CN110683938A - Preparation method of cannabidiol - Google Patents
Preparation method of cannabidiol Download PDFInfo
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- CN110683938A CN110683938A CN201910798560.9A CN201910798560A CN110683938A CN 110683938 A CN110683938 A CN 110683938A CN 201910798560 A CN201910798560 A CN 201910798560A CN 110683938 A CN110683938 A CN 110683938A
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Abstract
The invention provides a preparation method of cannabidiol, which comprises the steps of providing a plant source containing cannabidiol as a raw material, crushing the raw material, mixing the crushed raw material, water and biological enzyme to carry out enzymolysis reaction, and filtering to obtain enzymolysis liquid and enzymolysis residues; mixing the enzymolysis residues with an extraction solvent, and performing flash extraction at normal temperature, wherein the mass ratio of the enzymolysis residues to the extraction solvent is 1: 18-1: 20, carrying out solid-liquid separation on the extraction liquid obtained after flash extraction, and collecting the liquid phase to obtain a cannabidiol extracting solution; separating cannabidiol extract by alumina column chromatography to obtain eluent; treating the eluent with an organic nanofiltration membrane to obtain a membrane-passing solution; and crystallizing the membrane solution to obtain the cannabidiol. The method adopts a method combining biological enzymolysis and flash extraction to replace the traditional preparation method, effectively improves the extraction rate of cannabidiol, and further obtains a high-purity CBD product by utilizing a separation mode combining alumina column chromatography and an organic nanofiltration membrane, wherein the purity of CBD can reach more than 99%.
Description
Technical Field
The invention relates to the technical field of chemical industry, in particular to a preparation method of cannabidiol.
Background
Industrial hemp refers to a cannabis plant with a tetrahydrocannabinol content of less than 0.3% and its extract product, and has wide applications in various fields such as biopharmaceuticals, food additives, living goods, textile fibers, composite materials, and the like. The main cannabinol compounds in the hemp plant include Tetrahydrocannabinol (THC), Cannabinol (CBN), Cannabidiol (CBD), Cannabigerol (CBG), cannabichromene (CBC) and the like, wherein the former three compounds account for 90% of the cannabinol compounds.
Tetrahydrocannabinol (THC) in cannabis is the major psychoactive chemical component in cannabis, can produce excitement and addiction, and is the main cause of cannabis being identified as a drug. Cannabidiol (CBD) is a non-addictive component of cannabis and has a high medicinal value, thus drawing a great deal of attention. The research shows that the cannabidiol has good medical efficacy in aspects of epilepsy resistance, antipsychotic, depression resistance, pain relief and the like. Industrial research finds that the development of industrial hemp industry is highly dependent on the continuous embodiment of relevant values of Cannabidiol (CBD), so that the upgrading of CBD purification technology plays an important role in the development of industry.
However, the prior art, such as macroporous resin extraction method, silica gel column chromatography adsorption method, etc., or has the problem of low extraction purity; or the operation process is complicated and the process conditions are not easy to control; or the yield of the cannabidiol is low and the product quality is not good. In addition, in the prior art, organic solvents are used in large quantities for common solvent treatment, and the method is not beneficial to environmental protection and large-scale industrial production.
Therefore, there is a need for a new method for preparing cannabidiol, which solves the above problems in the prior art.
It is noted that the information disclosed in the foregoing background section is only for enhancement of background understanding of the invention and therefore it may contain information that does not constitute prior art that is already known to a person of ordinary skill in the art.
Disclosure of Invention
One of the main objects of the present invention is to overcome at least one of the above-mentioned drawbacks of the prior art, and to provide a method for preparing cannabidiol, which effectively increases the extraction rate of Cannabidiol (CBD) by using a combination of bio-enzymatic hydrolysis and flash extraction instead of the conventional preparation method, and further obtains a high purity CBD product by using a separation method combining alumina column chromatography and organic Nanofiltration membrane (OSN), wherein the CBD purity can be up to 99% or more.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a method for preparing cannabidiol, which comprises the following steps: providing a plant source containing cannabidiol as a raw material, crushing, mixing the crushed raw material, water and biological enzyme for enzymolysis reaction, and filtering to obtain an enzymolysis solution and enzymolysis residues; mixing the enzymolysis residues with an extraction solvent, and performing flash extraction at normal temperature, wherein the mass ratio of the enzymolysis residues to the extraction solvent is 1: 18-1: 20, carrying out solid-liquid separation on the extraction liquid obtained after flash extraction, and collecting the liquid phase to obtain a cannabidiol extracting solution; separating cannabidiol extract by alumina column chromatography to obtain eluent; treating the eluent with an organic nanofiltration membrane to obtain a membrane-passing solution; and crystallizing the membrane solution to obtain the cannabidiol.
According to one embodiment of the invention, the biological enzyme is selected from one or more of pectinase, cellulase, papain, protease, and amylase.
According to one embodiment of the present invention, the mass ratio of the pulverized raw material to water is 1: 1-1: and 4, the mass ratio of the crushed raw materials to the biological enzyme is 1000: 1-1000: 5.
According to one embodiment of the present invention, the mesh number of the pulverized raw material is 40 to 100 mesh.
According to one embodiment of the invention, the method further comprises the steps of homogenizing the crushed raw materials at high pressure, and then adding biological enzyme for enzymolysis reaction; wherein the high-pressure homogenization is performed for 1-3 times, and the time for each homogenization is 10-30 min.
According to one embodiment of the invention, the temperature of the enzymolysis reaction is 45-60 ℃, and the time of the enzymolysis reaction is 1-3 h.
According to one embodiment of the invention, the extraction rotation speed of flash extraction is 10000-15000 r/min, the extraction times are 1-3 times, and the extraction time is 60-120 s each time.
According to one embodiment of the present invention, the extraction solvent is selected from one or more of ethanol, methanol and acetone, and the volume percentage concentration of the extraction solvent is 75% to 80%.
According to one embodiment of the present invention, the alumina column chromatography separation comprises: pumping the cannabidiol extracting solution into an alumina chromatographic column, and then carrying out primary elution by adopting an alkaline solvent with the volume percentage concentration of 20-35%, wherein the flow rate of the primary elution is 1-2 BV/h, and the elution amount of the primary elution is 2 BV-2.5 BV; carrying out secondary elution by adopting an organic solvent with the volume percentage concentration of 40-55%, wherein the flow rate of the secondary elution is 1-2 BV/h, and the elution amount of the secondary elution is 2 BV-2.5 BV; carrying out three times of elution by adopting an organic solvent with the volume percentage concentration of 80-90%, wherein the flow rate of the three times of elution is 1-2 BV/h, and the elution amount of the three times of elution is 2 BV-2.5 BV; wherein the alkaline solvent is selected from ethanol, methanol or acetone with the pH value of 9-10, the organic solvent is selected from ethanol, methanol or acetone, and the mass ratio of the cannabidiol extract to the alumina is 36: 1-40: 1.
according to one embodiment of the invention, the organic nanofiltration membrane treatment comprises: treating the eluent by a first organic nanofiltration membrane, and then treating by a second organic nanofiltration membrane to obtain a membrane-passing solution; wherein the molecular weight cut-off of the first organic nanofiltration membrane is 600 Da-900 Da, and the molecular weight cut-off of the second organic nanofiltration membrane is 200 Da-350 Da.
According to one embodiment of the invention, the membrane feeding pressure of the eluent entering the first organic nanofiltration membrane is 290-470 psi, and the membrane feeding pressure of the eluent entering the second organic nanofiltration membrane is 490-870 psi.
According to one embodiment of the invention, the crystallization process comprises: concentrating the membrane-passing solution to 15-30 degrees of Be to obtain an extract, adding a mixed solvent into the extract, and then carrying out crystallization treatment at-4-20 ℃ to obtain cannabidiol; wherein the volume ratio of the mixed solvent is (1-2): (1-3): (1-2) petroleum ether, ethyl acetate and n-hexane, wherein the mass ratio of the mixed solvent to the extract is (3-5): 1.
the invention also provides cannabidiol obtained by the preparation method.
According to the technical scheme, the preparation method of the cannabidiol has the advantages and positive effects that:
the method for preparing the cannabidiol effectively improves the content of the cannabidiol in the cannabidiol extracting solution by utilizing a method combining biological enzymolysis reaction and flash extraction, and further obtains a high-purity CBD product by utilizing a separation mode combining alumina column chromatography and an organic nanofiltration membrane (OSN), wherein the purity of the CBD can reach more than 99%. Compared with the existing column chromatography separation method, the method has the advantages of simpler process, lower cost, better separation effect and stable product quality, and is suitable for large-scale industrial production.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention.
Figure 1 shows a process flow diagram for the preparation of cannabidiol in accordance with one embodiment of the invention.
Detailed Description
The following presents various embodiments or examples in order to enable those skilled in the art to practice the invention with reference to the description herein. These are, of course, merely examples and are not intended to limit the invention. The endpoints of the ranges and any values disclosed in the present application are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to yield one or more new ranges of values, which ranges of values should be considered as specifically disclosed herein.
Figure 1 shows a process flow diagram for the preparation of cannabidiol in accordance with one embodiment of the invention. As shown in figure 1, the method for preparing cannabidiol mainly comprises enzymolysis reaction, flash extraction, alumina column chromatography, organic nanofiltration membrane treatment and crystallization treatment. Specifically, the method comprises the following steps:
(1) enzymolysis reaction
First, a plant source containing cannabidiol is provided as a raw material and pulverized. Wherein the plant source is a plant of the genus Cannabiaceae (Cannabinaceae) cannabis (Cananabis) containing cannabidiol.
And uniformly mixing the crushed raw materials, water and biological enzyme, and carrying out enzymolysis reaction. In some embodiments, the mesh size of the comminuted material is 40 mesh to 100 mesh to provide better mixing of the material with water and biological enzymes. In some embodiments, the mass ratio of the pulverized raw material to water is 1: 1-1: 4, preferably 1: 1.5-1: 2, the raw materials and water are mixed unevenly when the ratio is too low, waste is caused when the ratio is too high, the cost is high, and the filtering time is long. The mass ratio of the crushed raw materials to the biological enzyme is 1000: 1-1000: 5, preferably 1000: 2-1000: 4. the ratio of raw materials to biological enzyme is too low, the enzymolysis effect is poor, the raw materials and the biological enzyme are insufficient, the waste is too high, and the cost is increased.
In some embodiments, before the subjecting the pulverized raw material to the enzymatic hydrolysis reaction, the method further comprises subjecting the pulverized raw material to high-pressure homogenization to mix the raw material with water more uniformly. The high-pressure homogenizing is carried out by a high-pressure homogenizer, and the material in a suspension state can flow through a containing cavity (high-pressure homogenizing cavity) with a special internal structure at a high speed under the action of ultrahigh pressure (up to 60000psi), so that the material is subjected to a series of changes of physical, chemical, structural properties and the like, and the homogenizing effect is finally achieved. In some embodiments, the high-pressure homogenization is performed 1-3 times, and each time of homogenization is 10-30 min.
In some embodiments, the biological enzyme may be one or more of pectinase, cellulase, papain, protease, amylase. The temperature of the enzymolysis reaction is 45-60 ℃, preferably 48-50 ℃, and the time of the enzymolysis reaction is 1-3 h, preferably 1.5-2 h. Macromolecular substances such as protein, cellulose and the like in the raw materials are firstly subjected to enzymolysis and separation by biological enzyme, so that the extraction efficiency and the purity of the subsequent flash extraction are higher. And filtering the solution after the enzymolysis reaction to obtain enzymolysis liquid and enzymolysis residues, wherein the enzymolysis residues contain a large amount of CBD components and can be further subjected to flash extraction.
(2) Flash extraction
And further adding the enzymolysis residues obtained by filtering after the enzymolysis reaction into a flash extractor for flash extraction. The flash extractor is used for crushing soft and hard tissues of plants, mainly depends on high-speed mechanical shearing force and ultra-dynamic molecular permeability technology, and can crush the roots, stems, leaves, flowers, fruits and other materials of the plants into fine particles within a few seconds at room temperature in the presence of a solvent, so that the effective components can rapidly reach the internal and external balance of the tissues, and the extraction purpose can be achieved by filtering.
In some embodiments, the enzymolysis slag and the extraction solvent are mixed for flash extraction at normal temperature, and the mass ratio of the enzymolysis slag to the extraction solvent is 1: 18-1: 20, preferably 1: 18.5-1: 19; the extraction solvent comprises one or more of ethanol, methanol and acetone, and the volume percentage concentration of the extraction solvent is 75-80%. The extraction rotating speed of flash extraction is 10000-15000 r/min, the extraction times are 1-3 times, and the extraction time is 60-120 s each time. For example, flash extraction can be performed 3 times, each time for 60s, and after 1 time extraction, the extraction can be performed after 2 minutes of intermediate rest. Extracting for 3 times, and separating to obtain total filtrate, i.e. cannabidiol extractive solution.
By performing flash extraction under the above conditions, the effective components can be retained to the maximum extent without damage by heating, the solvent consumption is small, the extraction time is short, and the efficiency is high. The content of cannabidiol in the cannabidiol extracting solution obtained by the method combining enzymolysis and flash extraction is higher and can generally reach 45-55%.
(3) Alumina column chromatography separation
The cannabidiol extract obtained after flash extraction and filtration is further subjected to alumina column chromatographic separation. Alumina column chromatography refers to column chromatography separation using alumina as a stationary phase adsorbent, generally at high pH, alumina is more stable than silica gel without bonded functional groups, and finer particles can ensure higher extraction efficiency.
In some embodiments, the alumina column chromatographic separation of the present invention comprises:
firstly, directly pumping the obtained cannabidiol extracting solution into an alumina chromatographic column, wherein the mass ratio of the cannabidiol extracting solution to alumina is 36: 1-40: 1, preferably 38: 1-39: 1. after the solution enters the column, the solution is kept for about 1 hour to ensure that the effective substances are fully absorbed in the resin. Then, elution is carried out once by using a low-concentration alkaline solvent. Wherein the flow rate of one elution is 1-2 BV/h, and the elution amount of one elution is 2 BV-2.5 BV.
In some embodiments, the alkaline solvent is ethanol, methanol or acetone with a pH of about 9-10, which is generally prepared by sodium hydroxide, sodium carbonate, sodium hydrogen hydrochloride, calcium oxide, and the like. The volume percentage concentration of the alkaline solvent is generally about 20 to 35 percent. Most of the toxic components of Tetrahydrocannabis (THC) and a part of the impurities can be removed by first performing one elution with a low concentration of an alkaline solvent.
Then, secondary elution is carried out by using an organic solvent with a medium concentration. Wherein the flow rate of the secondary elution is 1-2 BV/h, and the elution amount of the secondary elution is 2 BV-2.5 BV. In some embodiments, the medium concentration of organic solvent is selected from ethanol, methanol, or acetone at a concentration of 40% to 55% by volume.
Thereafter, elution was performed three times using a high-concentration organic solvent. Wherein the flow rate of the third elution is 1-2 BV/h, and the elution amount of the second elution is 2 BV-2.5 BV. In some embodiments, the high concentration organic solvent is selected from ethanol, methanol, or acetone at a concentration of 80% to 90% by volume.
By adopting the graded gradient elution mode, residual THC can be effectively further removed, and the content of the CBD effective component is improved. The THC content in the eluent obtained after the chromatographic separation of the alumina column is less than 0.3 percent.
(4) Organic nanofiltration membrane treatment
And (4) further carrying out organic nanofiltration membrane treatment on the eluent obtained in the step (3) to obtain a membrane passing liquid. The organic nanofiltration membrane (OSN) treatment of the present invention refers to a membrane separation method for separating nanoparticles or macromolecular compounds having a molecular weight within a certain range from an organic solvent system under pressure driving.
In some embodiments, the organic nanofiltration membrane process comprises: the eluent is processed by a first organic nanofiltration membrane, wherein the molecular weight cut-off of the first organic nanofiltration membrane is 600 Da-900 Da, and the membrane feeding pressure can be 290 psi-470 psi, preferably 350 psi-450 psi. And then treating the mixture by a second organic nanofiltration membrane to obtain a membrane passing solution, wherein the molecular weight cut-off of the second organic nanofiltration membrane is 200 Da-350 Da, and the membrane feeding pressure can be 490-870 psi, preferably 550-770 psi.
Through the organic nanofiltration membrane treatment in the grading way, impurity components with different molecular weights in the eluent can be further and better separated, the aim of purifying CBD is achieved, meanwhile, the method is simple, the decoloring effect is also considered, and the production efficiency is greatly improved. One part of the membrane passing liquid obtained after the organic nanofiltration membrane treatment and separation can be dried to directly obtain a hemp full-spectrum oil product, and the other part can be crystallized through the following step (5) to further obtain high-purity cannabidiol.
(5) Crystallization treatment
And further carrying out crystallization treatment on the membrane passing solution obtained after the separation by the organic nanofiltration membrane. Specifically, the crystallization treatment comprises:
concentrating the membrane-passing solution to 15-30 degrees of Be to obtain an extract, adding a mixed solvent into the extract, and then carrying out crystallization treatment at-4-20 ℃ to obtain cannabidiol; wherein the volume ratio of the mixed solvent is (1-2): (1-3): (1-2) petroleum ether, ethyl acetate and n-hexane, wherein the mass ratio of the mixed solvent to the extract is (3-5): 1.
the inventor finds that the prepared mixed solvent is used for crystallizing the membrane solution at low temperature, and the CBD product meeting the requirements can be obtained through one-time crystallization. The obtained CBD product has snow white color, less solvent residue, no pesticide residue, stable product quality and CBD purity of more than 99 percent.
The invention will be further illustrated by the following examples, but is not to be construed as being limited thereto. Unless otherwise specified, all reagents used in the invention are analytically pure.
Example 1
(1) Enzymolysis reaction
Pulverizing 1000g of cannabis plant containing cannabidiol into 40 mesh powder with a pulverizer, and pulverizing with 4 times of water for 3 times with a high pressure homogenizer for 10min each time. Pouring the mixed solution after high-pressure homogenization into a reaction kettle, and adding the biological enzyme. Wherein the adding amount of the biological enzyme is 1g, and the biological enzyme comprises papain, amylase and cellulase in a mass ratio of 1:1: 1. After carrying out enzymolysis reaction for 1.5 hours at the temperature of 45 ℃, filtering the solution through 100-mesh filter cloth, and discarding enzymolysis liquid to obtain enzymolysis residues.
(2) Flash extraction
Adding the enzymolysis residues obtained in the step (1) into a flash extractor, and using 75% ethanol in volume percentage concentration as an extraction solvent, wherein the mass ratio of the enzymolysis residues to the extraction solvent is 1:18. The flash extraction speed is 10000r/min, and the extraction time is 3 minutes at normal temperature. The extraction is carried out for 3 times, each time for 1min, and each time after 2 min of rest. Mixing the filtrates obtained after 3 times of extraction to obtain total filtrate, namely extractive solution of cannabidiol (1500 g), wherein the content of CBD is 49.5%.
(3) Alumina column chromatography separation
Pumping the cannabidiol extract obtained in the step (2) into a 500g alumina chromatographic column directly, keeping the solution for 1 hour after the solution enters the column, firstly performing primary elution by using 1000ml of 25% ethanol solvent with pH of 9, then performing secondary elution by using 1000ml of 45% ethanol solvent, then performing tertiary elution by using 1000ml of 85% ethanol solvent, and then collecting 810g of high-concentration eluent, wherein the THC content in the eluent is 0.02%.
(4) Organic nanofiltration membrane treatment
And (4) carrying out organic nanofiltration membrane treatment on the eluent obtained in the step (3), wherein the organic membrane with the molecular weight cutoff is firstly passed through, the membrane feeding pressure is 350psi, after all the organic membranes are passed through, the obtained solution is further passed through the organic membrane with the molecular weight cutoff of 300, and the membrane feeding pressure is 600psi, so that the decoloration membrane passing solution is obtained.
(5) Crystallization treatment
Concentrating the membrane passing liquid obtained in the step (4) to 30 degrees Be, adding 300g of mixed solvent, and mixing, wherein the volume ratio of the mixed solvent is 1:1:1 petroleum ether, ethyl acetate and n-hexane. The mixed solution is crystallized for 12 hours at-10 ℃, and the obtained solution is filtered, washed and dried to obtain crystals. HPLC detection shows that the cannabidiol content is 99.1%.
Example 2
Cannabidiol was prepared in the same manner as in example 1, except that the temperature of the enzymatic hydrolysis in step (1) was 50 ℃ and the reaction time was 1.9 hours, and the CBD content of the resulting cannabidiol extract was 99.3%.
Example 3
Cannabidiol was prepared in the same manner as in example 1, except that in step (2) flash extraction was performed for 1min and only 1 time. Wherein the CBD content of the cannabidiol extract obtained in the step (2) is 46.2%.
Example 4
Cannabidiol was prepared in the same manner as in example 1, except that the extraction solvent in step (2) was 77% ethanol by volume, and the mass ratio of the enzymolysis residue to ethanol was 1: 18.5. Wherein the CBD content of the cannabidiol extract obtained in the step (2) is 52.5%.
Example 5
Cannabidiol was prepared in the same manner as in example 1, except that the pressure across the first organic nanofiltration membrane in step (4) was changed from 550PSI to 360PSI, and the pressure across the second organic nanofiltration membrane was 400 PSI. After the membrane passing liquid obtained by 700PSi is crystallized, the purity of the CBD product is 93.8%.
Comparative example 1
Cannabidiol was prepared in the same manner as in example 1, except that no high pressure homogenizer was used for homogenization in step (1) and the bio-enzyme was directly added. Wherein the CBD content in the cannabidiol extract obtained in the step (2) is 34.5%.
Comparative example 2
Cannabidiol was prepared in the same manner as in example 1, except that the temperature of the enzymatic hydrolysis in step (1) was 41 ℃ and the reaction time was 5 hours, wherein the CBD content of the cannabidiol extract from step (2) was 33.3%.
Comparative example 3
Cannabidiol was prepared in the same manner as in example 1, except that the extraction solvent in step (2) was 65% ethanol by volume, and the mass ratio of the enzymolysis residue to ethanol was 1: 14. Wherein the CBD content in the cannabidiol extracting solution obtained in the step (2) is 31.7%.
Comparative example 4
Cannabidiol was prepared in the same manner as in example 1, except that the alumina column in step (3) was isocratically eluted only once with 1000ml of 50% v/v ethanol solvent at pH 9, and the THC content of the eluate obtained after elution was 2.85%.
Comparative example 5
Cannabidiol was prepared in the same manner as in example 1, except that the pressure across the first organic nanofiltration membrane in step (4) was 480psi and the pressure across the second organic nanofiltration membrane was 400 psi. After the obtained membrane-passing liquid is crystallized, the purity of the CBD product is 84.5 percent.
Comparative example 6
Cannabidiol was prepared in the same manner as in example 1, except that, instead of using the alumina column in step (3) for separation, the cannabidiol extract obtained after flash extraction was directly subjected to the organic nanofiltration membrane separation in step (4), and after crystallization, the purity of the CBD product was 78.2%.
Comparative example 7
Cannabidiol was prepared in the same manner as in example 1, except that the crystallization in step (5) was carried out using 385g of acetone solvent without using a mixed solvent, and the purity of the resulting CBD product was 84.5%.
It should be noted by those skilled in the art that the described embodiments of the present invention are merely exemplary and that various other substitutions, alterations, and modifications may be made within the scope of the present invention. Accordingly, the present invention is not limited to the above-described embodiments, but is only limited by the claims.
Claims (13)
1. A method of preparing cannabidiol, comprising:
providing a plant source containing cannabidiol as a raw material, crushing, mixing the crushed raw material, water and biological enzyme for enzymolysis reaction, and filtering to obtain an enzymolysis solution and enzymolysis residues;
mixing the enzymolysis residues with an extraction solvent, and carrying out flash extraction at normal temperature, wherein the mass ratio of the enzymolysis residues to the extraction solvent is 1: 18-1: 20, carrying out solid-liquid separation on the extraction liquid obtained after the flash extraction, and collecting the liquid phase to obtain a cannabidiol extracting solution;
carrying out chromatographic separation on the cannabidiol extracting solution by using an alumina column to obtain an eluent;
treating the eluent with an organic nanofiltration membrane to obtain a membrane-passing solution; and
and crystallizing the membrane solution to obtain the cannabidiol.
2. The method of claim 1, wherein the bio-enzyme is selected from one or more of pectinase, cellulase, papain, protease, and amylase.
3. The production method according to claim 1, wherein the mass ratio of the pulverized raw material to water is 1: 1-1: and 4, the mass ratio of the crushed raw materials to the biological enzyme is 1000: 1-1000: 5.
4. The method according to claim 1, wherein the mesh size of the pulverized raw material is 40 to 100 mesh.
5. The preparation method according to claim 1, further comprising homogenizing the pulverized raw material under high pressure, and adding the biological enzyme to perform the enzymatic hydrolysis reaction; wherein the high-pressure homogenization is performed for 1-3 times, and the time for each homogenization is 10-30 min.
6. The preparation method according to claim 1, wherein the temperature of the enzymolysis reaction is 45-60 ℃, and the time of the enzymolysis reaction is 1-3 h.
7. The method according to claim 1, wherein the flash extraction has an extraction speed of 10000-15000 r/min, an extraction frequency of 1-3 times, and an extraction time of 60-120 s.
8. The method according to claim 1, wherein the extraction solvent is selected from one or more of ethanol, methanol and acetone, and the volume percentage concentration of the extraction solvent is 75-80%.
9. The method of claim 1, wherein the alumina column chromatography separation comprises:
pumping the cannabidiol extracting solution into an alumina chromatographic column, and then carrying out primary elution by adopting an alkaline solvent with the volume percentage concentration of 20-35%, wherein the flow rate of the primary elution is 1-2 BV/h, and the elution amount of the primary elution is 2 BV-2.5 BV;
carrying out secondary elution by adopting an organic solvent with the volume percentage concentration of 40-55%, wherein the flow rate of the secondary elution is 1-2 BV/h, and the elution amount of the secondary elution is 2 BV-2.5 BV;
carrying out three times of elution by adopting an organic solvent with the volume percentage concentration of 80-90%, wherein the flow rate of the three times of elution is 1-2 BV/h, and the elution amount of the three times of elution is 2 BV-2.5 BV;
wherein the alkaline solvent is selected from ethanol, methanol or acetone with the pH value of 9-10, the organic solvent is selected from ethanol, methanol or acetone, and the mass ratio of the cannabidiol extracting solution to the alumina is 36: 1-40: 1.
10. the preparation method of claim 1, wherein the organic nanofiltration membrane treatment comprises: treating the eluent by a first organic nanofiltration membrane, and then treating by a second organic nanofiltration membrane to obtain a membrane passing solution; the molecular weight cut-off of the first organic nanofiltration membrane is 600 Da-900 Da, and the molecular weight cut-off of the second organic nanofiltration membrane is 200 Da-350 Da.
11. The preparation method of claim 10, wherein the membrane feeding pressure of the eluent entering the first organic nanofiltration membrane is 290-470 psi, and the membrane feeding pressure of the eluent entering the second organic nanofiltration membrane is 490-870 psi.
12. The method according to claim 1, wherein the crystallization treatment comprises: concentrating the membrane passing liquid to 15-30 degrees of Be to obtain an extract, adding a mixed solvent into the extract, and then carrying out crystallization treatment at-4-20 ℃ to obtain the cannabidiol; wherein the volume ratio of the mixed solvent is (1-2): (1-3): (1-2) petroleum ether, ethyl acetate and n-hexane, wherein the mass ratio of the mixed solvent to the extract is (3-5): 1.
13. cannabidiol obtained by the preparation method of any one of claims 1 to 12.
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