TRPM8 Antagonist for Vasomotor Symptom Relief

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for vasomotor symptoms such as hot flashes are not completely effective and often come with unwanted side effects, particularly for women concerned about hormone replacement therapy and those with a history of breast cancer or clotting disorders.

Innovation Solution

Administration of a Transient Receptor Potential Melastatin 8 (TRPM8) antagonist, represented by formula (I), which acts as a TRPM8 antagonist to treat or prevent vasomotor symptoms by reducing core body temperature and alleviating heat-related sensations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If estrogen replacement therapy is used to treat vasomotor symptoms, then the effectiveness in minimizing or preventing symptoms is improved, but the risk of serious complications increases

Engineering Contradiction:

Improveeffectiveness in minimizing vasomotor symptomsVSAvoidrisk of serious complications

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the beneficial effect of hormone replacement therapy (treating vasomotor symptoms) while eliminating the harmful components (hormones that cause complications). This is achieved by identifying and targeting the specific neural mechanism (TRPM8 channel) responsible for hot flash generation, thereby treating the symptom without administering hormones that carry health risks

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces an intermediary substance (TRPM8 antagonist compound) that acts on the neural pathway involved in hot flash generation. This intermediary blocks the TRPM8 channel, preventing the neuronal firing that triggers vasomotor symptoms, thereby providing an alternative mechanism that does not involve hormone replacement but still achieves symptom relief

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If SSRIs, SNRIs, gabapentin or clonidine are used to treat vasomotor symptoms, then the treatment coverage is improved, but unwanted side effects increase

Engineering Contradiction:

Improvetreatment coverage for vasomotor symptomsVSAvoidunwanted side effects

Core Design Contradiction:

Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces a new intermediary compound (TRPM8 antagonist) that acts specifically on the TRPM8 channel involved in hot flash pathophysiology. This provides a more targeted mechanism compared to the broader actions of SSRIs, SNRIs, gabapentin, or clonidine, thereby reducing off-target side effects while maintaining treatment effectiveness

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the therapeutic parameter from broad neurotransmitter modulation (as with SSRIs, SNRIs, gabapentin, or clonidine) to specific ion channel blockade (TRPM8 antagonist). This parameter change allows for more selective action on the hot flash pathway, improving the side effect profile while maintaining treatment coverage

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP3468557B1Compositions for treating or preventing vasomotor symptoms

Publication Date: 2023.07.26 TANABE PHARMA CORP

Figure 1~2
Figure 3
Figure 4

AI summary

The present disclosure is directed to compositions and methods for treating or preventing vasomotor symptoms such as hot flashes, comprising a Transient Receptor Potential Melastatin 8 (TRPM8) antagonist and administering a TRPM8 antagonist, respectively.