RU2003116896A

RU2003116896A - SYNERGETIC COMPOSITIONS THAT CONTAIN A RENIN INHIBITOR INTENDED FOR THE TREATMENT OF CARDIOVASCULAR DISEASES

Info

Publication number: RU2003116896A
Application number: RU2003116896/15A
Authority: RU
Inventors: Уилльям ХЕУИТТ; Даньель Луси ВАСЕЛЛА; Ранди Ли УЭББ
Original assignee: Новартис Аг
Priority date: 2000-11-17
Filing date: 2001-11-15
Publication date: 2004-12-10

Claims

1. A pharmaceutical composition comprising a renin inhibitor of formula (I)

or its pharmaceutically acceptable salt and at least one therapeutic agent selected from the group including

(I) an AT ₁ receptor antagonist or a pharmaceutically acceptable salt thereof,

(II) an inhibitor of HMG-CoA reductase or its pharmaceutically acceptable salt,

(III) an angiotensin converting enzyme (ACE) inhibitor or a pharmaceutically acceptable salt thereof,

(IV) a calcium channel blocker or a pharmaceutically acceptable salt thereof,

(V) an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof,

(VI) an aldosterone antagonist or a pharmaceutically acceptable salt thereof,

(VII) a double angiotensin converting enzyme / neutral peptidase inhibitor (ACE / NEP) or a pharmaceutically acceptable salt thereof,

(VIII) an endothelin antagonist or a pharmaceutically acceptable salt thereof; and

(IX) a diuretic or a pharmaceutically acceptable salt thereof.

and carrier.

2. The composition according to claim 1, where the renin inhibitor is present in the form of hemi-fumarate.

3. The composition according to claim 1 or 2, where, independently from each other, the AT ₁ receptor antagonist is valsartan or a pharmaceutically acceptable salt thereof, the HMG-CoA reductase inhibitor is fluvastatin and pitavastatin or their pharmaceutically acceptable salts, an angiotensin converting enzyme inhibitor ( ACE) is benazepril or enalapril or their pharmaceutically acceptable salts, the calcium channel blocker is amlodipine or its pharmaceutically acceptable salt, the aldosterone synthase inhibitor is Fadrozole (including its (+) enantiomer) or its pharmaceutically acceptable salt, the aldosterone antagonist is eplerenone, the double angiotensin converting enzyme / neutral peptidase inhibitor (ACE / NEP) is omapatrilate or its pharmaceutically acceptable salt, the endothelin antagonist is bosent its pharmaceutically acceptable salt and diuretic is hydrochlorothiazide.

4. The composition according to any one of claims 1 to 3, designed to prevent, slow down the development, treatment of a disease or condition selected from the group consisting of (a) hypertension, congestive heart failure, renal failure, especially chronic renal failure, restenosis after percutaneous intraluminal angioplasty and restenosis after surgery involving coronary artery bypass grafting, (b) atherosclerosis, insulin resistance and Syndrome X, type 2 diabetes mellitus, obesity, nephropathy, renal failure sufficiency, for example, chronic renal failure, hypothyroidism, the state after myocardial infarction (MI), coronary heart disease, age-related hypertension, familial dyslipidemic hypertension, increased collagen formation, fibrosis and hypertension that occurs after remodeling (antiproliferative effect of the combination), all these diseases or conditions are associated with or are not associated with hypertension, (c) endothelial dysfunction, accompanied or not accompanied by hypertension, (g) hyperlipidemia, hyperlipoproteinemia, atherosclerosis and hypercholesterolemia, (e) glaucoma.

5. The composition according to any one of claims 1 to 3, designed to prevent, slow the development, treatment of a disease or condition selected from the group comprising (e) isolated systolic hypertension (ISH), (g) diabetic retinopathy and (h) peripheral vascular disease.

6. The composition according to any one of claims 1 to 5, intended for simultaneous, separate or sequential administration.

7. A kit for preventing, slowing down or treating a disease or condition specified in claim 4, comprising (a) a first unit dosage form containing a certain amount of a renin inhibitor of formula (I) or a pharmaceutically acceptable salt thereof, (b) a second and t .d. a unit dosage form containing a certain amount of at least one therapeutic agent selected from the group comprising components (I) to (IX) or, if necessary, pharmaceutically acceptable salts in each case, and (c) a container containing the first, second, and t .d. standard dosage forms.

8. The use of a composition comprising a renin inhibitor of formula (I) or a pharmaceutically acceptable salt thereof in combination with at least one therapeutic agent selected from the group consisting of (I) an AT ₁ receptor antagonist or a pharmaceutically acceptable salt thereof, (II) an inhibitor HMG-Co-A reductase or its pharmaceutically acceptable salt, (III) an angiotensin converting enzyme (ACE) inhibitor or its pharmaceutically acceptable salt, (IV) a calcium channel blocker or its pharmaceutically acceptable salt, (V) an aldosterone synthase inhibitor or its a pharmaceutically acceptable salt, (VI) an aldosterone antagonist or a pharmaceutically acceptable salt thereof, (VII) a double angiotensin converting enzyme / neutral endopeptidase inhibitor (ACE / NEP) or a pharmaceutically acceptable salt thereof, (VIII) an endothelin antagonist or a pharmaceutically acceptable salt thereof and (IX) a diuretic or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the prevention, retardation or treatment of a disease or condition selected from the group consisting of (a) hypertension, acute heart failure, renal failure, primarily chronic renal failure, restenosis after percutaneous intraluminal angioplasty, and restenosis after surgery for coronary artery bypass grafting, (b) atherosclerosis, insulin resistance and syndrome X, type 2 diabetes mellitus, obesity, nephropate renal failure, for example, chronic renal failure, hypothyroidism, the condition after myocardial infarction (MI), coronary heart disease, hypertension, is associated with age, familial dyslipidemic hypertension, increased collagen formation, fibrosis and hypertension that occurs after remodeling (antiproliferative effect of the combination), while all these diseases or conditions are associated with hypertension or are not associated with it, (c) endothelial dysfunction, accompanied or not accompanied by hypertension, (g) hyperlipidemia, hyperlipoproteinemia, atherosclerosis and hypercholesterolemia, (e) glaucoma.

9. The use of a composition comprising a renin inhibitor of formula (I) or a pharmaceutically acceptable salt thereof in combination with at least one therapeutic agent selected from the group consisting of (I) an AT ₁ receptor antagonist or a pharmaceutically acceptable salt thereof, (II) an inhibitor HMG-Co-A reductase or its pharmaceutically acceptable salt, (III) an angiotensin converting enzyme (ACE) inhibitor or its pharmaceutically acceptable salt, (IV) a calcium channel blocker or its pharmaceutically acceptable salt, (V) an aldosterone synthase inhibitor or its a pharmaceutically acceptable salt, (VI) an aldosterone antagonist or a pharmaceutically acceptable salt thereof, (VII) a double angiotensin converting enzyme / neutral endopeptidase inhibitor (ACE / NEP) or a pharmaceutically acceptable salt thereof, (VIII) an endothelin antagonist or a pharmaceutically acceptable salt thereof and (IX) a diuretic or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the prevention, retardation or treatment of a disease or condition selected from the group comprising (e) isolated systolic hypertension (ISH), (g) diabetic retinopathy and (h) peripheral vascular disease.

10. A method for preventing, slowing down, treating a disease or condition selected from the group consisting of (a) hypertension, congestive heart failure, renal failure, especially chronic renal failure, restenosis after percutaneous intraluminal angioplasty and restenosis after surgery bypass surgery coronary artery, (b) atherosclerosis, insulin resistance and Syndrome X, type 2 diabetes mellitus, obesity, nephropathy, renal failure, for example, chronic renal deficiency, hypothyroidism, the state after myocardial infarction (MI), coronary heart disease, age-related hypertension, familial dyslipidemic hypertension, increased collagen formation, fibrosis and hypertension that occurs after remodeling (antiproliferative effect of the combination), while all these diseases or conditions associated with hypertension or not associated with it, (c) endothelial dysfunction, accompanied or not accompanied by hypertension, (d) hyperlipidemia, hyperlipoproteinemia, at Rosclerosis and hypercholesterolemia, (e) glaucoma, and in addition (e) isolated systolic hypertension (ISH), (g) diabetic retinopathy, and (h) peripheral vascular disease, which involves the administration of a warm-blooded animal, including a person in need of such treatment, effective combined amount of a composition comprising the renin inhibitor of formula (I) or a pharmaceutically acceptable salt thereof in combination with at least one therapeutic agent selected from the group consisting of (I) aT ₁ antagonist -recipe a or a pharmaceutically acceptable salt thereof; (II) an HMG-Co-A reductase inhibitor or a pharmaceutically acceptable salt thereof; (III) an angiotensin converting enzyme (ACE) inhibitor or a pharmaceutically acceptable salt thereof; (IV) a calcium channel blocker or a pharmaceutically acceptable salt thereof , (V) an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof, (VI) an aldosterone antagonist or a pharmaceutically acceptable salt thereof, (VII) a double angiotensin converting enzyme / neutral endopeptidase inhibitor (ACE / NEP), or a pharmaceutically acceptable thereof mummy salt, (VIII) an endothelin antagonist or a pharmaceutically acceptable salt thereof, and (IX) a diuretic or a pharmaceutically acceptable salt thereof.