WO2018032727A1 - 一种从大麻中提取大麻二酚的方法 - Google Patents
一种从大麻中提取大麻二酚的方法 Download PDFInfo
- Publication number
- WO2018032727A1 WO2018032727A1 PCT/CN2017/071993 CN2017071993W WO2018032727A1 WO 2018032727 A1 WO2018032727 A1 WO 2018032727A1 CN 2017071993 W CN2017071993 W CN 2017071993W WO 2018032727 A1 WO2018032727 A1 WO 2018032727A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ethanol
- extract
- cannabis
- extraction
- product
- Prior art date
Links
Images
Classifications
-
- 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
- C07C37/685—Processes comprising at least two steps in series
-
- 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
-
- 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
- C07C37/82—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by solid-liquid treatment; by chemisorption
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
Definitions
- the present invention relates to a method for extracting cannabidiol from cannabis, and more particularly to a method for extracting cannabidiol from industrial cannabis leaves.
- Cannabis (scientific name: Cannabis sativa L.) Cannabis, cannabis, also known as hemp, hemp, hemp, mountain seedlings, jute, has important agricultural and medicinal value. Cannabis contains a toxic ingredient, THC (tetrahydrocannabinol), which can make people addicted to drugs and can be used as drugs. It has been banned for quite a long time.
- THC tetrahydrocannabinol
- the raw material cannabis for industrial use is referred to as “industrial cannabis”.
- the content of tetrahydrocannabinol (THC) in cannabis leaves is less than three thousandths.
- the value of the toxic component, tetrahydrocannabinol can be directly used as a drug for drug use, and can be legally grown and industrialized.
- cannabinoids are a unique class of cannabis plants and are the main active components in cannabis plants. Research on it has been a hot spot in cannabis research.
- the main cannabinoids in cannabis plants are tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), cannabinol (CBG), cannabinoid phenol (CBC), etc. It accounts for more than 90% of cannabinoids.
- cannabidiol has no neurotoxicity and is of medicinal value.
- Related pharmacological studies have shown that it can hinder the effects of tetrahydrocannabinol on the human nervous system, and has pharmacological activities such as anti-caries, anti-rheumatic arthritis and anti-anxiety, and has great industrial development value.
- CN 104277917 A discloses an industrial hemp essential oil extraction method rich in cannabidiol and an extraction device thereof, which are connected by a filter, an oven, a pipe, a soaking tank, a rotary evaporator, an ultrasonic stirring tank, a dish Centrifuge, first liter membrane evaporator, proportioning tank, pressure chromatography silica gel column, eluate tank, second liter membrane evaporator, rotary evaporator, finished tank and solvent recovery tank, etc.
- CN 105505565 A discloses a method for extracting industrial hemp oil rich in cannabidiol, which is a method for extracting industrial hemp oil from industrial hemp using supercritical carbon dioxide fluid, and discharging the cooled industrial hemp powder into the material of the extraction kettle during extraction.
- CN 105535111 A discloses a hemp extract rich in cannabisdiol from the leaves of industrial hemp and a preparation method thereof. The preparation method firstly performs dry heat treatment on the leaves of the hemp, and then extracts by subcritical butane.
- the present invention aims to provide a method for extracting cannabidiol from cannabis to solve the problems of extracting cannabinol from the prior art and purifying the residual tetrahydrocannabinol.
- the present invention provides a method for extracting cannabidiol from cannabis, the method includes the following steps:
- step 6 concentrating the eluate obtained in step 6), adding ethanol to dissolve supersaturated to obtain a crystal;
- the preliminary product obtained in the step 8) is mixed with purified water and dried to obtain cannabinol.
- the cannabis according to the present invention is selected from one or a combination of two or more of industrial cannabis, intermediate cannabis or medicinal cannabis.
- the extraction site in the step 1) of the present invention is selected from one or a combination of two or more of the cannabis flower, the cannabis leaf, the cannabis root, the hemp stalk core, and the hemp seed meal.
- the extracting part in the step 1) of the present invention is a cannabis flower or a cannabis leaf.
- the cannabis extraction site in the step 1) of the present invention is pulverized to 10-80 mesh, for example, 10 mesh, 12 mesh, 14 mesh, 16 mesh, 18 mesh, 20 mesh, 25 mesh, 30 mesh. 35, 40, 45, 50, 60, 70, 80, etc.; further preferably 20 to 60 mesh; more preferably 25 to 50 mesh; most preferably 40 mesh.
- the cannabis flower and the leaf are pulverized to the aforementioned mesh number, so that the cannabidiol can be sufficiently extracted in the subsequent ethanol extraction step.
- the temperature at which the cannabis extraction portion is pulverized and dried is 60-200 ° C, for example, 60 ° C, 60.1 ° C, 61 ° C, 64 ° C, 65 ° C, 68 ° C, 70°C, 72°C, 75°C, 77°C, 80°C, 83°C, 85°C, 86°C, 87.5°C, 90°C, 90.5°C, 92.5°C, 95°C, 99°C, 100°C, 105°C, 110°C , 115 ° C, 120 ° C, 125 ° C, 130 ° C, 135 ° C, 140 ° C, 145 ° C, 150 ° C, 155 ° C, 160 ° C, 165 ° C, 170 ° C, 175 ° C, 180 ° C, 185 ° C, 190 ° C, 195 °C, 200 ° C, etc.; further preferably
- the time for the cannabis extraction portion to be pulverized and dried is 0.5-3h, for example, may be 0.5h, 0.6h, 0.7h, 0.8h, 0.9h, 1h, 1.1h, 1.2h, 1.3h, 1.4h, 1.5h, 1.6h, 1.7h, 1.8h, 1.9h 2h, 2.1h, 2.2h, 2.3h, 2.4h, 2.5h, 2.6h, 2.7h, 2.8h, 2.9h, 3h; further preferably 1-2.5h; more preferably 1.5-2h.
- the cannabis extraction site is pulverized and dried, preferably to a moisture content of 5% or less.
- the drying efficiency of the cannabis mosaic leaves is high, the drying is good, and the active ingredients therein are not destroyed.
- the step 1) is: the hemp flower, the leaf is pulverized to 10-80 mesh, and dried at a temperature of 60-200 ° C for 0.5-3 h, to a moisture content of 5% or less, to obtain a medicinal material. powder.
- the amount of the ethanol in the step 2) of the present invention is 2-8 times the amount of the medicinal material, for example, it may be 2 times, 2.2 times, 2.5 times, 2.7 times, 3 times, 3.5 times, 4 times, 4.5.
- the amount of the medicinal material is 5 times, 5.5 times, 6 times, 6.5 times, 7 times, 7.5 times, and 8 times; further preferably 3-7 times the amount of the medicinal material; more preferably 4-6 times the amount of the medicinal material.
- the number of times of ethanol extraction in step 2) of the present invention is 1-3 times.
- the extraction method of the ethanol extraction in the step 2) of the present invention is reflux extraction, ultrasonic extraction and/or soak extraction.
- the time of the reflux extraction is 0.5-3 h per extraction; the time of the ultrasonic extraction is 0.1-1 h per extraction; and the time of the extraction is 0.5-5 h per extraction.
- the step 2) is: extracting the medicinal material powder by using 2-3 times of 30-100% (V/V) ethanol of 2-8 times the amount of the medicinal material to obtain an extract.
- the relative density measured when the extract is concentrated to 50 ° C in the step 3) of the present invention is 1.05-1.35.
- the water content of the water sink in the step 4) of the present invention is 1-10 times the amount of the medicinal material, for example, it may be 1 time, 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times. 1.7, 1.8, 1.9, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6, 6.5, 7, 7.5, 8,
- the amount of the medicine is 8.5 times, 9 times, 9.5 times, 10 times; further preferably 2 to 8 times the amount of the medicine; more preferably 3 to 6 times the amount of the medicine.
- the temperature of the water sink in the step 4) of the present invention is 0-20 ° C, for example, 0 ° C, 0.1 ° C, 0.5 ° C, 0.8 ° C, 1 ° C, 1.2 ° C, 1.5 ° C, 1.75 ° C.
- the time of the water sediment in the step 4) of the present invention is 1-48 h, for example, 1 h, 1.1 h, 1.3 h, 1.5 h, 1.9 h, 2 h, 2.5 h, 3 h, 3.5 h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 8.5h, 9h, 9.5h, 10h, 10.5h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h 19h, 20h, 21h, 22h, 23h, 24h, 25h, 26h, 27h, 28h, 29h, 30h, 31h, 32h, 33h, 34h, 35h, 36h, 37h, 38h, 39h, 40h, 41h, 42h, 43h 44h, 45h, 46h, 47h, 48h; further preferably 2-36h; more preferably 5-30h.
- the step 4) is: using the purified water of 1-10 times the amount of the medicinal material to carry out water-sinking at a temperature of 0-20 ° C for 1-48 h to remove impurities, thereby obtaining Water sedimentation.
- the filler of the chromatography column used in the column chromatography in the step 6) of the present invention includes, but is not limited to, one or more of a macroporous resin, an MCI resin, and an octadecylsilane bonded silica gel.
- a macroporous resin and/or an MCI resin are preferably an MCI resin.
- the MCI resin is a novel resin designed by Mitsubishi Chemical of Japan based on Diaion and Sepabeads macroporous resin, and has a particle size of only 75-150 microns.
- the macroporous resin includes, but is not limited to, one or more of AB-8, D-101, XDA-8, LSA-7, D-941, DM-130, ADS-17, SP-825, and HPD-600.
- the column chromatography is to perform gradient elution on the column by using an elution solvent; the elution solvent is preferably ethanol and/or water; further preferably, the column is
- the step of gradient elution comprises first eluting impurities with 0-30% (v/v) ethanol, and then eluting with 40-80% (v/v) ethanol to obtain a target product fraction. More preferably, the step of eluting the gradient comprises first eluting impurities with 0-30% (V/V) ethanol, and then eluting with 40-80% (V/V) ethanol to obtain a target product portion. Finally, elution with 90-95% (v/v) ethanol to regenerate the column.
- the above gradient elution step not only makes the target product partially high in purity, but also allows the column to be continuously regenerated and recycled.
- the eluent obtained in the concentration step 6) in the step 7) of the present invention is a relative density of 1.05-1.35 measured when the eluate is concentrated to 50 °C.
- the temperature of the supersaturation and dissolution of the ethanol added in the step 7) of the present invention is 10-80 ° C, for example, 10 ° C, 10.1 ° C, 10.5 ° C, 10.7 ° C, 11 ° C, 12 ° C, 15 ° C. , 18 ° C, 20 ° C, 23°C, 25°C, 26°C, 29°C, 30°C, 35°C, 37°C, 40°C, 40.5°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C Further preferably, it is 20-60 ° C; more preferably 30-50 ° C.
- the concentration of the ethanol in the step 7) of the present invention is 60-100% (V/V).
- the step 7) of the present invention further comprises a step of recovering ethanol in the eluent.
- the step 7) is: concentrating the eluate obtained in the step 6) to a relative density of 1.05-1.35 measured at 50 ° C, and adding 60-100 at a temperature of 10-80 ° C.
- the % (V/V) ethanol was supersaturated and dissolved to obtain a crystal.
- the step 7) is: concentrating the eluate obtained in the step 6) to a relative density of 1.05-1.35 measured at 50 ° C, and recovering the ethanol in the eluate, 10 60-100% (V/V) ethanol was added to dissolve at a temperature of -80 ° C to obtain a crystal.
- the washing temperature is 0-24 ° C, for example, 0 ° C, 0.1 ° C, 0.5 ° C, 0.8 ° C, 1 ° C, 1.5 ° C, 2 ° C, 2.5 ° C, 3°C, 3.5°C, 4°C, 4.5°C, 5°C, 5.5°C, 6°C, 6.5°C, 7°C, 7.5°C, 8°C, 8.5°C, 9°C, 9.5°C, 10°C, 11°C, 12°C , 13 ° C, 14 ° C, 15 ° C, 16 ° C, 17 ° C, 18 ° C, 19 ° C, 20 ° C, 21 ° C, 22 ° C, 23 ° C, 24 ° C; further preferably 5-20 ° C; more preferably 10- 15 ° C.
- the concentration of the ethanol in the step 8) of the present invention is 5-40% (V/V).
- the step 8) is: washing the crystals at a temperature of 0-24 ° C, adding purified water or 5-40% (V/V) ethanol to obtain a preliminary product. .
- the drying method in the step 9) of the present invention includes, but is not limited to, one or more of spray drying, vacuum drying, freeze drying, near infrared drying, and microwave drying.
- the drying temperature in the step 9) of the present invention is not more than 65 °C.
- the step 9) of the present invention further comprises the step of pulverizing the obtained cannabisdiol into a powder; the pulverizing means comprises steam pulverization, and/or freeze pulverization; and the pulverized material temperature is not More than 65 ° C.
- a method of extracting cannabidiol from cannabis comprising the steps of:
- the column chromatography is prepared by one or more of a macroporous resin, an MCI resin, and an octadecylsilane bonded silica gel.
- the steps include: first eluting with 0-30% (V/V) ethanol, and then eluting with 40-80% (V/V) ethanol to obtain the target product portion, and finally using 90-95% (V/ V) ethanol elution to regenerate the column;
- step 8) The preliminary product of step 8) is mixed with purified water and dried at a temperature not exceeding 65 ° C to obtain cannabidiol.
- a method of extracting cannabidiol from a cannabis flower comprising the steps of:
- Step 6 performing column chromatography on the alcohol solution of the precipitate, wherein the column chromatography is prepared by one or more of a macroporous resin, an MCI resin, and an octadecylsilane bonded silica gel. Steps include: The impurity is eluted with 0-30% (V/V) ethanol, and then eluted with 40-80% (V/V) ethanol to obtain the target product fraction, and finally 90-95% (V/V) ethanol. Elution to regenerate the column;
- step 6) Concentration of the eluate obtained in step 6) to 50 ° C, the relative density measured is 1.05-1.35, the ethanol in the eluate is recovered, and 60-100% (V/V) is added at a temperature of 10-80 ° C. Ethanol is dissolved in supersaturation to obtain crystals;
- step 8) The initial product of step 8) is mixed with purified water, dried at a temperature not exceeding 65 ° C, and then pulverized to obtain cannabidiol.
- the description of "2-8 times the amount of the medicine” or “the amount of the medicine 1 to 10 times” in the present application means that the volume of the solvent such as ethanol or water is 2-8 times or 1 of the mass of the medicine. -10 times, for example, the medicinal material powder is 1 g, and the extraction solvent ethanol is used in an amount of 2 ml to 8 ml.
- the invention extracts cannabinol (CBD) from cannabis, and adopts the technical scheme which breaks the conventional knowledge in the field, and discards the petroleum ether, n-hexane and the second in the prior art which have high solubility to cannabidiol (CBD) in the prior art.
- Solvents such as methyl chloride, and the relatively low solubility of ethanol as the extraction solvent in the whole process, combined with the improved extraction process, unexpectedly found that the yield and purity of cannabidiol (CBD) were significantly improved, overcoming this In the field, there is a technical bias between the choice of extraction solvent and the yield of the product, and the product is not detected in the finished product.
- the safety of the product is guaranteed; and the reagents used are ethanol and water, which reduces The impact on the environment, operators, and product solvent residues; the packing of the column can be reused, which reduces the overall production cost, and also reduces the environmental pollution caused by the filler waste, which is conducive to industrial production.
- Figure 1 shows a chromatogram of product 1
- Figure 2 shows a chromatogram of product 2
- Figure 3 shows a chromatogram of product 3
- Figure 4 shows a chromatogram of product 4
- Figure 5 shows a chromatogram of product 5
- Figure 6 shows a chromatogram of product 6
- Figure 7 shows a chromatogram of product 7
- Figure 8 shows a chromatogram of Comparative Product 1
- Figure 9 shows a chromatogram of Comparative Product 2.
- Example 1 Preparation of cannabidiol by the following method
- the Examples section provides the preparation of cannabisdiol by using the method of the present invention under different technical parameters, and the amount of raw material industrial hemp flowers, leaves, roots, stalk cores and/or seed meal used in each example is 10 kg, the following is no longer explained.
- step 6) Concentrating the eluate obtained in step 6) to a relative density of 1.15 at 50 ° C, and dissolving with 100% (V / V) ethanol supersaturated at a temperature of 10 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed at a temperature of 0 ° C by adding purified water to obtain a preliminary product;
- step 9) mixing the preliminary product of step 8) with purified water, and drying in vacuum to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 10% (V/V) ethanol. Miscellaneous, then eluted with 40% (V/V) ethanol to obtain the target product fraction, and finally eluted with 90% (V/V) ethanol to regenerate the column;
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.25 at 50 ° C, and supersaturating with 60% (V / V) ethanol at a temperature of 80 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed at a temperature of 24 ° C by adding 5% (V / V) ethanol to obtain a preliminary product;
- step 9) mixing the preliminary product in step 8) with purified water, and freeze-drying to obtain cannabisdiol;
- step 6) Concentrating the eluate obtained in step 6) to a relative density of 1.2 measured at 50 ° C, and dissolving with 80% (V / V) ethanol supersaturated at a temperature of 45 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed at a temperature of 12 ° C by adding 40% (V / V) ethanol to obtain a preliminary product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the above-mentioned medicinal material powder is ultrasonically extracted three times, at a frequency of 60 Hz, using a 3-fold amount and 70% (V/V) of ethanol for 0.5 h each time to obtain an extract;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 15% (V/V) ethanol. Miscellaneous, eluting with 75% (v/v) ethanol to obtain the target product fraction, and finally eluting with 95% (v/v) ethanol to regenerate the column;
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.1 at 50 ° C, and dissolving with 80% (V / V) ethanol supersaturated at a temperature of 70 ° C to obtain a crystal;
- step 7) The crystal of step 7) is eluted by adding 10% (V/V) ethanol at a temperature of 10 ° C. Get the first product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 30% (V/V) ethanol. Miscellaneous, eluting with 75% (v/v) ethanol to obtain the target product fraction, and finally eluting with 95% (v/v) ethanol to regenerate the column;
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.1 at 50 ° C, and dissolving with 80% (V / V) ethanol supersaturated at a temperature of 70 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed with 10% (V/V) ethanol at a temperature of 10 ° C to obtain a preliminary product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 30% (V/V) ethanol. Miscellaneous, eluting with 75% (v/v) ethanol to obtain the target product fraction, and finally eluting with 95% (v/v) ethanol to regenerate the column;
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.1 at 50 ° C, and dissolving with 80% (V / V) ethanol supersaturated at a temperature of 70 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed with 10% (V/V) ethanol at a temperature of 10 ° C to obtain a preliminary product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 30% (V/V) ethanol. Miscellaneous, eluting with 75% (v/v) ethanol to obtain the target product fraction, and finally eluting with 95% (v/v) ethanol to regenerate the column;
- step 8) The crystal of step 7) is eluted by adding 10% (V/V) ethanol at a temperature of 10 ° C to obtain a preliminary product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 30% (V/V) ethanol. Miscellaneous, eluting with 75% (v/v) ethanol to obtain the target product fraction, and finally eluting with 95% (v/v) ethanol to regenerate the column;
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.1 at 50 ° C, and dissolving with 80% (V / V) ethanol supersaturated at a temperature of 70 ° C to obtain a crystal;
- step 8) The crystal of step 7) is eluted by adding 10% (V/V) ethanol at a temperature of 10 ° C to obtain a preliminary product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 30% (V/V) ethanol. Miscellaneous, eluting with 75% (v/v) ethanol to obtain the target product fraction, and finally eluting with 95% (v/v) ethanol to regenerate the column;
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.1 at 50 ° C, and dissolving with 80% (V / V) ethanol supersaturated at a temperature of 70 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed with 10% (V/V) ethanol at a temperature of 10 ° C to obtain a preliminary product;
- step 9) vacuum drying the first product of step 8) to obtain cannabisdiol;
- the alcohol solution of the precipitate is subjected to column chromatography, the packing of the column is MCI resin, the solvent is desolvated to ethanol and water, and the elution step comprises: first eluting with 10% (V/V) ethanol. Miscellaneous, then eluted with 40% (V/V) ethanol to obtain the target product fraction, and finally eluted with 90% (V/V) ethanol to make the layer Column regeneration
- step 6) concentrating the eluate obtained in step 6) to a relative density of 1.25 at 50 ° C, and supersaturating with 60% (V / V) ethanol at a temperature of 80 ° C to obtain a crystal;
- step 8) The crystal of step 7) is washed at a temperature of 24 ° C by adding 5% (V / V) ethanol to obtain a preliminary product;
- step 9) mixing the preliminary product in step 8) with purified water, and freeze-drying to obtain cannabisdiol;
- the polished flower leaves are placed in the infuser for soaking, the soaking solvent is n-hexane, the soaking temperature is 20 ° C, and the soaking time is 2 h;
- the CBD reference substance was accurately weighed, and methanol (1:1) was added to prepare a reference solution containing 0.1 mg per 1 ml, which was obtained; the tetrahydrocannabinol reference substance was accurately weighed, and methanol was added (1: 1) Prepare a solution of 0.01 mg of each control solution per 1 ml.
- Preparation of the test solution Take about 25mg of this product, accurately weighed, placed in a 25ml volumetric flask, add acetonitrile-water (1:1) 20ml, sonicated for 15 minutes, add acetonitrile-water (1:1) to the scale Shake well, filter through a microporous membrane (0.45 ⁇ m), and take the filtrate to obtain.
- the measurement method accurately absorbs 10 ⁇ l of each of the reference solution and the test solution, and injects into a liquid chromatograph, and the measurement is obtained.
- CBD can be seen from Table 1 and Figures 1 to 9 that the content of CBD (cannabisphenol) in the products 1, 2, 3, 4, 5, 6, and 7 prepared by the method of the present invention is significantly higher than that obtained by the prior art.
- the content of CBD Comparative Product 1 and Comparative Product 2
- no THC tetrahydrocannabinol
- THC was clearly detected in the product prepared by the prior art.
- the CBD obtained by the invention has higher content, purer purity and safer, and meets the relevant requirements of the regulations.
- the CBD reference substance was accurately weighed, and methanol (1:1) was added to prepare a reference solution containing 0.1 mg per 1 ml, which was obtained; the tetrahydrocannabinol reference substance was accurately weighed, and methanol was added (1: 1) Prepare a solution of 0.01 mg of each control solution per 1 ml.
- Preparation of the test solution Take about 1g of this product, accurately weighed, add 25ml of methanol, sonicate for 15 minutes, filter, add 25ml of methanol, sonicate for 15 minutes, combine the filtrate, dilute to 50ml, shake well, use micro The pore filter membrane (0.45 ⁇ m) was filtered, and the filtrate was taken to obtain.
- the measurement method accurately absorbs 10 ⁇ l of each of the reference solution and the test solution, and injects into a liquid chromatograph, and the measurement is obtained.
- the CBD reference substance was accurately weighed, and methanol (1:1) was added to prepare a reference solution containing 0.1 mg per 1 ml, which was obtained; the tetrahydrocannabinol reference substance was accurately weighed, and methanol was added (1: 1) Prepare a solution of 0.01 mg of each control solution per 1 ml.
- test solution 1 ml of the extract, made up to 25 ml, filtered through a microporous membrane (0.45 ⁇ m), and the filtrate was taken.
- the measurement method accurately absorbs 10 ⁇ l of each of the reference solution and the test solution, and injects into a liquid chromatograph, and the measurement is obtained.
- the detection method was the same as that of Experimental Example 1, and the results of the detection of the CBD content and the tetrahydrocannabinol content of the products prepared in Examples 8-10 are shown in Table 3.
- the method of the present invention is equally applicable to the extraction of CBD from cannabis roots, stalk cores, and flowers, leaves, and seed meal, and no THC (tetrahydrocannabinol) is detected in the product.
- Drug stability test chamber Long-term: SHH-250SD, Chongqing Yongsheng Experimental Instrument Factory;
- Drug stability test chamber (acceleration): SHH-250SD, Chongqing Yongsheng Experimental Instrument Factory;
- UV-visible spectrophotometer UV-2550, Shimadzu, Japan;
- CBD can be bisdiol
- the content of CBD varies only within 0.6% (the highest change in CBD content after storage for 3 months, 2 months, and 1 month is only 0.6%).
- the content of CBD of Comparative Product 1 and Comparative Product 2 was reduced from 83.1% to 73.8% (decline rate 9.3%) after 6 months accelerated stability test, from 81.2% to 69.1.
- the above-described embodiments of the present invention achieve the following technical effects: 1) By increasing the crystallization step, the content of cannabidiol (CBD) in the final product is increased to 96% or more. 2) By improving the process technology, the content of tetrahydrocannabinol in the finished product is controlled to be less than 0.3% (in the case of Example 1 - Example 7, tetrahydrocannabinol is not detected), in accordance with national laws and regulations, products Security is guaranteed.
- CBD cannabidiol
- the macroporous resin, MCI resin or ODS is used in the preliminary refining step to replace the silica gel in the prior art, so that the filler can be reused, the overall production cost is reduced, and the environmental pollution of the waste silica gel is reduced.
- the process according to the present invention can produce a product with high purity (content 95%) or more and safety (THC content 0.3% or less).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明公开一种从大麻中提取大麻二酚的方法。该方法包括以下步骤:将大麻的提取部位粉碎、烘干得到药材粉末;将药材粉末采用30-100%(V/V)的乙醇提取得到提取液;将提取液浓缩得到浸膏;将浸膏进行水沉,去除杂质得到水沉液;将水沉液离心并向获得的沉淀中加入10-100%(V/V)乙醇,溶解得到沉淀物的醇溶液;将沉淀物的醇溶液进行柱层析;浓缩柱层析后洗脱获得的洗脱液,加入乙醇过饱和溶解,获得结晶物;将结晶物加入纯化水或乙醇洗涤,得到初品;将初品用纯化水混匀,干燥,即得。本发明仅采用高度安全的乙醇作为溶剂,既提高了成品中大麻二酚纯度,又去除了精神毒性成分四氢大麻酚,提高产品安全性,适合工业化生产。
Description
本发明涉及一种从大麻中提取大麻二酚的方法,特别涉及一种从工业大麻花叶中提取大麻二酚的方法。
大麻(学名:Cannabis sativa L.)大麻科、大麻属植物,又名麻、汉麻、火麻、山丝苗、黄麻,具有重要的农用及药用价值。大麻中含有一种毒性成分THC(四氢大麻酚)可使人致幻成瘾,可作毒品,曾在相当长时期内禁种。
由于大麻的经济、药用价值极高,专供工业用途的原料大麻简称为“工业大麻”,其生长期大麻花叶中的四氢大麻酚(THC)含量小于千分之三,不具备提取毒性成分四氢大麻酚的价值或直接作为毒品吸食,可以合法进行规模化种植与工业化开发利用。
目前,人们已从大麻植株中分离出了500余种物质,其中大麻酚类化合物至少有86种。大麻酚类化合物是大麻植株中特有的一类物质,是大麻植物中主要的活性成分,有关它的研究一直是大麻研究的热点。大麻植株中主要的大麻酚类化合物有四氢大麻酚(THC)、大麻酚(CBN)、大麻二酚(CBD)、大麻萜酚(CBG)、大麻环萜酚(CBC)等,其中前三者占大麻酚类化合物的90%以上。
近年来,通过对大麻活性成分的研究发现,大麻二酚(cannabidiol)不具有神经毒性,药用价值明显。相关的药理研究表明,其能阻碍四氢大麻酚对人体神经系统的影响,并具有抗痉挛、抗风湿性关节炎、抗焦虑等药理活性,具有巨大产业开发价值。
目前,公开信息中有一些关于从工业大麻中提取大麻二酚或提取含大麻二酚的工业大麻油的方法的报道。例如,CN 104277917 A公开了一种富含大麻二酚的工业大麻精油提取方法及其提取设备,通过采用筛选器、烤炉、管道依次相连的浸泡池、旋转蒸发仪、超声搅拌罐、碟式离心机、第一升膜蒸发器、配比罐、加压层析硅胶柱、洗出液罐、第二升膜蒸发器、旋转蒸发仪、成品罐和溶剂回收罐等设备对工业大麻逐步进行筛选、烘烤、浸提、再处理、过滤、监测、上样、层析、浓缩和成品的操作步骤,最终提取出富含有效成分大麻二酚的工业大麻精油。CN 105505565 A公开了一种萃取富含大麻二酚的工业大麻油的方法,是采
用超临界二氧化碳流体从工业大麻中提取工业大麻油,萃取时将冷却后的工业大麻粉放入萃取釜的物料桶中,将CO2气体注入萃取釜,保持萃取釜内温度和压力在CO2气体的超临界状态与原料接触,使工业大麻粉中的工业大麻油等成分溶解于超临界流体之中,使含大麻二酚等成分的流体从萃取釜节流膨胀进入分离釜解析,得到工业大麻油并收集。CN 105535111 A公开了一种从工业火麻的花叶中提取富含大麻二酚的火麻浸膏及其制备方法,该制备方法首先对火麻花叶进行干热处理,再通过亚临界丁烷萃取技术,乙醇为夹带剂获得富含大麻二酚的粗浸膏;粗浸膏溶于一定比例的乙醇溶液并进行低温冬化处理;利用离心机离心或过滤机过滤去除蜡质;上清液加入活性炭进行脱色过滤处理;最后将上述所得滤液旋转蒸发除去乙醇,可获得富含CBD的火麻浸膏。其中与本发明最为接近的现有技术为CN 103739585 A,其公开了一种从工业大麻中提取二氢大麻酚(CBD)的工艺,包括采摘花叶、烘干、粉碎、浸泡萃取以及浓缩分离过程,通过对比研究,现有技术中所提及的从工业大麻中提取大麻二酚的方法,主要存在以下问题:
1)因原植物中大麻酚类成分复杂,极性相似成分较多,采用传统方法提取、精制后,最终产品中大麻二酚纯度不高。
2)提取纯化后,仍可检出精神毒性成分四氢大麻酚,产品安全性不能得到保证,产品流通受限,影响工业化生产和应用。
3)因大麻二酚在有机溶剂中的溶解度高于在乙醇中,故,为了提高大麻二酚的产率,行业中通常在提取、萃取、纯化等工艺步骤中采用石油醚、正己烷、二氯甲烷等有毒有机溶剂。但此类有机溶剂的使用会对环境产生危害,而且终产品中溶剂残留不能除尽,对产品安全性也有影响。
因此,目前亟需提供一种制备高纯度且无四氢大麻酚的大麻二酚的方法,并且无不良有机溶剂残留,该制备方法还应满足节能环保,经济适用的产业化发展需求。
发明内容
本发明旨在提供一种从大麻中提取大麻二酚的方法,以解决现有技术中提取大麻二酚纯度不高、精神毒性成分四氢大麻酚残留等问题。
为了实现上述目的,本发明提供了一种从大麻中提取大麻二酚的方法,该方
法包括以下步骤:
1)将大麻的提取部位粉碎、烘干,得到药材粉末;
2)将药材粉末采用30-100%(V/V)的乙醇提取,得到提取液;
3)将提取液浓缩,得到浸膏;
4)将浸膏进行水沉,去除杂质,得到水沉液;
5)将水沉液离心,在离心获得的沉淀中加入10-100%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析;
7)浓缩步骤6)得到的洗脱液,加入乙醇过饱和溶解,获得结晶物;
8)将结晶物,加入纯化水或乙醇洗涤,得到初品;
9)将步骤8)所得初品用纯化水混匀,干燥,即得大麻二酚。
优选的,本发明所述的大麻选自工业大麻、中间型大麻或药用大麻中的一种或两种以上的组合。
优选的,本发明所述的步骤1)中提取部位选自大麻花、大麻叶、大麻根、大麻秆芯和大麻籽粕中的一种或两种以上的组合。优选的,本发明所述的步骤1)中提取部位为大麻花、大麻叶。
优选的,本发明所述的步骤1)中所述大麻提取部位粉碎至10-80目,例如可以是10目、12目、14目、16目、18目、20目、25目、30目、35目、40目、45目、50目、60目、70目、80目等等;进一步优选为20-60目;更优选为25-50目;最优选为40目。在本发明的一个典型实施方式中,所述的步骤1)中将大麻花、叶粉碎至前述目数范围内,可以使得大麻二酚在后续的乙醇提取步骤中充分提取出来。
优选的,本发明所述的步骤1)中所述大麻提取部位粉碎后烘干的温度为60-200℃,例如可以是60℃、60.1℃、61℃、64℃、65℃、68℃、70℃、72℃、75℃、77℃、80℃、83℃、85℃、86℃、87.5℃、90℃、90.5℃、92.5℃、95℃、99℃、100℃、105℃、110℃、115℃、120℃、125℃、130℃、135℃、140℃、145℃、150℃、155℃、160℃、165℃、170℃、175℃、180℃、185℃、190℃、195℃、200℃等等;进一步优选为80-180℃;更优选为100-150℃。
优选的,本发明所述的步骤1)中所述大麻提取部位粉碎后烘干的时间为
0.5-3h,例如可以是0.5h、0.6h、0.7h、0.8h、0.9h、1h、1.1h、1.2h、1.3h、1.4h、1.5h、1.6h、1.7h、1.8h、1.9h、2h、2.1h、2.2h、2.3h、2.4h、2.5h、2.6h、2.7h、2.8h、2.9h、3h;进一步优选为1-2.5h;更优选为1.5-2h。
进一步地,本发明所述的步骤1)中所述大麻提取部位粉碎后烘干,优选为烘干至水分5%以下。在本发明的一个典型实施方式中,所述的步骤1)中在上述烘干条件下,大麻花叶的烘干效率高,干燥好,并且其中的有效成分不会被破坏。
在本发明的一个典型实施方式中,所述步骤1)为:大麻花、叶粉碎至10-80目,在60-200℃的温度下烘干0.5-3h,至水分5%以下,得到药材粉末。
优选的,本发明所述的步骤2)中所述乙醇的用量为2-8倍药材量,例如可以是2倍、2.2倍、2.5倍、2.7倍、3倍、3.5倍、4倍、4.5倍、5倍、5.5倍、6倍、6.5倍、7倍、7.5倍、8倍药材量;进一步优选为3-7倍药材量;更优选为4-6倍药材量。
优选的,本发明所述的步骤2)中所述乙醇提取的次数为1-3次。
优选的,本发明所述的步骤2)中所述乙醇提取的提取方式为回流提取、超声提取和/或浸泡提取。
进一步优选的,所述回流提取的时间为每次提取0.5-3h;所述超声提取的时间为每次提取0.1-1h;所述浸泡提取的时间为每次提取0.5-5h。
在本发明的一个典型实施方式中,所述步骤2)为:将药材粉末采用2-8倍药材量的30-100%(V/V)的乙醇提取1-3次,得到提取液。
优选的,本发明所述的步骤3)中所述将提取液浓缩为浓缩至50℃时测量的相对密度为1.05-1.35。
优选的,本发明所述的步骤4)中所述水沉的用水量为1-10倍药材量,例如可以是1倍、1.1倍、1.2倍、1.3倍、1.4倍、1.5倍、1.6倍、1.7倍、1.8倍、1.9倍、2倍、2.25倍、2.5倍、3倍、3.5倍、4倍、4.5倍、5倍、5.5倍、6倍、6.5倍、7倍、7.5倍、8倍、8.5倍、9倍、9.5倍、10倍药材量;进一步优选为2-8倍药材量;更优选为3-6倍药材量。
优选的,本发明所述的步骤4)中所述水沉的温度为0-20℃,例如可以是0℃、0.1℃、0.5℃、0.8℃、1℃、1.2℃、1.5℃、1.75℃、2℃、2.5℃、3℃、3.5℃、4℃、
4.5℃、5℃、5.5℃、6℃、6.5℃、7℃、7.5℃、8℃、8.5℃、9℃、9.5℃、10℃、10.5℃、11℃、11.5℃、12℃、12.5℃、13℃、13.5℃、14℃、14.5℃、15℃、15.5℃、16℃、16.5℃、17℃、17.5℃、18℃、18.5℃、19℃、19.5℃、20℃;进一步优选为2-18℃;更优选为5-15℃。
优选的,本发明所述的步骤4)中所述水沉的时间为1-48h,例如可以是1h、1.1h、1.3h、1.5h、1.9h、2h、2.5h、3h、3.5h、4h、4.5h、5h、5.5h、6h、6.5h、7h、7.5h、8h、8.5h、9h、9.5h、10h、10.5h、11h、12h、13h、14h、15h、16h、17h、18h、19h、20h、21h、22h、23h、24h、25h、26h、27h、28h、29h、30h、31h、32h、33h、34h、35h、36h、37h、38h、39h、40h、41h、42h、43h、44h、45h、46h、47h、48h;进一步优选为2-36h;更优选为5-30h。
在本发明的一个典型实施方式中,所述步骤4)为:将浸膏用其1-10倍药材量的纯化水在0-20℃的温度下进行水沉1-48h,去除杂质,得到水沉液。
优选的,本发明所述的步骤6)中所述柱层析所用的层析柱的填料包括但不限于大孔树脂、MCI树脂、十八烷基硅烷键合硅胶中的一种或多种;进一步优选为大孔树脂和/或MCI树脂;更优选为MCI树脂。所述MCI树脂是日本三菱化学在Diaion和Sepabeads大孔树脂的基础上设计的新型树脂,粒径仅75-150微米。所述大孔树脂包括但不限于AB-8、D-101、XDA-8、LSA-7、D-941、DM-130、ADS-17、SP-825和HPD-600中的一种或多种。
优选的,本发明所述的步骤6)中所述柱层析为采用洗脱溶剂对层析柱进行梯度洗脱;所述洗脱溶剂优选为乙醇和/或水;进一步优选的,所述梯度洗脱的步骤包括:先用0-30%(V/V)的乙醇洗脱除杂,再用40-80%(V/V)的乙醇洗脱获得目标产物部分。更优选的,所述梯度洗脱的步骤包括先用0-30%(V/V)的乙醇洗脱除杂,再用40-80%(V/V)的乙醇洗脱获得目标产物部分,最后用90-95%(V/V)的乙醇洗脱以使层析柱再生。上述梯度洗脱的步骤不仅使得目标产物部分纯度高,而且使层析柱不断再生,可循环使用。
优选的,本发明所述的步骤7)中所述浓缩步骤6)得到的洗脱液为将洗脱液浓缩至50℃时测量的相对密度为1.05-1.35。
优选的,本发明所述的步骤7)中所述加入乙醇过饱和溶解的温度为10-80℃,例如可以是10℃、10.1℃、10.5℃、10.7℃、11℃、12℃、15℃、18℃、20℃、
23℃、25℃、26℃、29℃、30℃、35℃、37℃、40℃、40.5℃、45℃、50℃、55℃、60℃、65℃、70℃、75℃、80℃;进一步优选为20-60℃;更优选为30-50℃。
优选的,本发明所述的步骤7)中所述乙醇的浓度为60-100%(V/V)。
进一步优选的,本发明所述的步骤7)中还包括对洗脱液中乙醇的回收步骤。
在本发明的一个典型实施方式中,所述步骤7)为:浓缩步骤6)得到的洗脱液至50℃时测量的相对密度为1.05-1.35,10-80℃的温度下加入60-100%(V/V)的乙醇过饱和溶解,获得结晶物。
在本发明的一个优选实施方式中,所述步骤7)为:浓缩步骤6)得到的洗脱液至50℃时测量的相对密度为1.05-1.35,对洗脱液中的乙醇进行回收,10-80℃的温度下加入60-100%(V/V)的乙醇过饱和溶解,获得结晶物。
优选的,本发明所述的步骤8)中所述洗涤的温度为0-24℃,例如可以是0℃、0.1℃、0.5℃、0.8℃、1℃、1.5℃、2℃、2.5℃、3℃、3.5℃、4℃、4.5℃、5℃、5.5℃、6℃、6.5℃、7℃、7.5℃、8℃、8.5℃、9℃、9.5℃、10℃、11℃、12℃、13℃、14℃、15℃、16℃、17℃、18℃、19℃、20℃、21℃、22℃、23℃、24℃;进一步优选为5-20℃;更优选为10-15℃。
优选的,本发明所述的步骤8)中所述乙醇的浓度为5-40%(V/V)。
在本发明的一个典型实施方式中,所述步骤8)为:将结晶物,在0-24℃的温度下,加入纯化水或5-40%(V/V)的乙醇洗涤,得到初品。
优选的,本发明所述的步骤9)中所述干燥的方式包括但不限于喷雾干燥、真空干燥、冷冻干燥、近红外干燥、微波干燥中的一种或几种。
优选的,本发明所述的步骤9)中所述干燥的温度为不超过65℃。
进一步优选的,本发明所述的步骤9)中还包括将获得的大麻二酚粉碎成粉的步骤;所述粉碎的方式包括汽流粉碎、和/或冷冻粉碎;所述粉碎的物料温度不超过65℃。
在本发明的一个优选实施方式中,提供了一种从大麻中提取大麻二酚的方法,包括以下步骤:
1)将大麻的提取部位粉碎至10-80目,在60-200℃的温度下烘干0.5-3h,至水分5%以下,得到药材粉末;
2)将药材粉末采用2-8倍药材量的30-100%(V/V)的乙醇提取1-3次,得
到提取液;
3)将提取液浓缩至50℃时测量的相对密度为1.05-1.35,得到浸膏;
4)将浸膏用其1-10倍药材量的纯化水,在0-20℃的温度下进行水沉1-48h,去除杂质,得到水沉液;
5)将水沉液离心,在离心获得的沉淀中加入10-100%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,所述柱层析所用的层析柱的填料为大孔树脂、MCI树脂、十八烷基硅烷键合硅胶中的一种或多种,具体步骤包括:先用0-30%(V/V)的乙醇洗脱除杂,再用40-80%(V/V)的乙醇洗脱获得目标产物部分,最后用90-95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时测量的相对密度为1.05-1.35,10-80℃的温度下加入60-100%(V/V)的乙醇过饱和溶解,获得结晶物;
8)将结晶物,在0-24℃的温度下,加入纯化水或5-40%(V/V)的乙醇洗涤,得到初品;
9)将步骤8)初品用纯化水混匀,在不超过65℃的温度下干燥,即得大麻二酚。
在本发明的另一个优选实施方式中,提供了一种从大麻花叶中提取大麻二酚的方法,包括以下步骤:
1)将大麻的花叶粉碎至10-80目,在60-200℃的温度下烘干0.5-3h,至水分5%以下,得到药材粉末;
2)将药材粉末采用2-8倍药材量的30-100%(V/V)的乙醇提取1-3次,得到提取液;
3)将提取液浓缩至50℃时测量的相对密度为1.05-1.35,得到浸膏;
4)将浸膏用其1-10倍药材量的纯化水,在0-20℃的温度下进行水沉1-48h,去除杂质,得到水沉液;
5)将水沉液离心,在离心获得的沉淀中加入10-100%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,所述柱层析所用的层析柱的填料为大孔树脂、MCI树脂、十八烷基硅烷键合硅胶中的一种或多种,具体步骤包括:先
用0-30%(V/V)的乙醇洗脱除杂,再用40-80%(V/V)的乙醇洗脱获得目标产物部分,最后用90-95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时测量的相对密度为1.05-1.35,对洗脱液中乙醇的进行回收,10-80℃的温度下加入60-100%(V/V)的乙醇过饱和溶解,获得结晶物;
8)将结晶物,在0-24℃的温度下,加入纯化水或5-40%(V/V)的乙醇洗涤,得到初品;
9)将步骤8)初品用纯化水混匀,在不超过65℃的温度下干燥后粉碎,即得大麻二酚。
需要说明的是,本申请中的“2-8倍药材量”或“1-10倍药材量”等描述,是指采用的溶剂如乙醇或水的体积是药材质量的2-8倍或1-10倍,比如,药材粉末为1g,提取溶剂乙醇的用量为2ml-8ml。
本发明从大麻中提取大麻二酚(CBD),采用打破本领域常规认识的技术方案,在工艺中摈弃了现有技术中对大麻二酚(CBD)溶解度较高的石油醚、正己烷、二氯甲烷等溶剂,而在工艺全程采用溶解度相对低的乙醇作为提取溶剂,并结合改进的提取工艺,出乎意料地发现大麻二酚(CBD)的得率、纯度均有明显提高,克服了本领域关于提取溶剂的选择与产品得率间的技术偏见,同时成品中未检出精神毒性成分四氢大麻酚,使产品的安全性得到了保障;并且,使用的试剂为乙醇和水,减少了对环境、操作人员、产品溶剂残留的影响;层析柱的填料可重复利用,使总体生产成本降低,也减少了填料废弃物对环境造成的污染,利于工业化生产。
构成本申请的一部分的说明书附图用来提供对本发明的进一步理解,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。在附图中:
图1示出了产物1的色谱图;
图2示出了产物2的色谱图;
图3示出了产物3的色谱图;
图4示出了产物4的色谱图;
图5示出了产物5的色谱图;
图6示出了产物6的色谱图;
图7示出了产物7的色谱图;
图8示出了对比产物1的色谱图;以及
图9示出了对比产物2的色谱图。
需要说明的是,在不冲突的情况下,本申请中的实施例及实施例中的特征可以相互组合。下面将参考附图并结合实施例来详细说明本发明。
实施例1:按照如下方法制备大麻二酚
实施例部分提供了采用本发明所述方法,在不同技术参数条件下,制备大麻二酚,各实施例中采用的原料工业大麻花、叶、根、秆芯和/或籽粕的量均为10千克,以下不再另做说明。
1)将工业大麻的花叶粉碎,过80目筛,在60℃的温度下烘干3h,得到药材粉末,测得其水分含量为4%;
2)将上述药材粉末采用其2倍量、30%(V/V)的乙醇回流提取3次,每次0.5h,得到提取液;
3)将上述提取液浓缩至50℃时测量的相对密度为1.05,得到浸膏;
4)将上述浸膏采用其1倍量的纯化水,在20℃的温度下水沉1h,去除杂质,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入100%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为AB-8,脱溶剂为乙醇和水,洗脱的步骤包括:先用30%(V/V)的乙醇洗脱除杂,再用80%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.15,在10℃的温度下,用100%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在0℃的温度下,加入纯化水洗涤,得到初品;
9)将步骤8)所述初品用纯化水混匀,真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物1。
实施例2:按照如下方法制备大麻二酚
1)将工业大麻的花叶粉碎,过10目筛,得到药材粉末。在200℃的温度下烘干0.5h,得到药材粉末,测得其水分含量为2.7%;
2)将上述药材粉末采用其2倍量、100%(V/V)的乙醇超声提取1次,每次1h,得到提取液;
3)将上述提取液浓缩至50℃时测量的相对密度为1.35,得到浸膏;
4)将上述浸膏用其10倍量的纯化水,在0℃的温度下水沉48h,去除杂质,得到水沉液;
5)将上述水沉液离心,转速10000转,在离心获得的沉淀中加入10%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用10%(V/V)的乙醇洗脱除杂,再用40%(V/V)的乙醇洗脱获得目标产物部分,最后用90%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.25,在80℃的温度下,用60%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在24℃的温度下,加入5%(V/V)乙醇洗涤,得到初品;
9)将步骤8)所述初品用纯化水混匀,冷冻干燥,即得大麻二酚;
10)冷冻粉碎步骤9)所得大麻二酚,即得产物2。
实施例3:按照如下方法制备大麻二酚
1)将工业大麻的花叶粉碎,过40目筛,在130℃的温度下烘干1.7h,得到药材粉末,测得其水分含量为3.1%。
2)将上述药材粉末采用其5倍量、60%(V/V)的乙醇浸泡提取2次,每次2.5h,得到提取液;
3)将上述提取液浓缩至50℃时测量的相对密度为1.2,得到浸膏;
4)将上述浸膏用其5倍量的纯化水,在10℃的温度下水沉24h,去除杂质,得到水沉液;
5)将上述水沉液离心,转速7500转,在离心获得的沉淀中加入60%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为ODS,脱溶剂为乙醇和水,洗脱的步骤包括:先用25%(V/V)的乙醇洗脱除杂,再用60%(V/V)的乙醇洗脱获得目标产物部分,最后用93%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时测量的相对密度为1.2,在45℃的温度下,用80%(V/V)的乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在12℃的温度下,加入40%(V/V)乙醇洗涤,得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物3。
实施例4:按照如下方法制备大麻二酚
1)将工业大麻的花叶粉碎,过40目筛,在120℃的温度下烘干1h,得到药材粉末,测得其水分含量为2.6%。
2)将上述药材粉末采用其3倍量、70%(V/V)的乙醇在60赫兹的频率下超声提取3次,每次0.5h,得到提取液;
3)将上述提取液浓缩至50℃时的相对密度为1.1,得到浸膏;
4)将上述浸膏用其5倍量的纯化水,在4℃的温度下水沉12h,去除杂质,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入80%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用15%(V/V)的乙醇洗脱除杂,再用75%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.1,在70℃的温度下,用80%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在10℃的温度下,加入10%(V/V)乙醇洗脱,
得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物4。
实施例5:按照如下方法制备大麻二酚
1)将工业大麻的花叶粉碎,过40目筛,在120℃的温度下烘干1h,得到药材粉末,测得其水分含量为2.6%;
2)将上述药材粉末采用其5倍量、80%(V/V)的乙醇在70赫兹的频率下超声提取2次,每次0.5h,得到提取液;
3)将上述提取液浓缩至50℃时的相对密度为1.1,得到浸膏;
4)将上述浸膏用其5倍量的纯化水,在4℃的温度下水沉12h,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入80%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用30%(V/V)的乙醇洗脱除杂,再用75%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对至密度为1.1,在70℃的温度下,用80%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在10℃的温度下,加入10%(V/V)乙醇洗涤,得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物5。
实施例6:按照如下方法制备大麻二酚
1)将工业大麻的花叶粉碎,过40目筛,在120℃的温度下烘干1h,得到药材粉末,测得其水分含量为2.6%。
2)将上述药材粉末采用其5倍量、80%(V/V)的乙醇回流提取2次,每次1.5h,得到提取液;
3)将上述提取液浓缩至50℃时的相对密度为1.1,得到浸膏;
4)将上述浸膏用其5倍量的纯化水,在4℃的温度下水沉12h,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入80%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用30%(V/V)的乙醇洗脱除杂,再用75%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.1,在70℃的温度下,用80%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在10℃的温度下,加入10%(V/V)乙醇洗涤,得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物6。
实施例7:按照如下方法制备大麻二酚
1)将工业大麻的花叶粉碎,过40目筛,在120℃的温度下烘干1h,得到药材粉末,测得其水分含量为2.6%。
2)将上述药材粉末采用其5倍量、80%(V/V)的乙醇浸泡提取2次,每次2.5h,得到提取液;
3)将上述提取液浓缩至50℃时的相对密度为1.1,得到浸膏;
4)将上述浸膏用其5倍量的纯化水,在4℃的温度下水沉12h,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入80%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用30%(V/V)的乙醇洗脱除杂,再用75%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.1,在70℃的温度
下,用80%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在10℃的温度下,加入10%(V/V)乙醇洗脱,得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物7。
实施例8:按照如下方法制备大麻二酚
1)将工业大麻的根粉碎,过10目筛,在120℃的温度下烘干1h,得到药材粉末,测得其水分含量为1.2%。
2)将上述药材粉末采用其8倍量、80%(V/V)的乙醇浸泡提取2次,每次3h,得到提取液;
3)将上述提取液浓缩至50℃时的相对密度为1.1,得到浸膏;
4)将上述浸膏用其10倍量的纯化水,在4℃的温度下水沉24h,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入80%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用30%(V/V)的乙醇洗脱除杂,再用75%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.1,在70℃的温度下,用80%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在10℃的温度下,加入10%(V/V)乙醇洗脱,得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物8。
实施例9:按照如下方法制备大麻二酚
1)将工业大麻的秆芯粉碎,过40目筛,在120℃的温度下烘干1h,得到药材粉末,测得其水分含量为1.8%。
2)将上述药材粉末采用其5倍量、80%(V/V)的乙醇回流提取2次,每次
1.5h,得到提取液;
3)将上述提取液浓缩至50℃时的相对密度为1.1,得到浸膏;
4)将上述浸膏用其5倍量的纯化水,在4℃的温度下水沉12h,得到水沉液;
5)将上述水沉液离心,转速5000转,在离心获得的沉淀中加入80%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用30%(V/V)的乙醇洗脱除杂,再用75%(V/V)的乙醇洗脱获得目标产物部分,最后用95%(V/V)的乙醇洗脱以使层析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.1,在70℃的温度下,用80%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在10℃的温度下,加入10%(V/V)乙醇洗涤,得到初品;
9)将步骤8)所述初品真空干燥,即得大麻二酚;
10)汽流粉碎步骤9)所得大麻二酚,即得产物9。
实施例10:按照如下方法制备大麻二酚
1)将工业大麻的花、叶、籽粕粉碎,过10目筛,在200℃的温度下烘干0.5h,得到药材粉末,测得其水分含量为2.4%;
2)将上述药材粉末采用其2倍量、100%(V/V)的乙醇超声提取1次,每次1h,得到提取液;
3)将上述提取液浓缩至50℃时测量的相对密度为1.35,得到浸膏;
4)将上述浸膏用其10倍量的纯化水,在0℃的温度下水沉48h,去除杂质,得到水沉液;
5)将上述水沉液离心,转速10000转,在离心获得的沉淀中加入10%(V/V)乙醇溶解,得到沉淀物的醇溶液;
6)将沉淀物的醇溶液进行柱层析,其层析柱的填料为MCI树脂,脱溶剂为乙醇和水,洗脱的步骤包括:先用10%(V/V)的乙醇洗脱除杂,再用40%(V/V)的乙醇洗脱获得目标产物部分,最后用90%(V/V)的乙醇洗脱以使层
析柱再生;
7)浓缩步骤6)得到的洗脱液至50℃时的相对密度为1.25,在80℃的温度下,用60%(V/V)乙醇过饱和溶解,获得结晶物;
8)将步骤7)所述结晶物,在24℃的温度下,加入5%(V/V)乙醇洗涤,得到初品;
9)将步骤8)所述初品用纯化水混匀,冷冻干燥,即得大麻二酚;
10)冷冻粉碎步骤9)所得大麻二酚,即得产物10。
对比实施例1:按照如下方法制备大麻二酚
1)采用盛花期的花叶,将其投入烘烤设备内,130℃烘干35min;
2)把烘干的花叶进行磨碎,粒径达到5-10目之间;
3)把磨好的花叶装入浸泡器内进行浸泡,浸泡溶剂采用石油醚,浸泡温度48℃,浸泡时间1h;
4)浸泡后,将花叶滤出,滤液在90℃下加热,得到浸膏;
5)层析分离:把吸附齐称量后装入层析分离器内;将浸膏均匀地放在吸附剂表面吸附CBD,吸附剂与浸膏按重量比25:1;采用石油醚进行洗脱,干燥即得对比产物1。
对比实施例2:按照如下方法制备大麻二酚
1)采用盛花期的大麻花叶,将其投入烘烤设备内,160℃烘干15min;
2)把烘干的花叶进行磨碎,粒径达到5-10目之间;
3)把磨好的花叶装入浸泡器内进行浸泡,浸泡溶剂采用正己烷,浸泡温度20℃,浸泡时间2h;
4)浸泡后,将花叶滤出,滤液在120℃下加热,得到浸膏;
5)层析分离:把吸附剂大孔树脂称量后装入层析分离器内;吸附剂与浸膏以1:1比例混匀吸附CBD;采用正己烷进行洗脱,干燥即得对比产物2。
实验实施例1:不同制法所得产物中CBD含量及四氢大麻酚的检出情况对比
检测方法:
色谱条件与系统适用性试验 以十八烷基硅烷键合硅胶为填充剂;以乙腈为流动相A,以水为流动相B,按A(%):B(%)=80:20进行等度洗脱;检测
波长为210nm。理论板数按CBD峰计算应不低于2500。
对照品溶液的制备 精密称取CBD对照品,加甲醇(1:1)制成每1ml各含0.1mg的对照品溶液,即得;精密称取四氢大麻酚对照品,加甲醇(1:1)制成每1ml各含0.01mg的对照品溶液,即得。
供试品溶液的制备 取本品约25mg,精密称定,置25ml量瓶中,加乙腈-水(1:1)20ml,超声处理15分钟,加乙腈-水(1:1)稀释至刻度,摇匀,用微孔滤膜(0.45μm)滤过,取续滤液,即得。
测定法 分别精密吸取对照品溶液与供试品溶液各10μl,注入液相色谱仪,测定,即得。
按照实施例1-7和对比实施例1-2制备得到的产物的CBD含量及四氢大麻酚含量检测结果参见表1及附图1至附图9。
表1.不同制法所得产物其CBD含量及THC检出情况对比
由表1和图1至图9可知,通过本发明的方法制备得到的产物1、2、3、4、5、6、7中CBD(大麻二酚)的含量明显高于现有技术制备所得CBD(对比产物1和对比产物2)的含量;采用本发明所述的技术其产物中无THC(四氢大麻酚)检出,而采用现有技术制备所得的产物中明显检出THC。进一步说明,采用本发明提取出来的CBD含量更高,纯度更纯,更安全,符合法规对产品的相关要求。
实验实施例2:不同提取方法对CBD提取率影响的比较
(1)原花叶药材含量检测方法
色谱条件与系统适用性试验 以十八烷基硅烷键合硅胶为填充剂;以乙腈为流动相A,以水为流动相B,按A(%):B(%)=80:20进行等度洗脱;检测波长为210nm。理论板数按CBD峰计算应不低于2500。
对照品溶液的制备 精密称取CBD对照品,加甲醇(1:1)制成每1ml各含0.1mg的对照品溶液,即得;精密称取四氢大麻酚对照品,加甲醇(1:1)制成每1ml各含0.01mg的对照品溶液,即得。
供试品溶液的制备 取本品约1g,精密称定,加甲醇25ml,超声处理15分钟,过滤,再加甲醇25ml,超声处理15分钟,合并滤液,定容至50ml,摇匀,用微孔滤膜(0.45μm)滤过,取续滤液,即得。
测定法 分别精密吸取对照品溶液与供试品溶液各10μl,注入液相色谱仪,测定,即得。
(2)提取液含量检测方法
色谱条件与系统适用性试验 以十八烷基硅烷键合硅胶为填充剂;以乙腈为流动相A,以水为流动相B,按A(%):B(%)=80:20进行等度洗脱;检测波长为210nm。理论板数按CBD峰计算应不低于2500。
对照品溶液的制备 精密称取CBD对照品,加甲醇(1:1)制成每1ml各含0.1mg的对照品溶液,即得;精密称取四氢大麻酚对照品,加甲醇(1:1)制成每1ml各含0.01mg的对照品溶液,即得。
供试品溶液的制备 提取液1ml,定容至25ml,用微孔滤膜(0.45μm)滤过,取续滤液,即得。
测定法 分别精密吸取对照品溶液与供试品溶液各10μl,注入液相色谱仪,测定,即得。
采用实施例5-7中的三种方法,即超声提取、回流提取和浸泡提取,得到步骤(2)中所述的提取液作为供试品溶液。具体提取率的实验结果见下表2。
表2.三种提取方法提取率试验(以CBD含量为指标)
由上表2可知,三种提取方法提取效率相当,提取方法的改变对提取率没有影响。在其它技术参数相同的条件下,利用浸泡提取所得产物7中CBD(大麻二酚)的含量与利用超声提取所得产物5中CBD(大麻二酚)的含量无明显差别。进一步说明,本发明的有益效果并非是由于仅是引入了超声提取这一工艺技术导致的。
实验实施例3:不同提取部位所得产物中CBD含量及四氢大麻酚的检出情况对比
检测方法同实验实施例1,对实施例8-10制备得到的产物的CBD含量及四氢大麻酚含量检测结果参见表3。
表3.不同提取部位所得产物其CBD含量及THC检出情况对比
由表3可知,本发明的方法同样适用于大麻根、秆芯以及花、叶、籽粕提取得到CBD,并且产物中均无THC(四氢大麻酚)检出。
实验实施例4:采用稳定性试验方法检测不同制法所得产物的稳定性
主要仪器:
药品稳定性试验箱(长期):SHH-250SD,重庆永生实验仪器厂;
药品稳定性试验箱(加速):SHH-250SD,重庆永生实验仪器厂;
高效液相色谱仪:Agilent1200;
分析天平:MS-105DU,瑞士梅特勒-托利多;
紫外可见分光光度计:UV-2550,日本岛津;
薄层色谱成像仪:TLC Visualizer,瑞士卡玛;
试验样品:
将按照上述各实施例和对比例的方法制备的样品分别进行加速稳定性试验,检测结果如表4至表12所示。
表4.产物1稳定性试验
表5.产物2稳定性试验
表6.产物3稳定性试验
表7.产物4稳定性试验
表8.产物5稳定性试验
表9.产物6稳定性试验
表10.产物7稳定性试验
表11.对比产物1稳定性试验
表12.对比产物2稳定性试验
由表4-12可知,通过本发明的实施例1-实施例7的方法制备得到的产物1-7中CBD(大麻二酚)的含量经6个月加速稳定性试验放置,稳定性良好,CBD的含量变化范围仅为0.6%以内(其中,存放3个月、2个月以及1个月后CBD含量的变化最高的也仅为0.6%)。而采用对比实施例方法制得对比产物1和对比产物2经6个月加速稳定性试验放置后CBD的含量分别从83.1%降到73.8%(下降率为9.3%),从81.2%降到69.1%(下降率为12.1%),稳定性较差;对比产物1和对比产物2经3个月的稳定性试验中,含量下降率分别为7.1%和10.1%,同样,稳定性显著差于用本发明方法制备得到产物。
从以上的描述中,可以看出,本发明上述的实施例实现了如下技术效果:1)通过增加结晶步骤,使终产品中大麻二酚(CBD)含量提高至96%以上。2)通过对工艺技术的改进,使成品中四氢大麻酚含量控制在0.3%以下(在实施例1-实施例7中,四氢大麻酚均未检出),符合国家法律法规要求,产品安全性得到保障。3)初步精制步骤中使用大孔树脂、MCI树脂或ODS代替现有技术中的硅胶,使得填料可重复利用,使总体生产成本降低,减少废弃物硅胶对环境的污染。4)采用乙醇和水作为提取溶剂,溶剂安全,对环境、操作人员危害小,产品溶剂残留大大改善;柱层析过程中采用不同纯度乙醇洗脱树脂柱,减少对环境污染,减少人员伤害。
另外,经实验室规模实验验证和中试放大验证,按照本发明所述工艺能生产出纯度高(含量95%)以上,安全(THC含量0.3%以下)产品。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,
所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。本发明的保护范围由所附的权利要求书限定,并且涵盖了权利要求的等同变换。
Claims (15)
- 一种从大麻中提取大麻二酚的方法,其特征在于,包括以下步骤:1)将大麻的提取部位粉碎、烘干,得到药材粉末;2)将所述药材粉末采用30-100%(V/V)的乙醇提取,得到提取液;3)将所述提取液浓缩,得到浸膏;4)将所述浸膏进行水沉,去除杂质,得到水沉液;5)将所述水沉液离心,在离心获得的沉淀中加入10-100%(V/V)乙醇溶解,得到沉淀物的醇溶液;6)将所述沉淀物的醇溶液进行柱层析;7)浓缩步骤6)得到的洗脱液,加入乙醇过饱和溶解,获得结晶物;8)将所述结晶物加入纯化水或乙醇洗涤,得到初品;9)将步骤8)所述初品用纯化水混匀,干燥,即得大麻二酚。
- 根据权利要求1所述的方法,其特征在于,所述步骤1)中大麻提取部位粉碎后烘干,包括在60-200℃温度条件下,烘干0.5-3h,至水分5%以下。
- 根据权利要求1所述的方法,其特征在于,所述步骤1)中大麻提取部位粉碎至10-80目。
- 根据权利要求1所述的方法,其特征在于,所述步骤2)的提取方式包括回流提取、超声提取和/或浸泡提取:所述的回流提取包括:采用2-8倍药材量的乙醇进行回流提取1-3次,每次0.5-3h;所述的超声提取包括:采用2-8倍药材量的乙醇进行超声提取1-3次,每次0.1-1h;所述的浸泡提取包括:采用2-8倍药材量的乙醇进行浸泡提取1-3次,每次0.5-5h。
- 根据权利要求1所述的方法,其特征在于,所述步骤3)具体包括:将提取液浓缩至50℃时测量,相对密度1.05-1.35。
- 根据权利要求1所述的方法,其特征在于,所述步骤4)具体包括:采用其1-10倍药材量的纯化水,在0-20℃的温度条件下,水沉1-48h。
- 根据权利要求1所述的方法,其特征在于,所述步骤6)中,将所述沉淀物的醇溶液进行柱层析的步骤包括:采用洗脱溶剂对层析柱进行梯度洗脱,所述梯 度洗脱的步骤包括:先用0-30%(V/V)的乙醇除杂,再用40-80%(V/V)的乙醇洗脱。
- 根据权利要求1或7所述的方法,其特征在于,所述柱层析的步骤中,所用的层析柱的填料包括大孔树脂、MCI树脂、十八烷基硅烷键合硅胶中的一种或多种。
- 根据权利要求8所述的方法,其特征在于,所述大孔树脂包括AB-8、D-101、XDA-8、LSA-7、D-941、DM-130、ADS-17、SP-825和HPD-600中的一种或多种。
- 根据权利要求1所述的方法,其特征在于,所述步骤7),包括在10-80℃温度条件下,用60-100%(V/V)乙醇过饱和溶解,获得所述结晶物。
- 根据权利要求1所述的方法,其特征在于,所述步骤8),包括在0-24℃温度条件下,加纯化水或5-40%(V/V)乙醇洗涤,得到所述初品。
- 根据权利要求1所述的方法,其特征在于,所述步骤9)中,干燥的方式包括喷雾干燥、真空干燥、冷冻干燥、近红外干燥以及微波干燥中的一种或多种,干燥温度不超过65℃。
- 根据权利要求1所述的方法,其特征在于,所述步骤9)后,进一步包括将获得的所述大麻二酚粉碎成粉的步骤,优选粉碎的方式包括汽流粉碎和/或冷冻粉碎,进一步优选粉碎时物料温度不超过65℃。
- 根据权利要求1所述的方法,其特征在于,所述的步骤1)中提取部位选自大麻花、大麻叶、大麻根、大麻秆芯和大麻籽粕中的一种或两种以上的组合。
- 根据权利要求14所述的方法,其特征在于,所述的步骤1)中提取部位选自大麻花、大麻叶。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/781,795 US10301242B2 (en) | 2016-08-16 | 2017-01-21 | Method for extracting cannabidiol from cannabis |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610674119.6 | 2016-08-16 | ||
CN201610674119.6A CN106278828A (zh) | 2016-08-16 | 2016-08-16 | 一种从工业大麻花叶中提取大麻二酚的方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2018032727A1 true WO2018032727A1 (zh) | 2018-02-22 |
Family
ID=57678143
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2017/071993 WO2018032727A1 (zh) | 2016-08-16 | 2017-01-21 | 一种从大麻中提取大麻二酚的方法 |
Country Status (3)
Country | Link |
---|---|
US (1) | US10301242B2 (zh) |
CN (2) | CN106278828A (zh) |
WO (1) | WO2018032727A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020119001A1 (zh) * | 2018-12-14 | 2020-06-18 | 香港同盛实业有限公司 | 一种利用高速逆流色谱分离纯化制备大麻二酚的方法 |
CN115260005A (zh) * | 2022-08-30 | 2022-11-01 | 晨光生物科技集团股份有限公司 | 一种纯化提取大麻二酚的方法与应用 |
Families Citing this family (98)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106278828A (zh) * | 2016-08-16 | 2017-01-04 | 云南汉素生物科技有限公司 | 一种从工业大麻花叶中提取大麻二酚的方法 |
US10239808B1 (en) | 2016-12-07 | 2019-03-26 | Canopy Holdings, LLC | Cannabis extracts |
CN107011125B (zh) * | 2017-05-06 | 2020-07-28 | 云南汉木森生物科技有限责任公司 | 一种富集大麻二酚的方法 |
US10189762B1 (en) | 2017-07-07 | 2019-01-29 | Orochem Technologies, Inc. | Process for purification and separation of cannabinoids, from dried hemp and cannabis leaves |
IT201700085508A1 (it) * | 2017-07-26 | 2019-01-26 | Inalco S R L | Metodo per la produzione di cannabinoidi da varietà di canapa industriale |
CN107227198A (zh) * | 2017-07-28 | 2017-10-03 | 云南汉木森生物科技有限责任公司 | 高提取率的大麻花叶油提取方法及其大麻花叶油 |
CN107382672A (zh) * | 2017-07-28 | 2017-11-24 | 云南汉木森生物科技有限责任公司 | 利用超临界二氧化碳萃取大麻二酚的方法及其大麻二酚产品 |
CN107325881A (zh) * | 2017-07-28 | 2017-11-07 | 云南汉木森生物科技有限责任公司 | 大麻花叶油的萃取方法及其大麻花叶油产品 |
CN107344908A (zh) * | 2017-07-28 | 2017-11-14 | 云南汉木森生物科技有限责任公司 | 大麻二酚的萃取方法及其大麻二酚产品 |
US10561693B2 (en) * | 2017-09-01 | 2020-02-18 | MariJ Pharmaceuticals, Inc. | Cultivation, processing, and synthesis of cannabidiols |
CN109574810B (zh) * | 2017-09-29 | 2021-11-09 | 汉义生物科技(北京)有限公司 | 一种同时提取cbd和cbdv的方法 |
CN109568389B (zh) * | 2017-09-29 | 2022-02-08 | 汉义生物科技(北京)有限公司 | 一种高纯大麻酚类提取物的制备方法 |
US9987567B1 (en) * | 2017-09-29 | 2018-06-05 | NextLeaf Solutions Ltd. | Cannabinoid extraction process and system |
CN107898826A (zh) * | 2017-11-01 | 2018-04-13 | 云南谷益美农业开发有限公司 | 含大麻二酚的火麻浸膏的制备方法 |
CN107997882A (zh) * | 2017-12-07 | 2018-05-08 | 云南汉木森生物科技有限责任公司 | 一种具有抗菌消炎、止痛功效的卫生巾及其制作方法 |
CN108078965A (zh) * | 2017-12-26 | 2018-05-29 | 云南汉木森生物科技有限责任公司 | 一种用于戒毒的药物及其制备方法 |
CN108083989B (zh) | 2018-01-10 | 2021-04-16 | 烟台汉麻生物技术有限公司 | 一种高纯度大麻二酚的制备方法 |
CN108272124B (zh) * | 2018-01-24 | 2020-10-23 | 四川中烟工业有限责任公司 | 一种近红外加热干燥烟丝的方法 |
CA3089994A1 (en) | 2018-01-31 | 2019-08-08 | Canopy Holdings, LLC | Hemp powder |
CN108314608B (zh) * | 2018-02-05 | 2020-11-03 | 昆明医科大学第一附属医院 | 一种大麻二酚的提取分离方法 |
US10851077B2 (en) | 2018-02-07 | 2020-12-01 | World Class Extractions Inc. | Method for extracting compositions from plants |
GB2587918B (en) * | 2018-03-07 | 2023-10-11 | Cleen Tech Inc | Continuous isolation of cannabidiol |
US11851415B2 (en) | 2018-03-07 | 2023-12-26 | Cleen Technology Inc. | Continuous isolation of cannabidiol and cannabinoids and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol |
US11192870B2 (en) | 2018-03-07 | 2021-12-07 | Socati Technologies—Oregon, Llc | Continuous isolation of cannabidiol and conversion of cannabidiol to delta 8-tetrahydrocannabinol and delta 9-tetrahydrocannabinol |
CN108433880A (zh) * | 2018-03-19 | 2018-08-24 | 烟台汉麻生物技术有限公司 | 一种汉麻卫生巾 |
CN108640820A (zh) * | 2018-04-13 | 2018-10-12 | 昆明拜欧生物科技有限公司 | 一种大麻二酚的制备方法 |
CN110407672A (zh) * | 2018-04-28 | 2019-11-05 | 上海弗华机电设备有限公司 | 一种熔融结晶在医用大麻提取大麻二酚中脱蜡工艺的应用方法 |
CN108379347A (zh) * | 2018-05-03 | 2018-08-10 | 云南汉木森生物科技有限责任公司 | 一种大麻花叶消炎止痛油膏及其制备方法 |
US10695316B2 (en) * | 2018-07-03 | 2020-06-30 | Virgil Macaluso | Methods of heating cannabis plant material |
WO2020028198A1 (en) | 2018-08-03 | 2020-02-06 | Biomass Oil Separation Solutions, Llc | Processes and apparatus for extraction of substances and enriched extracts from plant material |
US10570350B1 (en) | 2018-08-17 | 2020-02-25 | Evello International, LLC | Systems and methods of cannabis oil extraction |
US10688410B2 (en) | 2018-08-17 | 2020-06-23 | Evello International, LLC | Systems and methods of cannabis oil extraction |
CN109053388A (zh) * | 2018-08-20 | 2018-12-21 | 上海昶健生物科技有限公司 | 一种提取大麻二酚的方法 |
CA3119729A1 (en) | 2018-10-10 | 2020-04-16 | Treehouse Biotech, Inc. | Synthesis of cannabigerol |
CN109725080A (zh) * | 2019-01-02 | 2019-05-07 | 中国农业科学院麻类研究所 | 大麻二酚、大麻二酚酸、四氢大麻酚中一种或几种物质的定性定量检测方法 |
CN109734560A (zh) * | 2019-02-28 | 2019-05-10 | 西藏育宁生物科技有限责任公司 | 一种大麻二酚提取物及其制备方法 |
CN109700789A (zh) * | 2019-02-28 | 2019-05-03 | 西藏育宁生物科技有限责任公司 | 一种大麻二酚提取物的用途 |
CN109796311A (zh) * | 2019-03-25 | 2019-05-24 | 黑龙江阳光工业大麻研究院 | 一种从废弃试剂中提纯大麻二酚的方法 |
CN111849606B (zh) * | 2019-04-30 | 2021-05-11 | 云南汉盟制药有限公司 | 大麻油的制备方法及其制备的大麻油 |
CN111848364B (zh) * | 2019-04-30 | 2021-04-02 | 云南汉盟制药有限公司 | 从大麻中提取大麻二酚的方法 |
CN111848357A (zh) * | 2019-04-30 | 2020-10-30 | 黑龙江阳光工业大麻研究院 | 一种超高液相色谱法制备高纯度大麻二酚的方法 |
CN111848358A (zh) * | 2019-04-30 | 2020-10-30 | 黑龙江阳光工业大麻研究院 | 一种大孔树脂富集结合动态轴向压缩柱系统制备高纯度大麻二酚的方法 |
CN110055753A (zh) * | 2019-05-15 | 2019-07-26 | 中国农业科学院麻类研究所 | 一种纳米抗菌麻类纤维及其制备方法和应用 |
CN110133148A (zh) * | 2019-05-30 | 2019-08-16 | 汉义生物科技(北京)有限公司 | 一种大麻hplc指纹图谱测定方法 |
CN110123876A (zh) | 2019-05-30 | 2019-08-16 | 汉义生物科技(北京)有限公司 | 一种含有非精神活性大麻素的包合物及其制备方法 |
CN110041172A (zh) * | 2019-06-05 | 2019-07-23 | 云南绿新生物药业有限公司 | 一种利用微生物处理大麻花叶提高大麻二酚提取率的工艺 |
CN110251987B (zh) * | 2019-06-19 | 2020-12-18 | 中国农业科学院麻类研究所 | 一种提高大麻二酚含量的提取方法 |
CN110143854A (zh) * | 2019-06-23 | 2019-08-20 | 云南丰圣生物科技有限公司 | 一种同时提取cbd和cbdv的方法 |
CN111960926B (zh) * | 2019-06-28 | 2022-03-25 | 云南翰谷生物科技有限公司 | 大麻二酚晶体的制备方法 |
CN110143855A (zh) * | 2019-07-02 | 2019-08-20 | 黑龙江康源生物科技有限公司 | 一种工业大麻中大麻二酚的分离纯化方法 |
CN110229047A (zh) * | 2019-07-12 | 2019-09-13 | 李卫 | 一种大麻二酚的制备设备 |
CN110386860B (zh) * | 2019-07-17 | 2022-08-02 | 李卫 | 一种大麻二酚的高效提取方法 |
WO2021012044A1 (en) | 2019-07-22 | 2021-01-28 | Canopy Growth Corporation | Continuous crystallization of cannabinoids in a stirred-tank reactor |
CN110330409B (zh) * | 2019-07-24 | 2022-04-19 | 汉义生物科技(北京)有限公司 | 一种工业大麻提取物的制备方法 |
US10799546B1 (en) | 2019-07-26 | 2020-10-13 | Biomass Oil Separation Solutions, Llc | Modular, integrated process and apparatus for extracting, refining and remediating active substances from plant material |
CN110563560A (zh) * | 2019-08-13 | 2019-12-13 | 云南辰锦威生物科技有限公司 | 一种超低温冷冻干燥汉麻花叶的方法 |
CN110511119A (zh) * | 2019-08-13 | 2019-11-29 | 云南飞久逍科技有限公司 | 一种大麻二酚的提取方法 |
CN110563558B (zh) * | 2019-08-13 | 2023-06-27 | 云南辰锦威生物科技有限公司 | 一种超低温二次冻融分离纯化大麻二酚cbd单体的方法 |
CN110423187A (zh) * | 2019-08-22 | 2019-11-08 | 哈尔滨工业大学 | 一种隧道超声与热循环蒸馏联用萃取大麻二酚(cbd)方法 |
CN110642679B (zh) * | 2019-08-27 | 2022-07-22 | 桂林莱茵生物科技股份有限公司 | 一种制备大麻二酚联产大麻全谱油的方法 |
KR102277523B1 (ko) | 2019-10-04 | 2021-07-14 | 한국과학기술연구원 | 칸나비스 식물로부터 칸나비디올을 연속으로 제조하는 방법 및 그 용도 |
CN110746275A (zh) * | 2019-11-08 | 2020-02-04 | 河南汉麻生物科技有限公司 | 一种利用连续色谱系统分离大麻二酚的方法 |
US10946306B1 (en) | 2019-11-27 | 2021-03-16 | World Class Extractions Inc. | Solvent-based extraction methods |
CN110819435A (zh) * | 2019-11-27 | 2020-02-21 | 安徽香博士芳香技术研究院有限公司 | 一种基于cbd烟油的提取方法 |
CN111018675A (zh) * | 2019-12-10 | 2020-04-17 | 云南罗瑞生物科技有限公司 | 一种高效增量提取大麻二酚的方法 |
CN113009049A (zh) * | 2019-12-20 | 2021-06-22 | 浙江华谱新创科技有限公司 | 一种全谱大麻提取物油中thc的脱除工艺 |
WO2021161147A1 (en) | 2020-02-10 | 2021-08-19 | Cibid A/S | A method of extraction for plants belonging to the cannabaceae family |
CN111253221B (zh) * | 2020-02-21 | 2021-09-24 | 南京大学 | 一种大麻二酚分离纯化的方法 |
CN111807932A (zh) * | 2020-03-20 | 2020-10-23 | 浙江双子智能装备有限公司 | 一种从大麻中提取纯化大麻二酚的方法 |
CN111574332A (zh) * | 2020-04-14 | 2020-08-25 | 周宇平 | 一种用于提纯大麻二酚的结晶工艺 |
CN111763189A (zh) * | 2020-04-20 | 2020-10-13 | 云南古润生物科技有限责任公司 | 一种从工业大麻中分离纯化大麻酚的方法 |
CN111470953B (zh) * | 2020-04-24 | 2023-04-07 | 西安蓝晓科技新材料股份有限公司 | 从低含量工业大麻花叶中提取分离高纯度大麻二酚的方法 |
CN111302901A (zh) * | 2020-04-26 | 2020-06-19 | 江苏汉邦科技有限公司 | 一种利用大孔树脂层析技术制备高纯度大麻二酚的方法 |
CN111704529A (zh) * | 2020-06-16 | 2020-09-25 | 浙江寿仙谷医药股份有限公司 | 分离提取大麻二酚的方法 |
CN113801003B (zh) * | 2020-06-16 | 2023-09-15 | 晨光生物科技集团股份有限公司 | 一种大麻二酚的工业化提取方法 |
CN111747826A (zh) * | 2020-06-25 | 2020-10-09 | 黑龙江纳贝斯抗冠素生物科技有限公司 | 一种超声波逆流提取大麻二酚的方法 |
CN112167636A (zh) * | 2020-06-29 | 2021-01-05 | 武汉林宝莱生物科技有限公司 | 一种大麻二酚与虾青素软胶囊及其制备方法 |
CN112168864A (zh) * | 2020-06-29 | 2021-01-05 | 武汉林宝莱生物科技有限公司 | 一种大麻二酚与nmn制剂配方及其制备方法 |
CN112010738B (zh) * | 2020-08-05 | 2023-07-07 | 晨光生物科技集团股份有限公司 | 一种利用色谱分离生产大麻素化合物的工业化方法 |
CN112062658A (zh) * | 2020-08-21 | 2020-12-11 | 滇麻生物科技(曲靖)有限公司 | 一种从工业大麻中同时制备cbg、cbdv、cbd、thcv的方法 |
CN112011399A (zh) * | 2020-08-21 | 2020-12-01 | 滇麻生物科技(曲靖)有限公司 | 一种从工业大麻中制备多酚树脂油的方法 |
CN114380666B (zh) * | 2020-10-19 | 2024-01-26 | 腾冲晨光云麻生物科技有限公司 | 一种大麻二酚的工业化提取方法 |
CN112137935B (zh) * | 2020-10-26 | 2022-09-23 | 苏州唐基生物科技有限公司 | 一种组合物及其用途 |
CN112479830A (zh) * | 2020-12-14 | 2021-03-12 | 哈尔滨市产品质量监督检验院 | 从大麻花叶中提取纯化次大麻二酚和大麻二酚的方法 |
CN112939743A (zh) * | 2021-02-06 | 2021-06-11 | 广州贝塔健康生物科技有限公司 | 一种大麻二酚提取物的制备方法及其在化妆品中的应用 |
US11986833B2 (en) | 2021-02-08 | 2024-05-21 | Laurie Cantrell | Hemp flower material stripping machine and method |
CN112939744A (zh) * | 2021-03-01 | 2021-06-11 | 云南瀚通生物科技有限公司 | 一种大麻二酚的高效提取方法 |
CN112961036A (zh) * | 2021-03-01 | 2021-06-15 | 云南瀚通生物科技有限公司 | 一种高纯度大麻二酚的提取纯化方法 |
WO2022197511A1 (en) | 2021-03-19 | 2022-09-22 | W.R. Grace & Co.-Conn. | Stationary phase for purification of cannabidiol with high-performance liquid chromatography |
CN113136728A (zh) * | 2021-04-22 | 2021-07-20 | 无锡万斯家居科技股份有限公司 | 一种将大麻二酚提取物应用到家纺面料的方法 |
CN115504862B (zh) * | 2021-06-07 | 2024-07-05 | 南通新世元生物科技有限公司 | 一种大麻萜酚的制备方法 |
CN115504864A (zh) * | 2021-06-07 | 2022-12-23 | 南通新世元生物科技有限公司 | 从工业大麻中获取高纯度大麻二酚的方法 |
CN113511958A (zh) * | 2021-07-29 | 2021-10-19 | 云南巨漳生物科技有限公司 | 一种从工业大麻叶子中提取大麻二酚的方法 |
CN113730952B (zh) * | 2021-08-24 | 2022-09-06 | 浙江双子智能装备有限公司 | 一种工业大麻有效成分提取方法 |
US11779621B2 (en) | 2021-12-17 | 2023-10-10 | Jeff Braile | System and method for aerobic respiratory treatment |
IT202200006770A1 (it) * | 2022-04-06 | 2023-10-06 | S A L A R S Soc Azionaria Laboratori Alcaloidi Rifornimenti Sanitari S P A | Processo per l’estrazione di cannabinoidi di elevata purezza |
CN115028517A (zh) * | 2022-06-30 | 2022-09-09 | 黑龙江省科学院高技术研究院 | 一种大麻二酚的特异性分离工艺 |
CN115724724A (zh) * | 2022-11-23 | 2023-03-03 | 黑龙江省科学院大庆分院 | 一种动态轴向压缩柱纯化系统洗脱液结晶制备高纯大麻二酚的方法 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6403126B1 (en) * | 1999-05-26 | 2002-06-11 | Websar Innovations Inc. | Cannabinoid extraction method |
US20060167283A1 (en) * | 2002-09-23 | 2006-07-27 | Ian Flockhart | Method of preparing cannabidiol from plant material |
CN103739585A (zh) * | 2014-02-17 | 2014-04-23 | 辛荣昆 | 从工业大麻中提取二氢大麻酚(cbd)工艺 |
CN104277917A (zh) * | 2014-10-24 | 2015-01-14 | 汉康(云南)生物科技有限公司 | 一种富含大麻二酚的工业大麻精油提取方法及其提取设备 |
CN105505565A (zh) * | 2015-12-28 | 2016-04-20 | 贵州航天乌江机电设备有限责任公司 | 一种萃取富含大麻二酚的工业大麻油的方法 |
CN106278828A (zh) * | 2016-08-16 | 2017-01-04 | 云南汉素生物科技有限公司 | 一种从工业大麻花叶中提取大麻二酚的方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1536810B1 (en) * | 2002-08-14 | 2012-08-01 | GW Pharma Limited | Extraction of pharmaceutically active cannabinoids from plant materials |
CN105535111B (zh) * | 2016-02-16 | 2019-06-28 | 山西汉麻生物科技有限公司 | 一种富含大麻二酚的火麻浸膏及其制备方法 |
-
2016
- 2016-08-16 CN CN201610674119.6A patent/CN106278828A/zh active Pending
-
2017
- 2017-01-20 CN CN201710049805.9A patent/CN106831353B/zh active Active
- 2017-01-21 WO PCT/CN2017/071993 patent/WO2018032727A1/zh active Application Filing
- 2017-01-21 US US15/781,795 patent/US10301242B2/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6403126B1 (en) * | 1999-05-26 | 2002-06-11 | Websar Innovations Inc. | Cannabinoid extraction method |
US20060167283A1 (en) * | 2002-09-23 | 2006-07-27 | Ian Flockhart | Method of preparing cannabidiol from plant material |
CN103739585A (zh) * | 2014-02-17 | 2014-04-23 | 辛荣昆 | 从工业大麻中提取二氢大麻酚(cbd)工艺 |
CN104277917A (zh) * | 2014-10-24 | 2015-01-14 | 汉康(云南)生物科技有限公司 | 一种富含大麻二酚的工业大麻精油提取方法及其提取设备 |
CN105505565A (zh) * | 2015-12-28 | 2016-04-20 | 贵州航天乌江机电设备有限责任公司 | 一种萃取富含大麻二酚的工业大麻油的方法 |
CN106278828A (zh) * | 2016-08-16 | 2017-01-04 | 云南汉素生物科技有限公司 | 一种从工业大麻花叶中提取大麻二酚的方法 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020119001A1 (zh) * | 2018-12-14 | 2020-06-18 | 香港同盛实业有限公司 | 一种利用高速逆流色谱分离纯化制备大麻二酚的方法 |
US11267775B2 (en) | 2018-12-14 | 2022-03-08 | Techson Industry Company Limited | Method for preparing cannabidiol by separation and purification using high-speed countercurrent chromatography |
AU2019395470B2 (en) * | 2018-12-14 | 2022-09-15 | Techson Industry Technology Company Limited | Method for preparing cannabidiol by means of high-speed countercurrent chromatography separation and purification |
CN115260005A (zh) * | 2022-08-30 | 2022-11-01 | 晨光生物科技集团股份有限公司 | 一种纯化提取大麻二酚的方法与应用 |
CN115260005B (zh) * | 2022-08-30 | 2024-01-30 | 晨光生物科技集团股份有限公司 | 一种纯化提取大麻二酚的方法与应用 |
Also Published As
Publication number | Publication date |
---|---|
US10301242B2 (en) | 2019-05-28 |
CN106831353B (zh) | 2020-12-29 |
CN106278828A (zh) | 2017-01-04 |
US20180362429A1 (en) | 2018-12-20 |
CN106831353A (zh) | 2017-06-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2018032727A1 (zh) | 一种从大麻中提取大麻二酚的方法 | |
CN110304994B (zh) | 一种从工业大麻中提取高纯度大麻二酚的方法 | |
CN101597296B (zh) | 一种离子液体高效提取生产青蒿素的新方法 | |
CN110283048A (zh) | 大麻二酚晶体的制备方法 | |
CN100469774C (zh) | 一种银杏叶提取物及该提取物高纯度有效成分的分离生产方法 | |
CN111807932A (zh) | 一种从大麻中提取纯化大麻二酚的方法 | |
CN101824018B (zh) | 一种二氢杨梅素的纯化方法 | |
CN111960930A (zh) | 一种从工业大麻花叶中分离纯化大麻二酚的方法 | |
WO2020015316A1 (zh) | 辅酶q10的提取纯化方法及由其制备的辅酶q10 | |
CN101921277B (zh) | 一种从骆驼蓬中同时制备鸭嘴花碱和鸭嘴花酮碱的方法 | |
CN111039914A (zh) | 一种大麻酚的提取分离方法 | |
CN112661612A (zh) | 一种后脱羧协同超临界萃取大规模制备高纯度cbd的方法 | |
CN101759756A (zh) | 一种从迷迭香中制备熊果酸的方法 | |
CN110878010A (zh) | 一种大麻萜酚的提取分离方法 | |
CN112939742B (zh) | 一种大麻素的提取纯化方法 | |
CN102311435A (zh) | 一种高纯度钩藤碱的制备方法 | |
CN107573255A (zh) | 一种从辣椒果实中分离纯化辣椒碱和二氢辣椒碱的方法 | |
CN109400566B (zh) | 一种从卷柏属植物中提取分离高纯度穗花杉双黄酮的方法 | |
CN105837546A (zh) | 一种从草豆蔻中分离纯化桤木酮、松属素、小豆蔻明、山姜素的方法 | |
CN102432419B (zh) | 从紫茎泽兰中提取分离β-榄香烯的方法 | |
CN108997359A (zh) | 一种从甜菊糖生产废渣中提取叶绿素的方法 | |
CN111253221B (zh) | 一种大麻二酚分离纯化的方法 | |
CN102924545A (zh) | 一种木通皂苷d的富集和纯化方法 | |
CN102078400B (zh) | 一种枇杷叶总三萜酸提取物的制备方法 | |
CN111848357A (zh) | 一种超高液相色谱法制备高纯度大麻二酚的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17840705 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 17840705 Country of ref document: EP Kind code of ref document: A1 |