CN110304993A - The method of chromatography production high-purity cannabidiol - Google Patents
The method of chromatography production high-purity cannabidiol Download PDFInfo
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- CN110304993A CN110304993A CN201910433610.3A CN201910433610A CN110304993A CN 110304993 A CN110304993 A CN 110304993A CN 201910433610 A CN201910433610 A CN 201910433610A CN 110304993 A CN110304993 A CN 110304993A
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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
- C07C37/004—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by obtaining phenols from plant material or from animal material
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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Abstract
The invention discloses a kind of methods of chromatography production high-purity cannabidiol.Described method includes following steps: 1) using solvent extraction industrial hemp, obtain extract liquor, then carry out liquid chromatogram separation；The efflux of the 3rd~4 times of column volume is collected, as containing the solution of cannabidiol；2) efflux is successively through solvent removal and crystallization to get the cannabidiol for arriving high-purity.The present invention is a kind of using industrial hemp or the floral leaf stem of other hemps as raw material, extracts the method that CBD purity is greater than 99%, and the method achieve the large-scale industrial productions of high-purity C BD, effectively solves demand of the market to high-purity C BD product.
Description
Technical field
The present invention relates to a kind of methods of chromatography production high-purity cannabidiol.
Background technique
Industrial hemp is a kind of hemp for being approved legal plantation, is the kind of low toxic amount, and THC value is below 0.3%.This
A little industrial hemps (THC < 0.3%) are considered not having drugs utility value, but still whole body is treasured, and application, which includes at least, to be spun
It knits, papermaking, food, medicine, health, daily use chemicals, leather, automobile, building, decoration, the fields such as packaging, is the classical means of production.
And cannabidiol (CBD) is a kind of extract from industrial hemp nontoxic, edible and has medical value
High added value phenolic substances, have cough-relieving, antispastic, analgesic, calmness, sleeping isoreactivity.Currently, most of flourishing states in the world
Household its as raw material, develop numerous food, health care product, nutriment, drug and cosmetics.CBD is the non-habituation in hemp
Ingredient can hinder THC to influence nerve system of human body, have the pharmacological activity such as anti-spasm, resisting rheumatoid arthritis, antianxiety.
Currently, the patent and the rare report of article that produce in the world about the CBD industrial scale of high-purity, existing
Some production technologies are about the CBD for using supercritical extract to extract in raw material, then utilize the side crystallized in organic solvent
Method obtains the CBD product of high-purity.The production technology has the drawback that: 1. product yields are low；2. high production cost；3. equipment
Investment is big；4. pair ingredient requirement height；5. the production cycle is long.To solve the problems, such as existing production, it is desirable to provide it is a kind of prepare produce it is high-purity
Spend the industrialized process for preparing of CBD.
Summary of the invention
The object of the present invention is to provide a kind of method of chromatography production high-purity cannabidiol (CBD), prepared CBD products
Purity up to 99% or more, and industrialized production can be carried out.
The method of chromatography production high-purity cannabidiol provided by the present invention, includes the following steps:
1) solvent extraction industrial hemp is used, extract liquor is obtained, then carries out liquid chromatogram separation；Collect the 3rd~4 times of column
The efflux of volume, as containing the solution of cannabidiol；
2) efflux is successively through solvent removal and crystallization to get the cannabidiol for arriving high-purity.
In above-mentioned method, using the floral leaf stem of industrial hemp (i.e. the Chinese fiber crops) as raw material, moisture content less than 5%,
It is crushed and carries out the extraction after being less than 0.1mm for granularity.
In above-mentioned method, in step 1), the solvent can be methanol, ethyl alcohol, ethylene glycol, acetone, ethyl acetate, penta
It is any in alkane, n-hexane, heptane and petroleum ether, preferably methanol, ethyl alcohol, pentane, heptane or petroleum ether；
The dosage of the solvent are as follows: 6~8 times of column volume.
In above-mentioned method, in step 1), the condition of the liquid chromatogram separation is as follows:
Filler is C18；
Chromatographic column can be the stainless steel column of ratio of height to diameter 5:1, and volume can be 500L；
Mobile phase is the mixed liquor of at least one of methanol, ethyl alcohol, acetone, ethyl acetate and acetonitrile with water, volume content
It is 50~80%, such as 70~80%；
Isocratic elution；
Flowing velocity is 2~3 times of column volume.
Separated by the liquid chromatogram while obtaining the solution containing other cannabinoids, as cannabigerol (CBG),
The solution of the cannabinoids such as secondary cannabinol (CBV), cannabinol (CBN), tetrahydrocannabinol (THC).
In above-mentioned method, in step 2), the solvent removal in single-action concentration tank, Multi-effect concentration tank and film machine at least
It is carried out in one kind, the combination of preferably described film machine and the single-effect concentrator, removes and obtain high-purity C BD and other big after solvent
The oil of numb compound.
In above-mentioned method, in step 2), the crystallization carries out in ethyl alcohol, methanol, n-hexane or heptane, preferably in second
It is carried out in alcohol, heptane.
In above-mentioned method, in step 2), the condition of the crystallization is as follows:
Temperature is -2~-5 DEG C；
Time is 4~8 hours.
In above-mentioned method, in step 2), after the crystallization, the method also includes drying steps:
The drying carries out in vacuum oven, double-cone vacuum drier or microwave dryer.
In above-mentioned method, in step 2), the condition of the drying is as follows:
Temperature is 50~60 DEG C；
Time is 4~6 hours.
It is greater than 99% CBD crystalline product through drying to obtain purity.
The present invention is a kind of using industrial hemp or the floral leaf stem of other hemps as raw material, extracts CBD purity and is greater than 99%
Method, the method achieve the large-scale industrial productions of high-purity C BD, effectively solve market to the need of high-purity C BD product
It asks.
Detailed description of the invention
Fig. 1 is the flow chart that chromatography of the present invention produces high-purity cannabidiol method.
Specific embodiment
Experimental method used in following embodiments is conventional method unless otherwise specified.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
The condition of chromatographic isolation is as follows in following embodiments:
Filler is C18；
Chromatographic column is the stainless steel column of ratio of height to diameter 5:1, volume 500L；
Temperature is 15~25 DEG C.
The purity of CBD measures by the following method in following embodiments:
Agilent high pressure liquid chromatograph, model 1220；
Chromatographic column: EXTEND-C-18 4.6*250mm 5um；
Mobile phase: acetonitrile: phosphate aqueous solution=70:30；
Detection wavelength: 220nm
Flow velocity: 1.1ml/min
Column temperature: 35 DEG C.
Embodiment 1,
Flow chart is as shown in Figure 1.
Step 1: using pulverizer that raw material is crushed to 0.1 millimeter hereinafter, using industrial hemp floral leaf stem as raw material, contain
Water is less than 3%.
Step 2: in 400 kilograms of raw material primary loading solvent extraction equipments of crushing, with the methanol of 25 times of bulking values
It is extracted, collects the methanol extraction liquid containing CBD and other cannabinoids flowed out out of extraction equipment.
Step 3: methanol extraction liquid is deployed into water aqueous 30% solution, it is filtered to remove insoluble matter, clear liquid is beaten with pump
Enter in chromatographic system, isocratic elution, flowing speed are carried out as mobile phase using the aqueous solution (volume content) of 80% methanol-water
Degree is 2 times of column volume；The efflux that Fractional Collections are flowed out out of separation system, the efflux of preceding 2 times of column volumes are impurity, the
The efflux of 2~3 times of column volumes is the solution containing CBD, and the efflux of the 4th~6 times of column volume is to contain CBG, CBV, CBN
The solution of mixture.
Step 4: the methanol aqueous solution containing CBD and various compounds that third step is obtained uses film machine to recycle first respectively
The methanol of alcohol, recycling is reused；Remove the concentrate obtained after 90% or more methanol by film machine and enters single-action concentration
In device, removes remaining solvent and obtain the oil product of CBD and various compounds.
Step 5: CBD oil crystallizes in heptane solvent, crystallization temperature is -5 DEG C, and crystallization time is 5 hours, and crystallization terminates
Afterwards, crystal is filtered to obtain, crystalline mother solution removes solvent and returns to chromatographic fractionation system.
Step 6: the crystal being obtained by filtration enters in double-cone vacuum drier, temperature is raised to 60 DEG C, and dry 6 hours de-
Solvent is gone to obtain the CBD crystalline product of 99% or more purity.
Embodiment 2,
Flow chart is as shown in Figure 1.
Step 1: using pulverizer that Chinese fiber crops raw material is crushed to 0.1 millimeter hereinafter, using Chinese fried dough twist base of leaf as raw material, contain
Water is less than 5%.
Step 2: in 1000 kilograms of raw material primary loading solvent extraction equipments of crushing, with the second of 25 times of bulking values
Alcohol is extracted, and the alcohol extraction liquid containing CBD and other cannabinoids flowed out out of extraction equipment is collected.
Step 3: alcohol extraction liquid is deployed into water aqueous 40% ethanol water, it is filtered to remove insoluble matter, clear liquid
It is squeezed into chromatographic system with pump, isocratic elution, flowing is carried out as mobile phase using 70% ethanol water (volume content)
Speed is 2 times of column volume；The efflux of preceding 2 times of column volumes is impurity, and the efflux of the 2nd~3 times of column volume is to contain CBD's
Solution, the efflux of the 4th~6 times of column volume are the solution of the mixture containing CBG, CBV, CBN.
Step 4: the ethanol water containing CBD and various compounds that third step is obtained uses film machine to recycle second respectively
The ethyl alcohol of alcohol, recycling is reused；Remove the concentrate obtained after 90% or more ethyl alcohol by film machine and enters single-action concentration
In device, removes remaining solvent and obtain the oil product of CBD and various compounds.
Step 5: CBD oil crystallizes in heptane solvent, crystallization temperature is -5 DEG C, and crystallization time is 5 hours, and crystallization terminates
Afterwards, crystal is filtered to obtain, crystalline mother solution removes solvent and returns to chromatographic fractionation system.
Step 6: the crystal being obtained by filtration enters in double-cone vacuum drier, temperature is raised to 60 DEG C, and dry 6 hours de-
Solvent is gone to obtain the CBD crystalline product of 99% or more purity.
Embodiment 3,
Flow chart is as shown in Figure 1.
Step 1: use pulverizer that raw material is crushed to 0.1 millimeter hereinafter, using cannabis base of leaf as raw material, water content
Less than 5%.
Step 2: in 600 kilograms of raw material primary loading solvent extraction equipments of crushing, with the heptane of 25 times of bulking values
It is extracted, collects the heptane extraxtion liquid containing CBD and other cannabinoids flowed out out of extraction equipment；It is returned with inspissator
It receives heptane and obtains concentrate.
Step 3: 60% ethanol water of concentrate is heated 60 DEG C of dissolutions, solution temperature filters after dropping to room temperature
Remove insoluble matter, clear liquid pump squeeze into chromatographic system, using 70% ethanol water (volume content) be used as mobile phase into
Row isocratic elution, flowing velocity are 3 times of column volume；The efflux of preceding 2 times of column volumes is impurity, the stream of the 2nd~3 times of column volume
Liquid is the solution containing CBD out, and the efflux of the 4th~6 times of column volume is the solution of the mixture containing CBG, CBV, CBN.
Step 4: the ethanol water containing CBD and various compounds that third step is obtained uses film machine to recycle second respectively
The ethyl alcohol of alcohol, recycling is reused；Remove the concentrate obtained after 90% or more ethyl alcohol by film machine and enters single-action concentration
In device, removes remaining solvent and obtain the oil product of CBD and various compounds.
Step 5: CBD oil crystallizes in heptane solvent, and -5 DEG C of crystallization temperature, crystallization time 5 hours, after crystallization, mistake
Crystal is filtered to obtain, crystalline mother solution removes solvent and returns to chromatographic fractionation system.
Step 6: the crystal being obtained by filtration enters in double-cone vacuum drier, temperature is raised to 60 DEG C, and dry 6 hours de-
Solvent is gone to obtain 99% or more CBD crystalline product.
As can be seen from the above-described embodiment, the method for the present invention is mentioned using industrial hemp or the floral leaf stem of other hemps as raw material
The purity of CBD is taken to be greater than 99%, which realizes the large-scale industrial production of high-purity C BD, effectively solution market
Demand to high-purity C BD product.
Claims (9)
1. a kind of method of chromatography production high-purity cannabidiol, includes the following steps:
1) solvent extraction industrial hemp is used, extract liquor is obtained, then carries out liquid chromatogram separation；Collect the 3rd~4 times of column volume
Efflux, as containing the solution of cannabidiol；
2) efflux is successively through solvent removal and crystallization to get the cannabidiol for arriving high-purity.
2. according to the method described in claim 1, it is characterized by: using the floral leaf stem of industrial hemp as raw material, moisture
Content is crushed less than 5% and carries out the extraction after being less than 0.1mm for granularity.
3. method according to claim 1 or 2, it is characterised in that: in step 1), the solvent is methanol, ethyl alcohol, second two
Alcohol, it is any in acetone, ethyl acetate, pentane, n-hexane, heptane and petroleum ether；
The dosage of the solvent are as follows: 6-8 times of chromatography column volume.
4. any one of -3 the method according to claim 1, it is characterised in that: in step 1), the liquid chromatogram separation
Condition is as follows:
Filler is C18；
Mobile phase is the mixed liquor of at least one of methanol, ethyl alcohol, acetone, ethyl acetate and acetonitrile with water.
5. any one of -4 the method according to claim 1, it is characterised in that: in step 2), the solvent removal is in single-action
It is carried out at least one of concentration tank, Multi-effect concentration tank and film machine.
6. any one of -5 the method according to claim 1, it is characterised in that: in step 2), the crystallization is in ethyl alcohol, first
It is carried out in alcohol, n-hexane or heptane.
7. any one of -6 the method according to claim 1, it is characterised in that: in step 2), the condition of the crystallization is as follows:
Temperature is -2~-5 DEG C；
Time is 4~8 hours.
8. any one of -7 the method according to claim 1, it is characterised in that: in step 2), after the crystallization, the side
Method further includes drying steps:
The drying carries out in vacuum oven, double-cone vacuum drier or microwave dryer.
9. method according to claim 8, it is characterised in that: in step 2), the condition of the drying is as follows:
Temperature is 50~60 DEG C；
Time is 4~6 hours.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110746275A (en) * | 2019-11-08 | 2020-02-04 | 河南汉麻生物科技有限公司 | Method for separating cannabidiol by using continuous chromatographic system |
| CN110973159A (en) * | 2019-10-30 | 2020-04-10 | 广州市浪奇实业股份有限公司 | Antibacterial composition containing cannabidiol and application thereof |
| CN111574332A (en) * | 2020-04-14 | 2020-08-25 | 周宇平 | Crystallization process for purifying cannabidiol |
| CN113009049A (en) * | 2019-12-20 | 2021-06-22 | 浙江华谱新创科技有限公司 | Process for removing THC in full-spectrum hemp extract oil |
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| WO2016116628A1 (en) * | 2015-01-22 | 2016-07-28 | Phytoplant Research S.L. | Methods of purifying cannabinoids, compositions and kits thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110973159A (en) * | 2019-10-30 | 2020-04-10 | 广州市浪奇实业股份有限公司 | Antibacterial composition containing cannabidiol and application thereof |
| CN110973159B (en) * | 2019-10-30 | 2021-04-06 | 广州市浪奇实业股份有限公司 | Antibacterial composition containing cannabidiol and application thereof |
| CN110746275A (en) * | 2019-11-08 | 2020-02-04 | 河南汉麻生物科技有限公司 | Method for separating cannabidiol by using continuous chromatographic system |
| CN113009049A (en) * | 2019-12-20 | 2021-06-22 | 浙江华谱新创科技有限公司 | Process for removing THC in full-spectrum hemp extract oil |
| CN111574332A (en) * | 2020-04-14 | 2020-08-25 | 周宇平 | Crystallization process for purifying cannabidiol |
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Application publication date: 20191008 |