Plant extracts and alkaloids having antitussive activity

Abstract

The present invention provides plant extracts, isolated alkaloids, synthetic alkaloids and compositions having antitussive activity. In some preferred embodiments, the plant extracts and the isolated alkaloids are from a plant of a genus in the family Stemonaceae. In other preferred embodiments, the plant extracts and the isolated alkaloids are from a plant of the genus Stemona, Croomia, or Stichoneuron. In especially preferred embodiments, the plant extracts and the isolated alkaloids are from the plant Stemona tuberosa. The present invention further provides methods for isolating such plant extracts and alkaloids. In addition, the present invention provides methods for reducing or suppressing coughing by administering plant extracts, alkaloids and compositions having antitussive activity.

1 - 32 . (canceled)  
   
   
       33 . A Stemonaceae family plant extract having antitussive activity, wherein said Stemonaceae family plant extract inhibits a cough in a subject.  
   
   
       34 . The plant extract of  claim 33 , wherein the Stemonaceae family genus is selected from the group consisting of  Stemona, Croomia,  or  Stichoneuron.    
   
   
       35 . The plant extract of  claim 34 , wherein the genus is  Stemona  or  Croomia.    
   
   
       36 . The plant extract of  claim 35 , wherein the  Stemona  or  Croomia  genus species is selected from the group consisting of  S. collinsae, S. japonica, S. mairei, S. parviflora, S. sessilifolia, S. tuberosa, C. japonica,  and  C. heterosepala.    
   
   
       37 . The plant extract of  claim 36 , wherein the  Stemona  species is  Stemona tuberosa.    
   
   
       38 . The plant extract of  claim 33 , wherein said plant extract is an aqueous extract.  
   
   
       39 . The plant extract of  claim 33 , wherein said plant extract is a total alkaloid extract.  
   
   
       40 . The plant extract of  claim 33 , wherein said plant extract comprises a compound having the formula  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is a member selected from the group consisting of hydrogen and α(S)-methyl-γ(S)-butyroylactonyl;  
 R 2  is a member selected from the group consisting of β-oriented hydrogen and α-oriented hydrogen; and  
 R 3  is a member selected from the group consisting of β-oriented hydrogen and α-oriented hydrogen.  
 
   
   
       41 . The plant extract of  claim 33 , wherein said plant extract comprises a compound having the formula  
     
       
         
         
             
             
         
       
     
   
   
       42 . The plant extract of  claim 33 , wherein said plant extract comprises a combination of at least two or more compounds selected from the group consisting of Formulae Ia and Ib.  
   
   
       43 . A pharmaceutical composition, said composition comprising: 
 a Stemonaceae family plant extract having antitussive activity, wherein said Stemonaceae family plant extract inhibits a cough in a subject.    
   
   
       44 . The composition of  claim 43 , wherein the Stemonaceae family genus is selected from the group consisting of  Stemona, Croomia,  or  Stichoneuron.    
   
   
       45 . The composition of  claim 44 , wherein the genus is  Stemona  or  Croomia.    
   
   
       46 . The composition of  claim 45 , wherein the  Stemona  or  Croomia  genus species is selected from the group consisting of  S. collinsae, S. japonica, S. mairei, S. parviflora, S. sessilifolia, S. tuberosa, C. japonica,  and  C. heterosepala.    
   
   
       47 . The composition of  claim 46 , wherein the  Stemona  species is  Stemona tuberosa.    
   
   
       48 . The composition of  claim 43 , wherein said plant extract is an aqueous extract.  
   
   
       49 . The composition of  claim 43 , wherein said plant extract is a total alkaloid extract.  
   
   
       50 . The composition of  claim 43 , wherein said plant extract comprises a compound having the formula  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is a member selected from the group consisting of hydrogen and α(S)-methyl-γ(S)-butyroylactonyl;  
 R 2  is a member selected from the group consisting of β-oriented hydrogen and α-oriented hydrogen; and  
 R 3  is a member selected from the group consisting of β-oriented hydrogen and α-oriented hydrogen.  
 
   
   
       51 . Amended) The composition of  claim 43 , wherein said plant extract comprises a compound having the formula  
     
       
         
         
             
             
         
       
     
   
   
       52 . The composition of  claim 43 , wherein said plant extract comprises a combination of at least two or more compounds selected from the group consisting of Formulae Ia and Ib.  
   
   
       53 . A method for reducing coughing in a subject, said method comprising: 
 administering a pharmaceutically effective amount of a Stemonaceae family plant extract having antitussive activity, wherein said Stemonaceae family plant extract inhibits a cough in a subject.    
   
   
       54 . The method of  claim 53 , wherein the Stemonaceae family genus is selected from the group consisting of  Stemona, Croomia,  or  Stichoneuron.    
   
   
       55 . The method of  claim 54 , wherein the genus is  Stemona  or  Croomia.    
   
   
       56 . The method of  claim 55 , wherein the  Stemona  or  Croomia  genus species is selected from the group consisting of  S. collinsae, S. japonica, S. mairei, S. parviflora, S. sessilifolia, S. tuberosa, C. japonica,  and  C. heterosepala.    
   
   
       57 . The method of  claim 56 , wherein the  Stemona  species is  Stemona tuberosa.    
   
   
       58 . The method of  claim 53 , wherein said plant extract is an aqueous extract.  
   
   
       59 . The method of  claim 53 , wherein said plant extract is a total alkaloid extract.  
   
   
       60 . The method of  claim 53 , wherein said plant extract comprises a compound having the formula  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is a member selected from the group consisting of hydrogen and α(S)-methyl-γ(S)-butyroylactonyl;  
 R 2  is a member selected from the group consisting of β-oriented hydrogen and α-oriented hydrogen; and  
 R 3  is a member selected from the group consisting of β-oriented hydrogen and α-oriented hydrogen.  
 
   
   
       61 . The method of  claim 53 , wherein said plant extract comprises a compound having the formula  
     
       
         
         
             
             
         
       
     
   
   
       62 . The method of  claim 53 , wherein said plant extract comprises a combination of at least two or more compounds selected from the group consisting of Formulae Ia and Ib.  
   
   
       63 . A method for preparing a total alkaloid extract having antitussive activity from a Stemonaceae family plant, said method comprising: 
 (a) contacting a Stemonaceae family plant sample with an alcohol to form a liquor;    (b) evaporating said alcohol in said liquor to form a syrup;    (c) adjusting said syrup to an acid pH to form a supernatant fraction;    (d) adjusting the supernatant fraction to a basic pH, and then extracting with an organic solvent to form an organic solution; and    (e) evaporating said organic solvent to dryness to form a total alkaloid extract having antitussive activity.    
   
   
       64 . The method of  claim 63 , where the said total alkaloid extract comprises a combination of at least two or more compounds selected from the group consisting of Formulae Ia and Ib.  
   
   
       65 . A method for preparing an alkaloid having antitussive activity from the said total alkaloid extract of  claim 63 , further comprising: 
 separating, purifying and crystallizing said total alkaloid extract, thereby forming an isolated alkaloid having antitussive activity.    
   
   
       66 . The method of  claim 65 , wherein the said isolated alkaloid is a compound of the formula selected from the group consisting of Formulae Ia and Ib.  
   
   
       67 . A method for preparing an aqueous extract having antitussive activity from a Stemonaceae family plant, said method comprising: 
 (a) contacting a Stemonaceae family plant sample with an aqueous solvent to form a liquor; and    (b) evaporating said liquor to dryness to form an aqueous extract having antitussive activity.    
   
   
       68 . The method of  claim 67 , wherein the said aqueous extract comprises a combination of at least two or more compounds selected from the group consisting of Formulae Ia and Ib.