Di-isopropyl-phosphinoyl-alkanes as topical agents for the treatment of sensory discomfort
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.
1. A method of treating fatigue in a human subject experiencing fatigue, comprising:
topically applying a therapeutic composition to the human subject or instructing a user to topically apply the composition to the human subject wherein the composition has an amount of a compound with Formula 1 therein
wherein R is n-heptyl, n-octyl and/or n-nonyl and wherein the applied amount of Formula 1 compound in the composition is from 0.01 to 10 mg per unit dose.
2. The method as in claim 1 wherein the compound is 1-diisopropyl-phosphinoyl-heptane [DIPA-1-7].
3. The method as in claim 1 wherein the compound is 1-diisopropyl-phosphinoyl-octane [DIPA-1-8].
4. The method as in claim 1 wherein the compound is 1-diisopropyl-phosphinoyl-nonane [DIPA-1-9].
5. The method as in claim 1 wherein the composition is administered topically via a swab, wipe, pad, or towellette.
6. The method as in claim 1 wherein the composition is in the form of a paste, gel, lotion, cream, ointment, spray or aerosol.
7. The method as in claim 1 wherein the composition comprises water, isotonic saline, or an aqueous buffered solution.
8. The method as in claim 1 , wherein the fatigue is caused by chronic illness, cancer or cancer-related treatment, ageing, an impairment of vision, a neurological dysfunction, or a psychological dysfunction.
9. The method as in claim 1 , wherein the fatigue is fatigue caused by anxiety, depression, heat stress, cognitive dysfunction, excessive physical exertion, or excessive mental exertion.
10. The method as in claim 1 , wherein the fatigue is associated with a decreased ability to think, to concentrate, to study, or to perform work.
11. The method as in claim 1 , wherein the treatment improves hand-eye coordination in a sport, and improves performance in a game of chance or of mental skills.