WO2024082014A1 - Compositions comprenant de l'acide cannabidiolique et des acides gras - Google Patents

Compositions comprenant de l'acide cannabidiolique et des acides gras Download PDF

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Publication number
WO2024082014A1
WO2024082014A1 PCT/AU2023/051032 AU2023051032W WO2024082014A1 WO 2024082014 A1 WO2024082014 A1 WO 2024082014A1 AU 2023051032 W AU2023051032 W AU 2023051032W WO 2024082014 A1 WO2024082014 A1 WO 2024082014A1
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composition
omega
thc
acid
group
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PCT/AU2023/051032
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English (en)
Inventor
Patrick Steve CALABRIA
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Dolce Cann Global Pty Ltd
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Priority claimed from AU2022903123A external-priority patent/AU2022903123A0/en
Application filed by Dolce Cann Global Pty Ltd filed Critical Dolce Cann Global Pty Ltd
Publication of WO2024082014A1 publication Critical patent/WO2024082014A1/fr

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    • 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
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • 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
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • 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

Definitions

  • compositions and methods for treating disorders Field of the Invention [0001]
  • the present invention relates to compositions comprising cannabinoids.
  • the present invention also relates to pharmaceutical compositions, dosage forms and methods of treating 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 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 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
  • 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
  • Neurological Disorders Examples of neurological disorders that are “neuro-inflammatory based” include: Alzheimer’s disease (Alzheimer’s disease is the most prevalent chronic, progressive neurodegenerative disease, and cause of dementia); Parkinson’s disease; multiple sclerosis; amyotrophic lateral sclerosis; cerebral ischemia; traumatic brain injury; rheumatoid arthritis; chronic migraine; and epilepsy. C.
  • 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 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 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.
  • CBD cannabidiol
  • TGA Australian Therapeutic Goods Administration
  • the invention is a composition comprising the following: w/w % CBDA 10-90%; an essential fatty acid 0.1-5%; and an unsaturated fatty acid 3-15%.
  • the essential fatty acid is selected from the group consisting of: y-linolenic acid 0.1-5%; eicosanoic acid 0.1-5%; eicosenoic acid 0.1-5%; and eicosadienoic acid 0.1-5%.
  • the unsaturated fatty acid is selected from the group consisting of y-linolenic acid 0.5-2%; eicosanoic acid 0.5-2%; eicosenoic acid 0.5-2%; and eicosadienoic acid 0.5-2%.
  • the unsaturated fatty acid is selected from the group consisting of: omega 31-70%; omega 61-70%; omega 71-70%; and omega 91- 70%.
  • the composition comprises omega 35-60%; omega 65-60%; omega 75-60%; and omega 95-60%.
  • the composition comprises CBD 0.1-10%.
  • the composition comprises terpene 0.5-2%
  • the composition comprises THC ⁇ 0.3%.
  • the following components are not detectable: D9-THC-A; CBDV; CBG-A; CBG; THCV; CBN; D8-THC; and CBC.
  • the composition is selected from the group consisting of: w/w % CBDA 30-70%; omega 73-15%; and THC ⁇ 0.3%. And w/w % CBDA 40-60%; omega 74-11%; and THC ⁇ 0.2%.
  • the components are present in amounts selected from the group consisting of: w/w % CBD 1-5%; CBDA 30-70%; omega 73-15%; and THC ⁇ 0.3%. And w/w % CBD 1-5%; CBDA 40-60%; omega 74-11%; and THC ⁇ 0.2%.
  • the components are present in amounts selected from the group consisting of: w/w % CBD 1-5%; CBDA 30-70%; omega 7 -15%; THC ⁇ 0.3%; wherein the following components are not detectable: D9-THC-A CBDV CBG-A CBG THCV CBN D8-THC; and CBC. and w/w % CBD 1-5%; CBDA 40-60%; omega 74-11%; THC ⁇ 0.2%; wherein the following components are not detectable: D9-THC-A CBDV CBG-A CBG THCV CBN D8-THC; and CBC.
  • the components are present in amounts selected from the group consisting of: y-linolenic acid 0.1-5% eicosanoic acid 0.1-5%; eicosenoic acid 0.1-5%; and/or eicosadienoic acid 0.1-5%.
  • the components are present in amounts selected from the group consisting of: y-linolenic acid 0.1-5% eicosanoic acid 0.1-1%; eicosenoic acid 0.1-1%; and/or eicosadienoic acid 0.1-1%.
  • the components are present in amounts selected from the group consisting of: omega 31-50%; omega 61-60%; omega 73-15%; and/or omega 91-20%.
  • the components are present in amounts selected from the group consisting of: omega 310-30%; omega 620-60%; omega 78-10%; and/or omega 92.0-15%.
  • the composition comprises the following components: w/w % CBD 1-5%; CBDA 40-50%; terpenes 0.1-5%; THC ⁇ 0.2%. omega 31-50%; omega 61-60%; omega 73-15%; omega 91-20%.
  • the composition comprises the following components: w/w % CBD 1-5%; CBDA 45-50%; terpenes 0.1-5%; THC ⁇ 0.2%. omega 310-30%; omega 620-60%; omega 78-10%; and/or omega 92.0-15%.
  • the composition further comprises vitamins, minerals and amino acids.
  • the composition comprises components as presented in Table 10.
  • the composition comprises components as presented in Table 11.
  • the composition comprises components as presented in Table 12.
  • the composition comprises components as presented in Table 13.
  • 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 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 is derived from cannabis plant seeds.
  • the composition is combined with a CBD composition derived from flower material of a cannabis plant.
  • 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 nutraceutical composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is a medical food composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is a dietary supplement composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is a functional food composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is an animal food composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is a dosage form comprising the composition of the first aspect of the invention.
  • 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.
  • the CBDA component of the composition is selected from the group consisting of: 600mg; 400mg; 300mg; 200mg; 100mg; 50mg; 10mg; 5mg; 2mg; 1mg.
  • 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 disorder is a neurological disorder.
  • the neurological disorder is selected from the group consisting of: Alzheimer’s disease; Parkinson’s disease; multiple sclerosis; amyotrophic lateral sclerosis; cerebral ischemia; traumatic brain injury; rheumatoid arthritis; chronic migraine; epilepsy and autism spectrum disorder (ASD).
  • 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 (
  • the composition is administered concurrently, simultaneously or in combination with a CBD composition derived from cannabis plant flowers.
  • the invention is the use of the composition of the first aspect of the invention in the manufacture of a medicament for the treatment of a disorder.
  • the invention is a method of improving the condition of a subject, said method comprising administering to a subject in need thereof an effective amount of the dosage form of the invention.
  • the invention is the use of the composition of the first aspect of the invention in the manufacture of a medicament for improving the condition of a subject.
  • the invention is a process of extracting the composition of the first aspect of the invention from cannabis plant seed, said process comprising the steps of: grinding the cannabis plant seed to a sufficient grind size; contacting the grind produced by step a) with oil; mixing the grind and oil for a sufficient time period to form a mixture; pressing the mixture to reclaim the oil; centrifuging the oil to further refine the oil; and collecting the oil extract in a suitable container.
  • the invention is a process of extracting the composition of the first aspect of the invention from cannabis plant seed, said process comprising the steps of: grinding the cannabis plant seed to a sufficient grind size; contacting the grind produced by step a) with an alcohol; mixing the grind and alcohol for a sufficient time period to form a mixture; sonicating the mixture; centrifuging the mixture; and collecting the alcohol extract in a suitable container.
  • the alcohol is ethanol or isopropanol.
  • the invention is a product produced from the process of the invention.
  • the invention is a kit comprising the dosage form of the invention together with instructions for use.
  • the invention is the composition, methods and processes as described by the foregoing examples.
  • 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 [0073] Below is a brief description of each of the figures and drawings. [0074] Figure 1 is a UPLC mass 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 is a UPLC mass chromatogram for DOLCE164.
  • Figure 4 presents Quad MS chromatograms of DOLCE164 to identify CBDB and CBDP.
  • Figure 5 demonstrates that DOLCE164 normalises inflammation-induced viral replication as measured by iNOZ 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: w/w % CBDA 10-90%; an essential fatty acid 0.1-5%; and an unsaturated fatty acid 3-15%.
  • 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. [00102] In a further preferred embodiment, the invention provides a composition wherein the said listed cannabinoids are a mixture of plant derived and synthetic cannabinoids. [00103] 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. [00104] In a further preferred embodiment, the composition comprises less than 5% w/w terpenes. [00105] In a further preferred embodiment, the composition comprises less than 2% w/w organic plant material.
  • the composition comprises less than 2% w/w of plant phenols.
  • the composition comprises components selected from the group consisting of: flavonoids, proteins, sterols and esters.
  • 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.
  • 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; and at 6 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; and at 6 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.
  • the composition is adapted for the treatment of a 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 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 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.
  • Pharmaceutical Compositions [00132] 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.
  • 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); 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 and diluting agents; emulsifying agents; hydro
  • 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. 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.
  • 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.
  • the composition is stable at temperatures selected from the group consisting of: - 4°C, 4°C, 18°C and 25°C.
  • Other Compositions [00141] In another preferred embodiment, the composition is derived from cannabis plant seeds. [00142] In another preferred embodiment, the composition is combined with a CBD composition derived from flower material of a cannabis plant. [00143] In another aspect, the invention is a pharmaceutical composition comprising the composition of the first aspect of the invention together with a pharmaceutically acceptable carrier. [00144] In another aspect, the invention is a nutraceutical composition comprising the composition of the first aspect of the invention together with an acceptable carrier. [00145] In another aspect, the invention is a medical food composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is a dietary supplement composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is a functional food composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • the invention is an animal food composition comprising the composition of the first aspect of the invention together with an acceptable carrier.
  • Dosage Form [00149] 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.
  • 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.
  • 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.
  • the dosage form is form selected from the group consisting of: a solution, tablet, capsule, wafer, dry power sachet and vial [00152]
  • the dosage form is stored in a sealed and sterile container.
  • Method for treating [00153]
  • 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.
  • 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.
  • T 1/2 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.
  • 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 caused by neuro-inflammation.
  • the disorder is a neurological disorder or a non-neurological disorder.
  • the disorder is a neurological disorder.
  • the neurological disorder is selected from the group consisting of: Alzheimer’s disease; Parkinson’s disease; multiple sclerosis; amyotrophic lateral sclerosis; cerebral ischemia; traumatic brain injury; rheumatoid arthritis; chronic migraine; epilepsy and autism spectrum disorder (ASD).
  • 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 the 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 effect of the administered therapeutic composition can be monitored by standard diagnostic procedures.
  • Use of a composition in the manufacture of a medicament 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.
  • the invention is the use of the composition of the first aspect of the invention in the manufacture of a medicament for the treatment of a disorder.
  • the invention is a method of improving the condition of a subject, said method comprising administering to a subject in need thereof an effective amount of the dosage form of the invention.
  • the invention is the use of the composition of the first aspect of the invention in the manufacture of a medicament for improving the condition of a subject.
  • the invention also provides a process of extracting the composition of the first aspect of the invention from cannabis plant seed, said process comprising the steps of: 1) Grinding the cannabis plant seed 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 seed 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 seed, said process comprising the steps of: 1) Grinding the cannabis plant seed 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, and 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 [00184] The invention also provides a product produced from the process described above. Kit [00185] The invention also provides a kit comprising the dosage form of one aspect of the invention together with instructions for its use.
  • Devices are within the scope of the invention.
  • 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 [00187] 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.
  • 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.
  • 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.
  • 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 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), cannabinol (CBN) and cannabidivarin (CBDV) but which has >0.03% tetrahydrocannabinol (THC).
  • CBDDA cannabidiolic acid
  • CBD cannabidiol
  • CBD cannabinol
  • 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 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%.
  • 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.
  • 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) C C C C C C T T Organic plant material – including phenols 2% 2% [00208]
  • 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) C Cannabidiol acid (CBD-A) 45.28% 45% Cannabidiol (CBD) 1.39%; 1%; C C C C T T O [ [00211] Table 4 presents the accompanying elution times for the UPLC mass chromatograpm for Figure 3 (DOLCE164) and area under the peaks for the CBD peaks identified.
  • DOLCE164 oil and dried flower
  • Oil S samples were prepared as outlined above: For flowers, 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 [00217] 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. [00220]
  • 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.
  • DOLCE164 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.
  • DOLCE164 phosphate buffered saline
  • IL-1B+IFNy interleurkin-1B + interferon-y
  • DOLCE164 was applied with one hour before inflammation (pre-treat) or one hour after (post-treat).
  • 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 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 frame [00243]
  • Equipment The following equipment was used: 10mL glass scintillation bottles with lids; Cobram’s Estate olive oil; plant grinder (similar to a coffee 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.
  • C C C T C D C T CBD + (CBD-A*0.877) % amount 60.85 58.22
  • CBD cannabinol
  • G.2.1 METHODS OF SEED PREPARATION The seeds were extracted and prepared using the methods set out in Figure 8.
  • the analysis utilized gas chromatography mass spectrometry (GCMS) coupled with matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) (LoQ: 0.01 mg/ml, LoD: 0.01 mg/ml).
  • G.3 RESULTS [00251] See Tables 10, 11 and 12 for cannabinoid analysis. [00252] Table 10 presents cannabinoid analysis of DOLCE164 seed oil using olive oil, Sample Size: 8.
  • Table 14 presents the comparison to widely available hemp oil products. Analysis/ Component DOLCE164 Hemp Gold TM Go Healthy TM C E y E E E T O 3

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Abstract

La présente invention concerne des compositions comprenant de l'acide cannabidiolique et des acides gras ; des produits pharmaceutiques, des nutraceutiques, des aliments médicaux, des compléments alimentaires, des aliments fonctionnels, des aliments pour animaux et des formes galéniques comprenant cette composition, des procédés d'extraction de cette composition à partir de cannabis et des produits obtenus selon ce procédé ; et des procédés et des utilisations associés.
PCT/AU2023/051032 2022-10-21 2023-10-18 Compositions comprenant de l'acide cannabidiolique et des acides gras WO2024082014A1 (fr)

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AU2022903123A AU2022903123A0 (en) 2022-10-21 Compositions and methods for treating disorders

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Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011110866A1 (fr) * 2010-03-12 2011-09-15 Gw Pharma Limited Phytocannabinoïdes utilisés dans le traitement du cancer
WO2016004121A1 (fr) * 2014-07-01 2016-01-07 MJAR Holdings, LLC Souches de cannabis à teneur élevée en cannabidiol
WO2018175796A1 (fr) * 2017-03-24 2018-09-27 STAUFF, Deidra Compositions et procédés de soin de la peau
WO2019023668A1 (fr) * 2017-07-27 2019-01-31 Shaaban Basil Adil Composition de cannabinoïdes présentant un profil d'acides gras de l'excipient optimisé
WO2019199861A2 (fr) * 2018-04-09 2019-10-17 Ellevet Sciences Extrait de chanvre pour le traitement de la douleur chez les animaux
WO2019210401A1 (fr) * 2018-05-01 2019-11-07 Willinsky Michael Nouveau cannabinoïde anti-inflammatoire, analgésique, antidépresseur et procédés associés à la fabrication de celui-ci
WO2020093101A1 (fr) * 2018-11-09 2020-05-14 Agriculture Victoria Services Pty Ltd Plantes à profil cannabinoïde enrichi en cannabidiol
WO2020223510A1 (fr) * 2019-04-30 2020-11-05 Greenway Herbal Products, Llc Compositions de cannabinoïdes et procédés d'utilisation
WO2021188983A1 (fr) * 2020-03-20 2021-09-23 The Queen's Medical Center Compositions de cannabinoïdes
WO2022011393A1 (fr) * 2020-07-08 2022-01-13 Shaman Naturals, Llc Compositions pour la prévention et le traitement du diabète
WO2023076765A1 (fr) * 2021-10-29 2023-05-04 Greenway Herbal Products, Llc Compositions de cannabinoïdes et d'acides gras oméga et leurs méthodes d'utilisation
WO2023130161A1 (fr) * 2022-01-10 2023-07-13 Dolce Cann Global Pty Ltd Compositions et procédés de traitement de troubles non neurologiques avec des produits mixtes comprenant un mélange cannabinoïde riche en acide cannabidiolique (cbda) conjointement avec un principe actif supplémentaire
WO2023130160A1 (fr) * 2022-01-10 2023-07-13 Dolce Cann Global Pty Ltd Compositions et méthodes permettant le traitement de troubles non neurologiques à l'aide de produits combinés comprenant un mélange de cannabinoïdes riche en acide cannabidiolique (cbda).

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011110866A1 (fr) * 2010-03-12 2011-09-15 Gw Pharma Limited Phytocannabinoïdes utilisés dans le traitement du cancer
WO2016004121A1 (fr) * 2014-07-01 2016-01-07 MJAR Holdings, LLC Souches de cannabis à teneur élevée en cannabidiol
WO2018175796A1 (fr) * 2017-03-24 2018-09-27 STAUFF, Deidra Compositions et procédés de soin de la peau
WO2019023668A1 (fr) * 2017-07-27 2019-01-31 Shaaban Basil Adil Composition de cannabinoïdes présentant un profil d'acides gras de l'excipient optimisé
WO2019199861A2 (fr) * 2018-04-09 2019-10-17 Ellevet Sciences Extrait de chanvre pour le traitement de la douleur chez les animaux
WO2019210401A1 (fr) * 2018-05-01 2019-11-07 Willinsky Michael Nouveau cannabinoïde anti-inflammatoire, analgésique, antidépresseur et procédés associés à la fabrication de celui-ci
WO2020093101A1 (fr) * 2018-11-09 2020-05-14 Agriculture Victoria Services Pty Ltd Plantes à profil cannabinoïde enrichi en cannabidiol
WO2020223510A1 (fr) * 2019-04-30 2020-11-05 Greenway Herbal Products, Llc Compositions de cannabinoïdes et procédés d'utilisation
WO2021188983A1 (fr) * 2020-03-20 2021-09-23 The Queen's Medical Center Compositions de cannabinoïdes
WO2022011393A1 (fr) * 2020-07-08 2022-01-13 Shaman Naturals, Llc Compositions pour la prévention et le traitement du diabète
WO2023076765A1 (fr) * 2021-10-29 2023-05-04 Greenway Herbal Products, Llc Compositions de cannabinoïdes et d'acides gras oméga et leurs méthodes d'utilisation
WO2023130161A1 (fr) * 2022-01-10 2023-07-13 Dolce Cann Global Pty Ltd Compositions et procédés de traitement de troubles non neurologiques avec des produits mixtes comprenant un mélange cannabinoïde riche en acide cannabidiolique (cbda) conjointement avec un principe actif supplémentaire
WO2023130160A1 (fr) * 2022-01-10 2023-07-13 Dolce Cann Global Pty Ltd Compositions et méthodes permettant le traitement de troubles non neurologiques à l'aide de produits combinés comprenant un mélange de cannabinoïdes riche en acide cannabidiolique (cbda).

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ARJUN H. BANSKOTA: "Triacylglycerols and Other Lipids Profiling of Hemp By-Products", MOLECULES, MDPI AG, CH, vol. 27, no. 7, CH , pages 2339, XP093165015, ISSN: 1420-3049, DOI: 10.3390/molecules27072339 *
PAVLOVIC, R. ET AL.: "Phytochemical and Ecological Analysis of Two Varieties of Hemp (Cannabis sativa L.) Grown in a Mountain Environment of Italian Alps", FRONTIERS IN PLANT SCIENCE, vol. 10, October 2019 (2019-10-01), pages 1265, XP055767738, DOI: 10.3389/fpls.2019.01265 *

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