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International Patent Classification: TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, A61K 31/09 (2006.01) A61K9/00 (2006.01) KM, ML, MR, NE, SN, TD, TG)

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International Patent Classification: TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, A61K 31/09 (2006.01) A61K9/00 (2006.01) KM, ML, MR, NE, SN, TD, TG) ( International Patent Classification: TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, A61K 31/09 (2006.01) A61K9/00 (2006.01) KM, ML, MR, NE, SN, TD, TG). A61K 31/05 (2006.01) C07C 39/23 (2006.01) A61K 31/352 (2006.01) C07C 43/295 (2006.01) Published: A61K 36/185 (2006.01) C07C 311/60 (2006.01) — with international search report (Art. 21(3)) A61K 47/10 (2017.01) C07D 311/80 (2006.01) (21) International Application Number: PCT/CA20 19/050166 (22) International Filing Date: 08 February 2019 (08.02.2019) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/628,735 09 February 2018 (09.02.2018) US (71) Applicant: NEUTRISCI INTERNATIONAL INC. [CA/CA]; Suite 1A, 4015 - 1st Street SE, Calgary, Alberta T2G 4X7 (CA). (72) Inventors: REHMAN, Glen; c/o NeutriSci International Inc., Suite 1A - 4015 - 1st Street SE, Calgary, Alberta T2G 4X7 (CA). BUSHFIELD, Keith Patrick; c/o NeutriSci In¬ ternational Inc., Suite 1A - 4015 - 1st Street SE, Calgary, Alberta T2G 4X7 (CA). (74) Agent: ROACH, Mark; Flicks & Associates, 709 Main Street, Suite 300, Canmore, Alberta T1W 2B2 (CA). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW,KZ, LA, LC, LK, LR, LS, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (54) Title: COMPOSITIONS COMPRISING CO-CRYSTALS OF STILBENOIDS AND CANNABINOIDS (57) Abstract: A composition for oral administration comprising a cannabinoid in combination with a stilbenoid or derivative thereof and a solubility enhancing agent is described. Oral dosage forms, in the form of dissolvable tablet or capsule with enhanced bioavail¬ ability and processes for preparing them are also disclosed. The processes include lyophilisation of the cannabinoid powder or cannabi- noid-stilbenoid co-crystals to form a powder which is pressed into tablets. The powder may be generated from the co-crystals of the cannabinoid with pterostilbene or the powder may be formed by subsequently mixing the lyophilized cannabinoid with the stilbenoid before forming the tablet. Compositions Comprising Co-crystals of Stilbenoids and Cannabinoids FIELD OF THE INVENTION [0001] The invention relates to compositions comprising pterostilbene in formulations which improve the dissolution rate and bioavailability of cannabinoid compounds. BACKGROUND [0002] Cannabinoids are a group of compounds which are ligands to cannabinoid receptors (CBi, CB2) found in the human body. Cannabinoids were originally identified in Cannabis sativa L . Over the last few years, cannabinoids have been reported in the scientific literature to counter the symptoms of a broad range of conditions including multiple sclerosis and other forms of muscular spasm, including uterine and bowel cramps; movement disorders; pain, including migraine headache; glaucoma, asthma, inflammation, insomnia, and high blood pressure. There may also be utility for cannabinoids as an oxytoxic, anxiolytic, anti-convulsive, anti-depressant and anti psychotic agent, or anti-cancer agent, as well as an appetite stimulant. [0003] Over 60 chemically related compounds, collectively classified as cannabinoids, have been isolated from Cannabis sativa , and other species and strains of Cannabis including tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). In addition, various synthetic ligands for cannabinoid receptors have been developed during the last few years. The cannabinoids usually divided into groups of classical cannabinoids, non-classical cannabinoids, aminoalkylindol derivatives and eicosanoids. Classical cannabinoids are isolated from Cannabis sativa L or they can comprise synthetic analogs of these compounds. Non-classical cannabinoids are bi- or tricyclic analogs of tetrahydrocannabinol (THC) (without the pyran ring); aminoalkylindols form a group which differs structurally substantially from classical and non-classical cannabinoids. [0004] The pharmacological and toxicological studies of cannabinoids have focused mainly on THC (commercially available under the name Dronabinol) which in 1985 was approved by the FDA for the treatment of chemotherapy associated nausea and vomiting, and later for AIDS-associated wasting and anorexia. Dronabinol is a synthetic analog of THC which is marketed in USA as Marinol. In Marinol, THC is dissolved in sesame oil and it is administered orally as a capsule containing 5 or 10 mg of THC. [0005] There continues to be a need for enhancing bioavailability of drugs such as cannabinoids. Efforts to improve bioavailability of cannabinoids using natural compounds recognized as having health benefits are particularly desirable. SUMMARY [0006] In accordance with the invention, there is provided a cannabinoid composition in an oral dosage form comprising a cannabinoid in combination with a stilbenoid or a derivative thereof and a solubility enhancing agent. [0007] Another aspect of the invention is a process for preparing an oral dosage form containing a cannabinoid and a stilbenoid or a derivative thereof, the process comprising: mixing and/or bonding a cannabinoid oil with the stilbenoid or the derivative thereof and generating cocrystals of the cannabinoid and the stilbenoid; lyophilizing the cocrystals to form a powder; adding a solubility enhancing agent to the powder; and formulating the powder into the oral dosage form. [0008] Another aspect of the invention is a process for preparing an oral dosage form containing a cannabinoid and a stilbenoid or a derivative thereof, the process comprising: mixing an oil of the cannabinoid with a solubility enhancing agent; lyophilizing the oil to form a powder; adding the stilbenoid or the derivative thereof to the powder; and formulating the powder into the oral dosage form. [0009] In some embodiments of the composition, the composition is in an oral dosage form. [0010] In some embodiments, the cannabinoid is tetrahydrocannabinol (THC), cannabidiol (CBD), or cannabinol (CBN), or any combination thereof. [001 1] In some embodiments, the cannabinoid is THC. [0012] In some embodiments, the stilbenoid or derivative thereof is selected from the group consisting of: resveratrol, piceatannolin, pinosylvin, astringin, piceid, oxyresveratrol, amelopsin A , amelopsin B, vitisin A , combretastatin, combretastatin B-1, isonotholaenic acid, combretastatin A-1, combretastatin A-4, gnetucleistol E , pinostilbene, pterostilbene, isoharpontigenin, gnetucleistol D, 4-methoxyresveratrol, rhaponticin, and rhapontigenin, cavicularin ,1-hydroxyphenanthrene and juncusol . [0013] In some embodiments, the oral dosage form is configured for sublingual or buccal administration. [0014] In some embodiments, the oral dosage form is a dissolvable tablet or capsule. [0015] In some embodiments, the solubility enhancing agent is a carbohydrate. [0016] In some embodiments, the carbohydrate is mannitol. [0017] In some embodiments, the cannabinoid is present in an amount between about 1 mg to about 20 mg. [0018] In some embodiments, the stilbenoid or derivative thereof is present in an amount between about 10 mg to about 40 mg. DETAILED DESCRIPTION [0019] A number of possible alternative features are introduced during the course of this description. It is to be understood that, according to the knowledge and judgment of persons skilled in the art, such alternative features may be substituted in various combinations to arrive at different embodiments of the present invention. [0020] Embodiments of the invention described herein relate to oral dosage forms of co crystals of stilbenoids or derivatives thereof, and cannabinoids in compositions suitable for sublingual and/or buccal delivery, which have improved dissolution rates and enhanced bioavailability of cannabinoids. Other embodiments relate to forming tablets containing cannabinoids and stilbenoids without forming cocrystals thereof. [0021] The major problem of THC in oral administration is its low bioavailability due to its poor dissolution properties and high first-pass metabolism. The bioavailability of orally ingested THC ranges from only 6% to approximately 20% depending on the drug vehicle employed (see US Patent 8,415,507, incorporated herein by reference in its entirety). [0022] Stilbenoids are hydroxylated derivatives of stilbene and have a C6-C2-C6 structure. They belong to the family of phenylpropanoids and share most of their biosynthesis pathway with chalcones. Stilbenoids have been suggested to have a number of health benefits as antioxidants, antifungals, anti-aging effects, anti-cancer effects, obesity prevention effects, cardiovascular protective effects and protective effects for brain/cognitive mental health. Stilbenoids and derivatives thereof include, but are not limited to resveratrol, piceatannolin, pinosylvin, astringin,
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