1. A composition suitable for reconstitution into an aqueous suspension, comprising 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride, guar gum, wherein said guar gum is present as from 3% to 12% by weight of the weight of the composition, and polyvinylpyrrolidone, wherein said polyvinylpyrrolidone is present as from 2% to 14% by weight of the weight of the composition.
2. A composition according to claim 1 wherein said guar gum is present as from 3% to 8% by weight of the weight of the composition.
3. A composition according to claim 1 wherein said micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride has a particle size distribution such that more than 90% of the particles are between 0.61 and 10.0 microns.
4. A composition according to claim 1 wherein when said composition is reconstituted into an aqueous suspension, it has a pH of from 3.0 to 4.2.
5. A composition according to claim 4 wherein when said composition is reconstituted into an aqueous suspension, it has a pH of from 3.5 to 4.0.
6. Direct blend powder for use in a pharmaceutical composition, comprising
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 3% to 12% ww guar gum as a thickening agent,
iii) 2% to 14% ww polyvinylpyrrolidone (PVP) as a suspending agent,
iv) surfactant,
v) buffer,
vi) preservative,
vii) anti-adherent or glidant,
viii) sweetener, and
ix) flavor.
7. The powder of claim 6, comprising
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 3.0 to 8.0 ww % guar gum as a thickening agent,
iii) 3.0 to 12.0 ww % polyvinylpyrrolidone (PVP) as a suspending agent,
iv) 0.02 to 0.55 ww % Polysorbate 80 as a surfactant,
v) about 4.7 ww % citric acid and about 4.0 ww % sodium phosphate as buffer,
vi) 1.2 to 2.0 ww % methylparaben as an antimicrobial preservative,
vii) 0.32 to 0.64 ww % colloidal silicon dioxide as an anti-adherent,
viii) 5.0 to 11.0 ww % sucralose and 18.0 to 30.0 ww % mannitol as a sweetener, and
ix) 1.0 to 4.0 ww % lemon flavor.
8. The powder of claim 7, consisting of
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 3.0 to 8.0 ww % guar gum as a thickening agent,
iii) 3.0 to 12.0 ww % polyvinylpyrrolidone (PVP) as a suspending agent,
iv) 0.02 to 0.55 ww % Polysorbate 80 as a surfactant,
v) about 4.7 ww % citric acid and about 4.0 ww % sodium phosphate as buffer,
vi) 1.2 to 2.0 ww % methylparaben as an antimicrobial preservative,
vii) 0.32 to 0.64 ww % colloidal silicon dioxide as an anti-adherent,
viii) 5.0 to 11.0 ww % sucralose and 18.0 to 30.0 ww % mannitol as a sweetener, and
ix) 1.0 to 4.0 ww % lemon flavor.
9. An oral suspension pharmaceutical formulation, comprising
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 3% to 12% ww guar gum as a thickening agent,
iii) 2% to 14% ww polyvinylpyrrolidone (PVP) as a suspending agent,
iv) surfactant,
v) buffer,
vi) preservative,
vii) anti-adherent,
viii) sweetener,
ix) flavor, and
x) water.
10. An oral suspension comprising
a) a direct blend powder comprising
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 3.0 to 8.0 ww % guar gum as a thickening agent,
iii) 3.0 to 12.0 ww % polyvinylpyrrolidone (PVP) as a suspending agent,
iv) 0.02 to 0.55 ww % Polysorbate 80 as a surfactant,
v) about 4.7 ww % citric acid and about 4.0 ww % sodium phosphate as buffer,
vi) 1.2 to 2.0 ww % methylparaben as an antimicrobial preservative,
vii) 0.32 to 0.64 ww % colloidal silicon dioxide as an anti-adherent,
viii) 5.0 to 11.0 ww % sucralose and 18.0 to 30.0 ww % mannitol as a sweetener, and
ix) 1.0 to 4.0 ww % lemon flavor, and
b) purified water.
11. The powder of claim 6, comprising
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 12.0 to 20.0 ww % platform placebo granules (containing guar gum, polysorbate 80, and mannitol) as a thickening agent,
iii) 3.0 to 12.0 ww % polyvinylpyrrolidone (PVP) as a suspending agent,
iv) about 4.7 ww % citric acid and about 4.0 ww % sodium phosphate as buffer,
v) 5.0 to 11.0 ww % sucralose and 10.0 to 20.0 ww % mannitol as a sweetener,
vi) 1.2 to 2.0 ww % methylparaben as an antimicrobial preservative,
vii) 0.32 to 0.64 ww % colloidal silicon dioxide as an anti-adherent,
viii) and 1.0 to 4.0 ww % lemon flavor.
12. The powder of claim 6, consisting of
i) 35.0 to 50.0 ww % micronized 5-4-(2,3-dimethyl-2H-indazol-6-yl)methylamino-2-pyrimidinylamino-2-methylbenzenesulfonamide hydrochloride,
ii) 3.0 to 12.0 ww % guar gum as a thickening agent,
iii) 0.5 to 4.0 ww % Hypromellos (HPMC) as a suspending agent,
iv) about 4.7 ww % citric acid and about 4.0 ww % sodium phosphate as buffer,
v) 1.2 to 2.0 ww % methylparaben as an antimicrobial preservative,
vi) 0.32 to 0.64 ww % colloidal silicon dioxide as an anti-adherent,
vii) 5.0 to 14.0 ww % sucralose and 18.0 to 30.0 ww % mannitol as a sweetener, and
viii) 1.0 to 4.0 ww % lemon flavor.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-16. (canceled)
17. A composition comprising branched chain amino acids leucine, isoleucine and valine and at least one of methionine or phenylalanine,
wherein leucine, isoleucine and valine are present in the following molar ratios:
from 40 to 60% of leucine in molecular weight;
from 20 to 40% of isoleucine in molecular weight;
from 20 to 40% of valine in molecular weight,
the sum of the amounts of leucine, isoleucine and valine being between 30 to 60% of the sum in molecular weight of all the active ingredients.
18. The composition according to claim 17, further comprising at least one of threonine or lysine.
19. The composition according to claim 18, further comprising one or more amino acids selected in the group consisting of histidine, tryphtophan, tyrosine, cystine and cysteine.
20. The composition according to claim 19, further comprising cystine.
21. The composition according to claim 17, comprising methionine and phenylalanine.
22. The composition according to claim 17, comprising methionine and cystine.
23. The composition according to claim 17, comprising phenylalanine and cystine.
24. The composition according to claim 17, comprising methionine, phenylalanine and cystine.
25. The composition according to claim 17, further comprising cystine.
26. A composition comprising
the branched chain amino acids leucine, isoleucine and valine, and
at least one of methionine and phenylalanine, and
cystine,
wherein leucine, isoleucine and valine are present in the following molar ratios:
from 40 to 60% of leucine in molecular weight;
from 20 to 40% of isoleucine in molecular weight;
from 20 to 40% of valine in molecular weight,
the sum of the amounts of leucine, isoleucine and valine being between 30 to 60% of the sum in molecular weight of all the active ingredients.
27. The composition according to claim 26, further comprising at least one of threonine and lysine.
28. The composition according to claim 27, further comprising at least one further amino acids selected in the group consisting of histidine, tryphtophan, tyrosine, and cysteine.
29. The composition according to claim 17, wherein the stoichiometric ratio of leucine, isoleucine and valine is 2:1:1.
30. The composition according to claim 26, wherein the stoichiometric ratio of leucine, isoleucine and valine is 2:1:1.