Synergistic compositions that treat or inhibit pathological conditions associated with inflammatory response
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. Other embodiments relate to combinations of components, including at least one fraction isolated or derived from hops, tryptanthrin and conjugates thereof, rosemary, an extract or compound derived from rosemary, a triterpene species, or a diterpene lactone or derivatives or conjugates thereof.
1 - 86 . (canceled)
87 . 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 composition comprising a fraction isolated or derived from hops and a second component selected from the group consisting of rosemary, an extract derived from rosemary, a compound derived from rosemary, a triterpene species, a diterpene lactone species, and tryptanthrin.
88 . The method of claim 87 , wherein the non-target cells are also contacted with said fraction isolated or derived from hops.
89 . The method of claim 87 , wherein the contacting step is in vivo.
90 . The method of claim 86 , wherein the COX-2 activity is modulated by inhibition of COX-2 gene.
91 . 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 isolated or derived from hops and a second component selected from the group consisting of rosemary, an extract derived from rosemary, a compound derived from rosemary, a triterpene species, a diterpene lactone, and tryptanthrin.
92 . The method of claim 91 , wherein the fraction isolated or derived from hops is selected from the group consisting of alpha acids, isoalpha acids, reduced isoalpha acids; tetra-hydroisoalpha acids, hexa-hydroisoalpha acids, beta acids, and spent hops.
93 . The method of claim 91 , wherein the fraction isolated or 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.
94 . The method of claim 91 , wherein the fraction isolated or 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 .
95 . The method of claim 91 , wherein the fraction isolated or 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 .
96 . The method of claim 91 , wherein the fraction isolated or derived from hops comprises a compound selected from the group consisting of humulone, cohumulone, adhumulone, isohumulone, isocohumulone, isoadhumulone, dihydro-isohumulone, dihydro-isocohumulone, dihydro-adhumulone, tetrahydro-isohumulone, tetrahydro-isocohumulone, tetrahydro-adhumulone, hexahydro-isohumulone, hexahydro-isocohumulone, and hexahydro-adhumulone.
97 . The method of claim 91 , wherein the second component is an extract derived from rosemary.
98 . The method of claim 91 , wherein the second component is a triterpene species.
99 . The method of claim 91 , wherein the composition further comprises a third component different from the second component, the third component is selected from the group consisting of rosemary, an extract derived from rosemary, a compound derived from rosemary, a triterpene species, a diterpene lactone, and tryptanthrin.
100 . The method of claim 99 , wherein the second and third components are an extract derived from rosemary and tryptanthrin, respectively.
101 . The method of claim 91 , wherein the second component is a compound derived from rosemary that is selected from the group consisting of 1,8-cineole, 19-alpha-hydroxyursolic acid, 2-β-hydroxyoleanolic acid, 3-O-acetyloleanolic acid, 3-O-acetylursolic acid, 6-methoxy-luteolin-7-glucoside, 6-methoxyluteolin, 6-methoxyluteolin-7-glucoside, methoxyluteolin-7-methylether, 7-ethoxy-rosmanol, 7-methoxy-rosmanol, alpha-amyrin, alpha-humulene, alpha-hydroxyhydrocaffeic acid, alpha-pinene, alpha-terpinene, alpha-terpinenyl acetate, alpha-terpineol, alpha-thujone, apigenin, apigenin-7-glucoside, curcumene, benzyl-alcohol, β-amyrenone, β-amyrin, β-elemene, β-pinene, betulin, betulinic acid, borneol, bornyl-acetate, caffeic acid, camphene, camphor, camosic acid, carnosol, carvacrol, carvone, caryophyllene, caryophyllene-oxide, chlorogenic acid, diosmetin, gamma-terpinene, hesperidin, isoborneol, limonene, luteolin, luteolin-3′-O-(3″-O-acetyl)-β-D-glucuronide, luteolin-3′-O-(4″-O-acetyl)-β-D-glucuronide, luteolin-3′-O-P-D-glucuronide, luteolin-7-glucoside, methyl-eugenol, myrcene, neo-chlorogenic acid, nepetin, octanoic acid, oleanolic acid, p-cymene, piperitenone, rosmanol, rosmaric acid, rosmaricine, rosmaridiphenol, rosemarinic acid, rosmarinol, rosmariquinone, sabinene, sabinyl acetate, salicylates, salicylic acid-2-β-D-glucoside, squalene, terpinen-4-ol, terpinolene, thymol, trans-anethole, trans-carveol, ursolic acid, verbenone, and zingiberene.
102 . The method of claim 101 , wherein the second component is a triterpene species or a diterpene lactone species that is conjugated to a member selected from the group consisting of mono- or di-saccharides, amino acids, sulfates, succinate, acetate, and glutathione.
103 . The method of claim 91 , wherein the second component is a triterpene species that is selected from the group consisting of 18-a-glycyrrhetinic acid, 18-β-glycyrrhetinic acid, 2-a-3-a-dihydrooxyurs-12-3n-28-onic acid, 3-a-hydroxyursolic acid, 3-oxo-ursolic acid, betulin, betulinic acid, celastrol, eburicoic acid, friedelin, glycyrrhizin, gypsogenin, oleanolic acid, oleanolic acid-3-acetate, pachymic acid, pinicolic acid, sophoradiol, soyasapogenol A, soyasapogenol B, tripterin, triptophenolide, tumulosic acid, ursolic acid, ursolic acid-3-acetate, uvaol, and β-sitosterol.
104 . The method of claim 91 , wherein the second component is tryptanthrin that is conjugated to a member selected from the group consisting of mono- or di-saccharides, amino acids, sulfates, succinate, acetate, and glutathione.
105 . The method of claim 91 , wherein a ratio of the first component to the second component is in the range of about 100:1 to about 1:100.
106 . The method of claim 105 , wherein the ratio of the first component to the second component is in the range of about 50:1 to about 1:50.
107 . The method of claim 91 , 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.
108 . The method of claim 91 , wherein the composition further comprises a pharmaceutically acceptable carrier.
109 . The method of claim 91 , wherein the composition is administered orally, topically, parenterally, or rectally.
110 - 115 . (canceled)