Novel Physiological Coolants Modulating TRPM8 Receptors

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Solution Overview

Problem

Existing physiological coolants, such as menthol, have disadvantages like strong odor, high volatility, bitter taste, and skin irritation, limiting their effectiveness and suitability for use in cosmetics, nutrition, and pharmaceuticals.

Innovation Solution

Development of new physiological coolants represented by general formulae (I) to (IV), which modulate the TRPM8 receptor, providing a long-lasting, intense, and rapid cooling sensation without the drawbacks of traditional coolants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If menthol is used as a physiological coolant, then a strong cooling effect is achieved, but strong odor, high volatility, bitter taste, and skin irritation occur

Engineering Contradiction:

Improvecooling effectVSAvoidodor, volatility, bitter taste, skin irritation

Core Design Contradiction:

TemperatureVSObject-generated harmful factors

Solution Approach 1:

The patent modifies the chemical structure of menthol by changing parameters such as molecular weight, functional groups, and stereochemistry to create derivatives that maintain TRPM8 receptor activation while reducing harmful properties. Specific examples include using menthol derivatives with modified side chains or different chiral configurations that provide comparable cooling effects with reduced volatility and irritation.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent combines menthol with other cooling agents or functional additives to create composite formulations that leverage synergistic effects. This approach allows the mixture to achieve enhanced cooling performance while the additional components help mask undesirable odor and taste characteristics, or reduce skin irritation through complementary mechanisms.

Inventive Principle:

Principle #40Composite materials

2Temperature

If higher concentrations of menthol are used to strengthen the cooling effect, then the cooling intensity increases, but skin irritation and anaesthetic effect increase

Engineering Contradiction:

Improvecooling intensityVSAvoidskin irritation, anaesthetic effect

Core Design Contradiction:

TemperatureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the pharmacological parameters of menthol by using derivatives with different binding affinities to TRPM8 receptors. These modified compounds can achieve comparable or enhanced cooling effects at lower concentrations, thereby avoiding the harmful skin irritation and anaesthetic effects associated with high concentrations of parent menthol.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs rapidly metabolized menthol derivatives that provide intense but transient cooling effects. These compounds are designed to be quickly processed by the body, delivering the desired cooling stimulus without prolonged accumulation that would lead to irritation or anaesthetic effects, effectively using a temporary action mechanism.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Temperature

If existing coolant formulations are used, then cooling effect is achieved, but the cooling duration is limited and intensity is insufficient

Engineering Contradiction:

Improvecooling sensationVSAvoidcooling duration and intensity

Core Design Contradiction:

TemperatureVSDuration of action of moving object

Solution Approach 1:

The patent uses menthol derivatives with optimized pharmacokinetic properties that provide continuous TRPM8 receptor activation over extended periods. The modified molecular structures enable sustained release and prolonged receptor binding, ensuring continuous cooling sensation without the rapid decline in effect seen with conventional menthol formulations.

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The patent modifies the pharmacological parameters of the coolant by using derivatives with enhanced receptor affinity and prolonged half-life. These parameter changes result in extended cooling duration and maintained intensity, as the modified compounds remain active at the receptor site longer than parent menthol, providing sustained cooling effects.

Inventive Principle:

Principle #35Parameter changes

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 new coolants achieve a strong and prolonged cooling effect with minimal bitterness and irritation, making them suitable for various applications including cosmetics, nutrition, and pharmaceuticals.

Implementation Method 1

Both individual components and mixtures can be used as physiological coolants. It should be noted that not all compounds that influence receptors in vitro, which are (also) involved in mediating a physiological cooling effect, actually produce such an effect in vivo on the skin or mucous membranes.

Methodology Applied

Scientific EffectReceptor modulation:

Implementation Method 2

The application of menthol activates TRPM8, causing a Ca2+ influx into the cold-sensitive neurons. The resulting electrical signal is then perceived as a cold sensation.

Methodology Applied

Scientific EffectSignal transduction:

Data Source

PatentUS20250163006A1New Coolants, and Preparations Containing Same

Publication Date: 2025.05.22 SYMRISE GMBH & CO KG

AI summary

The present invention relates to novel physiological coolants, mixtures of coolants containing these novel agents, mixtures of the coolants with flavors, the use of these coolants, and articles and end preparations for the consumer containing the physiological coolants or mixtures of coolants.