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WO2020252277A1 - Fabrication de delta 8 thc, de delta 10 thc et/ou de cannabinol à partir de cbd - Google Patents

Fabrication de delta 8 thc, de delta 10 thc et/ou de cannabinol à partir de cbd Download PDF

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Publication number
WO2020252277A1
WO2020252277A1 PCT/US2020/037456 US2020037456W WO2020252277A1 WO 2020252277 A1 WO2020252277 A1 WO 2020252277A1 US 2020037456 W US2020037456 W US 2020037456W WO 2020252277 A1 WO2020252277 A1 WO 2020252277A1
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Prior art keywords
thc
cbd
extract
isolate
homolog
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Michael S. Hartman
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Isomerz Inc
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Isomerz Inc
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
    • A01H5/00—Angiosperms, i.e. flowering plants, characterised by their plant parts; Angiosperms characterised otherwise than by their botanic taxonomy
    • A01H5/02—Flowers
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
    • A01H5/00—Angiosperms, i.e. flowering plants, characterised by their plant parts; Angiosperms characterised otherwise than by their botanic taxonomy
    • A01H5/12—Leaves
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
    • A01H6/00—Angiosperms, i.e. flowering plants, characterised by their botanic taxonomy
    • A01H6/28—Cannabaceae, e.g. cannabis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)

Definitions

  • the present application relates to methods of making of delta 8 tetrahydrocannabinol ( D 8 THC), delta 10 tetrahydrocannabinol ( D 10 THC) and/or cannabinol (CBN) with or without using a solvent.
  • D 8 THC delta 8 tetrahydrocannabinol
  • D 10 THC delta 10 tetrahydrocannabinol
  • CBN cannabinol
  • Delta-8-THC is an analog of tetrahydrocannabinol (THC) with antiemetic, anxiolytic, appetite-stimulating, analgesic, and neuroprotective properties.
  • D 8 THC binds to the cannabinoid G-protein coupled receptor CB1, located in the central nervous system. This agent exhibits a lower psychotropic potency than Delta-9-THC (D 9 THC), the primary form of THC found in cannabis.
  • D 8 THC is chemically different fromD 9 THC by only a few atomic bonds. While D 8 THC only exists naturally in fractions of a percent, it may be used in a variety of applications, offering unique effects.
  • D 10 THC is a derivative and isomer of CBD and D 9 THC.
  • Cannabinol (CBN) is a mildly psychoactive cannabinoid found only in trace amounts in Cannabis, mostly in aged Cannabis.
  • Some embodiments relate to a method of making delta 8 tetrahydrocannabinol (D 8 THC), delta 10 tetrahydrocannabinol (D 10 THC) and/or cannabinol (CBN), the method including: a) providing an extract or composition that comprises at least one of delta 9 tetrahydrocannabinol (D9 THC) or a cannabidiol (CBD);
  • the extract or composition includes CBD.
  • the CBD is converted to D 8 THC.
  • At least 50% of the CBD is converted to D 8 THC.
  • At least 99% of the CBD is converted to D 8 THC.
  • At least 90% of the CBD is converted to D 8 THC.
  • substantially all CBD is converted to D 8 THC.
  • the extract or composition is heated to at least 55 degrees centigrade.
  • At least 1.0 g of iodine is employed.
  • a ratio of 0.001:1 w/w of iodine to CBD is used.
  • the method further includes the addition of calcium carbonate to the heated extract or composition.
  • the method further includes the addition of sodium thiosulphate.
  • the extract or composition is prepared by CO 2 extraction. [0019] In some examples, a ratio of 40 g of extract or composition is employed to 1.2g of elemental iodine.
  • the extract or composition is first heated to at least 55 degrees centigrade for 20 minutes while stirring and then heated to at least 55 centigrade for at least 20 minutes.
  • the extract or composition is first heated to 90 degrees centigrade.
  • the method includes stirring and heating to at least 100 degrees centigrade.
  • the process does not include the addition of a solvent.
  • the process does not involve a use of a solvent between providing a extract or composition and production of D 8 THC.
  • no organic solvent is employed during a heating step b).
  • no organic solvent is employed during a, b, c, or d.
  • no organic solvent is employed during the process.
  • the extract or composition is CO 2 extracted from hemp.
  • the extract or composition is decarboxylated.
  • the extract or composition is CO 2 extracted from hemp and the extract or composition is then decarboxlated in order to produce the extract or composition used as the starting material.
  • Some embodiments relate to a method of making D 8 THC, the method including:
  • the catalyst is a metallic catalyst.
  • the catalyst is a non-metallic catalyst.
  • the extract is a plant extract.
  • Some embodiments relate to a method of making D 8 THC and/or CBN (and/or homologs thereof), the method including:
  • CBD CBD (or a homolog thereof) is converted into D8 THC and/or CBN (Cannabinol) (or a homolog thereof).
  • the CBD homolog is cannabidivarin (CBDV).
  • the reaction produces at least Tetrahydrocannabivarin (THCV).
  • the isolate comprises between 20-95% CBD (or CBDV).
  • the CBD is converted to D 8 THC.
  • the halogen or a free radical generator includes iodine.
  • any of the embodiments provided herein regarding a halogen or free radical generator can employ a halogen containing molecule.
  • At least 50% of the CBD is converted to D 8 THC.
  • at least 99% of the CBD is converted to D 8 THC.
  • At least 90% of the CBD is converted to D 8 THC.
  • substantially all CBD is converted to D 8 THC and CBN.
  • substantially all CBDV is converted to D 8 THCV and CBV.
  • CBDV is converted to D 8 THCV and CBV.
  • the isolate is heated to at least 70 degrees centigrade.
  • At least 1.0 g of iodine is employed.
  • At least ratio of 0.001:1 w/w of iodine to CBD (or CBDV) isolate is used.
  • iodine to CBD (or CBD) isolate is used.
  • the CBD isolate (or CBDV isolate) is between 20 and 99% CBD and comprises at least one of propane or butane.
  • the reaction is carried out between 1 torr and 3 million torr.
  • the method further includes the addition of sodium thiosulphate as a quencher.
  • the isolate is prepared by CO 2 extraction.
  • the isolate is first heated to at least 55 degrees centigrade for 20 minutes while stirring and then heated to at least 55 centigrade for at least 20 minutes.
  • the isolate is first heated to 90 degrees centigrade.
  • the process does not comprise the addition of a solvent.
  • the process is performed in a solvent.
  • the isolate is decarboxylated.
  • Some embodiments relate to a method of making D 8 THC and/or CBN or a homolog thereof, the method comprising:
  • CBD or homolog thereof is converted into D8 THC (or a homolog thereof) and/or CBN (or a homolog thereof).
  • the isolate is from a plant.
  • FIG. 1 depicts some embodiments of a reaction scheme in which a“CBD homolog” (formula A) is converted to a“THC homolog” (including, for example, THCV) as in formula C and/or a“CBN homolog” (including, for example, CBV) as in formula D.
  • a“CBD homolog” formula A
  • a“THC homolog” including, for example, THCV
  • a“CBN homolog” including, for example, CBV
  • D 8 THC, D 10 THC and/or CBN are provided herein.
  • Some embodiments relate to using D 9 THC or a CBD (cannabidiol) as a starting agent in the production of D 8 THC, D 10 THC and/or CBN via a solvent-less method.
  • the methods involve heat and/or iodine (or any halogen or free radical generator as an alternative to iodine).
  • the method is applied to an isolate, which can include, for example, a hemp isolate.
  • the method is applied to any isolate, that has been isolated from, for example, hemp.
  • the hemp isolate contains between 95 and 20% CBD in terms of purity.
  • the isolate can also contain pentane and/or butane.
  • the reaction starts with CBD and produces D 8 THC and/or CBN.
  • the method can be applied to homologs thereof.
  • the reaction starts with CBDV to convert it to D 9 THCV and then onto D 8 THCV and CBV (cannabidivarin). Any of the embodiments (including those in the claims) provided herein with respect to one of these embodiments can be applied to the homolog embodiments as well.
  • the reaction to produce D 8 THC and/cannabinol from CBD can be quenched with sodium thiosulfate.
  • the method involves an isolate of greater than 95% purity of CBD that can be converted into D 8 THC and CBN with (and optionally solely) using iodine (or other options provided herein) and heat.
  • the reaction comprises or consists of that outlined below (and in FIG.1):
  • R1 and R2 can be any alkyl group.
  • R1 and R2 are separately selected from any alkyl that is 1-20 carbon atoms in length.
  • the term“alkyl,” alone or in combination, refers to a fully saturated aliphatic. In certain embodiments, alkyls are optionally substituted.
  • an alkyl comprises 1 to 20 carbon atoms (whenever it appears herein, a numerical range, such as“1 to 20” or“C 1 -C 20 ”, refers to each integer in the given range; e.g.,“C 1 -C 20 alkyl” means that an alkyl group comprising only 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms).
  • alkyls include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, tert-amyl, pentyl, hexyl, heptyl, octyl and the like.
  • any of the compounds provided with respect to the options of R1 and R2 in the reaction diagram above can be applied in the context of any one of more of the embodiments and claims recited herein (simply by inserting the particular starting formula and following the reaction through, in place of the CBD embodiments provided in the claims below.
  • the term“CBD homolog” denotes those options encompassed within formula A above.
  • the term“THC homolog” (such as THCV) denotes those options encompassed within formula C above.
  • CBN homolog (such as CBV) denotes those options encompassed within formula D above.
  • R1 is 5 and R2 is one carbon.
  • the method in FIG.1 further comprises:
  • the reaction comprises or consists of that outlined below:
  • CBD or homologs thereof denotes both the general class of CBD:
  • CBDV cannabidivarin
  • Cannabinol denotes a compound with the following structure:
  • the reaction is a generalized reaction in the presence of iodine, or another halogen, or a free radical generating species.
  • the reaction is one as outlined in FIG.1.
  • the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • the reaction is carried out under atmospheric pressure. In some embodiments, the reaction is carried out between 1 torr and 3 million torr. In some embodiments, prior to adding the quencher, the reaction is allowed to continue for at least 30 minutes, for example, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24 hours or more, including 1, 2, 3, 4, 5, 6, 7 or more days, include 1, 2, or 3 or more months. In some embodiments, the reaction is one as outlined in FIG.1. In some embodiments, the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • the reaction is carried out under neutral or acidic conditions. In some embodiments, the reaction is one as outlined in FIG.1. In some embodiments, the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • this is a one-pot process.
  • the reaction is one as outlined in FIG. 1.
  • the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • the oxane (tetrahydropyran) ring closure occurs (CBD to D9 THC) followed by an isomerization of the double bond around the 9 th carbon (THC carbon numbering shown below).
  • this produces a more potent local analgesic isomer from CBD, delta 8 THC when topically applied reduces inflammation and pain.
  • CBDV is used as a starting compound (as a CBD homolog)
  • the reaction produces an isomer (THCV) that increases sensitivity to insulin as well as functions as an appetite suppressant in higher doses.
  • a method of making delta 8 tetrahydrocannabinol ( D 8 THC) is provided.
  • the method comprises:
  • D 9 THC delta 9 tetrahydrocannabinol
  • CBD cannabidiol
  • a-d can be applied to the homolog reaction process shown in FIG.1.
  • the extract or composition is heated to 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 106°C, 107°C, 108°C, 109°C, 110°C, 115°C, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C,
  • the reaction is one as outlined in FIG. 1. In some embodiments, the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • the w/w ratio of iodine to CBD to the heated extract or composition is 0.0005:1, 0.0010:1, 0.0015:1, 0.0020:1, 0.0025:1, 0.0030:1, 0.0035:1, 0.0040:1, 0.0045:1, 0.0050:1, 0.0055:1, 0.0060:1, 0.0065:1, 0.0070:1, 0.0075:1, 0.0080:1, 0.0085:1, 0.0090:1, 0.0095:1, 0.0100:1, 0.0150:1, 0.0200:1, 0.0250:1, 0.0300:1.
  • the reaction is one as outlined in FIG.1.
  • the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • step (d) the heating is continued for 20 min., 25 min., 30 min., 35 min., 40 min., 45 min., 50 min., 55 min., 1 hr., 1.5 hr, 2 hr., 2.5 hr, 3 hr., 3.5 hr, 4 hr., 4.5 hr., 5 hr., 5.5 hr, 6 hr., 6.5 hr, 7 hr., 7.5 hr, 8 hr., 8.5 hr, 9 hr., 9.5 hr,10 hr, 12 hr, 13hr, 14 hr, 15 hr, 16 hr, 17 hr, 18 hr, 19 hr, 20 hr, 21 hr, 22 hr, 23 hr, 24 hr, 48 hr or 72 hr, including any range defined between any two of the preceding values.
  • the reaction is one as outlined in FIG.1. In some embodiments, the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • the extract or composition comprises CBD.
  • the CBD is converted to D 8 THC.
  • the amount of CBD converted to D 8 THC is 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.9%, 99.99%, 99.999%, or greater.
  • the reaction is one as outlined in FIG.1.
  • the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • At least 50% of the CBD is converted to D 8 THC.
  • At least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% 95%, 96% 97%, 98%, 99%, 99.9%, 99.99%, 99.999%, or greater of the CBD is converted to D 8 THC.
  • at least 99% of the CBD is converted to D 8 THC.
  • at least 90% of the CBD is converted to D 8 THC.
  • substantially all CBD is converted to D 8 THC.
  • the extract or composition is heated to at least 55 degrees centigrade.
  • the extract or composition is heated to 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C,
  • At least 1.0 g of iodine is employed. In some examples, at least 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1.0 g. 1.5 g, 2.0 g, 2.5 g, 3.0 g, 3.5 g, 4.0 g, 4.5 g, 5.0 g or 10 g of iodine is employed. [0103] In some examples, a ratio of 0.001:1 w/w of iodine to CBD is used.
  • the w/w ratio of iodine to CBD to the heated extract or composition is 0.0001:1, 0.0005:1, 0.0010:1, 0.0015:1, 0.0020:1, 0.0025:1, 0.0030:1, 0.0035:1, 0.0040:1, 0.0045:1, 0.0050:1, 0.0055:1, 0.0060:1, 0.0065:1, 0.0070:1, 0.0075:1, 0.0080:1, 0.0085:1, 0.0090:1, 0.0095:1, 0.0100:1, 0.0150:1, 0.0200:1, 0.0250:1, 0.0300:1, 0.0500:1, 0.1000:1, 0.5000:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1.
  • the method further comprises the addition of calcium carbonate to the heated extract or composition.
  • method further comprises the addition of sodium thiosulphate.
  • the extract or composition is prepared by CO 2 extraction.
  • Cannabis oil is usually extracted on a commercial scale either through the use of solvents such as hexane or butane, or through more modern supercritical/subcritical CO 2 (carbon dioxide) processes.
  • Carbon dioxide-based extraction is considered to be more environmentally friendly, considerably safer, cleaner, cheaper and less toxic than using fossil fuel-based extraction, and results in a consistent product that is more palatable.
  • carbon dioxide is a gas. At 60.4 psi it is a liquid and at -78°C, at standard pressure, it is a solid (dry ice).
  • Supercritical liquids can pass through porous solids and also dissolve materials, making them ideal as a solvent.
  • The“tunability” of supercritical CO 2 extraction enables targeting maximum outputs of cannabidiol depending on the type and quality of cannabis material being used; while keeping undesirable compounds such as chlorophyll out of the product.
  • a pump forces pressurized carbon dioxide gas at the optimum supercritical temperature (ScCO 2 ) into the extractor chamber.
  • the supercritical carbon dioxide interacts with the cannabis, dissolving the cannabinoid compounds it contains.
  • the supercritical CO 2 carries the cannabis oil particles past a pressure release valve to a cyclonic separator.
  • the pressure is lower and the carbon dioxide and cannabis oil separates.
  • the cannabis oil, waxes and resins descend in the separator where they are captured by a collection vessel.
  • the resulting substance is processed further into various products, such as CBD-rich“cannabis oil”, free of any solvents.
  • a ratio of 40 g of extract or composition is employed to 1.2g of elemental iodine (i.e., a 33.33:1 ratio of extract/composition to elemental iodine).
  • the ratio of extract/composition to elemental iodine is 5:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1 or 100:1.
  • the extract or composition is first heated to at least 55 degrees centigrade for 20 minutes while stirring and then heated to at least 55 centigrade for at least 20 minutes.
  • the extract or composition is heated to 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 100°C, 101°C
  • the heating is continued for 20 min., 25 min., 30 min., 35 min., 40 min., 45 min., 50 min., 55 min., 1 hr., 1.5 hr, 2 hr., 2.5 hr, 3 hr., 3.5 hr, 4 hr., 4.5 hr., 5 hr., 5.5 hr, 6 hr., 6.5 hr, 7 hr., 7.5 hr, 8 hr., 8.5 hr, 9 hr., 9.5 hr or 10 hr, including any range defined between any two of the preceding values.
  • the extract or composition is first heated to 90 degrees centigrade.
  • the method comprises stirring and heating to at least 100 degrees centigrade.
  • the process does not comprise the addition of a solvent, such as ethanol, butane, propane, isopropyl, or alcohol.
  • a solvent such as ethanol, butane, propane, isopropyl, or alcohol.
  • the process does not involve a use of a solvent between providing an extract or composition and production of D 8 THC.
  • no organic solvent is employed during a heating step b).
  • no organic solvent is employed during a, b, c, or d.
  • no organic solvent is employed during the process.
  • the extract or composition is CO 2 extracted from hemp.
  • the extract or composition is CO 2 extracted from a plant.
  • plants that are extracted are marijuana (cannabis) and hemp.
  • D 9 THC levels in hemp are significantly lower than those in marijuana. The D 9 THC levels of hemp can rise if the plant becomes stressed by dry conditions, wind or other weather events.
  • the extract or composition is decarboxylated.
  • THC Tetrahydrocannabinolic acid
  • THC Tetrahydrocannabinolic acid
  • THCA contains an additional carboxyl group which makes for a different chemical structure compared to THC.
  • THCA is the precursor to THC and it is converted to THC as it is exposed to heat and oxygen over time. This process is known as decarboxylation.
  • THCA begins to convert to THC. Once dry, while there are trace amounts of THC in the plant, heating over time further converts THCA into THC.
  • the extract or composition is CO 2 extracted from hemp and the extract or composition is then decarboxylated in order to produce the extract or composition used as the starting material.
  • Some embodiments relate to a method of making D 8 THC, the method comprises:
  • the extract or composition is heated to 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 106°C, 107°C, 108°C, 109°C, 110°C, 115°C, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C,
  • the catalyst is a metallic catalyst.
  • the metallic catalyst is selected from those known in the art of organic chemistry.
  • the catalyst is a non-metal catalyst.
  • the non-metal catalyst is selected from those known in the art of organic chemistry.
  • the extract/composition : metallic catalyst ratio is 1:0.00001; 1:00005, 1:00010, 1:00015, 1:00020, 1:00025, 1:00030, 1:00035, 1:00040, 1:00045, 1:00050, 1:0010, 1:0015, 1:0020, 1:0025, 1:0050, 1:0100 or 1:0200.
  • the heating is continued for 20 min., 25 min., 30 min., 35 min., 40 min., 45 min., 50 min., 55 min., 1 hr., 1.5 hr, 2 hr., 2.5 hr, 3 hr., 3.5 hr, 4 hr., 4.5 hr., 5 hr., 5.5 hr, 6 hr., 6.5 hr, 7 hr., 7.5 hr, 8 hr., 8.5 hr, 9 hr., 9.5 hr or 10 hr.
  • the extract is a plant extract.
  • Some embodiments relate to a method of making D 8 THC and/or CBN (and/or homologs thereof), the method comprising:
  • CBD CBD (or a homolog thereof) is converted into D 8 THC and/or CBN (Cannabinol) (or a homolog thereof).
  • the reaction is one as outlined in FIG. 1.
  • the reaction is a method to convert a CBD homolog to one or both of a CBN homolog and/or a THC homolog, for example, as shown in FIG.1.
  • CBD and numerous analogs thereof are well known (Morales et al. 2017 “An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol” Frontiers in Pharmacology 8: 422).
  • the extract or composition is heated to 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 106°C, 107°C, 108°C, 109°C, 110°C, 115°C, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C,
  • the ratio of halogen or a free radical generator to CBD is 0.0001:1, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0010:1, 0.0010:1, 0.0020:1, 0.0025:1, 0.0030:1, 0.0040:1, 0.0050:1 or 0.01:1.
  • the halogen or a free radical generator is selected from iodine, and those known in the art of organic chemistry.
  • CBD homolog is cannabidivarin (CBDV).
  • the reaction produces at least Tetrahydrocannabivarin (THCV).
  • the isolate comprises between 20-95% CBD (or CBDV).
  • the isolate comprises 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% CBD or an analog thereof, such as CBDV.
  • the CBD is converted to D 8 THC.
  • the halogen or a free radical generator comprises iodine.
  • At least 50% of the CBD is converted to D 8 THC.
  • At least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the CBD is converted to D 8 THC.
  • At least 99% of the CBD is converted to D 8 THC. In some examples, at least 90% of the CBD is converted to D 8 THC. In some examples, substantially all CBD is converted to D 8 THC and CBN. In some examples, substantially all CBDV is converted to D 8 THCV and CBV. In some examples, CBDV is converted to D 8 THCV and CBV. [0158] In some examples, the isolate is heated to at least 70 degrees centigrade.
  • the isolate is heated to at least 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 106°C, 107°C, 108°C, 109°C, 110°C, 115°C, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C,
  • At least 1.0 g of iodine is employed.
  • At least 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1.0 g. 1.5 g, 2.0 g, 2.5 g, 3.0 g, 3.5 g, 4.0 g, 4.5 g, 5.0 g or 10 g of iodine is employed, including any range defined between any two of the preceding values
  • At least ratio of 0.001:1 w/w of iodine to CBD (or CBDV) isolate is used.
  • the w/w ratio of iodine to CBD (or CBDV) in the isolate is 0.0001:1, 0.0005:1, 0.0010:1, 0.0015:1, 0.0020:1, 0.0025:1, 0.0030:1, 0.0035:1, 0.0040:1, 0.0045:1, 0.0050:1, 0.0055:1, 0.0060:1, 0.0065:1, 0.0070:1, 0.0075:1, 0.0080:1, 0.0085:1, 0.0090:1, 0.0095:1, 0.0100:1, 0.0150:1, 0.0200:1, 0.0250:1, 0.0300:1, 0.0500:1, 0.1000:1, 0.5000:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1, including any range defined between any two of the preceding values
  • iodine to CBD (or CBDV) isolate is used.
  • the CBD isolate (or CBDV isolate) is between 20 and 99% CBD and comprises at least one of propane or butane.
  • the CBD isolate (or CBDV isolate) is 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%, including any range defined between any two of the preceding values
  • the reaction is carried out between 1 torr and 3 million torr. [0168] In some examples, the reaction is carried out at a pressure of about 1 torr, 2 torr, 3 torr, 4 torr, 5 torr, 6 torr, 7 torr, 8 torr, 9 torr, 10 torr, 20 torr, 30 torr, 40 torr, 50 torr, 60 torr, 70 torr, 80 torr, 90 torr, 100 torr, 200 torr, 300 torr, 400 torr, 500 torr, 600 torr, 700 torr, 800 torr, 900 torr, 1 x 10 3 torr, 5 x 10 3 torr, 1 x 10 4 torr, 5 x 10 4 torr, 1 x 10 5 torr, 5 x 10 5 torr, 1 x 10 6 torr, 2 x 10 6 torr or 3 x
  • the method further comprises the addition of sodium thiosulphate as a quencher.
  • the isolate is prepared by CO 2 extraction.
  • the isolate is first heated to at least 55 degrees centigrade for 20 minutes while stirring and then heated to at least 55 centigrade for at least 20 minutes.
  • the extract or composition is heated to 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 100°C, 101°C
  • the heating is continued for 20 min., 25 min., 30 min., 35 min., 40 min., 45 min., 50 min., 55 min., 1 hr., 1.5 hr, 2 hr., 2.5 hr, 3 hr., 3.5 hr, 4 hr., 4.5 hr., 5 hr., 5.5 hr, 6 hr., 6.5 hr, 7 hr., 7.5 hr, 8 hr., 8.5 hr, 9 hr., 9.5 hr or 10 hr, including any range defined between any two of the preceding values
  • the isolate is first heated to 90 degrees centigrade.
  • the process does not comprise the addition of a solvent.
  • the process is performed in a solvent.
  • the isolate is decarboxylated.
  • Some embodiments relate to a method of making D 8 THC and/or CBN or a homolog thereof, the method comprising:
  • CBD or homolog thereof is converted into D 8 THC (or a homolog thereof) and/or CBN (or a homolog thereof).
  • the extract or composition is heated to 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 100°C, 101°C
  • the heating is continued for 20 min., 25 min., 30 min., 35 min., 40 min., 45 min., 50 min., 55 min., 1 hr., 1.5 hr, 2 hr., 2.5 hr, 3 hr., 3.5 hr, 4 hr., 4.5 hr., 5 hr., 5.5 hr, 6 hr., 6.5 hr, 7 hr., 7.5 hr, 8 hr., 8.5 hr, 9 hr., 9.5 hr or 10 hr.
  • the isolate is from a plant.
  • the plant is selected from marijuana (cannabis) and hemp.
  • Example 1 In lieu of the isolate, a plant extract is used instead of the isolate.
  • An extract is obtained that comprises at least one of delta 9 tetrahydrocannabinol ( D 9 THC) or a cannabidiol (CBD).
  • D 9 THC delta 9 tetrahydrocannabinol
  • CBD cannabidiol
  • the extract is heated to at least 70 degrees centigrade to make a heated extract.
  • At least 0.0005:1 weight to weight of iodine to CBD is added to the heated extract.
  • the heated extract is for at least 20 minutes while stirring, such that the ( D 9 THC or CBD is converted into D8 THC, delta 10 tetrahydrocannabinol ( D 10 THC) and/or cannabinol (CBN).
  • D 9 THC or CBD is converted into D8 THC, delta 10 tetrahydrocannabinol ( D 10 THC) and/or cannabinol (CBN).
  • An extract is obtained that comprises at least one of D 9 THC or a CBD;
  • the extract is heated to at least 70 degrees centigrade to make a heated extract.
  • a catalyst is added to the heated extract or composition, wherein the extract or composition to catalyst is present in a ratio of about 1 : 0.0005 (grams of extract or composition to grams of catalyst) to about 1:1 (grams of extract or composition to grams of catalyst).
  • An isolate is obtained that comprises at least a CBD (or a homolog thereof).
  • the isolate is heated to between 55 and 800 degrees centigrade to make a heated isolate
  • the isolate is heated for an additional at least 30 minutes, such that the CBD (or a homolog thereof) is converted into D 8 THC and/or CBN (Cannabinol) (or a homolog thereof).
  • Example 4 Method of making D 8 THC and/or CBN or a homolog thereof
  • An isolate is obtained that comprises a CBD or a homolog thereof.
  • the isolate is heated to at least 55 degrees centigrade to make a heated isolate.
  • a free radical generator is added to the heated isolate, wherein the isolate to free radical generator is present in a ratio of about 1:0.0001 (grams of isolate to grams of free radical generator) to about 1:10 (grams of isolate to grams of free radical generator).
  • the isolate is heated for an additional at least 20 minutes while stirring, such that the CBD or homolog thereof is converted into D8 THC (or a homolog thereof) and/or CBN (or a homolog thereof).
  • Example 1-4 can be employed for the reaction scheme noted above in the alternative. This allows for the conversion of a CBD homolog to one or both of a CBN homolog and/or a THC homolog (as shown in FIG.1).
  • FIG. 1 While various embodiments are provided herein in terms of an isolate, in some embodiments, any one of these embodiments can be modified and applied to an extract.

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Abstract

L'invention concerne un procédé de fabrication de delta 8-tétrahydrocannabinol (Δ8 THC) ou de ses homologues, de delta 10-tétrahydrocannabinol (Δ10 THC) ou de ses homologues et/ou de cannabinol (CBN) ou de ses homologues, le procédé consistant à : a) fournir un extrait ou d'une composition qui comprend au moins un parmi le delta 9-tétrahydrocannabinol (Δ9 THC) et ses homologues et un cannabidiol (CBD) et ses homologues ; b) chauffer l'extrait ou la composition ; c) ajouter de l'iode au CBD ou ses homologues à l'extrait ou à la composition chauffé ; et d) continuer à chauffer tout en agitant, de telle sorte que le (Δ9 THC) ou le CBD ou ses homologues soient transformés en (Δ8 THC), en delta 10-tétrahydrocannabinol (Δ10 THC) et/ou en cannabinol (CBN) (y compris des homologues de l'un quelconque des précédents). Dans certains cas, un catalyseur est ajouté à l'extrait chauffé. Dans certains cas, un halogène ou un générateur de radicaux libres est ajouté à l'isolat chauffé.
PCT/US2020/037456 2019-06-13 2020-06-12 Fabrication de delta 8 thc, de delta 10 thc et/ou de cannabinol à partir de cbd Ceased WO2020252277A1 (fr)

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US12281091B1 (en) 2024-01-03 2025-04-22 Florascience Inc. Methods of preparing cannabinoids or derivatives thereof
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Publication number Priority date Publication date Assignee Title
WO2021139740A1 (fr) 2020-01-08 2021-07-15 成都百裕制药股份有限公司 Dérivé tétrahydrocannabinol et son procédé de préparation et son utilisation médicale
US12281091B1 (en) 2024-01-03 2025-04-22 Florascience Inc. Methods of preparing cannabinoids or derivatives thereof
WO2025147239A1 (fr) * 2024-01-03 2025-07-10 Florascience Inc. Procédés de préparation de cannabinoïdes ou de dérivés de ceux-ci
US12371412B2 (en) 2024-01-03 2025-07-29 Florascience Inc. Methods of preparing cannabinoids or derivatives thereof

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