WO2021179088A1 - Compositions enrichies en terpène et leurs utilisations - Google Patents

Compositions enrichies en terpène et leurs utilisations Download PDF

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Publication number
WO2021179088A1
WO2021179088A1 PCT/CA2021/050333 CA2021050333W WO2021179088A1 WO 2021179088 A1 WO2021179088 A1 WO 2021179088A1 CA 2021050333 W CA2021050333 W CA 2021050333W WO 2021179088 A1 WO2021179088 A1 WO 2021179088A1
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composition
terpene
composition according
cannabinoid
terpenes
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PCT/CA2021/050333
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English (en)
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Jamie SAVARD
Thong Trinh
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Hexo Operations Inc.
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Publication of WO2021179088A1 publication Critical patent/WO2021179088A1/fr

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    • 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
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A24B15/167—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes in liquid or vaporisable form, e.g. liquid compositions for electronic cigarettes
    • A—HUMAN NECESSITIES
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/18—Treatment of tobacco products or tobacco substitutes
    • A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
    • A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
    • A24B15/302—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances by natural substances obtained from animals or plants
    • A24B15/303—Plant extracts other than tobacco
    • 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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • 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
    • 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
    • A61K31/11—Aldehydes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • 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 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • 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

Definitions

  • the present disclosure relates to vaporizable compositions.
  • the present disclosure relates to compositions comprising terpenes in a diamond construction and optionally at least one cannabinoid, wherein the compositions are suitable for recreational and/or therapeutic uses. Methods of making and using said compositions are also encompassed by the present disclosure.
  • Vaporizable cannabinoid products are expected to grow in popularity due to the existing and/or expected legalization of these product forms in Canada and other countries (e.g., United States) globally. It is desirable to enhance the vaping experience by providing a specific aroma profile.
  • the formulator may wish to recreate a specific aromatic profile that is typically associated with the cannabis strain (e.g., earthy and piney aroma for OG Kush). Ideally, the recreated aroma profile will be perceived as being authentic to the aroma profile from the cannabis strain.
  • the formulator may, for example, wish to enhance the user experience by providing a specific fragrance character (e.g., fruity, spicy or green) that may be different from what is typically associated with that cannabis strain.
  • the formulator may wish to enhance the longevity and/or fidelity (i.e. , consistency) to a specific aroma profile preferably over the lifetime of the composition in use.
  • Cannabis can produce anywhere from about 100 to about 140 different terpenes, each of which may contribute to the distinctive blend of terpenes responsible for imparting the distinctive aroma profile for every cannabis strain (see Hillig 2004, “A chemotaxonomic analysis of terpenoid variation in Cannabis”, Biochem System and Ecology, 875-891).
  • a myrcene dominant aroma profile may be used to classify the profile that may in fact contain 16 other terpenes. As a result, these approaches could be considered misleading. Also, due to the somewhat subjective nature of aroma character identification, there has been no universal convention for objectively classifying and effectively formulating terpenes into blends that would impart a specific aroma profile consistently.
  • the inventors have developed a set of rules for objectively classifying terpenes according to their volatility for the purpose of formulating terpene mixtures, preferably complex mixtures having a unique diamond construction.
  • the new rules operate irrespective of formulators performing the formulation.
  • the new rules objectively classify the terpenes into low, moderate or high volatile terpene materials for formulating into terpene mixtures, particularly ones having a diamond construction.
  • a composition comprising a terpene component comprising: (a) at least one low volatile terpene having a vapor pressure less than about 0.005 Torr (0.000667 kPa) at 25°C present in an amount of from about 5 wt.% to about 37 wt.% relative to the total weight of the terpene component; (b) at least one moderate volatile terpene having a vapor pressure in the range of about 2.300 Torr (0.307 kPa) to about 0.005 Torr (0.000667 kPa) at 25°C present in an amount of from about 40 wt.% to about 94 wt.% relative to the total weight of the terpene component; and (c) at least one high volatile terpene having a vapor pressure greater than about 2.300 Torr (0.307 kPa) at 25°C present in an amount of from about 1 wt.% to about 23 wt.% relative to the total weight of the terpene component
  • Figure 1 is a diagram of a terpene diamond construction for enhancing an entourage effect in a user according to an embodiment of the present disclosure.
  • aroma profile means the description of how the aroma is perceived by the consumer at any moment in time. It is a result of the combination of the low, moderate and high volatile terpenes, if present, of an aroma.
  • An aroma profile is composed of two characteristics: “intensity” and “character”. The “intensity” relates to the perceived strength whilst “character” refers to the odour impression or quality of the aroma (e.g., fruity, floral, woody, etc.).
  • the “composition” of the present invention refers to a liquid, solid, or semi solid composition (e.g., distillate, extract, etc.) comprising an effective amount of a terpene formulation to enhance the effect of the cannabinoid to deliver the desired user experience profile.
  • the cannabinoid may be provided separately from or included in the composition of the present invention. In some embodiments, this involves recreating a known user experience associated with a specific cannabis strain based on the quantified user experience profile. In some embodiments, the composition may be formulated for oral or nasal administration.
  • the term “consumer” means both the user of the composition and the observer nearby or around the user.
  • diamond construction means a terpene formulation in which the relative weight percentages of the terpenes classified according to their volatility (/.e., low, moderate or high). Of note is that a diamond constructed terpene formulation has a substantially greater amount of the terpenes having a moderate volatility as compared to the low and high volatile terpenes. Examples of terpene formulations with a diamond construction are shown in Figure 1.
  • the term “effective amount” refers to an amount of one or more terpenes and optionally cannabinoids sufficient for the subject consuming the composition to feel a desired effect after vaporization and inhalation of the composition.
  • terpenes also known as “terpenoids” and can be used interchangeably
  • terpenes 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.
  • Suitable examples of the terpenes include those provided herein below.
  • cannabinoids are odorless
  • terpenoids are generally responsible for the unique odor of cannabis, with each variety of cannabis having a slightly different profile that can potentially be used as a tool for identification of different varieties. It also provides a unique and complex organoleptic profile for each variety that is appreciated by both novice users and connoisseurs.
  • some terpenes interact with neurological receptors.
  • a few terpenes produced by cannabis plants also bind weakly to cannabinoid receptors.
  • Some terpenes can alter the permeability of cell membranes and allow either more or less THC to enter, while other terpenes can affect serotonin and dopamine chemistry as neurotransmitters.
  • Terpenoids are lipophilic, and can interact with lipid membranes, ion channels, a variety of different receptors (including both G-protein coupled odorant and neurotransmitter receptors), and enzymes. Some are capable of absorption through human skin and passing the blood brain harrier.
  • Terpenes can be acquired commercially and are available in various purities. There are suppliers of pure and homogenous terpenes, contract laboratories that synthesize terpenes, and contract laboratories that purify terpenes from natural products, e.g., essential oils (see, e.g., Sigma-Aldrich, St. Louis, Mo.; TCI America, Portland, Oreg.; Arizona Chemical, Jacksonville, Fla.).
  • the term “pure” in reference to a “terpene” means that it is over about 85% pure, over about 90% pure, over about 95% pure, over about 98% pure, over about 99% pure, over about 99.5% pure, or over about 99.99% pure.
  • the term “pure” does not account for any solvent that may be used for dissolving the terpene, such as a solvent that is ethanol, acetone, tetrahydrofuran, and so on. Solvents suitable for dissolving terpenes are well-known in the art.
  • terpene material and “terpene materials” relate to a terpene or a mixture of terpenes that are used to impart a unique aromatic profile to a composition.
  • vapor pressure refers to the partial pressure in air at a defined temperature (e.g., 25°C) and standard atmosphere (e.g., 760 mmHg) for a given chemical species.
  • Vapor pressure is related to the rate of evaporation of a terpene which is defined in an open environment where terpene is leaving the system.
  • the new classification approach better reflects the technical properties of terpenes with respect to evaporation.
  • Vapor pressure for the terpenes can be readily determined by their CAS registry number using SciFinderTM. SciFinderTM uses reference program Advanced Chemistry Development (ACD/Labs) Software Version 2019. Vapor pressure is expressed in 1 Torr, which is equal to 0.133 kilopascal (kPa).
  • the herein described vaporizable compositions are typically used for recreational or medicinal uses.
  • the herein described vaporizable 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.
  • neuroactive 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.
  • treating is used herein to mean 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 “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 inventors have surprisingly discovered a new approach of objectively classifying terpenes and then formulating those terpenes into complex terpene mixtures that can complement the cannabinoid, which may be provided separately from or included in the composition of the present disclosure, and have an entourage effect in a user.
  • the approach described in the present application to achieve an entourage effect is to formulate the terpenes into a diamond construction to provide for a specific ratio of various terpenes to cannabinoid, the various terpenes being categorized according to their volatility, as further described below.
  • the inventors have discovered that in the absence of the diamond construction there may be a lesser or no entourage effect associated with the use of the composition. Therefore, the levels of the terpenes need to be carefully chosen.
  • the present disclosure provides for a composition
  • a composition comprising a terpene component comprising: (a) at least one low volatile terpene having a vapor pressure less than about 0.005 Torr (0.000667 kPa) at 25°C present in an amount of from about 5 wt.% to about 37 wt.% relative to the total weight of the terpene component; (b) at least one moderate volatile terpene having a vapor pressure in the range of about 2.300 Torr (0.307 kPa) to about 0.005 Torr (0.000667 kPa) at 25°C present in an amount of from about 40 wt.% to about 94 wt.% relative to the total weight of the terpene component; and (c) at least one high volatile terpene having a vapor pressure greater than about 2.300 Torr (0.307 kPa) at 25°C present in an amount of from about 1 wt.% to about 23 wt.% relative to
  • the composition according to the present disclosure comprises the terpene component present in an amount of from about 1 wt.% to about 30 wt.%, from about 3 wt.% to about 20 wt.%, or from about 5 wt.% to about 15 wt.% relative to the total weight of the composition.
  • the terpene component is present in an amount of from about 1 wt.%, 2 wt.%, 3 wt.%, 4 wt.%, 5 wt.%, or 6 wt.% to about 10 wt.%, 11 wt.%, 12 wt.%, 13 wt.%, 14 wt.% or 15 wt.%, relative to the total weight of the composition.
  • the terpene component of the composition having an entourage effect may comprise the terpenes described below.
  • the terpene component comprises at least one low volatile terpene having a vapor pressure less than about 0.005 Torr (0.000667 kPa) at 25°C.
  • the composition according to the present disclosure comprises at least 1 low volatile terpene, or at least 2 low volatile terpenes.
  • the compositions of the present disclosure can comprise low levels of the at least one low volatile terpene present in an amount of from about 5 wt.% to about 37 wt.%.
  • the at least one low volatile terpene may be present in an amount of from at least about 5 wt.%, 6 wt.%, 7 wt.%or 8 wt.%, 9 wt.%, 10 wt.%, to less than about 35 wt.%, 36 wt.%, or 37 wt. %, relative to the total weight of the terpene component. If there is more than one low volatile terpenes, then the ranges provided hereinabove cover the total of all the low volatile terpenes.
  • Preferable examples of low volatile terpenes are selected from the group consisting of Low Volatile Terpene Materials as provided in Table 1 below and mixtures thereof.
  • the low volatile terpenes are selected from the group consisting of phytol, alpha bisabolol, caryophyllene acetate, maltol isobutyrate, and mixtures thereof.
  • the terpene component comprises at least one moderate volatile terpene having a vapor pressure in the range of about 2.300 Torr (0.307 kPa) to about 0.005 Torr (0.000667 kPa) at 25°C.
  • the composition according to the present disclosure may comprise at least 1 moderate volatile terpene, at least 2 moderate volatile terpenes or at least 3 moderate volatile terpenes.
  • the compositions of the present disclosure may comprise the moderate volatile terpenes present in an amount of from about 40 wt.% to about 94 wt.%, relative to the total weight of the terpene component.
  • the at least one moderate volatile terpene may be present in an amount of from at least about 40 wt.%, at least about 45 wt.%, at least about 50 wt.%, or at least about 55 wt.% to less than about 94 wt.%, less than about 90 wt.%, less than about 85 wt.%, less than about 80 wt.%, or less than about 75 wt.%, relative to the total weight of the terpene component. If there is more than one moderate volatile terpene, then the amount provided hereinabove represents the combined total of all the moderate volatile terpenes.
  • Moderate volatile terpenes may be selected from the group of Moderate Volatile Terpene Materials provided in Table 2 below, and mixtures thereof.
  • the moderate volatile terpene may be selected from the group consisting of humulene (a-caryophyllene), valencene, beta caryophyllene, citral, orange terpenes, linalool, gamma terpinene, alpha-terpineol, terpineolene, d-limonene, natural myrcene, alpha terpinene, and mixtures thereof.
  • the terpene component comprises at least one high volatile terpene having a vapor pressure greater than about 2.300 Torr (0.307 kPa) at 25°C.
  • the composition according to the present disclosure may comprise at least 1 high volatile terpene or at least 2 high volatile terpenes.
  • the compositions of the present disclosure can comprise the high volatile terpenes in an amount of from about 1 wt.% to about 23 wt.%, relative to the total weight of the terpene component.
  • the at least one high volatile terpene may be present in an amount of from at least about 1 wt.%, at least about 2 wt.%, at least about 4 wt.%, or at least about 5 wt.% to less than about 23 wt.%, less than about 22 wt.%, less than about 21 wt.%, or less than about 20 wt.%, relative to the total weight of the terpene component. If there is more than one high volatile terpene, then the amount provided hereinabove represents the combined total of all the high volatile terpenes.
  • High volatile terpenes may be selected from the group of High Volatile Terpene Materials provided in Table 3 below, and mixtures thereof.
  • the high volatile terpene may be selected from the group consisting of beta terpinene, beta pinene, delta 3 carene, alpha pinene, and mixtures thereof.
  • compositions of the present disclosure may optionally comprise at least one cannabinoid.
  • Cannabinoids are commonly used for recreational purposes to produce physiological effects associated with a feeling, mood and/or emotion.
  • cannabinoids are generally understood to include any chemical compounds that act upon a cannabinoid receptor.
  • Cannabinoids may include endocannabinoids (i.e., produced naturally by humans and animals), phytocannabinoids (i.e. , found in cannabis and some other plants), and semi-synthetic or synthetic cannabinoids (i.e., manufactured artificially, for example cannabinoids produced in yeast, for example as described in WO WO2018/148848).
  • phytocannabinoids 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 (CBGM), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), cannabinodiol (CBND),
  • Cannabidiol means one or more of the following compounds: A2-cannabidiol, D5- 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.
  • Examples of synthetic cannabinoids include, but are not limited to, naphthoylindoles, naphthylmethylindoles, naphthoylpyrroles, naphthylmethylindenes, phenylacetylindoles, cyclohexylphenols, tetramethylcyclopropylindoles, adamantoylindoles, indazole carboxamides, and quinolinyl esters.
  • the at least one cannabinoid in the cannabinoid composition as described herein may be in an acid form or a non-acid form, the latter also referred to as the decarboxylated form, since the non-acid form can be generated by decarboxylating the acid form.
  • the cannabinoid can be in its acid or non-acid form or may be a mixture of both acid and non-acid forms.
  • the cannabinoid is cannabidiol (CBD), tetrahydrocannabinol (THC) or a mixture thereof.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • CBD cannabinoid
  • suitable mixtures of the cannabinoid that can be used in the present disclosure include a mixture of THC and CBD. Certain specific ratios of cannabinoids may be useful to produce the desired feeling, mood and/or emotion.
  • the cannabinoid is a mixture of THC and CBD, for example in a weight ratio (w/w) of from about 1:1000 to about 1000:1.
  • the (w/w) ratio of THC to CBD in the composition 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, about 1:16, about 1:15, about 1:14, about 1:13, about 1 :12, about 1:11, about 1:10,
  • the cannabinoid or each of the cannabinoids may be an isolated cannabinoid having > 90%, > 95%, > 98%, > 98%, > 99% or > 99.5%, purity present in at least one carrier oil or solvent. It is especially preferred that the cannabinoids have high purity (/.e., Pharmacopoeia Grade substances, which may be obtained from a natural source or via synthetic means) to enable sufficient solubility in a liquid composition or to lead to substantially homogeneous distribution in a solid or semi-solid composition.
  • Suitable carriers and solvents for cannabinoids are known in the art.
  • Non-limiting examples of carrier oils or solvent suitable for use with cannabinoids include: borage oil, castor oil, a citrus oil (e.g., lemon oil, orange oil), coconut oil, corn oil, cottonseed oil, a flax seed oil, a grape seed oil, a marine oil (e.g., a fish oil, an algal oil, a fungal oil), a mustard oil, a nut oil (e.g., peanut oil, almond oil, cashew oil, walnut oil), olive oil, palm oil (and/or a fraction thereof), palm kernel oil, peppermint oil, poppy seed oil, rapeseed oil (e.g., a canola oil), a rice bran oil, safflower oil, sesame oil, soybean oil, hydrogenated
  • the composition according to the present disclosure comprises the at least one cannabinoid present in an amount of from about 70 wt.% to about 99 wt.%, preferably from about 80 wt.% to about 97 wt.%, or preferably from about 85 wt.% to about 95 wt.% relative to the total weight of the composition.
  • the cannabinoids for use with or inclusion in the compositions as described herein may be obtained from any source material comprising cannabinoids known in the art.
  • suitable examples of source material comprising cannabinoids include, but are not limited to, cannabis or hemp plant material (e.g., flowers, seeds, trichomes, and kief), milled cannabis or hemp plant material, extracts obtained from cannabis or hemp plant material (e.g., resins, waxes and concentrates), and distilled extracts or kief.
  • pure or isolated cannabinoids and/or source materials comprising cannabinoids may be combined with water, lipids, hydrocarbons (e.g., butane), ethanol, acetone, isopropanol, or mixtures thereof.
  • the composition comprises or is used with an effective amount of the at least one cannabinoid for producing physiological effects associated with a feeling, a mood and/or an emotion.
  • the composition comprising the at least one cannabinoid may comprise the at least one cannabinoid in an amount of from about 0.001 mg/ml_ to about 500 mg/ml_, from about 0.005 mg/ml_ to about 300 mg/ml_, from about 0.01 mg/ml_ to about 100 mg/ml_, from about 0.5 mg/ml_ to about 50 mg/ml_, from about 0.1 mg/ml_ to about 20 mg/ml_ or from about 0.1 mg/ml_ to about 10 mg/ml_, or any ranges therein, of the at least one cannabinoid.
  • Cannabinoid provided at such an amount can be particularly effective in producing physiological effects associated with a feeling, a mood and/or an emotion.
  • the at least one cannabinoid may be used with or included in the composition in a weight ratio of from about 100:1 to about 1:1, from about 20:1 to about 2:1, or from about 10:1 to about 4:1 cannabinoid:terpene.
  • composition according to the present disclosure may additionally comprise the usual and conventional ancillary components or ingredients that are known to one skilled in the art. It will be appreciated that selected components or ingredients for the compositions must be chemically and physically compatible with one another. Furthermore, and as would be known to a person of skill in the art, the composition of the present invention may also comprise ingredients commonly included in liquid or solid formulations, based on the application in which the composition shall be used.
  • the present disclosure may relate to a composition for use in a vaping device.
  • the composition may be a liquid vaporizable composition for pulmonary administration.
  • the cannabinoid composition for use in a vaping device may be formulated for vaporization and/or inhalation using a heat vaporizer or a nebulizer.
  • the composition may be a solid composition formulated for use in a heating or vaporizing device.
  • compositions described herein may be for use in an edible.
  • Ingredients used in edible products are commonly known in the art.
  • compositions of the present disclosure may comprise an aroma enhancer as described herein below. Suitable examples of the aroma enhancer are known to those skilled in the art or disclosed in US Patent No. 3,625,709. [0067]
  • the aroma enhancer may be present in an amount of from about 0.01 wt.% to about 15 wt.%, from about 0.1 wt.% to about 18 wt.%, from about 1 wt.% to about 12 wt.%, from about 2 wt.% to about 10 wt.%, from about 5 wt.% to about 8 wt.%, relative to the total weight of the composition. If there is more than one aroma enhancer then the amount provided hereinabove represents the combined total of all the aroma enhancers.
  • An aroma enhancer of the present disclosure may be a liquid or a solid at ambient temperatures.
  • the aroma enhancer may be fully miscible with the terpenes to form a single phase liquid or substantially homogeneous solid.
  • co-solvents well known to those skilled in the art can be added to aid in the solubility of the terpenes.
  • the compositions according to the present disclosure may be in liquid form and have a viscosity at room temperature suitable for use in a vaping device.
  • cannabinoids and/or terpenes undergo solvent extractions and winterization. The extracted products are then reconstituted in suitable solvents.
  • the viscosity of the terpenes and optional cannabinoids may be high due to the inherent physiochemical properties of the reconstituted solvents.
  • the cannabinoids and/or terpenes may be diluted in a suitable solvent (e.g., carrier oil as described herein above), to obtain a viscosity that is appropriate for proper operation of the vaping device.
  • the solvent into which the terpenes and the optional cannabinoids are formulated can be made more viscous to increase the concentrations of the terpenes and the optional cannabinoids. In some embodiments, the solvent into which the terpenes and the optional cannabinoids are formulated can be made less viscous to decrease the concentrations of the terpenes and the optional cannabinoids.
  • viscosity modifier refers to any additive that can modify the composition viscosity to a desired viscosity level (either higher or lower). Typical examples include, without limitations, solvents, and gelling agents.
  • Such viscosity modifiers may be, for example and without wishing to be limiting, Aerosil (silicon dioxide), cetostearyl alcohol, cetyl alcohol, stearyl alcohol, Gelucire 33/01, Gelucire 39/01; Gelucire 43/01 ; glyceryl behenate (Compritol 888 ATO); glyceryl palmitostearate (Precirol AT05); Softisan 100; Softisan 142; Softisan 378; Softisan 649; hydroxypropyl cellulose and mixtures thereof.
  • the rheological measurements to measure viscosity of a solution can be carried out using a rheometer, for example, a Brookfield R/S Plus controlled-shear-rate rheometer (Brookfield Engineering Labs, Middleboro-MA, USA) with concentric cylinder geometry (CC25) or a Rheosys Merlin II with 25mm concentric cylinder.
  • the tests can be performed at various temperatures, for example but without being limited at 10°C, room temperature, 30°C, 50°C, and/or 70°C.
  • the temperature can be controlled by, for example, a LAUDA 3200 thermostatic bath (Lauda, Lauda- Konigshofen - Germany), properly attached to the rheometer.
  • the shear stress and apparent viscosity data can be obtained in a controlled rate method, for example one ranging from 0 to 300 s-1 on the upward curve, and 300 to 0 s-1 on the downward curve.
  • the total run time for each ascending and descending curve can be any suitable time, for example 5 min; shear stress and apparent viscosity values can be obtained at any suitable interval, for example every 7.5 s, resulting in 40 points. All the analyses can be carried out in duplicate. pH Modifiers
  • the composition of the present disclosure may include one or more pH adjusting agents to improve stability. It is believed that pH modifiers can also control cannabinoid release, if cannabinoids are included in the composition.
  • the pH of the composition is from about 5 to about 9, or from about 5.5 to about 7.5. Alternatively, the pH can be greater than about 6, greater than about 7, or from about 8 to about 10.
  • the pH of the composition may be modified using any acceptable means. Suitable examples of pH modifiers include, but are not limited to, organic acid or base, for example, but not limited to tartaric acid, phosphoric acid, hydrochloric acid, maleic acid, sodium hydroxide, citric acid and the like, known to those of ordinary skill in the art.
  • the pH is typically measured using a weight ratio of 1:3 of com position: water, whereby 1 gram of the composition is mixed into 3 grams of deionized water, and then the pH is assessed with an industry-accepted pH probe that is calibrated under ambient conditions.
  • the pH may be measured by a pH meter with Automatic Temperature Compensating (ATC) probe.
  • ATC Automatic Temperature Compensating
  • the pH meter may be capable of reading to 0.001 pH unit.
  • the composition of the present disclosure comprises effective amounts of one or more stabilizers to promote stability of the composition against unacceptable degradation.
  • the stabilizers may comprise one or more anti-oxidants, one or more organic bases, and/or other stabilizers known to those skilled in the art.
  • the stabilizers comprise povidone (polyvinylpyrrolidone, PVP).
  • the term “stability”, as it applies to the cannabinoid composition of the present disclosure, means that at least about 80 wt.%, or at least about 90 wt.% of the cannabinoids and/or terpenes in the cannabinoid composition are in undegraded form after exposure of the composition to standard storage conditions.
  • Storage conditions may be storage at (i) 2-8°C, (ii) 25°C/60% relative humidity (RH) for 6-24 months; (iii) 30°C/60% relative humidity (RH) for 6 months; (iv) 40°C/60% relative humidity (RH) for 1-8 months; or (v) any combination thereof.
  • the composition may be a liquid, solid, or semi-solid vaporizable composition formulated for vaporization and/or inhalation using a heat vaporizer or a nebulizer.
  • the composition when the composition is formulated for pulmonary administration via nebulizer, the composition may comprise from about 15 wt.% to about 50 wt.% ethanol, from about 15 wt.% to about 60 wt.% buffered aqueous solution, from about 0.1 wt.% to about 25 wt.% propylene glycol and from about 1 wt.% to about 30 wt.% polyethylene glycol.
  • compositions described herein may be for use in an edible.
  • Ingredients used in edible products are commonly known in the art.
  • the concentration of the terpenes and cannabinoids can be easily correlated to the number of vaporization events (e.g., puffs) by the consumer.
  • Some consumers desire to obtain a quick effect with the minimum number of puffs. In these instances, compositions with higher terpene/cannabinoid concentrations are desired. Other consumers may prefer a slower effect over a plurality of puffs. In these instances, compositions with lower terpene/cannabinoid concentrations are preferred.
  • the consumer vaporizing and inhaling the composition may adjust the amount of terpenes and cannabinoids (provided separately or in the composition of the present disclosure) inhaled according to the desired cannabinoid and/or terpene intake; for example, if the carrier oil is of relatively low terpene/cannabinoid concentration, the consumer can inhale a little more (e.g., more puffs or larger puffs), or if the carrier oil is of relatively high terpene/cannabinoid concentration, the consumer can inhale a little less (e.g., less puffs or smaller puffs), to achieve the desired effect.
  • the carrier oil is of relatively low terpene/cannabinoid concentration
  • the carrier oil is of relatively high terpene/cannabinoid concentration
  • the composition according to the present disclosure has a characteristic aroma profile, which is a description of how the aroma is perceived by the human nose at any moment in time.
  • the aroma profile is a result of the combination of the low, moderate and high volatile terpenes of a composition.
  • An aroma profile is composed of two characteristics: “intensity” and “character”. The “intensity” refers to the perceived strength whilst “character” refers to the aroma impression or quality of the terpenes. Accordingly, the aroma profile therefore can be characterized by aroma character, aroma intensity or both.
  • the aroma profile associated with a composition of the present disclosure remains consistent, or substantially consistent, to an initial impression of the aroma profile to a consumer. In some embodiments, the aroma profile associated with a composition of the present disclosure remains consistent over time during vaporization and inhalation. The consistency in the aroma profile is characterized by consistency in the aroma character, consistency in the aroma intensity, or both. In one embodiment, the aroma profile remains consistent over one or more vaporization events (i.e. , puffs).
  • the term “initial impression” refers to the aroma profile upon (vaporization and) inhalation of the composition initially by the consumer.
  • enhanced fidelity it can mean that the perception by the consumer of the fidelity of the aroma profile contributed by the terpenes is markedly increased or enhanced as compared to controls.
  • Increased or “enhanced” in this context of “fidelity” means that the consumer perceives the aroma profile of a composition as not changing from their initial impression or that the changes are minimal from when the composition was first vaporized and inhaled. In other words, the fidelity of the perceived aroma profile of the composition is maintained over time.
  • the aroma profile associated with a composition of the present disclosure changes over time during the vaporization and inhalation.
  • the changes in the aroma profile may be characterized by changes in aroma character, changes in aroma intensity, or both.
  • the changes in the aroma profile may occur over one or more vaporization events (i.e. , puffs).
  • the present disclosure provides the formulator options to formulate compositions having new aroma profiles not previously possible.
  • composition of the present disclosure according to any embodiments described herein is useful for exhibiting an entourage effect.
  • composition of the present disclosure may be used in a conventional manner.
  • the composition of the present disclosure can be formulated for inhalation into the lungs (e.g., by a heat vaporizer (“vape”) or nebulizer).
  • vape heat vaporizer
  • the present disclosure relates to a method for vaporizing (and inhalation) of a composition as described herein.
  • the method comprises vaporization and inhalation by a consumer of an effective amount of a composition according to the present disclosure.
  • the “effective amount” vaporized and inhaled will depend on the desired effect associated with a feeling of physical and/or emotional satisfaction in the consumer.
  • the present disclosure also relates to a method of formulating a terpene component comprising selecting at least one low volatile terpene having a vapor pressure less than about 0.005 Torr (0.000667 kPa) at 25°C, at least one moderate volatile terpene having a vapor pressure in the range of about 2.300 Torr (0.307 kPa) to about 0.005 Torr (0.000667 kPa) at 25°C, and at lest one high volatile terpene having a vapor pressure greater than about 2.300 Torr (0.307 kPa) at 25°C, each in an amount described elsewhere herein.
  • the at least one low volatile terpene, at least one moderate volatile terpene, and at least one high volatile terpene in the terpene component may be selected from those terpenes listed elsewhere herein.
  • the terpene component may be formulated to achieve a specific desired effect in a user, for example but not limited to enhancing the entourage effect.
  • the present disclosure further relates to a kit comprising the composition of the present disclosure and instructions for use.
  • SciFinderTM uses Advanced Chemistry Development (ACD/Labs) Software ( ⁇ 2019). If the CAS number for the specific terpene is unknown or does not exist, then the ACD/Labs reference program can be used to directly determine the vapor pressure. Vapor pressure is expressed in 1 Torr, which is equal to 0.133 kilopascal (kPa).
  • test compositions comprising terpene mixtures are made, as described in the Examples section in liquid oil concentrated cartridges, and control samples (i.e., formulations with terpenes not in a diamond construction) are given to panelists to evaluate.
  • the cartridges can be snapped into place with a vaporizer device (e.g., RUBI from KandyPensTM).
  • Descriptive analysis method used to identify and quantify the aroma profile of the samples involves the use of human subjects, preferably human subjects who have been specifically trained for this purpose (i.e., trained panelists). Each of the samples is evaluated by 5-10 trained panelists per session. The panelists vaporize and inhale the samples. In particular, the panelists place their noses within 2-5 cm from the source of the aroma and evaluate the perceived aroma profile (character and/or intensity) of the samples after multiple vaping incidents or “puffs”. Each puff lasts about 1-2 seconds. The trained panelists are requested to take 4 puffs and then asked to score the “character” and “intensity” of the aroma profile in a questionnaire.
  • the “character” of the aroma is scored using the aroma descriptors provided in Table 10 and the “intensity” of the aroma is scored on a scale of 1 to 10, with 1 being “none” and 10 being “very strong”.
  • the panelists complete separate questionnaires for the test samples and corresponding controls. After 5, 10, 15, 20, 25, 30, 45 or 60 minutes, the trained panelists repeat the above steps for a second evaluation. Additional evaluation(s) may be performed with each subsequent 5-, 10-, 15-, 20-, 25-, 30-, 45- or 60-minute intervals, if desired.
  • Terpene examples 1 and 2 are provided below in Tables 5 and 6, respectively, as a non limiting example of formulations of terpene mixtures intended to form the terpene component of the compositions of the present disclosure.
  • the exemplary formulations of the terpenes provide an aroma profile intended to enhance a pleasant mood (e.g., Table 11 - Relax Accord), enhance socialization (e.g., Table 12 - Fun Accord), or enhance sexual pleasure (e.g., Table 13 - Sex Accord) in a user, respectively.
  • terpene formulations are made by admixing the listed ingredients in the listed proportions (wt.%) at room temperature, wherein the wt.%is relative to the total weight of the terpene component.
  • Example 2 Compositions Comprising Terpene Mixtures
  • compositions A and B are examples of compositions according to the present disclosure, made with the Terpene Examples 1 and 2, respectively.
  • control compositions A1 and B1 are prepared by replacing the Terpene Examples 1 and 2 with terpene mixtures containing the same materials not in a diamond construction. All the compositions are prepared by admixture of the components described in Table 7, in the proportions indicated.
  • Compositions disclosed in Table 7 are sampled in accordance with the protocol described in the Test Methods Section and a panel of 5-10 experienced panelists evaluated the perceived aroma profile at initial time 0, then at various time points, typically in 5 minute intervals post sampling using an appropriate questionnaire. Panelists are asked to score the samples for the initial impression of the aroma profile (i.e., character and intensity), and the fidelity of the aroma profile to the initial impression. The results of the panelists are then averaged and plotted together with the confidence intervals. The results show the effect of the terpene component in a diamond construction for Compositions A and B. The diamond construction of the terpene component resulted in noticeable fidelity in the aroma profile.

Abstract

La présente invention concerne une composition comprenant : i) des terpènes dans une construction en diamant pour délivrer un profil d'arôme spécifique ; et ii) facultativement, au moins un cannabinoïde. La présente invention concerne également des procédés d'utilisation de la composition pour améliorer une expérience d'utilisateur associée à la composition.
PCT/CA2021/050333 2020-03-13 2021-03-11 Compositions enrichies en terpène et leurs utilisations WO2021179088A1 (fr)

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Citations (3)

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WO2018148152A1 (fr) * 2017-02-07 2018-08-16 Wayne Green Compositions à base de terpène, procédés de préparation et leurs utilisations
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CA2929280A1 (fr) * 2013-10-31 2015-05-14 Full Spectrum Laboratories, Ltd. Formulations de terpene et de cannabinoides
WO2018148152A1 (fr) * 2017-02-07 2018-08-16 Wayne Green Compositions à base de terpène, procédés de préparation et leurs utilisations
WO2019210402A1 (fr) * 2018-05-01 2019-11-07 Willinsky Michael Administration sélective d'inhalants terpènes/terpénoïdes volatiles

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