AMINO ACID COMPOSITIONS AND METHODS FOR THE TREATMENT OF MUSCLE DISEASES AND DISORDERS

1 . A composition comprising:

a) a leucine (L)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

b) an arginine (R)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

c) a glutamine (Q)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

d) N-acetylcysteine (NAC) or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid; and

e) an essential amino acid (EAA)-entity chosen from a histidine (H)-amino acid-entity, a lysine (K)-amino acid-entity, a phenylalanine (F)-amino acid-entity, and a threonine (T)-amino acid-entity or a combination of two, three, or four of the EAAs;

provided that:

the R-amino acid entity is present at a higher amount (wt. %) than the L-amino acid entity.

2 . (canceled)

3 . The composition of claim 1 , wherein one, two, three, or more of methionine (M), trytophan (W), valine (V), or cysteine (C) is absent, or if present, is present at less than 10 weight (wt.) %, 9 wt. %, 8 wt. %, 7 wt. %, 6 wt. %, 5 wt. %, 4 wt. %, 3 wt. %, 2 wt. %, or 1 wt. %.

4 . The composition of claim 1 , wherein the total wt. % of (a)-(e) is greater than the total wt. % of any other amino acid entity in the composition.

5 . The composition of claim 1 , wherein:

f) a wt. % of the R-amino acid entity in the composition is greater than the wt. % of the Q-amino acid entity;

g) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

h) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

i) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the EAA, or the combination of two, three, or four of the EAAs;

j) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs;

k) the wt. % of the L-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs; or

l) a combination of two, three, four, five, or six of (f)-(k).

6 .- 12 . (canceled)

13 . The composition of claim 1 , further comprising one or both of an isoleucine (I)-amino acid-entity and a valine (V)-amino acid-entity.

14 .- 38 . (canceled)

39 . A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient.

40 . (canceled)

41 . A method for improving muscle function, wherein the method comprises administering to a subject in need thereof an effective amount of a composition comprising:

a) a leucine (L)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

b) an arginine (R)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

c) a glutamine (Q)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

d) N-acetylcysteine (NAC) or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid; and

e) an essential amino acid (EAA)-entity chosen from a histidine (H)-amino acid-entity, a lysine (K)-amino acid-entity, a phenylalanine (F)-amino acid-entity, and a threonine (T)-amino acid-entity or a combination of two, three, or four of the EAAs;

provided that:

the R-amino acid entity is present at a higher amount (wt. %) than the L-amino acid entity.

42 . The method of claim 41 , wherein the subject has a disease or disorder chosen from a rare muscle disease, muscle atrophy, sarcopenia, muscle deterioration, muscle decay, cachexia, drug-induced myopathy, muscular dystrophy, myopenia, muscle weakness, perceived muscle weakness, ICU-acquired myopathy, burns-related myopathy, a neuromuscular disorder, ventilator-induced diaphragmatic dystrophy, hyponatremia, hypokalemia, a calcium deficiency, hypercalcemia, amyotrophic lateral sclerosis, and a bone weakness disease, or a combination thereof.

43 . The method of claim 41 , wherein the subject has or is identified as having decreased muscle function due to aging, injury, muscle atrophy, infection, disease, stroke, or a fracture or other trauma.

44 . The method of claim 41 , wherein the subject has had a rotator cuff surgery, knee surgery, hip surgery, joint replacement, injury repair surgery, or has worn a cast prior to administration of the composition.

45 .- 46 . (canceled)

47 . A method of providing amino acid entities to a subject comprising administering to the subject an effective amount of a composition comprising:

a) a leucine (L)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

b) an arginine (R)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

c) a glutamine (Q)-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

d) N-acetylcysteine (NAC) or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid; and

e) an essential amino acid (EAA)-entity chosen from a histidine (H)-amino acid-entity, a lysine (K)-amino acid-entity, a phenylalanine (F)-amino acid-entity, and a threonine (T)-amino acid-entity or a combination of two, three, or four of the EAAs;

provided that:

the R-amino acid entity is present at a higher amount (wt. %) than the L-amino acid entity.

48 . A method of manufacturing or making a composition comprising forming a composition comprising the following:

a) a L-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

b) an R-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

c) a Q-amino acid entity chosen from Table 2 or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid;

d) NAC or a salt thereof, a dipeptide or salt thereof, a tripeptide or salt thereof, or a combination of any of the aforesaid; and

e) an EAA-entity chosen from a H-amino acid-entity, a K-amino acid-entity, a F-amino acid-entity, and a T-amino acid-entity or a combination of two, three, or four of the EAAs; provided that:

the R-amino acid entity is present at a higher amount (wt. %) than the L-amino acid entity.

49 .- 50 . (canceled)

51 . The method of claim 41 , wherein one, two, three, or more of M, W, V, or C is absent, or if present, is present at less than 10 weight (wt.) %, 9 wt. %, 8 wt. %, 7 wt. %, 6 wt. %, 5 wt. %, 4 wt. %, 3 wt. %, 2 wt. %, or 1 wt. %.

52 . The method of claim 41 , wherein the total wt. % of (a)-(e) is greater than the total wt. % of any other amino acid entity in the composition.

53 . The method of claim 41 , wherein:

f) a wt. % of the R-amino acid entity in the composition is greater than the wt. % of the Q-amino acid entity;

g) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

h) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

i) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the EAA, or the combination of two, three, or four of the EAAs;

j) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs;

k) the wt. % of the L-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs; or

l) a combination of two, three, four, five, or six of (f)-(k).

54 . The method of claim 41 , wherein the composition further comprises one or both of an I-amino acid-entity and a V-amino acid-entity.

55 . The method of claim 41 , wherein the composition is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

56 . The method of claim 47 , wherein one, two, three, or more of methionine M, W, V, or C is absent, or if present, is present at less than 10 weight (wt.) %, 9 wt. %, 8 wt. %, 7 wt. %, 6 wt. %, 5 wt. %, 4 wt. %, 3 wt. %, 2 wt. %, or 1 wt. %.

57 . The method of claim 47 , wherein the total wt. % of (a)-(e) is greater than the total wt. % of any other amino acid entity in the composition.

58 . The method of claim 47 , wherein:

f) a wt. % of the R-amino acid entity in the composition is greater than the wt. % of the Q-amino acid entity;

g) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

h) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

i) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the EAA, or the combination of two, three, or four of the EAAs;

j) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs;

k) the wt. % of the L-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs; or

l) a combination of two, three, four, five, or six of (f)-(k).

59 . The method of claim 47 , wherein the composition further comprises one or both of an I-amino acid-entity and a V-amino acid-entity.

60 . The method of claim 47 , wherein the composition is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

61 . The method of claim 48 , wherein one, two, three, or more of M, W, V, or C is absent, or if present, is present at less than 10 weight (wt.) %, 9 wt. %, 8 wt. %, 7 wt. %, 6 wt. %, 5 wt. %, 4 wt. %, 3 wt. %, 2 wt. %, or 1 wt. %.

62 . The method of claim 48 , wherein the total wt. % of (a)-(e) is greater than the total wt. % of any other amino acid entity in the composition.

63 . The method of claim 48 , wherein:

f) a wt. % of the R-amino acid entity in the composition is greater than the wt. % of the Q-amino acid entity;

g) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

h) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the L-amino acid entity;

i) the wt. % of the R-amino acid entity in the composition is greater than the wt. % of the EAA, or the combination of two, three, or four of the EAAs;

j) the wt. % of the Q-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs;

k) the wt. % of the L-amino acid entity in the composition is greater than the wt. % of the EAA or the combination of two, three, or four of the EAAs; or

l) a combination of two, three, four, five, or six of (f)-(k).

64 . The method of claim 48 , wherein the composition further comprises one or both of an I-amino acid-entity and a V-amino acid-entity.

65 . The method of claim 48 , wherein the composition is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable excipient.