Solid compositions of triglycerides and uses thereof

Abstract

The present invention includes solid compositions of triglycerides with one or more fatty acids, such as triheptanoin and glycerol phenylbutyrate, and therapeutic use thereof. The solid compositions can be prepared by spray-drying or other processes.

1 . A composition comprising an active ingredient, wherein the active ingredient is in a form of a triglyceride;
 wherein the triglyceride has a purity greater than 95%;   wherein the composition comprises the triglyceride in at least about 50% by weight and the composition is substantially free of glycerol;   wherein the composition comprises water in no more than 1.0% by weight; and   wherein the composition comprises glycerol in less than 1.0% by weight after about four weeks of exposure to about 40° C. at about 75% relative humidity when packaged in a sealed container.   
     
     
         2 . The composition of  claim 1 , wherein the triglyceride comprises one or more odd-numbered carbon fatty acids selected from the group consisting of C 5 , C 7 , C 9 , C 11 , C 13 , C 15 , and any combinations thereof; and wherein the triglyceride has a purity greater than 98%. 
     
     
         3 . The composition of  claim 2 , wherein the triglyceride is triheptanoin oil. 
     
     
         4 . The composition of  claim 1 , wherein the triglyceride comprises one or more fatty acids selected from one or more phenylalkanoic acids and/or phenylalkenoic acids. 
     
     
         5 . The composition of  claim 4 , wherein the triglyceride has a structure of a compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , and R 3  are independently 
       
         
           
           
               
               
           
         
       
       and n is zero or an even number from 2-24 and m is an even number from 2-24. 
     
     
         6 . The composition of  claim 5 , wherein the triglyceride is glycerol phenylbutyrate. 
     
     
         7 . (canceled) 
     
     
         8 . The composition of  claim 1 , further comprising a solid carrier. 
     
     
         9 . (canceled) 
     
     
         10 . The composition of  claim 8 , wherein the solid carrier is selected from the group consisting of SiO 2 , TiO 2 , Al 2 O 3 , zeolites, Cab-O-Sil, and combinations thereof. 
     
     
         11 . The composition of  claim 1 , comprising one or more sustained release polymers. 
     
     
         12 . The composition of  claim 11 , wherein the sustained release polymer is a film-forming, water insoluble polymer. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The composition of  claim 11 , wherein the one or more sustained release polymer comprises one or more pH dependent polymers. 
     
     
         16 . (canceled) 
     
     
         17 . The composition of  claim 1 , which is in form of a powder. 
     
     
         18 .- 21 . (canceled) 
     
     
         22 . A composition comprising a plurality of solid particles, each particle comprising an active ingredient, wherein the active ingredient is in a form of a triglyceride;
 wherein the triglyceride is adsorbed onto a solid substance;   wherein the triglyceride has a purity greater than 95%;   wherein the composition comprises the triglyceride in at least about 50% by weight and the composition is substantially free of glycerol;   wherein the composition comprises water in no more than 1.0% by weight; and   wherein the composition comprises glycerol in less than 1.0% by weight after about four weeks of exposure to about 40° C. at about 75% relative humidity when packaged in a sealed container.   
     
     
         23 .- 41 . (canceled) 
     
     
         42 . The composition of  claim 1 , which further comprises a pharmaceutically acceptable excipient. 
     
     
         43 . The composition of  claim 1 , wherein the triglyceride has a purity greater than 97% after about four weeks of exposure to about 25° C. at about 60% relative humidity when packaged in a sealed container. 
     
     
         44 . The composition of  claim 1 , wherein the composition has a water content of no more than 0.35% by weight after about four weeks of exposure to about 25° C. at about 60% relative humidity when packaged in a sealed container. 
     
     
         45 . The composition of  claim 1 , wherein the triglyceride has a purity greater than 97% after about four weeks of exposure to about 40° C. at about 75% relative humidity when packaged in a sealed container. 
     
     
         46 . The composition of  claim 1 , wherein the composition has a water content of no more than 0.45% by weight after about four weeks of exposure to 40° C. at about 75% relative humidity when packaged in a sealed container. 
     
     
         47 . A method of treating a disease, disorder, or condition in a subject comprising orally administering to the subject a therapeutically effective amount of a composition of  claim 1 , wherein the disease, disorder, or condition is selected from any one or more of the following: a fatty acid oxidation disorder or deficiency; adult polyglucosan body disease; a mitochondrial fat oxidation defect; (a mitochondrial fat oxidation defect relating to carnitine palmitoyl transferase; a mitochondrial fat oxidation defect relating to carnitine palmitoyl transferase II; a mitochondrial fat oxidation defect relating to carnitine acylcarnitine translocase; a mitochondrial fat oxidation defect relating to very long chain acyl-CoA dehydrogenase; a mitochondrial fat oxidation defect relating to trifunctional protein; a mitochondrial fat oxidation defect relating to long chain hydroxyacyl-CoA dehydrogenase; a mitochondrial fat oxidation defect relating to multiple acyl-CoA dehydrogenase; a mitochondrial fat oxidation defect relating to short chain acyl CoA dehydrogenase; a mitochondrial fat oxidation defect relating to alpha glucosidase; a mitochondrial fat oxidation defect relating to brancher enzyme; a mitochondrial fat oxidation defect relating to debrancher enzyme; a mitochondrial fat oxidation defect relating to myophosphorylase; a mitochondrial fat oxidation defect relating to phosphofructokinase; a glycogen storage disease; (glycogen storage disease Type II; glucose transporter type 1 (GLUT1) deficiency syndrome; or a mitochondrial myopathy. 
     
     
         48 . The method of  claim 47 , wherein the composition is co-administered with a food, drink, or comestible composition. 
     
     
         49 . A method of treating a disease, disorder, or condition in a subject comprising orally administering to the subject a therapeutically effective amount of a composition of  claim 1 , wherein the disease, disorder, or condition is selected from urea cycle disorders (UCD) or hepatic encephalopathy (HE). 
     
     
         50 .- 63 . (canceled) 
     
     
         64 . The composition of  claim 1 , wherein the composition comprises glycerol in less than 0.5% by weight after about four weeks of exposure to about 40° C. at about 75% relative humidity when packaged in a sealed container. 
     
     
         65 . A composition comprising a triglyceride;
 wherein the triglyceride has a purity greater than 97%;   wherein the composition comprises the triglyceride in at least about 50% by weight and the composition is substantially free of glycerol;   wherein the composition comprises water in no more than 1.0% by weight; and   wherein the triglyceride has a purity greater than 97% after about four weeks of exposure to about 25° C. at about 60% relative humidity when packaged in a sealed container.