WO2021245655A1 - Compositions comprenant des cannabinoïdes et des anesthésiques volatils pour inhalation et leurs utilisations antivirales - Google Patents

Compositions comprenant des cannabinoïdes et des anesthésiques volatils pour inhalation et leurs utilisations antivirales Download PDF

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Publication number
WO2021245655A1
WO2021245655A1 PCT/IL2021/050638 IL2021050638W WO2021245655A1 WO 2021245655 A1 WO2021245655 A1 WO 2021245655A1 IL 2021050638 W IL2021050638 W IL 2021050638W WO 2021245655 A1 WO2021245655 A1 WO 2021245655A1
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Prior art keywords
liquid
composition
electronic cigarette
state
cartridge
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PCT/IL2021/050638
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English (en)
Inventor
Miron Hazani
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Roxx Labs Ltd.
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Publication of WO2021245655A1 publication Critical patent/WO2021245655A1/fr

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    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/075—Ethers or acetals
    • A61K31/08—Ethers or acetals acyclic, e.g. paraformaldehyde
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    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
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    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
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    • 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
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    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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    • A24F40/00—Electrically operated smoking devices; Component parts thereof; Manufacture thereof; Maintenance or testing thereof; Charging means specially adapted therefor
    • A24F40/10—Devices using liquid inhalable precursors
    • A—HUMAN NECESSITIES
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    • A24F40/00—Electrically operated smoking devices; Component parts thereof; Manufacture thereof; Maintenance or testing thereof; Charging means specially adapted therefor
    • A24F40/40—Constructional details, e.g. connection of cartridges and battery parts
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    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/0015—Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors
    • A61M2016/0018—Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical
    • A61M2016/0021—Accessories therefor, e.g. sensors, vibrators, negative pressure inhalation detectors electrical with a proportional output signal, e.g. from a thermistor
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    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/0003—Accessories therefor, e.g. sensors, vibrators, negative pressure
    • A61M2016/003—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter
    • A61M2016/0033—Accessories therefor, e.g. sensors, vibrators, negative pressure with a flowmeter electrical
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    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0468—Liquids non-physiological
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    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/02—General characteristics of the apparatus characterised by a particular materials
    • A61M2205/0272—Electro-active or magneto-active materials
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Definitions

  • the present disclosure generally relates to the field of cannabinoid compositions for pulmonary administration, and uses thereof in treating or preventing viral infections, in particular coronaviruses.
  • the cannabinoid compositions contain an inhaled volatile anesthetic and are administered in the form of an aerosol generated by an aerosol generating device.
  • COVID-19 coronavirus disease 2019 (COVID-19). Since then, COVID- 19 disease spread worldwide in more than 150 countries with millions of sick and hundreds of thousands deceased.
  • Current experimental drugs designed to treat COVID- 19 are administered in dosage forms suitable for enteral administration, such as oral, and for intravenous, intramuscular and subcutaneous administrations.
  • An inhalational anesthetic is a chemical compound possessing general anesthetic properties that can be delivered via inhalation. They are typically administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporizer and an anesthetic delivery system.
  • Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.
  • Electronic cigarettes are becoming a popular alternative to tobacco smoking because of the many advantages that they offer.
  • One of the main reasons that they are popular is due to the similar sensation the provide, compared to tobacco smoking with paper cigarettes.
  • E-cigarettes are also used to quit smoking and replace paper cigarettes.
  • electronic cigarettes are electronic aerosol-generating devices, which include a heating unit for vaporizing the composition to be inhaled.
  • Conventional electronic cigarettes are made with a mouth piece assembly, a vaporizer assembly, an electric connecting assembly, and an e-liquid storage assembly.
  • the inclusion of a vaporizer assembly is in contrast with other aerosol-generating devices, such as nebulizers and inhalers, which provide cold aerosols, and do not require heating.
  • e-cigarettes are typically smaller than other aerosol-generating devices, and may provide particularly effective delivery of the aerosol to the lungs.
  • WO 2020/194297 relates to the field of aerosol generation devices, and more particularly to electronic cigarettes configured to generation of aerosols from aqueous formulations of nicotine or cannabis products.
  • PCT/IL2021/050311 discloses aqueous compositions comprising a cannabinoid acid or a salt thereof, processes for the preparation thereof and uses thereof for inhalation.
  • compositions for treatment or prevention of diseases caused by a coronavirus are provided.
  • the compositions of the present invention are useful for treating COVID-19 disease.
  • the compositions of the present invention comprise cannabinoid(s) and an inhaled volatile anesthetic, and are for pulmonary administration.
  • the present composition may be provided in a dosage form suitable for aerosolization.
  • the dosage form may be an electronic aerosol generating device cartridge (e.g. electronic cigarette cartridge) containing the composition, which is adapted for aerosolization from an electronic aerosol generating device.
  • the composition may be for filling an electronic aerosol generating device.
  • the cannabinoid is provided a cannabinoic acid in its deprotonated form, e.g. in an aqueous solution having pH above 8.5, or as a non-aqueous composition comprising the natural cannabinoid(s) (e.g. CBD and/or THC).
  • the inhaled volatile anesthetic is halothane, isoflurane, sevoflurane, and/or desflurane.
  • the dosage form and administration of the current invention are more effective than currently known and experimented therapies, which include mainly oral administration by ingestion or through injection.
  • the current invention further provides methods of treatment of diseases caused by a coronavirus, according to some embodiments.
  • Said methods include administering, via inhalation, to a subject in need thereof a cannabinoid-inhaled volatile anesthetic composition in the form of an aerosol.
  • the administration disclosed herein is carried out using an electronic cigarette.
  • the administration disclosed herein is carried out using an electronic cigarette, as disclosed herein, which is specifically designed to provide aerosol having droplet at a diameter, which is effective in reaching the lungs and treating diseases caused by a coronavirus, such as COVID-19 disease.
  • the type of electronic cigarette for use in the methods of the invention includes a heating element.
  • an “aerosol”, as used herein, is a suspension of fine solid particles or liquid droplets in air or another gas.
  • a method for treating or preventing a disease caused by a coronavirus comprising administering, via inhalation, to a subject in need thereof a pulmonary composition comprising at least one cannabinoid and an inhaled volatile anesthetic.
  • the coronavirus is a human coronavirus.
  • the human coronavirus is selected from MERS-CoV, SARS- CoV and SARS-CoV-2.
  • the disease is COVID-19.
  • the composition is a non-aqueous solution, suspension or emulsion comprising at least one cannabinoid.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is not charged.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is selected from cannabidiol (CBD) and tetrahydrocannabinol (THC).
  • the composition is a non-aqueous solution, suspension or emulsion comprising at least one cannabinoid, selected from cannabidiol (CBD) and tetrahydrocannabinol (THC), and the inhaled volatile anesthetic.
  • the at least one cannabinoid in the non-aqueous solution, suspension or emulsion is at a concentration in the range of 5% to 60% w/w.
  • the non-aqueous solution, suspension or emulsion comprises glycerin, propylene glycol, or both.
  • the at least one cannabinoid is at a concentration in the range of 5% to 60%, w/w and the composition comprises glycerin, propylene glycol, or both.
  • the composition is an aqueous solution, suspension or emulsion comprising at least one cannabinoic acid or a salt thereof.
  • the at least one cannabinoic acid or a salt thereof is selected from the group consisting of: tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), salts thereof and combinations thereof.
  • the cannabinoid composition is an aqueous solution, suspension or emulsion comprising at least one cannabinoic acid or a salt thereof, selected from the group consisting of: tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), salts thereof and combinations thereof, and the inhaled volatile anesthetic.
  • THCA tetrahydrocannabinolic acid
  • CBDA cannabidiolic acid
  • the at least one cannabinoic acid in the aqueous solution, suspension or emulsion is at a concentration in the range of 2% to 6%, w/w. According to some embodiments, the aqueous solution, suspension or emulsion is at a concentration has a pH of at least 8.5. According to some embodiments, the at least one cannabinoic acid is at a concentration in the range of 2% to 6%, w/w, and wherein the composition has a pH of at least 8.5.
  • the inhaled volatile anesthetic is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • halothane isoflurane
  • sevoflurane isoflurane
  • desflurane is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • the composition further comprises at least one additive selected from the group consisting of a propellant, an anti-coughing agent and a flavorant.
  • the method comprises the steps of:
  • the aerosol generating device comprises: an evaporation heater configured to generate heat and to evaporate a liquid from a surface thereof; a processing unit; a first trigger configured to generate a first trigger activation signal; a liquid deposition mechanism comprising a liquid drawing element and a liquid container; and an outlet.
  • the aerosol generating device is an electronic cigarette comprising: a cartridge having a first end and a second end, the cartridge comprising: an evaporation heater configured to generate heat and to evaporate a liquid comprising the cannabinoid composition from a surface thereof; a liquid drawing element; a liquid container; and an outlet; and an actuator having a first end and a second end, the actuator comprising a processing unit, wherein the first end of the actuator is connectable with the second end of the cartridge, wherein the electronic cigarette further comprises a first trigger configured to generate a first trigger activation signal, and a liquid deposition mechanism comprising the liquid drawing element and the liquid container, wherein the liquid drawing element is spaced apart from the evaporation heater in at least a first state of the electronic cigarette, and wherein the liquid deposition mechanism is configured to transfer a discrete volume of the cannabinoid composition from the liquid drawing element to the evaporation heater in a second state of the electronic cigarette, wherein the liquid drawing element is in contact
  • the liquid deposition mechanism further comprises a biasing element, configured to trigger a dislocation of at least a portion of the liquid drawing element between a first position in the first state of the electronic cigarette and a second position in the second state of the electronic cigarette, wherein the liquid drawing element is spaced apart from the evaporation heater in the first position, and wherein the liquid drawing element is in contact with the evaporation heater in the second position.
  • a biasing element configured to trigger a dislocation of at least a portion of the liquid drawing element between a first position in the first state of the electronic cigarette and a second position in the second state of the electronic cigarette, wherein the liquid drawing element is spaced apart from the evaporation heater in the first position, and wherein the liquid drawing element is in contact with the evaporation heater in the second position.
  • the biasing element comprises a solenoid actuator, a rod and a solenoid plunger head, wherein the rod has a first end and a second end, wherein the second end is connected to the solenoid actuator, and the first end is connected to the solenoid plunger head, wherein the solenoid actuator is configured to dislocate the solenoid plunger head between a first position and a second position, wherein in the second state of the electronic cigarette, the solenoid plunger head is in the second position thereof and is pressing the portion of the liquid drawing element against the evaporation heater, and in the first state of the electronic cigarette, the solenoid plunger head is in the first position thereof and the liquid drawing element is spaced apart from the evaporation heater.
  • the liquid deposition mechanism further comprises a spraying mechanism, located within the cartridge and configured to create a spray from the pulmonary composition, wherein the spraying mechanism is in contact with the liquid drawing element and spaced apart from the evaporation heater in both the first state of the electronic cigarette and the second state of the electronic cigarette.
  • the liquid deposition mechanism further comprises a liquid deposition mechanism housing
  • the spraying mechanism comprises a piezo disc configured to create the spray from the pulmonary composition, wherein the piezo disc is in contact with the liquid drawing element and spaced apart from the evaporation heater in both the first state of the electronic cigarette and the second state of the electronic cigarette, wherein the piezo disc is accommodated within the liquid deposition mechanism housing.
  • the droplets of the aerosol delivered by the aerosol generating device are having a mass median aerodynamic diameter (MMAD) of no more than 5 microns.
  • MMAD mass median aerodynamic diameter
  • a cannabinoid composition provided in a dosage form suitable for aerosolization using an aerosol generating device, for use in treatment or prevention of a disease caused by a coronavirus, wherein the composition comprises cannabinoid and an inhaled volatile anesthetic.
  • the composition is a non-aqueous solution, suspension or emulsion comprising at least one cannabinoid.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is not charged.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is selected from cannabidiol (CBD) and tetrahydrocannabinol (THC).
  • the composition is a non-aqueous solution, suspension or emulsion comprising at least one cannabinoid, selected from cannabidiol (CBD) and tetrahydrocannabinol (THC), and the inhaled volatile anesthetic.
  • the at least one cannabinoid in the non-aqueous solution, suspension or emulsion is at a concentration in the range of 5% to 60% w/w.
  • the non-aqueous solution, suspension or emulsion comprises glycerin, propylene glycol, or both.
  • the at least one cannabinoid is at a concentration in the range of 5% to 60%, w/w and the composition comprises glycerin, propylene glycol, or both.
  • the composition is an aqueous solution, suspension or emulsion comprising at least one cannabinoic acid or a salt thereof.
  • the at least one cannabinoic acid or a salt thereof is selected from the group consisting of: tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), salts thereof and combinations thereof.
  • the cannabinoid composition is an aqueous solution, suspension or emulsion comprising at least one cannabinoic acid or a salt thereof, selected from the group consisting of: tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), salts thereof and combinations thereof, and the inhaled volatile anesthetic.
  • the at least one cannabinoic acid in the aqueous solution, suspension or emulsion is at a concentration in the range of 2% to 6%, w/w.
  • the aqueous solution, suspension or emulsion is at a concentration has a pH of at least 8.5.
  • the at least one cannabinoic acid is at a concentration in the range of 2% to 6%, w/w, and wherein the composition has a pH of at least 8.5.
  • the inhaled volatile anesthetic is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane. Each possibility represents a separate embodiment of the invention.
  • the composition further comprises at least one additive selected from the group consisting of a propellant, an anti-coughing agent and a flavorant.
  • the coronavirus is a human coronavirus.
  • the human coronavirus is selected from MERS-CoV, SARS- CoV and SARS-CoV-2.
  • the disease is COVID-19.
  • an aerosol generating device cartridge comprising a liquid container, wherein the liquid container contains the composition according to the present invention.
  • the electronic aerosol generating device cartridge further comprises: an evaporation heater configured to generate heat and to evaporate liquid compositions from a surface thereof, and a liquid deposition mechanism configured to transfer portions of the cannabinoid composition from the liquid container to the evaporation heater.
  • the evaporation heater is flat and wherein the evaporation heater is porous or the evaporation heater comprises capillaries or grooves therein.
  • the electronic aerosol generating device cartridge has a first state, in which the liquid deposition mechanism prevents fluid communication between the liquid container and the evaporation heater, and a second state, in which the liquid deposition mechanism allows fluid communication between the liquid container and the evaporation heater, wherein the electronic aerosol generating device cartridge is configured to intermittently transition between the first state and the second state.
  • the aerosol generating device is an electronic cigarette cartridge having a first end and a second end, the cartridge comprising: an evaporation heater configured to generate heat and to evaporate a liquid from a surface thereof; a liquid deposition mechanism comprising a liquid drawing element and the liquid container; wherein the liquid drawing element is spaced apart from the evaporation heater in at least a first state of the electronic cigarette cartridge, and wherein the liquid deposition mechanism is configured to transfer a discrete volume of said composition from the liquid drawing element to the evaporation heater in a second state of the electronic cigarette cartridge, wherein the liquid drawing element is in contact with the liquid container in both the first state of the electronic cigarette cartridge and the second state of the electronic cigarette cartridge.
  • the evaporation heater is flat and comprises a first flat surface facing the outlet and a second flat surface facing the fluid deposition mechanism, and wherein the liquid deposition mechanism is configured to transfer a discrete volume of the composition from the liquid drawing element to the second flat surface of the evaporation heater in the second state of the electronic cigarette cartridge.
  • the evaporation heater is at least partially permeable to the composition, and configured to receive the discrete volume of composition from the liquid drawing element to the second flat surface thereof, and to evaporate the composition through the first flat surface thereof in the second state of the electronic cigarette cartridge, such that the evaporated composition is released through the outlet.
  • the liquid deposition mechanism further comprises a biasing element, configured to trigger a dislocation of at least a portion of the liquid drawing element between a first position in the first state of the electronic cigarette a cartridge and a second position in the second state of the electronic cigarette, wherein the liquid drawing element is spaced apart from the evaporation heater in the first position, and wherein the liquid drawing element is in contact with the evaporation heater in the second position.
  • a biasing element configured to trigger a dislocation of at least a portion of the liquid drawing element between a first position in the first state of the electronic cigarette a cartridge and a second position in the second state of the electronic cigarette, wherein the liquid drawing element is spaced apart from the evaporation heater in the first position, and wherein the liquid drawing element is in contact with the evaporation heater in the second position.
  • the biasing element is positioned between the liquid drawing element and the second end of the actuator, and is configured to dislocate the portion of the liquid drawing element from the first position in the first state of the electronic cigarette cartridge in the direction of the first end of the cartridge, towards the second position in the second state of the electronic cigarette cartridge, and further configured to trigger dislocation of the liquid drawing element from the second position in the second state of the electronic cigarette cartridge in the direction of the second end of the actuator, towards the first position in the first state of the electronic cigarette cartridge.
  • the biasing element comprises a solenoid actuator, a rod and a solenoid plunger head, wherein the rod has a first end and a second end, wherein the second end is connected to the solenoid actuator, and the first end is connected to the solenoid plunger head, wherein the solenoid actuator is configured to dislocate the solenoid plunger head between a first position and a second position, wherein in the second state of the electronic cigarette cartridge, the solenoid plunger head is in the second position thereof and is pressing the portion of the liquid drawing element against the evaporation heater, and in the first state of the electronic cigarette, the solenoid plunger head is in the first position thereof and the liquid drawing element is spaced apart from the evaporation heater.
  • the liquid deposition mechanism further comprises a spraying mechanism, located within the cartridge and configured to create a spray from the composition, wherein the spraying mechanism is in contact with the liquid drawing element and spaced apart from the evaporation heater in both the first state of the electronic cigarette cartridge and the second state of the electronic cigarette cartridge.
  • the spraying mechanism is located between the liquid drawing element and the evaporation heater, wherein in the first state of the electronic cigarette cartridge the spraying mechanism does not create a spray, and wherein in the second state of the electronic cigarette cartridge, the spray is sprayed from the spraying mechanism in the direction of the first end of the actuator and contacts the evaporation heater.
  • the liquid deposition mechanism further comprises a liquid deposition mechanism housing
  • the spraying mechanism comprises a piezo disc configured to create the spray from the composition, wherein the piezo disc is in contact with the liquid drawing element and spaced apart from the evaporation heater in both the first state of the electronic cigarette cartridge and the second state of the electronic cigarette cartridge, wherein the piezo disc is accommodated within the liquid deposition mechanism housing.
  • an aerosol composition comprising 75-99% w/w water, 1-6% w/w least one cannabinoid and 0.02-2% inhaled volatile anesthetic, wherein the aerosol comprises droplets having a mass median aerodynamic diameter (MMAD) of no more than 5 microns.
  • the at least one cannabinoid is selected from cannabidiol (CBD) and tetrahydrocannabinol (THC), and the inhaled volatile anesthetic is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • an aerosol composition comprising 40-95% w/w non-aqueous solvent or diluent, 5-60% w/w least one cannabinoid and 0.02-2% inhaled volatile anesthetic, wherein the aerosol comprises droplets having a mass median aerodynamic diameter (MMAD) of no more than 5 microns.
  • MMAD mass median aerodynamic diameter
  • the non-aqueous solvent or diluent comprises glycerin, propylene glycol, or both.
  • the at least one cannabinoid is selected from cannabidiol (CBD) and tetrahydrocannabinol (THC), and the inhaled volatile anesthetic is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • the inhaled volatile anesthetic is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • the aerosol composition for use in the treatment or prevention of a disease caused by a coronavirus.
  • the aerosol composition comprises the same ingredients and amounts thereof as in any one of the cannabinoid compositions disclosed herein.
  • Certain embodiments of the present disclosure may include some, all, or none of the above advantages.
  • One or more technical advantages may be readily apparent to those skilled in the art from the figures, descriptions and claims included herein.
  • specific advantages have been enumerated above, various embodiments may include all, some or none of the enumerated advantages.
  • Figure 1 constitutes a schematic view of an electronic cigarette comprising a cartridge and an actuator, when connected, according to some embodiments.
  • Figure 2 constitutes a schematic view of an electronic cigarette comprising a cartridge and an actuator, when separated, according to some embodiments.
  • Figures 3A and 3B constitute schematic views of an electronic cigarette comprising a cartridge and an actuator, when connected, in a first state of the electronic cigarette ( Figure 3A) and, in a second state of the electronic cigarette ( Figure 3B).
  • Figure 4 constitutes a schematic view of an electronic cigarette comprising a cartridge and an actuator, when connected, according to some embodiments.
  • Figure 5 constitutes a schematic view of an electronic cigarette comprising a cartridge and an actuator, when separated, according to some embodiments.
  • compositions for treating or preventing a disease caused by a coronavirus are specifically effective in the treatment of COVID-19 disease caused by a human coronavirus, which is a rapidly spreading pandemic nowadays with millions of sick and hundreds of thousands diseased globally.
  • the delivery is preferably conducted by an electronic aerosol generating device. More preferably, the delivery is preferably conducted by an electronic aerosol generating device as disclosed herein, which is configured to provide aerosols having droplet profile, which is specifically suitable for treatment of COVID-19 by pulmonary medicament delivery.
  • the treatment provided by the current invention is effective, even with compositions for inhalation comprising cannabinoid(s) and inhaled volatile anesthetic(s), which are not considered anti-viral.
  • cannabinoid includes all major and minor cannnabinoids found in natural cannabis and hemp material that can be isolated from a natural source or reproduced by synthetic means. This includes delta-9-Tetrahydrocannabinol (THC), delta-9-Tetrahydrocannabinolic acid (THCA), delta-8-Tetrahydrocannabinol, Cannabidiol (CBD), Cannabidiolic acid (CBDA), Cannabinol (CBN), Cannabinolic acid (CBNA), tetrahydrocannabinovarin (THCV), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerolic acid (CBGA) and cannabichromene (CBC).
  • THC delta-9-Tetrahydrocannabinol
  • THCA delta-9-Tetrahydrocannabinolic acid
  • THCA delta-8-Tetrahydrocannabinol
  • CBD Canna
  • domain A of coronavirus S glycoproteins mediates attachment to oligosaccharide receptors, such as for HCoV-OC43 and BCoV, which interact with 9-O-Ac-Sia, or MERS-CoV, which binds to a2,3-linked (and to a lesser extent to a2,6-linked) sialic acids, with sulfated sialyl-Lewis X being the preferred binder.
  • oligosaccharide receptors such as for HCoV-OC43 and BCoV, which interact with 9-O-Ac-Sia, or MERS-CoV, which binds to a2,3-linked (and to a lesser extent to a2,6-linked) sialic acids, with sulfated sialyl-Lewis X being the preferred binder.
  • key saccharide-binding residues locate to the viral membrane distal side of the BCoV b-sandwich.
  • the receptor-interacting site is conserved in all coronavirus S glycoproteins known to attach to 9-O-Ac-sialoglycans and shares architectural similarity with the ligandbinding pockets of coronavirus HEs and influenza virus C/D HEF glycoproteins, thus highlighting common structural principles of recognition.
  • First stage of interaction involves electrostatic binding to a negatively charged group.
  • cannabinoids in the present cannabinoid composition application can serve as competitive inhibitors which bind through electrostatic or hydrophobic interactions.
  • inhaled volatile anesthetics such as halothane, isoflurane, sevoflurane, and desflurane
  • inhaled volatile anesthetics are known to be potent bronchodilators, and have been used for several decades as potentially life-saving therapy for the treatment of severe, refractory exacerbation of asthma.
  • the inhaled volatile anesthetics bronchodilatory site of action is the upper airways where the smooth muscles and receptors are located.
  • volatile anesthetics with bronchdilatory action should be given to the upper airways to minimize their anesthetic effect.
  • a pulmonary cannabinoid composition provided in a dosage form suitable for aerosolization using an aerosol generating device, for use in treatment or prevention of a disease caused by a coronavirus, wherein the composition comprises cannabinoid and an inhaled volatile anesthetic.
  • compositions for inhalation are provided.
  • compositions of the present invention are provided in a dosage form suitable for aerosolization using an electronic aerosol generating device, for use in treatment of a disease caused by a coronavirus, according to some embodiments.
  • the compositions of the present invention comprise at least one cannabinoid and an inhaled volatile anesthetic, according to some embodiments.
  • cannabinoid-inhaled volatile anesthetic compositions dedicated solely for the treatment or prevention of coronavirus related diseases
  • the present invention is also directed to liquid compositions per se, e.g. to compositions for inhalation, which are not limited to a specific treatment.
  • a liquid composition comprising at least one cannabinoid and an inhaled volatile anesthetic.
  • the liquid composition is a pulmonary composition.
  • the composition is provided in a dosage form suitable for aerosolization.
  • the composition is provided in a dosage form suitable for aerosolization using an aerosol generating device.
  • the composition is provided in a dosage form suitable for aerosolization using an electronic aerosol generating device.
  • compositions may refer to any of the present compositions - either the compositions for use or the compositions provided per se.
  • dosage forms which are “suitable for aerosolization using an aerosol generating device” means dosage form, which comprise compositions which are suitable or approve for aerosolization and inhalation, and are in a form intended for aerosolization ⁇
  • dosage forms, which are typically intended for aerosolization include, but not limited to, electronic cigarette cartridges comprising inhaled compositions, vaporizer cartridges comprising inhaled compositions, and filling compositions for such devices.
  • the composition is a solution.
  • solution refers to a homogeneous liquid dosage form that contains one or more chemical substances dissolved in a solvent or in a mixture of mutually miscible solvents.
  • the composition is a clear solution.
  • the term “clear solution” refers to essentially transparent solutions devoid of particles above 100 nm.
  • the term “clear solution” refers to essentially transparent solutions devoid of particles above 50 nm.
  • the term “clear solution” refers to essentially transparent solutions devoid of particles above 40 nm.
  • compositions that does not include, contain or comprise a particular compound or particles e.g. said composition comprises less than 0.1 %, less than 0.01 %, or less than 0.001 % of the such compounds or particles.
  • the composition is a suspension.
  • suspension refers to a heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation. The particles may be visible to the naked eye, usually must be larger than one micrometer.
  • a suspension is a heterogeneous mixture in which the solute particles do not dissolve, but get suspended throughout the bulk of the solvent, left floating around freely in the medium.
  • the internal phase (solid) is dispersed throughout the external phase (fluid) through mechanical agitation, e.g. with the use of certain excipients or suspending agents.
  • the composition is an emulsion.
  • emulsion refers to a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation.
  • one liquid the dispersed phase
  • the continuous phase the liquid that is dispersed in the other (the continuous phase).
  • Two liquids can form different types of emulsions.
  • oil and water can form, first, an oil-in-water emulsion, in which the oil is the dispersed phase, and water is the continuous phase. Second, they can form a water-in-oil emulsion, in which water is the dispersed phase and oil is the continuous phase.
  • emulsions are also possible, including a “water-in-oil-in-water” emulsion and an “oil-in-water-in-oil” emulsion.
  • cannabinoid compositions are oily, so that they may form emulsions with either water or with polar organic polyols, e.g. vegetable glycerin, propylene glycol and mixtures thereof.
  • the present pulmonary composition comprises at least one inhaled volatile anesthetic. According to some embodiments, the composition comprises at least two inhaled volatile anesthetics.
  • inhaled volatile anesthetic is interchangeable with “inhalational anesthetic” and refers to a chemical compound possessing general anesthetic properties that can be delivered via inhalation. They are typically administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporizer and an anesthetic delivery system.
  • Non-limiting examples of inhaled volatile anesthetics include: desflurane, isoflurane, nitrous oxide, sevoflurane, xenon, acetylene, chloroethane (ethyl chloride), chloroform, cryofluorane, cyclopropane, diethyl ether, divinyl ether, enflurane, ethylene, fluroxene, halothane, methoxyflurane, methoxypropane, trichloroethylene, aliflurane, halopropane, norflurane, roflurane, synthane, teflurane.
  • the inhaled volatile anesthetic is selected from the group consisting of: desflurane, isoflurane, nitrous oxide, sevoflurane, xenon, acetylene, chloroethane (ethyl chloride), chloroform, cryofluorane, cyclopropane, diethyl ether, divinyl ether, enflurane, ethylene, fluroxene, halothane, methoxyflurane, methoxypropane, trichloroethylene, aliflurane, halopropane, norflurane, roflurane, synthane, teflurane and combinations thereof.
  • desflurane isoflurane
  • nitrous oxide sevoflurane
  • xenon acetylene
  • chloroethane ethyl chloride
  • chloroform cryofluorane
  • cryopropane cyclopropane
  • diethyl ether
  • the inhaled volatile anesthetic is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • the inhaled volatile anesthetic is halothane. It is to be understood by the skilled in the art that halothane refers to the compound l,l,l-trifluoro-2-bromo-2-chloroethane.
  • the inhaled volatile anesthetic is isoflurane. It is to be understood by the skilled in the art that isoflurane refers to the compound l-chloro-2,2,2-trifluoroethyl difluoromethyl ether.
  • the inhaled volatile anesthetic is sevoflurane. It is to be understood by the skilled in the art that sevoflurane refers to the compound l,l,l,3,3,3-hexafluoro-2-(fluoromethoxy)propane.
  • the inhaled volatile anesthetic is desflurane. It is to be understood by the skilled in the art that desflurane refers to the compound 2-(difluoromethoxy)-l,l,l,2- tetrafluoroethane .
  • halothane refers to the compound 1,1,1 -trifluoro-2-bromo-2-chloroethane.
  • the inhaled volatile anesthetic is a volatile compound.
  • the inhaled volatile anesthetic has boiling point below 300°C, below 250°C or below 200°C. Each possibility represents a separate embodiment of the invention.
  • the inhaled volatile anesthetic is at a concentration in the range of 0.02% to 2%, w/w.
  • the concentration of the inhaled volatile anesthetic in the composition is in the range of 0.2 to 2 gr/L.
  • the composition comprises pharmaceutically active ingredients consisting essentially of and the cannabinoid and the inhaled volatile anesthetic.
  • the pharmaceutical composition comprises cannabinoid and the inhaled volatile anesthetic as the sole active ingredients.
  • the pulmonary compositions of the present invention are suitable for administration by inhalation as an aerosol created upon aerosolization of the composition by an electronic aerosol generating device, according to some embodiments.
  • an electronic aerosol generating device configured to create aerosols having droplets having a specific diameter.
  • droplets having the diameter profile as provided by the electronic aerosol generating device disclosed herein are highly effective in treating COVID-19 with a cannabinoid-based composition.
  • the composition is a non-aqueous solution, suspension or emulsion comprising at least one cannabinoid.
  • non-aqueous as used herein with reference to different compositions (e.g. in the form of solution, suspension or emulsion) is intended to mean that the composition does not include water as a solvent. It is not intended to mean, however, that the non-aqueous compositions are devoid from water, as some water may be, intentionally, or unintentionally, present therein. According to some embodiments, the non-aqueous solution, suspension or emulsion comprises less than 20% w/w, less than 15% w/w, less than 10% w/w, less than 7% w/w, less than 5% w/w, less than 2% w/w or less than 1% w/w water. Each possibility represents a separate embodiment of the present invention.
  • the composition is a non-aqueous solution.
  • the composition is a non-aqueous suspension.
  • the composition is a non-aqueous emulsion.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is not charged.
  • simple cannabinoids such as CBD and THC are not prone to ionization in standard conditions.
  • these compounds are aromatic alcohols, and thus may be deprotonated under severe conditions, such conditions are usually not feasible for compositions to be provided to human subjects.
  • CBD, THC, CBN and the like do not bear positive or negative charge.
  • Cannabinoic acids such as CBDA and THCA, however, are carboxylic acid, which are prone to deprotonation under basic pH conditions. Such deprotonations ionizes the molecules to form the respective salts, which are negatively charged. Nevertheless, cannabinoic acids in moderate pH conditions are in the acid (i.e. COOH) form, and are thus not considered charged.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is selected from cannabidiol (CBD), tetrahydrocannabinol (THC) or both.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • the cannabinoid in the non-aqueous solution is cannabidiol (CBD)
  • the cannabinoid in the non-aqueous solution is tetrahydrocannabinol (THC).
  • the composition is a non-aqueous solution, suspension or emulsion comprising at least one cannabinoid, selected from cannabidiol (CBD) and tetrahydrocannabinol (THC), and the inhaled volatile anesthetic.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • the at least one cannabinoid in the non-aqueous solution, suspension or emulsion is at a concentration in the range of 5% to 60% w/w. According to some embodiments, the at least one cannabinoid in the non-aqueous solution, suspension or emulsion is at a concentration in the range of 10% to 50% w/w.
  • the at least one cannabinoid in the non-aqueous solution, suspension or emulsion is at a concentration of at least 3% w/w, at least 5% w/w, at least 7% w/w, at least 10% w/w, at least 12% w/w, at least 15% w/w, at least 20% w/w, at least 25% w/w, at least 30% w/w, at least 35% w/w, or at least 40% w/w.
  • Each possibility represents a separate embodiment of the present invention.
  • the at least one cannabinoid in the non-aqueous solution, suspension or emulsion is at a concentration of no more than 80% w/w, no more than 70% w/w, no more than 65% w/w, no more than 60% w/w, no more than 55% w/w, no more than 50% w/w, no more than 45% w/w or no more than 40% w/w.
  • concentration of no more than 80% w/w, no more than 70% w/w, no more than 65% w/w, no more than 60% w/w, no more than 55% w/w, no more than 50% w/w, no more than 45% w/w or no more than 40% w/w.
  • the composition is a liquid or semi-liquid composition, wherein the liquid medium comprises a non-aqueous solvent.
  • the composition is a non-aqueous solution, suspension or emulsion, wherein the liquid medium comprises a non-aqueous solvent.
  • the non-aqueous solvent is a polyol.
  • the polyol is selected from glycerol, propylene glycol, or both.
  • the non-aqueous solvent comprises glycerol.
  • the non-aqueous solvent is glycerol.
  • the non-aqueous solvent comprises propylene glycol.
  • the non-aqueous solvent is propylene glycol.
  • the non-aqueous solvent comprises glycerol or propylene glycol.
  • the non-aqueous solvent comprises glycerol and propylene glycol.
  • the non-aqueous solvent comprises a polyol combination of propylene glycol and vegetable glycerin.
  • the polyol combination comprises 20 to 50% propylene glycol and 50 to 80% vegetable glycerin.
  • the polyol combination comprises 25 to 35% propylene glycol and 65 to 75% vegetable glycerin.
  • the non-aqueous solution, suspension or emulsion comprises glycerin, propylene glycol, or both.
  • the non-aqueous solvent in the non-aqueous solution, suspension or emulsion is at a concentration in the range of 40% to 95% w/w. According to some embodiments, the at non-aqueous solvent in the non-aqueous solution, suspension or emulsion is at a concentration in the range of 50% to 90% w/w.
  • the non-aqueous solvent in the non-aqueous solution, suspension or emulsion is at a concentration of at least 30% w/w, at least 35% w/w, at least 40% w/w, at least 45% w/w, at least 50% w/w, at least 60% w/w, at least 65% w/w, at least 70% w/w, at least 75% w/w, at least 80% w/w, at least 85% w/w, at least 90%, at least 95% w/w, or at least 97% w/w.
  • Each possibility represents a separate embodiment of the present invention.
  • the non- aqueous solvent in the non-aqueous solution, suspension or emulsion is at a concentration of no more than 97% w/w, no more than 95% w/w, no more than 90% w/w or no more than 85% w/w.
  • the cannabinoid composition comprises at least one neutral cannabinoid at a concentration in the range of 5% to 60%, an inhaled volatile anesthetic, selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane, at a concentration in the range of 0.02% to 2%, w/w and glycerin, propylene glycol, or both at a concentration in the range of 40% to 95%.
  • an inhaled volatile anesthetic selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane, at a concentration in the range of 0.02% to 2%, w/w and glycerin, propylene glycol, or both at a concentration in the range of 40% to 95%.
  • the composition is an aqueous solution, suspension or emulsion comprising at least one cannabinoid.
  • aqueous as used herein with reference to different compositions (e.g. in the form of solution, suspension or emulsion) is intended to mean that the composition includes water as a solvent.
  • the aqueous cannabinoid composition is in liquid form.
  • the cannabinoid composition comprises at least 40% w/w water.
  • the cannabinoid composition comprises at least 50% w/w water.
  • the cannabinoid composition comprises at least 60% w/w water.
  • the cannabinoid composition comprises at least 70% w/w water.
  • the cannabinoid composition comprises at least 75% w/w water.
  • the cannabinoid composition comprises at least 80% w/w water.
  • the cannabinoid composition comprises at least 85% w/w water.
  • the cannabinoid composition comprises at least 90% w/w water. It is to be understood that the phrase "cannabinoid composition comprises at least 90% w/w water" means that each gram of the total composition includes at least 900 milligrams of water and at most 100 milligrams of materials other than water. According to some embodiments, the cannabinoid composition comprises more than 90% w/w water.
  • the cannabinoid composition is substantially devoid of organic solvents.
  • substantially devoid of organic solvents means that a preparation or composition according to the invention that generally contains less than 3% organic solvents, such as less than 1% or less than 0.5%.
  • the cannabinoid composition less than 10% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 8% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 6% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 5% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 4% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 3% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 2% w/w organic solvents.
  • the cannabinoid composition less than 1% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 0.5% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 0.4% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 0.3% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 0.2% w/w organic solvents. According to some embodiments, the cannabinoid composition less than 0.1% w/w organic solvents. According to some embodiments, the organic solvent is selected from the group consisting of: dichloromethane, chloroform.
  • the composition is a liquid or semi-liquid composition.
  • the composition of the current invention is in the form of a liquid mixture.
  • the composition of the current invention is in the form of an aqueous mixture.
  • the liquid mixture is selected from liquid solution, liquid suspension and liquid emulsion.
  • the aqueous mixture is selected from aqueous solution, aqueous suspension and aqueous emulsion.
  • the composition is an aqueous solution.
  • the composition is an aqueous suspension.
  • the composition is an aqueous emulsion.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is a charged cannabinoid.
  • cannabinoids simple cannabinoids, such as CBD, THC, CBN and the like do not bear positive or negative charge.
  • cannabinoic acids in moderate pH conditions are also not considered charged.
  • Cannabinoic acids such as CBDA and THCA, however, are carboxylic acid, which are prone to deprotonation under basic pH conditions. Such deprotonations ionizes the molecules to form the respective salts, which are negatively charged.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is a negatively charged cannabinoid.
  • the cannabinoid in the non- aqueous solution, suspension or emulsion is a negatively charged deprotonated cannabinoid acid.
  • the cannabinoid in the non-aqueous solution, suspension or emulsion is selected from CBDA, THCA and a combination thereof.
  • the CBDA and/or THCA in the aqueous composition are deprotonated.
  • the CBDA and/or THCA in the aqueous composition are negatively charged.
  • cannabinoic acid and “cannabinoid acid” as used herein, are interchangeable and refer to a carboxylic acid derivative of cannabinoids.
  • tetrahydrocannabinolic acid and “THC acid” (abbreviated “THCA”) are interchangeable and refer to common derivatives of THC, which are substituted in position 2 of the aromatic ring by a carboxylic acid.
  • THC has two dominant isomers, ⁇ 9 -THC and ⁇ 8 -THC. Accordingly, THCA has corresponding ⁇ 9 and ⁇ 8 isomers.
  • tetrahydrocannabinols ⁇ 9 -THC and ⁇ 8 -THC
  • tetrahydrocannabinolic acids ⁇ 9 -THCA and ⁇ 8 -THCA
  • THC isomers
  • derivatives of THC may include other substituents. Therefore, the term tetrahydrocannabinolic acid includes corresponding structures, in which position 3 is substituted by a group, which is either an n-C 5 H 11 or a different chemical group.
  • THC tetrahydrocannabinolic acid
  • the natural THC includes two vicinal asymmetric positions, position 6a and position 10a, as shown above.
  • the two vicinal asymmetric positions exist in trans relative configuration, and both are designated R absolute configuration.
  • the (6aR,10aR) absolute configuration is the preferred configuration for tetrahydrocannabinolic acids of the current invention, however, said tetrahydrocannabinolic acids are not limited to this configuration
  • positions 6a and 10a of the THCA acid are in trans relative configuration.
  • position 6a has R absolute configuration.
  • position 10a has R absolute configuration.
  • the THCA acid has the (6aR,10aR) absolute configuration.
  • CBDA canbidiolic acid
  • CBD acid can be interchangeable and refer to common derivatives of CBD, which are substituted in position 2 of the aromatic ring by a carboxylic acid.
  • CBAD and THCA are organic acids, and thus are better soluble in water, when the pH is elevated, compared to their non-ionized counterparts. Specifically, at higher (more basic) pH organic acids are present as salts, which are typically more water soluble then their corresponding acids.
  • the at least one cannabinoid compound comprises THCA-salt. According to some embodiments, the at least one cannabinoid compound comprises THCA-sodium salt.
  • M cation; THCA salt or THCA basic salt
  • M metal; THCA metal salt;
  • the at least one cannabinoid compound comprises CBDA-salt. According to some embodiments, the at least one cannabinoid compound comprises CBDA-sodium salt.
  • M cation; CBDA salt or CBDA basic salt
  • M metal; CBDA metal salt
  • the basic (pH of at least 8.5 or at least 9, or at least 10) is suitable for delivery to electronic aerosol generating device users (e.g. vaporizer/electronic cigarette users).
  • electronic aerosol generating device users e.g. vaporizer/electronic cigarette users
  • the basic cannabinoid composition comprises non-volatile bases, which are not aerosolized, and organic material, comprising THCA/CBDA, present mainly as basic salts, e.g. THCA-sodium salt/CBDA-sodium salt.
  • the inhalable aerosol Upon heating and aerosolization with the electronic vaporizer, THCA-sodium salt/CBDA-sodium salt, which is/are in equilibrium with THCA, undergo/es decarboxylation to form THC/CBD, which is/are aerosolized together with the water medium.
  • THC and CBD are pH neutral, therefore, the aerosol is substantially neutral and suitable for the use of human subjects.
  • the inhalable aerosol has a pH in the range of 5.5 to 8.5.
  • the inhalable aerosol has a pH in the range of 6.0 to 7.5.
  • the inhalable aerosol has a pH in the range of 6.5 to 7.5.
  • the aqueous solution has a pH of at least 8.5. According to some embodiments, the aqueous solution has a pH of at least 8.6. According to some embodiments, the aqueous solution has a pH of at least 8.75. According to some embodiments, the aqueous solution has a pH of at least 9. According to some embodiments, the aqueous solution has a pH of at least 9.5. According to some embodiments, the aqueous solution has a pH of at least 10. According to some embodiments, the aqueous solution has a pH of at least 10.5. According to some embodiments, aqueous solution has a pH in the range of 9.5 to 11.5.
  • aqueous solution has a pH in the range of 9 to 11. According to some embodiments, aqueous solution has a pH in the range of 10 to 11. According to some embodiments, aqueous solution has a pH in the range of 10.5 to 11.5.
  • the composition for inhalation further comprises at least one buffer.
  • buffer refers to compounds which reduce the change of pH upon addition of small amounts of acid or base, or upon dilution.
  • buffering agent refers to a weak acid or weak base in a buffer solution.
  • the buffer is an acetate buffer.
  • the concentration of the at least one cannabinoid compound in the aqueous composition is in the range of 0.1% to 10% w/w. According to some embodiments, the concentration of the at least one cannabinoid compound in the aqueous composition is in the range of 0.5% to 10% w/w. According to some embodiments, the concentration of the at least one cannabinoid compound in the aqueous composition is in the range of 1% to 10% w/w. According to some embodiments, the concentration of the at least one cannabinoid compound in the aqueous composition is in the range of 2% to 10% w/w.
  • the concentration of the at least one cannabinoid compound in the aqueous composition is in the range of 4% to 6% w/w. According to some embodiments, the concentration of the at least one cannabinoid in the cannabinoid composition is within the range of 0.5 to 200 mg/ml. According to some embodiments, the concentration of the at least one cannabinoid in the cannabinoid composition is within the range of 1 to 150 mg/ml. According to some embodiments, the concentration of the at least one cannabinoid in the cannabinoid composition is within the range of
  • the concentration of the at least one cannabinoid in the cannabinoid composition is within the range of 10 to 100 mg/ml. According to some embodiments, the concentration of the at least one cannabinoid in the cannabinoid composition is within the range of 20 to 90 mg/ml According to some embodiments, the concentration of the at least one cannabinoid in the cannabinoid composition is within the range of 45 to 55 mg/ml.
  • the cannabinoid composition is an aqueous solution, suspension or emulsion comprising at least one cannabinoic acid or a salt thereof, selected from the group consisting of: tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), salts thereof and combinations thereof at a concentration in the range of 2% to 6%, w/w and an inhaled volatile anesthetic, selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane, at a concentration in the range of 0.02% to 2%, wherein the composition has a pH of at least
  • Aqueous cannabinoid acid solutions may be prepared, according to some embodiments, by a process comprising the steps of:
  • the process further comprises the steps of:
  • compositions for inhalation are provided.
  • the composition for inhalation of the current invention is a pharmaceutical composition.
  • the pharmaceutical composition further comprises at least one anti-infective agent. According to some embodiments, the pharmaceutical composition further comprises an anti-infective agent. According to some embodiments, the pharmaceutical composition further comprises at least two anti- infective agents.
  • the pharmaceutical composition of the present invention further comprises an additional active agent.
  • the additional active agent is an anti-infective agent.
  • the additional active agent is selected from the group consisting of antibiotics, anti-inflammatory agents, mucolytics, antiviral agents, antibacterial agents, antifungal agents, antiprotozoan agents and a combination thereof. Each possibility represents a separate embodiment.
  • the additional active agent is selected from antibiotics, anti-inflammatory agents, mucolytics and antiviral agents. Each possibility represents a separate embodiment.
  • the additional active ingredient is an anti-viral agent.
  • active agent refers to an agent that has biological activity, pharmacologic effects and/or therapeutic utility.
  • pharmaceutical composition refers to a composition comprising at least one active agent, optionally formulated together with one or more pharmaceutically acceptable carriers. Formulation of the pharmaceutical composition may be adjusted according to their intended use and administration route. In particular, the pharmaceutical composition may be formulated using a method known in the art so as to provide rapid, continuous or delayed release of the active ingredient after administration to mammals. According to one embodiment, the pharmaceutical composition is formulated for administration via inhalation.
  • pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U. S. Pharmacopeia or other generally recognized pharmacopeia for use in animals and, more particularly, in humans.
  • pharmaceutically acceptable carrier or “pharmaceutically acceptable excipient” as used herein refers to any and all solvents, dispersion media, preservatives, antioxidants, coatings, isotonic and absorption delaying agents, surfactants, fillers, disintegrants, binders, diluents, lubricants, glidants, pH adjusting agents, buffering agents, enhancers, wetting agents, solubilizing agents, surfactants, antioxidants the like, that are compatible with pharmaceutical administration.
  • the use of such media and agents for pharmaceutically active substances is well known in the art.
  • the pharmaceutical composition comprises a pharmaceutically acceptable carrier or excipient.
  • Useful pharmaceutically acceptable carriers include, for example, lactose, glucose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water and methylcellulose.
  • Other pharmaceutical carriers can be sterile liquids, such as water, alcohols (e.g., ethanol) and lipid carriers such as oils (including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like), phospholipids (e.g.
  • lecithin polyethylene glycols
  • glycerin polyethylene glycols
  • propylene glycol or other synthetic solvents.
  • Pharmaceutical acceptable diluents include, but are not limited to, sterile water, phosphate saline, buffered saline, aqueous dextrose and glycerol solutions, and the like. Each possibility is a separate embodiment of the invention.
  • the composition is for use that comprises administering a dose ranging from 2 to 1000 mg/day of the composition. According to some embodiments, the composition is for use that comprises administering a dose ranging from 2 to 200 mg/day of the cannabinoid(s).
  • the composition is co-administered with an additional active agent.
  • the additional active agent is an anti viral agent. Any additional active agent used to treat a coronavirus infection may be used, in any treatment regimen, that includes the compositions of the present invention.
  • the additional active agent may be administered before, simultaneously with, or after the compositions of the present invention.
  • the additional active agent is administered by a parenteral route, e.g. intravenous.
  • the composition of the current invention further comprises at least one additive selected from the group consisting of a propellant, an anti-coughing agent and a flavorant.
  • the composition further comprises at least one additive.
  • the at least one additive is selected from the group consisting of a propellant, an anti-coughing agent, a flavorant, and combinations thereof.
  • the composition comprises the at least one additive at a concentration of 0.1-1% w/w. According to some embodiments, the composition comprises the at least one additive at a concentration of 0.1-0.5% w/w. According to some embodiments, the composition comprises the at least one additive at a concentration of 0.1-0.3% w/w.
  • the additive is approved for use in inhaling solutions.
  • the additive in the basic aqueous cannabinoid compositions is stable at basic aqueous conditions.
  • the additive in the basic aqueous cannabinoid compositions is soluble at basic aqueous conditions.
  • the flavorant is a sweetener.
  • the sweetener is selected from the group of artificial sweeteners including saccharine, aspartame, dextrose, mannitol and fructose.
  • the additive is selected from menthol, eucalyptol, tyloxapol and a combination thereof. According to some embodiments, the additive is selected from menthol, eucalyptol, tyloxapol and a combination thereof, and is present at a concentration of 0.1-0.5% w/w based on the total weight of the composition.
  • the composition further comprises at least one preservative.
  • the preservative is selected from the group consisting of benzyl alcohol, propylparaben, methylparaben, benzalkonium chloride, phenylethyl alcohol, chlorobutanol, potassium sorbate, phenol, m-cresol, o- cresol, p- cresol, chlorocresol and combinations thereof.
  • anti-coughing agent refers to an active agent used for the suppression, alleviation or prevention of coughing and irritations and other inconveniencies in the large breathing passages that can, or may, generate coughing.
  • Anti-coughing agent include, but are not limited to antitussives, which are used for which suppress coughing, and expectorants, which alleviate coughing, while enhancing the production of mucus and phlegm. Anti-coughing agents may ease the administration of inhaled aerosols.
  • the at least one anti-coughing agent is selected from expectorants, antitussives or both.
  • the at least one anti-coughing agent is selected from the group consisting of menthol, dextromethorphan, dextromethorphan hydrobromide, hydrocodone, caramiphen dextrorphan, 3-methoxymorphinan or morphinan- 3-ol, carbetapentane, codeine, acetylcysteine and combinations thereof.
  • a suitable propellant is any fluorocarbon, e.g. a 1-4 hydrogen containing fluorocarbon (such as CHF 2 CHF 2 , CF 3 CH 2 F, CH 2 F 2 CH 3 and CF 3 CHFCF 3 ), a perfluorocarbon, e.g. a 1-4 carbon perfluorocarbon, (such as CF 3 CF 3 , CF 3 CF 2 CF 3 ); or any mixture of the foregoing, having a sufficient vapor pressure to render them effective as propellants.
  • Some typical suitable propellants include conventional chlorofluorocarbon (CFC) propellants such as mixtures of propellants 11, 12 and 114.
  • Non-CFC propellants such as 1,1,1,2-tetrafluoroethane (Propellant 134a), 1,1,1,2,3,3,3-heptafluoropropane (Propellant 227) or mixtures thereof are preferred.
  • a method for treating or preventing a disease caused by a coronavirus comprising administering, via inhalation, to a subject in need thereof a composition in the form of an aerosol, wherein the composition comprises cannabinoid(s) and an inhaled volatile anesthetic.
  • the composition is the pulmonary composition disclosed herein.
  • treating refers to taking steps to obtain beneficial or desired results, including clinical results.
  • beneficial or desired clinical results include, but are not limited to, ameliorating abrogating, substantially inhibiting, slowing or reversing the progression of a disease, condition or disorder, substantially ameliorating or alleviating clinical or esthetical symptoms of a condition, substantially preventing the appearance of clinical or esthetical symptoms of a disease, condition, or disorder, and protecting from harmful or annoying symptoms. Treating further refers to accomplishing one or more of the following: (a) reducing the severity of the disorder;
  • preventing refers to preventing the disease; for example, preventing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.
  • the method can thus be used as a preventive treatment in subjects that are suspected to develop a disease caused by a coronavirus, such as subjects that were exposed to infected patients, or subjects who show initial signs of infection (e.g. symptoms in the upper respiratory system).
  • the present invention is further beneficial for reducing the global spread of various coronaviruses which upon infecting the lungs, can cause severe and potentially life-threatening diseases.
  • composition of the current invention is a composition for inhalation.
  • composition for inhalation pulmonary composition
  • cannabinoid composition cannabinoid-based composition
  • aerosol generating device such as an electronic cigarette.
  • compositions for inhalation as disclosed herein are administered to the lungs, for example orally (by inhalation through the trachea) or nasally (by inhalation through the nose).
  • pulmonary administration is intended to encompass any suitable delivery method by which the composition is delivered to the lungs via the respiratory tract.
  • compositions for inhalation as disclosed herein are administered to the lungs through the throat of a subject. According to some embodiments, the compositions for inhalation as disclosed herein are administered to the lungs through the pharynx of a subject. According to some embodiments, the compositions for inhalation as disclosed herein are administered to the lungs through the nose of a subject.
  • compositions for inhalation are intended to the lungs and are administered through the pharynx and trachea to the lungs.
  • compositions for the respiratory system may also be delivered nasally (i.e. through the nose).
  • Nasal administration is less common, but is being developed by means of Orally Inhaled and Nasal Drug Product (OINDP).
  • OINDPs are defined by the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) as providing therapeutic benefit by delivery of a pharmaceutical substance to the lungs or nasal cavity.
  • OINDP is generally characterized by: (a) delivery of the drug at a specific range of particle sizes, which may be the drug particle alone, or bound to a carrier, or dissolved or suspended in a liquid droplet; and (b) targeted deposition to specific membranes.
  • the coronavirus is a human coronavirus.
  • the human coronavirus is a betacoronavirus.
  • the human coronavirus is selected from MERS-CoV, SARS-CoV and SARS-CoV-2. According to some embodiments, the human coronavirus is MERS-CoV. According to some embodiments, the human coronavirus is SARS-CoV. According to some embodiments, the human coronavirus is SARS- CoV-2.
  • the disease is COVID-19.
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as the 2019 novel coronavirus (2019-nCoV), is a positive-sense single-stranded RNA virus. It is contagious among humans and is the cause of coronavirus disease 2019 (COVID-19). There is no vaccine, but several antiviral drugs are already in clinical trials. SARS-CoV-2 has strong genetic similarity to known bat coronaviruses, making a zoonotic origin in bats likely, although an intermediate reservoir such as a pangolin is thought to be involved. From a taxonomic perspective SARS-CoV-2 is classified as a strain of the species severe acute respiratory syndrome-related coronavirus.
  • SARS- CoV-2 is the cause of the ongoing 2019-20 coronavirus outbreak, a Public Health Emergency of International Concern that originated in Wuhan, China. Because of this connection, the virus is sometimes referred to informally, among other nicknames, as the “Wuhan coronavirus”.
  • the coronavirus is a human coronavirus selected from the group consisting of Human coronavirus 229E (HCoV-229E), Human coronavirus OC43 (HCoV-OC43), Severe acute respiratory syndrome coronavirus (SARS-CoV), Human coronavirus NL63 (HCoV-NL63, New Haven coronavirus), Human coronavirus HKU1, Middle East respiratory syndrome-related coronavirus (MERS- CoV), and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • the human coronavirus is selected from MERS-CoV, SARS- CoV and SARS-CoV-2.
  • the composition for inhalation of the present invention is for use in treatment of a disease caused by a human coronavirus is selected from MERS-CoV, SARS-CoV and SARS-CoV-2.
  • the disease is COVID-19.
  • the composition for inhalation of the present invention is for use in treating COVID-19.
  • treating the disease comprises alleviating at least one of the symptoms of the disease.
  • treating the disease comprises at least one of reducing temperature, improving oxygenation, improvement in respiratory parameters such as rate, reduction in viral load and obtaining negative test for the virus e.g. for SARS-CoV-2.
  • the coronavirus treated by the present method is a human coronavirus.
  • the disease is affecting the human respiratory system.
  • the human coronavirus is selected from MERS-CoV, SARS-CoV and SARS-CoV-2.
  • the disease is COVID-19.
  • the method comprises administering a dosage ranging from 2 to 1000 mg/day of the composition to the subject in need thereof. According to some embodiments, the method comprises administering a dosage ranging from 2 to 100 mg/day of the cannabinoid to the subject in need thereof.
  • the administration of the present composition is to the respiratory system of the subject. According to some embodiments, the administration is to the lungs of the subject. According to some embodiments, the method comprises pulmonary administration of the composition.
  • the method further comprises co-administering the composition of the present invention with an additional active agent.
  • the additional active agent may be any other active pharmaceutical agent, which is effective in treating a disease caused by a coronavirus, and may be delivered by inhalation or by any other administration route.
  • the additional active agent is an antiviral agent.
  • the additional active agent may be administered before, simultaneously with, or after the compositions of the present invention.
  • the additional active agent is administered in a route other than pulmonary, i.e. orally through ingestion or intravenously.
  • the pharmaceutical composition is provided in a dosage form suitable for aerosolization using an aerosol generating device.
  • the precise dose to be employed of the presently disclosed composition depends on the progression of the disease, and should be decided according to the judgment of the practitioner and each patient's circumstances.
  • the administration schedule can be taken once-daily, twice-daily, thrice-daily, once-weekly, twice-weekly, thrice-weekly, once-monthly, twice-monthly, thrice-monthly, or any other administration schedule known to those of skill in the art.
  • the pharmaceutical composition is administered twice a week.
  • the administration may be continuous, i.e., every day, or intermittently.
  • intermittent administration can be administration in one to six days per week or it may mean administration in cycles (e.g. daily administration for two to eight consecutive weeks, then a rest period with no administration for up to one week) or it may mean administration on alternate days.
  • the use comprises co-administration of the pharmaceutical composition of the present invention with an additional active agent.
  • the additional active agent may be any other active pharmaceutical agent, which is effective in treating any infective disease, including diseases caused by a coronavirus, and may be delivered by inhalation or by any other administration route.
  • the additional active agent is an antiviral agent.
  • the additional active agent is administered in a route other than pulmonary, i.e. orally through ingestion or intravenously.
  • coadministration encompasses administration of a first and second agent in an essentially simultaneous manner.
  • the agents can be administered in a sequential manner in either order.
  • coadministration involves the separate administration of each agent, the agents may be administered sufficiently close in time to have the desired effect (e.g., complex formation).
  • sequential manner refers to an administration of two compounds at different times, and optionally in different modes of administration.
  • the agents can be administered in a sequential manner in either order.
  • substantially simultaneous manner refers to administration of two compounds with only a short time interval between them. According to some embodiments, the time interval is in the range of from 0.5 to 60 minutes.
  • the method comprises the steps of: (a) providing an aerosol generating device;
  • the method comprises the steps of:
  • the aerosol generating device is as disclosed herein.
  • a person skilled in the art would appreciate based on the below how to implement any one of the aerosol generating devices disclosed herein for generating the present aerosols from the present cannabinoid compositions.
  • the droplets of the aerosol delivered by the method of the present invention are having a mass median aerodynamic diameter (MMAD) of no more than 5 microns. According to some embodiments, the droplets of the aerosol delivered by the aerosol generating device are having a mass median aerodynamic diameter (MMAD) of no more than 5 microns.
  • the aerosol generating device whereby the aerosolization of the composition is achieved is an electronic cigarette.
  • the dosage form containing the composition is suitable for incorporation into an electronic cigarette.
  • compositions of the present invention are suitable for administration by inhalation as an aerosol created upon aerosolization of the composition by an aerosol generating device, which comprises a heating unit configured to vaporize the composition and to form an aerosol therefrom, according to some embodiments.
  • an aerosol generating device which comprises a heating unit configured to vaporize the composition and to form an aerosol therefrom, according to some embodiments.
  • a specialized aerosol generating device configured to create aerosols having droplets having a specific diameter (typically below 5 micron).
  • droplets having the diameter profile as provided by the aerosol generating device disclosed herein are highly effective in reaching the lower airways, such that the cannabinoid-inhaled volatile anesthetic composition of the invention provides effective treatment thereof.
  • vaporizing refers to a step of heating a condensed material (e.g. a solid, a liquid, a gas-liquid mixture or a solid-liquid mixture) to form gas of vapor therefrom.
  • a condensed material e.g. a solid, a liquid, a gas-liquid mixture or a solid-liquid mixture
  • vaporizing a composition to form an aerosol refers to heating the composition, thereby creating vapors or gas, which is spontaneously or through an external action transforms into an aerosol.
  • an electronic cigarette as presented in WO 2020/194297 is an exemplary device, which is configured to perform the vaporization, aerosolization an administration of the compositions of the present invention.
  • FIG. 1 and Figure 2 constitute schematic illustration of an electronic cigarette 100, according to some embodiments.
  • the terms "electronic cigarette” and “e-cigarette” as used herein, are interchangeable and refer to a device configured to produce a vapor or aerosol from a liquid or solid composition and comprises at least a heating unit for heating the composition, and an outlet for delivering out the formed aerosol composition for a user to inhale, typically through a mouthpiece.
  • Electronic cigarette 100 comprises a cartridge 106 comprising a cartridge housing 102 and a cartridge internal compartment 108.
  • Electronic cigarette 100 further comprises an actuator 114 comprising an actuator housing 104.
  • Electronic cigarette 100 further comprises an outlet 110, an evaporation heater 120, a first trigger 140, a liquid deposition mechanism 160 and a processing unit 190.
  • outlet 110 is formed on cartridge housing 102.
  • electronic cigarette 100 is configured to produce an aerosol 166
  • outlet 110 is configured to deliver aerosol 166 out of electronic cigarette 100. It is to be understood that the objective of electronic cigarettes is generally to produce an aerosol, and to deliver it through the outlet or mouthpiece of the electronic cigarette, through a mouth of an electronic cigarette user to the respiratory system of the user.
  • outlet 110 is connected to a mouthpiece. According to some embodiments, outlet 110 is mechanically connected to a mouthpiece. According to some embodiments, the mouthpiece is detachable.
  • evaporation heater 120 is accommodated within cartridge internal compartment 108.
  • electronic cigarettes including electronic cigarette 100 have an elongated shape, e.g. as depicted in Figures 1-5.
  • the term “longitudinal” refer to the direction of elongation of electronic cigarette 100.
  • the term “longitudinal axis” refers to the linear axis along the longitudinal direction.
  • top generally refer, longitudinally, to the side or end of any device or a component of a device, which is closer to outlet 110.
  • top referring to proximity to the mouthpiece or the user using e-cigarette.
  • bottom”, “below”, “down”, “under” and “downwards” generally refer, longitudinally, to the side or end of any device or a component of a device, which is farther than outlet 110.
  • bottom”, “below”, “down”, “under” and “downwards” are interchangeable with the term “distal”.
  • liquid deposition mechanism 160 delivers a discrete, known volume of liquid, or a plurality of discrete, known volumes of liquid, intermittently to evaporation heater 120.
  • Evaporation heater 120 is heated to an elevated temperature, which rapidly evaporates the discrete volume of liquid and generates aerosol 166 therefrom, according to some embodiments.
  • liquid deposition mechanism 160 cannot have more than two states, such as intermediate states.
  • each of the states described below may have non-identical forms and/or mechanisms of action.
  • liquid deposition mechanism 160 in a first state of electronic cigarette 100, is spaced apart from evaporation heater 120, such that liquid is not deposited onto evaporation heater 120, when electronic cigarette 100 is in the first state of operation.
  • liquid deposition mechanism 160 is delivering a discrete volume of liquid onto evaporation heater 120, and the discrete volume of liquid is evaporated and subsequently aerosolized, due to evaporation heater 120 being in an elevated evaporation temperature.
  • liquid deposition mechanism 160 may be spaced apart from evaporation heater 120 and deposit liquid thereon from distance, according to some embodiments.
  • an element of liquid deposition mechanism 160 may approach evaporation heater 120, such that contact is established between evaporation heater 120 and the element of liquid deposition mechanism 160.
  • the contact between evaporation heater 120 and an element of liquid deposition mechanism 160 enables the delivery of a discrete volume of liquid onto evaporation heater 120, and the discrete volume of liquid is evaporated by the heat of evaporation heater 120 and subsequently aerosolized to form aerosol 166.
  • anerosol refers to a dispersion of solid or liquid particles in a gas.
  • anerosol refers to a material that has been vaporized, nebulized, being in a form of spray or jet or otherwise converted from a solid or liquid form to an inhalable form including suspended solid or liquid particles.
  • evaporation and “substantial evaporation” are interchangeable and are intended to mean that at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, least 97%, least 98%, least 99%, least 99.5% or least 99.9% of the liquid is transformed from liquid to gaseous state.
  • evaporation heater 120 is located longitudinally between outlet 110 and liquid deposition mechanism 160. Specifically, as defined above with respect to directions, evaporation heater 120 is located above liquid deposition mechanism 160, and outlet 110 is located above evaporation heater 120. Therefore, upon operation of electronic cigarette 100 from the first state to the seconds state, liquid deposition mechanism 160 deposits the discrete volume of liquid on the bottom of evaporation heater 120, and vapor is released from the top of evaporation heater 120.
  • evaporation heater 120 is flat and comprises a first surface facing outlet 110 and a second surface facing liquid deposition mechanism 160.
  • electronic cigarette 100 comprises compartment of processing unit assembly 173, accommodated within actuator 114.
  • compartment of processing unit assembly 173 comprises processing unit assembly 174.
  • processing unit assembly 174 comprises processing unit 190.
  • electronic cigarette 100 comprises processing unit 190, accommodated within actuator 114.
  • processing unit 190 is configured to receive signals from first trigger 140.
  • first trigger 140 is configured to generate at least a first trigger activation signal.
  • evaporation heater 120 is configured to generate heat when first trigger 140 generates the first trigger activation signal.
  • second trigger 150 comprises a flow sensor or a pressure sensor 152, configured to detect the flow or the pressure, respectively, in electronic cigarette 100, and to generate signals indicative thereof.
  • flow sensor or pressure sensor 152 comprises a differential pressure sensor.
  • pressure sensor 152 is positioned within actuator 114.
  • electronic cigarette 100 further comprises a second trigger 150, configured to at least trigger activation or deactivation of at least one of evaporation heater 120 and liquid deposition mechanism 160.
  • second trigger 150 is configured to generate a variable second trigger activation signal, varying in at least one of: amplitude, wavelength or frequency of the signals.
  • processing unit 190 is configured to provide varying activation signals to liquid deposition mechanism 160, thereby controlling various parameters of liquid deposition mechanism 160 as a function of the second trigger activation signals generated by second trigger 150. Varying activation signals of liquid deposition mechanism 160 may include, but are not limited to variations in the amount of liquid drawn by liquid deposition mechanism 160 towards evaporation heater 120, or to rate of liquid transfer from liquid deposition mechanism 160 towards evaporation heater 120.
  • the signals produced by flow or pressure sensor 152 are received by processing unit 190.
  • processing unit 190 is configured to receive the flow or pressure signals.
  • the flow or pressure signals are indicative of the usage of electronic cigarette 100. For example, upon inhalation of a user from electronic cigarette 100 through outlet 110, the pressure drops and a reduced pressure signal is sent from flow or pressure sensor 152 to processing unit 190.
  • processing unit 190 is configured to receive the flow or pressure signals and to activate at least one of evaporation heater 120 and liquid deposition mechanism 160 in response thereto.
  • processing unit 190 is configured to receive the flow or pressure signals and to deactivate at least one of evaporation heater 120 and liquid deposition mechanism 160 in response thereto. For example, continuing the previous example, upon the user stopping to inhale through outlet 110, the pressure within electronic cigarette 100 will rise again and a respective pressure signal will be sent from flow or pressure sensor 152 to processing unit 190. In response processing unit 190 will terminate the activation of liquid deposition mechanism 160 and evaporation heater 120, according to some embodiments.
  • liquid deposition mechanism 160 is configured to control the operation of evaporation heater 120.
  • processing unit 190 is configured to activate evaporation heater 120 upon receiving first trigger activation signal from first trigger 140.
  • processing unit 190 is configured to deactivate at least one heating element.
  • processing unit 190 is configured to control operation of liquid deposition mechanism 160. According to some embodiments, processing unit 190 is configured to control operation of liquid deposition mechanism 160, such that liquid deposition mechanism 160 delivers a discrete volume of liquid to evaporation heater 120. According to some embodiments, processing unit 190 is configured to operate liquid deposition mechanism 160 to perform a transition from the first state to the second state of electronic cigarette 100. According to some embodiments, processing unit 190 is configured to operate liquid deposition mechanism 160 to perform a transition from the second state to the first state of electronic cigarette 100.
  • processing unit 190 is configured to operate liquid deposition mechanism 160 to perform a transition from the first state to the second state and to perform a transition from the second state to the first state of electronic cigarette 100 consecutively, so as to provide a discrete volume of liquid from liquid deposition mechanism 160 to evaporation heater 120.
  • processing unit 190 is configured to operate liquid deposition mechanism 160 to perform the following sequence of operations consecutively:
  • liquid deposition mechanism 160 (b) maintenance of liquid deposition mechanism 160 in the second state for a predetermined period of deposition time; wherein during the predetermined period of deposition time, liquid deposition mechanism 160 is configured to deliver a discrete volume of liquid to evaporation heater 120;
  • operation (c) a transition of liquid deposition mechanism 160 from the second state to the first state of electronic cigarette 100.
  • operation (b) is the only operation in which liquid deposition mechanism 160 is configured to deliver a liquid to evaporation heater 120.
  • processing unit 190 is configured to perform the sequence of operations a plurality of times upon receiving the first activation signal.
  • processing unit 190 is configured to activate liquid deposition mechanism 160 upon receiving first trigger activation signal from first trigger 140. According to some embodiments, processing unit 190 is configured to deactivate liquid deposition mechanism 160.
  • liquid deposition mechanism 160 comprises a liquid deposition mechanism housing 178, a liquid container 162, a liquid drawing element 164 and a solenoid mechanism comprising a solenoid actuator 170 connected to a solenoid plunger head 172 through a rod.
  • Figure 3A constitutes a cross sectional view of electronic cigarette 100 in the first state of operation and Figure 3B constitutes a cross sectional view of electronic cigarette 100 in the second state of operation.
  • Liquid container 162 is accommodated within cartridge internal compartment 108 of cartridge 106 and is configured to contain the liquid therein. In contrast with the discrete volume of liquid, which is small and typically sufficient for a single inhalation of aerosol 166 by a user of 100, liquid container 162 is configured to contain bulk amount of the liquid composition, wherein only small discrete volume(s) of the liquid are evaporated during the operation of electronic cigarette 100.
  • liquid drawing element 164 is fluidly attached to liquid container 162. According to some embodiments, liquid drawing element 164 is in constant contact with liquid container 162. According to some embodiments, liquid drawing element 164 is partially accommodated within liquid container 162.
  • liquid e.g. comprising the present composition
  • liquid container 162 for deliverance towards evaporation heater 120 via liquid drawing element 164.
  • liquid drawing element 164 comprises a material that is capable of incorporating, taking in, drawing in or soaking liquids, and upon applying physical pressure thereto or being in contact with another material, release a portion or the entire amount/volume of the absorbed liquid.
  • liquid drawing element 164 is affixed to at least one of cartridge housing 102, cartridge internal compartment 108 and liquid container 162. According to some embodiments, liquid drawing element 164 is affixed to at least one of cartridge housing 102, cartridge internal compartment 108 and liquid container 162, such that liquid drawing element 164 is in contact with liquid container 162 and capable of withdrawing liquid therefrom.
  • liquid drawing element 164 is flexible, such that upon physical pressure applied on liquid drawing element 164, it is configured to bend, while still being affixed to at least one of cartridge housing 102, cartridge internal compartment 108 and liquid container 162.
  • liquid drawing element 164 is configured to absorb liquid in an amount which is at least 100% of its weight. According to some embodiments, liquid drawing element 164 is configured to absorb liquid in an amount which is at least 50% of its weight.
  • liquid drawing element 164 is fabricated such that contact of liquid drawing element 164 with evaporation heater 120 for said the predetermined period of deposition time results in the delivery of a discrete volume of liquid to evaporation heater 120. According to some embodiments, liquid drawing element 164 is fabricated such that contact of liquid drawing element 164 with evaporation heater 120 for said the predetermined period of deposition time results in the delivery of a thin layer of liquid to evaporation heater 120. According to some embodiments, the thin layer of liquid e for has thickness in the range of 0.1mm to 0.5mm.
  • liquid container 162 contains the present composition. Therefore, wherever “liquid” is used it is meant the composition for inhalation of the present invention.
  • liquid drawing element 164 comprises cloth, wool, felt, sponge, foam, cellulose, yarn, microfiber or a combination thereof, having high tendency to absorb aqueous solutions.
  • the sponge is an open cell sponge.
  • the sponge is a closed cell sponge.
  • liquid drawing element 164 comprises fabric.
  • fibrous and/or woven fabric such as a wick, is a hydrophilic and liquid absorbing material, which may be used as the stationary liquid absorbing element(s), according to some embodiments.
  • liquid drawing element 164 is a hydrophilic liquid drawing element. According to some embodiments, liquid drawing element 164 is a hydrophilic sponge.
  • liquid drawing element 164 pressed against evaporation heater 120 in the second state of electronic cigarette 100.
  • liquid deposition mechanism 160 includes solenoid actuator 170, solenoid plunger head 172 and liquid deposition mechanism housing 178, according to some embodiments.
  • Figure 2 constitutes a view in which actuator 114 and cartridge 106 are separated, such that none of the elements of liquid deposition mechanism 160 is hidden.
  • Liquid deposition mechanism housing 178 is located inside actuator 114 and is configured to accommodate solenoid actuator 170. According to some embodiments, liquid deposition mechanism housing 178 is connected to actuator housing 104. According to some embodiments, solenoid actuator 170 is connected to liquid deposition mechanism housing 178.
  • liquid deposition mechanism housing 178 is rigidly attached to actuator housing 104.
  • solenoid actuator 170 is attached to liquid deposition mechanism housing 178 such that unintentional displacement of solenoid actuator 170 upwards or downward in the longitudinal direction is prevented.
  • liquid deposition mechanism housing 178 is attached to solenoid actuator 170, such that displacement of solenoid actuator 170 upwards or downward in the longitudinal direction is prevented.
  • solenoid actuator 170 is attached to liquid deposition mechanism housing 178 such that unintentional displacement of solenoid actuator 170 in a non-longitudinal direction is prevented.
  • solenoid actuator 170 is attached to liquid deposition mechanism housing 178, such that displacement of evaporation heater 120 in a non-longitudinal direction is prevented.
  • Non-longitudinal directions include any direction, which is not along the longitudinal axis, such as any direction orthogonal or angled with respect to the longitudinal axis.
  • restriction of movement enforced on solenoid actuator 170 by liquid deposition mechanism housing 178 refers to restriction of movement of the main body of solenoid actuator 170, but not of its rod or solenoid plunger head 172, which are moving parts, as detailed herein.
  • solenoid actuator 170 is connected to solenoid plunger head 172. According to some embodiments, solenoid actuator 170 is connected to solenoid plunger head 172 through a rod (not numbered).
  • cartridge 106 further comprises at least one cartridge opening 112 allowing passage there through of solenoid plunger head 172 from actuator 114 to cartridge internal compartment 108.
  • cartridge 106 further comprises at least one cartridge opening 112 allowing fluid communication between actuator 114 and cartridge 106.
  • fluid communication between cartridge 106 and actuator 114 may be required because (a) second trigger 150 may be a pressure sensor (e.g. sensor 152); (b) sensor 152 is located in actuator 114; and (c) sensor 152 senses pressure or flow changes correlating with a user inhalation through outlet 110, which is part of cartridge 106.
  • solenoid refers to a type of electromagnet, the purpose of which is to generate a controlled magnetic field through a coil wound into a tightly packed helix.
  • the electromagnetic solenoids are used for conversion of electric energy to linear movement.
  • solenoid actuator means one or more electric tubular coils and one or more associated armature members; the coils and members being mounted for relative axial movement with respect to each other.
  • solenoid actuator 170 is configured to receive electric current and to generate axial movements upon receiving the electric current. According to some embodiments, the axial movement of solenoid actuator 170 generates an axial movement of its rod along the along an axis perpendicular to each of evaporation heater 120 and liquid drawing element 164. According to some embodiments, the axial movement of solenoid actuator 170 generates a longitudinal axial movement of its rod. According to some embodiments, upon receiving the electric current solenoid actuator 170 is configured to generate longitudinal movement of its rod at a predetermined rate.
  • processing unit 190 is configured to control solenoid actuator 170. According to some embodiments, processing unit 190 is configured to pass current to solenoid actuator 170. According to some embodiments, upon receiving the electric current solenoid actuator 170 is configured to generate longitudinal movement of its rod at a controlled rate, wherein processing unit 190 is configured to control the controlled rate. According to some embodiments, processing unit 190 is configured to pass variable current to solenoid actuator 170, wherein the variable current is dictating the controlled rate.
  • axial and axial movement refer to a linear movement along the longitudinal axis of electronic cigarette 100.
  • solenoid plunger head 172 is functionally connected to solenoid actuator 170. According to some embodiments, upon axial movement generated by solenoid actuator 170, solenoid plunger head 172 moves along the longitudinal axis from a fist location to a second location. According to some embodiments, the first location is below the second location, as detailed above with respect to directions.
  • solenoid plunger head 172 in the first state of electronic cigarette 100, solenoid plunger head 172 is in the first location, and both solenoid plunger head 172 and liquid drawing element 164 are spaced apart from evaporation heater 120. According to some embodiments, in the first state of electronic cigarette 100, solenoid plunger head 172 is in the first location, and both solenoid plunger head 172 and liquid drawing element 164 not in contact with evaporation heater 120.
  • solenoid plunger head 172 in the second state of electronic cigarette 100, solenoid plunger head 172 is in the second location. According to some embodiments, when solenoid plunger head 172 approaches the second location, its pushes a portion of liquid drawing element 164 towards evaporation heater 120. According to some embodiments, in the second state of electronic cigarette 100, solenoid plunger head 172 reaches the second location, and a portion of liquid drawing element 164 contacts evaporation heater 120. According to some embodiments, when liquid drawing element 164 forms contact with evaporation heater 120, delivery of a discrete volume of liquid from liquid drawing element 164 to evaporation heater 120 is enabled.
  • processing unit 190 is configured to alternately operate solenoid actuator 170, such that solenoid plunger head 172 alternately dislocates between the first and second and configured to alternately deliver discrete volumes of liquid to evaporation heater 120.
  • any mechanism which is configured to move liquid drawing element 164 between a first and a second position is encompassed by the current invention, according to some embodiments.
  • Solenoid mechanisms are widely used for conversion of electric energy to axial movement and are depicted in Figures 1-3, however, other mechanisms, which are configured to push liquid drawing element 164 to intermittently contact evaporation heater 120 are also contemplated, according to some embodiments.
  • liquid deposition mechanism 160 is configured to transfer liquid to evaporation heater 120. According to some embodiments, liquid deposition mechanism 160 is configured to deliver a thin film or layer of the liquid to evaporation heater 120. According to some embodiments, liquid deposition mechanism 160 is configured to deliver a film liquid to evaporation heater 120 having a thickness in the range of 0.1 mm to 3 mm. According to some embodiments, the film has a thickness in the range of 0.1 mm to 2 mm. According to some embodiments, the film has a thickness in the range of 0.5 mm to 2 mm. According to some embodiments, the film has a thickness in the range of 0.75 mm to 1.5 mm.
  • liquid deposition mechanism 160 is configured to deliver a discrete volume of liquid to evaporation heater 120, wherein the discrete volume of liquid has a volume in the range of 2 ⁇ L to 100 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 3 ⁇ L to 50 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 4 ⁇ L to 45 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 5 ⁇ L to 40 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 6 ⁇ L to 35 ⁇ L.
  • the discrete volume of liquid has a volume in the range of 7 ⁇ L to 30 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 8 ⁇ L to 28 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 9 ⁇ L to 25 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 10 ⁇ L to 20 ⁇ L.
  • liquid deposition mechanism 160 is configured to transfer discrete volume of liquid to evaporation heater 120.
  • the liquid comprises the present composition.
  • Prior art liquid deposition mechanisms include liquid containers, which are in constant contact with the respective heater, or which deliver liquid constantly during the electronic cigarette operation through a delivery medium (typically a wick positioned in stationary contact with both the liquid container and the heater).
  • liquid deposition mechanism 160 of electronic cigarette 100 includes liquid container 162, which is configured to deliver liquid to liquid drawing element 164 constantly, but liquid drawing element 164 is separated from evaporation heater 120 in the first state of electronic cigarette 100, such that delivery of liquid is not constant.
  • liquid deposition mechanism 160 or parts thereof is configured to be in transient contact with evaporation heater 120, such that discrete amounts of the liquid are intermittently delivered from liquid deposition mechanism 160 to evaporation heater 120.
  • FIG. 4 and Figure 5 constitute schematic illustration of an electronic cigarette 100, according to some embodiments.
  • Electronic cigarette 100 comprises a cartridge 106 comprising a cartridge housing 102 and a cartridge internal compartment 108.
  • Electronic cigarette 100 further comprises an actuator 114 comprising an actuator housing 104.
  • Electronic cigarette 100 further comprises an outlet 110, an evaporation heater 120, a first trigger 140, a liquid deposition mechanism 160 and a processing unit 190.
  • Electronic cigarette 100 as described in Figures 4-5 differs from electronic cigarette 100 as described in Figures 1-3 mainly in the design of liquid deposition mechanism 160.
  • outlet 110 is formed on cartridge housing 102.
  • electronic cigarette 100 is configured to produce an aerosol 166
  • outlet 110 is configured to deliver aerosol 166 out of electronic cigarette 100. It is to be understood that the objective of electronic cigarettes is generally to produce an aerosol, and to deliver it through the outlet and/or mouthpiece of the electronic cigarette, through a mouth of an electronic cigarette user to the respiratory system of the user.
  • outlet 110 is connected to a mouthpiece (not shown). According to some embodiments, outlet 110 is mechanically connected to a mouthpiece. According to some embodiments, the mouthpiece is detachable.
  • evaporation heater 120 is accommodated within cartridge internal compartment 108.
  • electronic cigarettes including electronic cigarette 100 have an elongated shape, as depicted in Figures 1-5.
  • longitudinal refers to the direction of elongation of electronic cigarette 100.
  • longitudinal axis refers to the linear axis along the longitudinal direction.
  • liquid deposition mechanism 160 delivers a discrete, known volume of liquid, or a plurality of discrete, known volumes of liquid, intermittently to evaporation heater 120.
  • Evaporation heater 120 is heated to an elevated temperature, which rapidly evaporates the discrete volume of liquid and generates aerosol 166 therefrom, according to some embodiments.
  • liquid delivery from liquid deposition mechanism 160 to evaporation heater 120 has benefits, especially when aerosolizing aqueous compositions, and is achieved using a two-state liquid deposition mechanism 160, according to some embodiments
  • liquid deposition mechanism 160 in a first state of electronic cigarette 100, is spaced apart from evaporation heater 120, such that liquid is not deposited onto evaporation heater 120, when electronic cigarette 100 is in the first state of operation.
  • liquid deposition mechanism 160 is delivering a discrete volume of liquid onto evaporation heater 120, and the discrete volume of liquid is evaporated and subsequently aerosolized, due to evaporation heater 120 being in an elevated evaporation temperature.
  • liquid deposition mechanism 160 may be spaced apart from evaporation heater 120 and deposit liquid thereon from distance, according to some embodiments, and as detailed with respect to Figures 4-5.
  • evaporation heater 120 is located longitudinally between outlet 110 and liquid deposition mechanism 160. Specifically, as defined above with respect to directions, evaporation heater 120 is located above liquid deposition mechanism 160, and outlet 110 is located above evaporation heater 120. Therefore, upon operation of electronic cigarette 100 from the first state to the seconds state, liquid deposition mechanism 160 deposits the discrete volume of liquid on the bottom of evaporation heater 120, and vapor is released from the top of evaporation heater 120.
  • evaporation heater 120 is flat and comprises a first surface facing outlet 110 and a second surface facing liquid deposition mechanism 160.
  • electronic cigarette 100 comprises compartment of processing unit assembly 173, accommodated within actuator 114.
  • compartment of processing unit assembly 173 accommodates comprises processing unit assembly 174.
  • processing unit assembly 174 comprises processing unit 190.
  • electronic cigarette 100 comprises processing unit 190, accommodated within actuator 114.
  • processing unit 190 is configured to receive signals from first trigger 140.
  • first trigger 140 is configured to generate at least a first trigger activation signal.
  • evaporation heater 120 is configured to generate heat when first trigger 140 generates the first trigger activation signal.
  • liquid deposition mechanism 160 is configured to control the operation of evaporation heater 120.
  • processing unit 190 is configured to activate evaporation heater 120 upon receiving first trigger activation signal from first trigger 140.
  • processing unit 190 is configured to deactivate at least one heating element.
  • processing unit 190 is configured to control operation of liquid deposition mechanism 160. According to some embodiments, processing unit 190 is configured to control operation of liquid deposition mechanism 160, such that liquid deposition mechanism 160 delivers a discrete volume of liquid to evaporation heater 120. According to some embodiments, processing unit 190 is configured to operate liquid deposition mechanism 160 to perform a transition from the first state to the second state of electronic cigarette 100.
  • transition as used with respect to electronic cigarette 100 and liquid deposition mechanism 160 of Figures 4-5, is not limited to movement. This term may further encompass functional transition from a first state to a second state as follows: liquid deposition mechanism 160 and evaporation heater 120 are spaced apart and liquid deposition mechanism 160 is not operated to deposit liquids onto evaporation heater 120 (first state); and evaporation heater 120 and liquid deposition mechanism 160 remain in the same relative positions, but liquid deposition mechanism 160 is operated to deposit liquid onto evaporation heater 120 (second state).
  • processing unit 190 is configured to operate liquid deposition mechanism 160 to perform a transition from the second state to the first state of electronic cigarette 100. According to some embodiments, processing unit 190 is configured to operate liquid deposition mechanism 160 to perform a transition from the first state to the second state and vise versus, consecutively, to provide a discrete volume of liquid from liquid deposition mechanism 160 to evaporation heater 120. According to some embodiments, processing unit 190 is configured to operate liquid deposition mechanism 160 to perform the following sequence of operations consecutively:
  • liquid deposition mechanism 160 (b) maintenance of liquid deposition mechanism 160 in the second state for a predetermined period of deposition time; wherein during the predetermined period of deposition time, liquid deposition mechanism 160 is configured to deliver a discrete volume of liquid to evaporation heater 120;
  • the phrase "maintenance of liquid deposition mechanism 160 in the second state for a predetermined period of deposition time” means that liquid deposition mechanism 160 is delivering liquid to evaporation heater 120 throughout the predetermined period of time.
  • operation (b) is the only operation in which liquid deposition mechanism 160 is configured to deliver a liquid to evaporation heater 120.
  • processing unit 190 is configured to perform the sequence of operations a plurality of times upon receiving the first activation signal.
  • processing unit 190 is configured to activate liquid deposition mechanism 160 upon receiving first trigger activation signal from first trigger 140. According to some embodiments, processing unit 190 is configured to deactivate liquid deposition mechanism 160.
  • liquid deposition mechanism 160 comprises a liquid deposition mechanism housing 178, a liquid container 162, a liquid drawing element 164 and an ultrasonic mechanism comprising a piezo disc 180.
  • Figure 5 constitutes a cross sectional view of electronic cigarette 100 in the second state of operation, when actuator 114 and 106 are separated
  • Figure 4 constitutes a cross sectional view of electronic cigarette 100 in the second state of operation, when actuator 114 and 106 are joined.
  • Liquid container 162 is accommodated within cartridge internal compartment 108 of cartridge 106 and is configured to contain the liquid therein.
  • Liquid drawing element 164 is in contact with liquid container 162, according to some embodiments. According to some embodiments, liquid container 162 and liquid drawing element 164 are positioned in contact, such that delivery of liquids from liquid container 162 to liquid drawing element 164 is enabled. In contrast with the discrete volume of liquid, which are small and typically sufficient for a single inhalation of aerosol 166 by a user of 100, liquid container 162 is configured to contain bulk amount of the liquid composition, wherein only small discrete volume(s) of the liquid are evaporated during the operation of electronic cigarette 100.
  • liquid container 162 is surrounding liquid drawing element 164, such that transfer of liquid contained therein of liquid drawing element 164 is enabled through the circumference of liquid drawing element 164.
  • liquid drawing element 164 is fluidly attached to liquid container 162. According to some embodiments, liquid drawing element 164 is in constant contact with liquid container 162. According to some embodiments, liquid drawing element 164 is partially accommodated within liquid container 162.
  • liquid is provided in liquid container 162 for deliverance towards evaporation heater 120 via liquid drawing element 164.
  • liquid drawing element 164 comprises a material that is capable of incorporating, taking in, drawing in or soaking liquids, and upon applying physical pressure thereto or being in contact with another material, release a portion or the entire amount/volume of the absorbed liquid.
  • liquid drawing element 164 is affixed to at least one of cartridge housing 102, cartridge internal compartment 108 and liquid container 162. According to some embodiments, liquid drawing element 164 is affixed to at least one of cartridge housing 102, cartridge internal compartment 108 and liquid container 162, such that liquid drawing element 164 is in contact with liquid container 162 and capable of withdrawing liquid therefrom.
  • liquid drawing element 164 is configured to absorb liquid in an amount which is at least 100% of its weight. According to some embodiments, liquid drawing element 164 is configured to absorb liquid in an amount which is at least 50% of its weight.
  • liquid drawing element 164 is fabricated such that contact of liquid drawing element 164 with evaporation heater 120 for said the predetermined period of deposition time results in the delivery of a discrete volume of liquid to evaporation heater 120. According to some embodiments, liquid drawing element 164 is fabricated such that contact of liquid drawing element 164 with evaporation heater 120 for said the predetermined period of deposition time results in the delivery of a thin layer of liquid to evaporation heater 120. According to some embodiments, the thin layer of liquid has thickness in the range of 0.1mm to 0.5mm.
  • liquid drawing element 164 comprises cloth, wool, felt, sponge, foam, cellulose, yarn, microfiber or a combination thereof, having high tendency to absorb aqueous solutions.
  • the sponge is an open cell sponge.
  • the sponge is a closed cell sponge.
  • liquid drawing element 164 comprises fabric.
  • fibrous and/or woven fabric such as a wick, is a hydrophilic and liquid absorbing material, which may be used as the stationary liquid absorbing element(s), according to some embodiments.
  • liquid drawing element 164 is a hydrophilic liquid drawing element. According to some embodiments, liquid drawing element 164 is a hydrophilic sponge.
  • a liquid deposition mechanism such as liquid deposition mechanism 160 described in Figures 4-5, in which liquid drawing element 164 is intermittently providing discrete volumes of liquid to evaporation heater 120 from a distance, during the second state of operation of electronic cigarette 100 is preferably used with liquid solutions, such as aqueous solutions.
  • liquid drawing element 164 is essentially stationary during both the first state of electronic cigarette 100 and the second state of electronic cigarette 100. According to some embodiments, the distance between liquid drawing element 164 and evaporation heater 120 is substantially constant during both the first state of electronic cigarette 100 and the second state of electronic cigarette 100.
  • liquid deposition mechanism 160 includes liquid drawing element 164, liquid deposition mechanism housing 178, piezo disc 180 and a piezo slot 184.
  • Figure 5 constitutes a view in which actuator 114 and cartridge 106 are separated.
  • Liquid deposition mechanism housing 178 is located inside cartridge 106 and is configured to accommodate piezo disc 180.
  • liquid deposition mechanism housing 178 comprises piezo slot 184, which is configured to accommodate piezo disc 180.
  • liquid deposition mechanism housing 178 is connected to actuator housing 104.
  • piezo disc 180 is connected to liquid deposition mechanism housing 178.
  • liquid deposition mechanism housing 178 is rigidly attached to actuator housing 104.
  • piezo disc 180 is affixed to piezo slot 184, such that unintentional displacement of piezo disc 180 upwards or downward in the longitudinal direction is prevented.
  • piezo slot 184 is attached to piezo disc 180, such that displacement of piezo disc 180 upwards or downward in the longitudinal direction is prevented.
  • piezo disc 180 is attached to piezo slot 184 such that unintentional displacement of piezo disc 180 in a non-longitudinal direction is prevented.
  • piezo slot 184 is attached to piezo disc 180, such that displacement of piezo disc 180 in a non-longitudinal direction is prevented.
  • liquid deposition mechanism 160 comprises a liquid drawing element positioning compartment 156.
  • liquid drawing element positioning compartment 156 is formed within liquid deposition mechanism housing 178.
  • liquid drawing element positioning compartment 156 is positioned below liquid drawing element 164.
  • liquid drawing element positioning compartment 156 comprises a compartment for installing a positioning mechanism (not shown) for proper positioning of liquid drawing element 164 in the longitudinal axis, according to some embodiments.
  • the positioning mechanism is configured to cause a contact between piezo disc 180 and liquid drawing element 164.
  • liquid drawing element 164 comprises a top surface in contact with piezo disc 180 and a bottom surface in contact with the positioning mechanism.
  • the positioning mechanism is configured to apply pressure on the bottom surface of liquid drawing element 164, such that the top surface of liquid drawing element 164 contacts piezo disc 180.
  • the applied pressure is upwards in the longitudinal direction.
  • the positioning mechanism is configured to apply pressure on the bottom surface of liquid drawing element 164, such that the top surface of liquid drawing element 164 is pressed against piezo disc 180.
  • a piezo gasket 176 is accommodated within piezo slot 184, and is configured to fasten piezo disc 180 to piezo slot 184.
  • piezo gasket 176 comprises a silicone gasket.
  • piezo gasket 176 comprises a rubber gasket.
  • piezo gasket 176 comprises an O-ring.
  • piezo disc 180 is screwed to piezo slot 184.
  • piezo disc 180 is configured to convert electric current to mechanic stress. According to some embodiments, piezo disc 180 is configured to convert electric current to vibrations. According to some embodiments, piezo disc 180 is configured to convert electric current to vibrations having resonant frequency, which creates mist from liquid formulations. According to some embodiments, piezo disc 180 is configured to convert electric current to vibrations having resonant frequency, which creates mist from aqueous formulations. Thus, according to some embodiments, upon driving sufficient current through piezo disc 180 and upon depositing liquid thereon, it creates mist of the liquid.
  • piezo disc 180 has piezo resonant frequency in the range of lOOKHz-lOMHz. According to some embodiments, piezo disc 180 has piezo resonant frequency in the range of 100-250 KHz. According to some embodiments, piezo disc 180 has piezo resonant frequency in the range of 125-225 KHz. According to some embodiments, piezo disc 180 has piezo resonant frequency in the range of 140- 210 KHz. According to some embodiments, piezo disc 180 has piezo resonant frequency in the range of 150-200 KHz. According to some embodiments, piezo disc 180 has piezo resonant frequency in the range of 165-195 KHz. According to some embodiments, piezo disc 180 has piezo resonant frequency in the range of 175-185 KHz.
  • piezo disc 180 has capacitance in the range of 700- 2000pF. According to some embodiments, piezo disc 180 has capacitance in the range of 700-1700pF. According to some embodiments, piezo disc 180 has capacitance in the range of 800-1600pF. According to some embodiments, piezo disc 180 has capacitance in the range of 950-1450pF.
  • piezo disc 180 has harmonic impedance of not more than 500Ohm. According to some embodiments, piezo disc 180 has harmonic impedance of not more than 450Ohm. According to some embodiments, piezo disc 180 has harmonic impedance of not more than 400Ohm. According to some embodiments, piezo disc 180 has harmonic impedance of not more than 350Ohm.
  • piezo disc 180 has piezoelectric coefficient D33 of not more than 450 C/N. According to some embodiments, piezo disc 180 has piezoelectric coefficient D33 of not more than 400 C/N. According to some embodiments, piezo disc 180 has piezoelectric coefficient D33 of not more than 350 C/N. According to some embodiments, piezo disc 180 has piezoelectric coefficient D33 of not more than 300 C/N.
  • piezo disc 180 is made of a metal. According to some embodiments, piezo disc 180 is made of stainless steel. According to some embodiments, piezo disc 180 is made of SUS304 stainless steel.
  • piezo disc 180 is configured to receive electric current and to generate mist 182 from liquid upon receiving the electric current.
  • piezo disc 180 comprises a top flat surface facing evaporation heater 120 and a bottom flat surface in contact with liquid drawing element 164.
  • the bottom flat surface of piezo disc 180 is in contact with liquid drawing element 164 during both the first state and the second state of electronic cigarette 100.
  • piezo disc 180 is a perforated disc.
  • piezo disc 180 is a perforated disc, such that fluids may pass therethrough.
  • the bottom surface of piezo disc 180 is in contact with liquid contained in liquid drawing element 164 during both the first state and the second state of electronic cigarette 100.
  • piezo disc 180 upon application of electric current through piezo disc 180, piezo disc 180 converts liquid in contact with the bottom surface there to mist 182, which is released through the perforations of piezo disc 180 from the top surface of piezo disc 180.
  • mist 182 is released from the top surface of piezo disc 180 longitudinally upwards, such that it forms a discrete volume of liquid on the bottom surface of evaporation heater 120.
  • processing unit 190 is configured to control piezo disc 180, by providing current thereto. According to some embodiments, processing unit 190 is configured to control piezo disc 180 such that piezo disc 180 generates, intermittently a plurality of mists 182 at a predetermined rate. According to some embodiments, processing unit 190 is configured to control piezo disc 180 such that piezo disc 180 generates, intermittently a plurality of mists 182 at a rate controlled by processing unit 190.
  • processing unit 190 is configured to control piezo disc 180. According to some embodiments, processing unit 190 is configured to pass current to piezo disc 180. According to some embodiments, upon receiving the electric current, piezo disc 180 is configured to generate mists 182, intermittently at a controlled rate, wherein processing unit 190 is configured to control the controlled rate. According to some embodiments, processing unit 190 is configured to pass variable current to piezo disc 180 wherein the variable current is dictating the controlled rate. According to some embodiments, processing unit 190 is configured to pass variable current to piezo disc 180 wherein the variable current is dictating the mass of mist 182.
  • piezo disc 180 in the first state of electronic cigarette 100, piezo disc 180 is deactivated. According to some embodiments, in the first state of electronic cigarette 100, current is not driven through piezo disc 180. According to some embodiments, in the first state of electronic cigarette 100, processing unit 190 does not provide current to piezo disc 180. According to some embodiments, in the first state of electronic cigarette 100, piezo disc 180 does not generate mist 182.
  • piezo disc 180 in the second state of electronic cigarette 100, piezo disc 180 is activated. According to some embodiments, in the second state of electronic cigarette 100, current is driven through piezo disc 180. According to some embodiments, in the second state of electronic cigarette 100, processing unit 190 provide current to piezo disc 180. According to some embodiments, in the second state of electronic cigarette 100, piezo disc 180 generates mist 182. According to some embodiments, processing unit 190 is configured is activate and deactivate piezo disc 180 intermittently at a controlled rate, such that a plurality of mists 182 is delivered intermittently to evaporation heater 120.
  • processing unit 190 is configured to alternately operate piezo disc 180, such that piezo disc 180 delivers discrete volumes of liquid to evaporation heater 120, alternately.
  • liquid deposition mechanism 160 is configured to transfer liquid to evaporation heater 120. According to some embodiments, liquid deposition mechanism 160 is configured to deliver a thin film or layer of the liquid to evaporation heater 120. According to some embodiments, liquid deposition mechanism 160 is configured to deliver a film liquid to evaporation heater 120 having a thickness in the range of 0.1 mm to 3 mm. According to some embodiments, the film has a thickness in the range of 0.1 mm to 2 mm. According to some embodiments, the film has a thickness in the range of 0.5 mm to 2 mm. According to some embodiments, the film has a thickness in the range of 0.75 mm to 1.5 mm.
  • liquid deposition mechanism 160 is configured to deliver a discrete volume of liquid to evaporation heater 120, wherein the discrete volume of liquid has a volume in the range of 2 ⁇ L to lOO ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 3 ⁇ L to 50 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 4 ⁇ L to 45 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 5 ⁇ L to 40 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 6 ⁇ L to 35 ⁇ L.
  • the discrete volume of liquid has a volume in the range of 7 ⁇ L to 30 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 8 ⁇ L to 28 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 9 ⁇ L to 25 ⁇ L. According to some embodiments, the discrete volume of liquid has a volume in the range of 10 ⁇ L to 20 ⁇ L.
  • liquid deposition mechanism 160 is configured to transfer discrete volume of liquid to evaporation heater 120.
  • the liquid comprises the present composition for inhalation.
  • first trigger 140 may be a touch user interface, according to some embodiments.
  • the user interface may provide options to a user for determining parameters by which processing unit 190 controls liquid deposition mechanism 160 and/or evaporation heater 120.
  • the touch user interface is configured to provide to an electronic cigarette 100 user at least two sensorial options.
  • at least one control parameter of processing unit 190 over liquid deposition mechanism 160 are executed.
  • the at least one control parameter is selected from fluid deposition frequency and fluid deposition duty cycle.
  • the fluid deposition frequency is in the range of 0.5Hz to 100Hz. According to some embodiments, the fluid deposition frequency is in the range of 0.5Hz to 50Hz. According to some embodiments, the fluid deposition frequency is in the range of 0.75Hz to 40Hz. According to some embodiments, the fluid deposition frequency is in the range of lHz to 30Hz. According to some embodiments, the fluid deposition frequency is in the range of 1.5Hz to 25Hz. According to some embodiments, the fluid deposition frequency is in the range of 2Hz to 20Hz. According to some embodiments, the fluid deposition frequency is in the range of 2Hz to 10Hz.
  • the duty cycle is in the range of 5% to 80%.
  • the duty cycle is in the range of 7% to 70%.
  • the duty cycle is in the range of 10% to 60%.
  • the duty cycle is in the range of 12% to 50%.
  • the duty cycle is in the range of 14% to 40%.
  • the duty cycle is in the range of 15% to 35%.
  • the duty cycle is in the range of 20% to 30%.
  • fluid deposition frequency refers to the number of times in which liquid deposition mechanism 160 deposits discrete volume of liquid onto evaporation heater 120 per time unit.
  • fluid deposition frequency refers to the number of times in which electronic cigarette 100 transforms from the first state to the second state of action per time unit.
  • fluid deposition frequency refers to the time ratio between the first state and the second state of electronic cigarette 100. As detailed herein during the second state, a discrete volume of liquid is delivered to evaporation heater 120, and during the first state liquid is not delivered to evaporation heater 120. Thus, the phrase “fluid deposition frequency” refers to the relative duration in which evaporation heater 120 is being deposited with liquid.
  • the at least one control parameter of processing unit 190 over evaporation heater 120 are executed.
  • the at least one control parameter comprises evaporation heater 120 threshold temperature.
  • the threshold temperature is the temperature above which, processing unit 190 stops driving current- or reducing the current driven to evaporation heater 120, for its heating.
  • first trigger 140 is further configured to generate a deactivation signal, such that processing unit 190 is configured to deactivate both evaporation heater 120 and piezo disc 180 upon receiving first trigger deactivation signal from first trigger 140.
  • processing unit 190 is configured to regulate the temperature of evaporation heater 120 in the range of 95°C to 400°C, through control of the operation of both evaporation heater 120 and liquid deposition mechanism 160. According to some embodiments, processing unit 190 is configured to regulate the temperature of evaporation heater 120 below 400°C, below 350°C, or below 330°C, through control of the operation of liquid deposition mechanism 160 and/or evaporation heater 120. According to some embodiments, processing unit 190 is configured to receive at least one operation signal and to control operation of liquid deposition mechanism 160.
  • the regulation entails providing variable current to piezo disc 180 as detailed above. Specifically, it is to be understood that deposition of liquid over evaporation heater 120 effects its temperature.
  • actuator 114 and cartridge 106 are reversibly connectable, according to some embodiments.
  • cartridge 106 comprises liquid container 162. According to some embodiments, liquid container 162 is contained within cartridge internal compartment 108 of cartridge 106. According to some embodiments, cartridge 106 comprises outlet 110. According to some embodiments, outlet 110 is formed on cartridge housing 102 of cartridge 106. According to some embodiments, cartridge 106 comprises evaporation heater 120. According to some embodiments, evaporation heater 120 is contained within cartridge internal compartment 108 of cartridge 106. According to some embodiments, cartridge 106 comprises support 122. According to some embodiments, support 122 is connected to cartridge housing 102 of cartridge 106. According to some embodiments, cartridge 106 comprises liquid drawing element 164. According to some embodiments, liquid drawing element 164 is connected to cartridge housing 102 of cartridge 106.
  • cartridge 106 further comprises at least one cartridge opening 112 allowing fluid communication between actuator 114 and cartridge 106.
  • fluid communication between cartridge 106 and actuator 114 may be required because (a) second trigger 150 may be a pressure sensor (e.g. sensor 152); (b) sensor 152 is located in actuator 114; and (c) sensor 152 senses pressure or flow changes correlating with a user inhalation through outlet 110, which is part of cartridge 106.
  • second trigger 150 may be a pressure sensor (e.g. sensor 152);
  • sensor 152 is located in actuator 114; and
  • sensor 152 senses pressure or flow changes correlating with a user inhalation through outlet 110, which is part of cartridge 106.
  • cartridge 106 comprises cartridge power coupling 196.
  • cartridge power coupling 196 is contained within cartridge internal compartment 108 of cartridge 106.
  • cartridge 106 comprises evaporation heater electric contact 132 and cartridge electric contacts 134.
  • evaporation heater electric contact 132 and cartridge electric contacts 134 are contained within cartridge internal compartment 108 of cartridge 106.
  • cartridge electric contacts 134 are formed as crimp ring terminals.
  • cartridge electric contacts 134 are receiving current derived from battery 194.
  • the current to cartridge electric contacts 134 is monitored by processing unit 190, for achieving the evaporation heater 120 required temperature, as detailed herein.
  • the current to cartridge electric contacts 134 drives from battery 194 through cartridge power coupling 196 and actuator power coupling 198.
  • actuator 114 comprises power source compartment 192.
  • cartridge 106 comprises liquid deposition mechanism 160.
  • actuator 114 comprises flow or pressure sensor 152.
  • actuator 114 comprises power source compartment 192.
  • actuator 114 comprises processing unit assembly 173.
  • actuator 114 comprises compartment of processing unit assembly 174.
  • actuator 114 comprises processing unit 190.
  • electronic cigarette 100 further comprises a communication element (not shown) configured to enable wireless communication of electronic cigarette 100 with servers, databases and personal devices (e.g. computers, mobile phones) among others.
  • the communication element provides wireless communication through Bluetooth, WiFi, ZigBee and/or Z- wave.
  • an aerosolization filling composition comprising the composition as disclosed herein.
  • the filling is for use in the treatment or prevention of a coronavirus.
  • the present filling may be specified or approved by the relevant authorities to be used for the prevention or treatment of a disease caused by a coronavirus.
  • the aerosolization filling composition is selected from a vaporizer cartridge filling composition and an electronic cigarette cartridge filling composition. Each possibility represents a separate embodiment of the present invention. Optional cartridges are as presented hereinabove.
  • the aerosolization filling composition may be used for filling any one of the devices disclosed herein.
  • an aerosol comprising at least one cannabinoid and an inhaled volatile anesthetic.
  • the present aerosol may be formed according to the method of the present invention.
  • the present aerosol may be generated from any one of the present compositions using any one of the aerosol generating devices described herein.
  • any one of the embodiments described herein for the compositions, their constituents and amounts may be applied for the chemical composition of the present aerosol.
  • the person skilled in the art would appreciate that many of the compositional characteristics of the composition for inhalation disclosed herein, similarly apply for the aerosol of the current invention.
  • the person skilled in the art would appreciate that many of the therapeutic characteristics of the composition for inhalation disclosed herein, including types of therapies and diseases, similarly apply for the aerosol of the current invention.
  • the inhaled volatile anesthetic in the aerosol composition is selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane.
  • the inhaled volatile anesthetic is at a concentration in the aerosol composition in the range of 0.02% to 2%, w/w.
  • the concentration of the inhaled volatile anesthetic in the aerosol composition is in the range of 0.2 to 2 gr/L.
  • the aerosol is a non-aqueous aerosol.
  • the cannabinoid in the non-aqueous aerosol is selected from cannabidiol (CBD), tetrahydrocannabinol (THC) or both.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • the at least one cannabinoid in the non-aqueous aerosol is at a concentration in the range of 5% to 60% w/w.
  • the non-aqueous aerosol comprises glycerin, propylene glycol, or both.
  • the non-aqueous solvent in the non-aqueous aerosol is at a concentration in the range of 40% to 95% w/w.
  • the aerosol composition comprises at least one neutral cannabinoid at a concentration in the range of 5% to 60%, an inhaled volatile anesthetic, selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane, at a concentration in the range of 0.02% to 2%, w/w and glycerin, propylene glycol, or both at a concentration in the range of 40% to 95%.
  • an inhaled volatile anesthetic selected from the group consisting of: halothane, isoflurane, sevoflurane, and desflurane, at a concentration in the range of 0.02% to 2%, w/w and glycerin, propylene glycol, or both at a concentration in the range of 40% to 95%.
  • the non-aqueous aerosol of the present invention is produced by aerosolizing the non-aqueous as disclosed herein.
  • the aerosol is an aqueous aerosol.
  • the aqueous aerosol composition comprises at least 80% w/w water.
  • the aqueous aerosol composition less than 10% w/w organic solvents.
  • the cannabinoid in the aqueous aerosol is selected from cannabidiol (CBD), tetrahydrocannabinol (THC) or both.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • the aqueous aerosol is less basic compared to the original composition.
  • the aqueous aerosol has a pH in the range of 5.5 to 8.5.
  • the aqueous aerosol has a pH in the range of 6.0 to 7.5.
  • the aqueous aerosol has a pH in the range of 6.5 to 7.5.
  • the aerosol composition comprises cannabinoid(s) and the inhaled volatile anesthetic as the sole active ingredients.
  • the aerosol composition comprises cannabinoid(s) and the inhaled volatile anesthetic as the sole active ingredients.
  • the aerosol composition of the present invention further comprises an additional active agent, as described with respect to the pulmonary composition.
  • the aerosol composition comprises a pharmaceutically acceptable carrier or excipient.
  • the aerosol composition of the current invention further comprises at least one additive selected from the group consisting of a propellant, an anti-coughing agent, a preservative and a flavorant, as detailed with respect to the present pulmonary composition.
  • the aerosol composition is for use that comprises administering a dose ranging from 2 to 1000 mg/day of the composition, including sub ranges thereof. According to some embodiments, the composition is for use that comprises administering a dose ranging from 2 to 200 mg/day of the cannabinoid(s).
  • the aerosol composition is for use in the treatment or prevention of a disease caused by a coronavirus.
  • the efficacy and various uses and diseases are as detailed in the section dedicated to the composition for inhalation and the method of treatment or prevention.
  • the droplets of the aerosol disclosed herein are having an MMAD value within the range of 0.3 to 7 microns.
  • the MMAD is less than 5 microns.
  • the MMAD is between 1 and 3 microns.
  • the devices, systems and methods disclosed herein provide a relatively uniform or homogeneous wetting of the porous surface that may result in small diameter aerosol droplets having the MMAD value as specified herein, and confer the ability to yield such small diameter aerosol drops with high efficiency.
  • MMAD median aerodynamic diameter
  • droplets around 10 micron in diameter are suitable for deposition in the oropharynx and the nasal area; droplets around 3-5 micron in diameter are suitable for deposition in the central airways and droplets between 1-3 microns are suitable for delivery to the alveoli (droplets substantially smaller than 1 micron will also target the alveolar region) and may be useful for delivering pharmaceuticals to the systemic circulation).
  • the therapy provided by the present invention is directed to the latter, and indeed it was found that the upon aerosolization of the composition of the present invention with the aerosol generating device disclosed herein, an aerosol comprising droplet in the range of 1-3 microns is formed.
  • % w/w refers to % weight/weight as well known in the art. According to any one of the embodiments of the present invention the term “% w/w may be substituted by the term “% w/v”. the term “% w/v” refers to percent weight/volume as well known in the art.
  • patient refers to either a human or a non-human animal. According to some embodiments, the subject is human.
  • range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
  • the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.
  • the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

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  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
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Abstract

La présente invention concerne d'une manière générale le domaine des compositions cannabinoïdes pour une administration pulmonaire, et leurs utilisations dans le traitement ou la prévention d'infections virales, en particulier par des coronavirus. Spécifiquement, les compositions de cannabinoïdes contiennent un anesthésique volatil inhalé et sont administrées sous la forme d'un aérosol généré par un dispositif de génération d'aérosol.
PCT/IL2021/050638 2020-05-31 2021-05-30 Compositions comprenant des cannabinoïdes et des anesthésiques volatils pour inhalation et leurs utilisations antivirales WO2021245655A1 (fr)

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WO2016019353A1 (fr) * 2014-07-31 2016-02-04 MJAR Holdings, LLC Cigarettes électroniques, cartouches et préparations inhalables à base de composés de cannabis à usage thérapeutique et appareils et procédés permettant de les fabriquer et de les utiliser
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