-associated disorders, arthritis, asthma, bronchitis, menstrual cramps, tendonitis, bursitis, skin-related conditions, gastrointestinal conditions, cancer, ophthalmic diseases, pulmonary inflammation, nervous system disorders, allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, atherosclerosis, and central nervous damage.  
     
     
         27 . The method of  claim 20 , wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         28 . The method of  claim 20 , wherein the composition is administered orally, topically, parenterally, or rectally.  
     
     
         29 . A method of inhibiting prostaglandin synthesis selectively in target cells, the method comprising contacting the cells with a fraction derived from hops.  
     
     
         30 . The method of  claim 29 , wherein the fraction derived from hops is selected from the group consisting of-isoalpha acids, reduced isoalpha acids, tetra-hydroisoalpha acids, hexa-hydroisoalpha acids, beta acids, and spent hops.  
     
     
         31 . The method of  claim 29 , wherein the fraction derived from hops comprises a compound of a supragenus having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl;  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 ; and  
         wherein R, T, X, and Z are independently selected from the group consisting of H, F. Cl, Br, I, and π orbital, with the proviso that if one of R, T, X, or Z is a π orbital, then the adjacent R, T, X, or Z is also a π orbital, thereby forming a double bond.  
       
     
     
         32 . The method of  claim 29 , wherein the fraction derived from hops comprises a compound of Genus A having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .  
       
     
     
         33 . The method of  claim 29 , wherein the fraction derived from hops comprises a compound of Genus B having the formula:  
       
         
           
           
               
               
           
         
         wherein R′ is selected from the group consisting of carbonyl, hydroxyl, OR, and OCOR, wherein R is alkyl; and  
         wherein R″ is selected from the group consisting of CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , and CH(CH 3 )CH 2 CH 3 .  
       
     
     
         34 . The method of  claim 29 , wherein the fraction derived from hops comprises a compound selected from the group consisting of cohumulone, adhumulone, isohumulone, isocohumulone, isoadhumulone, dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.