JP7755751B2 - Aerosolizable Materials - Google Patents

Description

Field

The present disclosure relates to aerosolizable materials, methods for making the materials, and containers and systems containing and using the materials.

background

Aerosol delivery systems that generate aerosols for inhalation by a user are known in the art. Such systems typically include an aerosol generator capable of converting 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 that then condenses into an aerosol. In other instances, 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 through the use of pressure.

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 particular manner. For example, it may be preferable to formulate the aerosolizable material to produce an aerosol having a particular profile. It may also be preferable to formulate the aerosolizable material to ensure that the aerosolizable material meets certain standards for quality, consistency, etc.

It would therefore be desirable to provide aerosolizable materials that are formulated to be acceptable to users.

overview

In one aspect, an aerosolizable material is provided that includes 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 the carrier component is present at 70% w/w or greater based on the total weight of the aerosolizable material, and wherein the one or more antioxidants are not sensates and the one or more sensates are not antioxidants. The terms "sensate" and "antioxidant" are well known in the art and are discussed further below.

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

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

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 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, wherein the one or more antioxidants are not sensates and the one or more sensates are not antioxidants.

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

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.

In a further aspect, there is provided the use of one or more sensates to reduce or mask a user's physiological response 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 greater, based on the total weight of the aerosolizable material.

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.

[Appendix and brief description of 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 - provides chemical formulas for the sensates described herein.

1 shows a schematic diagram of the articles, aerosol delivery devices, and systems described herein.

Detailed Description

Cannabinoids are a class of natural or synthetic compounds that act on cannabinoid receptors (i.e., CB1 and CB2) in cells of the brain, inhibiting the release of neurotransmitters. 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), the 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), and the isomers Δ 6a, ^10a -tetrahydrocannabinol (Δ ^6a,10a -THC). -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).

While the legal status of particular cannabinoids varies by 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.

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 convert to Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC) in response to temperature and/or pH fluctuations. As a result, the precision of the specified cannabinoid content and/or concentration can vary greatly in formulations, while regulated and restricted cannabinoids may be unintentionally produced, thereby rendering the product illegal or unauthorized in certain jurisdictions. Therefore, it would be desirable to provide formulations containing one or more cannabinoids that maintain high purity during manufacturing and storage and that prevent loss or degradation of the formulation's one or more cannabinoids, e.g., cannabidiol (CBD), tetrahydrocannabinol (THC), or cannabinol (CBN).

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 regarding the 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 can still have a bitter taste or other off-notes associated with the taste, making inhaling the 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.

It has been discovered that by including one or more antioxidants in a cannabinoid-containing formulation, along 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 desired cannabinoid are formed, but also reduces or masks the user's physiological response 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 can provide additional sensations, blend with existing flavors, and/or reduce off-notes associated with the taste of cannabinoids, without compromising the stability or ease of use of the aerosolizable material in any way. This means that it may be feasible to include higher levels of cannabinoids in the material, if desired.

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.

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.

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. The isolate is an extract from a plant, such as a cannabis plant. The cannabinoid(s) of interest are typically present in a high degree of purity, for example, greater than 95%, greater than 96%, greater than 97%, greater than 98%, or about 99% pure. Synthetic cannabinoids are derived from chemical synthesis rather than being isolated from a plant or biological source.

In one embodiment, the cannabinoid(s) of interest are cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), the 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), Δ 12 -tetrahydrocannabinol (Δ ¹² -THC), Δ 13 -tetrahydrocannabinol (Δ 13 -THC), Δ 14 -tetrahydrocannabinol (Δ 14 -THC), Δ 15 -tetrahydrocannabinol (Δ 15 -THC), Δ ¹⁶ -tetrahydrocannabinol (Δ 16 -THC), Δ 17 -tetrahydrocannabinol (Δ ^{17 -THC), Δ 18 -tetrahydrocannabinol (Δ 18} -THC), Δ ¹⁹ -tetrahydrocannabinol (Δ 19 -THC), Δ 20 -tetrahydrocannabinol (Δ 20 -THC), Δ ²¹ -tetrahydrocannabinol (Δ ²¹ -THC), Δ 22 -tetrahydrocannabinol (Δ 22 -THC), Δ 23 -tetrahydrocannabinol (Δ 23 -THC), Δ 24 -tetrahydrocannabinol (Δ ²⁴ -THC), Δ ²⁵ -tetrahydrocannabinol (Δ 25 -THC), Δ 26 -tetrahydrocannabinol (Δ ^{26 -THC), Δ 27} -tetrahydrocanna 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).

In one embodiment, the cannabinoid(s) of interest are selected from cannabidiol (CBD), Δ ⁸ -tetrahydrocannabinol (Δ ⁸ -THC), Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC).

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

In one embodiment, the cannabinoid of interest is Δ ⁸ -tetrahydrocannabinol (Δ ⁸ -THC).

In one embodiment, the cannabinoid of interest is Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC).

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

In one embodiment, the cannabinoid is cannabidiol (CBD) or a pharmaceutically 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%.

Cannabinoids may be present in the aerosolizable material on a mg/ml basis of the aerosolizable material.

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.

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.

The aerosolizable material contains one or more sensate compounds at a specified concentration. The terms "sensate compound" or "sensate," used interchangeably herein, refer to a compound that elicits a sensation mediated by the trigeminal nerve in the user. The use of sensory compounds is well documented in the food and pharmaceutical industries, and the sensations evoked include cooling, warming, and tingling sensations. When used as an aerosolizable material, such sensations should be experienced in the user's oral cavity, nasal cavity, and/or skin. The present disclosure is not limited in this regard.

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

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 falls under the category of chemosensation, which occurs when small organic molecules activate specific receptors in the skin and/or mucous membranes. Therefore, the experience of a cooling, warming, and/or tingling sensation depends on the user's chemosensation. Chemosensation refers to the senses that are elements of the somatosensory system, typically mediated by the trigeminal nerve, and is also referred to in the art as "general chemosensation" or trigeminal chemosensation, as these senses are distinct from olfaction (the sense of smell) and taste.

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):

or a salt and/or solvate thereof,
wherein X is hydrogen or OR', R' is an alkyl or alkenyl group which may be taken together 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, _R1 and _R2 are each independently selected from hydrogen, OH, _ORa , _C (O) _NRbRc , and _C (O) _ORbRc , 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, a C(O)R _f group, or a C(O)-alkyl-C(O)R _f group, wherein the alkyl and alkenyl groups are optionally substituted with one or more substituents selected from 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 , wherein the alkyl and alkenyl groups are optionally substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , and CN;
R _b and R _c are each independently hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, wherein the alkyl group, alkenyl group, aryl group, and heteroaryl group are optionally substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , CN, and C(O)R _f .

In one embodiment, X is hydrogen.

In one embodiment, X is OR' and R' is an alkyl or alkenyl group which, 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, 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, together with _R1 , forms a 4- or 5-membered heterocyclyl group, which is optionally substituted with alkyl-OH, _R1 is OR _a , R _a is an alkyl group, and _R2 is absent or hydrogen.

In one embodiment, _R1 is selected from OH, _ORa , and C(O) _NRbRc , _{and R2} is either absent or selected from OH and _ORa . 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 OH and _ORa .

In one embodiment, X is hydrogen and _R1 is selected from OH, _ORa , and _C (O) _NRbRc , with the proviso that when _R1 is OH, the compound of formula (I) is not menthol. _R2 is either absent or selected from OH and _ORa . In one embodiment, X is hydrogen and _R1 is selected from _ORa and C(O) _NRbRc , and _R2 is either absent or selected from OH _{and ORa} .

In one embodiment, R ₁ is OR _a , where R _a is an alkyl group substituted with one or more OH substituents. R ₂ can be hydrogen.

In one embodiment, R ₁ is OR _a , where R _a is a C(O)R _f group or a C(O)-alkyl-C(O)R _f group, where R _f is an alkyl group optionally substituted with one or more OH substituents, or R _f is OH. R ₂ can be hydrogen.

In one embodiment, _R1 is C(O) _NRbRc , _{and Rb} and _Rc are each independently hydrogen, an alkyl group, an aryl group, an _aralkyl group, a heteroaryl group, or a heteroaralkyl group. In one embodiment, _R1 is C(O) _NRbRc , and at least one of _Rb and _Rc is hydrogen. _R2 can be hydrogen.

In one embodiment, _R1 is C(O) _NRbRc , where _Rb is hydrogen and _Rc is selected from _the group consisting of alkyl, aryl, aralkyl, and heteroaralkyl groups. _R2 can be hydrogen.

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, an alkyl group is a C _1-10 alkyl group. In one embodiment, an alkyl group is a C 1-8 alkyl group. In one embodiment, an alkyl group is _a C _1-6 alkyl group. In one embodiment, an alkyl group is a C _1-3 alkyl group. In one embodiment, alkyl groups include, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl. In one embodiment, alkyl groups include methyl, ethyl, propyl, or isopropyl.

As used herein, the term "alkenyl" includes both unsaturated straight-chain and branched alkenyl groups, which may be substituted (mono- or polysubstituted) or unsubstituted. In one embodiment, an alkenyl group is a _C2-10 alkenyl group. In one embodiment, an alkenyl group is a _C2-8 alkenyl group. In one embodiment, an alkenyl group is a _C2-6 alkenyl group. In one embodiment, an alkenyl group is a _C2-3 alkenyl group.

As used herein, the term "aryl" refers to a _C6-12 aromatic group that may be substituted (mono- or poly-substituted) or unsubstituted. Typical examples include phenyl and naphthyl. In one embodiment, the aryl group is phenyl.

The term "aralkyl" is used as a combination of the terms alkyl and aryl as given above. For example, an aryl group may be attached to a compound of formula (I) via a diradical alkylene bridge (-CH ₂ -) _n , where n is 1 to 10, and "aryl" is defined above. Alternatively, an alkyl group may be attached to a compound of formula (I) via a diradical aryl bridge, such as phenyl, and "alkyl" is defined above. In one embodiment, the term "aralkyl" refers to a phenyl-alkyl group, where the phenyl is attached to a compound of formula (I).

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 1 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.

In one embodiment, 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, heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, and pyrrolyl. In one embodiment, heteroaryl is pyridyl.

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 to 3 heteroatoms in the ring. In one embodiment, a heterocyclyl has 1 to 3 oxygen and/or nitrogen heteroatoms in the ring. In one embodiment, a heterocyclyl has 1 to 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.

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-oxopiperazinyl, These 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.

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

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 (one or more chiral carbon atoms) or tautomeric properties. The corresponding enantiomers and/or tautomers may be isolated/prepared by methods known in the art. Some compounds of Formula (I) may exist as stereoisomers and/or geometric isomers; for example, the 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, where appropriate, the use of all individual stereoisomers and geometric isomers of the compounds, as well as mixtures thereof. The terms used in the claims encompass these forms.

Suitable salts of compounds of formula (I) include suitable acid addition salts or base salts thereof. Such salts and solvates thereof will be known in the art. Suitable acid addition salts include carboxylates (e.g., formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, α-hydroxybutyrate, lactate, tartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methyl benzoate, hydroxybenzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, salts, such as suberate, sebacate, fumarate, malate, maleate, hydroxymaleate, hippurate, phthalate, or terephthalate salts; halide salts (e.g., chloride, bromide, or iodide salts); sulfonate salts (e.g., benzenesulfonate, methyl, bromo, or chlorobenzenesulfonate, xylenesulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, hydroxyethanesulfonate, 1- or 2-naphthalenesulfonate, or 1,5-naphthalenedisulfonate); or sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, or nitrate.

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 a cooling agent selected from the group consisting of menthyl succinate.

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.

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 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.

In one embodiment, the cooling agent is

is selected from the group consisting of:

The above chemical formula is also shown in Appendix 1, along with the trade name and chemical name.

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

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

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 listed in Appendix 1.

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.

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.

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.

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.

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

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

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.

In one embodiment, the one or more sensate agents include a warming agent or a tingling agent. In one embodiment, the warming agent or tingling agent is selected from the group consisting of vanilloid, 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, Sichuan pepper, cayenne pepper, uzazi, or mustard oil.

Vanilloids are compounds containing a vanillyl group, and many vanilloids bind to the transient receptor potential vanilloid type 1 (TRPV1) receptor, an ion channel that responds spontaneously to stimuli. Thus, TRPV1 is a component of the mammalian somatosensory system. Vanilloids include capsaicin (8-methyl-N-vanillyl-6-nonenamide) and nonivamide, as well as 3-phenylpropyl homovanillate, the primary 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.

Sanshool is hydroxy-alpha-sanshool, the compound responsible for the numbing and tingling sensation caused, for example, by eating Sichuan peppercorns and foods cooked with uzazi. The term "sanshool" comes from the Japanese pepper and the suffix "ol," meaning "alcohol." It is an agonist of TRPV1 and TRPA1 (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.

Cinnamyl phenylpropyl compounds share common structural characteristics of aryl-substituted primary alcohols/aldehydes/esters. Examples of 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.

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.

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, Sichuan pepper, cayenne pepper, uzazi, or mustard oil.

In one embodiment, the warming or tingling agent is selected from the group consisting of vanilloids, 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, or cayenne pepper.

In one embodiment, the warming or tingling agent comprises a combination of a vanilloid and a cinnamylphenylpropyl 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, for example, 3-phenylpropyl homovanilate and 3-phenylpropan-1-ol.

In one embodiment, the warming or tingling agent is a combination of a vanilloid, an ethyl ester, and a cinnamylphenylpropyl 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 includes a combination of a vanilloid, an ethyl ester, and 3-phenylpropan-1-ol, e.g., 3-phenylpropyl homovanilate and 3-phenylpropan-1-ol. The ethyl ester in any of these embodiments can be ethyl acetate.

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, Sichuan pepper, cayenne pepper, uzazi, or mustard oil.

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.

In one embodiment, the warming 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 warming or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Sichuan pepper, cayenne pepper, uzazi, or mustard oil.

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.

In one embodiment, the warming 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 warming or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Sichuan pepper, cayenne pepper, uzazi, or mustard oil.

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

Some compounds may exist as stereoisomers and/or geometric isomers; for example, these compounds may have one or more asymmetric and/or geometric centers and may therefore 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. The term "piperine" is used herein to refer to all individual geometric isomers and mixtures thereof.

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

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

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

In one embodiment, the one or more sensate agents consist of a cooling agent and a warming agent.

In one embodiment, the one or more sensate agents comprise a cooling agent and a tingling agent.

In one embodiment, the one or more sensate agents comprise a warming agent and a tingling agent.

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 can consist of a cooling agent, where 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, by way of example, the one or more sensate agents can consist of a warming agent or a tingling agent as defined above. In one embodiment, the one or more sensates are warming agents selected from the group consisting of hydroxy-alpha sanshool, capsaicin, piperine, zingerone, gingerol, shogaol, allyl isothiocyanate, and combinations thereof, or extracts 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 homovanilate, an ethyl ester such as ethyl acetate, and 3-phenylpropan-1-ol.

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 one or more sensate 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. While the 0.01-10% w/w range is used herein as an example, the present disclosure is not limited to this concentration range and the combination of specified sensate agents.

Furthermore, the sensate concentration can be combined with the previously defined concentration of at least one cannabinoid.

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

In another embodiment, one or more sensate agents 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 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 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 defined herein are present in the material in an amount of about 0.1% w/w to about 10% w/w.

In another embodiment, 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, 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, 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, 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.

In another embodiment, 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, 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, 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, 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.

In another embodiment, 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, 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, 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, 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.

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

In one embodiment, one or more sensate agents 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 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 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.

In another embodiment, one or more sensate agents 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 sensate agents 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 sensate agents 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 sensate agents 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.

In another embodiment, one or more sensate agents 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 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 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 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.

In another embodiment, one or more sensate agents 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 sensate agents 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 sensate agents 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 sensate agents 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.

In another embodiment, 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, 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 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 sensate agents 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 sensate agents 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.

One or more antioxidants are not sensates, and vice versa. This means that the aerosolizable material must contain an antioxidant and a sensate; a single compound cannot provide both antioxidant and sensate functions. One or more antioxidants may be selected from the enediol class of compounds. For example, in one embodiment, the one or more antioxidants are selected from the group consisting of ascorbic acid, sodium ascorbate, retinol, cholecalciferol, and combinations thereof.

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-lecithin, niacin, niacin, niacinamide, niacinamide, niacinamide α-lecithin, niacinamide β ... 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.

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.

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.

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

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

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

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

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

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

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

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

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

Those skilled in the art will understand that the concentration of antioxidant applies to the concentrations defined above for each of the one or more sensate agents and/or at least one cannabinoid. For example, 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 12% w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or greater, and the one or more antioxidants are each present in an amount of at least 500 ppm.

In another embodiment, one or more sensate agents 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 sensate agents 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.

In another embodiment, one or more sensate agents 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 sensate agents 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.

In another embodiment, one or more sensate agents 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 sensate agents 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.

In another embodiment, 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, 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 sensate agents 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.

Carrier Component The carrier component comprises one or more components that are 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 greater, based on the total weight of the aerosolizable material.

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

In some embodiments, the carrier component may further include 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.

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.

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.

In some embodiments, the w/w % amount of propylene glycol in the aerosolizable material is equal to or exceeds a threshold C _% based on the total weight of the material, the threshold being:
C _% = 11.416 x (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.

In some embodiments, the amount of propylene glycol in the system is above the threshold C _% . For example, the amount of propylene glycol can 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% above the threshold C %. Including more propylene glycol than the threshold can be important if the aerosolizable material attracts water during storage. Thus, this additional propylene glycol can prevent the CBD from settling during storage.

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. In some embodiments, the aerosolizable material contains less than 1% w/w water. In some embodiments, the aerosolizable material contains less than 0.5% w/w water. In some embodiments, the aerosolizable material is substantially free of water.

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.

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

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

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

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

Additional 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/nicotine bitartrate), nicotine-free tobacco substitutes, other alkaloids such as caffeine, or mixtures thereof. In other embodiments, the aerosolizable material is nicotine-free, meaning that nicotine is not included in the aerosolizable material.

In some embodiments, the additional component is selected from "fragrances" and/or "flavorings," which, where local regulations permit, may be used to create a desired taste or aroma in a product for adult consumers. Those skilled in the art will recognize that, in the context of this disclosure, fragrances or flavorings are not sensate compounds as defined herein. In some cases, fragrances or flavorings may be selected from 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, se). The ingredients may include one or more of the following: ginger, 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.

Fragrances can be added to the aerosolizable material as part of a so-called "fragrance block," in which one or more fragrances are blended together and then added to the aerosolizable material. The "fragrance block" can optionally include one or more sensate compounds.

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

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.

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

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 formulations including cannabinoids such as cannabidiol, it may be desirable to have a low pH to prevent conversion of cannabidiol to other cannabinoids and to stabilize the formulation. Additionally, 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.

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

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.

For the avoidance of doubt, the pH of the aerosolizable material applies to all aerosolizable materials described herein, including those containing additional components, i.e., fragrances.

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

In this regard, the inventors have found that when preparing aerosolizable materials 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 exceeds this range, this is an indication that one or more of the material's components are not stable in the material. This can affect the use of the aerosolizable material in many ways. For example, a user may perceive a lack of stability and may perceive the aerosolizable material as being of inferior 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 using the material. The inventors have found that stability issues can 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.

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.

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

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

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

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

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

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

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

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.

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 surfactant component that serves to improve the emulsification/dispersion of one or more of the components. However, for user tolerance reasons, it may not be desirable to include such a functional component. Thus, in some embodiments, the aerosolizable material does not include a surfactant component. Examples of surfactant components include medium chain triglycerides (MCTs) and tocopherol acetate.

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

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.

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

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

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

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

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.

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 (storage portion) for receiving the aerosolizable material as defined herein, an aerosol-generating component, an aerosol-generating region, and/or a mouthpiece.

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 (e.g., a heater), an aerosol-generating region, a transport element, and a mouthpiece.

The aerosolizable material can be transferred from a storage unit for receiving the aerosolizable material to the aerosol-generating component via a transfer element such as a wick, a pump, or the like. Those skilled in the art can select a suitable transfer element depending on the type of aerosolizable material to be transferred and the rate at which the aerosolizable material must be supplied. Particular mention may be made of transfer elements such as wicks formed from fibrous materials, foam materials, sintered materials, woven and nonwoven materials.

The airflow path typically extends through the article (optionally via a device) to the outlet. The path is oriented so that the generated aerosol is entrained in the airflow, thereby enabling the aerosol to be delivered to the outlet for inhalation by the user.

In one embodiment, the aerosol-generating component is a heater.

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

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

The article 30 includes a storage portion for aerosolizable material (liquid feedstock) 38 containing the aerosolizable material (liquid feedstock) 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 the 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. One or more portions of the wick 37 are in fluid communication with the aerosolizable material in the storage portion 38, and by wicking or capillary action, the aerosolizable material is drawn along or through the wick 37 to one or more portions of the wick 37 that are in contact with the heater 36.

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, causing evaporation, thus generating an aerosol. The aerosolizable material, wick 37, and heater 36 may be collectively referred to as an aerosol or vapor source. The wick 37 and heater 36 may be collectively referred to as a vaporizer or atomizer 15.

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.

As noted 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 therein. 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 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.

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 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.

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 nonwoven, 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 range from 100 to 300 g/ ^m² .

When the wick is generally planar, the wick thickness can range from 75 to 250 μm. A typical fiber diameter can be about 12 μm, and a typical average pore size (the size of the voids between the fibers) can be about 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.

It should also be noted that the material is described as planar, which refers to the relative dimensions of the sheet material and 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 concave and/or convex.

The wick element can have a variety of characteristics. It is formed from a porous material to enable the necessary wicking or capillary effect to draw the source liquid from the aerosolizable material reservoir (where the wick meets the aerosolizable material at the reservoir-contact site) through the wick element to the vaporization interface. 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. Depending on the material, pore size, and desired wicking rate, any level of porosity can be used. For example, a porosity of 30% to 85%, e.g., 40% to 70%, 50% to 80%, 35% to 75%, or 40% to 75% can be selected. Because porosity may or may not be uniform throughout the wick, the porosity may be an average porosity value for the entire wick element. For example, the pore size at the reservoir-contact site may be different from the pore size closer to the heater.

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

As an example, porous sintered ceramic is a useful material for use as a wick element. Any ceramic with suitable porosity can be used. When 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 and optionally applying pressure to cause it to agglomerate). Sintering then solidifies the ceramic, creating the porous wick.

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.

The aerosol delivery device 20 includes a power source (a rechargeable cell or battery 14, hereafter referred to as the 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 a battery section, or a control unit or section.

During operation of the device, the controller determines when a user initiates a request for aerosol generation. 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. The sensor 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.

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

In this particular example, device 20 and article 30 are detachable from one another by separation in a direction parallel to the longitudinal axis, as shown in FIG. 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, particularly connecting heater 36 to battery 14. The battery may be charged as known to those skilled in the art.

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

In some embodiments, the article comprises a housing containing the aerosolizable material. The housing may be transparent so that the aerosolizable material is visible from outside the housing. Alternatively, the housing may 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 destabilizing the aerosolizable material. In this regard, the inventors have believed that cannabinoids may be particularly susceptible to such photodestabilization. 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 inhibits/prevents the passage of ultraviolet light through the sealed container. Additionally, 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 containers, including blister packs that are hermetically sealed and/or have one or more hermetically sealed compartments for storing one or more items containing the aerosolizable materials described herein.

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

Preparation of the Material 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, one or more antioxidants, and 0.01 to 12% w/w of one or more sensate(s). The cannabinoid, carrier component, antioxidant(s), and sensate(s) are defined herein, including concentrations and chemical definitions.

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

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 maintains a high degree of stability. As defined herein, air impermeable means that the packaged material is closed or sealed to render it substantially air impermeable.

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 containing the aerosolizable material as defined herein. In this regard, the stability of the packaged material can be maintained during use.

In one embodiment, the packaged material is packaged in a container containing an aerosolizable material described herein and a gas, such as air, _CO2 , _N2 , or a noble gas. In this regard, the volume of the gas in the container is referred to as the headspace. It is preferable to reduce the volume of the headspace in the container so that the stability of the packaged material can be maintained. In one embodiment, there is a method for 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.

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.

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.

Recent consumer research has revealed that cannabidiol (CBD) in aerosolized CBD formulations, including aerosolized CBD formulations containing one or more flavorings or flavoring agents, tastes bitter. 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.

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.; containing 3-phenylpropyl homovanillate, 3-phenylpropan-1-ol, and ethyl acetate) was used as the tingling sensate. The sensate was used in combination with tropical, mint, and fruity flavored CBD aerosolizable materials.

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

Example 1
Prior to preparing the formulations shown in Table 1, solubility tests were conducted to determine whether ginger extract, WS-3, and SymHeat PV were each 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.

One hour after the addition of VG, it was determined that each sensate was solubilized in the PG/VG mixture.

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 60 mg/ml CBD-flavored propylene glycol and glycerol mixture. These are the formulations shown in Table 1 above.

Example 2
After successfully incorporating each sensate into the 60 mg/ml CBD-flavored propylene glycol and glycerol mixtures 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.

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 mitigate the negative sensory experiences typically associated with vaping CBD formulations, enabling the development of new CBD-containing aerosolizable materials that can complement both the taste of the material and the mood state of the consumer.

The various embodiments described herein are presented solely 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 intended to be 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 limitations on the scope of the invention as defined by the claims or equivalents thereof, and that other embodiments may be utilized and modifications may be made without departing from the scope of the invention as claimed. Various embodiments of the invention may suitably comprise, 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. Furthermore, this disclosure may include other inventions not claimed herein but which may be claimed in the future.

Appendix 1

Claims (46)

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 sensate agents, wherein the carrier component is present at 70% w/w or greater based on the total weight of the aerosolizable material, and wherein the one or more antioxidants are not the sensate agents, and the one or more sensate agents are not the antioxidants. 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. The one or more sensate agents are of formula (I):

or a salt and/or solvate thereof,
wherein X is hydrogen or OR', and R' is an alkyl or alkenyl group which can form a 3-5 membered heterocyclyl group together with _R1 , said heterocyclyl group being unsubstituted or 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; _R1 and _R2 are each independently selected from hydrogen, OH, _ORa , C(O) _NRbRc , and C(O _{) ORbRc} , 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, a C(O)R _f group, or a C(O)-alkyl-C(O)R _f group, wherein the alkyl and alkenyl groups are unsubstituted or substituted with one or more substituents selected from 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 , wherein the alkyl and alkenyl groups are unsubstituted or substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , and CN;
3. The aerosolizable material of claim 2, wherein R _b and R _c are each independently hydrogen, an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group, and the alkyl group, alkenyl group, aryl group, and heteroaryl group are unsubstituted or substituted with one or more substituents selected from OH, O-alkyl, NH ₂ , NH-alkyl, N-(alkyl) ₂ , NO ₂ , CN, and C(O)R _f . 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. The aerosolizable material of claim 2, wherein the one or more sensate agents include 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. 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. The aerosolizable material of claim 2, wherein the one or more sensate agents include a warming agent or a tingling agent. 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, Sichuan pepper, cayenne pepper, uzazi, or mustard oil. 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 , or a combination of 3-phenylpropyl homovanilate, ethyl acetate, and 3-phenylpropan-1-ol. 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, capsaicinoid, 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, Sichuan pepper, cayenne pepper, uzazi, or mustard oil. 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. 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. The aerosolizable material of claim 1, wherein the one or more sensate agents are present in the material in an amount of 0.01 to 10% w/w. The aerosolizable material of claim 1, wherein the one or more sensate agents are present in the material in an amount of 0.01 to 5% w/w. The aerosolizable material of claim 1, wherein the one or more sensate agents are present in the material in an amount of 0.01 to 2.5% w/w. and wherein the at least one cannabinoid is selected from the group consisting of cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), the 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), Δ ^{12 -tetrahydrocannabinol (Δ 12 -THC), Δ 13 -tetrahydrocannabinol (Δ 13 -THC), Δ 14} -tetrahydrocannabinol (Δ 14 -THC), Δ ^{15 -tetrahydrocannabinol (Δ 15 -THC), Δ 16 -tetrahydrocannabinol (Δ 16 -THC), Δ 17 -tetrahydrocannabinol (Δ 17 -THC), Δ 18} -tetrahydrocannabinol (Δ ¹⁸ -THC), Δ 19 -tetrahydrocannabinol (Δ ¹⁹ -THC), Δ 20 -tetrahydrocannabinol (Δ 20 -THC), Δ 21 -tetrahydrocannabinol (Δ 21 -THC), Δ ²² -tetrahydrocannabinol (Δ 22 -THC), Δ 23 -tetrahydrocannabinol (Δ 23 -THC), Δ 24 -tetrahydrocannabinol (Δ ²⁴ -THC), Δ ²⁵ -tetrahydrocannabinol (Δ 25 -THC), Δ 26 -tetrahydrocannabinol (Δ 26 -THC), Δ ²⁷ -tetrahydro 2. The aerosolizable material of claim 1, wherein the hydroxyl group 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, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabiditriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). 17. The aerosolizable material of claim 16, wherein the at least one cannabinoid is selected from 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 -THC), and cannabinol (CBN). 17. The aerosolizable material of claim 16, wherein the at least one cannabinoid is selected from cannabidiol (CBD), Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC), and cannabinol (CBN), or the at least one cannabinoid is cannabidiol. The aerosolizable material of claim 1, wherein the at least one cannabinoid is present in the material in an amount of 30 mg/ml or greater. 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. The aerosolizable material of claim 1, wherein the one or more antioxidants are selected from the enediol class of compounds. 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-resorcyl, pyrogallol, malic acid, niacin ... The aerosolizable material of claim 1, selected from the group consisting of rubidin, 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. The aerosolizable material of claim 1, wherein the one or more antioxidants are selected from ascorbic acid, sodium ascorbate, and combinations thereof. The aerosolizable material of claim 1, wherein the one or more antioxidants are each present in an amount of at least 500 ppm. The aerosolizable material of claim 24, wherein the one or more antioxidants are each present in an amount of at least 1000 ppm. The aerosolizable material of claim 1, 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. The aerosolizable material of claim 26, wherein the carrier component further comprises glycerol, or wherein the carrier component comprises at least 30% w/w glycerol. The aerosolizable material of claim 1, wherein the carrier component comprises at least 60% w/w propylene glycol or at least 70% w/w propylene glycol. The aerosolizable material of claim 1, wherein the carrier component is present in an amount of 80% w/w or more based on the total weight of the aerosolizable material. The aerosolizable material of claim 1, 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. The aerosolizable material of claim 1, wherein the material is nicotine-free. An article comprising the aerosolizable material of claim 1. The article described in claim 32, comprising a storage portion for receiving the aerosolizable material described in any one of claims 1 to 31, an aerosol-generating component, an aerosol-generating region, a transport element, and a mouthpiece. The article of claim 33, wherein the aerosol-generating component comprises a heater. The article of claim 33, wherein the transport element is a wick. An aerosol delivery system comprising an aerosol delivery device and the article described in claim 32. 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. The method of claim 37, characterized by the features of any one of claims 2 to 31. A sealed container containing the article described in claim 32. 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. The sealed container of claim 39, wherein the sealed container comprises a blister pack having one or more hermetically sealed compartments. A process for forming an aerosol, comprising: (i) providing an aerosolizable material according to any one of claims 1 to 31; and (ii) aerosolizing the material. Use of one or more sensates to reduce or mask a user's physiological response to at least one cannabinoid in an aerosolizable material, wherein the aerosolizable material comprises 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. The use described in claim 43, wherein the aerosolizable material is characterized by the features described in any one of claims 1 to 31. The use of claim 43, wherein the physiological response of the user is a sensory response. 46. The use of claim 45, wherein the sensory response comprises taste.