WO2023135408A1

WO2023135408A1 - Aerosolisable material

Info

Publication number: WO2023135408A1
Application number: PCT/GB2022/053336
Authority: WO
Inventors: Danielle TOWER; Andrew Burton; Tony Comerford; Alice HUGHES; Matthew SEAMAN
Original assignee: Nicoventures Trading Limited
Priority date: 2022-01-14
Filing date: 2022-12-21
Publication date: 2023-07-20

Abstract

The present disclosure relates to an aerosolisable material, a method of making said material, as well as containers and systems comprising and using said material.

Description

Aerosolisable material

Field

Background

Aerosol delivery systems which generate an aerosol for inhalation by a user are known in the art. Such systems typically comprise an aerosol generator which is capable of converting an aerosolisable material into an aerosol. In some instances, the aerosol generated is a condensation aerosol whereby an aerosolisable material is heated to form a vapor which is then allowed to condense into an aerosol. In other instances, the aerosol generated is an aerosol which results from the atomization of the aerosolisable material. Such atomization may be brought about mechanically, e.g. by subjecting the aerosolisable material to vibrations so as to form small particles of material that are entrained in airflow. Alternatively, such atomization may be brought about electrostatically, or in other ways, such as by using pressure etc.

Depending on the constituents of the aerosolisable material that are to be provided to a user, it may be preferable to formulate the aerosolisable material in a certain way. For example, it may be preferable to formulate the aerosolisable material so as to produce an aerosol with a particular profile. It may also be preferable to formulate the aerosolisable material so as to ensure the aerosolisable material meets certain standards of quality, consistency and the like.

It would thus be desirable to provide an aerosolisable material that is formulated so as to be acceptable to a user.

Summary

In one aspect, there is provided an aerosolisable material comprising at least one cannabinoid, a carrier constituent comprising at least 50% w/w propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material, one or more antioxidants, and 0.01 to 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. The terms “sensate” and “antioxidant” being well-known in the art and discussed further below.

In a further aspect there is provided an article comprising the aerosolisable material as defined herein. In a further aspect there is provided an aerosol provision system comprising an aerosol provision device and an article as defined herein.

In a further aspect there is provided a method for producing the aerosolisable material as defined herein, the method comprising combining at least one cannabinoid, a carrier constituent comprising at least 50% w/w propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material, one or more antioxidants, and 0.01 to 12% w/w of one or more sensates, wherein the one or more antioxidants and not sensates and the one or more sensates are not antioxidants.

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

In a further aspect there is provided a process for forming an aerosol, the process comprising: (i) providing an aerosolisable material as defined herein, and (ii) aerosolising the material.

In a further aspect there is provided a use of one or more sensates to mitigate or mask the physiological response of a user to at least one cannabinoid in an aerosolisable material, the aerosolisable material comprising the at least one cannabinoid and a carrier constituent comprising at least 50% propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material.

These aspects and other aspects will be apparent from the following detailed description. In this regard, particular sections of the description are not to be read in isolation from other sections.

Brief Description of the Annex and Drawings

Various embodiments will now be described in detail by way of example only with reference to the accompanying Annex and drawings in which:

Annex 1 - Provides the chemical formulae of sensates as described herein.

Figure 1 - Provides a schematic overview of an article, aerosol delivery device and system as described herein.

Detailed Description

Cannabinoids are a class of natural or synthetic chemical compounds that act on cannabinoid receptors (i.e. , CB1 and CB2) in cells that repress neurotransmitter release in the brain.

Cannabinoids are cyclic molecules exhibiting particular properties such as the ability to cross the blood-brain barrier with ease. Cannabinoids may be naturally occurring (phytocannabinoids) from plants such as cannabis, (endocannabinoids) from animals, or artificially manufactured (synthetic cannabinoids). Cannabis species express at least 85 different phytocannabinoids, and these may be divided into subclasses, including cannabigerols, cannabichromenes, cannabidiols, tetrahydrocannabinols, cannabinols and cannabinodiols, and other cannabinoids, such as cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), including its isomers Acetetrahydrocannabinol (A^{6a a}-THC), A^6a(7)-tetrahydrocannabinol (A^6a(7)-THC), A⁸- tetrahydrocannabinol (A⁸-THC), A⁹- tetrahydrocannabinol (A⁹-THC), A¹⁰-tetrahydrocannabinol (A¹⁰-THC), A^{9 11} -tetrahydrocannabinol (A^{9 11}-THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), Cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A).

Although the legal status of specific cannabinoids varies from jurisdiction to jurisdiction, certain active components, for example cannabidiol (CBD), tetrahydrocannabinol (THC) and cannabinol (CBN), are being considered for use in a wide variety of applications, such as in 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 depending on certain environmental conditions, such as exposure to air or light, or variation in temperature and pH. This may have unintended and detrimental consequences.

For example, CBD may oxidise and degrade when exposed to light and/or air to form cannabidiol hydroxyquinone (CBDHQ or HU-331) and its isomeric or functional derivatives. Furthermore, CBD may be converted to AMetrahydrocannabinol (A⁹-THC) in response to variations in temperature and/or pH. As a result, the accuracy of the specified cannabinoid content and/or concentration may vary widely in the formulations, while regulated and restricted cannabinoids may be produced unintentionally that will render the product as illicit or unlicensed in certain jurisdictions. As such, there is a desire to provide formulations comprising one or more cannabinoids that maintain a high degree of purity during manufacture and storage, and in turn prevent the loss or degradation of one or more cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC) or cannabinol (CBN), in a formulation.

In addition to these stability requirements for cannabinoid formulations, consumer feedback on CBD formulations used in aerosol delivery systems, otherwise referred to as CBD aerosolisable materials, has in some instances been negative with regards to sensorial experience. The natural taste of CBD is often described as ‘earthy’ or ‘grassy’, and whilst the addition of one or more flavouring agents has been previously used in an attempt to mask this taste, this has not always been successful. In particular, consumers have indicated that flavoured CBD aerosolisable materials still can have bitter taste or off notes associated with the taste such that the inhalation of the CBD aerosol may be unpleasant and unsatisfactory. Users may even decide to avoid CBD aerosolisable materials all together; being put off by the taste, aroma and/or other sensation experienced during use.

It has been found that by including one or more antioxidants within a cannabinoid containing formulation, together with 0.01 to 12% w/w of one or more sensates, it is possible to not only mitigate the extent to which derivatives of the cannabinoid of interest are formed, but provide a cannabinoid aerosolisable material which mitigates or masks the physiological response of a user to the cannabinoid in the material. Notably, the undesirable earthy, grassy or bitter taste discussed above is mitigated or masked by the one or more sensates as discussed further below. The sensates are able, in the unique context of a cannabinoid aerosolisable material, to provide additional sensations, harmonise with existing flavours and/or reduce the off notes associated with the taste of the cannabinoid, all without compromising the stability or usability of the aerosolisable material. This means that higher levels of cannabinoid may be feasibly included in the material, if so desired.

By the term “physiological response” is meant the body’s automatic or instinctive reaction to a stimulus, for example, sensorial responses including taste and smell, it does not include any psychoactive effect of the 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 under 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. An 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 around 99% purity. A synthetic cannabinoid is one which has been derived from a chemical synthesis as opposed to being isolated from a plant or biological source.

In one embodiment the cannabinoid(s) of interest are selected from cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), including its isomers A^6a’^10a-tetrahydrocannabinol (A^{6a a}-THC), A^6a<⁷ etrahydrocannabinol (A^6a<⁷>-THC), A⁸- tetrahydrocannabinol (A⁸-THC), A⁹- tetrahydrocannabinol (A⁹-THC), A¹⁰-tetrahydrocannabinol (A¹⁰-THC), A^{9 11} -tetrahydrocannabinol (A^{9 11}-THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (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), A⁸- tetrahydrocannabinol (A⁸-THC), A⁹- tetrahydrocannabinol (A⁹-THC) and cannabinol (CBN).

In one embodiment the cannabinoid(s) of interest are selected from cannabidiol (CBD), A⁸- tetrahydrocannabinol (A⁸-THC), A⁹- tetrahydrocannabinol (A⁹-THC).

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

In one embodiment the cannabinoid of interest is AMetrahydrocannabinol (A⁸-THC).

In one embodiment the cannabinoid of interest is AMetrahydrocannabinol (A⁹-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 aerosolisable material in the form of a cannabinoid isolate. In one embodiment the cannabinoid isolate comprises cannabidiol (CBD), wherein the cannabidiol (CBD) is present in a purity greater than 95%, greater than 96%, greater than 97%, greater than 98%, or around 99% purity.

The cannabinoid may be present in the aerosolisable material based on a mg/ml basis of the aerosolisable material.

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

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

Sensate Compounds

The aerosolisable material includes one or more sensates at a specified concentration. By the term “sensate compound” or “sensate” - used interchangeably herein - is meant a compound that triggers a sensation mediated by the trigeminal nerve of a user. The use of sensate compounds is well-documented in the food and pharmaceutical industry, and the triggered sensations include cooling, warming, and tingling sensations. When used in an aerosolisable material, such sensations should be experienced in the oral cavity, the nasal cavity and/or by the skin of the user. The present disclosure is not limited in this respect.

In one embodiment, the one or more sensates 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 each typically small organic molecules which deliver a cooling, warming or tingling sensation to a user upon contact with the oral cavity, nasal cavity and/or skin. This sensation falls under the category of chemesthetic sensations and arises because the small organic molecule activates certain receptors in the skin and/or mucous membranes. The experience of a cooling, warming and/or tingling sensation thus relies on chemesthesis of the user. Chemesthesis is also referred to in the art as the “common chemical sense” or trigeminal chemosensation because it typically refers to sensations that are mediated by the trigeminal nerve and which are elements of the somatosensory system, distinguishing them from olfaction (sense of smell) and taste.

In one embodiment, the one or more sensates comprise a cooling agent. The cooling agent is typically not menthol. In one embodiment the one or more sensates comprise a cooling agent which is a compound of formula (I) or a salt and/or solvate thereof:

wherein X is hydrogen or OR’, wherein R’ is an alkyl group or an alkenyl group which may be taken together with Ri to form a three to five-membered heterocyclyl group, wherein the heterocyclyl group is optionally substituted by one or more substituents selected from OH, O- alkyl, alkyl-OH, alkyl-O-alkyl, NH2, NH-alkyl, N-(alkyl)2, NO2 and ON; and wherein R1 and R2 are each independently selected from hydrogen, OH, OR_a, C(O)NRbR_c and C(O)ORbR_c; with the proviso that when R1 is OH the compound of formula (I) is not menthol; and when the double bond is present, R2 is absent; wherein R_a is an alkyl group, an alkenyl group, a C(O)Rf group, or a C(O)-alkyl-C(O)Rf group wherein the alkyl groups and alkenyl groups are optionally substituted by one or more substituents selected from OH, O-alkyl, NH₂, NH-alkyl, N-(alkyl)₂, NO2 and ON; and wherein R_f is an alkyl group, an alkenyl group, OH, O-alkyl, NH₂, NH-alkyl or N-(alkyl)₂, wherein the alkyl groups and alkenyl groups are optionally substituted by one or more substituents selected from OH, O-alkyl, NH₂, NH-alkyl, N-(alkyl)₂, NO₂ and ON; wherein R 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 groups, alkenyl groups, aryl groups and heteroaryl groups are optionally substituted by one or more substituents selected from OH, O-alkyl, NH₂, NH-alkyl, N-(alkyl)₂, NO2, ON and C(O)Rf.

In one embodiment X is hydrogen. In one embodiment X is OR’, wherein R’ is an alkyl group or an alkenyl group which is taken together with Ri to form a three to five-membered heterocyclyl group, wherein the heterocyclyl group is optionally substituted by OH, O-alkyl or alkyl-OH. In one embodiment X is OR’, wherein R’ is an alkyl group which is taken together with Ri to form a four or five-membered heterocyclyl group, wherein the heterocyclyl group is optionally substituted by alkyl-OH. In one embodiment X is OR’, wherein R’ is an alkyl group which is taken together with Ri to form a four or fivemembered heterocyclyl group, wherein the heterocyclyl group is optionally substituted by alkyl- OH, and wherein Ri is OR_a wherein R_a is an alkyl group and wherein R2 is absent or hydrogen.

In one embodiment Ri is selected from OH, OR_a and C(O)NRbR_c and R2 is either absent or selected from OH and OR_a. In one embodiment Ri is OH with the proviso that the compound of formula (I) is not menthol. In one embodiment Ri is OH and R2 is selected from OH and OR_a.

In one embodiment X is hydrogen and Ri is selected from OH, OR_a and C(O)NRbR_c, with the proviso that, when Ri is OH, the compound of formula (I) is not menthol. R2 is either absent or selected from OH and OR_a. In one embodiment X is hydrogen, Ri is selected from OR_a and C(O)NRbR_c and R2 is either absent or selected from OH and OR_a.

In one embodiment Ri is OR_a and R_a is an alkyl group substituted by one or more OH substituents. R2 may be hydrogen.

In one embodiment Ri is OR_a and R_a is a C(O)Rf group, or a C(O)-alkyl-C(O)Rf group, wherein Rf is an alkyl group optionally substituted by one or more OH substituents or Rf is OH. R2 may be hydrogen.

In one embodiment Ri is C(O)NRbR_c, wherein Rb and R_c are each independently hydrogen, an alkyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group. In one embodiment Ri is C(O)NRbR_c and at least one of Rb and R_c is hydrogen. R2 may be hydrogen.

In one embodiment Ri is C(O)NRbR_c, wherein Rb is hydrogen and R_c is selected from the group consisting of an alkyl group, an aryl group, an aralkyl group and a heteroaralkyl group. R2 may be hydrogen.

As used herein, the term “alkyl” includes both saturated straight chain and branched alkyl groups which may be substituted (mono- or poly-) or unsubstituted. In one embodiment the alkyl group is a C1-10 alkyl group. In one embodiment the alkyl group is a C1-8 alkyl group. In one embodiment the alkyl group is a C1-6 alkyl group. In one embodiment the alkyl group is a C1-3 alkyl group. In one embodiment the alkyl groups include, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl. In one embodiment the 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 poly-) or unsubstituted. In one embodiment the alkenyl group is a C2-10 alkenyl group. In one embodiment the alkenyl group is a C2-8 alkenyl group. In one embodiment the alkenyl group is a C2-6 alkenyl group. In one embodiment the alkenyl group is a C2-3 alkenyl group.

As used herein, the term “aryl” refers to a C6-12 aromatic group which may be substituted (mono- or poly-) or unsubstituted. Typical examples include phenyl and naphthyl etc. In one embodiment the aryl group is phenyl.

The term “aralkyl” is used as a conjunction of the terms alkyl and aryl as given above. For example an aryl group may be bonded to the compound of formula (I) through a diradical alkylene bridge, (-CH2-)n, where n is 1-10 and where “aryl” is as defined above. Alternatively an alkyl group may be bonded to the compound of formula (I) through a diradical aryl bridge, e.g. phenyl, where “alkyl is as defined above. In one embodiment the term “aralkyl” refers to a phenyl-alkyl group where the phenyl is bonded to the compound of formula (I).

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

In one embodiment the heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolyl, indolyl, quinolinyl, isoquinolinyl, quinazolinyl, quinoxalinnyl, furanyl, thiophenyl, furyl, pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, pyrazolyl benzofuranyl, and benzothiophenyl. Heteroaryl rings may be unsubstituted or substituted. In one embodiment the heteroaryl is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and pyrrolyl. In one embodiment the heteroaryl is pyridyl.

As used herein the term “heterocyclyl” refers to fully saturated or unsaturated, monocyclic groups, which have one or more oxygen, sulfur or nitrogen heteroatoms in the ring. In one embodiment the heterocyclyl has 1 to 3 heteroatoms in the ring. In one embodiment the heterocyclyl has 1 to 3 oxygen and/or nitrogen heteroatoms in the ring. In one embodiment the heterocyclyl has 1 to 3 oxygen heteroatoms in the ring. The nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be unsubstituted or substituted.

Exemplary monocyclic heterocyclic groups include, but are not limited to, 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, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1 ,3-dioxolane and tetra hydro- 1 ,1- dioxothienyl, triazolyl, and triazinyl.

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

All embodiments include, where appropriate, all enantiomers, tautomers and geometric isomers of the compounds of formula (I). The person skilled in the art will recognise compounds that possess optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and/or tautomers may be isolated/prepared by methods known in the art. Some of the compounds of formula (I) may also exist as stereoisomers and/or geometric isomers - e.g. they may possess one or more asymmetric and/or geometric centers and so may exist in two or more stereoisomeric and/or geometric forms. All embodiments include, where appropriate, the use of all the individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms.

Suitable salts of the compounds of formula (I) include suitable acid addition or base salts thereof. Such salts and solvates thereof will be known in the art. Suitable acid addition salts include carboxylate salts (e.g. formate, acetate, trifluoroacetate, propionate, isobutyrate, heptanoate, decanoate, caprate, caprylate, stearate, acrylate, caproate, propiolate, ascorbate, citrate, glucuronate, glutamate, glycolate, a-hydroxybutyrate, lactate, tartrate, phenylacetate, mandelate, phenylpropionate, phenylbutyrate, benzoate, chlorobenzoate, methylbenzoate, hydroxy benzoate, methoxybenzoate, dinitrobenzoate, o-acetoxybenzoate, salicylate, nicotinate, isonicotinate, cinnamate, oxalate, malonate, succinate, 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- naphthalene-sulfonate or 1,5-naphthalenedisulfonate salts) or sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate or nitrate salts.

In one embodiment, the one or more sensates comprise a cooling agent which is selected from the group consisting of:

N-ethyl-5-methyl-2-(propan-2-yl) cyclohexanecarboxamide, ethyl-2-(5-methyl-2-propan-2-yl cyclohexanecarbonyl amino) acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-2,3-trimethyl-2-propan-2-yl butanamide, N-(2-pyridin-2-yl)ethyl)menthyl carboxamide, menthone- 1,2-glycerol ketal, menthyl lactate, isopulegol, 3-menthoxypropan-1 ,2-diol, and menthyl succinate.

In one embodiment the cooling agent is selected from the group consisting of: N-ethyl-5-methyl-2-(propan-2-yl) cyclohexanecarboxamide, ethyl-2-(5-methyl-2-propan-2-yl cyclohexanecarbonyl amino) acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-2,3-trimethyl-2-propan-2-yl butanamide, N-(2-pyridin-2-yl)ethyl)menthyl carboxamide, menthone- 1,2-glycerol ketal, menthyl lactate, 3-menthoxypropan-1 ,2-diol, and menthyl succinate.

In one embodiment the cooling agent may be selected from the group consisting of: N-ethyl-5-methyl-2-(propan-2-yl) cyclohexanecarboxamide, ethyl-2-(5-methyl-2-propan-2-yl cyclohexanecarbonyl amino) acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-(2-pyridin-2-yl)ethyl)menthyl carboxamide, menthone- 1,2-glycerol ketal, menthyl lactate, isopulegol, 3-menthoxypropan-1 ,2-diol, and menthyl succinate, or from the group consisting of:

N-ethyl-5-methyl-2-(propan-2-yl) cyclohexanecarboxamide, ethyl-2-(5-methyl-2-propan-2-yl cyclohexanecarbonyl amino) acetate, N-(4-methoxyphenyl)-p-menthanecarboxamide, N-(2-pyridin-2-yl)ethyl)menthyl carboxamide, menthone- 1 ,2-glycerol ketal, menthyl lactate, 3-menthoxypropan-1 ,2-diol, and menthyl succinate.

In one embodiment, the cooling agent is selected from the group consisting of:

The above-depicted chemical formulae are also shown in Annex 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-[[(1 R,2S,5R)-5-methyl-2- propan-2-ylcyclohexanecarbonyl]amino] acetate, (1 R,2S,5R)-N-(4-methoxyphenyl-p- menthanecarboxamide, (1 R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone 1 ,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, 3-((-)-menthoxy)propane-1 ,2-diol, and (-)- menthyl succinate. These compounds are shown in Annex 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-[[(1 R,2S,5R)-5-methyl-2- propan-2-ylcyclohexanecarbonyl]amino] acetate, (1 R,2S,5R)-N-(4-methoxyphenyl-p- menthanecarboxamide, (1 R,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-[[(1 R,2S,5R)-5-methyl-2- propan-2-ylcyclohexanecarbonyl]amino] acetate, (1 R,2S,5R)-N-(4-methoxyphenyl-p- menthanecarboxamide, (1 R,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-[[(1 R,2S,5R)-5-methyl-2- propan-2-ylcyclohexanecarbonyl]amino] acetate, ((1 R,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-[[(1 R,2S,5R)-5-methyl-2- propan-2-ylcyclohexanecarbonyl]amino] acetate, ((1 R,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 (1 R,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 noted above, all embodiments include, where appropriate, all enantiomers and tautomers of the compounds. All embodiments include, where appropriate, the use of all the individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms.

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

Vanilloids are compounds which possess a vanillyl group, and a number of vanilloids bind to the transient receptor potential vanilloid type 1 or TRPVI receptor, an ion channel which naturally responds to stimuli. TRPV1 is therefore an element of the mammalian somatosensory system. Vanilloids include capsaicin (8-methyl-A/-vanillyl-6-nonenamide) and nonivamide as well as 3- phenylpropyl homovanillate, the major component of SymHeat PV used in the Examples herein. Other vanilloids include gingerols, zingerone, and shogaols 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 Annex 1.

Sanshools are exemplified by hydroxy-alpha-sanshool, a compound responsible for the numbing and tingling sensation caused by eating food cooked with Szechuan peppercorns and llzazi. The term “sanshool” is derived from the Japanese term for the Japanese pepper and the suffix “ol” meaning “alcohol”. It is an agonist of TRPV1 and TRPA1 (an ion channel best known as a sensor for pain, cold, and itch in humans and other mammals) and its chemical structure is shown in Annex 1.

Cinnamyl phenylpropyl compounds have a common structural characteristic of an aryl substituted primary alcohol/aldehyde/ester. They include 3-phenylpropyl cinnamate and 3- phenyl-1 -propanol, which each have a spicy taste and balsamic odour, as well as 3- phenylpropyl isobutyrate which has a fruity taste and odour. In one embodiment, the cinnamyl phenylpropyl compounds are selected from 3-phenylpropyl cinnamate, 3-phenyl-1 -propanol and combinations thereof.

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

In one embodiment, the warming agent or tingling agent is selected from the group consisting of sanshools, 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, Szechuan pepper, cayenne pepper, Uzazi or mustard oil. In one embodiment, the warming agent or tingling agent is selected from the group consisting of vanilloids, piperine, cinnamyl phenylpropyl compounds, ethyl esters, and combinations thereof, or the warming agent 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 agent or tingling agent comprises a combination of a vanilloid and a cinnamyl phenylpropyl compound. In one embodiment, the warming agent 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 agent or tingling agent comprises a combination of a vanilloid and 3-phenylpropan-1-ol, such as 3-phenylpropyl homovanillate and 3-phenylpropan-1-ol.

In one embodiment, the warming agent or tingling agent is a combination of a vanilloid, an ethyl ester and a cinnamyl phenylpropyl compound. In one embodiment, the warming agent 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 agent or tingling agent comprises a combination of a vanilloid, an ethyl ester and 3-phenylpropan-1-ol, such as 3-phenylpropyl homovanillate and 3-phenylpropan-1-ol. The ethyl ester may, in any of these embodiments, be ethyl acetate.

In one embodiment, the warming agent 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, sanshools, piperine, zingerone, shogaols (e.g. (6)-shogaol), allyl isothiocyanate, and combinations thereof, or the warming agent or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, llzazi or mustard oil.

In one embodiment, the warming agent 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 agent or tingling agent is selected from the group consisting of capsaicinoids, gingerols (e.g. [6], [8], [10] and/or [12]-gingerol), sanshools, piperine, zingerone, shogaols (e.g. (6)-shogaol), allyl isothiocyanate, and combinations thereof, or the warming agent or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, llzazi or mustard oil. In one embodiment, the warming agent 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 agent or tingling agent is an extract from ginger oil.

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

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

Some of the compounds may also exist as stereoisomers and/or geometric isomers - e.g. they may possess one or more asymmetric and/or geometric centers and so may exist in two or more stereoisomeric and/or geometric forms. All embodiments include, where appropriate, the use of all the individual stereoisomers and geometric isomers of those compounds, and mixtures thereof. The terms used in the claims encompass these forms. Piperine has, for example, four geometric isomers including chavicine, isochavicine and isopiperine. The term “piperine” is used herein to refer to all the individual geometric isomers, and mixtures thereof.

In one embodiment the one or more sensates consist of cooling agents.

In one embodiment the one or more sensates consist of warming agents.

In one embodiment the one or more sensates consist of tingling agents.

In one embodiment the one or more sensates consist of cooling agents and warming agents.

In one embodiment the one or more sensates consist of cooling agents and tingling agents.

In one embodiment the one or more sensates consist of warming agents and tingling agents.

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

The aerosolisable material includes the one or more sensates in an amount of 0.01 to 12% w/w. This concentration range and the concentrations defined below apply to the above definitions of the one or more sensates. For example, the concentration range of 0.01 to 10% w/w applies to the one or more sensates comprising a cooling agent, a warming agent, a tingling agent or a combination thereof. The concentration range of 0.01 to 10% w/w also applies to the one or more sensates with a narrower definition, e.g. consisting of cooling agents, warming agents or tingling agents, etc. The range of 0.01 to 10% w/w is being used here as an example, the present disclosure is not limited to the combination of this concentration range with the specified sensate.

Furthermore, the sensate concentrations are combinable with the above-defined concentrations of the at least one cannabinoid.

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

In another embodiment, the one or more sensate as defined herein is present in the material in an amount of no greater than about 10 % w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 10 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 10 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 10 %w/w.

In another embodiment the one or more sensate as defined herein is present in the material in an amount of no greater than about 8 % w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 8 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 8 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 8 %w/w.

In another embodiment the one or more sensate as defined herein is present in the material in an amount of no greater than about 5 % w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 5 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 5 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 5 %w/w.

In another embodiment the one or more sensate as defined herein is present in an amount of no greater than about 3 % w/w, e.g. no greater than about 2.5 % w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 2.5 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 2.5 %w/w. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 2.5 %w/w.

In some embodiments, the one or more sensate and its concentration is selected based on its solubility in a propylene glycol/glycerol system. For example, the aerosolisable material may include an amount of the one or more sensate in a carrier constituent comprising at least 50% propylene glycol, and glycerol, where the carrier constituent is present at 70% w/w or more of the aerosolisable material, such that the aerosolisable material has a turbidity of < 1.0 NTU. Turbidity and its measurement is discussed further herein.

In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 12 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 12 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 12 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In another embodiment, the one or more sensate as defined herein is present in the material in an amount of no greater than about 10 % w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 10 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 10 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 10 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more.

In another embodiment the one or more sensate as defined herein is present in the material in an amount of no greater than about 8 % w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 8 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 8 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 8 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more.

In another embodiment the one or more sensate as defined herein is present in the material in an amount of no greater than about 5 % w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 5 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 5 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 5 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more.

In another embodiment the one or more sensate as defined herein is present in an amount of no greater than about 3 % w/w, e.g. no greater than about 2.5 % w/w, and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 2.5 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.05 % w/w to about 2.5 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.1 % w/w to about 2.5 %w/w and the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more.

Antioxidant

The one or more antioxidants are not sensates and vice versa. This means that the aerosolisable material must include an antioxidant and a sensate; it is not possible for antioxidancy and sensory functionalities to be provided by a single compound. The one or more antioxidants may be are 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 selected from the group consisting of ascorbic acid, sodium ascorbate, alpha-keto glutaric acid, alpha-keto glutarate salt, 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, a-resorcylic, pyrogallol, malvidin, theaflavin, apigenin, eriodictyol, glycitein, chrysoeriol, kaempferol, luteolin, vitexin, isovitexin, orientin, cannflavin A, cannflavin B, cannflavin C, delphinidin, pelargonidin, epicatechin, myricetin, chrysin, naringenin, a-terpineol, tert-butylhydroquinone, and combinations thereof.

In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants. In one embodiment, the one or more antioxidants comprise 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 500ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 600ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 700ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 800ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 900ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least lOOOppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1100ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1200ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1300ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1400ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1500ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1600ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1700ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1800ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 1900ppm. In one embodiment, the one or more antioxidants are each present in an amount of at least 2000ppm.

In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least 500ppm. In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least 750ppm. In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least lOOOppm. In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least 1250ppm. In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least 1500ppm. In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least 1750ppm. In one embodiment, the one or more antioxidants comprise ascorbic acid and one or more additional antioxidants, wherein ascorbic acid is present in an amount of at least 2000ppm.

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

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

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

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

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

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

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

The person skilled in the art would understand that the antioxidant concentrations apply to the above-defined concentrations for each of the one or more sensates and/or at least one cannabinoid. For example, in one embodiment, the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 12 %w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and one or more antioxidants are each present in an amount of at least 500ppm.

In another embodiment, the one or more sensate as defined herein is present in the material in an amount of no greater than about 10 % w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 10 %w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm.

In another embodiment the one or more sensate as defined herein is present in the material in an amount of no greater than about 8 % w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 8 %w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm.

In another embodiment the one or more sensate as defined herein is present in the material in an amount of no greater than about 5 % w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 5 %w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm.

In another embodiment the one or more sensate as defined herein is present in an amount of no greater than about 3 % w/w, e.g. no greater than about 2.5 % w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm. In one embodiment the one or more sensate as defined herein is present in the material in an amount of from about 0.01 % w/w to about 2.5 %w/w, the at least one cannabinoid is present in the material in an amount of 5 mg/ml or more, and the one or more antioxidants are each present in an amount of at least 500ppm.

Carrier Constituent

The carrier constituent comprises one or more constituents capable of forming an aerosol, particularly when evaporated and allowed to condense. In particular, the carrier constituent comprises at least 50% w/w propylene glycol and the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material.

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

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

In one embodiment, propylene glycol is present in an amount of from 50%w/w to 90%w/w based on the total weight of the aerosolisable material. In one embodiment, propylene glycol is present in an amount of from 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 from 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 from 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 from 50%w/w to 70%w/w based on the total weight of the material.

In one embodiment, the carrier constituent comprises at least 60%w/w propylene glycol. In one embodiment, the carrier constituent comprises at least 65%w/w propylene glycol. In one embodiment the carrier constituent comprises at least 70%w/w propylene glycol.

In some embodiments, the w/w% amount of propylene glycol in the aerosolisable material, based on the total weight of the material, is equal to or above a threshold C%, the threshold being defined according to: C% = 11 .416 x (A)^{0 377}, wherein A is the amount of the at least one cannabinoid present in the material in mg/ml. It has been found that aerosolisable materials comprising at least one cannabinoid, such as cannabidiol, and propylene glycol conforming to the above threshold, are 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 may be about 1w/w%, 2w/w%, 3w/w%, 4w/w%, 5w/w%, 6w/w%, 7w/w%, 8w/w%, 9w/w% or 10w/w% above the threshold C%. Including more propylene glycol relative to the threshold can be important if the aerosolisable material attracts water during storage. This additional propylene glycol can therefore prevent the CBD from precipitating during periods of storage.

In some embodiments, the aerosolisable material comprises less than 12%w/w water. In some embodiments, the aerosolisable material comprises less than 11%w/w water. In some embodiments, the aerosolisable material comprises less than 10%w/w water. In some embodiments, the aerosolisable material comprises less than 5%w/w water. In some embodiments, the aerosolisable material comprises less than 1%w/w water. In some embodiments, the aerosolisable material comprises less than 0.5%w/w water. In some embodiments, the aerosolisable material comprises substantially no water.

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

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

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

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

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

Further Constituents

The aerosolisable material may comprise one or more further constituents. In particular, one or more further constituents may be selected from one or more additional active constituents, and/or one or more functional constituents. In some embodiments, the active constituent is a physiologically active constituent and may be selected from nicotine, nicotine salts (e.g. nicotine ditartrate/nicotine bitartrate), nicotine-free tobacco substitutes, other alkaloids such as caffeine, or mixtures thereof. In other embodiments, the aerolisable material is nicotine-free meaning that no nicotine is included in the aerosolisable material.

In some embodiments, the further constituent is selected from a "flavour" and/or "flavourant" which, where local regulations permit, may be used to create a desired taste or aroma in a product for adult consumers. It will be recognized by the person skilled in the art that a flavour or flavourant, in the context of the present disclosure, is not a sensate compound as defined herein. In some instances flavours or flavourants may include one or more of extracts (e.g., licorice, hydrangea, Japanese white bark magnolia leaf, chamomile, fenugreek, clove, Japanese mint, aniseed, cinnamon, herb, 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, sage, fennel, piment, anise, coriander, coffee, sugars and/or sugar substitutes (e.g., sucralose, acesulfame potassium, aspartame, saccharine, cyclamates, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), and other additives such as charcoal, chlorophyll, minerals, or botanicals. They may be imitation, synthetic or natural ingredients or blends thereof. They may be in any suitable form, for example, oil, liquid, or powder.

The flavour may be added to the aerosolisable material as part of a so-called “flavour block”, where one or more flavours are blended together and then added to the aerosolisable material. The “flavour block” may optionally include one or more of the sensate compounds.

The one or more other functional constituents may comprise one or more of colouring agents, preservatives, binders and/or fillers.

In one embodiment, the aerosolisable material may also comprise 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 a phosphoric acid. In one embodiment, the carboxylic acid may be any suitable carboxylic acid, such as a mono-carboxylic 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 an alternative embodiment, the aerosolisable material may be free of organic or inorganic acids and their corresponding salts. For example, the aerosolisable material may be free of carboxylic acids and free of phosphoric acids.

In one embodiment, the aerosolisable material has a pH of less than about 7.5. In this regard, the present inventors have found that when preparing a formulation comprising a cannabinoid, such as cannabidiol, it may be desirable to have a low pH in order to prevent the conversion of cannabidiol to other cannabinoids and to stabilise the formulation. Moreover, a low pH may also be desirable to prevent the formation of CBDHQ. In one embodiment, the aerosolisable material has a pH of less than about 7.0. In one embodiment, the aerosolisable material has a pH of less than about 6.5. In one embodiment, the aerosolisable material has a pH of from about 5.5 to 7.5. In one embodiment, the aerosolisable material has a pH of from about 5.5 to 7.4. In one embodiment, the aerosolisable material has a pH of from about 5.5 to 7.3. In one embodiment, the aerosolisable material has a pH of from about 5.5 to 7.2. In one embodiment, the aerosolisable material has a pH of from about 5.5 to 7.1. In one embodiment, the aerosolisable material has a pH of from about 5.5 to 7.

In one embodiment, the aerosolisable material has a pH of from about 6 to 7.5. In one embodiment, the aerosolisable material has a pH of from about 6 to 7.4. In one embodiment, the aerosolisable material has a pH of from about 6 to 7.3. In one embodiment, the aerosolisable material has a pH of from about 6 to 7.2. In one embodiment, the aerosolisable material has a pH of from about 6 to 7.1. In one embodiment, the aerosolisable material has a pH of from about 6 to 7.

For the avoidance of doubt, the pH of the aerosolisable material applies to all aerosolisable materials described herein, including those comprising further constituents, i.e. flavours.

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

In this regard, the present inventors have found that when preparing an aerosolisable material comprising a cannabinoid, it is important to ensure that the turbidity of the material is about 10 NTU or less. When the turbidity of the material is above this range, it is a sign that one or more of the constituents of the material is not present in the material in a stable manner. This could impact the use of the aerosolisable material in a number of ways. For example, the user may perceive the lack of stability and form an opinion that the aerosolisable material is of inferior quality. Alternatively or additionally, such instability may lead to inefficient transfer of one or more constituents from the aerosolisable material to the aerosol. Likewise, such instability may lead to the aerosolisable material causing suboptimal performance of any system or device using the material. The present inventors have found that issues of stability may be particular pronounced when the aerosolisable material comprises a cannabinoid and have thus found that ensuring the aerosolisable material has a turbidity of 10 NTU or less is important.

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

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

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

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

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

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

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

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

The turbidity of the aerosolisable material can be measured as is common in the art. For example, by using a TL2310 ISO Turbidimeter from Hach, Colorado, 80539-0389, United States.

In some embodiments, an acceptable turbidity is achieved without the use of functional constituents which influence the stability of the aerosolisable material. For example, it may be possible to decrease the turbidity of a liquid system by introducing surface active constituents which serve to improve the emulsification/dispersion of one or more of the constituents. However, it may not be desirable to include such functional constituents due to user acceptability. Therefore, in some embodiments, the aerosolisable material does not comprise a surface active constituent. Examples of surface active constituents include medium chain triglycerides (MCT) and tocopherol acetate.

In some embodiments, an acceptable turbidity is achieved without the use of any/significant amounts of water. In this regard, whilst water may otherwise assist in the preparation of aerosolisable materials since water containing materials may have a lower viscosity and therefore may be transferred more easily to an aerosol generating component, it has been found in the context of the present disclosure that water can negatively influence the stability of the aerosolisable material containing at least one cannabinoid. In some embodiments, the aerosolisable material comprises less than 12%w/w water. In some embodiments, the aerosolisable material comprises less than 11%w/w water. In some embodiments, the aerosolisable material comprises less than 10%w/w water. In some embodiments, the aerosolisable material comprises less than 5%w/w water.

In some embodiments, the aerosolisable material comprises less than 1%w/w water.

In some embodiments, the aerosolisable material comprises less than 0.5%w/w water. In some embodiments, the aerosolisable material comprises substantially no water.

In particular, it has been found that for certain formulations comprising a cannabinoid, such as cannabidiol, if the formulation comprises water in amounts of about 12%w/w, the cannabinoid is rendered unstable.

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

In this regard, the present inventors have found that the formulations maintain a high degree of stability, even when exposed to air and/or light, and/or variations in temperature.

Article

In a further aspect there is provided an article comprising the aerosolisable material as defined herein. The article may be a container, such as a bottle, or may be a component for use with an aerosol provision device. For example, the article may comprise an area (store) for receiving the aerosolisable material defined herein, an aerosol generating component, an aerosol generating area, and/or a mouthpiece.

In some embodiments, there is provided an article for use with an aerosol provision system, the article comprising a store comprising an aerosolisable material as defined herein, an aerosol generating component (such as a heater), an aerosol generating area, a transport element, and a mouthpiece.

Aerosolisable material may be transferred from the store for receiving an aerosolisable material to the aerosol generating component via a transport element, such as a wick, pump or the like. The skilled person is able to select suitable transport elements depending on the type of aerosolisable material that is to be transported and the rate at which it must be supplied. Particular mention may be made of transport elements, such as wicks, formed from fibrous materials, foamed materials, sintered materials, woven and non-woven materials. An airflow pathway typically extends through the article (optionally via the device) to an outlet. The pathway is oriented such that generated aerosol is entrained in the airflow such that it can be delivered to the outlet for inhalation by a user.

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

Typically, the area for receiving an aerosolisable material will allow for the article to be refilled with aerosolisable material as the aerosolisable material is depleted during use.

Figure 1 is a highly schematic diagram (not to scale) of an example aerosol provision 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 a dashed line (although aspects of the invention are applicable to e-cigarettes configured in other shapes and arrangements), and comprises two main components, namely an aerosol provision device 20 and an article 30.

The article 30 includes a store for aerosolisable material (source liquid) 38 containing an aerosolisable material (source liquid) from which an aerosol is to be generated. The article 30 further comprises an aerosol generating component (heating element or heater) 36 for heating aerosolisable material to generate the aerosol. A transport element or wicking element or wick 37 is provided to deliver aerosolisable material from the store 38 to the heating element 36. A part or parts of the wick 37 are in fluid communication with aerosolisable material in the store 38 and by a wicking or capillary action aerosolisable material is drawn along or through the wick 37 to a part or parts of the wick 37 which are in contact with the heater 36.

Vaporization of the aerosolisable material occurs at the interface between the wick 37 and the heater 36 by the provision of heat energy to the aerosolisable material to cause evaporation, thus generating the aerosol. The aerosolisable material, the wick 37 and the heater 36 may be collectively referred to as an aerosol or vapour source. The wick 37 and the heater 36 may be collectively referred to as a vaporizer or an atomiser 15.

Typically a single wick will be present, but it is envisaged that more than one wick could be present, for example, two, three, four or five wicks.

As described above, the wick may be formed a sintered material. The sintered material may comprise sintered ceramic, sintered metal fibers/powders, or a combination of the two. The (or at least one of/all of the) sintered wick(s) may have deposited thereon/embedded therein an electrically resistive heater. Such a heater may be formed from heat conducting alloys such as NiCr alloys. Alternatively, the sintered material may have such electrical properties such that when a current is passed there through, it is heated. Thus, the aerosol generating component and the wick may be considered to be integrated. In some embodiments, the aerosol generating 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 as a sheet, layer, film, substrate or the like. By this it is meant that a thickness of the wick is less or very much less than at least one of the length and the width of the wick. Thus, the wick thickness (its smallest dimension) is less or very much less than the longest dimension.

The wick may be made of a homogenous, granular, fibrous or flocculent sintered metal(s) so as to form said capillary structure. Wick elements can be made from a conductive material which is a nonwoven sintered porous web structure comprising metal fibres, such as fibres of stainless steel. For example, the stainless steel may be AISI (American Iron and Steel Institute) 316L (corresponding to European standard 1.4404). The material’s weight may be in the range of 100 - 300 g/m².

Where the wick is generally planar, the thickness of the wick may be in the range of 75 - 250 pm. A typical fibre diameter may be about 12 pm, and a typical mean pore size (size of the voids between the fibres) may be about 32 pm. An example of a material of this type is Bekipor (RTM) ST porous metal fibre media manufactured by NV Bekaert SA, Belgium, being a range of porous nonwoven fibre matrix materials made by sintering stainless steel fibres.

Note also that while the material is described as planar, this refers to the relative dimensions of the sheet material and the wick (a thickness many times smaller than the length and/or width) but does not necessarily indicate flatness, in particular of the final wick made from the material. A wick may be flat but might alternatively be formed from sheet material into a non-flat shape such as curved, rippled, corrugated, ridged, formed into a tube or otherwise made concave and/or convex.

The wick element may have various properties. It is formed from a porous material to enable the required wicking or capillary effect for drawing source liquid through it from an store for aerosolisable material (where the wick meets the aerosolisable material at a store contact site) to the vaporisation interface. Porosity is typically provided by a plurality of interconnected or partially interconnected pores (holes or interstices) throughout the material, and open to the outer surface of the material. Any level of porosity may be employed depending on the material, the size of the pores and the required rate of wicking. For example a porosity of between 30% and 85% might be selected, such as between 40% and 70%, between 50% and 80%, between 35% and 75% or between 40% and 75%. This might be an average porosity value for the whole wick element, since porosity may or may not be uniform across the wick. For example, pore size at the store contact site might be different from pore size nearer to the heater.

It is useful for the wick to have sufficient rigidity to support itself in a required within the article. For example, it may be mounted at or near one or two edges and be required to maintain its position substantially without flexing, bending or sagging.

As an example, porous sintered ceramic is a useful material to use as the wick element. Any ceramic with appropriate porosity may be used. If porous ceramic is chosen as the porous wick material, this is available as a powder which can be formed into a solid by sintering (heating to cause coalescence, possibly under applied pressure). Sintering then solidifies the ceramic to create the porous wick.

The article 30 further includes a mouthpiece 35 having an opening through which a user may inhale the aerosol generated by the vaporizer 15. The aerosol for inhalation may be described as an aerosol stream or inhalable airstream.

The aerosol delivery device 20 includes a power source (a re-chargeable cell or battery 14, referred to herein after as a battery) to provide power for the e-cigarette 10, and a controller (printed circuit board (PCB)) 28 and/or other electronics for generally controlling the e-cigarette 10. The aerosol delivery device can therefore also be considered as a battery section, or a control unit or section.

During operation of the device, the controller will determine that a user has initiated a request for the generation of an aerosol. This could be done via a button on the device which sends a signal to the controller that the aerosol generator should be powered. Alternatively, a sensor located in or proximal to the airflow pathway could detect airflow through the airflow pathway and convey this detection to the controller. A sensor may also 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 possibly in response to pressure changes detected by an air pressure sensor (not shown), the heater 36 vaporizes aerosolisable material delivered by the wick 37 to generate the aerosol, and this aerosol stream is then inhaled by a user through the opening in the mouthpiece 35. The aerosol is carried from the aerosol source to the mouthpiece 35 along an air channel (not shown in Figure 1) that connects the aerosol source to the mouthpiece opening as a user inhales on the mouthpiece.

In this particular example, the device 20 and article 30 are detachable from one another by separation in a direction parallel to the longitudinal axis, as shown in Figure 1, but are joined together when the system 10 is in use by cooperating engagement elements 21, 31 (for example, a screw, magnetic or bayonet fitting) to provide mechanical and electrical connectivity between the device 20 and the article 30, in particular connecting the heater 36 to the battery 14. The battery may be charged as is known to one skilled in the art.

In some embodiments, the article comprises/forms a sealed container. For example, the sealed container may be hermetically sealed. The present inventors have found that inclusion of the aerosolisable material in a sealed article assists in preventing water ingress into the system, which can prevent the cannabidiol from precipitating. The hermetically sealed container may comprise a blister pack with one or more hermetically sealed compartments for storage of one or more articles comprising the aerosolisable material described herein.

In some embodiments, the article comprises a housing within which the aerosolisable material is contained. The housing may be transparent such that the aerosolisable material can be viewed from outside of the housing. It may also be that the housing has a degree of opacity such that the passage of light through the housing is limited. This can be important so as to prevent light (such as ultra violet light) from entering the housing and compromising the stability of the aerosolisable material. In this regard, the present inventors have considered that cannabinoids may be particularly susceptible to such light destabilization. In some embodiments, the housing is formed from a material which inhibits/prevents the passage of ultra violet light there through. In some embodiments, it may be that the sealed container mentioned above is formed from a material which has a degree of opacity such that the passage of light through the sealed container is limited. Further, the sealed container mentioned above may be formed from a material which inhibits/prevents the passage of ultra violet light there through. This may be in addition to said sealed container being hermetically sealed and/or comprising a blister pack with one or more hermetically sealed compartments for storage of one or more articles comprising the aerosolisable material described herein.

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

Material In a further aspect there is provided a method for producing or preparing the aerosolisable material as defined herein, the method comprising combining at least one cannabinoid, a carrier constituent comprising at least 50% w/w propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material, one or more antioxidants, and 0.01 to 12% w/w of one or more sensates. The cannabinoid, carrier constituent, antioxidant(s) and sensate(s) are as defined herein, including the concentrations and chemical definitions.

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

In one embodiment the aerosolisable materials described herein are packaged materials, wherein the packaged materials are impermeable to air. In this regard, materials can be prepared with predefined amounts of one or more cannabinoids that maintain a high degree of stability. As defined herein, impermeable to air implies that the packaged materials are closed or sealed to provide substantial air impermeability.

In one embodiment the packaged materials are packaged in a container that is substantially impermeable to air and/or light (including LIV light), which can be used with an aerosol provision system. The container may correspond to a store comprising an aerosolisable material as defined herein. In this regard, the stability of the packaged materials may be maintained during use.

In one embodiment the packaged materials are packaged in a container, which comprise the aerosolisable materials described herein and a gas, such as air, CO2, N2 or a noble gas. In this regard, the volume of said gas in the container is referred to as the headspace. So that the stability of the packaged material can be maintained, it is preferable to reduce the volume of headspace in the container. In one embodiment there is a method of preparing a packaged material, comprising packaging an aerosolisable material as described herein in a container that is substantially impermeable to air and/or light (including LIV light), wherein the container further comprises a volume of gas no greater than 20% of the total volume of the container. In one embodiment the volume of gas is no greater than 15% of the total volume of the container. In one embodiment the volume of gas is no greater than 10% of the total volume of the container. In one embodiment the volume of gas is no greater than 5% of the total volume of the container. In one embodiment the volume of gas is no greater than 1% 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 ultra violet 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 producing an aerosol comprising generating an aerosol from an aerosolisable material as defined herein.

Examples

Recent consumer studies have identified the taste of cannabidiol (CBD) in aerosolized CBD formulations, including aerosolized CBD formulations with one or more flavourants or flavouring agents to be bitter. Experiments were conducted to determine whether one or more sensates could be used to provide additional sensations, harmonise with existing flavours and/or reduce the bitter or off notes associated with the taste of CBD.

The sensates involved in the experiments were a cooling agent, a warming agent, and a tingling agent. WS-3 (N-ethyl-5-methyl-2-propan-2-ylcyclohexane-1 -carboxamide) was used as the cooling agent. A ginger extract was used as the warming agent (obtained from Symrise Asia Pacific Pte. Ltd.; including 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.; including 3-phenylpropyl homovanillate, 3-phenylpropan-1-ol and ethyl acetate) was used as the tingling agent. The sensates were respectively used in combination with tropical, mint and fruity flavoured CBD aerosolisable materials.

The aerosolisable materials prepared are shown in Table 1 below. Formulations A, B and C are tropical flavoured, Formulations D and E are mint flavoured, and Formulations F and G are fruity flavoured.

Table 1

Example 1

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

Table 2

One hour following the addition of VG, it was determined that each of the sensates were solubilized into the PG/VG mixture.

Following successful dissolution of each sensate into the propylene glycol/glycerol mixture, a further solubility trial was conducted in which each sensate was incorporated into flavoured propylene glycol and glycerol mixtures. Finally, each sensate was tested for solubility and stability in 60 mg/ml CBD flavoured propylene glycol and glycerol mixtures, these are the formulations shown in Table 1 above.

Example 2

Following the successful inclusion of each of the sensates into the 60 mg/ml CBD flavoured propylene glycol and glycerol mixtures shown in Table 1 , the sensorial experience was assessed in a consumer study. The aim of this assessment was to ascertain consumer feedback on the sensory improvement of the CBD aerosolisable materials.

Surprisingly the inclusion of the one or more sensates in combination with the one or more antioxidants provided a stable CBD aerosolisable material, which delivered a positive sensory experience to the end user. Notably the one or more sensates mitigated the negative sensory experience typically associated with vaping CBD formulations and enables new CBD containing aerosolisable materials to be developed that can compliment both the taste of the material and mood state of the consumer.

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

Annex 1

Claims

1. An aerosolisable material comprising at least one cannabinoid, a carrier constituent comprising at least 50% w/w propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material, one or more antioxidants, and 0.01 to 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.

2. The aerosolisable material according to claim 1 , wherein the one or more sensates are selected from cooling agents, warming agents or tingling agents.

3. The aerosolisable material according to claim 2, wherein the one or more sensates comprise a cooling agent which is a compound of formula (I) or a salt and/or solvate thereof:

wherein X is hydrogen or OR’, wherein R’ is an alkyl group or an alkenyl group which may be taken together with Ri to form a three to five-membered heterocycyl group, wherein the heterocycyl group is optionally substituted by one or more substituents selected from OH, O-alkyl, alkyl-OH, alkyl-O-alkyl, NH₂, NH-alkyl, N-(alkyl)₂, NO₂ and ON; and wherein Ri and R₂ are each independently selected from hydrogen, OH, OR_a, C(O)NRbR_c and C(O)ORbR_c; with the proviso that when Ri is OH the compound of formula (I) is not menthol; and when the double bond is present, R₂ is absent; wherein R_a is an alkyl group, an alkenyl group, a C(O)Rf group, or a C(O)-alkyl- C(O)Rf group wherein the alkyl groups and alkenyl groups are optionally substituted by one or more substituents selected from OH, O-alkyl, NH₂, NH-alkyl, N-(alkyl)₂, NO₂ and ON; and wherein Rf is an alkyl group, an alkenyl group, OH, O-alkyl, NH₂, NH-alkyl or N-(alkyl)₂, wherein the alkyl groups and alkenyl groups are optionally substituted by one or more substituents selected from OH, O-alkyl, NH₂, NH-alkyl, N- (alkyl)₂, NO₂ and ON; wherein Rb 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 groups, alkenyl groups, aryl groups and heteroaryl groups are optionally substituted by one or more substituents selected from OH, O-alkyl, NH2, NH-alkyl, N-(alkyl)₂, NO₂, CN and C(O)R_f. The aerosolisable material according to claim 2, wherein the one or more sensates comprise a cooling agent which is N,2,3-trimethyl-2-propan-2-ylbutanamide. The aerosolisable material according to claim 2, wherein the one or more sensates comprise a cooling agent which is 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 aerosolisable material according to claim 5, wherein the one or more sensates comprise a cooling agent which is N-ethyl-5-methyl-2-(propan-2- yl)cyclohexanecarboxamide. The aerosolisable material according to claim 2, wherein the one or more sensates comprise a warming agent or a tingling agent. The aerosolisable material according to claim 7, wherein the warming agent or tingling agent is selected from the group consisting of vanilloids, sanshools, piperine, allyl isothiocyanate, cinnamyl phenylpropyl compounds, ethyl esters and combinations thereof, or wherein the warming agent or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, llzazi or mustard oil. The aerosolisable material according to claim 8, wherein the warming agent or tingling agent is a combination of a vanilloid, an ethyl ester and a cinnamyl phenylpropyl compound, preferably a combination of 3-phenylpropyl homovanillate, ethyl acetate and 3-phenylpropan-1-ol. The aerosolisable material according to claim 8, wherein the warming agent or tingling agent is selected from the group consisting of vanillyl ethyl ether, vanillyl propyl ether, capsaicinoids, gingerols, vanillyl butyl ether, vanillyl butyl ether acetate, sanshools, piperine, zingerone, shogaols, allyl isothiocyanate, and combinations

43 thereof, or wherein the warming agent or tingling agent is an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, llzazi or mustard oil The aerosolisable material according to claim 10, wherein the warming agent or tingling agent is selected from the group consisting of vanillyl ethyl ether, capsaicin, hydroxy-alpha-sanshool, piperine, zingerone, gingerols, shogaols, allyl isothiocyanate or combinations thereof, or wherein the warming agent or tingling agent is an extract from at least one of ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, llzazi or mustard oil. The aerosolisable material according to claim 11 , wherein the warming agent or tingling agent is selected from zingerone, gingerols, shogaols, and combinations thereof, or is an extract from ginger oil. The aerosolisable material according to any preceding claim, wherein the one or more sensates is present in the material in an amount of 0.01 to 10% w/w. The aerosolisable material according to any preceding claim, wherein the one or more sensates is present in the material in an amount of 0.01 to 5% w/w. The aerosolisable material according to any preceding claim, wherein the one or more sensates is present in the material in an amount of 0.01 to 2.5% w/w. The aerosolisable material according to any preceding claim, wherein the at least one cannabinoid is selected from cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), including its isomers Acetetrahydrocannabinol (A^6a’^10a-THC), AO-tetrahydrocannabinol (A^6a<⁷)-THC), A⁸- tetrahydrocannabinol (A⁸-THC), A⁹-tetrahydrocannabinol (A⁹-THC), A¹⁰- tetrahydrocannabinol (A¹⁰-THC), A⁹’¹¹-tetrahydrocannabinol (A^{9 11}-THC), cannabinol (CBN) and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), Cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivarinic acid (THCV A). The aerosolisable material according to claim 16, wherein the at least one cannabinoid is selected from cannabigerol (CBG), cannabichromene (CBC),

44 cannabidiol (CBD), A^{6a a}-Tetrahydrocannabinol (A^{6a a}-THC), A^6a(7)- Tetrahydrocannabinol (A^6a(7)-THC), AMetrahydrocannabinol (A⁸-THC), A⁹- tetrahydrocannabinol (A⁹-THC), A¹⁰-tetrahydrocannabinol (A¹⁰-THC), A^{9 11}- tetrahydrocannabinol (A^{9 11}-THC) and cannabinol (CBN). The aerosolisable material according to claim 16 or claim 17, wherein the at least one cannabinoid is selected from cannabidiol (CBD), AMetrahydrocannabinol (A⁹- THC), and cannabinol (CBN), preferably wherein the at least one cannabinoid is cannabidiol. The aerosolisable material according to any preceding claim, wherein the at least one cannabinoid is present in the material in an amount of 30 mg/ml or more. The aerosolisable material according to claim 19, wherein the at least one cannabinoid is present in the material in an amount of 60 mg/ml or more. The aerosolisable material according to any preceding claim, wherein the one or more antioxidants are selected from the enediol class of compounds. The aerosolisable material according to any preceding claim, wherein the one or more antioxidants are selected from the group consisting of ascorbic acid, sodium ascorbate, alpha-keto glutaric acid, alpha-keto glutarate salt, 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, a-resorcylic, pyrogallol, malvidin, theaflavin, apigenin, eriodictyol, glycitein, chrysoeriol, kaempferol, luteolin, vitexin, isovitexin, orientin, cannflavin A, cannflavin B, cannflavin C, delphinidin, pelargonidin, epicatechin, myricetin, chrysin, naringenin, a-terpineol, tertbutylhydroquinone, and combinations thereof. The aerosolisable material according to any preceding claim, wherein the one or more antioxidants are selected from ascorbic acid, sodium ascorbate and a combination thereof. The aerosolisable material according to any preceding claim, wherein the one or more antioxidants are each present in an amount of at least 500 ppm. The aerosolisable material according to claim 24, wherein the one or more antioxidants are each present in an amount of at least 1000 ppm. The aerosolisable material according to any preceding claim, wherein the carrier constituent further comprises one or more of glycerol, triethylene glycol, tetraethylene glycol, 1 ,3-butylene glycol, erythritol, meso-Erythritol, ethyl laurate, a diethyl suberate, triethyl citrate, triethylene glycol diacetate, triacetin, a diacetin mixture, benzyl benzoate, benzyl phenyl acetate, tributyrin, lauryl acetate, lauric acid, myristic acid, and propylene carbonate. The aerosolisable material according to claim 26, wherein the carrier constituent further comprises glycerol, preferably wherein the carrier constituent comprises at least 30% w/w glycerol. The aerosolisable material according to any preceding claim, wherein the carrier constituent comprises at least 60% w/w propylene glycol or at least 70% w/w propylene glycol. The aerosolisable material according to any preceding claim, wherein the carrier constituent is present at 80% w/w or more based on the total weight of the aerosolisable material. The aerosolisable material according to any preceding claim, wherein the carrier constituent comprises 60 to 90% w/w propylene glycol and 40 to 10% w/w glycerol based on the total weight of the carrier constituent. The aerosolisable material according to any preceding claim, wherein the material is nicotine-free. An article comprising the aerosolisable material as defined in any one of claims 1 to 31. The article according to claim 32, the article comprising a store for receiving the aerosolisable material of any one of claims 1 to 31, an aerosol generating component, an aerosol generating area, a transport element, and a mouthpiece. The article according to claim 33, wherein the aerosol generating component comprises a heater. The article according to claim 33 or claim 34, wherein the transport element is a wick. An aerosol provision system comprising an aerosol provision device and an article as defined in any one of claims 32 to 35. A method for producing the aerosolisable material as defined herein, the method comprising combining at least one cannabinoid, a carrier constituent comprising at least 50% w/w propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material, one or more antioxidants, and 0.01 to 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. The method according to claim 37, the method being characterized according to the features of any one of claims 2 to 31. A sealed container containing the article according to any one of claims 32 to 35. The sealed container according to claim 39, wherein the container is hermetically sealed and is formed from a material which inhibits or prevents the passage of ultra violet light there through. The sealed container according to claim 39 or claim 40, the sealed container comprising a blister pack with one or more hermetically sealed compartments. A process for forming an aerosol, the process comprising: (i) providing an aerosolisable material as defined in any one of claims 1 to 31, and (ii) aerosolising the material. Use of one or more sensates to mitigate or mask the physiological response of a user to at least one cannabinoid in an aerosolisable material, the aerosolisable material comprising the at least one cannabinoid and a carrier constituent comprising at least 50% propylene glycol, wherein the carrier constituent is present at 70% w/w or more based on the total weight of the aerosolisable material. The use according to claim 43, wherein the aerosolisable material is characterized according to the features of any one of claims 1 to 31. The use according to claim 43 or claim 44, wherein the physiological response of the user is a sensorial response. The use according to claim 45, wherein the sensorial response comprises taste.

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