Di-isopropyl-phosphinoyl-alkanes as topical agents for the treatment of sensory discomfort
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9895382-B2
Publication Date
2018-02-20
Expiration Date
Abstract
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.
Core Innovation
The invention relates to treating fatigue in a human subject experiencing fatigue by topically applying a therapeutic composition containing an amount of a compound with Formula 1. The composition includes compounds in which R is n-heptyl, n-octyl and/or n-nonyl, and the applied amount of the Formula 1 compound is from 0.01 to 10 mg per unit dose.
The document links the topical dynamic cool activity of Formula 1 compounds, including DIPA-1-7, DIPA-1-8, and DIPA-1-9, to TRPM8 agonism as a mechanistic basis for therapeutic effects. Sensory testing on skin is described in which dynamic cool is compared with cold and icy cold, and human forehead temperature measurement is described as showing cooling without changing skin temperature.
The document further describes evidence intended to support a TRPM8-mediated anti-nociception mechanism, including isolated vagus nerve evidence in which an effect is reduced in TRPM8 knockout. Topical activity is also described using rat wet-dog shaking studies described as showing strong topical activity with membrane penetration.
Claims Coverage
The document contains one independent claim. It covers a topical method of treating fatigue in a human subject using a therapeutic composition containing a Formula 1 compound, with R defined as n-heptyl, n-octyl and/or n-nonyl, and with an applied amount ranging from 0.01 to 10 mg per unit dose.
Topical treatment of human fatigue with Formula 1 dynamic cool compounds
A method of treating fatigue in a human subject experiencing fatigue by 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.
Defined Formula 1 substituents and applied dose range
The Formula 1 compound has R being n-heptyl, n-octyl and/or n-nonyl, and the applied amount of Formula 1 compound in the composition is from 0.01 to 10 mg per unit dose.
Overall, claim coverage centers on topical administration of a Formula 1 compound composition for treating fatigue, with the key defining elements being the specific R substituent selection and the stated applied amount range per unit dose.
Stated Advantages
Relief of fatigue, tiredness, and cognitive dysfunction.
Relief of sensory discomfort including irritation, itch, and pain.
Relief of ocular discomfort and heat discomfort or stress and related vasomotor symptoms.
Diagnostic and laboratory utility for neuropathic pain/allodynia and TRPM8 function.
Cooling effect described as occurring without changing skin temperature.
TRPM8-selective pharmacological activity versus TRPA1 and TRPV1.
Mechanistic support for anti-nociception described as reduced in TRPM8 knockout in isolated vagus nerve evidence.
Strong topical activity described in rat wet-dog shaking studies and described as involving membrane penetration.
Treats fatigue in a human subject experiencing fatigue using a topical therapeutic composition.
Documented Applications
Topical treatment of fatigue in a human subject experiencing fatigue.
Topical relief of sensory discomfort including irritation, itch, and pain.
Topical relief of ocular discomfort.
Topical relief of heat stress and vasomotor symptoms.
Diagnostic and laboratory use related to neuropathic pain/allodynia and TRPM8 function.
Fatigue/cognition enhancement use-case narratives.
Chronic illness fatigue.
Heat stress relief.
Dermatitis/itch and pain relief.
Ocular discomfort/dry eyes syndrome.
Nasal congestion.
Pharyngeal/esophageal discomfort.
Hot flashes/night sweats.
Interested in licensing this patent?