Nifedipine and PGF2α Antagonist Combination for Preterm Labor

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Solution Overview

Problem

There is a need for effective treatments or preventions for preterm labor that are therapeutically effective and physiologically safe, as preterm labor remains a leading cause of infant mortality and morbidity, and existing treatments for preterm birth are associated with significant healthcare costs and side effects.

Innovation Solution

The use of a combination of a PGF2α receptor antagonist, such as a 1,3-thiazolidine-2-carboxamide compound, and nifedipine, administered in reduced dosages and frequencies, to delay the onset of delivery and alleviate symptoms of preterm labor by reducing uterine contractions and preventing membrane rupture.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nifedipine is administered at higher dosages and frequencies to treat preterm labor, then therapeutic effectiveness is improved, but side effects increase

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent combines nifedipine (calcium channel blocker) with a PGF2α receptor antagonist to create a synergistic therapeutic effect. This combination allows for reduced dosages of nifedipine while maintaining or improving therapeutic effectiveness, thereby reducing side effects associated with high-dose monotherapy.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The treatment uses a composite pharmacological approach by combining two different mechanisms of action (calcium channel blocking and prostaglandin receptor antagonism) into a single therapeutic regimen, achieving enhanced efficacy with reduced individual drug dosages and minimized adverse reactions.

Inventive Principle:

Principle #40Composite materials

2Ease of operation

If a single agent is used to treat preterm labor, then treatment simplicity is improved, but therapeutic effectiveness is insufficient

Engineering Contradiction:

Improvetreatment simplicityVSAvoidtherapeutic effectiveness

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent merges two pharmacological agents with complementary mechanisms of action into a coordinated treatment protocol. This combination addresses the limitations of single-agent therapy by providing enhanced and more reliable therapeutic effectiveness while maintaining structured simplicity through defined dosing regimens.

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

This combination allows for prolonged pregnancy and delayed labor onset with reduced side effects from nifedipine treatment, maintaining therapeutic benefits while minimizing adverse reactions, thereby improving maternal and fetal health outcomes.

Implementation Method 1

a prostaglandin F2α (PGF2α) receptor antagonist in combination with nifedipine so as to slow the onset of delivery

Methodology Applied

Scientific EffectReceptor antagonism:

Implementation Method 2

administered a prostaglandin F2α (PGF2α) receptor antagonist in combination with a reduced dosage of a calcium channel inhibitor, such as nifedipine

Methodology Applied

Scientific EffectCalcium channel inhibition:

Data Source

PatentUS11534428B1Compositions and methods for delaying the incidence of labor

Publication Date: 2022.12.27 XOMA US LLC

AI summary

The invention 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 nifedipine 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. Using the compositions and methods described herein, a subject may be dosed with a PGF2α receptor antagonist and a reduced amount or frequency of nifedipine relative to the amount or frequency of nifedipine that would otherwise be used if the nifedipine were given in the absence of the PGF2α receptor antagonist.