A supramolecular eutectic gel efficiently targeting MC1R and its preparation and application

Abstract

The present invention relates to the field of cosmetics, and in particular to a supramolecular eutectic gel that efficiently targets MC1R, and its preparation and application. The supramolecular eutectic gel that efficiently targets MC1R according to the present invention comprises the following components in parts by weight: 1-5 parts of glabridin, 1-6.5 parts of glycyrrhetinic acid, 3-23 parts of C3-C4 alcohol, and 0.001-0.1 parts of a targeting active substance. The present invention compounds glabridin and glycyrrhetinic acid, with glycyrrhetinic acid serving as a hydrogen bond acceptor and glabridin serving as a hydrogen bond donor. In a small amount of C3-C4 alcohol, supramolecular eutectics can be formed through π-π stacking and hydrogen bonding, thereby improving the stability and skin permeability of glabridin. The targeting active substance has a significant binding effect with MC1R, achieving the effect of synergistically promoting efficient whitening. The present invention combines supramolecular eutectic and nanoliposome technology to obtain whitening liposomes, which have excellent whitening efficacy, clear targets, efficient penetration, high utilization rate, and are easy to mass produce.

Description

Technical Field

[0001] The present invention relates to the field of cosmetics, and in particular to a supramolecular eutectic gel that efficiently targets MC1R, and the preparation and application thereof. Background Art

[0002] In the beauty and skincare sector, whitening products have long been a popular topic among consumers. A wide variety of whitening products are currently available on the market. Commonly added whitening ingredients include niacinamide, tranexamic acid, and glutathione. Niacinamide effectively inhibits melanin production, blocking the transport of melanin to keratinocytes, achieving a whitening effect. It also offers certain oil-control and pore-minimizing benefits, repairing the skin barrier, and enhancing the skin's ability to retain moisture. However, some people may experience initial skin intolerance, such as redness and itching. High concentrations of niacinamide are unstable under certain conditions and may convert to niacin, causing skin irritation. Tranexamic acid offers significant whitening effects, indirectly reducing melanin production by inhibiting plasminogen activator. Its relatively stable properties make it less susceptible to environmental influences and less irritating, making it suitable for sensitive skin. In some products, tranexamic acid may be incompatible with other ingredients, impacting product stability. Therefore, its use alone has significant limitations, and it is often combined with other substances. Existing products also utilize other technologies, such as nanolipid carriers and ultrasound, to enhance whitening efficacy. For example, CN202310337523.4 utilizes liposomes to achieve a good whitening effect, with high stability and effective ingredients easily absorbed by the skin, significantly reducing melanin production and enhancing whitening efficacy. CN101401775B utilizes nanoemulsions to achieve a non-hazardous, non-significant toxic and side effect skin whitening effect with good stability, good transdermal absorption, and significant efficacy. The nanoemulsion system is safe, comfortable, and long-lasting, significantly improving the efficacy and safety of skin whitening. However, the energy conversion efficiency of large-scale ultrasonic oscillation production is relatively low.

[0003] Therefore, current whitening products each have their own advantages and disadvantages, and the target mechanisms of most whitening ingredients are still unclear, making it impossible to verify their targeting. As consumers' whitening needs become increasingly diversified, there is an urgent need for safe, effective, and targeted whitening products to provide people with a better whitening experience. Summary of the Invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a supramolecular eutectic gel that efficiently targets MC1R.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] In the first aspect, the present invention provides a supramolecular eutectic gel that efficiently targets MC1R, comprising the following components in parts by weight: 1-5 parts of glycyrrhizin, 1-6.5 parts of glycyrrhetinic acid, 3-23 parts of C3-C4 alcohol, and 0.001-0.1 parts of a targeting active substance; the C3-C4 alcohol comprises at least one of glycerol and 1,3-butanediol; the targeting active substance comprises at least one of palmitoyl tripeptide-8 and undecenoyl phenylalanine.

[0007] Glabridin has potential application value in cosmetics as a whitening raw material. It plays an important role in inhibiting tyrosinase activity (key enzyme) or blocking melanin transmission. Glycyrrhetinic acid is often used as an anti-inflammatory raw material. The present invention combines glabridin and glycyrrhetinic acid, which have similar structures (structural diagram as shown in FIG. Figure 1 、 Figure 2 As shown in the figure, glycyrrhetinic acid acts as a hydrogen bond acceptor and glabridin as a hydrogen bond donor. In a small amount of C3-C4 alcohol, they can form a supramolecular eutectic through π-π stacking and hydrogen bonding, thereby improving the stability and skin permeability of glabridin. In addition, palmitoyl tripeptide-8 or undecenoyl phenylalanine have a significant targeted binding effect with MC1R, thereby promoting the whitening active substances glabridin and glycyrrhetinic acid to act on MC1R to achieve an efficient whitening effect.

[0008] Preferably, the mass ratio of glabridin to glycyrrhetinic acid is glabridin: glycyrrhetinic acid = 1: (1-1.3).

[0009] The present invention has been found through research that when glabridin and glycyrrhetinic acid are compounded within the above range, the two have a better synergistic effect and better exert the whitening effect of the raw materials.

[0010] Preferably, the mass ratio of the glabridin, glycyrrhetinic acid and C3-C4 alcohol is (the sum of the masses of glabridin and glycyrrhetinic acid):C3-C4 alcohol=1:(1.5-2).

[0011] The present invention has found through research that the ratio of glabridin, glycyrrhetinic acid and C3-C4 alcohol has a great influence on the preparation of supramolecular eutectic gel, thereby affecting the stability of liposomes.

[0012] In a second aspect, the present invention provides a method for preparing the supramolecular eutectic gel, comprising the following steps: dissolving glycyrrhizin, glycyrrhetinic acid, C3-C4 alcohol, and targeted active ingredient at 70-75° C. and stirring uniformly, and rapidly cooling to obtain the supramolecular eutectic gel.

[0013] Preferably, the rapid cooling is carried out in a water bath at 0-5°C, preferably an ice water bath.

[0014] In the third aspect, the present invention provides a whitening liposome that efficiently targets MC1R, comprising the following components in percentage by mass: 5.001%-34.6% of the above-mentioned supramolecular eutectic gel that efficiently targets MC1R, 1-3% of a polyglycerol emulsifier, 4-8% of skin-affinity lipids, and the remainder being water; the polyglycerol emulsifier and the skin-affinity lipids form a phospholipid bilayer structure; the glycyrrhizin and glycyrrhetinic acid in the supramolecular eutectic gel are embedded in the phospholipid bilayer structure; the targeted active substance in the supramolecular eutectic gel is loaded on the surface of the phospholipid bilayer structure.

[0015] The present invention utilizes supramolecular eutectic and nanoliposome technology to prepare liposomes. In the preparation process of the present invention, polyglycerol emulsifiers and skin-affinity lipids form a phospholipid bilayer structure through self-assembly in water. The polyglycerol emulsifiers and skin-affinity lipids stack with each other, and the two can solidify the stable structure and increase the permeability; glycyrrhizin and glycyrrhetinic acid are embedded in the phospholipid bilayer through π-π stacking and hydrogen bond stacking under the action of C3-C4 alcohols; and the targeted active substance is embedded on the surface of the liposome to bind to the MC1R receptor.

[0016] Preferably, the particle size of the whitening liposomes that efficiently target MC1R is 20-28 nm.

[0017] Preferably, the polyglycerol emulsifier includes at least one of polyglyceryl-10 oleate, polyglyceryl-10 dimyristate, polyglyceryl-10 stearate, polyglyceryl-10 dioleate, and polyglyceryl-4 oleate.

[0018] More preferably, the polyglycerol emulsifier is polyglyceryl-10 dimyristate.

[0019] Preferably, the skin-affinity lipid comprises at least one of hydrogenated lecithin, stearic acid, phytosterol, jojoba oil, caprylic / capric triglyceride, squalane, ceramide, and cholesterol.

[0020] More preferably, the skin-substantive lipid is a combination of hydrogenated lecithin and cholesterol.

[0021] In a fourth aspect, the present invention provides a method for preparing the whitening liposomes that efficiently targets MC1R, comprising the following steps:

[0022] According to the mass percentage, the supramolecular eutectic gel efficiently targeting MC1R, polyglycerol emulsifier, skin-affinity lipid and water are mixed and stirred, and homogenized to obtain the whitening liposomes efficiently targeting MC1R.

[0023] The present invention utilizes supramolecular eutectic and nanoliposome technology in the preparation process, combining the dual advantages of eutectic technology and liposome technology to increase the solubility and stability of glycyrrhizin in water; the dual advantages of eutectic technology and liposome technology improve the skin permeability and skin utilization rate of the targeted active ingredient. At the same time, the palmitoyl tripeptide-8 or undecylenoyl phenylalanine added during the preparation process has a significant effect on the MC1R target, thereby achieving a good whitening effect. The whitening liposomes obtained by the present invention have a small particle size, high transparency and stability, can effectively promote the entry of the targeted active ingredient into the skin, improve its utilization rate on the skin, accurately act on the MC1R target, and have excellent whitening and skin care effects; the target is clear, the penetration is efficient, the retention time on the skin is long, the utilization rate is high, and it is easy to mass produce.

[0024] Preferably, the homogenization conditions are: first homogenize at 1400-1600 rpm for 2-5 min; then, perform high-pressure homogenization shearing at 30-50° C. and 400-600 bar.

[0025] Preferably, the shearing number is 4 times.

[0026] In a fifth aspect, the present invention provides the use of the above-mentioned supramolecular eutectic gel that efficiently targets MC1R or the above-mentioned whitening liposome that efficiently targets MC1R in whitening cosmetics.

[0027] In a sixth aspect, the present invention provides a whitening cosmetic comprising the above-mentioned supramolecular eutectic gel that efficiently targets MC1R or the above-mentioned whitening liposome that efficiently targets MC1R.

[0028] The beneficial effects of the present invention are:

[0029] The present invention compounds glabridin and glycyrrhetinic acid, which have similar structures. Glycyrrhetinic acid acts as a hydrogen bond acceptor and glabridin acts as a hydrogen bond donor. In a small amount of C3-C4 alcohol, they can form a supramolecular eutectic through π-π stacking and hydrogen bonding, thereby improving the stability and skin permeability of glabridin. Palmitoyl tripeptide-8 or undecylenoyl phenylalanine has a good binding effect on MC1R and has obvious targeting to MC1R, thereby achieving a highly efficient whitening effect.

[0030] The present invention also provides a whitening liposome, which utilizes supramolecular eutectic and nanoliposome technology in the preparation process. Combining the dual advantages, the eutectic technology and liposome technology can both increase the solubility and stability of glycyrrhizin in water; the dual advantages of the eutectic technology and liposome technology improve the skin permeability and skin utilization rate of the targeted active ingredient. At the same time, the palmitoyl tripeptide-8 or undecylenoyl phenylalanine added during the preparation process has a significant effect on the MC1R target, thereby achieving a good whitening effect. The whitening liposome obtained by the present invention has a small particle size, high transparency and stability, can effectively promote the targeted active ingredient to enter the skin, improve its utilization rate on the skin, accurately act on the MC1R target, and has an excellent whitening and skin care effect; the target is clear, the penetration is efficient, the retention time on the skin is long, the utilization rate is high, and it is easy to mass produce. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Schematic diagram of the structure of glabridin.

[0032] Figure 2 Schematic diagram of the structure of glycyrrhetinic acid.

[0033] Figure 3 This is a picture of the supramolecular eutectic gel prepared by the present invention. DETAILED DESCRIPTION

[0034] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0035] Unless otherwise specified, the experimental methods used in the present invention are all conventional methods, and the materials, reagents, etc. used are all commercially available unless otherwise specified.

[0036] Examples 1-7:

[0037] The embodiments of the whitening liposomes that efficiently target MC1R according to the present invention, the components and proportions of Examples 1-7 are shown in Table 1.

[0038] Table 1 Components and mass percentage ratios (%) of Examples 1-7

[0039]

[0040] The preparation method of the whitening liposomes that efficiently targets MC1R comprises the following steps:

[0041] (1) In a water bath, glabridin, glycyrrhetinic acid, glycerol / 1,3-butylene glycol, and undecylenoylphenylalanine / palmitoyl tripeptide-8 were mixed, dissolved and stirred at 70-75°C, and then added to an ice water pot (about 0-5°C) and rapidly cooled to obtain a supramolecular eutectic gel;

[0042] (2) stirring hydrogenated lecithin, polyglycerol-10 dimyristate, cholesterol, and water in a water bath at 60-65° C. to obtain a mixture;

[0043] (3) adding the mixture to the supramolecular eutectic gel and homogenizing at 1400-1600 rpm for 2-5 min to obtain an emulsion; high-pressure homogenization, conditions: 30-50° C., 400-600 bar pressure, cyclic shearing 4 times to obtain a uniform and transparent solution, which is the whitening liposome that efficiently targets MC1R.

[0044] Comparative Examples 1-12:

[0045] The comparative examples of the whitening liposomes that efficiently target MC1R according to the present invention, and the components and proportions of comparative examples 1-12 are shown in Table 2.

[0046] Table 2 Components and mass percentage ratios of comparative examples 1-12 (%)

[0047]

[0048] Among them, the only differences between Comparative Examples 1, 4, 7, and 11 and Example 1 are that Comparative Example 1 does not add glabridin, Comparative Example 4 does not add glycyrrhetinic acid, Comparative Example 7 does not add glycerol, and Comparative Example 11 does not add undecylenoylphenylalanine, and all are replaced by an equal amount of water.

[0049] The mass percentages of glabridin, glycyrrhetinic acid, glycerol, and undecylenoylphenylalanine in Comparative Examples 2, 5, 8, and 12 are beyond the scope of the present invention.

[0050] The only difference between Comparative Example 3 and Example 1 is that 3% of glabridin in Example 1 is replaced by 3% of arbutin in Comparative Example 3.

[0051] The only difference between Comparative Example 6 and Example 1 is that in Comparative Example 6, 3% of glycyrrhetinic acid in Example 1 is replaced by 3% of dipotassium glycyrrhizate.

[0052] The only difference between Comparative Example 9 and Example 1 is that in Comparative Example 10, 11% of glycerol in Example 1 is replaced by 11% of 1,2-hexanediol.

[0053] The only difference between Comparative Example 10 and Example 1 is that in Comparative Example 10, 0.002% of undecylenoylphenylalanine in Example 1 is replaced by 0.002% of tocopherol (vitamin E).

[0054] The preparation methods of the whitening liposomes with high efficiency and targeting MC1R described in Comparative Examples 1-12 are the same as those in Example 1 (comparative examples 3, 6, 9, and 10 are replaced with similar components).

[0055] Comparative Example 13:

[0056] A comparative example of the whitening liposomes efficiently targeting MC1R of the present invention, the components and proportions of the whitening liposomes efficiently targeting MC1R of Comparative Example 11 are the same as those of Example 1, and the preparation method comprises the following steps:

[0057] (1) In a water bath, glabridin, glycyrrhetinic acid, glycerol, and undecylenoylphenylalanine were mixed and dissolved at 70-75° C. and stirred to obtain a mixture A;

[0058] (2) stirring hydrogenated lecithin, polyglycerol-10 dimyristate, cholesterol, and water in a water bath at 60-65° C. to obtain a mixture B;

[0059] (3) Adding mixture B to mixture A, homogenizing at 1400-1600 rpm for 2-5 min to obtain an emulsion; high-pressure homogenization, conditions: 30-50° C., 400-600 bar pressure, cyclic shearing 4 times to obtain the whitening liposomes that efficiently target MC1R.

[0060] Comparative Example 14:

[0061] A comparative example of the whitening liposomes efficiently targeting MC1R according to the present invention. The components and proportions of the whitening liposomes efficiently targeting MC1R described in Comparative Example 12 are the same as those in Example 1. The only difference between the preparation method and Example 1 is that the homogenization pressure in step (3) is 700-800 bar.

[0062] Test Example 1: Liposome Characterization and Stability Testing

[0063] The particle size and stability of the whitening liposomes prepared in Examples 1-7 and Comparative Examples 1-14 were measured. The particle size and polydispersity coefficient were measured using a nanoparticle size potential analyzer. Stability test: The samples were placed under room temperature (25±0.5°C), high temperature (45±0.5°C), frozen (-15±0.5°C), and light (sunlight) environments for 39 weeks. After the placement, their appearance and whether they were stratified were observed. The results are shown in Table 3.

[0064] Table 3

[0065]

[0066] The present invention compounds glabridin and glycyrrhetinic acid, which have similar structures (structural schematic diagram as shown in FIG. Figure 1 、 Figure 2 As shown), glycyrrhetinic acid acts as a hydrogen bond acceptor and glabridin acts as a hydrogen bond donor, and a supramolecular eutectic can be formed in a small amount of C3-C4 alcohol through π-π stacking and hydrogen bonding. The results show that the whitening liposomes prepared by the technical solution of the present invention in Examples 1-7 have excellent stability and uniform particle size, and can form supramolecular eutectic gels (as shown). Figure 3No delamination or discoloration occurred after 39 weeks of storage at room temperature, high temperature, freezing or exposure to light.

[0067] Compared to Example 1 and Comparative Examples 1-10, Comparative Examples 1-9 did not add glycyrrhizin, glycyrrhetinic acid, or glycerol during preparation; or replaced glycyrrhizin, glycyrrhetinic acid, and C3-C4 alcohols with similar components; or the ratio of the three exceeded the scope of the present invention. All of these factors affected the formation of the supramolecular eutectic gel. Furthermore, an imbalance in the ratio of the three components also resulted in instability of the prepared liposomes, leading to precipitation. Comparative Example 10 replaced undecylenoylphenylalanine with tocopherol (vitamin E). Although a supramolecular eutectic gel was formed, the resulting liposomes had a larger particle size and were likely to experience subsequent unstable flocculation.

[0068] The preparation process of liposomes can also affect the formation of supramolecular eutectic gel and the stability of liposomes. In Comparative Example 13, no rapid cooling step was performed during the preparation process, and thus a supramolecular eutectic gel could not be formed. In Comparative Example 14, the homogenization pressure was changed, and the resulting liposomes showed an unstable phenomenon of precipitated crystals.

[0069] Since the whitening liposomes prepared in Comparative Examples 2, 5, 7, 8, 9, and 14 were found to be unstable and could not be stored for a long time during the stability test, no further research was conducted.

[0070] Test Example 2: Percutaneous penetration test

[0071] Test samples: Examples 1-7, Comparative Examples 1, 3, 4, 6, 10, 13.

[0072] Test method: Wash the pigskin with distilled water, then with physiological saline, and dry it with filter paper. A modified Franz diffusion cell was used for transdermal testing. The diffusion cell was insulated with a constant temperature (37°C) circulating water jacket. The skin was fixed between the donor chamber and the receiving chamber, with the skin surface facing the donor chamber. The effective permeation area S was 2.8 cm. 2, the receiving tank has a volume of 7.0mL, the receiving liquid is normal saline, 1.0g of the composition is evenly applied to the skin surface of the supply chamber, and the magnetic stirrer is turned on to stir at a speed of 300r / min. 0.5mL of the receiving liquid is taken out at 1, 8, 24, 48, and 72h (an equal amount of normal saline is added after each sampling), the sample is obtained and the supernatant is taken after centrifugation, and the content of glycyrrhizin and glycyrrhetinic acid is determined. After the sample permeates for 24h, the pigskin is removed and rinsed with pure water, the inner diameter range of the sample supply chamber is cut out, and then the part of the pigskin is cut into pieces and put into 3mL of pure water for ultrasonication for 30min, and then filtered with a 0.22μm filter membrane into a sample injection bottle to detect the content of glycyrrhizin and glycyrrhetinic acid (comparative examples 1 and 3 do not add glycyrrhizin and do not perform transdermal glycyrrhetinic acid penetration test, and comparative examples 4 and 6 do not add glycyrrhetinic acid and do not perform transdermal glycyrrhetinic acid penetration test). The cumulative transdermal drug release per unit area Q and the cumulative transdermal drug release at each time point were calculated. The results are shown in Tables 4 and 5.

[0073] Table 4 Transdermal Glabridin Permeation Results

[0074] sample <![CDATA[1h(μg / cm 2 )]]> 8h (μg / cm2) 16h (μg / cm2) 24h(μg / cm2 Example 1 6.01 46.92 61.31 90.61 Example 2 5.12 40.21 58.13 89.71 Example 3 4.82 32.42 45.23 69.13 Example 4 5.72 43.98 54.93 88.99 Example 5 5.92 45.91 60.99 90.12 Example 6 6.02 47.12 55.01 87.28 Example 7 6.01 45.03 57.08 89.12 Comparative Example 4 3.12 25.31 33.21 39.12 Comparative Example 6 1.23 21.33 29.13 42.12 Comparative Example 10 3.88 24.12 38.12 43.12 Comparative Example 13 1.02 18.32 20.31 29.31

[0075] As shown in Table 4, the whitening liposomes prepared by the technical solution of the present invention in Examples 1-7 have excellent transdermal permeability of glabridin, and the cumulative transdermal release of glabridin is 69.13 μg / cm 2 above.

[0076] Comparative Examples 4, 6, 10, and 13, compared to Example 1, showed that in Comparative Examples 4 and 6, glycyrrhetinic acid was not added during preparation or glycyrrhetinic acid was replaced with a similar component. The transdermal drug release of the prepared liposomes with glabridin decreased at all time points. In Comparative Example 10, undecylenoylphenylalanine was replaced with tocopherol (vitamin E), and the transdermal drug release of the prepared liposomes decreased at all time points. Comparative Example 13 did not form a supramolecular eutectic gel, resulting in a decrease in the amount of glabridin released from the prepared liposomes.

[0077] Table 5 Transdermal glycyrrhetinic acid penetration results

[0078] sample 1h (μg / cm22) 8h (μg / cm2) 16h (μg / cm2) 24h (μg / cm) Example 1 5.91 43.12 60.13 94.88 Example 2 5.21 45.93 59.12 94.71 Example 3 3.09 32.31 50.21 69.21 Example 4 5.44 41.23 50.38 92.33 Example 5 5.78 41.46 67.93 89.07 Example 6 5.39 44.09 60.11 91.76 Example 7 5.01 43.21 59.78 89.99 Comparative Example 1 4.12 39.12 44.12 53.12 Comparative Example 3 3.12 28.73 49.32 56.21 Comparative Example 10 3.41 32.21 40.12 60.93 Comparative Example 13 2.53 35.82 49.23 62.92

[0079] As shown in Table 5, the whitening liposomes prepared by the technical solution of the present invention in Examples 1-7 have excellent transdermal permeability of glycyrrhetinic acid, and the cumulative transdermal release of glycyrrhetinic acid in 24 hours is 69.21 μg / cm 2 above.

[0080] Comparative Examples 1, 3, 10, and 13 were compared with Example 1. In Comparative Examples 1 and 3, no glabridin was added during preparation or glabridin was replaced with a similar component. The transdermal drug release of the prepared liposome glycyrrhetinic acid decreased at all time points. Comparative Example 10 replaced undecylenoylphenylalanine with tocopherol (vitamin E), and the transdermal drug release of the obtained liposome decreased at all time points. Comparative Example 13 did not form a supramolecular eutectic gel, resulting in a decrease in the drug release of the obtained liposome glycyrrhetinic acid.

[0081] Test Example 3: MC1R targeting effect test

[0082] Test samples: Examples 1-7, Comparative Examples 4, 6, 10-13.

[0083] Test method:

[0084] The surface of the liposome is modified with a targeting active substance so that it can be targeted and bound to the melanocyte MC1R. Palmitoyl tripeptide-8 or undecylenoyl phenylalanine has a great influence on the efficacy targeting of the system, which in turn affects the efficacy of the liposome. This test marks fluorescence on glycyrrhizin to detect the targeting effect. Glycyrrhizin emits green fluorescence after being labeled with Cy2 fluorescence. The greater the intensity of green fluorescence emitted in the observed cells, the higher the content of glycyrrhizin absorbed by the cells. The effect of liposomes targeting melanocytes is verified by comparing the fluorescence intensity. After digestion and centrifugation of mouse melanoma cells (B16) with 0.25% trypsin, the cell suspension is prepared and cultured for 24±2h. Then, 0.0005% nanoliposomes are added. After culturing for 30min, the fluorescence intensity is observed under a fluorescence microscope (the samples of comparative examples 1 and 3 were not measured because glycyrrhizin was not added).

[0085] Table 6 Comparison of relative fluorescence intensity

[0086] sample Relative fluorescence intensity Example 1 0.632 Example 2 0.622 Example 3 0.432 Example 4 0.598 Example 5 0.601 Example 6 0.618 Example 7 0.611 Comparative Example 4 0.034 Comparative Example 6 0.012 Comparative Example 10 0.008 Comparative Example 11 0.019 Comparative Example 12 0.065 Comparative Example 13 0.156

[0087] The results are shown in Table 6. The whitening liposomes prepared by the technical solution of the present invention in Examples 1-7 can significantly target MC1R.

[0088] Comparative Examples 4, 6, 10-13, compared with Example 1, showed significantly reduced targeting of the MC1R to the liposomes prepared in Comparative Examples 4, 6, 10, 11, and 12. The liposomes did not contain glycyrrhetinic acid or undecylenoylphenylalanine during preparation; replaced glycyrrhetinic acid and undecylenoylphenylalanine with similar components; or had a ratio outside the scope of the present invention. Comparative Example 13 failed to form a supramolecular eutectic gel, resulting in reduced MC1R targeting.

[0089] Test Example 4: Whitening Efficacy Test

[0090] Test samples: Examples 1-7, Comparative Examples 1, 3, 4, 6, 10-13.

[0091] Test method:

[0092] The Demalab Combo skin analyzer was used to test the samples for their whitening efficacy in humans, according to the test standard "Test Method for the Whitening and Anti-Freckle Efficacy of Cosmetics" T / ZHCA 001-2018. 1% of the sample was added to a blank aqueous solution, and the MI and ITA values ​​of 30 volunteers aged 20 to 60 were compared before and 56 days after application. Lower MI values ​​indicate less melanin in the skin, resulting in fairer skin. The rate of change in MI values ​​was calculated according to formula (1); higher absolute values ​​indicate greater whitening efficacy.

[0093] MI value change rate (%) = (MI value at 56 days after use - MI value before use) / MI value before use × 100% - Formula (1)

[0094] Table 7 MI value test results

[0095]

[0096] The results are shown in Table 7. The whitening liposomes prepared by using the technical solution of the present invention in Examples 1-7 have excellent whitening effects.

[0097] Compared with Example 1, Comparative Examples 1, 3, 4, 6, and 10-13 did not add glabridin, glycyrrhetinic acid, or undecylenoylphenylalanine during the preparation; or replaced glabridin, glycyrrhetinic acid, and undecylenoylphenylalanine with similar components; or the ratios exceeded the scope of the present invention. The prepared liposomes had poor whitening effects. Comparative Example 13 did not form a supramolecular eutectic gel, resulting in poor whitening effect.

[0098] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A supramolecular eutectic gel that efficiently targets MC1R, characterized in that: The invention comprises the following components in parts by weight: 1-5 parts of glabridin, 1-6.5 parts of glycyrrhetinic acid, 3-23 parts of C3-C4 alcohol, and 0.001-0.1 parts of a targeting active substance; the C3-C4 alcohol is at least one of glycerol and 1,3-butanediol; the targeting active substance is at least one of palmitoyl tripeptide-8 and undecenoylphenylalanine; the mass ratio of glabridin to glycyrrhetinic acid is glabridin: glycyrrhetinic acid = 1: (1-1.3); the mass ratio of glabridin, glycyrrhetinic acid, and C3-C4 alcohol is (the sum of the masses of glabridin and glycyrrhetinic acid): C3-C4 alcohol = 1: (1.5-2).

2. The method for preparing the supramolecular eutectic gel according to claim 1, wherein: The method comprises the following steps: dissolving glabridin, glycyrrhetinic acid, C3-C4 alcohol and targeted active substances at 70-75° C. and stirring evenly, and rapidly cooling to obtain the supramolecular eutectic gel.

3. A whitening liposome that efficiently targets MC1R, characterized in that: The following components are included in mass percentage: The supramolecular eutectic gel efficiently targeting MC1R according to claim 1 comprises 5.001%-34.6%, a polyglycerol emulsifier 1-3%, a skin-affinity lipid 4-8%, and water as the balance; the polyglycerol emulsifier and the skin-affinity lipid form a phospholipid bilayer structure; the glycyrrhizin and glycyrrhetinic acid in the supramolecular eutectic gel are embedded in the phospholipid bilayer structure; and the targeting active substance in the supramolecular eutectic gel is loaded on the surface of the phospholipid bilayer structure.

4. The whitening liposome efficiently targeting MC1R according to claim 3, characterized in that: The polyglycerol emulsifier includes at least one of polyglycerol-10 oleate, polyglycerol-10 dimyristate, polyglycerol-10 stearate, polyglycerol-10 dioleate, and polyglycerol-4 oleate; And / or, the skin-affinity lipid includes at least one of hydrogenated lecithin, stearic acid, phytosterol, jojoba oil, caprylic / capric triglyceride, squalane, ceramide, and cholesterol.

5. A method for preparing the whitening liposomes that efficiently targets MC1R according to any one of claims 3 to 4, characterized in that: The method comprises the following steps: mixing and stirring the supramolecular eutectic gel efficiently targeting MC1R, polyglycerol emulsifier, skin-affinity lipid and water according to mass percentage, and homogenizing to obtain the whitening liposome efficiently targeting MC1R.

6. The preparation method according to claim 5, wherein The homogenization conditions are: first homogenize at 1400-1600 rpm for 2-5 minutes; then, perform high-pressure homogenization shearing at 30-50° C. and 400-600 bar.

7. Use of the highly efficient MC1R-targeting supramolecular eutectic gel according to claim 1 or the highly efficient MC1R-targeting whitening liposome according to any one of claims 3 to 4 in the preparation of whitening cosmetics.

8. A whitening cosmetic, characterized in that: The invention comprises the supramolecular eutectic gel efficiently targeting MC1R as claimed in claim 1 or the whitening liposome efficiently targeting MC1R as claimed in any one of claims 3-4.

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