Eutectic of melissa extract and mannitol as well as preparation method and application of eutectic

Abstract

The invention relates to the technical field of co-crystals, in particular to a melissa extract and mannitol co-crystal and a preparation method and application thereof.The XRD pattern of the co-crystal at least has characteristic diffraction peaks at the positions where 2 theta angles are 13.65 degrees, 17.26 degrees, 18.72 degrees, 19.85 degrees, 20.40 degrees, 21.36 degrees, 25.12 degrees, 27.52 degrees, 28.14 degrees, 33.15 degrees, 33.96 degrees, 36.20 degrees and 43.89 degrees, and error tolerance of + / -0.2 degrees exists; a characteristic endothermic peak exists at 160.8 DEG C in a DSC spectrum, and an error tolerance of + / -0.2 DEG C exists. The preparation method comprises the following steps: dissolving mannitol and the melissa extract in water, and carrying out ultrasonic treatment, standing, crystallization, filtration and vacuum drying to obtain the eutectic crystal which can be applied to cosmetics, health care products, food and medicines. The eutectic crystal disclosed by the invention has the advantages of no irritation, high safety, good transdermal absorption and good stability.

Description

Technical Field

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

[0002] Bee balm extract is derived from the whole herb of Melissa officinalis, a perennial herb in the Lamiaceae family. Also known as lemon balm and lemongrass, it has upright stems, oval leaves, green calyxes, and a fragrant aroma. Native to the Mediterranean coast, it is now widely distributed in Europe, Central Asia, North America, and Asia, with France being the primary producer. Its active ingredients primarily include flavonoids (such as rosmarinic acid, chlorogenic acid, and caffeic acid), volatile oils (primarily citral, citronellal, and β-caryophyllene), and phenolic acids (such as ferulic acid). It exhibits antioxidant, anti-inflammatory, antibacterial, sedative, digestive, anti-fatigue, and immune-boosting properties, and is used to alleviate symptoms of chronic bronchitis, colds, fevers, and headaches.

[0003] Mannitol is a six-carbon sugar alcohol found widely in plants such as kelp and mushrooms. It can also be produced through chemical synthesis. Mannitol has moisturizing, antioxidant, soothing, high permeability, low calorie content, and no toxic side effects. It is widely used in medicine, food, cosmetics, and health supplements. Summary of the Invention

[0004] In response to the problems in the prior art that lemon balm extract has certain irritation and poor transdermal absorption and stability, the present invention proposes a lemon balm extract 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.

[0005] Specifically, the present invention is achieved through the following technical solution: a co-crystal of a melissa extract and mannitol, wherein the XRD spectrum of the melissa extract and mannitol co-crystal has characteristic diffraction peaks at least at 2θ angles of 13.65°, 17.26°, 18.72°, 19.85°, 20.40°, 21.36°, 25.12°, 27.52°, 28.14°, 33.15°, 33.96°, 36.20°, and 43.89°, with an error tolerance of ±0.2°; the DSC spectrum has a characteristic endothermic peak at 160.8°C, with an error tolerance of ±0.2°C.

[0006] As a preferred embodiment, the XRD pattern of the honeysuckle extract and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 9.40°, 10.94°, 14.65°, 23.41°, 25.70°, 26.99°, 28.53°, 30.35°, 31.03°, 31.47°, 36.63°, 39.57°, 40.84°, 44.58°, and 56.69°, with an error tolerance of ±0.2°; the grain sizes corresponding to the characteristic diffraction peaks are

[0007] As a preferred embodiment, the grain sizes corresponding to the characteristic diffraction peaks of 13.65°, 17.26°, 18.72°, 19.85°, 20.40°, 21.36°, 25.12°, 27.52°, 28.14°, 33.15°, 33.96°, 36.20°, and 43.89° are respectively

[0008] As a preferred embodiment, the infrared spectrum of the honey bee flower extract and mannitol cocrystal is at least 3382.29 cm -1 、3274.96cm -1 、1459.60cm -1 、1426.83cm -1 、1375.38cm -1 、1317.91cm -1 、1259.09cm -1 、1196.06cm -1 、1077.08cm -1 、1016.35cm -1 、949.40cm -1 、926.34cm -1 、878.36cm -1 、710.03cm -1 、624.64cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0009] The present invention also provides a method for preparing a co-crystal of Melissa officinalis extract and mannitol, comprising the following steps:

[0010] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0011] S2. Weigh the lemon balm extract according to the ratio and add it to the mannitol solution in S1, heating and stirring until the lemon balm extract is completely dissolved;

[0012] S3, ultrasonic treatment of the solution in step S2 for 2-4 hours;

[0013] S4, taking out the reaction solution in S3 and standing to wait for crystallization;

[0014] S5, filtering and vacuum drying the crystalline substance in S4 to obtain a crystalline powder of Melissa officinalis extract and mannitol.

[0015] Further, the mass ratio of mannitol, Melissa officinalis extract and deionized water is 2:1:7.

[0016] Further, in step S2, stirring is performed in a heat collecting constant temperature heating magnetic stirrer, the temperature is 30-50 DEG C, the rotation speed is 200 r / min, and the stirring is continuously performed for 1-2 hours until the Melissa officinalis extract is completely dissolved.

[0017] Further, in step S3, the ultrasonic power is 300 w-600 w, and the ultrasonic frequency is 20-50 kHz.

[0018] Further, in step S5, the vacuum degree is 50 Pa-70 Pa, and the temperature is 30-40 DEG C.

[0019] The last aspect of the present application also provides applications of the co-crystal of Melissa officinalis extract and mannitol in cosmetics, food, health products and medicines.

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

[0021] (1) The Melissa officinalis extract and mannitol form a stable co-crystal structure, which changes the release mode and action strength of the active ingredients, making it more gentle when contacting the skin, and the co-crystal product is verified by chicken embryo test and zebra fish experiment to have no irritation to the skin, significantly reducing the possible allergic reactions in cosmetic applications, greatly improving the safety of the product, and opening up a new path for the upgrading and application of cosmetic raw materials;

[0022] (2) The molecules of various active ingredients in the Melissa officinalis extract and the molecules of mannitol are combined by hydrogen bonds, van der Waals forces and other non-covalent bonds, thereby breaking through the skin barrier, so that the co-crystal can more efficiently penetrate into the deep layer of the skin, realize effective release and utilization of the active ingredients, and this excellent transdermal absorption performance not only accelerates the transmission of the Melissa officinalis extract and mannitol into the skin, but also promotes their uniform distribution in the skin tissue, thereby ensuring the full play of multiple functions such as anti-inflammatory, antioxidant and moisturizing, compared with traditional single ingredient or simple mixture, the co-crystal of the present application has made a significant breakthrough in improving the bioavailability of active ingredients;

[0023] (3) Compared with the raw material lemon balm extract, the stability of the lemon balm extract and mannitol co-crystal prepared by the present invention has been improved to a certain extent. The highly stable co-crystal can ensure that the lemon balm extract and mannitol continue to exert their efficacy in cosmetics, medicines, health products and foods. Even under complex and changeable storage conditions, the product performance can be kept stable for a long time, which also provides the possibility of extending the shelf life of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 is the XRD pattern of the lemon balm extract, mannitol, and the lemon balm extract and mannitol cocrystal of the present invention;

[0025] Figure 2 is a DSC graph of the eutectic of the lemon balm extract and mannitol of the present invention;

[0026] Figure 3 is a DSC graph of the lemon balm extract of the present invention;

[0027] Figure 4 It is the DSC diagram of mannitol of the present invention;

[0028] Figure 5 This is the infrared spectrum of the eutectic of the lemon balm extract and mannitol of the present invention;

[0029] Figure 6 This is a graph showing the irritation test of the lemon balm extract and mannitol co-crystal of the present invention (chicken embryo test results);

[0030] Figure 7 This is a test chart of the irritation of the lemon balm extract of the present invention (chicken embryo test results);

[0031] Figure 8 This is a comparative data chart of transdermal absorption of mannitol lemon balm extract co-crystal and lemon balm extract of the present invention;

[0032] Figure 9 This is a stability test chart of the mannitol lemon balm extract co-crystal and the lemon balm extract aqueous solution of the present invention. DETAILED DESCRIPTION

[0033] 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.

[0034] 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.

[0035] 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.

[0036] Example 1

[0037] A method for preparing a cocrystal of lemon balm extract and mannitol, comprising the following steps:

[0038] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0039] S2. Weigh the lemon balm extract and add it to the mannitol solution in S1. Stir the mixed solution in a heat-collecting constant temperature heating magnetic stirrer at 40°C and 200 rpm for 1.5 hours until it is completely dissolved.

[0040] S3, placing the solution in step S2 in an ultrasonic instrument for 3 hours, with an ultrasonic power of 450W and an ultrasonic frequency of 35kHz;

[0041] S4, take out the reaction solution in S3 and let it stand for 24 hours to wait for crystallization;

[0042] S5. Filter the crystals in S4, and then vacuum-dry them at 35° C. and a vacuum degree of 60 Pa, and grind them to obtain a eutectic powder of lemon balm extract and mannitol.

[0043] The mass ratio is shown in the following table:

[0044] Material Name Ratio Melissa extract 10％ Mannitol 20％ Deionized water 70％

[0045] Example 2

[0046] A method for preparing a cocrystal of lemon balm extract and mannitol, comprising the following steps:

[0047] S1. Weigh mannitol and deionized water according to the ratio, and stir to dissolve mannitol in the deionized water to form a mannitol solution;

[0048] S2. Weigh the lemon balm extract and add it to the mannitol solution in S1. Stir the mixed solution in a heat-collecting constant temperature heating magnetic stirrer at 50°C and 200 rpm for 30 minutes until it is completely dissolved.

[0049] S3, placing the solution in step S2 in an ultrasonic instrument for 2 hours, with an ultrasonic power of 600w and an ultrasonic frequency of 50kHz;

[0050] S4, take out the reaction solution in S3 and let it stand for 24 hours to wait for crystallization;

[0051] S5. Filter the crystals in S4, and then dry them in vacuo at 30° C. and a vacuum degree of 70 Pa to obtain a powder of eutectic of lemon balm extract and mannitol.

[0052] The mass ratio is shown in the following table:

[0053] Material Name Ratio Melissa extract 10％ Mannitol 20％ Deionized water 70％

[0054] Example 3

[0055] A method for preparing a cocrystal of lemon balm extract 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 the lemon balm extract and add it to the mannitol solution in S1. Stir the mixed solution in a heat-collecting constant temperature heating magnetic stirrer at 30°C and 200 rpm. Stir continuously for 1 hour until the mixture is completely dissolved.

[0058] S3, placing the solution in step S2 in an ultrasonic instrument for 4 hours, ultrasonic power 300w, ultrasonic frequency 20khz;

[0059] S4, take out the reaction solution in S3 and let it stand for 24 hours to wait for crystallization;

[0060] S5. Filter the crystals in S4, and then dry them in vacuo at 40° C. and a vacuum degree of 50 Pa to obtain a powder of eutectic of lemon balm extract and mannitol.

[0061] The mass ratio is shown in the following table:

[0062] Material Name Ratio Melissa extract 10％ Mannitol 20％ Deionized water 70％

[0063] The raw material and the honeysuckle extract-mannitol co-crystal obtained in Example 1 were subjected to X-ray diffraction analysis, and the specific test parameters were as follows:

[0064] Voltage, current: 40 kV, 40 mA

[0065] Detector: DteX250 (H)

[0066] Test range: 5-80°

[0067] Step size: 0.01°

[0068] Scan speed: 10.00 deg / min

[0069] Divergence slit: 10 mm;

[0070] The XRD pattern as shown in Figure 1 was obtained, and the XRD pattern of the honeysuckle extract-mannitol co-crystal had characteristic diffraction peaks at least at 2θ angles of 13.65°, 17.26°, 18.72°, 19.85°, 20.40°, 21.36°, 25.12°, 27.52°, 28.14°, 33.15°, 33.96°, 36.20°, and 43.89°, with an error tolerance of ±0.2°; the crystal grain sizes corresponding to the respective diffraction peaks were

[0071] The XRD pattern of the honeysuckle extract-mannitol co-crystal also had characteristic diffraction peaks at 2θ angles of 9.40°, 10.94°, 14.65°, 23.41°, 25.70°, 26.99°, 28.53°, 30.35°, 31.03°, 31.47°, 36.63°, 39.57°, 40.84°, 44.58°, and 56.69°, with an error tolerance of ±0.2°; the crystal grain sizes corresponding to the respective characteristic diffraction peaks were

[0072] The crystal grain sizes corresponding to the characteristic diffraction peaks 13.65°, 17.26°, 18.72°, 19.85°, 20.40°, 21.36°, 25.12°, 27.52°, 28.14°, 33.15°, 33.96°, 36.20°, and 43.89° were

[0073] From Figure 1It can be seen that the characteristic diffraction peaks of the co-crystal are different from those of the raw materials (the bee flower extract only has a characteristic diffraction peak at a 2θ angle of 46.8°, while mannitol mainly has characteristic diffraction peaks at 2θ angles of 14.80°, 18.98°, 21.31°, 23.55°, 23.69°, 28.58°, 33.77°, and 38.92°), indicating that the co-crystal was obtained.

[0074] The specific XRD data of the obtained eutectic of lemon balm extract and mannitol are shown in the following table:

[0075] Table 1 XRD data of eutectic of lemon balm extract and mannitol

[0076]

[0077]

[0078]

[0079] The DSC test was performed on the honeysuckle extract and mannitol cocrystal obtained in Example 1 and the raw materials. 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 Figures 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) Melissa officinalis extract: Melissa officinalis extract has a broad endothermic peak at 274.61°C;

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

[0082] 3) Co-crystal of Melissa officinalis extract and mannitol: A melting peak appeared at 160.8°C, which was different from the peak position of the raw material, indicating that a co-crystal was obtained.

[0083] The eutectic of Melissa officinalis extract 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 3382.29 cm -1 、3274.96cm -1 、1459.60cm -1 、1426.83cm -1 、1375.38cm -1 、1317.91cm -1 、1259.09cm -1 、1196.06cm -1 、1077.08cm-1 、1016.35cm -1 、949.40cm -1 、926.34cm -1 、878.36cm -1 、710.03cm -1 、624.64cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0084] Example 4 Efficacy Test (Sample 1# is the eutectic obtained in Example 1):

[0085] 1. Irritation test:

[0086] Test method: Chicken chorioallantoic membrane test for eye irritation / corrosion of cosmetics (SN / T 2329)

[0087] Determination of acute toxicity of water substances to freshwater fish (zebrafish) (GB / T13267-91)

[0088] Testing instruments: stereo microscope, fully automatic incubator

[0089] Sample Information:

[0090]

[0091] The results of the chicken embryo test are as follows:

[0092]

[0093] The zebrafish test results are as follows:

[0094]

[0095] According to the above chicken embryo test results tabular data and Figure 6 and Figure 7 It can be seen that the co-crystal of lemon balm extract and mannitol is non-irritating, and the lemon balm extract is slightly irritating; the zebrafish test results show that the safety of the co-crystal of lemon balm extract and mannitol is better than the raw lemon balm extract.

[0096] 2. Transdermal absorption test

[0097] Sample Information:

[0098]

[0099] (1) Test method for release from the surface of miniature pig skin:

[0100] Pig skin model: Xiaoba fragrant pig skin

[0101] Supply solution: 1# eutectic solution of bee balm extract and mannitol, 2# bee balm extract solution

[0102] Experimental methods:

[0103] Diffusion cell installation and skin condition testing:

[0104] 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;

[0105] 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;

[0106] Add sample supply solution: Take 400 μL of 1# and 2# supply solution respectively and add them to the supply pool;

[0107] The diffusion cell temperature was 34°C and the stirring speed was 450 rpm.

[0108] Sampling test after 4 hours:

[0109] 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;

[0110] 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;

[0111] ③Inside the skin: mince the skin, add 2 mL of 50% methanol and sonicate for 20 minutes;

[0112] ④ Receiving solution: Take 1 mL of receiving solution, filter it, and then ultrasonically degas it for 1 minute before injection.

[0113] (2) Test method for transdermal absorption of lemon balm extract:

[0114] Instrument: Xevo G3-Q TOF LC / MS

[0115] Chromatographic column: ACQUITY UPLC HSS BEH C18 (2.1*50mm, 1.7μm);

[0116] Mobile phase: Phase A: 0.1% formic acid in water, Phase B: 0.1% formic acid in acetonitrile;

[0117] Elution method: gradient method; B phase ratio: 0-30min, 5%-95%; 30-35min, 95%; 35.5-40min, 5%;

[0118] Flow rate: 0.3 mL / min;

[0119] Mass spectrometry conditions:

[0120] 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;

[0121] 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.

[0122] Test results:

[0123]

[0124]

[0125] From the above test results and Figure 8 It can be seen that with rosmarinic acid as the target and miniature pig skin as the model, it was found that the transdermal absorption of lemon balm extract and mannitol cocrystal was better than that of lemon balm extract.

[0126] 3. Stability test

[0127] HPLC method for the content of rosmarinic acid in lemon balm extract:

[0128] High performance liquid chromatograph: Waters E2695 high performance liquid chromatograph;

[0129] Chromatographic column: Wondasil C18-WR (150*4.6mm, 5μm);

[0130] Mobile phase: methanol: 0.1% phosphoric acid aqueous solution = 39:61 (volume ratio);

[0131] Elution method: isocratic elution;

[0132] Flow rate: 1.0 mL / min;

[0133] Detection wavelength: 330nm;

[0134] Column temperature: 28℃.

[0135] Test results:

[0136]

[0137] from Figure 9 As can be seen from the data in the above table, taking the content of lemon balm extract as an indicator, the 48-hour high-temperature stability test found that the stability of the mannitol and lemon balm extract co-crystal was better than that of the lemon balm extract.

[0138] 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 co-crystal of lemon balm extract and mannitol, characterized by: The XRD spectrum of the eutectic of the lemon balm extract and mannitol has characteristic diffraction peaks at least at 2θ angles of 13.65°, 17.26°, 18.72°, 19.85°, 20.40°, 21.36°, 25.12°, 27.52°, 28.14°, 33.15°, 33.96°, 36.20°, and 43.89°, with an error tolerance of ±0.2°; the DSC spectrum has a characteristic endothermic peak at 160.8°C, with an error tolerance of ±0.2°C.

2. The eutectic of Melissa officinalis extract and mannitol according to claim 1, characterized in that: The XRD pattern of the eutectic of the lemon balm extract and mannitol also has characteristic diffraction peaks at 2θ angles of 9.40°, 10.94°, 14.65°, 23.41°, 25.70°, 26.99°, 28.53°, 30.35°, 31.03°, 31.47°, 36.63°, 39.57°, 40.84°, 44.58°, and 56.69°, with an error tolerance of ±0.2°; The grain sizes corresponding to the characteristic diffraction peaks are 3. The eutectic of Melissa officinalis extract and mannitol according to claim 1, characterized in that: The grain sizes corresponding to the characteristic diffraction peaks of 13.65°, 17.26°, 18.72°, 19.85°, 20.40°, 21.36°, 25.12°, 27.52°, 28.14°, 33.15°, 33.96°, 36.20°, and 43.89° are 4. The eutectic of Melissa officinalis extract and mannitol according to claim 1, characterized in that: The infrared spectrum of the co-crystal of honey bee flower extract and mannitol is at least 3382.29 cm -1 、3274.96cm -1 、1459.60cm -1 、1426.83cm -1 、1375.38cm -1 、1317.91cm -1 、1259.09cm -1 、1196.06cm -1 、1077.08cm -1 、1016.35cm -1 、949.40cm -1 、926.34cm -1 、878.36cm -1 、710.03cm -1 、624.64cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

5. The method for preparing the co-crystal of Melissa officinalis extract 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 the lemon balm extract according to the ratio and add it to the mannitol solution in S1, heating and stirring until the lemon balm extract is completely dissolved; S3, sonicating the solution in step S2 for 2-4 hours; S4, taking out the reaction solution in S3 and letting it stand to wait for crystallization; S5. Filter and vacuum-dry the crystals in S4 to obtain a crystalline powder of lemon balm extract and mannitol.

6. The eutectic of Melissa officinalis extract and mannitol and the preparation method thereof according to claim 5, characterized in that: The mass ratio of mannitol, lemon balm extract and deionized water is 2:1:

7.

7. The method for preparing the co-crystal of Melissa officinalis extract and mannitol according to claim 5, characterized in that: In step S2, 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 200 r / min, and stirring is continued for 1 to 2 hours until the lemon balm extract is completely dissolved.

8. The method for preparing the co-crystal of Melissa officinalis extract and mannitol according to claim 5, characterized in that: In step S3, the ultrasonic power is 300w-600w, and the ultrasonic frequency is 20-50khz.

9. The method for preparing the co-crystal of Melissa officinalis extract and mannitol according to claim 5, characterized in that: In step S5, the vacuum degree is 50Pa-70Pa and the temperature is 30-40°C.

10. Use of the eutectic of Melissa officinalis extract and mannitol according to any one of claims 1 to 4 in cosmetics, foods, health products and medicines.

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