Details for Patent: 5,972,967

Title:	Compositions for inhibiting platelet aggregation
Abstract:	The invention is a pharmaceutical composition for intravenous administration to a patient comprising a) a pharmaceutically effective amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid; b) a pharmaceutically acceptable amount of a citrate buffer effective to provide a pH of between about 5 and 7; and c) a pharmaceutically acceptable amount of a tonicity adjusting agent effective to make the formulation substantially isotonic with the osmotic pressure of the biological system of the patient.
Inventor(s):	Gelotte; Karl M. (North Wales, PA)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Filing Date:	Nov 07, 1997
Application Number:	08/965,922
Claims:	1. An aqueous pharmaceutical composition for intravenous administration to a patient comprising a) a compound which is 2-(S)-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propi onic acid or a pharmaceutically acceptable salt thereof; b) a concentration of a citrate buffer buffer effective to provide a pharmaceutically acceptable pH; c) a concentration of a tonicity adjusting agent effective to make the formulation substantially isotonic with the osmotic pressure of the biological system of the patient. 2. A pharmaceutical composition of claim 1, wherein the compound is 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid, and the concentration of citrate buffer is about 2-20 mM. 3. A composition of claim 2, wherein the concentration of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid or a salt thereof is about 0.05 to about 0.25 mg/ml. 4. A composition of claim 2, wherein the concentration of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid is about 0.25 mg/ml, the concentration of citrate buffer is about 10 mM, the concentration of tonicity adjusting agent is sufficient to achieve a solution osmolarity of about 290 mOsmol/L, and the pH is about 6. 5. A composition of claim 3, wherein the concentration of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid or salt thereof is about 0.05 mg/ml, the concentration of citrate buffer is about 10 mM, the concentration of tonicity adjusting agent is sufficient to achieve a solution osmolarity of about 290 mOsmol/L, and the pH is about 6. 6. A method for inhibiting the aggregation of blood platelets in a mammal, comprising intravenously treating the mammal with a therapeutically effective amount of the composition of claim 2. 7. A method of claim 6 where the mammal is a human. 8. A method for inhibiting the aggregation of blood platelets in a mammal, comprising intravenously treating the mammal with a therapeutically effective amount of the composition of claim 1. 9. A method of claim 8 where the mammal is a human. 10. A composition of claim 1 comprising a concentration of a citrate buffer effective to provide a pH of between about 5 and 7, and a concentration of a tonicity adjusting agent sufficient to achieve a solution osmolarity of between about 50-500 mOsmol/L. 11. A composition of claim 10 comprising about 0.01-0.5 mg/ml of the compound, or a pharmaceutically acceptable salt thereof, about 2-100 mM citrate buffer, and a concentration of a tonicity adjusting agent sufficient to achieve a solution osmolarity of between about 50-500 mOsmol/L. 12. A composition of claim 11 comprising about 2-20 mM citrate buffer, and a concentration of a tonicity adjusting agent sufficient to achieve a solution osmolarity of about 290 mOsmol/L. 13. A composition of claim 1 wherein the compound is 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid or a salt thereof in a concentration of about 0.25 mg/ml, the concentration of citrate buffer is about 10 mM, the concentration of tonicity adjusting agent is sufficient to achieve a solution osmolality of about 316 mOsmol/kg, and the pH is about 6. 14. A composition of claim 1 wherein the compound is 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid or a salt thereof in a concentration of about 0.05 mg/ml, the concentration of citrate buffer is about 10 mM, the concentration of osmolality of about 315 mOsmol/kg, and the pH is about 6. 15. A composition prepared by mixing a) an amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid hydrochloride salt sufficient to obtain a final solution 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid concentration of between 0.01 mg/ml and 0.5 mg/ml; b) an amount of sodium citrate and an amount of citric acid sufficient to obtain a final solution pH of between 5 and 7; and c) an amount of tonicity adjusting agent sufficient to provide solution osmolarity of between about 50 and 500 mOsmol/L. 16. A composition of claim 15, wherein the amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid hydrochloride salt is sufficient to obtain a final solution 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid concentration of between 0.05 mg/ml and 0.25 mg/ml. 17. A composition of claim 15, wherein the amount of sodium citrate and the amount of citric acid is sufficient to obtain a pH of between about 5.8 and 6.2. 18. A composition of claim 15, wherein the amount of tonicity adjusting agent is sufficient to provide solution osmolarity of about 290 mOsmol/L. 19. A composition of claim 15, wherein a) the amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid hydrochloride salt is sufficient to obtain a final solution 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl}propion ic acid concentration of about 0.05 mg/ml; b) the amount of sodium citrate and an amount of citric acid is sufficient to obtain a final solution pH of about 6; and c) the amount of tonicity adjusting agent is sufficient to provide solution osmolarity of about 290 mOsmol/L. 20. A composition of claim 15, wherein a) the amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid hydrochloride salt is sufficient to obtain a final solution 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid concentration of about 0.25 mg/ml; b) the amount of sodium citrate and an amount of citric acid is sufficient to obtain a final solution pH of about 6; and c) the amount of tonicity adjusting agent is sufficient to provide solution osmolarity of about 290 mOsmol/L. 21. A composition prepared by mixing a) an amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid hydrochloride salt is sufficient to obtain a final solution 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid concentration of about 0.25 mg/ml; b) an amount of sodium citrate and an amount of citric acid is sufficient to obtain a final solution pH of about 6; and c) an amount of tonicity adjusting agent is sufficient to provide solution osmolality of about 316 mOsmol/kg. 22. A composition prepared by mixing a) an amount of 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl]propion ic acid hydrochloride salt is sufficient to obtain a final solution 2-S-(n-Butylsulfonylamino)-3-[4-(4-(piperidin-4-yl)butyloxy)phenyl}propion ic acid concentration of about 0.05 mg/ml; b) an amount of sodium citrate and an amount of citric acid is sufficient to obtain a final solution pH of about 6; and c) an amount of tonicity adjusting agent is sufficient to provide solution osmolality of about 315 mOsmol/kg.