Amino acid compositions and methods for the treatment of liver diseases

Abstract

This disclosure provides pharmaceutical compositions comprising amino acid entities and uses thereof. Methods for improving liver function and for treating liver diseases comprising administering an effective amount of the compositions to a subject in need thereof are also disclosed.

1 .- 25 . (canceled) 
     
     
         26 . A method for improving mitochondrial function in a subject, wherein the method comprises administering to the subject an effective amount of a composition comprising:
 (a) a leucine amino acid entity chosen from:
 (i) L-leucine or a salt thereof, 
 (ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine, or 
 (iii) β-hydroxy-β-methylbutyrate (HMB) or a salt thereof; 
   (b) an arginine amino acid entity chosen from:
 (i) L-arginine or a salt thereof, 
 (ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-arginine, 
 (iii) ornithine or a salt thereof, 
 (iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising ornithine, 
 (v) creatine or a salt thereof, or 
 (vi) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising creatine; 
   (c) L-glutamine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine; and   (d) N-acetylcysteine (NAC) or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC,   wherein when the composition is in powder form at least 50 wt. % of the total wt. of the composition is one or more amino acid entities in free form, and   wherein the total wt. % of (a)-(d) is greater than the total wt. % of other amino acid entities in the composition.   
     
     
         27 . The method of claim  1 , wherein the subject has non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). 
     
     
         28 . The method of claim  1 , wherein the composition further comprises L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine. 
     
     
         29 . The method of claim  1 , wherein the composition further comprises L-valine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-valine. 
     
     
         30 . The method of claim  1 , wherein the composition further comprises both of:
 (e) L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine; and   (f) L-valine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-valine.   
     
     
         31 . The method of claim  1 , wherein one or both of the arginine amino acid entity and the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine are present at a higher amount (wt. %) than the leucine amino acid entity. 
     
     
         32 . The method of claim  1 , wherein the composition further comprises a serine amino acid entity chosen from L-serine or glycine. 
     
     
         33 . The method of claim  1 , wherein:
 (1) the wt. % of the (c) in the composition is greater than the wt. % of the arginine amino acid entity of (b);   (2) the wt. % of the (c) in the composition is greater than or equal to the wt. % of the leucine amino acid entity of (a);   (3) the wt. % of the arginine amino acid entity of (b) in the composition is greater than the wt. % of the leucine amino acid entity of (a); or   (4) a combination of two or three of (1)-(3).   
     
     
         34 . The method of claim  1 , wherein (a)-(d) are each a free amino acid or a salt thereof, and wherein the composition further comprises L-isoleucine or a salt thereof and L-valine or a salt thereof. 
     
     
         35 . The method of  claim 34 , wherein a ratio of the L-leucine or a salt thereof of (a), the L-isoleucine or a salt thereof, the L-valine or a salt thereof, the L-arginine or a salt thereof of (b), the L-glutamine or a salt thereof of (c), and the NAC or a salt thereof of (d) is, respectively, 1+/−15%:0.5+/−15%:0.5+/−15%:1.5+/−15%:2+/−15%:0.15+/−15% or 1+/−15%:0.5+/−15%:0.5+/−15%:1.5+/−15%:2+/−15%:0.3+/−15%. 
     
     
         36 . The method of  claim 34 , wherein the composition further comprises a L-serine, and wherein a ratio of the L-leucine or a salt thereof of (a), the L-isoleucine or a salt thereof, the L-valine or a salt thereof, the L-arginine or a salt thereof of (b), the L-glutamine or a salt thereof of (c), the NAC or a salt thereof of (d), and the L-serine is, respectively, 12+/−15%:6+/−15%:3+/−15%:9+/−15%:12+/−15%:2.7+/−15%:18+/−15%. 
     
     
         37 . The method of claim  1 , wherein methionine, tryptophan, and cysteine are present at less than 2 wt. % of the composition when the composition is in powder form. 
     
     
         38 . The method of claim  1 , wherein methionine, tryptophan, or cysteine are absent in the composition. 
     
     
         39 . The method of claim  1 , wherein:
 (1) the ratio of the leucine amino acid entity of (a) to the arginine amino acid entity of (b) is at least 1:4, and not more than 3:4;   (2) the ratio of the leucine amino acid entity of (a) to the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine of (c) is at least 1:4, and not more than 3:4; or   (3) the ratio of the arginine amino acid entity of (b) to the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine of (c) is at least 1:4, and not more than 6:7.   
     
     
         40 . The method of claim  1 , wherein the ratio of: (a) the leucine amino acid entity, (b) the arginine amino acid entity, (c) the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine, and (d) the N-acetylcysteine (NAC) or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC is: 1+/−15%:1.5+/−15%:2+/−15%:0.15+/−15%; 1+/−15%:1.5+/−15%:2+/−15%:0.3+/−15%; 1+/−15%:1.81+/−15%:2+/−15%:0.15+/−15%; or 1+/−15%:0.75+/−15%:1+/−15%:0.225+/−15%. 
     
     
         41 . A method for improving mitochondrial function in a subject, wherein the method comprises administering to the subject an effective amount of a pharmaceutical composition consisting essentially of:
 (a) L-leucine or a salt thereof;   (b) L-arginine or a salt thereof;   (c) L-glutamine or a salt thereof,   (d) N-acetylcysteine (NAC) or a salt thereof,   (e) L-isoleucine or a salt thereof,   (f) L-valine or a salt thereof, and   (g) one or more pharmaceutically acceptable excipients.   
     
     
         42 . A method for improving mitochondrial function in a subject, wherein the method comprises administering to the subject an effective amount of a composition comprising:
 (a) L-leucine or a salt thereof,   (b) L-arginine or a salt thereof,   (c) L-glutamine or a salt thereof,   (d) N-acetylcysteine (NAC) or a salt thereof,   (e) L-isoleucine or a salt thereof, and   (f) L-valine or a salt thereof.