CN110304994B

CN110304994B - Method for extracting high-purity cannabidiol from industrial cannabis sativa

Info

Publication number: CN110304994B
Application number: CN201910585027.4A
Authority: CN
Inventors: 吴平
Original assignee: Individual
Current assignee: Individual
Priority date: 2019-07-01
Filing date: 2019-07-01
Publication date: 2022-04-01
Anticipated expiration: 2039-07-01
Also published as: CN110304994A

Abstract

The invention discloses a method for extracting high-purity cannabidiol from industrial cannabis sativa. The method comprises the steps of raw material pretreatment, subcritical extraction, winterization, heat treatment, short-path molecular distillation, crystallization refining and the like. The THC content in the prepared CBD product meets the relevant legal regulations, the CBD content is more than 98.0 percent, the purity reaches more than 99.8 percent, the single impurity is less than 0.1 percent, the total impurity is less than 0.2 percent, and the THC is not detected. Compared with the existing extraction method, the method has the advantages of high efficiency, energy conservation, environmental protection and high product purity.

Description

Method for extracting high-purity cannabidiol from industrial cannabis sativa

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a method for extracting purified cannabidiol from industrial hemp flower leaves and hemp seed shells.

Technical Field

Industrial hemp (cannbis Sativa L.) also known as hemp, jute, is an annual herbaceous plant belonging to the family cannabinaceae, the genus cannabis. The hemp has a long planting history, is closely related to the life of human for a long time, not only provides fiber and grease for human, but also makes great contribution to human health. Archaeologists discovered hemp resin 2700 years ago in a cave located in Turpan, Xinjiang, China, which is the oldest evidence to date for stopping human use of hemp.

Cannabis contains cannabis phenols as main active ingredient, and these phenols are classified into psychoactive phenols such as Tetrahydrocannabinol (THC) and non-psychoactive phenols such as Cannabidiol (CBD). Currently, marinol (thc) is a drug from cannabis which is being used clinically,

(THC/CBD), epididolex (CBD) oral liquid, cannabinol structure modifier Nabilone and the like. In addition, there are dozens of drugs in clinical trials using CBD as a main active ingredient. In Europe and America, the CBD and the hemp oil rich in the CBD are widely applied to medicines, health care products, cosmetics, foods and the like, and have wide market prospects.

At present, the extraction of cannabinol substances mainly comprises solvent extraction and supercritical CO₂Fluid extraction methods and subcritical fluid extraction methods. The purification method is column chromatography, and only the chromatography packing is different.

CN 104277917 a discloses a method for extracting cannabidiol-containing resin oil from industrial hemp and an extraction device thereof. After extracting the hemp extract by a solvent extraction method, further obtaining the industrial hemp oil rich in CBD by a column chromatography separation and purification method, wherein the main procedures comprise screening, baking, leaching, column chromatography and the like.

Patent application publication No. CN 10967865A discloses a method for separating cannabidiol. Dissolving the existing hemp extract in a mixed solvent of normal hexane and ethyl acetate, adding KOH aqueous solution for extraction, standing for layering, respectively carrying out spin drying on an organic phase and an aqueous phase both containing CBD to obtain a solid, and washing with water to obtain the CBD with the enrichment rate of 80% and the purity of 84-90%.

Patent application with publication number CN109646992 discloses a method for extracting cannabidiol concentrate from industrial hemp. The method comprises the steps of crushing hemp flowers and leaves, extracting with alkaline water, and adjusting acid to obtain precipitate. And extracting the obtained precipitate by using an organic solvent, and concentrating to finally obtain a concentrate with the cannabidiol content of 41.3-43.2% and the tetrahydrocannabinol content of 1.41-1.52%.

Patent application with publication number CN109627148 discloses a method for preparing cannabidiol. The method utilizes eutectic solvent to extract crushed hemp leaves, and the obtained crude extract is separated by resin. The cannabidiol obtained by the method has the recovery rate of 81.46 percent and the purity of 28.93 percent.

Patent application publication No. CN 109369344A discloses a method for separating and extracting cannabidiol from industrial cannabis plant. The method comprises air drying stems, leaves and seeds of industrial hemp, pulverizing, soaking in 95% ethanol/water solution, ultrasonic extracting, suspending the crude product in water, extracting with petroleum ether, concentrating the extract, and separating and purifying with normal phase column and reverse phase column. The purity of the finally obtained CBD is 92-98%.

Application publication No. CN 109232191A discloses a method for extracting cannabidiol from industrial hemp leaves. The method comprises the steps of taking industrial hemp leaves, drying and crushing, adding a mixed solution of cell wall decomposition enzyme cellulase and pectinase, hydrolyzing, and then adding n-hexane for stirring and extracting; performing rotary evaporation on the extracted supernatant to obtain an oily substance; adding methanol into the oily matter, centrifuging at low temperature to obtain supernatant, decolorizing the supernatant with activated carbon, filtering to obtain filtrate, and rotary steaming; and then adding chloroform into the rotary evaporation product to dissolve the rotary evaporation product, and filtering the solution through an organic membrane to obtain the industrial cannabidiol solution. The cannabidiol solution prepared by the method is used for chromatographic analysis, and the purity of the cannabidiol prepared and the content of tetrahydrocannabinol are not mentioned.

Patent application publication No. CN 109053388A discloses a method for extracting cannabidiol. Drying flowers and leaves of the big hemp plants, grinding and crushing the flowers and leaves into coarse powder, and performing countercurrent extraction on the coarse powder and the coarse powder in opposite directions by using ethanol in a countercurrent extraction device to ensure that the solvent extracts effective components in the coarse powder to obtain an extracting solution; heating the extractive solution under reduced pressure, and volatilizing excessive ethanol in the extractive solution to obtain cannabidiol concentrated solution; adding pure water into the concentrated solution of cannabidiol for dilution, performing gradient elution by using a chromatographic column, and collecting target eluent; mixing the target eluates, and concentrating under reduced pressure at 50-70 deg.C to obtain secondary concentrated solution of cannabidiol; and adding 90% w/w ethanol supersaturated solution into the secondary concentrated solution of cannabidiol to obtain crystals, and washing and drying the crystals by pure water to obtain the cannabidiol product.

The patent application publication No. CN 108998248A discloses a preparation method of industrial cannabis sativa leaf absolute oil rich in cannabidiol. Drying and crushing flowers and leaves of industrial hemp to obtain hemp powder, soaking the hemp powder in edible oil to obtain hemp soaking oil, and performing auxiliary extraction on the hemp soaking oil at the temperature of 20-80 ℃ by using an ultrasonic extraction instrument to obtain extracted oil; extracting the oil with edible ethanol to obtain ethanol extractive solution; and putting the ethanol extract into a rotary evaporator, and concentrating to obtain the hemp flower and leaf absolute oil.

Application publication No. CN 108314608A discloses a method for extracting and separating cannabidiol. The method adopts alcohol extraction, adopts alkaline solution to enhance the water solubility of cannabidiol, extracts enriched cannabidiol by organic solvent, purifies and enriches by polyamide resin column, neutral alumina and bonded silica gel column, and obtains high-purity cannabidiol by crystallization.

Application publication No. CN 107898826A discloses a preparation method of cannabidiol-containing cannabis sativa extract. Taking mature industrial hemp fructus cannabis, drying, removing impurities, and crushing for later use; extracting the crushed fructus cannabis material with ethanol, wherein the concentration of the ethanol is 95-100% (V/V), and the ratio of the material to the liquid is 1:5-1: 20; filtering out the leaching liquor, and obtaining the industrial hemp and fructus cannabis extract after decompression and concentration; dissolving the fructus Cannabis extract in ethanol, and performing low temperature winterization; centrifuging the suspension after winterization by using a centrifuge or a filtering technology; decoloring the supernatant obtained by centrifugation by using activated carbon and filtering; and (3) carrying out rotary evaporation treatment on the filtered filtrate to obtain the cannabidiol-rich cannabis sativa extract. The extraction rate of the cannabis extract prepared by the method is 3.5-4.8%, and the content of cannabidiol is 18.28-25.0%.

Patent application publication No. CN 106831353A discloses a method for extracting cannabidiol from cannabis sativa. The method comprises pulverizing the extracted part of Cannabis sativa L, and oven drying to obtain medicinal powder; extracting the medicinal powder with alcohol, precipitating with water, dissolving the obtained precipitate with alcohol, and performing column chromatography; concentrating the eluent, adding ethanol for supersaturation and dissolution to obtain a crystal; washing with purified water or ethanol to obtain primary product; and (4) uniformly mixing the primary product with purified water, and drying to obtain the CBD product.

Patent CN 208500803U discloses a preparation device for cannabidiol. The equipment comprises a flower and leaf crushing and drying device, a supercritical extraction device, a continuous filtering device, a chromatography and purification device and a drying and crystallization device; the supercritical extraction device adopts supercritical carbon dioxide liquid for extraction, the continuous filtering device comprises a dissolving cavity, a homogenizer and a filtering cavity, a primary filter membrane and an ultramicro filter membrane are arranged in the filtering cavity, and a first chromatographic column and a second chromatographic column which are connected through a concentration and redissolution device are arranged in the chromatographic filtering device. The equipment dissolves cannabidiol extract obtained by extraction, performs two-stage membrane treatment, and filters out particle impurities, pigments and colloid; then macromolecular impurities are separated out through the first chromatography, and impurities with similar molecular weight are separated through the second chromatography. The purity of the obtained cannabidiol can reach 95 percent.

Application publication No. CN 107227198A discloses a method for extracting cannabis sativa leaf oil with high extraction rate and a method for extracting cannabis sativa leaf oil. The method comprises drying flowers and leaves of Cannabis sativa, pulverizing, grinding in a ball mill to destroy cell walls, and drying the ground powder again. And finally, extracting by using supercritical carbon dioxide to obtain the hemp flower leaf oil. The hemp flower leaf oil prepared by the method comprises 25-35% of cannabidiol, 50-60% of unsaturated fatty acid and 8-10% of terpenoid by weight.

Application publication No. CN 107011125 a discloses a method for enriching cannabidiol. Drying hemp flowers and leaves at 120 ℃ for 0.5-4 hours, crushing to over 50 meshes, performing carbon dioxide supercritical extraction at 30-55 ℃ under 13-30 MPa for 1-9 hours, and recovering carbon dioxide to obtain hemp flower and leaf primary extract; dissolving the hemp flower and leaf primary extract in ethanol or methanol, finely filtering to remove impurities, and evaporating the solvent to dryness for later use; filling pretreated filler into a chromatographic column, and loading by a wet method or a dry method, wherein the loading amount is 3-15 wt%; performing gradient elution or isocratic elution with one or more of water, methanol, ethanol, n-butanol, acetone and chloroform; collecting the elution fraction rich in cannabidiol.

The patent CN105505565 and the patent CN 105505565A also adopt supercritical CO₂The extraction technology extracts industrial hemp oil from industrial hemp.

Patent CN105535111A discloses a method for extracting cannabidiol-rich extract from industrial cannabis sativa leaves. The preparation method comprises the steps of firstly, carrying out dry heat treatment on flowers and leaves, then crushing, taking ethanol as an entrainer, extracting by using subcritical butane, dissolving an extract in the ethanol, carrying out low-temperature winterization treatment, carrying out centrifugation or filtration, then carrying out decoloration by using activated carbon, and finally removing the solvent by rotary evaporation to obtain the cannabis sativa extract rich in CBD. The extraction rate of the cannabis sativa extract prepared by the method is 3.0-5.0%, and the content of CBD is 18.0-25.0%.

Besides CBD, hemp contains a psychoactive ingredient THC, which belongs to drugs in other regions of the world except for a very few countries such as Paraguay, Canada and USA and is regulated by drug-arresting departments of various countries. In China, the THC content in the hemp related semi-finished products or products is qualified only if the THC content is less than or equal to 0.3 percent, so the problem that the THC content exceeds the standard is not solved by utilizing the method.

Patent application CN108929201A discloses a method for extracting cannabidiol by subcritical water extraction technology. The method comprises the steps of performing subcritical water extraction on dried, ground and crushed hemp plants by using a subcritical water extraction technology, concentrating an extract, removing impurities, diluting, performing gradient elution by using a chromatographic column, and concentrating and crystallizing a target eluent to obtain a cannabidiol product.

The subcritical water extraction technology does not use an organic solvent, is green and environment-friendly, but the critical temperature of subcritical water is 374 ℃, and the critical pressure is 21.7 MPa. The technology is used for production, the extraction temperature reaches 100-374 ℃, and the extraction pressure reaches 15-30 MPa. There is no significant advantage over the conventionally used subcritical extractant butane.

The subcritical extraction technology mainly uses butane and propane as solvents, has low boiling point and is nontoxic, and the problem of solvent residue is not needed to be worried about; the extraction process is under the conditions of secret, low temperature and no oxygen, so that the oxidative deterioration of materials is avoided, the low temperature reduces the content of extracted impurities, and the subsequent refining process is simplified; compared with the supercritical extraction technology, the subcritical extraction technology has the advantages of simple equipment structure and low working pressure, generally only 0.3-0.7 MPa is needed, and the working pressure of the supercritical extraction equipment generally exceeds 23.0 MPa. Therefore, the subcritical extraction technology is easily applied to industrial production. Compared with a solvent extraction method, the dosage of the organic solvent is less, the solvent loss is also extremely low, and because the subcritical extraction technology is mainly aimed at the extraction of fat-soluble substances, the polar impurities of the extract produced by the technology are less, and the subsequent processing technology is simplified. Has obvious technical advantages.

Unlike traditional distillation, molecular short path evaporation relies on the principle of differential boiling point separation, but relies on the difference in the mean free path of motion of different substances molecules to achieve separation. When the liquid mixture flows along the heating plate and is heated under a certain pressure condition in the distillation process, light and heavy molecules can escape from the liquid surface and enter into a gas phase, the free paths of the light and heavy molecules are different, so that the molecules of different substances can move for different distances after escaping from the liquid surface, if a condensing plate can be properly arranged (the distance of the condensing surface of an evaporation area is generally less than 100MM), the light molecules reach the condensing plate and are condensed and discharged, and the heavy molecules cannot reach the condensing plate and are discharged along the mixed liquid. Thus achieving the purpose of separating substances.

CN 108479098A discloses an application method of a molecular short path distiller for extracting cannabidiol from medical cannabis sativa, and the pressure required in the embodiment of the patent is 0.01-100 pa, which has extremely high requirements on vacuum equipment.

Since CBD is present in plants in the form of cannabidiolic acid (CBDA), CBDA is only decarboxylated to CBD at high temperatures. Therefore, a heat treatment process must be present throughout the production process. The existing methods are that flowers and leaves are directly treated in an oven at high temperature after being picked, so that the treatment capacity is extremely high, and the electric energy consumption is remarkable. In addition, off-gas with odor is generated during high temperature treatment, and a chimney with the height of 30 meters is usually required to be built for environmental protection. Therefore, decarboxylation of cannabidiolic acid to cannabidiol by heat treatment of the flower leaves is an uneconomical, energy-saving and less environmentally friendly method. The above cited patents, however, all mention the heat treatment step (some of which are not mentioned), are all heat treatment of the flower leaves.

CN 109803643 a discloses a process for decarboxylation of cannabidiolic acid in cannabis biomass and cannabis extracts, comprising heating cannabis extract or cannabis biomass in the presence of one or more divalent or monovalent agents to a temperature of 40 ℃ to 100 ℃; wherein the organic solvent extract preferably comprises an alcohol extract or hexane extract of cannabis or cannabis biomass, more preferably a lower alcohol selected from the group consisting of methanol, ethanol, propanol and butanol. The patent mentions a cannabis extract from supercritical CO₂Extract or liquid CO₂An extract, an organic solvent extract, an alcohol extract or a hexane extract; and inorganic base is added in the decarboxylation process, and the temperature is 40-100 ℃.

Some of the above-mentioned applied patents only relate to crude oil extraction, and no mention is made of refining of subsequent products to obtain products meeting the requirements of the regulations, for example, the content of extract CBD obtained in patent CN105535111A for preparing cannabis sativa extract by using subcritical extraction technology is 18.0-25.0%, and no mention is made of refining of subsequent products. However, the purification process is not exclusively a column chromatography technique, including patent CN108929201A, which utilizes subcritical water extraction technique.

Column chromatography methods have a number of disadvantages, for example, first, the operation is cumbersome, requiring multiple steps of packing, crude product loading, mobile phase elution, eluent concentration, and packing refill; secondly, the solvents used for chromatographic separation are considered to be health risks, and some solvents, such as methanol, chloroform, etc., may remain in the obtained product; thirdly, since the chromatographic columns are used in series from one batch to another, the product obtained by the column chromatography technique not only has frequent change of purity, insufficient stability of product quality, but also relatively low yield; fourth, the technique produces a large amount of solid waste, the filler.

According to the relevant regulations of related national departments, the content of tetrahydrocannabinol in the raw materials, products or waste materials is not higher than 0.3 percent. The patents cited above, only a few mention that the tetrahydrocannabinol content of the product (cannabidiol) is not higher than 0.3%. None of the above cited patents teach how waste with THC contents in excess of 0.3% can be processed in compliance.

Disclosure of Invention

The invention aims to overcome the inherent defects of a solvent extraction technology, a supercritical fluid extraction technology and a column chromatography purification technology, and provides a method which is economic, efficient, green and environment-friendly and is beneficial to industrial mass production, and high-purity cannabidiol is extracted and refined from industrial hemp, and is applied to the fields of medicines, health products, foods and cosmetics. The production link of the technology completely conforms to the relevant regulations of the state and the relevant departments on the development of the hemp industry.

The technical scheme of the invention is realized in the following mode.

The main steps of the process for producing Cannabidiol (CBD) by using industrial hemp raw material are as follows, including six steps of raw material pretreatment, subcritical extraction, winterization, heat treatment, short-path molecular distillation and crystallization refining, and the specific steps are as shown in a flow chart of figure 8.

A method for extracting high-purity cannabidiol from industrial cannabis sativa comprises the following steps.

S1, pretreating raw materials.

The industrial hemp is prepared by sorting, drying in the shade, crushing and granulating by spraying water.

S2, subcritical extraction.

The particles are subjected to subcritical extraction with an extraction solvent and the resulting extraction solution containing the extraction solvent is evaporated to obtain an extract.

And S3, winterization.

Fully dissolving the extract in a winterization solvent, and obtaining a concentrated solution after primary filtration, heat preservation winterization, secondary filtration and concentration.

And S4, heat treatment.

Distilling the concentrated solution under reduced pressure until no fraction is distilled out to obtain residue, and cooling.

S5, short path molecular distillation.

The residue was purified by short path molecular distillation and the light fraction was collected.

S6, crystallizing and refining.

Dissolving the light component in a solvent, cooling and crystallizing, filtering, and recrystallizing the obtained solid for multiple times to obtain the high-purity cannabidiol.

The above steps S1-S6 illustrate an embodiment of this technique, which ultimately results in a high purity CBD. In the actual production process, the regulated treatment of the waste is very important. Because the physical properties of THC and CBD are similar, the THC is enriched while CBD is enriched. Therefore, THC-rich production waste needs to be treated in a regulatory manner.

As can be seen from the chemical structure of THC, the double bond of cyclohexane and the phenolic hydroxyl group both have reducibility, and the chemical structure can be destroyed by oxidation. We tried that hydrogen peroxide, sodium hypochlorite aqueous solution, tert-butyl hydroperoxide, potassium permanganate solution and ozone can effectively oxidize THC to reduce its content to below 0.3%. Among them, the ozone effect is best, and potassium permanganate solution is the second.

In the S1, the crushing mesh number is 24-80 meshes, preferably 50-65 meshes, and more preferably 50 meshes; and water spraying granulation is carried out to ensure that the water content is 4-8%, the particle diameter is 1-2 cm, and the length is 2-4 cm.

In the S2, the extraction solvent is liquid butane, propane or natural gas, preferably liquid natural gas.

In the step S2, the temperature in subcritical extraction is raised to 35-55 ℃, the temperature is kept for 20-40 min, then the extraction liquid is subjected to reduced pressure evaporation to recover the extraction solvent, and the rest of the extract enters the next step.

In the S3, the winterization solvent is 95% ethanol, and the mass ratio of the extract to the winterization solvent is 1: (8-10), the winterization needs to be kept at the temperature of-80 to-40 ℃ slowly with stirring, and the temperature is kept for 6 to 15 hours.

In the S5, the short-path molecular distillation temperature is 150-180 ℃, the cooling temperature is 70-90 ℃, and the vacuum degree is 0.001-0.05 mbar.

In the S6, the mass ratio of the light component to the solvent is 1 (3-6), the crystallization temperature is-20-5 ℃, and the solvent is n-heptane or n-hexane, preferably n-heptane.

The method for extracting high-purity cannabidiol from industrial cannabis is characterized in that the total yield of the obtained cannabidiol is 0.95%, the purity is higher than 99.8%, the single impurity content is less than 0.1%, the total impurity content is not more than 0.2%, and tetrahydrocannabinol is not detected.

The industrial hemp is any plant raw material or semi-finished product containing cannabidiol components, including industrial fried dough twist, leaves, hemp seed shells and the like.

The THC-rich production waste can be treated with an oxidizing agent, which is an ozone or potassium permanganate solution.

The method comprises the steps of pretreating industrial hemp, and extracting by using a subcritical extraction technology to obtain a crude extract rich in CBD and THC; then dissolving the crude extract in ethanol at a certain ratio for winterization. After the wax, the colloid and the macromolecular fatty acid are separated out, obtaining clear filtrate by centrifugation or filtration; concentrating the filtrate in an alcohol recovery device to obtain concentrated extract; the extract is introduced into a vacuum tank for reduced pressure distillation until no fraction is distilled out, wherein the process is a process for converting CBDA into CBD by decarboxylation through heat treatment and a process for removing low-boiling-point terpene impurities in the extract; carrying out short-path molecular distillation on the concentrate while the concentrate is hot, and collecting light components; dissolving the light components in n-heptane or n-hexane in a certain proportion, slowly cooling the filtrate, adding CBD seed crystal, and crystallizing at constant temperature; and (3) recrystallizing the filtered solid to obtain a target product, and decolorizing by using activated carbon and/or activated clay in a crystallization link to improve the purity of the product. The invention utilizes subcritical extraction technology to extract materials, short-range molecular distillation technology to carry out primary separation and purification, recrystallization technology to refine products, and the method has simple process and high extraction rate. The THC content in the prepared CBD product meets the relevant legal regulations, the final content is more than 98%, the purity is more than 99.8%, the single impurity content is less than 0.1%, the total impurity content is less than 0.2%, and the THC is not detected. The whole link is efficient, energy-saving and environment-friendly.

Moreover, a large number of experiments and related researches show that the particle size of industrial hemp crushed, the solvent of subcritical extraction, winterization conditions, the solvent during crystallization and the like have great influence on the final purity in the extraction preparation: the extraction rate is influenced by the size of the crushed and granulated particles; natural gas, an extraction solvent, is superior to liquid butane and propane; the shorter the winterization time is, the too fast cooling is not beneficial to the precipitation of crystals; the solvent during crystallization has great influence on the crystallization effect, and n-heptane is superior to n-hexane; the purity and the impurity content of the product are comprehensively influenced by the factors.

Compared with the prior art, the invention has the innovation points that:

(1) compared with a solvent extraction method, the method for extracting the cannabidiol as the fat-soluble substance by using the subcritical extraction technology has the advantages that the content of the cannabidiol in the obtained extract is high, the content of polar impurities is low, and the subsequent purification process is simplified; compared with the supercritical carbon dioxide fluid extraction technology, the operation pressure is two orders of magnitude lower, and the equipment investment is low; the subcritical extraction technology is economical, energy-saving and environment-friendly.

(2) The method takes the hemp flowers and leaves and/or the hemp seed shells as raw materials, the hemp flowers and leaves and/or the hemp seed shells are crushed and then manufactured into particles, and then subcritical extraction is carried out, so that the specific surface area of the extraction materials is increased, the extraction efficiency is improved, the production operation is convenient, and the dust pollution in the production process is reduced.

(3) The invention adopts the working procedures of extraction first and then heat treatment for decarboxylation, avoids a large amount of peculiar smell waste gas generated in the process of dry heat treatment of the hemp flowers and leaves, and simultaneously greatly reduces the energy consumption, thereby saving energy and protecting environment.

(4) The invention combines the short-path molecular distillation technology with the recrystallization technology, replaces the column chromatography purification technology, avoids the use of a large amount of organic solvents and the waste treatment after the use of column chromatography fillers, is economic and environment-friendly, and ensures the stable product quality among each batch.

(5) In the whole production flow, only two solvents of ethanol and heptane (or hexane) are used, the solvent can be recycled, the loss rate is low, no production sewage is generated in the whole process, the solvent residue is extremely low whether the residue is the residue after extraction or the waste after short-range molecular distillation, and the solvent residue can be used as a fertilizer to return to the field.

(6) THC-containing waste materials generated in the production process meet the requirements of regulations after being oxidized by oxidants, wherein the oxidants have the best ozone effect, and potassium permanganate aqueous solution is used as the next oxidant.

In conclusion, the process technology of the preparation method of the high-purity cannabidiol provided by the invention is efficient, energy-saving, green and environment-friendly, and all production links meet the requirements of relevant regulations.

Drawings

FIG. 1 is Δ⁸-THC and Δ⁹-THC high performance liquid chromatogram.

FIG. 2 is a high performance liquid chromatogram of the light fraction obtained by the short path molecular distillation in example 1.

FIG. 3 shows the light fraction and Δ of the short path molecular distillation in example 1⁸-THC and Δ⁹-mixing high performance liquid chromatograms of THC samples.

FIG. 4 is a high performance liquid chromatogram of the high purity product obtained from the third crystallization in example 1.

FIG. 5 shows a yellow solid obtained by the first crystallization of example 1.

FIG. 6 shows a white solid obtained by the second crystallization of example 1.

FIG. 7 shows the high purity product obtained by the third crystallization of example 1.

FIG. 8 is a flow chart of the main steps for the production of Cannabidiol (CBD) from industrial hemp feedstock.

Fig. 9 is a flow diagram of the S2 subcritical extraction in a method of extracting high purity cannabidiol from industrial cannabis in an embodiment.

Detailed Description

For a better understanding of the present invention, reference is made to the following examples which are set forth to illustrate, but are not to be construed to limit the present invention. In the following specific examples, sample analysis was performed by an Agilent 1200 high performance liquid chromatograph, and the content, purity, and the like were measured by peak area calculation.

S1, pretreating raw materials.

The pretreatment comprises screening, drying, crushing and granulating the raw materials. Sorting industrial hemp flowers, leaves and hemp seed shells, removing impurities such as stems, branches, broken stones and the like, and drying in the shade. The method comprises the following steps of crushing by using a crusher with a dust removal function, wherein the mesh number of a crushing sieve is 24-80 meshes, conveying powder into a stirrer, spraying water properly, controlling the water content of the powder to be 4-8%, and then conveying the powder into a granulator for granulation, wherein the diameter of prepared granules is 1-2 cm, and the length of the prepared granules is 2-4 cm. Preferably, the mesh number of the crushing screen is 50-65 meshes, and more preferably 50 meshes.

S2, subcritical extraction.

Filling the prepared particles into an extraction bag, placing the extraction bag into an extraction tank, vacuumizing the extraction tank, injecting liquid butane, propane or natural gas, taking liquid to be less than solid but not more than 4/5 of the total volume of the tank body, heating to 35-55 ℃ for 20-40 minutes, transferring the extract liquid into an evaporation tank, decompressing, heating to gasify butane, transferring the butane into a butane storage tank through a compressor, and obtaining the liquid which is not gasified as our extract. Extracting each batch of materials for 1-3 times. In the whole production link, the loss of the extracting agent is 0.1-1%, and the granular waste residues can be returned to the field as fertilizer.

The subcritical extraction scheme of S2 is shown in FIG. 9.

And S3, winterization.

Dissolving the extract in alcohol (if not specifically stated, the alcohol in the invention is 95% ethanol), wherein the ratio of material to liquid is 1: 8-12 (mass ratio), filtering the solution by filter cloth after stirring and fully dissolving, pumping the solution into a heat-preservation winterization tank, slowly reducing the temperature to-80 to-40 ℃ while stirring, and maintaining the temperature for 6-15 hours, wherein the lower the temperature, the shorter the winterization time is, but the too fast temperature reduction is not beneficial to the precipitation of crystals.

Subsequently, the low temperature solution was filtered through a low temperature celite filter, and the low temperature filtrate was used as a cooling liquid for primary cooling of the extract alcohol solution. Concentrating the filtrate with single-effect alcohol concentrator, recovering alcohol, and making the concentrated solution enter the next process.

And S4, heat treatment.

And (4) putting the concentrated solution obtained in the step S3 into a reaction kettle for reduced pressure distillation, gradually reducing the pressure to be below 0.01-0.20 mbar, and gradually increasing the temperature to be 130-150 ℃ until no fraction is distilled out. Naturally cooling to 100-120 ℃, and transferring to the next working procedure.

S5, short path molecular distillation.

And (4) carrying out short-path molecular distillation on the distillation residue obtained in the step S4. The distillation temperature is 150-180 ℃, the cooling temperature is 70-90 ℃, and the vacuum degree is 0.001-0.05 mbar. The collected light components enter the next process. The sample was analyzed to contain approximately 78% CBD, 5% THC on a dry weight basis.

S6, crystallizing and refining.

And (3) dissolving the collected light components after the short-path molecular distillation in n-heptane in a crystallization tank, wherein the mass ratio of the distillate to the heptane is 1: 3-6, cooling the solution to-20-5 ℃, adding a CBD seed crystal, and maintaining the temperature for 4-24 hours for crystallization. And after filtering, collecting yellow solid to obtain a CBD crude product with the purity of 90-95%, dissolving the CBD crude product in 3 times of n-heptane by mass, adding 5% of activated carbon and 5% of activated clay by mass, heating to 40-60 ℃, stirring for 0.5-4 hours, and naturally cooling, cooling and crystallizing. And filtering and collecting white solid to obtain a CBD product with the purity of 98-99%, wherein the content of tetrahydrocannabinol is less than or equal to 0.3%. And dissolving the white solid in n-heptane with the mass 2 times that of the white solid again, heating to 40-50 ℃ for dissolving, and then slowly cooling to 0-5 ℃ and maintaining for 2-4 hours. Filtering, and collecting white solid to obtain refined product of CBD with purity of more than 99.8%, single impurity content of less than 0.1%, total impurity content of less than or equal to 0.2%, and no THC.

The above steps S1-S6 illustrate in detail the implementation of this technique, which ultimately results in a high purity CBD. In the production process, an important link is the regulated treatment of the waste. Because the physical properties of THC and CBD are similar, the THC is enriched while CBD is enriched. Therefore, the THC-rich production waste needs to be subjected to a standardized treatment.

And (4) preparing a sample solution.

1000.0mg of sample is accurately weighed, dissolved by methanol in a 100mL volumetric flask and subjected to constant volume to prepare 10 mg/mL test solution, and the test solution is filtered by a 0.22 mu L microporous filter membrane and then subjected to sample injection analysis.

And (5) comparing the article information.

Cannabidiol (CBD), available from Sigma Aldrich, specification 1.000mg/mL (1mL MeOH).

Cannabis diphenolic acid (CBDA) from Sigma Aldrich, specification 1.000mg/mL (1mL MeOH).

Δ⁹-tetrahydrocannabinol (Δ)⁹-THC), purchased from Sigma Aldrich, spec 1.000mg/mL (1mL MeOH).

Δ⁸-tetrahydrocannabinol (Δ)⁸-THC), purchased from Sigma Aldrich, spec 1.000mg/mL (1mL MeOH).

Take a.DELTA.of 100. mu.L⁸-THC solution and 50. mu.L of A⁹-THC solution, mixed to new THC control solution.

And (4) measuring the content of CBD/THC.

Respectively taking CBD, CBDA and delta⁹-THC、Δ⁸-carrying out liquid phase analysis on the THC, the THC mixed solution and the sample. The chromatographic column is Raptor^TMARC-18(cat. #9314A65, 150mm. times.4.6 mm ID), column temperature 40 ℃, mobile phase water with 0.1% TFA: chromatographic methanol with 0.1% TFA ═ 20: 80, the flow rate of the mobile phase is 1.0mL/min, the sample injection amount is 5 mu L, and the detection wavelength is 210 nm. Calculating the main contents of each sample according to the peak area, wherein the total content of CBD comprises CBD and CBDA, and the total content of THC comprises delta⁸-THC and Δ⁹-THC。

Example 1.

Picking out hemp flowers and leaves, removing impurities such as branches and trunks, broken stones and the like, and drying in the shade. The method comprises the steps of crushing by using a crusher with a dust removal function, enabling the mesh number of a crushing sieve to be 50 meshes, conveying powder into a stirrer, measuring moisture by using a simple moisture meter, controlling the water content of the powder to be 4-8%, conveying the powder into a granulator for granulation, and enabling the prepared granules to be 1 cm in diameter and 2-4 cm in length. Taking 5kg of prepared particles, filling the particles into an extraction bag, placing the extraction bag into a 29L extraction tank, vacuumizing the extraction tank, injecting liquefied natural gas until the particles are submerged but not more than 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 40 ℃ for 30 minutes, transferring the extract liquid into an evaporation tank, reducing the pressure and raising the temperature to gasify the liquefied natural gas, transferring the gasified natural gas into a natural gas storage tank through a compressor, and collecting the extract which is not gasified. The extracts are combined for two times of extraction to obtain 320g of extract, and the yield is 6.4 percent. Dissolving the extract in 3.2Kg of ethanol, filtering the solution with filter cloth, pumping the solution into a heat-preservation winterization tank, cooling to-60 to-50 ℃ under stirring, and maintaining the temperature for 6 hours. And then filtering the low-temperature solution by using a low-temperature diatomite filter, concentrating the filtrate by using an alcohol recovery device, recovering alcohol, pumping the concentrated solution into a vacuum tank for heat treatment while the concentrated solution is hot, carrying out reduced pressure distillation by gradient temperature rise and gradient reduced pressure, gradually raising the temperature to 150-160 ℃, and gradually reducing the pressure to 0.01-0.10 mbar until no fraction is distilled out. Naturally cooling to 100-120 ℃, weighing the residue, sampling and analyzing, and then carrying out short-range molecular distillation. The pressure was lower than 0.02 mbar, the heating temperature was 160 ℃ and the cooling temperature was 90 ℃ and 80g of light fraction were collected, yielding 25.0%. The collected lights were placed in a crystallization tank, 320g of n-heptane were dissolved, the solution was cooled to-20 ℃, CBD seeds were added and the temperature was maintained for 12 hours. Filtration collected 52.2g of yellow solid, 65.2% yield. Dissolving the yellow solid in 156.6g of n-heptane, heating to 50 ℃, completely dissolving the solid, adding 2.6g of activated carbon and 2.6g of activated clay, continuing stirring for 2 hours, filtering the solution with diatomite while the solution is hot, naturally cooling the filtrate to room temperature, cooling the filtrate to 0 +/-5 ℃ for crystallization, filtering the solution after 8 hours, and collecting 35.7g of white solid, wherein the yield is 68.4%, the content is more than 98.0%, and the THC content is less than 0.3%. The white solid was dissolved in 71.4g of n-heptane, dissolved by heating to 50 ℃ and then allowed to cool to room temperature, reduced to 5 ℃ at a rate of 5 ℃/h and stirred for a further 2 h. 32.4g of white solid was filtered and collected, yield 90.8%. By HPLC analysis, the content of CBD is more than 98.0%, the purity is more than 99.8%, the single impurity content is less than 0.1%, the total impurity content is less than 0.2%, and THC is not detected. The total CBD yield of the whole process is 0.95 percent.

Example 2.

Picking hemp flowers, leaves and seed shells, removing impurities such as branches and trunks, broken stones and the like, and drying in the shade. The method comprises the steps of crushing by using a crusher with a dust removal function, wherein the mesh number of a crushing sieve is 24 meshes, conveying powder into a stirrer, measuring moisture by using a simple moisture measuring instrument, controlling the moisture content of the powder to be 4-8%, conveying the powder into a granulator for granulation, and granulating the granules with the diameter of 1 cm and the length of 2-4 cm. Taking 5kg of the particles prepared in the example 1, filling the particles into an extraction bag, placing the extraction bag in a 29L extraction tank, vacuumizing the extraction tank, injecting liquid butane until the liquid butane is over solid particles but not over 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 35-40 ℃, maintaining the temperature for 20 minutes, transferring the extract into an evaporation tank, reducing the pressure and raising the temperature to gasify the butane, transferring the gasified butane into a butane storage tank through a compressor, and collecting the non-gasified extract. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 3.

Taking 5kg of the particles prepared in the example 2, filling the particles into an extraction bag, placing the extraction bag into a 29L extraction tank, vacuumizing the extraction tank, injecting liquid butane until the liquid butane is not over the solid particles but not over 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 35-40 ℃, maintaining the temperature for 30 minutes, transferring the extract into an evaporation tank, reducing the pressure and raising the temperature to gasify the butane, transferring the gasified butane into a butane storage tank through a compressor, and collecting the non-gasified extract. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 4.

Taking 5kg of the particles prepared in the example 2, filling the particles into an extraction bag, placing the extraction bag into a 29L extraction tank, vacuumizing the extraction tank, injecting liquid butane until the liquid butane is not over the solid particles but not over 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 35-40 ℃, maintaining the temperature for 40 minutes, transferring the extract into an evaporation tank, reducing the pressure and raising the temperature to gasify the butane, transferring the butane into a butane storage tank through a compressor, and collecting the non-gasified extract. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 5.

Taking 5kg of the particles prepared in the example 2, filling the particles into an extraction bag, placing the extraction bag into a 29L extraction tank, vacuumizing the extraction tank, injecting liquid butane until the liquid butane is not over the solid particles but not over 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 40-45 ℃, maintaining the temperature for 30 minutes, transferring the extract into an evaporation tank, reducing the pressure and raising the temperature to gasify the butane, transferring the butane into a butane storage tank through a compressor, and collecting the non-gasified extract. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 6.

Taking 5kg of the particles prepared in the example 2, filling the particles into an extraction bag, placing the extraction bag into a 29L extraction tank, vacuumizing the extraction tank, injecting liquid butane into the extraction tank until the liquid butane is over solid particles but not over 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 45-50 ℃, maintaining the temperature for 30 minutes, transferring the extract liquid into an evaporation tank, reducing the pressure and raising the temperature to gasify the butane, transferring the butane into a butane storage tank through a compressor, and collecting the non-gasified extract. Extracting twice, sampling, analyzing by HPLC, and calculating the CBD content and the total extraction rate respectively through peak areas.

TABLE 1 Effect of temperature and time on extraction

As can be seen from examples 2, 3 and 4 in Table 1, on a scale of 5kg, at 35-40 ℃, the extraction liquid is nearly saturated after 30 minutes of extraction, and the total extraction rate of CBD cannot be continuously improved after the extraction is continuously prolonged; it can be seen from examples 3, 5 and 6 that, also for 30min of extraction, the temperature has a greater influence on the extraction yield, the higher the temperature, the higher the extraction yield. But the extraction selectivity is reduced, the impurities are increased and the CBD content is obviously reduced due to the increase of the temperature. Therefore, when the subcritical extraction technology is used for extracting the industrial cannabidiol, when the scale of extracting 5Kg of material is large, the extraction temperature is 35-50 ℃, and the extraction time is 20-40 min; taking the extraction rate and the content of CBD into comprehensive consideration, the extraction temperature is preferably 40-45 ℃ and the time is 30 min.

Example 7.

The material was pretreated as in example 1, the mesh number of the crushing screen was changed to 50 mesh, and the remaining parameters were unchanged. 5kg of the granules obtained were placed in an extraction bag and placed in a 29L extraction tank and extracted under the extraction conditions of example 5. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 8.

The material was pretreated as in example 1, the mesh number of the crushing screen was changed to 65 mesh, and the remaining parameters were unchanged. 5kg of the granules obtained were placed in an extraction bag and placed in a 29L extraction tank and extracted under the extraction conditions of example 5. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 9.

The material was pretreated as in example 1, the mesh number of the crushing screen was changed to 80 mesh, and the remaining parameters were unchanged. 5kg of the granules obtained were placed in an extraction bag and placed in a 29L extraction tank and extracted under the extraction conditions of example 5. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

Example 10.

The material was pretreated as in example 1, the mesh number of the crushing screen was changed to 50 mesh, and the remaining parameters were unchanged. Putting 5kg of prepared particles into an extraction bag, placing the extraction bag in a 29L extraction tank, vacuumizing the extraction tank, injecting liquid propane until the solid particles are not covered but the solid particles are not more than 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 40-45 ℃ and maintaining the temperature for 30 minutes, transferring the extract liquid into an evaporation tank, reducing the pressure and raising the temperature to gasify butane, transferring the gasified butane into a propane storage tank through a compressor, and collecting the non-gasified extract. The extraction was performed twice, samples were analyzed by HPLC, and the CBD extraction rate was calculated by peak area.

Example 11.

The material was pretreated as in example 1, the mesh number of the crushing screen was changed to 50 mesh, and the remaining parameters were unchanged. Putting 5kg of prepared particles into an extraction bag, placing the extraction bag in a 29L extraction tank, vacuumizing the extraction tank, injecting liquid natural gas until the particles are not larger than 4/5 of the total volume of the tank body, raising the temperature of the extraction tank to 40-45 ℃, maintaining the temperature for 30 minutes, transferring the extract liquid into an evaporation tank, decompressing and heating the extraction tank to gasify butane, transferring the gasified butane into a natural gas storage tank through a compressor, and collecting the non-gasified extract. Extracting twice, sampling, analyzing by HPLC, and respectively calculating the CBD extraction rate by peak areas.

TABLE 2 impact of comminuted particle size and extractant on extraction

As can be seen from example 5 in Table 1 and examples 7, 8 and 9 in Table 2, the particle size of the material to be crushed has a certain influence on the extraction. Too large or too small a particle size is not conducive to extraction. Therefore, the material crushing particle size is preferably 24-80 meshes, preferably 50-65 meshes, and preferably 50 meshes in consideration of energy consumption. As can be seen from examples 7, 10 and 11 in table 2, the extractant has a certain influence on the extraction, and the liquid butane, the liquid propane and the liquid natural gas have little influence on the total extraction rate of CBD, but have a large influence on the CBD content in the extract (93.8%, 94.7% and 95.2%, respectively), and the CBD content in the first extraction is 20.0%, 23.7% and 26.8%, respectively, which indicates that the extractant has selectivity on CBD, the liquid natural gas is superior to the liquid propane, and the liquid propane is superior to the liquid butane in the application process of the subcritical technology in the extraction of industrial hemp. Therefore, the extractant can be selected from liquid butane, liquid propane, liquid natural gas or mixtures thereof, preferably liquid propane or liquid natural gas, preferably liquid natural gas.

Example 12.

Dissolving 1Kg of extract obtained in example 11 in 10Kg of ethanol, stirring for dissolution, filtering the solution through a filter cloth, pumping the solution into a heat-preservation winterization tank, slowly cooling to-80 to-70 ℃ while stirring, and maintaining the temperature for 6 hours. And then filtering the low-temperature solution by using a low-temperature diatomite filter, concentrating the filtrate by using an alcohol recovery device, recovering alcohol, pumping the concentrated solution into a vacuum tank for heat treatment while the concentrated solution is hot, carrying out reduced pressure distillation by gradient temperature rise and gradient reduced pressure, gradually raising the temperature to 150-160 ℃, and gradually reducing the pressure to 0.01-0.10 mbar until no fraction is evaporated. And naturally cooling to 100-120 ℃, weighing the residue, sampling and analyzing, and then carrying out short-range molecular distillation. The pressure is lower than 0.02 mbar, the heating temperature is 160 ℃, the cooling temperature is 90 ℃, and the cold trap is used for placing liquid nitrogen, and the collected light components (newly added) enter the next working procedure.

Example 13.

Dissolving 1Kg of extract obtained in example 11 in 10Kg of ethanol, stirring for dissolution, filtering the solution through a filter cloth, pumping the solution into a heat-preservation winterization tank, slowly cooling to-70 to-60 ℃ while stirring, and maintaining the temperature for 6 hours. Then, the low-temperature solution is filtered by a low-temperature diatomite filter, and the filtrate is concentrated by an alcohol recovery device to recover alcohol. The concentrate was subjected to subsequent heat treatment and short path molecular distillation as in example 12, with the parameters unchanged.

Example 14.

Dissolving 1Kg of extract obtained in example 11 in 10Kg of ethanol, stirring for dissolution, filtering the solution through a filter cloth, pumping the solution into a heat-preservation winterization tank, slowly cooling to-60 to-50 ℃ while stirring, and maintaining the temperature for 6 hours. Then, the low-temperature solution is filtered by a low-temperature diatomite filter, and the filtrate is concentrated by an alcohol recovery device to recover alcohol. The concentrate was subjected to subsequent heat treatment and short path molecular distillation as in example 12, with the parameters unchanged.

Example 15.

Dissolving 1Kg of the extract obtained in example 11 in 10Kg of ethanol, stirring for dissolution, filtering the solution through a filter cloth, pumping the solution into a heat-preservation winterization tank, slowly cooling to-50 to-40 ℃ while stirring, and maintaining the temperature for 12 to 15 hours (overnight treatment). Then, the low-temperature solution is filtered by a low-temperature diatomite filter, and the filtrate is concentrated by an alcohol recovery device to recover alcohol. The concentrate was subjected to subsequent heat treatment and short path molecular distillation as in example 12, with the parameters unchanged.

Example 16.

Dissolving 1Kg of extract obtained in example 11 in 8Kg of ethanol, stirring for dissolution, filtering the solution through a filter cloth, pumping the solution into a heat-preservation winterization tank, slowly cooling to-60 to-50 ℃ while stirring, and maintaining the temperature for 6 hours. Because the solution is thick, a centrifuge is selected for centrifugation, and the filtrate is concentrated by an alcohol recovery device and then the alcohol is recovered. The concentrate was subjected to subsequent heat treatment and short path molecular distillation as in example 12, with the parameters unchanged.

TABLE 3 comparison of results obtained for different winterization conditions

As can be seen from examples 12, 13 and 14 in Table 3, the winterization temperature can meet the technical requirements within the range of-80 to-50 ℃ under the conditions of 10 times of solvent dosage and the same winterization time on the scale of 1 Kg. When the winterization temperature is increased to-50 to-40 ℃ (example 15), the winterization time is not enough for 6h, and after heat treatment and short-distance molecular distillation, the obtained light components are turbid, which indicates that waxy substances, colloid substances and macromolecular fatty acid ester substances are not completely removed, the winterization time needs to be prolonged to 12 to 15h, and even so, the CBD enrichment rate is not as good as that of examples 12 to 15(-80 to-50 ℃). If the amount of the solvent is reduced (example 16), the solvent becomes thicker after winterization, filtration is difficult, only a centrifuge can be selected for centrifugal treatment, and the theoretical CBD yield is generally lower than that of other winterization conditions because a part of CBD is wrapped in the precipitate. Therefore, the winterization condition is 8-10 times of solvent, the temperature is-80 to-40 ℃, and the time is 6-15 hours; preferably, 10 times of solvent is used, and the temperature is-70 to-50 ℃ and 6 hours; preferably 10 times of solvent, 60 ℃ below zero to 50 ℃ below zero, and 6 hours.

Example 17.

In a crystallization tank, 50g of the light fraction obtained in example 14 are dissolved in 300g of n-heptane, the solution is cooled to-20 ℃ and seed crystals of CBD are added and the temperature is maintained for 4 to 24 hours. After filtration, a yellow solid was collected.

Example 18.

In a crystallization tank, 50g of the light fraction obtained in example 14 are dissolved in 300g of n-heptane, the solution is cooled to-5 ℃ and seed crystals of CBD are added and the temperature is maintained for 4 to 24 hours. After filtration, a yellow solid was collected.

Example 19.

In a crystallization tank, 50g of the light fraction obtained in example 14 are dissolved in 300g of n-hexane, the solution is cooled to-20 ℃ and CBD seed crystals are added and the temperature is maintained for 4 to 24 hours. After filtration, a yellow solid was collected.

Example 20.

In a crystallization tank, 50g of the light fraction obtained in example 14 are dissolved in 150g of n-heptane, the solution is cooled to-20 ℃ and seed crystals of CBD are added and the temperature is maintained for 4 to 24 hours. After filtration, a yellow solid was collected.

Example 21.

In a crystallization tank, 50g of the light fraction obtained in example 14 are dissolved in 200g of n-heptane, the solution is cooled to-40 ℃ and seed crystals of CBD are added and the temperature is maintained for 4 to 24 hours. After filtration, a yellow solid was collected.

TABLE 4 influence of solvent type, volume, temperature and time on crystallization

As shown in examples 17 and 18 in Table 4, the temperature has a large influence on the crystallization, and the low temperature is more favorable for the formation of crystals; as shown in examples 17 and 19, the solvent strongly affected the crystallization, and n-hexane required a lower temperature than n-heptane, and even so, the yield was much lower than n-heptane (32.2% vs 67.4%); as shown in examples 17, 20 and 21, the amount of solvent used has an effect on the crystallization, the amount of solvent is small, the yield of solids and the theoretical yield of CBD are both improved, but the purity is reduced significantly (94.5% vs 90.0% vs 93.4%). Therefore, the crystallization solvent is n-hexane or n-heptane, the dosage of the solvent is 3-6 times of the mass, the crystallization temperature is-40 to-5 ℃, and the crystallization time is 4-24 hours; preferably, the solvent is n-heptane, the using amount of the solvent is 3-4 times of the mass of the solvent, the crystallization temperature is-20 ℃, and the crystallization time is 8-12 hours; preferably 4 times the amount of solvent and 12 hours of crystallization time.

Example 22.

The yellow solid obtained in example 17-21 was mixed thoroughly, 20g was dissolved in 60g of n-heptane, heated to 50 ℃ and the solid was completely dissolved, 1.0g of activated carbon was added, stirring was continued for 2 hours, the mixture was filtered through celite while hot, and the filtrate was cooled naturally to room temperature and then crystallized at 0 ± 5 ℃. After 8h, filter and collect the white solid.

Example 23.

The yellow solid obtained in the example 17-21 is fully mixed, 20g of the mixture is dissolved in 60g of n-heptane, the mixture is heated to 50 ℃, the solid is completely dissolved, 1.0g of activated clay is added, the mixture is continuously stirred for 2 hours, the mixture is filtered by diatomite while the mixture is hot, the filtrate is naturally cooled to the room temperature, and the mixture is cooled to 0 +/-5 ℃ for crystallization. After 8h, filter and collect the white solid.

Example 24.

The yellow solid obtained in the example 17-21 is fully mixed, 20g of the mixture is dissolved in 60g of n-heptane, the mixture is heated to 50 ℃, the solid is completely dissolved, 0.5g of activated carbon and 0.5g of activated clay are added, the mixture is continuously stirred for 2 hours, the mixture is filtered by diatomite while the mixture is hot, the filtrate is naturally cooled to the room temperature, and the mixture is cooled to 0 +/-5 ℃ for crystallization. After 8h, filter and collect the white solid.

Example 25.

The yellow solid obtained in the example 17-21 is fully mixed, 20g of the mixture is dissolved in 40g of n-heptane, the mixture is heated to 50 ℃, the solid is completely dissolved, 0.5g of activated carbon and 0.5g of activated clay are added, the mixture is continuously stirred for 2 hours, the mixture is filtered by diatomite while the mixture is hot, the filtrate is naturally cooled to the room temperature, and the mixture is cooled to 0 +/-5 ℃ for crystallization. After 8h, filter and collect the white solid.

TABLE 5 Effect of bleaching by different bleaching conditions

Examples

Mass of filter cake

Yield of solids

Content of CBD

THC content

Theoretical CBD yield

Traits

Example 22

17.3g

86.3％

98.5％

0.19％

90.9％

White solid

Example 23

17.1g

85.7％

98.3％

0.22％

90.1％

White solid

Example 24

16.9g

84.7％

99.1％

0.10％

89.8％

White solid

Example 25

17.9g

89.3％

98.3％

0.28％

93.9％

White solid

As shown in Table 5, both the activated carbon and the activated clay can be effectively decolorized, the purity of the CBD is further improved, after two times of crystallization, the content of the CBD is improved to more than 98 percent, the content of the THC is reduced to 0.3 percent, and the requirements of regulations are met.

Example 26.

15.0g of the white solid obtained in example 24 are dissolved in 30g of n-heptane, dissolved by heating to 50 ℃ and then cooled to room temperature, at a rate of 5 ℃ per hour, to 5 ℃ and stirred for a further 2 hours. 13.7g of white solid was collected by filtration, yield 91.3%. The content is more than 98.0%, the purity is more than 99.8%, the single impurity content is less than 0.1%, the total impurity content is less than or equal to 0.2%, and THC is not detected.

Claims

1. A method for extracting high-purity cannabidiol from industrial cannabis sativa is characterized by comprising the following steps:

s1, pretreatment of raw materials

The industrial hemp is subjected to sorting, drying in the shade, crushing and water spraying granulation;

s2, subcritical extraction

Carrying out subcritical extraction on the particles by using an extraction solvent, evaporating the obtained extraction liquid containing the extraction solvent to obtain an extract, and raising the temperature to 35-55 ℃ in the subcritical extraction for 20-30 min;

s3, winterization

Fully dissolving the extract in a winterization solvent, and performing primary filtration, heat preservation winterization, secondary filtration and concentration to obtain a concentrated solution, wherein the heat preservation winterization is performed by slowly cooling to-70 to-50 ℃ under stirring, and the heat preservation is performed for 6 to 15 hours;

s4, heat treatment

Placing the concentrated solution obtained in the step S3 into a reaction kettle for reduced pressure distillation, gradually reducing the pressure to be below 0.01-0.20 mbar, gradually increasing the temperature to be 130-150 ℃ until no fraction is evaporated, naturally cooling to be 100-120 ℃, and transferring to the next step;

s5, short path molecular distillation

Performing short-path molecular distillation on the residue obtained in the step S4 after distillation, wherein the distillation temperature is 150-180 ℃, the cooling temperature is 70-90 ℃, the vacuum degree is 0.001-0.05 mbar, and the collected light components enter the next step;

s6, crystallization purification

Dissolving the light components collected after the short-path molecular distillation in n-heptane in a crystallization tank, wherein the mass ratio of the distillate to the n-heptane is 1: 3-6, cooling the solution to-20-5 ℃, adding a CBD seed crystal, maintaining the temperature for 4-24 hours for crystallization, filtering, collecting yellow solid to obtain a CBD crude product with the purity of 90-95%, dissolving the CBD crude product in 3 times of mass of n-heptane, adding 5% of active carbon and 5% of activated clay, heating to 40-60 ℃, stirring for 0.5-4 hours, naturally cooling, cooling and crystallizing, filtering, collecting white solid to obtain a CBD product with the purity of 98-99%, wherein the content of tetrahydrocannabinol is less than or equal to 0.3%, dissolving the white solid in 2 times of mass of n-heptane again, heating to 40-50 ℃ for dissolution, slowly cooling to 0-5 ℃ and maintaining for 2-4 hours, filtering, and collecting the white solid to obtain a CBD refined product with the purity of more than 99.8%.

2. The method of claim 1, wherein the extraction process produces a THC-rich production waste that is treated in a regulatory manner by: treating the production waste rich in THC with an oxidant; the oxidant is hydrogen peroxide, sodium hypochlorite aqueous solution, tert-butyl hydroperoxide, potassium permanganate solution or ozone.

3. The method according to claim 1, wherein the crushing mesh number in the S1 is 24-80 meshes; and (3) water spraying granulation is carried out to ensure that the water content is 4-8%, the particle diameter is 1-2 cm, and the length is 2-4 cm.

4. The method of claim 1, wherein the extraction solvent in S2 is liquid butane, liquid propane or liquid natural gas; the extract was then evaporated under reduced pressure to recover the extraction solvent, and the remaining extract was taken to the next step.

5. The method according to claim 1, wherein the winterization solvent in S3 is 95% ethanol, and the mass ratio of the extract to the winterization solvent is 1: (8-10).

6. The method of any one of claims 1-5, wherein the high purity cannabidiol is obtained in a total yield of 0.95%, a purity greater than 99.8%, less than 0.1% single heteroatoms, no more than 0.2% total heteroatoms, and no detectable tetrahydrocannabinol.

7. The method according to any one of claims 1 to 5, wherein the industrial cannabis is any plant raw material or semi-finished product containing cannabidiol components, including industrial cannabis flowers, leaves, hemp seed hulls.