2-acetylnaphtho[2,3-b]furan -4,9-dione for use on treating cancer

Abstract

The invention provides naphthofuran compounds, polymorphs of naphthofuran compounds, naphthofuran compounds in particle form, purified compositions that contain one or more naphthofuran compounds, purified compositions that contain one or more naphthofuran compounds in particle form, and methods of using these naphthofuran compounds, polymorphs, purified compositions and/or particle forms to treat subjects in need thereof.

1 . A method of treating colorectal cancer in a human subject comprising administering to the subject a pharmaceutical composition, comprising:
 (a) 5 to 50% by weight of a therapeutically effective amount of a compound having D 50  less than 5.0 μm and the structure   
       
         
           
           
               
               
           
         
         (b) 5 to 80% by weight of a polyoxylglyceride having a hydrophilic-lipophilic balance (HLB) greater than 10 and selected from the group consisting of lauroyl polyoxylglycerides, stearoyl polyoxylglycerides, and combinations thereof, and 
         (c) 5 to 80% by weight of a polyoxylglyceride having a HLB less than 10 and selected from the group consisting of linoleoyl polyoxylglycerides, oleoyl polyoxylglycerides, lauroyl polyoxylglycerides, and combinations thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the composition further comprises a surfactant in an amount of 0.05 to 5% by weight. 
     
     
         3 . The method of  claim 1 , wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, sodium dodecyl sulfate, and combinations thereof. 
     
     
         4 . The method of  claim 2 , wherein the composition comprises, by weight, about 27.18% of the compound, about 0.27% of the surfactant, about 14.51% of the polyoxylglycerides of which HLB is more than 10, and about 58.04% of the polyoxylglycerides of which HLB is less than 10. 
     
     
         5 . The method of  claim 1 , comprising about 125 mg of the compound. 
     
     
         6 . The method of  claim 1 , comprising about 80 mg of the compound. 
     
     
         7 . The method of  claim 1 , wherein the weight ratio between the polyoxylglycerides of which HLB is more than 10 and the polyoxylglycerides of which HLB is less than 10 is from about 90/10 to about 10/90. 
     
     
         8 . The method of  claim 1 , wherein the weight ratio between the polyoxylglycerides of which HLB is more than 10 and the polyoxylglycerides of which HLB is less than 10 is from about 80/20 to about 20/80. 
     
     
         9 . The method of  claim 1 , wherein the polyoxylglyceride of which HLB is more than 10 is selected from the group consisting of lauroyl polyoxyl-32 glycerides, stearoyl polyoxyl-32 glycerides, and combinations thereof. 
     
     
         10 . The method of  claim 9 , wherein the polyoxylglyceride of which HLB is more than 10 is lauroyl polyoxyl-32 glyceride. 
     
     
         11 . The method of  claim 1 , wherein the polyoxylglyceride of which HLB is less than 10 is selected from the group consisting of linoleoyl polyoxyl-6 glycerides, oleoyl polyoxyl-6 glycerides, and combinations thereof. 
     
     
         12 . The method of  claim 11 , wherein the polyoxylglyceride of which HLB is less than 10 is linoleoyl polyoxyl-6 glyceride. 
     
     
         13 . The method of  claim 1 , wherein the composition is in the form of a capsule having a size of 1 or 2. 
     
     
         14 . The method of treating colorectal cancer in a human subject comprising administering to the subject a pharmaceutical composition comprising:
 (a) 5 to 50% by weight of a therapeutically effective amount of a compound having D 50  less than 5.0 μm and the structure   
       
         
           
           
               
               
           
         
         (b) 5 to 80% by weight of a lauroyl polyoxyl-32 glyceride having a hydrophilic-lipophilic balance (HLB) greater than 10; 
         (c) 5 to 80% by weight of a linoleoyl polyoxyl-6 glyceride having a HLB less than 10; and 
         (d) 0.05 to 5% by weight of sodium lauryl sulfate. 
       
     
     
         15 . The method of treating colorectal cancer in a human subject comprising administering to the subject a pharmaceutical composition comprising:
 (a) about 80 mg of a compound having D 50  less than 5.0 μm and the structure   
       
         
           
           
               
               
           
         
         (b) about 42.7 mg of a lauroyl polyoxyl-32 glyceride having a hydrophilic-lipophilic balance (HLB) greater than 10; 
         (c) about 170.9 mg of a linoleoyl polyoxyl-6 glyceride having a HLB less than 10; and 
         (d) about 0.8 mg of sodium lauryl sulfate.