COMPOSITIONS CONTAINING KINASE INHIBITORS
A composition comprises a kinase inhibitory compound, e.g., N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea, in a mixture comprising (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. The composition is suitable for dilution with an IV solution for administration to a subject in need thereof for treatment of a cancer.
1 . A composition comprising
(a) N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea or a salt thereof;
(b) polyethylene glycol;
(c) polyoxyethylated castor oil; and
(d) ethanol;
wherein the polyethylene glycol and the polyoxyethylated castor oil are present in a 1:1 ratio by weight.
2 . The composition of claim 1 comprising the free base of N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea.
3 . The composition of claim 1 , wherein the N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea or a salt thereof is present in a concentration of about 4 mg/mL to about 10 mg/mL.
4 . The composition of claim 1 , wherein the N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea or a salt thereof is present in a concentration of about 6 mg/mL.
5 . The composition of claim 1 , wherein the polyethylene glycol and the polyoxyethylated castor oil are each present in a range of about 42.5% w/w to about 47.5% w/w.
6 . The composition of claim 5 , wherein the polyethylene glycol and the polyoxethylated castor oil are each present in about 45% w/w.
7 . The composition of claim 1 , wherein the ethanol is present in about 10% by w/w.
8 . The composition of claim 1 , wherein the polyethylene glycol is polyethylene glycol 300.
9 . The composition of claim 1 , wherein the polyoxethylated castor oil is polyoxyl 35 castor oil.
10 . The composition of claim 1 , comprising a mixture of
polyethylene glycol 300, polyoxyl 35 castor oil, and ethanol in a ratio of 45:45:10% w/w, and N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea, wherein the N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea is present in a concentration of about 6 mg/mL.
11 . The composition of claim 1 , wherein the composition is diluted in an aqueous solution comprising 0.45% NaCl.
12 . The composition of claim 1 , wherein the composition is diluted in an aqueous solution comprising 0.9% NaCl.
13 . The composition of claim 1 , wherein the composition is diluted in an aqueous solution comprising 5% dextrose.
14 . The composition of claim 1 , wherein the dilution is a 5-20 fold dilution.
15 . The composition of claim 14 , wherein the dilution is a 15-16 fold dilution.
16 . A pharmaceutical composition comprising (a) N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea or a salt thereof;
(b) polyethylene glycol;
(c) polyoxyethylated castor oil;
(d) ethanol; and
(e) a pharmaceutically acceptable IV solution selected from the group consisting of a saline solution and a dextrose solution;
wherein the polyethylene glycol and the polyoxyethylated castor oil are present in a 1:1 ratio by weight.
17 . The pharmaceutical composition of claim 16 , comprising about 200 mg of the free base of N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea.
18 . The pharmaceutical composition of claim 16 , wherein the polyethylene glycol is polyethylene glycol 300.
19 . The pharmaceutical composition of claim 16 , wherein the polyoxethylated castor oil is polyoxyl 35 castor oil.
20 . The pharmaceutical composition of claim 16 , wherein the IV solution is a 0.45% saline solution.
21 . The pharmaceutical composition of claim 16 , wherein the IV solution is a 0.9% saline solution.
22 . The pharmaceutical composition of claim 16 , wherein the IV solution is a 5% dextrose solution.
23 . A method of treating cancer comprising administering to a subject having the disease a therapeutically effective amount of the pharmaceutical composition of claim 1 .
24 . The method of claim 23 , wherein the pharmaceutical composition is administered by intravenous administration.