Segmented Natriuretic Polypeptides Avoiding Hypotension
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Solution Overview
Problem
Current treatments for cardiovascular and renal conditions using natriuretic polypeptides often induce systemic hypotension, limiting their therapeutic efficacy and safety.
Innovation Solution
Development of natriuretic polypeptides with specific amino acid sequences less than 44 residues, such as those depicted in SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, which exhibit natriuretic activity without causing systemic hypotension, by activating cGMP and modulating renin and aldosterone production, thereby optimizing renal blood flow and reducing cardiac filling pressures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If natriuretic polypeptides are used to treat cardiovascular and renal conditions, then natriuretic activity is improved, but systemic hypotension occurs
Solution Approach 1:
The patent segments the natriuretic polypeptide into specific short sequences (15-43 amino acids) that target renal tissue specifically. By using segmented sequences like those in SEQ ID NO:1, 2, or 3 rather than full-length polypeptides, the invention achieves natriuretic effect while avoiding systemic hypotension through localized renal action
Solution Approach 2:
The invention applies local quality by designing polypeptides with sequences that have high affinity for renal natriuretic peptide receptors. The specific amino acid sequences are optimized to bind preferentially to renal tissue, concentrating the natriuretic effect at the target organ while minimizing systemic circulation effects that cause hypotension
2Quantity of substance
If natriuretic polypeptides are administered to increase natriuresis, then sodium excretion is improved, but blood pressure decreases
Solution Approach 1:
The patent uses segmented short polypeptide sequences (15-43 amino acids) that selectively act on renal sodium handling mechanisms. These sequences increase sodium excretion through renal natriuresis without causing the systemic vasodilation and blood pressure decrease associated with full-length natriuretic polypeptides
Solution Approach 2:
The invention uses short polypeptide sequences as intermediaries that activate renal natriuretic peptide receptors to increase sodium excretion. These sequences mediate the natriuretic effect through renal-specific mechanisms without triggering the systemic hemodynamic changes that lead to blood pressure decrease
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
These polypeptides effectively increase natriuresis, diuresis, and glomerular filtration rate while suppressing renin and angiotensin production, reducing cardiac filling pressures without lowering blood pressure, thus providing a safer and more targeted therapeutic approach for cardiovascular and renal conditions.
Implementation Method 1
the ability to activate cGMP
Implementation Method 2
the ability to increase glomerular filtration rate
Data Source
AI summary
This document provides natriuretic polypeptides. For example, this document provides polypeptides having a natriuretic activity. In some cases, a polypeptide provided herein can have natriuretic activities, while lacking the ability to lower blood pressure. This document also provides methods and materials for inducing natriuretic activities within a mammal.