Low Molecular-Weight TRPM8 Modulators to Reduce Irritation and Odor
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Solution Overview
Problem
Existing modulators of the TRPM8 receptor face issues with potency, duration of action, skin/mucosal irritation, odor, taste, solubility, and volatility, limiting their effectiveness in various applications such as cosmetics, pharmaceuticals, and insect repellents.
Innovation Solution
Development of new compounds that modulate the TRPM8 receptor, including agonists and antagonists, which can be used to induce a feeling of cold or counteract it, with specific structures and formulations suitable for different applications, such as topical use, pharmaceuticals, and insect repellents, and their incorporation into products like mouthwash, textiles, and packaging materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If traditional modulators like menthol are used to activate TRPM8, then the cold sensation is induced, but skin/mucosal irritation and adverse effects occur
Solution Approach 1:
The patent modifies the chemical structure of known TRPM8 modulators by changing molecular parameters such as adding fluorine atoms, altering carbon chain lengths, and modifying functional groups. This structural parameter changes allow the compounds to maintain TRPM8 activation capability while reducing irritant properties, thus resolving the contradiction between effectiveness and safety
Solution Approach 2:
The invention develops hybrid compounds that combine beneficial structural features from different known modulators while eliminating detrimental aspects. By creating composite molecular structures with specific combinations of hydrophobic and hydrophilic regions, the compounds achieve both high potency and reduced irritation
2Reliability
If high concentrations of modulators are used to enhance potency, then the cold sensation effect is improved, but odor and taste become more pronounced and undesirable
Solution Approach 1:
The patent employs systematic parameter changes in molecular structure, particularly modifying the hydrophobic-hydrophilic balance and adding polar groups like fluorine atoms. These changes increase water solubility and reduce volatility, allowing effective concentrations to be achieved without excessive odor or taste, thus resolving the contradiction between potency and sensory acceptability
3Reliability
If lipophilic modulators are used to enhance membrane permeability and potency, then the cold sensation effect is improved, but solubility in aqueous environments decreases
Solution Approach 1:
The invention systematically modifies molecular parameters by introducing polar functional groups, increasing hydrogen bonding capacity, and adjusting the ratio of hydrophobic to hydrophilic regions. These parameter changes optimize the balance between membrane permeability (for potency) and aqueous solubility, resolving the contradiction between these two essential properties
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
These new compounds provide improved potency, reduced irritation, and enhanced effectiveness in inducing a cold sensation or repellent effects, expanding the range of applications beyond traditional menthol-based solutions while minimizing adverse effects.
Implementation Method 1
forms pores in the cell membrane (respectively 4 units assemble into a tetramer), which selectively allow Ca2+
Implementation Method 2
The compound menthol has been shown to act as a natural modulator of the receptor TRPM8. By applying menthol, TRPM8 is activated, causing an influx of Ca2+
Data Source
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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 the objects and means produced using said modulators.