NEP Inhibitor–Azilsartan Composition for Stable Heart Failure Therapy

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Solution Overview

Problem

Current pharmaceutical compositions for cardiovascular diseases do not always achieve synergistic effects when combining drugs with different mechanisms of action, leading to suboptimal prevention and treatment outcomes, and there is a need for more effective and stable therapies with reduced side effects.

Innovation Solution

A combination of a neutral endopeptidase (NEP) inhibitor and an angiotensin II receptor antagonist, represented by the formula (I), which enhances therapeutic efficacy by providing stable and long-lasting hypotensive effects and heart rate reduction, while improving heart function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If drugs with different mechanisms of action are combined for cardiovascular disease treatment, then therapeutic coverage is expanded, but synergistic effects are not necessarily achieved and treatment outcomes remain suboptimal

Engineering Contradiction:
Improvetherapeutic effectVSAvoidtreatment efficacy
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent combines an angiotensin II receptor antagonist (ARB) with a neutral endopeptidase (NEP) inhibitor in a single pharmaceutical composition. This merging of two drugs with different mechanisms of action creates a synergistic effect that produces stable and long-lasting hypotensive effects, directly resolving the contradiction by achieving both expanded therapeutic coverage and enhanced treatment efficacy through proven synergistic interaction

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If higher dosages or more frequent administration is used to achieve desired therapeutic effect, then treatment efficacy is improved, but side effects increase

Engineering Contradiction:
Improvetherapeutic effectVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

By combining ARB and NEP inhibitor in specific proportions within a single pharmaceutical composition, the patent achieves synergistic therapeutic effects that allow for lower dosages of each individual component while maintaining or enhancing overall efficacy. This reduces the harmful side effects associated with higher dosages while preserving the desired therapeutic outcome

Inventive Principle:
Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combination achieves unexpected synergistic effects, offering more stable and prolonged blood pressure and heart rate reductions, effectively treating acute and chronic heart failures with lower dosages and frequency, and reducing side effects.

Implementation Method 1

Inhibition of NEP increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), bradykinin and adrenomedullin levels, thus playing a role in diuresis

Methodology Applied
Scientific EffectDiuresis:

Implementation Method 2

Inhibition of NEP increases atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), bradykinin and adrenomedullin levels, thus playing a role in diuresis, vasodilation

Methodology Applied
Scientific EffectVasodilation:

Implementation Method 3

blocking the binding of Ang II to its specific receptor therefore contributes to the protection of heart and blood vessels

Methodology Applied
Scientific EffectReceptor blocking:

Data Source

PatentEP3524250B1Pharmaceutical composition comprising a neutral endopeptidase (NEP) inhibitor and an azilsartan ester derivative and use thereof for treating cardiovascular diseases
Publication Date: 2025.07.16 WUHAN LL SCI & TECH DEV CO LTD
  • EP3524250B1 patent drawingFigure 1
  • EP3524250B1 patent drawingFigure 2~3
  • EP3524250B1 patent drawingFigure 4~5

AI summary

The present invention relates to a pharmaceutical composition comprising: (a) at least one neutral endopeptidase inhibitor or a pharmaceutically acceptable salt or ester thereof, (b) at least one compound represented by formula (I) or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier. Combined administration showed better medicinal effects than separate administration.