Abstract: The present discovery generally pertains to the formulation of therapeutic compounds to treat the symptoms of esophageal disorders. More specifically, the present discovery pertains to two 1-di-alkyl-phosphinoyl-alkanes (DIPA) called DIPA-1-8 and DIPA-1-9. These compounds are formulated as a shaped medicament and swallowed to suppress the symptoms of esophageal reflux and dyspepsia. The DIPA act by creating sensations of coolness and cold on the pharyngeal and esophageal lining. Some of the symptoms relieved include cough, chronic cough, heartburn, chest pain, bloat, belching, and dyspepsia. A preferred embodiment is DIPA-1-9 dissolved in a gel matrix. An aspect of the invention is to design the medicament to be intercepted, impeded, ensnarled, or trapped in the pharyngeal valleculae and pyriform sinuses before it passes down the esophagus.

Abstract: Wearing a face mask or a filtering facepiece respirator, especially in hot weather for more than one hour, causes discomfort. But, in a viral pandemic, a barrier to filter inhaled and exhaled air is necessary to protect against airborne pathogens. The sensations of heat abstraction, that is, coolness and cold, can be captured by the rational design of optimized molecules. The topical application of these molecules alleviates the discomfort of wearing a face mask covering. Several entities were identified by synthesis and experiment as having the ideal properties for achieving this purpose. The preferred embodiments are certain 1-diisopropyl-phosphinoyl-alkanes described as DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds.” The applicant found that topical delivery of DIPA compounds to the facial skin, especially to the surface of the external nares (nostrils), alleviates face mask discomfort.

Abstract: Wearing a face mask or a filtering facepiece respirator, especially in hot weather for more than one hour, causes discomfort. But, in a viral pandemic, a barrier to filter inhaled and exhaled air is necessary to protect against airborne pathogens. The sensations of heat abstraction, that is, coolness and cold, can be captured by the rational design of optimized molecules called TRPM8 receptor agonists. The topical application of these molecules alleviates the discomfort of wearing a face mask covering. Several entities were identified by synthesis and experiment as having the ideal properties for achieving this purpose. The preferred embodiments are certain 1-diisopropyl-phosphinoyl-alkanes described as DIPA-1-5, DIPA-1-6, DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds.” The applicant found that topical delivery of DIPA compounds to the facial skin, especially to the surface of the nares (nostrils), alleviates face mask discomfort.

Abstract: The present invention pertains to methods of using certain 1-di-isopropyl-phosphinoylalkanes as described herein (DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds”) for the treatment of ocular discomfort that is caused by eye strain; eye surgery; an airborne irritant or pollutant that interacts with the eye surface; heat discomfort; extended wear of contact lenses; excessive exposure to the sun; asthenopia; conjunctivitis; or a dry eye syndrome. The present invention also pertains to pharmaceutical compositions comprising such compounds, and media contain those pharmaceutical compositions.

Abstract: Wearing a face mask or a filtering facepiece respirator, especially in hot weather for more than one hour, causes discomfort. But, in a viral pandemic, a barrier to filter inhaled and exhaled air is necessary to protect against airborne pathogens. The sensations of heat abstraction, that is, coolness and cold, can be captured by the rational design of optimized molecules called TRPM8 receptor agonists. The topical application of these molecules alleviates the discomfort of wearing a face mask covering. Several entities were identified by synthesis and experiment as having the ideal properties for achieving this purpose. The preferred embodiments are certain 1-diisopropyl-phosphinoyl-alkanes described as DIPA-1-5, DIPA-1-6, DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds.” The applicant found that topical delivery of DIPA compounds to the facial skin, especially to the surface of the nares (nostrils), alleviates face mask discomfort.

Abstract: Wearing a face mask or a filtering facepiece respirator, especially in hot weather for more than one hour, causes discomfort. But, in a viral pandemic, a barrier to filter inhaled and exhaled air is necessary to protect against airborne pathogens. The sensations of heat abstraction, that is, coolness and cold, can be captured by the rational design of optimized molecules. The topical application of these molecules alleviates the discomfort of wearing a face mask covering. Several entities were identified by synthesis and experiment as having the ideal properties for achieving this purpose. The preferred embodiments are certain 1-diisopropyl-phosphinoyl-alkanes described as DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds.” The applicant found that topical delivery of DIPA compounds to the facial skin, especially to the surface of the external nares (nostrils), alleviates face mask discomfort.

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 in combination with an intranasal steroid or an intranasal antihistamine immediately relieves nasal discomfort and enhances patient adherence to the use of the nasal medications.

Abstract: Heat abstraction from the body's surfaces causes sensations of cold from the skin, orbit, nose, mouth, throat, upper esophagus, airways, and anogenital surfaces. The detection of heat abstraction at these sites is via TRPM8, a neuronal protein linked to nerve membranes. Chemical agents that act on TRPM8 can also produce sensations of cold, but the surface of the lower gastrointestinal tract (LGIT) does not “feel cold”, yet it contains cells with TRPM8. The pharmacology of TRPM8 in the LGIT is an unexplored subject. Menthol has a relaxant effect on gut smooth muscle, but this action is not via TRPM8. Here, a class of selective TRPM8 agonists, called 1-Dialkyl-phosphinoyl-alkanes (Dapa) were synthesized, and the potency and selectivity on TRP channels were characterized. Certain Dapa molecules were shown to inhibit neural signals in isolated vagus nerve and to exert anti-inflammatory effects in a model of heat-injury.

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 in combination with an intranasal steroid or an intranasal antihistamine immediately relieves nasal discomfort and enhances patient adherence to the use of the nasal medications.

Abstract: Heat abstraction from the body's surfaces causes sensations of cold from the skin, orbit, nose, mouth, throat, upper esophagus, airways, and anogenital surfaces. The detection of heat abstraction at these sites is via TRPM8, a neuronal protein linked to nerve membranes. Chemical agents that act on TRPM8 can also produce sensations of cold, but the surface of the lower gastrointestinal tract (LGIT) does not “feel cold”, yet it contains cells with TRPM8. The pharmacology of TRPM8 in the LGIT is an unexplored subject. Menthol has a relaxant effect on gut smooth muscle, but this action is not via TRPM8. Here, a class of selective TRPM8 agonists, called 1-Dialkyl-phosphinoyl-alkanes (Dapa) were synthesized, and the potency and selectivity on TRP channels were characterized. Certain Dapa molecules were shown to inhibit neural signals in isolated vagus nerve and to exert anti-inflammatory effects in a model of heat-injury.

Abstract: The body has a number of sensitive surfaces that are subject to injury by physical, chemical and biological agents. The results of injury are, for example, signs of inflammation such as redness, swelling, feeling of heat, pain and loss of function, and discomfort such as itching, irritation, burning sensations, and dysesthesia. The nasal membranes, the ocular surface, the lips and gingiva, and the genital surfaces are examples of such sensitive surfaces. Topical agents can be delivered to these surfaces using pre-medicated single unit applicators, such as swabs, wipes, or cotton-tips attached to handles, but for high frequency use, there is an advantage to using a reservoir bottle of medicated solution together with a packet of single applicators. In this invention, an apparatus embodiment for topically delivering a pharmaceutical comprises a specially designed container, together with a package of single applicators.

Abstract: Eye drops are the traditional method for delivering drugs to the ocular surface but this method is considered inefficient and does not work well for soothing agents because sensory discomfort is evoked from the corneal surface by the pulsatile delivery of the agent. By contrast, eye wipes moistened with an evenly dispersed liquid composition of a soothing or cooling agent selectively delivers the active ingredient to receptors in the skin above the eyes, on the edges of the eyelids, and on the conjunctiva and do not evoke eye irritation. The delivered agent is now able to evoke sensations of refreshment and soothing on the ocular surface and to relieve eye discomfort.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-D-Ala-esters compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of reducing skin irritation, itch, and/or pain.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-amino acid esters compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of reducing cough and pharyngeal irritation, itch, and/or pain.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-amino lactone compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of alleviating the discomforts of irritation, itch, and pain in the skin and in the linings of the oral cavity and upper respiratory tract, for example, in methods of treatment of cough.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-amino acid esters compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of reducing cough and pharyngeal irritation, itch, and/or pain.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-amino lactone compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of alleviating the discomforts of irritation, itch, and pain in the skin and in the linings of the oral cavity and upper respiratory tract, for example, in methods of treatment of cough.

Abstract: The present invention pertains generally to the field of ocular treatment, and more specifically to the use of a liquid cooling agent composition comprising a cooling agent for the treatment of (e.g., the alleviation of symptoms of; the amelioration of) eye discomfort. The preferred cooling agent is (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexanecarboxylic acid 2,3-dihydroxy-propyl ester (referred to herein as CPS-030). The liquid cooling agent composition is topically administered to at least a portion of the external surface of the eyelid (preferably the closed eyelid) of the eye to be treated. Preferably, the liquid cooling agent composition is carried on or in a wipe, pad, or towelette, for example, an eye wipe.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-amino acid ester and N-alkylcarbonyl-amino lactone compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of alleviating the discomforts of irritation, itch, and pain in the skin and in the linings of the oral cavity and upper respiratory tract, for example, in methods of treatment of cough and/or asthma.

Abstract: The present invention generally relates to refreshing, soothing, and cooling compounds that affect sensory processes. More particularly, the present invention pertains to certain N-alkylcarbonyl-D-Ala-esters compounds as described herein; compositions and articles comprising such compounds; and methods of treatment, for example, methods of reducing skin irritation, itch, and/or pain.