Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K33/00—Medicinal preparations containing inorganic active ingredients
  • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
  • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
  • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
  • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
  • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7007—Drug-containing films, membranes or sheets
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
  • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• gag reflex The pharyngeal reflex, gag reflex, or laryngeal spasm
• the gag reflux is the end result of a reflex arc comprised of a series of physiological steps that occur in rapid succession to produce the reflex.
• a sensory receptor receives an environmental stimulus, such as an object reaching nerves in the back of the throat, which in turn sends a message via an afferent nerve to the central nervous system (CNS).
• CNS central nervous system
• the CNS receives this message and sends an appropriate response via an efferent nerve to effector cells located in the same area as the initial stimulus, which carry out an appropriate physical response (i.e., a gag reflex).
• the gag reflex is a form of coughing, which, along with other aerodigestive reflexes such as reflexive pharyngeal swallowing, prevents objects in the oral cavity from entering the throat except as part of normal swallowing. As such, the gag reflex is an important physiological response to prevent choking.
• Gag reflex sensitivity can vary widely. For example, some people lack a gag reflex, while others experience a hypersensitive gag reflex. This hypersensitivity can lead to issues in various situations, such as when attempting to swallow medications in pill form, swallowing large bites of food, or even when undergoing oral examination, such as when visiting the dentist. In many instances, a hypersensitive gag reflex results in choking, retching and vomiting.
• U.S. Pat. No. 4,634,591 provides a method of treating or inhibiting gagging or retching in a patient by sublingual application of a soluble tablet comprising electrolytes in the same proportion as they are found in the blood stream and/or gastric secretions of the patient. These electrolytes may include sodium, potassium, calcium, magnesium, chloride, bicarbonate, and phosphate.
• the method calls for placing the tablet under the patient's tongue for 2-5 minutes so that a substantial portion of the tablet may be dissolved and absorbed into the patient's system. Where the patient is a severe gagger, it may be necessary to follow with a second tablet in order to obtain the necessary result. Therefore, although the formulations of Westerman are reported to suppress and stop the gag reflex, these methods are inefficient, tedious and may be incompatible for use with children and other patients who experience difficulty with sublingual administration.
• the present invention meets and overcomes these challenges.
• a composition for controlling a gag reflex in the patient comprising sodium chloride and a souring agent.
• the composition comprises sodium chloride and a souring agent in a ratio of 1:4.
• the composition comprises a powder form.
• the composition comprises a form selected from the group of a powder, a liquid, a dissolving film, and an oral disintegrating tablet.
• a composition is provided comprising citric acid as a souring agent.
• a method for controlling a gag reflex in a patient comprising steps for: i) preparing a composition according to the present invention; and ii) administering the composition to the tongue of a patient.
• a method of the invention further comprises a step for delaying an oral procedure after the step of administrating the composition to the tongue of the patient.
• a step for delaying the oral procedure comprises a delay of less than 20 seconds.
• a therapeutic effect of a composition of the present invention glass greater than 12 hours.
• the present invention relates to compositions and methods for controlling a gag reflex in a patient.
• the present invention relates to oral compositions that are applied to the patient's tongue just prior to accessing the oral cavity of the patient, especially in a manner which may induce a gag reflex.
• the compositions of the present invention are rapid-acting oral formulations comprising a mixture of sodium chloride and a souring agent.
• one potential mechanism by which the present invention operates is the combination of i) increased saliva production resulting from the sodium chloride, and ii) stimulation of the swallowing reflex resulting from the souring agent, wherein these combined physiological reactions mask or otherwise suppress the patient's gag reflex.
• a composition in accordance with the present invention comprises sodium chloride.
• Sodium chloride may be used in any suitable form, including but not limited to powder form, crystalline form, liquid suspension form, and slurry form.
• a composition of the present invention comprises sodium chloride in the form of table salt.
• a composition in accordance with the present invention further comprises a souring agent.
• a souring agent is understood to describe any compound, ingredient, chemical or other substance that imparts a sour or acidic taste to a patient when placed on the patient's tongue.
• Souring agents may be used in suitable form, including but not limited to powder form, liquid form, crystalline form, liquid suspension form, and slurry form.
• Non-limiting examples of souring agents include citric acid, lemon juice, lemon juice powder, lime juice, lime juice powder, amchur, sour plum, sour plum juice, sour plum juice powder, sumac, tamarind, tamarind powder, vinegar, vinegar powder, umeboshi vinegar, umeboshi vinegar powder, verjuice, verjuice powder, and the like.
• a composition comprises a mixture of sodium chloride and two or more souring agents.
• a composition comprises a mixture of sodium chloride and a single souring agent.
• a composition comprising a mixture of a sodium chloride and a souring agent, wherein the ratio of the two components is selected to provide a therapeutic benefit that suppresses a patient's gag reflex.
• a composition is provided comprising a mixture of sodium chloride and a souring agent, wherein the ratio of sodium chloride to souring agent is 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1 or 1:1.
• a composition comprising a mixture of sodium chloride and a souring agent, wherein the ratio of souring agent to sodium chloride is 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1 or 1:1.
• a composition comprising sodium chloride and citric acid.
• sodium chloride is present in the composition in an amount of approximately 90 parts, approximately 80 parts, approximately 70 parts, approximately 60 parts, approximately 50 parts, or less than 50 parts by volume based on 100 parts by volume of the composition. In some embodiments, the sodium chloride is present in the composition in an amount of approximately 80 parts by volume based on 100 parts by volume of the composition.
• citric acid is present in the composition in an amount of approximately 5 parts, approximately 10 parts, approximately 15 parts, approximately 20 parts, approximately 25 parts, approximately 30 parts, approximately 35 parts, approximately 40 parts, approximately 45 parts, approximately 50 parts, or greater than 50 parts by volume based on 100 parts by volume of the composition. In some embodiments, the citric acid is present in the composition in an amount of approximately 20 parts by volume based on 100 parts by volume of the composition.
• the sodium chloride is present in the composition in an amount of approximately 80 parts by volume
• citric acid is present in the composition in an amount of approximately 20 parts by volume based on 100 parts by volume of the composition.
• the composition comprises about 15% by weight, about 20% by weight, about 25% by weight, about 30% by weight, about 35% by weight, about 40% by weight, about 45% by weight, about 50% by weight, or greater than 50% by weight sodium chloride relative to the total weight of the composition. In some embodiments, the composition comprises about 38% by weight sodium chloride relative to the total weight of the composition.
• the composition comprises about 90% by weight, about 85% by weight, about 80% by weight, about 75% by weight, about 70% by weight, about 65% by weight, about 60% by weight, about 55% by weight, about 50% by weight, or less than 50% by weight citric acid relative to the total weight of the composition. In some embodiments, the composition comprises about 62% by weight citric acid relative to the total weight of the composition.
• the composition comprises about 38% by weight sodium chloride and about 62% by weight citric acid relative to the total weight of the composition.
• a composition comprising a dry powder form.
• the composition is an admixture of sodium chloride and a souring agent in a dry powder form according to one or more ratios disclosed herein.
• the composition is an admixture of sodium chloride and citric acid in a dry powder form.
• a dry powder composition is provided by admixing specific volumes and/or weights of sodium chloride and a souring agent to achieve desired ratios of the components in the final composition. Admixing may be accomplished by machine or may be done manually.
• one or more of the composition components is pretreated to achieve a desired physical state of the component prior to admixing the component into the final composition. For example, in some embodiments it is desirable to pretreat one or more of the components to achieve a desired granule size, for example by grinding, pulverizing, and/or filtering the component(s) through a sieve.
• one or more processing steps may be required to produce a powdered form of the souring agent, such as dehydrating or freeze drying a liquid form of the souring agent.
• Some embodiments of the invention may further include additives or other excipients, as discussed below.
• a composition comprising a dissolving film or oral drug strip that rapidly dissolves on the patient's tongue.
• the dissolving film is a polymer comprising sodium chloride and a souring agent, such as, for example, citric acid.
• the dissolving film further comprises one or more excipients selected from the group consisting of strip-forming polymers, plasticizers, sweetening agents, saliva stimulating agents, flavoring agents, coloring agents, stabilizing agents, thickening agents, and other suitable excipients, wherein the excipient is compatible for use in oral pharmaceutical dosage forms.
• a composition comprising an orally disintegrating tablet configured to rapidly dissolve on the patient's tongue.
• an orally disintegrating tablet of the present invention is a loose compression comprising sodium chloride and a souring agent, for example, citric acid.
• an orally disintegrating tablet of the present invention is provided in a single dosage form in a sealed blister pack to protect the tablet from damage, moisture, and oxidation.
• a composition comprising an oral spray, wherein the spray comprises sodium chloride and a souring agent, such as citric acid, in liquid forms, and wherein the oral spray is configured for application to the patient's tongue.
• a souring agent such as citric acid
• a composition comprising an oral paste or ointment comprising sodium chloride and a souring agent, such as citric acid, wherein the oral paste or ointment is configured for application to the patient's tongue.
• a composition comprising a mouthwash comprising sodium chloride and a souring agent, such as citric acid, wherein the mouthwash is configured for application to the patient's tongue by being held in the patient's mouth passively or swilled or swished around the patient's mouth for an effective treatment period.
• an effective treatment period is less than one second, approximately one second, approximately 2 second, approximately 3 seconds, approximately 4 seconds, approximately 5 seconds, approximately 6 seconds, approximately 7 seconds, approximately 8 seconds, approximately 9 seconds, approximately 10 seconds, greater than 10 seconds, or less than 20 seconds.
• an effective dose of a mouthwash of the present invention is 1 ml, approximately 1 ml, approximately 2 ml, approximately 3 ml, approximately 4 ml, approximately 5 ml, approximately 6 ml, approximately 7 ml, approximately 8 ml, approximately 9 ml, approximately 10 ml, from approximately 10 ml to 20 ml, from approximately 10 ml to 30 ml, from approximately 15 ml to 25 ml, or from approximately 15 ml to 20 ml.
• the patient may swallow the mouthwash following treatment.
• the patient is instructed to spit out the mouthwash following treatment.
• a method for preventing or suppressing a gag reflex comprises applying a composition of the present invention to a patient's tongue just prior to accessing the oral cavity of the patient.
• the composition may be applied to the patient's tongue by wetting an applicator that is subsequently contacted with the powdered composition, wherein the wetted state of the applicator causes a therapeutic amount of the powdered composition to adhere to the wetted applicator. The wetted applicator and adhered powdered composition is then applied to the patient's tongue.
• an applicator comprises at least one of a tongue depressor, a cotton swab, a gloved finger, or the patient's ungloved finger. In some embodiments, a measured portion of the powdered composition is applied directly to the patient's tongue.
• the composition is applied to the patient's tongue directly using a suitable applicator.
• a metered dose of the composition may be sprayed directly on the patient's tongue.
• these dosage forms are prepared with therapeutically effective amounts of the composition, wherein these dosage forms are applied directly to the patient's tongue.
• a therapeutically effective dosage of a composition of the present invention comprises less than 0.5 grams sodium chloride and less than 0.12 grams citric acid, in a volume of 0.125 teaspoons or 0.616 ml, less than 0.25 grams sodium chloride and less than 0.06 grams citric acid, in a volume of 0.0625 teaspoons or 0.308 ml, less than 0.125 grams sodium chloride and less than 0.003 grams citric acid, in a volume of 0.03125 teaspoons or 0.154 ml, or less than 0.0625 grams sodium chloride and less than 0.0015 grams citric acid, in a volume of 0.015625 teaspoons or 0.077 ml.
• a method of the present invention comprises a delay between application or administration of the composition to the patient's tongue and accessing the oral cavity of the patient. In some instances the delay is less than 10 seconds, less than 8 seconds, less than 5 seconds, less than 3 seconds, or less than 1 second. In some embodiments, a therapeutic effect of the composition lasts for greater than 30 minutes, greater than 1 hour, greater than 2 hours, greater than 4 hours, greater than 8 hours, greater than 12 hours, greater than 16 hours, greater than 20 hours, or greater than 24 hours.
• An anti-gag composition was prepared by mixing dry ingredients of sodium chloride and citric acid in a ratio of 1:4. Single dosage amounts of the anti-gag composition were prepared and sealed in individual, single-use containers.
• a patient with acute gag sensitivity was treated with an anti-gag composition of the present invention prior to undergoing oral examination as part of dental treatment.
• a tongue depressor was wetted and contacted with the anti-gag composition, thereby adhering a therapeutically effective amount of the anti-gag composition to the wetted tongue depressor.
• the tongue depressor and the therapeutically effective amount of the anti-gag composition was then applied to the top surface of the patient's tongue, whereupon the anti-gag composition dissolved on the patient's tongue.
• Oral examination of the patient commenced within less than 30 seconds of administering the anti-gag composition. The patient was able to undergo oral examination and complete dental treatment without manifesting a gag reflex.
• the active agents of the present invention include and/or may be substituted with any compatible analogs or pharmaceutically acceptable salts thereof, including any stereoisomers, including enantiomeric forms and diastereomeric forms, all of which are contemplated within the scope of this disclosure.
• Individual stereoisomers of the compounds of the disclosure may, for example, be substantially free of other isomers, or may be admixed, for example, as racemates or with all other, or other selected, setereoisomers, as may apply.
• the specific ingredient ratios may be adjusted, as disclosed herein, and as may be desired to meet the specific needs of a patient.
• the inclusion and/or exclusion of various excipients are also contemplated within the scope of this disclosure.

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• 2020
  • 2020-11-20 US US17/100,677 patent/US20210196748A1/en not_active Abandoned
  • 2020-12-11 WO PCT/US2020/064604 patent/WO2021138025A1/en active Application Filing
  • 2020-12-11 CA CA3163259A patent/CA3163259A1/en active Pending
  • 2020-12-11 KR KR1020227025334A patent/KR102671524B1/ko active IP Right Grant
  • 2020-12-11 BR BR112022012998A patent/BR112022012998A2/pt not_active Application Discontinuation
  • 2020-12-11 AU AU2020417185A patent/AU2020417185A1/en active Pending
  • 2020-12-11 EP EP20911237.4A patent/EP4084869A4/en active Pending
  • 2020-12-11 JP JP2022539396A patent/JP7492772B2/ja active Active
• 2021
  • 2021-05-07 US US17/315,164 patent/US11458162B2/en active Active
• 2022
  • 2022-10-03 US US17/937,665 patent/US11813286B2/en active Active
  • 2022-10-03 US US17/937,660 patent/US11701383B2/en active Active
• 2023
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