Di-isopropyl-phosphinoyl-alkanes (DAPA) compounds as topical agents for the treatment of sensory discomfort
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Publication Number
US-11684628-B2
Publication Date
2023-06-27
Expiration Date
Abstract
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention 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; psoriasis; ocular discomfort; heat discomfort; heat stress; flushing and/or night sweats (vasomotor symptoms) in post-menopausal women; post-operative hypothermia; post-anaesthetic shivering; fatigue; tiredness; depression; cognitive dysfunction; and to enhance cognitive function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.
Core Innovation
The invention relates to di-isopropyl-phosphinoyl-alkane compounds, including DIPA-1-6 through DIPA-1-9, as topical agents for evoking a sustained dynamic cool sensation on facial, ocular, periorbital skin and head/scalp. The compounds produce dynamic cool and cool sensation without lowering tissue temperature, and the disclosure describes compound-dependent dynamic cool properties with different use profiles.
The patent describes the compounds as TRPM8 full-efficacy agonists and relates dynamic cooling to TRPM8-dependent effects and calcium entry. DIPA-1-7 and DIPA-1-8 are identified as significantly more potent for dynamic cool, while DIPA-1-7 is linked to TRPM8 target engagement and DIPA-1-9 is described as least irritating for ocular use.
The disclosure further reports objective dynamic-cooling behavior in vivo, including wet-dog shaking or shivering-linked cooling behavior, and contrasts responsiveness with capsaicin and TRPV1. Topical pharmaceutical compositions are described with pharmaceutically acceptable carriers or diluents, and formulation and application examples include wipes/towelettes and creams.
Claims Coverage
The claim set covers a selected compound from a specified set of di-isopropyl phosphine-derived compounds, together with dependent claims to particular compounds and pharmaceutical compositions with quantitative concentration constraints. The inventive coverage centers on the selected compound or compounds and their formulation in topical pharmaceutical compositions.
Selected compound from the specified compounds
A compound selected from the following compounds.
Phosphine-derived compound (DIPA-1-7)
The compound of claim 1 is the particular illustrated chemical structure labeled DIPA-1-7.
Phosphine-derived compound (DIPA-1-9)
The compound of claim 1 is the specific named or depicted phosphine-derived compound DIPA-1-9.
Pharmaceutical composition with a pharmaceutically acceptable carrier or diluent
A pharmaceutical composition that includes the compound together with a pharmaceutically acceptable carrier or diluent.
Quantitative wt/vol concentration range in a pharmaceutical composition
A pharmaceutical composition containing the compound at a concentration of 0.005–2.0% wt/vol.
Liquid pharmaceutical composition concentration range in mg/mL
A liquid pharmaceutical composition comprising the compound at a concentration of 0.5–20 mg/mL.
Coverage centers on selecting from the specified compounds, narrowing to particular phosphine-derived embodiments, and covering pharmaceutical compositions that include pharmaceutically acceptable carrier or diluent with defined concentration ranges in wt/vol or mg/mL for liquid compositions.
Stated Advantages
Evokes a sustained dynamic cool sensation on facial, ocular, periorbital skin and head/scalp without lowering tissue temperature.
DIPA-1-7 is described as potent dynamic cooling with anti-fatigue for hours.
DIPA-1-8 is described as longer acting but lower intensity.
DIPA-1-9 is described as least irritating for ocular use.
DIPA-1-6 is described as more systemic for vasomotor symptoms.
Documented Applications
Topical treatment to evoke dynamic cool sensation on facial, ocular, periorbital skin and head/scalp.
Relief of sensory discomfort, itch, pain, skin dysesthesia, dermatitis, and psoriasis.
Use for fatigue and heat stress contexts.
Use to address ocular discomfort.
Use for cognitive dysfunction.
Use for post-menopausal hot flushes and night sweats (vasomotor symptoms).
Use in post-operative hypothermia and post-anaesthetic shivering contexts.
Diagnostic or adjunct use.
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