Novel TRPM8 Modulators for Cooling Without Irritation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current TRPM8 modulators face deficiencies in strength of effect, duration of effect, skin/mucosa irritation, odor, taste, solubility, and volatility, limiting their application in cosmetics, nutrition, textiles, OTC products, and pharmaceuticals.
Innovation Solution
Development of novel TRPM8 receptor modulators, including specific compounds and methods for their use, which can act as agonists or antagonists to induce a sensation of coldness, suitable for various applications such as cosmetics, pharmaceuticals, and textiles, with improved properties over existing modulators.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Temperature
If menthol is used as a TRPM8 modulator, then the cooling effect is achieved, but skin/mucosa irritation and anesthetic effect occur at elevated concentrations
Solution Approach 1:
The patent develops novel TRPM8 modulators that act as short-acting alternatives to menthol, providing the desired cooling effect without the prolonged irritation and anesthetic effects associated with elevated menthol concentrations. These compounds are designed to be metabolized or eliminated more quickly, reducing cumulative harmful effects on skin and mucosa.
Solution Approach 2:
The invention changes the chemical parameters of the TRPM8 modulator by developing structurally unrelated compounds with different physicochemical properties compared to menthol. These novel modulators maintain TRPM8 activation capability while having reduced affinity for irritant receptors and different volatility profiles, thereby reducing irritation and anesthetic side effects.
2Temperature
If high concentrations of TRPM8 modulators are used to enhance cooling effect, then the sensation of coldness is intensified, but irritation and anesthetic effect increase
Solution Approach 1:
The novel modulators are designed with shorter duration of action, allowing for more frequent application at lower concentrations to achieve cumulative cooling effects without building up anesthetic side effects. This enables sustained use without the progressive numbness associated with high-concentration menthol.
Solution Approach 2:
The patent modifies the concentration-response relationship by introducing compounds with higher potency at lower concentrations, allowing effective cooling sensation to be achieved at concentrations that do not trigger anesthetic effects. The novel modulators have optimized affinity for TRPM8 compared to their affinity for other receptors that mediate anesthetic effects.
3Temperature
If existing TRPM8 modulators are used, then cooling effect is produced, but deficiencies in strength of effect, duration of effect, solubility, and volatility remain
Solution Approach 1:
The patent systematically varies chemical parameters of the modulator molecules to optimize multiple properties simultaneously. The novel compounds feature modified molecular weight, hydrophobicity, and functional groups that improve solubility in cosmetic and pharmaceutical formulations while maintaining or enhancing TRPM8 activation potency and extending duration of effect through optimized metabolic stability.
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 novel modulators provide enhanced efficacy and reduced side effects, extending the cooling effect on skin or mucosa compared to traditional menthanecarboxylic acid N-ethylamide, and are suitable for diverse applications including skincare, haircare, pharmaceuticals, and textiles.
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, which brings about a Ca2+ influx into the cold-sensitive neurons
Implementation Method 3
Low temperatures (preferably 10-25° C.) stimulate this receptor, resulting in a signal transduction which is interpreted by the nervous system as a sensation of coldness
Data Source
AI summary
The invention relates to new types of modulators of the cold menthol receptor TRPM8, to methods of modulating the TRPM8 receptor using these modulators; and in particular the use of the modulators for inducing a sensation of coldness; and also the articles and compositions produced using these modulators.