WO2022011460A1 - Compositions de cannabis transmuqueuses à propriétés de pénétration accrues - Google Patents

Compositions de cannabis transmuqueuses à propriétés de pénétration accrues Download PDF

Info

Publication number
WO2022011460A1
WO2022011460A1 PCT/CA2021/050956 CA2021050956W WO2022011460A1 WO 2022011460 A1 WO2022011460 A1 WO 2022011460A1 CA 2021050956 W CA2021050956 W CA 2021050956W WO 2022011460 A1 WO2022011460 A1 WO 2022011460A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
oil
cannabinoid
glyceryl
administration
Prior art date
Application number
PCT/CA2021/050956
Other languages
English (en)
Inventor
Genevieve BERTHIAUME
Francois Chouinard
James Mcmillan
Original Assignee
Hexo Operations Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hexo Operations Inc. filed Critical Hexo Operations Inc.
Publication of WO2022011460A1 publication Critical patent/WO2022011460A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—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 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • This application generally relates to the field of cannabis compositions and, more specifically, to compositions including a cannabinoid that are designed for increased transmucosal absorption.
  • Cannabis produces desirable psychoactive and/or physiological effects associated with a feeling of physical and/or emotional satisfaction and/or can be useful in the treatment of variety of diseases and conditions (e.g., pain, anxiety, inflammatory disorders, immune disorders, metabolic disorders, and the like).
  • diseases and conditions e.g., pain, anxiety, inflammatory disorders, immune disorders, metabolic disorders, and the like.
  • Cannabis formulations intended for transmucosal delivery are typically formulated as oil formulations (e.g., with a carrier oil) or as aqueous formulations (e.g., as an emulsion).
  • oil formulations e.g., with a carrier oil
  • aqueous formulations e.g., as an emulsion
  • cannabis formulations intended for transmucosal delivery have presented practical disadvantages, which may limit user experience and/or impair user compliance.
  • the present disclosure relates to a composition
  • a composition comprising (i) a cannabinoid component including a cannabinoid, and (ii) a monohydric alcohol.
  • the monohydric alcohol is in an amount sufficient to obtain an improvement compared to other oil-based composition comprising a cannabinoid, while being below a threshold amount.
  • the composition is a liquid composition for administration to the mucosal surface of the subject.
  • the threshold amount can be an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject.
  • the threshold amount can be an amount beyond which the monohydric alcohol significantly destabilizes the cannabinoid component in the composition.
  • the improved cannabinoid-associated effect can be an increased transmucosal permeation of the composition, a faster onset time, less variable onset time and/or cannabinoid-effect intensity across users, or any combinations thereof.
  • the present disclosure relates to a composition
  • a composition comprising a cannabinoid component including a cannabinoid, and a monohydric alcohol in an amount sufficient to increase transmucosal permeation of the cannabinoid while being below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject, the composition being a liquid composition for administration to the mucosal surface of the subject.
  • the present disclosure relates to a composition
  • a composition comprising a cannabinoid component comprising a cannabinoid, and a monohydric alcohol in an amount sufficient to (i) increase transmucosal permeation of the composition, (ii) reduce variability of a cannabinoid-associated effect between a plurality of users, preferably reduce variability of onset time and/or reduce variability of cannabinoid-effect intensity across users, and (iii) optionally, maintain stability of the cannabinoid component over a period of at least 5 days, preferably at least 6 days, more preferably at least 7 days, even more preferably 8 days, yet even more preferably 9 days, the composition being a liquid composition for administration to a mucosal surface of a user.
  • composition may have one or more of the following features:
  • the monohydric alcohol includes ethanol.
  • the monohydric alcohol is present in an amount of about 30 wt.% or less, preferably about 20 wt.% or less, more, more preferably from about 5 wt.% to about 20 wt.%, even more preferably from about 5 wt.% to about 15 wt.%, even more preferably from about 10 wt.% to about 15 wt.%. .
  • the cannabinoid includes tetrahydrocannabinoid (THC).
  • THC includes one or more of the following compounds: Dd-tetrahydrocannabinol
  • Dd-THC A9-cis-tetrahydrocannabinol (cis-THC), A9-tetrahydrocannabinol (A9-THC), A9-tetrahydrocannabinolic acid A (THCA-A), D10-tetrahydrocannabinol (DIO-THC), tetrahydrocannabivarin (THCV), A9-tetrahydrocannabinol-C4, D9- tetrahydrocannabinolic acid-C4 (THCA-C4), and synhexyl (n-hexyl-A3THC).
  • THC is Dd-tetrahydrocannabinol (Dd-THC), A9-tetrahydrocannabinol (A9-THC), or a combination thereof.
  • Dd-THC Dd-tetrahydrocannabinol
  • A9-THC A9-tetrahydrocannabinol
  • CBD cannabidiol
  • CBD includes one or more of the following compounds: A2-cannabidiol, A5-cannabidiol
  • the CBD is A2-cannabidiol.
  • the cannabinoid includes a mixture of THC and CBD in a (w/w) ratio of between about 1 :1000 and about 1000:1.
  • the cannabinoid is present in an amount of from about 0.001 mg/mLto about 100 mg/ml_, preferably from about 0.1 mg/ml_ to about 50 mg/ml_.
  • the cannabinoid is an isolated cannabinoid having a purity of 50-60%, or > 80%, or > 95%.
  • composition further comprises a flavour agent and/or a flavour enhancer.
  • flavour agent includes a terpene.
  • flavour enhancer is an extract from a natural source or an artificial flavour enhancer.
  • flavour enhancer is selected from the group consisting of cinnamon, cucumber, mint, orange, lime, citrus, cookie dough, chocolate, vanilla, jasmine, lychee, almond, banana, grape, pear, pineapple, pine, oak, apple, pumpkin, grapefruit, watermelon, cotton sugar, durian, longan, taro, sapote, toffee nut, caramel, lotus, mango, mangosteen, coconut, coffee, strawberry, passion fruit, blueberry, raspberry, kiwi, walnut, cocoa, cherimoya, custard apple, papaya, fig, plum, nectarine, peaches, guava, honeydew, jackfruit, kumquat, loquat, palm, pomelo, persimmon, quince, cassia, sage, marjoram, lemon, orange, and tamarind flavour, or any combinations thereof.
  • flavour agent and/or flavour enhancer is present in an amount of ⁇ 12 wt.%, or ⁇ 10 wt.%, or ⁇ 8 wt.%, or ⁇ 5 wt.%.
  • the cannabinoid component further comprises a carrier oil.
  • the carrier oil is selected from borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils, glycerin/glycerol, glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl, monolinoleate, glyceryl palmitate, glyceryl palmitostearate, glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl 3-oleate, polyglyceryl 4-oleate, polyglyceryl 10-te
  • the carrier oil is MCT oil.
  • composition is an oil-based composition and the carrier oil is present in an amount of about 50 wt.% or more, preferably from about 50 wt.% to about 90 wt.%.
  • composition is a water-based composition in the form of an emulsion and the composition further comprises an emulsifier and water.
  • the emulsifier includes a polysorbate-type non-ionic surfactant.
  • the emulsifier is selected from polyoxyethylene monostearate (PEG 400 Monostearate), polyoxyethylene monooleate (PEG 400 Monoleate), polyoxyethylene sorbitan monolaurate (Tween ® 20), polyoxyethylene sorbitan monolaurate (Tween ® 21), polyoxyethylene sorbitan monopalmitate (Tween ® 40), polyoxyethylene sorbitan monostearate (Tween ® 60), polyoxyethylene sorbitan monostearate (Tween ® 61), polyoxyethylene sorbitan tristearate (Tween ® 65), polyoxyethylene sorbitan monooleate (Tween ® 80), polyoxyethylene sorbitan monooleate (Tween 81), polyoxyethylene sorbitan trioleate (Tween ® 85), polyoxyethylene-(15)-stearic acid (Pegosperse 1500MS), polyoxyethylene-(20)-stearyl alcohol (Brij 78), polyoxyethylene-(23
  • the cannabinoid component in the water-based composition further comprises a carrier oil, preferably as defined above.
  • the water-based composition comprises the carrier oil in an amount of from about 5 wt.% to about 20 wt.%.
  • the emulsion has a D 90 of about 200 nm or less, preferably of about 150 nm or less, more preferably of about 120 nm or less.
  • the emulsion has a particle size distribution of from about 20 nm to about 120 nm, preferably from about 30 nm to about 80 nm, more preferably from about 40 nm to about 60 nm.
  • the present disclosure relates to a cannabis product for administration to a mucosal surface of a subject, the product comprising a container enclosing the composition as described herein and an outlet nozzle for administration of the composition to the mucosal surface of the subject.
  • the cannabis product may have one or more of the following features:
  • the present disclosure relates to a method for reducing cannabinoid-associated effect variability between users, comprising providing the cannabis composition as described above, and administering the composition to a user mucosal surface.
  • the method may have one or more of the following features:
  • composition is enclosed in a cannabis article configured for administration of the composition to a user mucosal surface.
  • composition is administered by pipetting or dropping.
  • composition is administered with a spray or mist administration device.
  • administration device is a vaporizer or atomizer.
  • composition is administered via nasal, oral, vaginal, ocular or rectal administration route.
  • the composition is administered to the mucosal surface via nasal routes, oral routes, or both.
  • reducing the cannabinoid-associated effect variability between users includes reducing onset time and/or cannabinoid-effect intensity.
  • FIG. 1A shows charted self-reported onset times for ElixirTM THC (circles) and the composition of Example 2 (“Distillate Tincture”, squares) results in a simple diagram, with the average onset time indicated by the horizontal line.
  • the results show an overall reduction in onset time for a composition in accordance with the present disclosure, as well as narrower distribution of plotted onset times, indicating improved consistency in onset across users.
  • FIG. 1B shows the results of FIG. 1 A, with the 25 th percentile (bottom line of box), 75 th percentile (top line of box), median (“middle” line in box), as well as maximum and minimum values (whiskers) for each dataset indicated.
  • FIG. 2 shows charted self-reported onset times for a distillate oil-based spray without ethanol and with ethanol, with the average onset time indicated by the horizontal line as well its standard error of the mean (SEM).
  • FIG. 3 shows charted self-reported onset times for a distillate water-based spray (nanoemulsion) without ethanol and with ethanol, with the average onset time indicated by the horizontal line as well its standard error of the mean (SEM).
  • the present inventors have surprisingly and unexpectedly designed a composition comprising a cannabinoid for administration to a mucosal surface of a subject that, upon administration to the subject, demonstrates improvements compared to known oil-based cannabis compositions for mucosal administration (e.g., compared to the ElixirTM oral spray product from Hexo Corporation Inc., Canada) or compared to known cannabis tincture oral compositions (e.g., SativexTM oromucosal spray, GW Pharmaceuticals pic, UK.) that typically include 50 vol% ethanol.
  • known oil-based cannabis compositions for mucosal administration e.g., compared to the ElixirTM oral spray product from Hexo Corporation Inc., Canada
  • known cannabis tincture oral compositions e.g., SativexTM oromucosal spray, GW Pharmaceuticals pic, UK.
  • Such improvements can be an increased transmucosal permeation of the composition, a faster onset time, less variable onset time and/or cannabinoid-effect intensity across users, or any combinations thereof.
  • compositions that comprise (i) a cannabinoid component including a cannabinoid and (ii) a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain an improvement compared to other oil- based composition comprising a cannabinoid, while being below a threshold amount.
  • the composition is a liquid composition for administration to the mucosal surface of the subject.
  • the threshold amount can be an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject.
  • a monohydric alcohol such as ethanol when contacting a mucosal surface of a subject may produce a hot stinging sensation when used in certain concentrations (also referred to herein as a “burning sensation”).
  • the stinging sensation may cause undesirable user experience as well as negatively affect transmucosal delivery.
  • the stinging sensation so produced may cause reflex swallowing - thus, reducing transmucosal absorption because a proportion of the dose may then be involuntarily swallowed by stimulation of the swallowing reflex.
  • the composition of the present disclosure may advantageously improve compliance (e.g. temporary abstinence from swallowing in the case of oral administration) and thus may improve transmucosal absorption.
  • the threshold amount can be an amount beyond which the monohydric alcohol significantly destabilizes the cannabinoid component in the composition.
  • the present inventors also surprisingly discovered that presence of a monohydric alcohol in water-based nanoemulsions allows for increased permeation of the cannabinoids without significantly disrupting the nanoemulsion (e.g., less than about 65% increase in particle size over a period of at least 5, 6, 7, 8, or 9 days), which was surprising at least because monohydric alcohols such as ethanol are known to destabilize nanostructures of emulsions.
  • ethanol has been used to increase permeation of molecules through mucosal membranes
  • ethanol was not known to the inventors knowledge to affect permeation of nanoparticles such as the droplets of a nanoemulsion, as these droplets are believed to be absorbed through mucosal membranes via a different mechanism than molecules.
  • Cannabinoid Component includes a cannabinoid
  • composition of the present disclosure comprises a “cannabinoid component” that includes a cannabinoid.
  • cannabinoid generally refers to any chemical compound that acts upon a cannabinoid receptor such as CB1 and CB2.
  • cannabinoids include, but are not limited to, cannabichromanon (CBCN), cannabichromene (CBC), cannabichromevarin (CBCV), cannabicitran (CBT), cannabicyclol (CBL), cannabicyclovarin (CBLV), cannabidiol (CBD, defined below), cannabidiolic acid (CBDA), cannabidiol monomethylether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), cannabidiphorol (CBDP), cannabidivarin (CBDV), cannabielsoin (CBE), cannabifuran (CBF), cannabigerol (CBG), cannabigerol monomethylether (
  • CBN cannabinol methylether
  • CBDN cannabinol propyl variant
  • cannabinol-C2 CBN-C2
  • cannabinol-C4 CBN-C4
  • cannabiorcol CBN-C1
  • cannabiripsol CBR
  • cannabitriol cannabitriol
  • THC cannabitriolvarin
  • CBV cannabivarin
  • DCBF dehydrocannabifuran
  • A7-cis-iso tetrahydrocannabivarin tetrahydrocannabinol
  • A9-tetrahydrocannabinolic acid including either or both isomers 2-COOH-THC (THC A- A) and 4-COOH-THC (THCA-B), A9-tetrahydrocannabiorcol (THC-C1), tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabivarin (THCV), ethoxy-cannabitriolvarin (CBTVE), trihydroxy-A9- tetrahydrocannabinol (triOH-THC), 10-ethoxy-9hydroxy-A6a-tetrahydrocannabinol, 8,9- dihydroxy-A6a-tetra
  • Cannabidiol means one or more of the following compounds: A2-cannabidiol, A5-cannabidiol (2-(6-isopropenyl-3-methyl-5-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D4- cannabidiol (2-(6-isopropenyl-3-methyl-4-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D3- cannabidiol (2-(6-isopropenyl-3-methyl-3-cyclohexen-l-yl)-5-pentyl-l,3-benzenediol); D3,7- cannabidiol (2-(6-isopropenyl-3-methylenecyclohex-l-yl)-5-pentyl-l,3-benzenediol); D2- cannabidiol (2-(6-isopropenyl-3-
  • Tetrahydrocannabinol means one or more of the following compounds: D8- tetrahydrocannabinol (Dd-THC), Dd-tetrahydrocannabivahn (Dd-THCV), A9-cis- tetrahydrocannabinol (cis-THC), A9-tetrahydrocannabinol (D9-THO), D10-tetrahydrocannabinol (DIO-THC), A9-tetrahydrocannabinol-C4 (THC-C4), A9-tetrahydrocannabinolic acid-C4 (THCA- C4), synhexyl (n-hexyl-A3THC).
  • THC means one or more of the following compounds: A9-tetrahydrocannabinol and D8- tetrahydrocannabinol.
  • Synthetic cannabinoids and semisynthetic cannabinoids encompass a variety of distinct chemical classes, for example and without limitation: the classical cannabinoids structurally related to THC, the non-classical cannabinoids (cannabimimetics) including the aminoalkylindoles, 1 ,5-diarylpyrazoles, quinolines, and arylsulfonamides as well as eicosanoids related to endocannabinoids.
  • a cannabinoid can be identified because its chemical name will include the text string “*cannabi*”.
  • cannabinoids that do not use this nomenclature, such as for example those described herein.
  • each of the acid and/or decarboxylated forms are contemplated as both single molecules and mixtures.
  • salts of cannabinoids are also encompassed, such as salts of cannabinoid carboxylic acids.
  • any and all isomeric, enantiomeric, or optically active derivatives are also encompassed.
  • reference to a particular cannabinoid includes both the “A Form” and the “B Form”.
  • THCA has two isomers, THCA-A in which the carboxylic acid group is in the 1 position between the hydroxyl group and the carbon chain (A Form) and THCA-B in which the carboxylic acid group is in the 3 position following the carbon chain (B Form).
  • the cannabinoid is a cannabinoid dimer.
  • the cannabinoid may be a dimer of the same cannabinoid (e.g., THC-THC) or different cannabinoids.
  • the cannabinoid may be a dimer of THC, including for example cannabisol.
  • the cannabinoid is THC (Dd-THC and/or DQ-THC), CBD, CBG, CBN, THCV, CBC, or any combinations thereof, in similar or different amounts.
  • the cannabinoid is THC.
  • the cannabinoid is CBD.
  • cannabinoids can be used in combination to achieve a desired effect in a user. Certain specific ratios of cannabinoids may be useful to produce the feeling of physical and/or emotional satisfaction and/or may be useful in the treatment or management of specific diseases or conditions.
  • the cannabinoid component includes or is a mixture of THC and CBD.
  • the mixture of THC and CBD may be characterized with a w/w ratio of THC to CBD of between about 1:1000 and about 1000:1.
  • the (w/w) ratio of THC to CBD may be about 1 :1000, about 1 :900, about 1 :800, about 1:700, about 1 :600, about 1:500, about 1 :400, about 1:300, about 1 :250, about 1:200, about 1 :150, about 1 :100, about 1 :90, about 1 :80, about 1 :70, about 1 :60, about 1 :50, about 1 :45, about 1 :40, about 1 :35, about 1 :30, about 1 :29, about 1 :28, about 1 :27, about 1 :26, about 1 :25, about 1 :24, about 1:23, about 1 :22, about 1 :21, about 1 :20, about 1 :19, about 1 :18, about 1 :17
  • the composition includes the cannabinoid in a concentration of about 0.001 mg/ml_ or more.
  • the composition may comprise the cannabinoid in an amount of from about 0.001 mg/ml_ to about 100 mg/ml_, including any amount therebetween or any ranges therein.
  • the composition may comprise the cannabinoid in an amount of from about 0.002 mg/ml_ to about 100 mg/ml_, from about 0.1 mg/mLto about 75 mg/ml_, or from about 0.1 mg/ml_ to about 50 mg/ml_, or from about 0.1 mg/ml_ to about 25 mg/ml_, including any amount therebetween or any ranges therein.
  • the person of skill will be able to design a composition having a desired cannabinoid content without undue effort, based on the teachings described herein.
  • the composition includes the cannabinoid in an amount of from about 1 wt.% to about 50 wt.% (the weight percentage being of the cannabinoid relative to total weight of the composition), including any amount therebetween or any ranges therein.
  • the composition includes the cannabinoid in an amount of from about 2.5 wt.% to about 50 wt.%, including any amount therebetween or any ranges therein, such as from about 5 wt.% to about 30 wt.% or from about 7.5 wt.% to about 25 wt.%, including any amount therebetween or any ranges therein.
  • Cannabinoids may be obtained from any suitable source material including, but not limited to, cannabis or hemp plant material (e.g., flowers, seeds, trichomes, and kief from cannabis plants) or manufactured (for example cannabinoids produced in yeast, for example as described in WO WO2018/148848).
  • the term “cannabis plant(s)” encompasses wild type Cannabis (including but not limited to the species Cannabis sativa, Cannabis indica and Cannabis ruderalis) and also variants thereof, including cannabis chemovars (or “strains”) that naturally contain different amounts of the individual cannabinoids.
  • the cannabinoid is obtained from a cannabis extract (e.g., resin, wax, concentrate, and distillate).
  • a “cannabis extract” refers to an extract obtained from a cannabis plant material according to any procedure known in the art; such extracts yield cannabinoids in pure or isolated form.
  • a cannabis extract may be obtained by a process including an extraction step from plant materials using for example organic solvent extraction, such as extraction with C0 2 , butane, ethanol, and the like.
  • a cannabis extract may be obtained by a process including an extraction step from plant materials using for example heat decarboxylation to convert cannabinoids in their acid forms to neutral forms followed by or after C0 2 extraction (under sub-critical or super-critical conditions), providing a crude extract.
  • the crude extract may then be “winterized,” that is, extracted with ethanol to remove lipids and waxes, as described for example in US 7,700,368, US 2004/0049059, and US 2008/0167483, which are incorporated herein by reference.
  • the method for obtaining the cannabis extract may further include purification steps such as a distillation step to further purify, isolate, or crystallize one or more cannabinoids, which is referred to herein as a “distillate”; US20160346339, which is incorporated herein by reference, describes a process for extracting cannabinoids from cannabis plant material using solvent extraction followed by filtration, and evaporation of the solvent in a distiller to obtain a distillate.
  • the distillate may be further cut with one or more terpenes.
  • the distillate may be further purified, for example using chromatographic and other separation methods known in the art, to obtain an “isolate.”
  • pure or isolated cannabinoids such as those provided in a cannabis extract, may be combined with water, lipids, hydrocarbons, or mixtures thereof.
  • the cannabinoid may be an isolated cannabinoid, for example having 50-75% purity (as in the case of a crude C0 2 extract), or > 80% purity (as in the case of a distillate), or >95% purity (as in the case of an isolate).
  • the cannabinoid may have a purity such as 50%-60%, or >65%, or >70%, or > 75%, or > 80%, or > 90%, or > 95%, or > 98%, or > 98%, or > 99%, or > 99.5%.
  • the composition may include up to 10% by weight cannabinoid.
  • the composition may include from about 0.01% by weight to about 10% by weight, more particularly from about 0.1% by weight to about 8% by weight, even more particularly from about 0.5% by weight to about 5% by weight, and even more particularly still from about 1.0% by weight to about 3% by weight of cannabinoid.
  • the composition may include about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10% by weight of cannabinoid.
  • the composition includes about 25 mg/mL total cannabinoids.
  • the cannabinoid component includes one or more cannabinoid distillates and isolates, and in particular, the cannabinoid component includes CBD distillates and/or isolates; THC distillates and/or isolates; or a combination of THC and CBD distillates and/or isolates. In some embodiments, the cannabinoid component includes THC distillates and/or isolates.
  • the cannabinoids may be introduced in the form of pure cannabinoids or as a cannabis concentrate.
  • pure cannabinoids is meant to refer to a single cannabinoid or a mixture of different cannabinoids that is free of other compounds.
  • the pure cannabinoids may be contained in solution in a diluent or other medium or may be a liquid or solid form of the pure cannabinoids absent any diluent.
  • the pure cannabinoids are synthetic or semi-synthetic cannabinoids.
  • Nonlimiting exemplary embodiments of a cannabis concentrate include a cannabinoid distillate, a cannabinoid isolate, a cannabis oil, or any other type of extract containing one or more cannabinoids.
  • the cannabinoid component may comprise other ingredients, including but not limited to one or more carrier oils, one or more terpenes, one or more emulsifiers, one or more flavor enhancer and/or flavor agent, or any combination thereof.
  • carrier oil refers to any suitable carrier oil.
  • carrier oils include borage oil, coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils, glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl, monolinoleate, glyceryl palmitate, glycerin/glycerol, glyceryl palmitostearate, glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl 10-oleate, polyglyceryl 10-oleate
  • the carrier oil can reduce the viscosity of the cannabinoids and/or provide other suitable properties. Further, at least in the case of solid cannabinoids (e.g., crystalline CBD), the carrier oil aids in its dissolution of the cannabinoid.
  • a combination of carrier oils may be used in the composition described herein. When more than one carrier is used, they may be used at any amount relative to the other. In an embodiment, a first carrier oil and a second carrier oil may be used at a ratio between 10:1 and 1 :10 by weight to each other.
  • the two carrier oils may be used at about a ratio of 3:1 , 2:1 , 1 :1 , 1 :2 or 1 :3 by weight to each other. In an embodiment, the two carrier oils may be used at about a 1 : 1 by weight ratio to each other.
  • the carrier oil may contribute to providing rapid onset of the cannabinoid in the composition described herein.
  • the carrier oil may improve the rate of absorption and/or onset of a medicinal, therapeutic and/or recreational effect of the cannabinoid.
  • the rapid onset occurs within 60 minutes, within 30 minutes, with 15 minutes, or less from administration of the composition to a subject.
  • the compositions are oil-based compositions and include the carrier oil in an amount of about 50 wt.% or more, preferably from about 50 wt.% to about 90 wt.%, including any amounts therein or any ranges therefrom.
  • the oil-based compositions may include the carrier oil in an amount of about 50 wt.%, about 60 wt.%, about 70 wt.%, about 80 wt.%, or about 90 wt.%.
  • the compositions are water-based compositions in the form of an emulsion.
  • the compositions can include the carrier oil in an amount of about 40 wt.% or less, preferably from about 5 wt.% to about 20 wt.%.
  • the water- based compositions may include the carrier oil in an amount of about 5 wt.%, about 10 wt.%, about 15 wt.%, or about 20 wt.%.
  • Terpenes refers to refer to a class of chemical components comprised of the fundamental building block of isoprene, which can be linked to form linear structures or rings. Terpenes may include hemiterpenes (single isoprenoid unit), monoterpenes (two units), sesquiterpenes (three units), diterpenes (four units), sesterterpenes (five units), triterpenes (six units), and so on. At least some terpenes are expected to interact with, and potentiate the activity of, cannabinoids.
  • terpenes known to be extractable from cannabis include aromadendrene, bergamottin, bergamotol, bisabolene, borneol, 4-3-carene, caryophyllene, cineole/eucalyptol, p-cymene, dihydroj asmone, elemene, farnesene, fenchol, geranylacetate, guaiol, humulene, isopulegol, limonene, linalool, menthone, menthol, menthofuran, myrcene, nerylacetate, neomenthylacetate, ocimene, perillylalcohol, phellandrene, pinene, pulegone, sabinene, terpinene, terpineol, 4-terpineol, terpinolene, and derivatives thereof.
  • terpenes include nerolidol, phytol, geraniol, alpha- bisabolol, thymol, genipin, astragaloside, asiaticoside, camphene, beta-amyrin, thujone, citronellol, 1 ,8-cineole, cycloartenol, and derivatives thereof.
  • emulsifier refers to a compound that can stabilize the cannabinoid in the water-based composition described herein, forming an emulsion.
  • the emulsion is in the form of a nanoemulsion.
  • the term “nanoemulsion” means an emulsion which is mainly constituted of particles having a particle size distribution which is less than about 1000 nm.
  • the emulsion is made of at least 95%, or at least 96%, or at least 97%, or at least 98%, or at least 99% of particles in the nanometric range (i.e., from Oto 1000 nm).
  • the nanoemulsion described herein has Dgo of about 200 nm or less, preferably of about 150 nm or less, more preferably of about 120 nm or less.
  • the nanoemulsion described herein has a particle size distribution of from about 20 nm to about 120 nm, preferably from about 30 nm to about 80 nm, more preferably from about 40 nm to about 60 nm.
  • particle size refers to a volume based particle size measured, for example, by dynamic light scattering (DLS) which is a non-invasive, well- established technique for measuring the size and size distribution of molecules and particles typically in the submicron region.
  • DLS dynamic light scattering
  • the DLS instrument has a laser light source which is used to illuminate the particles. Then, the generated scattered light fluctuates at a speed depending on the particle size. With the velocity of the Brownian motion, derived from the analysis of these fluctuations, and the Stokes-Einstein equation, particle size can be obtained. The particle size is reported as a volume equivalent sphere diameter.
  • Suitable emulsifiers include, but are not limited to, polysaccharide-based emulsifiers, protein-based emulsifiers, small molecule surfactants, and mixtures thereof.
  • suitable polysaccharide-based emulsifiers include, but are not limited to, gum arabic, modified starches such as octenyl succinate modified starches, modified cellulose such as methyl cellulose, hydroxypropyl cellulose, methyl hydroxypropyl cellulose, and carboxymethylcellulose, certain types of pectin such as beet pectin, soy soluble polysaccharide, corn fiber gum, and mixtures thereof.
  • suitable protein-based emulsifiers include, but are not limited to, globular proteins such as whey protein and whey protein ingredients such as whey protein concentrate, whey protein isolate, and highly purified protein fractions such as b-lactoglobulin and a- lactalbumin, flexible proteins such as gelatin and caseins such as sodium caseinate, calcium caseinate, and purified protein fractions, such as b-casein.
  • Milk-derived proteins e.g., caseins, in either monomeric or micellar form, or whey proteins
  • Milk proteins function as surface active ingredients in emulsions because of their amphiphilic structure, and they contribute to the stability of the emulsion droplets by a combination of electrostatic and steric stabilization mechanisms.
  • small molecule surfactants include, but are not limited to, polysorbate- type non-ionic surfactant, sugar esters such as sucrose monopalmitate, sucrose monostearate, sucrose distearate, sucrose polystearate, quillaja saponin (Q-NaturaleTM) and components thereof, sorbitan esters (SpansTM) such as Span 20 (sorbitan monolaurate), Span 40 (sorbitan monopalmitate), Span 60 (sorbitan monostearate), Span 80 (sorbitan monooleate).
  • sugar esters such as sucrose monopalmitate, sucrose monostearate, sucrose distearate, sucrose polystearate, quillaja saponin (Q-NaturaleTM) and components thereof
  • sorbitan esters SpansTM
  • Span 20 sorbitan monolaurate
  • Span 40 sorbitan monopalmitate
  • Span 60 sorbitan monostearate
  • Span 80 sorbitan mono
  • Emulsifiers such as lecithin, gum arabic, and octenyl succinate starches produce an emulsion with a negative charge on the surface of the droplet, which attracts pro-oxidant metal ions. This can be overcome using proteins, typically those derived from milk or soya.
  • the emulsifier includes a polysorbate-type non-ionic surfactant.
  • a polysorbate-type non-ionic surfactant for example, polyoxyethylene monostearate (PEG 400 Monostearate), polyoxyethylene monooleate (PEG 400 Monoleate), polyoxyethylene sorbitan monolaurate (Tween ® 20), polyoxyethylene sorbitan monolaurate (Tween ® 21), polyoxyethylene sorbitan monopalmitate (Tween ® 40), polyoxyethylene sorbitan monostearate (Tween ® 60), polyoxyethylene sorbitan monostearate (Tween ® 61), polyoxyethylene sorbitan tristearate (Tween ® 65), polyoxyethylene sorbitan monooleate (Tween ® 80), polyoxyethylene sorbitan monooleate (Tween 81), polyoxyethylene sorbitan trioleate (Tween ® 85), polyoxyethylene-(15)-stearic acid (
  • the emulsifier includes a mixture of a polysorbate-type nonionic surfactant and another emulsifier, such as lecithin.
  • the cannabinoid composition may include up to about 10% by weight emulsifier.
  • the cannabinoid composition includes the emulsifier in an amount of from about 0.01% by weight to 10% by weight, more particularly from about 0.1% by weight to about 8% by weight, even more particularly from about 0.5% by weight to about 5% by weight, and even more particularly still from about 1.0% by weight to about 3% by weight.
  • the cannabinoid composition may include the emulsifier in an amount of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10% by weight.
  • the cannabinoid composition of the present disclosure may include a ratio by weight of emulsifier to cannabinoid of from 10:1 to 1 :10, including any ratio value therein or any range of ratio values there in-between.
  • the ratio of emulsifier to cannabinoid may be of about 3:1 , about 2:1 , about 1:1 , about 1 :2, about 1 :3, and the like.
  • the cannabinoid composition may include a ratio by weight of emulsifier to carrier oil of from 5:1 to 1 :1, including any ratio value therein or any range of ratio values there in-between.
  • the ratio of emulsifier to carrier oil may be of about 3:1 , about 2:1 , about 1:1 , about 1:2, about 1 :3, and the like.
  • the ratio of emulsifier to carrier oil is of about 2:1 .
  • the cannabinoid component may include other ingredients in addition to the above described additional ingredients.
  • the composition includes a monohvdric alcohol
  • composition of the present disclosure further comprises a monohydric alcohol in an amount sufficient to increase transmucosal permeation of the composition while being below a threshold amount, the threshold amount being an amount beyond which the monohydric alcohol causes a significant stinging sensation upon contacting a mucosal surface of a subject.
  • the monohydric alcohol is present in an amount of about 30 wt.% or less, preferably about 20 wt.% or less.
  • the composition may include the monohydric alcohol in an amount of from about 5 wt.% to about 30 wt.%, more preferably from about 5 wt.% to about 20 wt.%, even more preferably from about 5 wt.% to about 15 wt.%, yet even more preferably from about 10 wt.% to about 15 wt.%, including any values therein.
  • the composition may include the monohydric alcohol in an amount of about 5 wt.%, about 10 wt.%, about 15 wt.%, or about 20 wt.%.
  • the monohydric alcohol includes ethanol.
  • the monohydric alcohol is ethanol.
  • the composition may include water in an amount of ⁇ 2 wt.%, or ⁇ 1.5 wt.%, or ⁇ 1.2 wt.%, or ⁇ 1 wt.%, or ⁇ 0.5 wt.%. In some embodiments, the composition may be water-free.
  • the composition of the present disclosure does not have a disagreeable taste.
  • a disagreeable taste can be a taste that is perceived such as, for example but not limited to, unpleasant, sharp, bitter, or synthetic.
  • the composition containing cannabinoids may be perceived to have a synthetic or bitter taste.
  • the composition may contain an effective amount of a flavor agent to mask the disagreeable taste.
  • the composition may include the flavor agent in an amount of ⁇ 10 wt.% , or ⁇ 8 wt.%, or ⁇ 5 wt.%.
  • the flavor agent may be present in an amount of from about 0.01 wt.% to about 10 wt.%, preferably from about 0.01 wt.% to about 4 wt.%, preferably from about 0.1 wt.% to about 3 wt.%, preferably from about 0.5 wt.% to about 2 wt.%, or a combination thereof.
  • the flavor agent may be one or more terpene as described above.
  • the composition may contain an effective amount of a flavor enhancer.
  • the flavor enhancer may be a natural extract or a synthetic extract.
  • the composition may include the flavor enhancer in an amount of from about 0.01 wt.% to about 5 wt.%, preferably from about 0.01 wt.% to about 1 wt.%.
  • the flavor enhancer may be selected from the group consisting of extracts of cinnamon, monk fruit, cucumber, mint, orange, lime, citrus, cookie dough, chocolate, vanilla, jasmine, lychee, almond, banana, grape, pear, pineapple, pine, oak, apple, pumpkin, grapefruit, watermelon, cotton sugar, durian, longan, taro, sapote, toffee nut, caramel, lotus, mango, mangosteen, coconut, coffee, strawberry, passion fruit, blueberry, raspberry, kiwi, walnut, cocoa, cherimoya, custard apple, papaya, fig, plum, nectarine, peaches, guava, honeydew, jackfruit, kumquat, loquat, palm, pomelo, persimmon, quince, and tamarind, or any combinations thereof.
  • flavor enhancer examples include, but are not limited to, mint oils, wintergreen, clove bud oil, cassia, sage, parsley oil, marjoram, lemon, orange, propenyl guaethol, heliotropine, 4-cis-heptenal, diacetyl, methyl-p-tert-butyl phenyl acetate, methyl salicylate, ethyl salicylate, 1-menthyl acetate, oxanone, a-irisone, methyl cinnamate, ethyl cinnamate, butyl cinnamate, ethyl butyrate, ethyl acetate, methyl anthranilate, iso-amyl acetate, iso-amyl butyrate, allyl caproate, eugenol, eucalyptol, thymol, cinnamic alcohol, octanol,
  • the composition of the present disclosure may be included in an article of manufacture comprising a dispenser, such as for example a spray dispenser or mist dispenser, which may use mechanical and/or electric means to dispense the composition.
  • a dispenser such as for example a spray dispenser or mist dispenser, which may use mechanical and/or electric means to dispense the composition.
  • the composition of the present disclosure can be formulated for delivery to, for example, the nasal and/or oral cavity, using spray devices or mist dispenser devices known in the art such as for example, via a pump action or pressurized administration vessel such as an aerosol spray (e.g., compressed air-, jet-, ultrasonic-, and piezoelectric nebulizers available from Pfeiffer and Valois).
  • aerosol spray e.g., compressed air-, jet-, ultrasonic-, and piezoelectric nebulizers available from Pfeiffer and Valois.
  • Such devices are familiar to the skilled artisan and can provide metered doses of the compositions, such as
  • the formulation of the composition is such that it provides a fine micellized mist spray comprising the cannabinoid suitable for mucosal delivery for effective transdermal absorption across the mucosa.
  • the fine mist ensures maximum surface coverage and therefore optimum delivery via transmucosal delivery, for example via the nasal and/or oral mucosa.
  • the composition is packaged into a cannabis product configured for administration to a mucosal surface of a subject.
  • the product can comprise a container enclosing the composition and an outlet nozzle for administration of the composition to the mucosal surface of the subject.
  • the cannabis product can be an oral spray, preferably a sublingual liquid spray form and/or a buccal liquid spray form.
  • procedures may be employed during manufacturing of the composition to reduce or avoid contamination with bacteria, yeast, or mold.
  • the composition may be processed and/or made such that there is less than 100,000 CFU of total viable aerobic bacteria count; less than 100,000 CFU/g of total yeast and mold count, preferably less than 10,000 CFU/g; less than 1000 CFU of bile-tolerant gram negative bacteria; less than 1000 CFU/g of total conforms count, preferably less than 100 CFU/g; or any combinations thereof.
  • Cannabis compositions described herein can be used for recreational and/or medicinal uses.
  • the cannabis compositions can be used to achieve a desired effect in a user, such as a psychoactive effect, a physiological effect, or a treatment of a condition.
  • a psychoactive effect it is meant a substantial effect on mood, perception, consciousness, cognition, or behavior of a subject resulting from changes in the normal functioning of the nervous system.
  • physiological effect it is meant an effect associated with a feeling of physical and/or emotional satisfaction.
  • treatment of a condition it is meant the treatment or alleviation of a disease or condition by absorption of cannabinoid(s) at sufficient amounts to mediate the therapeutic effects.
  • the methods according to the present disclosure comprise administering to a mucosa surface of a subject, preferably a nasal and/or oral mucosa (e.g., sublingual), an effective amount of the composition according to the present disclosure.
  • treating means obtaining a desired pharmacologic and/or physiologic effect.
  • the effect may be prophylactic, in terms of completely or partially preventing a disease, condition, or symptoms thereof, and/or may be therapeutic in terms of a partial or complete cure for a disease or condition and/or adverse effect, such as a symptom, attributable to the disease or disorder.
  • Treatment covers any treatment of a disease or condition of a mammal, such as a dog, cat or human, preferably a human.
  • the disease or condition is selected from the group consisting of: pain, anxiety, an inflammatory disorder, a neurological disorder, a psychiatric disorder, a malignancy, an immune disorder, a metabolic disorder, a nutritional deficiency, an infectious disease, a gastrointestinal disorder, and a cardiovascular disorder.
  • the disease or condition is pain.
  • the disease or condition is associated with the feeling of physical and/or emotional satisfaction.
  • the cannabinoid composition provides substantially no psychoactive effect or no psychoactive effect.
  • the “effective amount” administered and rate and time-course of administration will depend on the desired effect associated with a feeling of physical and/or emotional satisfaction in the subject.
  • the “effective amount” administered and rate and time-course of administration will depend on the nature and severity of the disease or condition being treated and typically also takes into consideration the condition of the individual subject, the method of administration and the like.
  • the present disclosure further relates to a method for reducing cannabinoid-associated effect variability between users.
  • the method includes providing a cannabis composition for administration to a mucosal surface of a user.
  • the cannabis composition has been described elsewhere herein and for conciseness sake will not be further described here.
  • the composition is enclosed in a cannabis article configured for administration of the composition to a mucosal surface of the user (e.g., sublingual).
  • the method may further include administration of the composition to the mucosal surface.
  • the composition may be administered by hand (e.g., pipetting or dropping) or applied utilizing a spray or mist apparatus, such as for example, a vaporizer or atomizer.
  • the scope of the present disclosure should be considered to cover one or more distinct applications of the composition or the continuous release of a composition via a vaporizer, mist generator, or other type of atomizer.
  • the composition may be administered via nasal or oral (e.g., buccal administration or sublingual administration), vaginal, ocular or rectal administration route.
  • the composition is administered to the mucosal surface via nasal routes, oral routes, or both.
  • the oral mucosa route of administration is attractive because it is a non-invasive route of administration, with the advantage of avoiding the first-pass metabolism, sustained action and ease of use.
  • the sublingual mucosa (i.e., mouth) and buccal mucosa (i.e., inside of the cheeks) are preferred due to the fact that permeability is greater there and it is possible to realize transmucosal absorption of the cannabinoid administration, resulting in a systemic effect.
  • the administered cannabinoids are absorbed transmucosally in the oral cavity within about 90 minutes, about 60 minutes, about 40 minutes, about 30 minutes, about 20 minutes, about 15 minutes, or about 10 minutes after administration.
  • the subject may experience an onset of the effect associated with the cannabinoid in an average time as low as about 10 minutes.
  • compositions of the present disclosure may thus also provide faster onset of a desirable psychoactive and/or physiological effect in a subject, particularly compared to art- known comparative compositions.
  • the compositions of the present disclosure may provide a less variable onset time across subjects, thus providing a more consistent and reliable onset of the desired psychoactive and/or physiological effect.
  • the present disclosure further relates to a kit or commercial package comprising the composition of the present disclosure and instructions for use.
  • the present disclosure relates to methods for producing a liquid composition containing a cannabinoid for administration to a mucosal surface of a subject.
  • the method includes mixing a cannabinoid component as described herein with a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain the desired effect while being below a threshold amount, as described elsewhere in this text.
  • the method optionally includes adding the herein described flavour agent and/or flavour enhancer.
  • the present disclosure relates to methods for producing an article of manufacture for administration of a composition containing a cannabinoid to a mucosal surface of a user.
  • the method includes mixing a cannabinoid component as described herein with a monohydric alcohol, where the monohydric alcohol is in an amount sufficient to obtain the desired effect while being below a threshold amount, as described elsewhere in this text.
  • the composition is a water-based composition
  • the method may include an emulsification step (or a self-emulsification step) with the addition of one or more emulsifier(s) thus forming an emulsion, e.g., a nanoemulsion.
  • Emulsification processes are known in the art and for conciseness sake will not be further described here (e.g., the reader can refer to W02020037413, WO/2020/037411, WO/2020/037412, WO/2020/037408, WO/2020/037410, and WO/2020/037409, which are each herein incorporated by reference in their entirety).
  • the method can further include filling a liquid reservoir of the article of manufacture (e.g., a spraying, dropping, mist-generating, or pipetting article).
  • a liquid reservoir of the article of manufacture e.g., a spraying, dropping, mist-generating, or pipetting article.
  • the step of filling the liquid reservoir may be performed by the same person formulating the composition or may be performed by another individual, for example.
  • the method of the present disclosure may include a further step of releasing the composition such that another individual receiving the composition can proceed to fill the liquid reservoir with the composition.
  • oil-based compositions were prepared with a cannabinoid component comprising 25-50 mg/mL of a cannabinoid and with a monohydric alcohol in accordance with embodiments of the present disclosure.
  • the cannabinoid component was first provided. A distillate comprising THC, CBD, or a mixture thereof (prepared in-house at the Applicant’s facilities) was dispensed in carrier oil, then heated to 70-80°C and stirred until homogenous (e.g., 5-10 minutes). Carrier oils used in these compositions included MCT oil, extra virgin olive oil, and/or hempseed oil. The resulting cannabinoid component was cooled to room temperature. Ethanol (USP grade > 94%) was then added to the cannabinoid component. The resulting composition was then stirred for 5 minutes. If included, natural flavor agents and flavor enhancers were then added and stirred until homogenous (e.g., 2-3 minutes). Turbidity and/or ethanol-caused burning sensation was improved by letting the composition equilibrate over a period of at least 24h. The quantities of components used is listed in Table 1 below.
  • compositions were prepared in accordance with the process set forth in Example 1.
  • the compositions were strawberry, lemon-lime and peppermint flavored compositions.
  • the ingredients are listed in Tables 1.1 to 1.3 below.
  • Example 3 Specific unflavored oil-based composition
  • a specific oil-based composition was prepared with a cannabinoid component including a THC distillate and with ethanol as monohydric alcohol in accordance with the process set forth in Example 1.
  • Example 2 The composition of Example 2 was incorporated into a spraying device, which was configured to provide a dosage of 2.5 mg of THC per spray.
  • a comparative commercially available spray device comprising an oil-based composition including a THC concentrate (cannabis extract obtained with C0 2 extraction) was also provided (ElixirTM THC spray, HEXO; 25 mg/mL THC and >95 wt.% MCT oil).
  • oil-based compositions were prepared with a cannabinoid component comprising a THC distillate and with ethanol as monohydric alcohol (“test composition”), or without ethanol (“reference composition”).
  • test and reference compositions according to Table 3 were each incorporated into respective spraying devices, which were configured to provide a dosage of 5 mg of THC per spray.
  • Table 4 and Fig. 2 shows the results on the onset times for the spray with and without ethanol.
  • Participants who did not feel any subjective effects were excluded.
  • a faster onset with the composition of the spray with ethanol was reported relative to the spray without ethanol.
  • the average onset time of about 21 minutes (median onset time of about 25 minutes) with the spray without ethanol was reduced to about 13 minutes (median onset time of about 14 minutes) for the spray with ethanol.
  • SEM standard error of the mean
  • water-based compositions in the form of a nanoemulsion were prepared with a cannabinoid component comprising 25-50 mg/ml_ of a cannabinoid and with a monohydric alcohol in accordance with embodiments of the present disclosure.
  • the cannabinoid component was first provided.
  • the ingredients making up the cannabinoid component are mixed under suitable conditions to ensure substantial mixing.
  • suitable conditions may include heating on a hot plate to 80 °C with a stir bar at medium agitation for about 5 minutes, but the reader will appreciate that other conditions may be implemented to obtain similar results.
  • the water phase was then provided.
  • the ingredients making up the water phase are mixed under suitable conditions to ensure substantial mixing.
  • suitable conditions may include adding surfactant and/or emulsifier to water and mixing on stirring plate at medium speed until complete dissolution, and then heating on a hot plate to °40 C with a stir bar at medium agitation for about 5 minutes.
  • surfactant and/or emulsifier may include adding surfactant and/or emulsifier to water and mixing on stirring plate at medium speed until complete dissolution, and then heating on a hot plate to °40 C with a stir bar at medium agitation for about 5 minutes.
  • the cannabinoid component was then added stepwise into the water phase while mixing at about 5000 rpm with a L5M-A lab homogenizer (Silverson, USA). After mixing, the resulting solution was homogenized with a PandaPLUS 2000 valve homogenizer (GEA, USA) to obtain a nanoemulsion characterized with a particle size of from about 60 nm to 90 nm, as measured with a DLS particle size analyzer (Anton Parr, Canada). [0128] The monohydric alcohol was then added to the nanoemulsion and mixed on a stirring plate at medium speed for about 5 to 10 minutes.
  • Example 6 Specific water-based compositions.
  • nanoemulsion compositions were prepared in accordance with the process set forth in Example 5 and using different amounts of monohydric alcohol.
  • the stability of the particle size in the resulting water-based compositions was tested up to 9 days postmanufacturing.
  • the nanoemulsion particle size is substantially stable up to 9 days post-manufacturing with up to 30% ethanol content.
  • Example 8 Specific water-based compositions
  • water-based compositions were prepared according to the process set forth in Example 5 using ethanol as monohydric alcohol.
  • the ingredients of the water-base formulations are listed in the following table 10.
  • the oil phase was added in a step-wise manner (e.g., dropwise) to the water phase and mixed between 20-25 °C.
  • Example 8 Sensory trial using water-based compositions
  • water-based compositions were prepared with a cannabinoid component comprising THC and with ethanol as monohydric alcohol (“test composition”), or without ethanol (“reference composition”).
  • test and the reference compositions demonstrated a nanoparticle size of about 70 nm.
  • the test and reference compositions according to Table 11 were each incorporated into respective spraying devices, which were configured to provide a dosage of 2.5 mg of THC per spray.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Dispersion Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente divulgation concerne une composition comprenant un cannabinoïde pour une administration à une surface muqueuse d'un sujet qui, lors de l'administration au sujet, fait preuve d'améliorations par rapport aux compositions de cannabis connues, par exemple en termes de pénétration transmuqueuse accrue de la composition, de délai d'action réduit, de réponse moins variable entre des sujets, plus particulièrement en termes de délai d'action et/ou d'intensité d'effet cannabinoïde, ou de toute combinaison de ces derniers. Ceci est obtenu par la fabrication d'une composition comprenant un constituant cannabinoïde et un alcool monohydrique, l'alcool monohydrique étant en une quantité suffisante pour obtenir l'effet souhaité tout en étant inférieure à une quantité seuil, la quantité seuil étant une quantité au-delà de laquelle l'alcool monohydrique provoque une sensation de picotement considérable lors de la mise en contact avec la surface muqueuse du sujet. Cette composition peut être utilisée pour des applications thérapeutiques ou de loisir.
PCT/CA2021/050956 2020-07-13 2021-07-12 Compositions de cannabis transmuqueuses à propriétés de pénétration accrues WO2022011460A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202063051127P 2020-07-13 2020-07-13
US63/051,127 2020-07-13
US202163141309P 2021-01-25 2021-01-25
US63/141,309 2021-01-25

Publications (1)

Publication Number Publication Date
WO2022011460A1 true WO2022011460A1 (fr) 2022-01-20

Family

ID=79555904

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2021/050956 WO2022011460A1 (fr) 2020-07-13 2021-07-12 Compositions de cannabis transmuqueuses à propriétés de pénétration accrues

Country Status (1)

Country Link
WO (1) WO2022011460A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2361869A (en) * 2000-03-09 2001-11-07 Pharmasol Ltd Cannabis-containing compositions for sublingual aerosol delivery
CA2683217A1 (fr) * 2007-03-29 2008-10-09 Yissum, Research Development Company Of The Hebrew University Of Jerusal Em Ltd Compositions pour administration nasale
CA2972247A1 (fr) * 2013-01-30 2015-08-06 Mentor Ip, Llc Thc sans fumee et son procede d'administration
CA3038473A1 (fr) * 2016-09-29 2018-04-05 Nissim Garti Formulations diluables de cannabinoides et leurs procedes de preparation
US20190167583A1 (en) * 2016-07-01 2019-06-06 GW Research Limited Oral cannabinoid formulations
CA3118898A1 (fr) * 2018-11-07 2020-05-14 Columbia Care Llc Formes posologiques sublinguales et buccales d'extraits cannabinoides et leur procede d'utilisation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2361869A (en) * 2000-03-09 2001-11-07 Pharmasol Ltd Cannabis-containing compositions for sublingual aerosol delivery
CA2683217A1 (fr) * 2007-03-29 2008-10-09 Yissum, Research Development Company Of The Hebrew University Of Jerusal Em Ltd Compositions pour administration nasale
CA2972247A1 (fr) * 2013-01-30 2015-08-06 Mentor Ip, Llc Thc sans fumee et son procede d'administration
US20190167583A1 (en) * 2016-07-01 2019-06-06 GW Research Limited Oral cannabinoid formulations
CA3038473A1 (fr) * 2016-09-29 2018-04-05 Nissim Garti Formulations diluables de cannabinoides et leurs procedes de preparation
CA3118898A1 (fr) * 2018-11-07 2020-05-14 Columbia Care Llc Formes posologiques sublinguales et buccales d'extraits cannabinoides et leur procede d'utilisation

Similar Documents

Publication Publication Date Title
US11013715B2 (en) Nanoemulsion hydrophobic substances
US20200330378A1 (en) Taste-enhanced cannabinoid submicron emulsion syrup compositions
AU2018100837A4 (en) Sleep Disorder Compositions and Treatments Thereof
US10206888B2 (en) Cannabis-based therapeutic product for treatment of chronic pain
US20190134125A1 (en) Enhanced smokable therapeutic cannabis product and method for making same
US20170367386A1 (en) Terpene flavoring compositions
US20190275268A1 (en) Multi-use cartridge for ingestion of cannabis-based products
WO2020037412A1 (fr) Systèmes d'auto-émulsification à base de cannabinoïde pour compositions infusées
JP2022535438A (ja) 熱ゲル化カンナビノイド組成物、並びにその製造方法及び使用方法
US20220241199A1 (en) Cannabinoid emulsion composition and method of manufacture
US20220241192A1 (en) Microemulsion Delivery Systems for Water-Based Beverages
US20220233441A1 (en) Microemulsion delivery systems for cannabis extracts and terpenes
US20190321306A1 (en) Cannabis-based therapeutic product for treatment of chronic pain
KR20210153052A (ko) 자폐증 스펙트럼 장애와 관련된 클러스터 증상을 치료하기 위한 제제
BR112020027060A2 (pt) Composição de canabinoide e método para tratar tept e/ou ansiedade
WO2022011460A1 (fr) Compositions de cannabis transmuqueuses à propriétés de pénétration accrues
US20230338329A1 (en) Cannabinoid emulsion composition and method of manufacturing
US20200094003A1 (en) Multi-use cartridge for ingestion of cannabis-based products
CN107847540B (zh) 防止或改善打鼾的乳化组合物
US20210046041A1 (en) Device and method for administering an active ingredient
US20220183972A1 (en) Nanoemulsion hydrophobic substances
WO2021179088A1 (fr) Compositions enrichies en terpène et leurs utilisations
US20240293347A1 (en) Composition and methods of treatment using transdermal hormone supplementation
WO2021179087A1 (fr) Compositions améliorées au terpène et leurs utilisations
JP2022022823A (ja) 電子タバコ用液体組成物及びそれを有する電子タバコ

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21841581

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21841581

Country of ref document: EP

Kind code of ref document: A1