AU2022433868B2

AU2022433868B2 - Aerosolisable material

Info

Publication number: AU2022433868B2
Application number: AU2022433868A
Authority: AU
Inventors: Andrew Burton; Tony Comerford; Alice HUGHES; Matthew SEAMAN; Danielle TOWER
Original assignee: Nicoventures Trading Ltd
Current assignee: Nicoventures Trading Ltd
Priority date: 2022-01-14
Filing date: 2022-12-21
Publication date: 2026-02-12
Anticipated expiration: 2042-12-21
Also published as: MX2024008725A; WO2023135408A1; JP7755751B2; JP2025501925A; EP4463019A1; US20250098726A1; IL313847A; CA3242529A1; AU2022433868A1

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 27 Nov 2025

Field

Background

Aerosol delivery systems which generate an aerosol for inhalation by a user are known in 2022433868

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.

It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.

Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

Summary 27 Nov 2025

In a first aspect, the present invention provides 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 the sensates and the one or more sensates are not the antioxidants. 2022433868

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.

1a

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

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(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 6a,10a_

tetrahydrocannabinol (A6a,1Ha)-THC), 6a(7)-tetrahydrocannabinol (A6a(7)-THC), -

tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A°-THC), 110-tetrahydrocannabinol

(A ¹0-THC), 9,11-tetrahydrocannabinol (A9,11-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 A9-tetrahydrocannabinol (A°-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

PCT/GB2022/053336

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 (A6a,10a-THC) 6a(7)-tetrahydrocannabinol (A6a(7)-THC), - tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A°-THC), 10-tetrahydrocannabinol

19,11-tetrahydrocannabinol (A9,11-THC), cannabinol (CBN) and cannabinodiol

(CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV),

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), -

tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A°-THC) and cannabinol (CBN).

In one embodiment the cannabinoid(s) of interest are selected from cannabidiol (CBD), -

tetrahydrocannabinol (A8-THC), A9-tetrahydrocannabinol (A°-THC).

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

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

In one embodiment the cannabinoid of interest is A9-tetrahydrocannabinol (A°-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

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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

PCT/GB2022/053336

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:

X

R1

R2

wherein X is hydrogen or OR', wherein R' is an alkyl group or an alkenyl group which may be

taken together with R1 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, NO and CN; and wherein R1 and R2 are

each independently selected from hydrogen, OH, ORa, C(O)NRbRo and C(O)ORbRR; 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 Ra is an alkyl group, an alkenyl group, a C(O)R group, or a C(O)-alkyl-C(O)R 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, NO and CN; 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 CN;

wherein Rb and Rc 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, NO, CN and C(O)R.

In one embodiment X is hydrogen.

PCT/GB2022/053336

In one embodiment X is OR', wherein R' is an alkyl group or an alkenyl group which is taken

together with R1 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 R1 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 R1 to form a four or five-

membered heterocyclyl group, wherein the heterocyclyl group is optionally substituted by alkyl-

OH, and wherein R1 is ORa wherein Ra is an alkyl group and wherein R2 is absent or hydrogen.

In one embodiment R1 is selected from OH, ORa and C(O)NRbRo and R2 is either absent or

selected from OH and ORa. In one embodiment R1 is OH with the proviso that the compound of

formula (I) is not menthol. In one embodiment R1 is OH and R2 is selected from OH and ORa.

In one embodiment X is hydrogen and R1 is selected from OH, ORa and C(O)NRb,Rc, with the

proviso that, when R1 is OH, the compound of formula (I) is not menthol. R2 is either absent or

selected from OH and ORa. In one embodiment X is hydrogen, R1 is selected from ORa and

C(O)NRRc and R2 is either absent or selected from OH and ORa.

In one embodiment R1 is ORa and Ra is an alkyl group substituted by one or more OH

substituents. R2 may be hydrogen.

In one embodiment R1 is ORa and Ra is a C(O)R group, or a C(O)-alkyl-C(O)R, 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 R1 is C(O)NRbR, wherein Rb and Rc are each independently hydrogen, an

alkyl group, an aryl group, an aralkyl group, a heteroaryl group, or a heteroaralkyl group. In one

embodiment R1 is C(O)NRbRo and at least one of Rb and Rc is hydrogen. R2 may be hydrogen.

In one embodiment R1 is C(O)NRbR, wherein Rb is hydrogen and Rc 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 tetrahydro-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,

hydroxybenzoate, 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,

PCT/GB2022/053336

bromide or iodide salts), sulfonate salts (e.g. benzenesulfonate, methyl-, bromo- or chloro-

benzenesulfonate, 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:

IN-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-glycerolk 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-(2-pyridin-2-yl)ethyl)menthyl carboxamide,

menthone-1,2-glycerolketal,

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)menthylcarboxamide,

menthone-1,2-glycerol ketal,

menthyl lactate,

isopulegol,

11

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 ket

menthyl lactate,

3-menthoxypropan-1,2-diol and

menthyl succinate.

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

If IN H N H N CO2E1 COEt N il 0 o o 0 0 OCH3 HN--- HN WS-3 WS-5 WS-12 WS-23 Evercoof 190

I 0 o 0 N L I OH AO 0 OH ON law O 2 O 0 ON : 0 OH CN OH OH OH 0 o OR Evercool ¹ 180 (-)-Isopulego Frescolat® ML Frescolat ML (-)-Menthyl succinate Coolact 10 Frescolat® MGA Frescolat MGA

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, lethyl-2-[(1R,2S,5R)-5-methyl-2-

propan-2-ylcyclohexanecarbonyl]amino] acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-

menthanecarboxamide, (1R,2S,5R)-N-(2-(pyridin-2-yl)ethyl)menthylcarboxamide, (-)-menthone

1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol, 3-((-)-menthoxy)propane-1,2-diol, and (-)-

menthyl succinate. These compounds are shown in Annex 1.

ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide lethyl-2-[[(1R,2S,5R)-5-methyl-2-

propan-2-ylcyclohexanecarbonyl]amino] acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-

1,2-glycerol ketal, (-)-menthyl lactate, 3-((-)-menthoxy)propane-1,2-diol, and (-)-menthyl

succinate.

ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-

propan-2-ylcyclohexanecarbonyl]amino] acetate, (1R,2S,5R)-N-(4-methoxyphenyl-p-

1,2-glycerol ketal, (-)-menthyl lactate,(-)-isopulegol, and 3-((-)-menthoxy)propane-1,2-diol.

lethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide, ethyl-2-[[(1R,2S,5R)-5-methyl-2-

propan-2-ylcyclohexanecarbonyl]amino) acetate, ((1R,2S,5R)-N-(2-(pyridin-2-

yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal, (-)-menthyl lactate, (-)-isopulegol,

and 3-((-)-menthoxy)propane-1,2-diol.

propan-2-ylcyclohexanecarbonyl]amino] acetate, ((1R,2S,5R)-N-(2-(pyridin-2-

yl)ethyl)menthylcarboxamide, (-)-menthone 1,2-glycerol ketal (-)-menthyl lactate, and 3-((-)-

menthoxy)propane-1,2-diol.

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

yl)ethyl)menthylcarboxamide.

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

yl)cyclohexanecarboxamide.

As 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, Uzazi 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 TRPV1 receptor, an ion channel which naturally

responds to stimuli. TRPV1 is therefore an element of the mammalian somatosensory system.

Vanilloids include capsaicin (8-methyl-N-vanillyl-6-nonenamide) and nonivamide as well as 3-

phenylpropyl homovanillate, the 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. 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

Uzazi. 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.

sanshools, allyl isothiocyanate, cinnamyl phenylpropyl compounds, ethyl esters, and

horseradish oil, Szechuan pepper, cayenne pepper, Uzazi or mustard oil.

PCT/GB2022/053336

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.

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, Uzazi or mustard oil.

vanillyl ethyl ether, vanillyl propyl ether, vanillyl butyl ether, vanillyl butyl ether acetate, and

combinations thereof.

capsaicinoids, gingerols (e.g. [6], [8], [10] and/or [12]-gingerol), sanshools, piperine, zingerone,

long pepper, Szechuan pepper, cayenne pepper, Uzazi or mustard oil.

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.

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, Uzazi or mustard oil.

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-

PCT/GB2022/053336

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 Uzazi. 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

in an amount of from about 0.05 % w/w to about 8 %w/w. In one embodiment the one or more

about 8 %w/w.

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

in an amount of from about 0.05 % w/w to about 5 %w/w. In one embodiment the one or more

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.

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.

PCT/GB2022/053336

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

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

about 10 %w/w and the at least one cannabinoid is present in the material in an amount of 5

mg/ml or more.

an amount of no greater than about 8 % w/w and the at least one cannabinoid is present in the

defined herein is present in the material in an amount of from about 0.01 % w/w to about 8

in an amount of from about 0.05 % w/w to about 8 %w/w and the at least one cannabinoid is

about 8 %w/w and the at least one cannabinoid is present in the material in an amount of 5

mg/ml or more.

an amount of no greater than about 5 % w/w and the at least one cannabinoid is present in the

in an amount of from about 0.05 % w/w to about 5 %w/w and the at least one cannabinoid is

about 5 %w/w and the at least one cannabinoid is present in the material in an amount of 5

mg/ml or more.

no greater than about 3 % w/w, e.g. no greater than about 2.5 % w/w, and the at least one

PCT/GB2022/053336

cannabinoid is present in the material in an amount of 5 mg/ml or more. In one embodiment the

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

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.

10 Antioxidant 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 1000ppm. 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.

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.

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

additional antioxidants, wherein ascorbic acid is present in an amount of at least 1000ppm. In

additional antioxidants, wherein ascorbic acid is present in an amount of at least 1250ppm. In

additional antioxidants, wherein ascorbic acid is present in an amount of at least 1500ppm. In

additional antioxidants, wherein ascorbic acid is present in an amount of at least 1750ppm. In

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.

least 750ppm.

PCT/GB2022/053336

least 1000ppm.

least 1250ppm.

least 1500ppm.

least 1750ppm.

least 2000ppm.

acid is present in an amount of from 500 to 4000ppm and sodium ascorbate is present in an

amount of from 500 to 4000ppm.In 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.

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

PCT/GB2022/053336

more antioxidants are each present in an amount of at least 500ppm.

an amount of no greater than about 8 % w/w, the at least one cannabinoid is present in the

present in the material in an amount of from about 0,01 % w/w to about 8 %w/w, the at least

more antioxidants are each present in an amount of at least 500ppm.

an amount of no greater than about 5 % w/w, the at least one cannabinoid is present in the

present in the material in an amount of from about 0.01 % w/w to about 5 %w/w, the at least

more antioxidants are each present in an amount of at least 500ppm.

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

PCT/GB2022/053336

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) O.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

24

PCT/GB2022/053336

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.

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.,

PCT/GB2022/053336

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 limitation,

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

PCT/GB2022/053336

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 remulsification/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.

PCT/GB2022/053336

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.

PCT/GB2022/053336

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

PCT/GB2022/053336

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

um. A typical fibre diameter may be about 12 um, and a typical mean pore size (size of the

voids between the fibres) may be about 32 um. 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

PCT/GB2022/053336

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

PCT/GB2022/053336

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.

provision device and an article as defined herein.

Material Preparation

PCT/GB2022/053336

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 UV 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 UV 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

A B C D E F G Ingredient % w/w % w/w % w/w % w/w % w/w % w/w % w/w

Glycerol 24.2685 24.2685 24.2685 24.2451 24.2451 24.2607 24.2607

PG 64.9 64.0 64.2 59.64 59.64 59.84 63.39 63.59

Ascorbic Acid 0.1 0.1 0.1 0.1 0.1 0.1 0.1

PCT/GB2022/053336

Sodium Ascorbate 0.1 0.1 0.1 0.1 0.1 0.1 0.1

Flavour 1 5.0 5.0 5.0

Flavour 2 5.0 5.0

Flavour 3 2.36 2.36 2.36

Flavour 4 2.0 2.0

Flavour 5 5.0 5.0

Flavour 6 0.61 0.61

Ginger Extract 0.1

SymHeat PV 1.0 1.0 1.0

WS-3 0.8 0.8 0.8

CBD Isolate (>98.5% purity) 5.5315 5.5315 5.5315 5.5549 5.5549 5.5393 5.5393

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

Sensate PG (w/w%) Sensate (w/w%) VG (w/w%) Soluble

Symheat PV 1 69 30 WS-3 69.2 0.8 30 30 Ginger Extract 69.9 0.1 30

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

PCT/GB2022/053336

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

Chemical Name Trade Chemical Structure

Name (if

applicable)

(1S,2R,5S)-N-ethyl-5-methyl-2- WS-3 (propan-2-

yl)cyclohexanecarboxamide

lethyl-2-[[(1R,2S,5R)-5-methyl-2- WS-5 propan-2-

ylcyclohexanecarbonyl]amino] CO-EI acetate

(1R,2S,5R)-N-(4-methoxyphenyl-p- WS-12 menthanecarboxamide

OCH

N,2,3-trimethyl-2-propan-2- WS-23 ylbutanamide

(1R,2S,5R)-N-(2-(pyridin-2- Evercool®

yl)ethyl)menthylcarboxamide 190 IZ

N

N-p-benzeneacetonitrile Evercool Evercool®R N

menthanecarboxamide 180

o O N --- H H

(-)-menthone 1,2-glycerol ketal Frescolat® Frescolat®

MGA OH

(-)-menthyl lactate Frescolat® Frescolat®

ML

3-((-)-menthoxy)propane-1,2-diol Coolact® 10

OH OH

(-)-menthyl succinate Monomenthyl succinate

OH

(-)-Isopulegol -- CH3

H2C

CH3 OH CH OH

Hydroxy-alpha sanshool --

N H OH

Capsaicin -- HO

Piperine -

N

Zingerone - O

HO

Gingerol -- OH

HO HO OCH3

[6]-shogaol -

######## HO ........

Allyl isothiocyanate -

N S

Vanillyl butyl ether -

O CH3

HO OCH33 OCH 3-phenylpropyl homovanillate - H2C

OH

O 0 0

Claims

Claims 27 Nov 2025

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 the sensates and the one or more sensates are not the antioxidants. 2022433868

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:

(I)

wherein X is hydrogen or OR’, wherein R’ is an alkyl group or an alkenyl group which may be taken together with R1 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 CN; and wherein R1 and R2 are each independently selected from hydrogen, OH, ORa, C(O)NRbRc and C(O)ORbRc; with the proviso that when R1 is OH the compound of formula (I) is not menthol; and when the double bond is present, R2 is absent;

wherein Ra 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 CN; 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 CN; wherein Rb and Rc are each independently hydrogen, an alkyl group, an alkenyl 27 Nov 2025 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)Rf; or wherein the one or more sensates comprise a cooling agent which is N,2,3-trimethyl- 2-propan-2-ylbutanamide. 2022433868

4. 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, preferably wherein the one or more sensates comprise a cooling agent which is N- ethyl-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide.

5. The aerosolisable material according to claim 2, wherein the one or more sensates comprise a warming agent or a tingling agent, 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, preferably a combination of a vanilloid, an ethyl ester and a cinnamyl phenylpropyl compound, more preferably a combination of 3-phenylpropyl homovanillate, ethyl acetate and 3-phenylpropan-1-ol; or

an extract from at least one of horseradish oil, ginger oil, black pepper, long pepper, Szechuan pepper, cayenne pepper, Uzazi or mustard oil; or

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 thereof, preferably vanillyl ethyl ether, capsaicin, hydroxy-alpha-sanshool, piperine, zingerone, gingerols, shogaols, allyl isothiocyanate or combinations thereof, more preferably zingerone, gingerols, shogaols, and combinations thereof, or is an extract from ginger oil.

6. The aerosolisable material according to any one of the preceding claims, wherein the 27 Nov 2025

one or more sensates is present in the material in an amount of 0.01 to 10% w/w, preferably 0.01 to 5% w/w, more preferably 0.01 to 2.5% w/w.

7. The aerosolisable material according to any one of the preceding claims, wherein the at least one cannabinoid is selected from cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), including its isomers Δ6a,10a- tetrahydrocannabinol (Δ6a,10a-THC), Δ6a(7)-tetrahydrocannabinol (Δ6a(7)-THC), Δ8- 2022433868

tetrahydrocannabinol (Δ8-THC), Δ9-tetrahydrocannabinol (Δ9-THC), Δ10- tetrahydrocannabinol (Δ10-THC), Δ9,11-tetrahydrocannabinol (Δ9,11-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); preferably wherein the at least one cannabinoid is selected from cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), Δ6a,10a-Tetrahydrocannabinol (Δ6a,10a- THC), Δ6a(7)-Tetrahydrocannabinol (Δ6a(7)-THC), Δ8-tetrahydrocannabinol (Δ8-THC), Δ9-tetrahydrocannabinol (Δ9-THC), Δ10-tetrahydrocannabinol (Δ10-THC), Δ9,11- tetrahydrocannabinol (Δ9,11-THC) and cannabinol (CBN); more preferably wherein the at least one cannabinoid is selected from cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC), and cannabinol (CBN); most preferably wherein the at least one cannabinoid is cannabidiol.

8. The aerosolisable material according to any one of the preceding claims, wherein the at least one cannabinoid is present in the material in an amount of 30 mg/ml or more, preferably 60 mg/ml or more.

9. The aerosolisable material according to any one of the preceding claims, wherein the one or more antioxidants are selected from the enediol class of compounds, or 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, α- resorcylic, pyrogallol, malvidin, theaflavin, apigenin, eriodictyol, glycitein, chrysoeriol, kaempferol, luteolin, vitexin, isovitexin, orientin, cannflavin A, cannflavin B, cannflavin 27 Nov 2025

C, delphinidin, pelargonidin, epicatechin, myricetin, chrysin, naringenin, α-terpineol, tert-butylhydroquinone, and combinations thereof, preferably wherein the one or more antioxidants are selected from ascorbic acid, sodium ascorbate and a combination thereof.

10. The aerosolisable material according to any one of the preceding claims, wherein the one or more antioxidants are each present in an amount of at least 500 ppm, 2022433868

preferably at least 1000 ppm.

11. The aerosolisable material according to any one of the preceding claims, 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, preferably wherein the carrier constituent further comprises glycerol, more preferably wherein the carrier constituent comprises at least 30% w/w glycerol.

12. The aerosolisable material according to any one of the preceding claims, wherein the carrier constituent comprises at least 60% w/w propylene glycol or at least 70% w/w propylene glycol, or 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.

13. The aerosolisable material according to any one of the preceding claims, wherein the material is nicotine-free.

14. An article comprising the aerosolisable material as defined in any one of claims 1 to13, preferably wherein the article comprises a store for receiving the aerosolisable material of any one of claims 1 to 13, an aerosol generating component, an aerosol generating area, a transport element, and a mouthpiece, more preferably wherein the aerosol generating component comprises a heater, and/or wherein the transport element is a wick.

15. An aerosol provision system comprising an aerosol provision device and an article as defined in claim 14.

16. A method for producing the aerosolisable material according to any one of claims 1 27 Nov 2025

to 13, 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, preferably wherein the aerosolisable material is defined according to any one of claims 1 to 13. 2022433868

17. A sealed container containing the article according to claim 14, preferably wherein the container is hermetically sealed and is formed from a material which inhibits or prevents the passage of ultra violet light there through, more preferably the sealed container comprising a blister pack with one or more hermetically sealed compartments.

18. A process for forming an aerosol, the process comprising: (i) providing an aerosolisable material as defined in any one of claims 1 to 13, and (ii) aerosolising the material.

19. 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, preferably wherein the aerosolisable material is characterized according to the features of any one of claims 1 to 13.

20. The use according to claim 19, wherein the physiological response of the user is a sensorial response, preferably wherein the sensorial response comprises taste.

Battery 14

20

A 28 21

31 Weakes 36

15 30 Reservie 38 37 Liquid

(into Mouth)

35 Air Out 10

Figure 1