A preparation method of rare ginsenoside quasi-monomer compound ΔPPD

Abstract

The present invention provides a preparation method of a rare ginsenoside quasi-monomer compound ΔPPD, belonging to the technical field of biotechnology. The present invention uses pyrolysis of the stem and leaf extract of Araliaceae plants as a raw material, first dissolves it in ethyl acetate, and uses petroleum ether to precipitate impurities. After removing the solvent, the obtained liquid phase is chromatographed with a macroporous adsorption resin column, and gradient eluted with an ethanol-water solution. The eluate of 90% ethanol-water solution is collected for decolorization, and the decolorized crude product is adsorbed with silica gel and mixed with silica gel and then loaded on a column, and eluted step by step with a mixture of petroleum ether and ethyl acetate in different proportions, and the eluate of the mixture of petroleum ether and ethyl acetate in a specific volume ratio is collected, concentrated, dissolved, and crystallized. The obtained crystal is a rare ginsenoside quasi-monomer compound ΔPPD. The preparation method can efficiently obtain the rare ginsenoside quasi-monomer compound ΔPPD, has the characteristics of high yield and purity, and at the same time, the operation steps are simple, the cost is low, and it is suitable for large-scale promotion and application.

Description

Technical Field

[0001] The invention belongs to the technical field of biotechnology, and specifically relates to a method for preparing a rare ginsenoside quasi-monomer compound ΔPPD. Background Art

[0002] There are some ingredients with extremely low contents in processed ginseng and Panax notoginseng products such as wild ginseng, red ginseng, black ginseng and cooked Panax notoginseng. Because they are only soluble in low-polarity organic solvents such as ethanol or ethyl acetate and difficult to dissolve in water, they are called low-polarity rare ginsenosides, including transformation derivatives with multiple double bond structures formed by the simultaneous desugaring and dehydration of the side chains (Δ(20-21)PPD, Δ(20-22)PPD, Rh4, Rk3, etc.). It is reported that low-polarity rare ginsenosides not only have the original biological activity of ordinary prototype ginsenosides, but also have new drug activities such as anti-tumor and anti-viral, and have extremely high medicinal value and application prospects.

[0003]

[0004] In the prior art, Δ(20-21)PPD (see formula I) and Δ(20-22)PPD (see formula II) are collectively referred to as low-polarity rare ginsenoside quasi-monomer compound ΔPPD. The current preparation method thereof has the problems of low directional conversion rate, low product yield, and high difficulty in separation and purification (Japanese Publication No. 8-29119). In addition, the current patents also disclose methods for producing and preparing low-polarity rare ginsenoside quasi-monomer compound ΔPPD using expensive protopanaxatriol group raw materials or monomer raw materials ginsenoside F1, or using expensive protopanaxadiol group raw materials or monomer raw materials ginsenoside CK, but due to the high preparation cost, the problem of supply shortage cannot be solved (CN1249076C, CN1249077C and CN1269835C). CN108558976A patent discloses that n-propanol, sodium metal, and benzoyl peroxide are sequentially added to the pyrolysis Araliaceae plant stem and leaf extract containing low-grade rare ginsenosides, and oxygen is introduced to perform heating reaction, and the reaction product is sequentially extracted with n-hexane and ethyl acetate to obtain the target product and purified. Although this method effectively reduces costs and is large-scale preparation, the preparation process involves a steaming process, which will cause many side reactions, resulting in the preparation of a small amount of rare ginsenoside quasi-monomer compound ΔPPD, and the product is doped with a variety of impurities, which affects the product yield and purity. Summary of the invention

[0005] In view of this, the purpose of the present invention is to provide a method for preparing a rare ginsenoside quasi-monomer compound ΔPPD, and to achieve the purpose of preparing the rare ginsenoside quasi-monomer compound ΔPPD and its monomer components with high yield and high purity through simple column chromatography separation technology and crystallization technology.

[0006] The present invention provides a method for preparing a rare ginsenoside quasi-monomer compound ΔPPD, comprising the following steps:

[0007] The pyrolysis of the Araliaceae plant stem and leaf extract was dissolved in ethyl acetate, precipitated with petroleum ether, and the liquid phase was separated;

[0008] After removing the solvent from the liquid phase, a macroporous adsorption resin column is used for chromatography, and eluted with 70% and 90% ethanol aqueous solutions by volume concentration in sequence, and the eluate with 90% ethanol aqueous solution is collected for decolorization to obtain a decolorized crude product;

[0009] Adsorbing the decolorized crude product with silica gel to obtain adsorption silica gel;

[0010] The adsorption silica gel and silica gel are mixed onto a column, and eluted step by step with petroleum ether and ethyl acetate mixed solution No. 1 and petroleum ether and ethyl acetate mixed solution No. 2 in sequence, and the eluate of the petroleum ether and ethyl acetate mixed solution No. 2 is collected, and then the solvent is removed and then dissolved with petroleum ether, crystallized, and the crystals are separated to obtain a rare ginsenoside quasi-monomer compound ΔPPD;

[0011] The volume ratio of petroleum ether and ethyl acetate in petroleum ether and ethyl acetate mixture No. 1 is (18-22):1;

[0012] The volume ratio of petroleum ether and ethyl acetate in petroleum ether and ethyl acetate mixed solution No. 2 is (8-12):1.

[0013] Preferably, the mass volume ratio of the pyrolyzed Araliaceae plant stem and leaf extract to ethyl acetate is 1:(2-5);

[0014] The volume ratio of ethyl acetate to petroleum ether is 1:2.5-3.5.

[0015] Preferably, the precipitation further comprises dissolving in ethyl acetate, using petroleum ether to precipitate the precipitate, separating the extract, and mixing the extract with the liquid phase for macroporous adsorption resin column chromatography.

[0016] Preferably, the filler in the macroporous adsorption resin chromatography column is D101C resin.

[0017] Preferably, the decolorization method comprises solvent extraction and / or resin chromatography;

[0018] The decolorizing solvent used in the solvent extraction method includes at least one of the following: ethanol, ethyl acetate, petroleum ether and isopropyl acetate;

[0019] The chromatography resin used in the resin chromatography method includes basic anion resin.

[0020] Preferably, the silica gel adsorption method is to dissolve the decolorized crude product in ethyl acetate, mix it evenly with silica gel, remove the solvent, and obtain adsorption silica gel.

[0021] Preferably, the mass ratio of the decolorized crude product to silica gel is 1:(1-2.5).

[0022] Preferably, the mass ratio of the adsorption silica gel to silica gel is 1:2.

[0023] Preferably, the crystallization method is stirring at 20-27°C;

[0024] The stirring speed is 200-1500 rpm.

[0025] Preferably, the crystal comprises Δ(20-21)PPD and Δ(20-22)PPD.

[0026] The present invention provides a preparation method of a rare ginsenoside quasi-monomer compound ΔPPD, wherein the pyrolysis of the stem and leaf extract of Araliaceae plants is used as a raw material, first dissolved in ethyl acetate, precipitated with petroleum ether, and a liquid phase is separated; the liquid phase is chromatographed with a macroporous adsorption resin column after removing the solvent, first eluted with a volume concentration of 70% ethanol aqueous solution to remove impurities, and the eluate of 90% ethanol aqueous solution is collected for decolorization, and the crude product after decolorization is adsorbed with silica gel and mixed with silica gel on a column, and then eluted step by step with a mixed solution of petroleum ether and ethyl acetate in different proportions, and the eluate of the mixed solution No. 2 of petroleum ether and ethyl acetate with a volume ratio of (8-12):1 is collected, and the solvent is removed and then dissolved with petroleum ether, crystallized, and crystals are separated to obtain a rare ginsenoside quasi-monomer compound ΔPPD. The preparation method provided by the present invention can efficiently obtain a rare ginsenoside quasi-monomer compound ΔPPD, has the characteristics of high yield and purity, and the operation steps are simple, the cost is low, and it is suitable for large-scale promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the HPLC spectrum of the standard product of the rare ginsenoside quasi-monomer compound ΔPPD; wherein, 32.09 mg of the standard product was fixed to a 5 ml volumetric flask, and the injection volume was 10 μl;

[0028] Figure 2 This is the HPLC spectrum of the rare ginsenoside quasi-monomer compound ΔPPD sample; 10.13 mg of the sample was fixed to a 5 ml volumetric flask, and the injection volume was 10 μl;

[0029] Figure 3 This is the morphology diagram of the rare ginsenoside quasi-monomer compound ΔPPD sample. DETAILED DESCRIPTION

[0030] The present invention provides a method for preparing a rare ginsenoside quasi-monomer compound ΔPPD, comprising the following steps:

[0031] The pyrolysis of the Araliaceae plant stem and leaf extract was dissolved in ethyl acetate, precipitated with petroleum ether, and the liquid phase was separated;

[0032] After removing the solvent from the liquid phase, a macroporous adsorption resin column is used for chromatography, and eluted with 70% and 90% ethanol aqueous solutions by volume concentration in sequence, and the eluate with 90% ethanol aqueous solution is collected for decolorization to obtain a decolorized crude product;

[0033] Adsorbing the decolorized crude product with silica gel to obtain adsorption silica gel;

[0034] The adsorption silica gel and silica gel are mixed onto a column, and eluted step by step with petroleum ether and ethyl acetate mixed solution No. 1 and petroleum ether and ethyl acetate mixed solution No. 2 in sequence, and the eluate of the petroleum ether and ethyl acetate mixed solution No. 2 is collected, and then the solvent is removed and then dissolved with petroleum ether, crystallized, and the crystals are separated to obtain a rare ginsenoside quasi-monomer compound ΔPPD;

[0035] The volume ratio of petroleum ether and ethyl acetate in petroleum ether and ethyl acetate mixed solution No. 1 is (18-22):1; the volume ratio of petroleum ether and ethyl acetate in petroleum ether and ethyl acetate mixed solution No. 2 is (8-12):1.

[0036] The invention discloses a method for pyrolyzing the stem and leaf extract of Araliaceae plants, dissolving the extract in ethyl acetate, using petroleum ether to separate the precipitate, and separating the liquid phase.

[0037] In the present invention, the preparation method of the pyrolysis Araliaceae plant stem and leaf extract is preferably as follows: after the pyrolysis Araliaceae plant stem and leaf are powdered, the stem and leaf powder is placed in a steam pressure cooker for cooking, and then the cooked stem and leaf powder is vacuum dried to obtain the dried cooked stem and leaf powder, and the dried cooked stem and leaf powder is soaked in 95% ethanol, and then filtered, and the filtrate is concentrated to obtain the stem and leaf powder extract. The specific process parameters of the pyrolysis Araliaceae plant stem and leaf extract are recorded in the patent CN108558976 A. The pyrolysis Araliaceae plant stem and leaf extract is a product sold by the applicant, such as the ginsenoside capsules or pills of the Redson brand.

[0038] In the present invention, the amount of ethyl acetate added is not particularly limited, as long as the pyrolysis of the stem and leaf extract of Araliaceae plants is completely dissolved. However, considering the cost of solvent use, the mass volume ratio of the pyrolysis of the stem and leaf extract of Araliaceae plants and ethyl acetate is preferably 1: (2-5), more preferably 1: (3-4), and most preferably 1: 4. The volume ratio of ethyl acetate to petroleum ether is preferably 1: 2.5-3.5, more preferably 1: 3. Experiments show that when only ethyl acetate is used to treat the pyrolysis of the stem and leaf extract of Araliaceae plants, the impurity content in the obtained solution is high, which affects the effect of subsequent silica gel separation. When only petroleum ether is used to treat the pyrolysis of the stem and leaf extract of Araliaceae plants, the impurity content in the obtained solution is low, but the dissolution effect is not good, which affects the yield of the rare ginsenoside quasi-monomer compound ΔPPD separated from the pyrolysis of the stem and leaf extract of Araliaceae plants. Experiments have shown that when ethyl acetate and petroleum ether are mixed and treated with the extract in a volume ratio of 3: 1, most of the impurities can be effectively removed and the ΔPPD component can be effectively extracted completely.

[0039] In the present invention, in order to fully extract the rare ginsenoside quasi-monomer compound ΔPPD as much as possible, it also includes extracting the rare ginsenoside quasi-monomer compound ΔPPD from the precipitate. The extraction method of the precipitate preferably also includes dissolving in ethyl acetate, precipitating with petroleum ether, separating the extract, and mixing the extract with the liquid phase for macroporous adsorption resin chromatography column chromatography. The method of adding petroleum ether is preferably stirring while adding. The amount of ethyl acetate and petroleum ether used in the extraction process refers to the above-mentioned treatment and is not repeated here.

[0040] After obtaining the liquid phase, the invention removes the solvent in the liquid phase and then uses a macroporous adsorption resin chromatography column for chromatography, and sequentially elutes with 70% and 90% ethanol aqueous solutions by volume concentration, collects the eluate of 90% ethanol aqueous solution for decolorization, and obtains a decolorized crude product.

[0041] In the present invention, the filler in the macroporous adsorption resin chromatography column is preferably D101C resin, purchased from Xi'an Lanxiao Technology New Materials Co., Ltd. The dry powder obtained by removing the solvent in the liquid phase is preferably dissolved in an ethanol aqueous solution with a volume concentration of 75%, and the obtained solution is loaded onto the column. The speed of loading onto the column is preferably 0.5 column volumes to 5 column volumes, more preferably 2 column volumes. The elution volume of the ethanol aqueous solution with a volume concentration of 70% and 90% is 2 column volumes to 6 column volumes, more preferably 4 column volumes. The speed of elution is preferably 2 column volumes to 6 column volumes, more preferably 3 column volumes.

[0042] In the present invention, the decolorization method preferably includes solvent extraction and / or resin chromatography. The decolorization solvent used in the solvent extraction method preferably includes at least one of the following: ethanol, ethyl acetate, petroleum ether and isopropyl acetate. The chromatographic resin used in the resin chromatography method preferably includes a basic anion resin. The basic anion resin is preferably LX-T5, LX-94, etc. of Xi'an Lanxiao Technology Advanced Materials Co., Ltd., LK-30, D941, D945, D285 of Amicogen (China) Biopharmaceutical Co., Ltd. or LK30 of Amicogen (China) Biopharmaceutical Co., Ltd.

[0043] After decolorization, the present invention adsorbs the decolorized crude product with silica gel to obtain adsorbed silica gel.

[0044] In the present invention, the silica gel adsorption method is preferably to dissolve the decolorized crude product in ethyl acetate and then mix it evenly with silica gel, remove the solvent, and obtain adsorption silica gel. The mass ratio of the decolorized crude product to silica gel is preferably 1: (1-2.5), more preferably 1: (1.5-2). The amount of ethyl acetate used is preferably enough to dissolve the decolorized crude product into a saturated solution. The method for removing the solvent is preferably drying. The preparation of the adsorption silica gel is conducive to adsorbing the target in the silica gel mesopores.

[0045] After obtaining the adsorption silica gel, the adsorption silica gel and silica gel are mixed and loaded onto a column, and petroleum ether and ethyl acetate mixed solution No. 1 and petroleum ether and ethyl acetate mixed solution No. 2 are sequentially used for step-by-step elution, and the eluate of the petroleum ether and ethyl acetate mixed solution No. 2 is collected and the solvent is removed, and then the eluate is dissolved with petroleum ether, crystallized, and the crystals are separated to obtain the rare ginsenoside quasi-monomer compound ΔPPD.

[0046] In the present invention, the mass ratio of the adsorbed silica gel to the silica gel is preferably 1:2. Experiments show that when the silica gel is used in a smaller ratio, the separation effect is improved, and when the silica gel is used in a larger ratio, the separation effect is good, but the amount of elution solvent and silica gel used is increased, which increases the production cost. The present invention mixes the adsorbed silica gel and the silica gel in a mass ratio of 1:2 and performs chromatography, which is beneficial to ensuring the separation effect while reducing the amount of elution solvent and silica gel, taking into account the cost.

[0047] In the present invention, the crystallization method is preferably stirring at 20 to 27°C. The stirring speed is preferably 200 to 1500 rpm, more preferably 700 rpm. The crystals preferably include Δ(20-21)PPD and Δ(20-22)PPD. Through detection, it can be seen that the total content of Δ(20-21)PPD and Δ(20-22)PPD in the crystals is more than 95%.

[0048] The following is a detailed description of the preparation method of a rare ginsenoside quasi-monomer compound ΔPPD provided by the present invention in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0049] Example 1

[0050] A preparation method of rare ginsenoside quasi-monomer compound ΔPPD

[0051] (1) Take pyrolyzed Araliaceae plant stem and leaf extract (produced by the company), add ethyl acetate in a solid-liquid ratio of 1:4 and heat to dissolve completely, then add petroleum ether in an amount 3 times the volume of ethyl acetate, add while stirring, and precipitate. After leaving at room temperature, filter with suction to obtain a filtrate and a filter residue.

[0052] (2) Add ethyl acetate to the residue in a solid-liquid ratio of 1:4, heat and stir to dissolve completely, then add petroleum ether 3 times the volume of ethyl acetate while stirring, and a precipitate will precipitate. Cool to room temperature, filter with suction to obtain the second filtrate, and collect the residue.

[0053] (3) The first filtrate and the second filtrate are mixed, concentrated, and dried to obtain a dry powder.

[0054] (4) The dry powder was completely dissolved in 75% ethanol aqueous solution, loaded onto a macroporous adsorption resin chromatography column filled with D101C resin, and gradient eluted with 70% ethanol aqueous solution, 90% ethanol aqueous solution, and anhydrous ethanol, respectively. The eluate from 90% ethanol aqueous solution was collected and concentrated to dryness.

[0055] (5) The dry powder obtained in step (4) was completely dissolved in 90% ethanol, passed through 001×16 cationic resin (purchased from Amicogen (China) Biopharmaceutical Co., Ltd.), and the effluent was decolorized by anion exchange resin chromatography column. The effluent was concentrated and dried to obtain a decolorized dry powder of the rare ginsenoside quasi-monomer compound ΔPPD.

[0056] (6) Take the decolorized dry powder of the rare ginsenoside quasi-monomer compound ΔPPD, dissolve it completely with a small amount of ethyl acetate, add silica gel 2.5 times the mass of the dry powder, stir to adsorb it completely, and then dry it to obtain adsorption silica gel.

[0057] (7) The adsorbed silica gel and silica gel were mixed in a mass ratio of 1:2 and loaded onto a column, and eluted with a mixture of petroleum ether and ethyl acetate No. 1 (20:1, volume ratio) and a mixture of petroleum ether and ethyl acetate No. 2 (10:1, volume ratio) in sequence, and the eluate of the mixture of petroleum ether and ethyl acetate No. 2 was collected.

[0058] (8) After the eluate of the mixture of petroleum ether and ethyl acetate No. 2 is concentrated to remove the solvent, an appropriate amount of petroleum ether is added to dissolve it completely, and the mixture is stirred at room temperature to precipitate crystals. The mixture is separated by suction filtration to obtain crystals and mother liquor, which are dried separately.

[0059] (9) The compounds in the crystals were detected by high performance liquid chromatography (HPLC). The chromatographic conditions were: syncronis C18 column (4.6 mm × 250 mm), detection slope length of 210 nm, injection volume of 10 μl, column temperature of 35°C, flow rate of 1 ml / min; mobile phase A: acetonitrile, mobile phase B: water; gradient elution program: 0-10 min B: 70%-40%; 10-40 min B: 40%-0%; 40-51 min B: 0%; 51-52 min B: 0%-70%; 52-55 min B: 70%. Figure 1 is the HPLC chromatogram of the reference substance. Figure 2 is the high performance liquid chromatogram of the sample. Figure 3 For sample pictures.

[0060] The yield of the quasi-monomer compound ΔPPD is 9.83% and the purity is 98.26%. (The content of the quasi-monomer compound ΔPPD in the raw material is 22.44%)

[0061] Comparative Example 1

[0062] A preparation method of rare ginsenoside quasi-monomer compound ΔPPD

[0063] The rare ginsenoside quasi-monomer compound ΔPPD was prepared according to the method of Example 1, except that only ethyl acetate was used to dissolve the raw materials in step (1).

[0064] Comparative Example 2

[0065] A preparation method of rare ginsenoside quasi-monomer compound ΔPPD

[0066] The rare ginsenoside quasi-monomer compound ΔPPD was prepared according to the method of Example 1, except that in step (1), only petroleum ether was added to treat the raw material.

[0067] Comparative Example 3

[0068] A preparation method of rare ginsenoside quasi-monomer compound ΔPPD

[0069] The rare ginsenoside quasi-monomer compound ΔPPD was prepared according to the method of Example 1, except that the mass ratio of adsorption silica gel to silica gel in step (7) was 1:1.5.

[0070] Comparative Example 4

[0071] A preparation method of rare ginsenoside quasi-monomer compound ΔPPD

[0072] The rare ginsenoside quasi-monomer compound ΔPPD was prepared according to the method of Example 1, except that the eluent in step (7) included a mixture of petroleum ether and ethyl acetate No. 3 (15:1, volume ratio) and a mixture of petroleum ether and ethyl acetate No. 2 (5:1, volume ratio) for elution.

[0073] Comparative Example 1: With the same weight of raw materials, the yield of the quasi-monomer compound ΔPPD is 9.63% and the purity is 97.72%. However, due to the use of ethyl acetate alone for dissolution, the impurities dissolved out are relatively large, and the amount of D101C resin and LK30 resin used later is increased. According to calculation, D101C resin is used 23.43% more, and LK30 resin is used 120.05% more. (For the dissolution step, the purpose is to remove impurities initially. The higher the content of petroleum ether in the dissolving solution, the less impurities are in the obtained dissolving solution; conversely, the more impurities are contained. However, when the content of the quasi-monomer compound ΔPPD in the dry powder is less than 60%, after the adsorption and impurity removal by D101C resin and LK30 resin, the content of the quasi-monomer compound ΔPPD obtained is about 60%. The difference lies in the amount of D101C resin and LK30 resin used).

[0074] Comparative Example 2: When petroleum ether is used alone for dissolution, the yield of the dry powder of the solution is 20.50%, and the content is 67.27%; the quasi-monomer compound ΔPPD in the raw material is 22.44%, and when petroleum ether is used alone for dissolution, the recovery rate of the quasi-monomer compound ΔPPD is 61.45%. It can be seen that the quasi-monomer compound ΔPPD in the raw material cannot be completely dissolved by using petroleum ether for dissolution.

[0075] Comparative Example 3: When the mass ratio of adsorbed silica gel to silica gel is 1:1.5, the yield of the quasi-monomer compound ΔPPD is 4.36% and the purity is 97.05%.

[0076] Comparative Example 4: No crystals were precipitated by crystallization with petroleum ether. Due to the increase in the content of ethyl acetate in the eluent, elution was performed with a mixture of petroleum ether and ethyl acetate No. 3 (15:1, volume ratio) and a mixture of petroleum ether and ethyl acetate No. 2 (5:1, volume ratio), resulting in the elution of impurities with strong polarity, and the content of the quasi-monomer compound ΔPPD in the eluent was reduced. No crystals were precipitated by crystallization with petroleum ether again.

[0077] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a rare ginsenoside quasi-monomer compound ΔPPD, characterized in that: The following steps are involved: The pyrolysis of the Araliaceae plant stem and leaf extract was dissolved in ethyl acetate, precipitated with petroleum ether, and the liquid phase was separated; The mass volume ratio of the pyrolyzed Araliaceae plant stem and leaf extract and ethyl acetate is 1:(2-5); The volume ratio of ethyl acetate to petroleum ether is 1:2.5-3.5; After removing the solvent from the liquid phase, a macroporous adsorption resin column is used for chromatography, and eluted with 70% and 90% ethanol aqueous solutions by volume concentration in sequence, and the eluate with 90% ethanol aqueous solution is collected for decolorization to obtain a decolorized crude product; Adsorbing the decolorized crude product with silica gel to obtain adsorption silica gel; The adsorption silica gel and silica gel are mixed and loaded onto a column, and eluted step by step with petroleum ether and ethyl acetate mixed solution No. 1 and petroleum ether and ethyl acetate mixed solution No. 2 in sequence, and the eluate of the petroleum ether and ethyl acetate mixed solution No. 2 is collected and the solvent is removed, and then dissolved with petroleum ether, crystallized, and crystals are separated to obtain a rare ginsenoside quasi-monomer compound ΔPPD; the mass ratio of the adsorption silica gel to the silica gel is 1:2; The volume ratio of petroleum ether and ethyl acetate in petroleum ether and ethyl acetate mixture No. 1 is (18-22):1; The volume ratio of petroleum ether and ethyl acetate in petroleum ether and ethyl acetate mixture No. 2 is (8-12):1; The crystals are Δ(20-21)PPD and Δ(20-22)PPD.

2. The preparation method according to claim 1, characterized in that: The precipitation also includes dissolving in ethyl acetate, using petroleum ether to precipitate the precipitate, separating the extract, and mixing the extract with the liquid phase to perform macroporous adsorption resin chromatography column chromatography.

3. The preparation method according to claim 1, characterized in that: The filler in the macroporous adsorption resin chromatography column is D101C resin.

4. The preparation method according to claim 1, characterized in that: The decolorization method is solvent extraction and / or resin chromatography; The decolorizing solvent used in the solvent extraction method is at least one of the following: ethanol, ethyl acetate, petroleum ether and isopropyl acetate; The chromatography resin used in the resin chromatography method is a basic anion resin.

5. The preparation method according to claim 1, characterized in that: The silica gel adsorption method comprises dissolving the decolorized crude product in ethyl acetate, mixing the mixture evenly with silica gel, and removing the solvent to obtain adsorption silica gel.

6. The preparation method according to claim 1, characterized in that: The mass ratio of the decolorized crude product to the silica gel is 1: (1-2.5).

7. The preparation method according to claim 1, characterized in that: The crystallization method is stirring at 20-27°C; The stirring speed is 200-1500 rpm.

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