COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIVER DISEASES AND DISORDERS

1 . A composition comprising:

a) a leucine amino acid entity;

b) a arginine amino acid entity;

c) glutamine amino acid entity;

d) a N-acetylcysteine (NAC) entity; and

e) one or both of serine amino acid entity or a carnitine entity,

wherein the total wt. % of (a)-(e) is greater than the total wt. % of other amino acid entities in the composition (in dry form), and

wherein optionally one or both of:

the wt. % of the serine amino acid entity is at least 32 wt. % of the amino acid entity components or total components in the composition; or

the wt. % of the carnitine entity is at least 2 wt. % of the amino acid entity components or total components in the composition.

2 . The composition of claim 1 , wherein the composition further comprises: (f) an isoleucine amino acid entity.

3 . The composition of claim 1 , wherein the composition does not comprise a peptide of more than 20 amino acid residues in length, or if a peptide of more than 20 amino acid residues in length is present, the peptide is present at less than: 10 weight (wt.) % of the total wt. of the composition (in dry form).

4 . The composition of claim 2 , wherein one, two, three, four, five, or more of (a)-(f) are in free amino acid form in the composition.

5 . The composition of claim 1 , wherein the total wt. % of (a)-(e) is greater than the total wt. % of one, two, or three of other amino acid entity components, non-amino acid entity components, or non-protein components in the composition (in dry form).

6 . The composition of claim 1 , wherein the composition comprises a combination of 18 or fewer amino acid entities.

7 . (canceled)

8 . The composition of claim 1 , wherein one, two, three, or more of methionine, tryptophan, valine, or cysteine is absent from the composition, or if present, are present at less than: 10 wt. % of the total wt. of the composition (in dry form).

9 . The composition of claim 1 , wherein the composition comprises:

a) the leucine amino acid entity is 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) 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) creatine or a salt thereof; or

iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising creatine;

c) the glutamine amino acid entity is L-glutamine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-glutamine;

d) the NAC entity is NAC or a salt thereof or a dipeptide or salt thereof, comprising NAC; and

e) one or both of:

i) the serine amino acid entity is L-serine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-serine; or

ii) the carnitine entity is L-carnitine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-carnitine.

10 . The composition of claim 9 , wherein the composition further comprises: f) L-isoleucine or a salt thereof or a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine.

11 . The composition of claim 2 , wherein the composition comprises:

a) the leucine amino acid entity is L-leucine or a salt thereof;

b) the arginine amino acid entity is L-arginine or a salt thereof;

c) the glutamine amino acid entity is L-glutamine or a salt thereof;

d) the NAC entity is NAC or a salt thereof;

e) one or both of the serine amino acid entity is L-serine or a salt thereof or the carnitine entity is L-carnitine or a salt thereof; and

f) the isoleucine amino acid entity is L-isoleucine or a salt thereof.

12 . The composition of claim 1 , present in a unit dosage form comprising 6.7 g+/−20% of amino acid entities.

13 . The composition of claim 1 , wherein the composition is formulated with a pharmaceutically acceptable carrier.

14 - 20 . (canceled)

21 . A method for treating a liver disease or disorder, comprising administering to a subject in need thereof an effective amount of a composition comprising:

a) a leucine amino acid entity;

b) a arginine amino acid entity;

c) glutamine amino acid entity;

d) a N-acetylcysteine (NAC) entity; and

e) one or both of serine amino acid entity or a carnitine entity,

wherein the total wt. % of (a)-(e) is greater than the total wt. % of other amino acid entities in the composition (in dry form); and

wherein optionally one or both of:

the wt. % of the serine amino acid entity is at least 32 wt. % of the amino acid entity components or total components in the composition; or

the wt. % of the carnitine entity is at least 2 wt. % of the amino acid entity components or total components in the composition,

thereby treating the liver disease or disorder in the subject.

22 . The method of claim 21 , wherein the subject has a fatty liver disease or disorder.

23 - 26 . (canceled)

27 . A method of manufacturing a dry blended preparation or PGDBP, comprising at least 5 pharmaceutical grade amino acid entities, said method comprising:

forming a combination of at least 4 pharmaceutical grade amino acid entities and blending the combination for a time sufficient to achieve a dry blended preparation,

wherein the dry blended preparation comprises:

a) a leucine amino acid entity;

b) a arginine amino acid entity;

c) glutamine amino acid entity;

d) a N-acetylcysteine (NAC) entity; and

e) one or both of serine amino acid entity or a carnitine entity.

28 . The method of claim 27 , wherein the dry blended preparation further comprises (f) an isoleucine amino acid entity.

29 . The method of claim 27 , wherein:

(i) blending occurs at a temperature lower than 40° C.;

(ii) blending comprises blending or mixing in a blender or mixer at a speed of less than 1000 rpm; or

(iii) the method further comprises one, two, or three of direct blending, roller compaction, or wet granulation of the dry blended preparation.

30 . A composition comprising:

a) a leucine amino acid entity;

b) an isoleucine amino acid entity;

c) a arginine amino acid entity;

d) a N-acetylcysteine (NAC) entity; and

e) a carnitine entity,

wherein the total wt. % of (a)-(e) is greater than the total wt. % of other amino acid entities in the composition (in dry form), and

wherein optionally the wt. % of the carnitine entity is at least 2 wt. % of the amino acid entites or the total components in the composition (in dry form).

31 . The composition of claim 30 , wherein the composition further comprises: (f) one or both of a glutamine amino acid entity or a serine amino acid entity.

32 . (canceled)

33 . A method for treating a liver disease or disorder, comprising administering to a subject in need thereof an effective amount of a composition comprising:

a) a leucine amino acid entity;

b) an isoleucine amino acid entity;

c) a arginine amino acid entity;

d) a N-acetylcysteine (NAC) entity; and

e) a carnitine entity,

wherein the total wt. % of (a)-(e) is greater than the total wt. % of other amino acid entities in the composition (in dry form), and

wherein optionally the wt. % of the carnitine entity is at least 2 wt. % of the amino acid entities or the total components in the composition (in dry form),

thereby treating the liver disease or disorder in the subject.

34 . The composition of claim 30 , wherein the composition comprises:

a) the leucine amino acid entity is 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) the isoleucine amino acid entity is chosen from:

i) L-isoleucine or a salt thereof;

ii) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising L-isoleucine;

c) 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) creatine or a salt thereof; or

iv) a dipeptide or salt thereof, or tripeptide or salt thereof, comprising creatine;

d) the NAC entity is NAC or a salt thereof or a dipeptide or salt thereof, comprising NAC; and

e) the carnitine entity is L-carnitine or a salt thereof or a dipeptide or salt thereof,

or tripeptide or salt thereof, comprising L-carnitine.

35 . The composition of claim 31 , wherein the composition comprises:

a) the leucine amino acid entity is L-leucine or a salt thereof;

b) the isoleucine amino acid entity is L-isoleucine or a salt thereof;

c) the arginine amino acid entity is L-arginine or a salt thereof;

d) the NAC entity is NAC or a salt thereof;

e) the carnitine entity is L-carnitine or a salt thereof; and

f) one or both of the glutamine amino acid entity is L-glutamine or a salt thereof or the serine amino acid entity is L-serine or a salt thereof.

36 . The composition of claim 30 , wherein the composition does not comprise a peptide of more than 20 amino acid residues in length, or if a peptide of more than 20 amino acid residues in length is present, the peptide is present at less than: 10 weight (wt.) % of the total wt. of the composition (in dry form).

37 . The composition of claim 31 , wherein one, two, three, four, five, or more of (a)-(f) are in free amino acid form in the composition.

38 . The composition of claim 30 , wherein the composition comprises a combination of 18 or fewer amino acid entities.

39 . The composition of claim 30 , wherein one, two, three, or more of methionine, tryptophan, valine, or cysteine is absent from the composition, or if present, are present at less than: 10 wt. % of the total wt. of the composition (in dry form).

40 . The composition of claim 30 , wherein the composition is formulated with a pharmaceutically acceptable carrier.