An almond acid ionic liquid, its preparation method and application

Abstract

The present invention relates to the technical field of compounds for medicine and cosmetics, and particularly relates to an mandelic acid ionic liquid, a preparation method and an application thereof. The present invention combines matrine and mandelic acid through an ionic bond to obtain the mandelic acid ionic liquid, which increases the water solubility and percutaneous permeability of the two monomers. The mandelic acid ionic liquid simultaneously improves the low solubility of matrine and the permeability of mandelic acid. While increasing the available range of the two substances, the mandelic acid ionic liquid simultaneously has the advantages of both matrine and mandelic acid; moreover, the mandelic acid ionic liquid has good permeability, cell and biocompatibility, good solubility and no irritation, and has the characteristics of oil control, soothing, high bioavailability and stable properties when applied to cosmetics.

Description

Technical Field

[0001] The present invention relates to the technical field of compounds for medicine and cosmetics, and particularly to a mandelic acid ionic liquid, its preparation method and application. Background Art

[0002] Mandelic acid, also known as amygdalic acid and phenyglycolic acid, was first extracted from peach leaves and willow leaves and has the same source as salicylic acid; mandelic acid is a lipophilic fruit acid with a high affinity for the skin. Since its chemical structure is similar to that of antibiotics, it can inhibit the proliferation of various bacteria; high-concentration mandelic acid can remove the cutin on the skin, but mandelic acid has a certain irritation to the skin, which will damage the skin barrier function and cause peeling; and mandelic acid with too high concentration has the risk of causing skin burns.

[0003] Matrine, with the molecular formula C 15 H 24 N2O, is an alkaloid prepared by extracting the dry roots, plants and fruits of Sophora flavescens, a leguminous fabric, with organic solvents such as ethanol. Its main effects in cosmetics and daily chemical products are moisturizing, antioxidant and anti-aging, promoting the production of collagen and also promoting the proliferation of fibroblasts; however, when matrine is used in cosmetic formulations, there are certain defects, such as a relatively high pH and easy discoloration.

[0004] Therefore, the prior art still needs to be improved and developed. Summary of the Invention

[0005] In view of the above deficiencies of the prior art, the purpose of the present invention is to provide a mandelic acid ionic liquid, its preparation method and application, aiming to solve the problems of poor solubility and strong irritation when matrine and mandelic acid are used as monomers.

[0006] The technical solution of the present invention is as follows:

[0007] A mandelic acid ionic liquid, the chemical structural formula of the mandelic acid ionic liquid is .

[0008] A preparation method of a mandelic acid ionic liquid, comprising the steps of:

[0009] Mix matrine and mandelic acid to obtain a mixture;

[0010] The mixture is under an inert gas atmosphere, and after stirring treatment, ultrasonic treatment and microwave reaction, the mandelic acid ionic liquid is obtained.

[0011] The preparation method of the mandelic acid ionic liquid, wherein the molar ratio of matrine to mandelic acid is (0.9 - 1.5):(0.9 - 1.5).

[0012] The preparation method of the mandelic acid ionic liquid, wherein the stirring treatment is carried out in an oil bath; the temperature of the oil bath is 80 - 110°C, and the time of the stirring treatment is 10 - 25 h.

[0013] The preparation method of the mandelic acid ionic liquid, wherein the ultrasonic input power of the ultrasonic treatment is 280 - 320 W, the ultrasonic frequency of the ultrasonic treatment is 40 kHz, the temperature of the ultrasonic treatment is 30 - 80°C, and the time of the ultrasonic reaction is 2 - 6 h.

[0014] The preparation method of the mandelic acid ionic liquid, wherein the microwave power of the microwave reaction is 40 - 60 W or 20 - 40 W, and the time of the microwave reaction is 5 - 25 min.

[0015] The preparation method of the mandelic acid ionic liquid, wherein the inert gas includes one or more of nitrogen, helium, neon, and argon.

[0016] An application of a mandelic acid ionic liquid in the preparation of cosmetics.

[0017] The application as described above, wherein the cosmetics include an aqueous solution of the mandelic acid ionic liquid; the aqueous solution of the mandelic acid ionic liquid is prepared from deionized water and the mandelic acid ionic liquid.

[0018] Beneficial effects: The present invention provides a mandelic acid ionic liquid, its preparation method and application. The chemical structural formula of the mandelic acid ionic liquid is . In the present invention, matrine and mandelic acid are combined through an ionic bond to obtain a mandelic acid ionic liquid. After the formation of the mandelic acid ionic liquid, the electron cloud distribution in the two monomers changes, increasing the molecular polarity in the mandelic acid ionic liquid, enhancing the hydrogen bond-related interaction and van der Waals force-related interaction with water, increasing the solubility of the mandelic acid ionic liquid in water, and thus increasing the water solubility of the two monomers. After matrine and mandelic acid are combined into a mandelic acid ionic liquid, the charge distribution in the mandelic acid ionic liquid changes, making its potential closer to the skin's isoelectric point, easier to open the skin's barrier membrane, and promoting skin absorption. The increase in the water solubility of the mandelic acid ionic liquid can also strengthen the hydration effect inside and outside the skin surface cells, thereby increasing the transdermal permeability. The mandelic acid ionic liquid simultaneously improves the low solubility of matrine and the permeability of mandelic acid. While increasing the available range of the two substances, the mandelic acid ionic liquid simultaneously has the advantages of both matrine and mandelic acid; moreover, the mandelic acid ionic liquid has good permeability, cell and biocompatibility, good solubility and no irritation, and has characteristics such as oil control, soothing, high bioavailability, and stable properties when applied to cosmetics. Description of the Drawings

[0019] Figure 1 Schematic diagram of the molecular structure of mandelic acid ionic liquid crystal in Example 1;

[0020] Figure 2 FTIR spectra of matrine, mandelic acid and mandelic acid ionic liquid in Example 1;

[0021] Figure 3 SEM images of matrine, mandelic acid and mandelic acid ionic liquid in Example 1;

[0022] Figure 4 Cytotoxicity test diagram of mandelic acid ionic liquid aqueous solution in Experimental Example 1;

[0023] Figure 5 Cytotoxicity test diagram of matrine aqueous solution in Comparative Example 1;

[0024] Figure 6 Cytotoxicity test diagram of mandelic acid aqueous solution in Comparative Example 2;

[0025] Figure 7 Trend chart of SOD enzyme activity changes in Experimental Example 1 and Comparative Examples 1-2;

[0026] Figure 8 Bar chart of the trend of changes in reactive oxygen species (ROS) content in Experimental Example 1 and Comparative Examples 1-2;

[0027] Figure 9 Penetration test diagram of Experimental Example 2 and Comparative Examples 3-5;

[0028] Figure 10 Count diagram of exfoliated keratinocytes in the aqueous solution of mandelic acid ionic liquid in Experimental Example 2;

[0029] Figure 11 Microscopic photograph diagram of exfoliated keratinocytes in the aqueous solution of mandelic acid ionic liquid in Experimental Example 2;

[0030] Figure 12 Comparison diagram of the cleaning grease rate and immediate oil control rate of the shampoos prepared in Experimental Example 2 and Comparative Example 5;

[0031] Figure 13 Long-term oil control rate result diagram of the shampoos prepared in Experimental Example 2 and Comparative Example 5;

[0032] Figure 14 Self-evaluation oil output change rate result diagram of the shampoos prepared in Experimental Example 2 and Comparative Example 5;

[0033] Figure 15 ASFS score change rate result diagram of the shampoos prepared in Experimental Example 2 and Comparative Example 5;

[0034] Figure 16 Graph of the change rate of dandruff quantity for the shampoo prepared in Experimental Example 2 and Comparative Example 5;

[0035] Figure 17 Graph of the change rate of dandruff area for the shampoo prepared in Experimental Example 2 and Comparative Example 5. Detailed implementation manners

[0036] The present invention provides an amygdalic acid ionic liquid, its preparation method and application. To make the purpose, technical solution and effects of the present invention clearer and more definite, the present invention is further described in detail below. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0037] Those skilled in the art of the present technology can understand that, unless otherwise defined, all terms (including technical terms and scientific terms) used here have the same meaning as the general understanding of those of ordinary skill in the field to which the present invention belongs. It should also be understood that terms such as those defined in a general dictionary should be understood to have a meaning consistent with the meaning in the context of the prior art, and will not be interpreted with an idealized or overly formal meaning unless specifically defined as here.

[0038] The present invention provides an amygdalic acid ionic liquid, and the chemical structural formula of the amygdalic acid ionic liquid is.

[0039] In this embodiment, the two monomers of natural extract matrine and amygdalic acid are combined through an ionic bond to obtain the amygdalic acid ionic liquid, which can not only improve the solubility of the monomers themselves, reduce irritation, but also promote the permeability of the monomers, thereby improving the bioavailability. The amygdalic acid ionic liquid maximally retains the characteristics of the two substances of matrine and amygdalic acid itself, making it have higher solubility, applicability in cosmetic formulations and biological effects; it has the characteristics of oil control, soothing, bioavailability, and stable properties when applied to cosmetics.

[0040] In addition, the present invention also provides a preparation method of the amygdalic acid ionic liquid, including the steps:

[0041] Step S10: Mix matrine and amygdalic acid to obtain a mixture;

[0042] Step S20: The mixture is under an inert gas atmosphere, and after being subjected to stirring treatment, ultrasonic treatment, and microwave reaction, the amygdalic acid ionic liquid is obtained.

[0043] In this embodiment, the preparation method of the mandelic acid ionic liquid combines different ionic liquid preparation methods such as oil bath, ultrasound, and microwave during the preparation process, enabling the prepared mandelic acid ionic liquid to maximally retain the characteristics of matrine and mandelic acid themselves, and the reaction is more thorough. While improving the available range of the two substances, it provides a method for efficiently preparing mandelic acid ionic liquid; the mandelic acid ionic liquid prepared by the preparation method has better solubility, applicability in cosmetic formulations, and biological efficacy; and has good permeability, cell and biocompatibility, and has characteristics such as oil control, soothing, high bioavailability, and stable properties when applied to cosmetics.

[0044] In some embodiments, the molar ratio of matrine to mandelic acid is (0.9 - 1.5):(0.9 - 1.5); mixing matrine and mandelic acid in this molar ratio to prepare the mandelic acid ionic liquid can enable the reaction to proceed fully and improve the reaction yield.

[0045] In a preferred embodiment, the molar ratio of matrine to mandelic acid is 1:1; adopting the above specific molar ratio is more conducive to the reaction of matrine and mandelic acid to form an ionic liquid with a specific structure.

[0046] In some embodiments, the stirring treatment is carried out in an oil bath; the temperature of the oil bath is 80 - 110°C, and the time of the stirring treatment is 10 - 25 h; stirring treatment under the condition of oil bath heating can provide the required temperature for the reaction, allowing matrine and mandelic acid to contact fully and enabling the reaction to proceed smoothly.

[0047] In some embodiments, the ultrasonic input power of the ultrasonic treatment is 280 - 320 W, the ultrasonic frequency of the ultrasonic treatment is 40 kHz, the temperature of the ultrasonic treatment is 30 - 80°C, and the time of the ultrasonic reaction is 2 - 6 h; ultrasonic treatment can accelerate the reaction rate of matrine and mandelic acid, enabling matrine and mandelic acid to combine through ionic bonds.

[0048] In some embodiments, the microwave power of the microwave reaction is 40 - 60 W or 20 - 40 W, and the time of the microwave reaction is 5 - 25 min; under this microwave power and reaction time, the reaction is complete, accelerating the combination of matrine and mandelic acid through ionic bonds to form mandelic acid ionic liquid.

[0049] Specifically, placing the mixture of matrine and mandelic acid in a reaction kettle, under the protection of an inert gas, through the stirring treatment, the ultrasonic treatment and the microwave reaction, and adopting the process parameters within the above ranges, can enable the reaction to proceed fully, improve the reaction yield, enable the matrine and the mandelic acid to be combined through an ionic bond to form a mandelic acid ionic liquid, increase the water solubility and percutaneous permeability of the two monomers, and the prepared mandelic acid ionic liquid has better solubility, cosmetic formulation applicability and biological efficacy.

[0050] In some embodiments, the inert gas includes one or more of nitrogen, helium, neon, and argon; stirring, ultrasonic treatment, and microwave reaction of the mixed solution under an inert gas can improve the purity of the prepared mandelic acid ionic liquid, avoid oxidation, and destroy the biological activity.

[0051] In addition, the present invention also provides an application of a mandelic acid ionic liquid in the preparation of cosmetics.

[0052] In this embodiment, the mandelic acid ionic liquid has good permeability, cell and biocompatibility, and the ionic liquid obtained by combining matrine and mandelic acid through an ionic bond using the above preparation method has the advantages of good solubility and no irritation, and has characteristics such as oil control, soothing, high bioavailability, and stable properties when applied to cosmetics.

[0053] In some embodiments, the cosmetic includes an aqueous solution of a mandelic acid ionic liquid; the aqueous solution of the mandelic acid ionic liquid is prepared from deionized water and the mandelic acid ionic liquid.

[0054] Specifically, the mandelic acid ionic liquid is miscible with water in any proportion to obtain an aqueous solution of the mandelic acid ionic liquid.

[0055] The following further gives examples to illustrate the present invention in detail. It should also be understood that the following examples are only used to further illustrate the present invention and cannot be construed as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention all fall within the protection scope of the present invention.

[0056] Example 1

[0057] Take 1 mol of matrine and 1 mol of mandelic acid, mix them and place them in a reaction kettle. Under the protection of an argon atmosphere, stir in an oil bath at 90 °C for 24 h, then under the conditions of an ultrasonic input power of 300 W, an ultrasonic frequency of 40 kHz, and a temperature of 50 °C, carry out an ultrasonic reaction for 5 h. As the reaction progresses, slowly supplement argon to ensure that the temperature and pressure in the kettle are maintained within the corresponding ranges. Subsequently, carry out a microwave reaction at a microwave power of 40 - 60 W for 10 min to ensure the reaction is complete, and obtain a mandelic acid ionic liquid.

[0058] Example 2

[0059] Take 1 mol of matrine and 1 mol of mandelic acid, mix them and place them in a reaction kettle. Under the protection of an argon atmosphere, stir in an oil bath at 90 °C for 48 h, and then under the conditions of an ultrasonic input power of 300 W, an ultrasonic frequency of 40 kHz, and a temperature of 70 °C, carry out ultrasonic reaction for 3 h. As the reaction proceeds, slowly supplement argon to ensure that the temperature and pressure in the kettle are maintained within the corresponding ranges. Subsequently, under a microwave power of 20 - 40 W, carry out microwave reaction for 20 min to ensure complete reaction, and obtain mandelic acid ionic liquid.

[0060] Example 3

[0061] Take 1 mol of matrine and 1 mol of mandelic acid, mix them and place them in a reaction kettle. Under the protection of an argon atmosphere, stir in an oil bath at 100 °C for 12 h, and then under the conditions of an ultrasonic input power of 300 W, an ultrasonic frequency of 40 kHz, and a temperature of 30 °C, carry out ultrasonic reaction for 5 h. As the reaction proceeds, slowly supplement argon to ensure that the temperature and pressure in the kettle are maintained within the corresponding ranges. Subsequently, under a microwave power of 40 - 60 W, carry out microwave reaction for 15 min to ensure complete reaction, and obtain mandelic acid ionic liquid.

[0062] The mandelic acid ionic liquid obtained in Example 1 was crystallized by adding an ethanol solvent under low-temperature conditions to obtain a single crystal of mandelic acid ionic liquid. After testing, the melting point was 70 - 75 °C, meeting the conditions of ionic liquid. The obtained single crystal was subjected to X-ray single crystal diffraction testing, as Figure 1 shown. The specific testing parameters were: SuperNova, Dual, Mo at zero, AtlasS2 diffractometer, temperature 170.00(10) K, and structure analysis was carried out using Olex2 and ShelXL.

[0063] Specifically, the X-ray single crystal ray testing results of the mandelic acid ionic liquid are shown in Table 1:

[0064]

[0065] The atomic coordinates (×10 4 ) and equivalent isotropic atomic displacement parameters (Å 2 ×10 3 ) analysis data of the mandelic acid ionic liquid are shown in Table 2. U(eq) is defined as one-third of the trace of the orthogonal U ij tensor.

[0066]

[0067] The anisotropic atomic displacement parameter analysis data of the mandelic acid ionic liquid are shown in Table 3. Among them, the anisotropic atomic displacement factor power is in the form: -2π 2 [h2 a *2 U 11 +2hka * b * U 12 +…].

[0068]

[0069] The bond length analysis data of each chemical bond of mandelic acid ionic liquid are shown in Table 4.

[0070]

[0071] The bond angle (°) analysis data of each chemical bond of mandelic acid ionic liquid are shown in Table 5.

[0072]

[0073] The hydrogen bond analysis data of mandelic acid ionic liquid are shown in Table 6.

[0074]

[0075] The torsional angle (°) analysis data of each chemical bond of mandelic acid ionic liquid are shown in Table 7.

[0076]

[0077] The hydrogen atom coordinates (Å×10 4 ) and isotropic atomic displacement parameters (Å×10 3 ) analysis data of mandelic acid ionic liquid are shown in Table 8.

[0078]

[0079] Figure 2 This is the infrared test chart of mandelic acid ionic liquid, matrine and mandelic acid. It can be seen that the mandelic acid ionic liquid has the same characteristic peaks as matrine at wavenumbers of 1500 cm -1 , 1600 cm -1 , 2900 cm -1 , etc., and has the same characteristic peaks as mandelic acid at wavenumbers of 1100 cm -1 , 1300 cm -1 , 1700 cm -1 , etc. This indicates that in the mandelic acid ionic liquid, the characteristic functional groups of matrine and mandelic acid have not changed. In addition, there is a relatively broad characteristic peak of the ionic liquid at 3000 - 3500 cm -1 , indicating the formation of mandelic acid ionic liquid. Figure 3 This is the scanning electron microscope test chart of mandelic acid ionic liquid, matrine and mandelic acid, indicating that the mandelic acid ionic liquid has morphological characteristics different from those of matrine and mandelic acid.

[0080] Experimental Example 1

[0081] Provide an aqueous solution of mandelic acid ionic liquid. Specifically, add the mandelic acid ionic liquid to deionized water, and the volume ratio of the mandelic acid ionic liquid to deionized water is 80:20 to prepare an aqueous solution of mandelic acid ionic liquid.

[0082] Experimental Example 2

[0083] Provide an aqueous solution of mandelic acid ionic liquid. Specifically, add the mandelic acid ionic liquid to deionized water, and the volume ratio of the mandelic acid ionic liquid to deionized water is 4:96 to prepare an aqueous solution of mandelic acid ionic liquid.

[0084] Comparative Example 1

[0085] Provide an aqueous solution of matrine. Specifically, add matrine with an equimolar amount to the aqueous solution of mandelic acid ionic liquid in Experimental Example 1 to deionized water, and adjust the pH to prepare an aqueous solution of matrine.

[0086] Comparative Example 2

[0087] Provide an aqueous solution of mandelic acid. Specifically, add mandelic acid with an equimolar amount to the aqueous solution of mandelic acid ionic liquid in Experimental Example 1 to deionized water, and adjust the pH to prepare an aqueous solution of mandelic acid.

[0088] Comparative Example 3

[0089] Provide an aqueous solution of matrine. Specifically, add matrine with an equimolar amount to the aqueous solution of mandelic acid ionic liquid in Experimental Example 2 to deionized water to prepare an aqueous solution of matrine.

[0090] Comparative Example 4

[0091] Provide an aqueous solution of mandelic acid. Specifically, add mandelic acid with an equimolar amount to the aqueous solution of mandelic acid ionic liquid in Experimental Example 2 to deionized water to prepare an aqueous solution of mandelic acid.

[0092] Comparative Example 5

[0093] Provide an aqueous solution of matrine and mandelic acid. Specifically, add matrine and mandelic acid with an equimolar amount to the aqueous solution of mandelic acid ionic liquid in Experimental Example 2 to deionized water to prepare an aqueous solution of matrine and mandelic acid.

[0094] Performance Test:

[0095] (I). Cytotoxicity Test:

[0096] 1) Inoculate cells into a 96-well plate at a density of 1.5x10 4 cells / well, 100 μL per well, and incubate for 24 h.

[0097] 2) After the cells adhered for 24 h, discard the culture medium, add 100 μL of the mandelic acid ionic liquid aqueous solution in Experimental Example 1 to each well to prepare a test sample solution, and set up a blank group and a zero-adjustment group.

[0098] 3) After the cells were incubated for 24 h, add 10 μL of MTT solution to each well and culture in an incubator for 4 h.

[0099] 4) Discard the culture medium, add 150 μL of DMSO to each well, shake for 10 min, and then measure the absorbance at 490 nm (OD 490 nm), compare with the control sample not treated with the test substance and calculate the results.

[0100] Figures 4 - 6 It is a cytotoxicity test chart of the samples provided in Experimental Example 1 and Comparative Examples 1-2. The concentration of the mandelic acid ionic liquid aqueous solution is in volume ratio. From Figures 4 - 6 it can be seen that the mandelic acid ionic liquid aqueous solution has a cell viability of more than 90% at a concentration of about 0.781 mg / mL, the matrine aqueous solution has a cell viability of more than 90% at a concentration of 0.3125 mg / mL, and the mandelic acid aqueous solution has a cell viability of more than 90% at a concentration of 0.3125 mg / mL.

[0101] (II) Antioxidant test:

[0102] Use UVB (300 mJ / cm 2 ) as the stimulation condition, keratinocytes as the detection model, and use the WST method and flow cytometry detection methods to dilute the samples provided in Experimental Example 1 and Comparative Examples 1-2 according to the cytotoxicity test to mandelic acid ionic liquid aqueous solution (0.0251% (v / v)), matrine aqueous solution (0.124 mg / mL), and mandelic acid aqueous solution (0.076 mg / mL) for SOD and ROS antioxidant tests.

[0103] Figure 7 It is a trend chart of the change in SOD enzyme activity. The results show that compared with the blank control group, the SOD enzyme activity of the negative control group decreased significantly, indicating that the stimulation condition of this test is effective. Compared with the negative control group, the SOD enzyme activity of the positive control (VE) group increased significantly, indicating that the positive control of this test is effective. Compared with the negative control group, the SOD enzyme activities of the samples matrine - 0.124 mg / mL, mandelic acid - 0.076 mg / mL, and mandelic acid ionic liquid aqueous solution - 0.0251% increased significantly, and the promotion rates were 9.63%, 27.83%, and 62.14% respectively.

[0104] Figure 8It is a bar graph showing the changing trend of the content of reactive oxygen species (ROS). The results show that, compared with the blank control group, the ROS content in the negative control group increased significantly, indicating that the stimulation conditions of this test are effective. Compared with the negative control group, the ROS content in the positive control (VE) group decreased significantly, indicating that the positive control of this test is effective. Compared with the negative control group, the ROS contents of the samples matrine - 0.124 mg / mL, mandelic acid - 0.076 mg / mL, and aqueous solution of mandelic acid ionic liquid - 0.0251% all decreased significantly, and the inhibition rates were 5.95%, 25.29%, and 35.52% respectively.

[0105] The antioxidant tests of SOD and ROS show that the aqueous solution of mandelic acid ionic liquid provided in Experimental Example 1 has better antioxidant properties than the aqueous solutions of matrine and mandelic acid provided in Comparative Examples 1 - 2.

[0106] (III) Transdermal effect test:

[0107] The transdermal effect tests were carried out on Experimental Example 2 and Comparative Examples 3 - 5. The specific test method is as follows:

[0108] 1) The samples provided in Experimental Example 2 and Comparative Examples 3 - 5, which are used for the subsequent penetration tests, are respectively denoted as aqueous solution of mandelic acid ionic liquid, matrine, mandelic acid, and aqueous solution of matrine and mandelic acid.

[0109] 2) The dorsal skin of GF Kunming mice was used. The subcutaneous fat layer and connective tissue were carefully dissected, rinsed thoroughly with physiological saline, and placed in physiological saline for standby.

[0110] 3) The transdermal experiment was carried out using the Franz cell method. The exposed mouse skin area in the diffusion cell of the Franz diffusion device was 1.13 cm 2 , and the volume of the receiving chamber was 15 mL.

[0111] 4) 1.0 mL of the test liquid to be measured was respectively taken and applied to the skin surface. 15 mL of the commercially available PBS buffer solution (pH≈7.4) receiving liquid was added to the receiving pool, and it was placed in a constant temperature water bath at 32 ± 0.5 °C with a stirring speed of 350 rad / min.

[0112] 5) Test of the subcutaneous permeation amount: 2 mL of the receiving liquid was taken at different time points, with 3 parallel samples at each time point. After sampling, 2 mL of the receiving liquid was immediately replenished into the receiving chamber. The receiving liquid taken at different time points was filtered through a 0.22 μm microporous filter membrane, and the concentration of the receiving liquid was measured by liquid phase detection.

[0113] From Figure 9It can be seen that under the same experimental conditions, the permeation amount per unit area of the samples provided in Experimental Example 2 and Comparative Examples 3-5 continuously increases with time. From the permeation amount per unit area, it can be known that the permeation effect of matrine is matrine in mandelic acid ionic liquid (3242.32 μg / cm 2 )> matrine in aqueous solution of matrine and mandelic acid > matrine, and the permeation effect of mandelic acid is mandelic acid in mandelic acid ionic liquid (2306.45 μg / cm 2 )> mandelic acid in aqueous solution of matrine and mandelic acid > mandelic acid. The results show that the permeation amounts of matrine and mandelic acid in mandelic acid ionic liquid are better than those of their equimolar physical mixture solution and their corresponding equimolar monomers.

[0114] (IV) Patch test:

[0115] The sample aqueous solution of mandelic acid ionic liquid provided in Experimental Example 2 was used for patch test. The specific test method is as follows:

[0116] 1) Select qualified patch test equipment. Using the closed patch test method, place 0.020 g - 0.025 g of the test substance in the patch test equipment, and apply it to the flexor side of the forearm of the subject with a low-sensitization tape.

[0117] 2) After 24 hours, remove the test substance, and observe the skin reaction at 0.5, 24, and 48 hours after removal respectively. Record the results according to the skin reaction grading standard in the "Technical Specifications for Cosmetics Safety" (2015 edition).

[0118] Table 9 is the patch test statistical table of Experimental Example 2. It can be seen from Table 9 that among the 32 people who underwent the human skin closed patch test with the sample aqueous solution of mandelic acid ionic liquid provided in Experimental Example 2, 0 cases showed skin adverse reactions.

[0119]

[0120] (V) Exfoliation detection:

[0121] The sample aqueous solution of mandelic acid ionic liquid provided in Experimental Example 2 was used for exfoliation detection. The specific test method is as follows:

[0122] 1) Administration

[0123] The sample aqueous solution of mandelic acid ionic liquid provided in Experimental Example 2 was used for patch test. The specific test method is as follows:

[0124] 1. After thawing and cleaning the pigskin, fix the skin between the supply chamber and the receiving chamber of the Franz cell diffusion cell, with the stratum corneum of the skin facing the supply chamber and the dermal layer facing the receiving chamber; add 7.0 mL of the receiving solution to the receiving chamber. After stretching and fixing the suckling pigskin tightly, add 1.5 mL of the receiving solution (PBS) to the receiving chamber through a sampler, drain the air, and make the dermal layer of the skin closely contact with the receiving solution.

[0125] 2. Add the sample to the skin surface in the supply chamber, add 50 μL of the sample to the surface of the pigskin (add PBS buffer solution to the surface of the control group as a blank control), spread the sample evenly from the central part of the skin radially to the edge, and the exposed area of the sample is 3.14 cm 2 . There are 3 replicates and parallels for each sample, keep a constant temperature water bath at (32 ± 1) °C, and ensure that there are no bubbles in the water bath sandwich.

[0126] 3. After incubating for 24 h, put on finger cots and knead the area where the sample is used. After kneading for two minutes, add 0.5 mL of the cleaning solution (0.1% Triton X-100) to the supply chamber, and pipette to wash the exfoliated keratinocytes on the skin surface.

[0127] 4. Transfer the cleaning solution to a 1.5 mL centrifuge tube for standby.

[0128] 2) Cell counting

[0129] Place the 1.5 mL EP tube containing the cleaning solution on the mini mixer (MIX-2500), adjust it to the maximum rotation speed, oscillate for 2 minutes, then take 10 μL of the cleaning solution and spot it on the cell counting plate, and use an automatic cell counter for cell counting to measure the keratinocyte density in the cleaning solution. Set two detection holes for each replicate (parallel), and take the average value as the cell density of this group.

[0130] 3) Microscopic photography

[0131] After cell counting, place the cell counting plate under an inverted microscope and take pictures and observe at a magnification of 10×.

[0132] Specifically, Table 10 is the grouping of the exfoliation detection test in Example 2.

[0133]

[0134] Figure 10 and Figure 11 are the cell counting diagram and microscopic photograph diagram of the exfoliation test of the sample provided in Experimental Example 2. From Figure 10 and Figure 11It can be seen that compared with the BC group, the number of exfoliated keratinocytes in the PC group increased significantly after treatment, indicating that the positive control of this test was effective. Compared with the BC group, the number of exfoliated keratinocytes in the sample increased significantly after treatment with the mandelic acid ionic liquid aqueous solution, indicating that the mandelic acid ionic liquid aqueous solution has a better exfoliating effect.

[0135] (6) Oil control and anti-dandruff test:

[0136] The sample mandelic acid ionic liquid aqueous solution provided in Experimental Example 2 and the sample matrine mandelic acid aqueous solution provided in Comparative Example 5 were prepared into shampoo according to the basic cosmetic formula and recorded as Experimental Example 2 shampoo and Comparative Example 5 shampoo respectively, and the oil control and dandruff removal tests were performed. The specific test method is as follows:

[0137] 1) Before using the sample

[0138] 1. The subject must not wash or comb their hair for 48 ± 4 hours.

[0139] 2. Qualified subjects complete the informed consent form;

[0140] 3. The subjects rested for 30 minutes in an environment with a temperature of 21 ± 1°C and a relative humidity of 50 ± 10% RH.

[0141] 4. Use a scalp oiliness meter and hair ultrasound dermatoscope to collect oiliness data on the head, take pictures of scalp dandruff, score the scalp dandruff, scan the dandruff for 60 seconds, and complete a questionnaire;

[0142] 5. Washing hair: Wash half of the hair with water as a blank control area, and use the sample on the other half of the hair for 60 seconds.

[0143] 2) Single-use sample immediately or after 6 hours

[0144] 1. The subjects rested for 30 minutes in an environment with a temperature of 21 ± 1°C and a relative humidity of 50 ± 10% RH.

[0145] 2. Retest the scalp oil data in the blank area and sample area;

[0146] 3) After using the sample for 14 days

[0147] 1. Do not wash your hair within 48 ± 4 hours before the visit, and the time before each visit should be basically the same. Do not comb your hair on the day of the visit;

[0148] 2. On the day of the return visit, take pictures of the scalp and dandruff, score the scalp and dandruff, sweep the scalp for 60 seconds, and complete the questionnaire;

[0149] 4) After using the sample for 28 days

[0150] 1. Do not wash your hair within 48 ± 4 hours before each visit, and keep the time of not washing hair before each visit basically the same. Do not comb your hair by yourself on the day of the visit.

[0151] 2. On the day of the follow-up visit, take pictures of the scalp dandruff, score the scalp dandruff condition, sweep the dandruff for 60 s, measure the scalp oil data, and fill out the questionnaire.

[0152] 5) Instructions for using the sample

[0153] Clean and care for the hair and scalp according to the normal hair care method, use it once every 2 - 3 days, 3 times a week, and use an adequate amount according to the daily care needs.

[0154] Figure 12 For the comparison of the oil cleaning rate and the immediate oil control rate at 6 h of using the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 for the subjects, the oil cleaning rate of the group using the shampoo of Experimental Example 2 was 97.32%, which was significantly better than 93.33% of the group using the shampoo of Comparative Example 5 (P < 0.01). The immediate oil control rate at 6 h of the group using the shampoo of Experimental Example 2 was 85.90%, which was significantly better than 77.19% of the group using the shampoo of Comparative Example 5 (P < 0.05).

[0155] Figure 13 For the comparison of the oil rate of using the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 with the baseline value for 28 D for the subjects, the oil rate of the group using the shampoo of Experimental Example 2 was significantly reduced by 71.00% (P < 0.01), and the oil rate of the group using the shampoo of Comparative Example 5 was significantly reduced by 36.71% (P < 0.01), indicating that the shampoo of Experimental Example 2 has a long-term oil control effect and is significantly better than the shampoo of Comparative Example 5 (P < 0.001).

[0156] Figure 14 For the comparison of the self-evaluated oil output of using the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 with the baseline value for 14 D and 28 D for the subjects, the self-evaluated oil output of the group using the shampoo of Experimental Example 2 was significantly reduced by 38.57% (P < 0.01) and 52.58% (P < 0.01) respectively, and the self-evaluated oil output of the group using the shampoo of Comparative Example 5 was significantly reduced by 37.84% (P < 0.05) and 49.85% (P < 0.01) respectively. The self-evaluation shows that both the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 can effectively reduce the oil output.

[0157] Figure 15For the subjects, when using the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 for 14 D and 28 D and comparing with the baseline value, the scores of adherent scalp scales (ASFS) in the shampoo group of Experimental Example 2 were significantly reduced by 42.54% (P<0.001) and 68.48% (P<0.01) respectively, and the scores of adherent scalp scales (ASFS) in the shampoo group of Comparative Example 5 were significantly reduced by 33.90% (P<0.01) and 60.89% (P<0.001) respectively, indicating that the shampoo of Experimental Example 2 has the effect of improving dandruff and is superior to the shampoo of Comparative Example 5.

[0158] Figure 16 For the subjects, when using the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 for 14 D and 28 D and comparing with the baseline value, the amount of dandruff in the shampoo group of Experimental Example 2 was reduced by 18.92% and 50.00% respectively (P<0.05), and the amount of dandruff in the shampoo group of Comparative Example 5 was reduced by 0.76% and 29.99% respectively (P<0.05), indicating that the shampoo of Experimental Example 2 has the effect of reducing the amount of dandruff and is superior to the shampoo of Comparative Example 5.

[0159] Figure 17 For the subjects, when using the shampoo of Experimental Example 2 and the shampoo of Comparative Example 5 for 14 D and 28 D and comparing with the baseline value, the dandruff area in the shampoo group of Experimental Example 2 was reduced by 23.66% and 57.84% respectively, and the dandruff area in the shampoo group of Comparative Example 5 was reduced by 12.48% and 35.53% respectively, indicating that the shampoo of Experimental Example 2 has a better effect on reducing the dandruff area than the shampoo of Comparative Example 5.

[0160] The shampoo prepared from the sample of mandelic acid ionic liquid aqueous solution provided in Experimental Example 2 and the shampoo prepared from the sample of matrine mandelic acid aqueous solution provided in Comparative Example 5 were tested for oil control and anti-dandruff. The results showed that the mandelic acid ionic liquid aqueous solution has the effect of scalp oil control and is significantly superior to the matrine mandelic acid aqueous solution; the mandelic acid ionic liquid aqueous solution has the effect of scalp anti-dandruff and is superior to the matrine mandelic acid aqueous solution.

[0161] In summary, the present invention provides a mandelic acid ionic liquid, its preparation method, application, and aqueous solution. The chemical structural formula of the mandelic acid ionic liquid is . The present invention uses matrine and mandelic acid to combine through an ionic bond to obtain a mandelic acid ionic liquid, which increases the water solubility and percutaneous permeability of the two monomers. The mandelic acid ionic liquid simultaneously improves the low solubility of matrine and the permeability of mandelic acid, while increasing the available range of the two substances, making the mandelic acid ionic liquid have the advantages of both matrine and mandelic acid; moreover, the mandelic acid ionic liquid has good permeability, cell and biocompatibility, good solubility and no irritation, and has characteristics such as oil control, soothing, high bioavailability, and stability when applied to cosmetics.

[0162] It should be understood that the application of the present invention is not limited to the above examples. For those of ordinary skill in the art, improvements or modifications can be made according to the above description, and all such improvements and modifications should fall within the protection scope of the appended claims of the present invention.

Claims

1. A mandelic acid ionic liquid, characterized in that The chemical structural formula of the mandelic acid ionic liquid is 。 2. A method for preparing the mandelic acid ionic liquid according to claim 1, characterized in that: Including steps: mixing matrine and mandelic acid to obtain a mixture; The mixture is subjected to stirring treatment, ultrasonic treatment and microwave reaction under an inert gas atmosphere to obtain the mandelic acid ionic liquid.

3. The preparation method of mandelic acid ionic liquid according to claim 2, wherein The molar ratio of the matrine to the mandelic acid is (0.9-1.5):(0.9-1.5).

4. The method for preparing mandelic acid ionic liquid according to claim 2, wherein The stirring treatment is carried out in an oil bath; the temperature of the oil bath is 80-110° C., and the stirring treatment time is 10-25 hours.

5. The method for preparing mandelic acid ionic liquid according to claim 2, wherein The ultrasonic input power of the ultrasonic treatment is 280-320 W, the ultrasonic frequency of the ultrasonic treatment is 40 kHz, the temperature of the ultrasonic treatment is 30-80° C., and the ultrasonic reaction time is 2-6 h.

6. The method for preparing the mandelic acid ionic liquid according to claim 2, wherein The microwave power of the microwave reaction is 40-60W or 20-40W, and the time of the microwave reaction is 5-25min.

7. The method for preparing the mandelic acid ionic liquid according to claim 2, wherein The inert gas includes one or more of nitrogen, helium, neon, and argon.

8. Use of the mandelic acid ionic liquid according to claim 1 in the preparation of cosmetics.

9. The use according to claim 8, characterized in that The cosmetic comprises a mandelic acid ionic liquid aqueous solution; the mandelic acid ionic liquid aqueous solution is prepared from deionized water and the mandelic acid ionic liquid.

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