Method for extracting cannabidiol from cannabis

Abstract

A method of extracting cannabidiol from hemp. The method may include the following steps: performing grinding and drying on an extraction part of the hemp to obtain crude drug powder; extracting the crude drug powder with 30-100% (V/V) ethanol to obtain an extracting solution; concentrating the extracting solution to obtain an extractum; performing water precipitation on the extractum to remove impurities, thereby obtaining a water precipitation solution; centrifuging the water precipitation solution, and adding 10-100% (V/V) ethanol to dissolve the obtained precipitate, thereby obtaining a precipitate alcohol solution; performing column chromatography on the precipitate alcohol solution; concentrating the eluate obtained by elution after column chromatography, and adding ethanol for supersaturation and dissolution to obtain a crystal; adding purified water or ethanol to wash the crystal, thereby obtaining a primary product; and uniformly mixing the primary product with purified water, and drying to obtain the cannabidiol.

Claims

1. A method of extracting cannabidiol from hemp, comprising: 1) performing grinding and drying on an extraction part of the hemp to obtain crude drug powder; 2) extracting the crude drug powder with 30-100% (V/V) ethanol to obtain an extracting solution; 3) concentrating the extracting solution to obtain an extractum; 4) performing water precipitation on the extractum to remove impurities to obtain a water precipitation solution; 5) centrifuging the water precipitation solution, and adding 10-100% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution; 6) performing column chromatography on the precipitate alcohol solution; 7) concentrating the eluate obtained in step 6), and adding ethanol for supersaturation and dissolution to obtain a crystal; 8) adding purified water or ethanol to wash the crystal, thereby obtaining a primary product; and 9) uniformly mixing the primary product in step 8) with purified water, and drying to obtain the cannabidiol.

2. The method according to claim 1, wherein the drying after grinding the extraction part of the hemp in step 1) comprises: drying for 0.5-3 h under the temperature condition of 60-200 C. until the water content is 5% or below.

3. The method according to claim 1, wherein the extraction part of the hemp in step 1) is ground to 10-80 meshes.

4. The method according to claim 1, wherein the extraction manner in step 2) comprises reflux extraction, ultrasonic extraction and/or soaking extraction: the reflux extraction includes: performing reflux extraction 1-3 times by using ethanol which is 2-8 times the amount of the crude drug powder, 0.5-3 h each time; the ultrasonic extraction includes: performing ultrasonic extraction 1-3 times by using ethanol which is 2-8 times the amount of the crude drug powder, 0.1-1 h each time; and the soaking extraction includes: performing soaking extraction 1-3 times by using ethanol which is 2-8 times the amount of the crude drug powder, 0.5-5 h each time.

5. The method according to claim 1, wherein the step 3) further comprises: concentrating the extracting solution until the relative density is measured to be 1.05-1.35 at 50 C.

6. The method according to claim 1, wherein the step 4) further comprises: performing water precipitation under the temperature condition of 0-20 C. for 1-48 h by using purified water which is 1-10 times the amount of the crude drug powder.

7. The method according to claim 1, wherein performing column chromatography on the precipitate alcohol solution in step 6) comprises: performing gradient elution on a chromatographic column by using an elution solvent; and the step of gradient elution includes: performing impurity removal by using 0-30% (V/V) ethanol first, and performing elution by using 40-80% (V/V) ethanol.

8. The method according to claim 1, wherein the step of column chromatography, a filler used in the chromatographic column includes one or more of macroporous resin, MCI resin and octadecyl silane bonded silica gel.

9. The method according to claim 8, wherein the macroporous resin comprises: one or more of AB-8, D-101, XDA-8, LSA-7, D-941, DM-130, ADS-17, SP-825 and HPD-600.

10. The method according to claim 1, wherein the step 7) further comprises: performing supersaturation and dissolution by using 60-100% (V/V) ethanol under the temperature condition of 10-80 C. to obtain the crystal.

11. The method according to claim 1, wherein the step 8) further comprises: adding purified water or 5-40% (V/V) ethanol for washing under the temperature condition of 0-24 C. to obtain the primary product.

12. The method according to claim 1, wherein the drying manner in step 9) comprises: one or more of spray drying, vacuum drying, freeze drying, near-infrared drying and microwave drying, and the drying temperature does not exceed 65 C.

13. The method according to claim 1, wherein after step 9), the method further comprises: the step of grinding the cannabidiol into powder, wherein the grinding manner includes jet grinding and/or cryogenic grinding, and the material temperature during grinding does not exceed 65 C.

14. The method according to claim 1, wherein the extraction part in step 1) is selected from one or combination of more than two of hemp flowers, hemp leaves, hemp roots, hemp stalk cores and hemp seed cakes.

15. The method according to claim 14, wherein the extraction part in step 1) is selected from hemp flowers and hemp leaves.

16. The method according to claim 1, wherein the hemp in step 1) is selected from one or combination of more than two of industrial hemp, intermediate hemp or medicinal hemp.

Description

DESCRIPTION OF DRAWINGS

(1) The accompanying drawings, which constitute a part of this application, are used to provide a further understanding of the present invention, and the exemplary embodiments of the present invention and the description thereof are used to explain the present invention and do not constitute improper limitations to the present invention. In the accompanying drawings:

(2) FIG. 1 shows a chromatogram of the product 1;

(3) FIG. 2 shows a chromatogram of the product 2;

(4) FIG. 3 shows a chromatogram of the product 3;

(5) FIG. 4 shows a chromatogram of the product 4;

(6) FIG. 5 shows a chromatogram of the product 5;

(7) FIG. 6 shows a chromatogram of the product 6;

(8) FIG. 7 shows a chromatogram of the product 7;

(9) FIG. 8 shows a chromatogram of the comparative product 1; and

(10) FIG. 9 shows a chromatogram of the comparative product 2.

DETAILED DESCRIPTION

(11) It should be noted that the embodiments in the application and the features in the embodiments can be combined with each other under the condition of no conflict. The present invention will be described in detail below with reference to the accompanying drawings and in conjunction with the embodiments.

Embodiment 1: Preparation of Cannabidiol According to the Following Method

(12) The embodiment part provides the preparation of cannabidiol under different technical parameter conditions by using the methods of the present invention. The amount of the raw material adopted in each embodiment, such as industrial hemp flowers, leaves, roots, stalk cores and/or seed cakes, is respectively 10 kg, and no further explanation is given below.

(13) 1) grinding industrial hemp flowers and leaves, sifting through an 80-mesh sieve, and drying at the temperature of 60 C. for 3 h to obtain crude drug powder, of which the water content is measured to be 4%;

(14) 2) performing reflux extraction on the crude drug powder with 30% (V/V) ethanol, which is 2 times the amount of the crude drug powder, 3 times, 0.5 h each time, to obtain an extracting solution;

(15) 3) concentrating the extracting solution until the relative density is measured to be 1.05 at 50 C., thereby obtaining an extractum;

(16) 4) performing water precipitation for the extractum at the temperature of 20 C. for 1 h by using purified water which is 1 times the amount of the extractum, so as to remove impurities, thereby obtaining a water precipitation solution;

(17) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 100% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(18) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is AB-8, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 30% (V/V) ethanol for impurity removal, performing elution with 80% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(19) 7) concentrating the eluate obtained in step 6) until the relative density is 1.15 at 50 C., and adding 100% (V/V) ethanol for supersaturation and dissolution at the temperature of 10 C. to obtain a crystal;

(20) 8) adding purified water at the temperature of 0 C. to wash the crystal in step 7), thereby obtaining a primary product;

(21) 9) uniformly mixing the primary product in step 8) with purified water, and performing vacuum drying to obtain the cannabidiol; and

(22) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 1.

Embodiment 2: Preparation of Cannabidiol According to the Following Method

(23) 1) grinding industrial hemp flowers and leaves, sifting through a 10-mesh sieve to obtain crude drug powder, and drying at the temperature of 200 C. for 0.5 h to obtain crude drug powder, of which the water content is measured to be 2.7%;

(24) 2) performing ultrasonic extraction on the crude drug powder with 100% (V/V) ethanol which is 2 times the amount of the crude drug powder, 1 time, 1 h each time, to obtain an extracting solution;

(25) 3) concentrating the extracting solution until the relative density is measured to be 1.35 at 50 C., thereby obtaining an extractum;

(26) 4) performing water precipitation for the extractum at the temperature of 0 C. for 48 h by using purified water which is 10 times the amount of the extractum, so as to remove impurities, thereby obtaining a water precipitation solution;

(27) 5) centrifuging the water precipitation solution at the speed of 10000 rpm, and adding 10% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(28) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 10% (V/V) ethanol for impurity removal, performing elution with 40% (V/V) ethanol to obtain a target product part, and finally, performing elution with 90% (V/V) ethanol to regenerate the chromatographic column;

(29) 7) concentrating the eluate obtained in step 6) until the relative density is 1.25 at 50 C., and adding 60% (V/V) ethanol for supersaturation and dissolution at the temperature of 80 C. to obtain a crystal;

(30) 8) adding 5% (V/V) ethanol at the temperature of 24 C. to wash the crystal in step 7), thereby obtaining a primary product;

(31) 9) uniformly mixing the primary product in step 8) with purified water, and performing freeze drying to obtain the cannabidiol; and

(32) 10) performing cryogenic grinding on the cannabidiol obtained in step 9) to obtain the product 2.

Embodiment 3: Preparation of Cannabidiol According to the Following Method

(33) 1) grinding industrial hemp flowers and leaves, sifting through a 40-mesh sieve, and drying at the temperature of 130 C. for 1.7 h to obtain crude drug powder, of which the water content is measured to be 3.1%;

(34) 2) performing soaking extraction on the crude drug powder with 60% (V/V) ethanol which is 5 times the amount of the crude drug powder, 2 times, 2.5 h each time, to obtain an extracting solution;

(35) 3) concentrating the extracting solution until the relative density is measured to be 1.2 at 50 C., thereby obtaining an extractum;

(36) 4) performing water precipitation for the extractum at the temperature of 10 C. for 24 h by using purified water which is 5 times the amount of the extractum, so as to remove impurities, thereby obtaining a water precipitation solution;

(37) 5) centrifuging the water precipitation solution at the speed of 7500 rpm, and adding 60% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(38) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is ODS, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 25% (V/V) ethanol for impurity removal, performing elution with 60% (V/V) ethanol to obtain a target product part, and finally, performing elution with 93% (V/V) ethanol to regenerate the chromatographic column;

(39) 7) concentrating the eluate obtained in step 6) until the relative density is measured to be 1.2 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 45 C. to obtain a crystal;

(40) 8) adding 40% (V/V) ethanol at the temperature of 12 C. to wash the crystal in step 7), thereby obtaining a primary product;

(41) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(42) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 3.

Embodiment 4: Preparation of Cannabidiol According to the Following Method

(43) 1) grinding industrial hemp flowers and leaves, sifting through a 40-mesh sieve, and drying at the temperature of 120 C. for 1 h to obtain crude drug powder, of which the water content is measured to be 2.6%;

(44) 2) performing ultrasonic extraction on the crude drug powder with 70% (V/V) ethanol which is 3 times the amount of the crude drug powder, under the frequency of 60 Hz, 3 times, 0.5 h each time, to obtain an extracting solution;

(45) 3) concentrating the extracting solution until the relative density is 1.1 at 50 C., thereby obtaining an extractum;

(46) 4) performing water precipitation for the extractum at the temperature of 4 C. for 12 h by using purified water which is 5 times the amount of the extractum, so as to remove impurities, thereby obtaining a water precipitation solution;

(47) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 80% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(48) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 15% (V/V) ethanol for impurity removal, performing elution with 75% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(49) 7) concentrating the eluate obtained in step 6) until the relative density is 1.1 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 70 C. to obtain a crystal;

(50) 8) adding 10% (V/V) ethanol at the temperature of 10 C. to elute the crystal in step 7), thereby obtaining a primary product;

(51) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(52) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 4.

Embodiment 5: Preparation of Cannabidiol According to the Following Method

(53) 1) grinding industrial hemp flowers and leaves, sifting through a 40-mesh sieve, and drying at the temperature of 120 C. for 1 h to obtain crude drug powder, of which the water content is measured to be 2.6%;

(54) 2) performing ultrasonic extraction on the crude drug powder with 80% (V/V) ethanol, which is 5 times the amount of the crude drug powder, under the frequency of 70 Hz, 2 times, 0.5 h each time, to obtain an extracting solution;

(55) 3) concentrating the extracting solution until the relative density is 1.1 at 50 C., thereby obtaining an extractum;

(56) 4) performing water precipitation for the extractum at the temperature of 4 C. for 12 h by using purified water which is 5 times the amount of the extractum, thereby obtaining a water precipitation solution;

(57) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 80% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(58) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 30% (V/V) ethanol for impurity removal, performing elution with 75% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(59) 7) concentrating the eluate obtained in step 6) until the relative density is 1.1 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 70 C. to obtain a crystal;

(60) 8) adding 10% (V/V) ethanol at the temperature of 10 C. to wash the crystal in step 7), thereby obtaining a primary product;

(61) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(62) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 5.

Embodiment 6: Preparation of Cannabidiol According to the Following Method

(63) 1) grinding industrial hemp flowers and leaves, sifting through a 40-mesh sieve, and drying at the temperature of 120 C. for 1 h to obtain crude drug powder, of which the water content is measured to be 2.6%;

(64) 2) performing reflux extraction on the crude drug powder with 80% (V/V) ethanol, which is 5 times the amount of the crude drug powder, 2 times, 1.5 h each time, to obtain an extracting solution;

(65) 3) concentrating the extracting solution until the relative density is 1.1 at 50 C., thereby obtaining an extractum;

(66) 4) performing water precipitation for the extractum at the temperature of 4 C. for 12 h by using purified water which is 5 times the amount of the extractum, thereby obtaining a water precipitation solution;

(67) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 80% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(68) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 30% (V/V) ethanol for impurity removal, performing elution with 75% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(69) 7) concentrating the eluate obtained in step 6) until the relative density is 1.1 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 70 C. to obtain a crystal;

(70) 8) adding 10% (V/V) ethanol at the temperature of 10 C. to wash the crystal in step 7), thereby obtaining a primary product;

(71) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(72) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 6.

Embodiment 7: Preparation of Cannabidiol According to the Following Method

(73) 1) grinding industrial hemp flowers and leaves, sifting through a 40-mesh sieve, and drying at the temperature of 120 C. for 1 h to obtain crude drug powder, of which the water content is measured to be 2.6%;

(74) 2) performing soaking extraction on the crude drug powder with 80% (V/V) ethanol which is 5 times the amount of the crude drug powder, 2 times, 2.5 h each time, to obtain an extracting solution;

(75) 3) concentrating the extracting solution until the relative density is 1.1 at 50 C., thereby obtaining an extractum;

(76) 4) performing water precipitation for the extractum at the temperature of 4 C. for 12 h by using purified water which is 5 times the amount of the extractum, thereby obtaining a water precipitation solution;

(77) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 80% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(78) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 30% (V/V) ethanol for impurity removal, performing elution with 75% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(79) 7) concentrating the eluate obtained in step 6) until the relative density is 1.1 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 70 C. to obtain a crystal;

(80) 8) adding 10% (V/V) ethanol at the temperature of 10 C. to elute the crystal in step 7), thereby obtaining a primary product;

(81) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(82) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 7.

Embodiment 8: Preparation of Cannabidiol According to the Following Method

(83) 1) grinding industrial hemp roots, sifting through a 10-mesh sieve, and drying at the temperature of 120 C. for 1 h to obtain crude drug powder, of which the water content is measured to be 1.2%;

(84) 2) performing soaking extraction on the crude drug powder with 80% (V/V) ethanol, which is 8 times the amount of the crude drug powder, 2 times, 3 h each time, to obtain an extracting solution;

(85) 3) concentrating the extracting solution until the relative density is 1.1 at 50 C., thereby obtaining an extractum;

(86) 4) performing water precipitation for the extractum at the temperature of 4 C. for 24 h by using purified water which is 10 times the amount of the extractum, thereby obtaining a water precipitation solution;

(87) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 80% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(88) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 30% (V/V) ethanol for impurity removal, performing elution with 75% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(89) 7) concentrating the eluate obtained in step 6) until the relative density is 1.1 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 70 C. to obtain a crystal;

(90) 8) adding 10% (V/V) ethanol at the temperature of 10 C. to elute the crystal in step 7), thereby obtaining a primary product;

(91) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(92) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 8.

Embodiment 9: Preparation of Cannabidiol According to the Following Method

(93) 1) grinding industrial hemp stalk cores, sifting through a 40-mesh sieve, and drying at the temperature of 120 C. for 1 h to obtain crude drug powder, of which the water content is measured to be 1.8%;

(94) 2) performing reflux extraction on the crude drug powder with 80% (V/V) ethanol, which is 5 times the amount of the crude drug powder, 2 times, 1.5 h each time, to obtain an extracting solution;

(95) 3) concentrating the extracting solution until the relative density is 1.1 at 50 C., thereby obtaining an extractum;

(96) 4) performing water precipitation for the extractum at the temperature of 4 C. for 12 h by using purified water which is 5 times the amount of the extractum, thereby obtaining a water precipitation solution;

(97) 5) centrifuging the water precipitation solution at the speed of 5000 rpm, and adding 80% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(98) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 30% (V/V) ethanol for impurity removal, performing elution with 75% (V/V) ethanol to obtain a target product part, and finally, performing elution with 95% (V/V) ethanol to regenerate the chromatographic column;

(99) 7) concentrating the eluate obtained in step 6) until the relative density is 1.1 at 50 C., and adding 80% (V/V) ethanol for supersaturation and dissolution at the temperature of 70 C. to obtain a crystal;

(100) 8) adding 10% (V/V) ethanol at the temperature of 10 C. to wash the crystal in step 7), thereby obtaining a primary product;

(101) 9) performing vacuum drying on the primary product in step 8) to obtain the cannabidiol; and

(102) 10) performing jet grinding on the cannabidiol obtained in step 9) to obtain the product 9.

Embodiment 10: Preparation of Cannabidiol According to the Following Method

(103) 1) grinding industrial hemp flowers, leaves and seed cakes, sifting through a 10-mesh sieve, and drying at the temperature of 200 C. for 0.5 h to obtain crude drug powder, of which the water content is measured to be 2.4%;

(104) 2) performing ultrasonic extraction on the crude drug powder with 100% (V/V) ethanol, which is 2 times the amount of the crude drug powder, 1 time, 1 h each time, to obtain an extracting solution;

(105) 3) concentrating the extracting solution until the relative density is measured to be 1.35 at 50 C., thereby obtaining an extractum;

(106) 4) performing water precipitation for the extractum at the temperature of 0 C. for 48 h by using purified water which is 10 times the amount of the extractum, so as to remove impurities, thereby obtaining a water precipitation solution;

(107) 5) centrifuging the water precipitation solution at the speed of 10000 rpm, and adding 10% (V/V) ethanol to dissolve the precipitate obtained by centrifuging, thereby obtaining a precipitate alcohol solution;

(108) 6) performing column chromatography on the precipitate alcohol solution, wherein a filler of the chromatographic column is MCI resin, the elution solvent is ethanol and water, and the elution includes the steps of: performing elution with 10% (V/V) ethanol for impurity removal, performing elution with 40% (V/V) ethanol to obtain a target product part, and finally, performing elution with 90% (V/V) ethanol to regenerate the chromatographic column;

(109) 7) concentrating the eluate obtained in step 6) until the relative density is 1.25 at 50 C., and adding 60% (V/V) ethanol for supersaturation and dissolution at the temperature of 80 C. to obtain a crystal;

(110) 8) adding 5% (V/V) ethanol at the temperature of 24 C. to wash the crystal in step 7), thereby obtaining a primary product;

(111) 9) uniformly mixing the primary product in step 8) with purified water, and performing freeze drying to obtain the cannabidiol; and

(112) 10) performing cryogenic grinding on the cannabidiol obtained in step 9) to obtain the product 10.

Comparative Embodiment 1: Preparation of Cannabidiol According to the Following Method

(113) 1) adding flowers and leaves in the full-bloom stage into a drying plant, and drying at 130 C. for 35 mM;

(114) 2) grinding the dried flowers and leaves until the particle size reaches 5-10 meshes;

(115) 3) soaking the ground flowers and leaves in a soaking device, wherein the soaking solvent is petroleum ether, the soaking temperature is 48 C., and the soaking time length is 1 h;

(116) 4) after the soaking, filtering out the flowers and leaves, and heating the filtrate at 90 C. to obtain an extractum; and

(117) 5) chromatographic separation: weighing an adsorbent, adding the adsorbent into a chromatographic separator, uniformly putting the extractum on the adsorbent surface to adsorb CBD (the weight ratio of the adsorbent to the extractum is 25:1), performing elution by using petroleum ether, and drying to obtain the comparative product 1.

Comparative Embodiment 2: Preparation of Cannabidiol According to the Following Method

(118) 1) adding hemp flowers and leaves in the full-bloom stage into a drying plant, and drying at 160 C. for 15 min;

(119) 2) grinding the dried flowers and leaves until the particle size reaches 5-10 meshes;

(120) 3) soaking the ground flowers and leaves in a soaking device, wherein the soaking solvent is n-hexane, the soaking temperature is 20 C., and the soaking time length is 2 h;

(121) 4) after the soaking, filtering out the flowers and leaves, and heating the filtrate at 120 C. to obtain an extractum; and

(122) 5) chromatographic separation: weighing an adsorbent macroporous resin, adding the adsorbent macroporous resin into a chromatographic separator, uniformly mixing the adsorbent and the extractum in a ratio of 1:1 to adsorb CBD, performing elution by using n-hexane, and drying to obtain the comparative product 2.

Experimental Embodiment 1: Comparison of CBD Content and Tetrahydrocannabinol Detection Results in Products Obtained by Different Preparation Methods

(123) Detection Method:

(124) Chromatographic Condition and System Suitability Test:

(125) octadecyl silane bonded silica gel is used as a filler; isocratic elution is performed by using acetonitrile as a mobile phase A and water as a mobile phase B according to A (%):B (%)=80:20; and the detection wavelength is 210 nm. The number of theoretical plates calculated according to the CBD peak should be not lower than 2500.

(126) Preparation of Reference Substance Solutions:

(127) precisely weighing a CBD reference substance, and adding methanol (1:1) to prepare a reference substance solution, every 1 ml of which contains 0.1 mg of the CBD reference substance; and precisely weighing a tetrahydrocannabinol reference substance, and adding methanol (1:1) to prepare a reference substance solution, every 1 ml of which contains 0.01 mg of the tetrahydrocannabinol reference substance.

(128) Preparation of Test Sample Solution:

(129) taking about 25 mg of the product which is precisely weighed, putting the product in a 25 ml measuring flask, adding 20 ml of acetonitrile-water (1:1), performing ultrasonic treatment for 15 minutes, adding acetonitrile-water (1:1) for dilution to the calibration, shaking uniformly, performing filtration through a microporous filter membrane (0.45 m), and taking the subsequent filtrate.

(130) Determination Method:

(131) respectively precisely sucking 10 l of the reference substance solution and 10 l of the test sample solution, injecting the reference substance solution and test sample solution into a liquid chromatograph, and performing determination.

(132) The CBD content and tetrahydrocannabinol content detection results of the products prepared according to the embodiments 1-7 and comparative embodiments 1-2 are referred to Table 1 and FIG. 1 to FIG. 9.

(133) TABLE-US-00001 TABLE 1 Comparison of CBD content and THC detection results in products obtained by different preparation methods THC Product Name Chromatogram CBD Content (wt %) Content (wt %) Product 1 FIG. 1 97.4 ND Product 2 FIG. 2 96.3 ND Product 3 FIG. 3 98.5 ND Product 4 FIG. 4 98.9 ND Product 5 FIG. 5 98.5 ND Product 6 FIG. 6 97.4 ND Product 7 FIG. 7 99.5 ND Comparative FIG. 8 83.1 0.11 Product 1 Comparative FIG. 9 81.2 0.24 Product 2

(134) It can be seen from Table 1 and FIG. 1 to FIG. 9 that the contents of CBD (cannabidiol) in the products 1, 2, 3, 4, 5, 6 and 7 prepared by the methods of the present invention are obviously higher than the contents of CBD (comparative product 1 and comparative product 2) prepared by the prior art; and no THC (tetrahydrocannabinol) is detected in the products prepared by the techniques of the present invention, but THC is obviously detected in the products prepared by the prior art, which further illustrates that the CBD extracted by using the present invention has higher content, higher purity and higher safety and complies with related requirements of laws and regulations on products.

Experimental Embodiment 2: Comparison of Effects of Different Extraction Methods on CBD Extraction Rate

(135) (1) Raw Flower and Leaf Crude Drug Content Detection Method

(136) Chromatographic Condition and System Suitability Test:

(137) octadecyl silane bonded silica gel is used as a filler; isocratic elution is performed by using acetonitrile as a mobile phase A and water as a mobile phase B according to A (%):B (%)=80:20; and the detection wavelength is 210 nm. The number of theoretical plates calculated according to the CBD peak should be not lower than 2500.

(138) Preparation of Reference Substance Solutions:

(139) precisely weighing a CBD reference substance, and adding methanol (1:1) to prepare a reference substance solution, every 1 ml of which contains 0.1 mg of the CBD reference substance; and precisely weighing a tetrahydrocannabinol reference substance, and adding methanol (1:1) to prepare a reference substance solution, every 1 ml of which contains 0.01 mg of the tetrahydrocannabinol reference substance.

(140) Preparation of Test Sample Solution:

(141) taking about 1 g of the product which is precisely weighed, adding 25 ml of methanol, performing ultrasonic treatment for 15 minutes, performing filtration, adding 25 ml of methanol, performing ultrasonic treatment for 15 minutes, combining the filtrates, making up to 50 ml, shaking uniformly, performing filtration through a microporous filter membrane (0.45 m), and taking the subsequent filtrate.

(142) Determination Method:

(143) respectively precisely sucking 10 l of the reference substance solution and 10 l of the test sample solution, injecting the reference substance solution and test sample solution into a liquid chromatograph, and performing determination.

(144) (2) Extracting Solution Content Detection Method

(145) Chromatographic Condition and System Suitability Test:

(146) octadecyl silane bonded silica gel is used as a filler; isocratic elution is performed by using acetonitrile as a mobile phase A and water as a mobile phase B according to A (%):B (%)=80:20; and the detection wavelength is 210 nm. The number of theoretical plates calculated according to the CBD peak should be not lower than 2500.

(147) Preparation of Reference Substance Solutions:

(148) precisely weighing a CBD reference substance, and adding methanol (1:1) to prepare a reference substance solution, every 1 ml of which contains 0.1 mg of the CBD reference substance; and precisely weighing a tetrahydrocannabinol reference substance, and adding methanol (1:1) to prepare a reference substance solution, every 1 ml of which contains 0.01 mg of the tetrahydrocannabinol reference substance.

(149) Preparation of Test Sample Solution:

(150) taking 1 ml of the extracting solution, making up to 25 ml, performing filtration through a microporous filter membrane (0.45 m), and taking the subsequent filtrate.

(151) Determination Method:

(152) respectively precisely sucking 10 l of the reference substance solution and 10 l of the test sample solution, injecting the reference substance solution and test sample solution into a liquid chromatograph, and performing determination.

(153) The three methods in the embodiments 5-7, namely ultrasonic extraction, reflux extraction and soaking extraction, are adopted to obtain the extracting solution in step (2) as the test sample solution. Specific experimental results of the extraction rate are shown in Table 2 below.

(154) TABLE-US-00002 TABLE 2 Extraction rate tests of three extraction methods (using CBD content as an index) Ultrasonic Reflux Soaking Flower and Extraction Extraction Extraction Leave Crude (Embodi- (Embodi- (Embodi- Drug ment 5) ment 6) ment 7) Weight or Volume 10 kg 92.6 L 91.8 L 92.7 L CBD Content 49.8 g 48.1 g 48.0 g 48.2 g Extraction Rate % 96.6 96.3 96.8

(155) From Table 2 above, it can be seen that the extraction rates of the three extraction methods are similar, and the change of the extraction method has no effect on the extraction rate. Under the condition that other technical parameters are identical, there was no significant difference between the content of CBD (cannabidiol) in the product 7 obtained by soaking extraction and the content of CBD (cannabidiol) in the product 5 obtained by ultrasonic extraction, which further illustrates that the beneficial effects of the present invention are not due to the introduction of the ultrasonic extraction technique.

Experimental Embodiment 3: Comparison of CBD Content and Tetrahydrocannabinol Detection Results in Products Prepared from Different Extraction Parts

(156) The detection method is the same as that of the experimental embodiment 1. The CBD content and tetrahydrocannabinol content detection results of the products prepared in the embodiments 8-10 are referred to Table 3.

(157) TABLE-US-00003 TABLE 3 Comparison of CBD content and THC detection results in products prepared from different extraction parts Product Name CBD Content (wt %) THC Content (wt %) Product 8 95.3 ND Product 9 94.8 ND Product 10 95.2 ND

(158) From Table 3, it can be seen that the method of the present invention is also suitable for performing extraction on hemp roots, stalk cores, flowers, leaves and seed cakes to obtain CBD, and no THC (tetrahydrocannabinol) is detected in the products.

Experimental Embodiment 4: Detection of Stability of Products Prepared by Different Preparation Methods by Using Stability Test Methods

(159) Main Instruments:

(160) Drug stability test chamber (long-term): SHH-250SD, Chongqing Yongsheng Experiment Instrument Factory;

(161) Drug stability test chamber (accelerated): SHH-250SD, Chongqing Yongsheng Experiment Instrument Factory;

(162) HPLC: Agilent1200;

(163) Analytical balance: MS-105DU, METTLER TOLEDO in Switzerland;

(164) Ultraviolet-visible spectrophotometer: UV-2550, SHIMADZU in Japan

(165) TLC Visualizer: TLC Visualizer, CAMAG in Switzerland;

(166) Test Samples:

(167) Accelerated stability tests are performed on the samples prepared according to the methods of the above-mentioned embodiments and comparative embodiments, and the test results are shown in Tables 4 to 12.

(168) TABLE-US-00004 TABLE 4 Product 1 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test 2015 Nov. 3 2015 Dec. 3 2016 Jan. 3 2016 Feb. 3 2016 May 3 Item: Method: Acceptance Criteria Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 97.4 97.6 97.2 97.7 97.5 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count does <10 ND ND ND <10 Detection not exceed 1000 cfu/g Method Fungal and yeast <10 ND ND ND <10 in count does not Chinese exceed 100 cfu/g Pharmacopoeia No E. coli should be ND ND ND ND ND detected

(169) TABLE-US-00005 TABLE 5 Product 2 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 3 2015 Dec. 3 2016 Jan. 3 2016 Feb. 3 2016 May 3 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 96.3 96.6 96.4 96.7 96.2 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count <10 ND ND ND <10 Detection does not exceed Method in 1000 cfu/g Chinese Fungal and yeast <10 ND ND ND <10 Pharmacopoeia count does not exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(170) TABLE-US-00006 TABLE 6 Product 3 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 98.5 98.6 98.7 98.2 98.8 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count <10 ND ND ND <10 Detection does not exceed Method in 1000 cfu/g Chinese Fungal and yeast <10 ND ND ND <10 Pharmacopoeia count does not exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(171) TABLE-US-00007 TABLE 7 Product 4 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Acceptance Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 98.9 98.7 98.4 98.3 98.6 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count does <10 ND ND ND <10 Detection not exceed 1000 cfu/g Method in Fungal and yeast <10 ND ND ND <10 Chinese count does not Pharmacopoeia exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(172) TABLE-US-00008 TABLE 8 Product 5 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 98.5 98.4 98.9 98.5 98.4 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count <10 ND ND ND <10 Detection does not exceed Method in 1000 cfu/g Chinese Fungal and yeast <10 ND ND ND <10 Pharmacopoeia count does not exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(173) TABLE-US-00009 TABLE 9 Product 6 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 97.4 97.2 97.8 97.5 97.4 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count <10 ND ND ND <10 Detection does not exceed Method in 1000 cfu/g Chinese Fungal and yeast <10 ND ND ND <10 Pharmacopoeia count does not exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(174) TABLE-US-00010 TABLE 10 Product 7 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 99.5 99.6 99.6 99.8 99.7 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count <10 ND ND ND <10 Detection does not exceed Method in 1000 cfu/g Chinese Fungal and yeast <10 ND ND ND <10 Pharmacopoeia count does not exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(175) TABLE-US-00011 TABLE 11 Comparative product 1 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 83.1 82.2 80.1 76.1 73.8 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count does <10 ND ND ND <10 Detection not exceed 1000 cfu/g Method in Chinese Pharmacopoeia Fungal and yeast <10 ND ND ND <10 count does not exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(176) TABLE-US-00012 TABLE 12 Comparative product 2 stability test Time Point: Beginning 1st Month 2nd Month 3rd Month 6th Month Date of Sampling: Test Test Acceptance 2015 Nov. 8 2015 Dec. 8 2016 Jan. 8 2016 Feb. 8 2016 May 8 Item: Method: Criteria: Detection Results Trait Visual White, light yellow Acceptable Acceptable Acceptable Acceptable Acceptable powder or crystal Identification TLC The chromatogram Acceptable Acceptable Acceptable Acceptable Acceptable of the test sample and the chromatogram of the reference substance show the fluorescent spots of the same color in the corresponding positions. Content HPLC CBD content 95% 81.2 77.2 74.7 71.1 69.1 Determination HPLC THC content 0.1% ND ND ND ND ND Microbe Microbial Bacterial count <10 ND ND ND <10 Detection does not exceed Method 1000 cfu/g in Fungal and yeast <10 ND ND ND <10 Chinese count does not Pharmacopoeia exceed 100 cfu/g No E. coli should be ND ND ND ND ND detected

(177) From Tables 4-12, it can be seen that the content of CBD (cannabidiol) in the products 1-7 prepared by the methods of Embodiment 1 to Embodiment 7 of the present invention is stable after the 6-month accelerated stability test. The content change range of CBD is only less than 0.6% (wherein the maximum change of CBD content is only 0.6% after storage of 3 months, 2 months and 1 month). However, the contents of CBD in the comparative product 1 and comparative product 2 prepared by the comparative embodiment methods are respectively decreased from 83.1% to 73.8% (the decrease rate is 9.3%) and from 81.2% to 69.1% (the decrease rate is 12.1%) after the 6-month accelerated stability test, so the stability is low; and in the 3-month stability test, the content decrease rates of the comparative product 1 and comparative product 2 are respectively 7.1% and 10.1%, so the stability is obviously lower than that of the products prepared by the methods of the present invention.

(178) From the above description, it can be seen that the above-mentioned embodiments of the present invention achieve the following technical effects: 1) By adding the step of crystallization, the cannabidiol (CBD) content in the final product is increased to 96% or above. 2) By improving the technique, the tetrahydrocannabinol content in the finished product is controlled to 0.3% or below (tetrahydrocannabinol is not detected in embodiment 1 to embodiment 7), which complies with national laws and regulations, so that the product safety is guaranteed. 3) In the step of primary purification, the macroporous resin, MCI resin or ODS is used instead of the silica gel in the prior art, so that the filler can be recycled, thereby lowering the overall production cost, and reducing the environmental pollution caused by the waste silica gel. 4) By using the ethanol and water as the extraction solvents, the solvents are safe and have small damage to the environment and operating personnel, and the product solvent residues are greatly improved; and in the column chromatography process, ethanols with different purities are used to elute the resin column, thereby reducing the environmental pollution and the personal injuries.

(179) In addition, laboratory-scale experimental verification and pilot scale-up verification show that the technique in the present invention can produce products with high purity (above 95%) and safety (THC content 0.3% or below).

(180) The foregoing descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various changes and modifications. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention shall fall into the protection scope of the present invention. The protection scope of the present invention is defined by the appended claims, and covers the equivalent changes of the claims.