Selective EP2 Agonists for Preterm Labor Tocolysis
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Solution Overview
Problem
Current tocolytic drugs are ineffective in safely and cost-effectively managing preterm labor, as they either have adverse effects or fail to prolong pregnancy beyond a few days and exacerbate the pro-inflammatory environment in the uterus.
Innovation Solution
The use of selective prostaglandin EP2 receptor agonists that activate anti-labour cyclic AMP pathways without inducing pro-inflammatory signals, delaying labor and inhibiting uterine contractions in preterm pregnant subjects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If beta-adrenergic receptor agonists are used as tocolytic drugs, then uterine contractions are inhibited, but adverse effects on the mother's cardiovascular system occur
Solution Approach 1:
The patent changes the molecular target parameter from beta-adrenergic receptors to prostaglandin EP2 receptors, fundamentally altering the mechanism of action. This parameter change allows achieving tocolytic efficacy through a different receptor system that does not compromise cardiovascular safety, thereby resolving the contradiction between efficacy and harmful effects.
2Reliability
If atosiban (oxytocin receptor antagonist) is used, then uterine contractions are inhibited, but pro-inflammatory pathways are activated and cost increases
Solution Approach 1:
The patent converts the harmful pro-inflammatory activation caused by atosiban into a beneficial effect by using a selective EP2 agonist that activates anti-labour cAMP pathways without inducing pro-labour G protein-dependent pro-inflammatory pathways. This transforms the previously harmful inflammatory response into a protective anti-labour mechanism.
Solution Approach 2:
The patent changes the receptor activation parameter from oxytocin receptor antagonism to selective EP2 receptor agonism with biased signaling. This parameter change enables differentiation between pro-labour and anti-labour pathways, allowing activation of only the beneficial anti-labour cAMP pathway while avoiding the harmful pro-inflammatory G protein pathway.
3Reliability
If butaprost (EP2 agonist) is used, then uterine contractions are inhibited, but pro-inflammatory signalling is also activated
Solution Approach 1:
The patent refines the EP2 agonist parameter by developing a selective agonist that differentiates between the two signaling pathways of EP2. This parameter refinement enables activation of only the anti-labour cAMP pathway while blocking the pro-labour G protein pathway, thereby eliminating the harmful pro-inflammatory signaling while maintaining tocolytic efficacy.
Solution Approach 2:
The patent segments the EP2 receptor signaling into two distinct pathways: the beneficial anti-labour cAMP pathway and the harmful pro-labour G protein pathway. By using a selective agonist, the patent activates only the segmented cAMP pathway while leaving the G protein pathway inactive, thus separating the beneficial from the harmful effects.
4Duration of action of moving object
If current tocolytic drugs are used, then labor is temporarily inhibited, but pregnancy cannot be prolonged beyond a few days
Solution Approach 1:
The patent establishes continuity of useful action by developing a tocolytic mechanism that can be sustained for extended periods. The selective EP2 agonist provides continuous activation of the anti-labour cAMP pathway, enabling prolonged pregnancy extension beyond the limited duration of conventional tocolytics while maintaining safety and efficacy throughout the extended period.
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
This approach provides a safe, efficacious, and long-acting treatment for preterm labor, reducing healthcare costs and minimizing inflammatory responses, potentially protecting the developing fetus's brain and lungs.
Implementation Method 1
such agonists only activate the anti-labour cyclic AMP (cAMP) pathways of EP2
Implementation Method 2
without inducing signals that induce pro-labour G protein-dependent pro-inflammatory pathways
Data Source
AI summary
The present invention relates to compounds for use in the delaying of labour and/or inhibition of uterine contractions in pre-term pregnant subjects. Such compounds include selective prostaglandin EP2 receptor agonists which specifically activate the anti-labour cyclic AMP (cAMP) pathways of EP2, without inducing signals that induce pro-labour G protein-dependent pro-inflammatory pathways, as observed with other conventional EP2 agonists within the art. The invention also refers to methods and uses of such compounds.