TRPM8 Modulators for Stronger Cooling With Less Irritation
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Solution Overview
Problem
Existing TRPM8 modulators have deficiencies in strength of effect, duration of effect, skin/mucosa irritation, odor, taste, solubility, and volatility, limiting their applications in cosmetics, pharmaceuticals, and other fields.
Innovation Solution
Development of novel polynuclear organic compounds that modulate the TRPM8 receptor, including agonists and antagonists, which can induce a sensation of coldness and have improved properties such as enhanced activity and reduced irritation, suitable for use in cosmetics, pharmaceuticals, and as insect repellents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If existing TRPM8 modulators (menthol, derivatives, Icilin, WS-23) are used to activate the receptor and induce cold sensation, then the desired cooling effect is achieved, but skin/mucosa irritation and anesthetic effects occur at elevated concentrations
Solution Approach 1:
The patent modifies the chemical parameters of existing TRPM8 modulators by changing molecular structure (e.g., adding fluorine atoms, modifying ring structures, adjusting substituent positions) to optimize the balance between efficacy and irritation. This structural parameter optimization allows achieving the desired cold sensation with reduced irritant properties.
Solution Approach 2:
The patent develops composite molecular structures combining beneficial features of different modulator classes (menthol derivatives, Icilin-like compounds, WS-23 analogs) into novel hybrid molecules that exhibit synergistic effects, providing strong TRPM8 activation with reduced side effects.
2Duration of action of moving object
If existing TRPM8 modulators are applied to achieve cooling effects, then the sensation of coldness is produced, but the duration of effect is insufficient
Solution Approach 1:
The patent employs molecular structures that bind to TRPM8 with high affinity and prolonged residence time, achieving sustained activation. The modified compounds exhibit slower dissociation rates from the receptor, extending the duration of cooling effect without requiring excessive concentrations.
3Adaptability or versatility
If existing TRPM8 modulators are used for cooling effects, then the desired sensation is achieved, but deficiencies in solubility and volatility limit their applications
Solution Approach 1:
The patent introduces polar and non-polar functional groups at specific positions on the molecular scaffold to optimize solubility characteristics. Hydrophilic groups (e.g., hydroxyl, carboxyl) enhance water solubility for topical formulations, while hydrophobic regions maintain membrane permeability and receptor binding affinity.
Solution Approach 2:
The patent systematically varies molecular weight, functional group composition, and structural rigidity to tune volatility and solubility parameters. These parameter optimizations enable the modulators to meet formulation requirements for diverse applications including cosmetics, pharmaceuticals, and consumer products.
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 modulators provide effective TRPM8 receptor modulation with improved activity and reduced side effects, enabling their use in various applications including cosmetics, pharmaceuticals, and insect repellents, while inducing a sensation of coldness and offering therapeutic benefits.
Implementation Method 1
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Data Source
AI summary
The invention relates to novel modulators of the cold menthol receptor TRPM8, to a method for modulating the TRPM8 receptor using said modulators; to the use of the modulators for induction of cold sensation; and to objects and means produced using said modulators.