Industrial production method of cannabidiol

Abstract

The invention provides an industrial production method of cannabidiol, which comprises the following steps: 1) dissolving a cannabis sativa extract with a non-polar solvent, and carrying out first extraction with an alcoholic solution with a first concentration to obtain an oil phase 1 and a water phase 1, the cannabidiol content in the cannabis sativa extract being 40-60%; 2) performing secondary extraction on the oil phase 1 by using an alcoholic solution with a second concentration to obtain an oil phase 2 and a water phase 2; 3) carrying out third extraction on the oil phase 2 by using an alcoholic solution with a third concentration to obtain an oil phase 3 and a water phase 3; and 4) combining the water phase 2 and the water phase 3, concentrating, and crystallizing the concentrate, wherein the first concentration is more than the third concentration and the second concentration is less than the third concentration. According to the method provided by the invention, the production equipment is simple, the column chromatography separation is avoided, the production efficiency is greatly improved, and the ideal yield is obtained.

Description

Technical Field

[0001] The present invention belongs to the field of raw material medicine preparation, and specifically relates to an industrial production method of cannabidiol. Background Art

[0002] CBD is the abbreviation of Cannabidiol, also known as cannabidiol, which is one of the main components of cannabis plants. Its molecular structure contains a benzene ring and a longer side chain. The structural formula is as follows: CBD The chemical structure of CBD gives it a variety of pharmacological effects, such as anti-inflammatory, antioxidant, anti-anxiety, anticonvulsant, etc. CBD can reduce inflammatory responses, relieve pain and muscle spasms, and reduce anxiety and psychological stress. It also has a certain effect on the treatment of neurological diseases such as epilepsy and Parkinson's disease. In the field of medicine, CBD can be used not only to treat neurological diseases, but also to treat cancer, diabetes, etc.

[0003] Due to the continuous expansion of the use of cannabidiol, the research on the preparation process of cannabidiol has been very active in recent years. CN 114380666A discloses an industrial extraction method of cannabidiol, which starts from cannabis flowers and leaves and uses a non-polar solvent and alcohol to combine through five steps. Although the process is not complicated, only an ointment is obtained, and the THC content is above 2.3%. Another document of the applicant in the same year, CN 113801003A, also obtained an ointment, but the wax content was reduced. CN 111978156A discloses a method for preparing cannabidiol, which uses supercritical fluid chromatography to separate a sample solution containing cannabidiol to obtain high-purity cannabidiol, wherein gradient elution chromatographic separation is applicable, which is not suitable for industrial scale production. CN110997607A discloses a method for producing cannabinoids from industrial hemp, which alternately uses methanol-water solution and alkane to extract CBD from hemp biomass, separates CBDA and CBD in the process, decarboxylates CBDA, and then crystallizes CBD crystals with a purity of 98%. This method is relatively simple to operate, suitable for industrialization, and the process is not complicated. However, the transfer rate of CBD is low, and the CBD transfer rate is not higher than 40% from the concentrated extract. CN 111792981A discloses a method for purifying cannabidiol, which directly crystallizes and recrystallizes the extract of industrial hemp crude extract after removing a large amount of impurities by solvent method to produce high-purity cannabidiol. This method does not require chromatography equipment, large-scale heating equipment and concentration equipment, and has low production cost. However, the CBD transfer rate is still not high.

[0004] So far, there is still a need in the art for a CBD extraction method that is easy to industrialize and has a higher transfer rate. Summary of the invention

[0005] One of the purposes of the present invention is to provide a new method for industrial production of cannabidiol, which overcomes the defect of low transfer rate in the prior art and meets the growing medical and health needs for cannabidiol. Another object of the present invention is to provide a method for producing cannabidiol that avoids the use of column chromatography separation.

[0006] The method for extracting cannabidiol from industrial hemp extract according to the present invention comprises the following steps: 1) dissolving the cannabis extract with a non-polar 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 content of cannabidiol in the cannabis extract is 40-60%; 2) extracting the oil phase 1 for the second time with an alcohol solution of a second concentration to obtain an oil phase 2 and an aqueous phase 2; 3) extracting the oil phase 2 for the third time with an alcohol solution of a third concentration to obtain an oil phase 3 and an aqueous phase 3; 4) combining aqueous phase 2 and aqueous phase 3, concentrating the concentrate and crystallizing the concentrate, wherein the first concentration is less than the third concentration and less than the second concentration.

[0007] In a specific embodiment, the non-polar 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.

[0008] In a specific embodiment, the alcohol solution is an aqueous solution of methanol, ethanol or isopropanol.

[0009] In a preferred specific embodiment, the alcohol solution is an ethanol solution, the first concentration is 60-65%, and the amount is 6-8 times the weight of the cannabis extract; the second concentration is 90-92%, and the amount is 10-15 times the weight of the cannabis extract, preferably 12-15 times; the third concentration is 80-88%, and the amount is 8-12 times the weight of the cannabis extract, preferably 10-12 times.

[0010] In a preferred specific embodiment, the alcohol solution is a methanol solution, the first concentration is 65-75%, and the dosage is 6-8 times the weight of the cannabis extract; the second concentration is 88-95%, and the dosage is 12-15 times the weight of the cannabis extract; the third concentration is 80-88%, and the dosage is 10-12 times the weight of the cannabis extract.

[0011] In a preferred specific embodiment, the alcohol solution is an isopropanol solution, the first concentration is 55-63%, and the dosage is 6-8 times the weight of the cannabis extract; the second concentration is 76-86%, and the dosage is 10-12 times the weight of the cannabis extract; the third concentration is 65-73%, and the dosage is 10-12 times the weight of the cannabis extract.

[0012] The method of the present invention is used to extract cannabidiol from industrial hemp extract, the production equipment is simple, column chromatography separation is avoided, the production efficiency is greatly improved, and a relatively ideal yield is obtained. The method of the present invention is suitable for 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 can achieve a higher yield without column chromatography separation, and has high industrial convenience. DETAILED DESCRIPTION

[0013] The technical concept of the present invention is described in detail below in conjunction with specific embodiments. It is easy to understand that the embodiments described in this disclosure are only for illustrative purposes, and are not all implementation methods of the present invention. Those skilled in the art can obtain other ways to implement the present invention without creative work after obtaining the description of the basic concept of the present invention in this disclosure and combining the given embodiments, and can also make further improvements on the basis of the basic concept of the present invention. All these variant embodiments or improvements belong to the scope defined by the claims of this application.

[0014] In the present invention, the term "transfer rate" refers to the percentage of cannabidiol (CBD) transferred from the cannabis extract to another physical state or phase. The term "total transfer rate" refers to the percentage of the amount of CBD crystals obtained in the final product to the amount of CBD in the extract, and the total transfer rate is the yield of the product.

[0015] Preparation In a typical embodiment of the present invention, the raw material used is an extract of industrial hemp extracted by supercritical extraction. Generally speaking, supercritical extraction extracts using carbon dioxide as a medium in the prior art can all be used in the present invention, but preferably, the content of cannabidiol (CBD) in the extraction extract used in the present invention is not less than 40%, and ideally between 40% and 60%. In the present invention, the parts of industrial hemp used are flowers and leaves, and the selected materials are crushed, baked and granulated, and then sent to a supercritical extraction device for extraction. The baking process removes part of the moisture on the one hand, and also decarboxylates CBDA to convert it into CBD. A prior publication of the applicant, CN 112279752A, records 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 heat-treated again to achieve complete decarboxylation. Another prior publication of the applicant, CN 112386948A, discloses in detail a method for decarboxylating cannabidiol acid in industrial hemp extracts, wherein the extract obtained by supercritical extraction is advected in a baking tray to form a thin layer with an average thickness of 1 to 7 mm, and then placed in a vacuum oven, and heated at 70 to 110° C. for 2 to 3 hours under a vacuum degree in the range of -0.06 to -0.09 MPa. The method can improve the conversion rate of CBDA in the obtained product. The present invention preferably adopts the supercritical extraction extract obtained by the method.

[0016] Nevertheless, the present invention does not exclude industrial hemp extracts obtained by other means, for example, products obtained by extracting industrial hemp with alkanes (typically hexane or heptane) under normal pressure, as long as the CBD content is between 40% and 60%, may be applicable to the method of the present invention. Therefore, the present disclosure refers to the raw materials applicable to the method of the present invention as hemp extracts.

[0017] First extraction In an extraction reactor, the cannabis extract is contacted with a non-polar solvent to prepare an extract solution, wherein the non-polar solvent is suitably selected from the group consisting of pentane, hexane, heptane, octane, methylcyclohexane and mixtures thereof, wherein hexane and heptane are preferably used. Then, a first concentration of alcohol solution is added, wherein the alcohol is selected from methanol, ethanol and isopropanol, wherein ethanol is preferred.

[0018] In the present invention, the concentration and dosage of the non-polar solvent and the alcohol solution have an important influence on the production efficiency. The hemp extract contains cannabinoids, flavonoids and terpenes. The present invention uses a first concentration alcohol solution with a higher water content to extract the components with higher water solubility in the hemp extract, such as cannabinoid acids and flavonoids. By selecting a suitable solvent dosage, these substances can be taken out as much as possible while retaining as much cannabidiol as possible.

[0019] In a preferred embodiment of the present invention, heptane is used as the non-polar solvent, and the amount of the 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 the present disclosure, unless otherwise specified, the concentration of the alcohol solution is measured in mass percentage. If the amount of heptane is too large and the amount of alcohol solution is too small, too few water-soluble components (such as flavonoids) are removed. This part of the components is easier to remain in aqueous phase 2 and aqueous phase 3 in the subsequent extraction and is not easy to separate from cannabinoid diols. If the amount of heptane is too small and the amount of alcohol solution is too large, too many cannabinoid components will enter the aqueous phase, ultimately reducing the product yield. In addition, 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 taken away, which will reduce the product yield.

[0020] In another specific embodiment of the present invention, the non-polar solvent is hexane, and the amount of the solvent is 2-4 times the amount of the cannabis extract, and the alcohol solution uses a methanol solution with a mass concentration of 65-75%, preferably 68-72%, and most preferably 70%, and the amount is 6-8 times the amount of the cannabis extract. In a specific embodiment of the present invention, the non-polar solvent is heptane, and the amount of the solvent is 2-4 times the amount of the cannabis extract, and the alcohol solution uses an isopropanol solution with a mass concentration of 50-65%, and the amount is 6-8 times the amount of the cannabis extract.

[0021] 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 the stirring is completed, it is allowed to stand for 1-2 hours, and the lower aqueous phase 1 is separated for other use, and the oil phase 1 enters the next step.

[0022] Second extraction Next, an alcohol solution of a second concentration is added to the oil phase 1 in the extraction kettle, wherein the second concentration is greater than the first concentration. Usually, an alcohol is selected throughout the process for extracting the oil phase, especially the second extraction and the third extraction. Nevertheless, the present invention does not exclude the use of different alcohols for the first extraction and the second extraction, which should be feasible in theory. In a specific embodiment of the present invention, 85-92% ethanol is selected, and the volume is 10-15 times the volume of the oil phase 1. The second 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 the stirring is completed, it is allowed to stand for 1-2 hours, and the lower aqueous phase 2 is separated, and the oil phase 2 enters the next link. In a more preferred embodiment, 88-92% ethanol is used, and the volume is 12-15 times the volume of the oil phase 1. The present invention extracts the oil phase 1 with an alcohol solution of a second concentration, extracts the cannabinoids containing CBD therein as much as possible, and leaves terpenes and other low-polar substances in the oil phase 2. In the present invention, the size of the second concentration and the amount of the alcohol solution have an impact on the components and product yields in the water phase 2 and the oil phase 2. If the second concentration is too high or the amount is too large, too many fat-soluble components will be brought into the water phase 2; if the amount of the alcohol solution is too small, more cannabinoids will remain in the oil phase 2 and reduce the product yield.

[0023] The inventors found that the second concentration will be different when different alcohol solutions are used. In a specific embodiment, it is suitable to use 90-92% ethanol, and the volume is 12-15 times the volume of oil phase 1. In the present invention, when a methanol solution is used, the concentration of the methanol solution is preferably between 92-95%, and the amount is 10-15 times the amount of the cannabis extract, preferably 12-15 times the amount. When other concentrations are selected, the transfer rate and crystallization yield are both reduced. When an isopropanol solution is used, the concentration of the isopropanol solution is preferably 77-85% isopropanol solution, and the amount is 10-15 times the amount of the cannabis extract, preferably 10-12 times the amount. When other concentrations are selected, the transfer rate and crystallization yield are both reduced.

[0024] The third extraction Next, add an alcohol solution of a third concentration to the oil phase 2 in the extraction kettle, wherein the third concentration is less than or equal to the second concentration but greater than the first concentration. In a preferred embodiment of the present invention, 80-88% ethanol is selected, and the volume is 8-12 times, preferably 10-12 times, of the volume of the oil phase 1. The 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 the stirring is completed, let it stand for 1-2 hours, separate the lower aqueous phase 3 and enter the next step, and the oil phase 3 is reserved for other uses.

[0025] The present invention extracts the oil phase 2 by using the alcohol solution of the third concentration, extracts the cannabinoids including CBD therein as much as possible, and leaves terpenes and other low-polar substances in the oil phase 3. In the present invention, the third concentration and the amount of the alcohol solution have an impact on the components in the water phase 3 and the oil phase 3 and the product yield. If the third concentration is too high or the amount is too large, too many fat-soluble components will be brought into the water phase 3; if the third concentration is too low and the amount of the alcohol solution is too small, more cannabinoids will remain in the oil phase 2 and the product yield will be reduced.

[0026] In another specific embodiment of the present invention, a 80-88% methanol solution is used, and the amount used is 10-15 times the amount of the cannabis extract, preferably 10-12 times the amount. In another specific embodiment, a 65-73% isopropanol solution is used, and the amount used is 10-15 times the amount of the cannabis extract, preferably 10-12 times the amount.

[0027] In the present invention, the values ​​of the second concentration and the third concentration are not interchangeable. If the alcohol solution of the third concentration is used for the second extraction, and then the alcohol solution of the second concentration is used for the third extraction, the yield will be reduced. The possible reason is that based on the material composition of the oil phase 1 obtained by the first extraction of the present invention, the content of cannabinoid components such as CBD is relatively high. When the second concentration alcohol solution with a lower water content is used as the second extractant, it can still be extracted advantageously. After the second extraction, the content of cannabinoids in the oil phase 2 is reduced. At this time, the third concentration alcohol solution with a higher water content is used as the extractant for the third extraction, and cannabinoids such as CBD can continue to be advantageously extracted. On the contrary, if the oil phase 1 is first extracted with the alcohol solution of the third concentration with a higher water content as the second extractant, not only can more cannabinoids not be extracted, but more flavonoids will also be extracted. In addition, during the third extraction, due to the low water content of the third extractant, more highly fat-soluble substances will enter the water phase 3, and finally enter the next step, which not only leads to the total transfer rate of the two-step extraction not being improved, but also introduces more impurities, reducing the yield of subsequent crystallization.

[0028] crystallization After the second and third extractions, the obtained aqueous phases 2 and 3 are combined into aqueous phase 4, which usually contains 70-80% of the total amount of CBD in the cannabis extract. Aqueous phase 4 is concentrated and crystallized to obtain CBD crystals.

[0029] The CBD crystallization in this step is firstly achieved by concentrating the aqueous phase 4 to remove the solvent as much as possible to obtain a paste or viscous concentrate, and then adding 1-3 volumes, preferably 1-2, and even more preferably 1-1.5 volumes of solvent compared to the weight of the concentrate under stirring. 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, for 10-30 minutes, typically 10-20 minutes. Then the temperature is slowly lowered to 10 to -20°C for crystallization.

[0030] The method of the present invention can be used to extract industrial hemp extracts with an extraction content between 40-60%, and is particularly suitable for extracting industrial hemp extracts with an extraction content between 40-50%. It can achieve a higher yield without column chromatography separation, and has high industrial convenience.

[0031] In the following examples, the following materials and devices were used: HPLC: Primaide 1210Auto sample high performance liquid chromatograph, Hitachi PID detector, TeChrom chromatography workstation; Chromatographic column: Octadecylsilane bonded silica gel column Column temperature: 30°C Mobile phase: acetonitrile-0.1% acetic acid solution (75:25) Flow rate: 1.0ml / min Injection volume: 10µl Detection wavelength: 220nm Analysis time: 40min Example 1 Preparation: The industrial hemp flower and leaf powder was spread flat on a baking tray, baked at 130°C for 3 hours, cooled to room temperature, and granulated. 150 kg of industrial hemp flower and leaf particles were loaded into the silo of the supercritical extraction device, and a mixed solvent of heptane and ethanol (heptane: ethanol = 1:1) with a weight of 10-15% of the weight of the hemp particles was added as an entrainer. The extraction temperature was set to 45°C and the pressure was 30 MPa, and then carbon dioxide was introduced for supercritical extraction to obtain 13.7 kg of industrial hemp extract, in which the cannabidiol content was 42.71%.

[0032] First extraction 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, stir and mix at room temperature for 3 hours, let it stand for 2 hours, separate the lower aqueous phase 1, and leave the oil phase 1 in the equipment.

[0033] Second extraction Add 14 kg of 90-92% ethanol to the oil phase 1, stir for 2 hours and then let stand for 1-2 hours, then separate the lower aqueous phase 2, and leave the oil phase 2 in the equipment.

[0034] The third extraction Add 10-11 kg of ethanol with a concentration of 82-86% to the oil phase 2, stir for 2 hours, let stand for 1-2 hours, and then separate the lower aqueous phase 3.

[0035] The aqueous phase 2 and the aqueous phase 3 were combined and concentrated under reduced pressure at a temperature not exceeding 50° C. into a paste to obtain 459.4 g of a concentrate, which contained 79% CBD according to liquid chromatography, and the transfer rate of the two extractions was 85%.

[0036] crystallization: The concentrate was dissolved in 0.7 kg of heptane, maintained at 50-55°C for 10-30 min, and then slowly cooled to -15°C. The cooling process was completed within 4 hours. The product was filtered, washed, and dried to obtain 259.8 g of CBD crystals with a purity of 99.2%. The total transfer rate, i.e., yield, was 61.2%.

[0037] Example 2 First extraction Take 1kg of cannabis extract (containing 440g of CBD) and place it in a homogenizer. Add 3kg of heptane and stir to dissolve. Then add 6-8kg of 60-65% ethanol. Stir and mix at room temperature for 3 hours. Let it stand for 2 hours, separate the lower aqueous phase 1, and leave the oil phase 1 in the equipment.

[0038] Second extraction Add 14 kg of 85% ethanol to the oil phase 1, stir for 2 hours and then let stand for 1-2 hours, then separate the lower aqueous phase 2, and leave the oil phase 2 in the equipment.

[0039] The third extraction 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.

[0040] The aqueous phase 2 and the aqueous phase 3 were combined and concentrated under reduced pressure at a temperature not exceeding 50° C. into a paste to obtain 489 g of a concentrate, which contained 72% CBD according to liquid chromatography, and the transfer rate of the two extractions was 80%.

[0041] crystallization The concentrate was dissolved in 700 g of heptane, maintained at 50-55° C. for 10-30 min, and then slowly cooled to -15° C. The cooling process was completed within 8 hours, filtered, washed with solvent, and dried to obtain 236 g of CBD crystals with a purity of 99.0% and a total transfer rate, i.e., a yield of 53.1%.

[0042] This embodiment uses a lower concentration of ethanol solution for the second extraction than Example 1, and the combined transfer rate of the second and third extractions is slightly lower, and the yield of the CBD product is slightly lower.

[0043] Example 3 First extraction Take 1kg of hemp extract (containing 440g of CBD) and place it in a homogenizer, add 3kg of heptane and stir to dissolve, then add 6-8kg of 60-65% ethanol, stir and mix at room temperature for 3 hours, let it stand for 2 hours, separate the lower water phase 1, and leave the oil phase 1 in the equipment.

[0044] Second extraction Add 14 kg of 82% ethanol to the oil phase 1, stir for 2 hours and then let stand for 1-2 hours, then separate the lower aqueous phase 2, and leave the oil phase 2 in the equipment.

[0045] The third extraction 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.

[0046] The aqueous phase 2 and the aqueous phase 3 were combined and concentrated under reduced pressure at a temperature not exceeding 50° C. into a paste to obtain 491.8 g of a concentrate, which contained 68% CBD according to liquid chromatography, and the transfer rate of the two extractions was 76%.

[0047] crystallization The concentrate was dissolved in 0.7 kg of heptane, maintained at 50-55°C for 10-30 min, and then slowly cooled to -15°C. The cooling process was completed within 8 hours. The product was filtered, washed, and dried to obtain 236 g of CBD crystals with a purity of 99.0%. The total transfer rate, i.e., yield, was 49.5%.

[0048] Compared with Example 2, this example uses a lower concentration of ethanol solution for the second extraction and a higher concentration of alcohol solution for the third extraction. The combined transfer rate of the second and third extractions is slightly lower, and the yield of the CBD product is slightly lower.

[0049] Example 4 First extraction Take 1kg of cannabis extract (containing 440g of CBD) and place it in a homogenizer. Add 3kg of heptane and stir to dissolve. Then add 6kg of 70% methanol. Stir and mix at room temperature for 3 hours. Let it stand for 2 hours, separate the lower aqueous phase 1, and leave the oil phase 1 in the equipment.

[0050] Second extraction Add 12 kg of 93% methanol to the oil phase 1, stir for 2 hours and then let stand for 1-2 hours, then separate the lower aqueous phase 2, and leave the oil phase 2 in the equipment.

[0051] The third extraction 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.

[0052] The aqueous phase 2 and the aqueous phase 3 were combined and concentrated under reduced pressure at a temperature not exceeding 40° C. into a paste to obtain 502.6 g of a concentrate, which contained 77% CBD according to liquid chromatography, and the transfer rate of the two extractions was 88%.

[0053] crystallization The concentrate was dissolved in 600 g of pentane, maintained at 50°C for 10-30 min, and then slowly cooled to -20°C. The cooling process was completed within 8 hours. The concentrate was filtered, washed, and dried to obtain 278.8 g of CBD crystals with a purity of 99.0% and a total transfer rate, i.e., a yield of 63.3%.

[0054] This example uses methanol solution as the extractant and achieves a good yield at the selected concentration, although methanol solvent is not as industrially safe as ethanol.

[0055] Example 5 First extraction 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. Stir and mix at room temperature for 3 hours. Let it stand for 2 hours, separate the lower aqueous phase 1, and leave the oil phase 1 in the equipment.

[0056] Second extraction Add 1.2 kg of 82% isopropanol to the oil phase 1, stir for 2 hours and then let stand for 1-2 hours, then separate the lower aqueous phase 2, and leave the oil phase 2 in the equipment.

[0057] The third extraction 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.

[0058] The aqueous phase 2 and the aqueous phase 3 were combined and concentrated under reduced pressure at a temperature not exceeding 40° C. into a paste to obtain 44.1 g of a concentrate, which contained 73% CBD according to liquid chromatography, and the transfer rate of the two extractions was 74%.

[0059] crystallization The concentrate was dissolved in 80 g of pentane, maintained at 50°C for 10-30 min, and then slowly cooled to -20°C. The cooling process was completed within 10 hours. The concentrate was filtered, washed, and dried to obtain 22.7 g of CBD crystals with a purity of 98.1.0% and a total transfer rate, i.e., a yield of 52.3%.

[0060] This example uses isopropanol solution as the extractant, and also achieves a better yield at the selected concentration.

[0061] The technical solution of the present invention is explained above in conjunction with the embodiments. It should be pointed out that for ordinary technicians in this technical field, without departing from the technical concept of the solution of the present invention, other similar implementation means based on the technical concept of the present invention are also within the protection scope of the embodiments of the present invention.

Claims

1. An industrial production method of cannabidiol, comprising the following steps: 1) dissolving the cannabis extract with a non-polar 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 content of cannabidiol in the cannabis extract is 40-60%; 2) extracting the oil phase 1 for the second time with an alcohol solution of a second concentration to obtain an oil phase 2 and an aqueous phase 2; 3) extracting the oil phase 2 for the third time with an alcohol solution of a third concentration to obtain an oil phase 3 and an aqueous phase 3; 4) Combine aqueous phase 2 and aqueous phase 3, concentrate and crystallize the concentrate, in, The first concentration is less than the third concentration and less than the second concentration.

2. The method according to claim 1, wherein: The non-polar 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.

3. The method according to claim 1, wherein: The alcohol solution is an aqueous solution of methanol, ethanol or isopropanol.

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

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

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

7. The method according to claim 1, wherein: The cannabis extract is a supercritical extraction extract.

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

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

10. The method according to claim 9, wherein: The concentrate is dissolved with a crystallization solvent at 50-55°C for 10-30 min, and then crystallized at a temperature of 0 to -20°C.

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