Patent EA-004435-B1 (EA)
Title: Synergistic effects of amlodipine and atorvastatin
IPC: A61K31/44
Filed: 2000-04-18
Abstract: 1. A pharmaceutical composition comprising: (a) a therapeutically effective amount of amlodipine; (b) a therapeutically effective amount of hydroxylated atorvastatin metabolite having the formula and (c) pharmaceutically acceptable formulation agents, wherein effective amounts of amlodipine and hydroxylated atorvastatin metabolite are coordinated so that essentially inhibits peroxide lipid oxidation in human lipoprotein of low concentration or in lipid membrane for therapeutic effect. 2. The pharmaceutical composition of claim 1, wherein amlodipine comprises a therapeutically effective derivative of amlodipine. 3. The pharmaceutical composition of claim 2, wherein the therapeutically effective derivative of amlodipine comprises amlodipine besylate. 4. The pharmaceutical composition of claim 1, wherein said pharmaceutical composition reduces the risk of arterial and related heart disease. 5. The pharmaceutical composition of claim 4, wherein said arterial and related heart disease is selected from the group consisting of hypertension, hyperlipidemia, atherosclerosis, arteriosclerosis, coronary artery disease, myocardial infarction, congestive heart failure, stroke, and angina pectoris. 6. The pharmaceutical composition of claim 1, wherein said pharmaceutical composition lowers blood pressure. 7. The pharmaceutical composition of claim 6, wherein said pharmaceutical composition lowers blood pressure to a level consistent with a reduced risk of arterial and related heart disease. 8. The pharmaceutical composition of claim 6, wherein said pharmaceutical composition lowers blood pressure to a level statistically equivalent to normal. 9. The pharmaceutical composition of claim 1, wherein said pharmaceutical composition lowers systemic lipid concentrations. 10. The pharmaceutical composition of claim 9, wherein said pharmaceutical composition lowers systemic lipid concentrations to a level consistent with a reduced risk of arterial and related heart disease. 11. The pharmaceutical composition of claim 9, wherein said pharmaceutical composition lowers systemic lipid concentrations to a level statistically equivalent to normal. 12. The pharmaceutical composition of claim 1, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations. 13. The pharmaceutical composition of claim 12, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations to a level consistent with a reduced risk of arterial and related heart disease. 14. The pharmaceutical composition of claim 12, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations to a level statistically equivalent to normal. 15. The pharmaceutical composition of claim 1, wherein said pharmaceutical composition concomitantly lowers blood pressure and systemic lipid concentrations. 16. The pharmaceutical composition of claim 15, wherein said pharmaceutical composition concomitantly lowers blood pressure and systemic lipid concentrations to a level consistent with a reduced risk of arterial and related heart disease. 17. The pharmaceutical composition of claim 15, wherein said pharmaceutical composition concomitantly lowers blood pressure and systemic lipid concentrations to a level statistically equivalent to normal. 18. The pharmaceutical composition of claim 1, wherein said pharmaceutical composition synergistically lowers blood pressure and systemic lipid concentrations. 19. The pharmaceutical composition of claim 18, wherein said pharmaceutical composition synergistically lowers blood pressure and systemic lipid concentrations to a level consistent with a reduced risk of arterial and related heart disease. 20. The pharmaceutical composition of claim 18, wherein said pharmaceutical composition synergistically lowers blood pressure and systemic lipid concentrations to a level statistically equivalent to normal. 21. The pharmaceutical composition of any of claims 15-17 and 18-20, wherein the concomitant lowering of blood pressure and systemic lipid concentrations results at least partially from reduced lipid oxidation. 22. The pharmaceutical composition comprising: (a) therapeutically effective amount of combination of amlodipine and hydroxylated atorvastatin metabolite having the formula and (b) pharmaceutically acceptable formulation agents, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations results at least partially from reduced lipid oxidation. 23. The pharmaceutical composition of claim 22, wherein amlodipine comprises a therapeutically effective derivative of amlodipine. 24. The pharmaceutical composition of claim 23, wherein the therapeutically effective derivative of amlodipine comprises amlodipine besylate. 25. The pharmaceutical composition of claim 22, wherein said pharmaceutical composition reduces the risk of arterial and related heart disease. 26. The pharmaceutical composition of claim 25, wherein said arterial and related heart disease is selected from the group consisting of hypertension, hyperlipidemia, atherosclerosis, arteriosclerosis, coronary artery disease, myocardial infarction, congestive heart failure, stroke, and angina pectoris. 27. The pharmaceutical composition of claim 22, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations to a level consistent with a reduced risk of arterial and related heart disease. 28. The pharmaceutical composition of claim 22, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations to a level statistically equivalent to normal. 29. A method of treating arterial and related heart disease comprising inhibition of peroxide lipid oxidation in human lipoprotein of low concentration or in lipid membrane by means of administering a therapeutically effective amount of a combination of amlodipine and hydroxylated atorvastatin metabolite having the formula 30. The pharmaceutical composition of claim 29, wherein amlodipine comprises a therapeutically effective derivative of amlodipine. 31. The pharmaceutical composition of claim 30, wherein the therapeutically effective derivative of amlodipine comprises amlodipine besylate. 32. The pharmaceutical composition of claim 29, wherein said arterial and related heart disease is selected from the group consisting of hypertension, hyperlipidemia, atherosclerosis, arteriosclerosis, coronary artery disease, myocardial infarction, congestive heart failure, stroke, and angina pectoris. 33. The method of claim 29, wherein amlodipine and the atorvastatin compound are administered in the same therapeutic. 34. The method of claim 29, wherein amlodipine and the atorvastatin compound are administered as separate therapeutics. 35. The method of claim 29, wherein amlodipine and the atorvastatin compound are administered at the same time. 36. The method of claim 29, wherein amlodipine and the atorvastatin compound are administered at different times. 37. The method of lowering of blood pressure and systemic lipid concentrations comprising inhibition of lipid oxidation by means of administering a therapeutically effective amount of a combination of amlodipine and an atorvastatin compound having the formula 38. The method of claim 37, wherein amlodipine comprises a therapeutically effective derivative of the amlodipine. 39. The method of claim 38, wherein the therapeutically effective derivative of amlodipine comprises amlodipine besylate. 40. The method of claim 37, wherein amlodipine and the atorvastatin compound are administered in the same therapeutic. 41. The method of claim 37, wherein amlodipine and the atorvastatin compound are administered as separate therapeutics. 42. The method of claim 37, wherein amlodipine and the atorvastatin compound are administered at the same time. 43. The method of claim 37, wherein amlodipine and the atorvastatin compound are administered at different times. 44. The pharmaceutical composition of claim 37, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations to a level consistent with a reduced risk of arterial and related heart disease. 45. The pharmaceutical composition of claim 37, wherein said arterial and related heart disease is selected from the group consisting of hypertension, hyperlipidemia, atherosclerosis, arteriosclerosis, coronary artery disease, myocardial infarction, congestive heart failure, stroke, and angina pectoris. 46. The pharmaceutical composition of claim 37, wherein said pharmaceutical composition lowers blood pressure and systemic lipid concentrations to a level statistically equivalent to normal. 47. The pharmaceutical composition of any of claims 37-46, wherein the lowering of blood pressure and systemic lipid concentrations results at least partially from reduced lipid oxidation. 48. A method of synergistically inhibiting lipid oxidation comprising administering a therapeutically effective amount of a combination of amlodipine and hydroxylated atorvastatin metabolite having the formula 49. The method of claim 48, wherein amlodipine comprises a therapeutically effective derivative of the amlodipine. 50. The method of claim 49, wherein the therapeutically effective derivative of amlodipine comprises amlodipine besylate. 51. The method of claim 48, wherein amlodipine and the atorvastatin compound are administered in the same therapeutic. 52. The method of claim 48, wherein amlodipine and the atorvastatin compound are administered as separate therapeutics. 53. The method of claim 48, wherein amlodipine and the atorvastatin compound are administered at the same time. 54. The method of claim 48, wherein amlodipine and the atorvastatin compound are administered at different times. 55. The method of claim 48, wherein said pharmaceutical composition inhibits lipid oxidation to an extent consistent with a reduced risk of arterial and related heart disease. 56. The method