WO2020021545A1 - Cannabidiol et glucosamine pour le traitement de maladies articulaires inflammatoires - Google Patents

Cannabidiol et glucosamine pour le traitement de maladies articulaires inflammatoires Download PDF

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WO2020021545A1
WO2020021545A1 PCT/IL2019/050832 IL2019050832W WO2020021545A1 WO 2020021545 A1 WO2020021545 A1 WO 2020021545A1 IL 2019050832 W IL2019050832 W IL 2019050832W WO 2020021545 A1 WO2020021545 A1 WO 2020021545A1
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cbd
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PCT/IL2019/050832
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Tamir GEDO
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Bol Pharma Ltd.
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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • 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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A61K31/10—Sulfides; Sulfoxides; Sulfones
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis

Definitions

  • This invention is directed to compositions comprising cannabidiol (CBD) and glucosamine and methods of using them for treating inflammatory joint diseases.
  • CBD cannabidiol
  • Inflammation is a localized protective reaction of cells/tissues of the body to allergic or chemical irritation, injury and/or infections.
  • the symptoms of inflammation are characterized by pain, heat, redness, swelling and loss of function that result from dilation of the blood vessels leading to an increased blood supply and from increased intercellular spaces resulting in the movement of leukocytes, protein and fluids into the inflamed regions
  • cytokines tumor necrosis factor and interleukins- 1, 12
  • Joint disease any of the diseases or injuries that affect human joints. Arthritis is the best- known joint disease. Diseases of the joints may be variously short-lived or exceedingly chronic, agonizingly painful or merely nagging and uncomfortable; they may be confined to one joint or may affect many parts of the skeleton. [0007] Two principal categories are distinguished: joint diseases in which inflammation is the principal set of signs or symptoms and joint diseases, called noninflammatory.
  • Arthritis is a generic term for inflammatory joint disease. Regardless of the cause, inflammation of the joints may cause pain, stiffness, swelling, and some redness of the skin about the joint. Effusion of fluid into the joint cavity is common, and examination of this fluid is often a valuable procedure for determining the nature of the disease.
  • the inflammation may be of such a nature and of such severity as to destroy the joint cartilage and underlying bone and cause irreparable deformities. Adhesions between the articulating members are frequent in such cases, and the resulting fusion with loss of mobility is called ankylosis.
  • synovitis Inflammation restricted to the lining of a joint (the synovial membrane) is referred to as synovitis.
  • Arthralgias simply are pains in the joints; as ordinarily used, the word implies that there is no other accompanying evidence of arthritis.
  • Bursitis inflammation of a synovial bursa, the lubricating sac located around joints or between tendons and muscles or bones. Bursitis may be caused by infection or injury, by arthritis or gout, by calcium deposition along a tendon or joint, or by minor, usually repetitive irritation. Bursitis commonly affects the knee (“housemaid’s knee”), the Achilles tendon at the back of the ankle (“soldier’s heel”), the elbow (“tennis elbow”), and the bottom of the pelvis (“weaver’s bottom”), but most common is bursitis of the shoulder, caused by calcium deposits and inflammation of the rotator tendon in the upper arm, spreading into the bursa above the shoulder joint. Bursitis of the shoulder may be extremely painful, making it impossible to raise the affected arm. Treatment of bursitis includes rest, heat, mild exercise, and medications that relieve inflammation and remove calcium deposits.
  • Joints may be infected by many types of microorganisms (bacteria, fungi, viruses) and occasionally by animal parasites. There are three routes of infection: by direct contamination, by way of the bloodstream, and by extension from adjacent bony infections (osteomyelitis). Direct contamination usually arises from penetrating wounds but may also occur during surgery on joints. Blood-borne infections may enter the joints through the synovial blood vessels. Commonly, however, foci of osteomyelitis occur first in the long bones near the end of the shaft or next to the joint. The infection then extends into the joint through natural openings or pathological breaches in the outside layer, or cortex, of the bone.
  • hematogenous (blood-bome) infectious arthritis affects one joint (monarthritis) or a very few joints (oligoarthritis) rather than many of them (polyarthritis) and usually affects large joints (knee and hip) rather than small ones. Infections of the joints, like infections elsewhere in the body, often cause fever and other systemic indications of inflammation. [0012] In several types of arthritis that resemble infectious joint disease, no causative agent has been isolated. Principal among these is rheumatoid arthritis. This disorder may appear at any age but is most usual in the fourth and fifth decades. A type that affects children is called juvenile rheumatoid arthritis.
  • Rheumatoid arthritis typically affects the same joints on both sides of the body. Almost any movable joint can be involved, but the fingers, wrists, and knees are particularly susceptible. The joints are especially stiff when the affected person awakes. Rheumatoid arthritis is not only a disease of the joints; fatigue and anemia indicate that there is a more generalized systemic involvement. A slight fever may sometimes be present. Lesions also occur in sites outside the joints. Involvement of bursas, tendons, and tendon sheaths is an integral part of the disease. Approximately one of five affected persons has nodules in the subcutaneous tissue at the point of the elbow or elsewhere. Inflammatory changes also are found sometimes in small arteries and the pericardium— the membrane enclosing the heart.
  • the collagen diseases are so called because in all of them abnormalities develop in the collagen-containing connective tissue. These diseases are primarily systemic and are frequently accompanied by joint problems.
  • SLE systemic lupus erythematosus
  • An association with rheumatoid arthritis is suggested by the fact that one-quarter of those with SLE have positive serological tests for rheumatoid factor, and perhaps as many patients with rheumatoid arthritis have positive lupus erythematosus tests.
  • SLE systemic lupus erythematosus
  • Another collagen disease generalized scleroderma, the skin becomes thickened and tight. Similar changes occur in other organs, particularly the gastrointestinal tract.
  • Erythema nodosum is a skin disease characterized by the formation of reddened nodules usually on the front of the legs. In the majority of cases, pain may arise in various joints, and sometimes swelling appears. Lymph nodes at the hilus of the lung (the site of entrance of bronchus, blood vessels, and nerves) are enlarged. The synovitis disappears in the course of several weeks or months.
  • erythema nodosum many cases of erythema nodosum are associated with drug hypersensitivity, with infections such as tuberculosis, coccidioidomycosis, and leprosy, and with sarcoidosis, a systemic disease in which nodules form in the lymph nodes and other organs and structures of the body. Synovitis of this sort occurs in 10 to 15 percent of patients with sarcoidosis.
  • Cannabis is known to have anti-inflammatory properties.
  • the endocannabinoid system CB2 receptors are predominantly found in the immune system, or immune -derived cells with the greatest density in the spleen. While found only in the peripheral nervous system, a report does indicate that CB2 is expressed by a subpopulation of microglia in the human cerebellum. CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis seen in animal models.
  • CBD Cannabidiol
  • a 9 -tetrahydrocannabinol A 9 -THC
  • CBD is neuroactive but only A 9 -THC is psychoactive (inducing the“high” feeling).
  • CBD is not psychoactive and even attenuates the D 9 - THC-induced psychoactivity.
  • strains with higher CBD concentrations are used for medical purposes, while strains having a higher concentration of A 9 -THC and lower CBD are used for recreational purposes.
  • Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids.
  • Glucosamine is one of the most abundant monosaccharides and is part of the structure of the polysaccharides, chitosan, and chitin. It is produced commercially by the hydrolysis of crustacean exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat. Glucosamine is marketed to support the structure and function of joints.
  • Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars (N-acetylgalactosamine and glucuronic acid). Chondroitin sulfate is an important structural component of cartilage and provides much of its resistance to compression. Along with glucosamine, chondroitin sulfate has become a widely used dietary supplement for treatment of osteoarthritis.
  • Methylsulfonylmethane is an organosulfur compound with the formula (CH 3 ) 2 S0 2 . It is also known by several other names including methyl sulfone and dimethyl sulfone (DMSO2). It occurs naturally in some primitive plants, is present in small amounts in many foods and beverages, and is marketed as a dietary supplement.
  • the present invention provides a composition comprising 2.5 to 30 weight percent cannabidiol (CBD), 3 to 50 weight percent chondroitin, 5 to 60 weight percent glucosamine, and optionally 30-75 weight percent methylsulfonylmethane (MSM).
  • CBD cannabidiol
  • MSM methylsulfonylmethane
  • the present invention provides a method for treating an inflammatory joint disease or reducing pain derived from an inflammatory joint disease in a subject in need thereof, comprising administering to said subject the composition of the invention, thereby treating an inflammatory joint disease or reducing pain derived from an inflammatory joint disease in a subject in need thereof.
  • the present invention provides a method for treating osteoarthritis or reducing pain derived from osteoarthritis in a subject in need thereof, comprising administering to said subject the composition of the invention, thereby treating osteoarthritis or reducing pain derived from osteoarthritis in a subject in need thereof.
  • the present invention provides a composition comprising 2.5 to 40 weight percent cannabidiol (CBD), 3 to 60 weight percent chondroitin, 5 to 80 weight percent glucosamine, and optionally methylsulfonylmethane (MSM).
  • CBD cannabidiol
  • MSM methylsulfonylmethane
  • the composition comprises 2.5 to 30 weight percent cannabidiol (CBD), 3 to 50 weight percent chondroitin, 5 to 60 weight percent Glucosamine, and optionally 30-75 weight percent MSM.
  • CBD cannabidiol
  • the composition comprises 10 to 30 weight percent CBD, 15 to 50 weight percent chondroitin, and 20 to 60 weight percent glucosamine. In some embodiments, the composition comprises 10 to 20 weight percent CBD, 25 to 40 weight percent chondroitin, and 25 to 50 weight percent glucosamine.
  • the composition comprises 1.5 to 15 weight percent CBD, 2 to 25 weight percent chondroitin, 5 to 20 weight percent glucosamine, and 20 to 85 weight percent MSM. In some embodiments, the composition comprises 2.5 to 10 weight percent CBD, 3 to 15 weight percent chondroitin, 5 to 20 weight percent glucosamine, and 30 to 75 weight percent MSM. In some embodiments, the composition comprises 4 to 8 weight percent CBD, 5 to 14 weight percent chondroitin, 8 to 15 weight percent glucosamine, and 45 to 70 weight percent MSM.
  • the composition comprises 10 to 250 mg/ml CBD, 100 to 1000 mg/ml chondroitin, and 100 to 1000 mg/ml glucosamine. In some embodiments, the composition comprises 20 to 200 mg/ml CBD, 150 to 1000 mg/ml chondroitin, and 150 to 1000 mg/ml glucosamine. In some embodiments, the composition comprises 50 to 150 mg/ml CBD, 150 to 600 mg/ml chondroitin, and 150 to 600 mg/ml glucosamine. In some embodiments, a composition as described herein comprises MSM.
  • a composition as described herein comprises 100 to 1000 mg/ml methylsulfonylmethane, 200 to 800 mg/ml methylsulfonylmethane, or 300 to 600 mg/ml methylsulfonylmethane.
  • a composition as described herein is administered once a day. In some embodiments, a composition as described herein is administered twice a day, three times a day, four times a day, five times a day, or six times a day.
  • chondroitin is chondroitin sulfate. In some embodiments, chondroitin chain can have 100 or more individual sugars, each of which can be sulfated in variable positions. In some embodiments, chondroitin comprises chondroitin-4-sulfate. In some embodiments, chondroitin comprises dermatan-4-sulfate. In some embodiments, chondroitin comprises 4S galactosamine.
  • chondroitin comprises iduronic acid. In some embodiments, chondroitin comprises chondroitin-6-sulfate. In some embodiments, chondroitin comprises chondroitin-2, 6-sulfate. In some embodiments, chondroitin comprises 2S glucuronic acid. In some embodiments, chondroitin comprises galactosamine. In some embodiments, chondroitin comprises 6S galactosamine. In some embodiments, chondroitin comprises chondroitin-4, 6-sulfate. In some embodiments, chondroitin comprises glucuronic acid.
  • glucosamine comprises glucosamine sulfate. In some embodiments, glucosamine comprises glucosamine hydrochloride. In some embodiments, glucosamine comprises N-acetylglucosamine. In some embodiments, glucosamine comprises D- glucosamine.
  • the composition of the invention comprises 50 to 500 mg/ml CBD, 50 to 200 mg/ml CBD, 100 to 300 mg/ml CBD, 50 to 400 mg/ml CBD, 200 to 500 mg/ml CBD, 100 to 250 mg/ml CBD, or 250 to 350 mg/ml cannabidiol.
  • the invention provides that a composition as described herein is for treating an inflammatory disease, reducing the severity of inflammation, reducing pain associated with inflammation or reducing the risk of developing inflammation in a subject.
  • the w/w ratio of CBD to chondroitin in the composition as described herein is 1: 1 to 1:6 w/w, 1:1 to 1:5 w/w, or 1: 1 to 1:2.5 w/w.
  • the w/w ratio of CBD to glucosamine in the composition as described herein is 1: 1 to 1:6 w/w, 1:1 to 1:5 w/w, or 1: 1 to 1:2.5 w/w.
  • the w/w ratio of glucosamine to MSM in the composition as described herein is 1: 1 to 1:6, 1: 1 to 1:5 w/w, 1:2 to 1:6 w/, 1:2 to 1:5 w/w, 1:2 to 1:4 w/w, or 1:2.5 to 1:5 w/w.
  • the w/w ratio of chondroitin to MSM in the composition as described herein is 1: 1 to 1:6 w/w, 1:1 to 1:5 w/w, 1:2 to 1:6 w/w, 1:2 to 1:5 w/w, 1:2 to 1:4 w/w, or 1:2.5 to 1:5 w/w.
  • the w/w ratio of glucosamine and chondroitin in the composition as described herein is 3: 1 to 1:3 w/w, 2: 1 to 1:2 w/w, or 1: 1.5 to 1.5: 1 w/w.
  • a composition as described herein comprises Tetrahydrocannabinol (THC). In some embodiments, a composition as described herein comprises 1 to 120 mg/ml THC. In some embodiments, a composition as described herein comprises 2 to 90 mg/ml THC. In some embodiments, a composition as described herein comprises 5 to 80 mg/ml THC. In some embodiments, a composition as described herein comprises 20 to 70 mg/ml THC. In some embodiments, a composition as described herein comprises 20 to 50 mg/ml THC. In some embodiments, a composition as described herein comprises 40 to 90 mg/ml THC.
  • THC Tetrahydrocannabinol
  • compositions as described herein comprise in some embodiments, CBD, or any functional derivative thereof (i.e. a CBD derivative possessing similar, equivalent, or increased efficacy).
  • the described compositions optionally further comprise at least one pharmaceutically acceptable carrier, diluent, excipient and/or additive.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that are substantially and/or essentially devoid of THC.
  • a composition comprising CBD or any functional derivative thereof, as described herein is substantially and/or essentially devoid of THC.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that comprise at least 80% CBD or any functional derivative thereof.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that comprise at least 90% CBD or any functional derivative thereof.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that comprise at least 92% CBD or any functional derivative thereof.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that comprise at least 95% CBD or any functional derivative thereof.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that comprise at least 97% CBD or any functional derivative thereof.
  • CBD or any functional derivative thereof refers to compounds and/or compositions that comprise at least 99% CBD or any functional derivative thereof.
  • substantially and/or essentially devoid of THC is less than 10% by weight or weight/weight THC. In some embodiments, substantially and/or essentially devoid of THC is less than 7% by weight or weight/weight THC. In some embodiments, substantially and/or essentially devoid of THC is less than 5% by weight or weight/weight THC. In some embodiments, substantially and/or essentially devoid of THC is less than 3% by weight or weight/weight THC. In some embodiments, substantially and/or essentially devoid of THC is less than 1% by weight or weight/weight THC. In some embodiments, substantially and/or essentially devoid of THC is less than 0.5% by weight or weight/weight THC.
  • substantially and/or essentially devoid of THC is less than 0.3% by weight or weight/weight THC. In some embodiments, substantially and/or essentially devoid of THC is less than 0.1% by weight or weight/weight THC.
  • purified or substantially purified refers to greater than 80% w/w, 85% w/w, 90%, w/w 95% w/w or 97% w/w cannabidiol, or a functional variant thereof, CBD, also termed 2-[(6R)-3- Methyl-6-prop-l-en-2-yl-lcyclohex-2-envyl]-5pentylbenzene-l,3-diol, has the molecular formula of C21H30O2.
  • the chemical structure of CBD is shown in Formula I:
  • CBD is insoluble in water but soluble in organic solvents, such as oil. Accordingly, CBD can be formulated for use in the described methods through use of any organic solvent known to the pharmaceutical arts, including, but not limited to edible oils. When formulated for oral administration, any edible oil can be used in the CBD formulation, including olive oil.
  • a CBD derivative is in some embodiments, a metabolite of CBD such as but not limited to: (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series.
  • a CBD derivative is characterized, in some embodiments, by a structure wherein at least one of the hydroxyl substituent groups is converted to a stable form thereof.
  • a CBD derivative is cannabinol comprising a quinone ring.
  • a CBD derivative is an endocannabinoid derivative.
  • a CBD derivative is described in Frank D King; G Lawton; A W Oxford Progress in medicinal chemistry. Vol. 44. Pages 207-331, Elsevier Science, 2006 ISBN: 0080462103 9780080462103 which is hereby incorporated by reference in its entirety.
  • a composition as described herein further comprises cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), or any combination thereof.
  • a composition as described herein further comprises at least two compounds selected from the group comprising: cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), or any combination thereof.
  • a composition as described comprises or has w/w ratio of CBD/CBC, CBG, CBN or any combination thereof of 50: 1 to 5: 1.
  • a composition as described comprises or has w/w ratio of a/b of 50: 1 to 5: 1.
  • a composition as described comprises or has w/w ratio of a/b of 40: 1 to 8:1.
  • a composition as described comprises or has w/w ratio of a/b of 30: 1 to 10:1.
  • a composition as described comprises or has w/w ratio of a/b of 25: 1 to 15: 1.
  • "a" is CBD.
  • “b” is CBC, CBG, CBN or any combination thereof. In some embodiments, “b” comprises at least two compounds selected from CBC, CBG, and CBN. In some embodiments, “b” comprises at least two compounds selected from CBD, CBC, CBG, and CBN. In some embodiments, “b” is the entire weight of the composition.
  • a composition as described herein is in an aqueous solution. In some embodiments, a composition as described herein is buffered in an aqueous solution. In some embodiments, a composition as described herein is buffered to physiological pH. In some embodiments, a composition as described herein comprises a powder. In some embodiments, a composition as described herein comprises a mixture of powders.
  • a composition as described herein comprises an oil soluble vitamin. In some embodiments, a composition as described herein comprises 0.5 to 300 mg/ml oil soluble vitamin. In some embodiments, a composition as described herein comprises 1 to 20 mg/ml oil soluble vitamin. In some embodiments, a composition as described herein comprises 5 to 30 mg/ml oil soluble vitamin. In some embodiments, a composition as described herein comprises 10 to 150 mg/ml oil soluble vitamin. In some embodiments, a composition as described herein comprises 50 to 300 mg/ml oil soluble vitamin.
  • an oil soluble vitamin is vitamin E. In some embodiments, an oil soluble vitamin is vitamin D. In some embodiments, an oil soluble vitamin is vitamin K. In some embodiments, an oil soluble vitamin is vitamin A. In some embodiments, an oil soluble vitamin is any combination of vitamin E, vitamin D, vitamin K and vitamin A.
  • a composition as described herein comprises a CBD- oil soluble vitamin composite.
  • the term "composite” refers to a material which is composed of at least CBD and an oil soluble vitamin wherein each of CBD and an oil soluble vitamin retains its identity while contributing desirable anti-inflammatory and or stability properties to the whole.
  • the composite is in the form of a matrix or a solution.
  • the composite is in the form of a core matrix.
  • the composite is in the form of an oil.
  • the composite is biostable.
  • biostable describes a compound or a polymer that remains intact under physiological conditions (e.g., is not degraded in vivo, and hence is non-biodegradable or non-biocleavable).
  • the composite is biocleavable.
  • the composition as described herein further comprises glycosaminoglycan (“GAG.
  • GAG glycosaminoglycan
  • a composition as described herein comprises a polyol.
  • a composition as described herein further comprises at least one additional anti-inflammatory agent polyol.
  • the composition as described herein has a synergistic anti inflammatory effect between CBD and chondroitin. In some embodiments, the composition as described herein has a synergistic anti-inflammatory effect between CBD and glucosamine. In some embodiments, the composition as described herein has a synergistic anti-inflammatory effect between CBD and MSM. In some embodiments, the composition as described herein has a synergistic anti-inflammatory effect between CBD, glucosamine, MSM, chondroitin, or any combination thereof.
  • the composition as described herein comprises a liposome.
  • the liposome is composed of the lipid soluble substances of the present invention.
  • the liposome encapsulates at least one water soluble ingredient as described herein.
  • the liposome encapsulates at least one water insoluble ingredient as described herein.
  • the liposome comprises CBD.
  • the composition further includes a co-solvent.
  • a co-solvent is a mixture of miscible solvents for to solubilizing water-insoluble ingredients of the invention.
  • a co-solvent is composed of one organic solvent and water.
  • a co-solvent comprises: propylene glycol, PEG 400, ethanol, water, a surfactant, glycerin, propylene glycol, ethanol, polyethylene glycol 300, polyethylene glycol 400, dimethylacetamide (DMA), N-methyl-2-pyrrolidone (NMP; Pharmasolve), dimethylsulfoxide (DMSO), Solutol HS 15, Cremophor EL, Cremophor RH 60, and polysorbate 80.
  • a co-solvent comprises a compound described in: Robert G. Strickley: Solubilizing Excipients in Oral and Injectable Formulations. Pharmaceutical Research, Vol. 21, No. 2 pp.
  • a composition as described herein is in the form of a liquid. In some embodiments, a composition as described herein is in the form of a liquid and/or a powder. In some embodiments, the composition comprises a buffer. In some embodiments, the composition comprises a buffer having a physiological pH.
  • a composition as described herein is formulated to a suitable route of administration, such as: oral, rectal, transmucosal, transnasal, buccal, intestinal or parenteral delivery, including intramuscular, topical, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.
  • a suitable route of administration such as: oral, rectal, transmucosal, transnasal, buccal, intestinal or parenteral delivery, including intramuscular, topical, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.
  • the pharmaceutical compositions are administered by intravenous, intra-arterial, or intramuscular injection of a liquid preparation.
  • liquid formulations include solutions, suspensions, dispersions, emulsions, oils and the like.
  • the pharmaceutical compositions are administered intravenously, and are thus formulated in a form suitable for intravenous administration.
  • the pharmaceutical compositions are administered intra-arterially, and are thus formulated in a form suitable for intra-arterial administration.
  • the pharmaceutical compositions are administered intramuscularly, and are thus formulated in a form suitable for intramuscular administration.
  • injectables, of the invention are formulated in aqueous solutions.
  • injectables, of the invention are formulated in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer.
  • physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer.
  • penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
  • the preparations described herein are formulated for parenteral administration, e.g., by bolus injection or continuous infusion.
  • formulations for injection are presented in unit dosage form, e.g., in ampoules or in multidose containers with optionally, an added preservative.
  • compositions are suspensions, solutions or emulsions in oily or aqueous vehicles, and contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
  • compositions for parenteral administration include aqueous solutions of the active preparation in water-soluble form.
  • suspensions of the active ingredients are prepared as appropriate oily or water based injection suspensions.
  • Suitable lipophilic solvents or vehicles include, in some embodiments, fatty oils such as sesame oil, or synthetic fatty acid esters such as ethyl oleate, triglycerides or liposomes.
  • Aqueous injection suspensions contain, in some embodiments, substances, which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran.
  • the suspension also contains suitable stabilizers or agents which increase the solubility of the active ingredients to allow for the preparation of highly concentrated solutions.
  • a composition as described herein is an intra- articular injectable composition. In some embodiments, a composition as described herein is a viscosupplementation composition. In some embodiments, a composition as described herein is in a gel form or semi gel form. In some embodiments, a dosage form of a composition comprises or consists 0.5 to 5 ml of a composition as described herein.
  • a dosage form of a composition comprises or consists 0.5 to 2 ml of a composition as described herein. In some embodiments, a dosage form of a composition comprises or consists 1 to 3 ml of a composition as described herein. In some embodiments, a dosage form of a composition as described herein is injected 1 to 5 times a week. In some embodiments, a dosage form of a composition as described herein is injected 2 to 5 times a week. In some embodiments, a dosage form of a composition as described herein is injected for a duration of one week to a year. In some embodiments, a dosage form of a composition as described herein is injected for a duration of one month to a year. In some embodiments, a dosage form of a composition as described herein is injected for a duration of two months week to ten months.
  • the composition as described herein is used to inhibit inflammation. In some embodiments, the composition as described herein is used to alleviate joint pain. In some embodiments, the composition as described herein is further used to rebuild a connective tissue.
  • the present invention provides a composition as defined above, for use in a method for treating an inflammatory joint disease.
  • the present invention provides a composition as defined above, for use in a method for reducing or alleviating pain resulting or derived from an inflammatory joint disease.
  • the present invention provides a method for treating an inflammatory joint disease in a subject in need thereof, comprising administering to the subject the composition of the invention, thereby treating an inflammatory joint disease in a subject in need thereof.
  • the present invention provides a method for reducing or alleviating pain resulting or derived from an inflammatory joint disease in a subject in need thereof, comprising administering to the subject the composition of the invention.
  • the present invention provides a method for treating articular degeneration in a subject in need thereof, comprising administering to the subject the composition of the invention, thereby treating articular degeneration in a subject in need thereof.
  • the present invention provides a method for treating osteoarthritis or reducing pain derived from osteoarthritis in a subject in need thereof, comprising administering to said subject the composition as described herein, thereby treating osteoarthritis or reducing pain derived from osteoarthritis in a subject in need thereof.
  • treating osteoarthritis comprises inhibiting: inflammation, cartilage degradation, subchondral bone sclerosis, osteophyte formation, or any combination thereof.
  • treating osteoarthritis comprises inhibiting disease progression.
  • a composition as described herein provides chondroprotective efficacy. In some embodiments, a composition as described herein enhances cartilage preservation.
  • a method for treating Amyloidosis or reducing pain derived from Amyloidosis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Amyloidosis or reducing pain derived from Amyloidosis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Arthritis Bursitis or reducing pain derived from Arthritis Bursitis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Diffuse Idiopathic Skeletal Hyperostosis (DISH)or reducing pain derived from Diffuse Idiopathic Skeletal Hyperostosis (DISH)in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Ganglion, Gout or reducing pain derived from Ganglion, Gout in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Ankylosing Spondylitis or reducing pain derived from Ankylosing Spondylitis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Lumbar Spinal Stenosis or reducing pain derived from Lumbar Spinal Stenosis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Hydroxyapatite Juvenile Arthritis or reducing pain derived from Hydroxyapatite Juvenile Arthritis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Pseudogout or reducing pain derived from Pseudogout in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating SAPHO Syndrome or reducing pain derived from SAPHO Syndrome in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Rheumatoid Arthritis or reducing pain derived from Rheumatoid Arthritis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Reactive Arthritis or reducing pain derived from Reactive Arthritis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Psoriatic Arthritis or reducing pain derived from Psoriatic Arthritis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Sacroiliac Joint Pain or reducing pain derived from Sacroiliac Joint Pain in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Septic Arthritis or reducing pain derived from Septic Arthritis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating Still's Disease or reducing pain derived from Still's Disease in a subject in need thereof comprising administering to said subject the composition as described herein.
  • a method for treating synovitis or reducing pain derived from synovitis in a subject in need thereof comprising administering to said subject the composition as described herein.
  • administering is injecting into an inflamed joint.
  • injecting into an inflamed joint is joint injection.
  • the methods described herein include joint aspiration.
  • administering is injecting into an inflamed joint.
  • the methods described herein include joint aspiration prior to injecting a composition of the invention into an inflamed joint.
  • administering is injecting into an inflamed soft tissue next to a joint (such as bursa).
  • administering is injecting into a soft tissue next to an inflamed joint.
  • the methods described herein overcome steroid injection complications which include aggravation of the pain due to irritation of the joint lining by crystals in the steroid solution.
  • composition as described herein are topical compositions.
  • the composition are oral or systemic compositions.
  • Oral or topical administration of a composition as described herein comprises a unit dosage form comprising lotions, creams, ointments, tablets, capsules, lozenges, chewable tablets, suspensions, emulsions and the like.
  • Such unit dosage forms comprise a safe and effective amount of the desired compound, or compounds, each of which is in some embodiments, from about 0.7 mg to about 280 mg/70 kg, or in some embodiments, about 0.5 mg to about 210 mg/70 kg.
  • tablets typically comprise conventional pharmaceutically-compatible adjuvants as inert diluents, such as calcium carbonate, sodium carbonate, mannitol, lactose and cellulose; binders such as starch, gelatin and sucrose; disintegrants such as starch, alginic acid and croscarmelose; lubricants such as magnesium stearate, stearic acid and talc.
  • glidants such as silicon dioxide can be used to improve flow characteristics of the powder-mixture.
  • coloring agents such as the FD&C dyes
  • sweeteners and flavoring agents such as aspartame, saccharin, menthol, peppermint, and fruit flavors, are useful adjuvants for chewable tablets.
  • Capsules typically comprise one or more solid diluents.
  • the selection of carrier components depends on secondary considerations like taste, cost, and shelf stability, which are not critical for the purposes of this invention, and can be readily made by a person skilled in the art.
  • the oral dosage form comprises predefined release profile.
  • the oral dosage form of the present invention comprises a dosage form (composition) or dosage forms having different release profile for various compounds described herein.
  • the oral dosage form of the present invention comprises a dosage form (composition) or dosage forms having the same release profile for various compounds described herein.
  • the oral dosage form of the present invention comprises an extended release tablets, capsules, lozenges or chewable tablets.
  • the oral dosage form of the present invention comprises a slow release tablets, capsules, lozenges or chewable tablets.
  • the oral dosage form of the present invention comprises an immediate release tablets, capsules, lozenges or chewable tablets.
  • the oral dosage form is formulated according to the desired release profile of the pharmaceutical active ingredient as known to one skilled in the art.
  • Peroral compositions in some embodiments, comprise liquid solutions, emulsions, suspensions, and the like.
  • pharmaceutically-acceptable carriers suitable for preparation of such compositions are well known in the art.
  • liquid oral compositions comprise from about 0.012% to about 0.933% w/w or w/v of the desired compounds as described herein, or in some embodiments, from about 0.033% to about 0.7% w/v or w/w.
  • compositions for use in the methods of this invention comprise solutions or emulsions, which in some embodiments are aqueous solutions or emulsions comprising a safe and effective amount of the compounds of the present invention and optionally, other compounds, intended for topical intranasal administration.
  • compositions comprise from about 0.01% to about 10.0% w/v or w/w of a subject compound.
  • compositions comprise from about 0.1% to about 2.0 w/w or w/v, which is used for systemic delivery of the compounds by the intranasal route.
  • the pharmaceutical compositions are administered topically to body surfaces, and are thus formulated in a form suitable for topical administration.
  • Suitable topical formulations include gels, ointments, creams, lotions, drops and the like.
  • the compounds of the present invention are combined with an additional appropriate therapeutic agent or agents, prepared and applied as solutions, suspensions, or emulsions in a physiologically acceptable diluent with or without a pharmaceutical carrier.
  • compositions of the present invention are manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.
  • compositions for use in accordance with the present invention is formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into preparations which, can be used pharmaceutically.
  • formulation is dependent upon the route of administration chosen.
  • compositions also comprise, in some embodiments, preservatives, such as benzalkonium chloride and thimerosal and the like; chelating agents, such as edetate sodium and others; buffers such as phosphate, citrate and acetate; tonicity agents such as sodium chloride, potassium chloride, glycerin, mannitol and others; antioxidants such as ascorbic acid, acetylcystine, sodium metabisulfote and others; aromatic agents; viscosity adjustors, such as polymers, including cellulose and derivatives thereof; and polyvinyl alcohol and acid and bases to adjust the pH of these aqueous compositions as needed.
  • the compositions also comprise, in some embodiments, local anesthetics or other actives.
  • the compositions can be used as sprays, mists, drops, and the like.
  • the active compounds can be delivered in a vesicle, in particular a liposome (see Langer, Science 249: 1527-1533 (1990); Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez- Berestein and Fidler (eds.), Liss, New York, pp. 353- 365 (1989); Lopez-Berestein, ibid., pp. 317-327; see generally ibid).
  • a liposome see Langer, Science 249: 1527-1533 (1990); Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez- Berestein and Fidler (eds.), Liss, New York, pp. 353- 365 (1989); Lopez-Berestein, ibid., pp. 317-327; see generally ibid).
  • the pharmaceutical composition or compositions are delivered in a controlled release system is formulated for intravenous infusion, implantable osmotic pump, transdermal patch, liposomes, or other modes of administration.
  • a pump is used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989).
  • polymeric materials can be used.
  • a controlled release system can be placed in proximity to the therapeutic target, i.e., the brain, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984). Other controlled release systems are discussed in the review by Langer (Science 249: 1527-1533 (1990).
  • the active ingredient is in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water-based solution, before use.
  • a suitable vehicle e.g., sterile, pyrogen-free water-based solution
  • Compositions are formulated, in some embodiments, for atomization and inhalation administration. In some embodiments, compositions are contained in a container with attached atomizing means.
  • the preparation of the present invention is formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides.
  • compositions suitable for use in context of the present invention include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose.
  • a therapeutically effective amount means an amount of active ingredients effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated.
  • compositions which can serve as pharmaceutically-acceptable carriers or components thereof are sugars, such as lactose, glucose and sucrose; starches, such as com starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose, and methyl cellulose; powdered tragacanth; malt; gelatin; talc; solid lubricants, such as stearic acid and magnesium stearate; calcium sulfate; vegetable oils, such as peanut oil, cottonseed oil, sesame oil, olive oil, com oil and oil of theobroma; polyols such as propylene glycol, glycerine, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers, such as the TweenTM brand emulsifiers; wetting
  • a pharmaceutically-acceptable carrier to be used in conjunction with the compound is basically determined by the way the compound is to be administered. If the subject compound is to be injected, in some embodiments, the pharmaceutically-acceptable carrier is sterile, physiological saline, with a blood-compatible suspending agent, the pH of which has been adjusted to about 7.4.
  • compositions further comprise binders (e.g. acacia, cornstarch, gelatin, carbomer, ethyl cellulose, guar gum, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone), disintegrating agents (e.g.
  • binders e.g. acacia, cornstarch, gelatin, carbomer, ethyl cellulose, guar gum, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone
  • disintegrating agents e.g.
  • cornstarch potato starch, alginic acid, silicon dioxide, croscarmelose sodium, crospovidone, guar gum, sodium starch glycolate), buffers (e.g., Tris- HCL, acetate, phosphate) of various pH and ionic strength, additives such as albumin or gelatin to prevent absorption to surfaces, detergents (e.g., Tween 20, Tween 80, Pluronic F68, bile acid salts), protease inhibitors, surfactants (e.g.
  • sodium lauryl sulfate sodium lauryl sulfate
  • permeation enhancers solubilizing agents (e.g., glycerol, polyethylene glycerol), anti-oxidants (e.g., ascorbic acid, sodium metabisulfite, butylated hydroxyanisole), stabilizers (e.g. hydroxypropyl cellulose, hyroxypropylmethyl cellulose), viscosity increasing agents(e.g. carbomer, colloidal silicon dioxide, ethyl cellulose, guar gum), sweeteners (e.g. aspartame, citric acid), preservatives (e.g., Thimerosal, benzyl alcohol, parabens), lubricants (e.g.
  • stearic acid magnesium stearate, polyethylene glycol, sodium lauryl sulfate), flow-aids (e.g. colloidal silicon dioxide), plasticizers (e.g. diethyl phthalate, triethyl citrate), emulsifiers (e.g. carbomer, hydroxypropyl cellulose, sodium lauryl sulfate), polymer coatings (e.g., poloxamers or poloxamines), coating and film forming agents (e.g. ethyl cellulose, acrylates, polymethacrylates) and/or adjuvants.
  • plasticizers e.g. diethyl phthalate, triethyl citrate
  • emulsifiers e.g. carbomer, hydroxypropyl cellulose, sodium lauryl sulfate
  • polymer coatings e.g., poloxamers or poloxamines
  • coating and film forming agents e.g. ethyl cellulose
  • Typical components of carriers for syrups, elixirs, emulsions and suspensions include ethanol, glycerol, propylene glycol, polyethylene glycol, liquid sucrose, sorbitol and water.
  • typical suspending agents include methyl cellulose, sodium carboxymethyl cellulose, cellulose (e.g. AvicelTM, RC-591), tragacanth and sodium alginate;
  • typical wetting agents include lecithin and polyethylene oxide sorbitan (e.g. polysorbate 80).
  • Typical preservatives include methyl paraben and sodium benzoate.
  • peroral liquid compositions also contain one or more components such as sweeteners, flavoring agents and colorants disclosed above.
  • compositions also include incorporation of the active material into or onto particulate preparations of polymeric compounds such as polylactic acid, polglycolic acid, hydrogels, etc, or onto liposomes, microemulsions, micelles, unilamellar or multilamellar vesicles, erythrocyte ghosts, or spheroplasts.)
  • polymeric compounds such as polylactic acid, polglycolic acid, hydrogels, etc, or onto liposomes, microemulsions, micelles, unilamellar or multilamellar vesicles, erythrocyte ghosts, or spheroplasts.
  • particulate compositions coated with polymers e.g. poloxamers or poloxamines
  • polymers e.g. poloxamers or poloxamines
  • compounds modified by the covalent attachment of water-soluble polymers such as polyethylene glycol, copolymers of polyethylene glycol and polypropylene glycol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone or polyproline.
  • the modified compounds exhibit substantially longer half- lives in blood following intravenous injection than do the corresponding unmodified compounds.
  • modifications also increase the compound's solubility in aqueous solution, eliminate aggregation, enhance the physical and chemical stability of the compound, and greatly reduce the immunogenicity and reactivity of the compound.
  • the desired in vivo biological activity is achieved by the administration of such polymer-compound abducts less frequently or in lower doses than with the unmodified compound.
  • preparation of effective amount or dose can be estimated initially from in vitro assays.
  • a dose can be formulated in animal models and such information can be used to more accurately determine useful doses in humans.
  • toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals.
  • the data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human.
  • the dosages vary depending upon the dosage form employed and the route of administration utilized.
  • the exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. [See e.g., Fingl, et al., (1975) "The Pharmacological Basis of Therapeutics", Ch. 1
  • dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved.
  • the amount of a composition to be administered will, of course, be dependent on the subject being treated, the severity of the affliction, the manner of administration, the judgment of the prescribing physician, etc.
  • compositions including the preparation of the present invention formulated in a compatible pharmaceutical carrier are also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.
  • compositions of the present invention are presented in a pack or dispenser device, such as an FDA approved kit, which contain one or more unit dosage forms containing the active ingredient.
  • the pack for example, comprise metal or plastic foil, such as a blister pack.
  • the pack or dispenser device is accompanied by instructions for administration.
  • the pack or dispenser is accommodated by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or human or veterinary administration. Such notice, in some embodiments, is labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert.
  • compositions of the present invention comprise a volatile oil.
  • compositions of the present invention comprise a volatile oil obtained from turmeric.
  • Ar-turmerone in some embodiments, is a constituent of a volatile oil.
  • compositions of the present invention comprise a water suspension to which oil is added for forming a mixture.
  • the present invention further provides a method for inhibiting or reducing inflammation in a subject in need thereof, comprising the step of administering to the subject a composition of the invention, thereby inhibiting or reducing inflammation in a subject in need thereof.
  • inflammation is an infection.
  • inflammation is a chronic infection such as HIV, inflammatory bowel disease, or septic episodes.
  • inflammation includes a catabolic illness.
  • inflammation is Crohn's disease.
  • inflammation is short bowel syndrome.
  • inflammation inflammation is arthritis.
  • inflammation inflammation is Acne Vulgaris.
  • inflammation is Alzheimer'S disease.
  • inflammation is Asthma.
  • inflammation is Atherosclerosis. In some embodiments, inflammation is an autoimmune disease. In some embodiments, inflammation is Celiac Disease. In some embodiments, inflammation is Prostatitis. In some embodiments, inflammation is Colitis. In some embodiments, inflammation is Dermatitis. In some embodiments, inflammation is Diverticulitis. In some embodiments, inflammation is Glomerulonephritis. In some embodiments, inflammation is Hepatitis. In some embodiments, inflammation is Hypersensitivities. In some embodiments, inflammation is Interstitial Cystitis. In some embodiments, inflammation is irritable Bowel Syndrome. In some embodiments, inflammation is Lupus Erythematous. In some embodiments, inflammation is Nephritis.
  • inflammation is Parkinson's disease. In some embodiments, inflammation is Pelvic Inflammatory Disease. In some embodiments, inflammation is a reperfusion injury. In some embodiments, inflammation is Rheumatoid Arthritis. In some embodiments, inflammation is Sarcoidosis. In some embodiments, inflammation is transplant rejection. In some embodiments, inflammation is Ulcerative Colitis. In some embodiments, inflammation is Vasculitis. In some embodiments, inflammation is ankylosing spondylitis.
  • the present invention provides methods for reducing oxidative stress with a composition or a combination of the compositions as described herein.
  • a composition or a combination of the compositions as described herein induce the de-novo production of anti-inflammatory agents such as but not limited to: IL-4 and IL-10.
  • compositions or a combination of the compositions as described herein inhibit the de-novo production of an inflammatory cytokine such as but not limited to TNF-alpha.
  • a method for treating a subject afflicted with an inflammatory disease comprising administering to the subject the composition or compositions as described herein, thereby treating a subject afflicted with an inflammatory disease.
  • treating an inflammatory disease is ameliorating an inflammatory disease.
  • treating an inflammatory disease is inhibiting the progression of an inflammatory disease.
  • treating an inflammatory disease is inhibiting inflammation.
  • treating an inflammatory disease is minimizing the risk of inflammation in a subject susceptible to oxidative stress.
  • a method for treating a subject afflicted with an inflammatory disease comprising daily administering to the subject: (a) 50 to 500 mg CBD; (b) 500 to 1800 mg Chondroitin, 500 to 1800 mg Glucosamine amd 3 to 8 g methylsulfonylmethane, thereby treating a subject afflicted with an inflammatory disease.
  • a method for treating a subject afflicted with an inflammatory disease comprising daily administering to the subject: (a) 150 to 400 mg CBD; (b) 800 to 1500 mg Chondroitin, 80 to 1500 mg Glucosamine amd 2 to 6 g methylsulfonylmethane, thereby treating a subject afflicted with an inflammatory disease.
  • the subject is a mammal. In some embodiments, the subject is a lab animal. In some embodiments, the subject is a pet. In some embodiments, the subject is a rodent. In some embodiments, the subject is a farm animal. In some embodiments, the subject is a human subject. In some embodiments, the subject is a peri-menopausal woman. In some embodiments, the subject is a woman suffering of estrogen excess.
  • the composition or compositions exert their inflammation inhibitory activity only in sites of inflammation.
  • inhibiting inflammation is specifically targeting inflammatory sites.
  • inhibiting inflammation is inhibiting an inflammation mediator at a site of inflammation and not at a site of no inflammatory activity.

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Abstract

La présente invention concerne une composition comprenant de 2,5 à 30 % en poids de cannabidiol (CBD), de 3 à 50 % en poids de chondroïtine, de 5 à 60 % en poids de glucosamine, et éventuellement de 30 à 75 % en poids de méthylsulfonylméthane (MSM), et des procédés d'utilisation de celui-ci pour traiter une maladie articulaire inflammatoire ou réduire la douleur provoquée par celle-ci.
PCT/IL2019/050832 2018-07-25 2019-07-23 Cannabidiol et glucosamine pour le traitement de maladies articulaires inflammatoires WO2020021545A1 (fr)

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WO2022035772A1 (fr) * 2020-08-10 2022-02-17 Flor Americas, Inc Formulations de cannabinoïdes pour des sujets vétérinaires ou humains
EP3817750A4 (fr) * 2018-07-02 2022-05-04 Companion Sciences, LLC Compositions d'associations de cannabidiol

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US20090247619A1 (en) * 2008-03-06 2009-10-01 University Of Kentucky Cannabinoid-Containing Compositions and Methods for Their Use
US20140011756A1 (en) * 2012-07-09 2014-01-09 Roberto Crea Method for Treatment of Inflammation
WO2015187097A1 (fr) * 2014-06-02 2015-12-10 The Beauty Nation Pte. Ltd. Composition pour la prévention et le traitement de la douleur articulaire et son procédé de préparation
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US20140011756A1 (en) * 2012-07-09 2014-01-09 Roberto Crea Method for Treatment of Inflammation
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EP3817750A4 (fr) * 2018-07-02 2022-05-04 Companion Sciences, LLC Compositions d'associations de cannabidiol
WO2022035772A1 (fr) * 2020-08-10 2022-02-17 Flor Americas, Inc Formulations de cannabinoïdes pour des sujets vétérinaires ou humains

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