A ginsenoside and mannitol co-crystal, and a preparation method and application thereof

Abstract

This invention relates to the field of eutectic technology, and particularly to a ginsenoside-mannitol eutectic, its preparation method, and its applications. The XRD pattern of this eutectic exhibits characteristic diffraction peaks at at least 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08° at 2θ angles, with an error tolerance of ±0.2°. The DSC pattern shows characteristic endothermic peaks at 168.4℃ and 359℃, with an error tolerance of ±0.2℃. The preparation method is as follows: mannitol is dissolved in pure water, and ginsenosides are dissolved in ethanol. The mixture is then homogenized, subjected to high-pressure reaction or ultrasonic treatment in a reactor, allowed to stand, crystallized, filtered, dried, and ground. The obtained eutectic can be used in cosmetics, food, health products, and pharmaceuticals. The eutectic of the present invention has the advantages of being non-irritating, highly safe, easily absorbed, and having good stability.

Description

Technical Field

[0001] This invention relates to the field of eutectic technology, and in particular to a ginsenoside and mannitol eutectic, its preparation method, and its application. Background Technology

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

[0003] (1) Dammarane-type saponins: including ginsenoside diol group (PDT), represented by Rb1, Rb2, Rc and Rd, mainly distributed in ginseng roots, with antioxidant, anti-inflammatory, cardiovascular protection and blood sugar and lipid regulation effects. It also includes ginsenoside triol group (PrT), represented by Rg1, Rg2 and Re, with higher content, with immune regulation, anti-fatigue, cognitive function improvement and DNA / RNA synthesis promotion effects.

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

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

[0006] However, most ginsenosides have poor water solubility and low bioavailability, making them difficult for the human body to absorb effectively, which limits their application in oral medications and cosmetics.

[0007] Mannitol, also known as wood molasses alcohol, is a white crystalline solid belonging to the hexanediol class of sugar alcohols. Its molecular structure contains six hydroxyl groups (-OH), giving it strong hygroscopic and polyol properties. As a natural or synthetic compound, it is widely used in the pharmaceutical, food, chemical, and cosmetic fields due to its good moisturizing, antioxidant, anti-inflammatory, soothing, mild, hypoallergenic, penetrating, and cardiovascular protective effects. Summary of the Invention

[0008] This invention solves the problem of poor absorption of ginsenosides in related technologies, and proposes a co-crystal of ginsenosides and mannitol, 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] To solve the above-mentioned technical problems, the present invention is achieved through the following technical solution: a cocrystal of ginsenosides and mannitol, wherein the XRD pattern of the cocrystal of ginsenosides and mannitol 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 pattern has characteristic endothermic peaks at 168.4℃ and 359℃, with an error tolerance of ±0.2℃.

[0010] As a preferred embodiment, the XRD pattern of the ginsenoside and mannitol cocrystal also exhibits 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 as follows:

[0011] As a preferred embodiment, the XRD pattern of the ginsenoside and mannitol cocrystal also exhibits 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 as follows:

[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 option, the infrared spectrum of the cocrystal of ginsenosides and mannitol is at least at 3275.55 cm⁻¹. -1 2938.19cm -1 1457.46cm -1 1429.13cm -1 1371.89cm -1 1315.44cm -1 1260.99cm -1 1195.47cm -11076.22cm -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 A characteristic peak is present at this location, with a range of ±0.2 cm. -1 Error tolerance.

[0014] In another aspect, the present invention provides a method for preparing a co-crystal of ginsenosides and mannitol, comprising the following steps:

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

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

[0017] S3. Add the ginsenoside solution dropwise to the mannitol solution and stir until well mixed;

[0018] S4. Take out the solution from step S3 and homogenize it in a high-pressure homogenizer at a pressure of 800-1200 bar; or take out the solution from step S3 and react it in a reaction vessel for 0.5-1 h at a pressure of 10-15 MPa and a temperature of 30-40 °C; or take out the solution from step S3 and sonicate it in an ultrasonic instrument for 2-4 h.

[0019] S5. Take out the reaction solution from S4 and let it stand and crystallize.

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

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

[0022] As a preferred embodiment, in step S2, the mixture is stirred in a heat-collecting constant-temperature magnetic stirrer at a temperature of 30℃~50℃, a speed of 150~250r / min, and a stirring time of 1~2h.

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

[0024] A final aspect of the invention also provides the application of ginsenoside and mannitol cocrystals in cosmetics, food, health products, and pharmaceuticals.

[0025] Compared with the prior art, the beneficial effects of the present invention are:

[0026] (1) The ginsenoside and mannitol co-crystal successfully prepared by the present invention rearranges the molecular structure through non-covalent bonds such as hydrogen bonds and van der Waals forces. This arrangement not only optimizes the physicochemical 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 discomfort symptoms such as skin redness, swelling and itching, and greatly improve 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 penetrate the skin barrier more efficiently and be fully absorbed and utilized by the human skin, so that the antioxidant, anti-inflammatory and other multiple effects of ginsenoside can be fully exerted.

[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 characteristic makes the co-crystal more reliable in the application of cosmetics, pharmaceuticals, health products and other fields. Whether in production, storage or use, the co-crystal can maintain the effectiveness of the active ingredients for a long time, thereby extending the shelf life and effect of the product. Attached Figure Description

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

[0030] Figure 2 This is the DSC diagram of the cocrystallization of ginsenosides and mannitol of this invention;

[0031] Figure 3 This is the DSC diagram of the ginsenosides of this invention;

[0032] Figure 4 This is the DSC chromatogram of mannitol according to the present invention;

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

[0034] Figure 6 This is a test diagram of the irritation of the cocrystallization of ginsenosides and mannitol of the present invention (chicken embryo test results);

[0035] Figure 7 This is a graph showing the irritation test results of ginsenosides in this invention (chicken embryo test results);

[0036] Figure 8 This is a graph showing the proportion of mannitol-ginsenoside cocrystals and ginsenosides after transdermal absorption, as presented in this invention.

[0037] Figure 9 This is a stability test diagram of mannitol-ginsenoside cocrystal and ginsenoside aqueous solution of the present invention. Detailed Implementation

[0038] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0039] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" 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, numerical expressions, and values ​​of the components and steps set forth in these embodiments do not limit the scope of the invention. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following figures denote similar items; therefore, once an item is defined in one figure, it need not be further discussed in subsequent figures.

[0041] Example 1

[0042] A method for preparing a co-crystal of ginsenosides and mannitol, comprising the following steps:

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

[0044] S2. Weigh out ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution (to accelerate dissolution, ultrasonic assistance can also be used at a temperature of 40℃).

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

[0046] S4. Take out the solution from 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 from S4, let it stand for 24 hours, and wait for crystallization.

[0048] S6. Filter the crystals from 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 table below:

[0050] Material name Proportion Ginsenoside 10％ Mannitol 20％ Pure water 30％ Ethanol 40％

[0051] Example 2

[0052] A method for preparing a co-crystal of ginsenosides and mannitol, comprising the following steps:

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

[0054] S2. Weigh out ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution (to accelerate dissolution, ultrasonic assistance can also be used at a temperature of 40℃).

[0055] S3. Slowly add the ginsenoside solution to the mannitol solution and stir evenly in a heat-collecting constant temperature magnetic stirrer. The stirring speed is 150 r / min, the temperature is 30℃, and the stirring time is 2h.

[0056] S4. Take out the solution from 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 from S4, let it stand for 24 hours, and wait for crystallization.

[0058] S6. Filter the crystals from 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 table below:

[0060] Material name Proportion Ginsenoside 10％ Mannitol 20％ Pure water 30％ Ethanol 40％

[0061] Example 3

[0062] A method for preparing a co-crystal of ginsenosides and mannitol, comprising the following steps:

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

[0064] S2. Weigh out ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution (to accelerate dissolution, ultrasonic assistance can also be used at a temperature of 40℃).

[0065] S3. Slowly add the ginsenoside solution to the mannitol solution and stir evenly in a heat-collecting constant temperature magnetic stirrer. The stirring speed is 250 r / min, the temperature is 50℃, and the stirring time is 1 h.

[0066] S4. Take out the solution from 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 from S4, let it stand for 24 hours, and wait for crystallization.

[0068] S6. Filter the crystals from 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 table below:

[0070] Material name Proportion Ginsenoside 10％ Mannitol 20％ Pure water 30％ Ethanol 40％

[0071] Example 4

[0072] Unlike Example 1, S4 involves taking the solution from step S3 and placing it in a reaction vessel to react for 45 minutes at a pressure of 13 MPa and a temperature of 35°C.

[0073] Example 5

[0074] Unlike Example 1, S4 involves taking the solution from step S3 and placing it in a reaction vessel to react for 30 minutes at a pressure of 15 MPa and a temperature of 40°C.

[0075] Example 6

[0076] Unlike Example 1, S4 involves taking the solution from step S3 and placing it in a reaction vessel for 60 minutes at a pressure of 10 MPa and a temperature of 30°C.

[0077] Example 7

[0078] Unlike Example 1, S4 involves taking the solution from step S3 and sonicating it in an ultrasonic instrument for 3 hours at a power of 250W and a frequency of 50kHz.

[0079] Example 8

[0080] Unlike Example 1, S4 involves taking the solution from step S3 and sonicating it in an ultrasonic instrument for 2 hours at a power of 250W and a frequency of 50kHz.

[0081] Example 9

[0082] Unlike Example 1, S4 involves taking the solution from step S3 and sonicating it in an ultrasonic instrument for 4 hours at a power of 250W and a frequency of 50kHz.

[0083] X-ray diffraction analysis was performed on the ginsenoside and mannitol cocrystal obtained in Example 1. The specific test parameters were as follows:

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

[0085] Detector: DteX250(H)

[0086] Test range: 5-80°

[0087] Step size: 0.01°

[0088] Scanning speed: 10.00 deg / min

[0089] Diverging slit: 10mm;

[0090] Get as Figure 1 The XRD pattern shown indicates that the cocrystal of ginsenosides and mannitol exhibits 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 each characteristic diffraction peak are as follows:

[0091] Furthermore, the XRD pattern of the ginsenoside / mannitol cocrystal also exhibits 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 as follows:

[0092] Furthermore, the XRD pattern of the ginsenoside / mannitol cocrystal also exhibits 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 as follows:

[0093] Table 1. XRD data of ginsenoside and mannitol cocrystals

[0094]

[0095]

[0096] The ginsenosides and mannitol cocrystals obtained in Example 1, as well as the raw materials, were subjected to DSC analysis. The test parameters were as follows: temperature 50–400 °C, heating rate 10.0 °C / min, Ar 20.0 mL / min. The results are as follows. Figures 2-4 As shown in the figure, the temperature corresponding to the peak value is the temperature inside the instrument's high-temperature furnace. 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 point occurs at 242.67℃;

[0098] 2) Mannitol: Melting point 169.19℃ / 169.54℃ (literature melting point 166℃);

[0099] 3) Cocrystal of ginsenosides and mannitol: There are two obvious melting peaks. The first peak is the melting point of 168.39℃, and the second peak is 359.04℃ (the melting point of ginsenosides is 242.67℃). The cocrystal of ginsenosides and mannitol is inconsistent with the DSC spectrum of the two raw materials, ginsenosides and mannitol, indicating that a cocrystal was obtained.

[0100] The ginsenosides and mannitol cocrystal obtained in Example 1 were subjected to infrared spectroscopy, and the results were as follows: Figure 5 The infrared spectrum shown Figure 5 The infrared spectrum of the cocrystal of ginsenosides and mannitol is shown at 3275.55 cm⁻¹. -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 A characteristic peak is present at this location, with a range of ±0.2 cm. -1 Error tolerance.

[0101] Example 4: Efficacy Test

[0102] 1. Stimulation test:

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

[0104] "Methods for Determination of Acute Toxicity of Aquatic 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] Based on the table data of the above chicken embryo test results and Figure 6 and Figure 7 The results showed that the 1.0% mannitol-ginsenoside cocrystal was non-irritating, while the raw ginsenoside was mildly irritating; zebrafish test results showed that the safety of the mannitol-ginsenoside cocrystal was higher than that of the raw ginsenoside.

[0113] 2. Transdermal absorption test

[0114] Sample information:

[0115]

[0116]

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

[0118] Pigskin model: Mini Baxiang pigskin

[0119] Supply solutions: 1# ginsenoside and mannitol co-crystal solution, 2# ginsenoside solution

[0120] Experimental methods:

[0121] Diffusion pool installation and skin condition testing:

[0122] Without adding receiving fluid, blot dry the skin with filter paper (weigh it) and place it on top of the receiving pool with the stratum corneum facing upwards. Add water to the supply pool to check if any liquid has seeped into the receiving pool. If no seepage occurs, discard the saline solution in the supply pool and wipe the supply pool and skin surface dry.

[0123] Add the following to the sample receiving solution for equilibration: 5 mL of physiological saline solution (weighed) until it is in complete contact with the skin and no air bubbles are released. Place it in a water bath for equilibration for 30 min.

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

[0125] The diffusion tank temperature was 34℃, and the stirring speed was 450rpm.

[0126] Sampling and testing after 4 hours:

[0127] ① Weigh the total weight of the supply solution in the supply tank (place it in a 25mL beaker or centrifuge tube; the gross weight of the supply tank needs to be weighed in advance), rinse with 50% methanol, and bring the volume to 10mL. Sonicate for 20 minutes and shake well, then filter and degas using ultrasonication.

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

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

[0130] ④ Take 1 mL of receiving liquid, filter it, degas it by sonication for 1 min, and then inject it into the sample.

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

[0132] Instrument: G3-Q TOF liquid chromatography-mass spectrometry

[0133] Chromatographic conditions:

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

[0135] Mobile phase: Phase A: 0.1% formic acid aqueous solution; Phase B: 0.1% formic acid acetonitrile solution

[0136] Elution method: gradient method; Phase B ratio: 0-30 min, 5%-95%; 30-35 min, 95%; 35.5-40 min, 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 gas 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 gas temperature 450 °C, carrier gas flow rate 50 L / H, desolvation gas flow rate 800 L / H.

[0139] Test results:

[0140]

[0141] Based on the above test results and Figure 8 As can be seen from the study, using ginsenosides as the target compound and miniature pig skin as the model, the transdermal absorption of mannitol-ginsenoside cocrystals was found to be significantly better than that of ginsenosides.

[0142] 3. Stability test

[0143] Instrument: Waters E2695 High Performance Liquid Chromatography System

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

[0145] Mobile phases: Phase A: aqueous solution; Phase B: acetonitrile;

[0146] Elution method: Gradient method;

[0147] Gradient program table: Different time ratios of acetonitrile in phase B: 0-20 min, 20%-32%; 21-30 min,

[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 table above, using ginsenoside content as an indicator, the stability of the 48-hour high-temperature stability test revealed that the stability of the cocrystal of mannitol and ginsenosides was better than that of ginsenosides.

[0155] The above are preferred embodiments of the present invention. Those skilled in the art can make changes and modifications to the above embodiments. Therefore, the present invention is not limited to the specific embodiments described above. Any obvious improvements, substitutions or modifications made by those skilled in the art based on the present invention are within the protection scope of the present invention.

Claims

1. A co-crystal of ginsenosides and mannitol, characterized in that: The XRD pattern of the ginsenoside and mannitol cocrystal exhibits characteristic diffraction peaks at at least 13.80°, 17.45°, 18.90°, 20.03°, 20.60°, 21.41°, 21.54°, 28.30°, 34.13°, and 44.08° at 2θ angles, with an error tolerance of ±0.2°. The DSC pattern shows characteristic endothermic peaks at 168.4℃ and 359℃, with an error tolerance of ±0.2°. An error tolerance of 0.2°C is maintained. The XRD pattern of the ginsenoside and mannitol cocrystal also exhibits 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 534 Å, 451 Å, 408 Å, 418 Å, 50 Å, 372 Å, 319 Å, 179 Å, 263 Å, 384 Å, 291 Å, 323 Å, and 362 Å, respectively. The XRD patterns of the ginsenoside and mannitol cocrystal also show 2θ angles of 11.15°, 25.88°, 29.61°, 30.53°, 31.20°, 34.32°, 36.79°, and 362 Å. Characteristic diffraction peaks are observed at 8.67°, 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 489 Å, 489 Å, 410 Å, 194 Å, 439 Å, 104 Å, 279 Å, 127 Å, 361 Å, 435 Å, 249 Å, 255 Å, 91 Å, and 115 Å, respectively.

2. The ginsenoside and mannitol cocrystal 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 637 Å, 448 Å, 317 Å, 419 Å, 421 Å, 303 Å, 837 Å, 382 Å, 425 Å, and 375 Å, respectively.

3. The ginsenoside and mannitol cocrystal according to claim 1, characterized in that: The infrared spectrum of the cocrystal of ginsenosides and mannitol is at least at 3275.55 cm⁻¹. -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 A characteristic peak is present at this location, with a range of ±0.2 cm. -1 Error tolerance.

4. The method for preparing the ginsenoside and mannitol cocrystal according to any one of claims 1-3, characterized in that, The steps are as follows: S1. Weigh out mannitol and pure water according to the ratio, and stir to dissolve mannitol in pure water to form a mannitol solution. S2. Weigh out ginsenosides and ethanol according to the ratio, and stir until the ginsenosides are completely dissolved to form a ginsenoside solution. S3. Add the ginsenoside solution dropwise to the mannitol solution and stir until well mixed; S4. Take out the solution from step S3 and homogenize it in a high-pressure homogenizer at a pressure of 800-1200 bar; or take out the solution from step S3 and react it in a reaction vessel for 0.5-1 h at a pressure of 10-15 MPa and a temperature of 30-40 °C; or take out the solution from step S3 and sonicate it in an ultrasonic instrument for 2-4 h. S5. Take out the reaction solution from S4 and let it stand and crystallize. S6. Filter, dry, and grind the crystals from S5 into fine powder.

5. The ginsenoside and mannitol cocrystal and its preparation method according to claim 4, characterized in that: The mass ratio of mannitol, ginsenosides, ethanol, and pure water is 2:1:4:

3.

6. The method for preparing ginsenoside and mannitol cocrystal according to claim 4, characterized in that: In step S2, the mixture is stirred in a heat-collecting constant-temperature magnetic stirrer at a temperature of 30℃~50℃, a speed of 150~250r / min, and a stirring time of 1~2h.

7. The method for preparing ginsenoside and mannitol cocrystal according to claim 4, characterized in that: In step S6, the product is dried in an oven at 30~50℃.

8. The application of the ginsenoside and mannitol cocrystal as described in any one of claims 1-3 in cosmetics.

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