Industrial production methods of cannabidiol

Abstract

This invention provides an industrial production method for cannabidiol (CBD), comprising: 1) dissolving cannabis extract in a nonpolar solvent and performing a first extraction with an alcohol solution of a first concentration to obtain an oil phase 1 and an aqueous phase 1, wherein the cannabis extract contains 40-60% CBD; 2) performing a second extraction with an alcohol solution of a second concentration to obtain an oil phase 2 and an aqueous phase 2; 3) performing a third extraction with an alcohol solution of a third concentration to obtain an oil phase 3 and an aqueous phase 3; 4) combining aqueous phases 2 and 3, concentrating the mixture, and crystallizing the concentrate in the order of the three concentrations: first concentration < third concentration < second concentration. This method uses simple production equipment, avoids column chromatography separation, greatly improves production efficiency, and achieves a relatively ideal yield.

Description

Technical Field

[0001] This invention belongs to the field of active pharmaceutical ingredient preparation, specifically relating to an industrial production method for cannabidiol. Background Technology

[0002] CBD is an abbreviation for Cannabidiol, also known as cannabidiol, and is one of the main components of the cannabis plant. Its molecular structure contains a benzene ring and a relatively long side chain, as shown in the following structural formula:

[0003] CBD

[0004] CBD's chemical structure endows it with a variety of pharmacological effects, such as anti-inflammatory, antioxidant, anti-anxiety, and anticonvulsant properties. CBD can reduce inflammatory responses, relieve pain and muscle spasms, and alleviate anxiety and psychological stress. It also has some therapeutic effects in treating neurological disorders such as epilepsy and Parkinson's disease. In the medical field, CBD is not only used to treat neurological diseases but also for treating cancer, diabetes, and other conditions.

[0005] Due to the expanding applications of cannabidiol (CBD), research on its preparation processes has been very active in recent years. CN 114380666A discloses an industrial extraction method for CBD, which involves five steps starting from cannabis flowers and leaves using a non-polar solvent and alcohol. While the process is not complex, it only yields an oil, and the THC content is above 2.3%. Another document from the same applicant in the same year, CN 113801003A, also yields an oil, but with a lower wax content. CN 111978156A discloses a method for preparing CBD, which uses supercritical fluid chromatography to separate a sample solution containing CBD to obtain high-purity CBD. However, this method is suitable for gradient elution chromatographic separation and is not suitable for large-scale industrial production. CN110997607A discloses a method for producing cannabinoids from industrial hemp, which involves alternately using methanol-water solution and alkanes to extract CBD from hemp biomass. During the process, CBDA and CBD are separated, and CBDA is decarboxylated, followed by crystallization to obtain CBD crystals with a purity of 98%. This method is relatively simple to operate, suitable for industrial application, and the process is not complex. However, the CBD transfer rate is low, not exceeding 40% from the concentrated extract. CN 111792981A discloses a method for purifying cannabidiol, which involves removing a large number of impurities from crude industrial hemp extract using a solvent method, followed by direct crystallization and recrystallization to obtain high-purity cannabidiol. This method does not require chromatography equipment, large heating equipment, or concentration equipment, resulting in low production costs. However, the CBD transfer rate remains low.

[0006] To date, there is still a need in the field for a CBD extraction method that is easy to industrialize and has a higher transfer rate. Summary of the Invention

[0007] One objective of this invention is to provide a novel method for the industrial production of cannabidiol (CBD), overcoming the shortcomings of low transfer rates in existing technologies, in order to meet the growing pharmaceutical and healthcare demand for CBD.

[0008] Another object of the present invention is to provide a method for producing cannabidiol that avoids the use of column chromatography for separation.

[0009] The method for extracting cannabidiol from industrial hemp extract according to the present invention comprises the following steps:

[0010] 1) The cannabis extract is dissolved in a non-polar solvent and subjected to a first extraction with an alcohol solution of the first concentration to obtain oil phase 1 and aqueous phase 1, wherein the cannabis extract contains 40-60% cannabidiol;

[0011] 2) The oil phase 1 was extracted a second time with an alcohol solution of a second concentration to obtain oil phase 2 and aqueous phase 2;

[0012] 3) The oil phase 2 was extracted for the third time with an alcohol solution of the third concentration to obtain the oil phase 3 and the aqueous phase 3;

[0013] 4) Combine aqueous phase 2 and aqueous phase 3, concentrate and crystallize the concentrate, wherein the first concentration < the third concentration < the second concentration.

[0014] In one specific embodiment, the nonpolar solvent is pentane, hexane, heptane, octane, methylcyclohexane or a mixture thereof, and is used in an amount of 6-8 times the weight of the cannabis extract.

[0015] In one specific embodiment, the alcohol solution is an aqueous solution of methanol, ethanol, or isopropanol.

[0016] In a preferred embodiment, the alcohol solution is an ethanol solution, the first concentration is 60-65%, and the amount used is 6-8 times the weight of the cannabis extract; the second concentration is 90-92%, and the amount used is 10-15 times the weight of the cannabis extract, preferably 12-15 times; the third concentration is 80-88%, and the amount used is 8-12 times the weight of the cannabis extract, preferably 10-12 times.

[0017] In a preferred embodiment, the alcohol solution is a methanol solution, the first concentration is 65-75%, and the amount used is 6-8 times the weight of the cannabis extract; the second concentration is 88-95%, and the amount used is 12-15 times the weight of the cannabis extract; the third concentration is 80-88%, and the amount used is 10-12 times the weight of the cannabis extract.

[0018] In a preferred embodiment, the alcohol solution is an isopropanol solution, the first concentration is 55-63%, and the amount used is 6-8 times the weight of the cannabis extract; the second concentration is 76-86%, and the amount used is 10-12 times the weight of the cannabis extract; the third concentration is 65-73%, and the amount used is 10-12 times the weight of the cannabis extract.

[0019] The method of this invention for extracting cannabidiol from industrial hemp extract features simple production equipment, avoids column chromatography separation, greatly improves production efficiency, and achieves a relatively ideal yield. This method is applicable to industrial hemp extracts with a content between 40-60%, and is particularly suitable for extracting industrial hemp extracts with a content between 40-50%. It achieves high yields without the need for column chromatography separation, offering significant industrial convenience. Detailed Implementation

[0020] The technical concept of the present invention will be described in detail below with reference to specific embodiments. It is readily understood that the embodiments described in this disclosure are merely illustrative and not all implementations of the present invention. Those skilled in the art, upon obtaining the description of the basic concept of the present invention in this disclosure and in conjunction with the given embodiments, can obtain other ways of implementing the present invention without creative effort, and can also make further improvements based on the basic concept of the present invention. All such variations or improvements fall within the scope defined by the claims of this application.

[0021] In this invention, the term "transfer rate" refers to the percentage of cannabidiol (CBD) transferred from cannabis extract to another physical or phase state. The term "total transfer rate" refers to the percentage of CBD crystals obtained as the final product relative to the total amount of CBD in the extract; the total transfer rate is the product yield.

[0022] Material preparation

[0023] In a typical embodiment of the present invention, the raw material used is an extract from industrial hemp obtained through supercritical extraction. Generally, supercritical extraction extracts using carbon dioxide as a medium in the prior art can be used in the present invention. However, preferably, the extract used in the present invention contains not less than 40% cannabidiol (CBD), ideally between 40% and 60%. In the present invention, the industrial hemp used are the flowers and leaves. The selected materials are crushed, roasted, and granulated, and then sent to a supercritical extraction device for extraction. The roasting process removes some moisture and decarboxylates CBDA, converting it into CBD. A prior publication of the applicant, CN 112279752A, describes a specific method for supercritical extraction of industrial hemp, and the extract obtained by this method can be used in the present invention. Preferably, after supercritical extraction, the extract is subjected to heat treatment again to achieve complete decarboxylation. Another prior publication of this applicant, CN 112386948A, details a method for decarboxylating cannabidiol (CBDA) from industrial hemp extract. This method involves spreading the extract obtained through supercritical extraction in a drying tray to form a thin layer with an average thickness of 1–7 mm, then placing it in a vacuum oven and heating it at a vacuum level of -0.06 to -0.09 MPa and a temperature range of 70–110°C for 2–3 hours. This method can improve the conversion rate of CBDA in the obtained product. This invention preferentially uses the supercritical extract obtained by this method.

[0024] Nevertheless, this invention does not exclude industrial hemp extracts obtained through other means, such as products obtained by extracting industrial hemp with alkanes (typically hexane or heptane) under normal pressure, provided that their CBD content is between 40% and 60%, which may be suitable for the methods of this invention. Therefore, this disclosure refers to raw materials suitable for the methods of this invention as hemp extracts.

[0025] First extraction

[0026] In an extraction reactor, cannabis extract is contacted with a nonpolar solvent to prepare an extract solution. The nonpolar solvent is suitably selected from the group consisting of pentane, hexane, heptane, octane, methylcyclohexane, and mixtures thereof, with hexane and heptane being preferred. Then, a first concentration of alcohol solution is added, the alcohol being selected from methanol, ethanol, and isopropanol, with ethanol being preferred.

[0027] In this invention, the concentration and amount of the nonpolar solvent and alcohol solution have a significant impact on production efficiency. Cannabis extract contains cannabinoids, flavonoids, and terpenes. This invention uses a first-concentration alcohol solution with a high water content to extract the highly water-soluble components of cannabis extract, such as cannabinoids and flavonoids. By selecting an appropriate solvent amount, these substances can be extracted as much as possible while retaining as much cannabidiol as possible.

[0028] In a preferred embodiment of the invention, heptane is used as the nonpolar solvent, and the amount of solvent is 2-4 times the weight of the cannabis extract. An ethanol solution with a mass concentration of 60-65% is used, and the amount is 6-8 times the weight of the cannabis extract. In this disclosure, unless otherwise specified, all references to alcohol solution concentration are by mass percentage. If the amount of heptane is too large and the amount of alcohol solution is too small, insufficient removal of highly water-soluble components (e.g., flavonoids) will occur. These components are more likely to remain in aqueous phases 2 and 3 during subsequent extractions and are less likely to separate from cannabidiol. If the amount of heptane is too small and the amount of alcohol solution is too large, excessive cannabinoids will enter the aqueous phase, ultimately reducing the product yield. Furthermore, the concentration of the alcohol solution also affects the process effect. If the water content in the alcohol solution is too high, fewer impurities will be extracted; if the water content is too low, more CBD will be removed, reducing the product yield.

[0029] In another specific embodiment of the present invention, hexane is used as the nonpolar solvent, and the amount of solvent used is 2-4 times that of the cannabis extract. The alcohol solution used is a methanol solution with a mass concentration of 65-75%, preferably 68-72%, and most preferably 70%, and the amount used is 6-8 times that of the cannabis extract. In another specific embodiment of the present invention, heptane is used as the nonpolar solvent, and the amount of solvent used is 2-4 times that of the cannabis extract. The alcohol solution used is an isopropanol solution with a mass concentration of 50-65%, and the amount used is 6-8 times that of the cannabis extract.

[0030] The first extraction process is preferably carried out at a temperature of 15-40°C, preferably at room temperature, and the stirring time can be 1-4 hours, preferably 2-4 hours. After stirring, let it stand for 1-2 hours, separate the lower aqueous phase 1 for other uses, and the oil phase 1 enters the next step.

[0031] Second extraction

[0032] Next, a second concentration of alcohol solution, greater than the first concentration, is added to the oil phase 1 in the extraction vessel. Typically, one alcohol is selected for oil phase extraction throughout the process, especially for the second and third extractions. However, this invention does not preclude the use of different alcohols for the first and second extractions, which should theoretically be feasible. In one specific embodiment, 85-92% ethanol is used, with a volume 10-15 times that of oil phase 1. The second extraction is preferably carried out at a temperature of 15-40°C, preferably at room temperature, with a stirring time of 1-4 hours, preferably 2-4 hours. After stirring, the mixture is allowed to stand for 1-2 hours, and the lower aqueous phase 2 is separated, with oil phase 2 proceeding to the next stage. In a more preferred embodiment, 88-92% ethanol is used, with a volume 12-15 times that of oil phase 1. This invention uses a second concentration of alcohol solution to extract oil phase 1, extracting as much CBD-containing cannabinoids as possible, while leaving terpenes and other low-polarity substances in oil phase 2. In this invention, the concentration of the second alcohol solution and the amount of alcohol solution used affect the composition of the aqueous phase 2 and the oil phase 2, as well as the product yield. If the concentration of the second alcohol solution is too high or the amount used is too large, too many fat-soluble components will be carried into the aqueous phase 2; if the amount of alcohol solution used is too small, more cannabinoids will remain in the oil phase 2, thus reducing the product yield.

[0033] The inventors discovered that the second concentration of the solution varies depending on the type of alcohol used. In one specific embodiment, 90-92% ethanol is suitable, with a volume 12-15 times that of the oil phase. In this invention, when a methanol solution is used, the concentration of the methanol solution is preferably between 92-95%, and the amount used is 10-15 times, preferably 12-15 times, the amount of cannabis extract. Using other concentrations results in a decrease in both the transfer rate and the crystallization yield. When an isopropanol solution is used, the concentration of the isopropanol solution is preferably 77-85%, and the amount used is 10-15 times, preferably 10-12 times, the amount of cannabis extract. Using other concentrations results in a decrease in both the transfer rate and the crystallization yield.

[0034] Third extraction

[0035] Next, a third concentration of alcohol solution is added to the oil phase 2 in the extraction vessel. This third concentration is less than and greater than the second concentration but greater than the first concentration. In a preferred embodiment of the invention, 80-88% ethanol is selected, with a volume 8-12 times, preferably 10-12 times, the volume of the oil phase 1. This second extraction process is carried out at a temperature of 15-40°C, preferably at room temperature, and the stirring time can be 1-4 hours, preferably 2-4 hours. After stirring, the mixture is allowed to stand for 1-2 hours, and the lower aqueous phase 3 is separated and proceeds to the next stage, while the oil phase 3 is reserved for other uses.

[0036] This invention uses a third-concentration alcohol solution to extract oil phase 2, aiming to extract as many CBD-containing cannabinoids as possible, while leaving terpenes and other low-polarity substances in oil phase 3. In this invention, the third concentration and the amount of the alcohol solution used affect the composition of aqueous and oil phases 3 and the product yield. If the third concentration is too high or the amount used is too large, excessive fat-soluble components will be carried into aqueous phase 3; if the third concentration is too low or the amount of alcohol solution used is too small, more cannabinoids will remain in oil phase 2, reducing the product yield.

[0037] In another specific embodiment of the invention, an 80-88% methanol solution is used, in an amount 10-15 times, preferably 10-12 times, of the cannabis extract. In another specific embodiment, a 65-73% isopropanol solution is used, in an amount 10-15 times, preferably 10-12 times, of the cannabis extract.

[0038] In this invention, the values ​​of the second and third concentrations are not interchangeable. If a third-concentration alcohol solution is used for the second extraction, followed by a third extraction using a second-concentration alcohol solution, the yield will decrease. A possible reason is that, based on the composition of the oil phase 1 obtained from the first extraction, the content of cannabinoids such as CBD is relatively high. Using a second-concentration alcohol solution with lower water content as the second extractant can still preferentially extract these components. After the second extraction, the cannabinoid content in oil phase 2 decreases. At this point, using a third-concentration alcohol solution with higher water content as the extractant for the third extraction is necessary to continue to preferentially extract CBD and other cannabinoids. Conversely, if a third-concentration alcohol solution with higher water content is used as the second extractant for oil phase 1, not only will more cannabinoids not be extracted, but more flavonoids will also be extracted. Furthermore, during the third extraction, due to the low water content of the third extractant, more highly lipid-soluble substances will enter the aqueous phase 3 and eventually proceed to the next step. Ultimately, this not only fails to improve the overall transfer rate of the two extraction steps but also introduces more impurities, reducing the yield of subsequent crystallization.

[0039] crystallization

[0040] After the second and third extractions, the resulting aqueous phases 2 and 3 are combined into aqueous phase 4, which typically contains 70-80% CBD of the total cannabis extract. Aqueous phase 4 is then concentrated and crystallized to obtain CBD crystals.

[0041] In this step, CBD crystallization is achieved by first concentrating the aqueous phase 4 to remove as much solvent as possible, obtaining a paste-like or viscous concentrate. Then, while stirring, 1-3 volumes, preferably 1-2, or even more preferably 1-1.5 volumes, of solvent are added relative to the weight of the concentrate. Suitable solvents are selected from the group consisting of pentane, hexane, heptane, octane, and methylcyclohexane, preferably hexane, heptane, or their isomers such as methylcyclohexane, or mixtures thereof. The concentrate can be dissolved at a temperature of 40-55°C, preferably 50-55°C, and maintained for 10-30 minutes, typically 10-20 minutes. Then, the temperature is slowly lowered to 10 to -20°C for crystallization.

[0042] The method of the present invention can be used to extract industrial hemp extract with a content between 40-60%, and is especially suitable for extracting industrial hemp extract with a content between 40-50%. It can achieve a high yield without column chromatography separation and has high industrial convenience.

[0043] The following materials and apparatus are used in the following embodiments:

[0044] High performance liquid chromatography:

[0045] Primaide 1210 Auto sample high-performance liquid chromatograph, Hitachi PID detector, TeChrom chromatography workstation;

[0046] Chromatographic column: Octadecylsilane-bonded silica column

[0047] Column temperature: 30℃

[0048] Mobile phase: Acetonitrile-0.1% acetic acid solution (75:25)

[0049] Flow rate: 1.0 ml / min

[0050] Injection volume: 10µl

[0051] Detection wavelength: 220nm

[0052] Analysis time: 40 min

[0053] Example 1

[0054] Preparation of materials:

[0055] Industrial hemp flower and leaf powder was spread evenly on a baking tray and baked at 130℃ for 3 hours. After cooling to room temperature, it was granulated. 150 kg of industrial hemp flower and leaf granules were loaded into the hopper of a supercritical extraction device. A mixed solvent of heptane and ethanol (heptane:ethanol = 1:1) of 10-15% by weight of the hemp granules was added as an entrainer. The extraction temperature was set at 45℃ and the pressure at 30 MPa. Then, carbon dioxide was introduced for supercritical extraction, yielding 13.7 kg of industrial hemp extract. The content of cannabidiol (CBD) in the extract was determined to be 42.71%.

[0056] First extraction

[0057] Take 1 kg of cannabis extract and place it in a homogenizer. Add 3 kg of heptane and stir to dissolve. Then add 6-8 kg of 60-65% ethanol and stir to mix at room temperature for 3 hours. Let it stand for 2 hours and separate the lower aqueous phase 1. The oil phase 1 remains in the equipment.

[0058] Second extraction

[0059] Add 14 kg of 90-92% ethanol to oil phase 1, stir for 2 hours, let stand for 1-2 hours, then separate the lower aqueous phase 2, leaving oil phase 2 in the equipment.

[0060] Third extraction

[0061] Add 10-11 kg of 82-86% ethanol to the oil phase 2, stir for 2 hours, let stand for 1-2 hours, and then separate the lower aqueous phase 3.

[0062] Aqueous phases 2 and 3 were combined and concentrated under reduced pressure at no more than 50°C to form a paste, yielding 459.4g of concentrate. Liquid chromatography analysis showed that it contained 79% CBD, and the transfer rate of the two extractions was 85%.

[0063] crystallization:

[0064] The concentrate was dissolved in 0.7 kg of heptane and maintained at 50-55 °C for 10-30 min. Then it was slowly cooled to -15 °C over 4 hours. After filtration, washing and drying, 259.8 g of CBD crystals with a purity of 99.2% and a total transfer rate (yield) of 61.2% were obtained.

[0065] Example 2

[0066] First extraction

[0067] Take 1 kg of cannabis extract (containing 440 g of CBD) and place it in a homogenizer. Add 3 kg of heptane and stir to dissolve. Then add 6-8 kg of 60-65% ethanol and stir to mix at room temperature for 3 hours. Let it stand for 2 hours and separate the lower aqueous phase 1. The oil phase 1 remains in the equipment.

[0068] Second extraction

[0069] Add 14 kg of 85% ethanol to oil phase 1, stir for 2 hours, let stand for 1-2 hours, then separate the lower aqueous phase 2, leaving oil phase 2 in the equipment.

[0070] Third extraction

[0071] Add 10 kg of 80% ethanol to the oil phase 2, stir for 2 hours, let stand for 1-2 hours, and then separate the lower aqueous phase 3.

[0072] Aqueous phases 2 and 3 were combined and concentrated into a paste under reduced pressure at a temperature not exceeding 50°C, yielding 489g of concentrate. Liquid chromatography analysis showed that it contained 72% CBD, and the transfer rate of the two extractions was 80%.

[0073] crystallization

[0074] The concentrate was dissolved in 700g of heptane and maintained at 50-55℃ for 10-30min. Then it was slowly cooled to -15℃, and the cooling process was completed within 8 hours. After filtration, solvent washing, and drying, 236g of CBD crystals with a purity of 99.0% and a total transfer rate (yield) of 53.1% were obtained.

[0075] This embodiment used a lower concentration of ethanol solution for the second extraction compared to Example 1. The combined transfer rate of the second and third extractions was slightly lower, and the yield of CBD product was also slightly lower.

[0076] Example 3

[0077] First extraction

[0078] Take 1 kg of cannabis extract (containing 440 g of CBD) and place it in a homogenizer. Add 3 kg of heptane and stir to dissolve. Then add 6-8 kg of 60-65% ethanol and stir to mix at room temperature for 3 hours. Let it stand for 2 hours and separate the lower aqueous phase 1, leaving the oil phase 1 in the equipment.

[0079] Second extraction

[0080] Add 14 kg of 82% ethanol to oil phase 1, stir for 2 hours, let stand for 1-2 hours, then separate the lower aqueous phase 2, leaving oil phase 2 in the equipment.

[0081] Third extraction

[0082] Add 10 kg of 90% ethanol to the oil phase 2, stir for 2 hours, let stand for 1-2 hours, and then separate the lower aqueous phase 3.

[0083] Aqueous phases 2 and 3 were combined and concentrated under reduced pressure at no more than 50°C to form a paste, yielding 491.8g of concentrate. Liquid chromatography analysis showed that it contained 68% CBD, and the transfer rate of the two extractions was 76%.

[0084] crystallization

[0085] The concentrate was dissolved in 0.7 kg of heptane and maintained at 50-55 °C for 10-30 min. Then it was slowly cooled to -15 °C. The cooling process was completed within 8 hours. After filtration, washing and drying, 236 g of CBD crystals with a purity of 99.0% and a total transfer rate (yield) of 49.5% were obtained.

[0086] This embodiment used a lower concentration of ethanol solution for the second extraction and a higher concentration of alcohol solution for the third extraction compared to Example 2. The combined transfer rate of the second and third extractions was slightly lower, and the yield of CBD product was also slightly lower.

[0087] Example 4

[0088] First extraction

[0089] Take 1 kg of cannabis extract (containing 440 g of CBD) and place it in a homogenizer. Add 3 kg of heptane and stir to dissolve. Then add 6 kg of 70% methanol and stir at room temperature for 3 hours. Let it stand for 2 hours and separate the lower aqueous phase 1. The oil phase 1 remains in the equipment.

[0090] Second extraction

[0091] Add 12 kg of 93% methanol to oil phase 1, stir for 2 hours, let stand for 1-2 hours, then separate the lower aqueous phase 2, leaving oil phase 2 in the equipment.

[0092] Third extraction

[0093] Add 10 kg of 82% methanol to the oil phase 2, stir for 2 hours, let stand for 1-2 hours, and then separate the lower aqueous phase 3.

[0094] Aqueous phases 2 and 3 were combined and concentrated under reduced pressure at a temperature not exceeding 40°C to form a paste, yielding 502.6 g of concentrate. Liquid chromatography analysis showed that it contained 77% CBD, and the transfer rate of the two extractions was 88%.

[0095] crystallization

[0096] The concentrate was dissolved in 600g of pentane and maintained at 50℃ for 10-30min. Then it was slowly cooled to -20℃, and the cooling process was completed within 8 hours. After filtration, washing and drying, 278.8g of CBD crystals with a purity of 99.0% and a total transfer rate (yield) of 63.3% were obtained.

[0097] This embodiment uses methanol solution as the extractant, and a good yield was achieved at the selected concentration, although methanol solvent is not as safe as ethanol in terms of industrial applications.

[0098] Example 5

[0099] First extraction

[0100] Take 100g of cannabis extract (containing 43.5g of CBD) and place it in a homogenizer. Add 400ml of heptane and stir to dissolve. Then add 700ml of 60% isopropanol and stir to mix for 3 hours at room temperature. Let it stand for 2 hours and separate the lower aqueous phase 1. The oil phase 1 remains in the equipment.

[0101] Second extraction

[0102] Add 1.2 kg of 82% isopropanol to oil phase 1, stir for 2 hours, let stand for 1-2 hours, then separate the lower aqueous phase 2, leaving oil phase 2 in the equipment.

[0103] Third extraction

[0104] Add 1 kg of 70% isopropanol to the oil phase 2, stir for 2 hours, let stand for 1-2 hours, and then separate the lower aqueous phase 3.

[0105] Aqueous phases 2 and 3 were combined and concentrated under reduced pressure at a temperature not exceeding 40°C to form a paste, yielding 44.1g of concentrate. Liquid chromatography analysis showed that it contained 73% CBD, and the transfer rate of the two extractions was 74%.

[0106] crystallization

[0107] The concentrate was dissolved in 80g of pentane and maintained at 50℃ for 10-30min. Then it was slowly cooled to -20℃, and the cooling process was completed within 10 hours. After filtration, washing and drying, 22.7g of CBD crystals were obtained with a purity of 98.1% and a total transfer rate (yield) of 52.3%.

[0108] In this embodiment, isopropanol solution was used as the extractant, and a good yield was achieved at the selected concentration.

[0109] The technical solution of the present invention has been described above in conjunction with the embodiments. It should be noted that for those skilled in the art, other similar implementation methods based on the technical concept of the present disclosure without departing from the technical concept of the present disclosure are also within the protection scope of the embodiments of the present disclosure.

Claims

1. An industrial method for producing cannabidiol, comprising the following steps: 1) The cannabis extract was dissolved in a nonpolar solvent and subjected to a first extraction with an alcohol solution of the first concentration to obtain oil phase 1 and aqueous phase 1, wherein, The cannabis extract is a supercritical fluid extraction extract, and the cannabis extract contains 40-60% cannabidiol. 2) The oil phase 1 was extracted a second time with an alcohol solution of a second concentration to obtain oil phase 2 and aqueous phase 2; 3) The oil phase 2 was extracted for the third time with an alcohol solution of the third concentration to obtain the oil phase 3 and the aqueous phase 3; 4) Combine aqueous phases 2 and 3, concentrate, and then crystallize the concentrate. Wherein, the first concentration < the third concentration < the second concentration, the nonpolar solvent is pentane, hexane, heptane, octane, methylcyclohexane or a mixture thereof, and the amount used is 6-8 times the weight of the cannabis extract, and the alcohol solution is an aqueous solution of methanol, ethanol or isopropanol.

2. The method according to claim 1, wherein, The alcohol solution is an ethanol solution, with a first concentration of 60-65% and an amount of 6-8 times the weight of the cannabis extract; a second concentration of 90-92% and an amount of 12-15 times the weight of the cannabis extract; and a third concentration of 80-88% and an amount of 10-12 times the weight of the cannabis extract.

3. The method according to claim 1, wherein, The alcohol solution is a methanol solution, with a first concentration of 65-75% and an amount of 6-8 times the weight of the cannabis extract; a second concentration of 88-95% and an amount of 12-15 times the weight of the cannabis extract; and a third concentration of 80-88% and an amount of 10-12 times the weight of the cannabis extract.

4. The method according to claim 1, wherein, The alcohol solution is an isopropanol solution, with a first concentration of 55-63% and an amount of 6-8 times the weight of the cannabis extract; a second concentration of 76-86% and an amount of 10-12 times the weight of the cannabis extract; and a third concentration of 65-73% and an amount of 10-12 times the weight of the cannabis extract.

5. The method according to claim 1, wherein, The crystallization solvent is selected from the group consisting of pentane, hexane, heptane, octane and methylcyclohexane.

6. The method according to claim 1, wherein, The amount of crystallization solvent used is 1-2 L per kilogram of the concentrate.

7. The method according to claim 6, wherein, Dissolve the concentrate in a crystallization solvent at 50-55°C and maintain for 10-30 minutes, then crystallize at 0 to -20°C.

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