KR20240105276A - Method of isolating cannabidiol from Cannabis sativa L. using supercritical fluid - Google Patents

Abstract

The present invention relates to a method for obtaining cannabidiol from hemp, comprising the steps of (A) decarboxylating hemp; And (B) extracting the decarboxylated hemp, including the process of increasing the pressure from 100 bar to 200 bar under supercritical fluid and then lowering the pressure from 200 bar to 100 bar. By including, performed in the prior art. It is possible to obtain cannabidiol with a purity of over 99% without performing the usual purification process.

Description

Method of obtaining cannabidiol from cannabis using supercritical fluid {Method of isolating cannabidiol from Cannabis sativa L. using supercritical fluid}

The present invention relates to a method of obtaining cannabidiol from hemp, which allows cannabidiol with a purity of 99% or more to be obtained without performing the conventional purification process.

In traditional medicine in China and Korea, Mazain (麻子仁) or Hwamain (火麻仁), obtained by removing the skin of hemp seeds, has been used for constipation, diabetes, pain diseases, menstrual irregularities, skin diseases and dysentery, and hemp leaves. There are records of use of cannabis (大麻草, hemp leaf) as an anthelmintic, hair protection, asthma, analgesic, anesthetic, and diuretic. In addition, horse root (麻根) was used for the treatment of dystocia and relieving blood clots, hemp root (麻皮) was used for bruises and fibroids, horseradish (麻化) was used for paralysis and itching, and horse powder (麻賁) was used to treat dystocia, constipation, etc. There are records of the use of cannabis according to the condition for each part of the plant, such as gout, gingivitis, and insomnia.

There are about 400 compounds in hemp, most of which are cannabinoids, terpenes, and phenolic compounds, of which there are about 90 types of cannabinoids, which are important natural ingredients in medicine and pharmaceuticals. There are also many ingredients found only in hemp.

Among cannabis components, substances known as psychoactive cannabinoids are tetrahydrocannabinol (THC), cannabinol (CBN), and cannabinodiol (CBDL), and cannabidiol (CBD) is As a non-psychoactive ingredient, it is known to have physiological effects through various receptors in the human body, including adrenergic receptors and cannabinoid receptors.

In particular, while scientists were researching the psychoactive mechanism of cannabis, they discovered a receptor in the brain that selectively binds cannabinoids in the brain in 1988, indicating that molecules similar to cannabinoids are also produced in our bodies, and these cannabinoid molecules are It is a fatty acid-type neurotransmitter produced in local areas of the brain and is called anandamide (Science, 1992, 258, 1946).

THC, the main active ingredient in cannabis used for medicinal purposes, is an agonist with strong affinity for CB1 receptors (distributed throughout the brain, including the cerebral cortex, hippocampus, cerebellum, and basal ganglia), and this appears to be the main mechanism of psychoactive action, but CBD In the case of numerous research results, it has been found to have beneficial effects such as anti-inflammatory, anti-epileptic, anti-emetic, and anti-cancer effects. It reduces side effects caused by THC (Current Pharmaceutical Design, 2012, 18, 4906., Bioorganic Medicinal Chemistry) , 2015, 23, 1377), endogenous cannabis through antagonism against CB1 and CB2 receptors (mainly distributed in peripheral tissues such as macrophages, bone marrow, lung, pancreas, and smooth muscle, and closely related to the immune system) agonists such as THC. It is known to inhibit the reuptake and decomposition of anandamide, an anandamide, and to be an agonist of the serotonin receptor (Neurochemcal Research, 2005, 30, 1037).

In addition, among cannabis ingredients, cannabichromene has anti-inflammatory, sedative, and antifungal effects, and CBN helps improve immune function by binding to CB2 receptors rather than CB1 (Frontiers in Plant Science 2016, 7, 19). Research on the pharmaceutical mechanisms of cannabis-containing ingredients is being conducted very actively.

In the United States, Epidiolex, a liquid drug containing CBD as the main ingredient approved by the Food and Drug Administration (FDA), is used for epilepsy in children, and is not a single CBD drug, but a hemp extract form of Cannador (THC). :CBD=2:1) is undergoing extensive and active research, including clinical trials for multiple sclerosis and serious chronic pain diseases.

Therefore, there is a need for technology to increase the extraction yield and increase the content of CBD, a non-psychoactive ingredient among the major pharmaceutical ingredients of hemp.

Republic of Korea Patent Publication No. 2021-0060410 US Patent Publication No. 2004-0033280

The purpose of the present invention is to provide a method of obtaining cannabidiol with a purity of 99% or more without performing the conventional purification process.

The method for obtaining cannabidiol from hemp of the present invention to achieve the above object includes the steps of (A) decarboxylating hemp; And (B) extracting the decarboxylated hemp, including the process of increasing the pressure from 100 bar to 200 bar under supercritical fluid and then lowering the pressure from 200 bar to 100 bar.

In step (A), decarboxylation may be performed at 100 to 150°C for 120 to 240 minutes, preferably at 115 to 130°C for 140 to 240 minutes.

In step (B), the pressure conditions under the supercritical fluid include (a) maintaining at 100 bar for 50 to 80 minutes; (b) increasing the pressure maintained at 100 bar to 200 bar; (c) step of lowering the pressure to 100 bar when it reaches 200 bar; and (d) the step of maintaining the pressure for 50 to 80 minutes when the pressure reaches 100 bar and then increasing the pressure to 200 bar; may be repeated.

The pressure boosting may be performed at a rate of 2 to 5 bar/min, respectively.

The pressure reduction may be to immediately lower the pressure from 200 bar to 100 bar.

The pressure increase may be performed for 30 to 40 minutes.

The extraction time under the supercritical fluid under the above pressure conditions may be 4 to 8 hours.

The supercritical fluid is supercritical carbon dioxide, supercritical ethane, supercritical propane, supercritical butane, supercritical pentane, supercritical hexane, supercritical heptane, supercritical dimethyl ether, supercritical tetrafluoromethane, and supercritical difluoro. It may be one selected from the group consisting of methane and supercritical fluoroethane.

After step (B), (C) dewaxing the extract extracted with the supercritical fluid; and (D) crystallizing the dewaxed extract to obtain cannabidiol.

The purity of the crystallized cannabidiol may be 99.0 to 100%.

The method of obtaining cannabidiol from hemp of the present invention can increase the cannabidiol (CBD) content and extraction rate in the extract by performing extraction while changing pressure conditions under supercritical fluid.

In particular, the present invention can obtain high purity cannabidiol (CBD) by lowering the content of impurities in the extract without performing the conventional purification process.

Accordingly, the cannabidiol (CBD) can be used in pharmaceuticals and quasi-drugs such as anti-epileptic, neuroprotective, vascular relaxation, anti-cancer, anti-inflammatory, anti-diabetic, antibacterial, analgesic, osteoporosis, immune or anti-emetic effects.

In addition, cannabidiol (CBD) can be used in general cosmetics or functional cosmetics with antioxidant or anti-inflammatory functions.

Figure 1 is a graph showing pressure conditions for extraction under supercritical fluid according to an embodiment of the present invention.
Figure 2 is a graph measuring extracts prepared according to Example 1 and Comparative Examples 1 to 3 of the present invention using a spectrophotometer.
Figure 3 is a chromatogram measuring the purity of cannabidiol after crystallization of the extract prepared according to Example 1 and Comparative Examples 1 to 3 of the present invention.

The present invention relates to a method of obtaining cannabidiol from hemp, which allows cannabidiol with a purity of 99% or more to be obtained without performing the conventional purification process.

Conventionally, in order to obtain cannabidiol from hemp, it must be processed in the following order: decarboxylation, extraction, dewaxing, purification, and crystallization. However, in the present invention, the purity can be maintained even if processed in the order of decarboxylation, extraction, dewaxing, and crystallization. High cannabidiol levels can be obtained.

That is, the present invention can obtain high-purity cannabidiol in high yield without performing a purification process by treating the extraction process in a different way than the conventional method.

Hereinafter, the present invention will be described in detail.

The method for obtaining cannabidiol of the present invention includes the steps of (A) decarboxylating hemp; And (B) extracting the decarboxylated hemp, including the process of increasing the pressure from 100 bar to 200 bar under supercritical fluid and then lowering the pressure from 200 bar to 100 bar. In addition, after step (B), (C) dewaxing the extract extracted with the supercritical fluid; and (D) crystallizing the dewaxed extract to obtain cannabidiol (CBD).

First, in step (A), hemp is decarboxylated.

The hemp ( Cannabis sativa L. ) is an annual plant of the Cannabaceae genus, which has been widely cultivated in tropical and temperate regions, mainly in Central Asia, for 12,000 years. It includes wild ginseng and various medicinal and pharmaceutical ingredients. Cannabis chemovars containing a variety of cannabinoid compounds and their variants, strains var. indica and var. Cannabis sativa subspecies sativa, including kafiristanica, Cannabis sativa subspecies indica, and Cannabis sativa subspecies ruderalis. and genetic crosses, self-crosses, or hybrid plants thereof.

The hemp contains cannabidiolic acid (CBDA), and the cannabidiolic acid (CBDA) is converted into cannabidiol (CBD) through decarboxylation.

Decarboxylation of the present invention is carried out at 100 to 150°C, preferably 115 to 130°C for 120 to 240 minutes, preferably 140 to 240 minutes. If the temperature and time during decarboxylation are outside the above range, the conversion rate from cannabidiolic acid (CBDA) to cannabidiol (CBD) may be significantly low. In particular, if the temperature during decarboxylation exceeds the above upper limit, decomposition may occur in the process of conversion to cannabidiol (CBD) by heating, and the conversion rate may rapidly decrease.

Next, in step (B), the decarboxylated hemp can be extracted by increasing the pressure from 100 bar to 200 bar under supercritical fluid and then lowering the pressure from 200 bar to 100 bar.

The present invention can obtain high purity cannabidiol (CBD) by further increasing the extraction rate of cannabidiol (CBD) and lowering the content of impurities by treating it under supercritical fluid while changing the pressure conditions.

The pressure conditions include (a) maintaining decarboxylated hemp at 100 bar for 50 to 80 minutes under supercritical fluid; (b) increasing the pressure maintained at 100 bar to 200 bar; (c) step of lowering the pressure to 100 bar when it reaches 200 bar; and (d) when the pressure is reduced and reaches 100 bar, the pressure is maintained for 50 to 80 minutes and then the pressure is increased to 200 bar. This is repeated.

Specifically, the pressure is maintained at 100 bar for 50 to 80 minutes, preferably 60 to 70 minutes (step (a)), and then the pressure is increased from 100 bar to 2 to 5 bar/min, preferably 3 to 4 bar/min. The pressure is increased for 30 to 40 minutes to reach 200 bar (step (b)), and then immediately lowered from 200 bar to 100 bar to lower the pressure (step (c)). When the pressure is reduced and reaches 100 bar, the pressure is reduced by 50 to The pressure is maintained for 80 minutes, preferably 60 to 70 minutes, and then the process of increasing the pressure to 200 bar is repeated, and extraction is performed for a total of 4 to 8 hours, preferably 4 to 6 hours. When the pressure is immediately lowered from 200 bar to 100 bar, it takes 1 to 2 minutes.

As in the present invention, when extraction is performed under the same pressure rather than by changing the pressure conditions under supercritical fluid, there is a problem that a large amount of impurities are contained and a purification process must be performed. When going through the above purification process, the extraction rate of cannabidiol (CBD) may be further lowered.

Steps (a) to (c) are one cycle, and when the pressure is maintained at 100 bar after one cycle (step (d)), if the pressure is maintained for a time different from step (a), impurities are Since this can occur in large quantities, it is desirable to keep the holding time the same in step (a).

Additionally, in step (a), if the pressure is maintained at 200 bar instead of 100 bar, a large amount of impurities may be contained; When maintaining the pressure at 100 bar, if the time is less than the lower limit above, the extraction rate of cannabidiol (CBD) may decrease, and if it exceeds the upper limit above, the extraction rate of cannabidiol (CBD) will be lowered and a large amount of impurities may be contained. You can.

In addition, if the pressure is maintained at 200 bar rather than lowered to 100 bar in step (c), almost all of the extract may be filled with impurities, and if the pressure is gradually lowered rather than immediately lowered to 100 bar upon pressure, the extract It may contain more than 80% by weight of impurities.

In addition, if the speed during pressure increase is less than the above lower limit, a large amount of impurities may be generated, and if the speed is higher than the above upper limit, the extraction rate of cannabidiol (CBD) may be lowered and impurities may be generated.

In addition, if the processing time during pressure increase is less than the lower limit, a large amount of impurities may be generated, and if it exceeds the upper limit, the extraction rate of cannabidiol (CBD) may be very low.

If the total extraction time in the case of extraction while changing the pressure conditions under supercritical fluid according to step (B) of the present invention is less than the lower limit, the desired extraction rate of cannabidiol (CBD) may not be obtained, and the upper limit may not be obtained. If it is excessive, a large amount of impurities may be generated.

The supercritical fluid is not particularly limited as long as it can obtain cannabidiol, but is preferably supercritical carbon dioxide, supercritical ethane, supercritical propane, supercritical butane, supercritical pentane, supercritical hexane, supercritical heptane, It may be one selected from the group consisting of supercritical dimethyl ether, supercritical tetrafluoromethane, supercritical difluoromethane, and supercritical fluoroethane, and more preferably, it may be supercritical carbon dioxide.

Next, in step (C), the extract extracted with the supercritical fluid is dewaxed with alcohol, and then in step (D), the dewaxed extract is crystallized to obtain cannabidiol (CBD).

The dewaxing and crystallization method is not particularly limited as long as it is generally used in the method of obtaining cannabidiol (CBD).

The purity of the crystallized cannabidiol is 99.0 to 100%, and the yield of cannabidiol (CBD) is 40 to 60%.

Hereinafter, preferred embodiments are presented to aid understanding of the present invention. However, the following examples are merely illustrative of the present invention, and it is clear to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention. It is natural that such variations and modifications fall within the scope of the attached patent claims.

[Measurement of decarboxylation efficiency]

Preparation Examples 1 to 9. 105°C

Decarboxylation was performed by placing dried and ground cannabis in a container and heating it to 105°C.

Preparation Examples 10 to 18. 120°C

Decarboxylation was performed by placing dried and ground cannabis in a container and heating it to 120°C.

Preparation Examples 19 to 27. 150°C

Decarboxylation was performed by placing dried and ground cannabis in a container and heating it to 150°C.

<Test Example Ⅰ>

The statistical program Grahpad prism (ver. 6, Sandiego, California, USA) was used to analyze the results of this experiment, and the measurement results of each experimental item were expressed as mean ± standard deviation (mean ± SD). The mean difference between groups was confirmed by one-way ANOVA, and statistical significance was tested at the P<0.05 level using the Tukey test.

Test Example 1. Measurement of conversion rate of cannabidiol (CBD)

The conversion rate of cannabidiolic acid (CBDA) to cannabidiol (CBD) was measured through decarboxylation. * Significance between temperatures at the same treatment time was confirmed (p＜0.0５).

Conversion was performed through High Performance Liquid Chromatography (HPLC) analysis.

[Equation 1]

CBD conversion rate (%) = 100 * (Current CBD content)/{(Initial CBD content) + (Initial CBDA content)}

division CBD content (%) CBDA content (%) CBD conversion rate (%) Manufacturing Example 1 105℃ 0 minutes 6.90±0.27 3.13±0.13 68.81±2.67 Production example 2 30 minutes 7.18±0.36 3.20±0.25 71.59±3.60 Production example 3 60 minutes 7.46±0.17 2.90±0.14 74.37±1.67 Production example 4 90 minutes 7.22±0.10 2.16±0.05 ^* 72.02±1.03 Production example 5 120 minutes 7.96±0.39 2.32±0.06 ^* 79.41±3.88 Production example 6 150 minutes 8.24±0.09 2.06±0.05 ^** 82.24±0.86 Production example 7 180 minutes 8.61±0.05 1.86±0.05 ^** 85.92±0.47 Production example 8 210 minutes 8.34±0.13 1.54±0.02 ^*** 83.18±1.25 Production example 9 240 minutes 8.93±0.65 ^* 1.43±0.13 ^*** 89.08±6.50 ^* Production example 10 120℃ 0 minutes 6.90±0.27 3.13±0.13 68.81±2.67 Production Example 11 30 minutes 6.86±0.37 2.95±0.18 ^* 68.44±3.71 Production example 12 60 minutes 7.58±0.41 2.47±0.12 ^*** 75.56±4.12 Production Example 13 90 minutes 8.26±0.19 1.73±0.00 ^*** 82.39±1.93 Production example 14 120 minutes 8.58±0.45 1.36±0.05 ^*** 85.53±4.50 Production Example 15 150 minutes 10.24±0.27 ^** 1.30±0.08 ^*** 102.15±2.72 ^* Production example 16 180 minutes 9.05±0.79 0.81±0.09 ^*** 90.30±7.90 Production Example 17 210 minutes 9.18±0.36 0.71±0.04 ^*** 91.52±3.63 Production Example 18 240 minutes 8.71±0.27 0.54±0.02 ^*** 86.83±2.70 Production example 19 150℃ 0 minutes 6.90±0.27 3.13±0.13 68.81±2.67 Production example 20 30 minutes 7.25±0.03 2.98±0.00 72.30±0.29 Production example 21 60 minutes 8.01±0.37 2.05±0.06 ^*** 79.92±3.67 Production example 22 90 minutes 9.10±0.35 ^** 0.90±0.06 ^*** 90.77±3.47 ^** Production example 23 120 minutes 9.34±0.15 ^*** 0.27±0.03 ^*** 93.15±1.51 ^*** Manufacturing example 24 150 minutes 8.15±0.05 ^* 0.04±0.01 ^*** 81.26±0.50 ^* Production example 25 180 minutes 7.87±0.06 0.00±0.00 ^*** 78.48±0.61 Production example 26 210 minutes 7.09±0.02 0.00±0.00 ^*** 70.75±0.22 Manufacturing Example 27 240 minutes 5.80±0.13 0.00±0.00 ^*** 57.81±1.25

As shown in Table 1 above, the conversion rate was less than 90% even at 240 minutes at 105 ℃, and the conversion rate was confirmed to be excellent at 150 minutes (102.15%) at 120 ℃ and 120 minutes (93.15%) at 150 ℃.

In the case of 150°C, it was confirmed that decomposition occurred during the conversion process to cannabidiol due to heating and the conversion rate decreased rapidly.

Accordingly, the following test was performed using the conditions of 120°C and 150 minutes, which had the best conversion rate.

[Measurement of extraction efficiency of cannabidiol (CBD)]

Example 1.

Dried and ground cannabis was placed in a container, heated to 120°C and treated for 150 minutes to obtain decarboxylated cannabis, and then extracted using carbon dioxide at 50°C using a 10L supercritical fluid extraction equipment (POSENTECH). Extraction was performed for 6 hours while changing pressure conditions (no auxiliary solvent was used). As shown in Figure 1, the pressure conditions are maintained at 100 bar for 60 minutes, then increased from 100 bar at a rate of 3.3 bar/min for 30 minutes to reach 200 bar, and then at 200 bar for 1 second. The extract was obtained by lowering the pressure to 100 bar (1 cycle), maintaining the pressure for 60 minutes when it reached 100 bar, and then increasing the pressure again to 200 bar for a total of 6 hours. That is, after repeating the above cycle three times, when 100 bar was reached, the pressure was maintained for 60 minutes and then the pressure was raised to 200 bar again to complete the extraction.

Comparative Example 1. 100 bar

Dried and ground cannabis was placed in a container, heated to 120°C and treated for 150 minutes to obtain decarboxylated cannabis, and then extracted under carbon dioxide (no auxiliary solvent) using a 10L supercritical fluid extraction equipment (POSENTECH). ) The extract was obtained by extraction at 50°C and 100 bar for 6 hours.

Comparative Example 2. 200 bar

The same procedure as Comparative Example 1 was performed, but extraction was performed at 200 bar instead of 100 bar for 6 hours to obtain an extract.

Comparative Example 3. 300 bar

The same procedure as Comparative Example 1 was performed, but extraction was performed at 300 bar instead of 100 bar for 6 hours to obtain an extract.

<Test Example Ⅱ>

The statistical program Grahpad prism (ver. 6, Sandiego, California, USA) was used to analyze the results of this experiment, and the measurement results of each experimental item were expressed as mean ± standard deviation (mean ± SD). The mean difference between groups was confirmed by one-way ANOVA, and statistical significance was tested at the P<0.05 level using the Tukey test.

Test Example 2. Measurement of cannabidiol (CBD) extraction rate, etc.

The cannabidiol (CBD) content, purity, and extraction rate in the extract prepared according to Example 1 and Comparative Examples 1 to 3 were measured. * Significance between each group was confirmed (p＜0.0５).

Cannabidiol (CBD) content, purity, and extraction rate were measured using High Performance Liquid Chromatography (HPLC). The column used was Column (Luna C18(2) Column 150 The column temperature was maintained at 28°C, the flow rate was 1.2 mL/min, and the sample was injected at 5 μL. Detection of sample components was analyzed at 220 nm using a Diode Array Detector (DAD). Mobile phase A used a 0.1% formic acid aqueous solution, and mobile phase B used acetonitrile containing 0.1% formic acid, and were analyzed under gradient conditions as shown in [Table 2] below. Calibration curve A calibration curve was prepared using each peak area on the chromatogram using the standard solution, and the contents of CBD and THC contained in the sample were quantified using the prepared calibration curve.

Time (min) Mobile phase A ^* Mobile phase B ^† 0 30 70 6 30 70 12 23 77 22 23 77 22.2 30 70 26 30 70

^* 0.1% Formic acid in water, ^† 0.1% Formic acid in acetonitrile

division Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Extraction yield (%) 9.2 2.8 10.5 10.8 CBD content (%) 4.4± ^0.03b 1.3± ^0.02c 4.8± ^0.07a 4.6± ^0.02a CBD purity (%) 83.5± ^0.02b 87.4± ^0.04a 82.8± ^0.18c 82.9± ^0.09c CBD extraction rate (%) 71.1± ^0.59a 19.2± ^0.31c 70.4± ^1.08ab 68.6± ^0.37b

As shown in Table 3 above, the extract prepared according to Example 1 of the present invention was confirmed to have a higher content and extraction rate of cannabidiol (CBD) in the extract compared to Comparative Examples 1 to 3.

On the other hand, in Comparative Example 1, the extraction yield, content and extraction rate of cannabidiol (CBD) in the extract were very low, and in Comparative Example 3, the content and extraction rate of cannabidiol (CBD) in the extract were low.

Test Example 3. Confirmation of impurities in extract

In order to measure impurities contained in the extracts prepared according to Example 1 and Comparative Examples 1 to 3, the absorbance of the impurities was confirmed at a wavelength of 400 to 700 nm using a spectrophotometer, and the absorbance values of the impurities were compared at a wavelength of 450 nm. did.

Figure 2 is a graph measuring extracts prepared according to Example 1 and Comparative Examples 1 to 3 of the present invention using a spectrophotometer.

[Table 4] below shows the absorbance values of impurities at 400 to 500 nm, especially 450 nm, which confirmed the light-absorbing substances in FIG. 2, and photos of the resulting extract.

The following chromatography (Medium Pressure Liquid Chromatography) is a chromatographic purification of the extract prepared in Comparative Example 2.

As shown in Figure 2 and Table 4, the absorbance value of the extract prepared according to Example 1 of the present invention was similar to Comparative Example 1, and was confirmed to be lower than Comparative Examples 2 and 3.

A higher absorbance value means a higher content of impurities, which results in a dark brown color. The extract of Example 1 was light brown in color and had a low absorbance value, confirming that the content of impurities in the extract was low.

In addition, it was confirmed that the extract of Example 1 of the present invention had a low content of impurities even without purification.

Summarizing the results of Test Examples 2 and 3, Comparative Example 1 has a low content of impurities in the extract, but the extraction yield, content of cannabidiol (CBD) in the extract, and extraction rate are very low, and Comparative Example 2 has a low content of impurities in the extract. Although the cannabidiol (CBD) content and extraction rate are excellent, the impurity content in the extract is high, and in Comparative Example 3, the cannabidiol (CBD) content and extraction rate in the extract are low and the impurity content in the extract is also high, so the cannabidiol content in the extract is high. It was confirmed that Example 1, which had high (CBD) content and extraction rate and low impurity content, was the best.

Test Example 4. Purity measurement after crystallization

Example 1, Comparative Examples 1 to 3 were added with 10 times ethanol (weight ratio of 1:10) to each extract, left at -80°C for 24 hours, and the resulting precipitate was filtered through filter paper and dewaxed. obtained extract. The dewaxed extract was concentrated using a rotary vacuum concentrator to remove ethanol, then 1 to 1.5 times the amount of pentane was added and completely dissolved at 40°C, and then kept at 5°C for 30 minutes and stirred. Next, the temperature was maintained at 0°C for 15 minutes and stirred, the temperature was lowered to -10°C over 60 minutes, and then stirred at -10°C for 30 minutes to perform crystallization.

Figure 3 is a chromatogram measuring the purity of cannabidiol after crystallization of extracts prepared according to Example 1 and Comparative Examples 1 to 3.

division Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 CBD content in sample after dewaxing (g) 27.00± ^0.15b 33.12± ^0.28a 31.72± ^0.68a 30.82± ^0.59a CBD recovery amount after crystallization (g) 13.24± ^0.31b 17.53± ^0.39a 9.82± ^0.10c 7.84± ^0.07c Crystallization recovery rate (%) 49.03± ^0.56a 52.93± ^0.88a 31.73± ^0.34c 25.44± ^0.45c CBD Isolate purity(%) 100 100 100 100

As shown in Figure 3 and Table 5 above, the cannabidiol purity after crystallization of the extracts prepared according to Example 1 and Comparative Examples 1 to 3 was confirmed to be 100%.

division Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 CBD yield (%) after extraction 4.4± ^0.1a 1.3± ^0.1c 4.8± ^0.4a 4.6± ^0.3a CBD yield (%) after dewaxing 3.5± ^0.1a 1.2± ^0.2c 3.5± ^0.2a 3.8± ^0.5a CBD yield (%) after crystallization 2.15± ^0.2a 0.68± ^0.1c 1.52± ^0.1b 1.17± ^0.2b

As shown in Table 6 above, it was confirmed that the yield of cannabidiol finally crystallized from the hemp raw material was obtained at a higher yield in Example 1 compared to Comparative Example 1, Comparative Example 2, and Comparative Example 3.

Claims (11)

(A) decarboxylating hemp; and
(B) extracting the decarboxylated hemp including increasing the pressure from 100 bar to 200 bar under supercritical fluid and then lowering the pressure from 200 bar to 100 bar; Method for obtaining cannabidiol from. The method of obtaining cannabidiol from hemp according to claim 1, wherein in step (A), decarboxylation is performed at 100 to 150° C. for 120 to 240 minutes. The method of obtaining cannabidiol from hemp according to claim 1, wherein in step (A), decarboxylation is performed at 115 to 130° C. for 140 to 240 minutes. The method of claim 1, wherein the pressure conditions under the supercritical fluid in step (B) are
(a) maintaining at 100 bar for 50 to 80 minutes;
(b) increasing the pressure maintained at 100 bar to 200 bar;
(c) step of lowering the pressure to 100 bar when it reaches 200 bar; and
(d) When the pressure reaches 100 bar, it is maintained for 50 to 80 minutes and then the pressure is increased to 200 bar. A method of obtaining cannabidiol from hemp, characterized in that the step is repeated. The method of obtaining cannabidiol from hemp according to claim 4, wherein the pressure increase is performed at a rate of 2 to 5 bar/min. The method of claim 4, wherein the pressure is lowered from 200 bar to 100 bar within 10 seconds. The method of obtaining cannabidiol from hemp according to claim 4, wherein the pressurization is performed for 30 to 40 minutes. The method of claim 1, wherein the extraction time under supercritical fluid under the pressure conditions is 4 to 8 hours. The method of claim 1, wherein the supercritical fluid is supercritical carbon dioxide, supercritical ethane, supercritical propane, supercritical butane, supercritical pentane, supercritical hexane, supercritical heptane, supercritical dimethyl ether, and supercritical tetrafluoromethane. , A method of obtaining cannabidiol from hemp, characterized in that it is one selected from the group consisting of supercritical difluoromethane and supercritical fluoroethane. The method of claim 1, further comprising: (C) dewaxing the extract extracted with the supercritical fluid after step (B); and (D) crystallizing the dewaxed extract to obtain cannabidiol. The method of claim 10, wherein the purity of the crystallized cannabidiol is 99.0 to 100%.