NK2R Agonist Induces Urinary Voiding Without Invasive Catheters
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Solution Overview
Problem
Current treatments for urinary voiding and defecation dysfunction, such as spinal cord injuries, are invasive, inconvenient, and often lead to complications like urinary tract infections and incontinence, with limited efficacy and significant side effects, affecting the quality of life and increasing healthcare costs.
Innovation Solution
Administration of a neurokinin 2 receptor (NK2R) agonist, specifically [Lys5,MeLeu9,Nle10]-NKA(4-10) or its pharmaceutically acceptable salt, on an as-needed basis via transmucosal, intramuscular, or subcutaneous routes, to induce rapid and short-duration urinary voiding and defecation, utilizing a pharmaceutical formulation with a carrier for effective administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If clean intermittent catheterization is used for urinary voiding dysfunction, then urine can be emptied from the bladder, but catheter associated urinary tract infections (CAUTI) occur frequently leading to complications and increased healthcare costs
Solution Approach 1:
The patent replaces the mechanical catheterization system with a pharmacological system using neurokinin-2 receptor agonists to stimulate bladder contraction and voiding. This substitution eliminates the need for foreign body insertion (catheter) while achieving the same functional outcome of bladder emptying, thereby preventing CAUTI complications
Solution Approach 2:
The patent changes the physiological parameter of bladder contractility by administering neurokinin-2 receptor agonists that bind to receptors in the bladder wall, increasing smooth muscle contraction force and frequency. This pharmacological parameter change enables effective voiding without mechanical intervention
2Reliability
If cholinergic agonists such as bethanechol are used to treat voiding dysfunction, then bladder contraction is stimulated, but severe side effects occur including sweating, spasticity, bradycardia, convulsions, hypotension, and bronchial constriction
Solution Approach 1:
The patent achieves localized action by targeting neurokinin-2 receptors specifically in the bladder smooth muscle. The agonist selectively binds to these receptors in the target organ, producing bladder contraction without activating cholinergic receptors in other organs, thereby eliminating systemic side effects while maintaining local therapeutic effect
Solution Approach 2:
The patent introduces a selective neurokinin-2 receptor agonist as an intermediary substance that mediates bladder contraction through a specific receptor pathway. This intermediary provides targeted action at the receptor level, avoiding the non-selective effects of cholinergic agonists that cause widespread side effects
3Reliability
If sphincterotomy, sphincter paralysis, or urethral stenting is used to empty the bladder, then the sphincter is prevented from closing the urethra, but the person becomes incontinent and experiences further complications
Solution Approach 1:
The patent employs periodic administration of neurokinin-2 receptor agonists to induce bladder contraction and voiding at scheduled intervals. This periodic pharmacological stimulation allows the sphincter to remain intact and functional between doses, maintaining continence control while achieving reliable bladder emptying when needed
Solution Approach 2:
The patent enables the bladder to perform its own voiding function through pharmacological stimulation of intrinsic smooth muscle contraction. The neurokinin-2 receptor agonist activates the bladder's own contractile mechanism, eliminating the need for external mechanical or surgical interventions that compromise sphincter function and continence
4Reliability
If large volume warm water enemas are used for fecal dysfunction, then feces can be expelled, but the patient must wait 30 minutes to an hour and the procedure is inconvenient
Solution Approach 1:
The patent replaces the mechanical enema system (large volume water infusion) with a pharmacological system using neurokinin-2 receptor agonists to stimulate colonic peristalsis and fecal expulsion. This substitution achieves the same therapeutic goal of bowel evacuation without requiring volume expansion and prolonged waiting time
Solution Approach 2:
The patent applies neurokinin-2 receptor agonists that rapidly stimulate colonic smooth muscle contraction and peristalsis, producing fecal expulsion within minutes. This preliminary pharmacological action eliminates the need for prolonged waiting periods required by enema procedures, providing rapid relief of fecal retention
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 NK2R agonist provides rapid onset and short-duration action for inducing urinary voiding and defecation, reducing the need for invasive procedures and minimizing side effects, thereby improving quality of life and reducing healthcare costs by offering a more effective and convenient treatment option.
Implementation Method 1
Administration of a neurokinin 2 receptor (NK2R) agonist, specifically [Lys5,MeLeu9,Nle10]-NKA(4-10) or its pharmaceutically acceptable salt
Data Source
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AI summary
Methods, pharmaceutical formulations, and kits are provided for using neurokinin 2 receptor agonists to effectuate voluntary "on-demand" voiding of urine and feces in mammals who cannot void without external invasion of the bladder and bowel or those who void involuntarily (i.e., those having urinary and/or fecal incontinence). The pharmaceutical formulations and kits can also be useful for inducing voiding of urine and defecation in mammals that do not have a voiding dysfunction such as, for example, in a person who is unaware of appropriate voiding behavior and may void unconsciously or in a pet at a convenient location at a specific time. The methods and compositions provide patients with voiding dysfunction control over when and where they void.