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BR-112021001374-B1 - Pharmaceutical composition for the treatment of hypertension and its use.

BR112021001374B1BR 112021001374 B1BR112021001374 B1BR 112021001374B1BR-112021001374-B1

Abstract

COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION. Pharmaceutical compositions are provided here that are useful for the treatment of hypertension, comprising an angiotensin II receptor blocker, a diuretic, and a calcium channel blocker.

Inventors

  • Stephen Macmahon
  • Anthony RODGERS

Assignees

  • The George Institute for Global Health

Dates

Publication Date
20260317
Application Date
20190726
Priority Date
20180726

Claims (20)

  1. 1. Pharmaceutical composition characterized by comprising: (a) telmisartan; (b) indapamide; and (c) amlodipine besylate, wherein a dose of each of (a), (b) and (c) is 40% to 80% of the therapeutic dose for lower hypertension (LHTD), and wherein the pharmaceutical composition further comprises at least one cholesterol-lowering active agent.
  2. 2. Pharmaceutical composition according to claim 1, characterized in that the dose of each of (a), (b) and (c) is 40% to 60% of the therapeutic dose for lower hypertension (LHTD).
  3. 3. Pharmaceutical composition, according to claim 1 or 2, characterized in that the dose of indapamide is 50% of the therapeutic dose for lower hypertension (LHTD).
  4. 4. Pharmaceutical composition, according to any one of claims 1 to 3, characterized in that the dose of indapamide is 0.625 milligrams (mg).
  5. 5. Pharmaceutical composition, according to any one of claims 1 to 4, characterized in that the dose of amlodipine besylate is 50% of the therapeutic dose for lower hypertension (LHTD).
  6. 6. Pharmaceutical composition, according to any one of claims 1 to 5, characterized in that the dose of telmisartan is 50% of the therapeutic dose for lower hypertension (LHTD).
  7. 7. Pharmaceutical composition, according to any one of claims 1 to 6, characterized in that the dose of telmisartan is 10 mg.
  8. 8. Pharmaceutical composition, according to claim 1, characterized in that the dose of telmisartan is 8 to 12 mg, the dose of indapamide is 0.5 to 0.75 mg and the dose of amlodipine is 1 to 1.5 mg or 1.5 to 2 mg.
  9. 9. Pharmaceutical composition, characterized by comprising (a) telmisartan; (b) indapamide; and (c) amlodipine besylate, wherein a dose of each of (a), (b) and (c) is 80% to 150% of the therapeutic dose for lower hypertension (LHTD), and wherein the pharmaceutical composition further comprises at least one cholesterol-lowering active agent.
  10. 10. Pharmaceutical composition according to claim 9, characterized in that the dose of each of (a), (b) and (c) is 80% to 120% of the therapeutic dose for lower hypertension (LHTD).
  11. 11. Pharmaceutical composition, according to claim 9 or 10, characterized in that the dose of indapamide is 100% of the therapeutic dose for lower hypertension (LHTD).
  12. 12. Pharmaceutical composition, according to any one of claims 9 to 11, characterized in that the dose of indapamide is 1.25 mg.
  13. 13. Pharmaceutical composition, according to any one of claims 9 to 12, characterized in that the dose of the calcium channel blocker is 100% of the therapeutic dose for lower hypertension (LHTD).
  14. 14. Pharmaceutical composition, according to any one of claims 9 to 13, characterized in that the dose of telmisartan is 100% of the lower hypertension therapeutic dose (LHTD) for telmisartan.
  15. 15. Pharmaceutical composition, according to any one of claims 9 to 14, characterized in that the dose of telmisartan is 20 mg.
  16. 16. Pharmaceutical composition, according to any one of claims 9 to 15, characterized in that the dose of telmisartan is 16 mg to 24 mg, the dose of indapamide is 1 mg to 1.5 mg and the dose of amlodipine besylate is 2 to 3.75 mg, 2 to 3 mg, 2.25 to 2.75 mg or 3.75 to 6.25 mg.
  17. 17. Pharmaceutical composition, according to any of the preceding claims, characterized in that at least one cholesterol-lowering active agent is ezetimibe, rosuvastatin, or a combination thereof.
  18. 18. Pharmaceutical composition, according to any of the preceding claims, characterized in that at least one cholesterol-lowering active agent is a combination of ezetimibe and rosuvastatin.
  19. 19. Pharmaceutical composition, according to claim 17 or 18, characterized in that the dose of ezetimibe is 10 mg and the dose of rosuvastatin is 10 mg.
  20. 20. Use of a composition, as defined in any one of claims 1 to 16, characterized in that it is used in the preparation of a medicament to treat at least one of hypertension and dyslipidemia in an individual in need thereof.

Description

CROSS-REFERENCE WITH RELATED REQUEST [001] This application claims the benefit of U.S. Provisional Application No. 62/703,802, filed July 26, 2018, which is incorporated by reference in the disclosure of this application. BACKGROUND TO THE REVELATION [002] High blood pressure, also known as hypertension, is a leading cause of preventable morbidity and mortality, and it is well established that treatments that lower blood pressure (BP) are beneficial. However, despite the abundance of blood pressure-lowering medications available, many patients continue to have insufficient blood pressure control, as evidenced by several large-scale population studies. Factors contributing to insufficient blood pressure control include poor adherence, complex guidelines recommending multiple titration steps, and treatment inertia. Furthermore, most treated patients receive only monotherapy, which has limited potency, even at high doses, where side effects are increased and tolerability is reduced. Consequently, there is a need for novel treatments to lower high blood pressure that are both effective and tolerable. SUMMARY OF REVELATION [003] A pharmaceutical composition is provided herein, in one aspect, comprising: (a) an angiotensin II receptor blocker; (b) a diuretic; and (c) a calcium channel blocker, wherein the dose of each (a), (b) and (c) is from about 40% to about 80% of the therapeutic dose for lower hypertension (LHTD), wherein the pharmaceutical composition further comprises at least one cholesterol-lowering active agent. In some embodiments, the pharmaceutical composition is essentially free of an angiotensin-converting enzyme inhibitor or a pharmaceutically acceptable salt thereof, a beta-blocker or a pharmaceutically acceptable salt thereof, a platelet-function-altering agent, a serum homocysteine-lowering agent, or a combination thereof. [004] In some embodiments, the diuretic is a thiazide-like diuretic. In some embodiments, the thiazide-like diuretic is quinethazone, clopamide, chlorthalidone, mefruside, clofenamide, metolazone, meticrane, xipamide, indapamide, chlorexolone, phenchizone, or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, the thiazide-like diuretic is indapamide or its hydrate. In some embodiments, the thiazide-like diuretic is indapamide. [005] In some embodiments, the calcium channel blocker is amlodipine, nifedipine, diltiazem, nimodipine, verapamil, isradipine, felodipine, nicardipine, nisoldipine, clevidipine, dihydropyridine, lercanidipine, nitrendipine, cilnidipine, manidipine, mibefradil, bepridil, barnidipine, nilvadipine, gallopamil, lidoflazine, aranidipine, dotarizine, diproteverine, or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, the calcium channel blocker is amlodipine or a pharmaceutically acceptable salt thereof. In some embodiments, the calcium channel blocker is amlodipine besylate. [006] In some embodiments, the angiotensin II receptor blocker is irbesartan, telmisartan, valsartan, candesartan, eprosartan, olmesartan, azilsartan, losartan or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, the angiotensin II receptor blocker is telmisartan. [007] In some embodiments, the dose of each (a), (b), and (c) is about 40% to about 60% of the therapeutic dose for lower hypertension (LHTD). In some embodiments, the diuretic is a thiazide-like diuretic, and the dose of the thiazide-like diuretic is about 50% of the therapeutic dose for lower hypertension (LHTD) for the thiazide-like diuretic. In some embodiments, the thiazide-like diuretic is indapamide, and the dose of indapamide is about 0.625 mg. In some embodiments, the dose of the calcium channel blocker is about 50% of the therapeutic dose for lower hypertension (LHTD) for the calcium channel blocker. In some embodiments, the calcium channel blocker is amlodipine besylate, and the dose of amlodipine besylate is about 1.25 mg. In some embodiments, the dose of the angiotensin II receptor blocker is approximately 50% of the therapeutic dose for lower hypertension (LHTD) for the angiotensin II receptor blocker. In some embodiments, the angiotensin II receptor blocker is telmisartan, and the dose of telmisartan is approximately 10 mg. In some embodiments, the angiotensin II receptor blocker is telmisartan, the diuretic is indapamide, and the calcium channel blocker is amlodipine besylate. In some embodiments, the dose of telmisartan is approximately 8 mg to approximately 12 mg, the dose of indapamide is approximately 0.5 mg to approximately 0.75 mg, and the dose of amlodipine besylate is approximately 1 mg to approximately 1.5 mg. In some formulations, the dose of telmisartan is approximately 10 mg, the dose of indapamide is approximately 0.625 mg, and the dose of amlodipine besylate is approximately 1.25 mg. [008] A pharmaceutical composition is provided in one aspect comprising: (a) telmisartan; (b) a thiazide-like diuretic; and (c) a calcium ch