WO2019211797A1 - Procédé de décarboxylation de cannabinoïdes acides dans un extrait de cannabis en suspension dans un fluide transporteur - Google Patents

Procédé de décarboxylation de cannabinoïdes acides dans un extrait de cannabis en suspension dans un fluide transporteur Download PDF

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Publication number
WO2019211797A1
WO2019211797A1 PCT/IB2019/053612 IB2019053612W WO2019211797A1 WO 2019211797 A1 WO2019211797 A1 WO 2019211797A1 IB 2019053612 W IB2019053612 W IB 2019053612W WO 2019211797 A1 WO2019211797 A1 WO 2019211797A1
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biomass
oil
cannabinoids
solvent
chamber
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PCT/IB2019/053612
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English (en)
Inventor
Tomasz Popek
Steven Splinter
Harmandeep KAUR
Anna BAKOWSKA-BARCZAK
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Radient Technologies Inc.
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Publication of WO2019211797A1 publication Critical patent/WO2019211797A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0211—Solvent extraction of solids in combination with an electric or magnetic field
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0215—Solid material in other stationary receptacles
    • B01D11/0219—Fixed bed of solid material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0292—Treatment of the solvent
    • B01D11/0296—Condensation of solvent vapours
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B63/00—Purification; Separation; Stabilisation; Use of additives
    • C07B63/02—Purification; Separation; Stabilisation; Use of additives by treatment giving rise to a chemical modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/50—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions decreasing the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
    • C07C37/86—Purification; separation; Use of additives, e.g. for stabilisation by treatment giving rise to a chemical modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/48—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/028—Flow sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0288—Applications, solvents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated

Definitions

  • the present disclosure is generally related to a method of decarboxylating a cannabis extract. More particularly, the present disclosure relates to a method of decarboxylating a cannabis extract suspended within a solvent or diluent.
  • Cannabis is a genus belonging to the family of cannabaceae. Three common species include Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The genus has been indigenous to Central Asia and the Indian subcontinent. Cannabis has a long history being used for medicinal, therapeutic, and recreational purposes. The importance of cannabis in therapeutics is
  • Cannabis is known, for example, to be capable of relieving nausea (such as that accompanying chemotherapy), pain, vomiting, spasticity in multiple sclerosis, and increase hunger in anorexia.
  • cannabis or “cannabis biomass” encompasses the Cannabis sativa plant and also variants thereof, including subspecies sativa, indica and ruderalis, cannabis cultivars, and cannabis chemovars (varieties characterised by chemical composition), which naturally contain different amounts of the individual cannabinoids, and also plants which are the result of genetic crosses.
  • cannabis chemovars variants characterised by chemical composition
  • the term “cannabis biomass” is to be interpreted accordingly as encompassing plant material derived from one or more cannabis plants.
  • Cannabis biomass contains a unique class of terpeno-phenolic compounds known as cannabinoids or phytocannabinoids, which have been extensively studied since the discovery of the chemical structure of tetrahydrocannabinol (Delta-9-THC), commonly known as THC. Over 113 phytocannabinoids have been identified.
  • cannabinoids are generally produced by glandular trichomes that occur on most aerial surfaces of the plant.
  • the cannabinoids are biosynthesized in the plant in acidic forms known as acidic cannabinoids.
  • cannabinoids may be slowly decarboxylated during drying of harvested plant material.
  • Decarboxylation may be hastened by heating the cannabis biomass, such as when the cannabis biomass is smoked or vaporized.
  • the principle cannabinoids present in cannabis are the Delta-9- tetrahydrocannabinolic acid (Delta-9-THCA) and cannabidiolic acid (CBDA).
  • the Delta-9-THCA does not have its own psychoactive properties as is, but may be decarboxylated to Delta-9- tetrahydrocannabinol (Delta-9-THC), which is the most potent psychoactive cannabinoid among known cannabinoids.
  • the neutral form of CBDA is cannabidiol (CBD), which is a major cannabinoid substituent in hemp cannabis.
  • CBD is non-psychoactive and is widely known to have therapeutic potential for a variety of medical conditions.
  • the proportion of cannabinoids in the plant may vary from spedes to species, as well as vary within the same species at different times and seasons. Furthermore, the proportion of cannabinoids in a plant may further depend upon soil, climate, and harvesting methods. Thus, based on the proportion of the cannabinoids present in a plant variety, the psychoactive and medicinal effects obtained from different plant varieties may vary.
  • a specific variety of cannabis may be considered more effective or potent than others (e.g ., in providing the desired physiological effect at a desired level in an individual).
  • some specific combinations of pharmacologically active compounds in a cannabis variety may be more desirable in comparison to other varieties.
  • the retention of the full mix of cannabinoids present in the original plant may be desirable for some varieties, while other varieties may be preferred in altered form due to the variances in the specific cannabinoid composition and concentrations. Such variance is further exacerbated by the presence of certain terpenoid or phenolic compounds, which may have pharmacological activity of their own and which may be desired at different concentrations in different combinations.
  • compounds may be extracted from cannabis by using conventional methods of extraction, such as maceration, decoction, or solvent extraction.
  • conventional methods may suffer from various limitations and disadvantages (e.g., extraction times may be very high so as to be impractical to scale).
  • subjecting the biomass to a prolonged extraction process may risk modification of the plant profile, negative effects on terpenes, or otherwise cause other undesirable effects that lower the quality or purity of the end product.
  • Traditional methods of extraction may therefore hamper quality and purity of the final product.
  • final concentrated or purified active compounds are often diluted or dispersed into an oil, fat or other lipid-based excipient or carrier to a desired concentration for certain uses (e.g., in a pharmaceutical, food, or cosmetic formulation).
  • SFE supercritical fluid extraction
  • traditional methods of extracting inactive cannabinoids from a raw cannabis biomass typically involve subjecting the raw cannabis biomass to a heating process in order to decarboxylate the cannabinoids prior to extraction.
  • Subjecting the biomass to a heating process may cause combustion, modification of the plant profile, negative effect on terpenes, or cause other undesirable effects that could lower quality or purity of a cannabis extract.
  • the process of decarboxylation of cannabis biomass can increase the amount of cannabinoids occurring as artefacts by oxidative degradation or isomerization.
  • extraction of cannabis biomass that has been subjected to a thermal decarboxylation can lead to loss of valuable compounds including terpenes.
  • decarboxylation of cannabis biomass prior to extraction does not provide an ability to control the amount of decarboxylation reaction to a desired percentage of neutral cannabinoids and so provide extract products with varying ratios of cannabinoid acids and corresponding neutral cannabinoids. So, traditional methods of extraction hamper quality and purity of the cannabis extract.
  • Embodiments of the present invention provide systems and methods for producing active cannabinoids from acidic carmabinoids.
  • the processes described herein include the decarboxylation of the acidic cannabinoids in order to release carbons from the carbon chain in order to achieve neutral cannabinoids.
  • a novel approach is provided for the
  • Exemplary methods for decarboxylating addic cannabinoids from a raw cannabis biomass may therefore include preparing a raw cannabis biomass, adding a solvent to form a slurry, extracting and separating out a quantity of acidic cannabinoids, adding a carrier fluid to the extracted acidic cannabinoids, and decarboxylating the addic cannabinoids by heating to a predetermined temperature for a predetermined period of time.
  • FIG. 1 is a block diagram representation of an exemplary system for decarboxylating a cannabis extract suspended within a carrier fluid.
  • FIG. 2 illustrates a flow chart for decarboxylating a cannabis extract suspended within a carrier fluid.
  • FIGS. 3A and 3B are tables indicating cannabinoid concentration of samples before and after decarboxylation.
  • FIG. 4A is a table indicating cannabinoid recovery from a cannabis biomass sample.
  • FIG. 4B is a table indicating cannabinoid recovery from a cannabis biomass sample pre-processed by decarboxylation.
  • FIG. 5 is a table providing the decarboxylation results obtained during a final formulation step.
  • FIG. 6 is a table providing the decarboxylation results obtained during the final formulation step.
  • FIG. 7 illustrates a flow chart 600 showing a method of decarboxylating a cannabis extract suspended within a carrier fluid.
  • Exemplary methods for decarboxylating acidic carmabinoids from a raw cannabis biomass may include preparing a raw cannabis biomass, adding a solvent to form a slurry, extracting and separating out a quantity of addic carmabinoids, adding a carrier fluid to the extracted addic carmabinoids, and decarboxylating the acidic carmabinoids by heating to a predetermined temperature for a predetermined period of time.
  • FIG. 1 is a block diagram representation of an exemplary system 100 for extracting pharmacologically active compounds from a cannabis biomass
  • FIG. 2 is a flow chart illustrating an exemplary method for the decarboxylation of the cannabis extract.
  • System 100 illustrated in FIG. 1 can includes a raw biomass holding chamber 102, into which a raw biomass may be provided in step 202 of FIG. 2.
  • a raw biomass may be present in the form of dried, ground, non-decarboxylated flowers (such as buds) of a cannabis plant.
  • the raw biomass can be any part of the cannabis plant which may contain cannabinoids including, but not limited to, leaves, stems, roots, and the like.
  • Said cannabis biomass can be provided to the raw biomass holding chamber 102 of system 100.
  • the average particle size of the raw biomass may lie between 0.5 mm 10 mm.
  • the raw biomass may contain target compounds that need to be extracted.
  • the raw biomass may be heated to approximately 125°C for approximately 45 minutes to decarboxylate the cannabinoid carboxylic acids into neutral cannabinoid forms.
  • the mass of decarboxylated cannabis following such treatment may be reduced from the originally provided mass (for example, 11.7% weight loss).
  • the raw biomass may be a dried, non- decarboxylated cannabis biomass.
  • the raw biomass may be a fresh, non- dried, non-decarboxylated cannabis biomass.
  • the raw biomass may be sampled and analyzed in a sampling chamber 120.
  • the raw biomass may be sampled and analyzed using several methods.
  • the raw biomass may be analyzed to determine cannabinoid content and create a cannabinoid profile (providing the specific cannabinoids present in die sample and concentrations thereof) of the sampled raw biomass.
  • Such analysis may be performed using an Ultra High Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS) detection technique.
  • UPLC-MS Ultra High Performance Liquid Chromatography coupled with Mass Spectrometry
  • a terpene profile of the raw biomass may be created using a Gas Chromatography-Mass Spectrometry (GC-MS) detection technique.
  • GC-MS Gas Chromatography-Mass Spectrometry
  • the sampling and analytical techniques may help in determining the cannabinoid content and cannabinoid profile of the raw biomass.
  • the cannabinoid profile can include the total cannabinoids content (wt%), concentration of individual cannabinoids (wt%), THCA+THC (wt%), CBD+CBDA (wt%), total THC equivalents (determined using the formula THC+THCA x 0.877 (wt%)), and total CBD equivalents (determined using the formula CBD+CBDA x 0.877 (wt%)).
  • the cannabinoid profile created can be used to determine the amount of acidic and neutral cannabinoids which may be extracted.
  • the raw biomass may be ground into small particles in biomass preparation chamber 104 to obtain a prepared biomass.
  • the size of particles of the ground biomass may range between about 0.5 mm to about 10 mm.
  • the grinding process may be performed utilizing one or more of a grinding machine, a shredding machine, a biomass pulverizing machine, and the like.
  • the prepared biomass may then be provided from biomass preparation chamber 104 to a prepared biomass holding chamber 106.
  • the prepared biomass may be used in the formation of a slurry in step 208.
  • the slurry may be formed in slurry formation chamber 108, where one or more solvents from a solvent holding chamber 110 and the prepared biomass from the prepared biomass chamber 106 are combined.
  • the solvent added to the prepared biomass may be selected with different dielectric and solvent parameter properties.
  • the solvent may be, for example, an edible or food-grade solvent or emulsifier used to standardize active compounds in
  • the solvent may be a water, an alcohol group, an alkane group, a ketone group, a polyunsaturated fatty acid (PUFA), corn oil, safflower oil, borage oil, flax oil, canola oil, cottonseed oil, soybean oil, olive oil, sunflower oil, coconut oil, palm oil, monoglycerides, diglycerides, triglycerides, medium chain triglycerides (MCT), long chain tryglycerides, lecithin, limonene, essential oils of spices, herbs, or other plants, fish oil, glycerol, glycols, or mixtures thereof.
  • PUFA polyunsaturated fatty acid
  • corn oil safflower oil, borage oil, flax oil
  • canola oil cottonseed oil
  • soybean oil olive oil
  • sunflower oil coconut oil
  • palm oil monoglycerides
  • diglycerides diglycerides
  • triglycerides medium chain triglycerides (MCT)
  • MCT may be used as the solvent. It should be understood that certain solvents may be preferable from a marketing standpoint and/or cost standpoint.
  • the solvent-to-biomass ratio may be maintained at approximately 5 l/kg to approximately 10 l/kg to ease the pumping operation of the slurry. In an embodiment, the solvent-to-biomass ratio may be maintained as low as possible so as to maximize the concentration of the pharmacologically active compounds in the extract product.
  • the cannabinoid profile created using the raw biomass material can be used in determining the amount of solvent required in order to achieve the desired solvent-to- biomass ratio of the slurry.
  • the slurry may be transferred from the slurry formation chamber 108 to an extraction chamber 112 where such slurry is subject to heat at step 210.
  • the slurry may be transported to the extraction chamber 112 using a set of mechanical conveyors (e.g ., a slurry pump, a screw conveyor, or a worm gear).
  • the slurry may be subjected to a thermal process, such as that provided by a microwave generator 114. It may be understood that the solvent(s) selected may require a specific temperature to facilitate an efficient transportation through the set of mechanical conveyors.
  • the solvent e.g., MCT
  • the solvent can be heated using thermal energy (e.g., from microwave generator 114) to a temperature that meets or exceeds the solvent's melting point.
  • the slurry may be transported into an extractor chamber 112 through a tube.
  • At least one portion of the extraction chamber 112, or the entire extraction chamber 112, can be microwave transparent.
  • the microwave transparent portion of the extraction chamber 112 may allow microwaves (e.g., microwaves generated using a magnetron of microwave generator 114) to pass through the extraction chamber 112 and heat the slurry inside.
  • the slurry may be heated within the extraction chamber 112 to a certain temperature by exposing the slurry to the microwave for a predefined time with a predefined, and controlled, microwave energy density range.
  • the slurry may be heated to a temperature range of approximately 20° C - 75° C with a contact time of approximately 1-30 minutes, and a microwave energy density range of approximately O.lkW per 1kg of biomass (0.1 kW/kg) to approximately 10 kW/kg.
  • the procedure (e.g., time, temperature, or energy range) used in the extraction process can be adjusted based on the cannabinoid profile of the raw biomass (e.g., the cannabinoid profile created in step 204) in order to achieve a desired extraction efficiency (% recovery of available cannabinoids).
  • the methods described herein can be conducted on an industrial scale. In at least one example, the methods can be performed on samples of over 1,000 kg to over 10,000 kgs of biomass per extraction.
  • the microwave energy, contact time and temperature range can be selected specifically to avoid decarboxylation or decomposition of the cannabinoids.
  • the heating process described herein can, in at least some examples, facilitate the extraction of various (pharmacologically active) compounds from the prepared biomass into the solvent.
  • the extraction chamber 112 may be filled completely with solvent prior to the extraction process in order to remove air and other gases from the extraction chamber 112.
  • the extraction chamber 112 may be purged with an inert gas such as nitrogen prior to the extraction process in order to remove air and other oxidizing gases from the extraction chamber 112.
  • the now-spent biomass and solvent(s) may be transferred to separation chamber 116, where the slurry is subject to filtration and separation at step 212.
  • separation can be performed within a filtration unit 116 and may result in the isolation of the slurry components from each other: the spent biomass and the solvent(s) containing the extracted compounds.
  • the separation process may be performed using filtration, centrifuge, and other similar processes. In a preferred embodiment, the separation process may include use of a filter press. In other embodiments, the spent biomass and extract mixture can be separated by centrifugation.
  • the spent biomass and the solvent(s) containing the extracted compounds may be transferred into a spent biomass holding chamber 118 and solvent recovery chamber 122, respectively. Additionally the desired extract is moved to a formulation chamber 124.
  • the spent biomass from spent biomass holding chamber 118 may be sampled and analyzed at step 214.
  • the sampling of the spent biomass may be performed in a sampling chamber 120.
  • the spent biomass may be sampled and analyzed to determine the remaining cannabinoid content of the spent biomass and create a carmabinoid profile.
  • analyses can be performed using several methods. For example, the analysis may be performed using an Ultra High Performance Liquid
  • the terpene profile of the biomass may be determined using a Gas Chromatography-Mass
  • the cannabinoid profile of the spent biomass can be used to determine the effectiveness of the extraction process. If the extraction efficiency is determined to be below a desired threshold, the system can be adjusted based on the obtained cannabinoid profile in order to increase efficiency.
  • the procedure e.g ., time, temperature, or energy range
  • the extraction process can be adjusted by increasing or decrease the amount of solvent is used in the extraction process.
  • the spent biomass e.g., waste biomass
  • the spent biomass may be then incinerated or mixed with a deactivating agent by disposal system 128.
  • the deactivating agent used may be clay.
  • the solvent recovered from the separation chamber 116 can be transferred to solvent recovery chamber 112 for later use.
  • the solvent may be recovered from the extract/solvent mixture using a distillation, an evaporation process, or any other suitable solvent removal or recovery process, such that the solvent may be reused in a later extraction process.
  • a desolventized extract can be obtained and transferred to formulation chamber 124.
  • the desolventized extract may be formulated using a carrier fluid provided by a carrier fluid holding chamber 126 in the formulation chamber 124.
  • the carrier fluid can be an edible or food- grade solvent such as a medium chain triglyceride oil (MCT oil) which can be used to form the formulated extract.
  • MCT oil medium chain triglyceride oil
  • the formulated extract may only be partially desolventized.
  • a partially desolventized extract can provide various benefits.
  • a partially desolventized extract may provide a different (e.g., thinner) viscosity than a fully desolventized extract, allowing the partially desolventized extract to be more easily transported and mixed with the carrier fluid.
  • a carrier fluid such as MCT oil
  • MCT oil may be suitable for human consumption and may be composed of any suitable combination of C-6; C-8; C-10; and C-12 fatty acids.
  • MCT oil may be composed of approximately 50% to approximately 65% C-8 and approximately 30% and approximately 45% C-10 fatty acids (e.g ., Mygliol).
  • the carrier fluid may be coconut oil or fractionated coconut oil.
  • the carrier fluid may be selected from the group comprising a polyunsaturated fatty acid (PUFA), com oil, safflower oil, borage oil, flax oil, canola oil, cottonseed oil, soybean oil, olive oil, sunflower oil, mono-, di- and triglyclerides, lecithin, limonene, fish oil, glycerol, glycols, or any other, or mixtures thereof.
  • PUFA polyunsaturated fatty acid
  • com oil com oil
  • safflower oil borage oil
  • flax oil canola oil
  • cottonseed oil soybean oil
  • olive oil sunflower oil
  • mono-, di- and triglyclerides lecithin, limonene, fish oil, glycerol, glycols, or any other, or mixtures thereof.
  • the mixture of partially desolventized extract and diluent may then be completely desolventized, resulting in a mixture of extract and diluent.
  • the formulated extract may be sampled and analyzed using sampling chamber 120.
  • the formulated extract may be analyzed using several methods.
  • the formulated extract may be analyzed to determine cannabinoid content and to create a cannabinoid profile, as described in detail above.
  • the analyses may be performed using a UPLC-MS detection technique.
  • the formulated extract comprising a mixture of the desolventized (or partially dexolventized) extract and the carrier fluid, may undergo a decarboxylation process in step 220.
  • the decarboxylation process can be performed in a decarboxylation unit 130.
  • the formulated extract may be decarboxylated by heating performed within a heating apparatus.
  • the heating apparatus may be a microwave heating apparatus as described above.
  • the microwaves may be generated using a magnetron which may heat the formulated extract inside a microwave heating apparatus.
  • the formulated extract may be heated to a predetermined temperature by exposing the formulated extract to the microwave for a predefined time within a predefined microwave energy range.
  • decarboxylation (e.g., heating) of the formulated extract can transform the acidic cannabinoids into their active (e.g., neutral) form.
  • the heating apparatus described herein is referred to as a microwave, it should be generally understood that any heating apparatus which is capable of controlling the degree of heating may be used.
  • the heating apparatus may be a conventional oven, oil baths, a jacketed, an agitated reactor vessel, a continuous-flow extractor.
  • the heating apparatus may be a continuous-flow microwave reactor operating under approximately atmospheric pressure.
  • the desired active cannabinoids may be obtained by heating the final formulated extract, causing the acidic cannabinoids to decarboxylate.
  • the heating may be conducted in the temperature range of from about 80°C to about 125°C for a time range of about 30 to about 300 minutes. In a preferred embodiment, the heating can be conducted at a temperature of about 100°C for a period of about 120 minutes. In an exemplary embodiment, the heating may be done at a temperature and time that is determined by the concentration of acidic cannabinoids in the formulated extract. In a preferred embodiment, the heating may be done using microwave energy and the time and temperature of heating that is carefully controlled.
  • the formulated extract may be separated a second separation chamber 132 in order to obtain the final formulated extract.
  • the separation process of step 222 may be performed using filtration, centrifugation, and other similar separation processes.
  • the final formulated extract may then be stored in a product holding chamber 134.
  • the final formulated extract may be formulated into a final formulated extract using at least one of a plurality of formulation methods.
  • Upon obtaining final formulated extract sampling and analysis may be performed at step 224.
  • the analysis may be done using a sampling chamber 120.
  • the final formulated extract may be sampled and analyzed by using at least one of several techniques.
  • analysis of the final formulated extract may be performed to detect cannabinoid content and create a cannabinoid profile of the formulation.
  • the analysis may be performed using a UPLC-MS/MS detection technique.
  • a terpene profile of the final formulated extract may be detected using a GC-MS detection technique.
  • Such analytic techniques may help determine the cannabinoid content and create a cannabinoid profile of the final formulated extract ( i.e ., THCA, THC, CBDA, CBD, and total cannabinoids).
  • cannabinoid profile of the final formulation can be used to determine the efficiency of the decarboxylation process.
  • the procedure used in the decarboxylation process can be adjusted based on the cannabinoid profile in order to obtain a desired final formulation.
  • FIGS. 3A and 3B illustrate the effects of a decarboxylation process on the cannabinoid profile of a plurality of samples.
  • FIG. 3A provides the cannabinoid concentrations from a plurality of non-decarboxylated samples.
  • FIG. 3B illustrates the effects of a decarboxylation process on the cannabinoid profile of a plurality of samples.
  • the decarboxylation of samples 1-3 of FIG. 3B was performed using an oven as a heating apparatus. Samples 1-3 were heated in the oven to a temperature of approximately 125°C for a period of approximately 45 minutes.
  • THCA tetrahydrocannabinolic acid
  • the decarboxylation process can be performed prior to the extraction of the cannabinoids.
  • the decarboxylation process can include heating the raw biomass in a heating apparatus to a temperature from approximately 100°C to approximately 160°C for approximately 45 to approximately 60 minutes.
  • the decarboxylation process described herein causes a chemical reaction that converts the acidic cannabinoids to a neutral cannabinoid (such as a phenol), and releases carbon-dioxide (CO2) in the process.
  • CO2 carbon-dioxide
  • as the carbon atoms can be removed from the carbon chain of the cannabinoid, for example converting THCA to the neutral cannabinoid, tetrahydrocannabinol (THC).
  • FIGS. 4A and 4B provide a comparison of the results obtained during a decarboxylation of the biomass performed at the preparation step and a
  • the slurry that is formed may be extracted using a solvent, such as ethanol.
  • a solvent such as ethanol.
  • the solvent/extract mixture (the "miscella") may be separated from the solvent/spent biomass mixture.
  • the spent biomass solids may be collected for disposal.
  • the miscella may be then collected in a vacuum evaporator and the solvent distillate may be condensed and collected for re-use.
  • the extraction process can use an extraction solvent, such as ethanol, and heat the biomass using a heating source, such as a microwave, for a period of approximately 20 minutes.
  • the slurry may be formulated with formulating agent or carrier fluid (for example MCT oil), either prior to, or after, desolventization.
  • formulating agent or carrier fluid for example MCT oil
  • the formulated extract may then be separated (e.g., filtered) to remove any sediment in order to form the final formulated extract, as described in method 200 of FIG. 2, above.
  • the extraction process can be performed using biomass which has not been subjected to decarboxylation.
  • the slurry may be extracted using a solvent, for example, ethanol.
  • the miscella may then be separated from the
  • the spent biomass solids may be collected for disposal.
  • the miscella may be collected in a vacuum evaporator and the solvent distillate can be condensed and collected for re-use, as described above.
  • the extraction process performed without prior decarboxylation can be completed using an extraction solvent, such as ethanol, using a heating apparatus, such as a microwave. Said extraction process may be performed for a time period of approximately 5 minutes.
  • the efficiency (% recovery) of the extraction process can be determined using the amount of cannabinoids (e.g., THCA and THC) recovered from the biomass in the final extract formulation to determine the percentage of cannabinoid lost during the extraction process.
  • cannabinoids e.g., THCA and THC
  • performing a decarboxylation process after the extraction process may further improve the quality and purity of the extract. It should also be noted that since the melting point of THCA is about 75°C, and the melting point of THC is about 160°C, performing the extraction on cannabis biomass that has not yet been subjected to decarboxylation may allow for a faster solvent removal time (such as drying) from the extract, since the non-decarboxylated pre-process tends to form a harder product more quickly.
  • FIG. 5 is a table illustrating the results of various samples created during the final formulation step of a decarboxylation process as described with respect to method 200 of FIG. 2.
  • the formulated extract may be placed in a heating apparatus as the formulation process is performed.
  • the formulated extract may be heated to a predetermined temperature for a predetermined time, as described in detail above, to perform the decarboxylation process on the extract.
  • the time and temperature of the decarboxylation process may be controlled based upon the starting concentration of cannabinoids in the formulated extract.
  • the table presented in FIG. 5 indicates the time period required to achieve complete decarboxylation of THCA formulated in MCT oil at different temperatures and for different concentrations of THCA.
  • FIG. 6 shows the percentage of decarboxylation (% conversion of cannabinoid acids to their neutral forms) for various samples.
  • An extract may be obtained by performing the above described extraction process on a cannabis biomass which has not been subjected to
  • the formulated extract may then be heated in order to perform a
  • the amount of heating required for decarboxylation of the biomass to occur can be dependent on the level of microwave energy provided, the time period the formulated extract is heated, and the temperature at which the formulated extract is heated. These factors can be controlled so as to achieve a desired degree of decarboxylation (% of cannabinoid acids converted to the neutral forms) for each sample. The degree of
  • decarboxylation can be controlled through the sampling and analysis of the materials throughout the extraction and decarboxylation process (described with respect to FIG. 2).
  • the ability to control the degree of decarboxylation can allow various samples to be created having different decarboxylation ratios in the final extracted formulation.
  • Such formulations can provide different benefits such as extract stability, medicinal properties, therapeutic properties, recreational properties, and the like.
  • certain non- decarboxylated cannabinoids can provide medicinal, therapeutic, or recreational benefits that decarboxylated cannabinoids. Extracts containing various ratios of non-decarboxylated to decarboxylated cannabinoids can be used for different purposes based on the specific medicinal, therapeutic, and recreational properties each ratio provides.
  • a partially decarboxylated extract may provide improved stability in later processing (e.g ., a partially decarboxylated extract may provide better stability when baked, or dissolved in a liquid).
  • a method 700 for decarboxylating a cannabis extract within a solvent, such as a medium chain triglyceride, is provided in FIG. 7.
  • the method 700 can begin at step 702, where a raw biomass material can be prepared.
  • the raw biomass material may comprise at least the target compounds for the extraction process.
  • the raw biomass material may be present in the form of dried, ground, non-decarboxylated flowers and/or plant matter.
  • the raw biomass may include either fresh or frozen non- decarboxylated cannabis plants.
  • the method 700 can continue to step 704 wherein a slurry may be formed by adding a solvent to the raw biomass material.
  • the solvent added to the raw biomass material may be selected based on specific dielectric and solvent parameter properties.
  • the solvent may be selected from a group including, but not limited to, alcohol group, an alkane group, a ketone group, and mixtures of various solvents, including water.
  • the slurry may be transferred to an extraction chamber, at step 706, for the extraction of cannabinoids from the slurry.
  • the slurry may be transported to the extraction chamber using a set of mechanical conveyors.
  • the slurry may be heated to a predetermined temperature by exposing the slurry to heat (such as microwave heat), for a predefined period of time, within a predefined energy range.
  • the predetermined temperature may be a temperature sufficient to avoid decarboxylation of the cannabinoid acids to their neutral counterparts.
  • a carrier fluid can be added to the extracted acidic cannabinoids at step 708, to form a formulated extract of acidic cannabinoids.
  • the carrier fluid can be a medium chain triglyceride.
  • the final formulated extract may be obtained.
  • the extract formulated at step 208 may be heated to a temperature sufficient in order to partially or completely decarboxylate the acidic cannabinoids into their neutral form (e.g., active
  • the heated formulated extract may then be formulated into final formulated extract using a formulation method.
  • the final formulated extract may comprise the active cannabinoids obtained by the controlled decarboxylation method 700.
  • both the time and temperature of the heating process may be controlled or adjusted in order to achieve a desired degree of decarboxylation such that a final formulation having the desired medicinal, therapeutic, and recreational purposes is produced.

Abstract

L'invention concerne un procédé de décarboxylation de cannabinoïdes acides en cannabinoïdes neutres, pharmacologiquement actifs. Le procédé comprend les étapes consistant à préparer une biomasse de cannabis brute comprenant une pluralité de particules de matière végétale, ajouter un solvant à la biomasse préparée pour former une suspension, extraire et séparer une quantité de cannabinoïdes acides à partir de la suspension, ajouter un fluide transporteur à la quantité extraite de cannabinoïdes acides pour créer un extrait formulé, et chauffer l'extrait formulé pour décarboxyler la quantité de cannabinoïdes acides en une quantité de cannabinoïdes neutres, pharmacologiquement actifs. L'invention concerne également un système permettant de mettre en œuvre ledit procédé et de réaliser lesdites étapes, le système comprenant une chambre de préparation de biomasse, une chambre de formation de suspension, une chambre d'extraction définie comme un appareil d'extraction couplé à un appareil de chauffage, un moyen d'ajout d'un fluide transporteur de manière à former un extrait formulé avec les cannabinoïdes acides extraits, et une chambre de décarboxyation.
PCT/IB2019/053612 2018-05-03 2019-05-02 Procédé de décarboxylation de cannabinoïdes acides dans un extrait de cannabis en suspension dans un fluide transporteur WO2019211797A1 (fr)

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IT202200007457A1 (it) * 2022-04-14 2023-10-14 Daniele Tartaglia Procedimento estrattivo per l’ottenimento di un olio a base di fitocannabinoidi
IT202200007484A1 (it) * 2022-04-14 2023-10-14 Daniele Tartaglia Procedimento estrattivo per l’ottenimento di un estratto alcolico a base di fitocannabinoidi cbd, cbda, cbg, cbga, thc, thca, thcv, thcva
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WO2021133411A1 (fr) * 2019-12-27 2021-07-01 Cresco Labs Llc Procédé de post-traitement d'huile de cannabis
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IT202200007466A1 (it) * 2022-04-14 2023-10-14 Daniele Tartaglia Composizione cosmeceutica a base di acidi grassi estratti dalla cannabis
IT202200007478A1 (it) * 2022-04-14 2023-10-14 Daniele Tartaglia Procedimento estrattivo per l’ottenimento di una formulazione liquida a base di glicole propilenico e fito cannabinoidi liposolubili per sigarette elettroniche
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IT202200007484A1 (it) * 2022-04-14 2023-10-14 Daniele Tartaglia Procedimento estrattivo per l’ottenimento di un estratto alcolico a base di fitocannabinoidi cbd, cbda, cbg, cbga, thc, thca, thcv, thcva
IT202200007457A1 (it) * 2022-04-14 2023-10-14 Daniele Tartaglia Procedimento estrattivo per l’ottenimento di un olio a base di fitocannabinoidi
IT202200011351A1 (it) * 2022-05-30 2023-11-30 Daniele Tartaglia Procedimento estrattivo per l’ottenimento di un olio a base di fitocannabinoidi con contenuto nullo di thc
WO2024088287A1 (fr) * 2022-10-27 2024-05-02 云南麻叶生物科技有限公司 Procédé de décarboxylation pour fleurs et feuilles de chanvre industrielles

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