FIELD

[0001] This invention relates to the preparation of extracts from cannabis plants. In particular, the invention relates to methods of preparing cannabis compositions and tinctures.

BACKGROUND

[0002] The cannabis plant, including the flowers of Cannabis sativa, indica and rudralis, contain more than 500 different chemical compounds. These compounds include cannabinoids, amino acids, proteins, glycoproteins, enzymes, terpenes, flavonoids, non-cannabinoid phenols, nitrogenous compounds, sterols, sugars, fatty acids, hydrocarbons, simple alcohols, simple aldehydes, simple ketones, simple acids, simple esters and lactones, steroids, vitamins, pigments and other elements. Some of these compounds are biologically active while others are benign, for example, several of the cannabinoids are biologically active. Such biologically active cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), tetrahydrocannabivarin (THCV), cannabicyclol (CBL), cannabivarin (CBV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT) and acids thereof. The relative amounts of these compounds in cannabis vary for different chemovar. For example, some chemovar are high in THC while others contain high amounts of CBD or both THC and CBD. Therefore, extracts from these different chemovar may show different biological activities.

[0003] The roots of cannabis plants also contain several biologically important compounds. These compounds are mainly monoterpenes, triterpenoids, alkaloids, sterols, A/-(p-hydroxy-p-phenylethyl)-p-hydroxy-frans-cinnamamide and choline. Cannabis root is not a significant source of THC, CBD or other known phytocannabinoids.

[0004] Due to the hydrophobic nature of the compounds from cannabis plants, they are mostly excreted from the body without being absorbed when consumed orally. For extracts prepared as tablets, troches, pastes with food or infused to foods, most of the active ingredients disintegrate in the digestive system and only a minimal percentage of the biologically active compounds absorb to the body through buccal, sublingual or gastrointestinal routes. For extracts prepared as drinks, some cannabinoids are highly sensitive to the presence and/or pH of water and undergo rearrangements to produce different compounds which change the taste, quality and activity of the drink. In addition, separation of a hydrophobic organic fraction in solution occurs during long-term storage. For example, extracts infused into glycerine or honey, the cannabinoids are insoluble or only partially soluble in these carriers and thus, the cannabinoids tend to separate out and lose their homogeneity during storage.

[0005] Furthermore, cannabinoid extracts often have an unpleasant and/or bitter taste due to the presence of substantial amounts of various secondary metabolites which makes oral consumption challenging.

SUMMARY

[0006] In one aspect, the present invention provides a method of preparing cannabis tinctures.

[0007] In various aspects, the present disclosure provides a method of extraction, the method comprising extracting volatile compounds from biomass to produce an extract of volatile compounds and residual biomass, wherein the biomass comprises cannabis flowers; extracting the residual biomass with an organic solvent at a temperature between about -25°C and about -80°C for about 5 minutes or less to produce a concentrated oil comprising non-volatile compounds; and combining the extract of volatile compounds and the concentrated oil to form a combined extract. The method may also comprise extracting compounds from cannabis roots to produce a cannabis root extract and combining the combined extract with the cannabis root extract to form a three-component combined extract. In various embodiments, the extract of volatile compounds comprises cannabis terpenes. Also disclosed is an extract of cannabis prepared according to such methods. [0008] In another aspect, the present disclosure provides a method of preparing a composition, the method comprising extracting volatile compounds from biomass to produce an extract of volatile compounds and residual biomass, wherein the biomass comprises cannabis flowers; extracting the residual biomass with an organic solvent at a temperature between about -25°C and about -80°C for about 5 minutes or less to produce a liquid phase comprising non-volatile compounds; concentrating the liquid phase by removing the organic solvent to produce a concentrated oil; combining the extract of volatile compounds and the concentrated oil to form a combined extract; and diluting the combined extract with a diluent, wherein the volatile and non-volatile compounds dissolve in the diluent to form the composition. The method may also comprise extracting compounds from cannabis roots to produce a cannabis root extract and combining the combined extract with the cannabis root extract to form a three-component combined extract. In various embodiments, the extract of volatile compounds comprises cannabis terpenes. Also disclosed is a tincture for oral consumption prepared according to such methods.

[0009] In a further aspect, the present disclosure provides a method of extraction, the method comprising extracting biomass with an organic solvent at a temperature between about -25°C and about -80°C for about 10 minutes or less to produce a concentrated oil comprising non-volatile compounds, wherein the biomass comprises cannabis flowers; decarboxylating the cannabinoids in the concentrated oil; and combining the concentrated oil and terpenes to form a combined extract. The method may also comprise extracting compounds from cannabis roots to produce a cannabis root extract and combining the combined extract with the cannabis root extract to form a three-component combined extract. The terpenes may be from one or more of cannabis oil, grapefruit oil, lemongrass oil, lemon oil, lime oil, mint oil, orange oil, peach oil, passionfruit oil, raspberry oil, clove oil, cinnamon oil or cardamom oil. Also disclosed is an extract of cannabis prepared according to such a method.

[0010] In a further aspect, the present disclosure provides a method of preparing a tincture, the method comprising extracting biomass with an organic solvent at a temperature between about -25°C and about -80°C for about 10 minutes or less and removing the solvent to produce a concentrated oil comprising cannabinoids, wherein the biomass comprises cannabis flowers; and combining the concentrated oil with terpenes to form the tincture. The method may further comprise extracting compounds from cannabis roots to produce a cannabis root extract and combining the tincture with the cannabis root extract. The method may further comprise decarboxylating the cannabinoids in the concentrated oil prior to the combining step. The terpenes for use in the methods may be cannabis terpenes or citrus terpenes. Also disclosed is a tincture for oral consumption prepared according to such methods.

[0011] Other aspects and features of the present invention will become apparent to those of ordinary skill in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying claims.

DETAILED DESCRIPTION

[0012] In the context of the present application, various terms are used in accordance with what is understood to be the ordinary meaning of those terms.

[0013] In various embodiments, the disclosure provides methods of extracting compounds from plant material and preparing them for oral consumption or administration. In other embodiments, the disclosure provides methods of preparing cannabis extracts comprising water-insoluble and/or lipophilic compounds for oral consumption as a tincture. The term“lipophilic compounds” refers to compounds that are soluble in lipids and some organic solvents while being substantially insoluble or only sparsely soluble in water. Most lipophilic compounds have low bioavailability following oral consumption and are excreted from the body.

[0014] In accordance with one aspect of the invention, a method of extraction is provided. In various embodiments, the methods disclosed herein allow for the extraction of all compounds from plant material, whether biologically active or not, while minimizing extraction of chlorophyll and other pigments.

[0015] The methods comprise extracting volatile compounds from biomass to produce an extract of volatile compounds and residual biomass. The biomass may be cannabis flowers. The term“volatile compounds” refers to compounds that have a high vapour pressure at the conditions used for extracting the biomass. The high vapour pressure of volatile compounds results from a low boiling point, which causes the compounds to evaporate or sublimate from the liquid or solid form of the compound. For example, the volatile compounds may have a boiling point between about 80°C and about 300°C.

[0016] The volatile compounds from cannabis flowers comprise terpenes. The term “terpene” refers to any organic compound found in the essential oils of plants that is based on isoprene (2-methyl-1 ,3-butadiene), where each terpene comprises at least two isoprene units. The terpenes in the volatile compounds from cannabis flowers comprise hydrocarbons, simple alcohols, simple aldehydes, simple ketones, simple acids, simple esters and lactone-type structures. The terpenes can include one or more of a-bisabolol, a-phelandrene, a-pinene, a-terpineol, borneol, b-caryophyllene, b-pinene, cadinene, camphene, camphor, citral, citronellol, D-3-carene, 1 ,8-cineole, eucalyptol, eugenol, y- terpene, geraniol, humulene, limonene, linalool, myrcene, nerol, nerolidiol, ocimene, p- cymene, phytol, pulegone, terpineol-4-ol, terpineol, terpinolene or valencene. In various embodiments, the terpenes may increase the homogeneity and stability of the extracts, compositions and/or tinctures for oral consumption. The terpenes may possess anti microbial and anti-fungal activity and may act as a preservative for long-term storage of the extracts, compositions and/or tinctures for oral consumption.

[0017] In various embodiments, the step of extracting volatile compounds is conducted at a temperature sufficient to decarboxylate the compounds in the biomass to their biologically active forms. Decarboxylation may be necessary in order to obtain the biologically active forms of the compounds. If the extraction process of volatile compounds is steam distillation, the compounds in the biomass may be decarboxylated without the use of thermally induced decarboxylation after a solvent extraction step.

[0018] The residual biomass is then extracted with an organic solvent to produce a liquid phase comprising non-volatile compounds. The term “non-volatile compounds” refers to compounds that do not readily evaporate under the conditions used for extracting the biomass. Examples of non-volatile compounds include the cannabinoids, nitrogenous compounds, amino acids, proteins, glycoproteins, enzymes, sugars and related compounds, hydrocarbons, fatty acids, steroids, noncannabinoid phenols, flavonoids, vitamins, and pigments. The solvent extraction of the residual biomass may be performed at low temperature, for example, between about -25°C and about -80°C, and may be conducted within a short period of time, such as, for example, less than about 10 minutes, less than about 9 minutes, less than about 8 minutes, less than about 7 minutes, less than about 6 minutes, less than about 5 minutes, less than about 4 minutes, less than about 3 minutes, less than about 2 minutes, less than about 1 minute, less than about 30 seconds or any amount of time therebetween. In various embodiments, the temperature for solvent extraction is about -25°C. In various embodiments, conducting the solvent extraction at low temperature and for a short period of time may avoid extraction of chlorophyll and/or other undesirable pigments into the liquid phase.

[0019] The organic solvent may be a polar organic solvent, a medium polar organic solvent or a non-polar organic solvent. For example, the solvent may be ethanol, methanol, propanol, isopropyl alcohol, butanol, tetrahydrofuran, ethyl acetate, acetone, chloroform, diethyl ether, dichloromethane, acetonitrile, dimethylformamide, acetic acid, toluene, 1 ,4-dioxane, dimethyl sulfoxide, pentane, hexane or cyclohexane. Preferably, the solvent is a polar organic solvent such as, for example, ethanol, methanol, ethyl acetate, acetone, chloroform, diethyl ether or combinations thereof.

[0020] Following extraction, the liquid phase may be concentrated by removing the organic solvent to form a concentrated oil. The concentrated oil (or the concentrated liquid phase) may be standardized and used in a subsequent dilution step.

[0021] If the extraction step to isolate the volatile compounds is not performed before the solvent extraction step, then the volatile compounds are lost during removal of the organic solvent. Thus, in order to obtain a combined extract consisting of both volatile and non-volatile compounds, the volatile compounds must be isolated prior to solvent extraction. If the biomass is subject to solvent extraction without the prior extraction of the volatile compounds, the obtained concentrated oil comprising non-volatile compounds requires decarboxylation in order for some cannabinoids to be in their biologically active form, as described above. Without decarboxylation, the concentrated oil comprises cannabinoid acids. [0022] In various embodiments, the residual biomass is dried prior to solvent extraction. For example, steam distilled residual biomass may be dried before solvent extraction. If the residual biomass has a high moisture content, the final extract may compromise water which may affect the homogeneity of the extract and the consistency of the final product.

[0023] In various embodiments, a new batch of biomass containing volatile compounds may be used for extraction with the organic solvent. This step may protect the cannabinoid acids (for example, THCA, CBDA, THCVA, CBNA, CBLA and CBGA) from thermal conversion caused during the extraction of volatile compounds from the biomass. Most volatile compounds in the biomass are evacuated from the extract during the solvent evaporation. In various embodiments, the biomass is from the same strain of cannabis plant used for steam distillation to extract the volatile compounds.

[0024] In various embodiments, the extract of volatile compounds, including cannabis terpenes, and the concentrated oil are combined to form a combined extract. The amount or ratio of each of the extract of volatile compounds and the concentrated oil may be adjusted to achieve a suitable ratio of terpenes in the combined extract similar to that which is present in the cannabis flowers.

[0025] In other embodiments, the concentrated oil is combined with terpenes from sources other than cannabis to form the combined extract. These terpenes may be extracted from other biomass or synthetically produced. In various embodiments, the terpenes are citrus terpenes. Terpenes from other biomass can be from one or more of grapefruit oil, lemongrass oil, lemon oil, lime oil, mint oil, orange oil, peach oil, passionfruit oil, raspberry oil, clove oil, cinnamon oil and cardamom oil. Suitable synthetic terpenes for use in the extracts and compositions for oral administration of the present disclosure would be known by a person of ordinary skill in the art.

[0026] In various embodiments, extracts from roots of cannabis plants may be used in the extracts and compositions disclosed herein. Compounds from the roots of cannabis plants, including, for example, monoterpenes, triterpenoids, alkaloids, sterols, N-(p- hydroxy-p-phenylethyl)-p-hydroxy-frans-cinnamamide and choline, are heavy molecules and present in the inner tissues of the roots. Therefore, they can be extracted with a hot solvent, such as grain alcohol, using a Soxhlet extraction technique or another reasonably high temperature extraction technique using a suitable solvent. In various embodiments, the root biomass is from the same cannabis strain as the flowers used in the extraction described above. In various embodiments, the root biomass is thoroughly cleaned and dried to a minimal moisture content before use.

[0027] In various embodiments, the extract of volatile compounds, the concentrated oil or the combined extract may be mixed with the cannabis root extract to form a three- component combined extract. In various embodiments, the composition of the three- component combined extract may be adjusted to obtain a desirable amount of terpenes in the three-component combined extract.

[0028] In various embodiments, the combined extract or the three-component combined extract may comprise less than about 15%, less than about 12%, less than about 10%, less than about 7%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, less than about 1 %, less than about 0.5%, less than about 0.25% by weight to total weight of the extract, or any percentage therebetween, of terpenes.

[0029] In various embodiments, the disclosed extracts include a full blend of compounds, including both volatile and non-volatile compounds found in cannabis flowers and the compounds found in cannabis roots, and not only the known biologically active cannabinoids. In various embodiments, the combined extract and the three-component combined extract may have enhanced bioavailability and/or activity following oral consumption as compared to bioavailability and/or activity following oral consumption of the cannabinoids alone. The presence of the volatile compounds, including terpenes, and the compounds from the cannabis roots, in the extracts and compositions disclosed herein may enhance the activity of the cannabinoids. In various embodiments, the composition of the combined extract or the three-component combined extract is about the same as what is present in the cannabis flowers and roots, in terms of proportion of cannabinoids to other compounds.

[0030] Following the preparation of the combined extract or the three-component combined extract, the concentration of the volatile and non-volatile compounds in the extract may be standardized and used for preparation of compositions for oral consumption, including tinctures for oral consumption. Extracts from different strains of cannabis flower and roots may have different types and ratios of cannabinoids and as a result, these extracts may be combined to form a combined extract or a three-component combined extract with different ratios of cannabinoids. For example, compositions or tinctures with THC, CBD, CBN or combinations with other available cannabinoids, such as THCA, CBDA, CBGA, THCV, CBDV, CBG, CBC, CBL, CBV, CBCV, CBGV, CBGM, CBE and CBT, can be prepared. These cannabinoid combinations can be prepared by mixing appropriate amounts of two or more extracts together. Furthermore, the combined extract or the three-component combined extract may be combined with a synthetic or isolated form of one or more cannabinoids to produce an extract with certain ratios of compounds. In various embodiments, in order to prepare a composition that does not contain any chlorophyll or plant pigments, purely isolated or synthetic cannabinoids can be used to prepare compositions or tinctures, to which cannabis or non-cannabis terpenes can be added, as described above.

[0031] Food colouring may also be added to the composition or tincture in order to provide a certain appearance to the solution or to improve the taste of the composition or tincture. In various embodiments, the food colouring may comprise a compound which improves the biological activity of the cannabinoids. Examples of suitable food colouring for use with extracts, compositions and tinctures disclosed herein include turmeric extracts, cinnamon extracts, beetroot extracts, carrot extracts, caramel, blueberry extracts, and blackberry extracts.

[0032] In various embodiments, the combined extract or three-component combined extract is diluted with a diluent to obtain the necessary amount of cannabinoids and terpenes in the compositions or tincture for oral consumption. The diluent may dissolve all compounds in the extract to form a homogeneous solution and is a liquid above about 0°C or above about 10°C. The volatile and non-volatile compounds and the compounds from the cannabis roots are lipophilic and soluble in organic solvents and oils which may be the diluent. The diluent may comprise one or more naturally occurring triglycerides, grain alcohol (95% ethanol) or polyhydroxy alcohol (glycerol). In various embodiments, the diluent does not contain large quantities of residual water. In various embodiments, the diluent is food grade and edible. For example, triglycerides formed from long chain or medium chain saturated or unsaturated fatty acids ranging from 8 to 24 carbon atoms may be the diluent. In various embodiments, food grade edible oils such as cottonseed oil, soybean oil, safflower oil, sesame oil, sunflower oil, castor oil, corn oil, palm oil, grapeseed oil, coconut oil, peanut oil, canola oil, hydrogenated soybean oil, hydrogenated vegetable oils, hydrogenated sesame oil, poppy seed oil and olive oil are used as the diluent. In various embodiments, the preferred diluent depends on the composition of the combined extract or the three-component combined extract and a person of ordinary skill in the art can determine the preferred diluent through routine experimentation.

[0033] In various embodiments, the terpenes in the combined extract and the three- component combined extract may act as a dissolution co-solvent for cannabinoids and may maintain the homogeneity of the extracts and compositions during storage.

[0034] As described above, an amount of the combined extract or the three- component combined extract may be produced as a tincture for oral consumption. In various embodiments, the tinctures may provide efficient delivery of cannabinoids into the body through sublingual, buccal or gastrointestinal routes. The composition may be suitable for delivery to the gastrointestinal tract and avoid hepatic first-pass metabolism via oral consumption.

EXAMPLES

[0035] These examples illustrate various aspects of the invention, evidencing a variety of conditions for preparing cannabis compositions and tinctures. Selected examples are illustrative of advantages that may be obtained compared to alternative preparation methods, and these advantages are accordingly illustrative of particular embodiments and not necessarily indicative of the characteristics of all aspects of the invention.

[0036] As used herein, the term“about” refers to an approximately +/-10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to. Example 1 : Preparation of extracts from cannabis flowers

[0037] 908 grams (2.0 lbs) of dried and cleaned flowers from a high THC strain of

Cannabis sativa L. were steam distilled for three hours. The steam distilled oil fraction containing the volatile compounds collected in the receiving unit was transferred into a clean container and dried using anhydrous sodium sulphate. The dried oil fraction was filtered to remove solid particles to obtain a clear oily liquid as a filtrate. The total weight of the filtrate, or volatile extracts, containing the volatile compounds was 3.8 g.

[0038] The residual biomass from the steam distillation contains non-volatile compounds. This residual biomass was dried at room temperature for four days to a constant weight. The dried residual biomass was mixed with 10 L of ethanol (95%) and extracted at -25°C under atmospheric pressure for 30 seconds. The liquid was separated from the solid biomass and extraction was repeated with an additional 8.0 L of ethanol at -25°C. The combined ethanol extracts were filtered under suction. The solvent was removed from the filtrate using a rotary evaporator under reduced pressure at 45°C to obtain a concentrated oil (liquid phase as an oily resin).

[0039] Concentrations of cannabinoids in the concentrated oil were determined by HPLC. Analysis showed that the concentrated oil contained THC (83.47%) as the major cannabinoid and THCA (0.10%), CBDA (0.04%), CBD (0.19%), and CBN (0.13%) as minor components. The final weight of the concentrated oil was 192.0 g.

Example 2: Preparation of a cannabis root extract

[0040] Roots obtained from Cannabis sativa L. were cleaned using distilled water and dried at 25°C for 7 days to a constant weight. Dried and ground roots (274 g) were extracted with 2.0 L of hot ethanol (95%) in a Soxhlet extractor for 15 hours. Extracts were filtered, and rotary evaporated under reduced pressure at 45°C to obtain a concentrated root extract. The final weight of the concentrated root extract was 46.6 g.

Example 3: Preparation of a three-component combined extract from cannabis flowers and roots [0041] The concentrated oil obtained from Example 1 (119.80 g), the volatile extracts (2.37 g) obtained from steam distillation in Example 1 and the concentrated root extract from Example 2 (18.0 g) were added to grapeseed oil (4490 g). This mixture was stirred at room temperature for 30 minutes. The concentration of THC in this mixture was 20 mg/mL.

Example 4: Preparation of a combined extract from cannabis flowers

[0042] The concentrated oil obtained from Example 1 (119.80 g) was added to grapeseed oil (4514 g) and the volatile extracts (2.37 g) from Example 1. This mixture was stirred at room temperature for 30 minutes. The concentration of THC in this mixture was 20 mg/mL.

Example 5: Preparation of a cannabis flower extract

[0043] 908 grams (2.0 lbs) of dried and cleaned flowers from a high THC strain of

Cannabis sativa L. was mixed with 10 L of ethanol (95%) and extracted at -25°C under atmospheric pressure for 30 seconds. The liquid was separated from the solid biomass and extraction was repeated one more time with 8.0 L of ethanol at -25°C. The combined ethanol extracts were filtered under suction. The solvent was removed from the filtrate using a rotary evaporator under reduced pressure at 45°C to obtain the concentrated extract as an oily resin. The concentrated extract was decarboxylated at 80°C for 3.0 hours. The concentration of cannabinoids in this extract was determined by HPLC. Analysis showed that the extract contained THC (73.43%) as the major cannabinoid and THCA (0.25%), CBDA (0.08%), CBD (0.25%) and CBN (0.20%) as minor compounds. The final weight of the sample was 188.0 g.

Example 6: Preparation of a composition from cannabis flower extract, cannabis root extract and citrus terpenes

[0044] The extract from Example 5 (136.2 g), root extract (18.0 g) from Example 2 and food grade orange oil (16.0 g, terpene) were added to a triglyceride solution (4466 g, grapeseed oil). The mixture was stirred at room temperature for 30 minutes. The concentration of THC in this mixture was 20 mg/mL.

Example 7: Preparation of a composition from cannabis flower extract and citrus terpenes

[0045] The extract from Example 5 (136.2 g) and food grade orange oil (16.0 g, terpene) was added to a triglyceride solution (4484 g, grapeseed oil). The mixture was stirred at room temperature for 30 minutes. The concentration of THC in this mixture was 20 mg/mL.

[0046] Other compositions prepared according to the methods described above are shown in Table 1.

Table 1. Preparation of Various Compositions

[0047] Although various embodiments of the invention are disclosed herein, many adaptations and modifications may be made within the scope of the invention in accordance with the common general knowledge of those skilled in this art. Such modifications include the substitution of known equivalents for any aspect of the invention in order to achieve the same result in substantially the same way. Numeric ranges are inclusive of the numbers defining the range. The word "comprising" is used herein as an open-ended term, substantially equivalent to the phrase "including, but not limited to", and the word "comprises" has a corresponding meaning. As used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a thing" includes more than one such thing. Citation of references herein is not an admission that such references are prior art to the present invention. Any priority document(s) and all publications, including but not limited to patents and patent applications, cited in this specification are incorporated herein by reference as if each individual publication were specifically and individually indicated to be incorporated by reference herein and as though fully set forth herein. The invention includes all embodiments and variations substantially as hereinbefore described and with reference to the examples and drawings.