TRPM8 Modulator Compounds for Strong 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 (e.g., menthol) 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 applies parameter changes by modifying the chemical structure of TRPM8 modulators through systematic variation of molecular parameters (R1-R6 substituents, ring structures, molecular weight). This allows optimization of the balance between efficacy and irritation, creating compounds with improved safety profiles while maintaining or enhancing the desired cooling effect.
Solution Approach 2:
The patent employs composite materials by designing molecules that combine multiple structural elements (polynuclear frameworks with various substituent groups) to achieve synergistic effects. The composite molecular structures integrate hydrophobic and hydrophilic regions, aromatic and aliphatic components, which together provide both potent TRPM8 modulation and reduced irritation compared to single-structure modulators.
2Reliability
If high concentrations of menthol are applied to achieve stronger TRPM8 activation, then the cooling sensation is enhanced, but anesthetic effects and irritation increase
Solution Approach 1:
The patent applies local quality by introducing specific functional groups at particular positions (R1-R6) of the molecular framework. Each substituent position is optimized to provide localized interactions with the TRPM8 receptor that enhance cooling sensation while avoiding the activation of adjacent neural pathways that would produce anesthetic effects.
Solution Approach 2:
The patent inverts the conventional approach by designing antagonists and partial agonists alongside full agonists. Instead of simply increasing menthol concentration to enhance effect, the invention uses structurally related compounds with inverted or modified activity profiles to achieve sustained cooling without the threshold effects that lead to anesthesia.
3Reliability
If novel polynuclear organic compounds are developed to improve TRPM8 modulation, then activity and reduced irritation are achieved, but compound complexity and development cost increase
Solution Approach 1:
The patent applies segmentation by dividing the complex molecular structure into modular components (core polynuclear framework with interchangeable R1-R6 substituent groups). This modular architecture allows systematic optimization of individual segments to achieve desired efficacy and safety profiles while simplifying the overall development process through combinatorial design.
Solution Approach 2:
The patent achieves universality by creating a platform of polynuclear compounds with a common core structure that can serve multiple functions. The same molecular framework can produce agonists, antagonists, or partial agonists depending on substituent configuration, allowing a single compound series to address multiple application requirements (cosmetics, pharmaceuticals, insect repellents) without proportionally increasing complexity.
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 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 addressing previous limitations of existing compounds.
Implementation Method 1
in the cell membrane, forms pores (in each case 4 units combine to give a tetramer), which selectively allow Ca2+ ions to pass
Implementation Method 2
it has been shown that it acts as a natural modulator of the receptor TRPM8... By applying menthol, TRPM8 is activated
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.