Compositions and method of use of a-type procyanidins

Abstract

The invention relates to compositions, such as pharmaceuticals, foods, food additives, or dietary supplements, containing A-type procyanidins, and methods of use thereof, for prophylactic or therapeutic treatment of a human or a veterinary animal to treat or prevent NO-responsive health conditions, treat hypertension, cardiovascular disease, coronary artery disease and/or vascular circulation disorders, prevent or reduce the risk of heart attack, stroke, congestive heart failure and/or kidney failure, or to improve blood flow, for example renal blood flow. The composition may optionally contain an additional NO modulating agent and/or a cardiovascular-protective or therapeutic agent, or may be administered in combination with such an agent.

1 . A method of treating or preventing an NO-responsive disease or disorder by administering to a subject in need thereof an effective amount of an A-type procyanidin composed of n monomeric units of the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 (i) the monomeric units are connected via interflavan linkages 4→6 and/or 4→8; 
 (ii) at least two of the monomeric units are additionally linked by an A-type interflavan linkage (4→8; 2→O→7) or (4→6; 2→O→7); 
 (iii) n is 2 to 12; 
 or a pharmaceutically acceptable salt or derivative thereof, 
 and wherein the subject is a human or a veterinary animal. 
 
     
     
         2 . The method of  claim 1 , wherein the A-type procyanidin is isolated and purified. 
     
     
         3 . The method of  claim 1 , wherein the A-type procyanidin is A1 dimer. 
     
     
         4 . The method of  claim 3 , wherein the A1 dimer is isolated and purified. 
     
     
         5 . The method of  claim 1 , wherein the A-type procyanidin is A2 dimer. 
     
     
         6 . The method of  claim 5 , wherein the A2 dimer is isolated and purified. 
     
     
         7 . The method of  claim 1 , wherein the A-type procyanidin is A-type trimer. 
     
     
         8 . The method of  claim 7 , wherein the A-type trimer is substantially pure. 
     
     
         9 . The method of  claim 7 , wherein the A-type trimer has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The method of  claim 1 , wherein the NO-responsive disease or disorder is hypertension, cardiovascular disease, coronary artery disease, vascular circulation disorders and/or renal disease. 
     
     
         11 . The method of  claim 1 , wherein the subject is at risk of heart attack, stroke, congestive heart failure, and/or kidney failure. 
     
     
         12 . The method of  claim 1 , wherein the subject suffers from high blood pressure in combination with any of the following: diabetes, obesity, high cholesterol levels and/or smoking. 
     
     
         13 . A method of treating hypertension by administering to a subject in need thereof an effective amount of an A-type procyanidin composed of n monomeric units of the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 (i) the monomeric units are connected via interflavan linkages 4→6 and/or 4→8; 
 (ii) at least two of the monomeric units are additionally linked by an A-type interflavan linkage (4→8; 2→O→7) or (4→6; 2→O→7); 
 (iii) n is 2 to 12; 
 or a pharmaceutically acceptable salt or derivative thereof, 
 and wherein the subject is a human or a veterinary animal. 
 
     
     
         14 . The method of  claim 1 , wherein the A-type procyanidin is isolated and purified. 
     
     
         15 . The method of  claim 1 , wherein the A-type procyanidin is A1 dimer. 
     
     
         16 . The method of  claim 15 , wherein the AI dimer is isolated and purified. 
     
     
         17 . The method of  claim 1 , wherein the A-type procyanidin is A2 dimer. 
     
     
         18 . The method of  claim 17 , wherein the A2 dimer is isolated and purified. 
     
     
         19 . The method of  claim 1 , wherein the A-type procyanidin is A-type trimer. 
     
     
         20 . The method of  claim 19 , wherein the A-type trimer is substantially pure. 
     
     
         21 . The method of  claim 19 , wherein the A-type trimer has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 13 , wherein the subject suffers from any of the following: diabetes, obesity, high cholesterol levels and/or smoking. 
     
     
         23 . A pharmaceutical composition comprising an isolated and purified A1 dimer. 
     
     
         24 . A pharmaceutical composition comprising an isolated and purified A2 dimer.