Solvate of cannabidiol and method for purifying cannabidiol

Abstract

The present invention provides a solvate of cannabidiol.　In this solvate of cannabidiol, a solvent S1 of the solvate comprises an aprotic polar solvent.

Description

Solvates of cannabidiol and methods for purifying cannabidiol

[0001] The present invention relates to a solvate of cannabidiol and a method for purifying cannabidiol.

[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. 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.

[0003] Special Publication No. 2018-516281

[0004] An object of the present invention is to provide a solvate of cannabidiol, etc.

[0005] Cannabidiol (CBD) can be chemically (artificially) synthesized, for example, by reacting menthadienol with olivetol, but such a reaction typically produces 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 a 2:1 adduct), tetrahydrocannabinol (THC) [particularly, Δ9-THC (Δ ９ -THC), Δ8-THC(Δ ８ -THC)] (for example, represented by the following formula):

[0007] Positional isomer (abn-CBD)

[0008] Adduct (2:1 adduct)

[0009] Δ9-THC

[0010] 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 inventors' investigations, when such by-products are produced (for example, when they are produced in relatively large amounts or when by-products that are difficult to separate from CBD are produced), separation (purification) may be difficult even using conventional purification techniques, 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 result in 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 has been difficult to find reaction (production) conditions that produce CBD while suppressing such by-products. In particular, suppressing the production of one by-product may increase the likelihood of the production of other by-products, 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). Furthermore, it is difficult to simultaneously suppress the production of by-products (suppressing the production of a high level of by-products) and completely react olivetol, and unreacted olivetol may remain in the reaction mixture.

[0016] In this context, the present inventors have discovered that, for example, by reacting menthadienol with olivetol under specific conditions (methods), it is possible to produce CBD while efficiently suppressing the production of by-products, and that by subjecting a mixture containing other components such as olivetol and abn-CBD in addition to CBD to a specific treatment, it is possible to efficiently purify CBD (separate the other components).

[0017] The method discovered by the inventors allows for high levels of separation of other components (olivetol, by-products) in addition to CBD. However, even with this method, it is difficult to completely separate the other components, and CBD may contain trace amounts of other components.

[0018] Furthermore, according to the inventors' investigations, there are circumstances specific to CBD, such as the lack of solvents in which CBD dissolves poorly, the similarity in structure between CBD and by-products, and the tendency of highly polar components (olivetol, etc.) to interfere with CBD crystallization. For these reasons, unless other components are separated at an extremely high level, it can be difficult to obtain CBD that has been purified to an extremely high level by conventional methods such as crystallization, or to efficiently obtain CBD with sufficient yield or recovery efficiency.

[0019] Furthermore, these problems can occur even when CBD is not chemically (artificially) synthesized. For example, while CBD derived from natural ingredients (e.g., CBD purified from hemp) does not (is unlikely to) contain components derived solely from chemical synthesis (e.g., raw material components such as olivetol), it may still contain other components (e.g., other cannabinoids other than CBD [e.g., cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), cannabidivarin (CBDV), THC (Δ9-THC, etc.)]). In particular, these components often cannot be easily separated from CBD using conventional methods such as crystallization (or are difficult to separate), or even if separation is possible, it is extremely inefficient and impractical.

[0020] In this context, the inventors investigated whether it was possible to purify CBD from a mixture (crude CBD) containing CBD and other components (trace amounts of other components) from an entirely different perspective. They discovered that CBD forms solvates with specific solvents, and that by forming (utilizing) such solvates, it is possible to efficiently separate other components. After further investigation, they were able to complete the present invention.

[0021] That is, the present invention relates to the following inventions, etc.: [1] A solvate of cannabidiol, wherein solvent S1 of the solvate comprises an aprotic polar solvent. [2] The solvate according to [1], wherein solvent S1 comprises an amide-based solvent (amides). [3] The solvate according to [1] or [2], wherein solvent S1 comprises dimethylacetamide. [4] The solvate according to any one of [1] to [3], wherein dimethylacetamide is solvated in a ratio of 2 moles per mole of cannabidiol. [5] The solvate according to any one of [1] to [4], wherein the solvate is crystalline. [6] A method for producing a solvate of cannabidiol, wherein solvent S1 of the solvate comprises an aprotic polar solvent, by forming the solvate in a mixture containing cannabidiol and solvent S1 (solvent S1 mixture). [7] The method according to [6], wherein solvent S1 comprises an amide-based solvent (amides). [8] The method of [6] or [7], wherein solvent S1 contains dimethylacetamide, and the solvate is a solvate in which dimethylacetamide is solvated in a ratio of 2 moles per mole of cannabidiol. [9] The method of any of [6] to [8], wherein the mixture further contains solvent S2 different from solvent S1.

[10] The method of any of [6] to [9], wherein the mixture further contains an aliphatic hydrocarbon.

[11] The method of any of [6] to

[10] , wherein the mixture contains dimethylacetamide and an aliphatic hydrocarbon, and a solvate in which dimethylacetamide is solvated in a ratio of 2 moles per mole of cannabidiol is precipitated (crystallized) (obtaining a precipitate / solid / crystal containing the solvate, or forming the solvate in the form of a precipitate / solid / crystal containing the solvate).

[12] The method of any of [6] to

[11] , wherein the mixture further contains another cannabinoid.

[13] The method according to any one of [6] to

[12] , wherein the mixture contains at least one other cannabinoid selected from cannabigerol, cannabinol, cannabichromene, cannabidivarin, and tetrahydrocannabinol.

[14] The method of any of [6] to

[13] , wherein the mixture further comprises at least one other cannabinoid selected from cannabigerol, cannabinol, Δ-9-tetrahydrocannabinol, and Δ-8-tetrahydrocannabinol, and the ratio of cannabigerol, cannabinol, Δ-9-tetrahydrocannabinol, and Δ-8-tetrahydrocannabinol to the total amount of cannabidiol, cannabigerol, cannabinol, Δ-9-tetrahydrocannabinol, and Δ-8-tetrahydrocannabinol is 0.1% or more by area standard in HPLC.

[15] The method of any of [6] to

[14] , wherein the mixture (or cannabidiol) is derived from hemp (particularly cannabis).

[16] The method according to any one of [6] to

[15] , wherein the mixture further contains at least one selected from 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).

[17] A mixture comprising cannabidiol (CBD) and an adduct of 2 moles of menthadienol to 1 mole of olivetol (2:1 adduct), wherein the ratio of cannabidiol (CBD) to the total amount of cannabidiol (CBD), olivetol, a positional isomer of cannabidiol (abn-CBD), an adduct of 2 moles of menthadienol to 1 mole of olivetol (2:1 adduct), Δ-9-tetrahydrocannabinol (Δ9-THC), and Δ-8-tetrahydrocannabinol (Δ8-THC) is 60% or more by HPLC area standard, and wherein the mixture does not contain olivetol or contains olivetol in a ratio of 0.03 or less by HPLC area standard relative to cannabidiol (CBD), The method of any one of [6] to

[16] , which does not contain a positional isomer of cannabidiol (abn-CBD) or contains it in a ratio of 0.3 or less, based on an HPLC area, relative to cannabidiol (CBD), and contains an adduct formed by adding 2 moles of menthadienol to 1 mole of olivetol (2:1 adduct), based on an HPLC area, in a ratio of 0.0001 to 0.5, based on the cannabidiol (CBD).

[18] The method of any one of [6] to

[17] , further comprising a step of subjecting a mixture containing cannabidiol and at least one selected from olivetol and positional isomers of cannabidiol (abn-CBD) to an adsorption treatment to produce a purified product containing cannabidiol, and forming a solvate in a mixture containing the purified product obtained through this step and solvent S1 (solvent S1 mixture).

[19] The method further comprises the steps of reacting 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 a temperature of 40°C or higher, with a water content in the reaction system at the start of the reaction of 5% by mass or less (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, and subjecting the reaction mixture obtained through this step to an adsorption treatment to produce a purified product containing cannabidiol. The method according to any one of [6] to

[18] , wherein a solvate is formed in a mixture containing the purified product obtained through this step and solvent S1 (solvent S1 mixture).

[20] A method of producing (regenerating) cannabidiol by desolvating the solvate according to any one of [1] to [5].

[21] A method of producing (regenerating) cannabidiol by mixing (mixing and desolvating) the solvate according to any one of [1] to [5] with water.

[22] A method of mixing (mixing and desolvating) the solvate according to any one of [1] to [5] with water and a hydrophobic solvent capable of dissolving cannabidiol, and extracting (liquid-liquid separating) cannabidiol (desolvated cannabidiol) into a hydrophobic solvent layer (a layer containing the hydrophobic solvent, a layer separated from water, a separation layer).

[23] A method for producing (regenerating) cannabidiol, comprising the steps of: mixing (mixing and desolvating) the solvate according to any one of [1] to [5] with water and a hydrophobic solvent capable of dissolving cannabidiol; and extracting (separating) the cannabidiol (desolvated cannabidiol) into a layer of the hydrophobic solvent (a layer containing the hydrophobic solvent, a layer separated from water, a separation layer); and crystallizing (e.g., crystallizing) the cannabidiol (regenerated cannabidiol) obtained via the extraction step.

[24] Cannabidiol obtained by the method according to any one of

[20] to

[23] .

[25] The cannabidiol according to

[24] , wherein the proportion of cannabidiol to the total amount of cannabidiol, cannabigerol, cannabinol, Δ-9-tetrahydrocannabinol, and Δ-8-tetrahydrocannabinol is 97% or more based on the area of ​​HPLC.

[26] The cannabidiol according to

[24] or

[25] , wherein the proportion of cannabidiol (CBD) to the total amount of cannabidiol (CBD), olivetol, a positional isomer of cannabidiol (abn-CBD), an adduct of 2 moles of menthadienol to 1 mole of olivetol (2:1 adduct), Δ-9-tetrahydrocannabinol (Δ9-THC), and Δ-8-tetrahydrocannabinol (Δ8-THC) is 97% or more based on the area of ​​HPLC.

[27] Cannabidiol according to any one of

[24] to

[26] , which does not contain solvent S1 (dimethylacetamide, etc.) of the solvate or the proportion of solvent S1 of the solvate is 3% by mass or less.

[28] Cannabidiol according to any one of

[24] to

[27] , which contains solvent S1 of the solvate at 0.001% by mass or more.

[29] Cannabidiol according to any one of

[24] to

[28] , which contains solvent S1 of the solvate at 0.001% by mass or more and hydrocarbons (e.g., aliphatic hydrocarbons such as heptane) at 0.001% by mass or more.

[0022] According to the present invention, a solvate of cannabidiol can be provided.

[0023] Such solvates are useful, for example, for separating CBD (as a solvate) from a mixture containing CBD and other components (trace amounts of other components) [crude CBD, CBD containing (trace amounts of) other components (purified product, crude CBD)].

[0024] As mentioned above, it is difficult to completely separate CBD from other components, but these solvates, unlike CBD, appear to be easier to separate from other components. Therefore, by using these solvates (i.e., the CBD contained in crude CBD is treated as a solvate), it is easier to efficiently separate it from other components.

[0025] Moreover, the solvate is stable as a solvate, yet can be easily desolvated (thus regenerating CBD).

[0026] Therefore, by using such solvates, it is possible to efficiently (and easily) obtain CBD (especially high-purity CBD).

[0027] <Solvate> The solvate of the present invention is a solvate of cannabidiol (CBD) (CBD solvate, solvate of CBD).

[0028] In a solvate of CBD, the solvent (sometimes referred to as the solvent of the solvate, the solvent that forms the solvate, solvent S1, etc.) may typically include an aprotic polar solvent.

[0029] Specific examples of the solvent (solvent S1) in the solvate of CBD include nitrogen-containing solvents {e.g., amides [amide-based solvents, for example, N-substituted linear 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.

[0030] Solvates of CBD may include one or more solvents (e.g., aprotic polar solvents).

[0031] 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 solvents other than an aprotic polar solvent, and in particular may consist solely of an aprotic polar solvent.

[0032] 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.

[0033] In addition, in the solvate of CBD, the substance amount ratio (molar ratio) of CBD to the solvent (solvent S1) is not particularly limited, as long as the solvate is formed.

[0034] The solvates of CBD may in particular be crystalline (crystalline form).

[0035] An example of a solvate of CBD is a solvate of CBD with dimethylacetamide (sometimes referred to as DMA).

[0036] 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, but may be, for example, a solvate solvated with 2 moles of dimethylacetamide per mole of CBD (which may be referred to as CBD-2DMA, CBD·2DMA, etc.) (which may contain at least CBD-2DMA).

[0037] Such CBD-2DMA may, for example, exhibit at least one of the following physical properties (characteristics):

[0038] Powder X-ray (2θ) may have at least the characteristic peak shown in the following (A), and has at least the characteristic peak shown in the following (B) or (C) (characteristic peak including the peak shown in the following (A)).

[0039] (A) (approximately 5 peaks) 8.3±0.2°, 8.5±0.2°, 10.6±0.2°, 16.4±0.2°, 17.0±0.2°

[0040] (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°

[0041] (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°

[0042] ・ １ H-NMR (e.g., 400 MHz, CDCl ３ ): 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, 2H), 2.08 (s, 6 H), 2.18-2.28 (m, 3H), 2.37-2.46 (m, 3H), 2.94 (s, 6H), 3.01 (s, 6H), 3.82-3.8 7 (m, 1H), 4.56 (s, 1H), 4.65-4.67 (m, 1H), 5.56-5.58 (m, 1H), 6.13-6.30 (m, 1H)

[0043] Melting point: 52 to 55°C [by DSC (differential scanning calorimetry)]

[0044] Note that CBD-2DMA typically has lower solubility in various solvents, such as heptane, than CBD. Therefore, CBD-2DMA typically crystallizes more easily than CBD. Therefore, such solvates are particularly useful for efficiently separating (purifying) CBD from mixtures containing CBD and other components (e.g., by-products, olivetol).

[0045] Furthermore, CBD-2DMA appears to be relatively easy to release (desolvate) DMA in water, etc. Therefore, such solvates are also effective in generating (regenerating) CBD.

[0046] [Method for producing solvate of CBD] 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).

[0047] 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 / crystal containing the solvate, or forming the solvate in the form of a precipitate / solid / crystal containing the solvate). Such a method makes it easy to efficiently separate CBD as a solvate.

[0048] As the CBD (CBD used in production, CBD source), CBD (high-purity CBD) may be used, or a mixture containing CBD and other components (trace amounts of other components) may be used.

[0049] In particular, when a mixture containing CBD and other components is used (particularly when a solvate is precipitated using a mixture containing CBD and other components), CBD can be easily separated from the other components as a solvate.

[0050] Other components may include, depending on the origin of the CBD (e.g., natural (hemp, etc.) or chemically synthesized), cannabinoids (cannabinoids other than CBD, other cannabinoids), olivetol, menthadienol, abn-CBD, 2:1 adducts, etc.

[0051] Other cannabinoids include, for example, cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), cannabidivarin (CBDV), THC (Δ8-THC, Δ9-THC, Δ10-THC, etc.), cannabiolic acid (CBDA), cannabigerolic acid (CBGA), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), cannabicyclol (CBL), cannabinodiol (CBND), cannabielsoin (CBE), cannabinotriol (CBT), and the like.

[0052] The other components may be contained in the mixture either alone or in combination of two or more.

[0053] Of these other components, other cannabinoids (e.g., CBG, CBN, CBC, CBDV, THC, particularly CBG, CBN, and THC), olivetol, abn-CBD, 2:1 adducts, and the like are likely to be contained in the mixture.

[0054] Olivetol, menthadienol, abn-CBD, and the 2:1 adduct are often found in synthetically derived CBD (mixtures), while other cannabinoids may be found in mixtures, regardless of whether they are naturally derived or synthetically derived.

[0055] Mixtures containing CBD and other components are not particularly limited, and examples include mixtures of natural origin (e.g., hemp (cannabis, etc.) extracts, purified products of such extracts (mixtures with an increased proportion of CBD), etc.), and mixtures derived from reactions (chemical synthesis) (mixtures that have undergone chemical synthesis).

[0056] Examples of mixtures of natural origin (other components in mixtures of natural origin) include mixtures containing other cannabinoids (mixtures containing CBD and other cannabinoids).

[0057] Examples of the reaction-derived mixture include the reaction mixture and first purified product (crude CBD) described below. Of the reaction mixture and the first purified product, it is particularly preferable to use the first purified product (crude product, first purified product that has undergone the adsorption treatment described below) from the viewpoints of ease of precipitating CBD solvates and efficient production of highly pure CBD.

[0058] 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).

[0059] 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.

[0060] 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).

[0061] 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, etc.), ethane, 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, sulfolane), alcohols [e.g., alkanols (e.g., methanol, ethanol, isopropanol), etc.], polyols (e.g., alkanediols such as ethylene glycol, propylene glycol; glycerin, etc.), etc.], water, etc.

[0062] Representative examples of the solvent S2 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.), and ethers [for example, chain ethers (for example, diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (for example, tetrahydrofuran, dioxane, etc.)].

[0063] 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 linear or cyclic aliphatic hydrocarbon, a saturated or unsaturated hydrocarbon, or a linear or cyclic saturated aliphatic hydrocarbon)], etc.}.

[0064] The solvent S2 may be used alone or in combination of two or more kinds.

[0065] 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].

[0066] The aliphatic hydrocarbon may be used in combination with another solvent (a solvent other than an aliphatic hydrocarbon, for example, an ether). In such a case, the proportion of the other solvent in the entire 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.

[0067] 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).

[0068] 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), 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), etc.

[0069] The solvent (e.g., solvent S2) may or may not contain a protic solvent (e.g., water, alcohols, etc.), but 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), etc.). In particular, the solvent may not contain any water or 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), etc.).

[0070] In the mixture (solvent S1 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.

[0071] In the mixture (solvent S1 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.

[0072] 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 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.

[0073] In addition, 1 molar equivalent means that when the solvate is a solvate in which X moles of solvent (for example, 2 moles in the case of CBD-2DMA) are solvated with 1 mole of CBD, the amount is X moles (for example, 2 moles in the case of CBD-2DMA) per mole of CBD.

[0074] A solvate of CBD can be formed (produced) by reacting (contacting) CBD with solvent S1 in a mixture (solvent S1 mixture). The formation of such a solvate may typically be accompanied by crystallization (crystallization).

[0075] 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.

[0076] 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)].

[0077] 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.

[0078] Furthermore, in such mixing (stepwise mixing), the time required for mixing (mixing time, total time, time until completion of mixing) 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.

[0079] The reaction (crystallization) may be carried out in the absence or presence 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, solvates of CBD. Such seed crystals may be pre-prepared, for example, produced using high-purity CBD (using the method of the present invention), or may be produced 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).

[0080] The reaction (crystallization) may be carried out at room temperature (or ordinary temperature), under heating, or under cooling.

[0081] Specific examples of the reaction (crystallization) temperature include −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).

[0082] In particular, from the viewpoint of facilitating efficient formation of a solvate and facilitating precipitation of a solvate, the reaction (crystallization) temperature may be relatively low or not too high (e.g., 40°C or lower, 35°C or lower, 30°C or lower, 25°C or lower, 20°C or lower, 15°C or lower, 10°C or lower, or 5°C or lower).

[0083] 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.

[0084] The reaction (crystallization) may be carried out under stirring or by leaving the mixture to stand.

[0085] The reaction (crystallization) may be carried out in an inert atmosphere (for example, under nitrogen or argon).

[0086] In the reaction (crystallization), the vessel is not particularly limited, and a conventional vessel can be used.

[0087] Through the above reaction (crystallization), a solvate of CBD is formed (produced).

[0088] The CBD solvate can be separated (recovered) from the reaction (crystallization) mixture using conventional methods. For example, the crystallized (crystallized, precipitated) CBD solvate (crystals, crystallized product, solid content, solid) can be separated (recovered) by filtration, decantation, etc.

[0089] The separated CBD solvate (crystal, crystallized product, solid content, solid) may be washed (washing treatment) if necessary.

[0090] 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 solvent containing hydrocarbons (particularly, aliphatic hydrocarbons), preferably at least aliphatic hydrocarbons, may be used.

[0091] 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).

[0092] Furthermore, in solids (crystals, crystallized products, solid content, second purified products (e.g., purified products obtained via the first purified product), solvates of CBD), CBD can be almost entirely recovered as solvates 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, or substantially 1).

[0093] Furthermore, the solid (crystal, crystallized product, solid content, second purified product, solvate of CBD) may or may not contain other components (e.g., olivetol, components derived from the reaction (chemical synthesis) of by-products, etc.; other cannabinoids, etc.); however, due to the purification process (crystallization, formation of solvates) described above, even if it does contain other components, it is often only in trace amounts (highly purified).

[0094] For example, in a solid (crystal, crystallized product, solid content, second purified product, solvate of CBD), the ratio of CBD (or solvate of CBD) to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC [for example, the ratio based on the area (or peak area, for example, the area measured at a measurement wavelength of 210 nm, hereinafter the same applies to the area of ​​HPLC] of HPLC (high performance liquid chromatography) The [saturation ratio] can be selected, for example, from the range of 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).

[0095] In a solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly one derived from naturally occurring CBD), the ratio (e.g., HPLC area (peak area)) of CBD (or solvate of CBD) to the total amount of CBD (or solvate of CBD) and other cannabinoids [or CBG, CBN, CBC, CBDV, and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN, and THC (e.g., Δ9-THC, Δ8-THC)] The percentage based on the standard) can be selected, for example, from a range of 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).

[0096] In a mixture (e.g., a mixture containing naturally-occurring CBD and other cannabinoids, a mixture before the second purification, or a solvent S1 mixture), the ratio of CBD (e.g., a ratio based on HPLC area (peak area)) to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC is designated M1, and in the second purified product, the ratio of CBD (or a solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC to the total amount of CBD (or a solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC is designated M2. When the proportion of CBD (or CBD solvate) (e.g., the proportion 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 (e.g., 2% or more), and may be 3% 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), and particularly 15% or more (e.g., 16% or more, 17% or more, 18% or more, 19% or more, 20% or more).

[0097] In a mixture (e.g., a mixture containing naturally-occurring CBD and other cannabinoids, a mixture before second purification, a solvent S1 mixture), the ratio of CBD (or a solvate of CBD) and other cannabinoids [or CBG, CBN, CBC, CBDV, and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN, and THC (e.g., Δ9-THC, Δ8-THC)] (e.g., the ratio based on HPLC area (peak area)) is M1; in a solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly a naturally-occurring product), the ratio of CBD (or a solvate of CBD) and other cannabinoids [or CBG, CBN, When the ratio (for example, the ratio based on the HPLC area (peak area)) of CBD (or a solvate of CBD) to the total amount of CBC, CBDV, and THC (for example, Δ9-THC, Δ8-THC) [or CBG, CBN, and THC (for example, Δ9-THC, Δ8-THC)] is taken as M2, the value of M2-M1 may be greater than 0%, or 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).

[0098] The solid (crystal, crystallized product, solid content, second purified product, solvate of CBD, particularly the second purified product) may or may not contain olivetol, but even if it does contain olivetol, it will often contain only small amounts. For example, in the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of olivetol to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio on an HPLC area basis) 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.

[0099] In a mixture (e.g., a mixture containing naturally occurring CBD and other cannabinoids, a mixture before the second purification, or a solvent S1 mixture), the ratio of olivetol (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 is designated M1. In a second purified product, the ratio of olivetol (e.g., ratio based on HPLC area (peak area)) to the total amount of CBD (or solvates of CBD), olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC is designated M2. When the ratio of the area (peak area) of the peak to the area (ratio based on the area (peak area) of the peak) 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).

[0100] The solid (crystal, crystallized product, solid content, second purified product, solvate of CBD, particularly the second purified product) may or may not contain abn-CBD, but even if it does contain abn-CBD, it will often contain only a small amount. For example, in the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of abn-CBD to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio on an HPLC area basis) 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.

[0101] In a mixture (e.g., a mixture containing naturally occurring CBD and other cannabinoids, a mixture before the second purification, or a solvent S1 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., ratio based on HPLC area (peak area)) is designated M1; in a second purified product, the ratio of abn-CBD to the total amount of CBD (or a solvate of CBD), olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC (e.g., ratio based on HPLC area (peak area)) is designated M2. When the proportion of CBD (for example, the proportion based on the HPLC area (peak area)) is M2, the value of M1-M2 may be greater than 0%, and may be selected from a range of about 0.1% or more (for example, 0.5% or more), and may be 1% or more (for example, 1.2% or more), preferably 1.5% or more (for example, 1.8% or more), more preferably 2% or more (for example, 2.2% or more), and particularly 2.5% or more (for example, 2.8% or more, 3% or more, 3.2% or more, 3.5% or more, 3.8% or more, 4% or more).

[0102] The solid (crystal, crystallized product, solid content, second purified product, solvate of CBD, particularly the second purified product) may or may not contain the 2:1 adduct, but even if it does contain it, it will often contain only a small amount. For example, in the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of the 2:1 adduct to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio on an HPLC area basis) 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, 0.0001% or less), etc.

[0103] A solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly one derived from natural sources) may not contain other cannabinoids, or may contain them, but even if it does contain them, it will often contain small amounts. For example, in a solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly one derived from natural sources), the ratio of other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] to the total amount of CBD (or CBD solvate) and other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] The ratio (e.g., ratio based on HPLC area (peak area)) of CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] may be, for example, 20% or less (e.g., 18% or less, 16% 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% 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.

[0104] The solid (crystal, crystallized product, solid content, second purified product, solvate of CBD, particularly the second purified product) may or may not contain Δ9-THC, but even if it does contain it, it will often contain little. For example, in the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of Δ9-THC to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio on an HPLC area basis) 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, 0.0001% or less), etc.

[0105] The solid (crystal, crystallized product, solid content, second purified product, solvate of CBD, particularly the second purified product) may or may not contain Δ8-THC, but even if it does contain Δ8-THC, it often contains little. For example, in the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of Δ8-THC to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio on an HPLC area basis) 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, 0.0001% or less), etc.

[0106] The solid (crystal, crystallized product, solid content, second purified product, solvate of CBD, particularly the second purified product) may or may not contain Δ9-THC and Δ8-THC, but even if it does contain them, they often contain small amounts. For example, in the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of Δ9-THC and Δ8-THC to the total amount of CBD (or solvate of CBD), olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (e.g., ratio on an HPLC area basis) 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, 0.0001% or less), etc.

[0107] When the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) contains olivetol, the ratio of olivetol to CBD (or solvate of CBD) in the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) (i.e., ratio of olivetol / ratio of CBD (or solvate of CBD)) (e.g., 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), etc.

[0108] When the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) contains abn-CBD, the ratio of abn-CBD to CBD (or solvate of CBD) in the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) (i.e., ratio of abn-CBD / ratio of CBD (or solvate of CBD)) (e.g., 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), etc.

[0109] When the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) contains the 2:1 adduct, the ratio of the 2:1 adduct to CBD (or solvate of CBD) in the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) (i.e., ratio of 2:1 adduct / CBD (or solvate of CBD)) (e.g., ratio on an HPLC area basis) is For example, it 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.

[0110] When the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) contains Δ9-THC, the ratio of Δ9-THC to CBD (or solvate of CBD) in the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) (i.e., ratio of Δ9-THC / ratio of CBD (or solvate of CBD)) (e.g., ratio on an HPLC area basis) is For example, it 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.

[0111] When the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) contains Δ8-THC, the ratio of Δ8-THC to CBD (or solvate of CBD) in the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) (i.e., ratio of Δ8-THC / ratio of CBD (or solvate of CBD)) (e.g., ratio on an HPLC area basis) is For example, it 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.

[0112] When the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) contains Δ9-THC and Δ8-THC, the ratio of Δ9-THC and Δ8-THC to CBD (or solvate of CBD) in the solid (crystals, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product) [i.e., (total of the ratio of Δ9-THC and the ratio of Δ8-THC) / the ratio of CBD (or solvate of CBD)] (for example, The ratio based on the HPLC area) can be selected, for example, 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.

[0113] In the solid (crystal, crystallized product, solid fraction, second purified product, solvate of CBD, particularly the second purified product), the ratio of olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC to CBD (or solvate of CBD) [i.e., (the sum of the ratio of olivetol, the ratio of abn-CBD, the ratio of 2:1 adduct, the ratio of Δ9-THC, and the ratio of Δ8-THC) / CBD (or solvate of CBD)] The ratio of the hydroxybenzoate (solvent) (e.g., ratio based on HPLC area) can be selected, for example, from a range of 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), etc.

[0114] [Mixture Containing CBD and Other Components] As described above, in the production of a CBD solvate, a mixture (such as a naturally occurring mixture or a reaction-derived mixture) containing CBD and other components (trace amounts of other components) may be used as the CBD (CBD used in the production, CBD source). Such mixtures [mainly reaction (chemical synthesis)-derived mixtures (mixtures obtained via chemical synthesis)] will be described in detail below.

[0115] Other components include unreacted raw materials (e.g., olivetol, menthadienol), by-products (abn-CBD, 2:1 adducts, Δ9-THC, Δ8-THC, etc.), other components used in the reaction (e.g., catalyst), etc. The other components may also be other cannabinoids.

[0116] The other components may typically include at least one selected from olivetol and by-products (abn-CBD, 2:1 adducts, Δ9-THC, Δ8-THC, etc.). Note that such other components are often contained in the mixture resulting from the reaction.

[0117] Furthermore, the mixture may typically contain other cannabinoids as other components [for example, one selected from CBG, CBN, CBC, CBDV, and THC (e.g., Δ9-THC, Δ8-THC), particularly one selected from CBG, CBN, and THC (e.g., Δ9-THC, Δ8-THC)]. Such other cannabinoids are often contained in naturally-derived mixtures, but cannabinoids such as THC are also often contained in reaction-derived mixtures, as described above.

[0118] An example of such a mixture (one embodiment) is a mixture containing other cannabinoids. Note that such a mixture may be either a naturally occurring mixture or a reaction-derived mixture, and may particularly be a naturally occurring mixture.

[0119] The mixture containing other cannabinoids may be, for example, one obtained by separating (purifying) CBD from a naturally occurring raw material (e.g., hemp), or may be a commercially available product.

[0120] In such a mixture, the proportion of CBD (e.g., the proportion based on HPLC area (peak area)) relative to the total amount of CBD and other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, 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 65% ​​or more (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, 81% or more, 82% or more, 83% or more, 84% or more, 85% or more, 86% or more, 87% or more, 88% or more, 89% or more, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more), or 99.99% or less (for example, 99.9% or less, 99.8% or less, 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), etc.

[0121] In a mixture (a mixture containing other cannabinoids), the ratio (e.g., ratio based on HPLC area (peak area)) of other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] to the total amount of CBD and other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] can be selected from a range of, for example, 0.01% or more (e.g., 0.03% or more), and is preferably 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, 0.8% or more), particularly 1% or more (e.g., 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, 2.5% or more, 3% or more, 3.5% or more, 4% or more, 5% 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, 2% or less, 1.5% or less, 1% or less), etc.

[0122] Examples of the mixture (one embodiment of a mixture, a mixture derived from a reaction) include a reaction mixture, a first purified product (crude CBD), etc. Among the reaction mixture and the first purified product (e.g., a purified product obtained by subjecting a reaction mixture to an adsorption treatment), it is particularly preferable to use the first purified product (a crude product, a first purified product that has undergone the adsorption treatment described below) from the viewpoints of ease of precipitating a CBD solvate, ease of efficiently obtaining highly pure CBD, etc.

[0123] Below, we will discuss in detail such mixtures (especially reaction-derived mixtures) containing CBD and other components (trace amounts of other components).

[0124] (Reaction Mixture) The reaction mixture (CBD-containing reaction mixture, CBD) is not particularly limited, but is usually obtained by reacting menthadienol with olivetol. CBD is produced (generated) by such a reaction.

[0125] The ratio (usage ratio) of menthadienol to 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, and may be 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), and 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 may be 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.).

[0126] 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.).

[0127] 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).

[0128] 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.

[0129] 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).

[0130] 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.).

[0131] 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).

[0132] The Bronsted acid may be an organic acid or an inorganic acid.

[0133] 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.

[0134] Examples of inorganic acids include hydrogen halides (eg, hydrogen chloride, hydrogen bromide, hydrogen iodide), sulfuric acid, nitric acid, phosphoric acid, and the like.

[0135] The catalyst (acid catalyst) may be used alone or in combination of two or more kinds.

[0136] Representative catalysts include non-boron Lewis acids [eg, metal oxides, metal halides, metal triflates], carboxylic acids, sulfonic acids, inorganic acids, and the like.

[0137] 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.

[0138] 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)].

[0139] As described 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)].

[0140] 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, or boron trifluoride hydrate)]; however, 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) or the like, it is not necessary to use (concurrent use, substantially not use (concurrent use)] the specific catalyst.

[0141] 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 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 (and further, in combination with other conditions, suppressing the production of by-products and achieving good reactivity efficiently), 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).

[0142] 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, suppressing the production of by-products and achieving good reactivity efficiently), 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).

[0143] The reaction may be carried out in the presence of a solvent (in a solvent).

[0144] Examples of the solvent include hydrocarbons [for example, aliphatic hydrocarbons (for example, hexane, heptane, cyclohexane, 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, dioxane, etc.), etc.], glycol ethers (for example, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol diethyl ether, diethylene glycol monoethyl ether, etc.), glycol ether esters (for example, ethylene glycol monomethyl ether acetate, etc.), nitrogen-containing solvents {for example, amides [for example, N-substituted chain amides (for example, N-alkyl-substituted alkanamides such as N,N-dimethylformamide and N,N-dimethylacetamide; N,N-diphenylacetamide, etc.), cyclic amides (for example, 2-pyrrolidone and 1,3-dimethyl-2-imidazolidinone, etc.)], nitriles (for example, acetonitrile, etc.)}, sulfur-containing solvents (for example, sulfoxides such as dimethyl sulfoxide; sulfones such as dimethyl sulfone and sulfolane), alcohols [for example, alkanols (for example, methanol, ethanol, isopropanol), etc.], polyols (for example, alkanediols such as ethylene glycol and propylene glycol; glycerin, etc.), etc.], water, etc.

[0145] The above-mentioned Bronsted acid [for example, an organic acid (for example, acetic acid)] may be used as the solvent.

[0146] 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-polar (non-) solvent, etc. An aprotic solvent may be preferably used as the solvent.

[0147] The solvents may be used alone or in combination of two or more kinds.

[0148] Among these solvents, aprotic solvents and the like may be preferably used 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), and in particular, hydrocarbons (particularly, aromatic hydrocarbons such as toluene) may be preferably used.

[0149] Therefore, the solvent may contain at least an aprotic solvent or a hydrocarbon (particularly, an aromatic hydrocarbon such as toluene).

[0150] 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 (furthermore, in combination with other conditions, suppressing the production of by-products and achieving good reactivity efficiently), the solvent may preferably not contain a protic solvent or, if it contains a protic solvent, may contain a small amount of the protic solvent [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.].

[0151] In particular, it is preferable that the solvent (reaction system) does not contain water or contains only a small amount of water, from the viewpoints 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).

[0152] 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), and is 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 mass% or less, 0.12 mass% or less, 0.1 mass% or less, 0.08 mass% or less, 0.07 mass% or less, 0.06 mass% or less, 0.04 mass% or less, 0.03 mass% or less, 0.01 mass% or less.

[0153] 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.

[0154] 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.

[0155] 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).

[0156] 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 the solvent.

[0157] 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.].

[0158] In this way, when the raw material already contains water and it is necessary to reduce the protic solvent (water, etc.), the protic solvent may be separated or removed from the raw material or the reaction system by a conventional method (for example, distillation, etc.) (the water content may be adjusted to the above-mentioned range by separating or removing the protic solvent).

[0159] 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.

[0160] 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.

[0161] When a solvent is used, the ratio of the solvent to 1 part of 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.

[0162] 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 a plurality of components may be mixed in advance, or these may be combined.

[0163] In particular, 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), 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 reacting (allowing the catalyst to function), the mixture containing olivetol and the catalyst may be mixed with menthadienol (e.g., adding menthadienol dropwise into a system (mixture) containing olivetol and the catalyst).

[0164] The mixing may be carried out all at once or in stages, preferably in stages.

[0165] Such mixing (staged mixing) may be intermittent, continuous (continuous), or a combination thereof.

[0166] Furthermore, in such mixing (stepwise mixing), the time required for mixing (mixing time, total time, time until completion of mixing) 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), and 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.

[0167] The reaction may be carried out at room temperature (or ordinary temperature), under heating, or under cooling.

[0168] 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).

[0169] 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).

[0170] 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.

[0171] The reaction is considered to start when menthadienol and olivetol (and further the catalyst) coexist and are in a state where they can react, and the reaction is considered to end 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 carried out.

[0172] 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.

[0173] The reaction may be carried out under stirring.

[0174] The reaction may also be carried out under an inert atmosphere (for example, under nitrogen or argon).

[0175] The reaction may be carried out in a batch or continuous manner.

[0176] In the reaction, the reaction vessel is not particularly limited, and a conventional one can be used.

[0177] Cannabidiol is produced (manufactured) through the above reaction. Cannabidiol is usually obtained as a mixture containing cannabidiol (reaction mixture, reaction liquid). The present invention also encompasses such a mixture (reaction mixture).

[0178] The mixture (reaction mixture) may be concentrated (solvent removed), filtered, or the like.

[0179] 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)] varies depending 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%).

[0180] 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).

[0181] The CBD production rate (upper limit) 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.

[0182] 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)).

[0183] The mixture (particularly the reaction mixture) contains CBD and other ingredients, as described above.

[0184] In the mixture (e.g., 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 HPLC area (peak 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.

[0185] When a mixture (such as a reaction mixture) contains olivetol, the proportion of olivetol (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 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.

[0186] 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.

[0187] When a mixture (such as a reaction mixture) contains olivetol and abn-CBD, the proportion of olivetol and abn-CBD (e.g., 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, 0.2% 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.

[0188] When the mixture (such as a reaction mixture) 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 mixture (for example, the ratio based on HPLC area) can be selected from the range of, for example, 0.01% or more (for example, 0.05% or more), and is preferably 0.1% or more (for example, 0.3% or more), preferably 0.5% or more (for example, 0.7% or more), more preferably 1% or more (for example, 1.2% or more), particularly preferably 1.5% or more (for example, , 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 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.

[0189] When the mixture (reaction mixture, etc.) 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 (for example, the ratio based on HPLC area) can be selected from the 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, It may be 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 it may be 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.

[0190] When the mixture (reaction mixture, etc.) 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 (for example, the ratio based on HPLC area) can be selected from a range of, for example, 0.001% or more (for example, 0.005% or more), 0.01% or more (for example, 0.03% or more), preferably 0.05% or more (for example, 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.

[0191] 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 HPLC area) can be selected from the 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.

[0192] When the mixture (reaction mixture, etc.) contains olivetol, the ratio of olivetol to CBD in the mixture (i.e., olivetol ratio / CBD ratio) (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 is 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 or less, 1.9 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 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.

[0193] 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 is 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 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.

[0194] 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 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 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 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.

[0195] When a 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 on an HPLC area basis) can be selected from a range of, for example, 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), and 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.

[0196] When a mixture (such as a reaction mixture) contains abn-CBD and the 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 from a range of, for example, 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. 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 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.

[0197] When the mixture (reaction mixture, etc.) contains Δ9-THC, the ratio of Δ9-THC to CBD in the mixture (i.e., Δ9-THC ratio / CBD ratio) (e.g., ratio based on HPLC area) can be selected from a range of, for example, about 1 or less (e.g., 0.8 or less), and is 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 (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), etc.

[0198] 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 / the ratio of CBD) (for example, the ratio based on the HPLC area) can be selected from a range of, for example, about 0.1 or less (for example, 0.08 or less), and can be 0.05 or less (for example, 0.04 or less), preferably 0.03 or less (for example, 0.028 or less), more preferably 0.025 or less (for example, 0.022 or less), particularly 0.02 or less (for example, 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 ... 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 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, 0.001 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), etc.

[0199] When the mixture (reaction mixture, etc.) 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] (for example, the ratio based on the HPLC area) can be selected, for example, from a range of about 1 or less (for example, 0.8 or less), and is 0.5 or less (for example, 0.4 or less), preferably 0.3 or less (for example, 0.28 or less), more preferably 0.25 or less (for example, 0.22 or less), particularly 0.2 or less (for example, 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.

[0200] 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), 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 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.

[0201] In the mixture (reaction mixture, etc.), 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 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), particularly 2 or less (e.g., 1. 0.9 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 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.

[0202] (First Purified Product (Crude CBD)) As described above, the reaction mixture (mixture after the reaction) typically contains components other than CBD.

[0203] 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)).

[0204] 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.

[0205] In this regard, in the above-described mixture (reaction mixture), it is possible to relatively suppress the production of by-products (and thus obtain a mixture with relatively few by-products (low in CBD)). Therefore, by utilizing such a mixture (for example, the reaction mixture obtained by the method of the present invention), efficient purification is possible, as described above, in combination with the formation of solvates.

[0206] 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 (relative to CBD)). This method is described in detail below.

[0207] (Adsorption Step (First Purification Step)) First, the mixture is subjected to an adsorption treatment, if necessary.

[0208] Such adsorption treatment appears to facilitate relatively efficient separation of by-products, particularly olivetol and abn-CBD [facilitating selective separation (separation by adsorption)]. Therefore, such adsorption treatment is particularly effective for mixtures containing (particularly containing a relatively large amount of) olivetol or abn-CBD (a component that is at least one selected from olivetol and abn-CBD).

[0209] 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).

[0210] 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.

[0211] Examples of the solvent 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.), and ethers [for example, chain ethers (for example, diethyl ether, methyl t-butyl ether, etc.), cyclic ethers (for example, tetrahydrofuran, dioxane, etc.)]. , glycol ethers (for example, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol monomethyl ether, diethylene glycol monoethyl ether, etc.), glycol ether esters (for example, ethylene glycol monomethyl ether acetate, etc.), nitrogen-containing solvents {for example, amides [for example, N-substituted chain amides (for example, N-alkyl-substituted alkanamides such as N,N-dimethylformamide), cyclic amides (for example, 2-pyrrolidone, etc.)], etc.}, nitriles (for example, acetonitrile, etc.), sulfur-containing solvents (for example, sulfoxides such as dimethyl sulfoxide; sulfones such as dimethyl sulfone and sulfolane), alcohols [for example, alkanols (for example, methanol, ethanol, isopropanol), etc.], polyols (for example, alkanediols such as ethylene glycol and propylene glycol; glycerin, etc.), etc.], water, etc.

[0212] The solvents may be used alone or in combination of two or more kinds.

[0213] 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.

[0214] 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 linear or cyclic aliphatic hydrocarbon, a saturated or unsaturated hydrocarbon, or a linear or cyclic saturated aliphatic hydrocarbon)], etc.}.

[0215] 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].

[0216] 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.

[0217] 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)].

[0218] 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.

[0219] 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) by volume, 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.

[0220] 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 in 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, etc.) 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; or, if the same solvent is used but the amount (ratio) of the solvent is different, the amount of the solvent may be adjusted appropriately (for example, by concentration or mixing).

[0221] 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).

[0222] 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 (such as activated alumina ion exchange resins).

[0223] 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).

[0224] The shape of the adsorbent (silica, etc.) is not particularly limited, but examples thereof include granular shapes, and granular shapes include spherical shapes.

[0225] When the adsorbent is granular, 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).

[0226] The adsorbents may be used alone or in combination of two or more.

[0227] 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) relative to 1 part by mass of CBD (or the solids content (components other than the solvent) contained in the mixture), and 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).

[0228] 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 contained in the mixture (components other than the solvent)], and 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).

[0229] 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)], or a combination of these methods.

[0230] 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.

[0231] The mixing may be carried out under stirring.

[0232] The mixing may be carried out in an inert atmosphere (for example, under nitrogen or argon).

[0233] The container for mixing is not particularly limited, and a conventional container can be used.

[0234] The adsorption treatment conditions are not particularly limited and can be selected appropriately depending on the amount, type, etc. of the adsorbent. For example, adsorption may be performed 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, etc., and is not particularly limited. For example, the adsorption treatment time may be 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.

[0235] 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.

[0236] 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 adsorbed mixture. This method (washing step) can also recover CBD, etc., from the adsorbent (e.g., CBD that is attached to the adsorbent (not adsorbed)). Therefore, after the adsorption treatment, a further washing step (a step of washing the adsorbent (washing the adsorbent to recover CBD, etc.)) may be performed.

[0237] 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.

[0238] The amount of the washing solvent used can be appropriately selected depending on the amount of the adsorbent, etc.

[0239] 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.

[0240] Through the above-described steps [adsorption treatment (adsorption treatment step), and further, if necessary, a washing step, etc.], a purified product containing CBD [which may be 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}.

[0241] 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 to be 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).

[0242] In the first purified product, the proportion of CBD (e.g., proportion based on HPLC area (peak area)) relative to the total amount of CBD, olivetol, abn-CBD, the 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 more (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.

[0243] 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).

[0244] The first purified product may or may not contain olivetol, but even if it does, it often contains a small amount. For example, in the first purified product, the ratio of olivetol (e.g., ratio based on HPLC area) to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC 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.

[0245] 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%, 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, or the like.

[0246] In the mixture (mixture to be subjected to adsorption treatment, reaction mixture, etc.), the ratio of olivetol (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 is designated M1, and in the first purified product, the ratio of olivetol (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 is 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 0.01% 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).

[0247] The first 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 first purified product, the ratio of abn-CBD 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, 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.

[0248] When the first purified product contains abn-CBD, the ratio of abn-CBD 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 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or the like.

[0249] In the mixture, the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (for example, the ratio based on the HPLC area (peak area)) is M1, and in the first purified product, the ratio of abn-CBD to the total amount of CBD, olivetol, abn-CBD, the 2:1 adduct, Δ9-THC, and Δ8-THC (for example, the ratio based on the HPLC area (peak area)) is 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).

[0250] The first purified product may or may not contain olivetol and abn-CBD, but even if it does, it often contains 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 adduct, 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.

[0251] 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, 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 0.01%, 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, or the like.

[0252] In the mixture, the ratio of olivetol and abn-CBD to the total amount of CBD, olivetol, abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC (for example, 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 adduct, Δ9-THC, and Δ8-THC (for example, the ratio based on the HPLC area (peak area)) is designated M2. When M1 is set as M1, 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).

[0253] The first purified product may contain other components (for example, by-products).

[0254] For example, when the first purified product 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 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., 0.05% 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 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.

[0255] 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 (for example, the ratio based on HPLC area) can be selected from the 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), more preferably 0.5% or more (for example, 0.7% or more), particularly 0.8% or more (for example, , 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 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), etc.

[0256] 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 (for example, the ratio based on HPLC area) can be selected from the range of, for example, 0.001% or more (for example, 0.005% or more), 0.01% or more (for example, 0.03% or more), preferably 0.05% or more (for example, 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.

[0257] 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 (for example, the ratio based on HPLC area) can be selected from the 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), more preferably 0.5% or more (for example, 0.7% or more), particularly 0.8% or more (for example, 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 may be 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, 5.5% or less, 5% or less, 4.5% or less, 4% or less), etc.

[0258] 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.

[0259] 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).

[0260] When the first purified product contains abn-CBD, the ratio of abn-CBD to CBD in the first purified product (i.e., ratio of abn-CBD / ratio of CBD) (e.g., ratio on an HPLC area basis) 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.

[0261] 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 the 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 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).

[0262] 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.

[0263] 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).

[0264] 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 on an HPLC area basis) can be selected from a range of, for example, 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), and 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.

[0265] 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 on an HPLC area basis) 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.

[0266] 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 / the ratio of CBD) (for example, the ratio based on the HPLC area) can be selected from a range of, for example, about 1 or less (for example, 0.8 or less), and is preferably 0.5 or less (for example, 0.4 or less), preferably 0.3 or less (for example, 0.28 or less), more preferably 0.25 or less (for example, 0.22 or less), and particularly preferably 0.2 or less (for example, 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 (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), etc.

[0267] When the first purified product contains Δ8-THC, the ratio of Δ8-THC to CBD in the first purified product (i.e., Δ8-THC ratio / CBD ratio) (e.g., 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 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. 0.018 or less, 0.015 or less, 0.012 or less, 0.01 or less), or 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, 0.001 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).

[0268] 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 is preferably 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 preferably 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 (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.

[0269] 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 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.

[0270] In the mixture, the ratios of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC relative 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) were designated N1, and in the first purified product, the ratios of olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC relative to CBD [i.e., (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) were designated N2. When N1-N2 is the ratio of CBD to total CBD (the sum of the ratio of Δ9-THC, the ratio of Δ8-THC, and the ratio of Δ9-THC) / the ratio of CBD (e.g., the ratio on an HPLC area basis), 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).

[0271] 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 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.

[0272] In the mixture, the ratio of abn-CBD, 2:1 adduct, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of the ratio of abn-CBD, the ratio of 2:1 adduct, 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 adduct, Δ9-THC, and Δ8-THC to CBD [i.e., the sum of the ratio of abn-CBD, the ratio of 2:1 adduct, the ratio of Δ9-THC, and the ratio of Δ8-THC] / CBD] (e.g., the ratio based on HPLC area) was designated N2. When the ratio of the surface area of ​​the 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, 0.22 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).

[0273] <CBD production from solvates> CBD can be produced (manufactured, regenerated) from solvates of CBD [for example, solvates obtained via naturally-derived CBD (crude CBD), second purified products, crystals or crystallized products (obtained from naturally-derived CBD (crude CBD) or via a second purification step (for example, a step of obtaining a second purified product via a first purified product)].

[0274] 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 characteristics of the solvate of CBD, etc.

[0275] Specific methods include desolvation by heating the CBD solvate, and desolvation by dissolvation by dissolving the CBD solvate in a solvent.

[0276] 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.

[0277] The CBD produced can be separated (recovered) by any conventional method, particularly extraction.

[0278] 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). Examples of 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 linear or cyclic aliphatic hydrocarbon, a saturated or unsaturated hydrocarbon, or a linear or cyclic saturated aliphatic hydrocarbon)], etc.}.

[0279] 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 a higher CBD purity).

[0280] For example, 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 such trace amounts of olivetol and by-products from CBD.

[0281] CBD can then be obtained from the separated layer (e.g., the hydrophobic solvent layer).

[0282] The separation layer (for example, the hydrophobic solvent layer) may be further washed with a solvent (washing solvent) such as water.

[0283] The washing may be repeated once or twice or more times.

[0284] 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 separation layer (e.g., hydrophobic solvent layer). When washing is performed two or more times, the ratio (amount used, total amount) of the washing solvent per washing 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 separation layer (e.g., hydrophobic solvent layer).

[0285] CBD can be obtained by removing the solvent component from the separation layer (e.g., the hydrophobic solvent layer), or by crystallizing the CBD, which may allow for further purification (higher CBD purity) as described above.

[0286] CBD can be crystallized using a conventional method, and is not particularly limited to, for example, crystallization (recrystallization).

[0287] 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.)].

[0288] 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.

[0289] In crystallization (recrystallization), the proportion (amount used) of the solvent can be selected depending on the crystallization conditions and the like, and may be, for example, a proportion (concentration) that results in a solid content 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) to 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).

[0290] The reaction (crystallization) may be carried out in the presence of seed crystals.

[0291] The crystallization (recrystallization) may be carried out at room temperature (or ordinary temperature), under heating, or under cooling.

[0292] 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).

[0293] 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.

[0294] The crystallization (recrystallization) time can be appropriately selected depending on the degree of progress of crystallization (recrystallization), various crystallization (recrystallization) conditions, and the like, 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), 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), and the like.

[0295] The crystallization (recrystallization) may be carried out under stirring or by leaving the mixture to stand.

[0296] The crystallization (recrystallization) may be carried out in an inert atmosphere (for example, under nitrogen or argon).

[0297] In the crystallization (recrystallization), the vessel is not particularly limited, and a conventional vessel can be used.

[0298] Through the above reaction (crystallization), CBD is produced (manufactured, recovered, and recycled).

[0299] 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).

[0300] Furthermore, CBD may or may not contain components other than CBD (olivetol, by-products, other cannabinoids, etc.), but even if it does contain them, they will be in extremely small amounts (highly purified).

[0301] 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 and other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, 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%.

[0302] Furthermore, in CBD (regenerated CBD), 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 HPLC area (peak area)) 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%.

[0303] CBD (regenerated CBD) may or may not contain olivetol, but even if it does, it is often present in small amounts. For example, in CBD (regenerated CBD), the ratio of olivetol (e.g., ratio based on HPLC area) to the total amount of CBD, olivetol, abn-CBD, 2:1 adducts, Δ9-THC, and Δ8-THC 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.

[0304] CBD (regenerated CBD) may or may not contain abn-CBD, but even if it does, it often contains a small amount. 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.

[0305] CBD (regenerated CBD) may or may not contain 2:1 adducts, but even if it does, it often contains 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.

[0306] CBD (regenerated CBD) may or may not contain other cannabinoids, but even if it does contain other cannabinoids, it often contains small amounts. For example, in CBD (regenerated CBD), the ratio of other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] to the total amount of CBD and other cannabinoids [or CBG, CBN, CBC, CBDV and THC (e.g., Δ9-THC, Δ8-THC)] [or CBG, CBN and THC (e.g., Δ9-THC, Δ8-THC)] is For example, the ratio of the total amount of Δ9-THC, Δ8-THC) (for example, the ratio on an HPLC area basis) may be, for example, 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, 0.05% or less, 0.01% or less, 0.001% or less, 0.0001% or less, or the like.

[0307] 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 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.

[0308] CBD (regenerated CBD) may or may not contain Δ8-THC, but even if it does, it often contains little Δ8-THC. For example, in CBD (regenerated CBD), the ratio of Δ8-THC to the total amount of CBD, 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.

[0309] 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 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.

[0310] When the CBD (regenerated CBD) contains olivetol, the ratio of olivetol to CBD in the CBD (regenerated CBD) (i.e., the olivetol ratio / CBD ratio) (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.

[0311] 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 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, 0.0001 or less), etc.

[0312] When the CBD (regenerated CBD) contains 2:1 adducts, the ratio of the 2:1 adducts to CBD in the CBD (regenerated CBD) (i.e., the ratio of 2:1 adducts / 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.

[0313] When CBD (regenerated CBD) contains Δ9-THC, the ratio of Δ9-THC to CBD in the CBD (regenerated CBD) (i.e., Δ9-THC ratio / CBD ratio) (e.g., 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.

[0314] When the CBD (regenerated CBD) contains Δ8-THC, the ratio of Δ8-THC to CBD in the CBD (regenerated CBD) (i.e., Δ8-THC ratio / CBD ratio) (e.g., 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.

[0315] When the 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.

[0316] 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] (for example, , ratio based on the HPLC area) can be selected, for example, from a range of 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.

[0317] CBD (regenerated CBD) typically does not contain (or the amount is below the detection limit for) a solvent [residual solvent, for example, a solvent derived from a solvate (a solvent constituting 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 proportion of the solvent relative to the total 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 solvent derived from the solvate (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.

[0318] In addition, when CBD (regenerated CBD) contains a solvent (solvent component), the proportion of the solvent relative to the total CBD (CBD including residual solvent) may be equal to or greater than 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 solvent derived from the solvate (the solvent constituting the solvate, e.g., 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, 0.0001% 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.

[0319] The proportion of the solvent may be measured, for example, by gas chromatography.

[0320] The CBD (reconstituted CBD) may in particular be crystalline (in crystalline form).

[0321] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0322] The various analyses and measurements (calculations) were carried out as follows.

[0323] [HPLC] Measurement was performed using the following equipment and conditions: Equipment: LC-2010HT manufactured by Shimadzu Corporation Measurement wavelength: 210 nm Column: Xselect CSH C18 manufactured by Waters Corporation, 4.6 mm x 150 mm (particle size: 3.5 μm) Column temperature: 35°C Mobile phase A: 0.1% formic acid aqueous solution Mobile phase B: 0.1% formic acid acetonitrile solution Flow rate: 1.0 mL / min Gradient:

[0324]

[0325] The "%" in the composition indicates that the total peak area from 0.0 to 18.0 minutes is 100%.

[0326] [Powder X-ray (2θ)] Measurement was performed using the following equipment and conditions: Equipment: SmartLab manufactured by Rigaku Corporation Measurement method: Reflection method Type of light source: Cu tube Wavelength used: CuKβ rays Tube current: 200 mA Tube voltage: 45 Kv Sample plate: Circular non-reflective sample holder Incident angle of X-ray: 4 to 40°

[0327] [ １ H-NMR] Bruker Ascend ＴＭ 400.

[0328] [Melting Point] The endothermic peak temperature in DSC was measured using the following apparatus and conditions, and was taken as the melting point. Apparatus: DSC 3+ manufactured by Mettler Toledo K.K. Conditions: Approximately 1.2 mg of sample was weighed and placed in an aluminum pan, and the measurement was performed at a temperature range of 60°C to 70°C and a heating rate of 0.5°C / min.

[0329] [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) Injection port temperature: 200°C Detector temperature: 230°C Carrier gas: N ２ Flow control mode: constant flow Split ratio: 40:1 Injection volume: 1.0 μL 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), etc.

[0330] Example 1 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 a solid (crystal).

[0331] 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).

[0332] 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).

[0333] The analysis results are as follows:

[0334] Powder X-ray (2θ): It was confirmed that the characteristic peaks shown in (C) above (i.e., the following approximately 20 peaks) 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°

[0335] ・ １ H-NMR δppm: 0.88 (t, J=7.2Hz, 3H), 1.22-1.36 (m, 2H), 1.52-1.60 (m, 2H), 1.64-1.6 7 (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, 1H), 4.56 (s, 1H), 4.65-4.67 (m, 1H), 5.56-5.58 (m, 1H), 6.13-6.30 (m, 1H)

[0336] Melting point: 52 to 55°C [according to the above-mentioned device and conditions (DSC)]

[0337] The resulting solid (crystal, CBD-2DMA) had lower solubility in various solvents such as heptane than CBD.

[0338] 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.

[0339] There, zinc iodide (ZnI ２ 3.19 parts by mass (0.1 eq. relative to menthadienol) of menthadienol was added, 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 the mixture was allowed to react for 5 minutes after the dropwise addition, and then returned to room temperature over 1 hour, yielding a reaction mixture (reaction liquid).

[0340] The proportion of water in the reaction vessel (in the reaction system) was 0.04% by mass when menthadienol was added (at the start of the reaction, immediately before the addition).

[0341] The composition of the reaction solution was confirmed by HPLC, and 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 solution by HPLC using a standard (CBD standard) (the same applies hereinafter).

[0342] Synthesis Example 2 In a reaction vessel, tetrahydrofuran (20V) and boron trifluoride diethyl etherate (BF ３ OEt ２ ) (1.8 eq. relative to menthadienol) was added, and the temperature was adjusted to -10°C using a jacket.

[0343] To this was added (flowed) 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] 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 the addition (flowed) and then returned to room temperature over 1 hour to obtain a reaction mixture (reaction liquid).

[0344] The composition of the reaction solution was confirmed by HPLC, and was found to be 13.97% CBD, 31.365% olivetol, and 45.02% abn-CBD, with Δ9-THC and Δ8-THC below the detection limit.

[0345] 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.

[0346] [Example 2] (Crude Product Preparation Step) In the crude product preparation step, the mass of menthadienol used in the reaction was used as the basis for wt (mass) and V (volume). The reaction solution obtained in Synthesis Example 1 was concentrated under reduced pressure to 2.9 wt, 104.10 parts by mass of heptane (10V) was added, and the mixture was again concentrated under reduced pressure to replace the solvent with heptane.

[0347] To the concentrate, 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.

[0348] 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 then concentrated under reduced pressure to 1.6 wt to obtain a crude product (mixture, first purified product).

[0349] The composition of the crude product was confirmed by HPLC to be 79.91% CBD, 0.41% olivetol, 4.63% abn-CBD, 2.95% Δ9-THC, 0.72% Δ8-THC, and 7.9% 2:1 adduct. The quantitative value was calculated to be 55.7%.

[0350] (Purification Step) In the purification step, the quantitative values ​​of cannabidiol in the crude product (mixture, first purified product) were used as the basis for wt (mass), V (volume), and eq. (equivalent). 107.85 parts by mass of heptane (9V) and 12.96 parts by mass of methyl t-butyl ether (MTBE) (1V) were added to the obtained crude product, and after confirming that the solution had become a single layer, it was cooled to 10°C.

[0351] 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 Example 1 was added.

[0352] 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 then dried by blowing nitrogen for 20 minutes.

[0353] The obtained crystals (solid) were confirmed to be CBD·2DMA (containing CBD·2DMA) by the same method as above.

[0354] 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.

[0355] 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.

[0356] The composition of the organic layer after washing was confirmed by HPLC, and was found to be 99.63% CBD, 0.1% olivetol, and 0.27% abn-CBD, with no Δ9-THC, Δ8-THC, or 2:1 adducts detected. The quantitative value was calculated to be 51.8%.

[0357] In the subsequent purification 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 aged at 25°C for 1 hour.

[0358] Thereafter, the mixture was cooled to 0-5°C over 20 minutes, and after 45 minutes of crystallization aging, it was cooled to -15°C over 15 minutes. After 2 hours of crystallization aging, the crystals (solid) were filtered and washed with 12.07 parts by mass (1.1 V) 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 on the jacket to obtain 14.92 parts by mass of a solid (crystal).

[0359] The obtained solid (crystal) is １ H-NMR analysis confirmed that the solid was CBD. In other words, it was found that the obtained solid (crystal, CBD-2DMA) released DMA in water and became CBD (regenerated CBD).

[0360] The composition of the solid (CBD crystals) was confirmed by HPLC to be 100.00% CBD, with no detectable olivetol, abn-CBD, Δ9-THC, Δ8-THC, or 2:1 adduct. The CBD yield (assuming 100% reaction of menthadienol) was calculated to be 46.9% (calculated by subtracting the mass of the seed crystals).

[0361] Furthermore, the resulting solid (CBD crystals) contained very small amounts of residual solvent (176 ppm by mass of heptane and 251 ppm by mass of DMA). Therefore, various additions and modifications were made to the purification process, which resulted in a reduction in the amount of residual solvent. For example, when the aforementioned 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) of tap water, the proportion of DMA in the resulting solid (CBD) was below the detection limit (undetectable).

[0362] 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 a seed crystal.

[0363] [Example 3] (Crude Product Preparation Step) In the crude product preparation step, 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 was found to be 62.897% CBD, 13.764% olivetol, 10.695% abn-CBD, 3.067% Δ9-THC, 0.412% Δ8-THC, and 4.642% 2:1 adduct. The quantitative value was calculated to be 64.77%.

[0364] 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.

[0365] To the concentrated solution, 33 V 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 crude product.

[0366] The composition of the crude product was confirmed by HPLC to be 76.47% CBD, 0.28% olivetol, 3.7% abn-CBD, 4.32% Δ9-THC, 1.25% Δ8-THC, and 11.65% 2:1 adduct. The quantitative value was calculated to be 52.5%.

[0367] (Purification Step) In the purification step, the quantitative values ​​of cannabidiol in the crude product (mixture, first purified product) were used as the standards for wt (mass), V (volume), and eq. (equivalents). 9 V of heptane and 1 V of methyl t-butyl ether (MTBE) were added to the crude product, and after confirming that the solution had become one layer, it was cooled to 10°C.

[0368] 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.

[0369] 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 then dried by blowing nitrogen for 30 minutes.

[0370] 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.

[0371] 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.

[0372] The composition of the organic layer after washing was confirmed by HPLC, and was found to be 99.06% CBD, 0.03% olivetol, and 0.91% abn-CBD. Δ9-THC, Δ8-THC, and 2:1 adducts were not detected. The quantitative value was calculated to be 49.41%.

[0373] In the subsequent purification 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).

[0374] The composition of the solid (CBD crystals) was confirmed by HPLC to be 100.00% CBD, with no detectable olivetol, abn-CBD, Δ9-THC, Δ8-THC, or 2:1 adduct. The CBD yield (assuming 100% reaction of menthadienol) was calculated to be 40.3% (calculated by subtracting the mass of the seed crystals).

[0375] [Example 4] (Crude Product Preparation Step) In the crude product preparation step, 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 was found to be 62.897% CBD, 13.764% olivetol, 10.695% abn-CBD, 3.067% Δ9-THC, 0.412% Δ8-THC, and 4.642% 2:1 adduct. The quantitative value was calculated to be 64.77%.

[0376] The reaction mixture was concentrated and used in the next purification step.

[0377] (Purification Step) In the purification step, the quantitative values ​​of cannabidiol in the concentrate were used as the standards for wt (mass), V (volume), and eq. (equivalents). 4.5 V of heptane and 0.5 V of methyl t-butyl ether (MTBE) were added to the concentrate of the reaction solution, and after confirming that the solution had become a single layer, it was cooled to 0°C. 2 eq. of DMA was added dropwise, and crystals obtained from the CBD-2DMA crystals obtained in Example 1 were added as seed crystals.

[0378] After confirming the precipitation of crystals, 1 eq. of DMA was added dropwise, and the mixture was crystallized and aged at 0 to 5°C for 90 minutes. 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.

[0379] The obtained crystals (solid) were confirmed to be CBD·2DMA (containing CBD·2DMA) by the same method as above.

[0380] To the crystals (solid), 4 V of heptane and 4 V of tap water were added, and after stirring, it was confirmed that the solid had completely dissolved.

[0381] 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.

[0382] The composition of the organic layer after washing was confirmed by HPLC to be 94.37% CBD, 3.55% olivetol, and 2.07% abn-CBD, with no Δ9-THC, Δ8-THC, or 2:1 adducts detected. The quantitative value was calculated to be 45.13%.

[0383] In the subsequent purification steps, the quantitative value of cannabidiol in the organic layer after washing was 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 crystal precipitation 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).

[0384] The composition of the solid (CBD crystals) was confirmed by HPLC to be 94.51% CBD, 4.80% olivetol, and 0.69% abn-CBD, with no detectable Δ9-THC, Δ8-THC, or 2:1 adduct. The CBD yield (assuming 100% reaction of menthadienol) was calculated to be 25.6% (calculated by subtracting the mass of the seed crystals).

[0385] An oily component was slightly exuded onto the surface of the solid, which is believed to be olivetol.

[0386] Furthermore, 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 a seed crystal.

[0387] [Example 5] (Crude Product Preparation Step) In the crude product preparation step, 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 was found to be 62.897% CBD, 13.764% olivetol, 10.695% abn-CBD, 3.067% Δ9-THC, 0.412% Δ8-THC, and 4.642% 2:1 adduct. The quantitative value was calculated to be 64.77%.

[0388] 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.

[0389] 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.

[0390] 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 crude product.

[0391] The composition of the crude 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 adduct. The quantitative value was calculated to be 62.2%.

[0392] (Purification Step) In the purification step, the quantitative values ​​of cannabidiol in the crude product were used as the standards for wt (mass), V (volume), and eq. (equivalent). 9 V of heptane and 1 V of methyl t-butyl ether (MTBE) were added to the crude product, 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.

[0393] 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 blowing nitrogen for 15 minutes.

[0394] 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.

[0395] After separation, the organic layer was washed with 6 V of 10% DMA water and 12 V of tap water (twice at 6 V). After drying the washed organic layer with 1.1 wt of sodium sulfate, the solid was filtered off and the solution was concentrated under reduced pressure.

[0396] 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, with no Δ8-THC or 2:1 adduct detected. The quantitative value was calculated to be 56.27%.

[0397] Example 6: We used commercially available CBD. According to the COA (Certificate of Analysis), this CBD contained impurities derived from hemp, a natural product (crude CBD, crude product).

[0398] Specifically, the CBD purity was 87.940%, and the main impurities (cannabinoids other than CBD) were 1.573% CBG (cannabigerol), 1.891% CBN (cannabinol), 1.055% CBC (cannabichromene), and 0.345% CBDV (cannabidivarin).

[0399] (Purification Step) In the purification step, the obtained CBD was used as the basis for wt (mass), V (volume), and eq. (equivalent).

[0400] Heptane was added to the obtained CBD (crude CBD) to adjust the weight to 7.2 wt (CBD 1 wt, heptane 6.2 wt) (equivalent to 9 V of heptane), and MTBE (2 V) was added thereto and cooled to 10°C.

[0401] DMA (3.0 eq.) was further added dropwise thereto, and the mixture was cooled to −10° C., and after confirming crystallization, the mixture was aged for 2 hours (crystallization aging).

[0402] The slurry after aging was filtered, and the crystals were washed with a washing solvent [a mixture of heptane (3.1 V), MTBE (0.35 V), and DMA (0.1 V)] cooled to -10°C, and then dried by blowing nitrogen for 15 minutes or more to obtain crystals (solid).

[0403] When the filtrate of the slurry was analyzed by HPLC, impurities (CBN, etc.) were detected.

[0404] To the obtained solid (crystals) were added heptane (7V) and purified water (7V), and after stirring, it was confirmed that the solid had completely dissolved.

[0405] After separation, the organic layer was washed six times with purified water (7 V), and the washed organic layer was dried over sodium sulfate (1.5 wt). The sodium sulfate was then filtered off, and the solution was concentrated under reduced pressure to 1.3 wt.

[0406] The composition of the organic layer after washing was confirmed by HPLC, and it was found to be 99.2% CBD, with the quantitative value calculated to be 80.6%.

[0407] 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).

[0408] Heptane was added to the concentrated liquid to adjust the weight to 2.5 wt (CBD 1 wt, heptane 1.5 wt) (equivalent to 2V heptane), and the temperature was adjusted to 28°C.

[0409] After confirming the precipitation of crystals, the slurry was cooled to -15°C over 1 hour. After crystallization and aging at -15°C for 1 hour or more, the crystals (solid) were filtered and washed with heptane (1V) cooled to the same temperature. Further, after drying under aeration, the crystals were dried under reduced pressure at 40°C to obtain crystals (solid).

[0410] The composition of the obtained crystals (solid) was confirmed by HPLC, and it was found to be 99.5% CBD, with no CBG, CBN, Δ9-THC, Δ8-THC, etc. detected.

[0411] As is clear from the results of the Examples, the present invention allows the preparation of solvates of cannabidiol, even via mixtures containing olivetol and other cannabinoids.

[0412] Furthermore, by utilizing (forming or passing through) such a solvate of cannabidiol, cannabidiol could be efficiently purified (recovered).

[0413] In particular, according to the present invention, as described above, cannabidiol could be efficiently purified (recovered) even via a mixture containing olivetol and other cannabinoids. In particular, cannabidiol could be purified (recovered) even more efficiently by using (via) a mixture from which olivetol and the like had been relatively separated (removed), as in Examples 2 and 3. Additionally, as is clear from Example 6, cannabidiol could be efficiently purified (recovered) from a mixture regardless of its origin (e.g., chemically synthesized, naturally occurring, etc.).

[0414] According to the present invention, a solvate of cannabidiol or the like can be provided.

Claims

1. A solvate of cannabidiol, wherein the solvent S1 of the solvate comprises an aprotic polar solvent.

2. The solvate according to claim 1, wherein solvent S1 comprises an amide solvent.

3. The solvate of claim 1, wherein solvent S1 comprises dimethylacetamide.

4. The solvate according to claim 1, which is a solvate in which dimethylacetamide is solvated in a ratio of 2 moles per mole of cannabidiol.

5. The solvate of claim 1, which is crystalline.

6. A method for producing a solvate of cannabidiol, wherein the solvent S1 of the solvate comprises an aprotic polar solvent, by forming the solvate in a mixture comprising cannabidiol and solvent S1.

7. The method of claim 6, wherein solvent S1 comprises an amide solvent.

8. The method of claim 6, wherein solvent S1 comprises dimethylacetamide and the solvate is a solvate in which dimethylacetamide is solvated in a ratio of 2 moles per mole of cannabidiol.

9. The method of claim 6, wherein the mixture further comprises a solvent S2 different from solvent S1.

10. The method of claim 6, wherein the mixture further comprises an aliphatic hydrocarbon.

11. The method of claim 6, wherein the mixture comprises dimethylacetamide and an aliphatic hydrocarbon, and a solvate is precipitated in which dimethylacetamide is solvated in a ratio of 2 moles per mole of cannabidiol.

12. The method of claim 6, wherein the mixture further comprises other cannabinoids.

13. The method of claim 6, wherein the mixture contains at least one other cannabinoid selected from cannabigerol, cannabinol, cannabichromene, cannabidivarin, and tetrahydrocannabinol.

14. The method of claim 6, wherein the mixture further comprises at least one other cannabinoid selected from cannabigerol, cannabinol, delta-9-tetrahydrocannabinol, and delta-8-tetrahydrocannabinol, and the ratio of cannabigerol, cannabinol, delta-9-tetrahydrocannabinol, and delta-8-tetrahydrocannabinol to the total amount of cannabidiol, cannabigerol, cannabinol, delta-9-tetrahydrocannabinol, and delta-8-tetrahydrocannabinol is 0.1% or more by area on an HPLC scale.

15. The method of claim 6, wherein the mixture is derived from hemp.

16. The method of claim 6, wherein the mixture further contains at least one member selected from olivetol, positional isomers of cannabidiol, an adduct of two moles of menthadienol per mole of olivetol, delta-9-tetrahydrocannabinol, and delta-8-tetrahydrocannabinol.

17. The method of claim 6, wherein the mixture comprises cannabidiol and an adduct of 2 moles of menthadienol per mole of olivetol, wherein the ratio of cannabidiol to the total amount of cannabidiol, olivetol, positional isomers of cannabidiol, the adduct of 2 moles of menthadienol per mole of olivetol, Δ-9-tetrahydrocannabinol, and Δ-8-tetrahydrocannabinol is 60% or more by HPLC area basis, wherein the mixture is free of olivetol or contains olivetol in a ratio of 0.03 or less by HPLC area basis relative to cannabidiol, wherein the mixture is free of positional isomers of cannabidiol or contains olivetol in a ratio of 0.3 or less by HPLC area basis relative to cannabidiol, and wherein the adduct of 2 moles of menthadienol per mole of olivetol is in a ratio of 0.0001 to 0.5 by HPLC area basis relative to cannabidiol.

18. The method according to claim 6, further comprising a step of subjecting a mixture containing cannabidiol and at least one member selected from olivetol and positional isomers of cannabidiol to an adsorption treatment to produce a purified product containing cannabidiol, and forming a solvate in a mixture containing the purified product obtained through this step and solvent S1.

19. The method according to claim 6, further comprising the steps of: reacting menthadienol with olivetol in the presence of at least one catalyst selected from non-boron Lewis acids and Bronsted acids at a temperature of 40°C or higher, with a water content in the reaction system at the start of the reaction of 5% by mass or less, to produce a reaction mixture containing cannabidiol; and subjecting the reaction mixture obtained through this step to an adsorption treatment to produce a purified product containing cannabidiol, wherein a solvate is formed in a mixture containing the purified product obtained through this step and solvent S1.

20. A method for producing cannabidiol by desolvating the solvate according to any one of claims 1 to 5.

21. A method for producing cannabidiol, comprising mixing the solvate according to any one of claims 1 to 5 with water.

22. A method for extracting (liquid-separating) cannabidiol into a layer of the hydrophobic solvent by mixing the solvate according to any one of claims 1 to 5 with water and a hydrophobic solvent capable of dissolving cannabidiol.

23. A method for producing cannabidiol, comprising: an extraction step of mixing the solvate according to any one of claims 1 to 5, water, and a hydrophobic solvent capable of dissolving cannabidiol, and extracting the cannabidiol into a layer of the hydrophobic solvent; and a crystallization step of crystallizing the cannabidiol obtained via the extraction step.

24. Cannabidiol obtainable by the method according to any one of claims 20 to 23.

25. The cannabidiol according to claim 24, wherein the proportion of cannabidiol to the total amount of cannabidiol, cannabigerol, cannabinol, delta-9-tetrahydrocannabinol and delta-8-tetrahydrocannabinol is 97% or more based on HPLC area.

26. The cannabidiol according to claim 24, wherein the proportion of cannabidiol relative 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 97% or more based on the area of HPLC.

27. Cannabidiol according to claim 24, which does not contain solvent S1 of the solvate or the proportion of solvent S1 of the solvate is 3% by mass or less.

28. Cannabidiol according to claim 24, containing at least 0.001% by weight of solvent S1 of the solvate.

29. Cannabidiol according to claim 24, containing at least 0.001% by weight of solvent S1 of the solvate and at least 0.001% by weight of an aliphatic hydrocarbon.

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