Processes for solvent extraction of cannabinoids, terpenes and flavonoids from biomass

Abstract

In alternative embodiments, provided are industrial processes and methods for extracting or removing cannabinoids, flavonoids and terpenes from plant materials such as trichomes. In alternative embodiments, the cannabinoids, flavonoids and terpenes are extracted or removed from the plant materials using a non-polar, organic solvent, or a mixture of non-polar, organic solvent and polar, organic solvent.

Claims

1. A method of isolating tetrahydrocannabinol, a terpene, or cannabidiol from hemp or Cannabis, the method consisting essentially of: a) extracting hemp or Cannabis with a solvent selected from the group consisting of propanol, isopropanol, butanol, pentanol, hexanol, heptanol, and octanol to produce an extract consisting essentially of an extracted hemp or Cannabis consisting essentially of tetrahydrocannabinol, a terpene, or cannabidiol; b) distilling the extract to isolate the tetrahydrocannabinol, the terpene or the CBD, and c) winterizing the distilled, isolated tetrahydrocannabinol, terpene or cannabidiol to produce a winterized, isolated tetrahydrocannabinol, terpene or cannabidiol.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 illustrates an exemplary process as provided herein to extract and separate products Cannabis species.

(2) Like reference symbols in the various drawings indicate like elements.

DESCRIPTION OF THE INVENTION

(3) In alternative embodiments, provided are industrial processes and methods for extracting or removing cannabinoids and terpenes from plant trichomes. In alternative embodiments, the cannabinoids and terpenes are extracted or removed from the plant trichomes using a non-polar or an organic solvent.

(4) A key aspect of the industrial processes and methods as provided herein is understanding the nature and location of the target cannabinoids and terpenes when extracting from a plant trichome, e.g., from a hemp or a Cannabis. The cannabinoids, and many terpenes, are primarily located in the trichomes, which exist on the surface of the plant, primarily on the flower. The actual definition of trichome is fine outgrowths or appendages on plants, algae, lichens, and certain protists. Originating from the Greek word Trichoma, meaning growth of hair, these tiny microscopic mushroom-looking protuberances are the very factories that produce the hundreds of known cannabinoids, terpenes, and flavonoids.

(5) Cannabinoid synthesis within the trichome begins as Cannabis plants move into their bloom phase. As they begin to produce flowers, trichomes form along the outer surface of the above-ground plant vegetation and begin to transport vacuoles and plastids from their stalk into the gland head. At this point, cells within the gland head will begin to metabolize and form precursors for what will eventually become cannabinoids. The rate and concentration at which a Cannabis plant produces trichomes will be contingent on both genetics well as some environmental factors. Though plants containing higher concentrations of trichomes don't always produce the highest concentration of cannabinoids and/or terpenes, variables such as UV light greatly affect cannabinoid and terpene synthesis within the trichome head.

(6) Whether alive on a vine or harvested, trichomes are incredibly volatile and risk destruction and/or degradation at the hands of many catalysts, including but not limited to: physical contact or agitation, heat, light, oxygen and time. Not only do the trichomes themselves risk damage when exposed to these elements, but the essential oils within them risk degradation. There are ways to dramatically slow degradation of trichomes by carefully handling Cannabis flowers both during propagation and post harvest. By limiting physical contact and agitation to the flowers themselves, trichomes may be preserved on the plant for longer periods of time. Those looking to extend the shelf life of trichomes beyond that of the plants they came from often resort to extraction techniques. An extraction in this context may be defined as the process of either mechanically or chemically removing trichomes from the plant itself.

(7) With the location of the cannabinoids and terpenes determined we now need to understand the nature of the cannabinoids and terpenes present in the trichomes. Cannabinoids and cannabinoid acid species can be broadly understood as being non-polar. Terpenes and flavonoids present in the trichome as well can be broadly understood as non-polar. An aspect of the current industrial practice of hand separating the flowers from the stems causes physical damage to the trichomes and likely trichome losses. In addition, the drying process causes additional losses of volatile terpenes to the atmosphere. Therefore, methods as provided herein for extracting cannabinoids, terpenes and flavonoids from a whole wet plant will minimize the physical handling losses, and eliminating the drying process will help preserve valuable terpenes and eliminate the energy required for drying of the plant material.

(8) In alternative embodiments, an organic non-polar solvent is used to wash and dissolve cannabinoids and terpenes from e.g., a whole wet plant, trichome or trichome fraction, or the pubescent plant, algae or lichen. The use of an organic non-polar solvent to wash and dissolve the cannabinoids and terpenes present in the trichomes can be a straightforward protocol when water is present. The organic non-polar solvent saturated with cannabinoids and terpenes will phase separate from any water that may or may not be present in the extract solution after contacting.

(9) In alternative embodiments, a polar organic solvent, e.g., a polar organic solvent immiscible in water is used to wash and dissolve cannabinoids and terpenes from e.g., a whole wet plant, trichome or trichome fraction, or the pubescent plant, algae or lichen. In some embodiments, use of polar, organic solvents that is immiscible in water such as pentanol, hexanol or octanol also can be a straightforward protocol when water is presentthe polar, organic solvents immiscible in water (e.g., pentanol, hexanol or octanol) phase separates from water.

(10) In alternative embodiments, provided herein are batch, semi-continuous batch or continuous processes which offer significant improvements and advantages over current techniques used. In alternative embodiments, whole plants are mechanically harvested using e.g., a combine and sickle bar or a similar whole plant cutting device, and then taken for extraction, thereby eliminating the manual labor associated with hand harvesting and the energy needed for drying.

(11) In alternative embodiments, non-polar solvent used in processes and methods as provided herein comprise: aliphatic hydrocarbons, pentane, cyclopentane, hexane, cyclohexane, heptane, cyclohentane, a pentene, a cylcopentene, a hexene, a cylohexene, acetone, a benzene or a substituted benzene, toluene, a xylene (e.g., o-xylenes, m-xylene, p-xylene), methyl acetate, ethyl acetate, propyl acetate, butyl acetate, tetrahydrofuran, tetrahydropyran, diethyl ether, dipropyl ether, dibutyl ether, 1,4-dioxane, chloroform, dichloromethane, dichloroethane, freon, a terpene, a hemiterpene, a monoterpene, a diterpene, limonene, humulene, pinene, myrcene, or caryophylene or any combination or mixture thereof.

(12) In alternative embodiments, the trichome or trichome fraction, or the pubescent plant, algae or lichen, biomass used in extraction can comprise wet material, dried material, stock stems and leaves can be removed or present. Wet material can be present in combination with dried material at any ratio. The biomass can be sized reduced or a whole plant.

(13) In alternative embodiments, the trichome or trichome fraction, or the pubescent plant, algae or lichen, biomass (e.g., the hemp or Cannabis biomass) is processed with the at least one solvent, e.g., non-polar, organic solvent; polar, organic solvent, or mixture thereof. Techniques for processing comprise immersion, spraying, washing, intermittent immersion, continuous counter current or co-current liquid solid contacting. Solvent biomass contacting can range for a period of 1 minute to 48 hours.

(14) In one embodiment, hemp or Cannabis is used as the material to process. There are different ways to prepare the hemp or Cannabis for extraction. Typically flower of the female plant contain the highest quantities of cannabinoids. The preparation can comprise whole intact wet plant, whole intact dry plant material, chopped whole wet plant, chopped whole dry plant, wet flower and leaf, dry flower and leaf, or any combination thereof.

(15) In alternative embodiments, the plant material comprises flowering plants in the family Cannabaceae. Cannabis sativa, Cannabis indica, Cannabis ruderalis, hemp or any combination thereof.

(16) In alternative embodiments, the plant material is fed into a vessel using a surge bin, a metered hopper, or an auger or other device. If the device is to be used in a continuous fashion, the feed system will be configured to provide a constant volume of the prepared feedstock. In that regard, the feed method will require a reservoir of some type or in itself be a continuously fed device.

(17) In alternative embodiments, the plant material, e.g., the pubescent plant, algae or lichen, is contacted with the at least one solvent, e.g., non-polar, organic solvent; polar, organic solvent, or mixture thereof. In alternative embodiments, the methods comprise immersion, spraying, washing, counter current liquid solid contacting or any combination thereof.

(18) In alternative embodiments, the non-polar, organic solvent comprises at least one of: aliphatic hydrocarbons, pentane, cyclopentane, hexane, cyclohexane, heptane, acetone, benzene, toluene, xylenes, ethyl acetate, propyl acetate, butyl acetate, tetrahydrofuran, tetrahydropyran, diethyl ether, dipropyl ether, dibutyl ether, 1,4-dioxane, chloroform, dichloromethane, a terpene, a terpenoid, a hemiterpene, a monoterpene, a diterpene, limonene, humulene, pinene, myrcene, caryophylene, or any combination thereof.

(19) In alternative embodiments, the cannabinoids and terpenes are dissolved from the surface of the plant material by the one or more solvents (e.g., at least one non-polar, organic solvent; polar, organic solvent; or, mixture thereof) contacting the surface of the plant material. The extracted biomass is then processed for residual solvent, e.g., residual solvent is removed or substantially removed. Techniques known to those skilled in the art (e.g., for the contacting of the solvent with the plant material) comprise using a screw press (optionally a dewatering screw press) or a sludge press, spray drying, air stripping, gas stripping, vacuum stripping, heating, evaporation, washing or any combination thereof.

(20) In alternative embodiments, the cannabinoid, flavonoid and/or terpene rich solvent solution is then processed to separate the solvent from the cannabinoids and/or terpenes, or, in the case of winterization or crystallization, to separate the cannabinoids and/or terpenes from the solvent. Techniques that can be used for this separation can include any known to those skilled in the art, including batch distillation, continuous distillation, vacuum distillation, gas stripping, mole sieve filtration, nano filtration, filtration, winterization or crystallization, or any combination thereof. In alternative embodiments, the processed or recovered solvent or solvent mixture is then recycled, stored for future use and/or disposed.

(21) In alternative embodiments, a whole wet trichome or trichome fraction, or the pubescent plant, algae or lichen (collectively and individually referred to a biomass), e.g., hemp is fed through a conveyor into an extraction unit. The biomass, e.g., hemp, can be continuously sprayed with: the at least one non-polar, organic solvent, e.g., a terpene or terpene mixture or any combination thereof; or, a mixture of at least one polar, organic solvent and at least one non-polar and organic solvent; or, at least one polar, organic solvent, e.g., an organic alcohol.

(22) In alternative embodiments, the biomass, e.g., hemp, is contacted with the solvent for a period of time from 1 minute to 60 minutes, 1 minute to 120 minutes, 1 minute to 480 minutes. In alternative embodiments, the solvent drains through the biomass and is collected. In alternative embodiments, the collected solvent or solvent mixture is reintroduced, e.g., as the biomass continuously travels on a conveyor through a solvent contacting system. In alternative embodiments, the biomass, e.g., hemp, is contacted with the solvent or solvent mixture at the temperature ranging from between about 10 C. to the boiling point of the solvent used, or from between about 10 to 100 C. for a period of time from between 1 second to 480 minutes, or between about 1 minute (min) and 1 hour (hr), or between about 5 min and 2 hours, with or without agitation during all or part of the process.

(23) In alternative embodiments, the biomass is introduced to a mixing tank, with or without heating. In alternative embodiments, the biomass is introduced into the mixing tank at a temperature of between about 10 to 100 C., or between about 5 to 80 C., or the temperature of the biomass is in the mixing tank raised to or lowered to, or kept at, at a temperature of between about 10 to 100 C., or between about 5 to 80 C.

(24) In alternative embodiments, the solvent or solvent mixture is introduced to the tank in sufficient quantity as to provide for complete or near complete immersion of the biomass. In alternative embodiments, the biomass and solvent or solvent mixture are then subjected to mixing; however, mixing is not necessary but can improve extract yield. In alternative embodiments, the biomass is then removed or filtered from the solvent or solvent mixture.

(25) In alternative embodiments, the solvent or solvent mixture is then removed by evaporation and optionally the cannabinoids and/or terpenes are recovered. In alternative embodiments, the solvent or solvent mixture is then removed by a rotary evaporator or other evaporating equipment, optionally at the temperature below the boiling point of the solvent or solvent mixture under a pressure ranging from between about the atmosphere pressure down to about 0.001 torr.

(26) Winterization or Crystallization

(27) In alternative embodiments, the cannabinoids and/or terpenes are recovered from (or substantially recovered from), or isolated from the solvent or solvent mixture by a winterization or crystallization process.

(28) In alternative embodiments, before winterization or crystallization (or solidification) the initial cannabinoids and/or terpenes solvent mixture is (further) diluted with an organic solvent, e.g., a hexane or a terpene. In alternative embodiments, before winterization or crystallization the solvent mixture is diluted by between about 1% to 80%, or by between about 5% to 50%.

(29) In alternative embodiments, before winterization or crystallization (or solidification) the initial cannabinoids and/or terpenes solvent mixture is concentrated, e.g., a portion of the non-polar, organic solvent or polar, organic solvent is removed before the winterization or crystallization (or solidification), or cooling, process.

(30) In alternative embodiments, between about 1% to 90% of the non-polar, organic solvent or polar, organic solvent is removed before the winterization or crystallization (or solidification), or cooling, process.

(31) In alternative embodiments, the winterization or crystallization (or solidification), or cooling, process comprises cooling the mixture until crystals of cannabinoids, flavonoids and terpenes are formed, or until the cannabinoids, flavonoids and/or terpenes solidify. In alternative embodiments, the cooling process comprise further cooling after the crystallization (or solidification) begins. In alternative embodiments, the winterization or crystallization (or solidification), or cooling, process comprises cooling the mixture to a temperature of between about 10 C. to about 90 C., between about 20 C. to about 85 C., or between about 50 C. to about 80 C. In alternative embodiments, the winterization or crystallization (or solidification), or cooling, process comprises cooling for between about 10 to 30 minutes (min) to about 1, 2, 3, 4, 5 or 6 hours (hrs). In alternative embodiments, the winterization or crystallization (or solidification), or cooling, process lasts for between about 1 to 24 hrs. In alternative embodiments, the process comprises multiple cooling, crystal harvesting or isolation, and re-cooling cycles.

(32) In alternative embodiments, the winterization or crystallization (or solidification), or cooling, process comprises a process as described in U.S. Pat App Pub no US2017/0008870A1; U.S. Pat. No. 3,755,389; or U.S. Pat. No. 2,705,723.

(33) In alternative embodiments, the winterization or crystallization (or solidification), or cooling, process is done in a refrigerator, a freezer or using dry ice (or any system that lowers the temperature to about 109.3 degrees Fahrenheit (78.5 degrees C.)) or liquid nitrogen. The winterization or crystallization (or solidification), or cooling, process can be done under vacuum or pressure.

(34) In alternative embodiments, the solids or crystals of the cannabinoids, flavonoids and/or terpenes are separated from the liquid solvent by filtration. In alternative embodiments, the solids or crystals of the cannabinoids, flavonoids and/or terpenes are decanted away from the liquid solvent. In alternative embodiments, the solids or crystals of the cannabinoids, flavonoids and/or terpenes are sheet or ball crystals. In alternative embodiments, the solids or crystals of the cannabinoids, flavonoids and/or terpenes need to be scraped or physically removed from the container or reaction vessel from which they were cooled and subsequently crystallized or solidified.

(35) In alternative embodiments, the cannabinoid, flavonoid and/or terpene solids or crystals are at least 70% pure, or are between about 75% to 99.9% or 100% pure (e.g., free of impurities, or non-cannabinoid, flavonoid and/or terpene substances or solvent), or are about (or at least about) 75%, 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, 99.9% or 100% pure.

(36) It is understood that those skilled in the art might find alternative embodiments to the methods described herein, which are meant to describe the principles involved in the extraction conditions, which include the collection of the extractants and solvent, the collection of the extractants or solutes (the compounds of interest being isolated), and/or the removal of the spent material, the subsequent separation of the extractant from the solvent, and the optional step or steps of isolating one or more of the products of the extraction, where these alternative embodiments fall within the scope of this methods as provided herein.

(37) The invention will be further described with reference to the examples described herein; however, it is to be understood that the invention is not limited to such examples.

EXAMPLES

Example 1: Exemplary Methods

(38) 10 pounds of mature whole hemp plant was harvested. Between about 3 gram (g) to about 100 g samples of plant flower, leaf and stem was weighed for the experiments. The material was not dried or subjected to particle size reduction. Three (3) samples of whole wet plant material was then prepared for extraction. Sample 257-A (control sample) was immersed in 1,500 ml of 65:35 mixture of chloroform:methanol overnight; sample 257-B was subjected to 560 second immersions in ambient hexane; sample 257-C was immersed in hexane for 15 minutes at ambient temperature; sample 257-D was immersed in hexane for 15 minutes at 40 C; sample 257-E was immersed in hexane for 10 minutes at 60 C.

(39) 100 g of the weighed sample was immersed in dichloromethane (DCM) in a vessel at ambient temperature, and then the sample was taken out. This immersion was repeated 5 times. Another three 100 g samples were soaked in hexane in three different vessels with agitation under the conditions: at ambient temperature for 15 min; at 40 C. for 15 min; 60 C. for 15 min. A control sample was subjected to a 1,500 ml 65:35 mixture chloroform:methanol solution and let soak for 24 hours with agitation to represent 100% extraction of cannabinoids and used as a reference of total extractable cannabinoids.

(40) TABLE-US-00001 Weight of Percentage CBD CBD weight Percentage Extraction Method dried of CBD in weight extracted from of CBD in (100 g wet hemp in extract dried oil in dried 100 g wet 100 g wet Exp No. 1500 mL solvent) (g) (%) oil (g) hemp (g) hemp 257-A immersion in 5.3119 34.7 1.84 1.84 1.84 chloroform/methanol at ambient temperature overnight 257-B 5 60 sec immersion 2.2821 62.6 1.43 1.43 1.43 in dichloromethane 257-C immersion in 2.7476 64.7 1.78 1.78 1.78 ambient temperature hexane for 15 min 257-D immersion in 40 C. hexane 3.3073 66.2 2.19 2.19 2.19 for 15 min 257-E immersion in 60 C. hexane 2.2014 65.0 1.43 1.43 1.43 for 10 min

(41) A number of embodiments of the invention have been described. Nevertheless, it can be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.