A method for preparing 6-gingerol from piper nigrum

Abstract

This invention relates to a method for preparing 6-shogaol from chili peppers. It solves the technical problems of existing 6-shogaol extraction and purification methods, such as large solvent consumption and difficulty in recovery, significant safety hazards, unsuitability for large-scale production, cumbersome processes, long processing times, and low yields. The method of this invention includes the following steps: S1) Extracting and separating chili peppers using a supercritical CO2 method to obtain an oil paste; S2) Dissolving and saponifying with alkaline water, then concentrating to obtain a clear and transparent oil; S3) Performing molecular distillation to obtain a heavy phase component oil; S4) Eluting on a first silica gel column for adsorption, while simultaneously using thin-layer chromatography to detect the eluent, collecting the mixed eluent containing 6-shogaol, and concentrating to obtain a light red oily substance; S5) Eluting on a second silica gel column for adsorption, while simultaneously using thin-layer chromatography to monitor the eluent, collecting the eluent containing only a single point of 6-shogaol, and concentrating to obtain a light yellow oily substance; S6) Dissolving, decolorizing, and crystallizing at low temperature to obtain the 6-shogaol product.

Description

TECHNICAL FIELD

[0001] The application relates to a method for extracting and purifying an active substance in piper methysticum, in particular to a method for preparing 6-shogaol from piper methysticum. BACKGROUND

[0002] Piper methysticum, scientific name Zingiberaceae, is a family of monocotyledonous plants in the order of Zingiberales. Piper methysticum, also known as African pepper, is a perennial herb of Zingiberaceae, and is mainly produced in Ghana and West Africa. Piper methysticum is usually used as a seasoning, and can also be used to treat cough, enteritis, bronchitis, syphilis, cold and rheumatism, and has the effects of weight loss and insecticide. 6-shogaol (6-S) is a main component in Zingiberaceae, and has good anti-tumor and related pharmacological activities, such as antioxidant, anti-inflammatory, anti-emetic, protection of spinal cord injury and the like. 6-S shows good activity in anti-solid tumor cell proliferation. Figure 1 17 24 6-shogaol is a white to light yellow oily liquid with a molecular formula of CHO3, and is an alkyl phenol compound formed by dehydration of 6-gingerol. 6-shogaol has good anti-tumor and related pharmacological activities, such as antioxidant, anti-inflammatory, anti-emetic, protection of spinal cord injury and the like. 6-S shows good activity in anti-solid tumor cell proliferation.

[0003] A Chinese patent with the publication number CN101735030 A discloses a method for preparing 6-shogaol. In the method, ginger supercritical fluid extract is mixed with acid water liquid containing ethanol, and then heated to reflux. The acid water liquid is extracted with ethyl acetate, and then purified through a silica gel chromatographic column and finally purified through HPLC to obtain 6-shogaol. In the method, a large amount of hydrochloric acid and ethanol are used in the process of converting 6-shogaol, which increases the amount of solvent used and makes it difficult to recover the solvent. The use of hydrochloric acid and high-temperature heating is dangerous and causes damage to the equipment. Finally, the use of HPLC for purification is only suitable for the refinement of a small amount of product and is difficult to expand production.

[0004] A Chinese patent with the publication number CN107298642 B discloses a method for extracting and purifying 6-shogaol. In the method, ginger and dried ginger are used as raw materials, and then extracted with ethanol, petroleum ether and ethyl acetate, and then purified through a silica gel column and further purified through thin layer preparation chromatography. In the method, the steps are complicated, the time is long, the operation of thin layer preparation chromatography is difficult, and it is not easy to expand production.

[0005] The Chinese patent with the publication number CN106800502A "A method for extracting and separating 6-gingerol from Capsicum chinense" uses Capsicum chinense as raw material, subcritical extraction, organic solvent extraction, silica gel and reverse phase chromatography silica gel C18 filling material purification, crystallization and other steps. The process is complicated, a large amount of organic solvent is used, and only the extraction of 6-gingerol contained in Capsicum chinense is carried out, and the conversion process of other components such as capsaicin in Capsicum chinense is not carried out, so that the recovery rate and yield of 6-gingerol are low. SUMMARY

[0006] The purpose of the present application is to solve the technical problems of the existing 6-gingerol extraction and purification method: 1) a large amount of hydrochloric acid and ethanol solvents are used, which is difficult to recover, has a high safety hazard in operation, and uses HPLC purification, which is not suitable for large-scale production; 2) the extraction and purification process is complicated, time-consuming, and difficult to operate using thin layer preparation chromatography, which is not easy to expand production; 3) the conversion of other components such as capsaicin in Capsicum chinense is not carried out, resulting in low recovery rate and yield of 6-gingerol, and a method for preparing 6-gingerol from Capsicum chinense is provided.

[0007] The technical solution of the present application is:

[0008] The present application is a method for preparing 6-gingerol from Capsicum chinense, which is characterized by comprising the following steps:

[0009] S1) The dried Capsicum chinense is crushed and passed through a 20-60 mesh sieve, and CO2 supercritical extraction is carried out to obtain an oil paste;

[0010] S2) The oil paste is completely dissolved at room temperature using a first organic reagent, the filtrate is filtered, and alkali water is added for saponification, stirring at room temperature for 40-60 min, standing and separating, and taking the organic solvent phase; the saponification is repeated twice to take the organic solvent phase, and the water is washed to neutral, and concentrated to obtain a clear and transparent oil;

[0011] S3) The oil is loaded into the feed pipe of the molecular distillation equipment for molecular distillation, and the heavy phase component oil is collected;

[0012] The conditions for molecular distillation are: liquid nitrogen is added to the cold trap for condensation, the oil pump heating temperature is 130-150 DEG C, the rotation speed of the scraper is 260-270 rpm, and the vacuum degree is 50-70 mbar;

[0013] S4) The heavy phase component oil is adsorbed on the first silica gel column, and the first eluent is used for elution, and the eluent is detected by thin layer chromatography, and the mixed eluent containing 6-gingerol is collected, and the red oil is obtained by concentration;

[0014] In the thin layer chromatography detection, the thin layer chromatography developing agent is n-hexane: ethyl acetate: glacial acetic acid with a volume ratio of 8:3:0.2, and the spray color developing agent is 5% sulfuric acid formaldehyde solution;

[0015] The amount of the first silica gel is 2-4 times the amount of the heavy phase component oil;

[0016] S5) The light red oil is adsorbed on a second silica gel column, impurities are removed and eluted using a second eluent, and the eluent is monitored by thin layer chromatography. The eluent containing only a single point of 6-gingerol is collected, and the light yellow oil is obtained by concentration.

[0017] The amount of the second silica gel column is 8-12 times the amount of the light red oil.

[0018] S6) The light yellow oil is dissolved at 65-75°C using a second organic reagent, decolorized, and filtered to obtain the filtrate. The filtrate is crystallized at -10 to -5°C for 20-24 hours, quickly filtered, washed, and dried to obtain 6-gingerol product.

[0019] Further, in step S1), the CO2 supercritical method is used for extraction and separation under the following conditions: vacuum degree of 25-30 Mpa, temperature of 45-50°C, extraction time of 6-8 hours, and separation tank at 45-50°C and 3-5 Mpa.

[0020] Further, in step S2), the first organic reagent is one of petroleum ether and n-hexane, and the amount of the first organic reagent added is 6-10 times the amount of the oil paste. The alkali water is an aqueous solution of sodium hydroxide or potassium hydroxide, with a concentration of 6%-10%, and the amount of alkali water added is 8%-12% of the amount of the oil paste. The normal temperature is 23-28°C.

[0021] Further, in step S4), the first eluent is a mixed solvent formed by combining any one of n-hexane, cyclohexane, or petroleum ether with any one of isopropyl ether, ethyl acetate, or acetone. In the mixed solvent, the volume ratio of any one of n-hexane, cyclohexane, or petroleum ether to any one of isopropyl ether, ethyl acetate, or acetone is any one of 10:1, 8:2, or 7:3.

[0022] In step S4), after adsorption, the mixed solvent is prepared into eluents with volume ratios of 10:1, 8:2, and 7:3, and elution is performed in the order of 10:1, 8:2, and 7:3.

[0023] In the mixed solvent, the proportion of n-hexane or cyclohexane or petroleum ether is greater than the proportion of isopropyl ether or ethyl acetate or acetone.

[0024] Further, in step S5), the second eluent is the same as the first eluent.

[0025] In step S5), after adsorption, the same three volume ratios of eluent as in step S4) are used to sequentially elute in the same concentration order.

[0026] Further, in step S6), the second organic reagent is any one of ethanol, methanol, n-butanol and ethyl acetate, and the second organic reagent is added in an amount of 6-10 times the mass of the light yellow oil.

[0027] Further, the concentration conditions in steps S2), S4) and S5) are all as follows: concentration under vacuum at 65-75°C and -0.08Mpa~ -0.06Mpa until no solvent is recovered.

[0028] Further, in step S6), activated carbon is used for decolorization, the activated carbon is used in an amount of 2%-4% of the mass of the second organic reagent, and the decolorization time is 40-60min; the activated carbon is any one of 320 activated carbon, 767 activated carbon, KF03 activated carbon and Senhuan activated carbon.

[0029] Further, step S5) further comprises the following steps: collecting the eluent containing only the 6-gingerol single point, collecting the mixed eluent containing the 6-gingerol point, and returning the mixed eluent to step S4) for adsorption and elution.

[0030] Further, step S1 is specifically as follows:

[0031] The dried Capsicum Chinense is crushed and passed through a 40-mesh sieve, and then extracted by a CO2 supercritical method at 30Mpa and 50°C for 8h, and the separation kettle is separated at 50°C and 5Mpa to obtain the oil paste after CO2 supercritical extraction;

[0032] Step S2 is specifically as follows:

[0033] In the oil paste, 8 times the mass of n-hexane is added, and the mixture is stirred and dissolved at 25°C, the filtrate is obtained by filtration, 10% of the mass of the oil paste of sodium hydroxide aqueous solution is added to the filtrate, the concentration of the sodium hydroxide aqueous solution is 8%, the mixture is stirred at 25°C for 40-60min, and then the mixture is allowed to stand and separate into layers, and the organic solvent phase is taken; the saponification is repeated twice, the liquid is separated, the organic solvent phase is washed with purified water until neutral, and then the mixture is concentrated under vacuum at 70°C and -0.08Mpa~ -0.06Mpa until no liquid flows out, to obtain a clear and transparent oil;

[0034] Step S3 is specifically as follows:

[0035] The oil obtained in step S2) is loaded into a feed pipe of a molecular distillation device, liquid nitrogen is added into a cold trap for condensation, the oil pump is heated to an oil temperature of 140 DEG C, and heating is performed; the rotating speed of a scraper is set to 265 rpm, the vacuum degree is set to 56 mbar, and molecular distillation is performed; and the red heavy-phase component oil is collected;

[0036] Step S4 is specifically:

[0037] The heavy-phase component oil is adsorbed on a first silica gel column with a mass of 3 times the mass of the heavy-phase component oil, after adsorption, impurities are removed by using n-hexane, and the n-hexane and ethyl acetate are prepared into three mixed solvents with volume ratios of 10:1, 8:2 and 7:3; the silica gel column is eluted in sequence according to the order of 10:1, 8:2 and 7:3; the eluent is detected by using thin layer chromatography during elution; the mixed eluent containing 6-gingerol is collected until the eluent has no color after developing; and the eluent is concentrated at 70 DEG C and under vacuum of-0.08 Mpa to-0.06 Mpa until no solvent is recovered, so that a light red oil is obtained.

[0038] Step S5 is specifically:

[0039] The light red oil is adsorbed on a second silica gel column with a mass of 10 times the mass of the light red oil, after adsorption, the n-hexane and ethyl acetate are prepared into three mixed solvents with volume ratios of 10:1, 8:2 and 7:3, and the silica gel column is eluted in sequence according to the order of 10:1, 8:2 and 7:3; the eluent is monitored by using thin layer chromatography during elution; the eluent containing only a single point of 6-gingerol is collected; and the eluent is concentrated at 70 DEG C and under vacuum of-0.08 Mpa to-0.06 Mpa until no solvent is recovered, so that a light yellow oil is obtained.

[0040] Step S6 is specifically:

[0041] The light yellow oil is dissolved in anhydrous ethanol with a mass of 8 times the mass of the light yellow oil at 70 DEG C, 3% of the mass of the anhydrous ethanol is added to active carbon for stirring and decolorization for 60 min, and the eluent is filtered, the filtrate is placed in a refrigerator at-8 DEG C for crystallization for 22 h, after crystallization, the crystallization is quickly filtered, the crystallization is rinsed with anhydrous ethanol, and the solvent is dried at 60 DEG C and under vacuum of-0.08 Mpa to-0.06 Mpa, so that colorless to light yellow 6-gingerol product is obtained.

[0042] Advantages of the present application:

[0043] 1. The method for preparing 6-gingerol from H. annuum in the present application uses H. annuum as raw material, and after CO2 supercritical extraction, an extracted oil paste is obtained. The oil paste extracted by supercritical extraction of H. annuum contains a large part of fatty acids, so that the content of gingerol and 6-gingerol is low. By alkali water saponification, part of the fatty acids in the extracted oil paste are removed, so that the oil paste extracted by supercritical extraction becomes clear oil, so as to facilitate subsequent steps.

[0044] 2. The method for preparing 6-gingerol from the piper methysticum, the oil after saponification of alkali water is subjected to molecular distillation, the oil bath high-temperature heating is passed through the molecular distillation, and then vacuumizing is carried out under negative pressure, so that the piper methysticum oil is subjected to light-heavy phase separation, so that most of short-chain volatile fatty acids are in the light phase oil. Through the molecular distillation, the content of 6-gingerol in the heavy phase component oil of the piper methysticum is increased, and other components such as gingerols in the piper methysticum oil are converted into 6-gingerol through high temperature. Through the molecular distillation technology, the content of 6-gingerol is increased, and the yield of 6-gingerol is also increased. The method does not use corrosive acid and flammable and explosive organic solvent, is simple and convenient to operate, safe and reliable, and greatly reduces the cost.

[0045] 3. The method for preparing 6-gingerol from the piper methysticum, the heavy phase component oil after molecular distillation is subjected to coarse separation and fine separation of a silica gel column. The coarse separation column of the silica gel makes all the 6-gingerol be eluted and collected, and the coarse separation of the silica gel also achieves the effects of rough purification and decolorization of 6-gingerol. The fine separation column of the silica gel elutes through a solvent, and only the eluent of a single point of 6-gingerol is collected through a thin layer chromatography point plate, so that the content of 6-gingerol is greatly increased. The mixed eluent containing the point of 6-gingerol through the thin layer chromatography point plate can be returned to the separation of the coarse separation column and the fine separation column again, so that the 6-gingerol can achieve the maximum recovery of effective components.

[0046] 4. The method for preparing 6-gingerol from the piper methysticum, the single-point eluent of 6-gingerol of the fine separation column of the silica gel is subjected to decolorization through activated carbon, and then the 6-gingerol is further purified, so that the remaining small part of colored impurities are adsorbed on the activated carbon, and the content of 6-gingerol is further increased. Finally, low-temperature crystallization and rapid filtration are carried out, so that the content of 6-gingerol in the crystal reaches the final required content. Through the low-temperature crystallization, the crystallization is more thorough, and the melting of 6-gingerol due to low melting point is prevented, so that the content and yield of 6-gingerol reach the optimum.

[0047] 5. The method has the advantages of simple operation, mild test step condition, high product purity, high recovery rate and suitability for industrial production. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1 It is a structural formula of 6-gingerol;

[0049] Figure 2 It is a flow chart of the method for preparing 6-gingerol from the piper methysticum;

[0050] Figure 3The detection spectrum of 6-gingerol in the raw material in Example 1 of the method for preparing 6-gingerol from Pimenta racemosa is shown in the following table, and the content of 6-gingerol is 0.48;

[0051] Figure 4 The detection spectrum of 6-gingerol in the oil paste in Example 1 of the method for preparing 6-gingerol from Pimenta racemosa is shown in the following table, and the content of 6-gingerol is 10.15;

[0052] Figure 5 The detection spectrum of 6-gingerol in the product obtained in Example 1 of the method for preparing 6-gingerol from Pimenta racemosa is shown in the following table, and the content of 6-gingerol is 98.73. DETAILED DESCRIPTION

[0053] The specific process of the method for preparing 6-gingerol from Pimenta racemosa is shown in the following table. Figure 2 .

[0054] Example 1

[0055] S1: 5 kg of dried Pimenta racemosa (containing 0.48% of 6-gingerol, the detection spectrum is shown in the following table, and the detection data is shown in Table 1) is crushed, and then is extracted by CO2 supercritical method after being passed through a 40-mesh sieve, and the extraction is carried out at 30 Mpa and 50℃ for 8 h, and the separation kettle is separated at 50℃ and 5 Mpa to obtain the oil paste after CO2 supercritical extraction, and the content of 6-gingerol in the oil paste is 10.15%, and the detection spectrum is shown in the following table, and the detection data is shown in Table 2. Figure 3 Figure 4

[0056] S2: The oil paste in step S1 is added with 8 times of n-hexane to be dissolved under stirring at 25℃, and the filtrate is obtained by filtration, and 10% of sodium hydroxide aqueous solution by weight of the oil paste is added to the filtrate, and the concentration of the sodium hydroxide aqueous solution is 8%, and the mixture is stirred at 25℃ for 60 min, and then is left to separate into two layers, and the organic solvent phase is taken, and the saponification is carried out twice, and the organic solvent phase is washed with purified water until neutral, and then is concentrated at 70℃ and under a vacuum of-0.08 Mpa to-0.06 Mpa until no liquid flows out, to obtain clear and transparent oil.

[0057] S3: The oil obtained in step S2 is loaded into the feeding pipe of a molecular distillation device, liquid nitrogen is added into the cold trap to be condensed, the oil pump is heated to 140℃, and the heating is carried out; the rotating speed of the scraper is set to 265 rpm, and the vacuum degree is set to 56 mbar, and the molecular distillation is carried out under the above conditions, and the heavy phase component oil is collected from the heavy component bottle.

[0058] ​​S4: The heavy phase component oil of step S3 is adsorbed on a first silica gel column with an oil amount 3 times that of the oil, after adsorption, impurities are removed with n-hexane, and the n-hexane and ethyl acetate are prepared into a mixed solvent with a volume ratio of 10:1, 8:2, and 7:3, and the silica gel column is eluted in order of 10:1, 8:2, and 7:3, thin layer chromatography is used to monitor the eluent, the mixed eluent containing 6-gingerol is collected, and the solvent is recovered by concentration under vacuum at 70°C, -0.08Mpa~ -0.06Mpa until no solvent is left, to obtain a light red oil.

[0059] S5: The oil of step S4 is adsorbed on a second silica gel column with an oil amount 10 times that of the oil, after adsorption, the n-hexane and ethyl acetate are prepared into a mixed solvent with a volume ratio of 10:1, 8:2, and 7:3, and the silica gel column is eluted in order of 10:1, 8:2, and 7:3, thin layer chromatography is used to monitor the eluent, the eluent containing only 6-gingerol is collected, and the solvent is recovered by concentration under vacuum at 70°C, -0.08Mpa~ -0.06Mpa until no solvent is left, to obtain a light yellow oil.

[0060] In the thin layer chromatography detection, the thin layer chromatography developing agent is n-hexane: ethyl acetate: glacial acetic acid with a volume ratio of 8:3:0.2, the spray color developing agent is 5% sulfuric acid formaldehyde solution, and the eluent is collected after high-temperature heating color development, and the subsequent example thin layer chromatography detection method is consistent.

[0061] S6: The oil of step S5 is dissolved in 8 times the mass of anhydrous ethanol at 70°C, 3% of the mass of the anhydrous ethanol is added to the activated carbon of the Sun Ring, stirring is performed for 60 minutes, filtration is performed, the filtrate is placed in a refrigerator at -8°C for crystallization for 22 hours, after crystallization is completed, the crystallization is quickly filtered, the crystallization is rinsed with anhydrous ethanol, and the solvent is dried under vacuum at 60°C, -0.08Mpa~ -0.06Mpa, to obtain a light yellow oil product.

[0062] The weight of the obtained oil product is 22.6g, the content of 6-gingerol is 98.73%, the detection spectrum is shown in Figure 5 , and the detection data is shown in Table 3.

[0063] Table 1

[0064] Ingredient Retention time / min Peak area / AU*s Peak height / AU Content / % 6-Gingerol 14.133 125157 54763 0.48

[0065] Table 2

[0066] Ingredient Retention time / min Peak area / AU*s Peak height / AU Content / % 6-Gingerol 13.583 242458 23606 10.15

[0067] Table 3

[0068] Ingredient Retention time / min Peak area / AU*s Peak height / AU Content / % 6-Gingerol 13.583 1151708 112017 98.73

[0069] Example 2

[0070] S1: 5 kg of dried Capsicum (6-gingerol content 0.48%) was pulverized, passed through a 20-mesh sieve, and then extracted by a CO2 supercritical method at 25 MPa and 45°C for 8 h. The separation kettle was separated at 45°C and 3 MPa to obtain the oil paste after CO2 supercritical extraction, and the content of 6-gingerol in the oil paste was 10.08%.

[0071] S2: The oil paste of step S1 was dissolved in 8 times the amount of n-hexane at 25°C, and the filtrate was obtained by filtration. An aqueous solution of sodium hydroxide with a concentration of 6% was added to the filtrate in an amount of 8% of the oil paste, and stirred at 28°C for 60 min. After standing and separating the layers, the organic solvent phase was obtained, saponified twice, and separated. The organic solvent phase was washed with purified water until neutral, and then concentrated at 70°C and -0.08 MPa to -0.06 MPa under vacuum until no liquid flowed out, to obtain a clear and transparent oil.

[0072] S3: The oil obtained in step S2 was loaded into the feed pipe of a molecular distillation device, liquid nitrogen was added to the cold trap for condensation, and the oil pump was heated to an oil temperature of 135°C. The speed of the scraper was set to 263 rpm, and the vacuum degree was set to 70 mbar. Molecular distillation was carried out under these conditions, and the heavy component oil was collected in the heavy phase component oil bottle. The red heavy phase component oil was used as is.

[0073] S4: The heavy phase component oil of step S3 was adsorbed on a first silica gel column with 3 times the amount of oil, and after adsorption, n-hexane was used to remove impurities. Petroleum ether and ethyl acetate were mixed to prepare three mixed solvents with volume ratios of 10:1, 8:2, and 7:3, and the silica gel column was eluted in the order of 10:1, 8:2, and 7:3. Thin layer chromatography was used to monitor the eluent, and the mixed eluent containing 6-gingerol was collected and concentrated at 70°C and -0.08 MPa to -0.06 MPa under vacuum until no solvent was recovered, to obtain a light red oil.

[0074] S5: The oil of step S4 was loaded onto a second silica gel column with 10 times the amount of oil, and after adsorption, petroleum ether and ethyl acetate were mixed to prepare three mixed solvents with volume ratios of 10:1, 8:2, and 7:3, and the silica gel column was eluted in the order of 10:1, 8:2, and 7:3. Thin layer chromatography was used to monitor the eluent, and the eluent containing only 6-gingerol was collected and concentrated at 70°C and -0.08 MPa to -0.06 MPa under vacuum until no solvent was recovered, to obtain a light yellow oil.

[0075] S6: The oil of step S5 was dissolved in 8 times the amount of ethyl acetate at 70°C, and then 3% of 320 activated carbon was added to the solution and stirred for 60 min to decolorize. The solution was filtered, and the filtrate was cooled and crystallized at -8°C for 22 h. After crystallization, the crystal was quickly filtered and washed with anhydrous ethanol. The crystal was crystallized at 55°C and -0.08 MPa to -0.06 MPa under vacuum, and then dried at 55°C and -0.08 MPa to -0.06 MPa under vacuum for 24 h to obtain 6-gingerol.

[0076] -0.06 Mpa vacuum, to obtain a light yellow oil product. The weight of the oil product obtained is 22.1 g, and the content of 6-gingerol is 98.69%.

[0077] Example 3

[0078] S1: 5 kg of dried Capsicum annuum (6-gingerol content 0.48%) was crushed and sieved through a 60-mesh sieve, and then extracted by CO2 supercritical extraction at 30 Mpa and 45°C for 8 h. The separation kettle was separated at 50°C and 3 Mpa to obtain the oil paste after CO2 supercritical extraction, and the content of 6-gingerol in the oil paste was 10.36%;

[0079] S2: The oil paste of step S1 was dissolved by adding 8 times the amount of n-hexane at 25°C, and the filtrate was obtained by filtration. A 12% sodium hydroxide aqueous solution was added to the filtrate, the concentration of the sodium hydroxide aqueous solution was 10%, and the mixture was stirred at 23°C for 40 min. After standing and separating the layers, the organic solvent phase was obtained, and the saponification was repeated twice. After washing the organic solvent phase with purified water until it was neutral, the mixture was concentrated at 70°C and -0.08 Mpa to -0.06 Mpa vacuum until no liquid flowed out, to obtain a clear and transparent oil.

[0080] S3: The oil of step S2 was loaded into the feed tube of a molecular distillation device, liquid nitrogen was added to the cold trap for condensation, and the oil pump was heated to 150°C. The speed of the scraper was set to 260 rpm, and the vacuum degree was set to 50 mbar. Under these conditions, molecular distillation was carried out, and the heavy phase component oil was collected for use.

[0081] S4: The heavy phase component oil of step S3 was loaded onto a silica gel column with 2 times the amount of oil, and after adsorption, n-hexane was used to remove impurities. Petroleum ether and isopropyl ether were mixed to prepare a mixed solvent with a volume ratio of petroleum ether to isopropyl ether of 10:1, 8:2, and 7:3. The silica gel column was eluted in the order of 10:1, 8:2, and 7:3, and thin layer chromatography was used to monitor the eluent. The mixed eluent containing 6-gingerol was collected, and concentrated at 70°C and -0.08 Mpa to -0.06 Mpa vacuum until no solvent was recovered, to obtain a light red oil.

[0082]

[0083] ​S5: The oil of step S4 was loaded onto a second silica gel column with 12 times the oil amount, and after adsorption, a mixture solvent of petroleum ether and isopropyl ether with a volume ratio of 10:1, 8:2 and 7:3 was used to elute the silica gel column in order of 10:1, 8:2 and 7:3. Thin layer chromatography was used to monitor the eluent, and the eluent containing only 6-gingerol was collected. The eluent was concentrated at 70°C under vacuum at -0.08Mpa to -0.06Mpa until no solvent was recovered, and a light yellow oil was obtained.

[0084] S6: The oil of step S5 was dissolved in 6 times the mass of anhydrous ethanol at 65°C, and 4% of the liquid amount of 320 activated carbon was added to stir for 60 min. The filtrate was placed in a refrigerator at -10°C to crystallize for 20 h. After crystallization, the crystal was quickly filtered, and the crystal was rinsed with anhydrous ethanol. The crystal was dried under vacuum at 60°C at -0.08Mpa to -0.06Mpa to remove the solvent, and a light yellow oil product was obtained. The weight of the oil product was 22.8g, and the content of 6-gingerol was 98.70%.

[0085] Example 4

[0086] S1: 5kg of dried Borneo pepper (6-gingerol content 0.48%) was crushed and passed through a 40 mesh sieve. CO2 supercritical extraction was performed at 30Mpa and 45°C for 6h, and the separation kettle was separated at 45°C and 5Mpa to obtain the oil paste after CO2 supercritical extraction. The content of 6-gingerol in the oil paste was 10.19%.

[0087] S2: The oil paste of step S1 was added with 6 times the amount of n-hexane and stirred at 23°C to dissolve. The filtrate was added with 8% of a potassium hydroxide aqueous solution by weight of the oil paste, and the concentration of the potassium hydroxide aqueous solution was 8%. The mixture was stirred at 28°C for 60 min, and then was allowed to stand to separate into layers. The organic solvent phase was saponified twice, and then was washed with purified water until neutral. The mixture was concentrated at 75°C under vacuum at -0.08Mpa to -0.06Mpa until no liquid was discharged, and a clear and transparent oil was obtained.

[0088] S3: The oil of step S2 was loaded into the feed tube of a molecular distillation device, liquid nitrogen was added to the cold trap for condensation, and the oil pump was heated to 130°C. The rotation speed of the scraper was set to 270rpm, and the vacuum degree was set to 50mbar. The molecular distillation was performed under these conditions, and the heavy component oil was collected.

[0089] S4: The heavy phase component oil of step S3 is put on a first silica gel column with 4 times the oil amount, after adsorption, impurities are removed with n-hexane, and the silica gel column is eluted with a mixture solvent of petroleum ether and acetone in a volume ratio of 10:1, 8:2, and 7:3 in sequence, eluent is monitored with thin layer chromatography, and mixed eluent containing 6-gingerol is collected and concentrated at 70°C and under vacuum of -0.08Mpa to -0.06Mpa until no solvent is recovered, to obtain a light red oil.

[0090] S5: The oil of step S4 is put on a second silica gel column with 12 times the oil amount, after adsorption, a mixture solvent of petroleum ether and acetone in a volume ratio of 10:1, 8:2, and 7:3 is used to elute the silica gel column in sequence, eluent is monitored with thin layer chromatography, and eluent containing only 6-gingerol is collected and concentrated at 70°C and under vacuum of -0.08Mpa to -0.06Mpa until no solvent is recovered, to obtain a light yellow oil.

[0091] S6: The oil of step S5 is dissolved with 10 times the mass of methanol at 75°C, 2% KF03 activated carbon is added, stirring is performed for 40 min, filtration is performed, the filtrate is placed in a refrigerator at -5°C for crystallization for 24 h, after crystallization, rapid filtration is performed, the crystal is rinsed with anhydrous ethanol, and the crystal is dried under vacuum at 55°C and under vacuum of -0.08Mpa to -0.06Mpa to remove solvent, to obtain a light yellow oil product. The weight of the obtained oil product is 21.9 g, and the content of 6-gingerol is 98.46%.

[0092] Example 5

[0093] S1: 5 kg of dried heaven pepper (6-gingerol content 0.48%) is crushed and passed through a 60-mesh sieve, CO2 supercritical extraction is performed at 30Mpa and 45°C for 8 h, and the separation kettle is separated at 50°C and 5Mpa to obtain oil paste after CO2 supercritical extraction, and the content of 6-gingerol in the oil paste is 10.28%.

[0094] S2: The oil paste of step S1 is added with 8 times the amount of petroleum ether and stirred to dissolve at 25°C, the filtrate is filtered, 12% potassium hydroxide aqueous solution is added to the filtrate, the concentration of the potassium hydroxide aqueous solution is 6%, stirring is performed at 25°C for 60 min, the solution is left to separate, the organic solvent phase is taken, saponification is performed twice, the organic solvent phase is washed with purified water until neutral, and then concentrated at 70°C and under vacuum of -0.08Mpa to -0.06Mpa until no liquid flows out, to obtain clear and transparent oil.

[0095] S3: The oil of step S2 was loaded into the feed pipe of the molecular distillation equipment, liquid nitrogen was added into the cold trap for condensation, the oil pump was heated to 150°C, and heating was performed; the rotating speed of the scraper was set to 270 rpm, and the vacuum degree was set to 60 mbar, and molecular distillation was performed under the above conditions, liquid was generated in the heavy component outlet bottle, and the red heavy phase component oil was collected for use.

[0096] S4: The heavy phase component oil of step S3 was loaded onto a first silica gel column with an oil amount of 3 times the oil amount, after adsorption, impurities were removed with n-hexane, and cyclohexane and ethyl acetate were mixed to prepare a mixed solvent with a volume ratio of cyclohexane: ethyl acetate of 10:1, 8:2 and 7:3, and the silica gel column was eluted in sequence with the mixed solvents with a volume ratio of 10:1, 8:2 and 7:3, thin layer chromatography was used to monitor the eluent, the mixed eluent containing 6-gingerol was collected, and the solvent was concentrated at 70°C and under a vacuum of -0.08 Mpa to -0.06 Mpa until no solvent was recovered, to obtain a light red oil.

[0097] S5: The oil of step S4 was loaded onto a second silica gel column with an oil amount of 10 times the oil amount, after adsorption, cyclohexane and ethyl acetate were mixed to prepare a mixed solvent with a volume ratio of cyclohexane: ethyl acetate of 10:1, 8:2 and 7:3, and the silica gel column was eluted in sequence with the mixed solvents with a volume ratio of 10:1, 8:2 and 7:3, thin layer chromatography was used to monitor the eluent, and the eluent containing only a single point of 6-gingerol was collected, and the solvent was concentrated at 70°C and under a vacuum of -0.08 Mpa to -0.06 Mpa until no solvent was recovered, to obtain a light yellow oil.

[0098] S6: The oil of step S5 was dissolved in 10 times the mass of n-butanol at 75°C, 4% of the liquid amount of 767 activated carbon was added, stirring was performed for 60 min, and the mixture was filtered, the filtrate was placed in a refrigerator at -5°C for crystallization for 20 h, after crystallization, the crystallization was quickly filtered, the crystallization was rinsed with anhydrous ethanol, and the solvent was dried under a vacuum at 60°C and under a vacuum of -0.08 Mpa to -0.06 Mpa, to obtain a light yellow oil product. The weight of the obtained oil product was 22.5 g, and the content of 6-gingerol was 98.38%.

[0099] -0.06Mpa vacuum, to obtain a light yellow oil product. The weight of the obtained oil product was 22.5 g, and the content of 6-gingerol was 98.38%.

[0100] The raw material content detection spectrum of Example 2-Example 5 was the same as Figure 3 , the oil content detection spectrum was similar to Figure 4 , and the product content detection spectrum was similar to Figure 5 , and can be seen in Figures 3-5 .

Claims

1. A process for the preparation of 6-shogaol from Zingiber zerumbet, characterized by, The method comprises the following steps: S1) crushing dried Capsicum baccatum Linn, passing through a 20-60 mesh sieve, and extracting and separating by a CO2 supercritical method to obtain an oil paste; S2) completely dissolving the oil paste by using a first organic reagent at room temperature, filtering to obtain a filtrate, adding lye to perform saponification, stirring at room temperature for 40-60 min, standing to separate layers, and taking an organic solvent phase; repeating saponification twice to take an organic solvent phase, washing with purified water until neutral, and concentrating to obtain a clear and transparent oil; S3) loading the oil into a feeding pipe of a molecular distillation device to perform molecular distillation, and collecting a heavy phase component oil; The molecular distillation conditions are that liquid nitrogen is added into a cold trap to perform condensation, the oil pump heating temperature is 130-150 DEG C, the scraper speed is 260-270 rpm, and the vacuum degree is 50-70 mbar; S4) adsorbing the heavy phase component oil on a first silica gel column, eluting by using a first eluent, simultaneously detecting an eluent by using a thin layer chromatography, collecting mixed eluent containing 6-gingerol, and concentrating to obtain a light red oil; The first eluent is a mixed solvent formed by any one of n-hexane, cyclohexane and petroleum ether combined with any one of isopropyl ether, ethyl acetate and acetone; in the mixed solvent, the volume ratio of any one of n-hexane, cyclohexane and petroleum ether to any one of isopropyl ether, ethyl acetate and acetone is any one of 10:1, 8:2 and 7:3; After adsorption, the mixed solvent is prepared into eluents with three volume ratios of 10:1, 8:2 and 7:3, and elution is sequentially performed in the order of 10:1, 8:2 and 7:3; In the mixed solvent, the proportion of n-hexane or cyclohexane or petroleum ether is greater than that of isopropyl ether or ethyl acetate or acetone; In the thin layer chromatography detection, the thin layer chromatography developing agent is n-hexane: ethyl acetate: glacial acetic acid with a volume ratio of 8:3:0.2, and the spraying color developing agent is 5% sulfuric acid formaldehyde solution; The amount of the first silica gel is 2-4 times the mass of the heavy phase component oil; S5) adsorbing the light red oil on a second silica gel column, removing impurities and eluting by using a second eluent, simultaneously monitoring the eluent by using a thin layer chromatography, collecting eluent containing only a 6-gingerol single point, and concentrating to obtain a light yellow oil; The second eluent is the same as the first eluent; The amount of the second silica gel column is 8-12 times the mass of the light red oil; After adsorption, the same three volume ratios of eluents as in step S4) are used to sequentially perform elution in the same concentration order; S6) dissolving the light yellow oil by using a second organic reagent at 65 DEG C-75 DEG C, decolorizing, filtering to obtain a filtrate, crystallizing at-10 DEG C--5 DEG C for 20-24 h, quickly filtering the crystal, rinsing the crystal, and drying to obtain 6-gingerol product.

2. The method according to claim 1, wherein in step S1), the CO2 supercritical method for extraction and separation is performed under the following conditions: a vacuum degree of 25-30 Mpa, a temperature of 45-50 DEG C, and an extraction time of 6-8 h, and the separation kettle is separated at 45-50 DEG C and 3-5 Mpa. ​ 3.The method of claim 1 or 2, wherein the first organic reagent is one of petroleum ether and n-hexane, and the first organic reagent is added in an amount of 6-10 times the mass of the oil paste; the alkali water is an aqueous solution of sodium hydroxide or potassium hydroxide, the concentration of the alkali water is 6%-10%, and the alkali water is added in an amount of 8%-12% of the mass of the oil paste; and the normal temperature is 23-28℃. 4.The method of claim 1, wherein the second organic reagent is one of ethanol, methanol, n-butanol, and ethyl acetate, and the second organic reagent is added in an amount of 6-10 times the mass of the light yellow oil. 5.The method of claim 4, wherein the concentration in steps S2), S4), and S5) is performed at 65-75℃ under a vacuum of-0.08Mpa to-0.06Mpa until no solvent is recovered. 6.The method of claim 5, wherein the decolorization in step S6) is performed using activated carbon, and the activated carbon is used in an amount of 2%-4% of the mass of the second organic reagent, and the decolorization is performed for 40-60min. 7.The method of claim 6, wherein the activated carbon is one of 320 activated carbon, 767 activated carbon, KF03 activated carbon, and Senhuan activated carbon. 8.The method of claim 5, wherein step S5) further comprises the following steps: collecting the eluent containing only the single point of 6-shogaol, and collecting the mixed eluent containing the point of 6-shogaol, and returning the mixed eluent to step S4) for adsorption and elution. 9.The method of claim 1, wherein step S1 is performed as follows: the dried and crushed piper methysticum is passed through a 40-mesh sieve, and then extracted by a CO2 supercritical method at 30Mpa and 50℃ for 8h, and the separation kettle is separated at 50℃ and 5Mpa to obtain the oil paste after CO2 supercritical extraction. 10.The method of claim 1, wherein step S2 is performed as follows: n-hexane is added to the oil paste in an amount of 8 times the mass of the oil paste, and then stirred and dissolved at 25℃, and the filtrate is obtained by filtration, and then an aqueous solution of sodium hydroxide is added to the filtrate in an amount of 10% of the mass of the oil paste, and the concentration of the aqueous solution of sodium hydroxide is 8%, and then stirred at 25℃ for 40-60min, and then separated by layering, and then the organic solvent phase is obtained, and then the saponification is repeated twice, and then the organic solvent phase is washed with purified water until neutral, and then concentrated at 70℃ under a vacuum of-0.08Mpa to-0.06Mpa until no liquid flows out, and then a clear and transparent oil is obtained. 11.The method of claim 1, wherein step S3 is performed as follows: the oil obtained in step S2) is loaded into the feed pipe of a molecular distillation device, liquid nitrogen is added to the cold trap for condensation, the oil pump is heated to an oil temperature of 140℃, and then heated, the rotating speed of the wiper is set to 265rpm, and the vacuum degree is set to 56mbar, and then molecular distillation is performed, and then the oil of the red heavy phase component is collected.

7. A process for the preparation of 6-shogaol from Zingiber casmerium according to claim 6, wherein, 12.The method of claim 1, wherein step S4 is performed as follows:

8. A process for the preparation of 6-shogaol from Zingiber casmerium according to claim 7, wherein, ​ ​ ​ ​ ​ ​ ​ The heavy phase component oil is adsorbed on a first silica gel column with 3 times the mass of the oil, and after adsorption, impurities are removed using n-hexane. The n-hexane and ethyl acetate are mixed to form three mixed solvents with volume ratios of 10:1, 8:2, and 7:3, and the silica gel column is eluted in order with the three mixed solvents. The eluent is detected using thin layer chromatography, and the mixed eluent containing 6-gingerol is collected until the eluent is colorless. The eluent is concentrated at 70°C and -0.08Mpa to -0.06Mpa under vacuum until the solvent is recovered, and a light red oil is obtained. Step S5 is specifically: The light red oil is adsorbed on a second silica gel column with 10 times the mass of the oil, and after adsorption, the n-hexane and ethyl acetate are mixed to form three mixed solvents with volume ratios of 10:1, 8:2, and 7:3, and the silica gel column is eluted in order with the three mixed solvents. The eluent is monitored using thin layer chromatography, and the eluent containing only 6-gingerol is collected. The eluent is concentrated at 70°C and -0.08Mpa to -0.06Mpa under vacuum until the solvent is recovered, and a light yellow oil is obtained. Step S6 is specifically: The light yellow oil is dissolved in 8 times the mass of anhydrous ethanol at 70°C, and 3% of the mass of the anhydrous ethanol is added to the mixture to stir for 60 minutes. The mixture is filtered, and the filtrate is stored at -8°C to crystallize for 22 hours. The crystallization is completed, and the crystallization is quickly filtered. The crystallization is rinsed with anhydrous ethanol, and the solvent is dried at 60°C and -0.08Mpa to -0.06Mpa under vacuum. A colorless to light yellow 6-gingerol product is obtained.

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