Amino acid compositions and methods for the treatment of liver diseases
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. A composition comprising:
(a)
L-leucine or a salt thereof, or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine;
(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.
2. The composition 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.
3. The composition of claim 1 , wherein methionine, tryptophan, or cysteine are absent in the composition.
4. The composition of claim 1 , wherein:
(1) the wt. % of the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine in the composition is greater than the wt. % of the arginine amino acid entity;
(2) the wt. % of the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine in the composition is equal to or greater than the wt. % of the leucine or a salt thereof, or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine; or
(3) the wt. % of the arginine amino acid entity in the composition is greater than the wt. % of the L-leucine or salt thereof, or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine.
5. The composition of claim 1 , wherein:
the wt. % of the arginine amino acid entity in (b), the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine in (c), and the NAC or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC in (d) in combination is at least 50% of the composition, when the composition is in powder form, but not more than 90% of the composition, when the composition is in powder form.
6. The composition of claim 1 , wherein:
(1) the ratio of the leucine or a salt thereof, or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine to the arginine amino acid entity is at least 1:4, and not more than 3:4;
(2) the ratio of the leucine leucine or a salt thereof, or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine to the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine is at least 1:4, and not more than 3:4; or
(3) the ratio of the arginine amino acid entity to the L-glutamine or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine is at least 1:4, and not more than 6:7.
7. The composition of claim 1 , wherein the wt. ratio of: (a) leucine or a salt thereof, or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-leucine, (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 NAC or salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC is, respectively, 1+/−15%:1.5+/−15%:2+/−15%:0.15+/−15%; 1+/−15%:1.5+/−15%:2+/−15%:0.3+/−15%; or 1+/−15%:0.75+/−15%:1+/−15%:0.225+/−15%.
8. The composition of claim 1 , further comprising one or both of:
(1) L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine; or
(2) L-valine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-valine.
9. The composition of claim 8 , wherein the composition comprises:
(a) L-leucine or a salt thereof;
(b) L-arginine or a salt thereof;
(c) L-glutamine or a salt thereof;
(d) NAC or a salt thereof;
(e) L-isoleucine or a salt thereof; and
(f) L-valine or a salt thereof.
10. The composition of claim 9 , wherein the composition comprises:
(a) L-leucine or a salt thereof;
(b) L-arginine or a salt thereof;
(c) L-glutamine or a salt thereof;
(d) NAC or a salt thereof;
(e) L-isoleucine or a salt thereof; and
(f) L-valine or a salt thereof;
wherein the wt. ratio of the L-leucine or a salt thereof, the L-isoleucine or a salt thereof, the L-valine or a salt thereof, the L-arginine or a salt thereof, the L-glutamine or a salt thereof, and the NAC or salt thereof 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%.
11. The composition of claim 1 , wherein at least one of (a)-(d) is a free amino acid.
12. The composition of claim 1 , wherein at least one of (a)-(d) is in a salt form.
13. The composition of claim 1 , wherein the composition comprises a combination of not more than 15 different amino acid entities.
14. The composition of claim 1 , further comprising a serine amino acid entity chosen from L-serine, L-glycine, or a combination thereof.
15. The composition of claim 1 , wherein:
the arginine amino acid entity is 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, or
iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising ornithine.
16. The composition of claim 1 , wherein the wt. % of the NAC or a salt thereof or the dipeptide or salt thereof, or tripeptide or salt thereof, comprising NAC is at least 1%, but not more than 10% or the composition, when the composition is in powder form.
17. The composition of claim 1 , further comprising L-serine or a salt thereof.
18. A dietary composition comprising the composition of claim 1 .
19. A pharmaceutical composition comprising the composition of claim 1 .
20. 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) 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.