Eutectic of plantain herb 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 plantain herb extract and mannitol co-crystal and a preparation method and application thereof.The XRD spectrum of the co-crystal at least has characteristic diffraction peaks at the positions where 2 theta angles are 9.89 degrees, 19.61 degrees, 20.58 degrees, 21.35 degrees, 22.26 degrees, 24.84 degrees, 25.49 degrees, 28.10 degrees, 36.34 degrees, 40.60 degrees and 45.14 degrees, and the error tolerance of + / -0.2 degrees exists; characteristic endothermic peaks exist at 156.5 DEG C and 329.1 DEG C in a DSC spectrum, and error tolerance of + / -0.2 DEG C exists; the preparation method comprises the following steps: dissolving the mannitol and the plantain herb extract in water, and carrying out ultrasonic treatment, standing, crystallization, filtration, vacuum drying and grinding to obtain the eutectic 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 plantain extract and mannitol, and a preparation method and application thereof. Background Art

[0002] Plantain is a globally distributed herb. Its extracts are rich in various bioactive ingredients, including flavonoids, polysaccharides, phenylethanoid glycosides, iridoids, triterpenes, and verbascosides. They are widely used in cosmetics, pharmaceuticals, foods, and health supplements. Plantain extracts have anti-inflammatory, antioxidant, moisturizing, antibacterial, and wound-healing properties, and are highly safe, making them suitable for a variety of applications.

[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 plantain extracts have certain irritation and poor transdermal absorbability and stability, the present invention proposes a co-crystal of plantain extract and mannitol, and a preparation method and application thereof. The obtained co-crystal has the advantages of being non-irritating, highly safe, having good transdermal absorbability and good stability.

[0005] Specifically, the present invention is achieved through the following technical scheme: a co-crystal of plantain extract and mannitol, the XRD spectrum of the co-crystal of plantain extract and mannitol has characteristic diffraction peaks at least at 2θ angles of 9.89°, 19.61°, 20.58°, 21.35°, 22.26°, 24.84°, 25.49°, 28.10°, 36.34°, 40.60°, and 45.14°, with an error tolerance of ±0.2°; the DSC spectrum has characteristic endothermic peaks at 156.5°C and 329.1°C, with an error tolerance of ±0.2°C.

[0006] As a preferred embodiment, the XRD pattern of the plantain extract and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 19.97°, 32.31°, 35.19°, 35.53°, 54.52°, 55.6°, and 64.62°, 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 9.89°, 19.61°, 20.58°, 21.35°, 22.26°, 24.84°, 25.49°, 28.10°, 36.34°, 40.60°, and 45.14° are respectively

[0008] As a preferred embodiment, the infrared spectrum of the plantain extract and mannitol cocrystal is at least 3275.89 cm -1 、3250.89cm -1 、3216.77cm -1 、3112.80cm -1 、2930.83cm -1 、2865.58cm -1 、1445.73cm -1 、1342.23cm -1 、1270.04cm -1 、1196.19cm -1 、1149.61cm -1 、1083.22cm -1 、1021.73cm -1 、929.47cm -1 、868.77cm -1 、800.15cm -1 、705.34cm -1 、675.80cm -1 、623.52cm -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 plantain 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 plantain extract according to the ratio and add it to the mannitol solution in S1, heating and stirring until the plantain extract is completely dissolved;

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

[0013] S4, take out the reaction solution in S3 and let it stand for 24 hours to wait for crystallization;

[0014] S5. Filter the crystals in S4, vacuum-dry, and grind to obtain a crystalline powder of plantain extract and mannitol.

[0015] Furthermore, the mass ratio of mannitol, plantain extract and deionized water is 2:1:7.

[0016] Furthermore, in step S2, stirring is performed in a heat-collecting constant temperature heating magnetic stirrer at a temperature of 30-50° C. and a rotation speed of 200 r / min, and stirring is continued for 1-2 hours until the plantain extract is completely dissolved.

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

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

[0019] The last aspect of the present invention also provides the use of plantain extract and mannitol co-crystal in cosmetics, food, 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 plantain extract, the plantain extract and mannitol cocrystal prepared by the present invention has no skin irritation according to the chicken embryo test results, and the zebrafish test results show that its safety is better than that of plantain extract, thereby effectively reducing the skin redness, itching and other allergic discomfort symptoms that may occur in cosmetics and applications, greatly improving the product safety in health products, food, and pharmaceutical applications;

[0022] (2) The surface release test on miniature pig skin showed that the co-crystal of plantain extract and mannitol prepared by the present invention has a better transdermal absorption effect than the plantain extract. This may be because the co-crystal optimizes the intermolecular interaction and arrangement, thereby improving its ability to penetrate the skin barrier, thereby promoting the full play of the multiple effects of plantain extract and mannitol, such as anti-inflammatory, antioxidant, moisturizing, antibacterial, soothing and calming.

[0023] (3) Compared with the raw material plantain extract, the stability of the plantain extract and mannitol co-crystal prepared by the present invention has been significantly improved, so that the active ingredients can be kept stable and not easily deteriorated in the application of cosmetics, food, health products, and medicines, and it also provides the possibility of extending the shelf life of the product. The highly stable co-crystal can ensure that the plantain extract and mannitol can continue to exert their multiple effects such as anti-inflammatory, antioxidant, moisturizing, antibacterial, soothing and calming in skin care products. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The XRD patterns of the plantain extract, mannitol, and the cocrystal of the plantain extract and mannitol of the present invention are shown;

[0025] Figure 2 is a DSC graph of the plantain extract and mannitol co-crystal of the present invention;

[0026] Figure 3 It is the DSC diagram of mannitol of the present invention;

[0027] Figure 4 is a DSC graph of the plantain extract of the present invention;

[0028] Figure 5 This is the infrared spectrum of the plantain extract and mannitol co-crystal of the present invention;

[0029] Figure 6 This is a graph showing the irritation test of the plantain 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 plantain extract of the present invention (chicken embryo test results);

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

[0032] Figure 9 This is a stability test chart of the mannitol plantain extract co-crystal and the plantain extract 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 plantain 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 plantain 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 h 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 to obtain a co-crystal powder of the plantain extract and mannitol.

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

[0044] Material Name Ratio Plantain Extract 10％ Mannitol 20％ Deionized water 70％

[0045] Example 2

[0046] A method for preparing a cocrystal of plantain 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 plantain 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 1 hour until the mixture 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 cocrystal of plantain extract and mannitol.

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

[0053] Material Name Ratio Plantain Extract 10％ Mannitol 20％ Deionized water 70％

[0054] Example 3

[0055] A method for preparing a cocrystal of plantain 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 plantain 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 for 2 h 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 cocrystal of plantain extract and mannitol.

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

[0062] Material Name Ratio Plantain Extract 10％ Mannitol 20％ Deionized water 70％

[0063] X-ray diffraction analysis was performed on the plantain extract and mannitol cocrystal obtained in Example 1 and the raw materials. The specific test parameters were:

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

[0065] Detector: DteX250(H)

[0066] Test range: 5-80°

[0067] Step size: 0.01°

[0068] Scanning speed: 10.00deg / min

[0069] Divergence slit: 10mm;

[0070] Get as Figure 1 The XRD pattern shown in the figure shows that the XRD pattern of the cocrystal of plantain extract and mannitol has characteristic diffraction peaks at least at 2θ angles of 9.89°, 19.61°, 20.58°, 21.35°, 22.26°, 24.84°, 25.49°, 28.10°, 36.34°, 40.60°, and 45.14°, with an error tolerance of ±0.2°. The grain sizes corresponding to the characteristic diffraction peaks are

[0071] The XRD pattern of the cocrystal of plantain extract and mannitol also has characteristic diffraction peaks at 2θ angles of 19.97°, 32.31°, 35.19°, 35.53°, 54.52°, 55.6°, and 64.62°, with an error tolerance of ±0.2°; the grain sizes corresponding to each characteristic diffraction peak are

[0072] Plantain extract has no corresponding characteristic diffraction peaks; 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°.

[0073] from Figure 1 It can be seen from the figure that the characteristic diffraction peaks of the eutectic are different from those of the raw materials, indicating that the eutectic is obtained.

[0074] The specific XRD data of the obtained plantain extract and mannitol co-crystal are shown in the following table:

[0075] Table 1 XRD data of plantain extract and mannitol cocrystal

[0076]

[0077]

[0078] The plantain extract and mannitol cocrystal obtained in Example 1 and the raw materials were subjected to DSC test. The test parameters were as follows: temperature 50-400 ° C, heating rate 10.0 ° C / min, Ar 20.0 mL / 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:

[0079] 1) Plantain extract: no melting peak;

[0080] 2) Mannitol: has a melting peak at 169.2°C;

[0081] 3) Cocrystal of plantain extract and mannitol: Two melting peaks appeared, one at 156.5°C and the other at 329.14°C, which were different from the peak positions of the raw materials, indicating that a cocrystal was obtained.

[0082] The plantain extract obtained in Example 1 and the mannitol cocrystal were subjected to infrared testing to obtain the following Figure 5 The infrared spectrum shown, Figure 5 The eutectic is shown at 3275.89 cm -1 、3250.89cm -1 、3216.77cm -1 、3112.80cm -1 、2930.83cm -1 、2865.58cm -1 、1445.73cm -1 、1342.23cm -1 、1270.04cm -1 、1196.19cm -1 、1149.61cm -1 、1083.22cm -1 、1021.73cm -1 、929.47cm -1 、868.77cm -1 、800.15cm -1 、705.34cm -1 、675.80cm -1 、623.52cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

[0083] Example 4 Efficacy Test (Sample 1# is the eutectic obtained in Example 1):

[0084] 1. Irritation test:

[0085] Test method: Chicken chorioallantoic membrane test for eye irritation / corrosion of cosmetics (SN / T 2329)

[0086] Determination of acute toxicity of water substances to freshwater fish (zebrafish) (GB / T 13267-91)

[0087] Testing instruments: stereo microscope, fully automatic incubator

[0088] Sample Information:

[0089]

[0090] The results of the chicken embryo test are as follows:

[0091]

[0092] The zebrafish test results are as follows:

[0093]

[0094] According to the above chicken embryo test results tabular data and Figure 6 and Figure 7 It can be seen that 1.0% plantain extract and mannitol co-crystal is non-irritating, and plantain extract is slightly irritating; the zebrafish test results show that the safety of plantain extract and mannitol co-crystal is better than that of raw plantain extract.

[0095] 2. Transdermal absorption test

[0096] Sample Information:

[0097]

[0098] (1) Test method for release from the surface of miniature pig skin:

[0099] Pig skin model: Xiaoba fragrant pig skin

[0100] Supply liquid: 1# plantain extract and mannitol eutectic solution, 2# plantain extract solution

[0101] Experimental methods:

[0102] Diffusion cell installation and skin condition testing:

[0103] 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;

[0104] 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.

[0105] Add sample supply solution: Take 400 μL of 1# and 2# supply solution respectively and add them to the supply pool;

[0106] The diffusion cell temperature was 34°C and the stirring speed was 450 rpm.

[0107] Sampling test after 4 hours:

[0108] 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;

[0109] 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;

[0110] ③Inside the skin: mince the skin, add 2 mL of 50% methanol and sonicate for 20 minutes;

[0111] ④ Receiving solution: Take 1 mL of receiving solution, filter it, and then ultrasonically degas it for 1 minute before injection.

[0112] (2) Test method for transdermal absorption of plantain extract:

[0113] Instrument: G3-Q TOF LC / MS

[0114] Chromatographic conditions:

[0115] Chromatographic column: ACQUITY UPLC HSS T3 (3.0*100 mm, 1.8 μm);

[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: 0-5min, 70%-10%; 5-10min, 40-970%; 10-15min, 970%; 15.5-20min, 70%;

[0118] Flow rate: 0.3 mL / min;

[0119] 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.

[0120] Test results:

[0121]

[0122]

[0123] From the above test results and Figure 8 It can be seen that using verbascoside as the target and miniature pig skin as the model, it was found that the transdermal absorption of mannitol and plantain extract co-crystal was better than that of plantain extract.

[0124] 3. Stability test

[0125] Test method for plantain extract content:

[0126] High performance liquid chromatograph: Waters E2695 high performance liquid chromatograph

[0127] Chromatographic column: Wondasil C18-WR (150*4.6mm, 5μm);

[0128] Mobile phase: 0.70% phosphoric acid aqueous solution: acetonitrile = 30:70 (volume ratio);

[0129] Elution method: isocratic method;

[0130] Flow rate: 1.0 mL / min;

[0131] Detection wavelength: 332nm;

[0132] Analysis time: 10 minutes.

[0133] Test results:

[0134]

[0135] from Figure 9 As can be seen from the data in the above table, taking the content of plantain extract as an indicator, the 48-hour high-temperature stability test found that the stability of the co-crystal of mannitol and plantain extract was better than that of plantain extract.

[0136] 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 plantain extract and mannitol, characterized by: The XRD spectrum of the plantain extract and mannitol cocrystal has characteristic diffraction peaks at least at 2θ angles of 9.89°, 19.61°, 20.58°, 21.35°, 22.26°, 24.84°, 25.49°, 28.10°, 36.34°, 40.60°, and 45.14°, with an error tolerance of ±0.2°; the DSC spectrum has characteristic endothermic peaks at 156.5°C and 329.1°C, with an error tolerance of ±0.2°.

2. The plantain extract and mannitol co-crystal according to claim 1, characterized in that: The XRD pattern of the plantain extract and mannitol cocrystal also has characteristic diffraction peaks at 2θ angles of 19.97°, 32.31°, 35.19°, 35.53°, 54.52°, 55.6°, and 64.62°, with an error tolerance of ±0.2°; The grain sizes corresponding to the characteristic diffraction peaks are 3. The co-crystal of plantain extract and mannitol according to claim 1, characterized in that: The grain sizes corresponding to the characteristic diffraction peaks of 9.89°, 19.61°, 20.58°, 21.35°, 22.26°, 24.84°, 25.49°, 28.10°, 36.34°, 40.60°, and 45.14° are 4. The plantain extract and mannitol co-crystal according to claim 1, characterized in that: The infrared spectrum of the cocrystal of plantain extract and mannitol is at least 3275.89 cm -1 、3250.89cm -1 、3216.77cm -1 、3112.80cm -1 、2930.83cm -1 、2865.58cm -1 、1445.73cm -1 、1342.23cm -1 、1270.04cm -1 、1196.19cm -1 、1149.61cm -1 、1083.22cm -1 、1021.73cm -1 、929.47cm -1 、868.77cm -1 、800.15cm -1 、705.34cm -1 、675.80cm -1 、623.52cm -1 There is a characteristic peak at ±0.2cm -1 error tolerance.

5. The method for preparing the co-crystal of plantain 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 plantain extract according to the ratio and add it to the mannitol solution in S1, heating and stirring until the plantain 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 the crystals in S4, vacuum-dry, and grind to obtain a crystalline powder of plantain extract and mannitol.

6. The plantain extract and mannitol co-crystal and the preparation method thereof according to claim 5, characterized in that: The mass ratio of mannitol, plantain extract and deionized water is 2:1:

7.

7. The method for preparing the co-crystal of plantain 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 30-50° C. and a rotation speed of 200 r / min, and stirring is continued for 1-2 hours until the plantain extract is completely dissolved.

8. The method for preparing the co-crystal of plantain 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 plantain 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 plantain extract and mannitol co-crystal according to any one of claims 1 to 4 in cosmetics, foods, health products and medicines.

Images