RU2002129569A - NEW MEDICAL APPLICATION OF ALDOSTEROSYNTHASE INHIBITORS INDIVIDUALLY OR IN COMBINATION WITH AT1-RECEPTOR ANTAGONISTS - Google Patents

NEW MEDICAL APPLICATION OF ALDOSTEROSYNTHASE INHIBITORS INDIVIDUALLY OR IN COMBINATION WITH AT1-RECEPTOR ANTAGONISTS Download PDF

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RU2002129569A
RU2002129569A RU2002129569/15A RU2002129569A RU2002129569A RU 2002129569 A RU2002129569 A RU 2002129569A RU 2002129569/15 A RU2002129569/15 A RU 2002129569/15A RU 2002129569 A RU2002129569 A RU 2002129569A RU 2002129569 A RU2002129569 A RU 2002129569A
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hypertension
renal failure
pharmaceutically acceptable
combination
restenosis
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Роналд Эдуард СТИЛ (US)
Роналд Эдуард СТИЛ
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Новартис АГ (CH)
Новартис Аг
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    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
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Claims (10)

1. Применение фармацевтической композиции, содержащей (I) ингибитор альдостеронсинтазы или его фармацевтически приемлемую соль индивидуально или в сочетании с (II) антагонистом AT1-рецептора или антагонистом АТ1-рецептора в сочетании с диуретиком или в каждом случае с его фармацевтически приемлемой солью и (III) фармацевтически приемлемый носитель, для предупреждения, замедления развития, лечения болезни или состояния, выбранных из группы, включающей (а) гипертензию, застойную сердечную недостаточность, почечную недостаточность, прежде всего хроническую почечную недостаточность, рестеноз после чрезкожной внутрипросветной ангиопластики и рестеноз после хирургической операции, связанной с шунтированием коронарной артерии, (б) атеросклероз, устойчивость к инсулину и синдром X, сахарный диабет типа 2, ожирение, нефропатию, почечную недостаточность, например, хроническую почечную недостаточность, гипотиреоидизм, состояние после инфаркта миокарда (МИ), коронарные заболевания сердца, гипертензию, связанную с возрастом, семейную дислипидемическую гипертензию, повышенное образование коллагена, фиброз и гипертензию, возникающую после ремоделирования (антипролиферативное действие комбинации), при этом все указанные заболевания или состояния связаны с гипертензией или не связаны с ней, и (в) эндотелиальную дисфункцию, сопровождающуюся или не сопровождающуюся гипертензией.1. The use of a pharmaceutical composition comprising (I) an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof individually or in combination with (II) an AT 1 receptor antagonist or an AT 1 receptor antagonist in combination with a diuretic or, in each case, a pharmaceutically acceptable salt thereof and (III) a pharmaceutically acceptable carrier 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 for coronary artery bypass grafting, (b) atherosclerosis, insulin resistance and Syndrome X, type 2 diabetes mellitus, obesity, nephropathy, renal failure, for example, chronic renal insufficiency, hypothyroidism, the state after myocardial infarction (MI), coronary heart disease, age-related hypertension, familial dyslipidemic hypertension, increased image collagen formation, fibrosis, and hypertension that occurs after remodeling (the antiproliferative effect of the combination), while all these diseases or conditions are associated with or are not associated with hypertension, and (c) endothelial dysfunction, with or without hypertension. 2. Применение по п.1, где антагонист AT1-рецептора выбирают из группы, включающей валсартан, лосартан, кандесартан, эпросартан, ирбесартан, саприсартан, тасосартан, телмисартан, соединение, обозначенное как Е-1477, которое имеет следующую формулу:2. The use according to claim 1, where the AT 1 receptor antagonist is selected from the group consisting of valsartan, losartan, candesartan, eprosartan, irbesartan, saprisartan, tasosartan, telmisartan, a compound designated as E-1477, which has the following formula:
Figure 00000001
Figure 00000001
 соединение, обозначенное как SC-52458, которое имеет следующую формулу:a compound designated as SC-52458, which has the following formula:
Figure 00000002
Figure 00000002
 и соединение, обозначенное как ZD-8731, которое имеет следующую формулу:and the compound designated as ZD-8731, which has the following formula:
Figure 00000003
Figure 00000003
 или в каждом случае их фармацевтически приемлемые соли.or in each case their pharmaceutically acceptable salts. 3. Применение по п.2, где антагонист AT1-рецептора представляет собой валсартан или его фармацевтически приемлемую соль.3. The use of claim 2, wherein the AT 1 receptor antagonist is valsartan or a pharmaceutically acceptable salt thereof. 4. Применение по любому из пп.1-3, где ингибитор альдостеронсинтазы выбирают из группы, включающей анастрозол, фадрозол (включая его (+)-энантиомер) и эксеместан, или в каждом случае, если это возможно, их фармацевтически приемлемые соли.4. The use according to any one of claims 1 to 3, wherein the aldosterone synthase inhibitor is selected from the group consisting of anastrozole, fadrozole (including its (+) enantiomer) and exemestane, or in each case, if possible, their pharmaceutically acceptable salts. 5. Применение по любому из пп.1-4, где ингибитор альдостеронсинтазы представляет собой (+)-энантиомер гидрохлорида фадрозола формулы5. The use according to any one of claims 1 to 4, wherein the aldosterone synthase inhibitor is the (+) - enantiomer of fadrosol hydrochloride of the formula
Figure 00000004
Figure 00000004
 6. Применение по любому из пп.1-5, где диуретик представляет собой гидрохлортиазид.6. The use according to any one of claims 1 to 5, where the diuretic is hydrochlorothiazide. 7. Применение фармацевтической композиции, содержащей ингибитор альдостеронсинтазы или его фармацевтически приемлемую соль, для приготовления лекарственного средства, предназначенного для предупреждения, замедления развития, лечения болезни или состояния, выбранных из группы, включающей (α) гипертензию, застойную сердечную недостаточность, почечную недостаточность, прежде всего хроническую почечную недостаточность, рестеноз после чрезкожной внутрипросветной ангиопластики и рестеноз после хирургической операции, связанной с шунтированием коронарной артерии, (β) атеросклероз, устойчивость к инсулину и синдром X, сахарный диабет типа 2, ожирение, нефропатию, почечную недостаточность, например, хроническую почечную недостаточность, гипотиреоидизм, состояние после инфаркта миокарда (МИ), коронарные заболевания сердца, гипертензию, связанную с возрастом, семейную дислипидемическую гипертензию, повышенное образование коллагена, фиброз и гипертензию, возникающую после ремоделирования (антипролиферативное действие комбинации), при этом все указанные заболевания или состояния связаны с гипертензией или не связаны с ней, и (γ) эндотелиальную дисфункцию, сопровождающуюся или не сопровождающуюся гипертензией.7. The use of a pharmaceutical composition comprising an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the prevention, retardation, treatment of a disease or condition selected from the group consisting of (α) hypertension, congestive heart failure, renal failure, previously total chronic renal failure, restenosis after percutaneous intraluminal angioplasty, and restenosis after shunt surgery coronary artery disease, (β) atherosclerosis, insulin resistance and X syndrome, type 2 diabetes mellitus, obesity, nephropathy, renal failure, for example, chronic renal failure, hypothyroidism, post-myocardial infarction (MI), coronary heart disease, hypertension, age-related familial dyslipidemic hypertension, increased collagen formation, fibrosis and hypertension that occurs after remodeling (antiproliferative effect of the combination), with all these diseases or thawing is associated with hypertension or not associated with it, and (γ) endothelial dysfunction, with or without hypertension. 8. Фармацевтическая композиция, содержащая (I) ингибитор альдостеронсинтазы или его фармацевтически приемлемую соль индивидуально или в сочетании с (II) антагонистом AT1-рецептора или антагонистом AT1-рецептора в сочетании с диуретиком или в каждом случае с его фармацевтически приемлемой солью и (III) фармацевтически приемлемый носитель, для предупреждения, замедления развития, лечения болезни или состояния, выбранных из группы, включающей (а) гипертензию, застойную сердечную недостаточность, почечную недостаточность, прежде всего хроническую почечную недостаточность, рестеноз после чрезкожной внутрипросветной ангиопластики и рестеноз после хирургической операции, связанной с шунтированием коронарной артерии, (б) атеросклероз, устойчивость к инсулину и синдром X, сахарный диабет типа 2, ожирение, нефропатию, почечную недостаточность, например, хроническую почечную недостаточность, гипотиреоидизм, состояние после инфаркта миокарда (МИ), коронарные заболевания сердца, гипертензию, связанную с возрастом, семейную дислипидемическую гипертензию, повышенное образование коллагена, фиброз и гипертензию, возникающую после ремоделирования (антипролиферативное действие комбинации), при этом все указанные заболевания или состояния связаны с гипертензией или не связаны с ней, и (в) эндотелиальную дисфункцию, сопровождающуюся или не сопровождающуюся гипертензией.8. A pharmaceutical composition comprising (I) an aldosterone synthase inhibitor or a pharmaceutically acceptable salt thereof individually or in combination with (II) an AT 1 receptor antagonist or an AT 1 receptor antagonist in combination with a diuretic or, in each case, a pharmaceutically acceptable salt thereof and ( III) a pharmaceutically acceptable carrier for the prevention, retardation, 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 for coronary artery bypass grafting, (b) atherosclerosis, insulin resistance and X syndrome, type 2 diabetes mellitus, obesity, nephropathy, renal failure, for example, chronic renal failure , hypothyroidism, the state after myocardial infarction (MI), coronary heart disease, age-related hypertension, familial dyslipidemic hypertension, increased collagen formation gene, fibrosis, and hypertension that occurs after remodeling (the antiproliferative effect of the combination), while all these diseases or conditions are associated with or are not associated with hypertension, and (c) endothelial dysfunction, with or without hypertension. 9. Способ предупреждения, замедления развития, лечения болезни или состояния, выбранных из группы, включающей (а) гипертензию, застойную сердечную недостаточность, почечную недостаточность, прежде всего хроническую почечную недостаточность, рестеноз после чрезкожной внутрипросветной ангиопластики и рестеноз после хирургической операции, связанной с шунтированием коронарной артерии, (б) атеросклероз, устойчивость к инсулину и синдром X, сахарный диабет типа 2, ожирение, нефропатию, почечную недостаточность, например, хроническую почечную недостаточность, гипотиреоидизм, состояние после инфаркта миокарда (МИ), коронарные заболевания сердца, гипертензию, связанную с возрастом, семейную дислипидемическую гипертензию, повышенное образование коллагена, фиброз и гипертензию, возникающую после ремоделирования (антипролиферативное действие комбинации), при этом все указанные заболевания или состояния связаны с гипертензией или не связаны с ней, и (в) эндотелиальную дисфункцию, сопровождающуюся или не сопровождающуюся гипертензией, предусматривающий введение теплокровному животному, в том числе человеку, нуждающемуся в таком лечении, терапевтически эффективного количества ингибитора альдостеронсинтазы в свободной форме или в форме фармацевтически приемлемой соли.9. 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 insufficiency, hypothyroidism, the condition 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, and (c) endothelial dysfunction, accompanied or not accompanied by hypertension, involving the introduction of warm-blooded The animal, including a human, in need of such treatment a therapeutically effective amount of an aldosterone synthase inhibitor in free form or in pharmaceutically acceptable salt form. 10. Способ по п.9, дополнительно предусматривающий введение терапевтически эффективного количества антагониста At1-рецептора или антагониста AT1-рецептора в сочетании с диуретиком в каждом случае в свободной форме или в форме фармацевтически приемлемой соли.10. The method of claim 9, further comprising administering a therapeutically effective amount of an At 1 receptor antagonist or an AT 1 receptor antagonist in combination with a diuretic, in each case, in free form or in the form of a pharmaceutically acceptable salt.
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