Systems and methods for producing CBDA-rich extracts and compositions

Abstract

A method for producing a plurality of grades of CBDA-rich extract using various extraction and purification steps that can be selected, adjusted, or both to produce a desired grade of CBDA-rich extract. A purified CBDA-rich extract may be refined to obtain even higher grades of CBDA-rich extract. Each of the extraction, purification, and optional refining steps occur at a temperature of less than or equal to 80°C. One or more grades of CBDA-rich extract may be incorporated into a product / composition.

Description

SYSTEMS AND METHODS FOR PRODUCING CBDA-RICH EXTRACTS AND COMPOSITIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of US Provisional Patent ApplicationNo. 63 / 496,282 filed on April 14, 2023, with the United States Patent and Trademark Office, the contents of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION

[0002] The inventions disclosed herein are related to extraction and purification processes and methods of manufacture of extracts rich in CBDA, more particularly to full spectrum CBDA-rich extracts and broad spectrum CBDA-rich extracts (BSCBDAE) and compositions comprising the same for use in treatment of certain mammalian disorders.BACKGROUND OF THE INVENTION

[0003] The recent delineation of the endocannabinoid system including cannabinoid (CB) receptors (CB1 and CB2) in humans has resulted in an increased interest in therapeutic uses of cannabinoids obtained from plants, or phytocannabinoids. While A-9- tetrahydrocannabinol (THC) may be the most notorious phytocannabinoid, cannabidiol (CBD) has gained traction for its therapeutic potential without the adverse psychoactive effects of THC. In fact, in 2019 the World Health Organization (WHO) concluded that CBD posed no public health risk and was virtually absent in causing dependency or addiction.

[0004] Within humans, endogenous cannabinoids, or endocannabinoids, are naturally produced within the body. The two most well-studied endocannabinoids are anandamide and 2-arachidonoylglycerol (2- AG). Generally, an endocannabinoid acts on one or moreCB receptors to cause a cellular response. Alterations of these receptors have been associated with neurogenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. The endocannabinoids, receptors, signaling pathways, and cellular responses are currently being investigated to understand their roles in both normal and disease states.

[0005] Phytocannabinoids may act on one or more CB receptors or otherwise influence receptor activation, which is one reason their potential as therapeutics is attractive. Plants that produce cannabinoids include, but are not limited to kava, rosemary, liverwort, electric daisy, echinacea, cacao, helichrysum, pepper trees, black truffles, as well as a strain of yeast (Pichia pastoris) with the unique ability to synthesize A-9-tetrahydrocannabinolic acid (THCA), which is the precursor to THC. The most well-known cannabinoid producing plants, however, are thosebelonging to the Cannabaceae family such as those of the Cannabis genus. Whether there are distinct species is subject to debate as at least two of the identified species, C. sativa and C. indica, cross breed in nature and by human design. It appears that virtually all Cannabis varieties can be considered crosses as plants have been bred to produce a desired profile with regard to biomass and cannabinoid content although many still distinguish plants by species. The United States avoids issues of nomenclature by defining hemp as a Cannabis plant with a THC content of 0.3% or less by dried weight. The byproducts of hemp plants, including cannabinoids, are federally legal as defined in section 7606 of the 2014 Farm Bill and made permanent in the 2018 Farm Bill.

[0006] Regardless of how defined, different strains or varieties of Cannabis plants can provide different cannabinoid profiles and growing conditions may affect the resultant cannabinoid profiles of plants within a particular strain. Phytocannabinoids tend to be concentrated in Cannabis plants in a viscous resin produced in glandular epidermal outgrowths known as trichomes. The resin is also rich in terpenes, which are largely responsible for the distinct odor of the Cannabis plant. Trichomes are most abundant in female inflorescence, but they may be found elsewhere. Furthermore, phytocannabinoid production is not limited to trichomes; they may be produced in other plant structures but nowhere near the same amounts as produced by trichomes.

[0007] Chemically, many phytocannabinoids are 21 -carbon terpenophenolic compounds obtained by the alkylation of an alkyl resorcinol with a monoterpene unit. A few phytocannabinoids, however, do not follow this precise 21 -carbon structure. This is primarily due to variation in the length of the sidechain attached to an aromatic ring, which is often a pentyl (5-carbon) or a propyl (3-carbon) chain. To date, over 100 phytocannabinoids have been identified specifically in Cannabis plants, and there may more than 144 known phytocannabinoids in all. A few examples of other known phytocannabinoids include cannabigerol (CBG), cannabichromene (CBC), cannabidivarin (CBDV), and cannabinol (CBN). While the purpose of cannabinoids in plants remains unclear, the most popular hypothesis suggests they act to protect the producing plant from insects, bacteria, fungi, ultraviolet radiation, and drying.

[0008] Terpenes are a large class of organic compounds produced by a wide number of plants including conifers and leafy plants, such as Cannabis. Terpenes often have a strong andreadily identifiable odor and are the primary constituent of many essential oils. Thus, the terpenes obtained from many types of plants are used for their aromatic boutique and for other purposes such as certain medicinal properties. Certain terpenes have a chemical profile that is similar to that of cannabinoids and are cannabinoid analogs.

[0009] As with many plant-based products, humans do not want to consume copious amounts of a plant to obtain the benefit provided particular plant. Thus, to obtain the phytocannabinoids, we have inhaled the smoke of a burned plant. There are a number of negative side effects associated with inhaling the smoke including negative societal implications. Efforts have been made to extract phytochemicals from plants, including phytocannabinoids from hemp plants, to allow the phytochemicals to be taken orally and / or topically instead of inhaled. However, many processes to generate oral and / or topical plant-based products are unregulated and phytochemical extracts may be of varying quality with varying levels of impurities. Such variations are unacceptable if a plant-based product is to be used in treatment of certain medical conditions.

[0010] Plant-based extracts and products derived from plant-based extracts require both specific processes for extraction and specific processes for cleansing the plant extract. The specific extraction and subsequent processing produce different final products and different yields. Furthermore, extraction and subsequent processing may also vary depending on the source material used. In order to create end products from plant-based extracts that have consistent results, all parts of the process from source material to end product are important to obtain product consistency and quality. Notably, certain chemicals used to extract and process phytochemicals can be harmful to a person if ingested. Many of these materials, however, are necessary to extract and to produce sufficient yields of the desired phytochemical.

[0011] Because of their natural source, widespread use, low risk of addiction or dependency, and relative safety, CBD and related phytochemicals have been flagged for in-depth investigation of potential therapeutic roles. Applicant has created improved processes to extract and purify one or more cannabinoids from hemp plants; the one or more cannabinoids to be used alone or in pharmaceutical formulations. Such products may be administered orally, topically, via mucosa, and / or other routes of administration to treat a number of mammalian diseases or disorders. The methodologies and extraction processes defined herein provide improvements inyield, reduction in the energy needed to perform the extraction, and improvements in the quality of the resultant products.SUMMARY OF THE INVENTION

[0012] The embodiments here are related to methods and systems for manufacturing and methods for producing CBDA-rich extracts at a plurality of concentrations. Embodiments may produce any of the plurality of CBDA-rich extracts within a pharmaceutically acceptable form.

[0013] In a preferred embodiment, a tunable method for producing a plurality of grades of CBDA-rich extracts comprising: (a) at about 80°C or less, mixing Cannabis saliva green material (GM) with a solvent or chilled / iced water and collecting an extraction product; (b) at about 80°C or less, filtering, pressing, removing the solvent, winterizing, or combinations thereof the extraction product and collecting a CBDA-rich extract or a purified extraction product; and (c) at about 80°C or less, optionally crystallizing or separating tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THC A), or both from the purified extraction product, wherein extracting, purifying, or refining methods, and combinations thereof are adjustable to collect a particular grade of CBDA-rich extract.

[0014] In a further embodiment, the method wherein mixing comprises mixing the GM with the solvent selected from an ethanol -based solvent, a supercritical CCh-based solvent, or an oil. In a further embodiment, the method wherein mixing comprises mixing the GM in a drum with the ethanol -based solvent selected from the group consisting of ethanol, completely denatured ethanol, 100% 200 proof ethanol, or combinations thereof, or the oil selected from the group consisting of hemp seed oil, medium-chain triglyceride (MCT) oil, olive oil, sunflower seed oil, coconut oil, or combinations thereof, filtering the extraction product, and collecting a raw extract or a filtered extraction product, a CBDA concentration in the raw extract is between about 1% and about 25%.

[0015] In a further embodiment, the method wherein collecting the filtered extraction product is followed by removing the ethanol, completely denatured ethanol, or 100% 200 proof ethanol and collecting a crude extract or a crude extraction product, a CBDA concentration in the crude extract is between about 25% to about 65%. In a further embodiment, the method wherein collecting the crude extraction product is followed by winterizing the crude extraction product and collecting a winterized ethanol extract or a winterized extraction product, aCBDA concentration of the winterized ethanol extract is between about 50% to about 70%.

[0016] In a further embodiment, the method further comprising dissolving the winterized extraction product in a hexane-based solvent, running the dissolved winterized extraction product through centrifugal partition chromatography, collecting at least THC-free fractions, removing the hexane-based solvent and water from the THC-free fractions, and collecting a broad spectrum CBDA extract, wherein a CBDA concentration in the broad spectrum CBDA extract is from about 50% to about 80%.

[0017] In a further embodiment, the method further comprising crystallizing CBDA by mixing the winterized extraction product with a solvent, chilling the mixed winterized extraction product to a temperature of less than 0°C for at least 12 hours followed by incubating the mixed winterized extraction product at a temperature of between about 20°C and 25°C for at least 12 hours to complete one freeze-thaw cycle, separating crystallized CBDA from the solvent, removing residual solvent, and collecting a CBDA isolate extract. In a further embodiment, the method wherein the freeze-thaw cycle is repeated from one additional time to 10 additional times before separating crystallized CBDA from the solvent.

[0018] In a further embodiment, the method wherein collecting the raw extract further comprises, determining if the raw extract has a desired concentration of CBDA, and if not, performing another extraction cycle by adding the raw extract back to the drum, the drum containing either GM, fresh GM, or both, mixing GM, fresh GM or both with the raw extract, collecting and filtering a subsequent extraction product, and repeating the extraction cycle until a CBDA concentration of the raw extract is between about 1% and 25%.

[0019] In a further embodiment, the method wherein mixing comprises mixing the GM with a supercritical CCh-based solvent in a pressurized extraction chamber, followed by separating the supercritical CCh-based solvent from the extraction product, optionally evaporating any remaining supercritical CCh-based solvent, winterizing the extraction product and collecting a winterized CO2 extract or a winterized extraction product, wherein a CBDA concentration in the winterized CO2 extract is between about 50% and about 70%, and wherein the supercritical CCh-based solvent optionally includes a cosolvent selected from the group consisting of ethanol, completely denatured ethanol, acetone or combinations thereof.

[0020] In a further embodiment, the method further comprising crystallizing the winterized extraction product to collect a CBDA isolate extract by mixing the winterized extraction product with a solvent and performing a freeze-thaw cycle of chilling the mixed winterized extractionproduct to a temperature of less than 0°C for at least 12 hours followed by incubating the mixed winterized extraction product at a temperature of between about 20°C and 25°C for at least 12 hours, separating crystallized CBDA formed during the freeze-thaw cycle from the solvent, removing residual solvent, and collecting a CBDA isolate extract collecting the CBDA isolate having a CBDA concentration of between about 86% to about 99.9%. In a further embodiment, the method wherein the freeze-thaw cycle is repeated from one additional time to 10 additional times before separating crystallized CBDA from the solvent.

[0021] In a further embodiment, the method further comprising dissolving the winterized extraction product in a hexane-based solvent and running the dissolved winterized extract through centrifugal partition chromatography and collecting at least THC-free fractions, removing the hexane-based solvent and water from the THC-free fractions and collecting a broad spectrum CBDA extract, the CBDA concentration of the broad spectrum CBDA extract is between about 50% to about 80%.

[0022] In a further embodiment, the method wherein mixing comprises mixing the GM with chilled / iced water and collecting the extraction product followed by sequentially fdtering the extraction product through one or more screens having decreasing mesh sizes to separate trichome-rich particles from impurities and collecting a hash extract or a hash extraction product from 80-micron or less screens, wherein a CBDA concentration in the hash extract is between about 40% and about 80%. In a further embodiment, the method further comprising pressing the hash extraction product using pressure and low heat, and collecting a rosin, wherein a CBDA concentration of the rosin is greater than about 40%. In a further embodiment, the method further comprising dissolving the hash extraction product in a cold ethanol-based solvent and collecting a further purified hash extract or further purified hash extraction product, wherein a CBDA concentration of the further purified hash extract is greater than about 40%.

[0023] In a further embodiment, the method further comprising preparing the GM by ensuring that the GM is less than six months old, contains less than 0.3% tetrahydrocannabinol, tetrahydrocannabinolic acid, or both, has an awbelow 0.7, or combinations thereof, and chopping, grinding, or both the GM to about 0.25 inches.

[0024] In a preferred embodiment, an adaptable processing method to produce a CBDA-rich extract, the produced CBDA-rich extract having a target concentration of CBDA selected from various possible target concentrations of CBDA comprising: (a) preparing Cannabis sativa greenmaterial (GM) to have a particle size of about 0.25 inches; (b) collecting an extraction product using one of drum extraction process, a supercritical CO2 extraction process, or chilled / iced water extraction process, wherein the temperature of each of the drum extraction process, supercritical CO2 extraction process and chilled / iced water extraction process does not exceed 80°C; (c) collecting one or more of a raw extract, a crude extract, a hash extract, or a rosin, or collecting a purified extraction product using at least one of filtering, solvent removal, or combinations thereof to purify an extract, extraction product, or both, wherein the temperature of each of filtering, pressing, and removing solvent, takes place at a temperature that does not exceed 80°C; (d) collecting a winterized extract or winterized extraction product, wherein winterizing further purifies a purified extraction product; and (e) optionally removing THC, THCA, or both from the winterized extraction product or the crude extract, the optional removal of THC, THCA, or both taking place at a temperature that does not exceed 80°C.

[0025] In a further embodiment, the method wherein purifying the extract, extraction product or both includes filtering a drum extraction product, a hash extraction product, or a supercritical CO2 extraction product. In a further embodiment, the method wherein purifying the extract, extraction product or both includes removing ethanol, an ethanol -based solvent, or both from a drum extraction product, a hash extraction product, or a supercritical CO2 extraction product.

[0026] In a further embodiment, the method wherein purifying the extract, extraction product or both comprises removing ethanol, completely denatured ethanol, or acetone from a supercritical CO2 extraction product.

[0027] In a further embodiment, the method wherein winterizing comprises dissolving the purified extraction product in an ethanol-based solvent, incubating dissolved, purified extraction product at a temperature of about -80°C for at least 24 hours.

[0028] In a further embodiment, the method wherein removing THC, THCA or both comprises crystallizing the winterized extraction product to produce a CBDA isolate extract. In a further embodiment, the method wherein crystallizing the winterized extraction product includes mixing the winterized extraction product with hexane, and subjecting the mixed, winterized extraction product to a freeze-thaw cycle of chilling to less than 0°C for at least 12 hours followed by incubating at between about 20°C to about 25°C for at least 12 hours.

[0029] In a further embodiment, the method further comprising repeating the freeze-thaw cycle at least one additional time, wherein freezing takes place at a temperature of less than about -10°C.

[0030] In a further embodiment, the method further comprising repeating the freeze-thaw cycle at least three additional time, and if crystals are not observed after the third time, adding seed crystals to the mixed, winterized extraction product, and repeating the freeze-thaw cycle at least one additional time.

[0031] In a further embodiment, the method further comprising separating hexane from crystallized CBDA. In a further embodiment, the method further comprising removing residual solvent from crystallized CBDA using a vacuum oven set at less than 80°C and a pressure of less than 40 torr.

[0032] In a further embodiment, the method wherein removing THC, THCA, or both comprising refining the winterized extraction product or the purified extraction product using centrifugal partition chromatography (CPC) by adding the purified extraction product or the winterized extraction product to a hexane-based solvent that has been prepared by separating a mixture of hexane:methanol:water (5:4: 1) into two phases, loading the mixed purified extraction product or winterized extraction product onto a CPC apparatus, separating the dissolved purified extraction product or winterized extraction product into waste fractions, reclaim fractions, and THC-free fractions; removing solvent and water from THC-free fractions, and collecting a broad spectrum CBDA extract. In a further embodiment, the method further comprising reprocessing the reclaim fractions to remove solvent, rerunning the reprocessed reclaim fractions on the CPC apparatus, collecting waste and THC-free fractions, removing solvent and water from the THC-free fractions, and collecting a broad spectrum CBDA extract.

[0033] In a preferred embodiment, a product comprising: a CBDA-rich extract obtained from a production process that is tunable to produce a plurality of grades of CBDA-rich extract comprising: (a) at about 80°C or less, mixing Cannabis sativa green material (GM) with a solvent or chilled / iced water and collecting an extraction product; (b) at about 80°C or less, filtering, pressing, removing the solvent, winterizing, or combinations thereof the extraction product and collecting a CBDA-rich extract or a purified extraction product; and (c) at about 80°C or less, optionally crystallizing or separating tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), or both from the purified extraction product, whereinextracting, purifying, or refining methods, and combinations thereof are adjustable to collect a particular grade of CBDA-rich extract; a fat or an oil; and wherein said product comprises between about 1% and 99% of CBDA-rich extract.

[0034] In a preferred embodiment, a tunable method for producing a plurality of grades of CBDA-rich extracts comprising: (a) extracting CBDA from Cannabis sativa green material (GM) by mixing the GM with a solvent or chilled / iced water at about 80°C or less and collecting an extraction product; (b) purifying the extraction product by filtering, pressing, removing the solvent, winterizing, or combinations thereof at about 80°C or less and collecting a CBDA-rich extract, a purified extraction product, or both; (c) refining the purified extraction product at about 80°C or less by crystallizing the purified extraction product or by separating tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), or both from the purified extraction product; and (d) wherein the extracting, purifying, and refining steps and combinations thereof are adjustable to collect a particular grade of CBDA-rich extract.

[0035] In a further embodiment, the method wherein extracting further comprises mixing the GM with a solvent selected from an ethanol-based solvent, a supercritical CCh-based solvent, and an oil-based solvent.

[0036] In a further embodiment, the method wherein extracting further comprises mixing the GM in a drum with an ethanol -based solvent selected from the group consisting of: ethanol, completely denatured ethanol, 100% ethanol that is 200 proof, and combinations thereof.

[0037] In a further embodiment, the method wherein before being added to the drum, the ethanol-based solvent is cooled to a temperature: (a) at or below about 0°C; or (b) between about 0°C and -20°C; or (c) between about -20°C and -80°C.

[0038] In a further embodiment, the method wherein extracting further comprises mixing the GM in a drum with an oil-based solvent selected from the group consisting of: hemp seed oil, medium-chain triglyceride (MCT) oil, olive oil, sunflower seed oil, coconut oil, and combinations thereof.

[0039] In a further embodiment, the method wherein purifying further comprises filtering the extraction product and wherein collecting further comprises collecting a CBDA-rich raw extract, a filter-purified extraction product, or both wherein a CBDA concentration in the CBDA-rich raw extract is between about 1% and about 25% by weight.

[0040] In a further embodiment, the method wherein purifying further comprises removing the solvent and wherein collecting further comprises collecting a CBDA-rich crude extract, a crude purified extraction product, or both wherein the CBDA concentration in the CBDA-rich crude extract is between about 25% and about 65% by weight.

[0041] In a further embodiment, the method wherein purifying further comprises winterizing and wherein collecting further comprises collecting a CBDA-rich winterized ethanol extract, a winterized purified extraction product, or both wherein a CBDA concentration of the CBDA-rich winterized ethanol extract is between about 50% and about 70% by weight.

[0042] In a further embodiment, the method wherein refining by separating THC, THCA, or both comprises melting the purified extraction product and dissolving a resultant melt in a hexane-based solvent, running a resultant dissolved product through centrifugal partition chromatography (CPC), collecting at least THC-free fractions, removing the hexane-based solvent and water from the THC-free fractions, and collecting a broad spectrum CBDA extract wherein a CBDA concentration in the broad spectrum CBDA extract is from about 50% to about 80% by weight.

[0043] In a further embodiment, the method wherein refining by crystallizing CBDA comprises mixing the purified extraction product with a solvent and chilling to a temperature of less than 0°C for at least 12 hours, which is followed by incubating at a temperature of between about 20°C and 25°C for at least 12 hours to complete a freeze-thaw cycle, separating crystallized CBDA that results from at least one freeze-thaw cycle from the solvent, removing residual solvent, and collecting a CBDA isolate extract.

[0044] In a further embodiment, the method wherein the freeze-thaw cycle is repeated from one additional time to ten additional times before separating crystallized CBDA from the solvent.

[0045] In a further embodiment, the method wherein collecting the raw extract further comprises determining if the raw extract has a desired concentration of CBDA and if not, performing another extraction cycle by adding the raw extract back to the drum, the drum containing either GM, fresh GM, or both; mixing the GM, the fresh GM or both with the raw extract; collecting and filtering a subsequent extraction product; and repeating the extraction cycle until a CBDA concentration of the raw extract is between about 1% and 25% by weight.

[0046] In a further embodiment, the method wherein extracting comprises mixing the GM with a supercritical CCh-based solvent in a pressurized extraction chamber, followed byseparating the supercritical CCh-based solvent from the extraction product, and evaporating any remaining supercritical CCh-based solvent.

[0047] In a further embodiment, the method wherein purifying comprises winterizing the extraction product and collecting a CBDA-rich winterized CO2 extract or a winterized, purified extraction product wherein a CBDA concentration in the CBDA-rich winterized CO2 extract is between about 50% and about 70% by weight.

[0048] In a further embodiment, the method wherein the solvent optionally includes a cosolvent selected from the group consisting of: ethanol, completely denatured ethanol, acetone, and combinations thereof.

[0049] In a further embodiment, the method wherein refining by crystallizing comprises mixing the purified extraction product with a solvent and performing a freeze-thaw cycle of chilling the mixed purified extraction product to a temperature of less than 0°C for at least 12 hours followed by incubating at a temperature of between about 20°C and 25°C for at least 12 hours, separating crystallized CBDA formed during the freeze-thaw cycle from the solvent, removing residual solvent, and collecting a CBDA isolate extract having a CBDA concentration of between about 86% and about 99.9% by weight.

[0050] In a further embodiment, the method wherein the freeze-thaw cycle is repeated from one additional time to 10 additional times before separating crystallized CBDA from the solvent.

[0051] In a further embodiment, the method wherein refining by separating THC, THCA, or both comprises melting the purified extraction product and dissolving a resultant melt in a hexane-based solvent, thereafter running the dissolved melt through centrifugal partition chromatography (CPC) and collecting at least THC-free fractions, removing the hexane-based solvent and water from the THC-free fractions and collecting a broad spectrum CBDA extract wherein the CBDA concentration of the broad spectrum CBDA extract is between about 50% and about 80% by weight.

[0052] In a further embodiment, the method wherein extracting comprises mixing the GM with chilled / iced water, wherein purifying comprises sequentially filtering the extraction product through one or more screens having decreasing mesh sizes to separate trichome-rich particles from impurities, and wherein collecting a CBDA-rich extract or a purified extraction product comprises collecting a CBDA-rich hash extract or a hash extraction product from screens havinga mesh size of 80 microns or less wherein a CBDA concentration in the CBDA-rich hash extract is between about 40% and about 80% by weight.

[0053] In a further embodiment, the method wherein purifying further comprises pressing the hash extraction product using pressure and low heat and collecting a CBDA-rich rosin wherein a CBDA concentration of the CBDA-rich rosin is greater than about 40% by weight.

[0054] In a further embodiment, the method further comprising dissolving the hash extraction product in a cold ethanol -based solvent and collecting a further purified hash extract or further purified hash extraction product wherein a CBDA concentration of the further purified hash extract is greater than about 40% by weight.

[0055] In a further embodiment, the method further comprising preparing the GM by: (a) ensuring that the GM is less than six months old; contains less than 0.3% tetrahydrocannabinol, tetrahydrocannabinolic acid, or both; has an awbelow 0.7; or combinations thereof; and (b) reducing the GM to a particle size of about 0.25 inches by chopping, grinding, or both.

[0056] In a preferred embodiment, an adaptable processing method to produce a CBDA-rich extract, the produced CBDA-rich extract having a target concentration of CBDA selected from various possible target concentrations of CBDA, the method comprising: (a) preparing Cannabis sativa green material (GM) to have a particle size of about 0.25 inches; (b) collecting an extraction product using one of a drum extraction process, a supercritical CO2 extraction process, or a chilled / iced water extraction process wherein the temperature of each of the drum extraction process, supercritical CO2 extraction process, and chilled / iced water extraction process does not exceed 80°C; (c) collecting a purified extract or a purified extraction product wherein purifying is selected from one or more of filtering, removing a solvent, pressing, winterizing, and combinations thereof wherein each of filtering, pressing, winterizing, and removing a solvent takes place at a temperature that does not exceed 80°C; and (d) removing THC, THCA, or both from the purified extraction product, the removal of THC, THCA, or both taking place at a temperature that does not exceed 80°C.

[0057] In a further embodiment, the method wherein collecting a purified extract, a purified extraction product, or both comprises filtering a drum extraction product, a hash extraction product, or a supercritical CO2 extraction product.

[0058] In a further embodiment, the method wherein collecting a purified extract comprises removing ethanol, an ethanol-based solvent, or both from a drum extraction product, a hash extraction product, or a supercritical CO2 extraction product.

[0059] In a further embodiment, the method wherein collecting a purified extract comprises removing ethanol, completely denatured ethanol, or acetone from a supercritical CO2 extraction product.

[0060] In a further embodiment, the method wherein collecting a purified extract comprises dissolving the purified extraction product in an ethanol-based solvent and incubating the dissolved purified extraction product at a temperature of about -80°C for at least 24 hours.

[0061] In a further embodiment, the method wherein removing THC, THCA, or both comprises crystallizing the purified extraction product to produce a CBDA isolate extract.

[0062] In a further embodiment, the method wherein removing THC, THCA, or both comprises crystallizing the purified extraction product, mixing the purified extraction product with hexane, and subjecting the mixed purified extraction product to a freeze-thaw cycle of chilling to less than 0°C for at least 12 hours followed by incubating at between about 20°C to about 25°C for at least 12 hours.

[0063] In a further embodiment, the method further comprising repeating the freeze-thaw cycle at least one additional time wherein freezing takes place at a temperature of less than about -10°C.

[0064] In a further embodiment, the method further comprising repeating the freeze-thaw cycle at least three additional time and if crystals are not observed after the third time, adding seed crystals to the mixed winterized extraction product and repeating the freeze-thaw cycle at least one additional time.

[0065] In a further embodiment, the method further comprising separating hexane from crystallized CBDA.

[0066] In a further embodiment, the method further comprising removing residual solvent from crystallized CBDA using a vacuum oven set at less than 80°C and a pressure of less than 40 torr.

[0067] In a further embodiment, the method wherein removing THC, THCA, or both comprises refining the purified extraction product using centrifugal partition chromatography (CPC) by mixing the purified extraction product with a hexane-based solventthat has been prepared by separating a mixture of hexane:methanol:water (5:4: 1) into two phases; loading a mixed purified extraction product onto a CPC apparatus; separating the mixed purified extraction product into waste fractions, reclaim fractions, and THC-free fractions; removing solvent and water from THC-free fractions; and collecting a broad spectrum CBDA extract.

[0068] In a further embodiment, the method further comprising reprocessing the reclaim fractions to remove solvent, rerunning the reprocessed reclaim fractions on the CPC apparatus, collecting waste and THC-free fractions, removing solvent and water from the THC-free fractions, and collecting a broad spectrum CBDA extract.

[0069] In a preferred embodiment, a product comprising: (a) a CBDA-rich extract obtained from a production process that is tunable to produce a plurality of grades of CBDA-rich extract comprising: (i) extracting CBDA from Cannabis sativa green material (GM) by mixing the GM with a solvent or chilled / iced water at about 80°C or less and collecting an extraction product; and (ii) purifying the extraction product at about 80°C or less by filtering the extraction product, pressing the extraction product, removing the solvent from the extraction product, winterizing the extraction product, or combinations thereof and collecting a CBDA-rich extract or a purified extraction product; and (iii) wherein the extracting and / or purifying steps are adjustable to collect a particular grade of CBDA-rich extract; (b) a fat or an oil; and (c) wherein said product comprises between about 1% and 99% by weight of CBDA-rich extract.

[0070] In a further embodiment, the product further comprising refining the purified extraction product at about 80°C or less by separating tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THC A), or both from the purified extraction product.

[0071] In a preferred embodiment, a method for producing a CBDA-rich extract comprising: (a) extracting CBDA from Cannabis sativa green material (GM) by cycling an ethanol-based solvent that has been precooled to at or below about 0°C through GM disposed in a drum for a predetermined time; (b) when the predetermined time has expired, filtering a post-extraction solvent before collecting, after collecting, or both; and (c) evaporating a filtered post-extraction solvent to obtain a crude CBDA-rich extract.

[0072] In a further embodiment, the method wherein cycling the ethanol-based solvent through GM disposed in a drum further comprises filtering the ethanol-based solvent through a synthetic filter disposed in the drum to create a false bottom.

[0073] In a further embodiment, the method wherein the GM disposed in the drum has been processed to obtain a particle size of about 0.25 inches.

[0074] In a further embodiment, the method wherein the ethanol-based solvent has been cooled to: (a) between about 0°C and -20°C; or (b) between about -20°C and -80°C; or (c) about -80°C.

[0075] In a further embodiment, the method wherein the ethanol-based solvent is:(a) denatured ethanol; and / or (b) a mixture of 5% heptane and 95% ethanol at 200 proof; and / or(c) 100% ethanol at 200 proof.

[0076] In a further embodiment, the method further comprising winterizing the crude extract.

[0077] In a further embodiment, the method further comprising removing THC, THCA, or both.

[0078] In a further embodiment, the method wherein removing THC, THCA, or both comprises crystalizing CBDA.

[0079] In a further embodiment, the method wherein removing THC, THCA, or both comprises running a purified extract through a CPC machine.

[0080] In a preferred embodiment, a method for producing a CBDA-rich extract comprising: (a) extracting CBDA from Cannabis sativa green material (GM) by cycling an edible oil through GM disposed in a drum for a predetermined time at a temperature that is less than 80°C and warm enough for the edible oil to be liquid; (b) when the predetermined time has expired, filtering a post-extraction oil before collecting, after collecting, or both; and (c) collecting a CBDA-rich extract.

[0081] In a further embodiment, the method wherein cycling the edible oil through GM disposed in a drum further comprises filtering the edible oil through a synthetic filter disposed in the drum to create a false bottom.

[0082] In a further embodiment, the method wherein the GM disposed in the drum has been processed to obtain a particle size of about 0.25 inches.

[0083] In a further embodiment, the method wherein the edible oil is: (a) hemp seed oil; and / or (b) cold pressed hemp seed oil; and / or (c) medium-chain triglyceride (MCT) oil; and / or(d) coconut oil; and / or (e) sunflower seed oil; and / or (I) olive oil.

[0084] In a further embodiment, the method further comprising determining if a CBDA potency is at a target level.

[0085] In a further embodiment, the method further comprising increasing the potency of the CBDA-rich extract by cycling the CBDA-rich extract for a predetermined time or until the target potency is reached, the CBDA-rich extract cycled through: (a) the same GM disposed in the drum; and / or (b) fresh GM disposed in the drum.

[0086] In a further embodiment, the method further comprising decreasing the potency of the CBDA-rich extract by adding an additional amount of the same or different edible oil to obtain the target potency.BRIEF DESCRIPTION OF THE FIGURES

[0087] FIG. 1 depicts a flow diagram of a production process with tunable stages to obtain a CBDA-rich extract having a desired constitution.

[0088] FIG. 2 depicts a flow diagram of various steps for extracting substances from Cannabis green material using a solvent and a specialized drum for extraction.

[0089] FIG. 3 depicts a flow diagram of various steps for extracting substances from Cannabis green material using a supercritical CO2 solvent and system.

[0090] FIG. 4 depicts a flow diagram of various steps for winterizing an extraction product.

[0091] FIG. 5 depicts a flow diagram of various steps for solventless / ice water extraction and purification of CBDA-rich material.

[0092] FIG. 6 depicts a flow diagram of various steps for refining an extraction / purification product.

[0093] FIG. 7 depicts an exemplary process for removing THC from a full spectrum CBDA extract / extr action or purification product, to produce a broad spectrum CBDA extract (BSCBDAE).DETAILED DESCRIPTION OF THE INVENTION

[0094] Various embodiments are described more fully hereinafter with reference to the accompanying drawings, which form a part hereof, and which show, by way of illustration, specific exemplary embodiments by which the innovations may be practiced. The embodiments may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the embodiments to those skilled in the art. Among other things, the various embodiments may be methods, formulations, compositions, and the like. Some embodiments may be in the order described, including all steps, and other embodimentsmay be in a different order than described, include some of the defined steps, or both. The following detailed description is, therefore, not to be taken in a limiting sense. As with all methods detailed herein, all or part of the steps shown in the figures may be performed in the order shown or a different order. Moreover, CBDA extraction and purification are tunable to provide a desired outcome and thus, steps may be changed, rearranged, added, dropped, and the like to achieve the desired result.DEFINITIONS

[0095] As used herein, the term “about” means plus or minus 5% of the numerical value of the number with which it is being used. Therefore, about 50% means in the range of 45%-55%. As a nonlimiting example, a temperature of about 150°C, means a range of 142.5°C to 157.5°C, inclusive of the endpoints and all numbers therebetween.

[0096] “Broad spectrum CBDA extract (BSCBDAE)” as used herein BSCBDAE is a composition derived from the Cannabis genus of plants which has undergone at least some purification in order to refine the extract. Typically, BSCBDAE comprises between 50% and 80% CBDA and least one additional cannabinoid, selected from the group consisting of A9-THC, THCA, THCV, A8-THC, CBC, CBCA, CBG, CBGA, CBD, CBDV, CBN, CBL, and combinations thereof the sum of which is between 0.1% and 40%.

[0097] As used here, the term “CBDA-rich extract” is a composition derived from the Cannabis genus of plants (including hemp). Typically, a CBDA-rich extract contains cannabidiolic acid (CBDA), and more typically comprises both CBDA and at least one additional cannabinoid, selected from the group consisting of A9-THC, THCA, THCV, A8-THC, CBC, CBCA, CBG, CBGA, CBD, CBDV, CBN, CBL, and combinations thereof at between 0.1% and 40%. CBDA-rich extracts according to the present invention are typically enriched in CBDA, and may comprise between 1% and 99.9% CBDA, preferably between 20% and 99.9% CBDA, more preferably between 50% and 99.9% CBDA, even more preferably between 70% and 99.9% CBDA, and most preferably between 80% and 99.9% CBDA. Raw extract, crude extract, winterized extracts, hash extracts, BSCBDAE, and CBDA isolate / isolate extracts and their respective extraction and / or purification products are forms of CBDA-rich extracts utilized herein, as nonlimiting examples of the CBDA-rich extracts.

[0098] “Composition,” “consumer product,” “end user product,” and the like as used herein are intended to encompass a product comprising the specified ingredients in a specified amount,as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.

[0099] CBDA isolate” as used herein encompasses a crystallized concentration of CBDA molecules to a purity of greater than about 85%.

[0100] As used herein, the term “full spectrum fFS)” is a composition derived from the Cannabis genus of plants which contains CBDA and quantities of THC, THCA, or both above 0, preferably, between 0.01% and 5%, most preferably being between 0.01% and 0.3%. The FS extract / extraction product may comprise additional cannabinoids.

[0101] Source material” as used herein encompasses the cannabis plants (e.g., C. sativa) that are harvested to be used in an extraction process.

[0102] Cannabis-based green material,” and “green material,” and “GM” as used herein encompass the parts of the source material producing the most cannabinoids including the flowers / inflorescence and perhaps some leaf material. Preferably, “cannabis-based green material,” “green material,” and “GM” refer to inflorescence and leaf material of plants of the cannabis genus.

[0103] ‘Extract” as used herein encompasses an end result of an extraction, purification, or refining, process such as a CBDA-rich extract and combinations thereof. To a lesser extent, “extract” also encompasses and extraction or purification product that is to undergo additional processing, which are also distinguished as an “extraction product” and / or “purification product.” An extract and its complementary extraction product and / or purification product may be essentially the same and either may undergo additional processing.

[0104] Concentrate / concentrated extract” as used herein encompasses extracted materials from the extract that remain after the extraction solvent has been removed.

[0105] “Potency” generally refers to the percentage / concentration of CBDA in an extract or extraction / purification product. The greater the percentage / concentration of CBDA the greater the potency. Potency, concentration, and percentage may all be used interchangeably.

[0106] Grade” generally refers to the potency and or purity of a particular CBDA-rich extract. Although not required, potency and purity generally increase with an increased grade.

[0107] “Product” generally refers to the end of a step, stage, process, method or the like. A particular extract, extraction product, or both may be a product.

[0108] Crude extract” as used herein refers to a CBDA-rich extract or an extraction product resulting from cold alcohol-based extraction using a drum extraction process.

[0109] ‘Residue” as used herein encompasses the material left behind after an extraction, purification, or refining process.

[0110] ‘Distillate” as used herein encompasses the material removed (i.e., which is evaporated and recondensed) in a distillation or evaporation step.

[0111] ‘ ‘At least a portion of’ as used herein refers to at least 5%, preferably at least 10%, more preferably at least 20%, still more preferably at least 50%, and most preferably at least 75%, for example from 75% to 99%, from 75% to 95%, or from 75% to 90%. Thus, distilling at least a portion of the extraction solvent off of the extract typically means distilling at least 5%, preferably at least 10%, more preferably at least 20%, still more preferably at least 50%, and most preferably at least 75%, for example from 75% to 99%, from 75% to 95%, or from 75% to 90%, of the extraction solvent off of the extract. Similarly, removing at least a portion of water-soluble substances from the concentrate typically means removing at least 5%, preferably at least 10%, more preferably at least 20%, still more preferably at least 50%, and most preferably at least 75%, for example from 75% to 99%, from 75% to 95%, or from 75% to 90%, of the water-soluble substances from the concentrate.

[0112] “Nonpolar solvent” as used herein refers to a solvent having a polarity index of 3.5 or less in accordance with the values calculated by Burdick and Jackson (list available at https: / / macro.lsu.edu / howto / solvents / polarity%20index.htm). Preferably, the nonpolar solvent is selected from pentane, hexane, heptane, toluene, the fraction of petroleum ether boiling between 30°C-40°C, the fraction of petroleum ether boiling between 40°C-60°C, toluene, xylene, diethyl ether and dichloromethane. Most preferably, the nonpolar solvent is hexane.

[0113] ‘Room temperature” as used herein generally refers to temperatures of about 20°C to about 25°C.

[0114] “THC-free fraction” as used herein is a fraction obtained from centrifugal partition chromatography which contains less than 0.1% or less A-9-tetrahydrocannabinol (THC), preferably 0.008% or less, and more preferably less than 0.0027% THC.

[0115] “Reclaim fraction” as used herein is a fraction obtained from centrifugal partition chromatography which contains more than 2% A-9-tetrahydrocannabinol (THC). Such a fractioncan be recycled in the centrifugal partition step in order to obtain more of the desired BSCBDAE product as described herein.

[0116] ‘Waste fraction” as used herein is a fraction obtained from centrifugal partition chromatography which contains less than a target amount of CBDA such a less than about 1% cannabidiolic acid (CBDA) and is either recycled or discarded following the centrifugal partition chromatography step.

[0117] “Extraction” generally refers to obtaining the materials / substances / particles from the GM that are dissolved / dispersed in an extraction solvent or chilled / iced water. An extraction product may contain one or more soluble / dispersible substances from the GM including, without limitation, waxes, sugars, cellulose, chlorophyll, dirt, cellular debris, and of course, cannabinoids and other phytonutrients.

[0118] Ralph Mechoulam coined the term “entourage effect” to describe the inexplicable synergy that manifests when multiple naturally occurring compounds extracted from Cannabis plants are consumed in tandem. This effect is thought to be the result of multipathway activation and signaling from various nutrients in a hemp extract comprising more than just isolated CBD alone. CBDA, the precursor to CBD may be responsible for at least some of the multipathway activation and signaling as CBDA may have greater bioavailability and efficacy than CBD, at least in some instances, and it may act on different signaling and other pathways than CBD.

[0119] Extracting cannabinoids and other phytochemicals from C. sativa plants, however, is riddled with numerous challenges toward commercial viability of products. Extracting cannabidiolic acid (CBDA), which is the precursor to cannabidiol, is especially challenging due to its delicacy. That is, CBDA may decarboxylate to CBD when exposed to heat and / or light, and over time. Thus, extraction and purification processes must be exacting to obtain commercially viable amounts of CBDA from C. sativa plant matter. Furthermore, extraction processes are not necessarily selective for CBDA, and will extract CBDA together with other desirable and undesirable components from the source plant material. The more processing an extract that is initially rich in CBD undergoes, the greater potential for CBDA to decarboxylate to CBD or to otherwise be lost while removing impurities and other undesirable substances. Thus, many CBDA production processes end with unsustainably low yields, leading to high prices for the generated extraction product oil.

[0120] We have discovered improved ways to extract CBDA and other phytonutrients from C. sativa plants and to purify and / or refine at least some of such CBDA-rich extractions. The resultant high quality CBDA-rich extracts are suitable for personal, pharmaceutical use, or both. Our CBDA extraction and purification system uses tunable / adjustable processes to extract and purify CBDA-rich extracts of various grades. Various grades of CBDA-rich extracts are desirous in that some implementations may call for a less purified extract with a greater potential “entourage effect” and other implementations may call for a more purified or the most purified CBDA-rich extract while still maintaining an “entourage effect.” The CBDA-rich extracts resultant from processes described herein may include multiple naturally occurring cannabinoids extracted from C. sativa plants in addition to CBDA. Such extracts can also include, without limitation, additional naturally occurring phytonutrients such as essential fatty acids, flavonoids, terpenes, vitamins, and minerals such as, without limitation, omega-3 and omega-6 fatty acids, antioxidants, potassium, magnesium, iron, zinc, calcium, phosphorus, vitamin E, and other molecules. Broad spectrum CBDA extracts (BSHE) are produced by removing detectable amounts of THC from CBDA-rich extracts that may contain a small amount of THC while retaining other cannabinoids including CBDA. BSCBDAE also includes some or all of the additional noncannabinoid phytonutrients that are found in other CBDA-rich extracts. Thus, to obtain the benefits of CBDA and other naturally occurring phytonutrients, one should use a CBDA-rich extract such as those produced by the processes described herein.

[0121] FIG. 1 is an overview of an improved production process / system (10) including one or more tunable steps for producing a CBDA-rich extract. Generally, the system (10) includes the following process steps: prepare GM (12), extract CBDA from the prepared GM (14), purify the CBDA-rich extract (16), and optionally refine the purified CBDA-rich extract (18). In this production process (10) extraction (14) may use a solvent (20) or be considered solventless (22). The results of the extraction (14) may be purified (16) by one or more of filtration (24), being pressed (25), solvent removal (26), and winterization (28). If additional refining is desired, the result of purification (16) may be refined such as by crystallization (30) or chromatography (32). The particulars of each of the forgoing production steps are addressed in the ensuing paragraphs and associated figures.PREPARE GREEN M TERIAL

[0122] Referring to FIG. 1, a tunable production process (10) is shown. Quality production begins with the plant source material, which begins with the grower. Furthermore, the source material may even play a part in determining which methods, steps, and end points are suitable for CBDA extraction (14), purifying (16), refining (18), or combinations thereof. Thus, the plant source material may play a significant role in embodiments detailed herein, without limitation. Plant source material used to produce CBDA-rich extracts detailed herein are recognized by the United States Department of Agriculture (USDA) as “hemp” having less than 0.3% w / w THC and are of the Cannabis genus and sativa species (e.g., C. sativa). The harvested source material should have less than 0.01 ppm pesticides and, after drying, a sustained water activity (aw) of less than 0.8, and preferably less than 0.7 to prevent mold growth. To assist growers in providing the best product possible, experiments were conducted emulating packing and / or weather conditions experienced by many growers. Generally, source material was packed at different rates and access to fresh air was controlled to mimic actual packed source material in barns. For the best results, it was found that source material should dry to have an awbelow 0.8 before packing. Once the awis below 0.8, mold growth is not observed when packed. Drying to have an awbelow 0.8 took about 24 hours at room temperature if source material is loosely packed.

[0123] Weather may also affect source material awespecially if hung in bams and threshed. From experiments designed to test hemp source material awin wet weather, it was determined that one or two days of rain did not detrimentally affect the awof the source material as it hung in a barn, but continuous rain over a few days raised the awabove acceptable limits, increasing susceptibility to mold growth. With the forgoing in mind, growers may plan for optimal growing, harvesting, and packing of source material to initially obtain an acceptable awand to maintain that awwhile the source material is in their hands.

[0124] Overall yield depends not only on the quality of the source material, but also the freshness of the source material. Optimal results using the tunable production process (10) starts with source material that goes through processing within six months of harvest, although embodiments are not so limited. After about six months, we found that CBDA yield decreases, possibly due to environmentally induced decarboxylation of CBDA to CBD. Furthermore, we found that optimal results were obtained when the source material prepared for extraction was limited to green material (GM), which generally refers to the parts of the hemp plant thatproduce the most cannabinoids such as flowers / inflorescence and leaves. Preparing GM (12) may include inspecting the GM from the grower before extraction such as by visual inspection for mold or other infestations and by testing, if not previously done. For example, the GM can be tested to ensure that it contains less than 0.3% w / w THC and less than 0.01 ppm pesticides, and that is has an awbelow 0.7. Preparing the GM (12) may also include, without limitation, chopping / grinding the GM to about 0.25 inches and weighing to a predetermined weight that is optimal for a given extraction process. Thus, regardless of how the CBDA is to be extracted from the GM, the GM should be prepared (12) as detailed above for optimal CBDA recovery, although embodiments are not limited thereto.EXTRACT / PURIFY CBDA

[0125] Referring to FIG. 2 a tunable process (200) for extracting CBDA using an extractor drum is shown. The extractor drum used in this extraction process is fitted with a mesh screen to create a false bottom and to help keep particulate GM from the extraction solvent that collects at the bottom of the extractor drum. When ready, the prepared GM may be loaded into the extractor drum (212). During loading, the prepared GM may need to occasionally be tamped down to fit the entire predetermined weight into the extractor drum. The extractor drums we use are large enough to hold about 50 kg to about 150 kg of GM total at a mass ratio of about 1 kg GM to about 4 kg solvent and up to about 10 kg solvent, although embodiments are not limited thereto.

[0126] Before loading the GM into the extractor drum, the solvent to be used for the particular extraction process should be determined (210). There are two different solvent systems that may be used in the drum extraction process (200). One solvent system uses edible oil, and the other solvent system is based on an alcohol. Oils that can be used to extract CBDA from GM include, without limitation, edible / food-grade oils such as, without limitation, hemp seed oil, medium-chain triglyceride (MCT) oil, coconut oil, sunflower seed oil, olive oil, and the like. Regardless of the particular oil used, the oil is at a temperature that allows it to remain liquid such as room temperature and less than 80°C. In contrast, alcohol-based extraction solvents should be cooled to a temperature at or below freezing before being added to the drum. The alcohol-based solvent may be cooled in a solvent tank to a temperature between about 0°C and about -20°C, and even more preferably to about -80°C before use. In an embodiment, the alcohol-based extraction solvent is denatured ethanol. A useful ethanol-based extraction solventis completely denatured alcohol formulation CDA-12A-1 (completely denatured alcohol) from Greenfield Global, which comprises 5% heptane and 95% 200 proof ethanol, or a100% 200 proof ethanol, although embodiments are not limited thereto. When the ethanol -based solvent is at a desired temperature or when ready to start the extraction cycle with an oil, the solvent may be pumped into the extractor drum until it reaches a desired volume, but at least as much as is needed to saturate the GM within the extractor drum.

[0127] When the extractor drum is filled with the appropriate amounts of prepared GM and determined extraction solvent, the GM is run through an extraction cycle (214). Generally, during the extraction cycle (214) the extraction solvent flows through and mixes with the GM and collects in the false bottom of the extractor drum. The extraction solvent at the bottom of the drum is pumped back to the top of the extractor drum to percolate though and mix with the GM and collect in the false bottom where it is again pumped back to the top of the extractor drum. The cycling of the extraction solvent continues for about one hour at atmospheric pressure, although embodiments are not limited thereto. For any given extraction cycle, the time may be more or less than an hour. In some instances, an extraction cycle may last for 2-3 hours. This is especially true when oil is used as an extraction solvent. Thereafter, the extraction product resulting from the extraction cycle (214) is collected (216). In an embodiment, the extraction product may be filtered before collection (216) by being pumped through a fine mesh filter (218) to remove any particulate GM before going into a collection tank. In an embodiment, the collected (216) extraction product may undergo additional filtration (218) after being pumped through the fine mesh filter. In a particular embodiment, oil-based extraction products may be purified by being filtered through a 150-micron mesh filter before collection (216), after collection (216), or both.

[0128] After filtration (218), an extraction product may be tested to determine its potency. Determining potency at this stage is valuable especially for oil-based extractions. Furthermore, potency at this stage can be tuned for various levels of potency. For example, a target CBDA potency for extraction products may be greater than 1% CBDA, greater than 2% CBDA, greater than 5% CBDA, and even greater than 10% CBDA. Thus, if a target CBDA potency is below a desired level, one or more extraction cycles (220) may be performed.

[0129] With respect to oil-based extractions, if the CBDA potency of a raw extract (222) is lower than desired, the GM (e.g., already in the drum), fresh GM, or both may undergo anotherextraction cycle (214) where the raw extract (222) may be added back (220) to the drum to be the determined solvent for extracting CBDA from the GM that was already in the drum or fresh GM added to the drum or both. The GM in the drum then undergoes an extraction cycle (214) to increase the concentration of CBDA in the extraction product. When the extraction cycle (214) is complete, the extraction product is collected (216), filtered (218), and tested for potency as described above. In this way, the potency of CBDA in a quantity of extraction product may be increased until it reaches a desired level. The food-grade / edible oil with a desired potency of CBDA contained therein is a raw extract that may be incorporated into end user / consumer products. Raw extracts are less processed than other CBDA-rich extracts produced by the tunable process (10) and thus may have more botanicals such as flavonoids, terpenes, and the like than other, more processed CBDA-rich extracts. The potency of a raw extract, however, may not reach the levels found in CBDA-rich extracts that undergo alternative forms of extraction and / or additional processing. Cannabinoid concentrations expected in a raw extract are detailed in Table 1. The concentrations of cannabinoids in Table 1, however, may be more variable than other extraction / purification processes in view of the number of extraction cycles needed to get a desired CBDA potency.

[0130] TABLE 1: EXPECTED CANNABINOID PROFILE OF A RAW EXTRACT USING HEMP SEED OIL AS AN EXTRACTION SOLVENT AND EXTRACTING GM TO OBTAIN A CBDA POTENCY OF BETWEEN ABOUT 1% AND 25%

[0131] With respect to alcohol-based extractions, the GM in the extractor drum may be subject to one or more additional extraction cycles (220). For instance, if the amount of CBDAin the collected / filtered extract (216, 218) is not at a desired concentration, or if the source material is known to produce less than desirable quantity of CBDA after a single extraction cycle (214), or for any other reason, fresh / unused alcohol -based solvent may be added to the extraction drum for a subsequent extraction cycle (220). In this case, however, the extraction drum is filled with cold (e.g., from about 0°C to about -80°C) alcohol-based extraction solvent to a volume that is about ’ / a to Vi of the volume used for the first extraction cycle (214). The subsequent extraction cycle (220) circulates the alcohol-based solvent in the same way as the first extraction cycle (214) for at least about an hour to extract any additional soluble material. If multiple subsequent extractions are performed, the alcohol-based solvent from each extraction cycle can be combined after collection (216) and filtration (218). When the desired number of extraction cycles are complete, the GM within the drum is discarded.

[0132] In the above described extraction scenarios, % yield of CBDA in a resultant extract was affected by solvent used. For example, with respect to nonedible oil-based solvents, we compared yields using hexane, ethanol, and completely denatured ethanol as extraction solvents. Hexane produced suboptimal results whereas ethanol alone had better results. Drum-type CBDA extraction using completely denatured alcohol, however, produced the best yields especially when it was chilled as described above. In fact, the more the ethanol-based solvent was chilled, the better the yield. With respect to oil-based extractions, we determined that hemp seed oil, and in particular cold pressed hemp seed oil, was better than extracting CBDA as compared to other food-grade oils.

[0133] Other parameters were tested to see if their effect on yield. Surprisingly, the size of prepared GM influenced the outcome. This is especially true when the size of the GM was considered in combination with the false bottom of the extractor drum. Again, in an effort to keep as much debris, impurities, and other contaminants out of the extract as possible, filtering the extract through a natural material such as carbon, diatomaceous earth, or sand, was examined as was filtering through one or more synthetic filters. The synthetic filters, such as the one creating the false bottom and or the ones through which the extract is pumped to the holding tanks, sufficiently kept particulate GM out of the extract. Furthermore, it was found that the optimal size of the GM in combination with the synthetic filters is about 0.25 inches. This size allows for complete extraction of desired cannabinoids and other phytonutrients without being sosmall to generate losses due to fine cutting or grinding, which would also necessitate a more expensive and cumbersome filtering of particulate GM from the extract.

[0134] Another parameter examined during extraction redevelopment was the necessity of freezing the GM before extraction. Yields compared from extracts of frozen GM and room temperature GM showed that freezing the GM before extraction does not improve efficiency. The combination of the forgoing results decreased cost and time by omitting the freezing of the GM and filtering the extract through a natural material. It also increased our yield by allowing more quantities and types of cannabinoids to be extracted with completely denatured alcohol. The surprising result, however, was finding that the size of the prepared GM from which the cannabinoids are extracted greatly improved yield.

[0135] Referring back to FIG. 2, alcohol-based extraction products may undergo additional purification by removing some or all of the solvent to produce a crude extract (224). The alcohol-based solvent may be removed via distillation using rotatory evaporation or other suitable evaporator / still. Generally, to remove the alcohol -based solvent (or another solvent), temperatures should be set at about room temperature to about 75°C, or from about room temperature to less than 80°C, and the pressure should be less than 40 torr. In this way, the solvent evaporates away from the extraction product to a condenser where it is condensed back to a liquid and collected. If needed, the resultant crude extract may undergo one or more additional distillations to remove any remaining solvent, if any. After one or more distillation processes, the crude extract can be collected for use such as in an end user / consumer product. Alternatively, the crude extract may be a transitory product, hence a crude extraction product, where it may be further purified via winterization (FIG. 4) and / or refined as is described in FIG. 6 and FIG. 7, respectively. The cannabinoid profile of a crude extract obtained as described with respect to FIG. 2 is shown in Table 2.

[0136] TABLE 2: EXPECTED CANNABINOID PROFILE OF A CRUDE XTRICT USING COMPLETELY DENATURED ETHANOL AS AN EXTRACTION SOLVENT

[0137] Referring now to FIG. 3, an example of a supercritical CO2 extraction process (300) is detailed. Supercritical CO2 extraction (300) is an alternative extraction process to drum extraction (200); hence the overall production process (10) may be tuned to utilize supercritical CO2 extraction. Supercritical CO2 extraction may be used in favor of other extractions processes as an extraction product may be solvent free if using CO2 in a liquid supercritical state as a sole solvent and the extraction product may have a higher CBDA potency than extraction products obtained via drum extraction. Downsides to supercritical CO2 extraction are that usually the extraction chamber may hold less GM than the drum used in drum extraction, extraction times may be much longer than other extraction processes, a collected extraction product may require more postprocessing than with some other extraction processes and it is very costly.

[0138] As with drum extraction, prepared GM and solvent are loaded into vessel (302) for supercritical CO2 extraction. A supercritical CO2 extraction chamber may hold about 10-20 kg GM, although embodiments are not limited to vessels of a given size. The solvent used for supercritical CO2 extraction is CO2 that is brought to a temperature and pressure to produce a supercritical fluid. Supercritical CO2 extraction, however, is not limited to liquid CO2 as an extraction solvent; rather, a cosolvent such as an alcohol, and more specifically ethanol, and even more specifically 5% ethanol; or completely denatured ethanol or acetone may be substituted, at the same percentages, for ethanol as a cosolvent, although embodiments are not so limited. Thereafter, an extraction cycle (304) may begin where the solvent(s) mix with the GM to extract soluble materials. In an embodiment, the pressure of the extraction chamber / vessel is from about 12 MPa to about 25 MPa (e.g., average of about 127,510 torr) and the temperature of less than 80°C. An extraction cycle (304) may last from about 2 hours to about 6 hours, although time may be increased or decreased for a particular extraction cycle. Aswith drum extraction (200), CO2 extraction (300) will remove CBDA-rich oils, waxes, resins, and other materials from the GM.

[0139] When an extraction cycle (304) is finished, the pressure inside of the vessel may be decreased so that the supercritical fluid enters a gaseous state to diffuse away from the GM and extraction product to a condenser (306). In an embodiment (without limitation) condensed CO2 may be recycled and used again as an extraction solvent. CO2 may be condensed at a temperature of about 40°F-60°F and a pressure of about 130-150 psi. Additionally, the extraction product may be filtered as it drains from the extraction vessel and collected (308). In the instance where a cosolvent is used together with supercritical CO2 fluid, the cosolvent may be evaporated (310) if it is not removed with the gaseous CO2. Cosolvent evaporation is as described with respect to step (224) in the drum extraction (200) process. After the extraction product is collected, either from the extraction chamber (308) or after cosolvent removal (310), or both, the supercritical CO2 extraction product may be purified via winterization.

[0140] CBDA may also be extracted from GM via an ice water extraction process (400) such as the one detailed in FIG. 4. This process (400) uses a chilled water wash (402) and graded separation (404) to release and separate extracted CBDA-rich trichomes (e.g., hash extract) from undesired impurities. Generally, chilled / iced water extraction starts with GM that is mixed with chilled / iced water and agitated to separate the trichomes from the plant material. Trichomes, the resin glands on cannabis flowers, contain cannabinoids, terpenes, and other compounds responsible for the unique effects and flavors of C. sativa. The ice water and agitation help to freeze the trichomes, causing them to break off from the plant material and sink. Ice water extraction (400) is desirable in that it is considered solventless, can result in a CBDA-rich extract / extract! on product having fewer impurities compared to other types of extraction methods, and does not use heat, which helps prevent CBDA decarboxylation to CBD.

[0141] In an embodiment, the GM, may or may not be prepared as detailed above and it may optionally be frozen / freeze dried. Freezing or freeze drying the GM before washing may increase the brittleness of trichomes, which, in turn, helps the resin-rich trichomes to break off from the rest of the GM during the wash cycle (402). Before the wash cycle (402), the washer is usually filled with water chilled to a temperature just above freezing so that the water is cold but not frozen. In an embodiment, the water may be prechilled before adding to the washer, chilled in the washer with ice, or both. Furthermore, GM may be added to the chilled water directly or itmay be placed in a container such as a mesh bag. In an embodiment the mesh may be greater than or equal to 190 microns such as about 220 microns. In an embodiment, the GM is allowed to soak for about 15 to 30 minutes to mix before agitation. Alternatively, the GM may be mixed with the chilled / ice water and agitated soon after being added to the washer. Mixing and agitation may take place for about 20 to 30 minutes, although embodiments are not limited thereto. Agitation in the cold water wash helps cause the trichomes to become brittle and break off from the plant matter. After agitation, the GM may rest in the wash water for about 5 to 15 minutes. In an embodiment, the GM may be agitated and allowed to rest one or more times before being collected from the wash water. In an embodiment, the GM may remain in the same wash water for the additional agitation and rest cycles, or the wash water may be collected as part of an extraction product and replaced with fresh wash water (which may also be collected after washing as part of an extraction product). In an embodiment, collected wash water (i.e., part of the extraction product) may be run through the graded sieving / straining system to capture (404) and collect (406) hash extract / extraction product as described below.

[0142] CBDA-rich materials such as resins and oils found in trichomes may be separated from other plant-based impurities using graduated sieves, filters, strainers, or the like (404). The extraction product from the wash cycle, including collected trichomes, removed wash water, or both may be filtered through mesh sieves, strainers, or the like to separate larger particles from smaller particles. In an embodiment, mesh bags or other screens are nested in order of decreasing pore sizes and used as filters to collect the smaller particulate trichomes while allowing water to drain through. Collected trichomes / trichome particles are a hash extract / extraction product, which is usually dried and stored for later use such as in end user / consumer products.

[0143] Screen mesh sizes may range from about 25 microns to about 220 microns such as 25, 45, 73, 90, 120, 160, 190, or 220 microns, although embodiments are not limited to the sizes. That is, mesh size is a tunable function that can adjusted to produce a targeted outcome. As one nonlimiting possibility, a 120-micron, 90-micron, 73-micron, and 25-micron mesh screens may be used to filter a chilled / iced water extraction product. In an embodiment, the filters are submerged in an ice bath to help further grind / separate particles of assorted sizes. Generally, the screen with the smallest mesh size is the last screen in the system and the screen with the largest mesh size is the first in the system. The remaining screens are layered therebetween in order ofscreen mesh size. In this way, smaller particles may pass through screens leaving larger particles behind. In this example, particles collected at the 120- and 90-micron mesh screens are removed and discarded. Particles captured by the 73-micron mesh and 25-micron mesh, however, are collected (408) as a hash extract / extraction product. In an embodiment, particles captured after being filtered through at least a 90-micron mesh screen may be captured by an 80-micron mesh screen and / or mesh screens less than 80 microns and collected. Thus, the sieving / filtering system may be tuned to collect hash extracts having desired purity levels; the smaller the particles collected, the purer the substance. In an embodiment, GM, including trichomes, may be rewashed and rerun through the graded sieving / straining system.

[0144] After collection, the hash extract / extraction product may be dried (408) to remove water. Drying may be by any suitable means. In an embodiment, a vacuum oven operating at less than about 40 torr may be used to remove water and dry the hash extract / extraction product. Oven temperature, however, should be maintained at or below 80°C. The expected cannabinoid profile of a hash extract is detailed in Table 3, below. This extract may be used as is in consumer / end user products.

[0145] TABLE 3: EXPECTED CANNABINOID PROFILE OF A CBDA-RICH HASH EXTRACT

[0146] Still referring to FIG. 4, should a more concentrated extract be desired, the dried hash extraction product may be pressed (410) such as by a rosin press. Generally, the dried hash extraction product may be placed between plates and pressed to exude a CBDA-rich rosin. Heat may or may not be applied to the plates. If heat is applied to the plates, the temperature of the plates should not exceed 80°C. Should a greater temperature be required, the time spent at thehigher temperature should be reduced to deter cannabinoid decarboxylation. The resultant rosin can be collected, stored and / or used in consumer / end user products. The cannabinoid profile of the rosin may be similar to the above, with concentration exceeding the lowest percentages. This is especially true where high heat (e.g., over 80°C) is used where the percentages of CBD and THC may be increased to as much as 30% due to excess decarboxylation.

[0147] As an alternative to pressing, the dried hash extraction product may be further purified by cold ethanol extraction (412). Cold ethanol extraction is generally the same as cold ethanol-based drum extraction as described with respect to FIG. 2, except on a smaller scale and using the hash extraction product instead of GM as a source material. The cannabinoid profile of the resultant extract / extr action product may be similar to the above, with concentration exceeding the lowest percentages.

[0148] As yet another alternative, a hash extraction product may be winterized, as described below in FIG. 5.

[0149] An example of a winterization process (500) is detailed in FIG. 5. As with other processes, the winterization process (500) is tunable to produce a desired outcome for a particular CBDA-rich extract / extr action product. Generally, winterization removes impurities such as waxes, lipids, and other impurities from a CBDA-rich extract / extraction product. A supercritical CO2 extraction product usually undergoes winterization to remove impurities, although for some implementations it may not be desired or required. Furthermore, crude extracts the result from drum extraction using an alcohol as a solvent, and solventless extracts that result from ice water extraction may be winterized to remove impurities, although it is not required. This is especially true for solventless / ice water extraction products as most, if not all, impurities are removed during the extraction / purification process.

[0150] Referring to FIG. 5, regardless of which extraction product / CBDA-rich extract is to undergo winterization, the extract may be dissolved in a suitable solvent (502). Suitable solvents include polar solvents, preferably alcohol, and even more preferably an ethanol-based solvent such as 190 proof ethanol or denatured ethanol. In an embodiment the solvent used for winterization is food grade or pharmaceutical grade. The quantity of solvent used for winterization should be enough to dissolve most, if not all, or the starting extract. In an embodiment, a ratio of 10 parts solvent to 1 part starting extract provides an acceptable winterization result.

[0151] Thereafter, impurities are precipitated out of the dissolved (at least in part) extract / extraction product (504). In an embodiment, impurity precipitation may be achieved by chilling the dissolved extract / extraction product to a temperature of from about -20°C to about -80°C for at least 24 hours and up to about 72 hours, although embodiments are not limited thereto. Chilling at these temperatures for the suggested times causes impurities such as waxes, lipids, and the like to congeal and precipitate out of solution. It was found that chilling to lower temperatures (e.g., between about -70°C and about -80°C) decreases the time needed for the impurities to congeal and increases the purity of the winterization product. Thus, although the forging parameters are suitable, preferred temperatures are below -20°C, even more preferably below -50°C, and most preferably between -70°C and about -80°C. Time for precipitation to form was found to be inverse to temperature so that the more chilled, the less time needed cause a precipitate to form. Thus, optimal parameters for winterization to purify an extract / extraction product are chilling to less -70°C and about -80°C for about 24 hours to 48 hours.

[0152] Precipitated impurities can be separated (506) from the non-precipitated extract / extraction product by filtration or any other suitable separation procedure. As a nonlimiting example, the result of the prior step may be filtered by vacuum filtration, gravitational filtration, centrifugation, or the like so that the precipitate formed by winterization is separated from the remaining liquid. The liquid containing extract may be used in a consumer useable / end user product, or it may need additional purification before being ready for use in a consumer / end user product. Winterized CO2 extract (without the use of a cosolvent) is a nonlimiting example of a CBDA-rich material that is ready for use in a consumer product. The cannabinoid profile of such a winterized CO2 extract is detailed in Table 3, below. If residual solvent needs to be removed from the winterized product, it can be distilled off as previously detailed in FIG. 2, step (224), or a distillation process similar thereto, without limitation. Moreover, any of the resultant CBDA-rich extracts may be refined to obtain a CBDA-rich extract having a different cannabinoid profile than those listed in Table 3.

[0153] TABLE 4: EXPECTED CANNABINOID PROFILE OF A CBDA-RICH EXTRACT WHEREIN THEEX RACTION PROCESS USED CO 2 AS AN E TRACTION SOLVENT, AN ETHANOL-BASED EXTRACTIONSOLVENT, OR CHILLED / ICED WATER EXT CTION

[0154] Some purified extracts / extractions products may be further processed via refining, which may remove some or all THC chemical variants. As is shown in FIG. 6, a purified extract may be refined via a crystallization process (600), which, in addition to removing THC variants will concentrate CBDA so that it is at least about 70% of the refined extract. To begin crystallization, the selected purified extr act / extract! on product (e.g., crude extract, winterized extract, hash extract, and the like) is mixed with a solvent (602) such as hexane, although embodiments are not so limited. Generally, about one part purified extract / extr action product should be mixed with about 5 parts to about 10 parts of solvent. Thereafter, the mixture may be chilled for at least about 12 hours. Chilling may take place in a freezer at a temperature that is less than 0°C. In a preferred embodiment, the temperature is between about -10°C to about -20°C. As with winterization, it was found that crystallization results improved(e.g., greater purity) with lower temperatures. After chilling, the mixture can be brought to room temperature and incubated for a total of at least 12 hours (606). In an embodiment, the freeze-thaw cycle (604, 606) may be repeated an additional one time to five times, and even up to 10 times. In an embodiment, if crystals fail to develop after about three freeze-thaw cycles, seed crystals may be added to the solution to stimulate CBDA crystallization. In an embodiment and without limitation, about 0.5 g of seed crystals may be a sufficient amount to stimulateCBDA crystallization. After the desired number of freeze-thaw cycles, a solid precipitate of CBDA crystals / crystal lattice has formed.

[0155] CBDA crystals can be separated from the solvent (608) via any suitable separation technique such as fdtration, centrifugation, decanting, and the like. As one nonlimiting example, CBDA crystals may be separated from solvent by vacuum filtration maintained at a temperature that is less than or equal to 0°C. If solvent remains after filtration, the residual solvent may be removed (610) such as by vacuum oven. To prevent CBDA from decarboxylating to CBD, the temperature of the oven should not exceed 70°C and the pressure should be maintained at or less than 40 torr. Depending on the amount of residual solvent present, this step may take from between about 1 hour and about 3 hours, although embodiments are not so limited. The CBDA-rich product that results from one or more steps of the crystallization process (600) is a CBDA isolate extract that is usually a white, THC-free powder having a cannabinoid profile as detailed in Table 5. This powder should be stored at between about 2°C and 8°C in a light protective bottle. Moreover, it should not be incorporated into consumer products that require heat or should be added to those types of products after cooled enough to prevent substantial CBDA decarboxylation to CBD.

[0156] TABLE 5: EXPECTED CANNABINOID PROFILE OF CBDA ISOLATE OBTAINED VIA CRYSTALLIZATION

[0157] Chromatographic methods can be an alternative refinement process for some types of purified extracts / extraction products. An example of chromatographic-based refining method (700) is shown in FIG. 7. This type of refining can also increase the concentration ofCBDA in the result of the refinement process and may also remove some / all THC chemical variants. The primary steps for using chromatography to refine a purified extract / extraction product includes, without limitation, (i) separating THC / THC variants from CBDA and other cannabinoids using centrifugal partition chromatography (CPC), and (ii) removing solvents from THC-free fractions obtained via CPC.

[0158] CPC is a type of chromatography that uses two liquids, one as a stationary phase, and the other as a mobile phase. The stationary phase is immobilized by a strong centrifugal force and the mobile phase moves through the stationary phase to separate different molecules. This technique typically requires a two-phase mixture of solvents. Different compounds can be separated based on the components of the particular solvent system and the partition coefficients of the molecules in the selected solvent system. Thus, by using two different solvents together with CPC, similar substances can be separated. Generally, using CPC, as one liquid is introduced into the machine, another exits from the CPC machine. Molecules having different partition coefficients will come off of the CPC machine at different times and / or in different fractions due to separation through the stationary phase in the CPC machine.

[0159] An example of a solvent system that may be used to separate THC from other cannabinoids includes a nonpolar solvent (e.g., hexane) and two polar solvents (e.g., methanol and water). The ratio of these solvents is important as is the density of the nonpolar solvent mixture. For freshly prepared (702) solvents, the ratio of hexane to methanol to water is 5 :4: 1. Per the CBDA refining process (700) removed solvents can be recycled and reused. Nevertheless, the ratio of the solvents (5:4: 1) should be maintained for proper THC removal. Generally, removed solvents may be collected and allowed to separate in a container where they will form an upper layer that is primarily hexane, and a lower layer that is primarily water and methanol. After separate layer formation, the two layers are transferred to respective containers. The density of the lower phase is adjusted by adding water and / or methanol (as indicated by the particular instance) until the density is about 0.852 g / cm3at 70°F. The solvents may then be ready for reuse.

[0160] To prepare purified CBDA for CPC separation, the desired amount of purified CBDA is warmed in an oven until it is fully dissolved. The warming temperature, however, should not exceed 80°C. After warming, the CBDA-rich extract is added to the upper phase (e.g., hexane)such that the ratio of hexane to CBDA extract is about 2:1 (704). The purified CBCA should be completely dissolved in hexane (e.g., “sample”) before being loaded into the CPC machine.

[0161] For THC removal to occur, the CPC machine is filled with clean stationary phase mixture of water and methanol and the centrifuge within the CPC machine starts rotating. Thereafter, the CBDA sample (e.g., in mobile phase) is loaded into the CPC machine and allowed to separate (706). Additional mobile phase may be added to the machine during THC removal. Clean stationary phase solvent may also be added to the CPC machine. Meanwhile, fractions coming off of the CPC machine are collected (708). Fractions can be monitored via a UV absorbance spectrum. At the beginning and the end of a CPC run, where cannabinoids are not expected to come off the machine, the UV absorbance spectrum is expected to be low. In contrast, the presence of cannabinoids will cause the UV absorbance spectrum to show high points. This absorbance spectrum lets an operator of the CPC machine know when cannabinoids are coming through the system. Cannabinoids without THC have a different absorbance spectrum than those with THC, so it is possible to estimate which fractions are THC-free and which are not. Thus, per the solvent system, sample loading, and CPC parameters, fractions can be divided into three categories: waste, THC-free, and reclaim. Simplified parameters of the CPC run method are outlined in Table 6. Since non-THC cannabinoids (e.g., CBDA) dissolve better in the lower phase than THC, they come off the CPC machine first. Conversely, as THC dissolves better in the upper phase, it will come off the CPC machine later in the process. Reclaim is a mix of THC and CBDA that can be separated in a second pass through the CPC.

[0162] TABLE 6: TIME, INPUT, OUTPUT, AND FLOW PARAMETERS FOR AN EXEMPLARY CPC RUN

[0163] Before reclaim fractions can be rerun on the CPC, solvent is first removed (710). As a nonlimiting example, solvent may be distilled off of the reclaim fractions as was described above in FIG. 2, step (224). Solvent may be removed from the reclaim fraction after one or more distillations. After distillation, a reclaim oil remains, which may be prepared and rerun on the CPC machine. The run of reclaim oil is similar to that of the initial run except that the ratio of hexane to reclaim oil is 2.5 (hexane) to 1 (reclaim oil) and only two fractions are collected: THC-free and waste.

[0164] Before continuing with solvent removal, THC-free fractions may be internally verified to be truly THC-free, although embodiments are not so limited. If found to contain THC the fractions can be rerun through the CPC (e.g., as reclaim fractions) and reverified as being THC-free. THC-free fractions may be combined for solvent removal such as via a horizontal wiped film evaporator.

[0165] To remove solvent (712) from the THC-free fractions using the horizontal wiped film evaporator, a heating jacket may be set to heat the evaporator from about 60°C to about 80°C, but no higher and at full vacuum, which is about 100 torr. As the THC-free fractions move into the evaporator, they are spread into a thin layer by the wipers, to enhance solvent evaporation. The solvent vapors move to the condenser, which is set at 4°C to condense the vapors back to liquid solvent, which as mentioned may be recycled and reused. After about 4 hours, the undistilled portion, which contains concentrated CBDA sans THC is collected.

[0166] As solvent may still be present in the concentrated CBDA extract, a second distillation may optionally be performed such as on a rotary evaporator (712), with the bath set at 80°C or less under the strongest possible vacuum to distill off any remaining solvent. Vaporized solvent can travel to a condenser set at about -20°C to be condensed back to a liquid, which may be recycled and reused.

[0167] As water may be present in the CBDA-rich extract, it may also be removed (714). Before doing so, the CBDA-rich extract may be allowed to cool for at least about 1 hour, but a longer time will not affect yield. Once cooled, water may be removed from the CBDA-rich extract using an evaporator (714) such as a rotary evaporator, without limitation. To do so, the vacuum is turned on, but not the heat. The vacuum causes the CBDA-rich oil to clump and separate from the water. After being under vacuum for at least 1 hour, water should be completely separated from the clumped CBDA-rich oil. To remove the water from the clumpedCBDA-rich oil, it may be decanted, suctioned or the like before returning the oil to the evaporator to distill off the remainder of the water (714). For example, at a temperature of about 80°C or less and a vacuum pressure of about less than 150 millitorr, water will evaporate away from the CBDA-rich oil. When the CBDA-rich oil changes from cloudy to clear and there is little to no bubbling of the oil, the water has been distilled off and the CBDA-rich oil, which is a Broad spectrum CBDA extract (BSCBDAE) is collected (716) and may be sent to an independent lab for testing, although embodiments are not so limited.

[0168] TABLE 7: EXEMPLARY EXPECTED CANNABINOID PROFILE OF BSCBDAE:

[0169] A simplified approach to the formulations is that the BSCBDAE includes between 60%-95% of a CBDA, THC (all variants) of 0%-0.1%, but preferably not detectable, and additional cannabinoids between 0% and 10%, whereas CBDA-rich extracts other than BSCBDAE and CBDA isolate may include 0.01% to 10% THC, but preferably between 0.01% and 0.3% as required in certain jurisdictions.

[0170] CBDA-rich extracts may be utilized in a number of ways. Unfortunately, CBDA-rich extracts can have a bitter flavor so it is helpful to add these extracts to a suitable carrier for oral, mucosal, chewable, or other such dosage forms where taste may be an issue. Oils such as long- chain triglyceride (LCT) oils or medium-chain triglyceride (MCT) oils, hemp seed oil, and the like are readily available. In an embodiment, the CBDA-rich extract is added v / v into a mixture of cold pressed hemp seed oil, coconut oil, or the like, or combinations thereof. This makes the resulting oil palatable for oral administration. In an embodiment, CBDA-rich extracts having higher CBDA concentrations may be added at about 1%— 10% v / v with cold pressed hemp seedoil and the MCT oil (e.g., coconut oil) each at between 10% and 99% v / v. Raw CBDA extract, however may be at the desired concentration after purification and thus not need to be added to an oil such as the ones above as an oil was used as an extraction solvent. Conversely, if the concentration of CBDA in a raw extract is higher than desired, it may be diluted to the desired concentration using a compatible oil. Furthermore, a flavoring can be added at about 0.1% to 5.0% v / v. Flavors include well known examples including but not limited to citrus flavors, fruit flavors, mint or wintergreen, and the like, which may be natural or synthetic.

[0171] In certain embodiments, the CBDA-rich extract can be added to the carrier at up to 99% of the total volume or weight of the composition, inclusive of all ranges from 1%— 99%.

[0172] A preferred embodiment is made by combining two or more different CBDA-rich extracts w / w into a mixture of cold pressed hemp seed oil and MCT oil, and further comprising a terpene blend. In other embodiments, the two or more CBDA-rich extracts are added only to an MCT oil, or only to a cold pressed hemp seed oil. In preferred embodiments, a composition comprises between 40% and 70% cold pressed hemp seed oil, and between 30% and 50% MCT oil, and between 1% and 20% of one or more CBDA-rich extracts. More preferably, the embodiment further comprises a terpene mix or other mixture to improve the profile of the composition.

[0173] In certain embodiments, a terpene blend is included at between 0.1% and 2.0% v / v. A particular blend may comprise one, two, three, or more terpenes. A terpene blend may include P-myrcene, P-caryophyllene, linalool, a-pinene, citral, D-limonene, and / or eucalyptol. A particular terpene blend comprises a terpene profile including P-myrcene at 15%— 25%, P-caryophyllene at 15%— 25%, linalool at 5%— 15%, a-pinene at 5%— 15%, citral at 15%-40%, .D-limonene at 10%-30%, and eucalyptol at 0.1%- 5%. In preferred embodiments, the terpene blend includes at least one, two, three, four, five, six or all seven of the recited seven terpenes. Preferably, the range of each of the terpenes is from between about 0.1% to about 50% of the total volume of the terpene blend. Most preferably, the terpene blend comprises at least 5 terpenes with each terpene representing a concentration of no more than 40% of the total volume of the terpene blend. The particular terpene blend utilized may depend on the particular CBDA-rich extract used. For example, raw extract will include more natural terpenes than a CBDA isolate, thus, different terpene blends, if any, may be selected for the raw extract as compared to the isolate.

[0174] A composition comprising a CBDA-rich extract, cold pressed hemp seed oil, coconut oil, and a terpene blend is optimized for use as a tincture for oral administration. In preferred embodiments, a flavor is further added at between 0.1% to 2.0% v / v of the composition. Such application is provided for sublingual application wherein the CBDA-rich extract is intended for uptake through the oral mucosa. It is understood that the material is often eventually swallowed, and that additional material is taken through the rear of the mouth, the esophagus as well as into the stomach and undergoes first pass metabolism. In certain embodiments, the CBDA-rich extract is a refined CBDA-rich extract. In further embodiments, the compositions may be formulated into a softgel, wherein the gel coating is produced to form as a dissolvable shell around a quantity of the composition. Such manufacture is well understood by one of ordinary skill in the art. In further embodiments, the composition is admixed into gelatin or another carrier, with the addition of one or more excipients, including but not limited to a flavorant, a sweetener, a color, for manufacture of a gummy product.

[0175] For topical administration, the carrier may further include an emulsifying agent. In certain embodiments, a fat may be further included, such as shea butter, which can be utilized as the carrier in place of the MCT oil. In such embodiments, the composition comprises CBDA-rich extract, cold pressed hemp seed oil, a second oil or fat, and optionally a terpene blend. In preferred embodiments, the second oil or fat is shea butter. In certain embodiments, the CBDA-rich extract is a refined CBDA-rich extract. Accordingly, a product may comprise between 1% to 50% of a CBDA-rich extract and between 99% and 50% of additional excipients, including the carrier and other components, which is suitable for topical administration.

[0176] CBDA-rich extracts may be manufactured and bottled. In a subsequent processing step, the CBDA-rich extract may be encapsulated in a gelatin material for oral administration. Typical soft gelatin capsules comprise between 0.4 mL and 0.6 mL per capsule of the oils. The manufacture of the gelatin capsule may include further excipients necessary to make the gelatin shell.

[0177] A further embodiment is directed toward a mucosal composition. In preferred embodiments, the mucosal composition may be intended for the oral mucosa, the nasal mucosa, the vaginal mucosa, or the rectal mucosa. In preferred embodiments, the mucosal composition is an intravaginal composition. The intravaginal compositions comprise a CBDA-rich extract at between 1% and 99% and a carrier, preferably a fat or an oil. Additional excipients may beincluded for stabilizing the formulation and for modifying the flowability or character of the final product. A preferred fat is shea butter. The intravaginal composition may further comprise a terpene blend as detailed herein. In certain embodiments, the pH of a CBDA-rich extract is modified, for example from a native pH of about 10.5 to an acidic pH of 6 or less or even 4 or less. An acidic buffer solution, comprising an appropriate conjugate acid and base can be utilized by one of ordinary skill in the art to make the pH acidic, such as between 3.5 and 6, and serve as the pH modifier. Osmolality modifiers may also be utilized, including the addition of salts, such as sodium chloride, to the composition. In certain embodiments, a mucoadhesive agent is included, wherein the mucoadhesive agent is chitosan, hydroxyethyl cellulose, methyl cellulose, polyacrylic acid, poly vinyl pyrrolidone, poly vinyl alcohol, polyethylene glycol, or combinations thereof.

[0178] It will be appreciated that the embodiments and illustrations described herein are provided by way of example and that the present invention is not limited to what has been particularly disclosed. Rather, the scope of the present invention includes both combinations and sub combinations of the various features described above, as well as variations and modifications thereof that would occur to persons skilled in the art upon reading the forgoing description and that are not disclosed in the prior art. Therefore, the various methods, formulations, and compositions detailed herein may include one or all of the limitations of an embodiment, be performed in any order, or may combine limitations from different embodiments, as would be understood by those implementing the various methods and systems detailed herein.

Claims

What is claimed is:

1. A tunable method for producing a plurality of grades of CBDA-rich extracts comprising: a. extracting CBDA from Cannabis sativa green material (GM) by mixing the GM with a solvent or chilled / iced water at about 80°C or less and collecting an extraction product; b. purifying the extraction product by filtering, pressing, removing the solvent, winterizing, or combinations thereof at about 80°C or less and collecting a CBDA-rich extract, a purified extraction product, or both; c. refining the purified extraction product at about 80°C or less by crystallizing the purified extraction product or by separating tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THC A), or both from the purified extraction product; and d. wherein the extracting, purifying, and refining steps and combinations thereof are adjustable to collect a particular grade of CBDA-rich extract.

2. The method of claim 1 wherein extracting further comprises mixing the GM with a solvent selected from an ethanol-based solvent, a supercritical CCh-based solvent, and an oil-based solvent.

3. The method of claim 1 or 2 wherein extracting further comprises mixing the GM in a drum with an ethanol-based solvent selected from the group consisting of: ethanol, completely denatured ethanol, 100% ethanol that is 200 proof, and combinations thereof.

4. The method of any one of claims 1 to 3 wherein before being added to the drum, the ethanol-based solvent is cooled to a temperature: a. at or below about 0°C; or b. between about 0°C and -20°C; or c. between about -20°C and -80°C.

5. The method of any one of claims 1 to 4 wherein extracting further comprises mixing the GM in a drum with an oil-based solvent selected from the group consisting of: hemp seed oil, medium-chain triglyceride (MCT) oil, olive oil, sunflower seed oil, coconut oil, and combinations thereof.

6. The method of any one of claims 1 to 5 wherein purifying further comprises filtering the extraction product and wherein collecting further comprises collecting a CBDA-rich raw extract, a filter-purified extraction product, or both wherein a CBDA concentration in the CBDA-rich raw extract is between about 1% and about 25% by weight.

7. The method of any one of claims 1 to 4 and 6 wherein purifying further comprises removing the solvent and wherein collecting further comprises collecting a CBDA-rich crude extract, a crude purified extraction product, or both wherein the CBDA concentration in the CBDA-rich crude extract is between about 25% and about 65% by weight.

8. The method of any one of claims 1 to 4, 6, and 7 wherein purifying further comprises winterizing and wherein collecting further comprises collecting a CBDA-rich winterized ethanol extract, a winterized purified extraction product, or both wherein a CBDA concentration of the CBDA-rich winterized ethanol extract is between about 50% and about 70% by weight.

9. The method of any one of claims 1 to 4 and 6 to 8 wherein refining by separating THC, THCA, or both comprises melting the purified extraction product and dissolving a resultant melt in a hexane-based solvent, running a resultant dissolved product through centrifugal partition chromatography (CPC), collecting at least THC-free fractions, removing the hexane-based solvent and water from the THC-free fractions, and collecting a broad spectrum CBDA extract wherein a CBDA concentration in the broad spectrum CBDA extract is from about 50% to about 80% by weight.

10. The method of any one of claims 1 to 4 and 6 to 8 wherein refining by crystallizing CBDA comprises mixing the purified extraction product with a solvent and chilling to a temperature of less than 0°C for at least 12 hours, which is followed by incubating at a temperature of between about 20°C and 25°C for at least 12 hours to complete a freeze-thaw cycle, separating crystallized CBDA that results from at least one freeze-thaw cycle from the solvent, removing residual solvent, and collecting a CBDA isolate extract.

11. The method of claim 10 wherein the freeze-thaw cycle is repeated from one additional time to ten additional times before separating crystallized CBDA from the solvent.

12. The method of claim 6 wherein collecting the raw extract further comprises determining if the raw extract has a desired concentration of CBDA and if not, performing another extraction cycle by adding the raw extract back to the drum, the drum containing either GM, fresh GM, or both; mixing the GM, the fresh GM or both with the raw extract; collecting and filtering a subsequent extraction product; and repeating the extraction cycle until a CBDA concentration of the raw extract is between about 1% and 25% by weight.

13. The method of claim 1 or 2 wherein extracting comprises mixing the GM with a supercritical CCh-based solvent in a pressurized extraction chamber, followed by separating the supercritical CCh-based solvent from the extraction product, and evaporating any remaining supercritical CCh-based solvent.

14. The method of any one of claims 1, 2, and 13 wherein purifying comprises winterizing the extraction product and collecting a CBDA-rich winterized CO2 extract or a winterized, purified extraction product wherein a CBDA concentration in the CBDA-rich winterized CO2 extract is between about 50% and about 70% by weight.

15. The method of any one of claims 1, 2, and 12 to 14 wherein the solvent optionally includes a cosolvent selected from the group consisting of: ethanol, completely denatured ethanol, acetone, and combinations thereof.

16. The method of any one of claims 1, 2, and 12 to 15 wherein refining by crystallizing comprises mixing the purified extraction product with a solvent and performing a freeze-thaw cycle of chilling the mixed purified extraction product to a temperature of less than 0°C for at least 12 hours followed by incubating at a temperature of between about 20°C and 25°C for at least 12 hours, separating crystallized CBDA formed during the freeze-thaw cycle from the solvent, removing residual solvent, and collecting a CBDA isolate extract having a CBDA concentration of between about 86% and about 99.9% by weight.

17. The method of claim 16 wherein the freeze-thaw cycle is repeated from one additional time to 10 additional times before separating crystallized CBDA from the solvent.

18. The method of any one of claims 1, 2, and 12 to 15 wherein refining by separating THC, THCA, or both comprises melting the purified extraction product and dissolving a resultant melt in a hexane-based solvent, thereafter running the dissolved melt through centrifugal partition chromatography (CPC) and collecting at least THC-free fractions, removing the hexane-based solvent and water from the THC-free fractions and collecting a broad spectrum CBDA extract wherein the CBDA concentration of the broad spectrum CBDA extract is between about 50% and about 80% by weight.

19. The method of claim 1 wherein extracting comprises mixing the GM with chilled / iced water, wherein purifying comprises sequentially filtering the extraction product through one or more screens having decreasing mesh sizes to separate trichome-rich particles from impurities, and wherein collecting a CBDA-rich extract or a purified extraction product comprises collecting a CBDA-rich hash extract or a hash extraction product from screens having a mesh size of 80 microns or less wherein a CBDA concentration in the CBDA-rich hash extract is between about 40% and about 80% by weight.

20. The method of claim 19 wherein purifying further comprises pressing the hash extraction product using pressure and low heat and collecting a CBDA-rich rosin wherein a CBDA concentration of the CBDA-rich rosin is greater than about 40% by weight.

21. The method of claim 20 further comprising dissolving the hash extraction product in a cold ethanol-based solvent and collecting a further purified hash extract or further purified hash extraction product wherein a CBDA concentration of the further purified hash extract is greater than about 40% by weight.

22. The method of any preceding claim further comprising preparing the GM by: a. ensuring that the GM is less than six months old; contains less than 0.3% tetrahydrocannabinol, tetrahydrocannabinolic acid, or both; has an awbelow 0.7; or combinations thereof; andb. reducing the GM to a particle size of about 0.25 inches by chopping, grinding, or both.

23. An adaptable processing method to produce a CBDA-rich extract, the produced CBDA-rich extract having a target concentration of CBDA selected from various possible target concentrations of CBDA, the method comprising: a. preparing Cannabis sativa green material (GM) to have a particle size of about 0.25 inches; b. collecting an extraction product using one of a drum extraction process, a supercritical CO2 extraction process, or a chilled / iced water extraction process wherein the temperature of each of the drum extraction process, supercritical CO2 extraction process, and chilled / iced water extraction process does not exceed 80°C; c. collecting a purified extract or a purified extraction product wherein purifying is selected from one or more of filtering, removing a solvent, pressing, winterizing, and combinations thereof wherein each of filtering, pressing, winterizing, and removing a solvent takes place at a temperature that does not exceed 80°C; and d. removing THC, THCA, or both from the purified extraction product, the removal of THC, THCA, or both taking place at a temperature that does not exceed 80°C.

24. The method of claim 23 wherein collecting a purified extract, a purified extraction product, or both comprises filtering a drum extraction product, a hash extraction product, or a supercritical CO2 extraction product.

25. The method of claim 23 or 24 wherein collecting a purified extract comprises removing ethanol, an ethanol-based solvent, or both from a drum extraction product, a hash extraction product, or a supercritical CO2 extraction product.

26. The method of any one of claims 23 to 25 wherein collecting a purified extract comprises removing ethanol, completely denatured ethanol, or acetone from a supercritical CO2 extraction product.

27. The method of any one of claims 23 to 26 wherein collecting a purified extract comprises dissolving the purified extraction product in an ethanol-based solvent andincubating the dissolved purified extraction product at a temperature of about 80°C for at least 24 hours.

28. The method of any one of claims 23 to 27 wherein removing THC, THCA, or both comprises crystallizing the purified extraction product to produce a CBDA isolate extract.

29. The method of any one of claims 23 to 27 wherein removing THC, THCA, or both comprises crystallizing the purified extraction product, mixing the purified extraction product with hexane, and subjecting the mixed purified extraction product to a freeze-thaw cycle of chilling to less than 0°C for at least 12 hours followed by incubating at between about 20°C to about 25°C for at least 12 hours.

30. The method of claim 29 further comprising repeating the freeze-thaw cycle at least one additional time wherein freezing takes place at a temperature of less than about -10°C.

31. The method of claim 30 further comprising repeating the freeze-thaw cycle at least three additional time and if crystals are not observed after the third time, adding seed crystals to the mixed winterized extraction product and repeating the freeze-thaw cycle at least one additional time.

32. The method of claim 31 further comprising separating hexane from crystallized CBDA.

33. The method of claim 32 further comprising removing residual solvent from crystallized CBDA using a vacuum oven set at less than 80°C and a pressure of less than 40 torr.

34. The method of any one of claims 23 to 27 wherein removing THC, THCA, or both comprises refining the purified extraction product using centrifugal partition chromatography (CPC) by mixing the purified extraction product with a hexane- based solvent that has been prepared by separating a mixture of hexane:methanol:water (5:4: 1) into two phases; loading a mixed purified extraction product onto a CPC apparatus; separating the mixed purified extraction product into waste fractions, reclaim fractions, and THC-free fractions; removing solvent and water from THC-free fractions; and collecting a broad spectrum CBDA extract.

35. The method of claim 34 further comprising reprocessing the reclaim fractions to remove solvent, rerunning the reprocessed reclaim fractions on the CPC apparatus, collecting waste and THC-free fractions, removing solvent and water from the THC-free fractions, and collecting a broad spectrum CBDA extract.

36. A product compri sing : a. a CBDA-rich extract obtained from a production process that is tunable to produce a plurality of grades of CBDA-rich extract comprising:

1. extracting CBDA from Cannabis sativa green material (GM) by mixing the GM with a solvent or chilled / iced water at about 80°C or less and collecting an extraction product; and2. purifying the extraction product at about 80°C or less by filtering the extraction product, pressing the extraction product, removing the solvent from the extraction product, winterizing the extraction product, or combinations thereof and collecting a CBDA-rich extract or a purified extraction product; and3. wherein the extracting and / or purifying steps are adjustable to collect a particular grade of CBDA-rich extract; b. a fat or an oil; and c. wherein said product comprises between about 1% and 99% by weight of CBDA-rich extract.

37. The product of claim 36 further comprising refining the purified extraction product at about 80°C or less by separating tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THC A), or both from the purified extraction product.

38. A method for producing a CBDA-rich extract comprising: a. extracting CBDA from Cannabis sativa green material (GM) by cycling an ethanol-based solvent that has been precooled to at or below about 0°C through GM disposed in a drum for a predetermined time; b. when the predetermined time has expired, filtering a post-extraction solvent before collecting, after collecting, or both; and c. evaporating a filtered post-extraction solvent to obtain a crude CBDA-rich extract.

39. The method of claim 38 wherein cycling the ethanol-based solvent through GM disposed in a drum further comprises filtering the ethanol-based solvent through a synthetic filter disposed in the drum to create a false bottom.

40. The method of claim 38 or 39 wherein the GM disposed in the drum has been processed to obtain a particle size of about 0.25 inches.

41. The method of any one of claims 38 to 40 wherein the ethanol -based solvent has been cooled to: a. between about 0°C and -20°C; or b. between about -20°C and -80°C; or c. about -80°C.

42. The method of any one of claims 38 to 41 wherein the ethanol -based solvent is: a. denatured ethanol; and / or b. a mixture of 5% heptane and 95% ethanol at 200 proof; and / or c. 100% ethanol at 200 proof.

43. The method of any preceding claim further comprising winterizing the crude extract.

44. The method of any preceding claim further comprising removing THC, THCA, or both.

45. The method of claim 44 wherein removing THC, THCA, or both comprises crystalizing CBDA.

46. The method of claim 44 wherein removing THC, THCA, or both comprises running a purified extract through a CPC machine.

47. A method for producing a CBDA-rich extract comprising: a. extracting CBDA from Cannabis sativa green material (GM) by cycling an edible oil through GM disposed in a drum for a predetermined time at a temperature that is less than 80°C and warm enough for the edible oil to be liquid; b. when the predetermined time has expired, filtering a post-extraction oil before collecting, after collecting, or both; and c. collecting a CBDA-rich extract.

48. The method of claim 47 wherein cycling the edible oil through GM disposed in a drum further comprises filtering the edible oil through a synthetic filter disposed in the drum to create a false bottom.

49. The method of claim 47 or 48 wherein the GM disposed in the drum has been processed to obtain a particle size of about 0.25 inches.

50. The method of any one of claims 47 to 48 wherein the edible oil is: a. hemp seed oil; and / or b. cold pressed hemp seed oil; and / or c. medium-chain triglyceride (MCT) oil; and / or d. coconut oil; and / or e. sunflower seed oil; and / or f. olive oil.

51. The method of any one of claims 47 to 48 further comprising determining if a CBDA potency is at a target level.

52. The method of any one of claims 47 to 51 further comprising increasing the potency of the CBDA-rich extract by cycling the CBDA-rich extract for a predetermined time or until the target potency is reached, the CBDA-rich extract cycled through: a. the same GM disposed in the drum; and / or b. fresh GM disposed in the drum.

53. The method of any one of claims 47 to 52 further comprising decreasing the potency of the CBDA-rich extract by adding an additional amount of the same or different edible oil to obtain the target potency.

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