Ginsenoside and mannitol eutectic crystal as well as preparation method and application thereof

Abstract

The invention relates to the technical field of eutectic crystals, in particular to a ginsenoside and mannitol eutectic crystal as well as a preparation method and application thereof, an XRD (X-Ray Diffraction) pattern of the eutectic crystal at least has characteristic diffraction peaks at 2 theta angles of 13.80 degrees, 17.45 degrees, 18.90 degrees, 20.03 degrees, 20.60 degrees, 21.41 degrees, 21.54 degrees, 28.30 degrees, 34.13 degrees and 44.08 degrees, and has error tolerance of + / -0.2 degrees; in a DSC spectrum, characteristic endothermic peaks exist at 168.4 DEG C and 359 DEG C, and error tolerance of + / -0.2 DEG C exists. The preparation method comprises the following steps: dissolving mannitol in pure water and ginsenoside in ethanol, mixing, homogenizing or carrying out high-pressure reaction or ultrasonic treatment in a reaction kettle, standing, crystallizing, filtering, drying and grinding. The prepared eutectic crystal can be applied to cosmetics, food, health care products and medicines. The eutectic crystal provided by the invention has the advantages of no irritation, high safety, easy absorption and good stability.

Description

Technical Field

[0001] The present invention relates to the technical field of co-crystals, and in particular to a ginsenoside and mannitol co-crystal, a preparation method thereof, and an application thereof. Background Art

[0002] Ginsenosides are active ingredients extracted from the Araliaceae plant Panax ginseng. Based on their chemical structure and aglycone type, they are mainly divided into the following three categories:

[0003] (1) Dammarane saponins: including the ginsenoside group (PDT), represented by Rb1, Rb2, Rc, and Rd, which are mainly distributed in the roots of ginseng and have antioxidant, anti-inflammatory, cardiovascular protection, and blood sugar and blood lipid regulation effects. It also includes the ginsenoside group (PrT), represented by Rg1, Rg2, and Re, which have high content and have the effects of immune regulation, anti-fatigue, improving cognitive function, and promoting DNA / RNA synthesis.

[0004] (2) Oleanane saponins: including Ro, Rh3, etc., which are widely distributed in nature, but relatively less studied. They mainly have the effects of regulating immunity, anti-inflammation, antioxidant, and improving sleep quality.

[0005] (3) Rare saponins: Most of them are metabolic transformation products, such as Rh1, Rh2, Rk1, aPPD, etc., which have anti-tumor, neuroprotective and metabolic regulation effects.

[0006] However, most ginsenoside components have poor water solubility and low bioavailability, making them difficult to be effectively absorbed by the human body, which limits their application in oral medications and cosmetics.

[0007] Mannitol, also known as mannitol, is a white crystalline solid belonging to the hexane group of sugar alcohols. Its molecular structure contains six hydroxyl (-OH) groups, giving it strong hygroscopicity and polyol properties. As a natural or synthetic compound, it is widely used in the pharmaceutical, food, chemical, and cosmetic industries due to its moisturizing, antioxidant, anti-inflammatory, soothing, mild, hypoallergenic, permeation-enhancing, and cardiovascular protective properties. Summary of the Invention

[0008] The present invention solves the problem of poor absorption of ginsenosides in related technologies, and proposes a ginsenoside and mannitol co-crystal and its preparation method and application. The obtained co-crystal has the advantages of being non-irritating, highly safe, having good transdermal absorption and good stability.

[0009] In order to solve the above technical problems, the present invention is achieved through the following technical solutions: a ginsenoside and mannitol co-crystal, wherein the XRD spectrum of the ginsenoside and mannitol co-crystal has characteristic diffraction peaks at least at 2θ angles of 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08°, with an error tolerance of ±0.2°; and characteristic endothermic peaks at 168.4°C and 359°C in the DSC spectrum, with an error tolerance of ±0.2°C.

[0010] As a preferred embodiment, the XRD pattern of the ginsenoside and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 9.58°, 14.78°, 23.59°, 25.29°, 26.25°, 27.16°, 27.69°, 28.68°, 31.65°, 33.33°, 35.69°, 36.33°, and 39.72°, with an error tolerance of ±0.2°; the grain sizes corresponding to the characteristic diffraction peaks are

[0011] As a preferred embodiment, the XRD pattern of the ginsenoside and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 11.15°, 25.88°, 29.61°, 30.53°, 31.20°, 34.32°, 36.79°, 38.67°, 40.93°, 43.56°, 47.61°, 48.49°, 56.75°, and 65.72°, with an error tolerance of ±0.2°; the grain sizes corresponding to the characteristic diffraction peaks are

[0012] As a preferred embodiment, the grain sizes corresponding to the characteristic diffraction peaks of 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08° are respectively

[0013] As a preferred solution, the infrared spectrum of the ginsenoside and mannitol cocrystal is at least 3275.55 cm -1 、2938.19cm -1 、1457.46cm -1 、1429.13cm -1 、1371.89cm -1 、1315.44cm -1 、1260.99cm -1 、1195.47cm -1、1076.22cm -1 、1040.18cm -1 、1018.33cm -1 、951.34cm -1 、926.81cm -1 、882.12cm -1 、714.11cm -1 、653.03cm -1 、628.01cm -1 、519.35cm -1 、494.64cm -1 、476.55cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0014] Another aspect of the present invention provides a method for preparing a ginsenoside-mannitol cocrystal, comprising the following steps:

[0015] S1. Weigh mannitol and pure water according to the ratio, and stir to dissolve mannitol in the pure water to form a mannitol solution;

[0016] S2. Weigh ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution;

[0017] S3, adding the ginsenoside solution dropwise to the mannitol solution and stirring evenly;

[0018] S4. The solution in step S3 is taken out and homogenized in a high-pressure homogenizer at a pressure of 800 bar to 1200 bar; or the solution in step S3 is taken out and placed in a reactor to react for 0.5 to 1 hour at a pressure of 10 to 15 MPa and a temperature of 30 to 40° C.; or the solution in step S3 is taken out and ultrasonicated in an ultrasonic instrument for 2 to 4 hours;

[0019] S5. Take out the reaction solution in S4 and let it stand for crystallization;

[0020] S6. Filter, dry, and grind the crystals in S5 into fine powder.

[0021] As a preferred solution, the mass ratio of mannitol, ginsenoside, ethanol and pure water is 2:1:4:3.

[0022] As a preferred solution, in step S2, stirring is performed in a heat-collecting constant temperature heating magnetic stirrer at a temperature of 30°C to 50°C, a rotation speed of 150 to 250 r / min, and a stirring time of 1 to 2 hours.

[0023] As a preferred solution, in step S6, the product is dried in an oven at 30-50°C.

[0024] The last aspect of the present invention also provides the use of ginsenoside and mannitol co-crystal in cosmetics, food, health products and medicines.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) The ginsenoside and mannitol co-crystals successfully prepared by the present invention rearrange their molecular structure through non-covalent bonds such as hydrogen bonds and van der Waals forces. This arrangement not only optimizes the physical and chemical properties of the co-crystal, but also significantly reduces its irritation to the skin. Therefore, in cosmetic applications, the co-crystal can effectively reduce the occurrence of allergic symptoms such as skin redness, swelling, and itching, greatly improving the safety of cosmetic products.

[0027] (2) The ginsenoside and mannitol co-crystal obtained by the present invention has excellent transdermal absorption performance, thereby effectively improving the problem that ginsenoside itself has poor absorption and is difficult to be effectively utilized by the skin. The co-crystal can more efficiently penetrate the skin barrier and be fully absorbed and utilized by the human skin, thereby fully exerting the multiple effects of ginsenosides such as antioxidant and anti-inflammatory.

[0028] (3) In addition, the ginsenoside and mannitol co-crystal prepared by the present invention also has significant advantages in terms of stability. Compared with single ginsenoside, the stability of the co-crystal is significantly improved. This feature makes the co-crystal more reliable in the application of cosmetics, medicines, health care products and other fields. Whether in production, storage or use, the co-crystal can maintain the effectiveness of the active ingredient for a long time, thereby extending the shelf life and use effect of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 is the XRD pattern of ginsenoside, mannitol and ginsenoside mannitol cocrystal of the present invention;

[0030] Figure 2 is a DSC graph of the co-crystal of ginsenoside and mannitol of the present invention;

[0031] Figure 3 is a DSC graph of ginsenosides of the present invention;

[0032] Figure 4 It is the DSC diagram of mannitol of the present invention;

[0033] Figure 5 This is the infrared spectrum of the ginsenoside and mannitol cocrystal of the present invention;

[0034] Figure 6 This is a graph showing the irritation test of the ginsenoside and mannitol co-crystal of the present invention (chicken embryo test results);

[0035] Figure 7 This is a test chart of the irritation of ginsenosides of the present invention (chicken embryo test results);

[0036] Figure 8 This is a data chart showing the percentage of mannitol-ginsenoside cocrystal and ginsenoside after transdermal absorption of the present invention;

[0037] Figure 9 This is a stability test chart of the mannitol ginsenoside cocrystal and ginsenoside aqueous solution of the present invention. DETAILED DESCRIPTION

[0038] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0039] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.

[0040] Unless otherwise specifically stated, the relative arrangement of the parts and steps, the numerical expressions and the numerical values ​​set forth in these embodiments do not limit the scope of the present invention. At the same time, it should be understood that, for ease of description, the sizes of the various parts shown in the drawings are not drawn according to the actual proportional relationship. The techniques, methods and equipment known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, the techniques, methods and equipment should be considered as part of the authorization specification. In all examples shown and discussed here, any specific values ​​should be interpreted as being merely exemplary and not as limiting. Therefore, other examples of the exemplary embodiments may have different values. It should be noted that similar numbers and letters represent similar items in the following figures, and therefore, once an item is defined in one figure, it does not need to be further discussed in subsequent figures.

[0041] Example 1

[0042] A method for preparing a ginsenoside-mannitol cocrystal comprises the following steps:

[0043] S1. Weigh mannitol and pure water according to the ratio in the table below, and stir to dissolve mannitol in the pure water to form a mannitol solution;

[0044] S2. Weigh ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution (to accelerate dissolution, ultrasonication can also be used at 40°C to assist);

[0045] S3. Slowly add the ginsenoside solution dropwise to the mannitol solution and stir evenly in a heat-collecting constant-temperature heating magnetic stirrer at a speed of 200 r / min, a temperature of 40° C., and a stirring time of 1.5 h;

[0046] S4. Take out the solution in step S3 and put it into a high-pressure homogenizer for homogenization at a pressure of 1000 bar;

[0047] S5. Take out the reaction solution in S4 and let it stand for 24 hours to wait for crystallization;

[0048] S6. Filter the crystals in S5 using quantitative filter paper, dry them in an oven at 40°C, and grind them into fine powder.

[0049] The mass ratio is shown in the following table:

[0050] Material Name Ratio Ginsenosides 10％ Mannitol 20％ pure water 30％ ethanol 40％

[0051] Example 2

[0052] A method for preparing a ginsenoside-mannitol cocrystal comprises the following steps:

[0053] S1. Weigh mannitol and pure water according to the ratio in the table below, and stir to dissolve mannitol in the pure water to form a mannitol solution;

[0054] S2. Weigh ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution (to accelerate dissolution, ultrasonication can also be used at 40°C to assist);

[0055] S3. Slowly add the ginsenoside solution dropwise to the mannitol solution and stir evenly in a heat-collecting constant-temperature heating magnetic stirrer at a speed of 150 r / min, a temperature of 30° C., and a stirring time of 2 h.

[0056] S4. Take out the solution in step S3 and put it into a high-pressure homogenizer for homogenization at a pressure of 800 bar;

[0057] S5. Take out the reaction solution in S4 and let it stand for 24 hours to wait for crystallization;

[0058] S6. Filter the crystals in S5 using quantitative filter paper, dry them in an oven at 30°C, and grind them into fine powder.

[0059] The mass ratio is shown in the following table:

[0060] Material Name Ratio Ginsenosides 10％ Mannitol 20％ pure water 30％ ethanol 40％

[0061] Example 3

[0062] A method for preparing a ginsenoside-mannitol cocrystal comprises the following steps:

[0063] S1. Weigh mannitol and pure water according to the ratio in the table below, and stir to dissolve mannitol in the pure water to form a mannitol solution;

[0064] S2. Weigh ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution (to accelerate dissolution, ultrasonication can also be used at 40°C to assist);

[0065] S3. Slowly add the ginsenoside solution dropwise to the mannitol solution and stir evenly in a heat-collecting constant-temperature heating magnetic stirrer at a speed of 250 r / min, a temperature of 50° C., and a stirring time of 1 h.

[0066] S4. Take out the solution in step S3 and put it into a high-pressure homogenizer for homogenization at a pressure of 1200 bar;

[0067] S5. Take out the reaction solution in S4 and let it stand for 24 hours to wait for crystallization;

[0068] S6. Filter the crystals in S5 using quantitative filter paper, dry them in an oven at 50°C, and grind them into fine powder.

[0069] The mass ratio is shown in the following table:

[0070] Material Name Ratio Ginsenosides 10％ Mannitol 20％ pure water 30％ ethanol 40％

[0071] Example 4

[0072] The difference from Example 1 is that in step S4, the solution in step S3 is taken out and placed in a reactor to react for 45 minutes at a pressure of 13 MPa and a temperature of 35°C.

[0073] Example 5

[0074] The difference from Example 1 is that in step S4, the solution in step S3 is taken out and placed in a reactor to react for 30 minutes at a pressure of 15 MPa and a temperature of 40°C.

[0075] Example 6

[0076] The difference from Example 1 is that in step S4, the solution in step S3 is taken out and placed in a reactor to react for 60 minutes at a pressure of 10 MPa and a temperature of 30°C.

[0077] Example 7

[0078] The difference from Example 1 is that in step S4, the solution in step S3 is taken out and ultrasonicated in an ultrasonic instrument for 3 hours at a power of 250 W and a frequency of 50 kHz.

[0079] Example 8

[0080] The difference from Example 1 is that in step S4, the solution in step S3 is taken out and ultrasonicated in an ultrasonic instrument for 2 hours at a power of 250 W and a frequency of 50 kHz.

[0081] Example 9

[0082] The difference from Example 1 is that in step S4, the solution in step S3 is taken out and ultrasonicated in an ultrasonic instrument for 4 hours at a power of 250 W and a frequency of 50 kHz.

[0083] The ginsenoside and mannitol cocrystal obtained in Example 1 was subjected to X-ray diffraction analysis, and the specific test parameters were:

[0084] Voltage, current: 40kV, 40mA

[0085] Detector: DteX250(H)

[0086] Test range: 5-80°

[0087] Step size: 0.01°

[0088] Scanning speed: 10.00deg / min

[0089] Divergence slit: 10mm;

[0090] Get as Figure 1 The XRD pattern of the cocrystal of ginsenoside and mannitol is shown in FIG. 1 , and the XRD pattern of the cocrystal of ginsenoside and mannitol has characteristic diffraction peaks at 2θ angles of 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08°, with an error tolerance of ±0.2°; the grain sizes corresponding to the characteristic diffraction peaks are

[0091] Furthermore, the XRD pattern of the ginsenoside and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 9.58°, 14.78°, 23.59°, 25.29°, 26.25°, 27.16°, 27.69°, 28.68°, 31.65°, 33.33°, 35.69°, 36.33°, and 39.72°, with an error tolerance of ±0.2°; the grain sizes corresponding to each characteristic diffraction peak are

[0092] Furthermore, the XRD pattern of the ginsenoside and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 11.15°, 25.88°, 29.61°, 30.53°, 31.20°, 34.32°, 36.79°, 38.67°, 40.93°, 43.56°, 47.61°, 48.49°, 56.75°, and 65.72°, with an error tolerance of ±0.2°; the grain sizes corresponding to each characteristic diffraction peak are

[0093] Table 1 XRD data of ginsenoside-mannitol cocrystal

[0094]

[0095]

[0096] The ginsenosides and mannitol cocrystals obtained in Example 1 and the raw materials were subjected to DSC testing. The test parameters were as follows: temperature 50-400°C, heating rate 10.0°C / min, Ar 20.0mL / min. The results are as follows: Figure 2-4 As shown in the figure, the temperature corresponding to the peak is the temperature inside the high-temperature furnace of the instrument. Since the sample temperature is lower than the furnace temperature at the same time, the sample temperature is analyzed by software as follows:

[0097] 1) Ginsenosides: melting peak melting point appears at 242.67℃;

[0098] 2) Mannitol: melting point 169.19°C / 169.54°C (melting point in literature 166°C);

[0099] 3) Ginsenoside and mannitol co-crystal: There are two obvious melting peaks, the first peak is a melting point of 168.39°C, and the second peak is 359.04°C (the melting point of ginsenoside is 242.67°C). The DSC spectra of the ginsenoside and mannitol co-crystal are inconsistent with those of the two raw materials ginsenoside and mannitol, indicating that a co-crystal was obtained.

[0100] The ginsenosides and mannitol cocrystals obtained in Example 1 were subjected to infrared testing to obtain the following Figure 5 The infrared spectrum shown, Figure 5 The infrared spectrum of ginsenoside and mannitol cocrystal is 3275.55 cm -1 、2938.19cm -1 、1457.46cm -1 、1429.13cm -1 、1371.89cm -1 、1315.44cm-1 、1260.99cm -1 、1195.47cm -1 、1076.22cm -1 、1040.18cm -1 、1018.33cm -1 、951.34cm -1 、926.81cm -1 、882.12cm -1 、714.11cm -1 、653.03cm -1 、628.01cm -1 、519.35cm -1 、494.64cm -1 、476.55cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0101] Example 4 Efficacy Test:

[0102] 1. Irritation test:

[0103] Test method: Chicken chorioallantoic membrane test for eye irritation / corrosion of cosmetics (SN / T 2329)

[0104] Determination of acute toxicity of water substances to freshwater fish (zebrafish) (GB / T13267-91)

[0105] Testing instruments: stereo microscope, fully automatic incubator

[0106] Sample Information:

[0107]

[0108] The results of the chicken embryo test are as follows:

[0109]

[0110] The zebrafish test results are as follows:

[0111]

[0112] According to the above chicken embryo test results tabular data and Figure 6 and Figure 7 The results showed that 1.0% mannitol-ginsenoside cocrystals were non-irritating, while raw ginsenosides were mildly irritating. The zebrafish test results showed that mannitol-ginsenoside cocrystals were safer than raw ginsenosides.

[0113] 2. Transdermal absorption test

[0114] Sample Information:

[0115]

[0116]

[0117] (1) Test method for release from the surface of miniature pig skin:

[0118] Pig skin model: Xiaoba fragrant pig skin

[0119] Supply solution: 1# ginsenoside and mannitol eutectic solution, 2# ginsenoside solution

[0120] Experimental methods:

[0121] Diffusion cell installation and skin condition testing:

[0122] Without adding receiving solution, use filter paper to absorb the moisture of the skin (weigh it) and place it on the top surface of the receiving pool with the skin stratum corneum facing up. Add water to the supply pool to test whether there is liquid infiltration in the receiving pool. If there is no infiltration, discard the saline in the supply pool and wipe the water on the supply pool and skin surface;

[0123] The sample receiving solution was balanced by adding 5 mL of physiological saline solution (weighed) until it was in complete contact with the skin and no bubbles were expelled, and then placed in a water bath for 30 minutes to balance;

[0124] Add sample supply solution: Take 400 μL of 1# and 2# supply solution respectively and add them to the supply pool;

[0125] The diffusion cell temperature was 34°C and the stirring speed was 450 rpm.

[0126] Sampling test after 4 hours:

[0127] ① Weigh the total weight of the supply liquid in the supply pool (place it in a 25mL beaker or centrifuge tube, and weigh the gross weight of the supply pool in advance), rinse with 50% methanol and dilute to 10mL, shake it with ultrasonic waves for 20 minutes, and filter and ultrasonically degas;

[0128] ② Weigh the total weight of the skin surface (the skin weight needs to be weighed in advance), rinse with 50% methanol or wipe the surface with a cotton swab, then dilute to 2 mL, shake well, filter, and ultrasonically degas;

[0129] ③ Cut the skin into pieces, add 2 mL of 50% methanol and sonicate for 20 minutes;

[0130] ④ Take 1 mL of receiving solution, filter it, and then ultrasonically degas it for 1 minute before injecting it into the sample.

[0131] (2) Ginsenoside transdermal absorption test method:

[0132] Instrument: G3-Q TOF LC / MS

[0133] Chromatographic conditions:

[0134] Chromatographic column: ACQUITY UPLC HSS BEH C18 (2.1*50mm, 1.7μm);

[0135] Mobile phase: Phase A 0.1% formic acid in water Phase B 0.1% formic acid in acetonitrile

[0136] Elution method: gradient method; B phase ratio: 0-30min, 5%-95%; 30-35min, 95%; 35.5-40min, 5%;

[0137] Flow rate: 0.3 mL / min;

[0138] Mass spectrometry conditions: negative ion mode, capillary voltage 2.5 kV, cone voltage 40 V, source default voltage 80 V, source temperature 120°C, desolvation temperature 450°C, carrier gas flow rate 50 L / H, desolvation gas flow rate 900 L / H; positive ion mode, capillary voltage 2.5 kV, cone voltage 40 V, source default voltage 80 V, source temperature 120°C, desolvation temperature 450°C, carrier gas flow rate 50 L / H, desolvation gas flow rate 800 L / H.

[0139] Test results:

[0140]

[0141] From the above test results and Figure 8 It can be seen that with ginsenosides as the target and miniature pig skin as the model, it was found that the transdermal absorption of mannitol-ginsenoside cocrystal was significantly better than that of ginsenosides.

[0142] 3. Stability test

[0143] Instrument: Waters E2695 high performance liquid chromatograph

[0144] Chromatographic column: Wondasil C18-WR (150*4.6mm, 5μm);

[0145] Mobile phase: A phase aqueous solution; B phase acetonitrile;

[0146] Elution method: gradient method;

[0147] Gradient program table: Phase B acetonitrile different time ratios: 0-20min, 20%-32%; 21-30min,

[0148] 32-43%, 31-40min, 43-100%; 45min-50min, 100%; 51-60min, 20%;

[0149] Flow rate: 1.0 mL / min;

[0150] Detection wavelength: 210nm;

[0151] Analysis time: 60 min.

[0152] Test results:

[0153]

[0154] from Figure 9 As can be seen from the data in the above table, taking the ginsenoside content as an indicator, the 48-hour high temperature stability test found that the stability of the mannitol and ginsenoside cocrystal was better than that of ginsenoside.

[0155] The above are preferred embodiments of the present invention. Those skilled in the art to which the present invention belongs can also change and modify the above embodiments. Therefore, the present invention is not limited to the above specific embodiments. Any obvious improvements, replacements or modifications made by those skilled in the art on the basis of the present invention fall within the scope of protection of the present invention.

Claims

1. A ginsenoside and mannitol cocrystal, characterized by: The XRD spectrum of the ginsenoside and mannitol cocrystal has characteristic diffraction peaks at least at 2θ angles of 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08°, with an error tolerance of ±0.2°; the DSC spectrum has characteristic endothermic peaks at 168.4°C and 359°C, with an error tolerance of ±0.2°C.

2. The ginsenoside and mannitol co-crystal according to claim 1, characterized in that: The XRD pattern of the ginsenoside and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 9.58°, 14.78°, 23.59°, 25.29°, 26.25°, 27.16°, 27.69°, 28.68°, 31.65°, 33.33°, 35.69°, 36.33°, and 39.72°, with an error tolerance of ±0.2°; The grain sizes corresponding to the characteristic diffraction peaks are 3. The ginsenoside and mannitol co-crystal according to claim 1, characterized in that: The XRD pattern of the ginsenoside and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 11.15°, 25.88°, 29.61°, 30.53°, 31.20°, 34.32°, 36.79°, 38.67°, 40.93°, 43.56°, 47.61°, 48.49°, 56.75°, and 65.72°, with an error tolerance of ±0.2°; The grain sizes corresponding to the characteristic diffraction peaks are 4. The ginsenoside and mannitol co-crystal according to claim 1, characterized in that: The grain sizes corresponding to the characteristic diffraction peaks of 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08° are 5. The ginsenoside and mannitol co-crystal according to claim 1, characterized in that: The infrared spectrum of ginsenoside and mannitol cocrystal is at least 3275.55 cm -1 、2938.19cm -1 、1457.46cm -1 、1429.13cm -1 、1371.89cm -1 、1315.44cm -1 、1260.99cm -1 、 1195.47cm -1 、1076.22cm -1 、1040.18cm -1 、1018.33cm -1 、951.34cm -1 、 926.81cm -1 、882.12cm -1 、714.11cm -1 、653.03cm -1 、628.01cm -1 、 519.35cm -1 、494.64cm -1 、476.55cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

6. The method for preparing the ginsenoside and mannitol cocrystal according to any one of claims 1 to 5, characterized in that: Here are the steps: S1. Weigh mannitol and pure water according to the ratio, and stir to dissolve mannitol in the pure water to form a mannitol solution; S2. Weigh ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution; S3, adding the ginsenoside solution dropwise to the mannitol solution and stirring evenly; S4. The solution in step S3 is taken out and homogenized in a high-pressure homogenizer at a pressure of 800 bar to 1200 bar; or the solution in step S3 is taken out and placed in a reactor to react for 0.5 to 1 hour at a pressure of 10 to 15 MPa and a temperature of 30 to 40° C.; or the solution in step S3 is taken out and ultrasonicated in an ultrasonic instrument for 2 to 4 hours; S5. Take out the reaction solution in S4 and let it stand for crystallization; S6. Filter, dry, and grind the crystals in S5 into fine powder.

7. The ginsenoside and mannitol co-crystal and the preparation method thereof according to claim 6, characterized in that: The mass ratio of mannitol, ginsenoside, ethanol and pure water is 2:1:4:

3.

8. The method for preparing the ginsenoside and mannitol co-crystal according to claim 6, wherein: In step S2, stirring is performed in a heat-collecting constant-temperature heating magnetic stirrer at a temperature of 30° C. to 50° C., a rotation speed of 150 to 250 r / min, and a stirring time of 1 to 2 h.

9. The method for preparing ginsenoside and mannitol cocrystal according to claim 6, characterized in that: In step S6, the product is dried in an oven at 30-50°C.

10. Use of the ginsenoside and mannitol co-crystal according to any one of claims 1 to 5 in cosmetics, foods, health products, and medicines.

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