Method for purifying cannabidiol

Abstract

To provide a novel method for purifying cannabidiol.SOLUTION: An adsorption treatment is performed on a mixture comprising cannabidiol and at least one species selected from olivetol and a positional isomer of cannabidiol (abn-CBD).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for purifying cannabidiol. [Background technology]

[0002] Cannabidiol (CBD), for example, is represented by the following formula and is one of the cannabinoids contained in hemp, and is used for various purposes such as pharmaceuticals. [ka] For example, Patent Document 1 discloses a stable pharmaceutical formulation for oral administration containing about 0.1 to about 40% cannabinoid; and about 10 to about 95% lipid. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2018-516281 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a method for purifying cannabidiol, etc. [Means for solving the problem]

[0005] Cannabidiol (CBD) can be chemically (artificially) synthesized, for example, by reacting menthadienol with olivetol, but such reactions typically produce by-products (by-products, reaction by-products) in addition to CBD.

[0006] These by-products mainly include positional isomers (hereinafter referred to as abn-CBD), adducts (an adduct in which 2 moles of menthadienol are added to 1 mole of olivetol, hereinafter referred to as 2:1 adducts), tetrahydrocannabinol (THC) [especially Δ9-THC (Δ9 -THC), Δ8-THC(Δ 8 -THC)] (for example, represented by the following formula):

[0007] [ka] Positional isomer (abn-CBD)

[0008] [ka] Adduct (2:1 adduct)

[0009] [ka] Δ9-THC

[0010] [ka] Δ8-THC

[0011] The production of such by-products leads to a decrease in the yield of CBD and a decrease in the efficiency of CBD recovery (purification).

[0012] Furthermore, according to the investigations of the present inventors, when such by-products are produced (for example, when a relatively large amount is produced or when by-products that are difficult to separate from CBD are produced), separation (purification) may be difficult even when conventional purification techniques are used, or even if separation (purification) is possible, the separation (purification) process may be complicated.

[0013] Furthermore, if separation is not sufficient and by-products are mixed with CBD, this may interfere with the function of CBD or cause other effects or side effects (for example, THC is the main component of marijuana).

[0014] Therefore, it is preferable to suppress the production of such by-products as much as possible during the reaction stage.

[0015] However, it is difficult to find reaction (manufacturing) conditions that produce CBD while suppressing these by-products. In particular, suppressing the production of one by-product can make other by-products more likely to be produced, making it extremely difficult to find conditions that suppress all by-products (for example, suppressing the by-production of abn-CBD and 2:1 adducts, as well as the by-production of THC).

[0016] In this situation, the present inventors have discovered that CBD can be produced while efficiently suppressing the production of by-products by, for example, reacting menthadienol with olivetol under specific conditions (methods).

[0017] However, even with the method discovered by the present inventors, it was difficult to suppress the production of by-products to a high level.

[0018] Furthermore, although the method discovered by the present inventors can suppress the production of by-products, it is difficult to simultaneously suppress the production of by-products (suppress the production of by-products at a high level) and completely react olivetol, and there are cases where unreacted olivetol remains in the reaction mixture.

[0019] In this situation, the inventors conducted extensive research to solve the above-mentioned problems, and as a result, discovered that CBD can be efficiently purified (other components can be separated) by subjecting a mixture containing CBD as well as other components such as olivetol and abn-CBD to a specific treatment. After further research, the inventors have completed the present invention.

[0020] That is, the present invention relates to the following inventions. [1] A method for producing a purified product containing cannabidiol by adsorption treating a mixture containing cannabidiol and at least one selected from olivetol and positional isomers of cannabidiol (abn-CBD) (a method for producing a purified product containing cannabidiol by separating at least one selected from olivetol and positional isomers of cannabidiol (abn-CBD) from the mixture). [2] The method according to [1], wherein the mixture is a mixture containing a solvent (solvent mixture). [3] The method according to [1] or [2], wherein the mixture contains a solvent containing at least an aliphatic hydrocarbon (e.g., heptane). [4] The method according to any one of [1] to [3], wherein a mixture containing a solvent is brought into contact with an adsorbent. [5] The method according to any one of [1] to [4], wherein silica gel is brought into contact with a mixture containing a solvent that includes at least an aliphatic hydrocarbon (such as heptane). [6] The method according to any one of [1] to [5], wherein the mixture contains olivetol, and the ratio of olivetol to cannabidiol (CBD) is 0.05 to 2 on an HPLC area basis. [7] The method according to any one of [1] to [6], wherein the mixture contains a positional isomer of cannabidiol (abn-CBD), and the ratio of the positional isomer of cannabidiol (abn-CBD) to cannabidiol (CBD) is 0.05 to 2 on an HPLC area basis. [8] the mixture comprises olivetol and a positional isomer of cannabidiol (abn-CBD); The ratio of olivetol to cannabidiol (CBD) is 0.05 to 2 based on the HPLC area standard. The method according to any one of [1] to [7], wherein the ratio of a positional isomer of cannabidiol (abn-CBD) to cannabidiol (CBD) is 0.05 to 2 based on the area of HPLC. [9] the mixture comprises olivetol, In the mixture, the ratio of olivetol to cannabidiol (CBD) is N1 based on the HPLC area standard, In the purified product, the ratio of olivetol to cannabidiol (CBD) is N2 based on the HPLC area standard. The method according to any one of [1] to [8], wherein the value of N1-N2 is 0.03 or more.

[10] the mixture comprises a positional isomer of cannabidiol (abn-CBD); In the mixture, the ratio of the positional isomer of cannabidiol (abn-CBD) to the total cannabidiol (CBD) is defined as N1 based on the HPLC area standard. In the purified product, the ratio of cannabidiol positional isomer (abn-CBD) to cannabidiol (CBD) is N2 based on the HPLC area standard. The method according to any one of [1] to [9], wherein the value of N1-N2 is 0.03 or more.

[11] the mixture comprises olivetol and a positional isomer of cannabidiol (abn-CBD); In the mixture, the ratio of olivetol and positional isomers of cannabidiol (abn-CBD) to cannabidiol (CBD) is defined as N1 based on the HPLC area standard. In the purified product, the ratio of olivetol and positional isomers of cannabidiol (abn-CBD) to cannabidiol (CBD) is N2 based on the HPLC area standard. The method according to any one of [1] to

[10] , wherein the value of N1-N2 is 0.05 or more.

[12] Menthadienol and olivetol, In the presence of at least one catalyst (acid, acid catalyst) selected from non-boron Lewis acids and Bronsted acids (e.g., organic acids, inorganic acids), At temperatures above 40°C, The method includes a step of reacting at a water content of 5% by mass or less in the reaction system at the start of the reaction (e.g., 4% by mass or less, 3% by mass or less, 2% by mass or less, 1.5% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.3% by mass or less, 0.25% by mass or less, 0.2% by mass or less, 0.18% by mass or less, 0.15% by mass or less, 0.12% by mass or less, 0.1% by mass or less, 0.08% by mass or less, 0.05% by mass or less, etc.), to produce a reaction mixture containing cannabidiol, The reaction mixture obtained through this step is subjected to an adsorption treatment (used as a mixture containing cannabidiol and at least one selected from olivetol and a positional isomer of cannabidiol (abn-CBD)), according to any one of the methods described in [1] to

[11] .

[13] A purified cannabidiol (crude cannabidiol) comprising cannabidiol (CBD) and an adduct in which 2 moles of menthadienol are added to 1 mole of olivetol (2:1 adduct), The ratio of cannabidiol (CBD) to the total amount of cannabidiol (CBD), olivetol, a positional isomer of cannabidiol (abn-CBD), an adduct in which 2 moles of menthadienol are added to 1 mole of olivetol (2:1 adduct), Δ-9-tetrahydrocannabinol (Δ9-THC), and Δ-8-tetrahydrocannabinol (Δ8-THC) is 60% or more based on the area standard of HPLC, Olivetol is not included or is included at a ratio of 0.03 or less to cannabidiol (CBD) on an HPLC area basis, The product does not contain a positional isomer of cannabidiol (abn-CBD) or contains it at a ratio of 0.3 or less based on the area of cannabidiol (CBD) by HPLC, A purified product (crude cannabidiol) containing an adduct of 1 mole of olivetol and 2 moles of menthadienol (2:1 adduct) at a ratio of 0.0001 to 0.5 based on HPLC area to cannabidiol (CBD). [Effects of the Invention]

[0021] According to the present invention, a method for purifying cannabidiol can be provided.

[0022] This method allows CBD to be efficiently purified (other components separated) from a mixture containing CBD as well as other components such as olivetol and abn-CBD.

[0023] According to the inventor's investigations, when CBD contains such other components, it appears that further purification of CBD (higher level purification of CBD) is more likely to be inhibited. Therefore, the method of the present invention is particularly useful in producing highly purified (highly pure) CBD (in other words, the CBD obtained by the method of the present invention is useful as CBD to be used for further high-level purification (crude CBD, first purified product)). DETAILED DESCRIPTION OF THE INVENTION

[0024] In the present invention, a mixture containing cannabidiol (CBD) and other components (typically, at least one selected from olivetol and positional isomers of cannabidiol (abn-CBD)) is subjected to an adsorption treatment (at least an adsorption treatment).

[0025] By using this method (adsorption treatment), a purified product containing CBD (purified CBD, crude CBD, first purified product) can be produced (other components can be separated).

[0026] The mixture (the mixture to be subjected to the adsorption treatment) is not particularly limited as long as it contains CBD and other components (particularly, at least one selected from olivetol and positional isomers of cannabidiol (abn-CBD)), and may be a reaction mixture.

[0027] Such a reaction mixture may be, for example, a reaction mixture obtained by reacting menthadienol with olivetol.

[0028] In particular, in the present invention, a mixture (reaction mixture) in which the production of by-products (e.g., abn-CBD) is suppressed (and further, the amount of unreacted olivetol is relatively small) may be used.

[0029] As mentioned above, even in such a mixture, it is difficult to completely prevent the by-products and olivetol from remaining, which is why the method of the present invention is effective.

[0030] However, even when using the method of the present invention, if too much by-products or olivetol remains, the purification efficiency may decrease, or it may become difficult to sufficiently purify the CBD (crude CBD) for advanced purification.

[0031] From this perspective, the present invention may suitably utilize a mixture in which the production of by-products (for example, abn-CBD) is suppressed (and further, the amount of unreacted olivetol is relatively small). For example, the method discovered by the present inventors (method for producing CBD) can be used to produce such a mixture.

[0032] The mixture, including the method discovered by the present inventors, will be described in detail below.

[0033] [Mixture] The mixture (the mixture subjected to the adsorption process) contains other components in addition to CBD.

[0034] Other components include unreacted raw materials (e.g., olivetol, menthadienol), by-products (abn-CBD, 2:1 adducts, Δ9-THC, Δ8-THC, etc.), and other components used in the reaction (e.g., catalysts).

[0035] Of these, the method of the present invention appears to be able to easily separate (by adsorption) olivetol and abn-CBD, among other components. In other words, the present invention appears to be able to easily purify a mixture containing CBD and at least one selected from olivetol and abn-CBD (by separating olivetol and abn-CBD from the mixture and purifying CBD).

[0036] Therefore, a mixture containing at least one selected from olivetol and abn-CBD (particularly olivetol and abn-CBD) may be used.

[0037] Such a mixture may typically be a reaction mixture (a mixture obtained by a method for producing CBD).

[0038] (How CBD is produced) The method for producing CBD is not particularly limited, but typically, cannabidiol is produced (generated) by reacting menthadienol with olivetol.

[0039] The ratio (usage ratio) of menthadienol and olivetol is not particularly limited, and they may be equal in amount, or either may be used in excess. For example, the ratio may be selected from a range of about 0.3 moles or more (e.g., 0.5 moles or more) of olivetol per mole of menthadienol, 0.6 moles or more (e.g., 0.7 moles or more), preferably 0.8 moles or more (e.g., 0.85 moles or more), more preferably 0.9 moles or more (e.g., 0.95 moles or more, 0.97 moles or more, 0.99 moles or more), or 1 mole or more (e.g., more than 1 mole, 1.01 moles or more, 1.02 moles or more, 1.03 moles or more, 1.04 moles or more, 1.05 moles or more, etc.).

[0040] The ratio (upper limit) of olivetol to 1 mole of menthadienol is not particularly limited, but may be selected from a range of about 5 moles or less (e.g., 4 moles or less), preferably 3 moles or less (e.g., 2 moles or less), more preferably 1.5 moles or less (e.g., 1.3 moles or less, 1.25 moles or less, 1.2 moles or less, 1.15 moles or less, 1.12 moles or less, 1.1 moles or less, etc.), or may be 1 mole or less (e.g., 0.99 moles or less, 0.98 moles or less, 0.97 moles or less, 0.95 moles or less, 0.93 moles or less, 0.9 moles or less, etc.).

[0041] The ratio of olivetol to 1 mole of menthadienol may be within a range combining the upper and lower limits (for example, 0.3 to 1 mole, or more than 1 mole and 1.5 moles or less) (the same applies hereinafter).

[0042] In the present invention, a specific catalyst [at least one selected from non-boron Lewis acids and Bronsted acids (protonic acids)] may be present (may be used) in the reaction.

[0043] Examples of non-boron Lewis acids include non-boron compounds such as oxides (e.g., metal oxides), halides (e.g., fluorides, chlorides, bromides, iodides, etc.) (e.g., metal halides), alkoxides (e.g., metal alkoxides), triflates (e.g., metal triflates), and other complexes (e.g., acetylacetonate complexes, acetoacetate ester complexes).

[0044] Examples of metals (non-boron-based metals, metals other than boron) include typical metals (elements) and transition metals (transition elements), such as metals (elements) of Groups 3 to 12 of the periodic table (e.g., scandium, yttrium, lanthanum, titanium, zirconium, hafnium, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, iron, ruthenium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver, gold, zinc, cadmium, etc.) and metals (elements) of Groups 1 to 17 of the periodic table, such as metals of Groups 13 to 16 of the periodic table (e.g., aluminum, gallium, indium, thallium, tin, lead, arsenic, antimony, bismuth, etc.).

[0045] Specific examples of non-boron Lewis acids include oxides (e.g., metal oxides such as aluminum oxide), halides [e.g., metal halides such as zinc halides (e.g., zinc chloride, zinc bromide, zinc iodide)], alkoxides [e.g., metal alkoxides such as titanium alkoxides (titanium tetramethoxide, titanium tetraethoxide), zirconium alkoxide], triflates (e.g., metal triflates such as scandium triflate, silver triflate, zinc triflate), acetylacetone complexes (e.g., metal acetylacetonates such as aluminum acetylacetonate), and acetoacetate complexes (e.g., metal acetoacetate complexes such as aluminum ethylacetoacetate diisopropylate).

[0046] The Bronsted acid may be an organic acid or an inorganic acid.

[0047] Examples of organic acids include carboxylic acids {e.g., fatty acids [e.g., monocarboxylic acids (e.g., alkanoic acids) such as formic acid, acetic acid, propionic acid, lactic acid, and trifluoroacetic acid; polycarboxylic acids (e.g., alkanoic acids) such as oxalic acid, malonic acid, succinic acid, glutaric acid, tartaric acid, malic acid, and citric acid], aromatic carboxylic acids (e.g., benzoic acid, phthalic acid, and terephthalic acid)}, sulfonic acids (e.g., alkanesulfonic acids such as methanesulfonic acid and trifluoromethanesulfonic acid; arenesulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid), and the like.

[0048] Examples of inorganic acids include hydrogen halides (eg, hydrogen chloride, hydrogen bromide, hydrogen iodide), sulfuric acid, nitric acid, phosphoric acid, and the like.

[0049] The catalysts (acid catalysts) may be used alone or in combination of two or more kinds.

[0050] Representative catalysts include non-boron Lewis acids (eg, metal oxides, metal halides, metal triflates), carboxylic acids, sulfonic acids, inorganic acids, and the like.

[0051] Among these catalysts, non-boron Lewis acids may be preferably used from the viewpoint of suppressing the formation of by-products and achieving good reactivity (furthermore, in combination with other conditions, suppressing the formation of by-products and achieving good reactivity efficiently), and among these, metal halides (for example, zinc halides such as zinc chloride, zinc bromide, and zinc iodide) may be preferably used.

[0052] Therefore, the catalyst may contain at least a non-boron Lewis acid [for example, a metal halide (for example, a zinc halide such as zinc chloride, zinc bromide, or zinc iodide, particularly zinc iodide)].

[0053] As mentioned above, the reaction is usually carried out in the presence of a specific catalyst [at least one selected from non-boron Lewis acids and Bronsted acids (protonic acids)].

[0054] In such cases, a specific catalyst may be used in combination (concurrent use) with a boron-based Lewis acid [for example, a boron trifluoride complex (for example, a boron trifluoride diethyl ether complex, a boron trifluoride monoalkylamine complex, boron trifluoride hydrate, etc.)], but from the viewpoint of suppressing the production of by-products and achieving good reactivity (and further, in combination with other conditions, suppressing the production of by-products and achieving good reactivity efficiently), it may not be used [concurrent use, substantially used (concurrent use)].

[0055] The proportion (usage proportion) of the catalyst (specific catalyst) may be selected depending on the type of catalyst and other conditions, and may be selected, for example, from a range of about 0.0001 moles (or molar equivalent, the same applies hereinafter) or more per mole of menthadienol or olivetol (e.g., menthadienol). From the viewpoint of suppressing the production of by-products and achieving good reactivity (and further, in combination with other conditions, making it easier to efficiently achieve suppression of by-product production and good reactivity), the proportion may be about 0.001 moles or more (e.g., 0.003 moles or more), preferably 0.005 moles or more (e.g., 0.007 moles or more), and more preferably 0.01 moles or more (e.g., 0.03 moles or more), or may be about 0.05 moles or more (e.g., 0.07 moles or more, 0.08 moles or more, 0.1 moles or more).

[0056] The proportion (upper limit of) the catalyst (specific catalyst) may be selected, for example, from a range of about 20 moles or less (e.g., 15 moles or less, 10 moles or less, 8 moles or less) relative to 1 mole of menthadienol or olivetol (e.g., menthadienol). From the viewpoint of suppressing the production of by-products and achieving good reactivity (furthermore, in combination with other conditions, it is easy to efficiently achieve suppression of by-product production and good reactivity), the proportion may be about 5 moles or less (e.g., 3 moles or less), preferably 2 moles or less (e.g., 1.2 moles or less), and more preferably 1 mole or less (e.g., less than 1 mole, 0.8 moles or less), or may be 0.5 moles or less (e.g., 0.4 moles or less, 0.3 moles or less, 0.2 moles or less, 0.15 moles or less, 0.1 moles or less).

[0057] The reaction may be carried out in the presence of (in) a solvent.

[0058] Examples of the solvent include hydrocarbons [for example, aliphatic hydrocarbons (e.g., hexane, heptane, cyclohexane, methylcyclohexane, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene, etc.)], halogenated solvents (e.g., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), esters (e.g., aliphatic esters such as methyl acetate, ethyl acetate, butyl acetate, etc.), carbonates (e.g., ethylene carbonate, propylene carbonate, etc.), ethers [for example, chain ethers (e.g., diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (e.g., tetrahydrofuran, dioxane, etc.), etc.], glycol ethers (e.g., ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol diethyl ether, diethylene glycol monomethyl ether, etc.), glycol ether esters (e.g., ethylene glycol monomethyl ether acetate, etc.), nitrogen-containing solvents {e.g., amides [e.g., N-substituted chain amides (e.g., N-alkyl-substituted alkanamides such as N,N-dimethylformamide and N,N-dimethylacetamide; N,N-diphenylacetamide, etc.), cyclic amides (e.g., 2-pyrrolidone and 1,3-dimethyl-2-imidazolidinone, etc.)], nitriles (e.g., acetonitrile, etc.)], sulfur-containing solvents (e.g., sulfoxides such as dimethyl sulfoxide; sulfones such as dimethyl sulfone and sulfolane), alcohols [e.g., alkanols (e.g., methanol, ethanol, isopropanol), etc.], polyols (e.g., alkanediols such as ethylene glycol and propylene glycol; glycerin, etc.)], water, etc.

[0059] The above-mentioned Bronsted acid [for example, an organic acid (for example, acetic acid)] may be used as the solvent.

[0060] The solvent may be, for example, any of (a solvent classified into) an aprotic solvent, a protic solvent (water, alcohols, organic acids, etc.), a polar solvent, a non-(non)polar solvent, etc. An aprotic solvent may be preferably used as the solvent.

[0061] The solvents may be used alone or in combination of two or more.

[0062] Among these solvents, aprotic solvents and the like may be preferably used from the viewpoint of suppressing the generation of by-products and achieving good reactivity (furthermore, in combination with other conditions, it is easy to efficiently achieve suppression of the generation of by-products and good reactivity), and in particular, hydrocarbons (particularly, aromatic hydrocarbons such as toluene) may be preferably used.

[0063] Therefore, the solvent may contain at least an aprotic solvent or a hydrocarbon (particularly, an aromatic hydrocarbon such as toluene).

[0064] The solvent may or may not contain a protic solvent (for example, water, alcohols, organic acids, etc.); however, from the viewpoint of suppressing the production of by-products and achieving good reactivity (and further, in combination with other conditions, making it easier to efficiently achieve suppression of the production of by-products and good reactivity), it is preferable that the solvent does not contain a protic solvent, or if it does contain a protic solvent, it may contain a small amount [for example, 10 mass % or less (for example, 5 mass % or less, 3 mass % or less, 1 mass % or less, 0.5 mass % or less, 0.1 mass % or less), etc.].

[0065] In particular, it is preferable that the solvent (reaction system) does not contain water or contains only a small amount of water, from the viewpoint of suppressing the production of by-products and achieving good reactivity (furthermore, in combination with other conditions, it is easy to efficiently achieve suppression of the production of by-products and good reactivity).

[0066] When the solvent (reaction system) contains water, the proportion of water may be selected from a range of about 10% by mass or less (e.g., 8% by mass or less) of the reaction system (e.g., the total amount of menthadienol, olivetol, catalyst, and solvent), 5% by mass or less (e.g., 4% by mass or less, 3.5% by mass or less), preferably 3% by mass or less (e.g., 2.5% by mass or less), more preferably 2% by mass or less (e.g., 1.5% by mass or less), particularly preferably 1.2% by mass or less (e.g., 1% by mass or less, 0.9% by mass or less, 0.8% by mass or less, 0.7% by mass or less, 0.6% by mass or less, 0.5% by mass or less, 0.4% by mass or less, 0.3% by mass or less, 0.28% by mass or less), particularly preferably 0.25% by mass or less (for example, 0.22% by mass or less, 0.2% by mass or less, 0.18% by mass or less, 0 .15% by mass or less, 0.12% by mass or less, 0.1% by mass or less, 0.08% by mass or less, 0.07% by mass or less, 0.06% by mass or less, 0.05% by mass or less, 0.04% by mass or less, 0.03% by mass or less, 0.01% by mass or less).

[0067] When the solvent (reaction system) contains water, the proportion of water may be selected from a range of about 10% by mass or less of the solvent, and may be 5% by mass or less (e.g., 3% by mass or less), preferably 2% by mass or less (e.g., 1.5% by mass or less), and more preferably 1% by mass or less (e.g., 0.5% by mass or less, 0.1% by mass or less), etc.

[0068] When the solvent (reaction system) contains water, the proportion of water may be selected from a range of about 20 parts by mass or less (e.g., 15 parts by mass or less) relative to 100 parts by mass of menthadienol or olivetol (e.g., menthadienol), and may be 10 parts by mass or less (e.g., 8 parts by mass or less), preferably 5 parts by mass or less (e.g., 3 parts by mass or less), and more preferably 2 parts by mass or less (e.g., 1.5 parts by mass or less, 1 part by mass or less, 0.5 parts by mass or less, 0.3 parts by mass or less, 0.1 parts by mass or less), etc.

[0069] In addition, water is produced (as a by-product) by the reaction between menthadienol and olivetol, and therefore the above-mentioned water ratio may be the ratio of water before the reaction (or at the start of the reaction, at the early stage of the reaction, or when by-product water is excluded).

[0070] Furthermore, during the reaction, the proportion of water may be maintained (retained) at a relatively low proportion (range) as described above. For example, the proportion of water during the reaction may be 10% by mass or less (e.g., 5% by mass or less, 3% by mass or less, 2% by mass or less, 1% by mass or less, 0.8% by mass or less, 0.5% by mass or less, 0.4% by mass or less, 0.3% by mass or less, 0.2% by mass or less, 0.1% by mass or less) of the reaction system (e.g., the total amount of menthadienol, olivetol, catalyst, and solvent) or solvent.

[0071] The protic solvent (water, etc.) may be contained in advance in the raw materials (components) used in the reaction [for example, olivetol, catalyst (Bronsted acid, etc.), aprotic solvent, etc.].

[0072] In this way, when the raw materials already contain water and it is necessary to reduce the protic solvent (water, etc.), the protic solvent may be separated or removed from the raw materials or reaction system by a conventional method (for example, distillation, etc.) (the water ratio may be set as described above by separating or removing the protic solvent).

[0073] As mentioned above, water is produced as a by-product in the reaction, and the reaction may be carried out while separating and removing this by-product water by an appropriate method.

[0074] When a solvent is used, the ratio (concentration) of components other than the solvent (solid content) to the total amount of the solvent and components other than the solvent (e.g., menthadienol, olivetol, and catalyst) may be, for example, about 0.1% by mass or more (e.g., 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more), or may be 99% by mass or less (e.g., 95% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 12% by mass or less, 10% by mass or less), etc.

[0075] When a solvent is used, the ratio of the solvent to olivetol or menthadienol (e.g., menthadienol) may be about 0.01 or more (e.g., 0.05 or more, 0.1 or more, 0.3 or more, 0.5 or more) on a volume basis, or may be 1000 or less (e.g., 800 or less, 500 or less, 300 or less, 200 or less, 150 or less, 120 or less, 100 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less), etc.

[0076] The method of mixing the raw materials (components) used in the reaction (olivetol, menthadienol, catalyst, solvent, etc.) is not particularly limited, and they may be mixed all together, mixed in stages, mixed partially, or multiple components may be mixed in advance, or these may be combined.

[0077] In particular, from the viewpoint of suppressing the production of by-products and achieving good reactivity (and furthermore, in combination with other conditions, it is easy to efficiently achieve suppression of the production of by-products and good reactivity), one of the components of menthadienol or olivetol (e.g., menthadienol) may be mixed (e.g., added dropwise) into a system (mixture) containing one of the components of menthadienol or olivetol (e.g., olivetol) and a catalyst (and further a solvent) [the menthadienol and olivetol may be reacted by mixing (e.g., adding dropwise)]. In particular, from the viewpoint of efficiently carrying out the reaction (allowing the catalyst to function), a mixture containing olivetol and the catalyst may be mixed with menthadienol (for example, menthadienol may be added dropwise to a system (mixture) containing olivetol and the catalyst).

[0078] The mixing may be carried out all at once or in stages, preferably in stages.

[0079] Such mixing (staged mixing) may be intermittent, continuous (continuous), or a combination thereof.

[0080] Furthermore, in such mixing (stepwise mixing), the time required for mixing (mixing time, total time, time until mixing is completed) depends on the amount of the other component, etc., but can be selected from a range of, for example, about 30 seconds or more (e.g., 40 seconds or more), and may be about 1 minute or more (e.g., 2 minutes or more), preferably 3 minutes or more (e.g., 4 minutes or more), more preferably 5 minutes or more (e.g., 7 minutes or more), or may be 8 minutes or more (e.g., 10 minutes or more, 12 minutes or more, 15 minutes or more, 18 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more), etc.

[0081] The reaction may be carried out at room temperature (or ordinary temperature), under heating, or under cooling.

[0082] Specific reaction temperatures include, for example, -100°C or higher (e.g., -80°C or higher, -60°C or higher, -40°C or higher, -20°C or higher, 0°C or higher, 10°C or higher, 20°C or higher, 30°C or higher, 35°C or higher, 40°C or higher, 45°C or higher, 50°C or higher, 55°C or higher, 60°C or higher, 65°C or higher, 70°C or higher, 75°C or higher, 80°C or higher, 85°C or higher, 90°C or higher, 95°C or higher, 100°C or higher, 105°C or higher, 110°C or higher), 300°C or lower (e.g., 250°C or lower, 200°C or lower, 180°C or lower, 160°C or lower, 150°C or lower, 140°C or lower, 130°C or lower, 120°C or lower, 110°C or lower, 100°C or lower, 95°C or lower, 90°C or lower, 85°C or lower, 80°C or lower).

[0083] In particular, from the viewpoint of suppressing the production of by-products and achieving good reactivity (furthermore, in combination with other conditions, suppressing the production of by-products and achieving good reactivity efficiently), the reaction temperature may be relatively high (for example, 30°C or higher, 35°C or higher, 40°C or higher, 45°C or higher, 50°C or higher, 55°C or higher, 60°C or higher, 65°C or higher, 70°C or higher, 75°C or higher, 80°C or higher, 85°C or higher, 90°C or higher, 95°C or higher, 100°C or higher, 105°C or higher, or 110°C or higher).

[0084] The reaction time can be appropriately selected depending on the degree of progress of the reaction (reaction rate, conversion rate), the type of catalyst, various reaction conditions, and the like, and is not particularly limited. For example, the reaction time may be 1 second or more (e.g., 3 seconds or more, 5 seconds or more, 10 seconds or more, 20 seconds or more, 30 seconds or more, 40 seconds or more, 50 seconds or more, 1 minute or more, 1.5 minutes or more, 2 minutes or more, 2.5 minutes or more, 3 minutes or more, 3.5 minutes or more, 4 minutes or more, 4.5 minutes or more, 5 minutes or more, 8 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more), or 24 hours or less (e.g., 18 hours or less, 12 hours or less, 10 hours or less, 8 hours or less, 6 hours or less, 5 hours or less, 4 hours or less, 3 hours or less, 2 hours or less, 1.5 hours or less, 1.2 hours or less, 1 hour or less, 50 minutes or less, 40 minutes or less, 30 minutes or less), and the like.

[0085] The reaction begins when menthadienol and olivetol (and furthermore the catalyst) coexist and are in a state where they can react, and ends when the reaction no longer proceeds (when all of the menthadienol or olivetol has reacted or been consumed) or when an operation (treatment) to slow down (quench) the reaction is performed.

[0086] For example, in the case of stepwise mixing as described above, the start of the reaction is defined as the time when mixing begins, and in the case of the reaction being carried out under heating, the end of the reaction is defined as the time when heating is stopped or cooling is started, and the time from the start of the reaction to the end of the reaction is defined as the reaction time.

[0087] The reaction may be carried out under stirring.

[0088] The reaction may also be carried out under an inert atmosphere (for example, under nitrogen or argon).

[0089] The reaction may be carried out in a batch or continuous manner.

[0090] In the reaction, the reaction vessel is not particularly limited, and a conventional one can be used.

[0091] Through the above reaction, cannabidiol is produced (manufactured). Cannabidiol is usually obtained as a mixture containing cannabidiol (reaction mixture, reaction liquid). The present invention also encompasses such a mixture (reaction mixture).

[0092] The mixture (reaction mixture) may be concentrated (solvent removed), filtered, or the like.

[0093] In the reaction mixture [after the reaction (completion), reaction system after the reaction (completion)], the reaction rate (conversion rate) of menthadienol or olivetol [when either one of the components (e.g., olivetol) is used in excess, the other component (e.g., menthadienol)] depends on the timing of reaction completion, etc., but can be selected from a range of, for example, 20 mol% or more (e.g., 30 mol% or more, 40 mol% or more), and may be 50 mol% or more (e.g., 60 mol% or more), preferably 70 mol% or more (e.g., 80 mol% or more), more preferably 90 mol% or more (e.g., 95 mol% or more), or may be 97 mol% or more (e.g., 98 mol% or more, 99 mol% or more, 100 mol%).

[0094] In the reaction mixture, the production rate (yield) of cannabidiol (CBD) can be selected from a range of, for example, 10 mol% or more (e.g., 15 mol% or more), and may be 20 mol% or more (e.g., 25 mol% or more), preferably 30 mol% or more (e.g., 35 mol% or more), more preferably 40 mol% or more (e.g., 45 mol% or more), and particularly 50 mol% or more (e.g., 52 mol% or more, 55 mol% or more, 58 mol% or more, 60 mol% or more).

[0095] The (upper limit of) CBD production rate can be selected from a range of, for example, about 99 mol% or less (e.g., 97 mol% or less, 95 mol% or less, 90 mol% or less), and may typically be 85 mol% or less (e.g., 80 mol% or less, 75 mol% or less, 70 mol% or less, 65 mol% or less), etc.

[0096] The CBD production rate refers to the proportion (mol %) of menthadienol or olivetol that produced cannabidiol (reacted to become cannabidiol) out of the menthadienol or olivetol used as raw material (if either component (e.g., olivetol) is used in excess, the other component (e.g., menthadienol)).

[0097] (Mixture composition) The mixture (particularly the reaction mixture) contains CBD and other ingredients, as described above.

[0098] In a mixture (e.g., a reaction mixture), the proportion of CBD relative to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC [e.g., the proportion based on the HPLC (high performance liquid chromatography) area (or peak area, e.g., the area measured at a measurement wavelength of 210 nm; the same applies hereinafter to the HPLC area)] can be selected from a range of, for example, 10% or more (e.g., 15% or more), and may be 20% or more (e.g., 25% or more), preferably 30% or more (e.g., 35% or more), more preferably 40% or more (e.g., 45% or more), particularly 50% or more (e.g., 52% or more, 55% or more, 58% or more, 60% or more), or may be 99% or less (e.g., 97% or less, 95% or less, 90% or less, 85% or less, 80% or less, 75% or less, 70% or less, 65% or less), etc.

[0099] When a mixture (such as a reaction mixture) contains olivetol, the proportion of olivetol (e.g., the proportion based on HPLC area) relative to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture can be selected from a range of, for example, 0.1% or more (e.g., 0.5% or more), and may be 1% or more (e.g., 2% or more), preferably 3% or more (e.g., 4% or more), more preferably 5% or more (e.g., 6% or more), particularly 7% or more (e.g., 8% or more, 9% or more, 10% or more, 11% or more, 12% or more), or may be 50% or less (e.g., 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 22% or less, 20% or less, 18% or less, 15% or less), etc.

[0100] When a mixture (such as a reaction mixture) contains abn-CBD, the proportion of abn-CBD (e.g., the proportion on an HPLC area basis) relative to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture can be selected from a range of, for example, 0.1% or more (e.g., 0.5% or more), and may be 1% or more (e.g., 2% or more), preferably 3% or more (e.g., 4% or more), more preferably 5% or more (e.g., 6% or more), particularly 7% or more (e.g., 8% or more, 9% or more, 10% or more, 11% or more, 12% or more), or may be 70% or less (e.g., 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 22% or less, 20% or less, 18% or less, 15% or less), etc.

[0101] When a mixture (such as a reaction mixture) contains olivetol and abn-CBD, the proportion of olivetol and abn-CBD relative to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (e.g., the proportion based on HPLC area) can be selected from a range of, for example, 0.2% or more (e.g., 1% or more), and may be 2% or more (e.g., 4% or more), preferably 5% or more (e.g., 8% or more), more preferably 10% or more (e.g., 12% or more), particularly 15% or more (e.g., 16% or more, 18% or more, 20% or more, 22% or more, 24% or more, 25% or more), or may be 80% or less (e.g., 70% or less, 65% or less, 60% or less, 55% or less, 50% or less, 45% or less, 40% or less, 35% or less, 30% or less), etc.

[0102] When a mixture (such as a reaction mixture) contains a 2:1 adduct, the ratio of the 2:1 adduct to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (e.g., the ratio based on the area of HPLC) can be selected from a range of, for example, 0.01% or more (e.g., 0.05% or more), 0.1% or more (e.g., 0.3% or more), preferably 0.5% or more (e.g., 0.7% or more), more preferably 1% or more (e.g., 1.2% or more), particularly 1.5% or more (e.g., , 1.8% or more, 2% or more, 2.2% or more, 2.5% or more, 2.8% or more, 3% or more, 3.2% or more, 3.5% or more, 3.8% or more, 4% or more, 4.2% or more, 4.5% or more, 4.8% or more, 5% or more, 5.2% or more, 5.5% or more), or it may be 50% or less (for example, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 22% or less, 20% or less, 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5.5% or less), etc.

[0103] When a mixture (such as a reaction mixture) contains Δ9-THC, the ratio of Δ9-THC to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (e.g., the ratio based on the area of HPLC) can be selected from a range of, for example, 0.01% or more (e.g., 0.03% or more), 0.05% or more (e.g., 0.1% or more), preferably 0.2% or more (e.g., 0.3% or more), and more preferably 0.5% or more (e.g., 0.7% or more), particularly 0.8% or more (e.g., 1% or more, 1.2% or more, 1.3% or more, 1.4% or more, 1.5% or more, 1.6% or more, 1.7% or more, 1.8% or more, 1.9% or more, 2% or more), or 20% or less (e.g., 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3% or less, 2.8% or less, 2.5% or less, 2.2% or less), etc.

[0104] When the mixture (such as a reaction mixture) contains Δ8-THC, the ratio of Δ8-THC to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (e.g., the ratio based on the HPLC area) can be selected from a range of, for example, 0.001% or more (e.g., 0.005% or more), 0.01% or more (e.g., 0.03% or more), preferably 0.05% or more (e.g., 0.07% or more), More preferably, it may be 0.1% or more (e.g., 0.12% or more), particularly 0.15% or more (e.g., 0.18% or more, 0.2% or more, 0.22% or more, 0.25% or more), or it may be 10% or less (e.g., 5% or less, 3% or less, 2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.55% or less, 0.5% or less, 0.45% or less, 0.4% or less, 0.35% or less, 0.3% or less), etc.

[0105] When a mixture (such as a reaction mixture) contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (for example, the ratio based on the HPLC area) can be selected from a range of, for example, 0.01% or more (for example, 0.03% or more), 0.05% or more (for example, 0.1% or more), preferably 0.2% or more (for example, 0.3% or more), and more preferably 0.5% or more (for example, , 0.7% or more), particularly 0.8% or more (e.g., 1% or more, 1.2% or more, 1.3% or more, 1.4% or more, 1.5% or more, 1.6% or more, 1.7% or more, 1.8% or more, 1.9% or more, 2% or more, 2.1% or more, 2.2% or more), or 20% or less (e.g., 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3.2% or less, 3% or less, 2.8% or less, 2.5% or less), etc.

[0106] When the mixture (such as a reaction mixture) contains olivetol, the ratio of olivetol to CBD in the mixture (i.e., the ratio of olivetol / CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 10 or less (e.g., 8 or less), and can be 5 or less (e.g., 4 or less), preferably 3 or less (e.g., 2.8 or less), more preferably 2.5 or less (e.g., 2.2 or less), and particularly preferably 2 or less (e.g., 1.8 or less, 1.5 or less, 1.6 or less). 2 or less, 1 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.32 or less, 0.3 or less, 0.28 or less, 0.25 or less, 0.22 or less), or it may be 0.001 or more (e.g., 0.005 or more, 0.01 or more, 0.03 or more, 0.05 or more, 0.07 or more, 0.08 or more, 0.1 or more, 0.12 or more, 0.15 or more, 0.18 or more, 0.2 or more), etc.

[0107] When a mixture (such as a reaction mixture) contains abn-CBD, the ratio of abn-CBD to CBD in the mixture (i.e., ratio of abn-CBD / ratio of CBD) (e.g., ratio based on HPLC area) can be selected from a range of, for example, about 10 or less (e.g., 8 or less), and can be 5 or less (e.g., 4 or less), preferably 3 or less (e.g., 2.8 or less), more preferably 2.5 or less (e.g., 2.2 or less), particularly 2 or less (e.g., 1.8 or less, 1.5 or less, 1.6 or less, 1.8 or less, 1.9 ... 0.2 or less, 1 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.32 or less, 0.3 or less, 0.28 or less, 0.25 or less, 0.22 or less, 0.2 or less), or it may be 0.001 or more (e.g., 0.005 or more, 0.01 or more, 0.03 or more, 0.05 or more, 0.07 or more, 0.08 or more, 0.1 or more, 0.12 or more, 0.15 or more, 0.18 or more), etc.

[0108] When a mixture (such as a reaction mixture) contains olivetol and abn-CBD, the ratio of olivetol and abn-CBD to CBD in the mixture (i.e., the sum of (the ratio of olivetol and the ratio of abn-CBD) / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected, for example, from a range of about 20 or less (e.g., 15 or less), and is preferably 10 or less (e.g., 8 or less), preferably 6 or less (e.g., 5.5 or less), and more preferably 5 or less (e.g., 4. 5 or less), particularly 4 or less (e.g., 3.5 or less, 3 or less, 2.5 or less, 2 or less, 1.8 or less, 1.6 or less, 1.5 or less, 1.2 or less, 1 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less), or it may be 0.002 or more (e.g., 0.01 or more, 0.02 or more, 0.05 or more, 0.1 or more, 0.15 or more, 0.18 or more, 0.2 or more, 0.25 or more, 0.3 or more, 0.35 or more, 0.4 or more), etc.

[0109] When the mixture (such as a reaction mixture) contains a 2:1 adduct, the ratio of the 2:1 adduct to CBD in the mixture (i.e., the ratio of the 2:1 adduct / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected from a range of about 3 or less (e.g., 2.5 or less), and may be 2 or less (e.g., 1.5 or less), preferably 1 or less (e.g., 0.8 or less), more preferably 0.5 or less (e.g., 0.3 or less), particularly 0.2 or less (e.g., 0.18 or less, 0.15 or less, 0.12 or less, 0.1 or less, 0.09 or less), or may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more), etc.

[0110] When a mixture (such as a reaction mixture) contains abn-CBD and a 2:1 adduct, the ratio of abn-CBD and the 2:1 adduct to CBD in the mixture (i.e., (the sum of the ratio of abn-CBD and the ratio of the 2:1 adduct) / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected, for example, from a range of about 15 or less (e.g., 12 or less), and is preferably 10 or less (e.g., 8 or less), preferably 5 or less (e.g., 4 or less), more preferably 3 or less (e.g., 2.8 or less), and particularly preferably 2.5 or less (e.g., 2. It may be 1 or less, 2 or less, 1.8 or less, 1.5 or less, 1.2 or less, 1 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.32 or less, 0.3 or less), or it may be 0.001 or more (e.g., 0.005 or more, 0.01 or more, 0.03 or more, 0.05 or more, 0.07 or more, 0.08 or more, 0.1 or more, 0.12 or more, 0.15 or more, 0.18 or more, 0.2 or more, 0.22 or more, 0.25 or more, 0.28 or more), etc.

[0111] When the mixture (reaction mixture, etc.) contains Δ9-THC, the ratio of Δ9-THC to CBD in the mixture (i.e., the ratio of Δ9-THC / CBD) (e.g., the ratio based on the HPLC area) can be selected from a range of, for example, about 1 or less (e.g., 0.8 or less), 0.5 or less (e.g., 0.4 or less), preferably 0.3 or less (e.g., 0.28 or less), more preferably 0.25 or less (e.g., 0.22 or less), particularly 0.2 or less (e.g., 0.18 or less, 0.15 or less, 0.12 or less). , 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.055 or less, 0.05 or less, 0.045 or less, 0.04 or less, 0.035 or less), or it may be 0.0001 or more (for example, 0.0005 or more, 0.001 or more, 0.003 or more, 0.005 or more, 0.007 or more, 0.008 or more, 0.012 or more, 0.015 or more, 0.018 or more, 0.02 or more, 0.022 or more, 0.025 or more, 0.028 or more, 0.03 or more), etc.

[0112] When the mixture (reaction mixture, etc.) contains Δ8-THC, the ratio of Δ8-THC to CBD in the mixture (i.e., the ratio of Δ8-THC / CBD) (e.g., the ratio based on the HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.08 or less), 0.05 or less (e.g., 0.04 or less), preferably 0.03 or less (e.g., 0.028 or less), more preferably 0.025 or less (e.g., 0.022 or less), particularly 0.02 or less (e.g., 0.018 or less, 0.015 or less, 0.012 or less, 0.016 or less, 0.018 or less, 0.019 or less, 0.020 or less, 0.021 or less, 0.022 or less, 0.023 or less, 0.024 or less, 0.025 or less, 0.026 or less, 0.027 or less, 0.028 or less, 0.029 ... It may be 0.01 or less, 0.009 or less, 0.008 or less, 0.007 or less, 0.006 or less, 0.0055 or less, 0.005 or less, 0.0045 or less, 0.004 or less), or it may be 0.00001 or more (e.g., 0.00005 or more, 0.0001 or more, 0.0003 or more, 0.0005 or more, 0.0007 or more, 0.0008 or more, 0.0012 or more, 0.0015 or more, 0.0018 or more, 0.002 or more, 0.0022 or more, 0.0025 or more, 0.0028 or more, 0.003 or more), etc.

[0113] When a mixture (such as a reaction mixture) contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to CBD in the mixture [i.e., (the sum of the ratio of Δ9-THC and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio based on the HPLC area) can be selected, for example, from a range of about 1 or less (e.g., 0.8 or less), and can be 0.5 or less (e.g., 0.4 or less), preferably 0.3 or less (e.g., 0.28 or less), more preferably 0.25 or less (e.g., 0.22 or less), particularly 0.2 or less (e.g., 0.18 or less, 0.25 or less). 0.15 or less, 0.12 or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.055 or less, 0.05 or less, 0.045 or less, 0.04 or less), or it may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.003 or more, 0.005 or more, 0.007 or more, 0.008 or more, 0.01 or more, 0.012 or more, 0.015 or more, 0.018 or more, 0.02 or more, 0.022 or more, 0.025 or more, 0.028 or more, 0.03 or more, 0.032 or more, 0.035 or more), etc.

[0114] In the mixture (reaction mixture, etc.), the ratio of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., (the sum of the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 30 or less (e.g., 25 or less), and is preferably 20 or less (e.g., 15 or less), preferably 10 or less (e.g., 8 or less), more preferably 5 or less (e.g., 4 or less), and particularly preferably 3 or less (e.g., 2 0.8 or less, 2.5 or less, 2.2 or less, 2 or less, 1.9 or less, 1.8 or less, 1.7 or less, 1.6 or less, 1.5 or less, 1.4 or less, 1.3 or less, 1.2 or less, 1.1 or less, 1 or less, less than 1, 0.95 or less, 0.9 or less, 0.85 or less, 0.8 or less, 0.75 or less), or it may be 0.001 or more (e.g., 0.01 or more, 0.03 or more, 0.05 or more, 0.1 or more, 0.15 or more, 0.2 or more, 0.25 or more, 0.3 or more, 0.35 or more, 0.4 or more, 0.45 or more, 0.5 or more, 0.55 or more, 0.6 or more, 0.65 or more, 0.7 or more), etc.

[0115] In a mixture (such as a reaction mixture), the ratio of abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of (the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 20 or less (e.g., 15 or less), and is preferably 10 or less (e.g., 8 or less), preferably 5 or less (e.g., 4 or less), more preferably 3 or less (e.g., 2.5 or less), and particularly preferably 2 or less (e.g., 1. 9 or less, 1.8 or less, 1.7 or less, 1.6 or less, 1.5 or less, 1.4 or less, 1.3 or less, 1.2 or less, 1.1 or less, 1 or less, less than 1, 0.95 or less, 0.9 or less, 0.85 or less, 0.8 or less, 0.75 or less, 0.7 or less, 0.65 or less, 0.6 or less, 0.55 or less), or it may be 0.001 or more (e.g., 0.005 or more, 0.01 or more, 0.02 or more, 0.05 or more, 0.1 or more, 0.15 or more, 0.2 or more, 0.25 or more, 0.3 or more, 0.35 or more, 0.4 or more, 0.45 or more, 0.5 or more), etc.

[0116] (Adsorption treatment (adsorption process, first purification process)) As noted above, the mixture (particularly the reaction mixture) includes components other than CBD.

[0117] Therefore, such a mixture may be further purified (CBD may be purified from the reaction mixture (components other than CBD (e.g., at least by-products) may be separated)).

[0118] The purification method (CBD purification (separation) method, purification technology, purification technique) is not particularly limited, and conventional methods (e.g., extraction, crystallization, recrystallization, distillation, chromatography, filtration, concentration) may be used.

[0119] On the other hand, according to the investigations of the present inventors, it appears that it is difficult to efficiently purify CBD simply by using conventional methods due to factors such as the similarity of structures and crystallization conditions, the difficulty of separating CBD from by-products and olivetol due to the fact that CBD is a highly polar component, CBD is easily soluble in a variety of solvents, and olivetol is likely to interfere with the crystallization of CBD.

[0120] In this regard, the mixture (reaction mixture) discovered by the inventors as described above makes it possible to relatively suppress the production of by-products (and thus to obtain a mixture with relatively few by-products (few relative to CBD)). Therefore, efficient purification is possible by using such a mixture (for example, a reaction mixture obtained by the method of the present invention).

[0121] The present inventors have discovered a method for more efficiently purifying such mixtures (mixtures in which the production of by-products is relatively suppressed, or mixtures in which the by-products are relatively small (low relative to CBD)) by adsorption treatment. This adsorption treatment (adsorption step (first purification step)) is described in detail below.

[0122] First, the mixture (reaction mixture, etc.) is subjected to adsorption treatment.

[0123] Such adsorption treatment appears to facilitate relatively efficient separation (selective separation (separation by adsorption) of by-products, particularly olivetol and abn-CBD.) Therefore, such adsorption treatment is particularly effective for mixtures containing (particularly containing relatively large amounts of) olivetol and abn-CBD (components that are at least one selected from olivetol and abn-CBD).

[0124] In particular, according to the inventors' investigations, olivetol is a highly polar component and tends to interfere with the crystallization of CBD, making the purification of CBD difficult or complicated. Therefore, it appears preferable to separate olivetol to a high degree (as much as possible). In particular, such adsorption treatment can be suitably carried out on mixtures that contain at least olivetol (especially those that contain a relatively large amount of olivetol).

[0125] The mixture (the mixture to be subjected to the adsorption treatment) may be a mixture containing a solvent (it may be a solvent mixture), such as the reaction mixture obtained by the method described above.

[0126] Examples of solvents include hydrocarbons [for example, aliphatic hydrocarbons (e.g., pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, methylcyclohexane, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene, etc.)], halogenated solvents (e.g., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), esters (e.g., aliphatic esters such as methyl acetate, ethyl acetate, butyl acetate, etc.), carbonates (e.g., ethylene carbonate, propylene carbonate, etc.), ethers [for example, chain ethers (e.g., diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (e.g., tetrahydrofuran, dioxane, etc.)]. , glycol ethers (e.g., ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol monomethyl ether, diethylene glycol monoethyl ether, etc.), glycol ether esters (e.g., ethylene glycol monomethyl ether acetate, etc.), nitrogen-containing solvents {e.g., amides [e.g., N-substituted chain amides (e.g., N-alkyl-substituted alkanamides such as N,N-dimethylformamide), cyclic amides (e.g., 2-pyrrolidone, etc.)], etc.}, nitriles (e.g., acetonitrile, etc.), sulfur-containing solvents (e.g., sulfoxides such as dimethyl sulfoxide; sulfones such as dimethyl sulfone and sulfolane), alcohols [e.g., alkanols (e.g., methanol, ethanol, isopropanol), etc.], polyols (e.g., alkanediols such as ethylene glycol and propylene glycol; glycerin, etc.), etc.], water, etc.

[0127] The solvents may be used alone or in combination of two or more.

[0128] Among these solvents, from the viewpoint of efficient separation (separation by adsorption treatment) of by-products (e.g., olivetol, abn-CBD, etc., particularly at least olivetol), aprotic solvents (e.g., aprotic solvents with low polarity) may be preferably used, and in particular, hydrocarbons (e.g., aliphatic hydrocarbons) may be preferably used.

[0129] Therefore, the solvent may contain at least an aprotic solvent or a hydrocarbon, and in particular may contain at least an aliphatic hydrocarbon {for example, an aliphatic hydrocarbon such as pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, or methylcyclohexane [for example, an aliphatic hydrocarbon having 5 or more carbon atoms (for example, 5 to 18 carbon atoms, 6 to 12 carbon atoms, 6 to 10 carbon atoms, etc.) (for example, a chain or cyclic aliphatic hydrocarbon, saturated or unsaturated hydrocarbon, or a chain or cyclic saturated aliphatic hydrocarbon)], etc.}.

[0130] When the solvent contains an aliphatic hydrocarbon, the proportion of the aliphatic hydrocarbon (e.g., heptane, etc.) relative to the entire solvent may be selected from the range of, for example, 1 vol% or more (e.g., 3 vol% or more), preferably 5 vol% or more (e.g., 10 vol% or more), and more preferably about 15 vol% or more (e.g., 20 vol% or more), and may be 25 vol% or more [e.g., 30 vol% or more, 35 vol% or more, 40 vol% or more, 50 vol% or more, more than 50 vol%, 60 vol% or more, 70 vol% or more, 80 vol% or more, 85 vol% or more, 90 vol% or more, 95 vol% or more, or (substantially) 100 vol% (almost) only aliphatic hydrocarbons].

[0131] Aliphatic hydrocarbons may be used in combination with other solvents (solvents other than aliphatic hydrocarbons, for example, aromatic hydrocarbons such as toluene). In such cases, the proportion of the other solvent in the total solvent may be, for example, 99% by volume or less (e.g., 97% by volume or less), preferably 95% by volume or less (e.g., 90% by volume or less), more preferably about 85% by volume or less (e.g., 80% by volume or less, 75% by volume or less, 70% by volume or less, 65% by volume or less), or may be 1% by volume or more (e.g., 3% by volume or more, 5% by volume or more, 10% by volume or more, 15% by volume or more, 20% by volume or more, 25% by volume or more, 30% by volume or more, 35% by volume or more), etc.

[0132] The solvent may or may not contain a protic solvent (e.g., water, alcohols, etc.); however, from the viewpoint of efficient separation (separation by adsorption treatment) of by-products (e.g., olivetol, abn-CBD, etc., particularly at least olivetol), the solvent may preferably contain no protic solvent or may contain only a small amount of water [e.g., 10% by volume or less of the solvent (e.g., 5% by volume or less, 3% by volume or less, 1% by volume or less, 0.5% by volume or less, 0.1% by volume or less)]. In particular, the solvent may contain no water or may contain only a small amount of water [e.g., 10% by volume or less of the solvent (e.g., 5% by volume or less, 3% by volume or less, 1% by volume or less, 0.5% by volume or less, 0.1% by volume or less)].

[0133] In a mixture containing a solvent, the proportion (concentration) of components other than the solvent (solid content) relative to the total amount of the solvent and components other than the solvent may be, for example, about 0.1% by mass or more (e.g., 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more), or may be 99% by mass or less (e.g., 95% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 12% by mass or less, 10% by mass or less), etc.

[0134] In a mixture containing a solvent, the ratio of solvent to CBD1 may be about 0.01 or more (e.g., 0.05 or more, 0.1 or more, 0.3 or more, 0.5 or more) on a volume basis, or may be 1000 or less (e.g., 800 or less, 500 or less, 300 or less, 200 or less, 150 or less, 120 or less, 100 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less), etc.

[0135] The mixture containing the solvent can be prepared by an appropriate method depending on the reaction mixture used, the type and amount of solvent, etc. For example, when the reaction mixture is one from which the reaction solvent (the solvent used in the reaction) has been separated (removed), the mixture can be prepared by mixing the solvents. In addition, when the reaction mixture is one containing the reaction solvent, if the reaction solvent and the adsorption solvent (the solvent used in the adsorption treatment) are different, the reaction solvent may be separated (for example, by concentration) and then mixed with the solvent used in the adsorption treatment; if the reaction solvent is the same, the reaction solvent may be used as the adsorption solvent as is; and if the amounts (ratios) of the solvents are different even when the solvents are the same, the amount of the solvent may be adjusted appropriately (for example, by concentration or mixing).

[0136] The adsorption treatment method is not particularly limited, but typically involves contacting an adsorbent (adsorption means) with a mixture (particularly a mixture containing a solvent).

[0137] Examples of adsorbents include silica (silica gel), alumina (activated alumina), zeolite, celite, diatomaceous earth, clay, activated clay, activated carbon, synthetic adsorbents, and ion exchange resins (activated alumina ion exchange resins, etc.).

[0138] Among these, silica may be preferably used from the viewpoint of efficient separation (selective separation) of by-products (for example, olivetol, abn-CBD, etc., particularly at least olivetol).

[0139] The shape of the adsorbent (silica, etc.) is not particularly limited, but examples thereof include granular shapes, and granular shapes include spherical shapes.

[0140] When the adsorbent is in a granular form, the particle size is not particularly limited, but may be, for example, an average particle size of 1 to 500 μm (eg, 3 to 300 μm, 5 to 100 μm).

[0141] The adsorbents may be used alone or in combination of two or more.

[0142] The amount of adsorbent (amount used) may be selected depending on the adsorption treatment method (mode of adsorption treatment), the type of adsorbent (adsorption capacity), the amount of by-products, etc., and is not particularly limited. For example, it may be selected from a range of about 0.01 parts by mass or more (e.g., 0.05 parts by mass or more, 0.1 parts by mass or more, 0.15 parts by mass or more) per 1 part by mass of CBD [or solids contained in the mixture (components other than the solvent)], or may be 0.2 parts by mass or more (e.g., 0.25 parts by mass or more), preferably 0.3 parts by mass or more (e.g., 0.35 parts by mass or more), and more preferably 0.4 parts by mass or more (e.g., 0.45 parts by mass or more, 0.5 parts by mass or more).

[0143] The amount (upper limit) of the adsorbent is not particularly limited, but may be selected from a range of about 300 parts by mass or less (e.g., 100 parts by mass or less) relative to 1 part by mass of CBD [or solids (components other than the solvent) contained in the mixture], or may be 80 parts by mass or less (e.g., 50 parts by mass or less), preferably 30 parts by mass or less (e.g., 20 parts by mass or less), and more preferably 10 parts by mass or less (e.g., 8 parts by mass or less, 5 parts by mass or less, 3 parts by mass or less, 2 parts by mass or less, 1 part by mass or less).

[0144] The adsorption treatment method (method of contacting the adsorbent with the mixture) is not particularly limited and can be appropriately selected depending on the form of the adsorbent, etc., and may be, for example, a method of mixing the adsorbent with the mixture, a method of passing the mixture through an adsorbent (for example, a method of passing the mixture through an adsorbent fixed by appropriate means (for example, a column packed with the adsorbent)), a method of combining these, or the like.

[0145] Among these, from the viewpoint of efficient separation of by-products (for example, olivetol, abn-CBD, etc., particularly at least olivetol), a method of mixing the adsorbent with the mixture may be preferably used.

[0146] The mixing may be carried out under stirring.

[0147] The mixing may also be carried out in an inert atmosphere (for example, under nitrogen or argon).

[0148] The container used for mixing is not particularly limited, and a conventional container can be used.

[0149] The adsorption treatment conditions are not particularly limited and can be appropriately selected depending on the amount, type, etc. of the adsorbent. For example, adsorption may be carried out at room temperature (or normal temperature), under heating, or under cooling. Specific adsorption temperatures include, for example, -30°C to 80°C (e.g., 0 to 60°C, 5 to 50°C, 10 to 40°C). The adsorption treatment time (e.g., the time for contacting the adsorbent with the mixture) can be selected depending on the type of adsorbent, the mode of the adsorption method, and the like, and is not particularly limited. For example, the time may be about 1 minute or more (e.g., 3 minutes or more), preferably 5 minutes or more (e.g., 10 minutes or less), more preferably 20 minutes or more (e.g., 30 minutes or more), or may be 24 hours or less (e.g., 12 hours or less, 6 hours or less, 3 hours or less), etc.

[0150] After the adsorption treatment, the adsorbent may be separated (for example, the adsorbent may be separated from a mixture containing the adsorbent) depending on the adsorption treatment (method), etc. The separation method can be appropriately selected depending on the adsorbent and the mode of the adsorption treatment, and examples thereof include filtration, decantation, etc.

[0151] The adsorbent may be washed (washed) as needed, and the washing solution (or solids (at least CBD, etc.) recovered from the washing solution (e.g., recovered by concentration, etc.)) may be mixed with the adsorption-treated mixture. This method (washing step) can also recover CBD, etc. from the adsorbent (e.g., CBD that has adhered to the adsorbent (not adsorbed)). Therefore, after the adsorption treatment, a further washing step (a step of washing the adsorbent (recovering CBD, etc.)) may be performed.

[0152] The washing solvent is not particularly limited, and the solvents exemplified above may be used. Preferred embodiments of the solvent are also the same as those described above. For example, hydrocarbons (particularly, aliphatic hydrocarbons), preferably solvents containing at least aliphatic hydrocarbons (e.g., aliphatic hydrocarbons, or aliphatic and aromatic hydrocarbons), may be used.

[0153] The amount of the washing solvent used can be appropriately selected depending on the amount of the adsorbent, etc.

[0154] After the adsorption treatment (and further washing treatment), the solvent (or solvent components, for example, the adsorption solvent, washing solvent, etc.) may be separated (by concentration, etc.) as needed.

[0155] Through the above-described steps [adsorption treatment (adsorption treatment step), and further, if necessary, a washing step, etc.], a purified product containing CBD [sometimes referred to as a first purified product, a crude product, etc. (in relation to the purified product described below)] can be obtained {the mixture can be purified [components other than CBD (particularly, at least one component selected from olivetol and abn-CBD) can be separated (selectively separated)] from the mixture}. The present invention also encompasses such purified products (first purified product, crude product) containing CBD.

[0156] Furthermore, even after undergoing adsorption treatment, etc., CBD can be almost completely recovered. For example, when the mass of CBD in the mixture (the mixture subjected to adsorption treatment) is A1 and the mass of CBD in the first purified product is A2, the value of A2 / A1 can be selected from a range of, for example, approximately 0.5 or more (e.g., 0.6 or more), and may be approximately 0.7 or more (e.g., 0.75 or more, 0.8 or more, 0.85 or more, 0.88 or more, 0.9 or more, 0.92 or more, 0.95 or more, 0.96 or more, 0.97 or more, 0.98 or more, 0.99 or more, or substantially 1).

[0157] In the first purified product, the proportion of CBD (e.g., the proportion based on the HPLC area (peak area)) relative to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC can be selected from a range of, for example, 40% or more (e.g., 45% or more), 50% or more (e.g., 52% or more), preferably 55% or more (e.g., 58% or more), more preferably 60% or more (e.g., 62% or more), and particularly preferably 65% or more. or higher (e.g., 66% or more, 67% or more, 68% or more, 69% or more, 70% or more, 71% or more, 72% or more, 73% or more, 74% or more, 75% or more, 76% or more, 77% or more, 78% or more, 79% or more, 80% or more), or 99.9% or less (e.g., 99.5% or less, 99% or less, 98% or less, 97% or less, 95% or less, 92% or less, 90% or less, 88% or less, 85% or less, 82% or less, 80% or less), etc.

[0158] When the ratio of CBD to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (e.g., the ratio based on the HPLC area (peak area)) is defined as M1, and the ratio of CBD to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (e.g., the ratio based on the HPLC area (peak area)) is defined as M2, the value of M2-M1 may be greater than 0%, or may be selected from a range of about 0.1% or more (e.g., 0.5% or more), and may be 1% or more (e.g., 1.5% or more), preferably 2% or more (e.g., 2.5% or more), more preferably 3% or more (e.g., 4% or more), and particularly 5% or more (e.g., 7% or more, 8% or more, 10% or more, 12% or more, 15% or more).

[0159] The first purified product may or may not contain olivetol, but even if it does, it often contains only a small amount. For example, in the first purified product, the ratio of olivetol to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., the ratio based on HPLC area) may be, for example, 20% or less (e.g., 15% or less, 12% or less, 10% or less, 8% or less, 5% or less, 3% or less, 2% or less, 1.5% or less, 1.2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less), etc.

[0160] In addition, when the first purified product contains olivetol, the ratio of olivetol to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (the lower limit of the ratio, for example, the ratio based on HPLC area) may be 0.0001%, 0.001%, 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, etc.

[0161] When the ratio of olivetol to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the mixture (e.g., the ratio based on the HPLC area (peak area)) is defined as M1, and the ratio of olivetol to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (e.g., the ratio based on the HPLC area (peak area)) is defined as M2, the value of M1-M2 may be greater than 0%, or may be selected from a range of about 0.01% or more (e.g., 0.1% or more, 0.3% or more, 0.5% or more), and may be 1% or more (e.g., 1.5% or more), preferably 2% or more (e.g., 2.5% or more), and more preferably 3% or more (e.g., 3.5% or more, 4% or more, 5% or more, 6% or more, 7% or more, 8% or more).

[0162] The first purified product may or may not contain abn-CBD, but even if it does, it will often contain only a small amount. For example, in the first purified product, the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 30% or less (e.g., 25% or less, 20% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less), etc.

[0163] In addition, when the first purified product contains abn-CBD, the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (lower limit of the ratio, for example, the ratio based on HPLC area) may be 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, etc.

[0164] In the mixture, the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., the ratio based on the HPLC area (peak area)) is defined as M1, and in the first purified product, the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., the ratio based on the HPLC area (peak area)) is defined as M2. The value of 1-M2 may be greater than 0%, and may be selected from a range of about 0.01% or more (e.g., 0.05% or more), and may be 0.1% or more (e.g., 0.2% or more), preferably 0.3% or more (e.g., 0.5% or more), more preferably 1% or more (e.g., 1.5% or more), particularly 2% or more (e.g., 3% or more, 3.5% or more, 4% or more, 4.5% or more, 5% or more, 5.5% or more, 6% or more, 6.5% or more, 7% or more, 7.5% or more).

[0165] The first purified product may or may not contain olivetol and abn-CBD, but even if it does, it will often contain small amounts. For example, in the first purified product, the ratio of olivetol and abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 40% or less (e.g., 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5.5% or less), etc.

[0166] In addition, when the first purified product contains olivetol and abn-CBD, the ratio of olivetol and abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (lower limit of the ratio, for example, the ratio based on HPLC area) may be 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, etc.

[0167] In the mixture, the ratio of olivetol and abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., the ratio based on the HPLC area (peak area)) is designated M1, and in the first purified product, the ratio of olivetol and abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., the ratio based on the HPLC area (peak area)) is designated M2. In this case, the value of M1-M2 may be greater than 0%, and may be selected from a range of about 0.05% or more (e.g., 0.1% or more), and may be 0.5% or more (e.g., 1% or more), preferably 2% or more (e.g., 3% or more), more preferably 5% or more (e.g., 7% or more), and particularly 8% or more (e.g., 9% or more, 10% or more, 11% or more, 12% or more, 13% or more, 14% or more, 15% or more, 16% or more, 17% or more, 18% or more, 19% or more, 20% or more).

[0168] The first purified product may contain other components (for example, by-products).

[0169] For example, when the first purified product contains the 2:1 adduct, the ratio of the 2:1 adduct to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (e.g., the ratio based on HPLC area) can be selected from a range of, for example, 0.01% or more (e.g., 0.05% or more), 0.1% or more (e.g., 0.3% or more), preferably 0.5% or more (e.g., 0.7% or more), more preferably 1% or more (e.g., 1.2% or more), and particularly preferably 1.5% or more (e.g., 1.8% or more). or more, 2% or more, 2.2% or more, 2.5% or more, 2.8% or more, 3% or more, 3.2% or more, 3.5% or more, 3.8% or more, 4% or more, 4.2% or more, 4.5% or more, 4.8% or more, 5% or more, 5.2% or more, 5.5% or more, 5.8 or more, 6 or more, 7.2 or more, 7.5 or more), or it may be 50% or less (for example, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 22% or less, 20% or less, 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less), etc.

[0170] When the first purified product contains Δ9-THC, the ratio of Δ9-THC to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (e.g., the ratio based on the HPLC area) can be selected from a range of, for example, 0.01% or more (e.g., 0.03% or more), 0.05% or more (e.g., 0.1% or more), preferably 0.2% or more (e.g., 0.3% or more), more preferably 0.5% or more (e.g., 0.7% or more), particularly 0.8% or more (e.g., , 1% or more, 1.2% or more, 1.3% or more, 1.4% or more, 1.5% or more, 1.6% or more, 1.7% or more, 1.8% or more, 1.9% or more, 2% or more, 2.1% or more, 2.2% or more, 2.3% or more, 2.4% or more, 2.5% or more, 2.6% or more, 2.7% or more, 2.8% or more), or may be 20% or less (for example, 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.5% or less, 3% or less), etc.

[0171] When the first purified product contains Δ8-THC, the ratio of Δ8-THC to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (e.g., the ratio based on the HPLC area) can be selected from a range of, for example, 0.001% or more (e.g., 0.005% or more), 0.01% or more (e.g., 0.03% or more), preferably 0.05% or more (e.g., 0.07% or more), and more preferably It may be 0.1% or more (e.g., 0.12% or more), particularly 0.15% or more (e.g., 0.2% or more, 0.25% or more, 0.3% or more, 0.35% or more, 0.4% or more, 0.45% or more, 0.5% or more, 0.55% or more, 0.6% or more, 0.65% or more, 0.7% or more), or it may be 10% or less (e.g., 8% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1.5% or less, 1% or less, 0.9% or less, 0.8% or less), etc.

[0172] When the first purified product contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC in the first purified product (e.g., ratio based on HPLC area) can be selected from the range of, for example, 0.01% or more (e.g., 0.03% or more), 0.05% or more (e.g., 0.1% or more), preferably 0.2% or more (e.g., 0.3% or more), more preferably 0.5% or more (e.g., 0.7% or more), particularly 0.8% or more (e.g., 1% or more, 1.2% or more, 1.3% or more). %, 1.4% or more, 1.5% or more, 1.6% or more, 1.7% or more, 1.8% or more, 1.9% or more, 2% or more, 2.1% or more, 2.2% or more, 2.3% or more, 2.4% or more, 2.5% or more, 2.6% or more, 2.7% or more, 2.8% or more, 2.9% or more, 3% or more, 3.1% or more, 3.2% or more, 3.3% or more, 3.4% or more, 3.5% or more, 3.6% or more), or it may be 20% or less (for example, 18% or less, 15% or less, 12% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5.5% or less, 5% or less, 4.5% or less, 4% or less), etc.

[0173] When the first purified product contains olivetol, the ratio of olivetol to CBD in the first purified product (i.e., the ratio of olivetol / CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 1 or less (e.g., 0.5 or less), and may be 0.3 or less (e.g., 0.25 or less), preferably 0.2 or less (e.g., 0.15 or less), more preferably 0.1 or less (e.g., 0.05 or less), particularly 0.03 or less (e.g., 0.02 or less, 0.01 or less, 0.009 or less, 0.008 or less, 0.007 or less, 0.006 or less), or may be 0.00001 or more (e.g., 0.00005 or more, 0.0001 or more, 0.0005 or more, 0.001 or more, 0.002 or more, 0.003 or more, 0.004 or more, 0.005 or more), etc.

[0174] When the ratio of olivetol to CBD in the mixture (i.e., the ratio of olivetol / the ratio of CBD) (e.g., the ratio based on the HPLC area (peak area)) is N1, and the ratio of olivetol to CBD in the first purified product (i.e., the ratio of olivetol / the ratio of CBD) (e.g., the ratio based on the HPLC area (peak area)) is N2, the value of N1-N2 may be greater than 0, and may be selected from a range of about 0.01 or more (e.g., 0.02 or more), and may be 0.03 or more (e.g., 0.05 or more), preferably 0.07 or more (e.g., 0.08 or more), and more preferably 0.1 or more (e.g., 0.12 or more, 0.15 or more).

[0175] When the first purified product contains abn-CBD, the ratio of abn-CBD to CBD in the first purified product (i.e., the ratio of abn-CBD / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 10 or less (e.g., 5 or less), and may be 3 or less (e.g., 2.5 or less), preferably 2 or less (e.g., 1.5 or less), more preferably 1 or less (e.g., 0.5 or less), particularly 0.3 or less (e.g., 0.2 or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less), or may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more), etc.

[0176] When the ratio of abn-CBD to CBD in the mixture (i.e., the ratio of abn-CBD / the ratio of CBD) (e.g., the ratio based on HPLC area (peak area)) is N1, and the ratio of abn-CBD to CBD in the first purified product (i.e., the ratio of abn-CBD / the ratio of CBD) (e.g., the ratio based on HPLC area (peak area)) is N2, the value of N1-N2 may be greater than 0, and may be selected from a range of about 0.01 or more (e.g., 0.02 or more), and may be 0.03 or more (e.g., 0.05 or more), preferably 0.07 or more (e.g., 0.08 or more), and more preferably 0.1 or more (e.g., 0.12 or more, 0.15 or more).

[0177] When the first purified product contains olivetol and abn-CBD, the ratio of olivetol and abn-CBD to CBD in the first purified product [i.e., (ratio of olivetol and abn-CBD) / ratio of CBD] (e.g., ratio based on HPLC area) can be selected from a range of, for example, about 10 or less (e.g., 7 or less), and may be 5 or less (e.g., 3 or less), preferably 2.5 or less (e.g., 2 or less), more preferably 1.5 or less (e.g., 1 or less), particularly 0.5 or less (e.g., 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less), or may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more), etc.

[0178] When the ratio of olivetol and abn-CBD to CBD in the mixture (i.e., (the sum of the ratio of olivetol and the ratio of abn-CBD) / the ratio of CBD) (e.g., the ratio based on the HPLC area (peak area)) is N1, and the ratio of olivetol and abn-CBD to CBD in the first purified product (i.e., (the sum of the ratio of olivetol and the ratio of abn-CBD) / the ratio of CBD) (e.g., the ratio based on the HPLC area (peak area)) is N2, the value of N1-N2 may be greater than 0, and may be selected from a range of about 0.01 or more (e.g., 0.03 or more), and may be 0.05 or more (e.g., 0.07 or more), preferably 0.1 or more (e.g., 0.15 or more), and more preferably 0.2 or more (e.g., 0.25 or more, 0.3 or more).

[0179] When the first purified product contains a 2:1 adduct, the ratio of the 2:1 adduct to CBD in the first purified product (i.e., the ratio of the 2:1 adduct / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected from a range of about 3 or less (e.g., 2.5 or less), and may be 2 or less (e.g., 1.5 or less), preferably 1 or less (e.g., 0.8 or less), more preferably 0.5 or less (e.g., 0.3 or less), particularly 0.2 or less (e.g., 0.18 or less, 0.15 or less, 0.12 or less, 0.1 or less), or may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more), etc.

[0180] When the first purified product contains abn-CBD and the 2:1 adduct, the ratio of abn-CBD and the 2:1 adduct to CBD in the first purified product (i.e., (the sum of the ratio of abn-CBD and the ratio of 2:1 adduct) / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 10 or less (e.g., 8 or less), and may be 5 or less (e.g., 4 or less), preferably 3 or less (e.g., 2 or less), more preferably 1 or less (e.g., 0.8 or less), particularly 0.5 or less (e.g., 0.4 or less, 0.3 or less, 0.2 or less, 0.15 or less), or may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.01 or more, 0.05 or more, 0.07 or more, 0.08 or more, 0.1 or more, 0.12 or more), etc.

[0181] When the first purified product contains Δ9-THC, the ratio of Δ9-THC to CBD in the first purified product (i.e., the ratio of Δ9-THC / CBD) (e.g., the ratio based on the HPLC area) can be selected, for example, from a range of about 1 or less (e.g., 0.8 or less), and can be 0.5 or less (e.g., 0.4 or less), preferably 0.3 or less (e.g., 0.28 or less), more preferably 0.25 or less (e.g., 0.22 or less), particularly 0.2 or less (e.g., 0.18 or less, 0.15 or less, 0.12 or less). or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.055 or less, 0.05 or less, 0.045 or less, 0.04 or less), or it may be 0.0001 or more (for example, 0.0005 or more, 0.001 or more, 0.003 or more, 0.005 or more, 0.007 or more, 0.008 or more, 0.012 or more, 0.015 or more, 0.018 or more, 0.02 or more, 0.022 or more, 0.025 or more, 0.028 or more, 0.03 or more), etc.

[0182] When the first purified product contains Δ8-THC, the ratio of Δ8-THC to CBD in the first purified product (i.e., the ratio of Δ8-THC / CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.08 or less), and is preferably 0.05 or less (e.g., 0.04 or less), preferably 0.03 or less (e.g., 0.028 or less), more preferably 0.025 or less (e.g., 0.022 or less), and particularly preferably 0.02 or less (e.g., 0. 0.018 or less, 0.015 or less, 0.012 or less, 0.01 or less), or 0.00001 or more (for example, 0.00005 or more, 0.0001 or more, 0.0003 or more, 0.0005 or more, 0.0007 or more, 0.0008 or more, 0.001 or more, 0.0012 or more, 0.0015 or more, 0.0018 or more, 0.002 or more, 0.0022 or more, 0.0025 or more, 0.0028 or more, 0.003 or more, 0.005 or more, 0.007 or more), etc.

[0183] When the first purified product contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to CBD in the first purified product [i.e., (the sum of the ratio of Δ9-THC and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio based on the HPLC area) can be selected, for example, from a range of about 1 or less (e.g., 0.8 or less), and can be 0.5 or less (e.g., 0.4 or less), preferably 0.3 or less (e.g., 0.28 or less), more preferably 0.25 or less (e.g., 0.22 or less), particularly 0.2 or less (e.g., 0.18 or less, 0.1 0.5 or less, 0.12 or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, 0.055 or less, 0.05 or less, 0.045 or less, 0.04 or less), or it may be 0.0001 or more (for example, 0.0005 or more, 0.001 or more, 0.003 or more, 0.005 or more, 0.007 or more, 0.008 or more, 0.01 or more, 0.012 or more, 0.015 or more, 0.018 or more, 0.02 or more, 0.022 or more, 0.025 or more, 0.028 or more, 0.03 or more, 0.032 or more, 0.035 or more), etc.

[0184] In the first purified product, the ratio of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., (the sum of the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio based on the HPLC area) can be selected, for example, from a range of about 20 or less (e.g., 10 or less), and is preferably 5 or less (e.g., 4 or less), preferably 3 or less (e.g., 2 or less), and more preferably It may be 1.5 or less (e.g., 1.2 or less), particularly 1 or less (e.g., less than 1, 0.95 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.3 or less, 0.25 or less), or it may be 0.0001 or more (e.g., 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.05 or more, 0.08 or more, 0.1 or more, 0.12 or more, 0.15 or more, 0.18 or more, 0.2 or more), etc.

[0185] In the mixture, the ratios of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of (the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio on an HPLC area basis) were designated N1, and in the first purified product, the ratios of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of (the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC] / the ratio of CBD] (e.g., the ratio on an HPLC area basis) were designated N2. When N2 is the ratio of CBD to CBD (e.g., the ratio based on HPLC area), the value of N1-N2 may be greater than 0, and may be selected from a range of about 0.01 or more (e.g., 0.02 or more), and may be 0.03 or more (e.g., 0.05 or more), preferably 0.07 or more (e.g., 0.08 or more), and more preferably 0.1 or more (e.g., 0.12 or more, 0.15 or more, 0.18 or more, 0.2 or more, 0.22 or more, 0.25 or more, 0.28 or more, 0.3 or more).

[0186] In the first purified product, the ratio of abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of (the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio based on the HPLC area) can be selected from a range of, for example, about 15 or less (e.g., 10 or less), and is preferably 5 or less (e.g., 4 or less), preferably 3 or less (e.g., 2 or less), and more preferably 1.5 or less (e.g., It may be 1.2 or less), particularly 1 or less (for example, less than 1, 0.95 or less, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.5 or less, 0.45 or less, 0.4 or less, 0.35 or less, 0.3 or less, 0.25 or less), or it may be 0.0001 or more (for example, 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, 0.05 or more, 0.08 or more, 0.1 or more, 0.12 or more, 0.15 or more, 0.18 or more, 0.2 or more), etc.

[0187] In the mixture, the ratio of abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / CBD] (e.g., the ratio based on HPLC area) was designated N1. In the first purified product, the ratio of abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and Δ8-THC] / CBD] (e.g., the ratio based on HPLC area) was designated N2. When the ratio of the surface area of LC to the surface area of the polymer is N2, the value of N1-N2 may be greater than 0, and may be selected from a range of about 0.01 or more (e.g., 0.02 or more), and may be 0.03 or more (e.g., 0.05 or more), preferably 0.07 or more (e.g., 0.08 or more), and more preferably 0.1 or more (e.g., 0.12 or more, 0.15 or more, 0.18 or more, 0.2 or more, 0.22 or more, 0.25 or more, 0.28 or more, 0.3 or more, 0.32 or more, 0.35 or more, 0.38 or more, 0.4 or more, 0.42 or more, 0.45 or more, 0.48 or more, 0.5 or more).

[0188] As described above, by going through the adsorption process, components other than CBD (particularly olivetol and abn-CBD) can be separated, and a purified product containing CBD can be obtained.

[0189] In such a purified product, components other than CBD are separated, but the product may be subjected to further purification (sometimes referred to as second purification, etc.), which may result in a higher level of CBD purification. Such second purification (purification step) is not particularly limited and conventional purification techniques can be used, but the inventors have discovered a method that can further efficiently purify CBD from such a purified product containing CBD (particularly the first purified product obtained through adsorption treatment). Such second purification will be described below.

[0190] [Second purification process] As described above, by going through the adsorption process, components other than CBD (particularly olivetol and abn-CBD) can be separated (highly separated and purified), and a purified product containing CBD [first purified product, crude product, crude cannabidiol (crude CBD)] can be obtained, but such separation (purification) can also be carried out by a different method (sometimes called second purification, etc.).

[0191] That is, a solvate of CBD can be formed in a mixture containing CBD, and the CBD can be purified. In addition, solvates of CBD can also be desolvated to produce (regenerate) CBD (purify CBD).

[0192] This method (another method, another purification method, second purification) will be described below.

[0193] In a solvate of CBD, the solvent (which may be referred to as a solvent of the solvate, a solvent that forms the solvate, solvent S1, etc.) may typically include an aprotic polar solvent.

[0194] Specific examples of the solvent (solvent S1) in the solvate of CBD include nitrogen-containing solvents {e.g., amides [amide-based solvents, e.g., N-substituted chain amides (e.g., N-substituted (e.g., N-alkyl) alkanamides such as N,N-dimethylformamide and N,N-dimethylacetamide; N,N-diphenylacetamide; cyclic amides (e.g., 2-pyrrolidone and 1,3-dimethyl-2-imidazolidinone); etc.], nitriles (e.g., acetonitrile); etc.}, sulfur-containing solvents (e.g., sulfoxides such as dimethyl sulfoxide; sulfones such as dimethyl sulfone and sulfolane); and the like.

[0195] A solvate of CBD may include one or more solvents (e.g., aprotic polar solvents).

[0196] Furthermore, in the solvate of CBD, the solvent containing an aprotic polar solvent (solvent S1) may consist solely of an aprotic polar solvent, or may contain a solvent other than an aprotic polar solvent, and in particular may consist solely of an aprotic polar solvent.

[0197] In the solvate of CBD, preferred solvents include amides (amide-based solvents), particularly N-substituted alkanamides such as N,N-dimethylacetamide (dimethylacetamide), from the viewpoint of ease of precipitation in a mixture and ease of separation.

[0198] In the solvate of CBD, the molar ratio between CBD and the solvent (solvent S1) is not particularly limited, as long as the solvate is formed.

[0199] The solvates of CBD may in particular be crystalline (crystalline form).

[0200] An example of a solvate of CBD is a solvate of CBD with dimethylacetamide (sometimes referred to as DMA).

[0201] In a solvate solvated with dimethylacetamide (which may be referred to as CBD·DMA, a CBD·DMA solvate, CBD-DMA, etc.), the molar ratio of CBD to dimethylacetamide is not limited, and may be, for example, a solvate solvated with dimethylacetamide at a ratio of 2 moles to 1 mole of CBD (which may be referred to as CBD-2DMA, CBD·2DMA, etc.) (which may contain at least CBD-2DMA).

[0202] Such CBD-2DMA may, for example, exhibit at least one of the following physical properties (characteristics):

[0203] ·Powder X-ray (2θ) It may have at least the characteristic peak shown in (A) below, and has at least the characteristic peak shown in (B) or (C) below (characteristic peaks including the peak shown in (A) below).

[0204] (A) (approximately 5 peaks) 8.3±0.2°, 8.5±0.2°, 10.6±0.2°, 16.4±0.2°, 17.0±0.2°

[0205] (B) (approximately 10 peaks) 8.3±0.2°, 8.5±0.2°, 10.6±0.2°, 13.4±0.2°, 16.4±0.2°, 17.0±0.2°, 18.9±0.2°, 22.7±0.2°, 24.6±0.2°, 26.5±0.2°

[0206] (C) (approximately 20 peaks) 8.3±0.2°, 8.5±0.2°, 10.6±0.2°, 11.8±0.2°, 13.4±0.2°, 15.4±0.2°, 15.8±0.2°, 16.4±0.2°, 17.0±0.2°, 18.9±0.2°, 19.9±0.2°, 21.4±0.2°, 22.7±0.2°, 22.9±0.2°, 23.2±0.2°, 23.7±0.2°, 24.6±0.2°, 26.5±0.2°, 27.1±0.2°, 27.7±0.2°

[0207] · 1 H-NMR (e.g. 400MHz, CDCl3): δppm: 0.88 (t, J=7.2Hz, 3H), 1.22-1.36 (m, 2H), 1.52-1 .60(m, 2H), 1.64-1.67(m, 3H), 1.75-1.85(m, 2H), 1.78-1.80(m, 3H), 2.07-2.13(m, 2 H), 2.08(s, 6H), 2.18-2.28(m, 3H), 2.37-2.46(m, 3H), 2.94(s, 6H), 3.01(s, 6H), 3.8 2-3.87(m, 1H), 4.56(s, 1H), 4.65-4.67(m, 1H), 5.56-5.58(m, 1H), 6.13-6.30(m, 1H)

[0208] Melting point: 52-55°C [by DSC (differential scanning calorimetry)]

[0209] In addition, CBD-2DMA generally has lower solubility in various solvents such as heptane than CBD. Therefore, CBD-2DMA generally appears to crystallize more easily than CBD. Therefore, such solvates are particularly effective for efficiently separating (purifying) CBD from mixtures containing CBD and other components (e.g., by-products, olivetol).

[0210] In addition, CBD-2DMA appears to be relatively easy to release (desolvate) DMA in water, etc. Therefore, such solvates are also effective in generating (regenerating) CBD.

[0211] The solvate of CBD is not particularly limited and can be produced by contacting (mixing) CBD with a solvent for the solvate (solvent that forms the solvate, solvent S1).

[0212] Typically, a solvate can be formed in a mixture containing CBD and solvent S1 (solvent S1 mixture), and in particular, a solvate can be precipitated (crystallized) in a mixture containing CBD and solvent S1 (solvent S1 mixture) (obtaining a precipitate, solid, or crystal containing the solvate, or forming the solvate in the form of a precipitate, solid, or crystal containing the solvate). Such a method makes it easy to efficiently separate CBD as a solvate.

[0213] In a more specific embodiment, the CBD solvate is precipitated from a reaction mixture or a mixture comprising the first purified product and a solvent (solvent mixture).

[0214] In particular, it is preferable to use the first purified product (crude product, first purified product that has undergone the above-mentioned adsorption treatment) from the viewpoints that it is easy to precipitate CBD solvate and it is easy to efficiently obtain highly pure CBD, among the reaction mixture and the first purified product.

[0215] That is, it is preferable to subject the reaction mixture to an adsorption treatment and then use the resulting purified product (first purified product, crude product, crude CBD) to form (precipitate) a CBD solvate.

[0216] The solvent S1 mixture may contain at least solvent S1 as a solvent, but from the viewpoint of facilitating efficient formation (precipitation) of a CBD solvate, it may also contain a solvent of the solvate and a solvent (sometimes referred to as solvent S2, etc.) different from the solvent of the solvate (e.g., an amide such as DMA) (solvent S1 may be used in combination with solvent S2).

[0217] Solvent S2 may be any solvent that does not form a solvate in combination with solvent S1, and solvent S2 itself may be a solvent that can form a solvate.

[0218] Solvent S2 may be any solvent different from solvent S1, but is preferably one that does not (substantially) dissolve the CBD solvate (a poor solvent for the CBD solvate).

[0219] The solvent S2 can be selected depending on the type of solvent S1 and the solvate, and examples thereof include hydrocarbons [for example, aliphatic hydrocarbons (for example, pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, methylcyclohexane, etc.), aromatic hydrocarbons (for example, benzene, toluene, xylene, ethylbenzene, etc.)], halogenated solvents (for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, etc.), ketones (for example, acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), esters (for example, aliphatic esters such as methyl acetate, ethyl acetate, butyl acetate, etc.), carbonates (for example, ethylene carbonate, propylene carbonate, etc.), ethers [for example, chain ethers (for example, diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (for example, tetrahydrofuran, Examples of suitable solvents include ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol monomethyl ether, diethylene glycol monoethyl ether, and the like, glycol ether esters (e.g., ethylene glycol monomethyl ether acetate, and the like), nitrogen-containing solvents {e.g., amides [e.g., N-substituted chain amides (e.g., N-alkyl-substituted alkanamides such as N,N-dimethylformamide), cyclic amides (e.g., 2-pyrrolidone, and the like], and the like}, nitriles (e.g., acetonitrile, and the like), sulfur-containing solvents (e.g., sulfoxides such as dimethyl sulfoxide; sulfones such as dimethyl sulfone and sulfolane), alcohols [e.g., alkanols (e.g., methanol, ethanol, and isopropanol)], polyols (e.g., alkanediols such as ethylene glycol and propylene glycol; glycerin, and the like), and water.

[0220] Here, the solvent may contain at least a solvent for the solvate (a solvent that forms a solvate, such as DMA), but from the viewpoint of facilitating efficient formation (precipitation) of a CBD solvate, the solvent may contain a solvent for the solvate (sometimes referred to as solvent S1, for example, an amide such as DMA) and a solvent different from the solvent for the solvate (sometimes referred to as solvent S2, for example).

[0221] Representative examples of the solvent S2 include hydrocarbons [for example, aliphatic hydrocarbons (e.g., pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, methylcyclohexane, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene, etc.)], ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), ethers [for example, chain ethers (e.g., diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (e.g., tetrahydrofuran, dioxane, etc.)], and the like.

[0222] Among these, solvent S2 may particularly contain at least an aliphatic hydrocarbon {for example, an aliphatic hydrocarbon such as pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, or methylcyclohexane [for example, an aliphatic hydrocarbon having 5 or more carbon atoms (for example, 5 to 18 carbon atoms, 6 to 12 carbon atoms, 6 to 10 carbon atoms, etc.) (for example, a chain or cyclic aliphatic hydrocarbon, saturated or unsaturated hydrocarbon, or a chain or cyclic saturated aliphatic hydrocarbon)], etc.}.

[0223] The solvent S2 may be used alone or in combination of two or more kinds.

[0224] When solvent S2 contains an aliphatic hydrocarbon, the proportion of the aliphatic hydrocarbon (e.g., heptane, etc.) relative to the entire solvent S2 may be selected from the range of, for example, 1 vol.% or more (e.g., 3 vol.% or more), preferably 5 vol.% or more (e.g., 10 vol.% or more), and more preferably about 15 vol.% or more (e.g., 20 vol.% or more), and may be 25 vol.% or more [e.g., 30 vol.% or more, 35 vol.% or more, 40 vol.% or more, 50 vol.% or more, more than 50 vol.%, 60 vol.% or more, 70 vol.% or more, 80 vol.% or more, 85 vol.% or more, 90 vol.% or more, 95 vol.% or more, or (substantially) 100 vol.% (almost) only aliphatic hydrocarbons].

[0225] Aliphatic hydrocarbons may be used in combination with other solvents (solvents other than aliphatic hydrocarbons, for example, ethers). In such cases, the proportion of the other solvent in the total solvent S2 may be selected from the range of, for example, 99% by volume or less (e.g., 97% by volume or less, 95% by volume or less), 90% by volume or less (e.g., 80% by volume or less), preferably 70% by volume or less (e.g., 60% by volume or less), more preferably 50% by volume or less (e.g., 40% by volume or less), or 1% by volume or more (e.g., 3% by volume or more, 5% by volume or more, 10% by volume or more), etc.

[0226] The proportion of solvent S1 in the total solvent is not particularly limited, but may be, for example, 0.1 vol. % or more (e.g., 0.5 vol. % or more), preferably 1 vol. % or more (e.g., 2 vol. % or more), and more preferably 3 vol. % or more (e.g., 5 vol. % or more).

[0227] When the solvent contains solvent S2, the proportion of solvent S2 in the entire solvent is not particularly limited, but may be selected from a range of, for example, 1 vol% or more (e.g., 3 vol% or more), preferably 5 vol% or more (e.g., 10 vol% or more), and more preferably about 15 vol% or more (e.g., 20 vol% or more), or may be 25 vol% or more (e.g., 30 vol% or more, 35 vol% or more, 40 vol% or more, 50 vol% or more, more than 50 vol%, 60 vol% or more, 70 vol% or more, 80 vol% or more, 85 vol% or more, 90 vol% or more), etc.

[0228] The solvent (e.g., solvent S2) may or may not contain a protic solvent (e.g., water, alcohols, etc.). However, from the viewpoint of facilitating efficient formation (precipitation) of a CBD solvate, it is preferable that the solvent does not contain any protic solvent or contains only a small amount of water (e.g., 10% by volume or less of the solvent (e.g., 5% by volume or less, 3% by volume or less, 1% by volume or less, 0.5% by volume or less, 0.1% by volume or less)). In particular, the solvent may contain no water or only a small amount of water (e.g., 10% by volume or less of the solvent (e.g., 5% by volume or less, 3% by volume or less, 1% by volume or less, 0.5% by volume or less, 0.1% by volume or less)).

[0229] In the mixture, the proportion (concentration) of components other than the solvent (solid content) relative to the total amount of the solvent and components other than the solvent is not particularly limited, and may be, for example, about 0.1% by mass or more (e.g., 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more), or may be 99% by mass or less (e.g., 95% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 12% by mass or less, 10% by mass or less), etc.

[0230] In the mixture, the ratio of solvent to CBD1 may be about 0.01 or more (e.g., 0.05 or more, 0.1 or more, 0.3 or more, 0.5 or more) on a volume basis, or may be 1000 or less (e.g., 800 or less, 500 or less, 300 or less, 200 or less, 150 or less, 120 or less, 100 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less), etc.

[0231] In the mixture, the ratio of solvent S1 to CBD may be, for example, 1 molar equivalent or more, more than 1 molar equivalent (e.g., 1.05 molar equivalents), preferably 1.1 molar equivalents or more (e.g., 1.2 molar equivalents or more), more preferably about 1.5 molar equivalents or more (e.g., 1.8 molar equivalents or more), or may be 2 molar equivalents or more (e.g., 2.5 molar equivalents or more, 3 molar equivalents or more), etc.

[0232] In addition, 1 molar equivalent means that when the solvate is a solvate in which X moles of solvent (e.g., 2 moles in the case of CBD-2DMA) are solvated with 1 mole of CBD, the amount is X moles (e.g., 2 moles in the case of CBD-2DMA) per mole of CBD.

[0233] A solvate of CBD can be formed (prepared) by reacting (contacting) CBD with a solvent S1 in a mixture. The formation of such a solvate may usually be accompanied by crystallization (crystallization).

[0234] In such a reaction (solvation reaction), the method of mixing the raw materials (components) to be used is not particularly limited, and they may be mixed all together, mixed stepwise, mixed partially, or a plurality of components may be mixed in advance, or these may be combined.

[0235] In particular, from the viewpoint of facilitating efficient formation of a solvate of CBD, solvent S1 may be mixed (e.g., added dropwise) into a system (mixture) containing CBD (e.g., a reaction mixture, a first purified product) [solvation may be achieved by mixing (e.g., adding dropwise)].

[0236] The mixing may be carried out all at once or in stages, preferably in stages. Such mixing (staged mixing) may be intermittent, continuous (continuous), or a combination thereof.

[0237] Furthermore, in such mixing (stepwise mixing), the time required for mixing (mixing time, total time, time until mixing is completed) depends on the amount of the other component, etc., but can be selected from a range of, for example, about 30 seconds or more (e.g., 40 seconds or more), and may be 1 minute or more (e.g., 2 minutes or more, 3 minutes or more, 5 minutes or more, 10 minutes or more, 30 minutes or more), etc.

[0238] The reaction (crystallization) may be carried out in the presence or absence of seed crystals. The use of seed crystals often facilitates crystallization under mild conditions (e.g., crystallization can be easily performed without using low temperatures). The seed crystals may be, for example, a solvate of CBD. Such seed crystals may be prepared in advance, for example, by using high-purity CBD (using the method of the present invention), or may be prepared by using a mixture containing CBD and other components (e.g., a reaction mixture, a first purified product, etc.) (using the method of the present invention).

[0239] The reaction (crystallization) may be carried out at room temperature (or ordinary temperature), under heating, or under cooling.

[0240] Specific reaction (crystallization) temperatures include, for example, -100°C or higher (e.g., -80°C or higher, -60°C or higher, -40°C or higher, -20°C or higher, -10°C or higher, 0°C or higher, 10°C or higher, 20°C or higher, 30°C or higher, 35°C or higher, 40°C or higher), 150°C or lower (e.g., 140°C or lower, 130°C or lower, 120°C or lower, 110°C or lower, 100°C or lower, 90°C or lower, 80°C or lower, 70°C or lower, 60°C or lower, 50°C or lower), and the like.

[0241] In particular, from the viewpoint of facilitating efficient formation of a solvate and facilitating precipitation of the solvate, the reaction (crystallization) temperature may be relatively low or not too high (e.g., 40°C or less, 35°C or less, 30°C or less, 25°C or less, 20°C or less, 15°C or less, 10°C or less, or 5°C or less).

[0242] The reaction (crystallization) time can be appropriately selected depending on the degree of progress of the solvation reaction (crystallization), various reaction (crystallization) conditions, etc., and is not particularly limited, and may be, for example, 30 seconds or more (e.g., 1 minute or more, 2 minutes or more, 5 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 40 minutes or more, 60 minutes or more, 1.5 hours or more, 2 hours or more), etc., or 48 hours or less (e.g., 36 hours or less, 24 hours or less, 18 hours or less, 12 hours or less, 6 hours or less, 5 hours or less, 4 hours or less, 3 hours or less), etc.

[0243] The reaction (crystallization) may be carried out under stirring or by leaving the mixture to stand.

[0244] The reaction (crystallization) may be carried out in an inert atmosphere (for example, under nitrogen or argon).

[0245] In the reaction (crystallization), the vessel is not particularly limited, and a conventional vessel can be used.

[0246] Through the above reaction (crystallization), a solvate of CBD is formed (produced).

[0247] The CBD solvate can be separated (recovered) from the reaction (crystallization) mixture using a conventional method. For example, the crystallized (crystallized, precipitated) CBD solvate (crystals, crystallized product, solid content, solid) can be separated (recovered) by filtration, decantation, etc.

[0248] The separated CBD solvate (crystal, crystallized product, solid content, solid) may be washed (washing treatment) if necessary.

[0249] The washing solvent is not particularly limited, and the solvents exemplified above (e.g., solvent S2) may be used. Preferred embodiments of the solvent are also the same as those described above. For example, a hydrocarbon (particularly, an aliphatic hydrocarbon), preferably a solvent containing at least an aliphatic hydrocarbon, may be used.

[0250] The amount of washing solvent used can be selected appropriately depending on the amount of CBD solvate (crystals, crystallized product, solid content, solid), and may be, for example, 0.1 parts by mass or more (e.g., 0.3 parts by mass or more, 0.5 parts by mass or more, 1 part by mass or more) or 100 parts by mass or less (e.g., 50 parts by mass or less, 10 parts by mass or less, 5 parts by mass or less) per part by mass of CBD solvate (crystals, crystallized product).

[0251] Furthermore, in solids (crystals, crystallized material, solid content, second purified product, solvate of CBD), CBD can be almost entirely recovered as a solvate of CBD. For example, when the mass of CBD in the mixture (solvent S1 mixture) is A1 and the mass of CBD in the second purified product (the mass of CBD in the solvate) is A2, the value of A2 / A1 can be selected, for example, from a range of about 0.7 or more, and may be about 0.8 or more (e.g., 0.85 or more, 0.88 or more, 0.9 or more, 0.92 or more, 0.93 or more, 0.94 or more, 0.95 or more, 0.96 or more, 0.97 or more, 0.98 or more, 0.99 or more, substantially 1).

[0252] Furthermore, the solid (crystal, crystallized product, solid content, second purified product, solvate of CBD) may or may not contain other components (olivetol, by-products, etc.); however, by undergoing the above-described purification (crystallization, formation of solvate), even if it does contain other components, it is often only in trace amounts (highly purified).

[0253] For example, in the second purified product (crystals, crystallized product, solid fraction, solid, solvate of CBD), the proportion of CBD (or solvate of CBD) relative to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., the proportion based on HPLC area (peak area)) can be selected from a range of, for example, 80% or more (e.g., 85% or more), and may be 88% or more (e.g., 89% or more), preferably 90% or more (e.g., 91% or more), more preferably 92% or more (e.g., 93% or more), and particularly 94% or more (e.g., 95% or more, 96% or more, 96.5% or more, 97% or more, 97.5% or more, 98% or more, 98.5% or more, 99% or more, 99.2% or more, 99.5% or more, 99.9% or more).

[0254] In the mixture (mixture before second purification, solvent S1 mixture), the ratio of CBD (e.g., ratio based on HPLC area (peak area)) to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC was designated M1, and in the second purified product, the ratio of CBD (or solvates of CBD) to the total amount of CBD (or solvates of CBD), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC was designated M2. When the ratio (for example, the ratio based on the HPLC area (peak area)) is taken as M2, the value of M2-M1 may be greater than 0%, and may be selected from a range of about 1% or more (for example, 2% or more), and may be 3% or more (for example, 4% or more), preferably 5% or more (for example, 8% or more), more preferably 10% or more (for example, 12% or more), and particularly 15% or more (for example, 16% or more, 17% or more, 18% or more, 19% or more, 20% or more).

[0255] The second purified product may or may not contain olivetol, but even if it does, it often contains a small amount. For example, in the second purified product, the ratio of olivetol (e.g., ratio based on HPLC area) to the total amount of CBD (or a solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC may be, for example, 10% or less (e.g., 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1.5% or less, 1.2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less), etc.

[0256] In the mixture (mixture before the second purification, solvent S1 mixture), the ratio of olivetol (e.g., the ratio based on the HPLC area (peak area)) to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC was designated M1. In the second purified product, the ratio of olivetol (e.g., the ratio based on the HPLC area (peak area)) to the total amount of CBD (or CBD solvate), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC was designated M2. When the sum of the total amount of the molten metal and the total amount of the molten metal is taken as M2, the value of M1-M2 may be more than 0%, and may be selected from a range of about 0.01% or more (e.g., 0.02% or more), and may be 0.03% or more (e.g., 0.05% or more), preferably 0.07% or more (e.g., 0.08% or more), more preferably 0.1% or more (e.g., 0.12% or more, 0.15% or more), or may be 0.2% or more (e.g., 0.5% or more, 1% or more, 1.5% or more, 2% or more, 2.5% or more, 3% or more, 3.5% or more).

[0257] The second purified product may or may not contain abn-CBD, but even if it does, it will often contain a small amount. For example, in the second purified product, the ratio of abn-CBD to the total amount of CBD (or CBD solvate), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 10% or less (e.g., 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1.5% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less), etc.

[0258] In the mixture (mixture before the second purification, solvent S1 mixture), the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area (peak area)) was designated M1. In the second purified product, the ratio of abn-CBD to the total amount of CBD (or solvates of CBD), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area (peak area)) was designated M2. When the ratio of the area of C (the peak area) to the area of C (the peak area) is taken as M2, the value of M1-M2 may be greater than 0%, and may be selected from a range of about 0.1% or more (e.g., 0.5% or more), and may be 1% or more (e.g., 1.2% or more), preferably 1.5% or more (e.g., 1.8% or more), more preferably 2% or more (e.g., 2.2% or more), and particularly 2.5% or more (e.g., 2.8% or more, 3% or more, 3.2% or more, 3.5% or more, 3.8% or more, 4% or more).

[0259] The second purified product may or may not contain the 2:1 adduct, but even if it does, it will often contain a small amount. For example, in the second purified product, the ratio of the 2:1 adduct to the total amount of CBD (or a solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., the ratio based on HPLC area) may be, for example, 3% or less (e.g., 2.5% or less, 2% or less, 1.5% or less, 1.2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0260] The second purified product may or may not contain Δ9-THC, but even if it does, it will often contain little. For example, in the second purified product, the ratio of Δ9-THC to the total amount of CBD (or CBD solvate), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 1% or less (e.g., 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0261] The second purified product may or may not contain Δ8-THC, but even if it does, it will often contain little. For example, in the second purified product, the ratio of Δ8-THC to the total amount of CBD (or CBD solvate), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 1% or less (e.g., 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0262] The second purified product may or may not contain Δ9-THC and Δ8-THC, but even if it does, it will often contain small amounts. For example, in the second purified product, the ratio of Δ9-THC and Δ8-THC to the total amount of CBD (or CBD solvates), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 1% or less (e.g., 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0263] When the second purified product contains olivetol, the ratio of olivetol to CBD (or a solvate of CBD) in the second purified product (i.e., the ratio of olivetol / CBD (or a solvate of CBD)) (e.g., the ratio based on HPLC area) can be selected from a range of about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), and particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less), etc.

[0264] When the second purified product contains abn-CBD, the ratio of abn-CBD to CBD (or a solvate of CBD) in the second purified product (i.e., the ratio of abn-CBD / CBD (or a solvate of CBD)) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less), etc.

[0265] When the second purified product contains a 2:1 adduct, the ratio of the 2:1 adduct to CBD (or a solvate of CBD) in the second purified product (i.e., the ratio of the 2:1 adduct / the ratio of CBD (or a solvate of CBD)) (e.g., the ratio on an HPLC area basis) can be selected from a range of about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), and particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0266] When the second purified product contains Δ9-THC, the ratio of Δ9-THC to CBD (or a solvate of CBD) in the second purified product (i.e., the ratio of Δ9-THC / CBD (or a solvate of CBD)) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0267] When the second purified product contains Δ8-THC, the ratio of Δ8-THC to CBD (or a solvate of CBD) in the second purified product (i.e., the ratio of Δ8-THC / CBD (or a solvate of CBD)) (e.g., the ratio based on HPLC area) can be selected from a range of about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0268] When the second purified product contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to CBD (or a solvate of CBD) in the second purified product [i.e., (the sum of the ratio of Δ9-THC and the ratio of Δ8-THC) / the ratio of CBD (or a solvate of CBD)] (e.g., the ratio on an HPLC area basis) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0269] In the second purified product, the ratio of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD (or CBD solvates) [i.e., the sum of (the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD (or CBD solvates)] (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.5 or less (e.g., 0.3 or less), and may be 0.1 or less (e.g., 0.08 or less), preferably 0.05 or less (e.g., 0.03 or less), more preferably 0.02 or less (e.g., 0.015 or less), and particularly 0.01 or less (e.g., 0.008 or less, 0.006 or less, 0.004 or less), etc.

[0270] (CBD production from solvates) CBD can be produced (manufactured, regenerated) from a solvate of CBD [second purified product, crystals (obtained through the second purification process), crystallized product].

[0271] The method for producing CBD is not particularly limited as long as it can release (desolvate) the (solvating) solvent (e.g., DMA) from the solvate of CBD and produce CBD, and can be selected appropriately depending on the properties of the solvate of CBD, etc.

[0272] Specific methods include desolvation of the CBD solvate by heating, and desolvation of the CBD solvate by dissolving it in a solvent (solvent).

[0273] Typically, a solvate of CBD (such as a DMA solvate of CBD) may be brought into contact with water (dissolved or dispersed in water) to produce CBD, accompanied by desolvation.

[0274] The CBD produced can be separated (recovered) using conventional methods, particularly extraction.

[0275] For example, by coexisting a solvent that is a poor solvent for water (a solvent that undergoes phase separation or liquid-liquid separation with water, a hydrophobic solvent) and that can dissolve CBD (a good solvent for CBD, an extraction solvent, for example, an aliphatic hydrocarbon such as heptane) (a hydrophobic solvent that can dissolve CBD and is used as an extraction solvent), the (produced) CBD can be migrated (separated, extracted) into the hydrophobic solvent layer (hydrophobic solvent layer, liquid-liquid separation layer). Such hydrophobic solvents include the solvents exemplified above, such as hydrocarbons. In particular, the hydrophobic solvent may contain at least an aliphatic hydrocarbon {for example, an aliphatic hydrocarbon such as pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, or methylcyclohexane [for example, an aliphatic hydrocarbon having 5 or more carbon atoms (for example, 5 to 18 carbon atoms, 6 to 12 carbon atoms, 6 to 10 carbon atoms, etc.) (for example, a chain or cyclic aliphatic hydrocarbon, saturated or unsaturated hydrocarbon, or a chain or cyclic saturated aliphatic hydrocarbon)], etc.}.

[0276] Such extraction may result in the CBD solvate containing other components (e.g., by-products) (even if they are present in trace amounts), and may allow for further purification (leading to even higher CBD purity).

[0277] For example, as mentioned above, by-products such as olivetol and abn-CBD are often present in trace amounts in solvates, but it is possible to obtain CBD of higher purity by further separating and removing these trace amounts of olivetol and by-products from CBD.

[0278] The CBD can then be obtained from the separated layer (e.g., the hydrophobic solvent layer).

[0279] The separation layer (for example, the hydrophobic solvent layer) may be further washed with a solvent (washing solvent) such as water.

[0280] The washing may be repeated once or more times.

[0281] The ratio (amount used, total amount) of the washing solvent may be, for example, 0.1 or more (e.g., 0.5 or more, 1 or more, 2 or more, 3 or more, 5 or more) or 30 or less (e.g., 20 or less, 15 or less, 10 or less, 8 or less) on a volume basis relative to 1 of the separation layer (e.g., the hydrophobic solvent layer). When washing is performed two or more times, the ratio of the washing solvent per washing (amount used, total amount) may be, for example, 0.01 or more (e.g., 0.05 or more, 0.1 or more, 0.2 or more, 0.3 or more, 0.5 or more) or 30 or less (e.g., 20 or less, 10 or less, 5 or less, 3 or less, 2 or less, 1.5 or less) on a volume basis relative to 1 of the separation layer (e.g., the hydrophobic solvent layer).

[0282] CBD may be obtained by removing the solvent component from the separation layer (e.g., the hydrophobic solvent layer), or by crystallizing the CBD. Crystallization may allow for further purification (higher purity of CBD) as described above.

[0283] CBD can be crystallized by a conventional method, and is not particularly limited to, for example, crystallization (recrystallization).

[0284] The solvent used for crystallization (recrystallization) is not particularly limited, and the above-mentioned solvents can be used. Examples thereof include hydrocarbons [for example, aliphatic hydrocarbons (for example, pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, methylcyclohexane, etc.), aromatic hydrocarbons (for example, benzene, toluene, xylene, ethylbenzene, etc.)], ketones (for example, acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.), ethers [for example, chain ethers (for example, diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (for example, tetrahydrofuran, dioxane, etc.)].

[0285] Among these, particularly, at least an aliphatic hydrocarbon {for example, an aliphatic hydrocarbon such as pentane, hexane, isohexane, heptane, 2-methylhexane, 2,2-dimethylpentane, octane, isooctane, nonane, decane, cyclopentane, cyclohexane, cycloheptane, or methylcyclohexane [for example, an aliphatic hydrocarbon having 5 or more carbon atoms (for example, 5 to 18 carbon atoms, 6 to 12 carbon atoms, 6 to 10 carbon atoms, etc.) (for example, a linear or cyclic aliphatic hydrocarbon, saturated or unsaturated hydrocarbon, or a linear or cyclic saturated aliphatic hydrocarbon)], etc.} may be used.

[0286] In crystallization (recrystallization), the proportion (amount used) of the solvent can be selected depending on the crystallization conditions, etc., and may be, for example, a proportion (concentration) that results in a solids concentration of 1% by mass or more (e.g., 5% by mass or more, 10% by mass or more, 20% by mass or more, 30% by mass or more) and 90% by mass or less (e.g., 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less).

[0287] The reaction (crystallization) may be carried out in the presence of seed crystals.

[0288] The crystallization (recrystallization) may be carried out at room temperature (or ordinary temperature), under heating, or under cooling.

[0289] Specific crystallization (recrystallization) temperatures include, for example, -100°C or higher (e.g., -80°C or higher, -60°C or higher, -40°C or higher, -20°C or higher, -10°C or higher, 0°C or higher, 10°C or higher, 20°C or higher, 30°C or higher, 35°C or higher, 40°C or higher), and 150°C or lower (e.g., 140°C or lower, 130°C or lower, 120°C or lower, 110°C or lower, 100°C or lower, 90°C or lower, 80°C or lower, 70°C or lower, 60°C or lower, 50°C or lower).

[0290] In particular, the crystallization (recrystallization) temperature may be relatively low or not too high (e.g., 40°C or less, 35°C or less, 30°C or less, 25°C or less, 20°C or less, 15°C or less, 10°C or less, 5°C or less). The crystallization (recrystallization) temperature may also be decreased stepwise.

[0291] The crystallization (recrystallization) time can be appropriately selected depending on the degree of progress of crystallization (recrystallization), various crystallization (recrystallization) conditions, etc., and is not particularly limited, and may be, for example, 30 seconds or more (e.g., 1 minute or more, 2 minutes or more, 5 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 25 minutes or more, 30 minutes or more, 40 minutes or more, 60 minutes or more, 1.5 hours or more, 2 hours or more), etc., or 48 hours or less (e.g., 36 hours or less, 24 hours or less, 18 hours or less, 12 hours or less, 6 hours or less), etc.

[0292] The crystallization (recrystallization) may be carried out under stirring or by leaving the mixture to stand.

[0293] The crystallization (recrystallization) may be carried out in an inert atmosphere (for example, under nitrogen or argon).

[0294] In the crystallization (recrystallization), the vessel is not particularly limited, and a conventional vessel can be used.

[0295] Through the above reaction (crystallization), CBD is produced (manufactured, recovered, and regenerated).

[0296] Furthermore, when the CBD is almost completely recovered, for example, when the mass of CBD in the CBD solvate is A1 and the mass of CBD (regenerated CBD) is A2, the value of A2 / A1 can be selected, for example, from a range of about 0.7 or more, and may be about 0.8 or more (e.g., 0.85 or more, 0.88 or more, 0.9 or more, 0.92 or more, 0.93 or more, 0.94 or more, 0.95 or more, 0.96 or more, 0.97 or more, 0.98 or more, 0.99 or more, or substantially 1).

[0297] Furthermore, CBD may or may not contain components other than CBD (olivetol, by-products, etc.), but even if it does contain them, they will be in extremely small amounts (highly purified).

[0298] For example, in CBD (regenerated CBD), the proportion of CBD (e.g., the proportion based on HPLC area (peak area)) relative to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC can be selected from a range of, for example, 88% or more (e.g., 90% or more), and may be 92% or more (e.g., 93% or more), preferably 95% or more (e.g., 96% or more), more preferably 97% or more (e.g., 97.5% or more), particularly 98% or more, 98.5% or more, 99% or more, 99.2% or more, 99.5% or more, 99.9% or more, 99.95% or more, or substantially 100%.

[0299] CBD (regenerated CBD) may or may not contain olivetol, but even if it does, it often contains small amounts. For example, in CBD (regenerated CBD), the ratio of olivetol to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 8% or less (e.g., 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1.5% or less, 1.2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.01% or less, 0.001% or less), etc.

[0300] CBD (regenerated CBD) may or may not contain abn-CBD, but even if it does, it will often contain small amounts. For example, in CBD (regenerated CBD), the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 8% or less (e.g., 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1.5% or less, 1.2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.01% or less, 0.001% or less), etc.

[0301] CBD (regenerated CBD) may or may not contain 2:1 adducts, but even if it does, it is often present in small amounts. For example, in CBD (regenerated CBD), the ratio of the 2:1 adducts to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 3% or less (e.g., 2.5% or less, 2% or less, 1.5% or less, 1.2% or less, 1% or less, 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0302] CBD (regenerated CBD) may or may not contain Δ9-THC, but even if it does, it often contains little. For example, in CBD (regenerated CBD), the ratio of Δ9-THC to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 1% or less (e.g., 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0303] CBD (regenerated CBD) may or may not contain Δ8-THC, but even if it does, it often contains little. For example, in CBD (regenerated CBD), the ratio of Δ8-THC to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 1% or less (e.g., 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0304] CBD (regenerated CBD) may or may not contain Δ9-THC and Δ8-THC, but even if it does, it often contains small amounts. For example, in CBD (regenerated CBD), the ratio of Δ9-THC and Δ8-THC to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area) may be, for example, 1% or less (e.g., 0.9% or less, 0.8% or less, 0.7% or less, 0.6% or less, 0.5% or less, 0.4% or less, 0.3% or less, 0.2% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less), etc.

[0305] When CBD (regenerated CBD) contains olivetol, the ratio of olivetol to CBD in the CBD (regenerated CBD) (i.e., the ratio of olivetol / CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0001 or less), etc.

[0306] When the CBD (regenerated CBD) contains abn-CBD, the ratio of abn-CBD to CBD in the CBD (regenerated CBD) (i.e., ratio of abn-CBD / ratio of CBD) (e.g., ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0001 or less), etc.

[0307] When CBD (regenerated CBD) contains a 2:1 adduct, the ratio of the 2:1 adduct to CBD in the CBD (regenerated CBD) (i.e., the ratio of the 2:1 adduct / the ratio of CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), and particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0308] When CBD (regenerated CBD) contains Δ9-THC, the ratio of Δ9-THC to CBD in the CBD (regenerated CBD) (i.e., the ratio of Δ9-THC / CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0309] When CBD (regenerated CBD) contains Δ8-THC, the ratio of Δ8-THC to CBD in the CBD (regenerated CBD) (i.e., the ratio of Δ8-THC / CBD) (e.g., the ratio based on HPLC area) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0310] When CBD (regenerated CBD) contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to CBD in the CBD (regenerated CBD) [i.e., (the sum of the ratio of Δ9-THC and the ratio of Δ8-THC) / the ratio of CBD] (e.g., the ratio on an HPLC area basis) can be selected from a range of, for example, about 0.1 or less (e.g., 0.05 or less), and may be 0.03 or less (e.g., 0.025 or less), preferably 0.02 or less (e.g., 0.015 or less), more preferably 0.01 or less (e.g., 0.008 or less), and particularly 0.005 or less (e.g., 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0311] When the CBD (regenerated CBD) contains at least one selected from olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC, the ratio of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC to CBD in the CBD (regenerated CBD) [i.e., (the sum of the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adducts, the ratio of Δ9-THC, and the ratio of Δ8-THC) / the ratio of CBD] (e.g., , ratio based on the HPLC area) can be selected from a range of, for example, about 0.5 or less (e.g., 0.3 or less), and may be 0.1 or less (e.g., 0.08 or less), preferably 0.05 or less (e.g., 0.03 or less), more preferably 0.02 or less (e.g., 0.015 or less), particularly 0.01 or less (e.g., 0.008 or less, 0.006 or less, 0.004 or less, 0.003 or less, 0.002 or less, 0.001 or less, 0.0005 or less, 0.0001 or less), etc.

[0312] CBD (regenerated CBD) typically does not contain (or contains below the detection limit of) a solvent [residual solvent, for example, a solvent derived from a solvate (a solvent that constitutes a solvate, for example, dimethylacetamide), a solvent used during regeneration (for example, an aliphatic hydrocarbon such as heptane)], or even if it contains a solvent, the amount may be very small. For example, when CBD (regenerated CBD) contains a solvent (solvent component), the ratio of the solvent to the entire CBD (CBD including residual solvent) may be, for example, 5% by mass or less (e.g., 4% by mass or less, 3.5% by mass or less, 3% by mass or less, 2.5% by mass or less, 2% by mass or less, 1.5% by mass or less, 1.2% by mass or less, 1% by mass or less, 0.8% by mass or less, 0.7% by mass or less, 0.6% by mass or less, 0.5% by mass or less, 0.3% by mass or less, 0.2% by mass or less, 0.1% by mass or less), etc. More specifically, the proportion (upper limit) of the solvate-derived solvent (the solvent that constitutes the solvate, for example, dimethylacetamide) relative to the total CBD may be 5% by mass or less, 4.5% by mass or less, 4% by mass or less, 3.5% by mass or less, 3% by mass or less, 2.5% by mass or less, 2% by mass or less, 1.5% by mass or less, 1.2% by mass or less, 1% by mass or less, 0.8% by mass or less, 0.5% by mass or less, 0.3% by mass or less, 0.2% by mass or less, 0.1% by mass or less, etc. In addition, the proportion (upper limit) of hydrocarbons (e.g., aliphatic hydrocarbons such as heptane) relative to the total CBD may be 3% by mass or less, 2.5% by mass or less, 2% by mass or less, 1.5% by mass or less, 1.2% by mass or less, 1% by mass or less, 0.8% by mass or less, 0.5% by mass or less, 0.3% by mass or less, 0.2% by mass or less, 0.1% by mass or less, 0.08% by mass or less, 0.05% by mass or less, etc.

[0313] In addition, when CBD (regenerated CBD) contains a solvent (solvent component), the ratio of the solvent to the entire CBD (CBD including residual solvent) may be above the detection limit, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.02% by mass or more, 0.03% by mass or more, 0.05% by mass or more, 0.06% by mass or more, 0.07% by mass or more, 0.08% by mass or more, 0.09% by mass or more, 0.1% by mass or more, etc. More specifically, the proportion (lower limit) of the solvate-derived solvent (the solvent that constitutes the solvate, for example, dimethylacetamide) relative to the total CBD may be 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, etc. In addition, the proportion (lower limit) of hydrocarbons (e.g., aliphatic hydrocarbons such as heptane) relative to the total CBD may be 0.0001% by mass or more, 0.0005% by mass or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more, etc.

[0314] The proportion of the solvent may be measured, for example, by gas chromatography.

[0315] The CBD (reconstituted CBD) may in particular be crystalline (crystalline form). [Example]

[0316] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0317] The various analyses and measurements (calculations) were carried out as follows.

[0318] [HPLC] Measurements were taken using the following equipment and conditions. Equipment: Shimadzu Corporation LC-2010HT Measurement wavelength: 210nm Column: Waters Corporation, Xselect CSH C18, 4.6 mm x 150 mm (particle size: 3.5 μm) Column temperature: 35°C Mobile phase A: 0.1% formic acid in water Mobile phase B: 0.1% formic acid in acetonitrile Flow rate: 1.0mL / min Gradient:

[0319] [Table 1]

[0320] The "%" in the composition indicates that the total peak area from 0.0 to 18.0 minutes is 100%.

[0321] [Powder X-ray (2θ)] Measurements were taken using the following equipment and conditions. Equipment: Rigaku SmartLab Measurement method: Reflection method Light source type: Cu tube Wavelength used: CuKβ ray Tube current: 200mA Tube voltage: 45Kv Sample plate: Circular anti-reflective sample holder X-ray incident angle: 4 to 40 degrees

[0322] [ 1 H-NMR] Bruker Ascend TM 400 was measured.

[0323] [Melting point] The endothermic peak temperature was measured in DSC under the following conditions and equipment, and was taken as the melting point. Equipment: Mettler-Toledo DSC 3+ Conditions: Approximately 1.2 mg of sample was weighed and placed in an aluminum pan. Measurement was performed at a temperature range of 60°C-70°C with a temperature rise rate of 0.5°C / min.

[0324] [Gas Chromatography] Measurement was performed under the following conditions. Detector: FID Column: DB-624 (30 m x 0.320 mm, 1.80 μm) Column temperature: 35°C (0 min) - 3°C / min - 70°C (0 min) - 9°C / min - 130°C (5 min) - 15°C / min - 230°C (0 min) Inlet temperature: 200℃ Detector temperature: 230℃ Carrier gas: N2 Flow control mode: Constant flow Split ratio: 40:1 Injection volume: 1.0μL Area measurement range: 30 minutes Sample dilution solvent: N-methylpyrrolidone The retention times of the residual solvents were MTBE (8.0 minutes), heptane (13.0 minutes), toluene (16.5 minutes), DMA (21.6 minutes), and the like.

[0325] [Synthesis Example 1] 21.63 parts by mass of Olivetol containing 9.3% by mass of water [i.e., 19.62 parts by mass of Olivetol (1.09 eq. relative to menthadienol) and 2.01 parts by mass of water] was subjected to azeotropic dehydration treatment three times with 171.52 parts by mass of toluene [13 V (13 times the volume of menthadienol)], and the weight was adjusted so that the toluene in the reaction vessel became 20 V.

[0326] To this was added 3.19 parts by mass of zinc iodide (ZnI2) (0.1 eq. relative to menthadienol), and the temperature was adjusted to 110°C. A solution of 15.22 parts by mass of menthadienol in 171.54 parts by mass of toluene (13 V) was added dropwise over 30 minutes [i.e., the total amount of solvent (toluene) was 33 V], and after reacting for 5 minutes after the dropwise addition, the mixture was allowed to return to room temperature over 1 hour to obtain a reaction mixture (reaction liquid).

[0327] The proportion of water in the reaction vessel (in the reaction system) was 0.04 mass % when menthadienol was added (at the start of the reaction, immediately before the addition).

[0328] The composition of the reaction mixture was confirmed by HPLC, and it was found to be 62.96% CBD, 13.26% olivetol, 12.17% abn-CBD, 2.20% Δ9-THC, 0.28% Δ8-THC, and 5.46% 2:1 adduct. The quantitative value was calculated to be 63.40%. The quantitative value is the yield (calculated value) obtained by calculating the amount of CBD in the liquid using a standard sample (CBD standard sample) by HPLC (the same applies below).

[0329] [Synthesis Example 2] Tetrahydrofuran (20V) and 85.3 mg (1.8 eq. relative to menthadienol) of boron trifluoride diethyl etherate (BF3OEt2) were added to the reaction vessel, and the temperature was adjusted to -10°C using the jacket.

[0330] To this was added (flowed in) 21.63 parts by mass of olivetol containing 9.3% by mass of water [i.e., 19.62 parts by mass of olivetol (1.09 eq. relative to menthadienol), 2.01 parts by mass of water] and a solution of 15.22 parts by mass of menthadienol in 171.54 parts by mass of toluene (13 V) [i.e., the total amount of solvent (toluene) was 33 V], and the mixture was reacted for 3.5 hours after addition (flowed in), and then returned to room temperature over 1 hour to obtain a reaction mixture (reaction liquid).

[0331] The composition of the reaction solution was confirmed by HPLC, and it was found to be 13.97% CBD, 31.365% olivetol, and 45.02% abn-CBD, with trace amounts of Δ9-THC and Δ8-THC (detection limit).

[0332] As is clear from the composition of each reaction solution, in the method of Synthesis Example 1, by selecting the synthesis method, the amount of unreacted components (olivetol) and by-products was relatively reduced compared to that in Synthesis Example 2, but unreacted components (olivetol) and by-products were still contained in the reaction mixture.

[0333] [Example 1] The mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). The reaction liquid obtained in Synthesis Example 1 was concentrated under reduced pressure to 2.9 wt, and 104.10 parts by mass of heptane (10V) was added, followed by concentration under reduced pressure again, and the solvent was replaced with heptane.

[0334] To the concentrated solution, 343.64 parts by mass of heptane (33V) and 45.66 parts by mass (3 wt) of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for 30 minutes.

[0335] The silica gel was filtered and washed with 103.42 parts by mass of a 3% by volume toluene-heptane solution (10V), and the filtrate was concentrated under reduced pressure to 1.6 wt to obtain a purified product.

[0336] The composition of the purified product was confirmed by HPLC, revealing 79.91% CBD, 0.41% olivetol, 4.63% abn-CBD, 2.95% Δ9-THC, 0.72% Δ8-THC, and 7.9% 2:1 adducts. The quantitative value was calculated to be 55.7%.

[0337] [Example 2] The mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). A reaction solution was obtained in the same manner as in Synthesis Example 1.

[0338] The composition of the reaction solution was confirmed by HPLC, and it was found to be CBD 64.94%, olivetol 13.217%, abn-CBD 12.14%, Δ9-THC 1.87%, Δ8-THC 0.2%, and 2:1 adduct 3.28%. The quantitative value was calculated to be 66.00%.

[0339] To this reaction solution, 10 V of heptane and 13 V of saturated aqueous sodium bicarbonate were added, followed by separation. The organic layer after separation was washed with 13 V of water and 13 V of 20% brine. To the resulting organic layer, 5.0 parts by mass (6.6 wt) of sodium sulfate was added, and after shaking and mixing for 5 minutes, the solid was removed by filtration.

[0340] To the filtrate, 6.6V of heptane and 4.56 parts by mass (6 wt) of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for about 30 minutes.

[0341] The silica gel was filtered and washed with 13 V of heptane, and the filtrate was concentrated under reduced pressure to 1.4 wt to obtain a purified product.

[0342] The composition of the purified product was confirmed by HPLC, and was found to be 82.07% CBD, 0.58% olivetol, 4.02% abn-CBD, 2.83% Δ9-THC, 0.24% Δ8-THC, and 5.93% 2:1 adduct. The quantitative value was calculated to be 50.0%.

[0343] [Example 3] The mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). A reaction solution was obtained in the same manner as in Synthesis Example 1. The composition of the reaction solution was confirmed by HPLC, and it was found to be 61.35% CBD, 14.54% olivetol, 13.141% abn-CBD, 2.518% Δ9-THC, 0.484% Δ8-THC, and 3.88% 2:1 adduct. The quantitative value was calculated to be 60.96%.

[0344] To the reaction mixture, 6.6 V of 3% aqueous sodium bicarbonate and 3.3 V of toluene were added, and after stirring, the mixture was separated. The resulting organic layer was washed with 6.6 V of water and 6.6 V of 20% brine. To the resulting organic layer, 30.04 parts by mass (2.0 wt) of sodium sulfate was added, and after stirring for 15 minutes, the solid was removed by filtration.

[0345] To the filtrate, 3.3 V of toluene and 45.66 parts by mass (3 wt) of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for 1 hour.

[0346] The silica gel was filtered and washed with 6.6 V of heptane, and the filtrate was concentrated under reduced pressure to 1.8 wt to obtain a purified product.

[0347] The composition of the purified product was confirmed by HPLC, and was found to be 73.00% CBD, 3.20% olivetol, 410.61% abn-CBD, 3.07% Δ9-THC, 0.52% Δ8-THC, and 5.96% 2:1 adduct. The quantitative value was calculated to be 57.7%.

[0348] [Example 4] To the purified product (concentrate, concentrated liquid) obtained in Example 3, 4.8V of heptane and 30.40 parts by mass (2 wt) of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for 40 minutes.

[0349] The silica gel was filtered and washed with 6 V of heptane, and the filtrate was concentrated under reduced pressure to 1.3 wt to obtain a purified product (additionally purified product).

[0350] The composition of the purified product (additionally purified product) was confirmed by HPLC, and was found to be CBD 81.76%, abn-CBD 2.93%, Δ9-THC 2.99%, Δ8-THC 0.52%, 2:1 adduct 8.10%, and no olivetol was detected. The quantitative value was calculated to be 44.2%.

[0351] [Example 5] The mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). A reaction solution was obtained in the same manner as in Synthesis Example 1.

[0352] The composition of the reaction mixture was confirmed by HPLC, and was found to be 63.548% CBD, 12.504% olivetol, 11.963% abn-CBD, 3.748% Δ9-THC, 0.511% Δ8-THC, and 4.07% 2:1 adduct. The quantitative value was calculated to be 65.51%.

[0353] To the reaction solution, 19.7 V of heptane and 3.04 parts by mass (4 wt) of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for 1 hour.

[0354] The silica gel was filtered and washed with 33 V of heptane, and the filtrate was concentrated under reduced pressure to 1.7 wt to obtain a purified product.

[0355] The composition of the purified product was confirmed by HPLC, revealing CBD 77.27%, olivetol 1.38%, abn-CBD 6.30%, Δ9-THC 4.53%, Δ8-THC 0.63%, and 2:1 adduct 5.84%. The quantitative value was calculated to be 59.2%.

[0356] [Example 6] The mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). A reaction solution was obtained in the same manner as in Synthesis Example 1.

[0357] The composition of the reaction mixture was confirmed by HPLC, and it was found to be CBD 62.897%, olivetol 13.764%, abn-CBD 10.695%, Δ9-THC 3.067%, Δ8-THC 0.412%, and 2:1 adduct 4.642%. The quantitative value was calculated to be 64.77%.

[0358] This reaction solution was concentrated under reduced pressure to 2.49 wt, and an operation of adding 6.6 V of heptane and concentrating under reduced pressure was repeated twice to replace the solvent with heptane.

[0359] To the concentrated solution, 33V of heptane and 45.6 parts by mass (3 wt) of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for 1 hour. The silica gel was filtered and washed with 10 V of a 3% by volume toluene-heptane solution, and the filtrate was concentrated under reduced pressure to 1.7 wt to obtain a purified product.

[0360] The composition of the purified product was confirmed by HPLC, revealing CBD 76.47%, olivetol 0.28%, abn-CBD 3.7%, Δ9-THC 4.32%, Δ8-THC 1.25%, and 2:1 adduct 11.65%. The quantitative value was calculated to be 52.5%.

[0361] [Example 7] The mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). A reaction solution was obtained in the same manner as in Synthesis Example 1.

[0362] The composition of the reaction mixture was confirmed by HPLC, and it was found to be CBD 62.897%, olivetol 13.764%, abn-CBD 10.695%, Δ9-THC 3.067%, Δ8-THC 0.412%, and 2:1 adduct 4.642%. The quantitative value was calculated to be 64.77%.

[0363] This reaction solution was concentrated under reduced pressure to 2.49 wt, and an operation of adding 6.6 V of heptane and concentrating under reduced pressure was repeated twice to replace the solvent with heptane.

[0364] To the concentrated solution, 33V of toluene and 2 wt of silica gel (particle size 40-50 μm, neutral, spherical) were added, and the mixture was stirred at room temperature for 1 hour.

[0365] The silica gel was filtered and washed with 16 V of heptane, and the filtrate was concentrated under reduced pressure to 2.0 wt to obtain a purified product.

[0366] The composition of the purified product was confirmed by HPLC to be 70.99% CBD, 5.14% olivetol, 9.56% abn-CBD, 4.26% Δ9-THC, 0.97% Δ8-THC, and 6.37% 2:1 adducts. The quantitative value was calculated to be 62.2%.

[0367] As is clear from the results of the examples, the method of the present invention made it possible to efficiently obtain a purified product containing cannabidiol from a mixture containing other components in addition to cannabidiol, such as olivetol and positional isomers of cannabidiol (abn-CBD) (the ratio of other components to cannabidiol could be reduced).

[0368] In particular, even when a mixture containing relatively few other components (and therefore considered difficult to separate further) was selected as such a mixture, the other components could still be separated efficiently.

[0369] Furthermore, such separation (purification) could be carried out more efficiently by selecting the solvent, etc. (for example, olivetol could be separated at a high level).

[0370] [Synthesis Example 3] Cannabidiol (CBD) was dissolved in DMA [1.6 V (1.6 times the volume of DMA relative to CBD)], 0.3 V of water was added, and the mixture was rapidly cooled to 5°C. After confirming the precipitation of a solid (crystal), the slurry was filtered to obtain the solid (crystal).

[0371] Separately, heptane (10 V), DMA (3 eq.) and toluene (0.3 V) were added to cannabidiol and the mixture was rapidly cooled to 5° C. to obtain a solid (crystal).

[0372] Analysis of the resulting solids (crystals) revealed that they were all compounds in which 2 moles of DMA were added (solvated) to 1 mole of cannabidiol (CBD-2DMA).

[0373] The analysis results are as follows:

[0374] ·Powder X-ray (2θ): It was confirmed that the characteristic peaks shown in (C) above (i.e., the approximately 20 peaks listed below) were present. 8.3±0.2°, 8.5±0.2°, 10.6±0.2°, 11.8±0.2°, 13.4±0.2°, 15.4±0.2°, 15.8±0.2°, 16.4±0.2°, 17.0±0.2°, 18.9±0.2°, 19.9±0.2°, 21.4±0.2°, 22.7±0.2°, 22.9±0.2°, 23.2±0.2°, 23.7±0.2°, 24.6±0.2°, 26.5±0.2°, 27.1±0.2°, 27.7±0.2°

[0375] · 1 H-NMR δppm: 0.88 (t, J = 7.2 Hz, 3H), 1.22-1.36(m, 2H), 1.52-1.60(m, 2H), 1.64-1.67(m, 3H), 1.75- 1.85(m, 2H), 1.78-1.80(m, 3H), 2.07-2.13(m, 2H), 2.08(s, 6H), 2.18-2. 28(m, 3H), 2.37-2.46(m, 3H), 2.94(s, 6H), 3.01(s, 6H), 3.82-3.87(m,1 H), 4.56(s, 1H), 4.65-4.67(m, 1H), 5.56-5.58(m, 1H), 6.13-6.30(m, 1H)

[0376] Melting point: 52-55°C [using the above-mentioned equipment and conditions (DSC)]

[0377] The resulting solid (crystal, CBD-2DMA) had lower solubility in various solvents, such as heptane, than CBD.

[0378] [Example 8] The quantitative values of cannabidiol in the purified product (first purified product) were used as the standards for wt (mass), V (volume), and eq. (equivalent). To the purified product (first purified product) obtained in Example 1, 107.85 parts by mass (9V) of heptane and 12.96 parts by mass (1V) of methyl t-butyl ether (MTBE) were added, and after confirming that the solution had become one layer, it was cooled to 10°C.

[0379] To this was added dropwise 4.58 parts by mass (1 eq.) of DMA, and 0.0127 parts by mass (0.07 wt% based on the quantitative value of CBD in the crude composition) of crystals (seed crystals) obtained based on the CBD·2DMA crystals obtained in Synthesis Example 3 were added.

[0380] After confirming the precipitation of crystals, 9.70 parts by mass (2 eq.) of DMA was added dropwise and the mixture was cooled to 0 to 5° C. After crystallization and aging at 0 to 5° C. for 2 hours, the crystals were filtered, washed with 43.17 parts by mass (3.5 V) of a washing solvent [heptane:MTBE:DMA=9:1:0.3 (volume ratio)], and dried by nitrogen blow for 20 minutes.

[0381] The resulting crystals (solid) were confirmed to be CBD·2DMA (containing CBD·2DMA) by the same method as above.

[0382] To the crystals (solid), 71.90 parts by mass of heptane (6V) and 105.12 parts by mass of tap water (6V) were added, and after stirring, it was confirmed that the solid had completely dissolved.

[0383] After separation, the organic layer was washed three times with 105.12 parts by mass (6V) of tap water, and the washed organic layer was dried over 35.04 parts by mass (2 wt) of sodium sulfate. The sodium sulfate was filtered off, and the solution was concentrated under reduced pressure to 1.0 wt.

[0384] The composition of the washed organic layer was confirmed by HPLC to be 99.63% CBD, 0.1% olivetol, and 0.27% abn-CBD. Δ9-THC, Δ8-THC, and 2:1 adducts were not detected. The quantitative value was calculated to be 51.8%.

[0385] In the subsequent steps, the quantitative value of cannabidiol in the organic layer after washing was used as the basis for wt (mass) and V (volume). 22.28 parts by mass of heptane (2V relative to the quantitative value of CBD) was added to the concentrated solution, and after heating to 30°C, 0.1722 parts by mass of CBD seed crystals (1 wt% relative to the quantitative value of CBD) were added. After confirming the precipitation of crystals, the solution was crystallized and matured at 25°C for 1 hour.

[0386] The mixture was then cooled to 0-5°C over 20 minutes, and after 45 minutes of crystallization and aging, cooled to -15°C over 15 minutes. After 2 hours of crystallization and aging, the crystals (solid) were filtered and washed with 12.07 parts by mass (1.1V) of heptane that had been cooled to the same temperature. The crystals (solid) were aerated and dried for 25 minutes, and then dried under reduced pressure at 40°C for 1 hour, yielding 14.92 parts by mass of solid (crystal).

[0387] The obtained solid (crystal) is 1 H-NMR analysis confirmed that it was CBD. In other words, it was found that the obtained solid (crystal, CBD-2DMA) releases DMA in water and becomes CBD (regenerates CBD).

[0388] The composition of the solid (CBD crystals) was confirmed by HPLC, revealing that it was 100.00% CBD, with no detectable olivetol, abn-CBD, Δ9-THC, Δ8-THC, or 2:1 adducts. The CBD yield (assuming 100% reaction of menthadienol) was calculated to be 46.9% (calculated by subtracting the mass of the seed crystals).

[0389] Furthermore, the obtained solid (CBD crystals) contained very small amounts of residual solvent (heptane: 176 ppm by mass, DMA: 251 ppm by mass). Therefore, various additions and changes were made to the purification process, which allowed us to reduce the amount of residual solvent. For example, when the procedure of washing the organic layer three times with 105.12 parts by mass (6V) of tap water was changed to washing the organic layer three times with 105.12 parts by mass (6V) of tap water and four times with 122.64 parts by mass (7V), the proportion of DMA in the resulting solid (CBD) was below the detection limit (it was not detectable).

[0390] In the above method, CBD·2DMA is used as a seed crystal, but it has been confirmed that crystals can be obtained (crystallization or precipitation occurs) even without seed crystals.

[0391] [Example 9] The quantitative values of cannabidiol in the purified product (first purified product) were used as the standards for wt (mass), V (volume), and eq. (equivalent). To the purified product (first purified product) obtained in Example 6, 9V of heptane and 1V of methyl t-butyl ether (MTBE) were added, and after confirming that the solution had become one layer, the mixture was cooled to 10°C.

[0392] 1 eq. of DMA was added dropwise thereto, and the crystals obtained based on the CBD·2DMA crystals obtained in Example 1 were added as seed crystals.

[0393] After confirming the precipitation of crystals, 2 eq. of DMA was added dropwise and the mixture was cooled to 0 to 5° C. After crystallization and aging at 0 to 5° C. for 1 hour, the crystals were filtered, washed with 1.8 V of a washing solvent [heptane:MTBE:DMA=9:1:0.3 (volume ratio)], and dried by nitrogen blowing for 30 minutes.

[0394] To the crystals (solid), 5.7 V of heptane and 5.7 V of tap water were added, and after stirring, it was confirmed that all of the solid had dissolved.

[0395] After separation, the organic layer was washed three times with 5.7 V of tap water, and the washed organic layer was dried over 7.05 parts by mass (4.3 wt) of sodium sulfate. The sodium sulfate was filtered off, and the solution was concentrated under reduced pressure to 1.0 wt, after which 3.0 V of heptane was added.

[0396] The composition of the washed organic layer was confirmed by HPLC to be 99.06% CBD, 0.03% olivetol, and 0.91% abn-CBD, with no detectable Δ9-THC, Δ8-THC, or 2:1 adducts. The quantitative value was calculated to be 49.41%.

[0397] In the subsequent steps, the quantitative value of cannabidiol in the organic layer after washing was used as the basis for wt (mass) and V (volume). 3V of heptane was added to the concentrated solution, and after heating to 25°C, 0.0009 parts by mass (0.06 wt%) of CBD seed crystals was added. After confirming the precipitation of crystals, the solution was crystallized and aged at 25°C for 1 hour. The solution was then cooled to -10°C and crystallized and aged for 1 hour. The crystals (solid) were filtered and washed with heptane cooled to the same temperature. The crystals (solid) were aerated and dried for 15 minutes, then dried under reduced pressure at 40°C for 1 hour, yielding 1.25 parts by mass of solid (crystal).

[0398] The composition of the solid (CBD crystals) was confirmed by HPLC, revealing that it was 100.00% CBD, with no detectable olivetol, abn-CBD, Δ9-THC, Δ8-THC, or 2:1 adducts. The CBD yield (assuming 100% reaction of menthadienol) was calculated to be 40.3% (calculated by subtracting the mass of the seed crystals).

[0399] [Reference example 1] The quantitative values of cannabidiol in the concentrate were expressed as wt (mass), V (volume), and eq. (equivalent). The crude product (reaction liquid) obtained in Example 6 was concentrated without purification to obtain a concentrate. 4.5 V of heptane and 0.5 V of methyl t-butyl ether (MTBE) were added to this concentrate, and after confirming that the solution had become a single layer, the mixture was cooled to 0°C. 2 eq. of DMA was added dropwise to the mixture, and the crystals obtained from the CBD·2DMA crystals obtained in Synthesis Example 1 were added as seed crystals.

[0400] After confirming the precipitation of crystals, 1 eq. of DMA was added dropwise, and the mixture was allowed to crystallize and mature for 90 minutes at 0-5°C. The crystals were then filtered, washed with a washing solvent [heptane:MTBE:DMA = 9:1:0.3 (volume ratio)], and dried by blowing nitrogen for 30 minutes.

[0401] The resulting crystals (solid) were confirmed to be CBD·2DMA (containing CBD·2DMA) by the same method as above.

[0402] To the crystals (solid), 4 V of heptane and 4 V of tap water were added, and after stirring, it was confirmed that all of the solid had dissolved.

[0403] After separation, the organic layer was washed with 4 V of tap water, and the washed organic layer was dried over 1 wt of sodium sulfate. The sodium sulfate was filtered off, washed with heptane, and then the solution was concentrated under reduced pressure.

[0404] The composition of the washed organic layer was confirmed by HPLC to be 94.37% CBD, 3.55% olivetol, and 2.07% abn-CBD, with no detectable Δ9-THC, Δ8-THC, or 2:1 adducts. The quantitative value was calculated to be 45.13%.

[0405] In the subsequent purification steps, the quantitative values of cannabidiol in the organic layer after washing were used as the basis for wt (mass) and V (volume). 4.8V of heptane was added to the concentrated solution, and after adjusting the temperature to 10°C, CBD seed crystals were added and the precipitation of crystals was confirmed. The solution was then cooled to 0°C and crystallized and aged at the same temperature. The crystals (solid) were filtered and washed with heptane cooled to the same temperature, yielding 0.7896 parts by mass of solid (crystal).

[0406] The composition of the solid (CBD crystals) was confirmed by HPLC to be 94.51% CBD, 4.80% olivetol, and 0.69% abn-CBD. Δ9-THC, Δ8-THC, and 2:1 adducts were not detected. The CBD yield (assuming 100% reaction of menthadienol) was calculated to be 25.6% (calculated by subtracting the mass of the seed crystals).

[0407] An oily component was slightly exuded onto the surface of the solid, which is believed to be olivetol.

[0408] In addition, although the above method uses CBD·2DMA as a seed crystal, it has been confirmed that crystals can be obtained (crystallization or precipitation occurs) even without seed crystals.

[0409] [Example 10] The quantitative values of cannabidiol in the purified product (first purified product) were used as the standards for wt (mass), V (volume), and eq. (equivalent). To the purified product (first purified product) obtained in Example 6, 9 V of heptane and 1 V of methyl t-butyl ether (MTBE) were added, and after confirming that the solution had become a single layer, the solution was cooled to 0° C. 3 eq. of DMA was added dropwise to the solution, and the precipitation of crystals was confirmed.

[0410] After crystallization and aging at 0 to 5°C for 1 hour, the crystals were filtered, washed with a washing solvent [heptane:MTBE:DMA = 9:1:0.3 (volume ratio)] (1.5V), and dried by nitrogen blow for 15 minutes.

[0411] To the crystals (solid), 7V of heptane and 7V of tap water were added, and after stirring, it was confirmed that all of the solid had dissolved.

[0412] After separation, the organic layer was washed with 6V of 10% DMA water and 12V of tap water (twice at 6V), and the washed organic layer was dried over 1.1 wt of sodium sulfate, after which the solid was filtered off and the solution was concentrated under reduced pressure.

[0413] The composition of the washed organic layer was confirmed by HPLC to be 93.55% CBD, 1.59% olivetol, 3.97% abn-CBD, and 0.89% Δ9-THC. Δ8-THC and the 2:1 adduct were not detected, and the quantitative value was calculated to be 56.27%.

[0414] As is clear from the results of Examples 8 to 10 and Reference Example 1, cannabidiol could be efficiently purified by the method of the present invention (purified product obtained by the method of the present invention). Furthermore, it was found that cannabidiol can be purified more efficiently by using the method of the present invention (purified products obtained by the method of the present invention), particularly purified products from which olivetol and the like have been separated and removed to a high degree (purified products obtained in Examples 1 and 6). [Industrial Applicability]

[0415] According to the present invention, a method for purifying cannabidiol and the like can be provided.

Claims

1. A method for producing a purified product containing cannabidiol by subjecting a mixture containing cannabidiol and at least one member selected from olivetol and positional isomers of cannabidiol to an adsorption treatment.

2. The method of claim 1 , wherein the mixture comprises a solvent.

3. The method according to claim 1, wherein the mixture comprises a solvent containing at least an aliphatic hydrocarbon.

4. The method of claim 1 , wherein the adsorbent is contacted with a mixture comprising a solvent.

5. 2. The method of claim 1, wherein the silica gel is contacted with a mixture containing a solvent that contains at least an aliphatic hydrocarbon.

6. 2. The method according to claim 1, wherein the mixture contains olivetol, and the ratio of olivetol to cannabidiol is 0.05 to 2 on an HPLC area basis.

7. 2. The method of claim 1, wherein the mixture comprises positional isomers of cannabidiol, and the ratio of the positional isomers of cannabidiol to cannabidiol is 0.05 to 2 on an HPLC area basis.

8. the mixture comprises positional isomers of olivetol and cannabidiol, The ratio of olivetol to cannabidiol is 0.05 to 2 based on the area of HPLC; 2. The method according to claim 1, wherein the ratio of the positional isomer of cannabidiol to cannabidiol is 0.05 to 2 based on the area of HPLC.

9. the mixture comprises olivetol, In the mixture, the ratio of olivetol to cannabidiol is N1 based on the HPLC area standard, In the purified product, the ratio of olivetol to cannabidiol is N2 based on the HPLC area standard.

2. The method of claim 1, wherein the value of N1-N2 is 0.03 or greater.

10. the mixture comprises positional isomers of cannabidiol; In the mixture, the ratio of the positional isomer of cannabidiol to cannabidiol is defined as N1 based on the area of HPLC; In the purified product, the ratio of cannabidiol positional isomers to cannabidiol is N2 based on the HPLC area standard.

2. The method of claim 1, wherein the value of N1-N2 is 0.03 or greater.

11. the mixture comprises positional isomers of olivetol and cannabidiol, In the mixture, the ratio of olivetol and positional isomers of cannabidiol to cannabidiol is defined as N1 based on the HPLC area; In the purified product, the ratio of olivetol and positional isomers of cannabidiol to cannabidiol is N2 based on the HPLC area standard.

2. The method of claim 1, wherein the value of N1-N2 is 0.05 or greater.

12. Menthadienol and olivetol, in the presence of at least one catalyst selected from non-boron Lewis acids and Bronsted acids; At temperatures above 40°C, The method includes a step of reacting at a water content of 5% by mass or less in the reaction system at the start of the reaction to produce a reaction mixture containing cannabidiol, 2. The method according to claim 1, wherein the reaction mixture obtained through this step is subjected to an adsorption treatment.

13. A purified product of cannabidiol comprising cannabidiol and an adduct of 2 moles of menthadienol to 1 mole of olivetol, the ratio of cannabidiol to the total amount of cannabidiol, olivetol, positional isomers of cannabidiol, an adduct in which 2 moles of menthadienol are added to 1 mole of olivetol, Δ-9-tetrahydrocannabinol, and Δ-8-tetrahydrocannabinol is 60% or more based on the area of HPLC; Olivetol is not contained or is contained in a ratio of 0.03 or less based on the area of HPLC relative to cannabidiol, The composition is free of positional isomers of cannabidiol or contains them in a ratio of 0.3 or less based on the area of cannabidiol by HPLC; A purified product containing an adduct of 2 moles of menthadienol added to 1 mole of olivetol in a ratio of 0.0001 to 0.5 based on the HPLC area of cannabidiol.

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