A targeting peptide glabridin and its preparation method and application

Abstract

The present invention discloses a targeting peptide glabridin and a preparation method and application thereof. The present invention prepares a targeting peptide glabridin with better permeability, targeted adhesion and whitening effect by cross-linking glabridin with RGD polypeptide, improves the problem of low bioavailability of glabridin, better exerts the whitening effect of glabridin, and expands the application of glabridin in the field of cosmetics.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and in particular relates to a targeting peptide glabridin and a preparation method and application thereof. Background Art

[0002] When human skin is stimulated by physical (ultraviolet, friction) and chemical (oxidant) conditions, keratinocytes will secrete a large amount of melanin and act on the underlying melanocytes based on the need to protect the skin. Melanin activates the downstream signaling pathway by binding to the melanocyte surface receptor MC1R, promoting the expression of the tyrosinase gene TYR, thereby promoting tyrosinase activity and causing a large amount of melanin production. Subsequently, melanin will be transported from the basal layer to the stratum corneum to protect the stratum corneum, and the skin will appear darker on the outside.

[0003] Studies have found that many types of plant extracts have shown excellent whitening effects, among which glabridin is the most prominent. Glabridin comes from a precious plant called Glycyrrhiza glabra and is a flavonoid substance. Glabridin is known as the "whitening gold" in the industry for its powerful whitening effect. It can reduce the production of melanin by inhibiting the activity of tyrosinase, and is widely used in skin care products and other fields, playing an important role in beauty, disease treatment and other fields. However, due to the insolubility of glabridin in water, the application of glabridin in cosmetics is limited, and it is difficult to exert its whitening effect. In clinical applications, it was found that glabridin used alone or in combination with conventional cosmetic excipients showed poor permeability and no targeted adhesion, resulting in an unobvious whitening effect.

[0004] In the prior art, in order to solve the above problems, the combination of cosmetic auxiliary materials such as emulsifiers and moisturizers is often used to synergize with glabridin, assist glabridin to reach the deep layer of the skin, and play a whitening role. This does help to improve the poor permeability of glabridin, but glabridin still does not have the ability to target melanocytes, cannot achieve precise whitening, and the comprehensive whitening effect is still unsatisfactory.

[0005] Therefore, preparing a glycyrrhizin with good permeability and targeted adhesion is an urgent problem to be solved. Summary of the invention

[0006] The purpose of the present invention is to provide a targeted peptide glabridin which has good permeability and targeted adhesion and exhibits stronger efficacy in whitening.

[0007] In order to achieve the above object, the technical solution adopted by the present invention comprises the following steps:

[0008] The targeting peptide glabridin is prepared according to the following steps:

[0009] 1) Weigh the raw materials:

[0010] 1 part of glabridin, 0.5-3 parts of succinic anhydride, 10-15 parts of organic solvent, 0.2-1 part of RGD polypeptide, and 0.5-3 parts of catalyst;

[0011] 2) Preparation of glabridin succinate monoester:

[0012] Put glabridin in a round-bottom flask, dissolve it with an organic solvent by ultrasonic, then add succinic anhydride, react at 30-50°C for 12-72 hours, recover the solvent to dryness under reduced pressure, add 0.5% dilute hydrochloric acid solution, precipitate solid, filter, wash and dry repeatedly to obtain glabridin succinic acid monoester;

[0013] 3) Preparation of targeting peptide glabridin:

[0014] The above-mentioned glabridin succinic acid monoester is dissolved in an organic solvent, and then a catalyst is added thereto, stirred to dissolve, and then RGD polypeptide is added thereto, and after reacting at 25-50° C. for 12-36 hours, the targeting peptide glabridin is obtained through dialysis and freeze-drying.

[0015] The organic solvent is pyridine, acetone, dimethyl sulfoxide or dichloromethane.

[0016] The catalyst is 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride, namely DMTMM.

[0017] The purity of the licorice root was determined to be 99%.

[0018] The beneficial effects of the present invention are:

[0019] 1) Compared with conventional glabridin, the targeted peptide glabridin prepared by the present invention has stronger permeability and can adhere to melanocytes, so that glabridin can inhibit tyrosinase activity for a long time, thereby reducing the production of melanin and achieving a whitening effect at the root. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The present invention is further described below in conjunction with the accompanying drawings.

[0021] Figure 1 This is the liquid phase spectrum of the targeting peptide glabridin.

[0022] Figure 2 Results for the targeting peptide glabridin based on the melanin content of mouse melanoma cells.

[0023] Figure 3 Tyrosinase enzymatic activity results for the targeting peptide glabridin based on mouse melanoma cells.

[0024] Figure 4The results of the targeted uptake experiment of the targeting peptide glabridin based on mouse melanoma cells.

[0025] Figure 5 This is the standard curve 1 for glabridin.

[0026] Figure 6 This is the standard curve 2 for glabridin.

[0027] Figure 7 The results of the cumulative penetration experiment of the targeting peptide glabridin.

[0028] Figure 8 The results of the diffusion percentage experiment of the targeting peptide glabridin.

[0029] Fig. 9 These are the results of the skin penetration coefficient experiment of the targeted peptide glabridin. DETAILED DESCRIPTION

[0030] The present invention will be further described in detail below in conjunction with the embodiments.

[0031] Unless otherwise specified, the raw materials or chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels.

[0032] Example 1

[0033] This embodiment provides a method for preparing a targeting peptide glabridin.

[0034] 1) Weigh the raw materials glabridin, RGD polypeptide, DMTMM, and succinic anhydride for use;

[0035] 2) Dissolve 1 g of glabridin in 15 ml of pyridine, then add 0.8 g of succinic anhydride, and react at 45°C with stirring for 72 h. Then, recover the solvent to dryness under reduced pressure, add 5 ml of 0.5% sodium citrate solution, disperse by ultrasound, collect by filtration, add 5 ml of dichloromethane, precipitate solid, and obtain glabridin succinic acid monoester by repeated filtration, washing and drying.

[0036] 3) 1 g of the obtained glabridin succinate monoester was dissolved in 10 ml of anhydrous dimethyl sulfoxide, and then 0.09 g of DMTMM was added thereto and stirred to dissolve, and then 0.29 g of RGD polypeptide was added thereto, and after reacting at 25° C. for 24 hours, the target peptide glabridin was obtained by dialysis and freeze-drying.

[0037] Example 2

[0038] This embodiment provides a method for preparing a targeting peptide glabridin.

[0039] 1) Weigh the raw materials glabridin, RGD polypeptide, DMTMM, and succinic anhydride for use;

[0040] 2) Dissolve 1g of glabridin in 15ml of acetone, then add 0.9g of succinic anhydride, dissolve by ultrasonication, add 0.1g of the catalyst lutidine, and react at 45°C with stirring for 24h, then recover the solvent to dryness under reduced pressure, add 5ml of 0.5% sodium citrate solution, disperse by ultrasonication, collect by filtration, add 5ml of dichloromethane, precipitate the solid, filter, wash and dry repeatedly to obtain glabridin succinic acid monoester.

[0041] 3) 1 g of the obtained glabridin succinate monoester was dissolved in 10 ml of anhydrous dimethyl sulfoxide, and then 0.09 g of DMTMM was added thereto and stirred to dissolve, and then 0.29 g of RGD polypeptide was added thereto, and after reacting at 25°C for 24 hours, the targeting peptide glabridin was obtained by dialyzing and freeze-drying.

[0042] Example 3

[0043] This embodiment provides a method for preparing a targeting peptide glabridin.

[0044] 1) Weigh the raw materials glabridin, RGD polypeptide, DMTMM, and succinic anhydride for use;

[0045] 2) Dissolve 1 g of glabridin in 10 ml of pyridine, then add 0.8 g of succinic anhydride, and react at 45°C with stirring for 24 hours. Recover the solvent to dryness under reduced pressure, add 5 ml of 0.5% sodium citrate solution, disperse by ultrasound, collect by filtration, add 5 ml of dichloromethane, precipitate solid, and obtain glabridin succinic acid monoester by repeated filtration, washing and drying.

[0046] 3) 1 g of the obtained glabridin succinate monoester was dissolved in 10 ml of anhydrous dimethyl sulfoxide, and then 0.09 g of DMTMM was added thereto and stirred to dissolve, and then 0.29 g of RGD polypeptide was added thereto, and after reacting at 25°C for 24 hours, the targeting peptide glabridin was obtained by dialyzing and freeze-drying.

[0047] experiment:

[0048] 1. Melanin content test and tyrosinase activity test based on mouse melanoma cells:

[0049] Experimental reagents:

[0050] 1640 culture medium (Gibco), DMEM culture medium (Gibco), fetal bovine serum (Lanzhou Rongye), PBS (Boster), α-melanocyte stimulating hormone (a-MSH APEX), L-DOPA (Solerbo), TritonX-100 (Solerbo).

[0051] Experimental equipment:

[0052] Microplate reader (Thermo Fisher), clean bench (Sujing Antai), -80°C refrigerator (Thermo Fisher), cell culture incubator (Thermo Fisher), cell counter (Thermo Fisher), inverted microscope (Leica), constant temperature drying oven.

[0053] Experimental methods:

[0054] (1) Cell recovery: Take out the frozen mouse melanoma cells from the liquid nitrogen tank for recovery. When the cells grow to 70%-80%, digest and count them.

[0055] (2) Cell inoculation and grouping: The cells were divided into blank group, model group, positive (VC) group and experimental group, with 3 replicate wells in each group. 4 The cells were seeded in a 12-well plate at a density of 10 cells / mL and cultured in a 37°C, 5% CO2 incubator for 24 h.

[0056] (3) Drug administration:

[0057] 1) Control group: 1 mL DMEM medium;

[0058] 2) Model group: 1 mL of DMEM medium containing 200 nmol / L α-MSH;

[0059] 3) Positive (VC) group: 1 mL of DMEM medium containing 200 nmol / L α-MSH and VC (final concentration: 500 ug / mL);

[0060] 4) Glabridin group: 1 mL of DMEM medium containing 200 nmol / L α-MSH and 0.3125% glabridin;

[0061] 5) Targeting peptide glabridin group: 1 mL of DMEM medium containing 200 nmol / L α-MSH and 0.3125% targeting peptide glabridin;

[0062] The above five groups of culture media were placed in a 37°C, 5% CO2 incubator and cultured for 48 h.

[0063] (4) Melanin content detection:

[0064] After aspirating the supernatant from each well, wash the cells three times with PBS, then fix the cells with 4% paraformaldehyde for 10 minutes, wash the cells three times with ultrapure water, and finally add 500uL 0.1% (W / V) L-DOPA solution for staining for 3 hours. Observe the cells under an inverted microscope at 10 times and take pictures.

[0065] Conclusion: Figure 2It can be seen that compared with the model group, the cell color of the glabridin-treated group was relatively lighter, indicating that glabridin can inhibit the melanin production of B16 cells to a certain extent; the color of the cells in the targeted peptide glabridin-treated group was mostly lighter, indicating that the targeted peptide glabridin can inhibit the melanin production of B16 cells to a large extent; and from the comparison in the figure, it can be observed that the effect of the targeted peptide glabridin-treated group in inhibiting melanin production is better than that of the glabridin group.

[0066] (5) Tyrosinase activity detection:

[0067] After the supernatant of each well was aspirated, it was washed with PBS. 400μL of cell lysis solution containing 1% (V / V%) TritonX-100 was added to each well, and the cells were frozen and lysed in a -80°C refrigerator for 30 minutes, and then taken out. The cell lysate of each well was collected and centrifuged, and 100μL of supernatant was taken to a 96-well plate, and 100μL of 0.1% (W / V) L-DOPA solution was added, and incubated at 37°C for 2h. The absorbance (A) of each well was measured at a wavelength of 495nm using an enzyme reader and the enzyme activity was calculated.

[0068] Statistics and analysis: GraphPad Prism was used for graphing, and the results were expressed as Mean±SD. The t-test was used for statistical analysis among the groups. All statistical analyses were two-tailed. When the t-test method was used for statistical analysis, the model group was compared with the control group, and the significance was indicated by #, P-value<0.05 was indicated by #, P-value<0.01 was indicated by ##, and P-value<0.001 was indicated by ###; the positive (VC) group, glabridin group, and targeted peptide glabridin group were compared with the negative group, and the significance was indicated by *, P-value<0.05 was indicated by *, P-value<0.01 was indicated by **, and P-value<0.001 was indicated by ***; the targeted peptide glabridin group was compared with the glabridin group, and P-value<0.05 was indicated by &, P-value<0.01 was indicated by &&, and P-value<0.001 was indicated by &&&.

[0069] Conclusion: Figure 2 It can be seen that compared with the control group, the tyrosinase activity of the model group was significantly enhanced, indicating that the model was successfully constructed. Compared with the negative group, the tyrosinase activity of the positive (VC) group, the glabridin treatment group, and the targeted peptide glabridin group were significantly inhibited. Compared with the glabridin treatment group, the inhibitory effect of the targeted peptide glabridin group on enzyme activity was more significant.

[0070] 2. Targeted Adhesion Test of Targeted Peptide Glabridin

[0071] Mouse melanoma cells were used as the research object. The distribution position and fluorescence intensity of the cells after the fluorescent samples were treated were detected to comprehensively evaluate the targeted adhesion effect of glabridin on mouse melanoma cells.

[0072] Experimental reagents

[0073] 1640 culture medium (Gibco), PBS (Solebol), Hoechst 33342 staining solution (Biyuntian), fetal bovine serum (Sijiqing), glycerol (Solebol).

[0074] Experimental Instruments

[0075] Clean bench (Sujing Antai), cell culture incubator (Thermo Fisher), cell counter (Thermo Fisher), centrifuge (Hunan Xiangyi), inverted fluorescence microscope (Leica).

[0076] Experimental methods:

[0077] (1) Cell recovery and plate inoculation: Take out the frozen mouse melanoma cells from the liquid nitrogen tank for recovery, digest and count the cells when they grow to 70%-80%. Inoculate the counted cells in a 12-well plate, place a cell slide in each well, add 1 mL of 1E4 / mL cell suspension, and culture in a 37°C 5% CO2 cell culture incubator for 24 hours.

[0078] (2) Grouping and processing:

[0079] (2.1) Fluorescent-labeled glabridin group: 1640 medium containing 0.05% fluorescent-labeled glabridin, 3 replicate wells per group;

[0080] (2.2) Fluorescently labeled targeting peptide glabridin: 1640 culture medium containing 0.05% fluorescently labeled targeting peptide glabridin, 3 replicate wells per group;

[0081] After incubating in a 37°C, 5% CO2 cell culture incubator for 2 hours, discard the supernatant, add 500uL PBS to each well for washing, take out the Hoechst 33342 staining solution from the -20°C refrigerator in advance and rewarm it at room temperature, discard the PBS, add 400uL staining solution to each well, incubate in a 37°C, 5% CO2 incubator away from light, aspirate and discard the staining solution from each well after 20-30 minutes, wash 2-3 times with 500uL PBS, and finally add 500uL PBS.

[0082] (3) Fluorescence microscopy photography: Different positions of three replicate wells in each group were photographed and analyzed under bright field, DAPI (cell nucleus) and FITC (fluorescently labeled sample) channels.

[0083] Conclusion: Figure 3It can be seen that within the same treatment time, the targeting peptide glabridin can better recognize and target adhere to the surface of mouse melanoma cells and enter the cells to exert its effect.

[0084] 3. Permeability test of targeted peptide glabridin

[0085] This test is based on the piglet skin-Franz cell system. The high performance liquid chromatography method is used to study the transdermal behavior of the test substance in the piglet skin and evaluate the skin permeability behavior of the test sample.

[0086] Experimental Instruments

[0087] Franz cell (Shanghai Kaikai), TK-12D transdermal absorption diffusion instrument (Shanghai Kaikai), low-temperature high-speed centrifuge (Hunan Xiangyi), KQ3200E ultrasonic cleaner (Kunshan Shumei), high performance liquid chromatograph (Shimadzu, Japan).

[0088] Experimental methods:

[0089] (1) Preparation of ex vivo piglet skin: The back skin of a one-month-old piglet stored at -20°C was removed, thawed at room temperature with deionized water, and then rinsed repeatedly with PBS buffer for 2-3 times.

[0090] (2) First, fix the suckling pig skin between the supply chamber and the receiving chamber of the Franz diffusion cell, with the side facing the supply chamber being the stratum corneum and the side facing the receiving chamber being the dermis;

[0091] (3) Add 7.0 mL of receiving solution into the receiving chamber. After tightening and fixing the piglet skin, add 1.0 mL of receiving solution (PBS) into the receiving chamber through the sampler. After exhausting all the air, make sure that the receiving solution is in close contact with the dermis of the skin.

[0092] (4) Sample loading: Add the sample to the skin surface in the supply chamber. The effective penetration area S is about 3.14 cm 2 . 0.5% (m / v) glabridin and 0.5% (m / v) targeted peptide glabridin were added to the surface of pig skin, and the samples were evenly spread from the center of the skin to the edge in a radial shape. Three replicates and parallels were set for each sample;

[0093] (5) Infiltration: After the sample is smeared, place it in a constant temperature water bath in the receiving pool. The receiving pool is set to (32±1)℃ in advance. Turn on the electromagnetic stirrer and stir at a speed of 300rpm to ensure that there are no bubbles in the water bath interlayer;

[0094] (6) Take sample solutions at 15 min, 1 h, 2 h, 4 h, and 24 h respectively and place them in EP tubes for testing.

[0095] After 24 hours of exposure, the contents of the samples in the skin, skin and subcutaneous parts of the experimental group were tested respectively. The specific testing methods are as follows:

[0096] Detection of the unpenetrated part of the skin: After 24 hours of exposure, use a 1.0 mL pipette to absorb and then repeatedly blow and wash the skin surface. Wash the receiving solution 5 times, a total of 5.0 mL, and place it in a 5 mL EP tube for subsequent detection;

[0097] Intradermal part detection: Use a sterilized scalpel to cut the skin along the edge of the supply chamber, cut the skin into pieces, add 5 mL of receiving solution and perform ultrasonic extraction for a total of 60 minutes. After the ultrasonic extraction is completed, the supernatant is aspirated and then tested;

[0098] Subcutaneous part detection: At each time point, 2.0 mL of receiving solution was drawn from the receiving chamber and placed in a 2 mL EP tube, followed by detection.

[0099] Transdermal content detection:

[0100] After the 24-hour exposure, the contents of the targeted peptide glabridin and glabridin on the skin, in the skin, and under the skin of each experimental group were tested. The specific treatment methods are as follows:

[0101] (1) Detection of the unpenetrated part of the skin: Use a 1.0 mL pipette to draw liquid and repeatedly blow and wash the skin surface. After washing with PBS 5 times, a total of 5.0 mL is placed in a 5 mL EP tube and then tested;

[0102] (2) Intradermal testing: Use a sterilized scalpel to cut the skin along the edge of the supply chamber, then cut the skin into pieces and add 5 mL of PBS and perform ultrasonic extraction for 60 min. After the ultrasonic extraction is completed, the supernatant is collected and then tested.

[0103] (3) Subcutaneous part detection: At each required time point, 2.0 mL of receiving solution was drawn from the receiving chamber and placed in a 2 mL EP tube, followed by detection.

[0104] The HPLC test results are shown in Table 1.

[0105] Statistics and Analysis:

[0106] (1) Cumulative penetration

[0107] Q=Cn×V+∑Ci×V0 (i=1···n-1)

[0108] Where:

[0109] Q: Cumulative penetration

[0110] V: Volume of receiving liquid in the receiving chamber

[0111] V0: The volume of each sample

[0112] Ci: Drug concentration in the receiving solution from the first sampling to the last sampling

[0113] Cn: sample concentration measured at the nth sampling point

[0114] (2) Diffusion percentage

[0115] P=Q / Po×100%

[0116] Where:

[0117] P: Diffusion percentage

[0118] Q: Cumulative permeation of the sample at each time point in the receiving chamber

[0119] Po: theoretical content of the sample in the release pool

[0120] Permeation rate and recovery rate detection:

[0121] (1) Make a regression equation with cumulative permeation (Y axis) versus permeation time (X axis). The slope of the equation is the permeation rate KP.

[0122] (2) Recovery rate = total content (skin, mid-skin, and subcutaneous) / sample amount × 100%.

[0123] Statistical analysis:

[0124] GraphPad Prism was used for drawing, and the results were expressed as Mean ± SD. t-test was used for statistical analysis and comparison among experimental groups. All statistical analyses were two-tailed. P-value < 0.05 is represented by *, P-value < 0.01 is represented by **, and P-value < 0.001 is represented by ***.

[0125] Results: As shown in Table 2 and Figure 5 As shown in the figure, let the concentration be the X-axis and the peak area be the Y-axis to draw the standard curve. The equation of the standard curve is: y = 52132.7x + 609869, R 2 = 0.9990.

[0126] As shown in Table 3 and Figure 6 As shown in the figure, the standard curve is drawn with concentration as the X-axis and peak area as the Y-axis, and the standard curve equation is obtained: y = 81386.8x + 4925.01, R 2 = 0.9999.

[0127] The cumulative permeation amount was calculated according to the above calculation formula to obtain the cumulative permeation amount of the samples at different time points. The results are shown in Table 4 and Figure 7 .

[0128] The diffusion percentage of the samples at different time points was calculated according to the above formula. The results are shown in Table 5 and Figure 8 .

[0129] According to the above formula, the cumulative permeation amount is used to make a regression equation for the permeation time. The slope of the equation is the permeation rate Kp. The results are shown in Table 6 and Fig. 9

[0130] The test results of the residue samples on and in the skin are shown in Tables 7 and 8.

[0131] The recovery rates are shown in Table 9.

[0132] Table 1 Chromatographic conditions

[0133]

[0134] Table 2 Peak area of ​​glabridin standard working solution

[0135]

[0136] Table 3 Peak area of ​​glabridin standard working solution

[0137]

[0138] Table 4 Summary of cumulative penetration results

[0139]

[0140] Note: Chart Q is the cumulative amount of skin permeation (μg), SD is the standard deviation.

[0141] Table 5 Diffusion percentage results

[0142]

[0143] Table 6 Sample penetration rate results

[0144]

[0145] Table 7 Test results of non-penetrated samples on skin

[0146]

[0147] Note: In the chart, X is the amount of non-penetrated substance on the skin after 24 hours (μg), and SD is the standard deviation.

[0148] Table 8 Test results of samples not penetrated into the skin

[0149]

[0150] Note: X in the chart is the amount retained in the skin after 24 hours (μg), SD is the standard

[0151] Table 9 Sample recovery rate

[0152]

[0153] Conclusion: After 24h of surface exposure, the cumulative permeation amount of glabridin in the targeted peptide glabridin group was 20.43μg, the diffusion percentage was 1.48%, and the recovery rate was 83.09%. This result shows that the targeted peptide glabridin has undergone permeation behavior; the cumulative permeation amount of glabridin in the sample glabridin group was 8.73μg, the diffusion percentage was 0.64%, and the recovery rate was 80.01%, indicating that the sample has undergone permeation behavior. The cumulative permeation amount of glabridin in the glabridin group was 8.73ug, the diffusion percentage was 0.64%, and the recovery rate was 80.01%, indicating that glabridin has undergone permeation behavior.

[0154] After 24 hours of surface exposure, the cumulative penetration amount and diffusion percentage of the targeted peptide glabridin group were significantly increased compared with the glabridin group, indicating that the penetration effect of the targeted peptide glabridin was better than that of glabridin.

Claims

1. A method for preparing a targeting peptide glabridin, characterized in that: The following steps are involved: 1) Weigh the raw materials: 1 part of glabridin, 0.5-3 parts of succinic anhydride, 10-15 parts of organic solvent, 0.2-1 part of RGD polypeptide, and 0.5-3 parts of catalyst; 2) Preparation of glabridin succinate monoester: Put glabridin in a round-bottom flask, dissolve it with an organic solvent by ultrasonic, then add succinic anhydride, react at 30-50°C for 12-72 hours, recover the solvent to dryness under reduced pressure, add 0.5% dilute hydrochloric acid solution, precipitate solid, filter, wash and dry repeatedly to obtain glabridin succinic acid monoester; 3) Preparation of targeting peptide glabridin: The above-mentioned glabridin succinate monoester is dissolved in an organic solvent, and then a catalyst is added thereto, stirred to dissolve, and then an RGD polypeptide is added thereto, and after reacting at 25-50° C. for 12-36 hours, dialyzed and freeze-dried, a targeting peptide glabridin is obtained; The organic solvent is any one of pyridine, acetone, dimethyl sulfoxide, and dichloromethane; The catalyst is 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride.

2. The method for preparing the targeting peptide glabridin according to claim 1, characterized in that: The purity of the glabridin is 99%.

3. A targeting peptide glabridin prepared by the method according to any one of claims 1 and 2.

4. Use of the targeting peptide glabridin according to claim 3 in cosmetics.

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