WO2023060323A1

WO2023060323A1 - Terpene-containing formulations and use thereof

Info

Publication number: WO2023060323A1
Application number: PCT/AU2022/051244
Authority: WO
Inventors: Joanne PATTERSON
Original assignee: Bod Science Limited
Priority date: 2021-10-15
Filing date: 2022-10-14
Publication date: 2023-04-20

Abstract

The present disclosure generally relates to formulations comprising a terpene blend of two or more terpenes selected from the group consisting of β-caryophyllene, limonene, linalool, α-pinene, α-humulene, nerolidol, myrcene, borneol, α-bisabolol, geraniol, and fenchone. The present disclosure also generally relates to the preparation and use of such formulations for medicinal, pharmaceutical and nutraceutical applications.

Description

TERPENE-CONTAINING FORMULATIONS AND USE THEREOF

FIELD

The present disclosure relates to formulations comprising a terpene blend of two or more terpenes selected from the group consisting of P-caryophyllene, limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone. The present disclosure also relates to the preparation and use of such formulations for medicinal, pharmaceutical and nutraceutical applications.

BACKGROUND

Cannabinoids, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), are known to activate receptors in the endocannabinoid system. There are three main commercial forms of CBD, which are based on purity. All forms have shown beneficial health effects, such as pain and anxiety. CBD isolate is the pure form of CBD and contains no THC. While full-spectrum and broad-spectrum CBD extracts contain other compounds of the cannabis plant, such as terpenes and other cannabinoids. Full-spectrum CBD extracts contain some THC, but usually at low quantities of less than 0.3%. Most broad-spectrum CBD extracts contain zero or trace amounts of THC, but generally less than the 0.3% contained in full-spectrum products. CBD isolate may offer certain health benefits although the effects may be reduced in comparison to a full-spectrum or broadspectrum CBD extract. The beneficial health effects for CBD isolate, full-spectrum and broad-spectrum CBD extracts can include: anti-seizure, muscle spasm relief, antianxiety, pain relief, treatment of psychotic disorder, antioxidant and anti-inflammatory. Research has suggested that the entourage effect may increase the effects of full-spectrum and broad-spectrum CBD products. Whilst CBD isolates and full-spectrum or broadspectrum CBD extracts derived from cannabis plants have their advantages, they also have disadvantages. The major down fall to cannabis-derived CBD products is that they are illegal under some federal and state laws, even those products that contain less than 0.3% THC.

Terpenes are a diverse class of compounds found in many plants and flowers, including cannabis plants, and are generally classified as generally recognized as safe (GRAS). These compounds create the characteristic scent of many plants and are said to be the building blocks for certain odours, vitamins, essential oils and cannabinoids. Although terpenes are primarily responsible for the smell of most plants, they can also act on the endocannabinoid system in a similar way to cannabinoids.

Terpenes are known to enhance the health benefits of products either alone or synergistically with other terpenes, THC, CBD, and other minor cannabinoids found in cannabis plants. Most research to date has focused on the health effects of individual terpenes. For example, linalool, a terpene found in lavender essential oil, has been shown to provide antianxiety effects. Another terpene, a-Pinene, naturally found in rosemary essential oil, may improve mental alertness. P-caryophyllene is a terpene present in various essential oils and has shown selective action on the endocannabinoid receptor and attracted considerable attention because of its several pharmacological activities.

Therefore, developing novel formulations comprising terpene blends, that may deliver similar, improved or enhanced beneficial health effects alone or with a CBD isolate, full-spectrum or broad-spectrum CBD extracts, with improved stability for use in the pharmaceutical and nutraceutical fields, is of interest and in demand.

Consequently, there is a need to provide alternative or improved terpene- containing formulations and processes for preparing terpene-containing formulations for use in medical, pharmaceutical and nutraceutical applications.

SUMMARY

The present inventors have prepared terpene-containing formulations comprising a terpene blend. The terpene blend comprises or consists of two or more terpenes, wherein at least one of the terpenes is selected from P-caryophyllene. The present inventors have also identified a process for preparing terpene-containing formulations comprising a terpene blend. It has been found that formulations prepared by the processes defined herein provide alternative or improved stable terpene-containing formulations comprising a unique blend of terpenes wherein at least one terpene is selected from -caryophyllene. One or more advantages of the present disclosure, according to at least some embodiments or examples as described herein, is that a terpene-containing formulation can be prepared from a terpene blend comprising or consisting of a combination of P-caryophyllene and one or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone. In one aspect there is provided a formulation comprising a terpene blend of two or more terpenes selected from the group consisting of P-caryophyllene, limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In embodiments, one of the two or more terpenes is P-caryophyllene.

In some embodiments, the terpene blend consists of a combination of P- caryophyllene and one or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In embodiments, P-caryophyllene may be provided in an amount of about 30 to about 70 wt.% based on total weight of the terpene blend.

In some embodiments, the formulation may further comprise or consist of a carrier, wherein the carrier is a liquid carrier or a solid carrier. The carrier may be present in the formulation in an amount of between about 2 and 99 wt% based on total weight of the formulation.

In embodiments, the formulation further comprises one or more active agents. The one or more active agents may be selected from a cannabinoid, an antimicrobial agent, an enzyme, an anti-fungal agent, an anti-bacterial agent, an insecticidal agent, or an anaesthetic.

In embodiments, the cannabinoid may be present in the form of a cannabinoid extract or an isolate thereof.

In embodiments, the active agent may be selected from the group consisting of cannabidiol (CBD), cannabidiol A (CBDA) cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabinol (CBN), cannabigerolic acid (CBGA), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether, palmitoylethanolamide (PEA), or a combination thereof.

In some embodiments, the formulation comprises the active agent in a concentration between about 0.001 mg/ml to about 1200 mg/ml/g

In some embodiments, the formulation further comprises one or more additional additives. The one or more additional additives may be selected from a stabiliser, diluent, adjuvant, dispersing agent, suspending agent, acidifying agent, adsorbent, alkalizing agent, anti-adherent, antioxidant, binder, buffering agent, colouring agent, complexing agent, filler, direct compression excipient, disintegrant, flavorant, fragrance, glidant, lubricant, opaquant, plasticizer, preservative, or sweetening agent.

In some embodiments, the formulation may be formulated for administration to a mammal by oral administration (e.g. sublingual or oromucosal), inhalation, nasal administration, or topical administration. The formulation may be in the form of a tablet, a pill, a capsule, a powder or granules, a liquid, a spray, a suspension, a gel, a cream, a dispersion, a solution, an emulsion, an ointment, or a lotion.

In another aspect there is provided a method of treating or preventing a disease, disorder or condition in a subject, comprising: administering to the subject a therapeutically effective amount of one or more of the formulations as described herein.

In another aspect there is provided a use of a formulation in the manufacture of a medicament for treating or preventing a disease, disorder or condition, wherein the formulation is as described herein.

In another aspect there is provided a formulation for use in treating or preventing a disease, disorder or condition, wherein the formulation is as described herein.

DETAILED DESCRIPTION

The present disclosure describes the following various non-limiting examples, which relate to investigations undertaken to identify appropriate terpene-containing formulations, methods of making, and use thereof. The present inventors have prepared a terpene-containing formulation comprising a terpene blend. The terpene blend comprises or consists of a combination of P-caryophyllene and one or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone. The present inventors have also identified a process for preparing the terpene- containing formulation comprising the terpene blend.

At least according to some embodiments or examples as described herein, the present disclosure provides an alternative or improved terpene-containing formulation comprising a unique terpene blend, wherein at least one terpene is selected from p- caryophyllene. General Definitions and Terms

With regards to the definitions provided herein, unless stated otherwise, or implicit from context, the defined terms and phrases include the provided meanings. In addition, unless explicitly stated otherwise, or apparent from context, the terms and phrases below do not exclude the meaning that the term or phrase has acquired by a person skilled in the relevant art. The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims.

All publications discussed and/or referenced herein are incorporated herein in their entirety.

Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Throughout this disclosure, unless specifically stated otherwise or the context requires otherwise, reference to a single step, formulation of matter, group of steps or group of formulations of matter shall be taken to encompass one and a plurality (i.e., one or more) of those steps, formulations of matter, groups of steps or groups of formulations of matter. Thus, as used herein, the singular forms “a”, “an” and “the” include plural aspects unless the context clearly dictates otherwise. For example, reference to “a” includes a single as well as two or more; reference to “an” includes a single as well as two or more; reference to “the” includes a single as well as two or more and so forth.

Those skilled in the art will appreciate that the disclosure herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the disclosure includes all such variations and modifications. The disclosure also includes all of the examples, steps, features, methods, formulations, formulations, and processes, referred to or indicated in this specification, individually or collectively, and any and all combinations or any two or more of said steps or features.

The term “and/or”, e.g., “X and/or Y” shall be understood to mean either “X and Y” or “X or Y” and shall be taken to provide explicit support for both meanings or for either meaning.

Unless otherwise indicated, the terms “first,” “second,” etc. are used herein merely as labels, and are not intended to impose ordinal, positional, or hierarchical requirements on the items to which these terms refer. Moreover, reference to a “second” item does not require or preclude the existence of lower-numbered item (e.g., a “first” item) and/or a higher-numbered item (e.g., a “third” item).

As used herein, the phrase “at least one of’, when used with a list of items, means different combinations of one or more of the listed items may be used and only one of the items in the list may be needed. The item may be a particular object, thing, or category. In other words, “at least one of’ means any combination of items or number of items may be used from the list, but not all of the items in the list may be required. For example, “at least one of item A, item B, and item C” may mean item A; item A and item B; item B; item A, item B, and item C; or item B and item C. In some cases, “at least one of item A, item B, and item C” may mean, for example and without limitation, two of item A, one of item B, and ten of item C; four of item B and seven of item C; or some other suitable combination.

It is to be appreciated that certain features that are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any sub-combination.

Throughout the present specification, various aspects and components of the invention can be presented in a range format. The range format is included for convenience and should not be interpreted as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range, unless specifically indicated. For example, description of a range such as from 1 to 5 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 5, from 3 to 5 etc., as well as individual and partial numbers within the recited range, for example, 1, 2, 3, 4, 5, 5.5 and 6, unless where integers are required or implicit from context. This applies regardless of the breadth of the disclosed range. Where specific values are required, these will be indicated in the specification.

Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

Throughout this specification, the term "consists of is intended to exclude elements which would materially affect the properties of the claimed formulation.

The terms "comprising", "comprise" and "comprises" herein are intended to be optionally substitutable with the terms "consisting essentially of, "consist essentially of, "consists essentially of, "consisting of, "consist of and "consists of, respectively, in every instance.

As used herein, the term about, unless stated to the contrary, refers to +/- 20%, typically +/- 10%, typically +/- 5%, of the designated value.

As used herein, the term “subject” refers to any organism that is susceptible to a disease or condition. For example, the subject can be an animal, a mammal, a primate, a livestock animal (e.g., sheep, cow, horse, pig), a companion animal (e.g., dog, cat), or a laboratory animal (e.g., mouse, rabbit, rat, guinea pig, hamster). In one example, the subject is a mammal. In one preferred embodiment, the subject is human. In one alternative embodiment, the subject is a non-human animal.

As used herein, the term “treating” includes alleviation of symptoms associated with a specific disease, disorder or condition.

As used herein, the term “prevention” includes prophylaxis of the specific disease, disorder or condition.

The term “therapeutically effective amount”, as used herein, refers to a formulation being administered in an amount sufficient to alleviate or prevent to some extent one or more of the symptoms of the disease, disorder or condition being treated. The result can be the reduction and/or alleviation of the signs, symptoms, or causes of a disease, disorder or condition, or any other desired alteration of a biological system.

The term, an “effective amount”, as used herein, refers to an amount of a formulation effective to achieve a desired pharmacologic effect or therapeutic improvement without undue adverse side effects. It is understood that “an effective amount” or “a therapeutically effective amount” can vary from subject to subject, due to variation in metabolism of the compound and any of age, weight, general condition of the subject, the condition being treated, the severity of the condition being treated, and the judgment of the prescribing physician.

Herein “weight %” may be abbreviated to as “wt%”

Terpene-Containing Formulations

Formulations suitable for use in the methods and uses described herein comprise a formulation comprising a terpene blend, i.e. a terpene-containing formulation. In some embodiments, the formulation comprising a terpene blend is presented as a pharmaceutical and/or nutraceutical formulation. In some embodiments, there is provided the use or method as described herein, wherein the formulation comprising a terpene blend, is administered in the form of a pharmaceutical and/or nutraceutical formulation.

The formulations described herein may contain a formulation comprising a terpene blend, by weight %, in at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, or 70. The formulations described herein may contain a formulation comprising a terpene blend, by weight %, in less than about 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, 2, or 1. The formulations described herein may contain a formulation comprising a terpene blend, by weight %, in a range provided by any two of these upper and/or lower values, for example between about 2 and 50 wt % or about 5 and 30 wt %.

As discussed below, a formulation comprising a terpene blend, may for example be administered in combination with one or more additional active agents. Thus, in some embodiments, the formulation comprises or consists of a formulation comprising a terpene blend, optionally a carrier, optionally one or more additives, and optionally one or more active agents, e.g. palmitoylethanolamide, cannabinoid or isolate thereof.

Generally, the formulation comprises a formulation comprising a terpene blend, in an amount that is a therapeutically effective amount. In some embodiments, the therapeutically effective amount is provided by a single dose. In some embodiments, the therapeutically effective amount is provided by one or more doses administered as part of a course of treatment, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 or greater than 27 doses. The person skilled in the art would understand that the amount of a terpene blend present in the formulation will vary depending on the other ingredients present in the formulation, the desired effect and the like. In some embodiments, the formulation comprises a formulation comprising a terpene blend in an amount between about 0.01 to 1200 mg, 0.05 to 500 mg, 0. 1 to 50 mg. In some embodiments, the formulation comprises a formulation comprising a terpene blend in an amount (as a weight % based on total weight of the formulation) between about 0.1 to 99 wt%, 0.1 to 90 wt%, 0.1 to 85 wt%, 0.1 to 80 wt%, 0.1 to 75 wt%, 0.1 to 70 wt%, 0.1 to 65 wt%, 0.1 to 60 wt%, 0.1 to 55 wt%, 0.1 to 50 wt%, 0.1 to 45 wt%, 0.1 to 40 wt%, 0.1 to 35 wt%, 0.1 to 30 wt%, 0.5 to 99 wt%, 1 to 99 wt%, 5 to 99 wt%, 10 to 99 wt%, 20 to 99 wt%, 30 to 99 wt%, 35 to 99 wt%, 40 to 99 wt%, 45 to 99 wt%, 50 to 99 wt%, 54 to 99 wt%, 60 to 99 wt%, 65 to 99 wt%, 70 to 99 wt%, 75 to 99 wt%, 80 to 99 wt%, 85 to 99 wt%, 90 to 99 wt%, 5 to 90 wt%, 20 to 80 wt%, 30 to 70 wt%, or 40 to 60 wt%.

In some embodiments, the terpene-containing formulation, may be administered in combination with a further active agent. In some embodiments, the methods and uses described herein also relate to co-administering one or more substances in addition to the terpene-containing formulation, to the subject. The term “co-administer” indicates that each of at least two substances are administered during a time frame wherein the respective periods of biological activity or effects overlap. Thus, the term includes sequential as well as coextensive administration of substances. Co-administration of more than one substance can be for therapeutic and/or prophylactic purposes. If more than one substance is co-administered, the routes of administration of the two or more substances need not be the same. The scope of the methods and uses described herein are not limited by the identity of the substance or substances which may be co-administered with the terpene-containing formulation.

It will be understood that the the terpene-containing formulation may also be a food or beverage, or provided into a food or beverage. The the terpene-containing formulation may be a veterinary product, such as a dog or cat food product, or a supplement. It will be appreciated that administration of the terpene-containing formulation may be provided in various forms depending on the application and subject. Terpene Blend

The terpene-containing formulation comprises a terpene blend. The terpene blend may comprise or consist of two or more terpenes selected from the group consisting of P-caryophyllene, limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In preferred embodiments, one of the two or more terpenes is P-caryophyllene.

In some embodiments, there is provided a formulation consisting of a terpene blend of two or more terpenes selected from the group consisting of P-caryophyllene, limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

The formulation optionally further comprises a carrier, optionally one or more additives, and optionally one or more active ingredients.

The formulation may comprise or consist of a terpene blend of two or more terpenes selected from the group consisting of P-caryophyllene, limonene, linalool, a- pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone; optionally a carrier, optionally one or more additives, and optionally one or more active ingredients.

In some embodiments, the only terpenes in the formulation are those two or more selected from the group consisting of P-caryophyllene, limonene, linalool, a-pinene, a- humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In some embodiments, the terpene blend may consist of a combination of P- caryophyllene and one or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In some embodiments, the terpene blend may consist of a combination of P- caryophyllene and two or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In some embodiments, the terpene blend may consist of a combination of P- caryophyllene and three or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

In any of the embodiments described herein, P-caryophyllene may be provided in an amount of about 30 to about 70 wt.% based on total weight of the terpene blend. The P-caryophyllene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 70, 65, 60, 55, 50, 45, 40, 35 or 30. The - caryophyllene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 30, 35, 40, 45, 50, 55, 60, 65 or 70. The P-caryophyllene can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, limonene may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The limonene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The limonene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The limonene can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, linalool may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The linalool can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The linalool can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The linalool can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, a-pinene may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The a-pinene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The a-pinene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The a-pinene can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, a-humulene may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The a-humulene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The a-humulene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The a-humulene can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, nerolidol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The nerolidol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The nerolidol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The nerolidol can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, myrcene may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The myrcene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The myrcene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The myrcene can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, borneol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The borneol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The borneol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The borneol can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, a-bisabolol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The a-bisabolol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The a-bisabolol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The a-bisabolol can be in a range provided by any two of these upper and/or lower amounts. In some embodiments, geraniol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The geraniol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The geraniol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The geraniol can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, fenchone may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The fenchone can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The fenchone can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The fenchone can be in a range provided by any two of these upper and/or lower amounts.

In embodiments, the selection of the one or more terpenes in combination with P-caryophyllene may be influenced by a particular disease, disorder or condition that is to be treated or prevented.

For applications related to anxiety, stress and/or sleeplessness (e.g. insomnia), the terpene blend may consist of a combination of P-caryophyllene with limonene, linalool, and a-humulene. For example, for anxiety, stress and/or sleeplessness (e.g. insomnia), the terpene blend may consist of a combination of P-caryophyllene in an amount of about 50 wt.% (based on the total weight of the terpene blend) with limonene in an amount of about 15 wt.%, linalool in an amount of about 15 wt.%, and a-humulene in an amount of about 20 wt.%.

For the treatment or prophylaxis of pain, the terpene blend may consist of a combination of P-caryophyllene with limonene, linalool, nerolidol, and myrcene.

For the treatment or prophylaxis of inflammation, the terpene blend may consist of a combination of P-caryophyllene with limonene, linalool, a-pinene, and a-humulene.

For the treatment or prophylaxis of cognition-related diseases, disorders or conditions, the terpene blend may consist of a combination of P-caryophyllene with linalool, a-pinene, nerolidol, and borneol. For the treatment or prophylaxis of sleep-related diseases, disorders or conditions, the terpene blend may consist of a combination of P-caryophyllene with limonene, linalool, myrcene, and a-bisabolol.

For the treatment or prophylaxis of gastrointestinal or digestion-related diseases, disorders or conditions, the terpene blend may consist of a combination of - caryophyllene with limonene, a-bisabolol, and geraniol.

For the treatment or prophylaxis of immune-related diseases, disorders or conditions, the terpene blend may consist of a combination of P-caryophyllene with limonene, linalool, a-pinene, and nerolidol.

In some embodiments, the source of terpenes may be from a botanical source. For example, but not limited to, the source of terpenes may be from oregano, cinnamon, clove, rosemary, thyme, pimento, and black pepper. It will be appreciated that most essential oils are composed of terpenes and terpenoids and these are typically synthesized within the cytoplasm of the cell. Terpenes are composed of isoprene units and are generally represented by the chemical formula (CsHsjn. Terpenes can be acyclic, monocyclic, bicyclic, or tricyclic. Owing to the diversity in their chemical structures, terpenes are classified into several groups such as monoterpenes (CioHie), sesquiterpenes (C15H24), diterpenes (C20H32), and triterpenes (C30H40). Some of the major terpene compounds include monoterpene hydrocarbons (p-cymene, limonene, a-pinene, and a- terpinene), oxygenated monoterpenes (camphor, carvacrol, eugenol, and thymol), diterpenes (cembrene C, kaurene, and camphorene), sesquiterpene hydrocarbons (J3- caryophyllene, germacrene D, and humulene), oxygenated sesquiterpenes (spathulenol, caryophyllene oxide), monoterpene alcohols (geraniol, linalool, and nerol), sesquiterpene alcohol (patchoulol), aldehydes (citral, cuminal), acids (geranic acid, benzoic acid), ketones (acetophenone, benzophenone), lactones (bergapten), phenols (eugenol, thymol, carvacrol, and catechol), esters (bornyl acetate, ethyl acetate), and coumarins (fumarin, benzofuran).

Carrier

The terpene-containing formulation may, for example, comprise a liquid carrier. The liquid carrier may be an aqueous liquid carrier. The liquid carrier may be selected from the group consisting of water, hemp oil, hemp seed oil, medium-chain triglyceride (MCT) oil, olive oil, rice bran oil, soya oil, coconut oil, palm oil, grape seed oil, vegetable glycerine, or combinations thereof, such as water and/or an oil. In some embodiments, the liquid carrier may be a water / oil emulsion or an oil / water emulsion.

The liquid carrier may be in an amount between about 30% and about 99% wt% based on total weight of the formulation. The aqueous liquid carrier can be provided in an amount (as a weight % based on total weight of the formulation) of less than about 99, 98, 95, 90, 85, 80, or 75. The aqueous liquid carrier can be provided in an amount (as a weight % based on total weight of the formulation) of at least about 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 98, or 99. The aqueous liquid carrier can be in a range provided by any two of these upper and/or lower amounts.

The terpene-containing formulation may, for example, comprise a solid carrier. The solid carrier may be selected from the group consisting of plant-based carriers, inorganic carrier, organic carrier, or combinations thereof. For example, the solid carrier may be selected for the group comprising hemp powder, sodium saccharine, cellulose, magnesium carbonate, magnesium stearate, sugar, lactose, mannitol, pectin, dextrin, starch, gelatin, silica, citric acid, maltodextrin, acacia, medium-chain triglyceride (MCT) powder, soy powder, pea protein, calcium hydrogen phosphate dihydrate, hypromellose microcrystalline cellulose, cyclodextrins, and combinations thereof.

In some embodiments, the terpene blend may be absorbed, adsorbed, or retained by the solid carrier.

The solid carrier may be in an amount between about 2 wt% and about 40 wt% based on total weight of the formulation. The solid carrier can be provided in an amount (as a weight % based on total weight of the formulation) of less than about 40, 35, 30, 25, 20, 15, 10, 5, or 2. The solid carrier can be provided in an amount (as a weight % based on total weight of the formulation) of at least about 2, 5, 10, 15, 20, 25, 30, 35, or 40. The solid carrier can be in a range provided by any two of these upper and/or lower amounts.

The solid carrier may be suitably one or more substances which may also act as diluents, flavorant, lubricants, suspending agents, binders or disintegrant. The solid carrier material may also include encapsulating material. Optional active agent

The terpene-containing formulation may, in addition to any relevant activity provided by the terpene blend, further comprise or consist of one or more active agents. In some embodiments, the one or more active agents may be selected from a cannabinoid, an antimicrobial agent, an enzyme, an anti-fungal agent, an anti-bacterial agent, an insecticidal agent, an antimicrobial agent, an anti-inflammatory agent, or an anaesthetic. In some embodiments, the one or more active agents may be a cannabinoid, cannabinoid extract or isolate thereof. In some embodiment, the one or more active agents may be a fatty acid amide. The active agent may be selected from the group consisting of cannabidiol (CBD), cannabidiol A (CBDA) cannabigerol (CBG), cannabichromene

(CBC), cannabicyclol (CBL), cannabinol (CBN), cannabigerolic acid (CBGA), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether, palmitoylethanolamide (PEA), or a combination thereof. For example, the active agent may be cannabidiol (CBD) or palmitoylethanolamide (PEA). In an example, the active agent may be cannabidiol

(CBD). In another example, the active agent may be palmitoylethanolamide (PEA).

In some embodiments, the cannabinoid isolate may have less than about 1, 0.5, or 0.3 wt% of any of tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV) and tetrahydrocannabinolic acid (THCA).

In some embodiments, the formulation comprises the active agent in a concentration between about 0.001 mg/ml to about 1200 mg/ml. For example, the formulation comprises the active agent in a concentration of about 100 ml per capsule.

Optional additive

The terpene-containing formulation may further include one or more additives. In some embodiments, the one or more additional additives may be selected from a stabiliser, diluent, adjuvant, dispersing agent, suspending agent, acidifying agent, adsorbent, alkalizing agent, anti-adherent, antioxidant, binder, buffering agent, colorant, complexing agent, fdler, direct compression excipient, disintegrant, flavorant, fragrance, glidant, lubricant, opaquant, plasticizer, preservative, or sweetening agent. For example, sweetening agents such as fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide a palatable preparation.

Methods of Preparing Formulations

The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art. All methods include the step of bringing a formulation comprising a terpene blend, into association with a carrier, one or more optional additives, and one or more optional active agents.

In general, the formulations are prepared by bringing a formulation comprising a terpene blend, into association with a liquid carrier to form a solution or a suspension, or alternatively, by bringing a formulation comprising a terpene blend, into association with formulation components suitable for forming a solid, optionally a particulate product, and then, if warranted, shaping the product into a desired delivery form.

In some embodiments, the formulation is formulated for oral delivery. Formulations for oral delivery may, for example, be in the form of tablets, lozenges, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups, or elixirs. The oral formulation may be in the form of a powder for preparing an oral solution or suspension. Orally administered formulations may contain one or more optional additives, for example, sweetening agents such as stevia, xylitol, mannitol, monk fruit, allulose, fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide a palatable preparation. Moreover, when in a tablet or pellet form, the formulation may be coated to delay disintegration and absorption in the gastrointestinal tract thereby providing a sustained action over an extended period of time. Oral formulations can include standard additives such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Such additives are preferably of pharmaceutical grade. The oral formulations described herein may be dosed 1, 2, 3, 4, 5 or more times daily.

Formulations are also provided which are suitable for administration as an aerosol, by inhalation. These formulations comprise a solution or suspension of a formulation comprising a terpene blend. The desired formulation may be placed in a small chamber and nebulized. Nebulization may be accomplished by compressed air or by ultrasonic energy to form a plurality of liquid droplets or solid particles comprising the formulations as defined herein.

In some embodiments, the formulation may be a topical formulation, such as an ointment, lotion, cream, gel, or liquid spray. Such topical formulations may include agents that promote penetration of the terpene blend and optional active agent through the epidermis. Various other additives known in the art may be included in the topical formulations.

In powders, the terpene blend may be mixed with one or more optional solid carriers, one or more optional additives and/or one or more optional active agents.

In the tablet, the terpene blend may be mixed with one or more optional solid carriers, one or more optional additives and/or one or more optional active agents, wherein the solid carrier has the necessary binding properties in suitable proportions and can be compacted in the shape and size desired.

The preparation of the solid form may also include the terpene blend, one or more optional additives and/or one or more optional active agents, with encapsulating material as the carrier providing a capsule, for example, in which the formulation (with or without other carriers) is surrounded by carrier, which is thus in association with it.

In liquids, the terpene blend may be mixed with one or more optional liquid carriers, one or more optional additives and/or one or more optional active agents. The preparation of the liquid form may be a microemulsion. The preparation of the liquid form may be a microencapsulation (e.g. by formation of micelles or other lipid-based particles). In some embodiments, the terpene-containing formulation can be formulated as a micelle formulation. The micelles may be formed using various known methodologies, such as Pharmako Biotechnologies’ Aquacelle® technology (https://www.pharmako.com.aU/s/PK019_AQUACELLE_INFO_SHEET_0819.pdf) or MicroMAX® technology developed by CSIRO. It will be appreciated that AquaCelle® is a self-micro-emulsifying delivery system (SMEDS) for micelle formation. Typically, the micelle formations may be verified by laser light obscuration analysis and Dynamic Light Scattering (DLS). In some embodiments, the present disclosure provides the formation of a micelle formulation, wherein the micelle formulation comprises a terpene blend and/or a mixture of a terpene blend with an active agent, as well as a method for the manufacture of a micelle formulation comprising a terpene blend and/or a mixture of a terpene blend and an active agent. For example, the micelle formulation may comprise a terpene blend, wherein the terpene blend comprises or consists of a combination of P- caryophyllene and one or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone. In some embodiments, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of -caryophyllene and one or more of limonene, linalool, a-pinene, a- humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone, optionally a carrier, optionally one or more additives, and optionally one or more active agents. For example, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of -caryophyllene and one or more of limonene, linalool, and a-humulene, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In a particular example, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene in an amount of about 50 wt.% (based on the total weight of the terpene blend) with limonene in an amount of about 15 wt.%, linalool in an amount of about 15 wt.%, and a-humulene in an amount of about 20 wt.%, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In other examples, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene with limonene, linalool, nerolidol, and myrcene, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In yet other examples, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene with limonene, linalool, a-pinene, and a-humulene, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In yet other examples, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene with linalool, a-pinene, nerolidol, and borneol, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In yet other examples, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene with limonene, linalool, myrcene, and a-bisabolol, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In yet other examples, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene with limonene, a-bisabolol, and geraniol, optionally a carrier, optionally one or more additives, and optionally one or more active agents. In yet other examples, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P-caryophyllene with limonene, linalool, a-pinene, and nerolidol, optionally a carrier, optionally one or more additives, and optionally one or more active agents.

The terpene blend, optional carrier, one or more optional additives, and one or more optional active agents may be selected from any one or more of the embodiments or examples as described herein.

In any of the embodiments described herein, P-caryophyllene may be provided in an amount of about 30 wt.% to about 70 wt.% based on total weight of the terpene blend. The P-caryophyllene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 70, 65, 60, 55, 50, 45, 40, 35 or 30. The P-caryophyllene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 30, 35, 40, 45, 50, 55, 60, 65 or 70. The P- caryophyllene can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, myrcene may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The myrcene can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The myrcene can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The myrcene can be in a range provided by any two of these upper and/or lower amounts. In some embodiments, borneol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The borneol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The borneol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The borneol can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, a-bisabolol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The a-bisabolol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The a-bisabolol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The a-bisabolol can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, geraniol may be provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend. The geraniol can be provided in an amount (as a weight % based on total weight of the terpene blend) of less than about 50, 45, 40, 35, 30, 25, 20, 15, 10 or 5. The geraniol can be provided in an amount (as a weight % based on total weight of the terpene blend) of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50. The geraniol can be in a range provided by any two of these upper and/or lower amounts.

The terpene blend, optional carrier, one or more optional additives, and one or more optional active agents may be selected from any one or more of the embodiments or examples as described herein. In a particular example, the micelle formulation may consist of a terpene blend, wherein the terpene blend consists of a combination of P- caryophyllene in an amount of about 50 wt.% (based on the total weight of the terpene blend) with limonene in an amount of about 15 wt.%, linalool in an amount of about 15 wt.%, and a-humulene in an amount of about 20 wt.%, optionally a carrier, optionally one or more additives, and optionally one or more active agents.

In some embodiments, the micelle formulation of a terpene blend and/or mixture of a terpene blend and an active agent can be obtained by adding AquaCelle CB3 with the terpene blend and/or a mixture of a terpene blend and an active agent to form a suspension. To obtain the desired final formulation, the suspension of micelles is mixed to produce a homogenous micelle formulation of a terpene blend and/or mixture of a terpene blend and an active agent.

The size of micelles in the micelle formulation may be in a range from about 0.01 pm to about 2.0 pm. In some embodiments, the size of the micelles in the micelle formulation may be at least about (pm) 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.7, 0.75, 0.8, 0.85, 0.90, 0.95, 1.0, 1.20, 1.40, 1.50, 1.60, 1.70, 1.80, 1.90 or 2.0. In some embodiments, the size of the micelles in the micelle formulation may be less than about (pm) 2.0, 1.95, 1.90, 1.80, 1.70, 1.60, 1.50, 1.40, 1.20, 1.0, 0.95, 0.90, 0.85, 0.8, 0.75, 0.7, 0.6, 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, or 0.05. The size of the micelles in the micelle formulation can be in a range provided by any two of these upper and/or lower values.

The concentration of the terpene blend in the micelle formulation may be in a range from about 0.001 mg/mL to about 0.5 mg/mL. In some embodiments, the concentration of the terpene blend in the micelle formulation may be in a range from about 0.005 mg/mL to about 0.2 mg/mL, from about 0.008 mg/mL to about 0.2 mg/mL, or from about 0.01 mg/mL to about 0.1 mg/mL. The concentration of the terpene blend in the micelle formulation may be at least about (mg/mL) 0.001, 0.002, 0.005, 0.008, 0.01, 0.02, 0.05, 0.08, 0.1, 0.2, or 0.5. The concentration of the terpene blend in the micelle formulation may be less than about (mg/mL) 0.5, 0.2, 0.1, 0.008, 0.005, 0.002, or 0.001. The concentration of the terpene blend in the micelle formulation can be in a range provided by any two of these upper and/or lower amounts. The concentration of the optional active agent in the micelle formulation may be in a range from about 0.1 mg/mL to about 1200 mg/mL. In some embodiments, the concentration of the active agent in the micelle formulation may be in a range from about 0.2 mg/mL to about 1000 mg/mL, from about 0.5 mg/mL to about 500 mg/mL. or from about 1 mg/mL to about 10 mg/mL. The concentration of the active agent in the micelle formulation may be at least about (mg/mL) 0.1, 0.2, 0.5, 0.8, 1, 2, 5, 10, 50, 100, 500, 1000, 1200. The concentration of the active agent in the micelle formulation may be less than about (mg/mL) 1200, 1000, 500, 100, 50, 10, 5, 2, 1, 0.8, 0.5, 0.2, or 0.1. The concentration of the active agent in the micelle formulation can be in a range provided by any two of these upper and/or lower amounts.

In some embodiments, the ratio of active agent to terpene blend in the micelle formulation may be from about 5 : 1 to about 10: 1.

Methods and Uses

The present disclosure provides for a method of treating or preventing a disease, disorder or condition in a subject, comprising: administering to the subject a therapeutically effective amount of one or more of the terpene-containing formulations as described herein.

The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing a disease, disorder or condition in a subject. The terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for the treatment and/or prevention of a disease, disorder or condition in a subject.

The present disclosure provides for a method of treating or preventing a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene, comprising: administering to the subject a therapeutically effective amount of one or more of the terpene-containing formulations as described herein wherein the terpene blend comprises P-caryophyllene.

The present disclosure also provides for a use of a terpene-containing formulation, wherein the terpene blend thereof comprises P-caryophyllene, as described herein, for treating or preventing a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene. The terpene-containing formulation, wherein the terpene blend thereof comprises P-caryophyllene, as described herein, may be used in the manufacture of a medicament for the treatment and/or prevention of a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene.

The present disclosure provides for a method of treating or preventing a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene and/or an active agent, comprising: administering to the subject a therapeutically effective amount of one or more of the terpene-containing formulations as described here, wherein the terpene-containing formulation further comprises an active agent as described herein.

The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene and an active agent, wherein the terpene-containing formulation further comprises an active agent as described herein. The terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for the treatment and/or prevention of a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene and an active agent, wherein the terpene-containing formulation further comprises an active agent as described herein.

The present disclosure provides for a method of treating or preventing a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene and/or a cannabinoid or cannabinoid isolate thereof, comprising: administering to a subject a therapeutically effective amount of one or more of the terpene-containing formulations as described here, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein.

The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene and/or a cannabinoid or cannabinoid isolate thereof, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. The terpene- containing formulation, as described herein, may be used in the manufacture of a medicament for the treatment and/or prevention of a disease, disorder or condition in a subject responsive to treatment with P-caryophyllene and/or cannabinoid or cannabinoid isolate thereof, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein.

In some embodiments, the terpene-containing formulations, as described herein, may be effective for influencing cannabinoid receptors in a subject.

The terpene-containing formulations may be administered to subjects in need of treatment related, but not limited, to pain, allergies, catabolic breakdown, inflammation, infection, auto-immune conditions, cancer, fatigue epilepsy, depression, migraine, bipolar disorders, anxiety disorder, insomnia, and drug dependency and withdrawal syndromes (e.g. alcohol withdrawal symptoms).

The present disclosure provides for a method of treating or preventing anxiety, stress, and/or sleeplessness (e.g. insomnia) in a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing anxiety, stress, and/or sleeplessness. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for treating or preventing anxiety, stress, and/or sleeplessness in a subject.

The present disclosure provides for a method of treating or preventing anxiety, stress, and/or sleeplessness (e.g. insomnia) in a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing anxiety, stress, and/or sleeplessness, wherein the terpene- containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for treating or preventing anxiety, stress, and/or sleeplessness in a subject, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. The present disclosure provides for a method of treating, preventing, or ameliorating pain in a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating, preventing, or ameliorating pain. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for treating, preventing, or ameliorating pain in a subject.

The present disclosure provides for a method of treating, preventing, or ameliorating pain in a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein, wherein the terpene-containing formulation further comprises a cannabinoid as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating, preventing, or ameliorating pain, wherein the terpene- containing formulation further comprises a cannabinoid as described herein. A terpene- containing formulation, as described herein, may be used in the manufacture of a medicament for treating, preventing, or ameliorating pain in a subject, wherein the terpene-containing formulation further comprises a cannabinoid as described herein.

In any of these embodiments, the cannabinoid may be in the form of a cannabinoid extract or an isolate thereof.

In some embodiments, the pain may be hyperalgesia. The hyperalgesia may be neuropathic pain. In some embodiments, the pain may be caused by or associated with a disease that causes damage to sensory neurones. In some embodiments, the method and/or use, may be for the prevention, treatment, or amelioration of bowel pain, pancreatic pain, pelvic/perineal pain, back pain, lower back pain, chest pain, cardiac pain, pelvic pain/PID, joint pain (for example, associated with tendonitis, bursitis, acute arthritis), neck pain, obstetric pain (labour or Caesarean-Section), cancer pain, HIN pain, phantom limb pain, post-operative pain, chronic neuropathic pain, failed back surgery pain, post physical trauma pain (including pain caused by a gunshot wound, a road traffic accident, or a bum), scar tissue pain, acute herpes Zoster pain, acute pancreatitis breakthrough pain (cancer), post-herpes neuralgia, or trigeminal neuralgia, or for the prevention, treatment, or amelioration of neuropathic or other pain caused by, or associated with diabetic neuropathy, polyneuropathy, fibromyalgia, myofascial pain syndrome, osteoarthritis, rheumatoid arthritis, sciatica or lumbar radiculopathy, spinal stenosis, temporomandibular joint disorder, renal colic, dysmenorrhoea/endometriosis. In a particular embodiment, the method and/or use, may be for the prevention, treatment, or amelioration of pain associated with neuralgia endometriosis.

In other embodiments, the hyperalgesia may be inflammatory pain. The pain may be caused by or associated with an inflammatory or immune disease. In some embodiments, the method and/or use, may be for the prevention, treatment, or amelioration of bowel pain, back pain, cancer pain, fibromyalgia, post-operative pain, or for the prevention, treatment, or amelioration of inflammatory or other pain caused by, or associated with arthritic conditions such as osteoarthritis, rheumatoid arthritis, rheumatoid spondylitis, gouty arthritis, or asthma, chronic obstructive pulmonary disease, fibrosis, multiple sclerosis, sepsis, septic shock, endotoxic shock, gram negative shock, toxic shock, hemorrhagic shock, adult respiratory distress syndrome, organ transplant rejection, pain secondary to cancer, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcosis, reperfusion injury, multiple sclerosis, myasfhenia gravis, allograft rejections, fever and myalgia due to infection, AIDS related complex (ARC), keloid formation, scar tissue formation, Crohn's disease, ulcerative colitis and pyresis, inflammatory bowel disease, irritable bowel syndrome, osteoporosis, cerebral malaria, or bacterial meningitis. In a particular embodiment, the inflammatory pain may be associated with fibromyalgia, Crohn's disease, or ulcerative colitis.

The present disclosure provides for a method of treating or preventing cognitive impairment and/or disorder in a subject, comprising: administering to a subject a therapeutically effective amount of a formulation, as described herein. The present disclosure also provides for a use of a formulation, as described herein, for treating or preventing cognitive impairment and/or disorder. A formulation, as described herein, may be used in the manufacture of a medicament for treating or preventing cognitive impairment and/or disorder in a subject. In some embodiments, the cognitive impairment and/or disorder may be associated with alertness, memory and/or focus.

The present disclosure provides for a method of treating or preventing cognitive impairment and/or disorder in a subject, comprising: administering to a subject a therapeutically effective amount of a formulation, as described herein, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. The present disclosure also provides for a use of a formulation, as described herein, for treating or preventing cognitive impairment and/or disorder, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. A formulation, as described herein, may be used in the manufacture of a medicament for treating or preventing cognitive impairment and/or disorder in a subject, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein. In some embodiments, the cognitive impairment and/or disorder may be associated with alertness, memory and/or focus.

The present disclosure provides for a method of sedating a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for sedation. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for sedating in a subject.

The present disclosure provides for a method of sedating a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein, wherein the terpene-containing formulation further comprises a cannabinoid as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for sedation, wherein the terpene-containing formulation further comprises a cannabinoid as described herein. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for sedating in a subject, wherein the terpene-containing formulation further comprises a cannabinoid as described herein. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for sedating in a subject, wherein the terpene-containing formulation further comprises a cannabinoid or cannabinoid isolate thereof as described herein.

The present disclosure provides for a method of treating or preventing gastrointestinal disorders in a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing gastrointestinal disorders. A terpene-containing formulation, as described herein, may be used in the manufacture of a medicament for treating or preventing gastrointestinal disorders in a subject. The present disclosure provides for a method of treating or preventing gastrointestinal disorders in a subject, comprising: administering to a subject a therapeutically effective amount of a terpene-containing formulation, as described herein, wherein the terpene- containing formulation further comprises a cannabinoid as described herein. The present disclosure also provides for a use of a terpene-containing formulation, as described herein, for treating or preventing gastrointestinal disorders, wherein the terpene- containing formulation further comprises a cannabinoid as described herein. A terpene- containing formulation, as described herein, may be used in the manufacture of a medicament for treating or preventing gastrointestinal disorders in a subject, wherein the terpene-containing formulation further comprises a cannabinoid as described herein. In some embodiments, the gastrointestinal disorder may be associated with bloating and/or constipation.

It will be appreciated that the dosage regimens and formulations as described herein may apply to any of the embodiments or examples of the methods as described herein.

Dosage regimen

As used herein, “therapeutically effective amount” refers to a terpene-containing formulation as described herein, being administered in an amount sufficient to alleviate or prevent to some extent one or more of the symptoms of the disorder or condition being treated, typically without undue adverse side effects or to achieve a desired pharmacological effect or therapeutic improvement with a reduced side effect profile. The results can be the reduction and/or alleviation of the signs, symptoms, or causes of a disease or condition, or any other desired alteration of a biological system. In some embodiments, the term “therapeutically effective amount” refers to a formulation as described herein, being administered in an amount sufficient to result in a reduction of symptoms associated with stress, anxiety, and/or sleeplessness (e.g. insomnia). Therapeutically effective amounts may, for example, be determined by routine experimentation, including but not limited to a dose escalation clinical trial. The phrase “therapeutically effective amount” includes, for example, a prophylactically effective amount. In some embodiments, a prophylactically effective amount is an amount sufficient to prevent stress, anxiety, and/or sleeplessness. It is understood that “an effective amount” or “a therapeutically effective amount” can vary from subject to subject, due to variation in metabolism of the compound and any of age, weight, general condition of the subject, the condition being treated, the severity of the condition being treated, and the judgment of the prescribing physician. An appropriate “effective amount” or “a therapeutically effective amount” in any individual case may be determined by one of ordinary skill in the art using routine experimentation.

The amount of a terpene-containing formulation as described herein, that will be effective in the treatment and/or prevention of a particular disorder or condition disclosed herein will depend on the nature of the disorder or condition, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. Such techniques are known to the person skilled in the art.

The precise dose to be administered to the subject will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each subject’s circumstances. For example, suitable dosage ranges for oral administration, are generally from about 0.001 milligram to 1000 milligrams of the formulation as described herein per kilogram body weight.

In some embodiments, the terpene-containing formulation as described herein, is administered in an amount so as to deliver a total daily dosage (in mg) of at least about 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 75, 100, 150, or 200. In some embodiments, the terpene-containing formulation as described herein, is administered in an amount so as to deliver a total daily dosage (in mg) of less than about 200, 150, 100, 75, 60, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, or 1. The total daily dosage may be provided in a range between at any two of these upper and/or lower amounts. For example, a total daily dosage may be provided in an amount of between about 1 and 100 mg, about 5 and 75 mg, about 10 and 50 mg, about 15 and 45 mg, or about 20 and 40 mg.

In some embodiments, a therapeutically effective amount of a terpene-containing formulation as described herein, is administered to the subject at a predetermined frequency. In some embodiments, a terpene-containing formulation as described herein, is administered to the subject according to a dosage regimen in which a terpene- containing formulation as described herein is administered once daily, twice daily, three times daily, or four times daily. In some embodiments, the terpene-containing formulation as described herein is administered to the subject according to a dosage regimen in which a terpene-containing formulation as described herein is administered once daily. In some embodiments, a terpene-containing formulation as described herein is administered to the subject according to a dosage regimen in which a terpene- containing formulation as described herein is administered twice daily. In some embodiments, a terpene-containing formulation as described herein is administered to the subject according to a dosage regimen in which a terpene-containing formulation as described herein is administered three times daily. In some embodiments, a terpene- containing formulation as described herein is administered to the subject according to a dosage regimen in which a terpene-containing formulation as described herein is administered four times daily.

In some embodiments, a terpene-containing formulation as described herein is administered to the subject according to a dosage regimen in which a terpene-containing formulation as described herein is administered multiple times daily.

In some embodiments, a therapeutically effective amount of a terpene-containing formulation as described herein, is administered to the subject at a predetermined frequency and/or duration. For example, administration according to any embodiments (e.g. frequency) as described herein may be for a duration of about, or at least about, 1 day, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months, 2 years, or 5 years. Administration of the therapeutically effective amount of a terpene-containing formulation as described herein, may be ongoing so long as a therapeutic effect is received by the subject. As used herein, the term “administer” and “administering” are used to mean introducing the terpene-containing formulation as described herein, into a subject. When administration is for the purpose of treatment, the terpene-containing formulation as described herein, is provided at, or after the onset of, a symptom of a particular disorder, such as stress, anxiety and/or sleeplessness (e.g. insomnia). The therapeutic administration of this substance serves to attenuate any symptom, or prevent additional symptoms from arising. When administration is for the purposes of preventing or reducing the likelihood of the disorder or consider, e.g. stress, anxiety, and/or sleeplessness, the terpene-containing formulation as described herein, is provided in advance of any visible or detectable symptom. The prophylactic administration of the terpene-containing formulation as described herein, serves to attenuate subsequently arising symptoms or prevent or reduce the likelihood of the symptoms from arising altogether.

A terpene-containing formulation as described herein, may be administered by any suitable route. Examples include, but are not limited to, oral, topical, or nasal administration. In some embodiments, a terpene-containing formulation as described herein, is administered orally. In some embodiments, a terpene-containing formulation as described herein, is applied topically.

A terpene-containing formulation as described herein, may be administered to the subject with respect to the subject’s fasted state, as would be understood by the person skilled in the art. For example, the subject may be administered a terpene-containing formulation as described herein before, with, or after a meal. In some embodiments, a terpene-containing formulation as described herein is administered to the subject before a meal (i.e., the subject being in a fasted state). In some embodiments, a terpene- containing formulation as described herein is administered to the subject with a meal. In some embodiments, a terpene-containing formulation as described herein at a certain interval (i.e., 30 minutes, 1 hour, 2 hours, 3 hours, etc.) following a meal.

Applications

The terpene-containing formulation described herein may formulated in an array of different forms. For example, the terpene-containing formulation may be formulated in formulations including those suitable oral administration, by topical administration or for inhalation to the lung, by aerosol. By way of example only, the formulation may be in the form of a tablet, capsule, caplet, powder, granule, an oral solution or suspension, a powder or tablet for preparing an oral solution or suspension, a topical formulation for application to the skin, or any other form that is effective and safe for administration.

In some embodiments, the formulation may be a liquid formulation, such as a liquid oil formulation.

In some embodiments, the formulation may be powder formulation.

In some embodiments, the formulation may be a pellet or tablet formulation, such as chewable tablets (e.g. pastilles, gummies and chewable softgel burstlets). In some embodiments, the formulation may be a capsule formulation, such as a softgel capsule.

In some embodiments, the formulation may be a topical formulation, such as an ointment, lotion, cream, gel, and spray. Such topical formulations may include agents that promote penetration of the terpene blend and optional active agent through the epidermis. Various other additives known in the art may be included in the topical formulations.

In some embodiments, the terpene -containing formulation is formulated for administration to a mammal by oral administration, topical administration, or by inhalation. In some embodiments, the terpene-containing formulation is formulated for administration to a mammal by topical administration or oral administration. In some embodiments, the terpene-containing formulation is formulated for administration to a mammal by oral administration. In some embodiments, the terpene-containing formulation is formulated for administration to a mammal by topical administration (e.g. for application to the skin).

In some embodiments, the terpene-containing formulation is in the form of a powder, dispersible granules, tablet, a pellet, a capsule, a liquid, a suspension, a gel, a cream, a dispersion, a solution, a spray, an emulsion, an ointment, or a lotion. In some embodiments, the formulation is in the form of a liquid (e.g. a liquid oil), powder, pellet or tablet, or a capsule.

Tablets, powders, and capsules may be used in a solid dosage form suitable for oral administration. In some embodiments, solid dosage form preparations, such as powders, granules, tablets and/or pellets, may be converted, shortly before use, to liquid dosage form preparations for oral administration, for example. These liquid dosage forms may include dissolved solutions, suspensions, and emulsions.

In some embodiments, liquid dosage form preparations may include solutions, suspensions, and emulsions. It will be appreciated that aqueous solutions, suspensions, and emulsions, suitable for oral use, are prepared by dissolving or dispersing the formulation in water or other suitable liquid (such as an oil carrier) and adding suitable additives.

Furthermore, it will be appreciated that the choice of carriers and/or additives will, at least in part, be dependent upon the mode of administration of the formulation.

As described below, it will also be appreciated that the terpene-containing formulations as discussed may further comprise one or more optional active agents, e.g. a cannabinoid or isolate thereof.

EXAMPLES

The present disclosure is further described by the following examples. It is to be understood that the following description is for the purpose of describing particular examples only and is not intended to be limiting with respect to the above description.

Example 1 General process for the preparation of formulations comprising a terpene blend

The micelle formulation of a terpene blend and/or mixture of a terpene blend and an active agent is obtained by adding AquaCelle CB3 with the terpene blend and/or a mixture of a terpene blend and an active agent to form a suspension. To obtain the desired final formulation, the suspension of micelles is mixed to produce a homogenous micelle formulation of a terpene blend and/or mixture of a terpene blend and an active agent.

Example la Preparation of Formula 1

90 g of AquaCelle CB3 was slowly added to 10g of a terpene blend comprising P-caryophyllene (about 60 wt%) with limonene (about 10 wt%), linalool (about 10 wt%), and a-humulene (about 20 wt%) to form a suspension of micelles, the suspension of micelles was mixed to produce a homogenous micelle formulation of a terpene blend of Formula 1.

Example lb Preparation of Formula 2

90 g of AquaCelle CB3 can be slowly added to 10g of a terpene blend comprising P-caryophyllene (about 30 to about 70 wt%) with limonene (about 5 to about 50 wt%), linalool (about 5 to about 50 wt%), and myrcene (about 5 to about 50 wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 2.

Example 1c Preparation of Formula 3

90 g of AquaCelle CB3 can be slowly added to 10g of a terpene blend comprising P-caryophyllene (about 30 to about 70 wt%) with limonene (about 5 to about 50 wt%), linalool (about 5 to about 50 wt%), a-pinene (about 5 to about 50 wt%), and a-humulene (about 5 to about 50 wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 3.

Example Id Preparation of Formula 4

90 g of AquaCelle CB3 can be slowly added to 10g of a terpene blend comprising P-caryophyllene (about 30 to about 70 wt%) with linalool (about 5 to about 50 wt%), a- pinene (about 5 to about 50 wt%), nerolidol (about 5 to about 50 wt%), and borneol (about 5 to about 50 wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 4.

Example le Preparation of Formula 5

90 g of AquaCelle CB3 can be slowly added to 10g of a terpene blend comprising P-caryophyllene (about 30 to about 70 wt%) with limonene (about 5 to about 50 wt%), linalool (about 5 to about 50 wt%), a-pinene (about 5 to about 50 wt%), myrcene (about 5 to about 50 wt%), and a-bisabolol (about 5 to about 50 wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 5.

Example If Preparation of Formula 6

90 g of AquaCelle CB3 can be slowly added to 10g of a terpene blend comprising P-caryophyllene (about 30 to about 70 wt%) with limonene (about 5 to about 50 wt%), a-bisabolol (about 5 to about 50 wt%), and geraniol (about 5 to about 50 wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 6.

Example 1 Preparation of Formula 7

90 g of AquaCelle CB3 can be slowly added to 10g of a terpene blend comprising P-caryophyllene (about 30 to about 70 wt%) with limonene (about 5 to about 50 wt%), linalool (about 5 to about 50 wt%), a-pinene (about 5 to about 50 wt%), and nerolidol (X wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 7.

Example Ih Preparation of Formula 8

90 g of AquaCelle CB3 can be slowly added to an amount of palmitoylethanolamide (PEA) and about 10 g of a terpene blend comprising p- caryophyllene (about 30 to about 70 wt%) with limonene (about 5 to about 50 wt%), linalool (about 5 to about 50 wt%), and a-humulene (about 5 to about 50 wt%) to form a suspension of micelles, the suspension of micelles can be mixed to produce a homogenous micelle formulation of a terpene blend of Formula 8.

Example 2 General process for the preparation of capsules

Soft gel capsules were prepared using the standard process for soft gel encapsulation (see for example https://www.saintytec.com/soft-gelatin-capsules- manufacturing-proce ss/) .

Firstly, an appropriate gelatin material is selected. The gelatin material will typically include: gelatin, plasticizer, water, and optional additives including colours, opacifying agents, sugars, etc. The gelatin material can then be heated for at least about 3 hours or until the gelatin turns to a molten liquid mass. The homogenous micelle formulation prepared according to Example 1 can be combined with the molten liquid mass to prepare the encapsulated soft gel capsules using an appropriate tooling system. Further processing of filled soft gelatin capsules includes drying the soft gelatin capsules; quality in soft gelatin capsules manufacturing process, and/or polishing and packaging of soft gelatin capsules.

Example 2a Capsule preparation of Formula 1

Capsules of Formula 1 can be prepared according to general process described above in Example 2.

Example 2b Capsule preparation of Formula 2

Capsules of Formula 2 can be prepared according to general process described above in Example 2.

Example 2c Capsule preparation of Formula 3

Capsules of Formula 3 can be prepared according to general process described above in Example 2.

Example 2d Capsule preparation of Formula 4

Capsules of Formula 4 can be prepared according to general process described above in Example 2.

Example 2e Capsule preparation of Formula 5

Capsules of Formula 5 can be prepared according to general process described above in Example 2.

Example 2f Capsule preparation of Formula 6

Capsules of Formula 6 can be prepared according to general process described above in Example 2. Example 2g Capsule preparation of Formula 7

Capsules of Formula 7 can be prepared according to general process described above in Example 2.

Example 2h Capsule preparation of Formula 8

Capsules of Formula 8 can be prepared according to general process described above in Example 2.

Claims

CLAIMS:

1. A formulation comprising a terpene blend of two or more terpenes, wherein the terpene blend consists of a combination of P-caryophyllene and one or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone, and wherein P-caryophyllene is provided in an amount of about 30 wt.% to about 70 wt.% based on total weight of the terpene blend.

2. The formulation of claim 1, wherein the terpene blend consists of a combination of P-caryophyllene and two or more of limonene, linalool, a-pinene, a-humulene, nerolidol, myrcene, borneol, a-bisabolol, geraniol, and fenchone.

3. The formulation of claim 1 or claim 2, wherein limonene is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

4. The formulation of any one of the preceding claims, wherein linalool is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

5. The formulation of any one of the preceding claims, wherein a-pinene is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

6. The formulation of any one of the preceding claims, wherein a-humulene is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

7. The formulation of any one of the preceding claims, wherein nerolidol is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

8. The formulation of any one of the preceding claims, wherein myrcene is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

9. The formulation of any one of the preceding claims, wherein borneol is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

10. The formulation of any one of the preceding claims, wherein a-bisabolol is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

11. The formulation of any one of the preceding claims, wherein geraniol is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

12. The formulation of any one of the preceding claims, wherein fenchone is provided in an amount of about 5 to about 50 wt.% based on total weight of the terpene blend.

13. The formulation of any one of the preceding claims, wherein the source of terpenes is from a botanical source.

14. The formulation of any one of the preceding claims, further comprising or consisting of a carrier, wherein the carrier is a liquid carrier or a solid carrier.

15. The formulation of claim 14, wherein the liquid carrier is an aqueous liquid carrier selected from the group comprising water, hemp oil, hemp seed oil, medium-chain triglyceride (MCT) oil, olive oil, rice bran oil, soya oil, coconut oil, palm oil, grape seed oil, vegetable glycerine, or combinations thereof.

16. The formulation of claim 14, wherein the solid carrier is selected from the group comprising plant-based carriers, inorganic carrier, organic carrier, or combinations thereof.

17. The formulation of claims 16, wherein the solid carrier is selected for the group comprising hemp powder, magnesium carbonate, magnesium stearate, sugar, lactose, pectin, dextrin, starch, gelatin, silica, citric acid, maltodextrin, acacia, medium-chain triglyceride (MCT) powder, soy powder, pea protein, calcium hydrogen phosphate dihydrate, hypromellose microcrystalline cellulose, cyclodextrins, or combinations thereof.

18. The formulation of any one of claims 14 to 17, wherein the carrier is present in the formulation in an amount of between about 2 wt% and about 99 wt% based on total weight of the formulation.

19. The formulation of any one of the preceding claims, wherein the formulation further comprises one or more active agents.

20. The formulation of claim 19, wherein the one or more active agents is selected from a cannabinoid, an antimicrobial agent, an enzyme, an anti-fungal agent, an antibacterial agent, an insecticidal agent, an antimicrobial agent or an anaesthetic.

21. The formulation of claim 19 or claim 20, wherein the active agent is selected from the group consisting of cannabidiol (CBD), cannabidiol A (CBDA) cannabigerol (CBG), cannabichromene (CBC), cannabicyclol (CBL), cannabinol (CBN), cannabigerolic acid (CBGA), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether, palmitoylethanolamide (PEA) or a combination thereof.

22. The formulation of claim 20 or claim 21, wherein the cannabinoid is present in the form of a cannabinoid extract or isolate having less than 1, 0.5, or 0.3 wt% of any of tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV) and tetrahydrocannabinolic acid (THCA).

23. The formulation of any one of claims 19 to 22, wherein the formulation comprises the active agent in a concentration between about 0.001 mg/ml to about 1200 mg/ml.

24. The formulation of any one of the preceding claims, wherein the formulation further comprises one or more additional additives.

25. The formulation of claim 24, wherein the one or more additional additives is selected from a stabiliser, diluent, adjuvant, dispersing agent, suspending agent, acidifying agent, adsorbent, alkalizing agent, anti-adherent, antioxidant, binder, buffering agent, colouring agent, complexing agent, fdler, direct compression excipient, disintegrant, flavorant, fragrance, glidant, lubricant, opaquant, plasticizer, preservative, or sweetening agent.

26. The formulation of any one of the preceding claims, wherein the formulation is formulated for administration to a mammal by oral administration, inhalation, nasal administration, or topical administration.

27. The formulation of any one of the preceding claims, wherein the formulation is in the form of a powder, a granule, a tablet, a pill, a capsule, a liquid, a spray, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, a cream, or a lotion.

28. A method of treating or preventing a disease, disorder or condition in a subject, comprising: administering to a subject a therapeutically effective amount of one or more of the formulations of any one of claims 1 to 27.

29. Use of a formulation in the manufacture of a medicament for treating or preventing a disease, disorder or condition, wherein the formulation is according to any one of claims 1 to 27.

30. A formulation for use in treating or preventing a disease, disorder or condition, wherein the formulation is according to any one of claims 1 to 27.