CN110304994A - A method of extracting high-purity cannabidiol from industrial hemp - Google Patents
A method of extracting high-purity cannabidiol from industrial hemp Download PDFInfo
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- CN110304994A CN110304994A CN201910585027.4A CN201910585027A CN110304994A CN 110304994 A CN110304994 A CN 110304994A CN 201910585027 A CN201910585027 A CN 201910585027A CN 110304994 A CN110304994 A CN 110304994A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D11/00—Solvent extraction
- B01D11/02—Solvent extraction of solids
- B01D11/0203—Solvent extraction of solids with a supercritical fluid
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D11/00—Solvent extraction
- B01D11/02—Solvent extraction of solids
- B01D11/0288—Applications, solvents
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/0004—Crystallisation cooling by heat exchange
- B01D9/0013—Crystallisation cooling by heat exchange by indirect heat exchange
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/72—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by liquid-liquid treatment
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/74—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by distillation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/84—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by crystallisation
Abstract
The method that the invention discloses a kind of to extract high-purity cannabidiol from industrial hemp.This method includes pretreatment, subcritical abstraction, winterization, heat treatment, short-range molecular distillation and crystal refining of raw material etc..THC content meets relevant laws and regulations in obtained CBD product, and CBD content is greater than 98.0%, and purity reaches 99.8% or more, and list is miscellaneous less than 0.1%, total miscellaneous less than 0.2%, and THC is not detected.Compared with existing extracting method, the method for the present invention is energy-efficient, environmentally protective, and product purity is high.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to one kind extraction purification from industrial hemp floral leaf, hemp seed and husk
The method of cannabidiol.
Technical background
Industrial hemp (Cananbis Sativa L.) also known as Chinese fiber crops, fire fiber crops, jute, are a kind of annual herb plants,
Belong to Cannabaceae, Cannabis.Hemp plantation is with a long history, closely related to the life of the mankind for a long time, not only mentions for the mankind
Fiber, grease have been supplied, has also been made that tremendous contribution for human health.Archaeology personnel are being located at one of Xinjiang, China Turfan
Cannabis resin before having found 2700 in cave, this is the most ancient evidence that the mankind so far use hemp.
Main active is cannabinoids substance in hemp, these phenolic substancess are divided into the phenol with psychotropic activity again
Substance, such as tetrahydrocannabinol (THC) and listless active phenolic substances, such as cannabidiol (CBD).Currently, clinically just
The drug from hemp used have Marinol (THC),(THC/CBD), Epidiolex (CBD) oral solution,
Cannabinoids structure of modification object Nabilone etc..In addition, using CBD as the medicine in clinical trial of main active
Object reaches as many as tens of kinds.In America and Europe, CBD and the cannabis oil rich in CBD have been widely used for drug, health care product, makeup at present
Product and food etc., wide market.
The extraction of cannabinoids substance mainly has solvent extraction, supercritical CO at present2Fluids extraction and sub-critical flow
Three kinds of body extraction.Purification process is column chromatography, and only chromatographic stuffing is different.
104277917 A of CN announcement opened it is a kind of from industrial hemp extract the method containing cannabidiol resinon and
Its extract equipment.After extracting cannabis extract using solvent extraction, further obtained by column chromatographic isolation and purification method
Industrial hemp oil rich in CBD, master operation include screening, baking, extraction, column chromatography etc..
Application publication number is a kind of method for separating cannabidiol of the patent application publication of CN10967865 A.The party
Existing Cannador is dissolved in the in the mixed solvent of n-hexane and ethyl acetate by method, and KOH aqueous solution extraction is added, quiet
After setting layering, respectively by containing CBD organic phase and water phase be spin-dried for after obtain solid, wash, obtain accumulation rate be 80%,
The CBD that purity is 84~90%.
Application publication number discloses one kind for the patent application of CN109646992 and extracts cannabidiol from industrial hemp
The method of enriched substance.After this method crushes hemp floral leaf, extracted using buck, then obtain sediment after adjusting acid.Gained is sunk
Starch is extracted using organic solvent, and it is 41.3~43.2% that cannabidiol content is finally obtained after concentration, tetrahydrocannabinol content
For 1.41~1.52% enriched substance.
Application publication number is that the patent application of CN109627148 discloses a kind of preparation method of cannabidiol.This method
Smashed marihuana is extracted using eutectic solvent, obtained crude extract is separated through resin.Utilize hemp obtained by this method
The diphenol rate of recovery is 81.46%, purity 28.93%.
Application publication number be 109369344 A of CN patent disclose one kind from industrial hemp plant separation and Extraction it is big
The method of numb diphenol.This method is crushed and is impregnated with 95% ethanol/water solution to industrial hemp stem, leaf and seed naturally dry, is surpassed
Sound heat mentions, and gained crude product is suspended in water, with petroleum ether extraction, is successively carried out with normal phase column and reversed-phase column after extract concentration
It isolates and purifies.The purity of final gained CBD is 92~98%.
Application publication number is that the patent of CN 109232191 A discloses cannabidiol in a kind of extraction industrial hemp leaf
Method.This method takes industrial hemp blade, drying and crushing, after cell wall clastic enzyme cellulase and pectin enzyme mixation is added,
Then n-hexane stirring extraction is added in hydrolysis；It is rotated extraction supernatant to obtain grease；First is added in grease
Alcohol, low-temperature centrifugation obtain supernatant supernatant activity carbon decoloring is filtered resulting filtrate and rotated again after decolorations；So
It is added in revolving product after chloroform dissolution and is filtered by organic film film afterwards, can be obtained two phenol solution of industrial hemp.This method
Made cannabidiol solution is used for chromatography, does not refer to the purity of obtained cannabidiol and the content of tetrahydrocannabinol.
The patent of 109053388 A of application publication number CN discloses a kind of method for extracting cannabidiol.Hemp is planted
The floral leaf of strain is dried, then grinds into coarse powder, is carried out in opposite directions both in countercurrent leaching device with ethyl alcohol
Countercurrent leaching makes solvent that the effective component in coarse powder is leached extracting solution out；By extracting solution heating under reduced pressure, extracting solution is vapored away
In extra ethyl alcohol, obtain the concentrate of cannabidiol；After pure water dilution is added in the concentrate of cannabidiol, using layer
It analyses column and carries out gradient elution, collect target eluent；Merge target eluent, is concentrated under reduced pressure in 50~70 DEG C, obtains hemp two
The secondary concentration liquid of phenol；The ethyl alcohol supersaturated solution of 90%w/w is added in the secondary concentration liquid of cannabidiol, is crystallized
Up to cannabidiol product after being dried after object with pure water.
It is net that the patent of 108998248 A of application publication number CN discloses a kind of industrial hemp floral leaf rich in cannabidiol
Oily preparation method.It is by the floral leaf drying of industrial hemp, crushes, obtains cannabigerol, impregnate cannabigerol with edible oil and obtain hemp
Impregnate oil, by hemp impregnate oil 20~80 DEG C at a temperature of, using ultrasonic wave extraction instrument carry out assisted extraction extracted
Oil；Extract oil is extracted with edible ethanol again, obtains alcohol extraction liquid；Alcohol extraction liquid is put into rotary evaporator, is concentrated to give
To hemp floral leaf absolute oil.
Application publication number is that 108314608 A of CN discloses a kind of extraction separation method of cannabidiol.This method is adopted
After alcohol extracting, using the water solubility of alkaline solution enhancing cannabidiol, with organic solvent extracting and enriching cannabidiol, through poly-
Amide resin column, neutral alumina and bonded silica gel column purification enrichment, crystallization obtain the cannabidiol of high-purity.
Application publication number is that the patent of 107898826 A of CN discloses a kind of preparation of numb medicinal extract of the fire containing cannabidiol
Method.Mature industrial hemp fructus cannabis is taken, drying, removal of impurities are spare after crushing；It is carried out with ethyl alcohol to fructus cannabis material is crushed
It extracts, concentration of alcohol is 95%-100% (V/V), solid-liquid ratio 1:5-1:20；Leaching liquor is filtered out, is work after reduced pressure
Sparetime university's fiber crops Fructus Cannabis extract；Resulting Fructus Cannabis extract is re-dissolved in ethyl alcohol, and carries out low temperature winterization processing；It utilizes
Centrifuge or filtering technique, the suspension after winterization is handled are centrifuged；Using active carbon, to the resulting supernatant of centrifugation
Liquid carries out decolorization and filters；Treated filtrate will be filtered and carry out rotary evaporation processing to get rich in cannabidiol
Fiery fiber crops medicinal extract.The recovery rate of the numb medicinal extract of the fire prepared with the method is 3.5%-4.8%, and the content of cannabidiol is 18.28-
25.0%.
Application publication number is that the patent of 106831353 A of CN discloses a kind of side that cannabidiol is extracted from hemp
Method.This method crushes the extract part of hemp, drying obtains medicinal powder；By medicinal powder alcohol extracting-water precipitating, the precipitating of acquisition
Column chromatography is carried out after alcohol is molten；Concentrate eluant is added ethyl alcohol supersaturation dissolution, obtains crystal；Purified water or ethanol washing obtain
To first product；First product is mixed with purified water, it is dry to get CBD product.
208500803 U of patent CN discloses a kind of Preparation equipment for cannabidiol.The equipment includes floral leaf powder
Broken drying device, supercritical extraction unit, continuous filter unit, chromatographic purifying device and drying crystalline device；It is wherein overcritical
Extraction equipment is extracted using supercritical carbon dioxide liquid, includes lysing chamber, homogenizer and filtering in continuous filter unit
Primary filter membrane and supermicro filtration membrane are arranged in filter chamber for chamber, chromatograph setting in filter device the by concentration weight dissolving device connection
One chromatographic column and the second chromatographic column.The equipment will be obtained by extraction cannabidiol medicinal extract and dissolve and carry out two-stage film process, filter out
Granule foreign, pigment and colloid；Then go out big molecular impurity, second of chromatography molecular weight by chromatography sub-argument for the first time
Similar impurity.Obtaining cannabidiol purity may be up to 95%.
107227198 A of application publication number CN discloses the cannabis leaf oil extracting method of a kind of high extraction and its big
The method of fried dough twist leaf oil.This method is by the flower of hemp and leaf crushed after being dried, then is ground in the ball mill to destroy cell
Wall dries the powder after grinding again.It is finally extracted using supercritical carbon dioxide, obtains cannabis leaf oil.It utilizes
Cannabis leaf oil made from this method by weight, including cannabidiol 25-35%, unsaturated fatty acid 50-60%, terpene
Compound 8-10%.
107011125 A of application publication number CN discloses a kind of method for being enriched with cannabidiol.By hemp floral leaf 120
It is 0.5~4 hour dry under the conditions of DEG C, 50 mesh or more are crushed to, carbon dioxide is super under conditions of 30~55 DEG C, 13~30MPa
Critical extraction 1~9 hour recycles carbon dioxide, obtains hemp floral leaf primary extract；By hemp floral leaf primary extract be dissolved in ethyl alcohol or
In methanol, fine filtering removes impurity, and solvent evaporated is spare；It is packed into the filler pre-processed in chromatographic column, with wet process or does
Method loading, applied sample amount are 3~15wt%；Appointed in one of water, methanol, ethyl alcohol, n-butanol, acetone and chloroform or they
The mixed liquor for anticipating several carries out gradient elution or isocratic elution；Collect the elution section time rich in cannabidiol.
Patent CN105505565 and 105505565 A of patent CN equally use supercritical CO2Abstraction technique is big from industry
Industrial hemp oil is extracted in fiber crops.
Patent CN105535111A discloses a kind of side for extracting from industrial hemp floral leaf and being rich in cannabidiol medicinal extract
Method.The preparation method will crush after floral leaf dry heat treatment first, using ethyl alcohol as entrainer, be extracted using subcritical butane,
Extraction medicinal extract is dissolved in progress low temperature winterization processing in ethyl alcohol, is decolourized after centrifugation or filtering using active carbon, most afterwards through rotating
The numb medicinal extract of fire rich in CBD is obtained after evaporation of solvent.The recovery rate of the numb medicinal extract of fire prepared with the method is 3.0~
The content of 5.0%, CBD are 18.0~25.0%.
In hemp other than CBD, also contain psychoactive compositions THC, in addition to Paraguay, Canada and U.S. etc. are few
Number country is outer, and THC belongs to drugs in other areas of the whole world, the supervision by drug law enforcement department, various countries.In China, hemp phase
It closes THC content in semi-finished product or product to be necessarily less than or just calculate qualification equal to 0.3%, therefore, not solved using the above method
The exceeded problem of THC content.
Patent application CN108929201A discloses a kind of method that Subcritical Water Extraction technology extracts cannabidiol.It should
Method using Subcritical Water Extraction technology to drying, grind after hemp plant carry out Subcritical Water Extraction, by extract liquor
It is diluted after concentrating and impurity removing, then gradient elution is carried out by chromatographic column, the cannabidiol after the concentration of target eluent, crystallization is produced
Product.
Subcritical Water Extraction technology is more environmentally protective really without using organic solvent, but subcritical water is critical
Temperature is 374 DEG C, critical pressure 21.7MPa.It is produced using the technology, extraction temperature reaches 100~374 DEG C, extraction
Pressurization reaches 15~30MPa.No clear superiority compared with conventional use of subcritical abstraction agent butane.
Subcritical abstraction technology solvent for use is mainly butane and propane, low boiling point and nontoxic, residual is asked without having to worry about molten
Topic；Extraction process is under conditions of secret, low temperature and anaerobic, avoids the oxidation deterioration of material, and low temperature to extract
Impurity content reduces, and simplifies subsequent refining procedure；Compared with supercritical extraction technique, subcritical abstraction technology device therefor
Structure is simple, and operating pressure is low, usually only needs 0.3~0.7 megapascal, and the operating pressure of supercritical extracting equipment is usually super
Cross 23.0 megapascal.So subcritical abstraction technology is readily applied to industrialized production.With solvent extraction ratio, organic solvent
Dosage is less, and solvent loss is also minimum, since subcritical abstraction technology is mainly in the extraction of liposoluble substance, utilizes this
The extract polar impurity of technology production is less, simplifies subsequent machining technology.With apparent technical advantage.
Molecule short distance, which is steamed, is different from Conventional espresso by boiling-point difference separation principle, but flat by different material molecular motion
The difference of equal free path realizes separation.Its distillation process works as liquid mixture, under some specific pressure condition, along heating
Plate is flowed and is heated, and light, weight molecule can escape liquid level and enter gas phase, since light, weight molecule free path is different,
The molecule of different material is different from moving distance after liquid level evolution, if (the disengagement area condensation of one piece of cold plate can be appropriately set
Identity distance is from generally less than 100MM), then light molecule reaches cold plate and is condensed discharge, and cold plate is not achieved along mixing in weight molecule
Liquid discharge.Achieve the purpose that substance separates in this way.
108479098 A of CN discloses the application side that molecule short-distance distiller extracts cannabidiol in medical cannabis
Method, required pressure is 0.01~100pa to the patent in embodiment, this requires vacuum equipment extremely high.
Since in plant, CBD is existed in the form of cannabidiolic acid (CBDA), and CBDA at high temperature just can decarboxylation
It is converted into CBD.Therefore, there must be heat treatment procedure in entire production technology.Existing method is all direct after picking floral leaf
High-temperature process in an oven, treating capacity is very big, and power consumption is surprising.In addition, peculiar smell can have been generated during the high temperature treatment process
Exhaust gas, needed for environmental protection, it usually needs construction up to 30 meters of chimney.So carrying out heat treatment to floral leaf makes hemp two
It is a kind of both uneconomical, also not energy-efficient, method more not environmentally that phenolic acid decarboxylation, which is converted into cannabidiol,.The patent of above-mentioned reference,
In every case it refers to (a part of patent does not refer to) of heat treatment procedure, is all that heat treatment is carried out to floral leaf without exception.
109803643 A of CN discloses the decarboxylation method used of cannabidiolic acid in hemp biological matter and Cannador,
It is included in the presence of one or more divalent or monovalent reagent and Cannador or hemp biological matter is heated to 40 DEG C extremely
100 DEG C of temperature；Wherein extractive with organic solvent preferably includes the alcohol extracting thing of hemp or hemp biological matter or hexane extracts
Object is more preferably selected from the lower alcohol for the group being made of methanol, ethyl alcohol, propyl alcohol and butanol.Cannador mentioned by the patent,
Its source is supercritical CO2Extract or liquid CO2Extract, extractive with organic solvent, alcohol extracting thing or hexane extract；And
And joined inorganic base in decarboxylation procedure, temperature is 40~100 degrees Celsius.
The patent of above-mentioned application, a part relate only to extraction crude oil, do not refer to the purification of subsequent product to be expired
The product of sufficient laws and regulations requirement such as prepares medicinal extract obtained by the patent CN105535111A of the numb medicinal extract of fire using subcritical abstraction technology
The content of CBD is 18.0~25.0%, does not refer to the purification of subsequent product.In every case it refers to refining step, all adopts without exception
With column chromatography technology, including the use of the patent CN108929201A of Subcritical Water Extraction technology.
Column chromatography method has shortcomings, for example, first, it is cumbersome, need filler to fill column, crude product loading, mobile phase
Elution, eluent are concentrated and multiple steps such as filler recharges；Second, the solvent that chromatography uses is considered as having
Health risk, some solvents, such as methanol, chloroform equal solvent are likely to remain in the product of acquisition；Third, due to chromatography
Column connects use from a batch to another batch, therefore with the variation of column chromatography technology product obtained not only purity
Take place frequently generation, and stable product quality is insufficient, and yield is relatively low；4th, which can generate a large amount of solid wastes
Object --- filler.
According to the pertinent regulations of national correlation department, either raw material, product or waste, wherein tetrahydrocannabinol
Content must not be higher than 0.3%.It is big that the patent of above-mentioned reference, only only a few are referred to tetrahydro in product (cannabidiol)
Numb phenol content is not higher than 0.3%.The patent of above-mentioned reference, THC content is more than 0.3% to discard in undeclared process
How object carries out closing rule processing.
Summary of the invention
It is an object of the invention to overcome solvent extraction technology, supercritical liquid extraction technique and column chromatographic purifying technology
Existing inherent shortcoming provides a kind of not only economical and efficient, but also environmentally protective, big from industry conducive to the method for industrialized production
High-purity cannabidiol is extracted and is refining to obtain in fiber crops, for the application of medicine, health care product, foods and cosmetics field.The technology
Production link complies fully with country and relevant department to the relevant regulations of hemp industry development.
The technical scheme is that be accomplished by the following way.
Key step process using industrial hemp raw material production cannabidiol (CBD) is as follows, including the pre- of raw material
Six processing, subcritical abstraction, winterization, heat treatment, short-range molecular distillation and crystal refining steps, specific steps flow chart are shown in
Fig. 8.
A method of it extracting high-purity cannabidiol from industrial hemp, includes the following steps.
S1, pretreatment of raw material.
Industrial hemp is sorted, dries in the shade, crushes, granulation of spraying water.
S2, subcritical abstraction.
Particle carries out subcritical abstraction with extractant, and the obtained extract liquor containing extractant is extracted through evaporation
Take object.
S3, winterization.
Extract is substantially soluble in winterization solvent, after prefiltration, heat preservation winterization, filtering and being concentrated again, must be concentrated
Liquid.
S4, heat treatment.
Concentrate is evaporated under reduced pressure to no fraction and steams, and obtains residue, cooling.
S5, short-range molecular distillation.
Residue is subjected to short-range molecular distillation purifying, collects light component.
S6, crystal refining.
Light component is dissolved in solvent and carries out decrease temperature crystalline, and obtained solid carries out repeated recrystallize after filtering, obtains high-purity hemp
Diphenol.
Above-mentioned steps S1~S6 elaborates the embodiment of the technology, finally obtains high-purity C BD.Actual production process
In, the conjunction ruleization processing of waste is particularly significant.Since THC and CBD physical property is approximate, while being enriched with CBD, and it is rich
Collect the process of THC.Therefore the production waste material rich in THC carries out closing ruleization processing.
It can be seen that hexamethylene double bond from THC chemical structure and phenolic hydroxyl group all have reproducibility, it can be broken by aoxidizing
The bad chemical structure.We have attempted hydrogen peroxide, aqueous sodium hypochlorite solution, tert-butyl hydroperoxide, liquor potassic permanganate and smelly
Oxygen, can the efficient oxidation THC so that its content is down to 0.3% or less.Wherein, ozone effect is best, secondly molten for potassium permanganate
Liquid.
In the S1, crushing mesh number is 24~80 mesh, preferably 50~65 mesh, more preferably 50 mesh；Water spray granulation makes to contain
Water is 4~8%, 1~2 centimetre of particle diameter, 2~4 centimetres of length.
In the S2, extractant is liquefied butane, propane or natural gas, preferably liquified natural gas.
In the S2, temperature rises to 35~55 DEG C of 20~40min of holding in subcritical abstraction, then by extract liquor through subtracting
Pressure evaporation recycling extractant, remaining extract enter next step.
In the S3, winterization solvent is 95% ethyl alcohol, and the mass ratio of extract and winterization solvent is 1:(8-10), heat preservation
Winterization needs while stirring slowly near -80~-40 DEG C, keeps the temperature 6~15 hours.
In the S5, short-range molecular distillation temperature is 150~180 DEG C, and cooling temperature is 70~90 DEG C, and vacuum degree is
0.001~0.05 millibar.
In the S6, light component and solvent quality ratio are 1:(3~6), crystallization temperature is -20~5 DEG C, and the solvent is
Normal heptane or n-hexane, preferably normal heptane.
A kind of method for extracting high-purity cannabidiol from industrial hemp, which is characterized in that gained cannabidiol
Total yield is 0.95%, and purity is greater than 99.8%, and list is miscellaneous less than 0.1%, always miscellaneous to be no more than 0.2%, and tetrahydro hemp is not detected
Phenol.
The industrial hemp is any material of vegetable origin or semi-finished product containing cannabidiol ingredient, including industrial hemp
Flower, leaf, hemp seed and husk etc..
The processing of the production waste material rich in THC can be used oxidant and be handled, and the oxidant is ozone or height
Potassium manganate solution.
The present invention pre-processes industrial hemp, is then obtained by extraction using subcritical abstraction technology rich in CBD
With the coarse extract of THC；Then coarse extract is dissolved in a certain proportion of ethyl alcohol and carries out winterization.When wax, colloid and macromolecular
After fatty acid is precipitated, using being centrifuged or be obtained by filtration clear filtrate；Filtrate is concentrated in alcohol recovery device, is obtained
Concentrated extract；Medicinal extract is imported in vacuum tank and is evaporated under reduced pressure, and until no fraction steams, which is both by CBDA heat
Processing decarboxylation is converted into the process of CBD, and removes the process of low boiling point terpenes impurity in extract；Concentrate while hot into
Row short-range molecular distillation collects light component；Light component is dissolved in a certain proportion of normal heptane or n-hexane, filtrate is slow
Cooling keeps the temperature crystallization after CBD crystal seed is added；Solid carries out being recrystallized to give target product after filtering, in crystallization link, utilizes
Active carbon and/or atlapulgite carry out the raising that decoloration is conducive to product purity.The present invention is carried out using subcritical abstraction technology
The extraction of material, short-range molecular distillation technology carry out initial gross separation purifying, and recrystallization technology carries out the purification of product, method work
Skill is simple, and extraction yield is high.THC content meets relevant laws and regulations in obtained CBD product, and final content is pure greater than 98%
99.8% or more degree, it is single miscellaneous less than 0.1%, it is total miscellaneous less than 0.2%, and THC is not detected.Entire link is not only energy-efficient, and
And it is environmentally protective.
Also, the present invention passes through to many experiments and correlative study discovery, in extracting preparation, what industrial hemp crushed
Particle size, the solvent of subcritical abstraction, winterization condition and crystallization when solvent etc. have to final purity it is biggish
Influence: crushing granulation size influences recovery rate；Extractant natural gas is better than liquefied butane and propane；The winterization time is shorter, drop
The too fast precipitation for being unfavorable for crystal of temperature；Solvent when crystallization has a significant impact to crystallization effect, and normal heptane is better than n-hexane；With
Upper variant factors influence the purity and impurity content of product.
Compared with prior art, innovation of the invention is:
(1) present invention is with subcritical abstraction technology extracting fat soluble material cannabidiol, the gained compared with solvent extraction
Medicinal extract cannabidiol content is high, and polar impurities are low, simplify subsequent purification process；Extract with supercritical carbon dioxide fluid
Technology is taken to compare, low two orders of magnitude of operation pressure, equipment investment is low；Subcritical abstraction technology, that is, economical and energy saving has green ring
It protects.
(2) present invention remanufactures into particle using hemp floral leaf and/or hemp kind shell as raw material after crushing, then carries out sub-
Critical extraction, this operation increase the specific surface area of extraction material, improve extraction efficiency, and facilitate production operation, reduce
Dust pollution in production process.
(3) present invention takes the process for first extracting and being heat-treated decarboxylation afterwards, production when avoiding a large amount of dry heat treatment hemp floral leaves
Raw has peculiar smell exhaust gas, while considerably reducing energy consumption again, i.e., energy saving and environmentally friendly.
(4) present invention is combined using short-range molecular distillation technology with recrystallization technology, instead of column chromatographic purifying skill
Art, the use and the offal treatment after column chromatographic stuffing use for avoiding a large amount of organic solvents are that is, economic and environment-friendly, also ensure that
Stable product quality between every batch of.
(5) present invention has only used two kinds of solvents of ethyl alcohol and heptane (or hexane) in entire production procedure, can be with
It recycles and the proportion of goods damageds is low, the generation of whole not production waste, residue or short distance molecule either extracted steam
Waste after evaporating, dissolvent residual is extremely low, can be used as fertilizer returning to the field.
(6) waste material containing THC generated in production process, meets laws and regulations requirement after oxidizing, these oxygen
In agent, ozone effect is best, is secondly potassium permanganate solution.
Shown in sum up, a kind of technology of the preparation method of high-purity cannabidiol mentioned by the present invention is not only high
Effect energy conservation, it is environmentally protective, and also each production link is all satisfied relevant laws and regulations requirement.
Detailed description of the invention
Fig. 1 is Δ8- THC and Δ9- THC high-efficient liquid phase chromatogram.
Fig. 2 is light component high-efficient liquid phase chromatogram obtained by 1 medium or short range molecular distillation of embodiment.
Fig. 3 is light component and Δ obtained by 1 medium or short range molecular distillation of embodiment8- THC and Δ9- THC sample mixed high-efficient liquid
Phase chromatogram.
Fig. 4 is that embodiment 1 crystallizes gained high purity product high-efficient liquid phase chromatogram for the third time.
Fig. 5 is that embodiment 1 crystallizes gained yellow solid for the first time.
Fig. 6 is white solid obtained by second of the crystallization of embodiment 1.
Fig. 7 is that embodiment 1 crystallizes gained high purity product for the third time.
Fig. 8 is the key step flow chart that cannabidiol (CBD) is produced using industrial hemp raw material.
Fig. 9 is that one of specific embodiment S2 from the method for extracting high-purity cannabidiol in industrial hemp is subcritical
The flow chart of extraction.
Specific embodiment
For a better understanding of the present invention, the present invention will be further described combined with specific embodiments below.Tool below
In body embodiment, with 1200 high performance liquid chromatograph of Agilent carry out sample analysis, according to calculated by peak area measure content and
Purity etc..
A method of it extracting high-purity cannabidiol from industrial hemp, specifically includes following steps.
S1, pretreatment of raw material.
Pretreatment includes screening, drying, crushing, the granulation of raw material.Industrial hemp flower, leaf, hemp seed and husk are divided
It picks, dries in the shade after removing the impurity such as stem branch, rubble.It being crushed using the pulverizer with dedusting function, the mesh number of grinding screen is 24~
80 mesh, powder are sent in blender, appropriate spray water, are controlled powder moisture 4~8%, are resent to granulation mechanism
Grain, 1~2 centimetre of made particle diameter, 2~4 centimetres of length.Preferably, the mesh number of grinding screen is 50~65 mesh, more preferably
50 mesh.
S2, subcritical abstraction.
It is fitted into making pellet in bag for extracting, as in extractor, liquefied butane, propane or day is injected after vacuumizing
Right gas did not had solid as minimum requirements, but must not exceed the 4/5 of tank body total volume using liquid, and temperature rises to 35~55 DEG C and holds
It is 20~40 minutes continuous, then extract liquor is transferred in evaporator, decompression heats up and is transferred to butane by compressor after making butane gasifying
In storage tank, unvaporized liquid is our extract.Every batch of materials abstraction 1~3 time.Entire production link, extractant
Loss between 0.1~1%, particle waste residue can be used as fertilizer returning to the field.
S2 subcritical abstraction flow chart is shown in Fig. 9.
S3, winterization.
Above-mentioned extract is dissolved in alcohol (if non-specified otherwise, heretofore described alcohol is 95% ethyl alcohol), feed liquid
Than 1:8-12 (mass ratio), after completely dissolution, solution is pumped into heat preservation winterization tank after filter-cloth filtering, while stirring slowly for stirring
It is down to -80~-40 degrees Celsius and maintains 6~15 hours at this temperature, temperature is lower, and the required winterization time is shorter, but cools down
The too fast precipitation for being unfavorable for crystal.
Then, which filters through low temperature diatomaceous earth filter, which is used for extract as coolant liquid
The primary cooling of alcoholic solution.Filtrate recovered alcohol, concentrate after the concentration of single-action alcohol inspissator enter lower step process.
S4, heat treatment.
Concentrate obtained by S3 step is placed in reaction kettle and is evaporated under reduced pressure, pressure is gradually down to 0.01~0.20 milli
Bar hereinafter, temperature gradually rises to 130~150 DEG C, until no fraction steams.100~120 DEG C are naturally cooling to, is transferred to down
One step process.
S5, short-range molecular distillation.
Residue after distillation obtained by step S4 is subjected to short-range molecular distillation.Vapo(u)rizing temperature is 150~180 DEG C, cooling temperature
Degree is 70~90 DEG C, and vacuum degree is 0.001~0.05 millibar.Collected light component enters the next step.By analysis, should
Contain about 78% CBD, 5% THC in terms of dry weight in sample.
S6, crystal refining.
In crystallizing tank, collected light component after above-mentioned short-range molecular distillation is dissolved in normal heptane, distillation and heptane
Mass ratio is 1:3~6, and solution is down to -20~5 degrees Celsius, and CBD crystal seed is added and the temperature is maintained to be tied for 4~24 hours
It is brilliant.After filtering, yellow solid is collected, obtains the CBD crude product that purity is 90~95%, which is dissolved in the positive heptan of 3 times of quality
In alkane, the active carbon of 5% mass fraction and the atlapulgite of 5% mass fraction is added, is heated to 40~60 degrees Celsius, stirring
0.5~4 hour, natural cooling decrease temperature crystalline.White solid is collected after filtering, obtain purity be 98~99% CBD product, four
The content of hydrogen cannabinol is less than or equal to 0.3%.Above-mentioned white solid is again dissolved in the normal heptane of 2 times of quality, it is heated to 40~
Then 50 DEG C of dissolutions are slowly dropped to 0~5 degree Celsius and maintain 2~4 hours.White solid is collected after filtering, and it is big to obtain purity
It is single miscellaneous less than 0.1% in 99.8% CBD highly finished product, it is always miscellaneous to be less than or equal to 0.2% and THC is not detected.
Above-mentioned steps S1~S6 illustrates the embodiment of the technology, finally obtains high-purity C BD.The production
Cheng Zhong, there are one the conjunction ruleization processing that important link is exactly waste.Since THC and CBD physical property is approximate, enrichment
While CBD, and the process of enrichment THC.Therefore the production waste material rich in THC carries out closing ruleization processing.
It can be seen that hexamethylene double bond from THC chemical structure and phenolic hydroxyl group all have reproducibility, it can be broken by aoxidizing
The bad chemical structure.We have attempted hydrogen peroxide, aqueous sodium hypochlorite solution, tert-butyl hydroperoxide, liquor potassic permanganate and smelly
Oxygen, can the efficient oxidation THC so that its content is down to 0.3% or less.Wherein, ozone effect is best, secondly molten for potassium permanganate
Liquid.
The preparation of sample solution.
1000.0mg sample accurately is weighed, with methanol dissolution and constant volume in 100mL volumetric flask, 10 mg/mL test is made
Solution, sample introduction is analyzed after 0.22 μ L filtering with microporous membrane.
Reference substance information.
Cannabidiol (CBD) is purchased from Sigma Aldrich, specification 1.000mg/mL (1mL MeOH).
Cannabidiolic acid (CBDA) is purchased from Sigma Aldrich, specification 1.000mg/mL (1mL MeOH).
Δ9Tetrahydrocannabinol (Δ9- THC), it is purchased from Sigma Aldrich, specification 1.000mg/mL (1mL MeOH).
Δ8Tetrahydrocannabinol (Δ8- THC), it is purchased from Sigma Aldrich, specification 1.000mg/mL (1mL MeOH).
Take the Δ of 100 μ L8The Δ of-THC solution and 50 μ L9- THC solution is mixed into new THC reference substance solution.
CBD/THC assay.
CBD, CBDA, Δ are taken respectively9-THC、Δ8- THC, THC mixed solution and sample carry out liquid phase analysis.Chromatographic column
For RaptorTMARC-18 (cat.#9314A65,150mm x 4.6mm ID), column temperature are 40 DEG C, and mobile phase is containing 0.1%TFA
Water: chromatography methanol=20:80 of 0.1%TFA, flow rate of mobile phase 1.0mL/min, sample volume are 5 μ L, and Detection wavelength is
210nm.According to main content each in calculated by peak area sample, wherein the total content of CBD includes CBD and CBDA, and THC always contains
Amount includes Δ8- THC and Δ9-THC。
Embodiment 1.
Hemp floral leaf is picked and is dried in the shade after removing the impurity such as limb, rubble.Utilize the pulverizer powder with dedusting function
Broken, the mesh number of grinding screen is 50 mesh, and powder is sent in blender, measures moisture using simple moisture teller, controls powder
Water content be 4~8%, be resent to granulator granulation, 1 centimetre of made particle diameter, 2~4 centimetres of length.Take 5 kilograms of institutes
Pelleting is fitted into bag for extracting, is placed in 29L extractor, and liquified natural gas is injected after vacuumizing to no mistake solid particle, but not
More than the 4/5 of tank body total volume, extractor temperature rises to 40 DEG C and continues 30 minutes, and then extract liquor is transferred in evaporator,
Decompression heating is transferred in natural gas storage tank after so that liquified natural gas is gasified by compressor, and unvaporized extract is collected.Extraction
Merge extract twice and obtains medicinal extract 320g, yield 6.4%.Extract is dissolved in 3.2Kg ethyl alcohol, solution is through filter-cloth filtering
After be pumped into heat preservation winterization tank, be down to while stirring -60~-50 DEG C and at this temperature maintenance 6 hours.Then, the low temperature is molten
Liquid is filtered through low temperature diatomaceous earth filter, and filtrate recovered alcohol, concentrate after alcohol recovery device is concentrated are pumped into vacuum while hot
Be heat-treated in tank, be evaporated under reduced pressure by gradient increased temperature and gradient, temperature gradually rises to 150~160 DEG C, pressure by
It is gradually down to 0.01~0.10 millibar, until no fraction steams.100~120 DEG C are naturally cooling to, residue is weighed and taken
Short-range molecular distillation is carried out after sample analysis.Pressure is lower than 0.02 millibar, and heating temperature is 160 DEG C, and cooling temperature is 90 DEG C, receives
Collect light component 80g, yield 25.0%.Collected light component being placed in crystallizing tank, the dissolution of 320g normal heptane, solution is down to-
20 DEG C, CBD crystal seed is added and maintains the temperature 12 hours.Yellow solid 52.2g, yield 65.2% are collected in filtering.By yellow
Solid is dissolved in 156.6g normal heptane, is heated to 50 DEG C, and solid all dissolves, and 2.6g active carbon is added and 2.6g activity is white
Soil continues stirring 2 hours, and while hot after diatomite filters, filtrate cooled to room temperature is cooled to 0 ± 5 DEG C of crystallization, 8h
After filter and collect white solid 35.7g, yield 68.4%, content is greater than 98.0%, THC content and is lower than 0.3%.White is solid
Body is dissolved in 71.4g normal heptane, is heated to 50 DEG C of dissolutions, then cooled to room temperature, is down to 5 with the speed of 5 DEG C/h
DEG C, continue to stir 2h.Filter and collect white solid 32.4g, yield 90.8%.It is analyzed through HPLC, CBD content is greater than
98.0%, purity is greater than 99.8%, and list is miscellaneous less than 0.1%, total miscellaneous less than 0.2%, and THC is not detected.Entire technique, CBD are total
Yield is 0.95%.
Embodiment 2.
Cannabis, leaf and kind shell are picked after removing the impurity such as limb, rubble and dried in the shade.Utilize the powder with dedusting function
Broken machine crushes, and the mesh number of grinding screen is 24 mesh, and powder is sent in blender, measures moisture, control using simple moisture teller
Powder moisture processed be 4~8%, be resent to granulator granulation, 1 centimetre of made particle diameter, 2~4 centimetres of length.Take 5
Kilogram embodiment 1, which makes pellet, to be fitted into bag for extracting, is placed in 29L extractor, and liquefied butane is injected after vacuumizing to excessively not solid
Body particle, but it is no more than the 4/5 of tank body total volume, extractor temperature rises to 35~40 DEG C and maintains 20 minutes, then will extraction
Liquid is transferred in evaporator, and decompression heating is transferred in butane storage tank after making butane gasifying by compressor, collects unvaporized extraction
Object.It is extracted twice, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 3.
It takes to make pellet in 5 kilograms of embodiments 2 and be fitted into bag for extracting, be placed in 29L extractor, inject liquid after vacuumizing
State butane to do not cross solid particle, but be no more than tank body total volume 4/5, extractor temperature rise to 35~40 DEG C and maintain 30
Minute, then extract liquor is transferred in evaporator, decompression heats up and is transferred to butane storage tank by compressor after making butane gasifying
In, collect unvaporized extract.It is extracted twice, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 4.
It takes to make pellet in 5 kilograms of embodiments 2 and be fitted into bag for extracting, be placed in 29L extractor, inject liquid after vacuumizing
State butane to do not cross solid particle, but be no more than tank body total volume 4/5, extractor temperature rise to 35~40 DEG C and maintain 40
Minute, then extract liquor is transferred in evaporator, decompression heats up and is transferred to butane storage tank by compressor after making butane gasifying
In, collect unvaporized extract.It is extracted twice, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 5.
It takes to make pellet in 5 kilograms of embodiments 2 and be fitted into bag for extracting, be placed in 29L extractor, inject liquid after vacuumizing
State butane to do not cross solid particle, but be no more than tank body total volume 4/5, extractor temperature rise to 40~45 DEG C and maintain 30
Minute, then extract liquor is transferred in evaporator, decompression heats up and is transferred to butane storage tank by compressor after making butane gasifying
In, collect unvaporized extract.It is extracted twice, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 6.
It takes 5 kilograms of embodiments 2 to make pellet to be fitted into bag for extracting, is placed in 29L extractor, injects liquid after vacuumizing
Butane to do not cross solid particle, but be no more than tank body total volume 4/5, extractor temperature rise to 45~50 DEG C and maintain 30 points
Extract liquor is then transferred in evaporator by clock, and decompression heating is transferred in butane storage tank after making butane gasifying by compressor,
Collect unvaporized extract.It is extracted twice, sampling is analyzed through HPLC, is calculated separately CBD content by peak area and is always extracted out
Rate.
Influence of 1 temperature and time of table to extraction
By in table 1 it can be seen from embodiment 2,3 and 4 in 5kg scale, at 35~40 DEG C, extract 30 minutes extract liquors
It is just nearly saturated, continue extend the time cannot continue improve the total extraction yield of CBD；The same extraction it can be seen from embodiment 3,5 and 6
30min is taken, temperature is affected to extraction yield, and temperature is higher, and extraction yield is higher.But temperature improves so that extraction selectivity drops
Low, impurity increases, and the decline of CBD content is obvious.So when carrying out two phenol extraction of industrial hemp using subcritical abstraction technology, when
When extracting 5Kg material scale, extraction temperature is 35~50 DEG C, and the time is 20~40min；The extraction yield of comprehensive consideration CBD and contain
Amount, it is preferred that 40~45 DEG C of extraction temperature, time 30min.
Embodiment 7.
Material is pre-processed by 1 method of embodiment, the mesh number of grinding screen is changed to 50 mesh, remaining parameter constant.Take 5
It kilogram makes pellet and to be fitted into bag for extracting, be placed in 29L extractor, extracted according to 5 extraction conditions of embodiment.Extraction two
Secondary, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 8.
Material is pre-processed by 1 method of embodiment, the mesh number of grinding screen is changed to 65 mesh, remaining parameter constant.Take 5
It kilogram makes pellet and to be fitted into bag for extracting, be placed in 29L extractor, extracted according to 5 extraction conditions of embodiment.Extraction two
Secondary, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 9.
Material is pre-processed by 1 method of embodiment, the mesh number of grinding screen is changed to 80 mesh, remaining parameter constant.Take 5
It kilogram makes pellet and to be fitted into bag for extracting, be placed in 29L extractor, extracted according to 5 extraction conditions of embodiment.Extraction two
Secondary, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 10.
Material is pre-processed by 1 method of embodiment, the mesh number of grinding screen is changed to 50 mesh, remaining parameter constant.Take 5
It kilogram makes pellet and to be fitted into bag for extracting, be placed in 29L extractor, LPG is injected after vacuumizing to not crossing solid particle,
But it is no more than the 4/5 of tank body total volume, extractor temperature rises to 40~45 DEG C and maintains 30 minutes, is then transferred to extract liquor
In evaporator, decompression heating is transferred in propane storage tank after making butane gasifying by compressor, collects unvaporized extract.Extraction
It takes twice, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
Embodiment 11.
Material is pre-processed by 1 method of embodiment, the mesh number of grinding screen is changed to 50 mesh, remaining parameter constant.Take 5
It kilogram makes pellet and to be fitted into bag for extracting, be placed in 29L extractor, liquified natural gas is injected after vacuumizing to not crossing solid
Grain, but it is no more than the 4/5 of tank body total volume, extractor temperature rises to 40~45 DEG C and maintains 30 minutes, then turns extract liquor
Enter in evaporator, decompression heating is transferred in natural gas storage tank after making butane gasifying by compressor, and unvaporized extraction is collected
Object.It is extracted twice, sampling is analyzed through HPLC, calculates separately CBD extraction yield by peak area.
The influence of 2 crushing material granularity of table and extractant to extraction
The grinding particle size of material has centainly extraction it can be seen from embodiment 7,8 and 9 in embodiment 5 in table 1 and table 2
Influence.Granularity is too big or too small is all unfavorable for extracting.So crushing material granularity selection is advisable in 24~80 mesh, preferably
, it is 50~65 mesh, it is contemplated that energy consumption, preferably 50 mesh.By in table 2 it can be seen from embodiment 7,10 and 11 extractant to extraction
It having a certain impact, liquefied butane, LPG and liquified natural gas influence less the total extraction yield of CBD, but in medicinal extract
CBD content is affected (respectively 93.8%, 94.7% and 95.2%), extracts for the first time, CBD content is respectively 20.0%,
23.7% and 26.8%, illustrate subcritical technology in the application process that industrial hemp extracts, extractant has selection to CBD
Property, liquified natural gas is better than liquefied butane better than LPG, LPG.So extractant can choose liquefied butane,
Or mixtures thereof LPG, liquified natural gas, it is preferred that LPG or liquified natural gas, preferably liquified natural gas.
Embodiment 12.
11 gained medicinal extract of 1Kg embodiment is dissolved in 10Kg ethyl alcohol, stirring and dissolving, solution is pumped into after filter-cloth filtering
Winterization tank is kept the temperature, be slowly dropped to -80~-70 DEG C while stirring and is maintained 6 hours at this temperature.Then, which passes through
The filtering of low temperature diatomaceous earth filter, filtrate recovered alcohol, concentrate after alcohol recovery device is concentrated are pumped into vacuum tank while hot
Heat treatment, is evaporated under reduced pressure, temperature gradually rises to 150~160 DEG C, and pressure is gradually dropped by gradient increased temperature and gradient
To 0.01~0.10 millibar, until no fraction steams.It is naturally cooling to 100~120 DEG C, residue is weighed and sampled point
Short-range molecular distillation is carried out after analysis.Pressure is lower than 0.02 millibar, and heating temperature is 160 DEG C, and cooling temperature is 90 DEG C, and cold-trap is put
Liquid nitrogen is set, light component collected by (newly-increased) enters the next step.
Embodiment 13.
11 gained medicinal extract of 1Kg embodiment is dissolved in 10Kg ethyl alcohol, stirring and dissolving, solution is pumped into after filter-cloth filtering
Winterization tank is kept the temperature, be slowly dropped to -70~-60 DEG C while stirring and is maintained 6 hours at this temperature.Then, which passes through
The filtering of low temperature diatomaceous earth filter, filtrate recovered alcohol after alcohol recovery device is concentrated.Concentrate is according to 12 method of embodiment
Carry out subsequent heat treatment and short-range molecular distillation, parameter constant.
Embodiment 14.
11 gained medicinal extract of 1Kg embodiment is dissolved in 10Kg ethyl alcohol, stirring and dissolving, solution is pumped into after filter-cloth filtering
Winterization tank is kept the temperature, be slowly dropped to -60~-50 DEG C while stirring and is maintained 6 hours at this temperature.Then, which passes through
The filtering of low temperature diatomaceous earth filter, filtrate recovered alcohol after alcohol recovery device is concentrated.Concentrate is according to 12 method of embodiment
Carry out subsequent heat treatment and short-range molecular distillation, parameter constant.
Embodiment 15.
11 gained medicinal extract of 1Kg embodiment is dissolved in 10Kg ethyl alcohol, stirring and dissolving, solution is pumped into after filter-cloth filtering
Winterization tank is kept the temperature, be slowly dropped to -50~-40 DEG C while stirring and maintains 12~15 hours (processing overnight) at this temperature.With
Afterwards, which filters through low temperature diatomaceous earth filter, filtrate recovered alcohol after alcohol recovery device is concentrated.Concentrate
Subsequent heat treatment and short-range molecular distillation, parameter constant are carried out according to 12 method of embodiment.
Embodiment 16.
11 gained medicinal extract of 1Kg embodiment is dissolved in 8Kg ethyl alcohol, stirring and dissolving, solution is pumped into guarantor after filter-cloth filtering
Warm winterization tank is slowly dropped to -60~-50 DEG C while stirring and maintains 6 hours at this temperature.Since solution is thicker, so choosing
Select centrifuge centrifugation, filtrate recovered alcohol after alcohol recovery device is concentrated.Concentrate carries out subsequent according to 12 method of embodiment
Heat treatment and short-range molecular distillation, parameter constant.
The different winterization condition acquired results of table 3 compare
By 3 12,13 and 14, table as it can be seen that under 1Kg scale, under 10 times of solvent usages and identical winterization time conditions, the winter
Change within the scope of temperature -80~-50 DEG C and is able to satisfy technical requirements.When winterization temperature rises to -50~-40 DEG C (embodiment 15),
The 6h winterization time is inadequate, and after thermally treated and short-range molecular distillation, gained light component is muddy, illustrates wax, colloid and macromolecular
Aliphatic ester substance does not eliminate, the winterization time need to extend to the 12~side 15h can, nonetheless, CBD accumulation rate is not yet
Such as embodiment 12~15 (- 80~-50 DEG C).If reducing solvent usage (embodiment 16), become thicker after solvent winterization, filters
It is more difficult, centrifuge centrifugal treating can only be selected, due to having wrapped up a part of CBD in sediment, so that theory CBD yield
Generally it is lower than other winterization conditions.Therefore, winterization condition be 8~10 times of solvents, -80~-40 DEG C, 6~15h；Preferably, 10
Times solvent, -70~-50 DEG C, 6h；It is preferred that 10 times of solvents, -60~-50 DEG C, 6h.
Embodiment 17.
In crystallizing tank, light component made from 50g embodiment 14 is dissolved in 300g normal heptane, solution is down to -20 DEG C,
CBD crystal seed is added and maintains the temperature 4~24 hours.After filtering, yellow solid is collected.
Embodiment 18.
In crystallizing tank, light component made from 50g embodiment 14 is dissolved in 300g normal heptane, solution is down to -5 DEG C, adds
Enter CBD crystal seed and maintains the temperature 4~24 hours.After filtering, yellow solid is collected.
Embodiment 19.
In crystallizing tank, light component made from 50g embodiment 14 is dissolved in 300g n-hexane, solution is down to -20 DEG C,
CBD crystal seed is added and maintains the temperature 4~24 hours.After filtering, yellow solid is collected.
Embodiment 20.
In crystallizing tank, light component made from 50g embodiment 14 is dissolved in 150g normal heptane, solution is down to -20 DEG C,
CBD crystal seed is added and maintains the temperature 4~24 hours.After filtering, yellow solid is collected.
Embodiment 21.
In crystallizing tank, light component made from 50g embodiment 14 is dissolved in the normal heptane of 200g, solution is down to -40
DEG C, CBD crystal seed is added and maintains the temperature 4~24 hours.After filtering, yellow solid is collected.
4 solvent type of table, the influence of cubical content, temperature and time to crystallization
As shown in embodiment 17 and 18 in table 4, temperature is affected to crystallization, and low temperature is more advantageous to the formation of crystal；Such as
Shown in embodiment 17 and 19, solvent is very big on crystallization influence, and n-hexane needs temperature more lower than normal heptane nonetheless to obtain
Rate is also far below normal heptane (32.2%vs 67.4%)；As shown in embodiment 17,20 and 21, solvent usage has centainly crystallization
Influence, quantity of solvent is few, and solid yield and CBD theoretical yield increase, but purity declines obvious (94.5%vs
90.0%vs 93.4%).So recrystallisation solvent is n-hexane or normal heptane, solvent usage is 3~6 times of quality, crystallization temperature
Be -40~-5 DEG C, crystallization time be 4~for 24 hours；Preferably, solvent is normal heptane, and solvent usage is 3~4 times of quality, crystallization temperature
Degree is -20 DEG C, and crystallization time is 8~12h；4 times of preferred solvent dosage, crystallization time 12h.
Embodiment 22.
After 17~21 gained yellow solid of embodiment is sufficiently mixed, takes 20g to be dissolved in 60g normal heptane, be heated to 50
DEG C, solid all dissolves, and 1.0g active carbon is added, and continues stirring 2 hours, while hot after diatomite filters, filtrate natural cooling
To room temperature, it is cooled to 0 ± 5 DEG C of crystallization.It is filtered after 8h and collects white solid.
Embodiment 23.
After 17~21 gained yellow solid of embodiment is sufficiently mixed, takes 20g to be dissolved in 60g normal heptane, be heated to 50
DEG C, solid all dissolves, and 1.0g atlapulgite is added, and continues stirring 2 hours, while hot after diatomite filters, filtrate is naturally cold
But to room temperature, it is cooled to 0 ± 5 DEG C of crystallization.It is filtered after 8h and collects white solid.
Embodiment 24.
After 17~21 gained yellow solid of embodiment is sufficiently mixed, takes 20g to be dissolved in 60g normal heptane, be heated to 50
DEG C, solid all dissolves, and 0.5g active carbon and 0.5g atlapulgite is added, and continues stirring 2 hours, filters while hot through diatomite
Afterwards, filtrate cooled to room temperature is cooled to 0 ± 5 DEG C of crystallization.It is filtered after 8h and collects white solid.
Embodiment 25.
After 17~21 gained yellow solid of embodiment is sufficiently mixed, takes 20g to be dissolved in 40g normal heptane, be heated to 50
DEG C, solid all dissolves, and 0.5g active carbon and 0.5g atlapulgite is added, and continues stirring 2 hours, filters while hot through diatomite
Afterwards, filtrate cooled to room temperature is cooled to 0 ± 5 DEG C of crystallization.It is filtered after 8h and collects white solid.
The decolorizing effect of the different decolorization conditions of table 5
| Embodiment | Filter cake quality | Solid yield | CBD content | THC content | Theoretical CBD yield | Character |
| Embodiment 22 | 17.3g | 86.3% | 98.5% | 0.19% | 90.9% | White solid |
| Embodiment 23 | 17.1g | 85.7% | 98.3% | 0.22% | 90.1% | White solid |
| Embodiment 24 | 16.9g | 84.7% | 99.1% | 0.10% | 89.8% | White solid |
| Embodiment 25 | 17.9g | 89.3% | 98.3% | 0.28% | 93.9% | White solid |
As shown in table 5, active carbon and atlapulgite can effectively decolourize, and further increase the purity of CBD, through twice
After crystallization, CBD content improves to 98% or more, THC content and is reduced to 0.3% once, meets laws and regulations requirement.
Embodiment 26.
24 gained 15.0g white solid of embodiment is dissolved in 30g normal heptane, 50 DEG C of dissolutions are heated to, it is then natural
It is cooled to room temperature, is down to 5 DEG C with the speed of 5 DEG C/h, continue to stir 2h.It filters and collects white solid 13.7g, yield
91.3%.Content is greater than 98.0%, and purity is greater than 99.8%, and list is miscellaneous less than 0.1%, always miscellaneous to be less than or equal to 0.2%, is not detected
THC。
Claims (10)
1. a kind of method for extracting high-purity cannabidiol from industrial hemp, which is characterized in that pretreatment, Asia including raw material
Six critical extraction, winterization, heat treatment, short-range molecular distillation, crystal refining steps.
2. a kind of method for extracting high-purity cannabidiol from industrial hemp, which comprises the following steps:
S1, pretreatment of raw material
Industrial hemp is sorted, dries in the shade, crushes, granulation of spraying water；
S2, subcritical abstraction
Particle carries out subcritical abstraction with extractant, and the obtained extract liquor containing extractant obtains extract through evaporation；
S3, winterization
Extract is substantially soluble in winterization solvent, after prefiltration, heat preservation winterization, filtering and being concentrated again, obtains concentrate；
S4, heat treatment
Concentrate is evaporated under reduced pressure to no fraction and steams, and obtains residue, cooling；
S5, short-range molecular distillation
Residue is subjected to short-range molecular distillation purifying, collects light component；
S6, crystal refining
Light component is dissolved in solvent and carries out decrease temperature crystalline, and obtained solid carries out repeated recrystallize after filtering, obtains high-purity cannabidiol.
3. method according to claim 1 to 2, which is characterized in that generate the life for being rich in THC in the extraction process
Waste material is produced, ruleization processing method is closed are as follows: is rich in the production waste material of THC using oxidizer treatment；The oxidant be hydrogen peroxide,
Aqueous sodium hypochlorite solution, tert-butyl hydroperoxide, liquor potassic permanganate or ozone, preferably ozone and liquor potassic permanganate.
4. according to the method described in claim 2, it is characterized in that, in the S1 crush mesh number be 24 ~ 80 mesh, preferably 50 ~
65 mesh, more preferably 50 mesh；Water spray granulation makes water content 4 ~ 8%, 1 ~ 2 centimetre of particle diameter, 2 ~ 4 centimetres of length.
5. according to the method described in claim 2, it is characterized in that, extractant is liquefied butane, propane or day in the S2
Right gas, preferably liquified natural gas；Temperature rises to 35 ~ 55 DEG C of 20 ~ 40min of holding in the S2 Subcritical extraction, then will extraction
Liquid is taken to recycle extractant through being evaporated under reduced pressure, remaining extract enters next step.
6. according to the method described in claim 2, it is characterized in that, winterization solvent is 95% ethyl alcohol, extract and winter in the S3
The mass ratio for changing solvent is 1:(8-10), heat preservation winterization needs while stirring slowly near -80 ~ -40 DEG C, keeps the temperature 6 ~ 15 hours.
7. according to the method described in claim 2, it is characterized in that, the S5 medium or short range molecular distillation temperature be 150 ~ 180 DEG C,
Cooling temperature is 70 ~ 90 DEG C, and vacuum degree is 0.001 ~ 0.05 millibar.
8. according to the method described in claim 2, it is characterized in that, light component and solvent quality ratio are 1:(3 ~ 6 in the S6),
Crystallization temperature is -20 ~ 5 DEG C, and the solvent is normal heptane or n-hexane, preferably normal heptane.
9. according to any method of claim 2-9, which is characterized in that the high-purity cannabidiol total yield is
0.95%, purity is greater than 99.8%, and list is miscellaneous less than 0.1%, always miscellaneous to be no more than 0.2%, and tetrahydrocannabinol is not detected.
10. according to any method of claim 2-9, which is characterized in that the industrial hemp contains hemp two to be any
Material of vegetable origin or semi-finished product of phenol ingredient, including industrial hemp flower, leaf, hemp seed and husk etc..
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910585027.4A CN110304994B (en) | 2019-07-01 | 2019-07-01 | Method for extracting high-purity cannabidiol from industrial cannabis sativa |
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Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574332A (en) * | 2020-04-14 | 2020-08-25 | 周宇平 | Crystallization process for purifying cannabidiol |
| CN111808670A (en) * | 2020-03-20 | 2020-10-23 | 浙江双子智能装备有限公司 | Method for extracting and purifying broad-spectrum hemp oil from hemp |
| CN111807932A (en) * | 2020-03-20 | 2020-10-23 | 浙江双子智能装备有限公司 | Method for extracting and purifying cannabidiol from cannabis sativa |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105535111A (en) * | 2016-02-16 | 2016-05-04 | 晋城市汉恩宝生物科技有限公司 | Cannabis sailve extract rich in cannabidiol and preparation method of cannabis sailve extract |
| WO2016153347A1 (en) * | 2015-03-23 | 2016-09-29 | Echo Pharmaceuticals B.V. | Cannabidiol isolate from industrial-hemp and use thereof in pharmaceutical and/or cosmetic preparations |
| CN107898826A (en) * | 2017-11-01 | 2018-04-13 | 云南谷益美农业开发有限公司 | The preparation method of the numb medicinal extract of fire containing cannabidiol |
| CN108290082A (en) * | 2015-09-30 | 2018-07-17 | 比诺里卡伦理有限公司 | Vacuum distillation for being enriched with cannabidiol |
| CN108479098A (en) * | 2018-05-03 | 2018-09-04 | 上海弗华机电设备有限公司 | Molecule short-distance distiller extracts the application process of cannabidiol in medical cannabis |
| CN108640820A (en) * | 2018-04-13 | 2018-10-12 | 昆明拜欧生物科技有限公司 | A kind of preparation method of cannabidiol |
| WO2019063848A1 (en) * | 2017-09-30 | 2019-04-04 | Bionorica Ethics Gmbh | Short path distillation in vacuum for enriching natural substances |
-
2019
- 2019-07-01 CN CN201910585027.4A patent/CN110304994B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016153347A1 (en) * | 2015-03-23 | 2016-09-29 | Echo Pharmaceuticals B.V. | Cannabidiol isolate from industrial-hemp and use thereof in pharmaceutical and/or cosmetic preparations |
| CN108290082A (en) * | 2015-09-30 | 2018-07-17 | 比诺里卡伦理有限公司 | Vacuum distillation for being enriched with cannabidiol |
| CN105535111A (en) * | 2016-02-16 | 2016-05-04 | 晋城市汉恩宝生物科技有限公司 | Cannabis sailve extract rich in cannabidiol and preparation method of cannabis sailve extract |
| WO2019063848A1 (en) * | 2017-09-30 | 2019-04-04 | Bionorica Ethics Gmbh | Short path distillation in vacuum for enriching natural substances |
| CN107898826A (en) * | 2017-11-01 | 2018-04-13 | 云南谷益美农业开发有限公司 | The preparation method of the numb medicinal extract of fire containing cannabidiol |
| CN108640820A (en) * | 2018-04-13 | 2018-10-12 | 昆明拜欧生物科技有限公司 | A kind of preparation method of cannabidiol |
| CN108479098A (en) * | 2018-05-03 | 2018-09-04 | 上海弗华机电设备有限公司 | Molecule short-distance distiller extracts the application process of cannabidiol in medical cannabis |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020233502A1 (en) * | 2019-05-17 | 2020-11-26 | 上海特化医药科技有限公司 | Method for preparing cannabidiol compound |
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| CN111807932A (en) * | 2020-03-20 | 2020-10-23 | 浙江双子智能装备有限公司 | Method for extracting and purifying cannabidiol from cannabis sativa |
| CN111574332A (en) * | 2020-04-14 | 2020-08-25 | 周宇平 | Crystallization process for purifying cannabidiol |
| CN111973654A (en) * | 2020-08-11 | 2020-11-24 | 江苏哈工药机科技股份有限公司 | Pretreatment process for extracting CBD full spectrum oil |
| WO2022049007A1 (en) * | 2020-09-02 | 2022-03-10 | GW Research Limited | Method of preparing cannabinoids |
| CN112057894A (en) * | 2020-09-08 | 2020-12-11 | 云南工麻生物科技有限公司 | Method for extracting cannabidiol |
| CN112279752A (en) * | 2020-10-30 | 2021-01-29 | 云南芙雅生物科技有限公司 | Carbon dioxide supercritical extraction method of cannabinoid for industrial cannabis sativa L |
| CN112279752B (en) * | 2020-10-30 | 2022-11-11 | 云南芙雅生物科技有限公司 | Supercritical carbon dioxide extraction method of cannabinoids for industrial cannabis sativa |
| CN112645802A (en) * | 2020-12-10 | 2021-04-13 | 云南昆船环保技术有限公司 | Preparation method of cannabidiol broad-spectrum oil capable of effectively removing tetrahydrocannabinol |
| CN113511958A (en) * | 2021-07-29 | 2021-10-19 | 云南巨漳生物科技有限公司 | Method for extracting cannabidiol from industrial cannabis sativa leaves |
| CN113880697A (en) * | 2021-11-15 | 2022-01-04 | 于立群 | Extraction method of cannabidiol |
| CN114213237A (en) * | 2021-11-18 | 2022-03-22 | 哈尔滨市汉博生物科技有限公司 | Method for extracting cannabidiolic acid from cannabis sativa |
| CN114181050A (en) * | 2021-12-21 | 2022-03-15 | 浙江双子智能装备有限公司 | Extraction method of fermented thallus cannabidiol |
| CN114773166A (en) * | 2022-04-26 | 2022-07-22 | 凯纳比斯药业有限公司 | Process for purifying effective components of antiepileptic medicine |
| CN115141085A (en) * | 2022-06-02 | 2022-10-04 | 上海天矩实业有限公司 | Extraction and purification method of bakuchiol |
| CN115141085B (en) * | 2022-06-02 | 2024-03-19 | 上海天矩实业有限公司 | Method for extracting and purifying bakuchiol |
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