Artemisinins with improved stability and bioavailability for therapeutic drug development and application

Abstract

A stable form of artemisinin wherein an artelinic acid or artesunic acid is complexed with cyclodextrin analogs, preferably, β-cyclodextrin. The complexed cyclodextrin artemisinin formulation shields the peroxide portion of the artemisinin backbone from hydrolytic decomposition rendering it stable in solution. Artelinic acid and cyclodextrin are placed into contact with one another to yield a 2:1 molecular species. Artesunic acid and cyclodextrin yield a 1:1 molecular species. The complexed cyclodextrin artemisinin formulation is effective for the treatment of malaria and is stable in solution for long periods of time.

1 - 57 . (canceled)  
     
     
         58 . A method of treating a patient having malaria: comprising administering to said patient a composition comprising a complexed cyclodextrin formulation of artemisinin, wherein said cyclodextrin is complexed with artelinic acid in a 2:1 molar ratio in aqueous solution.  
     
     
         59 . The method of  claim 58 , wherein said administering is by intravenous injection, oral dose, sublingual dose, or suppository.  
     
     
         60 . The method of  claim 58 , wherein said administering to said patient is by a dose of 4-6 milligrams of artelinic acid per kilogram of body weight.  
     
     
         61 . The method of  claim 58 , wherein said 40 milligrams of said artemisinin complexed with cyclodextrin is dissolved per milliliter of aqueous solution.  
     
     
         62 . A method of treating a patient with malaria: comprising administering to said patient an antimalarial composition comprising: 
 a complexed cyclodextrin formulation of artemisinin, wherein said cyclodextrin is complexed with artesunic acid in a 1:1 ratio in an aqueous solution.    
     
     
         63 . The method of  claim 62 , wherein said administering is by intravenous injection, oral dose, sublingual dose, or suppository.  
     
     
         64 . The method of  claim 62 , wherein said administering to said patient is by a dose of 4-6 milligrams of artesunic acid per kilogram of body weight.  
     
     
         65 . The method of  claim 62 , wherein said 40 milligrams of said artemisinin complexed with cyclodextrin is dissolved per milliliter of aqueous solution.