WO2023130161A1 - Compositions and methods for treating non-neurological disorders with combination products comprising a cannabinoid mixture rich in cannabidiolic acid (cbda) along with an additional active agent - Google Patents

Compositions and methods for treating non-neurological disorders with combination products comprising a cannabinoid mixture rich in cannabidiolic acid (cbda) along with an additional active agent Download PDF

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Publication number
WO2023130161A1
WO2023130161A1 PCT/AU2023/050008 AU2023050008W WO2023130161A1 WO 2023130161 A1 WO2023130161 A1 WO 2023130161A1 AU 2023050008 W AU2023050008 W AU 2023050008W WO 2023130161 A1 WO2023130161 A1 WO 2023130161A1
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composition
oil
cbda
cbd
group
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PCT/AU2023/050008
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French (fr)
Inventor
Patrick Steve CALABRIA
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Dolce Cann Global Pty Ltd
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Priority claimed from AU2022900042A external-priority patent/AU2022900042A0/en
Application filed by Dolce Cann Global Pty Ltd filed Critical Dolce Cann Global Pty Ltd
Publication of WO2023130161A1 publication Critical patent/WO2023130161A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

Definitions

  • the present invention relates to compositions comprising cannabinoids together with an additional active ingredient.
  • the present invention also relates to pharmaceutical compositions, dosage forms and methods of treating non-neurological disorders by administering the composition to a patient in need thereof.
  • Inflammation refers to the process whereby the body’s innate immune system is triggered following an inflammatory challenge such as those posed by injury, infection, exposure to a toxin, disease, or aging. Inflammation is implicated in contributing to a variety of diseases and illnesses including: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non-inflammatory); disorders affecting the pulmonary system (such as neumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such aass anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such aass bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteo
  • the innate immune response plays a significant role in both physiological and pathological conditions.
  • a number of diseases trigger a cascade of events broadly defined as inflammation.
  • T lymphocyte infiltration, and overproduction of inflammatory cytokines have been demonstrated in association with alteration in both animal and human tissues.
  • Inflammatory cytokines/markers or proinflammatory cytokines/markers are types of signaling molecules that are secreted from immune cells like helper T cells and macrophages and certain other cell types that promote the process of inflammation and general inflammatory processes.
  • IL-1 interleukin-1
  • IL-12 IL-12
  • IL-18 tumor necrosis factor alpha
  • IFN ⁇ interferon gamma
  • GM-CSF granulocyte-macrophage colony stimulating factor
  • Non-neurological disorders include: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non-inflammatory); disorders affecting the pulmonary system (such as pneumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such as anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such as bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteoporosis, paget's disease of the bone and rickets); non neurological cancers (such as breast cancer, skin cancers, prostate cancer, bladder cancer and liver cancer); blood borne disorders (such as common bloodborne diseases (including hepatio), and others.
  • non neurological cancers such
  • Cannabis sativa L. has a tradition of medical use. Medicinal cannabis has attracted significant interest due to its anti-inflammatory, anti-oxidative and anti-necrotic protective effects, as well as displaying a favourable safety and tolerability profile in humans, making it a promising candidate in many therapeutic avenues.
  • clinical use has been restricted because of untoward effects on the central nervous system and the possibility of abuse and addiction.
  • the plant exudes a resin containing a mix of cannabinoids with two principal components, ⁇ 9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
  • THC ⁇ 9-tetrahydrocannabinol
  • CBD cannabidiol
  • CBD cannabinoids
  • CB 1 receptors are mainly found in the terminals of central and peripheral neurons, and CB 2 receptors primarily in immune cells.
  • CBD at low concentrations, has weak CB 1 and CB 2 antagonistic effect.
  • CBD as an allosteric modulator of CB 1 can explain its therapeutic role in the treatment of central and peripheral nervous system disorders.
  • CBD has also shown to inhibit neutrophil chemotaxis and proliferation. It may also induce arachidonic acid release and reduce prostaglandin E2 (PGE2) and nitric oxide (NO) production.
  • PGE2 prostaglandin E2
  • NO nitric oxide
  • the anti-inflammatory, immunosuppressive effects are possibly mediated by activation of adenosine receptors, A 1A and A 2A and strychnine-sensitive ⁇ 1 and ⁇ 1 ⁇ glycine receptors and the inhibition of the equilibrative nucleoside transporter.
  • the activity of CBD may elicit different physiological effects from the same target.
  • the same glycine receptor is implicated in both anti-inflammation and suppression of neuropathic pain.
  • effects on serotonin 5HT1A receptors may generate anxiolytic, panicolytic and antidepressant effects, research has showed an in-depth review of the molecular pharmacology of CBD.
  • CBD cannabidiol
  • P450 enzymes predominantly by the CYP3A (2/4) and CYP2C (8/9/19) families of isozymes.
  • CBD cannabinoid
  • CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect cannabidiol-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect cannabidiol-induced anti-inflammatory processes.
  • Cannabidiol has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body. Allosteric regulation of a receptor is achieved through the modulation of the activity of a receptor on a functionally distinct site from the agonist or antagonist binding site.
  • GPCR G-Protein Coupled Receptor
  • Epidiolex ® is a plant-derived, pharmaceutical grade cannabidiol (CBD) medication which attained FDA approval for use in the United States in 2018. Epidiolex ® contains 100 mg of cannabidiol per milliliter (mL) of solutions and is taken orally twice daily.
  • the invention broadly resides in a composition comprising the following cannabinoids: about 50 w/w% of CBDA; and wherein all other cannabinoids come to about 15 w/w%.
  • the composition comprises the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBN1-3%; CBGA 1-10%; THC ⁇ 1%; and an additional active ingredient.
  • the composition comprises the following cannabinoids: w/w% CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 1-3% CBGA 5%; THC ⁇ 0.3%; and an additional active ingredient.
  • the composition comprises the following cannabinoids: w/w% CBDA 49%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN3% CBGA 5%; THC ⁇ 0.3%; and an additional active ingredient.
  • the composition comprises the following cannabinoids: w/w% CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBN 2% CBGA 4%; THC ⁇ 0.2%; and an additional active ingredient.
  • the composition comprises the following cannabinoids: w/w% CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBGA 4%; CBN 1%; THC ⁇ 0.2%; and an additional active ingredient.
  • the composition comprises cannabinoids in amounts selected from the group consisting of any one of the above-mentioned embodiments.
  • the invention is a pharmaceutical composition comprising the composition of the first aspect of the invention together with a pharmaceutically acceptable carrier.
  • the invention is a dosage form comprising the composition of the first aspect of the invention.
  • the invention is a method of treating a disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention.
  • the invention is the use of the composition of the invention in the manufacture of a medicament for the treatment of a disorder.
  • the invention is a process of extracting the composition of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with oil; 3) Mixing the grind and oil for a sufficient time period to form a mixture; 4) Pressing the mixture to reclaim the oil; 5) Centrifuging the oil to further refine the oil; and 6) Collecting the oil extract in a suitable container / steel vessel.
  • the invention is a process of extracting the composition of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with an alcohol; 3) Mixing the grind and alcohol for a sufficient time period to form a mixture; 4) Sonicating the mixture; 5) Centrifuging the mixture; and 6) Collecting the alcohol extract in a suitable container / steel vessel.
  • the invention is the product produced from the process of the invention
  • the invention is a kit comprising the dosage form of the invention together with instructions for its use.
  • the invention includes a composition, method and process as described by the examples following.
  • Further features of the present invention are more fully described in the following description of several non-limiting embodiments thereof. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad summary, disclosure or description of the invention as set out above. Brief Description of the Drawings [0034] Below is a brief description of each of the figures and drawings. [0035] Figure 1 is a UPLC mass spectrometry chromatogram of the cannabinoid standard mixture (10 ppm each) in; a) positive; and b) negative ionization mode.
  • Figure 2 is an in-source fragmentation of CBD and CBG from the reference solution.
  • Figure 3 shows mass spectrometry chromatograms for DOLCE164.
  • Figure 4 shows quad mass spectrometry chromatograms of CBD variants of DOLCE164 to identify CBDB and CBDP.
  • Figure 5 represents the normalization of inflammation-induced iNOS expression by DOLCE164. The figure shows that NTI164 normalises inflammation-induced iNOS expression.
  • Figure 6 demonstrates that DOLCE164 normalises viral loading related inflammation in cells as measured by TNF-gamma suppression.
  • Figure 7 demonstrates that DOLCE164 suppresses IL-beta in viral loaded cells.
  • a range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range which lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range.
  • a person skilled in the field will understand that a 10% variation in upper or lower limits of a range can be totally appropriate and is encompassed by the invention. More particularly, the variation in upper or lower limits of a range will be 5% or as is commonly recognised in the art, whichever is greater.
  • “Therapeutically effective amount” as used herein with respect to methods of treatment and in particular drug dosage shall mean that dosage that provides the specific pharmacological response for which the drug is administered in a significant number of subjects in need of such treatment. It is emphasized that “therapeutically effective amount,” administered to a particular subject in a particular instance will not always be effective in treating the diseases described herein, even though such dosage is deemed a “therapeutically effective amount” by those skilled in the art. It is to be further understood that drug dosages are, in particular instances, measured as oral dosages, or with reference to drug levels as measured in blood or measured as inter-intra epidermal delivery.
  • Amounts effective for such a use will depend on: the desired therapeutic effect; the potency of the biologically active material; the desired duration of treatment; the stage and severity of the disease being treated; the weight and general state of health of the patient; and the judgment of the prescribing physician. Treatment dosages need to be titrated to optimize safety and efficacy.
  • the appropriate dosage levels for treatment will thus vary depending, in part, upon the indication for which the active agent is being used, the route of administration, and the size (body weight, body surface or organ size) and condition (the age and general health) of the patient. Accordingly, the clinician may titre the dosage and modify the route of administration to obtain the optimal therapeutic effect.
  • a typical dosage may range from about 0.1 ⁇ g/kg to up to about 100 mg/kg or more, depending on the factors mentioned above. In other embodiments, the dosage may range from 0.1 ⁇ g/kg up to about 100 mg/kg; or 1 ⁇ g/kg up to about 100 mg/kg; or 5 ⁇ g/kg up to about 100 mg/kg.
  • the frequency of dosing will depend upon the pharmacokinetic parameters of the active agent and the formulation used. Typically, a clinician will administer the composition until a dosage is reached that achieves the desired effect.
  • the composition may therefore be administered as a single dose, or as two or more doses (which may or may not contain the same amount of the desired molecule) over time, or as a continuous infusion via an implantation device or catheter.
  • pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, microemulsions, gel suspensions and topical formulations and the like that are physiologically compatible.
  • the term “subject” generally includes mammals such as: humans; farm animals such as sheep, goats, pigs, cows, horses, llamas; companion animals such as dogs and cats; primates; birds, such as chickens, geese and ducks; fish; and reptiles.
  • the subject is preferably human.
  • “Non neurological disorders” are disorders that do not affect the brain as well as the nerves found throughout the human body and the spinal cord.
  • Other definitions for selected terms used herein may be found within the detailed description of the invention and apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the invention belongs.
  • the present invention provides a composition comprising the following cannabinoids: about 50 w/w% of CBDA; and wherein all other cannabinoids come to about 15 w/w%.
  • the composition comprises an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 2% CBD; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 5% CBG; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 2% CBDP; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 2% CBDB; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 5% CBGA; and an additional active ingredient.
  • the invention provides a composition comprising cannabinoids, wherein the ratio of CBDA to all other cannabinoids is between 4:1 and 2:1.
  • the invention provides a composition comprising cannabinoids, wherein the ratio of CBDA to all other cannabinoids is about 3:1.
  • the invention provides a composition comprising cannabinoids, wherein the ratio of CBDA to all other cannabinoids is about 3.21:1.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBN 1-3%; CBGA 1-10%; THC ⁇ 1%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 45-55%; CBD 1-3%; CBG 3-7%; CBDP 1-3%; CBDB 1-3%; CBGA 3-7%; CBN 1-3%; THC ⁇ 0.5%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 3% CBGA 5%; THC ⁇ 0.3%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 49%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 2% CBGA 5%; THC ⁇ 0.3%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 48.78%; CBD 1.89%; CBG 4.88%; CBDP 1.68%; CBDB 1.76%; CBN 1% CBGA 4.76%; THC ⁇ 0.18%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBN 2% CBGA 4%; THC ⁇ 0.2%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 45.28%; CBD 1.39%; CBG 3.88%; CBDP 1.18%; CBDB 1.56%; CBN 1%; CBGA 3.76%; THC ⁇ 0.18%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 62.78%; CBD 5.80%; CBG 0.44%; CBGA 1.26%; CBN 1.98%; THC ⁇ 0.70%; and an additional active ingredient.
  • the invention provides a composition comprising the following cannabinoids: w/w % CBDA 60.29%; CBD 5.34%; CBG 0.39%; CBGA 1.14%; CBN 0.85%; THC ⁇ 0.65%; and an additional active ingredient.
  • the invention provides a composition wherein the cannabinoids are present in amounts selected from the group consisting of: Composition 1 comprising: w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 3%; CBGA 5%; THC ⁇ 0.3%; and an additional active ingredient.
  • the invention provides a composition, wherein the quantity of the cannabinoids is determined by a method selected from the group consisting of: high performance chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (H 1 NMR); and mass spectrometry.
  • HPLC high performance chromatography
  • H 1 NMR proton nuclear magnetic resonance spectroscopy
  • mass spectrometry mass spectrometry.
  • the invention provides a composition derived from cannabis plant material.
  • the invention provides a composition wherein the said listed cannabinoids are synthetic.
  • the invention provides a composition wherein the said listed cannabinoids are a mixture of plant derived and synthetic cannabinoids.
  • the invention provides a composition further comprising an oil selected from the group consisting of: a synthetic oil; plant based oil; mineral oil; canola oil; and olive oil.
  • the composition comprises less than 5% w/w terpenes.
  • the composition comprises between 55% and 5%w/w organic plant material. In a further preferred embodiment, the composition comprises less than 10% w/w organic plant material.
  • the composition comprises less than 5% w/w organic plant material. In a further preferred embodiment, the composition comprises less than 2% w/w organic plant material. [0086] In a further preferred embodiment, the composition comprises less than 2% w/w of plant phenols. [0087] In a further preferred embodiment, the composition comprises components selected from the group consisting of: flavonoids, proteins, sterols and esters. [0088] In a further preferred embodiment, the composition is substantially pure. Preferably, the purity is determined by a method selected from the group consisting of: high performance chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (H 1 NMR); and mass spectrometry.
  • HPLC high performance chromatography
  • H 1 NMR proton nuclear magnetic resonance spectroscopy
  • the purity is selected from the group consisting of: greater than 75% purity; greater than 80% purity; greater than 85% purity; greater than 90% purity; greater than 95% purity; greater than 96% purity; greater than 97% purity; greater than 98% purity; greater than 99% purity; greater than 99.5% purity; greater than 99.6% purity; greater than 99.7% purity; greater than 99.8% purity; greater than 99.9% purity; greater than 99.95% purity; greater than 99.96% purity; greater than 99.97% purity; greater than 99.98% purity and greater than 99.99% purity.
  • the composition comprises less than 0.1 wt% organic impurities as measured a method selected from the group consisting of: high performance chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (H 1 NMR); and mass spectrometry.
  • HPLC high performance chromatography
  • H 1 NMR proton nuclear magnetic resonance spectroscopy
  • mass spectrometry mass spectrometry.
  • the composition is substantially free of atmospheric oxygen.
  • the composition is sterile.
  • the invention provides a composition wherein the cannabinoid component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml.
  • the invention provides a composition wherein the CBDA component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml.
  • the composition is a liquid.
  • the composition is an oil.
  • the composition demonstrates no cannabinoid degradation or decarboxylation when measured at a time point selected from the group consisting of: at 1 day; at 2 days; at 7 days; at 14 days; at 28 days; at 5 weeks; at 6 weeks; and at 32 weeks.
  • the composition demonstrates cannabinoid stability when measured at a time point selected from the group consisting of: at 1 day; at 2 days; at 7 days; at 14 days; at 28 days; at 5 weeks; at 6 weeks; and at 32 weeks.
  • the composition demonstrates no mutagenicity, carcinogenicity or genotoxicity when delivered at a concentration that delivers 120mg/ml of CBDA.
  • the composition is adapted to suppress the activity of any one of the following biomarkers: COX-2; iNOS; TNF-alpha; IL-2; IL-12 and GS-MCF.
  • the composition is adapted to suppress inflammation. More preferably, the composition is adapted for the treatment of a non-neurological disorder.
  • the invention provides a composition having a UPLC mass chromatogram corresponding to Figure 3 utilising the conditions described in Example 1.
  • the composition comprises an additional active ingredient.
  • the additional active ingredient is selected from the group consisting of: a polypeptide; an antibody; and a NSAID.
  • the NSAID is selected from the group consisting of: monoclonal anti-body therapies, biologics, interferon gamma therapy, interferon – beta therapies, aspirin, ibuprofen, naproxen, diclofenac, celecoxib, ketorolac, meloxicam, esomeprazole, naproxen, diclofenac, misoprostol, nabumetone, indomethacin, mefenamic acid, etodolac, piroxicam, ketoprofen, diflunisal, oxaprozin, flurbiprofen, sulindac, tolmetin, prednisolone and fenoprofen.
  • the NSAID is selected from the group consisting of: diclofenac, prednisolone and celebrex.
  • the ratio of cannabinoid component and the additional active ingredient is selected from the group consisting of: 1 unit w/w of cannabinoid : 1 unit w/w/ of the additional active ingredient; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1.
  • the ratio of the additional active ingredient and cannabinoid is selected from the group consisting of: 1 unit w/w of the additional active ingredient and 1 unit w/w/ of the cannabinoid; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1.
  • the ratio of CBDA and the additional active ingredient is selected from the group consisting of: 1 unit w/w of CBDA : 1 unit w/w/ of the additional active ingredient; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1.
  • the ratio of the additional active ingredient and CBDA is selected from the group consisting of: 1 unit w/w of the additional active ingredient and 1 unit w/w/ of the CBDA; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1.
  • the composition demonstrates synergistic biological activity.
  • the composition demonstrates a level of biological activity that is greater than the sum of: (1) the biological activity of the cannabinoid component when delivered in absence of the additional active ingredient; and (2) the biological activity of the additional active ingredient when delivered in absence of the cannabinoid component.
  • the biological activity is selected from the group consisting of: suppressing inflammation; suppressing inflammation; treating a non- neurological disorder; suppressing the activity of COX-2; suppressing the activity of iNOS; suppressing the activity of TNF-alpha; suppressing the activity of IL-2; suppressing the activity of IL-12 and suppressing the activity of GS-MCF.
  • the composition is selected from the group consisting of: a therapeutic composition; a pharmaceutical composition; a cosmetic composition; and a veterinary composition.
  • the composition of the invention is not a composition selected from the group consisting of: [00115] (a) Sample S06 disclosed in WO2021188983; [00116] (b) Sample S06 disclosed in WO2021188983 with the following CBD profile: CBDA (41.9%), CBD (1.9%), CBGA (1.3%), THC (0.2%), CBG (0.2%) (weight % in extract); [00117] (c) Sample Liffer disclosed in WO2021188983; [00118] (d) Sample Liffer disclosed in WO2021188983 with the following CBD profile: CBDA (57.9%), CBGA (1.6%), THC (0.7%), CBD (5.8%), CBG (0.3%) (weight % in extract); [00119] (e) CannBio1 disclosed in WO2020093101; [00120] (a) Sample S06 disclosed in WO2021188983; [00116
  • compositions [00137] The present invention also provides a pharmaceutical composition comprising the composition of the invention together with a pharmaceutically acceptable carrier.
  • Therapeutic compositions are within the scope of the present invention. Preferably the compositions are combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition (which may be for human or animal use). Suitable carriers and diluents include isotonic saline solutions, for example phosphate- buffered saline.
  • pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like.
  • the use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated.
  • Supplementary active ingredients can also be incorporated into the compositions. See, e.g., Remington's Pharmaceutical Sciences, 19th Ed. (1995, Mack Publishing Co., Easton, Pa.) which is herein incorporated by reference.
  • the pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, colour, isotonicity, odour, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition.
  • Suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulphite or sodium hydrogen-sulphite Vitamin E, Vitamin E phosphate – lipid soluble vitamins, nano emulsions); buffers (such as borate, bicarbonate, tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta- cyclodextrin), fillers; monosaccharides, disaccharides; and other carbohydrates (such as glucose, mannose, or dextrins); proteins (such as serum albumin, gelatin or immunoglob
  • the optimal pharmaceutical composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format, and desired dosage. Such compositions may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the composition of the invention.
  • the preferred form of the pharmaceutical composition depends on the intended mode of administration and therapeutic application.
  • the primary vehicle or carrier in a pharmaceutical composition is aqueous in nature.
  • a suitable vehicle or carrier may be water for injection, physiological saline solution, possibly supplemented with other materials.
  • Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles.
  • compositions comprise tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, which may further include sorbitol or a suitable substitute therefor.
  • pharmaceutical compositions may be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents in the form an aqueous solution.
  • the formulation components are present in concentrations that are acceptable to the site of administration.
  • buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8.
  • Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations of the invention in sustained- or controlled-delivery formulations.
  • sustained-sustained-release preparations include semipermeable polymer matrices in the form of shaped articles, for example, films, or microcapsules.
  • Sustained release matrices may include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and gamma ethyl-L-glutamate, ethylene vinyl acetate or poly-D(-)-3-hydroxybutyric acid.
  • Sustained-release compositions may also include liposomes, which can be prepared by any of several methods known in the art.
  • the pharmaceutical composition to be used for in vivo administration typically must be sterile. This may be accomplished by filtration through sterile filtration membranes.
  • the compositions generally are placed into a container having a sterile access port. Once the pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution.
  • the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36 hours; and greater than 48 hours.
  • the composition is stable for periods selected from the group consisting of: 6 months, 1 year and 2 years.
  • the composition is stable at temperatures selected from the group consisting of: - 4°C, 4°C, 18°C and 25°C.
  • Dosage Form [00146] Dosage forms are within the scope of the invention. In a preferred embodiment, the invention provides a dosage form comprising the composition as described in the first aspect of this invention. [00147] Preferably, the cannabinoid component of the composition of the dosage form is selected from the group consisting of: between 1mg and 1000mg; between 1mg and 500mg; between 1 and 100mg; less than 400mg; less than 300mg; less than 200mg and less than 100mg.
  • the cannabinoid component of the composition is selected from the group consisting of: 600mg; 400mg; 300mg; 200mg; 100mg; 50mg; 10mg; 5mg; 2mg; 1mg.
  • the CBDA component of the composition of the dosage form is selected from the group consisting of: between 1mg and 1000mg; between 1mg and 500mg; between 1 and 100mg; less than 400mg; less than 300mg; less than 200mg and less than 100mg.
  • the CBDA component of the composition is selected from the group consisting of: 600mg; 400mg; 300mg; 200mg; 100mg; 50mg; 10mg; 5mg; 2mg; 1mg.
  • the dosage form is form selected from the group consisting of: a solution, tablet, capsule, wafer, dry power sachet and vial / freeze dried.
  • the dosage form is stored in a sealed and sterile container.
  • the dosage form is administered at an amount to at least partially treat the disorder.
  • the therapeutically effective amount is an amount of cannabinoid selected from the group consisting of: between 1 to 100mg/kg/day; between 2 and 50mg/kg/day; between 5 and 40mg/kg/day; between 10 and 30mg/kg/day; between 20 and 25mg/kg/day; and 20mg/kg/day.
  • the therapeutically effective amount is an amount of cannabinoid vis selected from the group consisting of: 10mg/day; 15mg/day; 40mg/day; 400mg/day; 600mg/day; 800mg/day; 1280mg/day; 1500mg/day.
  • therapeutically effective amount is an amount of CBDA selected from the group consisting of: between 1 to 100mg/kg/day; between 2 and 50mg/kg/day; between 5 and 40mg/kg/day; between 10 and 30mg/kg/day; between 20 and 25mg/kg/day; and 20mg/kg/day.
  • the therapeutically effective amount is an amount of CBDA vis selected from the group consisting of: 10mg/day; 15mg/day; 40mg/day; 400mg/day; 600mg/day; 800mg/day; 1280mg/day; 1500mg/day.
  • Tmax occurs between 1 and 4 hours.
  • T1/2 occurs between 1.1 and 2.4 hours.
  • the therapeutically effective amount is administered to the subject to treat the disorder.
  • the therapeutically effective amount is administered to the subject utilising a dosing regimen selected from the group consisting of: twice hourly; hourly; once every six hours; once every 8 hours; once every 12 hours; once daily; twice weekly; once weekly; once every 2 weeks; once every 6 weeks; once a month; every 2 months; every 3 months; once every 6 months; and once yearly.
  • a dosing regimen selected from the group consisting of: twice hourly; hourly; once every six hours; once every 8 hours; once every 12 hours; once daily; twice weekly; once weekly; once weekly; once every 2 weeks; once every 6 weeks; once a month; every 2 months; every 3 months; once every 6 months; and once yearly.
  • the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: orally, intravenously, intramuscularly, intrathecally, subcutaneously, sublingually, buccally, rectually, vaginally, topically, parentally, mucosally, by the ocular route, by the otic route, nasally, by inhalation, cutaneously, transdermally, and systemically.
  • the disorder is caused by inflammation.
  • the disorder is a non-neurological disorder.
  • the non- neurological disorder is selected from the group consisting of: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non-inflammatory); disorders affecting the pulmonary system (such as neumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such as anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such as bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteoporosis, paget's disease of the bone and rickets); non neurological cancers (such as breast cancer, skin cancers, prostate cancer, bladder cancer and liver cancer); blood borne disorders (such as common bloodborne diseases (including hepatitis B
  • the treatment reduces inflammation.
  • the treatment suppresses the activity of any one of the following biomarkers: COX-2; iNOS; TNF-alpha; IL-2; IL-12 and GS-MCF.
  • a subject that can be treated with the invention will include humans as well as other mammals and animals.
  • the method comprises administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention together with an additional active ingredient.
  • the additional active ingredient is administered using a dosing regimen selected from the group consisting of: at the same time as administering the dosing form of the invention; before administering the dosing form of the invention; after administering the dosing form of the invention; concurrently with administering the dosing form of the invention; sequentially before administering the dosing form of the invention; and sequentially after administering the dosing form of the invention.
  • a dosing regimen selected from the group consisting of: at the same time as administering the dosing form of the invention; before administering the dosing form of the invention; after administering the dosing form of the invention; concurrently with administering the dosing form of the invention; sequentially before administering the dosing form of the invention; and sequentially after administering the dosing form of the invention.
  • the effect of the administered therapeutic composition can be monitored by standard diagnostic procedures.
  • Use of a composition in the manufacture of a medicament [00164] Uses are within the scope of this invention.
  • the invention also provides
  • the invention is the use of a composition comprising the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBGA 1-10%; CBN 1-3% and THC ⁇ 1%; in the manufacture of a medicament for the treatment of a non-neurological disorder and an additional active ingredient.
  • the cannabinoids of the composition are present in amounts selected from the group consisting of: [00167] Composition 1 comprising w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBGA 5%; CBN 3% and THC ⁇ 0.3%; and Composition 2 comprising w/w % CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBGA 4%; CBN 2% and [00168] THC ⁇ 0.2%; in the manufacture of a medicament for the treatment of a non-neurological disorder and an additional active ingredient.
  • the composition further comprises an oil selected from the group consisting of: a synthetic oil; plant based oil; mineral oil; canola oil; and olive oil.
  • the composition comprises less than 5% w/w terpenes.
  • the composition comprises less than 2% w/w organic plant material.
  • the composition comprises less than 2% w/w of plant phenols.
  • the cannabinoid component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml.
  • the CBDA component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml.
  • the composition has a UPLC mass chromatogram corresponding to Figure 3 utilising the conditions described in Example 1.
  • the invention also provides a process of extracting the composition of the first aspect of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with oil; 3) Mixing the grind and oil for a sufficient time period to form a mixture; 4) Pressing the mixture to reclaim the oil; 5) Centrifuging the oil to further refine the oil; and 6) Collecting the oil extract in a suitable container.
  • the cannabis plant material is derived from Cannabis sativa L.
  • the sufficient grind size is selected from the group consisting of: between 0.1mm and 3mm; between 1mm and 2mm; and between 0.5mm and 2.5mm.
  • the sufficient time period is selected from the group consisting of: between 30 minutes and 2 hours; between 45 minute and 1.5 hours; 1 hr.
  • the ratio of grind material to oil at step (2) is selected from the group consisting of: 400mg of grind: 1ml of oil; 300mg of grind : 1ml of oil; 200mg of grind : 1ml of oil; 100mg of grind : 1ml of oil; and 333mg of grind : 1ml of oil.
  • the oil is olive oil.
  • the invention also provides an alternative process of extracting the composition of the first aspect of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with an alcohol; 3) Mixing the grind and alcohol for a sufficient time period to form a mixture; 4) Sonicating the mixture; 5) Centrifuging the mixture; and 6) Collecting the alcohol extract in a suitable container.
  • the alcohol is ethanol.
  • the alcohol is selected from the group consisting of: ethanol, isopropyl alcohol, methyl alcohol, benzyl alcohol, 1,4-butanediol, 1,2,4-butanetriol, butanol, 1-butanol, 2-butanol, tert-butyl alcohol.
  • the sufficient grind size is selected from the group consisting of: between 0.1mm and 3mm; between 1mm and 2mm; and between 0.5mm and 2.5mm.
  • the sufficient time period is selected from the group consisting of: between 30 minutes and 2 hours; between 45 minute and 1.5 hours; 1 hr.
  • the ratio of grind material to alcohol at step (2) is selected from the group consisting of: 400mg of grind: 1ml of alcohol; 300mg of grind : 1ml of alcohol; 200mg of grind : 1ml of alcohol; 100mg of grind : 1ml of alcohol; 100mg of grind : 4ml of alcohol; 100mg of grind : 3ml of alcohol; 100mg of grind : 2ml of alcohol; and 333mg of grind : 1ml of alcohol.
  • Product of the Process [00187] The invention also provides a product produced from the process described above. Kit [00188] The invention also provides a kit comprising the dosage form of one aspect of the invention together with instructions for its use.
  • the invention provides a device, wherein the device comprises: (1) the composition as described in the first aspect of this invention; and (2) an applicator.
  • Method for stabilising [00190] Methods for stabilizing the composition are within the scope of the invention.
  • the said method protects the composition against degradation.
  • the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36 hours; greater than 48 hours.
  • glycerol, sorbitol, fructose, trehalose increase the surface tension and viscosity of the solution to prevent protein aggregation.
  • polymers e.g. polyethylene glycol, cellulose derivatives
  • stabilise the protein tertiary structure by increasing the viscosity of the solution to prevent protein aggregation and intra- and inter-molecular electrostatic interactions between amino acids in the protein.
  • Proteins e.g. human serum albumin
  • small amino acids with no net charge, such as alanine and glycine stabilise proteins through the formation of weak electrostatic interactions.
  • the medicaments of the present invention may include one or more pharmaceutically acceptable carriers.
  • pharmaceutically acceptable carriers may include one or more of the following examples: a.
  • surfactants and polymers including, however not limited to polyethylene glycol (PEG), polyvinylpyrrolidone , polyvinylalcohol, crospovidone, polyvinylpyrrolidone- polyvinylacrylate copolymer, cellulose derivatives, HPMC, hydroxypropyl cellulose, carboxymethylethyl cellulose, hydroxypropylmethyl cellulose phthalate, polyacrylates and polymethacrylates, urea, sugars, polyols, and their polymers, emulsifiers, sugar gum, starch, organic acids and their salts, vinyl pyrrolidone and vinyl acetate; and/or b.
  • PEG polyethylene glycol
  • polyvinylpyrrolidone polyvinylalcohol
  • crospovidone polyvinylpyrrolidone- polyvinylacrylate copolymer
  • cellulose derivatives HPMC, hydroxypropyl cellulose, carboxymethylethyl cellulose, hydroxypropy
  • binding agents such as various celluloses and cross-linked polyvinylpyrrolidone, microcrystalline cellulose; and/or (3) filling agents such as lactose monohydrate, lactose anhydrous, microcrystalline cellulose and various starches; and/or c. filling agents such as lactose monohydrate, lactose anhydrous, mannitol, microcrystalline cellulose and various starches; and/or d. lubricating agents such as agents that act on the increased ability of the dosage form to be ejected from the packaging cavity, and/or e.
  • sweeteners such as any natural or artificial sweetener including sucrose, xylitol, sodium saccharin, cyclamate, aspartame, and acesulfame K; and/or f. flavouring agents; and/or g. preservatives such as potassium sorbate, methylparaben, propylparaben, benzoic acid and its salts, other esters of parahydroxybenzoic acid such as butylparaben, alcohols such as ethyl or benzyl alcohol, phenolic chemicals such as phenol, or quarternary compounds such as benzalkonium chloride; and/or h. buffers; and/or i.
  • preservatives such as potassium sorbate, methylparaben, propylparaben, benzoic acid and its salts, other esters of parahydroxybenzoic acid such as butylparaben, alcohols such as ethyl or benzyl alcohol, phenolic chemicals such as phenol, or quarternary
  • diluents such as pharmaceutically acceptable inert fillers, such as microcrystalline cellulose, lactose, dibasic calcium phosphate, saccharides, and/or mixtures of any of the foregoing; and/or j. absorption enhancer such as glyceryl trinitrate; and/or k. other pharmaceutically acceptable excipients.
  • Medicaments of the invention suitable for use in animals and in particular in human beings typically must be sterile and stable under the conditions of manufacture and storage.
  • Combinations [00197] In another aspect, the composition of the first aspect of the invention is combined with a second composition.
  • the composition is combined with a second composition selected from the group consisting of: a composition derived from plant seeds; a plant seed extract; a composition derived from grape seeds; a grape seed extract; a proanthocyanidin; a composition derived from plant skin; wherein the plant is selected from the group consisting of: grapes; blueberries; raspberries; mulberries; and peanuts; a plant skin extract; a composition derived from grape skin; a grape skin extract; a phytoalexin; resveratrol.
  • the plant is selected from the group consisting of: grapes; blueberries; raspberries; mulberries; and peanuts.
  • the composition is combined with a senolytic or anti-aging molecule.
  • the molecule is selected from the group consisting of: resveratrol; nicotinamide mononucleotide; rapamycin; metaformin; quercetin; datatinib; quercetin with datatinib; fisetin; EGCG; NAD boosters; NAD +; sulforaphane; urolithin; mito- Q; honokiol; curcumin and analogs; berberine; n-acetyl-cystine; piperlongumine; resveratrol and pterotsilbine; spermidine; allicin; vitamin D3; vitamin K; tocotrienol (and with quercetin; HSP-90 inhibitors; yamanaka factors (Oct3/4; Sox2; Klf4; and/or c-Myc); rapa
  • the calorie restriction mimetic is selected from the group consisting of: resveratrol; metformin, oxaloacetate; rimonabant; lipoic acid; 2-deoxy-D- glucose; rapamycin; glucosamine; peroxisome proliferator-activated receptor gamma inhibitors, such as rosiglitazone and gugulipids; xxanadin (exenatide), a glucagon- like peptide-1 (GLP-1)modulator; adiponectin; acipimox; hydroxycitrate; dipeptidyl peptidase 4 (DPP-4) inhibitors; Iodoacetate; mannoheptulose (glycolytic inhibitor); modulators of neuropeptide Y (NPY); 4-phenylbutyrate; gymnemoside; spermidine.
  • resveratrol metformin, oxaloacetate
  • rimonabant lipoic acid
  • the invention also provides a composition, methods and processes as described by the foregoing examples.
  • the present invention will now be described with reference to the following non- limiting Examples. The description of the Examples is in no way limiting on the preceding paragraphs of this specification, however, is provided for exemplification of the methods and compositions of the invention. Examples [00203] It will be apparent to persons skilled in the milling and pharmaceutical arts that numerous enhancements and modifications can be made to the above described processes without departing from the basic inventive concepts. For example, in some applications the biologically active material may be pretreated and supplied to the process in the pretreated form. All such modifications and enhancements are considered to be within the scope of the present invention, the nature of which is to be determined from the foregoing description and the appended claims.
  • a EXAMPLE 1 – EXTRACTION AND PURIFICATION OF DOLCE164 A.1 STUDY AIM [00204] To extract and identify the most desirable components from the DOLCE164 plant strain using an inert oil - based extraction process.
  • the DOLCE164 plant is a full-spectrum medicinal cannabis plant (genus species Cannabis sativa) which the inventors subsequently identified to contain cannabidiolic acid (CBDA), cannabidiol (CBD), cannabigerolic acid (CBGA) and cannabidivarin (CBDV) but which has >0.03% tetrahydrocannabinol (THC).
  • CBDA cannabidiolic acid
  • CBD cannabidiol
  • CBDGA cannabigerolic acid
  • CBDV cannabidivarin
  • THC cannabidivarin
  • the DOLCE164 plant was cultivated, dried and packaged under an Office of Drug Control (ODC) license and permit as per Good Manufacturing Processes (GMP) and TGO 93 and 100 guidelines.
  • ODC Office of Drug Control
  • the grinder was cleaned with 70% EtOH and the grinding compartment was filled with dried plant material.
  • the material was ground on the finest of the three setting for 10 seconds (1-2 mm particle size).
  • the grounds was then mixed with 100ml of olive oil in an autoclaved Schott bottle at a ratio plant/oil of 333mg/mL. It was then placed on a stirrer at room temperature for 1 hour, stirred with magnetic flea (50rpm).
  • the oil plus plant mixture is then put into the Oz Design Brand 6 Litre Fruit, Wine and Cider Press to reclaim the oil component from the plant (the mash).
  • the reclaimed oil was then placed into 50mL falcon tubes and spun at 300g for 15 minutes at room temperature (Isolation 1).
  • the oil was then removed into a clean Schott bottle and keeping track of the volume reclaimed.
  • the recovery of the oil for Isolation 1 is approximately 40%. The mash is discarded following each isolation.
  • To the reclaimed oil we added a further 333mg/mL ground plant/oil (a further 100ml) material and repeated the 1 hour mix, and reclaimed and re-used oil, until a total of 999 ⁇ g/mL (3 x 100ml) of plant/oil mixture passed through (Isolation 2).
  • the recovery of the oil for Isolation 2 is approximately 50%.
  • For the final time we placed into falcon tubes and spin as discussed above (Isolation 3). The recovery of the oil at for Isolation 3 is approximately 50%.
  • the UPLC settings and conditions used were: Cortecs UPLC Shield RP 18, (0 A 1.6uM, 2.1 x 100 mm); Analytical flow rate: 0.7 ml/min; Mobile phase A: Water 0.1% TFA; Mobile phase B: Acetonitrile; Isocratic: 41:59 mobile phase A/mobile phase B; Temp: 35C; Detector: Acquity UPLC PDA; Injection volume: 0.7 uL for 1.0 mg/ml reference standard preparations, sample solutions scaled appropriately; Software: Empower 3CDS. Reference standard solutions were obtained from Novachem, Cerilliant Corporation (TX, USA). These were pre-dissolved solutions all previously shown to be suitable for the generation of calibration curve.
  • a mixture of 16 cannabinoids in methanol was prepared, containing 10 ppm each of cannabidivarin (CBDV), cannabidiol (CBD), cannabigerol (CBG), tetrahydrocannabivarin (THCV), cannabinol (CBN), ⁇ 9 -tetrahydrocannabinol ( ⁇ 9 -THC), ⁇ 8 -tetrahydrocannabinol ( ⁇ 8 - THC), cannabichromene (CBC), their respective acidic forms and cannabicyclol (CBL). All solvents used were LCMS grade, and standards were prepared by diluting with 90 % mobile phase B and 10 % deionized water.
  • Table 1 The parameters and conditions for UPLC and LCMS analysis A.3 RESULTS A.3.1 UPLC AND LCMS ANALYTICAL RESULTS
  • Figure 1 shows the separation of the cannabinoids in a mixed standard solution (that is a reference solution). Under the conditions of the experiment, neutral cannabinoids such as ⁇ 9 -THC, CBD and CBL ionize in positive mode, while their respective acidic forms ionize in negative mode. Although CBD and CBG coelute from the column, their molecular weights differ, and they can be identified by mass spectra.
  • Figure 2 shows a difference between the SID fragmentation patterns obtained for CBD and CBG (that is; as further reference solution).
  • Figure 3 presents the UPLC mass chromatogram for DOLCE164 extracted using the oil based method. These results found that the DOLCE164 extract (oil suspension) contained the following components presented in Table 2. Additional components will include flavonoids, proteins, phenols, sterols and esters. These are known components that make up 30-40 % of the full plant cannabis material.
  • Table 4 presents the accompanying exlution times for the UPLC mass chromatograpm for Figure 3 and area under the peaks for the CBD peaks identified.
  • Table 2 Components in DOLCE164 oil extracted (at two decimal places and rounded up beyond 0.5, and rounded down below 0.5)
  • Table 3 presents the DOLCE164 composition extracted using the ethanol extraction and the components quantified using the methods herein described.
  • Table 3 Components in DOLCE164 ethanol extracted (at two decimal places and rounded up beyond 0.5, and rounded down below 0.5)
  • Table 4 presents the accompanying elution times for the UPLC mass chromatograpm for Figure 3 (DOLCE164, oil extracted) and area under the peaks for the CBD peaks identified.
  • DOLCE164 oil and dried flower
  • Oil S samples were prepared as outlined above: For flower, a portion of homogenized plant material was added to acetonitrile or ethanol and sonicated for 20 minutes. The subsequent extract was filtered through a 0.22 ⁇ m syringe tip filter directly into a 2 mL sample vial for analysis. Concentrates were prepared similarly with isopropanol as the extraction solvent.
  • B.2.2 SAMPLING [0009] Samples of DOLCE164 were assayed on a weekly basis and CBDA was used as a main marker / stability indicator.
  • Linearity of primary cannabinoids (-) ⁇ 9 -THC and CBD were determined for 10 concentrations between 0.004 mg/mL and 1.000 mg/mL, prepared via serial dilution in methanol using appropriate standards as a representative demonstration of method linearity.
  • Table 5 outlines the cannabinoids used in the separation. [0012] Table 5: The cannabinoids used in the separation
  • SARS-CoV-2 infection activates innate and adaptive immune response, thus sustaining the resolution of COVID-19. While a rapid and well-coordinated immune response represents the first line of defence against viral infection, an excessive inflammatory innate response and dysregulated adaptive host immune defence may cause harmful tissue damage at both at the site of virus entry and at systemic level.
  • DOLCE164 Three different doses of DOLCE164 was assessed against its ability to regulate specific inflammation biomarkers relating to cytokine development and regulation: these include: iNOS activate, TNF – gamma and IL-Beta. iNOS expression is increased by viral loading.
  • the immortalized microglia cell line, BV2 was purchased from the American Tissue Culture Collection.
  • BV2 were cultured in RPMI media containing gentamycin and supplemented with 10% FBS for expansion and 5% fetal bovine serum (FBS) when plated for experiments. All cells were from between passage numbers 39 and 45. Cells were plated at 45,000 cells/mm2 and treated 24 hours after plating with phosphate buffered saline (PBS, as a control) or interleurkin-1B + interferon-y (IL-1B+IFNy, to induce inflammation). To test the effects of DOLCE164 to alter the inflammatory response, DOLCE164 was applied with one hour before inflammation (pre-treat) or one hour after (post-treat).
  • PBS phosphate buffered saline
  • IL-1B+IFNy interleurkin-1B + interferon-y
  • range determined from mass spec data 1.0 – 0.1ug CBDA.
  • Data for replicates within experiments were averaged and then data from at least three independent experiments was analysed using Graph Pad Prism or students-t-test.
  • C.3 RESULTS [0020] In viral induced inflammatory activated cells, DOLCE 164 normalizes expression towards control levels as showed by iNOS expression (see Figure 5), it also normalizes viral loading related inflammation in cells as measured by TNF-gamma suppression (see Figure 6) and suppresses IL-beta loaded cells (inflammation cells) (see Figure 7).
  • IL-17A acts on cellular targets, including keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts, to stimulate production of various antimicrobial peptides, chemokines, and proinflammatory and proliferative cytokines, which, in turn, promote tissue inflammation and bone remodeling
  • keratinocytes Human derived cells (keratinocytes) media was harvested following treatment initiation was centrifuged briefly to remove particulates (300 g for 10 min).
  • Cytokine and chemokine levels in the cell media were measured using a Bio-Plex 200 with a 96-well magnetic plate assay according to the manufacturer's instructions (Bio-Rad). Cytokines and chemokines measured included IL-1 ⁇ , IL-1 ⁇ , IL-2, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G- CSF, GM-CSF, IFN ⁇ , TNF ⁇ , CXCL1 (KC), CCL2 (MCP-1), and CCL5 (RANTES). All samples were run in duplicate and data were analyzed with the Bio-Plex Manager software.
  • F.1 STUDY AIM The compositional analysis of DOLCE164 extracted via oil, using UPLC/MS methods (as outlined in the above examples).
  • F.2 MATERIALS AND METHODS [ 0033] The ACQUITY UPLC H-Class System combined with the CORTECS UPLC Shield RP18 particle chemistry was used to provide a UPLC isocratic separation of main cannabinoids in a 10.5-minute cycle time. Samples of DOLCE 164 were assayed on a weekly basis and CBDA was used as a main marker as a stability indicator.
  • Results presented in Table 6 demonstrate that DOLCE164 is stable at room temperature within an inert oil media over 6 weeks. There is no decarboxylation or product degradation observed over this time f rame
  • Equipment The following equipment was used: 10mL glass scintillation bottles with lids; Cobram’s Estate olive oil; plant grinder (similar to a coffee or food grade grinder) pore size up to 50 ⁇ M-80 ⁇ M; Whatman paper, grade 1; pipettes; weight scale (transfer boats and spoons); Eppendorf tubes; 50mL falcon tubes; bench top centrifuge (Eppendorf Centrifuge 5702); Oz Design Brand 6 Litre Fruit, Wine and Cider Press.
  • the oil plus plant mixture is then put into the Oz Design Brand 6 Litre Fruit, Wine and Cider Press to reclaim the oil component from the plant (the mash).
  • the reclaimed oil was then placed into 50mL falcon tubes and spun at 300g for 15 minutes at room temperature (Isolation 1). The oil was then removed into a clean Schott bottle and keeping track of the volume reclaimed. The recovery of the oil for Isolation 1 is approximately 40%. The mash is discarded following each isolation.

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Abstract

The present invention relates to compositions comprising cannabinoids including cannabidiolic acid (CBDA), cannabidiol (CBD), cannabigerol (CBG), cannabidiphorol (CBDP), cannadibutol (CBDB), CBGA (cannabigerolic acid), CBN (cannabinol), tetrahydrocannabinol (THC) together with an additional active ingredient. The present invention also relates to pharmaceutical compositions, dosage forms and methods of treating non-neurological disorders by administering these composition to a patient in need thereof.

Description

COMPOSITIONS AND METHODS FOR TREATING NON-NEUROLOGICAL DISORDERS WITH COMBINATION PRODUCTS COMPRISING A CANNABINOID MIXTURE RICH IN CANNABIDIOLIC ACID (CBDA) ALONG WITH AN ADDITIONAL ACTIVE AGENT
Field of the Invention
[0001 ] The present invention relates to compositions comprising cannabinoids together with an additional active ingredient. The present invention also relates to pharmaceutical compositions, dosage forms and methods of treating non-neurological disorders by administering the composition to a patient in need thereof.
Background
[0002] The following discussion of the background art is intended to facilitate an understanding of the present invention only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application.
A. Inflammation
[0003] Inflammation refers to the process whereby the body’s innate immune system is triggered following an inflammatory challenge such as those posed by injury, infection, exposure to a toxin, disease, or aging. Inflammation is implicated in contributing to a variety of diseases and illnesses including: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non-inflammatory); disorders affecting the pulmonary system (such as neumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such aass anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such aass bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteoporosis, paget's disease of the bone and rickets); non neurological cancers (such as breast cancer, skin cancers, prostate cancer, bladder cancer and liver cancer); blood borne disorders (such as common bloodborne diseases (including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)) and viral hemorrhagic fevers (including ebola virus disease and lassa fever; and lipid metabolism disorders (such as familial combined hyperlipidemia (FCHL), familial defective apolipoprotein B-100, high total cholesterol (including 350 to 550 mg/dL), familial dysbetalipoproteinemia (including type 3 hyperlipoproteinemia), familial hypertriglyceridemia, heterozygous familial hypercholesterolemia and diabetes. [0004] The innate immune response plays a significant role in both physiological and pathological conditions. A number of diseases trigger a cascade of events broadly defined as inflammation. T lymphocyte infiltration, and overproduction of inflammatory cytokines have been demonstrated in association with alteration in both animal and human tissues. Inflammatory cytokines/markers or proinflammatory cytokines/markers are types of signaling molecules that are secreted from immune cells like helper T cells and macrophages and certain other cell types that promote the process of inflammation and general inflammatory processes. These include interleukin-1 (IL-1), IL-12, and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ) and granulocyte-macrophage colony stimulating factor (GM-CSF). These inflammatory cytokines are predominantly produced by and involved in the upregulation of inflammatory reactions and play an important role in mediating the innate immune response. B. Non-neurological Disorders [0005] Examples of non-neurological disorders include: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non-inflammatory); disorders affecting the pulmonary system (such as pneumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such as anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such as bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteoporosis, paget's disease of the bone and rickets); non neurological cancers (such as breast cancer, skin cancers, prostate cancer, bladder cancer and liver cancer); blood borne disorders (such as common bloodborne diseases (including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)) and viral hemorrhagic fevers (including ebola virus disease and lassa fever; and lipid metabolism disorders (such as familial combined hyperlipidemia (FCHL), familial defective apolipoprotein B-100, high total cholesterol (including 350 to 550 mg/dL), familial dysbetalipoproteinemia (including type 3 hyperlipoproteinemia), familial hypertriglyceridemia, heterozygous familial hypercholesterolemia and diabetes. [0006] Medicinal applications of cannabis [0007] Cannabis sativa L. has a tradition of medical use. Medicinal cannabis has attracted significant interest due to its anti-inflammatory, anti-oxidative and anti-necrotic protective effects, as well as displaying a favourable safety and tolerability profile in humans, making it a promising candidate in many therapeutic avenues. However, clinical use has been restricted because of untoward effects on the central nervous system and the possibility of abuse and addiction. The plant exudes a resin containing a mix of cannabinoids with two principal components, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The structure of CBD was described in the 1960s and has garnered attention due to the lack of psychotropic activity. Because of its excellent tolerability in humans, the lack of psychoactive action, and low abuse potential, it seems ideal for clinical trial. C. Cannabinoids [0008] In addition to its good safety profile and the lack of psychoactive effects, CBD also presents a wide range of therapeutic effects. Several experimental in vitro and in vivo studies demonstrate anti-inflammation and immune modifying, anti-psychotic, analgesic and anti-epileptic actions. For these reasons, CBD is currently one of the most studied cannabinoids. Compared to Δ9-THC, CBD shows a low affinity for cannabinoid receptor type 1 (CB1) and type 2 (CB2). CB1 receptors are mainly found in the terminals of central and peripheral neurons, and CB2 receptors primarily in immune cells. Several in vitro studies have shown that CBD, at low concentrations, has weak CB1 and CB2 antagonistic effect. [0009] Studies suggest that CBD behaves as a negative allosteric modulator of CB1, meaning that CBD does not activate the receptor directly but alters the potency and efficacy of CBD1's orthosteric ligands: Δ9-THC and 2-arachidonoylglycerol (2-AG). These preliminary results need further validation but may explain the ability of CBD to antagonise some of the effects of Δ9-THC reported in vitro, in vivo and human clinical studies. It has also been suggested that the role of CBD as an allosteric modulator of CB1 can explain its therapeutic role in the treatment of central and peripheral nervous system disorders. CBD has also shown to inhibit neutrophil chemotaxis and proliferation. It may also induce arachidonic acid release and reduce prostaglandin E2 (PGE2) and nitric oxide (NO) production. [0010] However, not all physiological effects of CBD are mediated by cannabinoid receptors. CBD has numerous targets outside the endocannabinoid system, and its action independent of the cannabinoid receptor is the subject of recent pharmacological studies. Some effects, such as anti-inflammatory and immunosuppressive action, are mediated by more than one target. The anti-inflammatory, immunosuppressive effects are possibly mediated by activation of adenosine receptors, A1Aand A2A and strychnine-sensitive α1 and α1β glycine receptors and the inhibition of the equilibrative nucleoside transporter. Furthermore, the activity of CBD may elicit different physiological effects from the same target. For example, the same glycine receptor is implicated in both anti-inflammation and suppression of neuropathic pain. While effects on serotonin 5HT1A receptors may generate anxiolytic, panicolytic and antidepressant effects, research has showed an in-depth review of the molecular pharmacology of CBD. Despite advances in the molecular pharmacology of CBD, the many pharmacological mechanisms of CBD remain uncharacterized. [0011] Published studies in animals demonstrated that the oral bioavailability of cannabidiol has been shown to be approximately between 13–19%. Plasma and brain concentrations are dose-dependent in animals, and bioavailability is increased with various oil formulations. Cannabinoids undergo extensive first pass metabolism and its metabolites are mostly excreted via the kidneys. [0012] Cannabinoids are metabolized extensively by the liver, where it is hydroxylated to 7-OH-CBD by P450 enzymes, predominantly by the CYP3A (2/4) and CYP2C (8/9/19) families of isozymes. This metabolite then undergoes significant further metabolism in the liver, and the resulting metabolites are excreted in the faeces and, to a much lesser extent, in the urine. [0013] It is known that cannabidiol acts on cannabinoid (CB) receptors (CB1 and CB2) of the endocannabinoid system, which are found in numerous areas of the body, including the peripheral and central nervous systems, including the brain. The endocannabinoid system regulates many physiological responses of the body including pain, memory, appetite, and mood. More specifically, CB1 receptors can be found within the pain pathways of the brain and spinal cord where they may affect cannabidiol-induced analgesia and anxiolysis, and CB2 receptors have an effect on immune cells, where they may affect cannabidiol-induced anti-inflammatory processes. [0014] Cannabidiol has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body. Allosteric regulation of a receptor is achieved through the modulation of the activity of a receptor on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of cannabidiol are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects. [0015] There has been some developments in the regulatory approval of CBD. Epidiolex® is a plant-derived, pharmaceutical grade cannabidiol (CBD) medication which attained FDA approval for use in the United States in 2018. Epidiolex® contains 100 mg of cannabidiol per milliliter (mL) of solutions and is taken orally twice daily. The Australian Therapeutic Goods Administration (TGA) approved Epidiolex in September 2020 for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome in patients two years of age or older [0016] There is a need in the art for improved cannabinoid compositions and effective treatments of non-neurological disorders. It is an objective of the invention to overcome one or more problems foreshadowed by the prior art. Summary of the Invention [0017] In a first aspect, the invention broadly resides in a composition comprising the following cannabinoids: about 50 w/w% of CBDA; and wherein all other cannabinoids come to about 15 w/w%. [0018] In a preferred embodiment, the composition comprises the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBN1-3%; CBGA 1-10%; THC <1%; and an additional active ingredient. [0019] In another preferred embodiment, the composition comprises the following cannabinoids: w/w% CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 1-3% CBGA 5%; THC <0.3%; and an additional active ingredient. [0020] In another preferred embodiment, the composition comprises the following cannabinoids: w/w% CBDA 49%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN3% CBGA 5%; THC <0.3%; and an additional active ingredient. [0021] In another preferred embodiment, the composition comprises the following cannabinoids: w/w% CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBN 2% CBGA 4%; THC <0.2%; and an additional active ingredient. [0022] In another preferred embodiment, the composition comprises the following cannabinoids: w/w% CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBGA 4%; CBN 1%; THC <0.2%; and an additional active ingredient. [0023] In a preferred embodiment, the composition comprises cannabinoids in amounts selected from the group consisting of any one of the above-mentioned embodiments. [0024] In a second aspect, the invention is a pharmaceutical composition comprising the composition of the first aspect of the invention together with a pharmaceutically acceptable carrier. [0025] In a third aspect, the invention is a dosage form comprising the composition of the first aspect of the invention. [0026] In a fourth aspect, the invention is a method of treating a disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention. [0027] In a fifth aspect, the invention is the use of the composition of the invention in the manufacture of a medicament for the treatment of a disorder. [0028] In a sixth aspect, the invention is a process of extracting the composition of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with oil; 3) Mixing the grind and oil for a sufficient time period to form a mixture; 4) Pressing the mixture to reclaim the oil; 5) Centrifuging the oil to further refine the oil; and 6) Collecting the oil extract in a suitable container / steel vessel. [0029] In a seventh aspect, the invention is a process of extracting the composition of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with an alcohol; 3) Mixing the grind and alcohol for a sufficient time period to form a mixture; 4) Sonicating the mixture; 5) Centrifuging the mixture; and 6) Collecting the alcohol extract in a suitable container / steel vessel. [0030] In an eighth aspect, the invention is the product produced from the process of the invention [0031] In a ninth aspect, the invention is a kit comprising the dosage form of the invention together with instructions for its use. [0032] In a ninth aspect, the invention includes a composition, method and process as described by the examples following. [0033] Further features of the present invention are more fully described in the following description of several non-limiting embodiments thereof. This description is included solely for the purposes of exemplifying the present invention. It should not be understood as a restriction on the broad summary, disclosure or description of the invention as set out above. Brief Description of the Drawings [0034] Below is a brief description of each of the figures and drawings. [0035] Figure 1 is a UPLC mass spectrometry chromatogram of the cannabinoid standard mixture (10 ppm each) in; a) positive; and b) negative ionization mode. [0036] Figure 2 is an in-source fragmentation of CBD and CBG from the reference solution. [0037] Figure 3 shows mass spectrometry chromatograms for DOLCE164. [0038] Figure 4 shows quad mass spectrometry chromatograms of CBD variants of DOLCE164 to identify CBDB and CBDP. [0039] Figure 5 represents the normalization of inflammation-induced iNOS expression by DOLCE164. The figure shows that NTI164 normalises inflammation-induced iNOS expression. [0040] Figure 6 demonstrates that DOLCE164 normalises viral loading related inflammation in cells as measured by TNF-gamma suppression. [0041] Figure 7 demonstrates that DOLCE164 suppresses IL-beta in viral loaded cells. Detailed Description of the Invention [0042] For convenience, the following sections generally outline the various meanings of the terms used herein. Following this discussion, general aspects regarding compositions, use of medicaments and methods of the invention are discussed, followed by specific examples demonstrating the properties of various embodiments of the invention and how they can be employed. [0043] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. The invention includes all such variations and modifications. The invention also includes all of the steps, features, formulations and compounds referred to or indicated in the specification, individually or collectively and any and all combinations or any two or more of the steps or features. [0044] Each document, reference, patent application or patent cited in this text is expressly incorporated herein in their entirety by reference, which means that it should be read and considered by the reader as part of this text. That the document, reference, patent application or patent cited in this text is not repeated in this text is merely for reasons of conciseness. None of the cited material or the information contained in that material should, however be understood to be common general knowledge. [0045] Manufacturer’s instructions, descriptions, product specifications, and product sheets for any products mentioned herein or in any document incorporated by reference herein, are hereby incorporated herein by reference, and can be employed in the practice of the invention. [0046] The present invention is not to be limited in scope by any of the specific embodiments described herein. These embodiments are intended for the purpose of exemplification only. Functionally equivalent products, formulations and methods are clearly within the scope of the invention as described herein. 1. DEFINITIONS [0047] The meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail. [0048] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term "about." The term "about" when used in connection with percentages can mean ±1%. [0049] The invention described herein may include one or more range of values (e.g. size, concentration etc.). A range of values will be understood to include all values within the range, including the values defining the range, and values adjacent to the range which lead to the same or substantially the same outcome as the values immediately adjacent to that value which defines the boundary to the range. For example, a person skilled in the field will understand that a 10% variation in upper or lower limits of a range can be totally appropriate and is encompassed by the invention. More particularly, the variation in upper or lower limits of a range will be 5% or as is commonly recognised in the art, whichever is greater. [0050] In this application, the use of the singular also includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. Also, terms such as “element” or “component” encompass both elements and components comprising one unit and elements and components that comprise more than one subunit unless specifically stated otherwise. Also, the use of the term “portion” can include part of a moiety or the entire moiety. [0051] Throughout this specification, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. [0052] “Therapeutically effective amount” as used herein with respect to methods of treatment and in particular drug dosage, shall mean that dosage that provides the specific pharmacological response for which the drug is administered in a significant number of subjects in need of such treatment. It is emphasized that “therapeutically effective amount,” administered to a particular subject in a particular instance will not always be effective in treating the diseases described herein, even though such dosage is deemed a “therapeutically effective amount” by those skilled in the art. It is to be further understood that drug dosages are, in particular instances, measured as oral dosages, or with reference to drug levels as measured in blood or measured as inter-intra epidermal delivery. Amounts effective for such a use will depend on: the desired therapeutic effect; the potency of the biologically active material; the desired duration of treatment; the stage and severity of the disease being treated; the weight and general state of health of the patient; and the judgment of the prescribing physician. Treatment dosages need to be titrated to optimize safety and efficacy. One skilled in the art will appreciate that the appropriate dosage levels for treatment will thus vary depending, in part, upon the indication for which the active agent is being used, the route of administration, and the size (body weight, body surface or organ size) and condition (the age and general health) of the patient. Accordingly, the clinician may titre the dosage and modify the route of administration to obtain the optimal therapeutic effect. A typical dosage may range from about 0.1 μg/kg to up to about 100 mg/kg or more, depending on the factors mentioned above. In other embodiments, the dosage may range from 0.1 μg/kg up to about 100 mg/kg; or 1 μg/kg up to about 100 mg/kg; or 5 μg/kg up to about 100 mg/kg. [0053] The frequency of dosing will depend upon the pharmacokinetic parameters of the active agent and the formulation used. Typically, a clinician will administer the composition until a dosage is reached that achieves the desired effect. The composition may therefore be administered as a single dose, or as two or more doses (which may or may not contain the same amount of the desired molecule) over time, or as a continuous infusion via an implantation device or catheter. Further refinement of the appropriate dosage is routinely made by those of ordinary skill in the art and is within the ambit of tasks routinely performed by them. Appropriate dosages may be ascertained through use of appropriate dose- response data. [0054] As used herein "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, microemulsions, gel suspensions and topical formulations and the like that are physiologically compatible. [0055] As used herein the term “subject” generally includes mammals such as: humans; farm animals such as sheep, goats, pigs, cows, horses, llamas; companion animals such as dogs and cats; primates; birds, such as chickens, geese and ducks; fish; and reptiles. The subject is preferably human. [0056] “Non neurological disorders” are disorders that do not affect the brain as well as the nerves found throughout the human body and the spinal cord. [0057] Other definitions for selected terms used herein may be found within the detailed description of the invention and apply throughout. Unless otherwise defined, all other scientific and technical terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the invention belongs. [0058] Features of the invention will now be discussed with reference to the following non-limiting description and examples. 2. EMBODIMENTS Composition [0059] The present invention provides a composition comprising the following cannabinoids: about 50 w/w% of CBDA; and wherein all other cannabinoids come to about 15 w/w%. [0060] Preferably, the composition comprises an additional active ingredient. [0061] In a preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 2% CBD; and an additional active ingredient. [0062] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 5% CBG; and an additional active ingredient. [0063] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 2% CBDP; and an additional active ingredient.. [0064] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 2% CBDB; and an additional active ingredient. [0065] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % about 50% of CBDA; about 5% CBGA; and an additional active ingredient. [0066] In a further preferred embodiment, the invention provides a composition comprising cannabinoids, wherein the ratio of CBDA to all other cannabinoids is between 4:1 and 2:1. [0067] In a further preferred embodiment, the invention provides a composition comprising cannabinoids, wherein the ratio of CBDA to all other cannabinoids is about 3:1. [0068] In a further preferred embodiment, the invention provides a composition comprising cannabinoids, wherein the ratio of CBDA to all other cannabinoids is about 3.21:1. [0069] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBN 1-3%; CBGA 1-10%; THC <1%; and an additional active ingredient. [0070] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 45-55%; CBD 1-3%; CBG 3-7%; CBDP 1-3%; CBDB 1-3%; CBGA 3-7%; CBN 1-3%; THC <0.5%; and an additional active ingredient. [0071] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 3% CBGA 5%; THC <0.3%; and an additional active ingredient. [0072] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 49%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 2% CBGA 5%; THC <0.3%; and an additional active ingredient. [0073] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 48.78%; CBD 1.89%; CBG 4.88%; CBDP 1.68%; CBDB 1.76%; CBN 1% CBGA 4.76%; THC <0.18%; and an additional active ingredient. [0074] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBN 2% CBGA 4%; THC <0.2%; and an additional active ingredient. [0075] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 45.28%; CBD 1.39%; CBG 3.88%; CBDP 1.18%; CBDB 1.56%; CBN 1%; CBGA 3.76%; THC <0.18%; and an additional active ingredient. [0076] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 62.78%; CBD 5.80%; CBG 0.44%; CBGA 1.26%; CBN 1.98%; THC <0.70%; and an additional active ingredient.. [0077] In a further preferred embodiment, the invention provides a composition comprising the following cannabinoids: w/w % CBDA 60.29%; CBD 5.34%; CBG 0.39%; CBGA 1.14%; CBN 0.85%; THC <0.65%; and an additional active ingredient. [0078] In a further preferred embodiment, the invention provides a composition wherein the cannabinoids are present in amounts selected from the group consisting of: Composition 1 comprising: w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 3%; CBGA 5%; THC <0.3%; and an additional active ingredient. and Composition 2 comprising: w/w % CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBN 2%; CBGA 4%; THC <0.2%; and an additional active ingredient. [0079] In a further preferred embodiment, the invention provides a composition, wherein the quantity of the cannabinoids is determined by a method selected from the group consisting of: high performance chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (H1 NMR); and mass spectrometry. [0080] In a further preferred embodiment, the invention provides a composition derived from cannabis plant material. [0081] In a further preferred embodiment, the invention provides a composition wherein the said listed cannabinoids are synthetic. [0082] In a further preferred embodiment, the invention provides a composition wherein the said listed cannabinoids are a mixture of plant derived and synthetic cannabinoids. [0083] In a further preferred embodiment, the invention provides a composition further comprising an oil selected from the group consisting of: a synthetic oil; plant based oil; mineral oil; canola oil; and olive oil. [0084] In a further preferred embodiment, the composition comprises less than 5% w/w terpenes. [0085] In a further preferred embodiment, the composition comprises between 55% and 5%w/w organic plant material. In a further preferred embodiment, the composition comprises less than 10% w/w organic plant material. In a further preferred embodiment, the composition comprises less than 5% w/w organic plant material. In a further preferred embodiment, the composition comprises less than 2% w/w organic plant material. [0086] In a further preferred embodiment, the composition comprises less than 2% w/w of plant phenols. [0087] In a further preferred embodiment, the composition comprises components selected from the group consisting of: flavonoids, proteins, sterols and esters. [0088] In a further preferred embodiment, the composition is substantially pure. Preferably, the purity is determined by a method selected from the group consisting of: high performance chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (H1 NMR); and mass spectrometry. Preferably, the purity is selected from the group consisting of: greater than 75% purity; greater than 80% purity; greater than 85% purity; greater than 90% purity; greater than 95% purity; greater than 96% purity; greater than 97% purity; greater than 98% purity; greater than 99% purity; greater than 99.5% purity; greater than 99.6% purity; greater than 99.7% purity; greater than 99.8% purity; greater than 99.9% purity; greater than 99.95% purity; greater than 99.96% purity; greater than 99.97% purity; greater than 99.98% purity and greater than 99.99% purity. [0089] In a further preferred embodiment, the composition comprises less than 0.1 wt% organic impurities as measured a method selected from the group consisting of: high performance chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (H1 NMR); and mass spectrometry. [0090] In a further preferred embodiment, the composition is substantially free of atmospheric oxygen. [0091] In a further preferred embodiment, the composition is sterile. [0092] In a further preferred embodiment, the invention provides a composition wherein the cannabinoid component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml. [0093] In a further preferred embodiment, the invention provides a composition wherein the CBDA component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml. [0094] In a further preferred embodiment, the composition is a liquid. [0095] In a further preferred embodiment, the composition is an oil. [0096] In a further preferred embodiment, the composition demonstrates no cannabinoid degradation or decarboxylation when measured at a time point selected from the group consisting of: at 1 day; at 2 days; at 7 days; at 14 days; at 28 days; at 5 weeks; at 6 weeks; and at 32 weeks. [0097] In a further preferred embodiment, the composition demonstrates cannabinoid stability when measured at a time point selected from the group consisting of: at 1 day; at 2 days; at 7 days; at 14 days; at 28 days; at 5 weeks; at 6 weeks; and at 32 weeks. [0098] In a further preferred embodiment, the composition demonstrates no mutagenicity, carcinogenicity or genotoxicity when delivered at a concentration that delivers 120mg/ml of CBDA. [0099] In a further preferred embodiment, the composition is adapted to suppress the activity of any one of the following biomarkers: COX-2; iNOS; TNF-alpha; IL-2; IL-12 and GS-MCF. [00100] Preferably, the composition is adapted to suppress inflammation. More preferably, the composition is adapted for the treatment of a non-neurological disorder. [00101] In a further preferred embodiment, the invention provides a composition having a UPLC mass chromatogram corresponding to Figure 3 utilising the conditions described in Example 1. [00102] In a further preferred embodiment, the composition comprises an additional active ingredient. [00103] Preferably, the additional active ingredient is selected from the group consisting of: a polypeptide; an antibody; and a NSAID. [00104] In one preferred embodiment, the NSAID is selected from the group consisting of: monoclonal anti-body therapies, biologics, interferon gamma therapy, interferon – beta therapies, aspirin, ibuprofen, naproxen, diclofenac, celecoxib, ketorolac, meloxicam, esomeprazole, naproxen, diclofenac, misoprostol, nabumetone, indomethacin, mefenamic acid, etodolac, piroxicam, ketoprofen, diflunisal, oxaprozin, flurbiprofen, sulindac, tolmetin, prednisolone and fenoprofen. [00105] More preferably, the NSAID is selected from the group consisting of: diclofenac, prednisolone and celebrex. [00106] In a further preferred embodiment, the ratio of cannabinoid component and the additional active ingredient is selected from the group consisting of: 1 unit w/w of cannabinoid : 1 unit w/w/ of the additional active ingredient; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1. [00107] In a further preferred embodiment, the ratio of the additional active ingredient and cannabinoid is selected from the group consisting of: 1 unit w/w of the additional active ingredient and 1 unit w/w/ of the cannabinoid; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1. [00108] In a further preferred embodiment, the ratio of CBDA and the additional active ingredient is selected from the group consisting of: 1 unit w/w of CBDA : 1 unit w/w/ of the additional active ingredient; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1. [00109] In a further preferred embodiment, the ratio of the additional active ingredient and CBDA is selected from the group consisting of: 1 unit w/w of the additional active ingredient and 1 unit w/w/ of the CBDA; 2:1; 3:1; 4:1; 5:1; between 10,000:1 and 1:1; between 1,000:1 and 1:1; between 500:1 and 1:1; between 100:1 and 1:1; between 50:1 and 1:1; and between 10:1 and 1:1. [00110] In a further preferred embodiment, the composition demonstrates synergistic biological activity. [00111] In a further preferred embodiment, the composition demonstrates a level of biological activity that is greater than the sum of: (1) the biological activity of the cannabinoid component when delivered in absence of the additional active ingredient; and (2) the biological activity of the additional active ingredient when delivered in absence of the cannabinoid component. [00112] In a further preferred embodiment, the biological activity is selected from the group consisting of: suppressing inflammation; suppressing inflammation; treating a non- neurological disorder; suppressing the activity of COX-2; suppressing the activity of iNOS; suppressing the activity of TNF-alpha; suppressing the activity of IL-2; suppressing the activity of IL-12 and suppressing the activity of GS-MCF. [00113] In a further preferred embodiment, the composition is selected from the group consisting of: a therapeutic composition; a pharmaceutical composition; a cosmetic composition; and a veterinary composition. [00114] In one preferred embodiment, the composition of the invention is not a composition selected from the group consisting of: [00115] (a) Sample S06 disclosed in WO2021188983; [00116] (b) Sample S06 disclosed in WO2021188983 with the following CBD profile: CBDA (41.9%), CBD (1.9%), CBGA (1.3%), THC (0.2%), CBG (0.2%) (weight % in extract); [00117] (c) Sample Liffer disclosed in WO2021188983; [00118] (d) Sample Liffer disclosed in WO2021188983 with the following CBD profile: CBDA (57.9%), CBGA (1.6%), THC (0.7%), CBD (5.8%), CBG (0.3%) (weight % in extract); [00119] (e) CannBio1 disclosed in WO2020093101; [00120] (f) CannBio1 disclosed in WO2020093101 with the following CBD profile: CBD (90.42%), THC (3.10%), CBG (1.17%), CBC (3.76%), CBN (0.03%), CBDV (1.36%), THCV (0.16%) (% of the total cannabinoid content); [00121] (g) The CBD profile presented in Table 10 of WO2020223510; [00122] (h) The CBD profile presented in Table 10 of WO2020223510 with the following CBD profile: CBC (0.125%), CBCA (1.170%), CBD (0.998%), CBDA (19.500%), CBDV (0.000%), CBDVA (0.091%), CBG (0.080%), CBGA (0.328%), D8-THC (0.000%), D9-THC (0.127%), THCA (0.652%) (weight % in extract); [00123] (i) The CBD profiles presented in Table 11 of WO2020223510; [00124] (j) The CBD profile presented in Table 11 of WO2020223510 with the following CBD profile: CBC (0.238%), CBCA (0.561%), CBD (3.02%), CBDA (12.100%), CBDV (0.000%), CBDVA (0.052%), CBG (0.141%), CBGA (0.401%), A8-THC (0.000%), A9-THC (0.247%), THCA (0.186%) (weight % in extract); [00125] (k) The CBD profiles presented in Table 1 of D4 WO2018175796; [00126] (l) The CBD profile presented in Table 1 of D4 WO2018175796 with the following CBD profile: BHO (THC (20.2%), CBD (0.1%), THCA (27.7%), CBDA (0.7%) (weight % in extract); [00127] (m) The CBD profile presented in Table 1 of D4 WO2018175796 with the following CBD profile: 2A PULP (THC (16.6%), CBD (0.9%), THCA (5.6%), CBDA (2.0%) (weight % in extract); [00128] (n) The CBD profile presented in Table 1 of D4 WO2018175796 with the following CBD profile: Herman (THC (9.7%), CBD (1.8%), THCA (8.1%), CBDA (17.5%) (weight % in extract)); [00129] (o) The CBD profiles presented in Table 1 of D4 WO2016004121A1; [00130] (p) The CBD profiles presented in Table 1 of D4 WO2016004121A1 with the following CBD profile: 21.77% CBDA, 0.94% CBD, 0.08% THCA and less than <0.001% each of THC, CBN, CBD-V, CBG, THC-V and CBC (weight % in extract); [00131] (q) The CBD profiles presented in Tables 2.9.1 and 2.9.2 of WO2011110866A1; [00132] (r) The CBD profile presented in Tables 2.9.1 and 2.9.2 of WO2011110866A1 with the following CBD profile: 68% CBDA, 5% CBD and 0.5% THC (weight % in extract); [00133] (s) The CBD profiles presented in TIZMAS P.S. et al.: “Effective determination of the principal nonpsychoactive cannabinoids in fiber-type Cannabis sativa L. by UPLC-PDA following a comprehensive design and optimization of extraction methodology”, ANALYTICA CHIMICA ACTA, January 2021, vol.1150, article 338200; [00134] (t) The CBD profiles from extracts derived from Fedora 17, Fibranova and Futura 75 presented Figure 3 of TIZMAS P.S. et al.: “Effective determination of the principal nonpsychoactive cannabinoids in fiber-type Cannabis sativa L. by UPLC-PDA following a comprehensive design and optimization of extraction methodology”, ANALYTICA CHIMICA ACTA, January 2021, vol.1150, article 338200; [00135] (u) The CBD profiles presented in VAGI E. et al.: “Cannabinoids Enriched Extracts from Industrial Hemp Residues”, PERIODICA POLYTECHNICA - CHEMICAL ENGINEERING, 2019, vol.63, no.2, pp.357-363; and [00136] (v) The CBD profiles from extracts derived from Figures 3, 4, 5, 8 presented in VAGI E. et al.: “Cannabinoids Enriched Extracts from Industrial Hemp Residues”, PERIODICA POLYTECHNICA - CHEMICAL ENGINEERING, 2019, vol.63, no. 2, pp. 357- 363. Pharmaceutical Compositions [00137] The present invention also provides a pharmaceutical composition comprising the composition of the invention together with a pharmaceutically acceptable carrier. [00138] Therapeutic compositions are within the scope of the present invention. Preferably the compositions are combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition (which may be for human or animal use). Suitable carriers and diluents include isotonic saline solutions, for example phosphate- buffered saline. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. See, e.g., Remington's Pharmaceutical Sciences, 19th Ed. (1995, Mack Publishing Co., Easton, Pa.) which is herein incorporated by reference. [00139] The pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, colour, isotonicity, odour, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. Suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulphite or sodium hydrogen-sulphite Vitamin E, Vitamin E phosphate – lipid soluble vitamins, nano emulsions); buffers (such as borate, bicarbonate, tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta- cyclodextrin), fillers; monosaccharides, disaccharides; and other carbohydrates (such as glucose, mannose, or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); colouring, flavouring (natural and natural derived products) and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (including artificial sweetners such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate 80, triton, tromethamine, lecithin, cholesterol, tyloxapol); stability enhancing agents (sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride), delivery vehicles, diluents, excipients and/or pharmaceutical adjuvants. [00140] The optimal pharmaceutical composition will be determined by one skilled in the art depending upon, for example, the intended route of administration, delivery format, and desired dosage. Such compositions may influence the physical state, stability, rate of in vivo release, and rate of in vivo clearance of the composition of the invention. The preferred form of the pharmaceutical composition depends on the intended mode of administration and therapeutic application. [00141] The primary vehicle or carrier in a pharmaceutical composition is aqueous in nature. For example, a suitable vehicle or carrier may be water for injection, physiological saline solution, possibly supplemented with other materials. Neutral buffered saline or saline mixed with serum albumin are further exemplary vehicles. Other exemplary pharmaceutical compositions comprise tris buffer of about pH 7.0-8.5, or acetate buffer of about pH 4.0-5.5, which may further include sorbitol or a suitable substitute therefor. In one embodiment of the present invention, pharmaceutical compositions may be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents in the form an aqueous solution. [00142] The formulation components are present in concentrations that are acceptable to the site of administration. For example, buffers are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a pH range of from about 5 to about 8. [00143] Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations of the invention in sustained- or controlled-delivery formulations. Techniques for formulating a variety of other sustained- or controlled-delivery means, such as liposome carriers, bio-erodible microparticles or porous beads and depot injections, are also known to those skilled in the art. Additional examples of sustained-sustained-release preparations include semipermeable polymer matrices in the form of shaped articles, for example, films, or microcapsules. Sustained release matrices may include polyesters, hydrogels, polylactides, copolymers of L-glutamic acid and gamma ethyl-L-glutamate, ethylene vinyl acetate or poly-D(-)-3-hydroxybutyric acid. Sustained-release compositions may also include liposomes, which can be prepared by any of several methods known in the art. [00144] The pharmaceutical composition to be used for in vivo administration typically must be sterile. This may be accomplished by filtration through sterile filtration membranes. In addition, the compositions generally are placed into a container having a sterile access port. Once the pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution. [00145] In yet a further preferred embodiment, the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36 hours; and greater than 48 hours. Preferably, the composition is stable for periods selected from the group consisting of: 6 months, 1 year and 2 years. In one example, the composition is stable at temperatures selected from the group consisting of: - 4°C, 4°C, 18°C and 25°C. Dosage Form [00146] Dosage forms are within the scope of the invention. In a preferred embodiment, the invention provides a dosage form comprising the composition as described in the first aspect of this invention. [00147] Preferably, the cannabinoid component of the composition of the dosage form is selected from the group consisting of: between 1mg and 1000mg; between 1mg and 500mg; between 1 and 100mg; less than 400mg; less than 300mg; less than 200mg and less than 100mg. More preferably the cannabinoid component of the composition is selected from the group consisting of: 600mg; 400mg; 300mg; 200mg; 100mg; 50mg; 10mg; 5mg; 2mg; 1mg. Preferably the CBDA component of the composition of the dosage form is selected from the group consisting of: between 1mg and 1000mg; between 1mg and 500mg; between 1 and 100mg; less than 400mg; less than 300mg; less than 200mg and less than 100mg. More preferably, the CBDA component of the composition is selected from the group consisting of: 600mg; 400mg; 300mg; 200mg; 100mg; 50mg; 10mg; 5mg; 2mg; 1mg. [00148] In a further embodiment, the dosage form is form selected from the group consisting of: a solution, tablet, capsule, wafer, dry power sachet and vial / freeze dried. [00149] Preferably, the dosage form is stored in a sealed and sterile container. Method for treating [00150] The invention also provides a method of treating a disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention. [00151] In a further preferred embodiment, the dosage form is administered at an amount to at least partially treat the disorder. [00152] In a further preferred embodiment, the therapeutically effective amount is an amount of cannabinoid selected from the group consisting of: between 1 to 100mg/kg/day; between 2 and 50mg/kg/day; between 5 and 40mg/kg/day; between 10 and 30mg/kg/day; between 20 and 25mg/kg/day; and 20mg/kg/day. Preferably, the therapeutically effective amount is an amount of cannabinoid vis selected from the group consisting of: 10mg/day; 15mg/day; 40mg/day; 400mg/day; 600mg/day; 800mg/day; 1280mg/day; 1500mg/day. [00153] In a further preferred embodiment, therapeutically effective amount is an amount of CBDA selected from the group consisting of: between 1 to 100mg/kg/day; between 2 and 50mg/kg/day; between 5 and 40mg/kg/day; between 10 and 30mg/kg/day; between 20 and 25mg/kg/day; and 20mg/kg/day. Preferably, the therapeutically effective amount is an amount of CBDA vis selected from the group consisting of: 10mg/day; 15mg/day; 40mg/day; 400mg/day; 600mg/day; 800mg/day; 1280mg/day; 1500mg/day. [00154] In a further preferred embodiment, Tmax occurs between 1 and 4 hours. [00155] In a further preferred embodiment, T1/2 occurs between 1.1 and 2.4 hours. [00156] In a further preferred embodiment, the therapeutically effective amount is administered to the subject to treat the disorder. [00157] Preferably the therapeutically effective amount is administered to the subject utilising a dosing regimen selected from the group consisting of: twice hourly; hourly; once every six hours; once every 8 hours; once every 12 hours; once daily; twice weekly; once weekly; once every 2 weeks; once every 6 weeks; once a month; every 2 months; every 3 months; once every 6 months; and once yearly. [00158] Preferably the therapeutically effective amount is administered to the subject using a method selected from the group consisting of: orally, intravenously, intramuscularly, intrathecally, subcutaneously, sublingually, buccally, rectually, vaginally, topically, parentally, mucosally, by the ocular route, by the otic route, nasally, by inhalation, cutaneously, transdermally, and systemically. [00159] In a further preferred embodiment, the disorder is caused by inflammation. [00160] Preferably, the disorder is a non-neurological disorder. More preferably, the non- neurological disorder is selected from the group consisting of: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non-inflammatory); disorders affecting the pulmonary system (such as neumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such as anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such as bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteoporosis, paget's disease of the bone and rickets); non neurological cancers (such as breast cancer, skin cancers, prostate cancer, bladder cancer and liver cancer); blood borne disorders (such as common bloodborne diseases (including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)) and viral hemorrhagic fevers (including ebola virus disease and lassa fever; and lipid metabolism disorders (such as familial combined hyperlipidemia (FCHL), familial defective apolipoprotein B-100, high total cholesterol (including 350 to 550 mg/dL), familial dysbetalipoproteinemia (including type 3 hyperlipoproteinemia), familial hypertriglyceridemia, heterozygous familial hypercholesterolemia and diabetes. [00161] In a further preferred embodiment, the treatment reduces inflammation. Preferably, the treatment suppresses the activity of any one of the following biomarkers: COX-2; iNOS; TNF-alpha; IL-2; IL-12 and GS-MCF. [00162] A subject that can be treated with the invention will include humans as well as other mammals and animals. [00163] In a further preferred embodiment, the method comprises administering to a patient in need thereof a therapeutically effective amount of the dosage form of the invention together with an additional active ingredient. In a preferred form, the additional active ingredient is administered using a dosing regimen selected from the group consisting of: at the same time as administering the dosing form of the invention; before administering the dosing form of the invention; after administering the dosing form of the invention; concurrently with administering the dosing form of the invention; sequentially before administering the dosing form of the invention; and sequentially after administering the dosing form of the invention. The effect of the administered therapeutic composition can be monitored by standard diagnostic procedures. Use of a composition in the manufacture of a medicament [00164] Uses are within the scope of this invention. The invention also provides a use of the composition of the first aspect of the invention in the manufacture of a medicament for the treatment of a disorder. [00165] In one preferred embodiment, the invention is the use of a composition comprising the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBGA 1-10%; CBN 1-3% and THC <1%; in the manufacture of a medicament for the treatment of a non-neurological disorder and an additional active ingredient. [00166] In a further embodiment, the cannabinoids of the composition are present in amounts selected from the group consisting of: [00167] Composition 1 comprising w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBGA 5%; CBN 3% and THC <0.3%; and Composition 2 comprising w/w % CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBGA 4%; CBN 2% and [00168] THC <0.2%; in the manufacture of a medicament for the treatment of a non-neurological disorder and an additional active ingredient. [00169] In a further embodiment, the composition further comprises an oil selected from the group consisting of: a synthetic oil; plant based oil; mineral oil; canola oil; and olive oil. [00170] In a further embodiment, the composition comprises less than 5% w/w terpenes. [00171] In a further embodiment, the composition comprises less than 2% w/w organic plant material. [00172] In a further embodiment, the composition comprises less than 2% w/w of plant phenols. [00173] In a further embodiment, the cannabinoid component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml. [00174] In a further embodiment, the CBDA component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml. [00175] In a further embodiment, the composition has a UPLC mass chromatogram corresponding to Figure 3 utilising the conditions described in Example 1. Processes [00176] The invention also provides a process of extracting the composition of the first aspect of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with oil; 3) Mixing the grind and oil for a sufficient time period to form a mixture; 4) Pressing the mixture to reclaim the oil; 5) Centrifuging the oil to further refine the oil; and 6) Collecting the oil extract in a suitable container. [00177] In a further preferred embodiment, the cannabis plant material is derived from Cannabis sativa L. [00178] In a further preferred embodiment, the sufficient grind size is selected from the group consisting of: between 0.1mm and 3mm; between 1mm and 2mm; and between 0.5mm and 2.5mm. [00179] In a further preferred embodiment, the sufficient time period is selected from the group consisting of: between 30 minutes and 2 hours; between 45 minute and 1.5 hours; 1 hr. [00180] In a further preferred embodiment, the ratio of grind material to oil at step (2) is selected from the group consisting of: 400mg of grind: 1ml of oil; 300mg of grind : 1ml of oil; 200mg of grind : 1ml of oil; 100mg of grind : 1ml of oil; and 333mg of grind : 1ml of oil. [00181] Preferably, the oil is olive oil. [00182] The invention also provides an alternative process of extracting the composition of the first aspect of the invention from cannabis plant material, said process comprising the steps of: 1) Grinding the cannabis plant material to a sufficient grind size; 2) Contacting the grind produced by step a) with an alcohol; 3) Mixing the grind and alcohol for a sufficient time period to form a mixture; 4) Sonicating the mixture; 5) Centrifuging the mixture; and 6) Collecting the alcohol extract in a suitable container. [00183] In a further preferred embodiment, the alcohol is ethanol. [00184] In a further preferred embodiment, the alcohol is selected from the group consisting of: ethanol, isopropyl alcohol, methyl alcohol, benzyl alcohol, 1,4-butanediol, 1,2,4-butanetriol, butanol, 1-butanol, 2-butanol, tert-butyl alcohol. [00185] In a further preferred embodiment, the sufficient grind size is selected from the group consisting of: between 0.1mm and 3mm; between 1mm and 2mm; and between 0.5mm and 2.5mm. In a further preferred embodiment, the sufficient time period is selected from the group consisting of: between 30 minutes and 2 hours; between 45 minute and 1.5 hours; 1 hr. [00186] In a further preferred embodiment, the ratio of grind material to alcohol at step (2) is selected from the group consisting of: 400mg of grind: 1ml of alcohol; 300mg of grind : 1ml of alcohol; 200mg of grind : 1ml of alcohol; 100mg of grind : 1ml of alcohol; 100mg of grind : 4ml of alcohol; 100mg of grind : 3ml of alcohol; 100mg of grind : 2ml of alcohol; and 333mg of grind : 1ml of alcohol. Product of the Process [00187] The invention also provides a product produced from the process described above. Kit [00188] The invention also provides a kit comprising the dosage form of one aspect of the invention together with instructions for its use. Device [00189] Devices are within the scope of the invention. In a preferred embodiment, the invention provides a device, wherein the device comprises: (1) the composition as described in the first aspect of this invention; and (2) an applicator. Method for stabilising [00190] Methods for stabilizing the composition are within the scope of the invention. [00191] In a further preferred embodiment, the said method protects the composition against degradation. [00192] In yet a further preferred embodiment, the composition retains its effective biological activity for a period selected from the group consisting of; greater than 24 hours; greater than 36 hours; greater than 48 hours. [00193] The addition of approved pharmaceutical excipients to stabilise the composition is preferred from a safety standpoint, as the simpler methodology is likely to produce a less variable outcome and the choice of excipient can be limited to those with Generally Regarded as Safe (GRAS) status. Excipients for the stabilisation of protein solutions can be classified into four broad categories: salts, sugars, polymers or protein/amino acids, based on their chemical properties and mechanism of action. Salts (e.g. chlorides, nitrates) stabilise the tertiary structure of proteins by shielding charges through ionic interactions. Sugars (e.g. glycerol, sorbitol, fructose, trehalose) increase the surface tension and viscosity of the solution to prevent protein aggregation. Similarly, polymers (e.g. polyethylene glycol, cellulose derivatives) stabilise the protein tertiary structure by increasing the viscosity of the solution to prevent protein aggregation and intra- and inter-molecular electrostatic interactions between amino acids in the protein. Proteins (e.g. human serum albumin) are able to stabilise the structure of other proteins through ionic, electrostatic and hydrophobic interactions. Similarly, small amino acids with no net charge, such as alanine and glycine, stabilise proteins through the formation of weak electrostatic interactions. [00194] As discussed above, the medicaments of the present invention may include one or more pharmaceutically acceptable carriers. The use of such media and agents for the manufacture of medicaments is well known in the art. Except insofar as any conventional media or agent is incompatible with the pharmaceutically acceptable material, use thereof in the manufacture of a pharmaceutical composition according to the invention is contemplated. Pharmaceutical acceptable carriers according to the invention may include one or more of the following examples: a. surfactants and polymers, including, however not limited to polyethylene glycol (PEG), polyvinylpyrrolidone , polyvinylalcohol, crospovidone, polyvinylpyrrolidone- polyvinylacrylate copolymer, cellulose derivatives, HPMC, hydroxypropyl cellulose, carboxymethylethyl cellulose, hydroxypropylmethyl cellulose phthalate, polyacrylates and polymethacrylates, urea, sugars, polyols, and their polymers, emulsifiers, sugar gum, starch, organic acids and their salts, vinyl pyrrolidone and vinyl acetate; and/or b. binding agents such as various celluloses and cross-linked polyvinylpyrrolidone, microcrystalline cellulose; and/or (3) filling agents such as lactose monohydrate, lactose anhydrous, microcrystalline cellulose and various starches; and/or c. filling agents such as lactose monohydrate, lactose anhydrous, mannitol, microcrystalline cellulose and various starches; and/or d. lubricating agents such as agents that act on the increased ability of the dosage form to be ejected from the packaging cavity, and/or e. sweeteners such as any natural or artificial sweetener including sucrose, xylitol, sodium saccharin, cyclamate, aspartame, and acesulfame K; and/or f. flavouring agents; and/or g. preservatives such as potassium sorbate, methylparaben, propylparaben, benzoic acid and its salts, other esters of parahydroxybenzoic acid such as butylparaben, alcohols such as ethyl or benzyl alcohol, phenolic chemicals such as phenol, or quarternary compounds such as benzalkonium chloride; and/or h. buffers; and/or i. diluents such as pharmaceutically acceptable inert fillers, such as microcrystalline cellulose, lactose, dibasic calcium phosphate, saccharides, and/or mixtures of any of the foregoing; and/or j. absorption enhancer such as glyceryl trinitrate; and/or k. other pharmaceutically acceptable excipients. [00195] Medicaments of the invention suitable for use in animals and in particular in human beings typically must be sterile and stable under the conditions of manufacture and storage. [00196] Combinations [00197] In another aspect, the composition of the first aspect of the invention is combined with a second composition. [00198] In another preferred embodiment, the composition is combined with a second composition selected from the group consisting of: a composition derived from plant seeds; a plant seed extract; a composition derived from grape seeds; a grape seed extract; a proanthocyanidin; a composition derived from plant skin; wherein the plant is selected from the group consisting of: grapes; blueberries; raspberries; mulberries; and peanuts; a plant skin extract; a composition derived from grape skin; a grape skin extract; a phytoalexin; resveratrol. Preferably, the plant is selected from the group consisting of: grapes; blueberries; raspberries; mulberries; and peanuts. [00199] In another preferred embodiment, the composition is combined with a senolytic or anti-aging molecule. Preferably, the molecule is selected from the group consisting of: resveratrol; nicotinamide mononucleotide; rapamycin; metaformin; quercetin; datatinib; quercetin with datatinib; fisetin; EGCG; NAD boosters; NAD +; sulforaphane; urolithin; mito- Q; honokiol; curcumin and analogs; berberine; n-acetyl-cystine; piperlongumine; resveratrol and pterotsilbine; spermidine; allicin; vitamin D3; vitamin K; tocotrienol (and with quercetin; HSP-90 inhibitors; yamanaka factors (Oct3/4; Sox2; Klf4; and/or c-Myc); rapamycin; [00200] In another preferred embodiment, the composition is combined with a calorie restriction mimetic. Preferably, the calorie restriction mimetic is selected from the group consisting of: resveratrol; metformin, oxaloacetate; rimonabant; lipoic acid; 2-deoxy-D- glucose; rapamycin; glucosamine; peroxisome proliferator-activated receptor gamma inhibitors, such as rosiglitazone and gugulipids; xxanadin (exenatide), a glucagon- like peptide-1 (GLP-1)modulator; adiponectin; acipimox; hydroxycitrate; dipeptidyl peptidase 4 (DPP-4) inhibitors; Iodoacetate; mannoheptulose (glycolytic inhibitor); modulators of neuropeptide Y (NPY); 4-phenylbutyrate; gymnemoside; spermidine. [00201] The invention also provides a composition, methods and processes as described by the foregoing examples. [00202] The present invention will now be described with reference to the following non- limiting Examples. The description of the Examples is in no way limiting on the preceding paragraphs of this specification, however, is provided for exemplification of the methods and compositions of the invention. Examples [00203] It will be apparent to persons skilled in the milling and pharmaceutical arts that numerous enhancements and modifications can be made to the above described processes without departing from the basic inventive concepts. For example, in some applications the biologically active material may be pretreated and supplied to the process in the pretreated form. All such modifications and enhancements are considered to be within the scope of the present invention, the nature of which is to be determined from the foregoing description and the appended claims. Furthermore, the following Examples are provided for illustrative purposes only, and are not intended to limit the scope of the processes or compositions of the invention. A EXAMPLE 1 – EXTRACTION AND PURIFICATION OF DOLCE164 A.1 STUDY AIM [00204] To extract and identify the most desirable components from the DOLCE164 plant strain using an inert oil - based extraction process. A.2 MATERIALS AND METHODS A.2.1 DOLCE164 PLANT MATERIAL [00205] The DOLCE164 plant is a full-spectrum medicinal cannabis plant (genus species Cannabis sativa) which the inventors subsequently identified to contain cannabidiolic acid (CBDA), cannabidiol (CBD), cannabigerolic acid (CBGA) and cannabidivarin (CBDV) but which has >0.03% tetrahydrocannabinol (THC). The DOLCE164 plant was cultivated, dried and packaged under an Office of Drug Control (ODC) license and permit as per Good Manufacturing Processes (GMP) and TGO 93 and 100 guidelines. A.2.2 EXTRACTION METHOD – OIL BASED [00206] Equipment: The following equipment was used: 10mL glass scintillation bottles with lids; Cobram’s Estate olive oil; plant grinder (similar to a coffee or food grade grinder) pore size up to 50µM; Whatman paper, grade 1; pipettes; weight scale (transfer boats and spoons); Eppendorf tubes; 50mL falcon tubes; bench top centrifuge (Eppendorf Centrifuge 5702); Oz Design Brand 6 Litre Fruit, Wine and Cider Press. [00207] Extraction: Pressing and Centrifugation: All work is undertaken at standard lab temperatures (18-22oC). The buds of DOLCE164 were stripped off hard stalks and the stalks discarded. The grinder was cleaned with 70% EtOH and the grinding compartment was filled with dried plant material. The material was ground on the finest of the three setting for 10 seconds (1-2 mm particle size). The grounds was then mixed with 100ml of olive oil in an autoclaved Schott bottle at a ratio plant/oil of 333mg/mL. It was then placed on a stirrer at room temperature for 1 hour, stirred with magnetic flea (50rpm). The oil plus plant mixture is then put into the Oz Design Brand 6 Litre Fruit, Wine and Cider Press to reclaim the oil component from the plant (the mash). The reclaimed oil was then placed into 50mL falcon tubes and spun at 300g for 15 minutes at room temperature (Isolation 1). The oil was then removed into a clean Schott bottle and keeping track of the volume reclaimed. The recovery of the oil for Isolation 1 is approximately 40%. The mash is discarded following each isolation. To the reclaimed oil, we added a further 333mg/mL ground plant/oil (a further 100ml) material and repeated the 1 hour mix, and reclaimed and re-used oil, until a total of 999µg/mL (3 x 100ml) of plant/oil mixture passed through (Isolation 2). The recovery of the oil for Isolation 2 is approximately 50%. For the final time, we placed into falcon tubes and spin as discussed above (Isolation 3). The recovery of the oil at for Isolation 3 is approximately 50%. We then collected the oil only and placed the oil into Eppendorf tubes for processing. This triplicate extraction method resulted in a total volume of 50ml of final product at a concentration of 48 mg of CBDA to 1ml of olive oil determined using UPLC potency testing using the methods described below. A.2.3 EXTRACTION METHOD – ETHANOL BASED [00208] Extraction: Pressing and Centrifugation: An alternative method includes an extraction based on the use of ethanol. In this method, 500 milligrams of ground plant material of DOLCE164 is mixed with 20 ml of ethanol in a 50ml centrifuge tube. The tubes are shaken vigorously for 60 seconds and then placed into a sonicate bath at 30C for 10 minutes. Samples are then placed on a shaker (200rpm) for 30 minutes. Once completed, placed in a centrifuge, and centrifuged at 4400 rcf for 5 minutes. The supernatant can then assessed in the various preclinical models. A.2.4 ANALYTICAL ANALYSIS [00209] Ultra performance liquid chromatography (UPLC) reverse–phase and liquid chromatography mass spec (LCMS) were used to identify the components in the DOLCE164 concentrate derived from the methods discussed above. The analysis was performed using an integrated (U)HPLC system and a single quadrupole mass spectrometer detector with electrospray ionization (ESI) interface. [00210] The UPLC settings and conditions used were: Cortecs UPLC Shield RP 18, (0 A 1.6uM, 2.1 x 100 mm); Analytical flow rate: 0.7 ml/min; Mobile phase A: Water 0.1% TFA; Mobile phase B: Acetonitrile; Isocratic: 41:59 mobile phase A/mobile phase B; Temp: 35C; Detector: Acquity UPLC PDA; Injection volume: 0.7 uL for 1.0 mg/ml reference standard preparations, sample solutions scaled appropriately; Software: Empower 3CDS. Reference standard solutions were obtained from Novachem, Cerilliant Corporation (TX, USA). These were pre-dissolved solutions all previously shown to be suitable for the generation of calibration curve. [00211] A mixture of 16 cannabinoids in methanol was prepared, containing 10 ppm each of cannabidivarin (CBDV), cannabidiol (CBD), cannabigerol (CBG), tetrahydrocannabivarin (THCV), cannabinol (CBN), Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8- THC), cannabichromene (CBC), their respective acidic forms and cannabicyclol (CBL). All solvents used were LCMS grade, and standards were prepared by diluting with 90 % mobile phase B and 10 % deionized water. Detailed analytical conditions for the UPLC-LCMS analysis are listed in Table 1. [00212] Table 1: The parameters and conditions for UPLC and LCMS analysis
Figure imgf000036_0001
A.3 RESULTS A.3.1 UPLC AND LCMS ANALYTICAL RESULTS [00213] Figure 1 shows the separation of the cannabinoids in a mixed standard solution (that is a reference solution). Under the conditions of the experiment, neutral cannabinoids such as Δ9-THC, CBD and CBL ionize in positive mode, while their respective acidic forms ionize in negative mode. Although CBD and CBG coelute from the column, their molecular weights differ, and they can be identified by mass spectra. In addition, Figure 2 shows a difference between the SID fragmentation patterns obtained for CBD and CBG (that is; as further reference solution). These highly specific results show the advantage of LCMS over LC-UV for analysis and identification of cannabinoids. [00214] Figure 3 presents the UPLC mass chromatogram for DOLCE164 extracted using the oil based method. These results found that the DOLCE164 extract (oil suspension) contained the following components presented in Table 2. Additional components will include flavonoids, proteins, phenols, sterols and esters. These are known components that make up 30-40 % of the full plant cannabis material. Table 4 presents the accompanying exlution times for the UPLC mass chromatograpm for Figure 3 and area under the peaks for the CBD peaks identified. [00215] Table 2: Components in DOLCE164 oil extracted (at two decimal places and rounded up beyond 0.5, and rounded down below 0.5)
Figure imgf000037_0001
[0001] Table 3 presents the DOLCE164 composition extracted using the ethanol extraction and the components quantified using the methods herein described. [0002] Table 3: Components in DOLCE164 ethanol extracted (at two decimal places and rounded up beyond 0.5, and rounded down below 0.5)
Figure imgf000037_0002
[0003] Table 4 presents the accompanying elution times for the UPLC mass chromatograpm for Figure 3 (DOLCE164, oil extracted) and area under the peaks for the CBD peaks identified. [0004] Table 4: elution times and area under the peaks
Figure imgf000038_0001
[0005] Please note that the rarer cannabinoids such as CBDB and CBDP are only detected using Quad MS (which is different to the routine HPLC used for the other cannabinoids). These results are presented in Figure 4. B EXAMPLE 2 – CHARACTERISATION OF THE STABILITY PROPERTIES OF DOLCE164 B.1 STUDY AIM [0006] To assess the stability of the DOLCE164 samples suspended in oil formulation at room temperature. B.2 MATERIALS AND METHODS B.2.1 SAMPLE PREPARATION [0007] Triplicate samples of DOLCE164 were prepared using the methods described above. [0008] For control samples, three representative pre-prepared concentrate samples DOLCE164 (oil and dried flower) were obtained as follows. Oil S=samples were prepared as outlined above: For flower, a portion of homogenized plant material was added to acetonitrile or ethanol and sonicated for 20 minutes. The subsequent extract was filtered through a 0.22 μm syringe tip filter directly into a 2 mL sample vial for analysis. Concentrates were prepared similarly with isopropanol as the extraction solvent. B.2.2 SAMPLING [0009] Samples of DOLCE164 were assayed on a weekly basis and CBDA was used as a main marker / stability indicator. The ACQUITY UPLC H-Class System combined with the CORTECS UPLC Shield RP18 particle chemistry was used to provide a UPLC isocratic separation of main cannabinoids in a 10.5-minute cycle time. Analytical methods using UPLC were used as described above. [0010] Reference standard solutions were obtained from Cerilliant Corporation (Round Rock, TX). These pre-dissolved solutions have been previously shown to be suitable for the generation of calibration curves. [0011] Preparation of standard curves were performed as follows. Linearity of primary cannabinoids (-)Δ9-THC and CBD were determined for 10 concentrations between 0.004 mg/mL and 1.000 mg/mL, prepared via serial dilution in methanol using appropriate standards as a representative demonstration of method linearity. Table 5outlines the cannabinoids used in the separation. [0012] Table 5: The cannabinoids used in the separation
Figure imgf000040_0002
B.3 RESULTS B.3.1 UPLC / MASS SPECTROMETRY ANALYTICAL RESULTS [0013] The ACQUITY UPLC H-Class System combined with the CORTECS UPLC Shield RP18 particle chemistry was used to provide a UPLC isocratic separation of main cannabinoids in a 10.5-minute cycle time. Samples of DOLCE164 were assayed on a weekly basis and CBDA was used as a main marker as a stability indicator. Results presented in Table 6 demonstrate that DOLCE164 is stable at room temperature within an inert oil media over 6 weeks. There is no decarboxylation or product degradation observed over this time frame . [0014] Table 6: Stability of DOLCE164 at room temperature
Figure imgf000040_0001
Figure imgf000041_0001
C EXAMPLE 3 – ASSESSMENTS INTO THE SUPPRESSION OF CYTOKINE MECHANISMS RELATING TO VIRAL REPLICATION STUDIES C.1 BACKGROUND AND AIM [0015] SARS-CoV-2 infection activates innate and adaptive immune response, thus sustaining the resolution of COVID-19. While a rapid and well-coordinated immune response represents the first line of defence against viral infection, an excessive inflammatory innate response and dysregulated adaptive host immune defence may cause harmful tissue damage at both at the site of virus entry and at systemic level. [0016] Three different doses of DOLCE164 was assessed against its ability to regulate specific inflammation biomarkers relating to cytokine development and regulation: these include: iNOS activate, TNF – gamma and IL-Beta. iNOS expression is increased by viral loading. C.2 MATERIAL AND METHODS [0017] The following DOLCE164 concentrations were used: 1/1000 dilution of extract – 10UL; 1/3000 dilution of extract – 3 UL and 1/10000 dilution of extract – 1UL. There was n=6 per experiment. [0018] The immortalized microglia cell line, BV2, was purchased from the American Tissue Culture Collection. BV2 were cultured in RPMI media containing gentamycin and supplemented with 10% FBS for expansion and 5% fetal bovine serum (FBS) when plated for experiments. All cells were from between passage numbers 39 and 45. Cells were plated at 45,000 cells/mm2 and treated 24 hours after plating with phosphate buffered saline (PBS, as a control) or interleurkin-1B + interferon-y (IL-1B+IFNy, to induce inflammation). To test the effects of DOLCE164 to alter the inflammatory response, DOLCE164 was applied with one hour before inflammation (pre-treat) or one hour after (post-treat). DOLCE164 extracted were applied at 10uL, 3uL or 1uL from isolated obtained using the original extraction protocol: range determined from mass spec data = 1.0 – 0.1ug CBDA. [0019] Data for replicates within experiments were averaged and then data from at least three independent experiments was analysed using Graph Pad Prism or students-t-test. C.3 RESULTS [0020] In viral induced inflammatory activated cells, DOLCE 164 normalizes expression towards control levels as showed by iNOS expression (see Figure 5), it also normalizes viral loading related inflammation in cells as measured by TNF-gamma suppression (see Figure 6) and suppresses IL-beta loaded cells (inflammation cells) (see Figure 7). D EXAMPLE 4 – COX-2 EXPRESSION STUDIES IN HUMAN MUSCLE CELLS | DISEASE MODEL ASTHMA (SMOOTH MUSCLE CELLS) D.1 BACKGROUND AND AIM [0021] Asthma is a chronic inflammatory disease in which COX-2 levels within the lung are elevated. Our preclinical studies conducted in cells using immunohistochemistry analysis demonstrated that DOLCE164 strains can suppress and inhibit the expression of COX-2 in human derived smooth muscle cells. D.2 MATERIALS AND METHODS D.2.1 COX-2 PROTEIN LEVELS ASSAY [0022] Cells were fixed for 10 min with 4% paraformaldehyde (PFA) in PBS. After 3 x 5 minutes washing with PBS, cells were incubated with primary antibodies (anti-COX2) 1:1000 overnight at 4oC, and after 3 x 5 minutes washing in PBS, cells were then incubated in appropriate fluorescent secondary antibody 1:250 (Invitrogen) for 2 hours at room temperature. After a final wash, as previous, cells nuclei were stained with DAPI in the mounting media. Photomicrographs were taken of the cells in three fields of view per well from duplicate wells and analysed using Fiji for area coverage of each marker. [0023] The concentration of DOLCE164 used was 10 U. D.3 RESULTS [0024] The results of the COX-2 protein levels assay are presented below in Table 7 as an average +/- SEM. [0025] Table 7: Results of the COX-2 protein levels assay
Figure imgf000043_0001
[0026] When compared to CBD alone, DOLCE strains were up to three times more powerful in suppressing COX-2 both pre and post inflammatory insult. E EXAMPLE 5 – STUDIES RELATING TO THE SUPPRESSION OF IL-17 | MODEL USED FOR SKIN DISORDERS SUCH AS PSORIASIS E.1 BACKGROUND AND AIM [0027] IL-17 is proved to be the key cytokine which drives psoriasis directly. Emerging evidence indicates that major sources of IL-17A in patients with psoriatic disease are mast cells, γδ T cells, αβ T cells, and innate lymphoid cells in lesional skin and synovial fluid. Within the skin and joints, IL-17A acts on cellular targets, including keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts, to stimulate production of various antimicrobial peptides, chemokines, and proinflammatory and proliferative cytokines, which, in turn, promote tissue inflammation and bone remodeling E.2 MATERIALS AND METHODS [0028] Human derived cells (keratinocytes) media was harvested following treatment initiation was centrifuged briefly to remove particulates (300 g for 10 min). Cytokine and chemokine levels in the cell media were measured using a Bio-Plex 200 with a 96-well magnetic plate assay according to the manufacturer's instructions (Bio-Rad). Cytokines and chemokines measured included IL-1α, IL-1β, IL-2, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G- CSF, GM-CSF, IFNγ, TNFα, CXCL1 (KC), CCL2 (MCP-1), and CCL5 (RANTES). All samples were run in duplicate and data were analyzed with the Bio-Plex Manager software. [0029] The concentration of DOLCE164 used was 1/1000 dilution of extract – 10U, 1/3000 dilution of extract – 3U and 1/10000 dilution of extract – 1U. E.3 RESULTS [0030] The results of the IL-2 protein levels assay are presented below in Table 8 as an average +/- SEM. [0031] Table 8: Results of the IL-2 protein levels assay
Figure imgf000044_0001
These results demonstrate a significant reduction is the expression of IL-17 caused by DOLCE164 versus CBD alone. F EXAMPLE 6 – FURTHER CHARACTERISATION OF DOLCE164 F.1 STUDY AIM [0032] The compositional analysis of DOLCE164 extracted via oil, using UPLC/MS methods (as outlined in the above examples). F.2 MATERIALS AND METHODS [0033] The ACQUITY UPLC H-Class System combined with the CORTECS UPLC Shield RP18 particle chemistry was used to provide a UPLC isocratic separation of main cannabinoids in a 10.5-minute cycle time. Samples of DOLCE164 were assayed on a weekly basis and CBDA was used as a main marker as a stability indicator. Results presented in Table 6 demonstrate that DOLCE164 is stable at room temperature within an inert oil media over 6 weeks. There is no decarboxylation or product degradation observed over this time frame [0034] Equipment: The following equipment was used: 10mL glass scintillation bottles with lids; Cobram’s Estate olive oil; plant grinder (similar to a coffee or food grade grinder) pore size up to 50µM-80µM; Whatman paper, grade 1; pipettes; weight scale (transfer boats and spoons); Eppendorf tubes; 50mL falcon tubes; bench top centrifuge (Eppendorf Centrifuge 5702); Oz Design Brand 6 Litre Fruit, Wine and Cider Press. [0035] Extraction: Pressing and Centrifugation: All work is undertaken at standard lab temperatures (18-22oC). The buds of DOLCE164 were stripped off hard stalks and the stalks discarded. The grinder was cleaned with 70% EtOH and the grinding compartment was filled with dried plant material. The material was ground on the finest of the three setting for 10 seconds (1-2 mm particle size). The grounds was then mixed with 100ml of olive oil in an autoclaved Schott bottle at a ratio plant/oil of 333mg/ml. It was then placed on a stirrer at room temperature for 1 hour, stirred with magnetic flea (50rpm). The oil plus plant mixture is then put into the Oz Design Brand 6 Litre Fruit, Wine and Cider Press to reclaim the oil component from the plant (the mash). The reclaimed oil was then placed into 50mL falcon tubes and spun at 300g for 15 minutes at room temperature (Isolation 1). The oil was then removed into a clean Schott bottle and keeping track of the volume reclaimed. The recovery of the oil for Isolation 1 is approximately 40%. The mash is discarded following each isolation. To the reclaimed oil, we added a further 333mg/mL ground plant/oil (a further 100ml) material and repeated the 1hour mix, and reclaimed and re-used oil, until a total of 999µg/mL (3 x 100ml) of plant/oil mixture passed through (Isolation 2). The recovery of the oil for Isolation 2 is approximately 50%. For the final time, we placed into falcon tubes and spin as discussed above (Isolation 3). The recovery of the oil at for Isolation 3 is approximately 50%. We then collected the oil only and placed the oil into Eppendorf tubes for processing. This triplicate extraction method resulted in a total volume of 50ml of final product at a concentration of 48 mg of CBDA to 1ml of olive oil determined using UPLC potency testing using the methods described below. F.3 RESULTS [0036] The results of the UPLC analysis are presented below in Table 9. [0037] Table 9 presents the DOLCE164 composition extracted using the ethanol extraction and the components quantified using the UPLC methods herein described
Figure imgf000045_0001
[0038] By expanding the pore size in the grinder system from 50µM to 80µM, we were able to extract cannabinol (CBN) 1-3% in the final oil extract product.

Claims

CLAIMS 1. A composition comprising the following cannabinoids: w/w % CBDA 40-60%; CBD 1-5%; CBG 1-10%; CBDP 1-5%; CBDB 1-5%; CBN 1-3%; CBGA 1-10%; THC <1%; and an additional active ingredient. 2. The composition of claim 1, wherein the cannabinoids are present in amounts selected from the group consisting of: Composition 1 comprising: w/w % CBDA 50%; CBD 2%; CBG 5%; CBDP 2%; CBDB 2%; CBN 3%; CBGA 5%; THC <0.3%; and an additional active ingredient. and Composition 2 comprising: w/w % CBDA 45%; CBD 1%; CBG 4%; CBDP 1%; CBDB 2%; CBN 2%; CBGA 4%; THC <0.
2%; and an additional active ingredient.
3. The composition of any one of the above mentioned claims, further comprising an oil selected from the group consisting of: a synthetic oil; plant based oil; mineral oil; canola oil; and olive oil.
4. The composition of any one of the above mentioned claims, wherein the composition comprises less than 5% w/w terpenes.
5. The composition of any one of the above mentioned claims, wherein the composition comprises less than 2% w/w organic plant material.
6. The composition of any one of the above mentioned claims, wherein the composition comprises less than 2% w/w of plant phenols.
7. The composition of any one of the above mentioned claims, wherein the cannabinoid component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml.
8. The composition of any one of the above mentioned claims, wherein the CBDA component of the composition is selected from the group consisting of: between 1 and 500mg/ml; between 10 and 100mg/ml; be at a concentration of 50mg/ml.
9. The composition of any one of the above mentioned claims having a UPLC mass chromatogram corresponding to Figure 3 utilising the conditions described in Example 1.
10. The composition of any one of the above mentioned claims, wherein additional active ingredient is selected from the group consisting of: diclofenac, prednisolone and celebrex.
11. A pharmaceutical composition comprising the composition of any one of claims 1 to 10 together with a pharmaceutically acceptable carrier.
12. A dosage form comprising the composition of any one of claims 1 to 10.
13. The dosage form of claim 12, wherein the CBDA component of the composition is selected from the group consisting of: between 1mg and 1000mg; between 1mg and 500mg; between 1 and 100mg; less than 400mg; less than 300mg; less than 200mg and less than 100mg.
14. The dosage form of any one of claims 12 to 13, wherein the CBDA component of the composition is selected from the group consisting of: 600mg; 400mg; 300mg; 200mg; 100mg; 50mg; 10mg; 5mg; 2mg; 1mg.
15. A method of treating a disorder, said method comprising administering to a patient in need thereof a therapeutically effective amount of the dosage form of claims 12 to 14.
16. The method of claim 15, wherein the disorder is a non-neurological disorder.
17. The method of any one of claims 15 to 16, wherein the non-neurological disorder is selected from the group consisting of: acute and chronic skin disorders (such as dermatitis, psoriasis, eczema and vitiligo); skin disorders (inflammatory and non- inflammatory); disorders affecting the pulmonary system (such as neumonitis, asthma and chronic inflammatory lung disease (including chronic obstructive pulmonary disease (COPD)); disorders affecting the blood (such as anemia of chronic disease, aplastic anemia, erythrocytosis, hemochromatosis, hypercoagulable disorder, immune thrombocytopenic purpura, iron deficiency anemia and leucocytosis); disorders affecting the bone (such as bone cancer, bone density, bone infections, osteogenesis imperfecta, osteonecrosis, osteoporosis, paget's disease of the bone and rickets); non neurological cancers (such as breast cancer, skin cancers, prostate cancer, bladder cancer and liver cancer); blood borne disorders (such as common bloodborne diseases (including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)) and viral hemorrhagic fevers (including ebola virus disease and lassa fever; and lipid metabolism disorders (such as familial combined hyperlipidemia (FCHL), familial defective apolipoprotein B-100, high total cholesterol (including 350 to 550 mg/dL), familial dysbetalipoproteinemia (including type 3 hyperlipoproteinemia), familial hypertriglyceridemia, heterozygous familial hypercholesterolemia and diabetes.
18. Use of the composition of claims 1 and 10 in the manufacture of a medicament for the treatment of a disorder.
19. A process of extracting the composition of claims 1 to 10 from cannabis plant material, said process comprising the steps of: (1) Grinding the cannabis plant material to a sufficient grind size; (2) Contacting the grind produced by step a) with oil; (3) Mixing the grind and oil for a sufficient time period to form a mixture; (4) Pressing the mixture to reclaim the oil; (5) Centrifuging the oil to further refine the oil; and (6) Collecting the oil extract in a suitable container.
20. A process of extracting the composition of claims 1 to 10 from cannabis plant material, said process comprising the steps of: (1) Grinding the cannabis plant material to a sufficient grind size; (2) Contacting the grind produced by step a) with an alcohol; (3) Mixing the grind and the alcohol for a sufficient time period to form a mixture; (4) Sonicating the mixture; (5) Centrifuging the mixture; and (6) Collecting the alcohol extract in a suitable container.
21. A product produced from the process of claims 19 or 20.
22. A kit comprising the dosage form of claims 12 to 15 together with instructions for use.
23. The composition, methods and processes as described by the foregoing examples.
PCT/AU2023/050008 2022-01-10 2023-01-10 Compositions and methods for treating non-neurological disorders with combination products comprising a cannabinoid mixture rich in cannabidiolic acid (cbda) along with an additional active agent WO2023130161A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024073812A1 (en) * 2022-10-06 2024-04-11 Neurotech International Ltd Methods for treating paediatric neurological disorders
WO2024082014A1 (en) * 2022-10-21 2024-04-25 Dolce Cann Global Pty Ltd Compositions comprising cannabidiolic acid and fatty acids

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011110866A1 (en) * 2010-03-12 2011-09-15 Gw Pharma Limited Phytocannabinoids in the treatment of cancer
WO2016004121A1 (en) * 2014-07-01 2016-01-07 MJAR Holdings, LLC High cannabidiol cannabis strains
WO2018175796A1 (en) * 2017-03-24 2018-09-27 STAUFF, Deidra Skin care compositions and methods
WO2019199861A2 (en) * 2018-04-09 2019-10-17 Ellevet Sciences Hemp extract for treatment of pain in animals
WO2019210401A1 (en) * 2018-05-01 2019-11-07 Willinsky Michael Novel anti-inflammatory, analgesic, anti-depressant cannabinoid and methods related to manufacture of same
WO2020093101A1 (en) * 2018-11-09 2020-05-14 Agriculture Victoria Services Pty Ltd Plants with a cannabinoid profile enriched for cannabidiol
WO2020223510A1 (en) * 2019-04-30 2020-11-05 Greenway Herbal Products, Llc Cannabinoid compositions and methods of using
WO2021188983A1 (en) * 2020-03-20 2021-09-23 The Queen's Medical Center Cannabinoid compositions

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011110866A1 (en) * 2010-03-12 2011-09-15 Gw Pharma Limited Phytocannabinoids in the treatment of cancer
WO2016004121A1 (en) * 2014-07-01 2016-01-07 MJAR Holdings, LLC High cannabidiol cannabis strains
WO2018175796A1 (en) * 2017-03-24 2018-09-27 STAUFF, Deidra Skin care compositions and methods
WO2019199861A2 (en) * 2018-04-09 2019-10-17 Ellevet Sciences Hemp extract for treatment of pain in animals
WO2019210401A1 (en) * 2018-05-01 2019-11-07 Willinsky Michael Novel anti-inflammatory, analgesic, anti-depressant cannabinoid and methods related to manufacture of same
WO2020093101A1 (en) * 2018-11-09 2020-05-14 Agriculture Victoria Services Pty Ltd Plants with a cannabinoid profile enriched for cannabidiol
WO2020223510A1 (en) * 2019-04-30 2020-11-05 Greenway Herbal Products, Llc Cannabinoid compositions and methods of using
WO2021188983A1 (en) * 2020-03-20 2021-09-23 The Queen's Medical Center Cannabinoid compositions

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Evaluating the Safety and Ecacy of Full-Spectrum Medicinal Cannabis (FEN164) in Children with ASD", AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY (ANZCTR), XP093059207, Retrieved from the Internet <URL:https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000760875> [retrieved on 20230629] *
FORMATO MARIALUISA, CRESCENTE GIUSEPPINA, SCOGNAMIGLIO MONICA, FIORENTINO ANTONIO, PECORARO MARIA TOMMASINA, PICCOLELLA SIMONA, CA: "(‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research", MOLECULES, vol. 25, no. 11, pages 2638, XP093080113, DOI: 10.3390/molecules25112638 *
NEUROTECH: "Preclinical Success with Targeted Combination Therapies: Prednisone + NTI164", ASX ANNOUNCEMENT, NEUROTECH INTERNATIONAL LTD, 1 December 2021 (2021-12-01), pages 1 - 5, XP093080227, Retrieved from the Internet <URL:https://www.investi.com.au/api/announcements/nti/1ab51ffb-762.pdf> [retrieved on 20230908] *
SINCLAIR SARAH: "World's first study of THC-free medical cannabis in autistic children is launched", CANNABIS HEALTH, PP INTELLIGENCE LTD., 10 May 2021 (2021-05-10), pages 1 - 3, XP093080221, Retrieved from the Internet <URL:https://cannabishealthnews.co.uk/2021/05/10/thc-free-medical-cannabis-in-autistic-children/> [retrieved on 20230908] *
TZIMAS PETROS S., PETRAKIS ELEFTHERIOS A., HALABALAKI MARIA, SKALTSOUNIS LEANDROS A.: "Effective determination of the principal non-psychoactive cannabinoids in fiber-type Cannabis sativa L. by UPLC-PDA following a comprehensive design and optimization of extraction methodology", ANALYTICA CHIMICA ACTA, ELSEVIER, AMSTERDAM, NL, vol. 1150, 1 March 2021 (2021-03-01), AMSTERDAM, NL , pages 338200, XP093059201, ISSN: 0003-2670, DOI: 10.1016/j.aca.2021.338200 *
VÁGI ERIKA, BALÁZS MARGIT, KOMÓCZI ATTILA, KISS ISTVÁN, MIHALOVITS MÁTÉ, SZÉKELY EDIT: "Cannabinoids Enriched Extracts from Industrial Hemp Residues", PERIODICA POLYTECHNICA. CHEMICAL ENGINEERING, BUDAPEST, HU, vol. 63, no. 2, HU , pages 357 - 363, XP093059204, ISSN: 0324-5853, DOI: 10.3311/PPch.12896 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024073812A1 (en) * 2022-10-06 2024-04-11 Neurotech International Ltd Methods for treating paediatric neurological disorders
WO2024082014A1 (en) * 2022-10-21 2024-04-25 Dolce Cann Global Pty Ltd Compositions comprising cannabidiolic acid and fatty acids

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