Identification of free-b-ring flavonoids as potent cox-2 inhibitors

Abstract

The present invention provides a novel method for inhibiting the cyclooxygenase enzyme COX-2. The method is comprised of administering a composition containing a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids to a host in need thereof. The present also includes novel methods for the prevention and treatment of COX-2 mediated diseases and conditions. The method for preventing and treating COX-2 mediated diseases and conditions is comprised of administering to a host in need thereof an effective amount of a composition containing a Free-B-Ring flavonoid or a composition containing a mixture of Free-B-Ring flavonoids and a pharmaceutically acceptable carrier.

1 - 11 . (canceled) 
     
     
         12 . A plant extract comprising a mixture of Free-B-Ring flavonoids having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently —H, —OH, —SH, —OR, —SR, —NH 2 , —NHR, —N(R) 2 , —N(R) 3   + X −  or a carbon, oxygen, nitrogen or sulfur glycoside of a single sugar or multiple sugars, wherein the sugars are aldopentoses, methyl-aldopentose, aldohexoses, ketohexose or derivatives thereof; 
 R is an alkyl group having between 1-10 carbon atoms; and 
 X is a hydroxyl, chloride, iodide, sulfate, phosphate, acetate, fluoride or carbonate counter ion, and 
 
       wherein at least one of the Free-B-Ring flavonoids is Baicalin, and the total Free-B-Ring Flavonoid content in the plant extract is greater than 75% on a weight/weight basis. 
     
     
         13 . The plant extract of  claim 12 , wherein the Baicalin is present in the plant extract in 62.5% on a weight/weight basis. 
     
     
         14 . The plant extract of  claim 12 , wherein the plant extract is extracted from the  Desmos, Achyrocline, Oroxylum, Buchenavia, Anaphalis, Cotula, Gnaphalium, Helichrysum, Centaurea, Eupatorium, Baccharis, Sapium, Scutellaria, Molsa, Colebrookea, Stachys, Origanum, Ziziphora, Lindera, Actinodaphne, Acacia, Derris, Glycyrrhiza, Millettia, Pongamia, Tephrosia, Artocarpus, Ficus, Pityrogramma, Notholaena, Pinus, Ulmus or Alpinia  plant genus. 
     
     
         15 . The plant extract of  claim 12 , wherein the plant extract is isolated from the  Scutellaria  plant genus. 
     
     
         16 . The plant extract of  claim 12 , wherein the plant extract is extracted from  Scutellaria orthocalyx, Scutellaria lateriflora, Scutellaria baicalensis  or  Scutellaria radix.    
     
     
         17 . The plant extract of  claim 12 , wherein the plant extract is extracted from  Scutellaria baicalensis.    
     
     
         18 . The plant extract of  claim 12 , wherein the plant extract is extracted from  Scutellaria baicalensis Georgi.    
     
     
         19 . The plant extract of  claim 12 , wherein the plant extract inhibits the activity of COX-2. 
     
     
         20 . The plant extract of  claim 12 , wherein the plant extract is extracted from a stem, stem bark, twig, tuber, root, root bark, young shoot, seed, rhizome, flower, leaf or aerial part of a plant. 
     
     
         21 . A composition comprising a pharmaceutically acceptable carrier and a plant extract comprising a mixture of Free-B-Ring flavonoids having the following structure: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently —H, —OH, —SH, —OR, —SR, —NH 2 , —NHR, —N(R) 2 , —N(R) 3   + X −  or a carbon, oxygen, nitrogen or sulfur glycoside of a single sugar or multiple sugars, wherein the sugars are aldopentoses, methyl-aldopentose, aldohexoses, ketohexose or derivatives thereof; 
 R is an alkyl group having between 1-10 carbon atoms; and 
 X is a hydroxyl, chloride, iodide, sulfate, phosphate, acetate, fluoride or carbonate counter ion, and 
 
       wherein at least one of the Free-B-Ring flavonoids is Baicalin, and the total Free-B-Ring Flavonoid content in the plant extract is greater than 75% on a weight/weight basis. 
     
     
         22 . The composition of  claim 21 , wherein the Baicalin is present in the plant extract in 62.5% on a weight/weight basis. 
     
     
         23 . The composition of  claim 21 , wherein the plant extract is extracted from the  Desmos, Achyrocline, Oroxylum, Buchenavia, Anaphalis, Cotula, Gnaphalium, Helichrysum, Centaurea, Eupatorium, Baccharis, Sapium, Scutellaria, Molsa, Colebrookea, Stachys, Origanum, Ziziphora, Lindera, Actinodaphne, Acacia, Derris, Glycyrrhiza, Millettia, Pongamia, Tephrosia, Artocarpus, Ficus, Pityrogramma, Notholaena, Pinus, Ulmus or Alpinia  plant genus. 
     
     
         24 . The composition of  claim 21 , wherein the plant extract is isolated from the  Scutellaria  plant genus. 
     
     
         25 . The composition of  claim 21 , wherein the plant extract is extracted from  Scutellaria orthocalyx, Scutellaria lateriflora, Scutellaria baicalensis  or  Scutellaria radix.    
     
     
         26 . The composition of  claim 21 , wherein the plant extract is extracted from  Scutellaria baicalensis.    
     
     
         27 . The composition of  claim 21 , wherein the plant extract is extracted from  Scutellaria baicalensis Georgi.    
     
     
         28 . The composition of  claim 21 , wherein the composition inhibits the activity of COX-2. 
     
     
         29 . The composition of  claim 21 , wherein the composition is formulated for enteral, parenteral or topical administration. 
     
     
         30 . The composition of  claim 21 , wherein the pharmaceutically acceptable carrier is physiological saline. 
     
     
         31 . The composition of  claim 21 , wherein the plant extract is extracted from a stem, stem bark, twig, tuber, root, root bark, young shoot, seed, rhizome, flower, leaf or aerial part of a plant.