Di-isopropyl-phosphinoyl-alkanes Penetrate Skin for Sustained Cooling
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Solution Overview
Problem
Current chemical cooling agents struggle to elicit sustained sensations of coolness and cold on the skin, particularly on the torso and limbs, due to the barrier posed by the keratinized stratum corneum layer, and lack selectivity in activating TRPM8 receptors, limiting their therapeutic and diagnostic applications.
Innovation Solution
Development of water-soluble di-isopropyl-phosphinoyl-alkanes (DIPA compounds) that penetrate the keratinized skin, selectively evoke intense and prolonged 'dynamic cool' sensations, and exhibit differential actions on neuropathic versus somatic pain, allowing for diagnostic differentiation and enhanced TRPM8 receptor study.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If chemical cooling agents are applied to the skin, then cooling sensations are produced, but the effects do not last long due to the barrier of the stratum corneum
Solution Approach 1:
The patent modifies the chemical structure of cooling agents by using p-menthane carboxamide compounds with specific molecular properties that enable them to penetrate the stratum corneum barrier while maintaining their cooling effect, thereby extending the duration of action
Solution Approach 2:
The patent employs specific chemical compounds as intermediaries that can traverse the stratum corneum barrier and deliver the cooling effect to the underlying nerve endings, solving the penetration problem while maintaining prolonged action
2Measurement precision
If chemical cooling agents are applied to the skin, then cooling sensations are produced, but selectivity in activating TRPM8 receptors is limited
Solution Approach 1:
The patent designs compounds with specific molecular characteristics that provide selective affinity for TRPM8 receptors, enabling precise targeting of cold-sensing neurons while minimizing off-target effects, thus improving measurement precision and selectivity
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
DIPA compounds provide robust, sustained cooling effects on the skin, counteracting fatigue and discomfort, and serve as selective reagents for TRPM8 function studies, offering diagnostic and therapeutic benefits for pain management and cognitive enhancement.
Implementation Method 1
The unusual property of the DIPA molecules is the ability to penetrate the keratinized layers of the skin [stratum corneum] to reach receptive targets underneath
Implementation Method 2
Chemical sensory/cooling agents are molecules that can mimic the sensations of heat abstraction without a change in tissue temperatures
Data Source
AI summary
The present discovery pertains generally to the field of therapeutic compounds. More specifically the present discovery pertains to certain di-isopropyl-phosphinoyl-alkanes as described herein, DIPA-1-5, DIPA-1-6, DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds”, that are useful, for example, in the treatment of disorders (e.g., diseases) including: sensory discomfort (e.g., caused by irritation, itch, or pain); a skin dysesthesia; dermatitis; ocular pain and discomfort; heat discomfort; heat stress; flushing and/or night sweats (vasomotor symptoms); post-operative hypothermia; post-anaesthetic shivering; nasal congestion and nasal obstruction; pharyngeal and esophageal discomfort; fatigue; tiredness; depression; cognitive dysfunction; and to enhance cognitive function. The applicant has found that localized delivery of DIPA compounds to the upper eyelid and/or facial skin has an alerting and enhancement effect on behavior and can be used to give a cosmetic refreshing look, to mental alertness, to reduce fatigue, and to improve work output. The present discovery also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy, in diagnosis of neuropathic pain, and in study of TRPM8 function.