Pseudo-ginseng stem leaf saponin and mannitol eutectic crystal and preparation method and application thereof

Abstract

The invention relates to the technical field of co-crystals, in particular to a pseudo-ginseng stem leaf saponin and mannitol co-crystal and a preparation method and application thereof, an XRD (X-Ray Diffraction) pattern of the co-crystal at least has characteristic diffraction peaks at 2 theta angles of 13.75 degrees, 17.36 degrees, 18.78 degrees, 19.93 degrees, 20.50 degrees, 21.43 degrees, 25.22 degrees, 27.61 degrees, 28.22 degrees, 33.24 degrees, 34.05 degrees and 43.98 degrees, and has error tolerance of + / -0.2 degrees; in a DSC spectrum, characteristic endothermic peaks exist at 167.2 DEG C, 231.7 DEG C and 334.8 DEG C, and error tolerance of + / -0.2 DEG C exists. The preparation method comprises the following steps: dissolving mannitol in pure water, dissolving panax notoginseng stem leaf saponin in ethanol, mixing, carrying out ultrasonic treatment, standing, crystallizing, filtering, drying and grinding to obtain the eutecticum, and the eutecticum can be applied to cosmetics, health care products, food and medicines. The eutectic has the advantages of being easy to absorb and good in stability.

Description

Technical Field

[0001] The present invention relates to the technical field of cocrystals, and in particular to a cocrystal of Panax notoginseng stem and leaf saponins and mannitol, and a preparation method and application thereof. Background Art

[0002] Panax notoginseng stem and leaf saponins are a class of active ingredients extracted from the stems and leaves of Panax notoginseng (Araliaceae), belonging to the triterpenoid saponin class. The main components of Panax notoginseng stem and leaf saponins include ginsenosides (such as Rb1, Rb3, and Rc) and notoginsenosides (such as R1, Fa, and Fc). These saponins have anti-inflammatory, antioxidant, circulation-enhancing, and lipid-lowering properties. However, saponins are sensitive to light, heat, and pH, and are easily degraded, affecting product stability and efficacy. Furthermore, saponin molecules are relatively large, with limited transdermal absorption, which may affect their bioavailability in the skin. Summary of the Invention

[0003] In response to the problems of poor transdermal absorbability and stability of Panax notoginseng stem and leaf saponins in the prior art, the present invention proposes a co-crystal of Panax notoginseng stem and leaf saponins and mannitol, as well as a preparation method and application thereof. The obtained co-crystal has the advantages of good transdermal absorbability and good stability.

[0004] Specifically, the present invention is achieved through the following technical scheme: a co-crystal of Panax notoginseng stem and leaf saponins and mannitol, the XRD spectrum of the co-crystal of Panax notoginseng stem and leaf saponins and mannitol has characteristic diffraction peaks at least at 2θ angles of 13.75°, 17.36°, 18.78°, 19.93°, 20.50°, 21.43°, 25.22°, 27.61°, 28.22°, 33.24°, 34.05°, and 43.98°, with an error tolerance of ±0.2°; the DSC spectrum has characteristic endothermic peaks at 167.2°C, 231.7°C, and 334.8°C, with an error tolerance of ±0.2°.

[0005] As a preferred embodiment, the XRD pattern of the cocrystal of Panax notoginseng stem and leaf saponins and mannitol also has characteristic diffraction peaks at 2θ angles of 9.50°, 11.05°, 25.79°, 27.08°, 28.64°, 30.44°, 31.56°, 35.59°, 36.25°, 36.69°, 39.65°, and 56.54°, with an error tolerance of ±0.2°; the grain sizes corresponding to the characteristic diffraction peaks are

[0006] As a preferred embodiment, the grain sizes corresponding to the characteristic diffraction peaks of 13.75°, 17.36°, 18.78°, 19.93°, 20.50°, 21.43°, 25.22°, 27.61°, 28.22°, 33.24°, 34.05°, and 43.98° are respectively

[0007] As a preferred embodiment, the infrared spectrum of the cocrystal of Panax notoginseng stem and leaf saponins and mannitol is at least 3421.86 cm -1 、3408.91cm -1 、3373.03cm -1 、3269.76cm -1 、3139.46cm -1 、2932.83cm -1 、1458.24cm -1 、1375.99cm -1 、1317.28cm -1 、1259.16cm -1 、1193.27cm -1 、1077.59cm -1 、1016.56cm -1 、949.92cm -1 、927.17cm -1 、878.24cm -1 、720.51cm -1 、648.35cm -1 、626.74cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0008] The present invention also provides a method for preparing a co-crystal of Panax notoginseng stem and leaf saponins and mannitol, comprising the following steps:

[0009] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0010] S2. Weigh Panax notoginseng stem and leaf saponins and anhydrous ethanol according to the ratio, and stir until the Panax notoginseng stem and leaf saponins are completely dissolved to form a Panax notoginseng stem and leaf saponin solution;

[0011] S3. Add the Panax notoginseng stem and leaf saponin solution dropwise to the mannitol solution, and heat and stir for 1-2 hours;

[0012] S4, sonicating the solution in step S3 for 2-4 hours;

[0013] S5, taking out the solution in S4 and letting it stand for crystallization;

[0014] S6. Filter the crystals in S5, vacuum dry, and grind into fine powder.

[0015] As a preferred embodiment, the mass ratio of mannitol, Panax notoginseng stem and leaf saponins, deionized water, and anhydrous ethanol is 2:1:3:4.

[0016] As a preferred solution, in step S3, stirring is performed in a heat-collecting constant-temperature heating magnetic stirrer at a temperature of 30 to 50° C. and a rotation speed of 150 to 250 r / min.

[0017] As a preferred solution, in step S4, the ultrasonic power is 300w-600w, and the ultrasonic frequency is 20-50khz.

[0018] As a preferred solution, in step S6, the vacuum degree is 50Pa-60Pa and the temperature is 30-40°C.

[0019] The last aspect of the present invention also provides the use of Panax notoginseng stem and leaf saponins and mannitol co-crystals in cosmetics, foods, health products and medicines.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] (1) Compared with the raw material Panax notoginseng stem and leaf saponins, the Panax notoginseng stem and leaf saponins and mannitol co-crystals obtained by the present invention have excellent transdermal absorption performance. By improving its absorbability, the co-crystals can more efficiently penetrate the skin barrier and be fully absorbed and utilized by human skin, thereby exerting the multiple effects of Panax notoginseng stem and leaf saponins, such as anti-inflammatory and antioxidant effects;

[0022] (2) The co-crystal of Panax notoginseng stem and leaf saponins and mannitol prepared by the present invention has significantly improved stability compared with single Panax notoginseng stem and leaf saponins. This feature makes the co-crystal more reliable in the application of cosmetics, medicines, health care products and other fields, and can maintain the effectiveness of the active ingredients for a long time, thereby extending the shelf life of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The XRD patterns of notoginseng stem and leaf saponins, mannitol, and the cocrystal of notoginseng stem and leaf saponins and mannitol of the present invention are shown;

[0024] Figure 2 This is a DSC graph of the co-crystal of Panax notoginseng stem and leaf saponins and mannitol of the present invention;

[0025] Figure 3 is a DSC graph of Panax notoginseng stem and leaf saponins of the present invention;

[0026] Figure 4 It is the DSC diagram of mannitol of the present invention;

[0027] Figure 5 This is the infrared spectrum of the co-crystal of Panax notoginseng stem and leaf saponins and mannitol of the present invention;

[0028] Figure 6This is a comparative data diagram of the transdermal absorption of Panax notoginseng stem and leaf saponins and mannitol cocrystal, and Panax notoginseng stem and leaf saponins of the present invention;

[0029] Figure 7 This is a graph showing the stability test of the Panax notoginseng stem and leaf saponins and mannitol cocrystal and the Panax notoginseng stem and leaf saponins aqueous solution of the present invention. DETAILED DESCRIPTION

[0030] 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.

[0031] 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.

[0032] Unless otherwise specifically stated, the relative arrangement of the parts and steps, numerical expressions and numerical values ​​set forth in these embodiments do not limit the scope of the present invention. The technology, methods and equipment known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the technology, methods and equipment should be considered as part of the authorization specification. In all examples shown and discussed here, any specific value should be interpreted as being merely exemplary, rather than as a limitation. 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.

[0033] Example 1

[0034] A method for preparing a cocrystal of Panax notoginseng stem and leaf saponins and mannitol, comprising the following steps:

[0035] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0036] S2. Weigh Panax notoginseng stem and leaf saponins and anhydrous ethanol according to the ratio, and stir until the Panax notoginseng stem and leaf saponins are completely dissolved to form a Panax notoginseng stem and leaf saponin solution;

[0037] S3. Slowly add the Panax notoginseng stem and leaf saponin solution dropwise to the mannitol solution, place the mixed solution in a heat-collecting constant temperature heating magnetic stirrer, set the speed at 200 r / min and the temperature at 40°C, and continue stirring for 1.5 h;

[0038] S4, ultrasonically treating the solution in step S3 for 3 h, with an ultrasonic power of 400 W and an ultrasonic frequency of 40 kHz;

[0039] S5. Take out the solution in S4 and let it stand for 24 hours to wait for crystallization;

[0040] S6. Filter the crystals in S5, dry them in a vacuum dryer at a vacuum degree of 55 Pa and a temperature of 35° C., and grind them into fine powder.

[0041] The mass ratio is shown in the following table:

[0042] Material Name Ratio Panax notoginseng stem and leaf saponins 10％ Mannitol 20％ Deionized water 30％ Anhydrous ethanol 40％

[0043] Example 2

[0044] A method for preparing a cocrystal of Panax notoginseng stem and leaf saponins and mannitol, comprising the following steps:

[0045] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0046] S2. Weigh Panax notoginseng stem and leaf saponins and anhydrous ethanol according to the ratio, and stir until the Panax notoginseng stem and leaf saponins are completely dissolved to form a Panax notoginseng stem and leaf saponin solution;

[0047] S3. Slowly add the Panax notoginseng stem and leaf saponin solution dropwise to the mannitol solution, place the mixed solution in a heat-collecting constant temperature heating magnetic stirrer, set the speed at 150 r / min and the temperature at 30°C, and continue stirring for 2 h;

[0048] S4, ultrasonically treating the solution in step S3 for 2 h, with an ultrasonic power of 600 W and an ultrasonic frequency of 50 kHz;

[0049] S5. Take out the solution in S4 and let it stand for 24 hours to wait for crystallization;

[0050] S6. Filter the crystals in S5, dry them in a vacuum dryer at a vacuum degree of 50 Pa and a temperature of 40° C., and grind them into fine powder.

[0051] The mass ratio is shown in the following table:

[0052]

[0053]

[0054] Example 3

[0055] A method for preparing a cocrystal of Panax notoginseng stem and leaf saponins and mannitol, comprising the following steps:

[0056] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0057] S2. Weigh Panax notoginseng stem and leaf saponins and anhydrous ethanol according to the ratio, and stir until the Panax notoginseng stem and leaf saponins are completely dissolved to form a Panax notoginseng stem and leaf saponin solution;

[0058] S3. Slowly add the Panax notoginseng stem and leaf saponin solution dropwise to the mannitol solution, place the mixed solution in a heat-collecting constant temperature heating magnetic stirrer, set the speed at 250 r / min and the temperature at 50°C, and continue stirring for 1 hour;

[0059] S4, ultrasonically treating the solution in step S3 for 4 h, with an ultrasonic power of 300 W and an ultrasonic frequency of 20 kHz;

[0060] S5. Take out the solution in S4 and let it stand for 24 hours to wait for crystallization;

[0061] S6. Filter the crystals in S5, dry them in a vacuum dryer at a vacuum degree of 60 Pa and a temperature of 30° C., and grind them into fine powder.

[0062] The mass ratio is shown in the following table:

[0063] Material Name Ratio Panax notoginseng stem and leaf saponins 10％ Mannitol 20％ Deionized water 30％ Anhydrous ethanol 40％

[0064] X-ray diffraction analysis was performed on the cocrystal of Panax notoginseng stem and leaf saponins and mannitol obtained in Example 1, and the specific test parameters were:

[0065] Voltage, current: 40kV, 40mA

[0066] Detector: DteX250(H)

[0067] Test range: 5-80°

[0068] Step size: 0.01°

[0069] Scanning speed: 10.00deg / min

[0070] Divergence slit: 10mm;

[0071] Get as Figure 1The XRD pattern shown in the figure shows that the XRD pattern of the cocrystal of Panax notoginseng stem and leaf saponins and mannitol has characteristic diffraction peaks at 2θ angles of 13.75°, 17.36°, 18.78°, 19.93°, 20.50°, 21.43°, 25.22°, 27.61°, 28.22°, 33.24°, 34.05°, and 43.98°, with an error tolerance of ±0.2°; the grain sizes corresponding to each characteristic diffraction peak are

[0072] The XRD pattern of the cocrystal of Panax notoginseng stem and leaf saponins and mannitol also has characteristic diffraction peaks at 2θ angles of 9.50°, 11.05°, 25.79°, 27.08°, 28.64°, 30.44°, 31.56°, 35.59°, 36.25°, 36.69°, 39.65°, and 56.54°, with an error tolerance of ±0.2°; the grain sizes corresponding to each characteristic diffraction peak are

[0073]

[0074] from Figure 1 It can be seen from the figure that the XRD pattern of the eutectic is different from that of the raw material, indicating that the eutectic is obtained.

[0075] The specific XRD data of the obtained Panax notoginseng stem and leaf saponins and mannitol co-crystal are shown in the following table:

[0076] Table 1 XRD data of Panax notoginseng stem and leaf saponins and mannitol cocrystal

[0077]

[0078]

[0079] The DSC test was performed on the cocrystal of Panax notoginseng stem and leaf saponins and mannitol obtained in Example 1, and the test parameters were as follows: temperature 50-400°C, heating rate 10.0°C / min, Ar 20.0mL / min, and the results were as follows: Figure 2-4 The temperature corresponding to the peak in the figure 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 melting temperature of the sample is analyzed by software as follows:

[0080] 1) Panax notoginseng stem and leaf saponins: melting point 234.76℃.

[0081] 2) Mannitol: melting point 169.2°C;

[0082] 3) Cocrystal of Panax notoginseng stem and leaf saponins and mannitol: Three melting peaks appeared, with the melting point of peak 1 at 167.2°C, peak 2 at 231.7°C, and peak 3 at 334.8°C. The melting peaks of the cocrystal were different from those of the two raw materials, indicating that a cocrystal was obtained.

[0083] The eutectic of Panax notoginseng stem and leaf saponins and mannitol obtained in Example 1 was subjected to infrared testing to obtain the following Figure 5 The infrared spectrum shown, Figure 5 The eutectic is shown at 3421.86 cm -1 、3408.91cm -1 、3373.03cm -1 、3269.76cm -1 、3139.46cm -1 、2932.83cm -1 、1458.24cm -1 、1375.99cm -1 、1317.28cm -1 、1259.16cm -1 、1193.27cm -1 、1077.59cm -1 、1016.56cm -1 、949.92cm -1 、927.17cm -1 、878.24cm -1 、720.51cm -1 、648.35cm -1 、626.74cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0084] Example 4 Efficacy Test (Sample 1# prepared from Example 1)

[0085] 1. Transdermal absorption test

[0086] Sample Information:

[0087] serial number Sample name concentration 1# Cocrystal of Panax notoginseng stem and leaf saponins and mannitol 1.0％ 2# Panax notoginseng stem and leaf saponins 1.0％

[0088] (1) Test method for release from the surface of miniature pig skin:

[0089] Pig skin model: Xiaoba fragrant pig skin;

[0090] Supply solution: 1# eutectic solution of Panax notoginseng stem and leaf saponins and mannitol, 2# Panax notoginseng stem and leaf saponins solution;

[0091] Experimental methods:

[0092] Diffusion cell installation and skin condition testing:

[0093] 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;

[0094] 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. The sample was then placed in a water bath for 30 minutes to balance.

[0095] Add sample supply solution: Take 400 μL of 1# and 2# supply solution respectively and add them to the supply pool;

[0096] The diffusion cell temperature was 34°C and the stirring speed was 450 rpm.

[0097] Sampling test after 4 hours:

[0098] ① Supply liquid: weigh the total weight of the supply pool (place it in a 25mL beaker or centrifuge tube, the gross weight of the supply pool needs to be weighed in advance), rinse with 50% methanol and dilute to 10mL, shake it by ultrasonic for 20min, filter and ultrasonically degas;

[0099] ② Skin surface: Weigh the total weight (the skin weight needs to be weighed in advance), rinse with 50% methanol or wipe the surface with a cotton swab and dilute to 2 mL, shake well, filter and ultrasonically degas;

[0100] ③Inside the skin: mince the skin, add 2 mL of 50% methanol and sonicate for 20 minutes;

[0101] ④ Receiving solution: Take 1 mL of receiving solution, filter it, and then ultrasonically degas it for 1 minute before injection.

[0102] (2) Ginsenoside Rb1 transdermal absorption test method:

[0103] Instrument: G3-Q TOF liquid chromatography-mass spectrometry;

[0104] Chromatographic column: ACQUITY UPLC HSS BEH C18 (2.1*50 mm, 1.7 μm);

[0105] Mobile phase: Phase A: 0.1% formic acid in water; Phase B: 0.1% formic acid in acetonitrile;

[0106] Elution method: gradient method; B phase ratio: 0-30min, 5%-95%; 30-35min, 95%; 35.5-40min, 5%;

[0107] Flow rate: 0.3 mL / min;

[0108] Mass spectrometry conditions:

[0109] 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;

[0110] 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.

[0111] Test results:

[0112]

[0113]

[0114] From the above test results and Figure 6 It can be seen that using ginsenoside Rb1 as the target and miniature pig skin as the model, it was found that the transdermal absorption of Panax notoginseng stem and leaf saponins and mannitol cocrystal was better than that of Panax notoginseng stem and leaf saponins.

[0115] 2. Stability test

[0116] Test method for the content of saponin in Panax notoginseng stems and leaves:

[0117] High performance liquid chromatograph: Waters E2695 high performance liquid chromatograph

[0118] Chromatographic column: Wondasil C18-WR (150*4.6mm, 5μm);

[0119] Mobile phase: Phase A: 0.05% phosphoric acid aqueous solution, Phase B: acetonitrile;

[0120] Elution method: gradient method;

[0121] Gradient program: Phase B acetonitrile at different time ratios: 0-27 min, 20%-46%;

[0122] 27.5-35min, 46-100%, 35.5-40min, 100%; 42min-52min, 20%;

[0123] Flow rate: 1.0 mL / min;

[0124] Detection wavelength: 203nm;

[0125] Analysis time: 52 minutes.

[0126] Test results:

[0127]

[0128] from Figure 7 As can be seen from the data in the above table, taking the content of Panax notoginseng stem and leaf saponins as an indicator, the high temperature stability was examined for 48 hours and it was found that the stability of the co-crystal of Panax notoginseng stem and leaf saponins and mannitol was better than that of Panax notoginseng stem and leaf saponins.

[0129] 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 cocrystal of Panax notoginseng stem and leaf saponins and mannitol, characterized in that: The XRD spectrum of the Panax notoginseng stem and leaf saponin and mannitol cocrystal has characteristic diffraction peaks at least at 2θ angles of 13.75°, 17.36°, 18.78°, 19.93°, 20.50°, 21.43°, 25.22°, 27.61°, 28.22°, 33.24°, 34.05°, and 43.98°, with an error tolerance of ±0.2°; the DSC spectrum has characteristic endothermic peaks at 167.2°C, 231.7°C, and 334.8°C, with an error tolerance of ±0.2°.

2. The Panax notoginseng stem and leaf saponins and mannitol eutectic according to claim 1, characterized in that: The XRD pattern of the co-crystal of Panax notoginseng stem and leaf saponins and mannitol also has characteristic diffraction peaks at 2θ angles of 9.50°, 11.05°, 25.79°, 27.08°, 28.64°, 30.44°, 31.56°, 35.59°, 36.25°, 36.69°, 39.65°, and 56.54°, with an error tolerance of ±0.2°; The grain sizes corresponding to the characteristic diffraction peaks are 3. The co-crystal of Panax notoginseng stem and leaf saponins and mannitol according to claim 1, characterized in that: The grain sizes corresponding to the characteristic diffraction peaks of 13.75°, 17.36°, 18.78°, 19.93°, 20.50°, 21.43°, 25.22°, 27.61°, 28.22°, 33.24°, 34.05°, and 43.98° are 4. The co-crystal of Panax notoginseng stem and leaf saponins and mannitol according to claim 1, characterized in that: The infrared spectrum of the cocrystal of Panax notoginseng stem and leaf saponins and mannitol is at least 3421.86 cm -1 、3408.91cm -1 、3373.03cm -1 、3269.76cm -1 、3139.46cm -1 、2932.83cm -1 、1458.24cm -1 、1375.99cm -1 、1317.28cm -1 、1259.16cm -1 、1193.27cm -1 、1077.59cm -1 、1016.56cm -1 、949.92cm -1 、927.17cm -1 、878.24cm -1 、 720.51cm -1 、648.35cm -1 、626.74cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

5. The method for preparing the co-crystal of Panax notoginseng stem and leaf saponins and mannitol according to any one of claims 1 to 4, characterized in that: Here are the steps: S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution; S2. Weigh Panax notoginseng stem and leaf saponins and anhydrous ethanol according to the ratio, and stir until the Panax notoginseng stem and leaf saponins are completely dissolved to form a Panax notoginseng stem and leaf saponin solution; S3. Add the Panax notoginseng stem and leaf saponin solution dropwise to the mannitol solution, and heat and stir for 1-2 hours; S4, sonicating the solution in step S3 for 2-4 hours; S5, taking out the solution in S4 and letting it stand for crystallization; S6. Filter the crystals in S5, vacuum dry, and grind into fine powder.

6. The Panax notoginseng stem and leaf saponins and mannitol co-crystal and preparation method thereof according to claim 5, characterized in that: The mass ratio of mannitol, Panax notoginseng stem and leaf saponins, deionized water, and anhydrous ethanol is 2:1:3:

4.

7. The method for preparing the co-crystal of Panax notoginseng stem and leaf saponins and mannitol according to claim 5, characterized in that: In step S3, stirring is performed in a heat-collecting constant-temperature heating magnetic stirrer at a temperature of 30 to 50° C. and a rotation speed of 150 to 250 r / min.

8. The method for preparing the co-crystal of Panax notoginseng stem and leaf saponins and mannitol according to claim 5, characterized in that: In step S4, the ultrasonic power is 300w-600w, and the ultrasonic frequency is 20-50khz.

9. The method for preparing the co-crystal of Panax notoginseng stem and leaf saponins and mannitol according to claim 5, characterized in that: In step S6, the vacuum degree is 50Pa-60Pa and the temperature is 30-40°C.

10. Use of the Panax notoginseng stem and leaf saponin and mannitol cocrystal according to any one of claims 1 to 4 in cosmetics, foods, health products, and medicines.

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