Aerosolizable Materials

Abstract

The present disclosure relates to aerosolizable materials, methods of making said materials, and containers and systems that contain and use said materials.

Description

Field

[0001] The present disclosure relates to aerosolizable materials, methods of making said materials, and containers and systems that contain and use said materials.

[0002] Aerosol delivery systems that generate aerosols for inhalation by a user are known in the art. Such systems typically include an aerosol generator that can convert an aerosolizable material into an aerosol. In some cases, the aerosol generated is a condensation aerosol, whereby the aerosolizable material is heated to form a vapor and then condenses into an aerosol. In other examples, the aerosol generated is an aerosol resulting from atomization of the aerosolizable material. Such atomization can be effected mechanically, for example, by subjecting the aerosolizable material to vibration to form small particles of the material that are entrained in an airflow. Alternatively, such atomization can be effected electrostatically or by other means, such as by using pressure, etc.

[0003] Depending on the components of the aerosolizable material to be provided to a user, it may be preferable to formulate the aerosolizable material in a certain way. For example, it may be preferable to formulate the aerosolizable material to generate an aerosol having a particular profile. It may be preferable to formulate the aerosolizable material to ensure that the aerosolizable material meets certain standards of quality, consistency, etc.

[0004] It would therefore be desirable to provide aerosolizable materials that are formulated to be acceptable to the user.

[0005] In one aspect, there is provided an aerosolizable material comprising at least one cannabinoid, a carrier component comprising at least 50% w / w propylene glycol, one or more antioxidants, and 0.01-12% w / w of one or more sensates, the carrier component being present at 70% w / w or greater based on the total weight of the aerosolizable material, the one or more antioxidants being not sensates, and the one or more sensates being not antioxidants. The terms "sensates" and "antioxidants" are well known in the art and are discussed further below.

[0006] In a further aspect, an article is provided that includes an aerosolizable material as defined herein.

[0007] In a further aspect, there is provided an aerosol delivery system comprising an aerosol delivery device and an article as defined herein.

[0008] In a further aspect there is provided a method for producing an aerosolizable material as defined herein, the method comprising combining at least one cannabinoid and a carrier component comprising at least 50% w / w propylene glycol, the carrier component being present at 70% w / w or more based on the total weight of the aerosolizable material, with one or more antioxidants and 0.01-12% w / w of one or more sensates, wherein the one or more antioxidants are not sensates and the one or more sensates are not antioxidants.

[0009] In a further aspect, there is provided a sealed container containing an article as defined herein.

[0010] In a further aspect, there is provided a process for forming an aerosol, the process comprising: (i) providing an aerosolizable material as defined herein; and (ii) aerosolizing the material.

[0011] In a further aspect, there is provided use of one or more sensory agents to reduce or mask a physiological response of a user to at least one cannabinoid in an aerosolizable material, the aerosolizable material comprising at least one cannabinoid and a carrier component comprising at least 50% propylene glycol, the carrier component being present at 70% w / w or more, based on the total weight of the aerosolizable material.

[0012] These and other aspects will become apparent from the following detailed description. In this regard, certain sections of the specification should not be read in isolation from other sections.

[0013] [Brief explanation of appendices and drawings] Various embodiments will now be described in detail, by way of example only, with reference to the accompanying Appendix and drawings in which: Appendix 1 - Shows the chemical formulas of the sensates described herein. [Brief description of the drawings]

[0014] [Figure 1] 1 shows a schematic diagram of the articles, aerosol delivery devices, and systems described herein. Detailed Description

[0015] Cannabinoids are a class of natural or synthetic compounds that act on cannabinoid receptors (i.e., CB1 and CB2) in cells that inhibit the release of neurotransmitters in the brain. Cannabinoids are cyclic molecules that exhibit certain properties, such as the ability to easily cross the blood-brain barrier. Cannabinoids can be naturally occurring from plants such as cannabis (phytocannabinoids), naturally occurring from animals (endocannabinoids), or artificially produced (synthetic cannabinoids). Cannabis species express at least 85 different phytocannabinoids, which are classified into subclasses including cannabigerol, cannabichromene, cannabidiol, tetrahydrocannabinol, cannabinol and cannabinodiol, as well as other cannabinoids, such as cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), isomers Δ 6a,10a -Tetrahydrocannabinol (Δ 6a,10a -THC), Δ 6a(7) -Tetrahydrocannabinol (Δ 6a(7) -THC), Δ 8 -Tetrahydrocannabinol (Δ 8 -THC), Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), Δ 10 -Tetrahydrocannabinol (Δ 10 -THC), Δ 9,11 -Tetrahydrocannabinol (Δ 9,11-THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A).

[0016] Although the legal status of certain cannabinoids varies from jurisdiction to jurisdiction, certain active ingredients, such as cannabidiol (CBD), tetrahydrocannabinol (THC), and cannabinol (CBN), are contemplated for use in a variety of applications, including formulations for use in aerosol delivery systems. However, the stability of cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC), and cannabinol (CBN), has been found to vary with certain environmental conditions, such as exposure to air or light, or fluctuations in temperature and pH. This can have unintended adverse consequences.

[0017] For example, CBD can oxidize and decompose upon exposure to light and / or air to form cannabidiol hydroxyquinone (CBDHQ or HU-331) and its isomers or functional derivatives. Additionally, CBD can respond to temperature and / or pH fluctuations with a Δ 9 -Tetrahydrocannabinol (Δ 9-THC). As a result, the precision of the specified cannabinoid content and / or concentration may vary widely in the formulation, while regulated and restricted cannabinoids may be unintentionally produced, thereby rendering the product illegal or unauthorized in certain jurisdictions. It is therefore desirable to provide a formulation containing one or more cannabinoids that maintains high purity during manufacture and storage and prevents loss or degradation of the one or more cannabinoids of the formulation, e.g., cannabidiol (CBD), tetrahydrocannabinol (THC), or cannabinol (CBN).

[0018] In addition to these stability requirements for cannabinoid formulations, consumer feedback on CBD formulations, also referred to as CBD aerosolizable materials, used in aerosol delivery systems has in some cases been negative with respect to sensory experience. The natural taste of CBD is often described as "earthy" or "grassy," and the addition of one or more flavoring agents has been used in the past in an attempt to mask this taste, but this has not always been successful. In particular, consumers have indicated that flavored CBD aerosolizable materials may still have a bitter taste or off-notes associated with the taste, making inhalation of CBD aerosol unpleasant and unsatisfying. Users may even be averse to the taste, aroma, and / or other sensations experienced during use and decide to avoid CBD aerosolizable materials altogether.

[0019] It has been found that by including one or more antioxidants in a cannabinoid-containing formulation together with 0.01-12% w / w of one or more sensates, it is possible to provide a cannabinoid aerosolizable material that not only reduces the extent to which derivatives of the cannabinoid of interest are formed, but also reduces or masks the physiological response of the user to the cannabinoids in the material. In particular, the undesirable earthy, grassy, ​​or bitter taste discussed above is reduced or masked by the one or more sensates, as discussed further below. In the unique context of a cannabinoid aerosolizable material, the sensates allow for additional sensations, blending with existing flavors, and / or reducing off-notes associated with the taste of the cannabinoid, without any loss of stability or ease of use of the aerosolizable material. This means that it may be feasible to include higher levels of cannabinoids in the material, if desired.

[0020] The term "physiological response" means the body's automatic or instinctive reaction to a stimulus, such as a sensory response including taste and smell, but does not include the psychoactive effects of at least one cannabinoid.

[0021] For ease of reference, these and further aspects of the present invention are now discussed under appropriate section headings, however, the teachings in each section are not necessarily limited to each particular section.

[0022] Cannabinoids In one embodiment, the cannabinoid is a synthetic cannabinoid. In one embodiment, the cannabinoid is added to the material in the form of an isolate. An isolate is an extract from a plant, such as a cannabis plant. The cannabinoid(s) of interest are typically present in a high purity, for example, greater than 95%, greater than 96%, greater than 97%, greater than 98%, or about 99% pure. Synthetic cannabinoids are those that are not isolated from a plant or biological source, but are derived from chemical synthesis.

[0023] In one embodiment, the cannabinoid(s) of interest is cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), isomer Δ 6a,10a -Tetrahydrocannabinol (Δ 6a,10a -THC), Δ 6a(7) -Tetrahydrocannabinol (Δ 6a(7) -THC), Δ 8 -Tetrahydrocannabinol (Δ 8 -THC), Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), Δ 10 -Tetrahydrocannabinol (Δ 10 -THC), Δ 9,11 -Tetrahydrocannabinol (Δ 9,11 Tetrahydrocannabinol (THC), including -THC, cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). In one embodiment, the cannabinoid(s) of interest are selected from cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), Δ 8 -Tetrahydrocannabinol (Δ 8 -THC), Δ 9 -Tetrahydrocannabinol (Δ 9 -THC), and cannabinol (CBN).

[0024] In one embodiment, the cannabinoid(s) of interest is cannabidiol (CBD), Δ 8 -Tetrahydrocannabinol (Δ 8 -THC), Δ 9 -Tetrahydrocannabinol (Δ9 -THC).

[0025] In one embodiment, the cannabinoid of interest is cannabidiol (CBD).

[0026] In one embodiment, the cannabinoid of interest is Δ 8 -Tetrahydrocannabinol (Δ 8 -THC).

[0027] In one embodiment, the cannabinoid of interest is Δ 9 -Tetrahydrocannabinol (Δ 9 -THC).

[0028] In one embodiment, the cannabinoid of interest is cannabinol (CBN).

[0029] In one embodiment, the cannabinoid is cannabidiol (CBD) or a pharma- ceutically acceptable salt thereof. In one embodiment, the cannabidiol (CBD) is synthetic cannabidiol (CBD). In one embodiment, the cannabidiol (CBD) is added to the aerosolizable material in the form of a cannabinoid isolate. In one embodiment, the cannabinoid isolate comprises cannabidiol (CBD), and the cannabidiol (CBD) is present at a purity of greater than 95%, greater than 96%, greater than 97%, greater than 98%, or about 99%.

[0030] The cannabinoids may be present in the aerosolizable material on a mg / ml basis of the aerosolizable material.

[0031] In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 300 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 250 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 200 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 150 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 100 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 90 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 80 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 70 mg / ml. In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml to about 60 mg / ml.

[0032] In one embodiment, the cannabinoid is present in an amount of about 5 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 10 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 15 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 20 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 25 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 30 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 35 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 40 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 45 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 50 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 55 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 60 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 65 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 70 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 80 mg / ml or greater. In one embodiment, the cannabinoid is present in an amount of about 90 mg / ml or greater.

[0033] Sensory Compounds The aerosolizable material contains one or more sensates at a specified concentration. The term "sensate compound" or "sensate", used interchangeably herein, refers to a compound that induces a sensation mediated by the trigeminal nerve in the user. The use of sensate compounds is well documented in the food and pharmaceutical industries, and the sensations induced include sensations of cooling, warmth, and tingling. When used as an aerosolizable material, such sensations should be experienced in the oral cavity, nasal cavity, and / or skin of the user. The present disclosure is not limited in this respect.

[0034] In one embodiment, the one or more sensate agents are selected from a cooling agent, a warming agent, or a tingling agent. The terms "cooling," "warming," and "tingling" are well understood in the art.

[0035] Cooling agents, warming agents, and tingling agents are typically small organic molecules that, upon contact with the oral cavity, nasal cavity, and / or skin, induce a cooling, warming, or tingling sensation in the user, respectively. This sensation belongs to the category of chemosensation, which occurs when small organic molecules activate specific receptors in the skin and / or mucous membranes. Thus, the experience of cooling, warming, and / or tingling sensations depends on the user's chemosensation. Chemosensation is also referred to in the art as "general chemosensation" or trigeminal chemosensation, since it refers to the senses that are elements of the somatosensory system, typically mediated by the trigeminal nerve, and distinguishes these senses from olfaction (sense of smell) and taste.

[0036] In one embodiment, the one or more sensate agents include a cooling agent. The cooling agent is typically not menthol. In one embodiment, the one or more sensate agents are represented by formula (I): [ka] or a salt and / or solvate thereof, wherein X is hydrogen or OR', R' is an alkyl or alkenyl group that may be combined with R1 to form a 3-5 membered heterocyclyl group, the heterocyclyl group being optionally substituted with one or more substituents selected from OH, O-alkyl, alkyl-OH, alkyl-O-alkyl, NH2, NH-alkyl, N-(alkyl)2, NO2, and CN, and R1 and R2 are hydrogen, OH, OR a , C(O)NR b R c , and C(O)OR b R c with the proviso that when R1 is OH the compound of formula (I) is not menthol, and when a double bond is present R2 is absent; R a is an alkyl group, an alkenyl group, C(O)R f group, or C(O)-alkyl-C(O)R f is a group, the alkyl and alkenyl groups being optionally substituted with one or more substituents selected from OH, O-alkyl, NH, NH-alkyl, N-(alkyl), NO, and CN; R f is an alkyl group, an alkenyl group, OH, O-alkyl, NH2, NH-alkyl, or N-(alkyl)2, the alkyl and alkenyl groups being optionally substituted with one or more substituents selected from OH, O-alkyl, NH2, NH-alkyl, N-(alkyl), NO2, and CN; R b and R c are each independently a hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, and the alkyl group, the alkenyl group, the aryl group, and the heteroaryl group are each independently OH, O-alkyl, NH, NH-alkyl, N-(alkyl), NO, CN, and C(O)R. f is optionally substituted by one or more substituents selected from:

[0037] In one embodiment, X is hydrogen.

[0038] In one embodiment, X is OR' and R' is an alkyl or alkenyl group which, taken together with R1, forms a 3- to 5-membered heterocyclyl group, which is optionally substituted with OH, O-alkyl, or alkyl-OH. In one embodiment, X is OR' and R' is an alkyl group which, taken together with R1, forms a 4- or 5-membered heterocyclyl group, which is optionally substituted with alkyl-OH. In one embodiment, X is OR' and R' is an alkyl group which, taken together with R1, forms a 4- or 5-membered heterocyclyl group, which is optionally substituted with alkyl-OH. In one embodiment, X is OR' and R' is an alkyl group which, taken together with R1, forms a 4- or 5-membered heterocyclyl group, which is optionally substituted with alkyl-OH, and R1 is OR a and R a is an alkyl group and R2 is absent or hydrogen.

[0039] In one embodiment, R is OH, OR a , and C(O)NR b R c and R2 is absent or selected from OH and OR a In one embodiment, R1 is OH, with the proviso that the compound of formula (I) is not menthol. In one embodiment, R1 is OH, and R2 is selected from the group consisting of OH and OR a is selected from.

[0040] In one embodiment, X is hydrogen and R is OH, OR a , and C(O)NR b R c with the proviso that if R1 is OH, then the compound of formula (I) is not menthol; R2 is absent or is selected from the group consisting of OH and OR a In one embodiment, X is hydrogen and R is OR a and C(O)NR b R c and R2 is absent or selected from OH and OR a The signal is selected from:

[0041] In one embodiment, R1 is ORa and R a is an alkyl group substituted with one or more OH substituents. R2 can be hydrogen.

[0042] In one embodiment, R1 is OR a and R a is C(O)R f Group or C(O)-alkyl-C(O)R f is a group, R f is an alkyl group optionally substituted with one or more OH substituents, or R f is OH. R2 can be hydrogen.

[0043] In one embodiment, R is C(O)NR b R c and R b and R c are each independently a hydrogen, an alkyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group. In one embodiment, R is C(O)NR b R c and R b and R c At least one of is hydrogen. R2 can be hydrogen.

[0044] In one embodiment, R is C(O)NR b R c and R b is hydrogen and R c is selected from the group consisting of alkyl, aryl, aralkyl, and heteroaralkyl groups. R2 can be hydrogen.

[0045] As used herein, the term "alkyl" includes both saturated straight-chain and branched alkyl groups, which may be substituted (mono- or polysubstituted) or unsubstituted. In one embodiment, the alkyl group is 1~10 In one embodiment, the alkyl group is 1~8 In one embodiment, the alkyl group is 1~6In one embodiment, the alkyl group is 1~3 It is an alkyl group. In one embodiment, the alkyl group can be, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl. In one embodiment, the alkyl group can be, for example, methyl, ethyl, propyl, or isopropyl.

[0046] As used herein, the term "alkenyl" includes both unsaturated linear and branched alkenyl groups, which may be substituted (mono- or polysubstituted) or unsubstituted. In one embodiment, the alkenyl group is 2~10 In one embodiment, the alkenyl group is 2~8 In one embodiment, the alkenyl group is 2~6 In one embodiment, the alkenyl group is 2~3 It is an alkenyl group.

[0047] As used herein, the term "aryl" refers to a C 6~12 Refers to an aromatic group. Typical examples include phenyl and naphthyl. In one embodiment, the aryl group is phenyl.

[0048] The term "aralkyl" is used as a combination of the terms alkyl and aryl given above. For example, an aryl group can be formed from the diradical alkylene bridge (-CH2-) n wherein n is 1 to 10 and "aryl" is defined above. Alternatively, the alkyl group may be attached to the compound of formula (I) via a diradical aryl bridge, such as phenyl, where "alkyl" is defined above. In one embodiment, the term "aralkyl" refers to a phenyl-alkyl group, where the phenyl is attached to the compound of formula (I).

[0049] As used herein, the term "heteroaryl" refers to a monovalent aromatic group of 1 to 12 carbon atoms having one or more oxygen, nitrogen, and sulfur heteroatoms in the ring. In one embodiment, there are 1 to 4 oxygen, nitrogen, and / or sulfur heteroatoms in the ring. In one embodiment, there are 1 to 3 oxygen, nitrogen, and / or sulfur heteroatoms in the ring. In one embodiment, there are 2 oxygen and / or nitrogen heteroatoms in the ring. In one embodiment, there is one oxygen or nitrogen heteroatom in the ring. The nitrogen and sulfur heteroatoms may be optionally oxidized. Such heteroaryl groups may have a single ring (e.g., pyridyl or furyl) or multiple fused rings, provided that the point of attachment is through a heteroaryl ring atom.

[0050] In one embodiment, the heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolylbenzofuranyl, and benzothiophenyl. The heteroaryl ring can be unsubstituted or substituted. In one embodiment, the heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, and pyrrolyl. In one embodiment, the heteroaryl is pyridyl.

[0051] As used herein, the term "heterocyclyl" refers to a fully saturated or unsaturated monocyclic group having one or more oxygen, sulfur, or nitrogen heteroatoms in the ring. In one embodiment, a heterocyclyl has 1-3 heteroatoms in the ring. In one embodiment, a heterocyclyl has 1-3 oxygen and / or nitrogen heteroatoms in the ring. In one embodiment, a heterocyclyl has 1-3 oxygen heteroatoms in the ring. The nitrogen and sulfur heteroatoms may be optionally oxidized or the nitrogen heteroatom may be optionally quaternized. A heterocyclic group may be unsubstituted or substituted.

[0052] Exemplary monocyclic heterocyclic groups include pyrrolidinyl, pyrrolyl, pyrazolyl, oxiranyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperaz ... Examples of aryl include, but are not limited to, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, triazolyl, and triazinyl.

[0053] In one embodiment, heterocyclyl is selected from the group consisting of oxiranyl, oxetanyl, tetrahydrofuryl, tetrahydropyranyl, and 1,3-dioxolane. In one embodiment, heterocyclyl is 1,3-dioxolane.

[0054] All embodiments include, where appropriate, all enantiomers, tautomers, and geometric isomers of the compounds of formula (I). Those skilled in the art will recognize compounds that have optical properties (one or more chiral carbon atoms) or tautomeric properties. The corresponding enantiomers and / or tautomers can be isolated / prepared by methods known in the art. Some compounds of formula (I) can exist as stereoisomers and / or geometric isomers, e.g., these compounds can have one or more asymmetric centers and / or geometric centers and therefore can exist in two or more stereoisomeric and / or geometric forms. All embodiments include, where appropriate, the use of all individual stereoisomers and geometric isomers of these compounds, as well as mixtures thereof. The terms used in the claims encompass these forms.

[0055] Suitable salts of the compounds of formula (I) include suitable acid addition or base salts thereof. Such salts and their solvates will be known in the art. Suitable acid addition salts include carboxylates (e.g., formates, acetates, trifluoroacetates, propionates, isobutyrates, heptanoates, decanoates, caprates, caprylates, stearates, acrylates, caproates, propiolates, ascorbates, citrates, glucuronates, glutamates, glycolates, alpha-hydroxybutyrates, lactates, tartrates, phenylacetates, mandelates, phenylpropionates, phenylbutyrates, benzoates, chlorobenzoates, methyl benzoate, hydroxybenzoates, methoxybenzoates, dinitrobenzoates, o-acetoxybenzoates, salicylates, nicotinates, isonicotinates, cinnamates, oxalates, malonates, succinates, and the like. salts, such as suberates, sebacates, fumarates, malates, maleates, hydroxymaleates, hippurates, phthalates, or terephthalates), halides (e.g., chlorides, bromides, or iodides), sulfonates (e.g., benzenesulfonates, methyl, bromo, or chlorobenzenesulfonates, xylenesulfonates, methanesulfonates, ethanesulfonates, propanesulfonates, hydroxyethanesulfonates, 1- or 2-naphthalenesulfonates, or 1,5-naphthalenedisulfonates), or sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, or nitrates.

[0056] In one embodiment, the one or more sensates are: N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, Ethyl-2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino)acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-2,3-trimethyl-2-propan-2-ylbutanamide, N-(2-pyridin-2-yl)ethyl)menthylcarboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, Isopulegol, 3-menthoxypropane-1,2-diol, and Menthyl Succinate The cooling agent is selected from the group consisting of:

[0057] In one embodiment, the cooling agent is N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, Ethyl-2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino)acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-2,3-trimethyl-2-propan-2-ylbutanamide, N-(2-pyridin-2-yl)ethyl)menthylcarboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, 3-menthoxypropane-1,2-diol, and Menthyl Succinate is selected from the group consisting of:

[0058] In one embodiment, the cooling agent is N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, Ethyl-2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino)acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-(2-pyridin-2-yl)ethyl)menthylcarboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, Isopulegol, 3-menthoxypropane-1,2-diol, and Menthyl Succinate or may be selected from the group consisting of or N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, Ethyl-2-(5-methyl-2-propan-2-ylcyclohexanecarbonylamino)acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-(2-pyridin-2-yl)ethyl)menthylcarboxamide, Menthone-1,2-glycerol ketal, Menthyl lactate, 3-menthoxypropane-1,2-diol, and Menthyl Succinate may be selected from the group consisting of:

[0059] In one embodiment, the cooling agent is [ka] is selected from the group consisting of:

[0060] The above chemical formulas are also given in Appendix 1 along with the trade names and chemical names.

[0061] In one embodiment, the cooling agent is not WS-23, i.e., N,2,3-trimethyl-2-propan-2-ylbutanamide.

[0062] In one embodiment, the cooling agent is WS-23, i.e., N,2-3-trimethyl-2-propan-2-ylbutanamide.

[0063] In one embodiment, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, 3-((-)-menthoxy)propane-1,2-diol, and (-)-menthyl succinate. These compounds are shown in Appendix 1.

[0064] In one embodiment, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, 3-((-)-menthoxy)propane-1,2-diol, and (-)-menthyl succinate.

[0065] In one embodiment, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-menthanecarboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, and 3-((-)-menthoxy)propane-1,2-diol.

[0066] In one embodiment, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, ((1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, and 3-((-)-menthoxy)propane-1,2-diol.

[0067] In one embodiment, the cooling agent is selected from the group consisting of (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, and 3-((-)-menthoxy)propane-1,2-diol.

[0068] In one embodiment, the cooling agent is (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide.

[0069] In another embodiment, the cooling agent is (1S,2R,5S)-N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide.

[0070] As stated above, all embodiments include, where appropriate, all enantiomers and tautomers of the compounds. All embodiments include, where appropriate, the use of all individual stereoisomers and geometric isomers of these compounds, as well as mixtures thereof. The terms used in the claims encompass these forms.

[0071] In one embodiment, the one or more sensates include a warming agent or a tingling agent. In one embodiment, the warming agent or tingling agent is selected from the group consisting of vanilloids, sanshool, piperine, allyl isothiocyanate, cinnamyl phenylpropyl compounds, ethyl esters, and combinations thereof, or the warming agent or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

[0072] Vanilloids are compounds that contain a vanillyl group, and many vanilloids bind to the Transient Receptor Potential Vanilloid Type 1 or TRPV1 receptor, an ion channel that naturally responds to stimuli. Thus, TRPV1 is an element of the mammalian somatosensory system. Vanilloids include capsaicin (8-methyl-N-vanillyl-6-nonenamide) and nonivamide, as well as 3-phenylpropyl homovanillate, the main component of SymHeat PV used in the examples herein. Other vanilloids include gingerol, zingerone, and shogaol, as well as vanillyl ethyl ether, vanillyl propyl ether, vanillyl butyl ether, and vanillyl butyl ether acetate. The chemical structures of capsaicin, 3-phenylpropyl homovanillate, gingerol, [6]-shogaol, and zingerone are shown in Appendix 1.

[0073] Sanshool is hydroxy-alpha-sanshool, the compound responsible for the numbing and tingling sensations caused by eating foods cooked with, for example, Sichuan peppercorns and uzazi. The term "sanshool" comes from the Japanese pepper and the suffix "ol", meaning "alcohol". It is an agonist of TRPV1 and TRPA1 (the ion channels best known as sensors of pain, cold, and itch in humans and other mammals), and its chemical structure is shown in Appendix 1.

[0074] Cinnamyl phenylpropyl compounds have the common structural characteristics of aryl-substituted primary alcohols / aldehydes / esters.Cinnamyl phenylpropyl compounds include 3-phenylpropyl cinnamate and 3-phenyl-1-propanol, which have a spicy taste and balsamic odor, respectively, and 3-phenylpropyl isobutyrate, which has a fruity taste and odor.In one embodiment, the cinnamyl phenylpropyl compound is selected from 3-phenylpropyl cinnamate, 3-phenyl-1-propanol, and combinations thereof.

[0075] In one embodiment, the warming or tingling agent is selected from the group consisting of vanilloids, sanshool, piperine, cinnamyl phenylpropyl compounds, ethyl esters, and combinations thereof, or the warming or tingling agent is an extract from at least one of ginger oil, black pepper, long pepper, Sichuan pepper, cayenne pepper, or uzazi.

[0076] In one embodiment, the warming or tingling agent is selected from the group consisting of sanshool, allyl isothiocyanate, cinnamyl phenylpropyl compounds, ethyl esters, and combinations thereof, or the warming or tingling agent is an extract from at least one of horseradish oil, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

[0077] In one embodiment, the hot or tingling agent is selected from the group consisting of vanilloids, piperine, cinnamyl phenylpropyl compounds, ethyl esters, and combinations thereof, or the hot or tingling agent is an extract from at least one of ginger oil, black pepper, long pepper, or cayenne pepper.

[0078] In one embodiment, the warming or tingling agent comprises a combination of a vanilloid and a cinnamyl phenylpropyl compound. In one embodiment, the warming or tingling agent comprises a combination of a vanilloid and 3-phenylpropyl cinnamate, 3-phenyl-1-propanol, or a combination thereof. In one embodiment, the warming or tingling agent comprises a combination of a vanilloid and 3-phenylpropan-1-ol, such as 3-phenylpropyl homovanilate and 3-phenylpropan-1-ol.

[0079] In one embodiment, the warming or tingling agent is a combination of a vanilloid, an ethyl ester, and a cinnamyl phenylpropyl compound. In one embodiment, the warming or tingling agent is a combination of a vanilloid, an ethyl ester, and 3-phenylpropyl cinnamate, 3-phenyl-1-propanol, or a combination thereof. In one embodiment, the warming or tingling agent comprises a combination of a vanilloid, an ethyl ester, and 3-phenylpropan-1-ol, such as 3-phenylpropyl homovanilate and 3-phenylpropan-1-ol. The ethyl ester in any of these embodiments can be ethyl acetate.

[0080] In one embodiment, the warming or tingling agent is selected from the group consisting of vanillyl ethyl ether, vanillyl propyl ether, capsaicinoids, gingerols (e.g., [6], [8],

[10] , and / or

[12] -gingerol), vanillyl butyl ether, vanillyl butyl ether acetate, sanshool, piperine, zingerone, shogaols (e.g., (6)-shogaol), allyl isothiocyanate, and combinations thereof, or the warming or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

[0081] In one embodiment, the warming or tingling agent is selected from the group consisting of vanillyl ethyl ether, vanillyl propyl ether, vanillyl butyl ether, vanillyl butyl ether acetate, and combinations thereof.

[0082] In one embodiment, the hot or tingling agent is selected from the group consisting of capsaicinoids, gingerols (e.g., [6], [8],

[10] , and / or

[12] -gingerol), sanshool, piperine, zingerone, shogaols (e.g., (6)-shogaol), allyl isothiocyanate, and combinations thereof, or the hot or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

[0083] In one embodiment, the warming or tingling agent is selected from the group consisting of gingerols (e.g., [6], [8],

[10] , and / or

[12] -gingerol), zingerone, shogaols (e.g., (6)-shogaol, and combinations thereof), or the warming or tingling agent is an extract from ginger oil.

[0084] In one embodiment, the hot or tingling agent is selected from the group consisting of vanillyl ethyl ether, capsaicinoids (e.g., capsaicin), gingerol, hydroxy-alpha-sanshool, piperine, zingerone, shogaol, allyl isothiocyanate, and combinations thereof, or the hot or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

[0085] As stated above, all embodiments include, where appropriate, all enantiomers and tautomers of the compounds. Those skilled in the art will recognize compounds that have optical properties (one or more chiral carbon atoms) or tautomeric properties. The corresponding enantiomers and / or tautomers can be isolated / prepared by methods known in the art.

[0086] Some compounds may exist as stereoisomers and / or geometric isomers, e.g., these compounds may have one or more asymmetric and / or geometric centers and therefore may exist in two or more stereoisomeric and / or geometric forms. All embodiments include the use of all individual stereoisomers and geometric isomers of these compounds, as well as mixtures thereof, where appropriate. The terms used in the claims encompass these forms. Piperine has four geometric isomers, including, for example, chavicine, isochavicin, and isopiperine. In this specification, the term "piperine" is used to refer to all individual geometric isomers, as well as mixtures thereof.

[0087] In one embodiment, the one or more sensate agents comprise a cooling agent.

[0088] In one embodiment, the one or more sensate agents comprise a warming agent.

[0089] In one embodiment, the one or more sensate agents comprise a tingling agent.

[0090] In one embodiment, the one or more sensates consist of a cooling agent and a warming agent.

[0091] In one embodiment, the one or more sensate agents consist of a cooling agent and a tingling agent.

[0092] In one embodiment, the one or more sensate agents consist of a warming agent and a tingling agent.

[0093] The above definitions of cooling agent, warming agent, and tingling agent apply to each of these embodiments. For example, the one or more sensate agents may be cooling agents, and the cooling agent is a compound of formula (I) or a salt and / or solvate thereof. In one embodiment, the one or more sensate agents are cooling agents selected from the group consisting of a compound of formula (I) or a salt and / or solvate thereof, or N,2,3-trimethyl-2-propan-2-ylbutanamide. Alternatively, as an example, the one or more sensate agents may be warming agents or tingling agents as defined above. In one embodiment, the one or more sensates are a warming agent selected from the group consisting of hydroxy-alpha sanshool, capsaicin, piperine, zingerone, gingerol, shogaol, allyl isothiocyanate, and combinations thereof, or an extract from horseradish oil, ginger oil, black pepper, long pepper, Sichuan pepper, cayenne pepper, mustard oil, or uzazi. In one embodiment, the one or more sensates are a tingling agent that is a combination of a vanilloid, such as 3-phenylpropyl homovanillate, an ethyl ester, such as ethyl acetate, and 3-phenylpropan-1-ol.

[0094] The aerosolizable material includes one or more sensate agents in an amount of 0.01-12% w / w. This concentration range and the concentrations defined below apply to the above definition of sensate agent or agents. For example, a concentration range of 0.01-10% w / w applies to one or more sensate agents including cooling agents, warming agents, tingling agents, or combinations thereof. A concentration range of 0.01-10% w / w also applies to one or more sensate agents with a narrower definition, such as cooling agents, warming agents, or tingling agents. Although the range of 0.01-10% w / w is used herein as an example, the present disclosure is not limited to this concentration range and combination of specified sensate agents.

[0095] Furthermore, the sensory agent concentration can be combined with a concentration of at least one cannabinoid as defined above.

[0096] In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of from about 0.01% w / w to about 12% w / w. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of from about 0.05% w / w to about 12% w / w. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of from about 0.1% w / w to about 12% w / w.

[0097] In another embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 10% w / w or less. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.01% w / w to about 10% w / w. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.05% w / w to about 10% w / w. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.1% w / w to about 10% w / w.

[0098] In another embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 8% w / w or less. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.01% w / w to about 8% w / w. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.05% w / w to about 8% w / w. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.1% w / w to about 8% w / w.

[0099] In another embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 5% w / w or less. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.01% w / w to about 5% w / w. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.05% w / w to about 5% w / w. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.1% w / w to about 5% w / w.

[0100] In another embodiment, the one or more sensate agents defined herein are present in an amount of about 3% w / w or less, for example, about 2.5% w / w or less. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.01% w / w to about 2.5% w / w. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.05% w / w to about 2.5% w / w. In one embodiment, the one or more sensate agents defined herein are present in the material in an amount of about 0.1% w / w to about 2.5% w / w.

[0101] In some embodiments, the one or more sensates and their concentrations are selected based on their solubility in propylene glycol / glycerol system.For example, the aerosolizable material comprises an amount of one or more sensates in a carrier component that comprises at least 50% propylene glycol and glycerol, and the carrier component is present at 70% w / w or more of the aerosolizable material, so that the aerosolizable material has a turbidity of 1.0 NTU or less.Turbidity and its measurement are further discussed herein.

[0102] In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.01% w / w to about 12% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.05% w / w to about 12% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.1% w / w to about 12% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more.

[0103] In another embodiment, one or more sensates as defined herein are present in the material in an amount of about 10% w / w or less, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 10% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.05% w / w to about 10% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.1% w / w to about 10% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more.

[0104] In another embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 8% w / w or less, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.01% w / w to about 8% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.05% w / w to about 8% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensate agents as defined herein are present in the material in an amount of about 0.1% w / w to about 8% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more.

[0105] In another embodiment, one or more sensates as defined herein are present in the material in an amount of about 5% w / w or less, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 5% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.05% w / w to about 5% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.1% w / w to about 5% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more.

[0106] In another embodiment, one or more sensates as defined herein are present in an amount of about 3% w / w or less, for example about 2.5% w / w or less, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 2.5% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.05% w / w to about 2.5% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.1% w / w to about 2.5% w / w, and at least one cannabinoid is present in the material in an amount of 5 mg / ml or more.

[0107] Antioxidants One or more antioxidants are not sensates, and vice versa. This means that the aerosolizable material must contain an antioxidant and a sensate, and it is not possible for a single compound to provide both antioxidant and sensate functions. One or more antioxidants can be selected from the enediol class of compounds. For example, in one embodiment, one or more antioxidants are selected from the group consisting of ascorbic acid, sodium ascorbate, retinol, cholecalciferol, and combinations thereof.

[0108] In one embodiment, the one or more antioxidants are ascorbic acid, sodium ascorbate, alpha-ketoglutaric acid, alpha-ketoglutarate, quercetin, retinol, cholecalciferol, vitamin K-hydroquinone, citric acid, tartaric acid, ferulic acid, propyl gallate, gallic acid, alpha lipoic acid, ascorbyl palmitate, lutein, lycopene, resveratrol, rutin, catechin, carnosol, rosmarinic acid, lipoic acid, alpha-leucine, glyceryl stearate ... The flavin is selected from the group consisting of solsil, pyrogallol, malvidin, theaflavin, apigenin, eriodictyol, glycitein, chrysoeriol, kaempferol, luteolin, vitexin, isovitexin, orientin, cannflavin A, cannflavin B, cannflavin C, delphinidin, pelargonidin, epicatechin, myricetin, chrysin, naringenin, α-terpineol, tert-butylhydroquinone, and combinations thereof.

[0109] In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants. In one embodiment, the one or more antioxidants include sodium ascorbate and one or more additional antioxidants. In one embodiment, the one or more antioxidants are ascorbic acid and / or sodium ascorbate. In one embodiment, the one or more antioxidants are ascorbic acid and sodium ascorbate. In one embodiment, the antioxidant is ascorbic acid. In one embodiment, the antioxidant is sodium ascorbate.

[0110] In one embodiment, the one or more antioxidants are each present in an amount of at least 500 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 600 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 700 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 800 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 900 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1000 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1100 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1200 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1300 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1400 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1500 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1600 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1700 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1800 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1900 ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 2000 ppm.

[0111] In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 500 ppm. In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 750 ppm. In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 1000 ppm. In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 1250 ppm. In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 1500 ppm. In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 1750 ppm. In one embodiment, the one or more antioxidants include ascorbic acid and one or more additional antioxidants, and the ascorbic acid is present in an amount of at least 2000 ppm.

[0112] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 500 ppm.

[0113] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 750 ppm.

[0114] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 1000 ppm.

[0115] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 1250 ppm.

[0116] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 1500 ppm.

[0117] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 1750 ppm.

[0118] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in any of the preceding amounts and the sodium ascorbate is present in an amount of at least 2000 ppm.

[0119] In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in an amount of 500-4000 ppm and the sodium ascorbate is present in an amount of 500-4000 ppm.In one embodiment, the antioxidants are ascorbic acid and sodium ascorbate, where the ascorbic acid is present in an amount of 500-2000 ppm and the sodium ascorbate is present in an amount of 500-3000 ppm.

[0120] Those skilled in the art will appreciate that the concentration of the antioxidant applies to the concentrations defined above for the one or more sensates and / or at least one cannabinoid, respectively. For example, in one embodiment, the one or more sensates defined herein are present in the material in an amount of about 0.01% w / w to about 12% w / w, the at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and the one or more antioxidants are each present in an amount of at least 500 ppm.

[0121] In another embodiment, one or more sensates as defined herein are present in the material in an amount of about 10% w / w or less, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 10% w / w, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm.

[0122] In another embodiment, one or more sensates as defined herein are present in the material in an amount of about 8% w / w or less, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 8% w / w, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm.

[0123] In another embodiment, one or more sensates as defined herein are present in the material in an amount of about 5% w / w or less, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 5% w / w, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm.

[0124] In another embodiment, one or more sensates as defined herein are present in an amount of about 3% w / w or less, for example about 2.5% w / w or less, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm. In one embodiment, one or more sensates as defined herein are present in the material in an amount of about 0.01% w / w to about 2.5% w / w, at least one cannabinoid is present in the material in an amount of 5 mg / ml or more, and one or more antioxidants are each present in an amount of at least 500 ppm.

[0125] Carrier components The carrier component comprises one or more components capable of forming an aerosol, particularly when evaporated and condensed. In particular, the carrier component comprises at least 50% w / w propylene glycol, and the carrier component is present at 70% w / w or more, based on the total weight of the aerosolizable material.

[0126] In one embodiment, the carrier component is present at 75% w / w or more, based on the total weight of the aerosolizable material. In one embodiment, the carrier component is present at 80% w / w or more, based on the total weight of the aerosolizable material. In one embodiment, the carrier component is present at 85% w / w or more, based on the total weight of the aerosolizable material. In one embodiment, the carrier component is present at 90% w / w or more, based on the total weight of the aerosolizable material.

[0127] In some embodiments, the carrier component may further comprise one or more of glycerol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, erythritol, meso-erythritol, ethyl laurate, diethyl suberate, triethyl citrate, triethylene glycol diacetate, triacetin, diacetin mixtures, benzyl benzoate, benzyl phenylacetate, tributyrin, lauryl acetate, lauric acid, myristic acid, and propylene carbonate.

[0128] In one embodiment, propylene glycol is present in an amount of 50% w / w to 90% w / w based on the total weight of the aerosolizable material. In one embodiment, propylene glycol is present in an amount of 50% w / w to 85% w / w based on the total weight of the material. In one embodiment, propylene glycol is present in an amount of 50% w / w to 80% w / w based on the total weight of the material. In one embodiment, propylene glycol is present in an amount of 50% w / w to 75% w / w based on the total weight of the material. In one embodiment, propylene glycol is present in an amount of 50% w / w to 70% w / w based on the total weight of the material.

[0129] In one embodiment, the carrier component comprises at least 60% w / w propylene glycol. In one embodiment, the carrier component comprises at least 65% w / w propylene glycol. In one embodiment, the carrier component comprises at least 70% w / w propylene glycol.

[0130] In some embodiments, the w / w% amount of propylene glycol in the aerosolizable material is below a threshold C based on the total weight of the material. % and the threshold is C % =11.416×(A) 0.377 is defined by A is the amount in mg / ml of at least one cannabinoid present in the material. Aerosolizable materials comprising at least one cannabinoid, such as cannabidiol, and propylene glycol complying with the above thresholds have been found to be particularly stable.

[0131] In some embodiments, the amount of propylene glycol in the system is greater than or equal to a threshold C % For example, the amount of propylene glycol exceeds the threshold C % The amount of propylene glycol may be about 1 w / w%, 2 w / w%, 3 w / w%, 4 w / w%, 5 w / w%, 6 w / w%, 7 w / w%, 8 w / w%, 9 w / w%, or 10 w / w% more. If the aerosolizable material attracts water during storage, it may be important to include more propylene glycol than the threshold value. Thus, this additional propylene glycol can prevent the CBD from settling out during storage.

[0132] In some embodiments, the aerosolizable material comprises less than 12% w / w water. In some embodiments, the aerosolizable material comprises less than 11% w / w water. In some embodiments, the aerosolizable material comprises less than 10% w / w water. In some embodiments, the aerosolizable material comprises less than 5% w / w water. In some embodiments, the aerosolizable material comprises less than 1% w / w water. In some embodiments, the aerosolizable material comprises less than 0.5% w / w water. In some embodiments, the aerosolizable material is substantially free of water.

[0133] In one embodiment, the carrier component further comprises glycerol. In one embodiment, the carrier component comprises at least 10% w / w glycerol. In one embodiment, the carrier component comprises at least 15% w / w glycerol. In one embodiment, the carrier component comprises at least 20% w / w glycerol. In one embodiment, the carrier component comprises at least 25% w / w glycerol. In one embodiment, the carrier component comprises at least 30% w / w glycerol.

[0134] In one embodiment, glycerol and propylene glycol are present in the aerosolizable material in the following amounts: 60-90% w / w propylene glycol, and 40-10% w / w glycerol, based on the total weight of glycerol and propylene glycol present in the material.

[0135] In one embodiment, glycerol and propylene glycol are present in the aerosolizable material in the following amounts: 70-80% w / w propylene glycol, and 30-20% w / w glycerol, based on the total weight of glycerol and propylene glycol present in the material.

[0136] In one embodiment, the aerosolizable material comprises about 70% w / w propylene glycol and about 30% glycerol.

[0137] In one embodiment, the aerosolizable material is liquid at about 25°C.

[0138] Further components The aerosolizable material may include one or more additional components. In particular, the one or more additional components may be selected from one or more additional active components and / or one or more functional components. In some embodiments, the active component is a physiologically active component and may be selected from nicotine, nicotine salts (e.g., nicotine bitartrate / bitartrate), nicotine-free tobacco substitutes, other alkaloids such as caffeine, or mixtures thereof. In other embodiments, the aerosolizable material is nicotine-free, which means that nicotine is not included in the aerosolizable material.

[0139] In some embodiments, the further component is selected from "flavors" and / or "flavorings" that may be used to create a desired taste or aroma in a product for adult consumers, if local regulations permit. Those skilled in the art will recognize that in the context of this disclosure, flavors or flavorings are not sensate compounds as defined herein. In some cases, the flavors or flavorings are extracts (e.g., licorice, hydrangea, magnolia leaf, chamomile, fenugreek, clove, mint, aniseed, cinnamon, herbs, wintergreen, cherry, berry, peach, apple, Drambuie, bourbon, Scotch, whiskey, spearmint, peppermint, lavender, cardamom, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, honey essence, rose oil, vanilla, lemon oil, orange oil, cassia, caraway, cognac, jasmine, ylang-ylang, The ingredients may include one or more of sage, fennel, bell pepper, anise, coriander, coffee, sugar and / or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, or botanicals. The ingredients may be imitation, synthetic, or natural ingredients, or blends thereof. The ingredients may be in any suitable form, such as an oil, liquid, or powder.

[0140] Perfumes can be added to the aerosolizable material as part of a so-called "perfume block," in which one or more flavors are blended together and then added to the aerosolizable material. The "perfume block" can optionally include one or more of a sensate compound.

[0141] The one or more other functional components may include one or more of a colorant, a preservative, a binder, and / or a filler.

[0142] In one embodiment, the aerosolizable material may also include one or more organic or inorganic acids and their corresponding salts. In one embodiment, the organic acid is a carboxylic acid and the inorganic acid is phosphoric acid. In one embodiment, the carboxylic acid may be any suitable carboxylic acid, such as a monocarboxylic acid. In one embodiment, the one or more organic or inorganic acids and their corresponding salts are selected from the group consisting of acetic acid, formic acid, benzoic acid, levulinic acid, succinic acid, oleic acid, sorbic acid, propionic acid, phenylacetic acid, and mixtures thereof.

[0143] In another embodiment, the aerosolizable material can be free of organic or inorganic acids and their corresponding salts. For example, the aerosolizable material can be free of carboxylic acids and phosphoric acids.

[0144] In one embodiment, the aerosolizable material has a pH of less than about 7.5. In this regard, the inventors have found that when preparing a formulation containing a cannabinoid such as cannabidiol, it may be desirable to have a low pH to prevent cannabidiol from converting to other cannabinoids and to stabilize the formulation. In addition, a low pH may also be desirable to prevent the formation of CBDHQ. In one embodiment, the aerosolizable material has a pH of less than about 7.0. In one embodiment, the aerosolizable material has a pH of less than about 6.5.

[0145] In one embodiment, the aerosolizable material has a pH of about 5.5-7.5. In one embodiment, the aerosolizable material has a pH of about 5.5-7.4. In one embodiment, the aerosolizable material has a pH of about 5.5-7.3. In one embodiment, the aerosolizable material has a pH of about 5.5-7.2. In one embodiment, the aerosolizable material has a pH of about 5.5-7.1. In one embodiment, the aerosolizable material has a pH of about 5.5-7.

[0146] In one embodiment, the aerosolizable material has a pH of about 6-7.5. In one embodiment, the aerosolizable material has a pH of about 6-7.4. In one embodiment, the aerosolizable material has a pH of about 6-7.3. In one embodiment, the aerosolizable material has a pH of about 6-7.2. In one embodiment, the aerosolizable material has a pH of about 6-7.1. In one embodiment, the aerosolizable material has a pH of about 6-7.

[0147] For the avoidance of doubt, the pH of the aerosolizable material applies to all aerosolizable materials described herein, including those that contain further components, i.e. fragrances.

[0148] In some embodiments, the aerosolizable material has a turbidity of about 10 NTU or less.

[0149] In this regard, the inventors have found that when preparing an aerosolizable material containing cannabinoids, it is important to ensure that the turbidity of the material is about 10 NTU or less. If the turbidity of the material is above this range, this is an indication that one or more of the components of the material are not stable in the material. This can affect the use of the aerosolizable material in many ways. For example, the user may perceive a lack of stability and may have the opinion that the aerosolizable material is of poor quality. Alternatively, or in addition, such instability may result in inefficient transfer of one or more components from the aerosolizable material to the aerosol. Similarly, such instability may result in the aerosolizable material causing suboptimal performance of any system or device that uses the material. The inventors have found that stability issues may be particularly pronounced when the aerosolizable material contains cannabinoids, and therefore it is important to ensure that the aerosolizable material has a turbidity of 10 NTU or less.

[0150] In some embodiments, the turbidity of the aerosolizable material is about 10 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 9 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 8 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 7 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 6 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 5 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 4 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 3 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 2 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 1.5 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 1 NTU or less. In some embodiments, the turbidity of the aerosolizable material is about 0.9 NTU or less.

[0151] In some embodiments, the turbidity of the aerosolizable material is about 0.8 NTU or less.

[0152] In some embodiments, the turbidity of the aerosolizable material is about 0.7 NTU or less.

[0153] In some embodiments, the turbidity of the aerosolizable material is about 0.6 NTU or less.

[0154] In some embodiments, the turbidity of the aerosolizable material is about 0.5 NTU or less.

[0155] In some embodiments, the turbidity of the aerosolizable material is about 0.4 NTU or less.

[0156] In some embodiments, the turbidity of the aerosolizable material is about 0.3 NTU or less.

[0157] In some embodiments, the turbidity of the aerosolizable material is about 0.2 NTU or less.

[0158] The turbidity of an aerosolizable material can be measured as is common in the art, for example, by using a TL2310 ISO turbidity meter from Hach, Colorado, 80539-0389, United States.

[0159] In some embodiments, acceptable turbidity is achieved without the use of functional components that affect the stability of the aerosolizable material. For example, it may be possible to reduce the turbidity of a liquid system by introducing a surface-active component that serves to improve the emulsification / dispersion of one or more of the components. However, for user tolerance, it may not be desirable to include such a functional component. Thus, in some embodiments, the aerosolizable material does not include a surface-active component. Examples of surface-active components include medium chain triglycerides (MCT) and tocopherol acetate.

[0160] In some embodiments, acceptable turbidity is achieved without using any / large amounts of water. In this regard, while water may aid in the preparation of aerosolizable materials, since water-containing materials may have a lower viscosity and therefore may be more easily transferred to aerosol-generating components, it has been found in the context of the present disclosure that water may adversely affect the stability of aerosolizable materials that contain at least one cannabinoid.

[0161] In some embodiments, the aerosolizable material contains less than 12% w / w water. In some embodiments, the aerosolizable material contains less than 11% w / w water. In some embodiments, the aerosolizable material contains less than 10% w / w water. In some embodiments, the aerosolizable material contains less than 5% w / w water.

[0162] In some embodiments, the aerosolizable material contains less than 1% water w / w.

[0163] In some embodiments, the aerosolizable material contains less than 0.5% w / w water, hi some embodiments, the aerosolizable material is substantially free of water.

[0164] In particular, for certain formulations containing a cannabinoid such as cannabidiol, it has been found that when the formulation contains water in an amount of about 12% w / w, the cannabinoid becomes unstable.

[0165] In one embodiment, the formulations described herein are storage stable.

[0166] In this regard, the inventors have found that the formulation maintains a high degree of stability even when exposed to air and / or light and / or temperature fluctuations.

[0167] Goods In a further aspect, an article is provided that includes an aerosolizable material as defined herein. The article may be a container, such as a bottle, or a component for use in an aerosol delivery device. For example, the article may include an area for receiving an aerosolizable material as defined herein (a storage portion), an aerosol generating component, an aerosol generating area, and / or a mouthpiece.

[0168] In some embodiments, an article is provided for use in an aerosol delivery system, the article comprising a storage portion containing an aerosolizable material as defined herein, an aerosol generating component (such as a heater), an aerosol-generating region, a transport element, and a mouthpiece.

[0169] The aerosolizable material may be transferred from a storage for receiving the aerosolizable material to the aerosol generating component via a transport element such as a wick, a pump, etc. Those skilled in the art may select a suitable transport element depending on the type of aerosolizable material to be transported and the rate at which the aerosolizable material must be delivered. Particular mention may be made of transport elements such as wicks formed from fibrous materials, foamed materials, sintered materials, woven and nonwoven materials.

[0170] The airflow path typically extends through the article (optionally through the device) to an outlet, the path being oriented such that the generated aerosol is entrained in the airflow, thereby allowing the aerosol to be delivered to the outlet for inhalation by the user.

[0171] In one embodiment, the aerosol generating component is a heater.

[0172] Typically, the area for receiving aerosolizable material allows for the article to be replenished with aerosolizable material when the aerosolizable material becomes depleted during use.

[0173] 1 is a highly schematic illustration (not to scale) of an exemplary aerosol delivery system to which embodiments are applicable, such as an e-cigarette 10. The e-cigarette has a generally cylindrical shape extending along a longitudinal axis indicated by the dashed line (although aspects of the invention are applicable to e-cigarettes constructed of other shapes and configurations) and comprises two main components: an aerosol delivery device 20 and an article 30.

[0174] The article 30 includes a storage portion for aerosolizable material (feed liquid) 38 that contains the aerosolizable material (feed liquid) from which the aerosol is generated. The article 30 further includes an aerosol generating component (heating element or heater) 36 for heating the aerosolizable material to generate an aerosol. A transport or wicking element or wick 37 is provided to deliver the aerosolizable material from the storage portion 38 to the heating element 36. A portion or portions of the wick 37 are in fluid communication with the aerosolizable material of the storage portion 38, and by wicking or capillary action, the aerosolizable material is drawn along or through the wick 37 to a portion or portions of the wick 37 that are in contact with the heater 36.

[0175] Vaporization of the aerosolizable material occurs at the interface between the wick 37 and the heater 36 by supplying thermal energy to the aerosolizable material to cause evaporation, thus generating an aerosol. The aerosolizable material, the wick 37, and the heater 36 may be collectively referred to as the aerosol or vapor source. The wick 37 and the heater 36 may be collectively referred to as the vaporizer or atomizer 15.

[0176] Typically there will be a single wick, but it is envisioned that there may be more than one wick, for example, two, three, four, or five wicks.

[0177] As mentioned above, the wick may be formed from a sintered material. The sintered material may include sintered ceramic, sintered metal fibers / powder, or a combination of the two. The sintered wick(s) (or at least one / all of them) may have an electric resistance heater deposited / embedded in it. Such a heater may be formed from a thermally conductive alloy, such as a NiCr alloy. Alternatively, the sintered material may have electrical properties such that the sintered material heats up when an electric current is passed through it. Thus, the aerosol generation component and the wick may be considered to be integrated. In some embodiments, the aerosol generation component and the wick are formed from the same material and form a single component.

[0178] In some embodiments, the wick is formed from a sintered metal material and is generally in the form of a planar sheet. Thus, the wick element may have a substantially thin, flat shape. For example, it may be considered to be a sheet, layer, film, substrate, etc. This means that the thickness of the wick is less than, or significantly less than, at least one of the length and width of the wick. Thus, the thickness of the wick (its smallest dimension) is less than, or significantly less than, its longest dimension.

[0179] The wick may be made of homogeneous, granular, fibrous, or flocculent sintered metal(s) to form a capillary structure. The wick element may be made of a conductive material that is a non-woven sintered porous web structure containing metal fibers, such as stainless steel fibers. For example, the stainless steel may be AISI (American Iron and Steel Institute) 316L (corresponding to European standard 1.4404). The weight of the material may be between 100 and 300 g / m 2 The range may be:

[0180] Where the wick is generally planar, the wick thickness may range from 75 to 250 μm. A typical fiber diameter may be around 12 μm, and a typical average pore size (size of the voids between the fibers) may be around 32 μm. An example of this type of material is Bekipor (RTM) ST porous metal fiber media, manufactured by NV Bekaert SA, Belgium, which is a range of porous non-woven fiber matrix materials made by sintering stainless steel fibers.

[0181] It should also be noted that the material is described as planar, which refers to the relative dimensions of the sheet material and the wick (thickness being many times smaller than length and / or width), but does not necessarily indicate flatness, particularly the flatness of the final wick made from the material. The wick may be flat, but may alternatively be formed from the sheet material into a non-planar shape, such as curved, undulating, corrugated, ribbed, formed into a tube, or otherwise made concave and / or convex.

[0182] The wick element may have a variety of characteristics. The wick element is formed from a porous material to allow the necessary wicking or capillary effect to draw the source liquid from the reservoir for the aerosolizable material (where the wick meets the aerosolizable material at the reservoir contact site) through the wick element to the vaporization interface. The porosity is typically provided by a plurality of interconnected or partially interconnected pores (holes or gaps) throughout the material, opening toward the outer surface of the material. Any level of porosity may be used depending on the material, the size of the pores, and the wicking rate required. For example, a porosity of 30% to 85%, e.g., 40% to 70%, 50% to 80%, 35% to 75%, or 40% to 75% may be selected. The porosity may or may not be uniform throughout the wick, so the porosity may be an average porosity value throughout the wick element. For example, the pore size at the reservoir contact site may be different from the pore size closer to the heater.

[0183] It is useful for the wick to be sufficiently rigid to support itself in the article, for example, the wick may be attached at or near one or two edges and may be required to maintain its position substantially without bending, buckling or sagging.

[0184] As an example, porous sintered ceramics are useful materials for use as wick elements. Any ceramic with suitable porosity may be used. When a porous ceramic is selected as the porous wick material, the porous wick material is available as a powder that can be formed into a solid by sintering (heating to cause coagulation, optionally under pressure). Sintering then solidifies the ceramic to create the porous wick.

[0185] The article 30 further includes a mouthpiece 35 having an opening through which a user can inhale the aerosol produced by the vaporizer 15. The aerosol for inhalation may be described as an aerosol stream or an inhalable air stream.

[0186] The aerosol delivery device 20 includes a power source (a rechargeable cell or battery 14, hereinafter referred to as a battery) for powering the e-cigarette 10, and a controller (printed circuit board (PCB)) 28 and / or other electronics for generally controlling the e-cigarette 10. Thus, the aerosol delivery device may also be considered to be a battery section, or a control unit or section.

[0187] During operation of the device, the controller determines that a user has initiated a request for generation of aerosol. This may be done via a button on the device that sends a signal to the controller that the aerosol generator should be powered. Alternatively, a sensor located in or proximal to the airflow path can detect airflow through the airflow path and communicate this detection to the controller. Sensors may be present in addition to the presence of a button, as the sensor may be used to determine certain usage characteristics, such as airflow, timing of aerosol generation, etc.

[0188] For example, in use, when heater 36 receives power from battery 14, as controlled by circuit board 28 which may respond to pressure changes detected by an air pressure sensor (not shown), heater 36 vaporizes aerosolizable material delivered by wick 37 to generate an aerosol, and this aerosol stream is then inhaled by the user through an opening in mouthpiece 35. The aerosol is transported from the aerosol source to mouthpiece 35 along an air channel (not shown in FIG. 1 ) connecting the aerosol source to the mouthpiece opening as the user inhales into the mouthpiece.

[0189] In this particular example, device 20 and article 30 are removable from one another by separation in a direction parallel to the longitudinal axis as shown in Figure 1, but when system 10 is in use, are coupled together by cooperating engagement elements 21, 31 (e.g., threaded, magnetic or bayonet fittings) to form a mechanical and electrical connection between device 20 and article 30, in particular connecting heater 36 to battery 14. The battery may be charged as known to those skilled in the art.

[0190] In some embodiments, the article comprises / forms a sealed container. For example, the sealed container can be hermetically sealed. The inventors have found that including an aerosolizable material in a sealed article can help prevent water from entering the system, thereby preventing cannabidiol from precipitating. The hermetically sealed container can include a blister pack having one or more hermetically sealed compartments for storing one or more articles including the aerosolizable material described herein.

[0191] In some embodiments, the article comprises a housing in which the aerosolizable material is contained. The housing may be transparent so that the aerosolizable material is visible from outside the housing. The housing may also have a degree of opacity such that the passage of light through the housing is limited. This may be important to prevent light (such as ultraviolet light) from entering the housing and compromising the stability of the aerosolizable material. In this regard, the inventors have considered that cannabinoids may be particularly susceptible to such photo-destabilization. In some embodiments, the housing is formed from a material that inhibits / prevents the passage of ultraviolet light through the housing. In some embodiments, the sealed container described above may be formed from a material that has a degree of opacity such that the passage of light through the sealed container is limited. Furthermore, the sealed container described above may be formed from a material that inhibits / prevents the passage of ultraviolet light through the sealed container. This may be in addition to the sealed container being hermetically sealed and / or including a blister pack having one or more hermetically sealed compartments for storing one or more articles comprising the aerosolizable material described herein.

[0192] In a further aspect, there is provided an aerosol delivery system comprising an aerosol delivery device and an article as defined herein.

[0193] Preparation of materials In a further aspect, there is provided a method for making or preparing an aerosolizable material as defined herein, the method comprising combining at least one cannabinoid and a carrier component comprising at least 50% w / w propylene glycol, the carrier component being present at 70% w / w or greater based on the total weight of the aerosolizable material, with one or more antioxidants and 0.01-12% w / w of one or more sensates. The cannabinoid, carrier component, antioxidant(s), and sensate(s) are defined herein, including concentrations and chemical definitions.

[0194] In some embodiments, the method excludes the step of adding water to the aerosolizable material.

[0195] In one embodiment, the aerosolizable material described herein is a packaged material, and the packaged material is impermeable to air.In this regard, the material can be prepared with a predetermined amount of one or more cannabinoids that maintain a high degree of stability.As defined herein, impermeable to air means that the packaged material is closed or sealed to provide substantial air impermeability.

[0196] In one embodiment, the packaged material is packaged in a container that is substantially impermeable to air and / or light (including UV light), and the packaged material can be used in an aerosol delivery system. The container can correspond to a repository that contains the aerosolizable material as defined herein. In this regard, the stability of the packaged material can be maintained during use.

[0197] In one embodiment, the packaged material is packaged in a container that includes the aerosolizable material described herein and a gas, such as air, CO2, N2, or a noble gas. In this regard, the volume of said gas in the container is referred to as the headspace. It is preferable to reduce the volume of the headspace of the container so that the stability of the packaged material can be maintained. In one embodiment, there is a method of preparing a packaged material, comprising packaging an aerosolizable material as described herein in a container that is substantially impermeable to air and / or light (including UV light), wherein the container further comprises a volume of gas that is 20% or less of the total volume of the container. In one embodiment, the gas volume is 15% or less of the total volume of the container. In one embodiment, the gas volume is 10% or less of the total volume of the container. In one embodiment, the gas volume is 5% or less of the total volume of the container. In one embodiment, the gas volume is 1% or less of the total volume of the container. The noble gas referred to herein may be argon.

[0198] In one embodiment, the packaged materials and containers described herein are sealed in one or more blister packs that are substantially impermeable to air and light (such as ultraviolet light). In this regard, the stability of the materials and packaged materials may be maintained during storage.

[0199] In a further aspect, there is provided a method or process for generating an aerosol comprising generating an aerosol from an aerosolizable material as defined herein. EXAMPLES

[0200] Recent consumer research has revealed that cannabidiol (CBD) tastes bitter in aerosolized CBD formulations, including aerosolized CBD formulations that include one or more flavorings or flavoring agents. Experiments were conducted to determine whether one or more sensates could be used to provide additional sensations, to match existing flavors, and / or to reduce bitterness or off-notes associated with the taste of CBD.

[0201] The sensates involved in the experiments were cooling, warming, and tingling sensates. WS-3 (N-ethyl-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide) was used as the cooling sensate. Ginger extract was used as the warming sensate (obtained from Symrise Asia Pacific Pte. Ltd.; contains camphene, 2,6,10-trimethyldodeca-2,6,9,11-tetraene, 2-methyl-6-(4-methylcyclohex-3-en-1-ylidene)hept-2-ene, pin-2(3)-ene, citral, d-limonene, cineole, geraniol, and p-mentha-1,4(8)-diene). SymHeat PV (obtained from Symrise Asia Pacific Pte. Ltd.; contains 3-phenylpropyl homovanillate, 3-phenylpropan-1-ol, and ethyl acetate) was used as the tingling sensate. The sensates were used in combination with tropical, minty, and fruity flavored CBD aerosolizable materials.

[0202] The aerosolizable materials prepared are shown below in Table 1. Formulations A, B, and C are tropical flavored, Formulations D and E are mint flavored, and Formulations F and G are fruity flavored.

[0203] [Table 1]

[0204] Example 1 Prior to preparing the formulations shown in Table 1, solubility tests were performed to determine whether each of the ginger extract, WS-3, and SymHeat PV was soluble in a mixture of propylene glycol and glycerol. Formulations containing a 70:30 ratio of propylene glycol (PG) and glycerol (VG) were made, and the w / w% of sensate loading was subtracted from the w / w% of propylene glycol, as is typical in the art. The formulations prepared are shown in Table 2 below, with the order of addition as seen in the table, reading from left to right.

[0205] [Table 2]

[0206] One hour after addition of VG, each sensate was determined to be solubilized in the PG / VG mixture.

[0207] After each sensate was successfully dissolved in a propylene glycol / glycerol mixture, further solubility testing was performed incorporating each sensate into a flavored propylene glycol and glycerol mixture. Finally, each sensate was tested for solubility and stability in a 60mg / ml CBD flavored propylene glycol and glycerol mixture. These are the formulations shown in Table 1 above.

[0208] Example 2 After successfully incorporating each sensate into the 60 mg / ml CBD-flavored propylene glycol and glycerol blends shown in Table 1, the sensory experience was evaluated in a consumer survey. The purpose of this evaluation was to ascertain consumer feedback regarding the sensory improvements of the CBD aerosolizable material.

[0209] Surprisingly, the inclusion of one or more sensates in combination with one or more antioxidants provides a stable CBD aerosolizable material, thereby providing a positive sensory experience to the end user. In particular, the one or more sensates reduce the negative sensory experience typically associated with the vaporization of CBD formulations, making it possible to develop new CBD-containing aerosolizable materials that can complement both the taste of the material and the mood state of the consumer.

[0210] The various embodiments described herein are presented only to aid in the understanding and teaching of the claimed features. These embodiments are provided only as a representative sample of embodiments and are not exhaustive and / or exclusive. It is understood that the advantages, embodiments, examples, functions, features, structures, and / or other aspects described herein should not be considered as limitations on the scope of the invention as defined by the claims or equivalents of the claims, and that other embodiments can be utilized and modifications can be made without departing from the scope of the invention as claimed. Various embodiments of the invention may suitably include, consist of, or consist essentially of any suitable combination of the disclosed elements, components, features, parts, steps, means, etc., other than those specifically described herein. Moreover, this disclosure may include other inventions not claimed herein but which may be claimed in the future.

[0211] Appendix 1 [Table 3] JPEG2025501925000007.jpg190149 JPEG2025501925000008.jpg195149 JPEG2025501925000009.jpg197149 JPEG2025501925000010.jpg67149

Claims

1. 1. An aerosolizable material comprising at least one cannabinoid, a carrier component comprising at least 50% w / w propylene glycol, one or more antioxidants, and 0.01-12% w / w of one or more sensates, said carrier component being present at 70% w / w or greater based on the total weight of the aerosolizable material, and wherein said one or more antioxidants are not sensates, and said one or more sensates are not antioxidants.

2. 10. The aerosolizable material of claim 1, wherein the one or more sensate agents are selected from a cooling agent, a warming agent, or a tingling agent.

3. The one or more sensate agents have the formula (I): 【Chemistry 1】 or a salt and / or solvate thereof, In the formula, X is hydrogen or OR′, and R′ is R １ and an alkyl or alkenyl group which may be taken together with the heterocyclyl group to form a 3- to 5-membered heterocyclyl group, said heterocyclyl group being OH, O-alkyl, alkyl-OH, alkyl-O-alkyl, NH ２ , NH-alkyl, N-(alkyl) ２ , NO ２ and CN; R １ and R ２ is hydrogen, OH, OR ａ , C(O)NR ｂ R ｃ , and C(O)OR ｂ R ｃ are each independently selected from １ is OH, the compound of formula (I) is not menthol, and when a double bond is present, R ２ does not exist; R ａ is an alkyl group, an alkenyl group, C(O)R ｆ group, or C(O)-alkyl-C(O)R ｆ groups, the alkyl and alkenyl groups being OH, O-alkyl, NH ２ , NH-alkyl, N-(alkyl) ２ , NO ２ and CN; R ｆ is an alkyl group, an alkenyl group, OH, O-alkyl, NH ２ , NH-alkyl, or N-(alkyl) ２ and the alkyl and alkenyl groups are OH, O-alkyl, NH ２ , NH-alkyl, N-(alkyl) ２ , NO ２ and CN; R ｂ and R ｃ are each independently a hydrogen atom, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, and the alkyl group, the alkenyl group, the aryl group, and the heteroaryl group are each independently an OH group, an O-alkyl group, an NH ２ , NH-alkyl, N-(alkyl) ２ , NO ２ , CN, and C(O)R ｆ 3. The aerosolizable material of claim 2, optionally substituted with one or more substituents selected from:

4. 3. The aerosolizable material of claim 2, wherein the one or more sensate agents include a cooling agent that is N,2,3-trimethyl-2-propan-2-ylbutanamide.

5. 3. The aerosolizable material of claim 2, wherein the one or more sensate agents comprise a cooling agent selected from the group consisting of N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[5-methyl-2-propan-2-ylcyclohexanecarbonyl]amino]acetate, N-(4-methoxyphenyl-p-menthanecarboxamide, N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, menthone 1,2-glycerol ketal, menthyl lactate, 3-(menthoxy)propane-1,2-diol, and menthyl succinate.

6. 6. The aerosolizable material of claim 5, wherein the one or more sensate agents include a cooling agent that is N-ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide.

7. 3. The aerosolizable material of claim 2, wherein the one or more sensate agents comprise a warming agent or a tingling agent.

8. 8. The aerosolizable material of claim 7, wherein the warming or tingling agent is selected from the group consisting of vanilloids, sanshool, piperine, allyl isothiocyanate, cinnamyl phenylpropyl compounds, ethyl esters, and combinations thereof, or the warming or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

9. 9. The aerosolizable material of claim 8, wherein the warming or tingling agent is a combination of a vanilloid, an ethyl ester, and a cinnamyl phenylpropyl compound, preferably a combination of 3-phenylpropyl homovanilate, ethyl acetate, and 3-phenylpropan-1-ol.

10. 9. The aerosolizable material of claim 8, wherein the warming or tingling agent is selected from the group consisting of vanillyl ethyl ether, vanillyl propyl ether, capsaicinoids, gingerol, vanillyl butyl ether, vanillyl butyl ether acetate, sanshool, piperine, zingerone, shogaol, allyl isothiocyanate, and combinations thereof, or the warming or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, uzazi, or mustard oil.

11. 11. The aerosolizable material of claim 10, wherein the warming or tingling agent is selected from the group consisting of vanillyl ethyl ether, capsaicin, hydroxy-alpha-sanshool, piperine, zingerone, gingerol, shogaol, allyl isothiocyanate, or a combination thereof, or the warming or tingling agent is an extract from at least one of ginger oil, black pepper, long pepper, Sichuan pepper, cayenne pepper, uzazi, or mustard oil.

12. 12. The aerosolizable material of claim 11, wherein the warming or tingling agent is selected from zingerone, gingerol, shogaol, and combinations thereof, or is an extract from ginger oil.

13. 13. The aerosolizable material of any one of claims 1 to 12, wherein the one or more sensate agents are present in the material in an amount of 0.01 to 10% w / w.

14. 14. The aerosolizable material of any one of claims 1 to 13, wherein the one or more sensate agents are present in the material in an amount of 0.01 to 5% w / w.

15. 15. The aerosolizable material of any one of claims 1 to 14, wherein the one or more sensate agents are present in the material in an amount of 0.01 to 2.5% w / w.

16. The at least one cannabinoid is cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), isomer Δ ６ａ，１０ａ -Tetrahydrocannabinol (Δ ６ａ，１０ａ -THC), Δ ６ａ（７） -Tetrahydrocannabinol (Δ ６ａ（７） -THC), Δ ８ -Tetrahydrocannabinol (Δ ８ -THC), Δ ９ -Tetrahydrocannabinol (Δ ９ -THC), Δ １０ -Tetrahydrocannabinol (Δ １０ -THC), Δ ９，１１ -Tetrahydrocannabinol (Δ ９，１１ 16. The aerosolizable material of any one of claims 1 to 15, wherein the aerosolizable component is selected from tetrahydrocannabinol (THC) including tetrahydrocannabinol (THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiol acid (CBDA), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A).

17. The at least one cannabinoid is cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), Δ ６ａ，１０ａ -Tetrahydrocannabinol (Δ ６ａ，１０ａ -THC), Δ ６ａ（７） -Tetrahydrocannabinol (Δ ６ａ（７） -THC), Δ ８ -Tetrahydrocannabinol (Δ ８ -THC), Δ ９ -Tetrahydrocannabinol (Δ ９ -THC), Δ １０ -Tetrahydrocannabinol (Δ １０ -THC), Δ ９，１１ -Tetrahydrocannabinol (Δ ９，１１ 17. The aerosolizable material of claim 16, wherein the aerosolizable material is selected from the group consisting of cannabinol (CBN), cannabinol (THC), and cannabinol (CBN).

18. The at least one cannabinoid is cannabidiol (CBD), Δ ９ -Tetrahydrocannabinol (Δ ９ 18. The aerosolizable material of claim 16 or 17, wherein the at least one cannabinoid is selected from cannabidiol (TCA), cannabinoid-THC, and cannabinol (CBN), preferably wherein the at least one cannabinoid is cannabidiol.

19. 19. The aerosolizable material of any one of claims 1 to 18, wherein the at least one cannabinoid is present in the material in an amount of 30 mg / ml or greater.

20. 20. The aerosolizable material of claim 19, wherein the at least one cannabinoid is present in the material in an amount of 60 mg / ml or greater.

21. 21. The aerosolizable material of any one of claims 1 to 20, wherein the one or more antioxidants are selected from the enediol class of compounds.

22. The one or more antioxidants may be selected from the group consisting of ascorbic acid, sodium ascorbate, alpha-ketoglutaric acid, alpha-ketoglutarate, quercetin, retinol, cholecalciferol, vitamin K-hydroquinone, citric acid, tartaric acid, ferulic acid, propyl gallate, gallic acid, alpha lipoic acid, ascorbyl palmitate, lutein, lycopene, resveratrol, rutin, catechin, carnosol, rosmarinic acid, lipoic acid, alpha-resorcyl, pyrogallol, malvidin, 22. The aerosolizable material of any one of claims 1 to 21, selected from the group consisting of theaflavin, apigenin, eriodictyol, glycitein, chrysoeriol, kaempferol, luteolin, vitexin, isovitexin, orientin, cannflavin A, cannflavin B, cannflavin C, delphinidin, pelargonidin, epicatechin, myricetin, chrysin, naringenin, alpha-terpineol, tert-butylhydroquinone, and combinations thereof.

23. 23. The aerosolizable material of any one of claims 1 to 22, wherein the one or more antioxidants are selected from ascorbic acid, sodium ascorbate, and combinations thereof.

24. 24. The aerosolizable material of any one of claims 1 to 23, wherein the one or more antioxidants are each present in an amount of at least 500 ppm.

25. 25. The aerosolizable material of claim 24, wherein the one or more antioxidants are each present in an amount of at least 1000 ppm.

26. 26. The aerosolizable material of any one of claims 1-25, wherein the carrier component further comprises one or more of glycerol, triethylene glycol, tetraethylene glycol, 1,3-butylene glycol, erythritol, meso-erythritol, ethyl laurate, diethyl suberate, triethyl citrate, triethylene glycol diacetate, triacetin, diacetin mixtures, benzyl benzoate, benzyl phenylacetate, tributyrin, lauryl acetate, lauric acid, myristic acid, and propylene carbonate.

27. 27. The aerosolizable material of claim 26, wherein the carrier component further comprises glycerol, preferably the carrier component comprises at least 30% w / w glycerol.

28. 28. The aerosolizable material of any one of claims 1 to 27, wherein the carrier component comprises at least 60% w / w propylene glycol, or at least 70% w / w propylene glycol.

29. 29. The aerosolizable material of any one of claims 1 to 28, wherein the carrier component is present at 80% w / w or more based on the total weight of the aerosolizable material.

30. 30. The aerosolizable material of any one of claims 1 to 29, wherein the carrier component comprises 60-90% w / w propylene glycol and 40-10% w / w glycerol, based on the total weight of the carrier component.

31. The aerosolizable material of any one of claims 1 to 30, wherein the material is nicotine-free.

32. An article comprising the aerosolizable material of any one of claims 1 to 31.

33. 33. The article of claim 32, comprising a storage portion for receiving the aerosolizable material of any one of claims 1 to 31, an aerosol generating component, an aerosol generating region, a transport element, and a mouthpiece.

34. The article of claim 33 , wherein the aerosol generating component comprises a heater.

35. 35. The article of claim 33 or 34, wherein the transport element is a wick.

36. An aerosol delivery system comprising an aerosol delivery device and an article according to any one of claims 32 to 35.

37. 1. A method for producing an aerosolizable material as defined herein, said method comprising combining at least one cannabinoid, a carrier component comprising at least 50% w / w propylene glycol, one or more antioxidants, and 0.01-12% w / w of one or more sensates, wherein said carrier component is present at 70% w / w or greater based on the total weight of said aerosolizable material, and wherein said one or more antioxidants are not sensates, and said one or more sensates are not antioxidants.

38. Method according to claim 37, characterized by the features according to any one of claims 2 to 31.

39. A sealed container containing an article according to any one of claims 32 to 35.

40. 40. The sealed container of claim 39, wherein the container is hermetically sealed and formed from a material that reduces or prevents the passage of ultraviolet light through the container.

41. 41. The sealed container of claim 39 or 40, wherein the sealed container comprises a blister pack having one or more hermetically sealed compartments.

42. 32. A process for forming an aerosol, comprising the steps of: (i) providing an aerosolizable material according to any one of claims 1 to 31; and (ii) aerosolizing the material.

43. 1. Use of one or more sensory agents to reduce or mask a user's physiological response to at least one cannabinoid in an aerosolizable material, the aerosolizable material comprising the at least one cannabinoid and a carrier component comprising at least 50% propylene glycol, the carrier component being present at 70% w / w or more, based on the total weight of the aerosolizable material.

44. The use according to claim 43, wherein the aerosolizable material is characterised by the features according to any one of claims 1 to 31.

45. 45. The use according to claim 43 or 44, wherein the physiological response of the user is a sensory response.

46. 46. ​​The use of claim 45, wherein the sensory response comprises taste.

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