GB2617823A

GB2617823A - A cannabidiol oil and uses thereof

Info

Publication number: GB2617823A
Application number: GB2205322.7A
Authority: GB
Inventors: Glynn Caroline
Original assignee: Chanelle Mccoy Cbd Ltd
Current assignee: Chanelle Mccoy Cbd Ltd
Priority date: 2022-04-11
Filing date: 2022-04-11
Publication date: 2023-10-25
Also published as: GB202205322D0

Abstract

A cannabidiol (CBD) oil comprising cannabidiol powder and a medium-chain triglyceride. The composition has enhanced stability and reduced oxidative degradation. The powder has a minimum cannabidiol content of 90% and comprises only the (-) -CBD enantiomer. The composition may be used to treat sleep disorders and autoimmune disorders. A method for preparing and packaging said oil composition is also disclosed.

Description

A cannabidiol oil and uses thereof

Field of the Invention

The present invention relates to the field of pharmaceutical preparation, and more particularly to a cannabidiol oil, a method for improving stability and reducing oxidative degradation of the cannabidiol oil and uses thereof.

Background to the Invention

Cannabidiol (CBD), chemically referred as 2-[1 R-3-methyl-6R-(1-methyletheny1)-2-cyclohexen-1-y1]-5-pentyl-1, 3-benzenediol or 2-[(6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-y1]-5-pentylbenzene-1, 3-diol, has the following structure: (Formula (I)) CBD is a non-psychoactive cannabinoid, which preferentially binds to the type 2 cannabinoid receptor (082) and has shown promise in treating numerous diseases and disorders as well as a muscle relaxant.

In the United States, an orally administered cannabidiol liquid has received orphan drug status for the treatment of Dravet Syndrome (form of epilepsy), under the brand name Epidolexe. CBD is also an active ingredient of Sativex®, which is an aerosolized mist for an oral administration containing a near 1:1 ratio of CBD and THC.

CBD has also been reported for the treatment of epilepsy (US Patent No. 9,125,859), for treating tumors associated with Tuberous Sclerosis Complex (GB Patent No. 2564383), and for treating degenerative skeletal muscle disease (European Patent No. 3206681).

CBD been an organic molecule, is inherently susceptible to degradation over the time due to oxidation, which affect the stability and shelf-life of CBD oil.

There has been attempts to prepare stable CBD formulation for oral administration as suggested in the US Publ. No. 20150342902, which uses various lipids to stable CBD.

CBD formulation with argan oil is disclosed in W02017160923 for treating various inflammatory disorders including arthritis including rheumatoid arthritis and osteoarthritis; dermatitis including eczema, psoriasis, dry skin, skin inflammations (such as those caused by tattoo, insect bites, poison ivy and jellyfish), allergic dermatitis, contact dermatitis, atopic dermatitis, and psoriasis; ulcerative colitis, and Crohn's disease.

US Patent Publication No. U52019201350A1 describes a composition comprising extended-release beads configured to release greater than 80% of a fat-soluble active therein over a period of 4 hours or more, wherein said active could be selected from cannabinoids such as CBD, wherein the composition could further include microcrystalline cellulose, stearic acid, and medium-chain triglycerides, wherein the composition could be formed into a two-piece liquid capsule; and that they can be utilized to treat various tumours, including but not limited to, neuroblastoma, mantle cell lymphoma, colon cancer, osteosarcoma, and glioma and to provide an analgesic effect, as a sleep aid, an appetite stimulant, to treat glaucoma, to relieve anxiety, and relieve nausea in a subject.

US Publication No. U52018250262A1 describes a modified release pharmaceutical compositions comprising one or more natural or synthetic cannabinoids, one or more release modifying agent(s) and one or more pharmaceutically acceptable excipient(s). The document describes CBD as having analgesic, antispasmodic, anti-convulsive, anxiolytic, antipsychotic, antinausea, and anti-rheumatoid arthritic properties.

International Patent Publication No. WO 2020/183455 describes a cannabinoid combination comprising, as the only cannabinoids, CBD and -tetrahydrocannabinol (THC), or enanfiomers, diastereomers, or racemates thereof, for use in the treatment of low back pain (LBP) in a subject together with at least one standard of care (SoC) pain medication, wherein the CBD:THC weight ratio in the cannabinoid combination is about of 4:1 to about 10:1. The application also states that the cannabinoid combination provides an improvement in at least one disease parameter selected from pain intensity, disability, sleep quality, mental and physical health.

However, the compositions described above contain psychoactive contaminants which may not be suitable for use with users who have an adverse effect to those contaminants.

It is an object of the subject application to overcome at least one of the above-mentioned problems.

Summary of the Invention

In one general aspect, the present invention provides a method for packaging an oil-containing CBD that are stored within a bottle packed under an inert gas, in such a way that oxidative degradation within the bottle is significantly reduced. The method is industrially scalable and designed to improve stability and enhance shelf-life of the CBD oil.

There is provided, in one aspect and as set out in the appended clams, a cannabidiol oil comprising cannabidiol powder and a medium-chain triglyceride, wherein the cannabidiol powder only contains the (-)-CBD enanfiomer and has a minimum cannabidiol content of 90%.

In one aspect, the cannabidiol powder is free from terpenes.

In one aspect, there is provided a cannabidiol oil comprising cannabidiol powder and a medium-chain triglyceride, wherein the cannabidiol powder only contains the (-)-CBD enantiomer, has a minimum cannabidiol content of at least 90% and is free of terpenes.

In one aspect, the cannabidiol oil has a minimum cannabidiol content of between about 30 95% and 99%.

In one aspect, the cannabidiol is administered in a daily dose of up to about 150mg. In one aspect, the cannabidiol is administered in a daily dose of up to about 100mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 75mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 60mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 50mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 40mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 25mg. In one aspect, the cannabidiol is administered in a daily dose of up to about 20mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 15mg.

In one aspect, the cannabidiol is administered in a daily dose of up to about 10mg.

In one aspect, the cannabidiol is administered in a daily dose of about 20mg.

In one aspect, the cannabidiol is administered in a daily dose of about 10mg.

In one aspect, the cannabidiol powder has a Doo (particle size distribution) between about 10pm to about 1000pm. In one aspect, the cannabidiol powder has a D50 (particle size distribution) between about 20pm to about 90pm. Preferably in a range of between about 25pm to about 85pm; more preferably in a range of between about 30pm to about 80pm; ideally in a range of between about 40pm to about 75pm, or in a range of between about 43pm to about 80pm or in a range of between about 40pm to about 48pm.

In one aspect, the particle size distribution of CBD powder is such that Dgo is in range of about 100pm to about 300pm; preferably in a range of about 110pm to about 280pm; more preferably between about 116pm to about 270pm; even more preferably in a range of about 120pm to about 260pm or in a range of about 130pm to about 250pm, or in a range of about 134pm to about 240pm, or ideally in a range of about 142pm to about 240pm.

In one aspect, the cannabidiol powder is sourced from plants selected from hemp (Cannabis sativa), Cannabis indica and Cannabis ruderalis, or hybrids thereof.

In one aspect, the cannabidiol powder is a synthetic cannabidiol powder. Preferably, the synthetic cannabidiol powder is sourced from a fruit of a citrus tree or a cannabis plant (and hybrids thereof). Preferably, the citrus tree is selected from an orange tree, a lemon tree, a lime tree, a mandarin tree, a kumquat tree, or a blood orange tree.

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The weight of the CBD powder in the cannabidiol oil is between about 150mg to about 1000 mg; preferably between about 200mg to about 750 mg; more preferably between about 250mg to about 650mg; more preferably between about 275 to about 600mg; and ideally between about 280mmg to about 560mg, or 250mg, 280mg, 300mg, 350mg, 400mg, 450mg, 500mg, 550mg, and 560mg. Preferably, the weight of the CBD powder in the cannabidiol oil is sufficient to give at least one daily dose of cannabidiol.

In one aspect, the medium-chain triglyceride is selected from coconut oil (Caprylic/Capric triglyceride), palm kernel oil, whole milk, and dairy butter. Preferably, the medium-chain triglyceride is coconut oil (Caprylic/Capric triglyceride). The total amount may vary from about 90% to about 99%; preferably between about 92% to about 99%; and ideally between about 94% to about 99% or between about 94% and 98% by weight of the total weight of oil.

The CBD oil can be prepared as unflavored or flavored. In one aspect, the cannabidiol oil further comprises a flavouring additive. The flavour is selected from, but not limited to, orange sweet oil, spearmint oil mentha spicata herb, mint, strawberry, banana, cherry, passion fruit, tangerine, cola, chocolate, vanilla, and the like.

In one aspect, the cannabidiol oil further comprises an acceptable food additive.

In one aspect, there is provided a cannabidiol oil as described for use in treating a sleep disorder.

In one aspect, the sleep disorder is selected from insomnia, sleep apnoea, narcolepsy, restless leg syndrome, parasomnias, REM sleep behaviour disorder, non-24-Hour Sleep Wake Disorder, excessive sleepiness, shift work disorder, jet lag syndrome, delayed sleep phase, advanced sleep phase, sleep terrors, sleepwalking, and periodic limb movement disorder. Preferably, the sleep disorder is insomnia.

In one aspect, the cannabidiol is administered in a daily dose of about 10mg to about 150mg. The daily dose can be administered a single dose once per day, a single dose twice per day, a single dose three times a day, a single dose four times a day, a single dose five times a day, or a single dose up to 10 times a day provided that the daily dose is not exceeded.

In one aspect there is provided a cannabidiol oil as described above for use in the treatment of an autoimmune disease.

In one aspect, the autoimmune disease is selected from osteoarthritis, rheumatoid arthritis, fibromyalgia, gout, childhood arthritis, psoriafic arthritis, inflammatory bowel disease (Crohn's Disease, Ulcerative Colitis), multiple sclerosis, Guillain-Barre Syndrome, Type 1 Diabetes mellitus, psoriasis, chronic inflammatory demyelinating polyneuropathy, Grave's Disease, Hashimoto's thyroiditis, myasthenia gravis, vasculifis, and Systemic Lupus Erythematosus (lupus). Preferably, the autoimmune disease is arthritis. Ideally, the arthritis is fibromyalgia.

In one aspect, the invention provides a method for preparing and packaging a CBD oil, which comprises step of: (a) preparing a premix of medium-chain triglyceride (MCT) oil and a pure or substantially pure CBD powder, (b) blending and heating the premix to obtain the CBD oil, (c) packaging the CBD oil in a packaging bottle treated with an inert gas, and (d) purging oxygen from the packaging bottle during step (c).

In a further aspect, the present invention provides a stable CBD oil comprising (a) a pure or a substantially pure CBD powder, (b) a medium-chain triglyceride (MCT) oil, and (c) a sitologically acceptable additive.

The CBD oil of the present invention contains a pure or a substantially pure CBD powder, a medium-chain triglyceride (MCT) oil, and a sitologically acceptable additive.

The weight of the CBD powder in the oil is between about 100mg to about 1000 mg; preferably between about 150mg to about 750mg; preferably between about 200mg to about 700 mg; more preferably between about 250mg to about 650mg; more preferably between about 275 to about 600mg; and ideally between about 280mg to about 560mg, or 250mg, 280mg, 300mg, 350mg, 400mg, 450mg, 500mg, 550mg, and 560mg. The CBD oil can be prepared as unflavored or flavored. Preferably, the weight of the CBD powder in the oil is sufficient to give at least one daily dose of cannabidiol.

The CBD oil of the present invention is obtained by (a) preparing a premix of medium-chain triglyceride (MCT) oil and substantially pure CBD powder, and (b) blending and heating the premix to obtain oil-containing CBD.

To enhance the shelf-life and stability of the CBD oil of the present invention, the CBD oil can be filled and packaged in an inert atmosphere so that oxygen is purged from the bottle the CBD oil is packaged in. For example, inert gases such as carbon dioxide or nitrogen can be used to purge oxygen from the bottle during packaging. Removing oxygen significantly reduces oxidative degradation of CBD oil. It should be noted that other inert gases could be used, for example, nitrogen, argon, krypton, neon, xenon and helium.

Definitions The term "cannabidiol oil" and "oil-containing cannabidiol" are used interchangeably, refers to formulation comprising pure or substantially pure CBD powder, medium-chain triglyceride, and an acceptable food additive. The source from which the synthetic CBD powder is synthesised is selected from hemp, the rind of the fruit of citrus trees which produce limonene (1-Methy1-4-(prop-1-en-2-yl)cyclohex-1-ene), and olivetol (5-IS pentylresorcinol) (a naturally occurring organic compound).

In the specification, the term "acceptable food additive" should be understood to mean a food supplement, a food enhancer (added to food items such as drinks and confectionary etc), vitamins, minerals, flavouring, colouring, and the like.

The term "medium-chain triglyceride (MCT)" should be understood to mean fatty acids that have a chain length of 6-12 carbon atoms. MCT oils generally contain either 100% caprylic acid (08), 100% capric acid (010), or a combination of the two.

The term "treated bottle" refers to any type or size of packaging bottle that is treated with any suitable inert gas, which includes blowing the packaging bottle with, for example, carbon dioxide or nitrogen, or manufacturing the packaging bottle under a blanket of the inert gas.

In the specification, the term "administration" should be understood to mean administration of the CBD oil using various delivery systems that are known in the art and that can be used to administer the invention, e.g., encapsulation, microparticles, microcapsules, liquid or tablet form. Methods of introduction include but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes. The CBD oil may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or

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mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active or inactive agents. Administration can be systemic or local. In addition, it may be desirable to introduce the compositions of the invention into the central nervous system by any suitable route, including intraventricular and intrathecal injection; intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir. Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. In one aspect, the CBD oil can be delivered in a controlled release system. In one aspect, a pump, a spraying device, a pipette or suitable dispensing device may be used.

It may be desirable to administer the compositions of the invention locally to the area in need of treatment; this may be achieved, for example and not by way of limitation, by topical application, by injection, by means of a catheter, by means of a suppository, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibres.

The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can take the form of solutions, 20 suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like.

The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E. W. Martin. Such compositions will contain a therapeutically effective amount of the therapeutic, preferably in purified form, together with a suitable amount of carrier to provide the form for proper administration to the patient. The formulation should suit the mode of administration.

The present invention also provides pharmaceutical compositions. Such compositions comprise a therapeutically effective amount of a therapeutic, and a pharmaceutically acceptable carrier. In a specific embodiment, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.

The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the Therapeutic is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol and the like.

In a preferred embodiment, the composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration to human beings. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition may also include a solubilizing agent and a local anaesthetic such as lignocaine to, ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachets indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the composition is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.

In the specification, the term "therapeutically effective amount" should be understood to mean an amount of the active required to illicit a therapeutic response in the individual taking the active.

In the specification, the term "sleep disorder" should be understood to mean conditions that affect sleep quality, timing, or duration and impact a person's ability to properly function while they are awake. These disorders can contribute to other medical problems, and some may also be symptoms for underlying mental health issues. There are more than 100 different sleeping and waking disorders. They can be grouped into four main categories: problems falling and staying asleep (for example, insomnia); problems staying awake (for example, excessive daytime sleepiness); problems sticking to a regular sleep schedule (for example, sleep rhythm problem); and unusual behaviours during sleep (for example, sleep-disruptive behaviours). Examples of such sleep disorders include insomnia, sleep apnoea, narcolepsy, restless leg syndrome, parasomnias, REM sleep behaviour disorder, non-24-Hour Sleep Wake Disorder, excessive sleepiness, shift work disorder, jet lag syndrome, delayed sleep phase, advanced sleep phase, sleep terrors, sleepwalking, and periodic limb movement disorder.

In the specification, the term "arthritis" should be understood to mean inflammation or swelling of one or more joints. It describes more than 100 conditions that affect the joints, tissues around the joint, and other connective tissues. Specific symptoms vary depending on the type of arthritis, but usually include joint pain and stiffness. Examples of arthritis include osteoarthrifis, rheumatoid arthritis, fibromyalgia, gout, childhood arthritis, and lupus.

In the specification, the term "modified atmospheric conditions" or "gas flushing" should be understood to mean a process in which various types of inert gas (most commonly nitrogen or carbon dioxide) or other gases (such as helium, neon, argon, krypton, and xenon), are injected inside, sucked out, and re-injected repetitively to remove oxygen from the container being filled with product. Gas flushing is a type of modified atmosphere packaging. Gas flushing is done to improve the shelf life of the product contained within.

Brief Description of the Drawings

The invention will be more clearly understood from the following description of an embodiment thereof, given by way of example only, with reference to the accompanying drawings, in which: Figure 1 shows a bar chart illustrating the assessment of sleep in subjects prior to talking the CBD oil of the claimed invention. 137 subjects rated their sleep less than 6 out of 10, and 43 subjects rated their sleep greater than 6 out of 10.

Figure 2 shows a bar chart illustrating the assessment of the qualify of sleep in subjects shown in Figure 1 after taking the CBD oil of the claimed invention. 21 subjects rated their sleep less than 6 out of 10 and 159 subjects rated their sleep greater than 6 out of 10.

Detailed Description of the Drawings 5 Materials and Methods Preparation of CBD oil Table 1 Method of producing CBD Oil Step Typical Manufacturing flow 1 Weigh 40 Kgs of MCT Oil into the blending tank. Turn on the stirrer in the blending tank 2 Weigh 6.501 Kgs of MCT Oil into a sanitised side mix container. Record the weight and include any wastage. Heat this oil to 50°C using the hot plate. Stir to ensure even heat distribution.

3 Weigh 3.024 Kgs of synthetic cannabidiol powder into a sanitised container. Record the weight and include any wastage. Add this powder to the heated MCT Oil and stir to completely dissolve.

4 Add the heated mixture to the blending tank 5-10 minutes gentle mixing 6 Weigh 0.475 kgs of flavouring, if required, to the sanitised side mix container. Then add to the blending tank. Record the weight and include any wastage 7 Take sample and check for appearance

Specification: Taste:

Specification: Appearance: light yellow liquid

8 Top and bottom tank samples to be checked and passed by quality only before filling commences 9 Take one sample of approximately 50m1 from the bulk into a clean container and pass to quality control. Retain until the final pack sample results have been received and confirmed as within specification.

Dose CO2 into mixing tank for 30 seconds CBD oil is packaged, typically, to deliver between 20mg to about 200mg of product, with or without a flavour. The flavours that can be used include peppermint and orange. All presentations will have a pipette or a spray dispensing device. It should be noted that an inhaler or nebuliser can also be used to administer the CBD oil.

Example /

Components used for the preparation of one example of the CBD oil of the invention are described in Table 2.

Table 2-Unflavoured (280mq) Ingredient ckw/w CBD powder 3.0240 MCT coconut oil (Caprylic/Capric 96.9760 Triglyceride) MCT coconut oil (40Kg) is added and stirred in a blending tank. MCT coconut oil (6.5kg) is added and heated at 50°C under stirring in a sanitized side mix container.

CBD powder (3.024kg) is added to the heated MCT oil in sanitized container and stirred till it is completely dissolved. The dissolved mixture is added to the blending tank and mixed gently for 5-10 minutes to obtain oil. The oil is filled and packaged within inert gas-treated bottles.

Example 2

Components used for the preparation of one example of the CBD oil of the invention with orange flavor are described in Table 3.

Table 3-Flavoured (280mg) Ingredient %w/w CBD powder 3.0240 MCT coconut oil (Caprylic/Capric 96.9760 Triglyceride) Orange Sweet Oil Dulcis] [Citrus Aurantium 0.9500% MCT coconut oil (40Kg) is added and stirred in a blending tank. MCT coconut oil (6.5kg) is added and heated at 50°C under stirring in a sanitized side mix container. CBD powder (3.024kg) is added to the heated MCT oil in sanitized container and stirred till it is completely dissolved. The dissolved mixture is added to the blending tank and mixed gently for 5-10 minutes. Orange sweet oil (0.475kg) flavor is added to the blending tank to obtain oil. The oil is filled and packaged within inert gas-treated bottles.

Example 3

Components used for the preparation of one example of the CBD oil of the invention with spearmint flavor are described in Table 4 Table 4-Flavoured (280mq) Ingredient ckw/w CBD powder 3.0240 MCT coconut oil (Caprylic/Capric 96.9760 Triglyceride) Spearmint oil Mentha Spicata Herb 0.9500% MCT coconut oil (40Kg) is added and stirred in a blending tank. MCT coconut oil (6.5kg) is added and heated at 50°C under stirring in a sanitized side mix container.

CBD powder (3.024kg) is added to the heated MCT oil in sanitized container and stirred fill it is completely dissolved. The dissolved mixture is added to the blending tank and mixed gently for 5-10 minutes. Spearmint oil Mentha Spicata Herb (0.475kg) flavor is added to the blending tank to obtain oil. The oil is filled and packaged within inert gas-treated bottles.

Example 4

Components used for the preparation of one example of the CBD oil of the invention with spearmint flavor are described in Table 5.

Table 5-Flavoured (560mq) Ingredient ckw/w CBD powder 6.048 MCT coconut oil (Caprylic/Capric 93.952 Triglyceride) Spearmint oil Mentha Spicata Herb 0.9500% MCT coconut oil (40Kg) is added and stirred in a blending tank. MCT coconut oil (6.501kg) is added and heated at 50°C under stirring in a sanitized side mix container. CBD powder (6.048kg) is added to the heated MCT oil in sanitized container and stirred fill it is completely dissolved. The dissolved mixture is added to the blending tank and mixed gently for 5-10 minutes. Spearmint oil Mentha Spicata Herb (0.475kg) flavor is added to the blending tank to obtain oil. The oil is filled and packaged within inert gas-treated bottles.

Please note that the CBD powder is 100% pure strength, with no additives or other cannabinoid derivatives, such as THC. Typically, the CBD powder is sourced from a natural source or is synthetically derived. When synthetically derived, the plant source that the CBD powder is synthesized from is selected from the rind of the fruit of citrus trees (orange, lemon (such as Citrus limon Ponderosa, Meyer, variegated pink-fleshed eureka lemon, eureka lemon), lime (such as Citrus hystrix (Kaffir), Citrus australasica (Australian red), Citrus aurantifolia (Palestine sweet lime, key lime), mandarin (Citrus reticulata), kumquat (Fortune//a crassiforia, Fortune//a obovate 'Fukusha', Fortune/la margarita), blood orange (Citrus sinensis)), cannabis plant, lichens, and hybrids thereof.

Dosage In liquid form, the CBD oil composition provides a daily dose of cannabidiol of between about 5mg to about 200mg; preferably between about 10mg and about 175mg; and ideally between about 10mg and about 150mg. In some instances, the recommended daily dose of the CBD oil of the claimed invention will provide a daily dose of about 10mg to about 60mg of cannabidiol.

Solubility Tests Solutions/suspensions at different CBD concentrations in DMSO (Le., 20, 16, 5.12, and 1.64 mg/mL) were investigated by scanning electron microscope (SEM)-energy disruptive spectroscopy (EDX) to detect the presence of undissolved CBD particles.

Dilutions were deposited on sample support, air dried, and detected particles were investigated by SEM-EDX. Regardless the dilution tested, elemental composition and particle morphology exclude the presence of CBD particulates. Detected particles are mainly composed of Na, K and Ca2+ and they are not carbon-based particles, as CBD. Solutions/suspensions at different concentration of CBD in corn oil (i.e., 18, 9, and 3.75 mg/mL) were investigated by ESEM-EDX to detect the presence of undissolved CBD particles. Drops of solutions were investigated at different magnifications and particulate matter identified in the drops was characterized by EDX. Regardless the dilution tested, C-0 based particles with morphology like pristine CBD were not detected.

Clinical Tests (A) Insomnia A retrospective survey was carried out assessing quality of sleep before (see Figure 1) and after (see Figure 2) participants taking the CBD oil of the claimed invention.

Survey ran for a total of 32 days. Participants were requested to rank their quality of sleep from 1-10 prior to and after taking a dose of CBD oil of the claimed invention daily. 189 subjects responded to the survey, from which 180 subjects fully completed the questionnaire, 9 did not complete the survey in full and were omitted from final analysis. Of the 180 surveyed who administered a dose of CBD oil of the claimed invention daily 92% noted an improvement in their sleep (see Figure 2).

In a separate study, the study design is a phase 2/3, multicentre, randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety, and tolerability and pharmacokinetics of CBD oil of the claimed invention in adults with sleep disturbance in which subjects are randomised to placebo or CBD treatment arms.

A total of 159 male and female healthy adults with sleep disturbance will be enrolled in a total of 3 treatment arms in parallel (53 participants/treatment arm). Eligible participants will be randomised to receive either placebo (Treatment Arm 1), or CBD at 2 different dose levels (Treatment Arm 2 and 3, respectively, the dose to be determined). Participants are 18 years and older. Pharmacokinefic sampling will be performed on elderly subjects to determine if any dose adjustment is required in this age group. Sub-group analysis will determine efficacy in younger participants (18-54 years) and older participants 55 years). The treatment duration will be 4 weeks.

Sleep diaries will be maintained every day. The primary efficacy endpoint will be evaluated at 5 days. The study will have met its primary endpoint if efficacy is demonstrated at Day 5 compared with placebo treatment. The 4-weeks of evaluation will inform treatment duration of effect and safety (adverse event collection).

Participants will receive a single sublingual dose of 0.35 mL (40mg) CMC CBD or placebo daily on Days 1-30 (total of 30 doses). The total study time for each participant in Part B will be up to 58 + 2 days which includes a 12-day screening period, a 2-day baseline period, a 30-day treatment period and a 14-day + 2 days follow up period. All participants in Part B will be required to attend the study clinic at screening visit and on Day 1 (first day of study treatment), Day 15, Day 31 and Day 44 +2 days (end of study visit). There will be no confinement period and all scheduled clinic visits will be conducted as outpatient visits.

Blood samples will be collected during the screening visit for hematology, and serum chemistry parameters. Laboratory test results will be assessed by the investigator, or medically qualified nominee, before confirmation of study eligibility. In the event of abnormal laboratory parameter values, blood tests may be repeated. Participants will be required to fast for at least 8 hours prior to each clinical laboratory blood sample collection timepoint (except in the instance of an ETV).

Hematology parameters that will be measured include: hemoglobin, hematocrit, red blood cell indices, thrombocyte count (platelets), reticulocyte count, white blood cell count with differential (including neutrophils, eosinophils, basophils, lymphocytes and monocytes).

The following serum chemistry parameters will be measured: sodium, potassium, magnesium, chloride, bicarbonate, phosphate, calcium, amylase, lipase, uric acid, albumin, globulins, protein, lactate dehydrogenase, creatine kinase, creafinine (including calculated estimated glomerular filtration rate [eGRF] using CKD-EPI formula), blood urea nitrogen, ALP, ALT, AST, GGT, total bilirubin, conjugated and unconjugated bilirubin, total cholesterol, high-density lipoprotein, low density lipoprotein, triglycerides, glucose.

The study is being performed to determine the efficacy of two different dose levels of CBD oil of the claimed invention in reducing sleep disturbance over a 30-day dosing period compared to placebo. This is determined by measuring the change from baseline on the Insomnia Severity Index (151) questionnaire score or Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance questionnaire score at Day 15 or Day 31. The study will also determine the efficacy of 2 dose levels of CBD oil of the claimed invention compared to placebo in the treatment of sleep disturbance. The study will consist of 3 parallel treatment arms with 53 participants per arm.

The main efficacy analysis will be change from baseline values for PROMIS sleep disturbance score or ISI score using the Full Analysis Set. The test is to evaluate the treatment effect by comparing each of the CBD dose groups vs placebo group. The Type 1 error level for the test will be 2.5% to adjust for multiplicity. The analysis will be conducted using mixed model for PROMIS change from baseline or ISI change from baseline separately with treatment group and baseline values of the questionnaire as fixed effects and random intercepts are assumed for subjects. Observed values and changes from baseline of efficacy measures (PROMIS sleep disturbance score or 151 score, sleep diary data, will be summarised at each scheduled timepoint by treatment arm using descriptive statistics (n, mean, standard deviation, minimum, maximum, median).

Results and Discussion Consumers of the CBD oil of claimed invention were invited to participate in a self-assessment survey regarding the quality of sleep prior to (Figure 1) and after taking the applicant CBD oil (Figure 2). Patients were not offered any financial inducement for participation: Survey ran for 32 days.

Participants were requested to rate their sleep before and after taking the CBD of claimed invention.

189 total response of which 180 were 'valuable'.

Valuable' means significant data could be pulled from these responses.

9 responses were removed from analysis due to not being completed in full; therefore no valuable data was obtainable from them.

A Sleep rating before and after taking the CBD oil of the claimed invention was obtained from each participant and from these results and the improvement factor was calculated by subtracting rating prior to taking the CBD oil of the claimed invention from rating after taking the CBD oil of the claimed invention. An improvement factor > 0 indicated product as effective for improving sleep.

An improvement factor of <1= 0 indicated product as ineffective for improving sleep.

Sleep ratings prior to taking the CBD of claimed invention outlined in Figure 1 show that of those, 59% of participants rated their sleep less than 6 out of 10 and 41% rated their sleep 6 out of 10 or greater Sleep ratings after taking the CBD of claimed invention outlined in Figure 2 show that of those, 12% participants rated their sleep less than 6 out of 10 and 88% rating their sleep 6 out of 10 or greater Overall out of 180 participants 136 (76%) noted an improvement in their sleep; noting sleep rating as >0 after taking the CBD of claimed invention.

Overall the average rating for sleep improvement was positive; on average participants felt their sleep improved by a factor of 3 indicating the on average the CBD of claimed invention improved quality of sleep across 180 participants * Overall average daily intake sitting at 27mg for those who noted a positive rate of change in their sleep with the range of intake between 10mg -80mg * Refer to Table 6 and Table 7 below for overview of statistical analysis Table 6 Overview of Totals and averages ii ue Total number of participants 180 Total of participants who noted CBD of claimed invention as 'Effective' (rating >0) 76% Average improvement rating +3 Table 7 'N. participants vs sleep rating Sleep rating % rate prior to taking CBD of claimed invention % rate after to taking CBD of claimed invention 1 3% 1% 2 8% 2% 3 13% 3% 4 17% 2% 18% 3% 6 17% 7% 7 9% 9% 8 9% 29% 9 3% 29% 2% 14%

Table 8 summary of sleep rating percentages

Sleep rating Prior to taking CBD of After taking CBD of Claimed invention Claimed invention <= 5 out of 10 59% 12% >/=6 out of 10 41% 88% As can be seen form the results of this study, majority of the participants had a significant improvement in their quality of sleep.

Further, the solubility of CBD powder (used in the cannabidiol oil of the claimed invention) in DMSO and corn oil was assessed by electron microscopy since the recommended approach based on ultrafiltration is not possible due to chemical sensitivity of filters to these solvents. Surprisingly, regardless of the concentration tested, undissolved particles in CBD were not detected in both DMSO and corn oil. This means that particulate size of the CBD powder used in the cannabidiol oil of the claimed invention ensures that the powder dissolves fully in the medium-chain triglyceride.

In the specification the terms "comprise, comprises, comprised and comprising" or any variation thereof and the terms "include, includes, included and including" or any variation thereof are considered to be totally interchangeable and they should all be afforded the widest possible interpretation and vice versa.

The invention is not limited to the embodiments hereinbefore described but may be varied in both construction and detail.

Claims

Claims 1. A cannabidiol oil comprising cannabidiol powder and a medium-chain triglyceride, wherein the cannabidiol powder only contains the (-)-CBD enantiomer and has a minimum cannabidiol content of 90%.
2. The cannabidiol oil according to Claim 1, wherein the cannabidiol powder is free from terpenes.
3. A cannabidiol oil comprising cannabidiol powder and a medium-chain triglyceride, wherein the cannabidiol powder only contains the (-)-CBD enantiomer, has a minimum cannabidiol content of at least 90% and is free of terpenes.
4. The cannabidiol oil according to any one of Claims 1 to 3 having a minimum cannabidiol content of between about 95% and 99%.
5. The cannabidiol oil according to any one of the preceding claims, wherein the cannabidiol is administered in a daily dose of up to about 150mg.
6. The cannabidiol oil according to Claim 5, wherein the cannabidiol is administered in a daily dose of up to about 100mg.
7. The cannabidiol oil according to Claim 5 or Claim 6, wherein the cannabidiol is administered in a daily dose of up to about 60mg.
8. The cannabidiol oil according to any one of Claims 5 to 7, wherein the cannabidiol is administered in a daily dose of up to about 20mg.
9. The cannabidiol oil according to any one of Claims 5 to 8, wherein the cannabidiol is administered in a daily dose of up to about 10mg.
10. The cannabidiol oil according to any preceding claims, wherein the cannabidiol powder has a Dso (particle size distribution) between about 10pm to about 100pm.
11. The cannabidiol oil according to any of the preceding claims, wherein the cannabidiol powder is sourced from plants selected from hemp (Cannabis sativa), Cannabis indica and Cannabis ruderalis.
12. The cannabidiol oil according to any one of the preceding claims, wherein the cannabidiol powder is a synthetic cannabidiol powder.
13. The cannabidiol oil according to Claim 12, wherein synthetic cannabidiol powder is sourced from a fruit of a citrus tree, a cannabis plant, and hybrids thereof.
14. The cannabidiol oil according to Claim 13, wherein the citrus tree is selected from an orange tree, a lemon tree, a lime tree, a mandarin tree, a kumquat tree, or a blood orange tree.
15.The cannabidiol oil according to any one of the preceding claims, wherein the medium-chain triglyceride is selected from coconut oil, palm kernel oil, whole milk, and dairy butter.
16.The cannabidiol oil according to Claim 15, wherein the medium-chain triglyceride is coconut oil.
17.The cannabidiol oil according to any one of the preceding claims, further comprising a flavouring additive.
18. The cannabidiol oil according to any one of the preceding claims, further comprising an acceptable food additive.
19. A cannabidiol oil according to Claim 1 or Claim 3 for use in treating a sleep disorder.
20. The cannabidiol oil of Claim 1 or Claim 3 for the use according to claim 19, wherein the sleep disorder is selected from insomnia, sleep apnoea, narcolepsy, restless leg syndrome, parasomnias, REM sleep behaviour disorder, non-24-Hour Sleep Wake Disorder, excessive sleepiness, shift work disorder, jet lag syndrome, delayed sleep phase, advanced sleep phase, sleep terrors, sleepwalking, and periodic limb movement disorder.
21. The cannabidiol oil of Claim 1 of Claim 3 for the use according to Claim 20, wherein the sleep disorder is insomnia.
22. The cannabidiol oil of Claim 1 or Claim 3 for the use according to Claim 19, wherein the cannabidiol is administered in a daily dose of about 10mg to about 150mg.
23. The cannabidiol oil of Claim 1 or Claim 3 for use in the treatment of an autoimmune disease.
24. The cannabidiol oil of Claim 1 or Claim 3 for the use according to claim 23, wherein the autoimmune disease is selected from osteoarthritis, rheumatoid arthritis, fibromyalgia, gout, childhood arthritis, psoriatic arthritis, inflammatory bowel disease (Crohn's Disease, Ulcerative Colitis), multiple sclerosis, Guillain-Barre Syndrome, Type 1 Diabetes mellitus, psoriasis, chronic inflammatory demyelinating polyneuropathy, Grave's Disease, Hashimoto's thyroiditis, myasthenia gravis, vasculitis, and Systemic Lupus Erythematosus (lupus).
25. A method for preparing and packaging the cannabidiol oil of Claim 1 or Claim 3, the method comprising the step of: (a) preparing a premix of medium-chain triglyceride (MCT) oil and a pure or substantially pure cannabidiol powder, (b) blending and heating the premix to obtain the cannabidiol oil, (c) packaging the cannabidiol oil in a packaging bottle treated with an inert gas, and (d) purging oxygen from the packaging bottle during step (c).