Atosiban and PGF2α Antagonist Combination for Preterm Labor
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Solution Overview
Problem
There is a need for effective treatments or prevention methods for preterm labor that are therapeutically effective and physiologically safe, as preterm labor remains a leading cause of infant mortality and morbidity, with existing treatments lacking in efficacy and safety.
Innovation Solution
The use of a combination of a prostaglandin F2α receptor antagonist, such as a 1,3-thiazolidine-2-carboxamide compound, and atosiban, administered to delay the onset of delivery and alleviate symptoms of preterm labor, including uterine contractions and membrane rupture, by prolonging pregnancy and allowing for critical organ development in preterm infants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments for preterm labor are used, then delivery may be delayed to some extent, but the therapeutic efficacy is insufficient and safety concerns remain
Solution Approach 1:
The patent combines atosiban (an oxytocin receptor antagonist) with a PGF2α receptor antagonist into a single compositional formulation. This merging of two distinct pharmacological agents works synergistically to provide both delayed delivery and reduced uterine contractions, thereby improving therapeutic efficacy while maintaining safety through coordinated action of the two compounds.
Solution Approach 2:
The invention creates a composite pharmaceutical composition containing both atosiban and PGF2α receptor antagonist in specific dosage ranges. This composite formulation leverages the complementary mechanisms of action of the two agents, where atosiban blocks oxytocin-induced contractions and the PGF2α antagonist blocks prostaglandin-induced contractions, achieving broader and more reliable preterm labor suppression.
2Reliability
If delivery is delayed to allow organ maturation, then neonatal survival chances improve, but the duration of treatment increases
Solution Approach 1:
The combined composition provides continuous and sustained suppression of uterine contractions through the complementary mechanisms of atosiban and PGF2α receptor antagonist. This continuous action maintains pregnancy stability over extended periods, enabling prolonged gestational age advancement and continuous organ maturation without treatment interruption, thereby improving neonatal survival outcomes.
3Reliability
If single-agent treatment is used, then treatment simplicity is maintained, but therapeutic effectiveness is limited
Solution Approach 1:
The patent merges two pharmacologically distinct agents (atosiban and PGF2α receptor antagonist) into a single combined composition, achieving synergistic therapeutic effectiveness. The atosiban component addresses oxytocin-mediated contractions while the PGF2α antagonist addresses prostaglandin-mediated contractions, providing comprehensive coverage of the two primary pathways involved in preterm labor.
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 of PGF2α receptor antagonist and atosiban effectively delays delivery, reduces uterine contractions, and suppresses membrane rupture, thereby increasing the chances of neonatal survival by allowing for vital organ maturation in preterm infants.
Implementation Method 1
administered a prostaglandin F2α (PGF2α) receptor antagonist in combination with an oxytocin receptor antagonist
Implementation Method 2
administered a prostaglandin F2α (PGF2α) receptor antagonist in combination with an oxytocin receptor antagonist, such as atosiban
Data Source
AI summary
The disclosure provides compositions and methods for delaying the onset of delivery in a pregnant subject, such as a pregnant human subject, that is undergoing or at risk of undergoing preterm labor at a gestational age of from about 24 weeks to about 34 weeks. Using the compositions and methods described herein, such subjects may be administered atosiban in combination with a prostaglandin F2α (PGF2α) antagonist. Exemplary PGF2α receptor antagonists that may be used for the treatment or prevention of preterm labor as described herein include 1,3-thiazolidine-2-carboxamide compounds, such as (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate or a pharmaceutically acceptable salt thereof (e.g., (3S)-3-({[(2S)-3-(biphenyl-4-ylsulfonyl)-1,3-thiazolidin-2-yl]carbonyl}-amino)-3-(4-fluorophenyl)propyl L-valinate hydrochloride). The compositions and methods described herein provide various clinical benefits. Delivery at an early gestational age is a leading cause of perinatal mortality. By delaying labor in pregnant human patients at an early gestational age, the compositions and methods of the disclosure provide unborn infants with additional time to develop vital organs and tissue systems, thereby significantly improving the likelihood of survival following delivery. The compositions and methods described herein may be used to delay the onset of delivery by one or more hours, days, or weeks, for example, so as to enable pregnant subjects to reach a gestational age at which parturition is substantially safer.