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Combination therapy comprising angiotensin receptor blockers and vasopressin receptor antagonists

A technology of vasopressin antagonist and angiotensin, which is applied in the fields of cardiovascular system diseases, drug combinations, blood diseases, etc.

Inactive Publication Date: 2011-09-07
JANSSEN PHARMA NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Significant risk and morbidity of renal failure progression despite this standard of care

Method used

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  • Combination therapy comprising angiotensin receptor blockers and vasopressin receptor antagonists
  • Combination therapy comprising angiotensin receptor blockers and vasopressin receptor antagonists
  • Combination therapy comprising angiotensin receptor blockers and vasopressin receptor antagonists

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0154] Efficacy in a rat remnant kidney model of nephropathy

[0155] The rat remnant kidney model is an animal model of severe progressive renal failure. In this model, a state of severe progressive renal failure is produced by renal mass reduction (RMR) by removing one kidney and ligating several branches of the renal artery, resulting in infarction and functional loss of two-thirds of the remaining kidney . The procedure caused severe hypertension, proteinuria, progressive renal failure, tubulointerstitial damage, and glomerulosclerosis (Olson JL, Hostetter TH, Rennke HG, Brenner BM, Venkatachalam MA: "Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass". Kidney Int 22:112-126, 1982).

[0156] Nephropathy manifests as a gradual increase in the amount of protein in the urine and an increase in arterial pressure. Furthermore, severe glomerular sclerosis, inflammatory cell infiltration, and tubular damage were measurable b...

example 2

[0164] Blood pressure in the rat remnant kidney model

[0165] The reduction in blood pressure may help slow the progression of renal disease in this animal model as well as in humans. Compound 1 tended to lower arterial pressure at 1 and 2 months of treatment, but this was not statistically significant compared to vehicle. Losartan and the combination of losartan and Compound 1 caused a statistically significant reduction in arterial pressure compared to the vehicle group. Combination therapy caused a slightly greater reduction in arterial pressure compared with losartan alone ( image 3 ).

example 3

[0167] Effects on water intake and diuresis in the remnant kidney model

[0168] Water intake and diuresis increased in all treatment groups after RMR (Table 2). During the course of the experiment, there were no significant differences in any of the treatment groups (Table 2). At the termination of the experiment, serum sodium and urinary sodium excretion were not different in any of the treatment groups (data not shown).

[0169]

[0170]

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PUM

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Abstract

The present invention relates to certain pharmaceutical compositions containing at least one vasopressin receptor antagonist and at least one angiotensin receptor blocker (ARB) and methods for preparing these compounds, compositions, intermediates and derivatives thereof and for the treatment of vasopressin and / or angiotensin-mediated disorders.

Description

[0001] Related patent application cross-reference [0002] This patent application claims the benefit of US Provisional Patent Application No. 61 / 104,282, filed October 10, 2008, which is incorporated herein by reference. technical field [0003] The present invention relates to pharmaceutical compositions comprising at least one vasopressin receptor antagonist and at least one angiotensin receptor blocker (ARB). The present invention also relates to methods of treating, ameliorating and / or inhibiting the progression of diseases mediated by vasopressin and / or angiotensin, including diabetic nephropathy, progressive renal failure, polycystic kidney disease, hyperemia Heart failure, hypertension, diseases causing hyponatremia and / or edema, and other diseases caused by overactivation of vasopressin V1a and V2 receptors, the method comprises administering the pharmaceutical composition to human patients. Background technique [0004] Vasopressin is a nonapeptide hormone secrete...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4178A61K31/4184A61K31/55A61K45/06
CPCA61K45/06A61K31/4184A61K31/4178A61K31/55A61P1/16A61P13/00A61P13/12A61P15/00A61P25/28A61P27/16A61P3/12A61P43/00A61P5/24A61P7/02A61P7/10A61P9/04A61P9/10A61P9/12A61K2300/00
Inventor B·达米亚诺L·哈斯克尔U·舒克拉
Owner JANSSEN PHARMA NV
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