Abstract: A beverage is a drinkable liquid. Described here is a beverage containing a cooling agent that will exert cooling sensations in the upper center of the chest and make a subject feel comfortable. The cooling agent is an agent that targets TRPM8 receptors on nerve cell membranes. The beverage can be imbibed without unpleasant taste and the goal is to make the whole body feel cooler for about 20 min or more after drinking. By choosing the right molecule and right concentration, cooling intensity, location, and duration in the chest is controlled. Surprisingly, the cooling agent was also effective when consumed with warm or hot beverages. The beverage contains selected 1-diisopropyl-phosphinoyl-alkanes and taste-modulating agents selected from sweeteners, extracts from hops, ginger, or cinchona. Various uses of this cooling beverage are proposed.

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.

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-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds”, that are useful, for example, in the treatment of the discomforts of dermatological disorders (e.g., diseases) The treatment is for the dysesthesia (e.g., caused by irritation, itch, or pain) due to dermatitis, urticaria; scalp itch; vulvar itch; lichen sclerosus; cholestatic itch; psoriasis; sebhorrheic dermatitis; allergic conjunctivitis; blepharitis; and pruritus of the elderly. The applicant has found that topical delivery of DIPA compounds to the skin alleviates the dysesthesia of these conditions in human subjects.

Abstract: The present discovery pertains generally to the field of therapeutic compounds. More specifically the present discovery pertains to a particular 1-di-alkyl-phosphinoyl-alkane, 1-(Diisopropyl-phosphinoyl)-nonane, referred to herein as “DIPA-1-9”. Surprisingly and unexpectedly, DIPA-1-9, is able to selectively treat (e.g., suppress) sensory discomfort arising from the lumenal epithelial lining of the pharynx and esophagus without side effects. Compared to structurally similar compounds, DIPA-1-9 did not have the problems of painful cold, stinging, or irritancy, or of adverse taste when applied in the oral cavity. To deliver the DIPA-1-9 to the lumenal epithelium of the pharynx and esophagus, an ideal formulation for delivery is a solution of DIPA-1-9 in syrup, at a concentration of 5 to 12 mg/mL and a delivery volume of less than 1 mL. The delivery unit can be a plastic vial with a design such that the syrup is poured onto the base of the tongue, next to the pillars of fauces.

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.

Abstract: Cough is a common experience and the most frequent reason why an individual seeks a visit to a physician. The prevalence of cough is about 10+% of the population. Cough is a manifestation of many aerodigestive tract disorders and especially consequential for serious lower airway diseases such as respiratory infections, chronic obstructive pulmonary disease (COPD) and asthma because increased coughing leads to emergency room visits and hospitalization. There is a need for methods to oversee coughing frequency in certain patients. Traditionally, all automated cough monitors have used cough sound as the signal for the measurement of cough. In the present invention movements of the diaphragm muscle, recorded by a motion sensor placed above the xiphoid process, are used for counting coughs. A device for such recordings is described and data were collected.

Abstract: The present discovery pertains generally to the field of therapeutic compounds. More specifically the present discovery pertains to a particular 1-di-alkyl-phosphinoyl-alkane, 1-(Diisopropyl-phosphinoyl)-nonane, referred to herein as “DIPA-1-9”. DIPA-1-9, is able to selectively treat (e.g., suppress) sensory discomfort arising from the airways without side effects. Compared to structurally similar compounds, DIPA-1-9 did not have the problems of excessive cold, stinging, or irritancy, or of adverse taste. To deliver the DIPA-1-9 to the upper airway it is formulated as a solution of DIPA-1-9 in water, a water-based solution, or syrup, at a concentration of 2 to 10 mg/mL and a delivery volume of less than 0.5 mL per unit dose. The drops of DIPA-1-9 are administered into the nasal cavity or onto the base of the tongue, next to the pillars of fauces. The DIPA-1-9 then reaches the nerve endings at the base of the epithelia and transduces signals of coolness and cold.

Abstract: The present discovery pertains generally to the field of therapeutic compounds. More specifically the present discovery pertains to a particular 1-di-alkyl-phosphinoyl-alkane, 1-(Diisopropyl-phosphinoyl)-nonane, referred to herein as “DIPA-1-9”. Surprisingly and unexpectedly, DIPA-1-9, is able to selectively treat (e.g., suppress) sensory discomfort arising from the lumenal epithelial lining of the pharynx and esophagus without side effects. Compared to structurally similar compounds, DIPA-1-9 did not have the problems of painful cold, stinging, or irritancy, or of adverse taste when applied in the oral cavity. To deliver the DIPA-1-9 to the lumenal epithelium of the pharynx and esophagus, an ideal formulation for delivery is a solution of DIPA-1-9 in syrup, at a concentration of 5 to 12 mg/mL and a delivery volume of less than 1 mL. The delivery unit can be a plastic vial with a design such that the syrup is poured onto the base of the tongue, next to the pillars of fauces.

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-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds”, that are useful, for example, in the treatment of dermatological disorders (e.g., diseases) including: sensory discomfort (e.g., caused by irritation, itch, or pain); a skin dysesthesia; atopic dermatitis; contact dermatitis; cholestatic itch; psoriasis; sebhorrheic dermatitis; milaria rubra; ocular pain and discomfort; heat discomfort; heat stress; flushing and/or night sweats (vasomotor symptoms); and pruritus of the elderly. The applicant has found that topical delivery of DIPA compounds to the skin alleviates skin discomfort. The present discovery pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy of dermatological disorders.

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; 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.

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.

Abstract: The present discovery pertains to the discovery of certain amphiphilic compounds that may be useful for the management of sebum secretion in subjects with acne, oily skin, or seborrheic dermatitis. These compounds are 1-dialkylphosphorylalkanes with the longest alkyl group being seven or more carbons. Preferably, a compound is dissolved in a dermatologically acceptable vehicle, and delivered to the skin in a solution, gel, lotion, cream, or ointment. The method of application may be with the surface of the finger, or via an applicator. The decrease is sebum secretion in certain subjects may result in skin conditions that enhance cosmetic appearance and ameliorate skin disorders.

Abstract: The present discovery pertains to the discovery of certain amphiphilic compounds that may be useful for the management of sebum secretion in subjects with acne, oily skin, or seborrheic dermatitis. These compounds are 1-dialkylphosphorylalkanes with the longest alkyl group being seven or more carbons. Preferably, a compound is dissolved in a dermatologically acceptable vehicle, and delivered to the skin in a solution, gel, lotion, cream, or ointment. The method of application may be with the surface of the finger, or via an applicator. The decrease is sebum secretion in certain subjects may result in skin conditions that enhance cosmetic appearance and ameliorate skin disorders.

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.

Abstract: The present discovery pertains generally to the field of therapeutic compounds. More specifically the present discovery pertains to certain di-alkyl-phosphinoyl-alkanes as described herein, DIPA-1-8 and DIPA-1-9, and 2-6 and 2-7 that are collectively referred to herein as “DAPA compounds”, that are useful in the treatment of disorders (e.g., diseases) including: sensory discomfort (e.g., caused by inflammation, irritation, itch, or pain) in the nasal cavity. The applicant has found that localized delivery of DAPA compounds with a swab to the Kiesselbach's area of the human nose will relieve the discomforts of rhinitis and other nasal cavity discomforts.

Abstract: The present discovery pertains generally to the field of therapeutic compounds. More specifically the present discovery pertains to certain di-alkyl-phosphinoyl-alkanes as described herein, DIPA-1-8 and DIPA-1-9, and 2-6 and 2-7 that are collectively referred to herein as “DAPA compounds”, that are useful in the treatment of disorders (e.g., diseases) including: sensory discomfort (e.g., caused by inflammation, irritation, itch, or pain) in the nasal cavity. The applicant has found that localized delivery of DAPA compounds with a swab to the Kiesselbach's area of the human nose will relieve the discomforts of rhinitis and other nasal cavity discomforts.

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; 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.

Abstract: The concept is put forward here that heat abstraction sensations, captured by topical application of a molecule, can be used to alleviate discomfort of non-keratinizng tissues. By synthesizing compounds and devising tests, a molecule name DAPA-2-5 was identified as having the selective desirable properties for achieving this purpose. DAPA-2-5 is a di-alkyl-phosphinoyl-alkane, and “DAPA-2-5” is 1-Di(sec-butyl)-phosphinoyl-pentane. DAPA-2-5 evokes a dynamic cooling sensation on non-keratinizing body surfaces (including, e.g., oropharyngeal, esophageal, and anogenital surfaces) which is not accompanied by stinging, irritation, or unpleasant tastes. Thus, it can be used to treat (e.g., suppress) sensory discomfort from non-keratinizing stratified epithelium (NKSE) selectively. This unusual selectivity, potency, and efficacy was also surprisingly exhibited in laboratory animal tests of inhibition of heat-induced edema, of eliciting skin irritation, and of inhibition of acid-induced swallowing.

Abstract: Short-chain 2- to 3-carbon alcohols are used as solvents for cooling agents in the preparation of topical therapeutic and cosmetic formulations. Some of these alcohols, especially ethanol, inhibit the ability of the cooling agent to activate its target receptor. In one embodiment of this invention, (R)-1,2-propanediol is used as an alcoholic solvent for the topical delivery of cooling agents to biological surfaces. This (R)-1,2-propanediol enantiomer has a minimum inhibitory effect on cooling with respect to standard 2- to 3-carbon alcoholic solvents, and functions to substantially protect the agents cooling activity from inhibition when in the presence of a short-chain alcohol such as ethanol.

Abstract: Short-chain 2- to 3-carbon alcohols are used as solvents for cooling agents in the preparation of topical therapeutic and cosmetic formulations. Some of these alcohols, especially ethanol, inhibit the ability of the cooling agent to activate its target receptor. In one embodiment of this invention, (R)-1,2-propanediol is used as an alcoholic solvent for the topical delivery of cooling agents to biological surfaces. This propanediol enantiomer has a minimum inhibitory effect on cooling with respect to standard 2- to 3-carbon alcoholic solvents, and functions to substantially protect the agent's cooling activity from inhibition when in the presence of a short-chain alcohol.