Highly efficient MC1r-targeting supramolecular co-crystal gel, and preparation and use thereof

Abstract

A highly efficient MC1R-targeting supramolecular co-crystal gel, and preparation and use thereof. The highly efficient MC1R-targeting supramolecular co-crystal gel comprises the following components in parts by weight: 1-5 parts of glabridin, 1-6.5 parts of glycyrrhetinic acid, 3-23 parts of a C3-C4 alcohol, and 0.001-0.1 parts of a targeting active substance. By means of compounding glabridin and glycyrrhetinic acid, in which glycyrrhetinic acid acts as a hydrogen bond acceptor, and glabridin acts as a hydrogen bond donor, a supramolecular co-crystal can be formed in a small amount of the C3-C4 alcohol by means of π-π stacking and hydrogen bonding, thereby improving the stability and skin permeability of glabridin. The targeting active substance exhibits a significant effect of binding to MC1R, synergistically promoting a highly efficient whitening effect. A whitening liposome is obtained by means of combining the supramolecular co-crystal technology with nanoliposome technology, and it features excellent whitening efficacy, clear target, efficient penetration, high utilization rate, and ease of mass production.

Description

A highly efficient supramolecular cocrystal gel targeting MC1R and its preparation and application

[0001] Cross-reference to related applications

[0002] This disclosure claims priority to Chinese Patent Application No. CN202510475360.5, filed on April 16, 2025, entitled "A Highly Efficient Targeting Supramolecular Cocrystal Gel for MC1R and Its Preparation and Application", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to the field of cosmetics, and in particular to a highly efficient supramolecular cocrystal gel that targets MC1R, its preparation and application. Background Technology

[0004] In the beauty and skincare industry, whitening products have always been a major focus for consumers. Currently, there are numerous types of whitening products on the market. Commonly added ingredients with whitening effects include niacinamide, tranexamic acid, and glutathione. Niacinamide effectively inhibits melanin production by blocking the transfer of melanin to keratinocytes, achieving a whitening effect; it also has some oil-controlling and pore-minimizing effects, and can repair the skin barrier and enhance the skin's moisturizing ability. However, some people may experience skin intolerance in the initial stages of use, such as redness and itching; high concentrations of niacinamide are unstable under certain conditions and may convert to nicotinic acid, causing skin discomfort. Tranexamic acid has a significant whitening effect by inhibiting plasminogen activator, indirectly reducing melanin production; it is relatively stable and not easily affected by the external environment; it is less irritating and suitable for sensitive skin. In some products, tranexamic acid may have poor compatibility with other ingredients, affecting product stability. Therefore, its use as a single ingredient is limited, and it is often used in combination with other substances. Existing products also utilize other technologies in their preparation process to enhance whitening efficacy, such as nanolipocarriers and ultrasound. For example, CN202310337523.4 utilizes liposomes to achieve good whitening effects, with high stability, easy absorption of active ingredients by the skin, significant reduction of melanin production, and enhanced whitening efficacy. CN101401775B utilizes nanoemulsions to achieve skin whitening effects that are harmless, have no obvious toxic side effects, are stable, have good transdermal absorption, and are significant. Moreover, 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 production using ultrasonic oscillation is relatively low.

[0005] Therefore, current skin whitening products each have their own advantages and disadvantages, and the target mechanisms of most skin whitening ingredients are still unclear, making it impossible to verify their targeting effectiveness. As consumers' skin whitening needs become increasingly diversified, there is an urgent need for a safe, efficient, and targeted skin whitening product to bring people a better skin whitening experience. Summary of the Invention

[0006] The purpose of this disclosure is to overcome the shortcomings of the existing technology and provide a highly efficient supramolecular cocrystal gel for targeting MC1R.

[0007] To achieve the above objectives, the technical solution adopted in this disclosure is as follows:

[0008] In a first aspect, this disclosure provides a highly efficient supramolecular cocrystal gel targeting 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 ingredient; wherein the C3-C4 alcohol comprises at least one of glycerol and 1,3-butanediol; and wherein the targeting active ingredient comprises at least one of palmitoyl tripeptide-8 and undecenoyl phenylalanine.

[0009] Glycyrrhizin has potential applications in cosmetics as a skin-whitening ingredient, playing an important role in inhibiting tyrosinase activity (a key enzyme) or blocking melanin transfer. Glycyrrhetinic acid is often used as an anti-inflammatory ingredient. This disclosure combines glycyrrhizin and glycyrrhetinic acid, which have similar structures (structural diagrams are shown in Figures 1 and 2). Glycyrrhetinic acid acts as a hydrogen bond acceptor, and glycyrrhizin acts as a hydrogen bond donor. In a small amount of C3-C4 alcohol, they can form a supramolecular cocrystal through π-π stacking and hydrogen bonding, improving the stability and skin permeability of glycyrrhizin. Furthermore, palmitoyl tripeptide-8 or undecenoyl phenylalanine has a significant targeted binding effect with MC1R, thereby promoting the action of the skin-whitening active ingredients glycyrrhizin and glycyrrhetinic acid on MC1R to achieve a highly effective skin-whitening effect.

[0010] Preferably, the mass ratio of glycyrrhizin to glycyrrhetinic acid is glycyrrhizin:glycyrrhetinic acid = 1:(1-1.3).

[0011] This study found that when glycyrrhizin and glycyrrhetinic acid are combined within the above-mentioned range, they exhibit a better synergistic effect, thus better enhancing the whitening efficacy of the raw materials.

[0012] Preferably, the mass ratio of glycyrrhizin, glycyrrhetinic acid and C3-C4 alcohol is (the sum of the masses of glycyrrhizin and glycyrrhetinic acid):C3-C4 alcohol = 1:(1.5-2).

[0013] This study found that the ratio of glycyrrhizin, glycyrrhetinic acid, and C3-C4 alcohol has a significant impact on the preparation of supramolecular cocrystal gels, thereby affecting the stability of liposomes.

[0014] Secondly, this disclosure provides a method for preparing the above-mentioned supramolecular cocrystal gel, comprising the following steps: dissolving and stirring glycyrrhizin, glycyrrhetinic acid, C3-C4 alcohol and targeting active ingredient at 70-75°C until homogeneous, and rapidly cooling to obtain the supramolecular cocrystal gel.

[0015] Preferably, rapid cooling is carried out in a water bath at 0-5°C, and more preferably in an ice-water bath.

[0016] Thirdly, this disclosure provides a highly efficient whitening liposome targeting MC1R, comprising the following components by mass percentage: 5.001%-34.6% of the aforementioned highly efficient MC1R-targeting supramolecular cocrystal gel, 1-3% of a polyglycerol emulsifier, 4-8% of a skin-friendly lipid, and the balance being water; wherein the polyglycerol emulsifier and the skin-friendly lipid form a phospholipid bilayer structure; wherein glycyrrhizin and glycyrrhetinic acid in the supramolecular cocrystal gel are embedded in the phospholipid bilayer structure; and wherein the targeting active ingredient in the supramolecular cocrystal gel is loaded on the surface of the phospholipid bilayer structure.

[0017] This disclosure utilizes supramolecular cocrystallization and nanoliposome technology to prepare liposomes. In the preparation process of this disclosure, polyglycerol emulsifiers and skin-friendly lipids self-assemble in water to form a phospholipid bilayer structure. The polyglycerol emulsifiers and skin-friendly lipids stack each other, which can solidify and stabilize the structure and increase the permeability. Glycyrrhizin and glycyrrhetinic acid are embedded in the phospholipid bilayer through π-π stacking and hydrogen bonding under the action of C3-C4 alcohols. The targeting active ingredient is embedded on the surface of the liposome and binds to the MC1R receptor.

[0018] Preferably, the particle size of the highly efficient MC1R-targeting whitening liposomes is 20-28 nm.

[0019] Preferably, the polyglycerol emulsifier includes at least one of polyglycerol-10 oleate, polyglycerol-10 dimyristic acid ester, polyglycerol-10 stearate, polyglycerol-10 dioleate, and polyglycerol-4 oleate.

[0020] More preferably, the polyglycerol emulsifier is polyglycerol-10 dimyristic acid ester.

[0021] Preferably, the skin-friendly lipids include at least one of hydrogenated lecithin, stearic acid, phytosterols, jojoba oil, caprylic / capric triglycerides, squalane, ceramides, and cholesterol.

[0022] More preferably, the skin-friendly lipid is a combination of hydrogenated lecithin and cholesterol.

[0023] Fourthly, this disclosure provides a method for preparing the highly efficient MC1R-targeting whitening liposomes, comprising the following steps:

[0024] According to the mass percentage, the highly efficient MC1R-targeting supramolecular cocrystal gel, polyglycerol emulsifier, skin-friendly lipids and water are mixed and stirred, and homogenized to obtain the highly efficient MC1R-targeting whitening liposome.

[0025] This disclosure utilizes supramolecular co-crystal and nanoliposome technologies in its preparation process, combining their dual advantages. Both co-crystal and liposome technologies increase the solubility and stability of glycyrrhizin in water; the combined advantages of these technologies enhance the skin penetration and bioavailability of the targeted active ingredient. Simultaneously, the addition of palmitoyl tripeptide-8 or undecenoyl phenylalanine during the preparation process has a significant effect on the MC1R target, thus achieving a good whitening effect. The whitening liposomes obtained in this disclosure have small particle size, high transparency, and stability, which can efficiently promote the entry of the targeted active ingredient into the skin, improve its bioavailability, and precisely target the MC1R target, exhibiting excellent whitening and skincare effects; the target is clearly defined, penetration is efficient, retention time on the skin is long, bioavailability is high, and mass production is easy.

[0026] Preferably, the homogenization conditions are as follows: first, homogenize at 1400-1600 rpm for 2-5 min; then, perform high-pressure homogenization shearing at 30-50℃ and 400-600 bar.

[0027] Preferably, the number of shearing operations is 4.

[0028] Fifthly, this disclosure provides the application of the above-mentioned highly efficient MC1R-targeting supramolecular cocrystal gel or the above-mentioned highly efficient MC1R-targeting whitening liposome in whitening cosmetics.

[0029] In a sixth aspect, this disclosure provides a whitening cosmetic product, comprising the above-mentioned highly effective MC1R-targeting supramolecular cocrystal gel or the above-mentioned highly effective MC1R-targeting whitening liposome.

[0030] The beneficial effects of this disclosure are as follows:

[0031] This disclosure combines glycyrrhizin and glycyrrhetinic acid, which have similar structures. Glycyrrhetinic acid acts as a hydrogen bond acceptor, while glycyrrhizin acts as a hydrogen bond donor. In a small amount of C3-C4 alcohol, they can form a supramolecular cocrystal through π-π stacking and hydrogen bonding, thereby improving the stability and skin permeability of glycyrrhizin. Palmitoyl tripeptide-8 or undecenoyl phenylalanine has a good binding effect on MC1R and obvious targeting of MC1R, thus achieving a highly effective whitening effect.

[0032] This disclosure also provides a skin-whitening liposome, which utilizes supramolecular co-crystallization and nanoliposome technology in its preparation process. Combining the advantages of both technologies, co-crystallization and liposomes increase the solubility and stability of glycyrrhizin in water. The combined advantages of these technologies improve the skin penetration and bioavailability of the targeted active ingredient. Simultaneously, the addition of palmitoyl tripeptide-8 or undecenoyl phenylalanine during preparation has a significant effect on the MC1R target, thus achieving a better skin-whitening effect. The skin-whitening liposomes obtained by this disclosure have small particle size, high transparency, and stability, effectively promoting the entry of the targeted active ingredient into the skin, improving its bioavailability, and precisely targeting the MC1R target, resulting in excellent skin-whitening and whitening effects. The target is clearly defined, allowing for efficient penetration, long retention time on the skin, high bioavailability, and easy mass production. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the specific embodiments of this disclosure or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this disclosure. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0034] Figure 1 is a schematic diagram of the structure of glycyrrhizin.

[0035] Figure 2 is a schematic diagram of the structure of glycyrrhetinic acid.

[0036] Figure 3 shows the supramolecular eutectic gel prepared in this disclosure. Detailed Implementation

[0037] The technical solutions of this disclosure will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of this disclosure, and not all embodiments. Based on the embodiments of this disclosure, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this disclosure.

[0038] Unless otherwise specified, the experimental methods used in this disclosure are conventional methods, and the materials and reagents used are commercially available unless otherwise specified.

[0039] Examples 1-7:

[0040] Examples of the highly effective MC1R-targeting whitening liposomes disclosed herein, the components and formulations of Examples 1-7 are shown in Table 1.

[0041] Table 1. Components and mass percentage ratios (%) of Examples 1-7

[0042] The preparation method of the highly efficient MC1R-targeting whitening liposomes includes the following steps:

[0043] (1) In a water bath, glycyrrhizin, glycyrrhetinic acid, glycerol / 1,3-butanediol and undecenoyl phenylalanine / palmitoyl tripeptide-8 are mixed, dissolved and stirred evenly at 70°C, and then added to an ice water pot (about 5°C) for rapid cooling to obtain supramolecular cocrystal gel.

[0044] (2) Hydrogenated lecithin, polyglycerol-10 dimyristic acid ester, cholesterol and water were stirred in a water bath at 60°C to obtain a mixture;

[0045] (3) Add the mixture to the supramolecular eutectic gel and homogenize at 1600 rpm for 3 min to obtain an emulsion; homogenize under high pressure, under the conditions of 40℃ and 400 bar pressure for 4 cycles to obtain a uniform and transparent solution, which is the whitening liposome that targets MC1R.

[0046] Comparative Examples 1-12:

[0047] The comparative examples of the highly efficient MC1R-targeting whitening liposomes disclosed herein, the components and formulations of Comparative Examples 1-12 are shown in Table 2.

[0048] Table 2 shows the components and their mass percentage ratios (%) for Comparative Examples 1-12.

[0049] Among them, the only differences between Comparative Examples 1, 4, 7, and 11 and Example 1 are that Comparative Example 1 did not contain glycyrrhizin, Comparative Example 4 did not contain glycyrrhetinic acid, Comparative Example 7 did not contain glycerol, and Comparative Example 11 did not contain undecenoyl phenylalanine, and all of them were replaced with an equal amount of water.

[0050] The mass percentages of glycyrrhizin, glycyrrhetinic acid, glycerol, and undecenoyl phenylalanine in Comparative Examples 2, 5, 8, and 12 are beyond the scope of this disclosure.

[0051] The only difference between Comparative Example 3 and Example 1 is that Comparative Example 3 replaces 3% glycyrrhizin in Example 1 with 3% arbutin.

[0052] The only difference between Comparative Example 6 and Example 1 is that Comparative Example 6 replaces 3% glycyrrhetinic acid in Example 1 with 3% dipotassium glycyrrhizate.

[0053] The only difference between Comparative Example 9 and Example 1 is that Comparative Example 10 replaces 11% glycerol in Example 1 with 11% 1,2-hexanediol.

[0054] The only difference between Comparative Example 10 and Example 1 is that Comparative Example 10 replaces 0.002% undecenoyl phenylalanine in Example 1 with 0.002% tocopherol (vitamin E).

[0055] The preparation methods of the highly efficient MC1R-targeting whitening liposomes described in Comparative Examples 1-12 are the same as those in Example 1 (with similar component substitutions in Comparative Examples 3, 6, 9, and 10).

[0056] Comparative Example 13:

[0057] A comparative example of the highly effective MC1R-targeting whitening liposomes disclosed herein, wherein the components and proportions of the highly effective MC1R-targeting whitening liposomes in Comparative Example 11 are the same as in Example 1, and the preparation method includes the following steps:

[0058] (1) In a water bath, glycyrrhizin, glycyrrhetinic acid, glycerol and undecenoyl phenylalanine are mixed and dissolved and stirred at 70°C to obtain mixture A;

[0059] (2) Hydrogenated lecithin, polyglycerol-10 dimyristic acid ester, cholesterol and water were stirred in a water bath at 60°C to obtain mixture B;

[0060] (3) Add mixture B to mixture A and homogenize at 1600 rpm for 3 min to obtain an emulsion; homogenize under high pressure, conditions: 40℃, 400 bar pressure for 4 cycles of shearing to obtain the highly efficient whitening liposomes targeting MC1R.

[0061] Comparative Example 14:

[0062] A comparative example of the highly efficient MC1R-targeting whitening liposomes disclosed herein. The components and proportions of the highly efficient MC1R-targeting whitening liposomes in Comparative Example 12 are the same as those in Example 1. The only difference between Comparative Example 1 and Example 1 is that the homogenization pressure in step (3) is 800 bar.

[0063] Test Example 1: Liposome Characterization and Stability Test

[0064] The particle size and stability of the whitening liposomes prepared in Examples 1-7 and Comparative Examples 1-14 were determined. The particle size and polydispersity index were determined by a nanoparticle size potential analyzer. For stability testing, the samples were placed in room temperature (25±0.5℃), high temperature (45±0.5℃), frozen (-15±0.5℃), and light (sunlight) environments for 39 weeks, respectively. After the placement, their appearance and whether they were separated into layers were observed. The results are shown in Table 3.

[0065] Table 3

[0066] This disclosure combines glycyrrhizin and glycyrrhetinic acid, which have similar structures (structural diagrams are shown in Figures 1 and 2). Glycyrrhetinic acid acts as a hydrogen bond acceptor, and glycyrrhizin acts as a hydrogen bond donor. In a small amount of C3-C4 alcohol, they can form a supramolecular cocrystal through π-π stacking and hydrogen bonding. The results show that the whitening liposomes prepared by the technical solution of this disclosure in Examples 1-7 have excellent stability and uniform particle size, and can all form supramolecular cocrystal gels (as shown in Figure 3). No delamination or discoloration occurred after 39 weeks of storage under various conditions, including room temperature, high temperature, freezing, and light exposure.

[0067] Compared to Examples 1 and 1-10, Examples 1-9 did not add glycyrrhizin, glycyrrhetinic acid, or glycerol during preparation; or replaced glycyrrhizin, glycyrrhetinic acid, and C3-C4 alcohol with similar components; or the ratio of the three components exceeded the scope of this disclosure. All of these factors would affect the formation of supramolecular cocrystal gels, and imbalances in the ratio of the three components would also lead to instability of the prepared liposomes and precipitation. In Comparative Example 10, undecenoyl phenylalanine was replaced with tocopherol (vitamin E). Although supramolecular cocrystal gels could be formed, the resulting liposomes had larger particle sizes, which might lead to unstable flocculation later.

[0068] The preparation process of liposomes can also affect the formation of supramolecular cocrystal gels and the stability of liposomes. In Comparative Example 13, a rapid cooling step was not performed during the preparation process, so a supramolecular cocrystal gel could not be formed. In Comparative Example 14, the homogenization pressure was changed, and the liposomes obtained showed unstable phenomena such as crystal precipitation.

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

[0070] Test Example 2: Transdermal Permeability Test

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

[0072] Test method: The pigskin was washed with distilled water, then rinsed with physiological saline, and dried with filter paper. A modified Franz diffusion cell was used for transdermal testing. The diffusion cell was kept warm with a constant-temperature (37℃) circulating water jacket. The skin was fixed between the supply chamber and the receiving chamber, with the skin surface facing the supply chamber. The effective penetration area S was 2.8 cm². 2The receiving chamber had a volume of 7.0 mL, and the receiving solution was physiological saline. 1.0 g of the composition was evenly applied to the skin surface of the supply chamber, and a magnetic stirrer was turned on and stirred at 300 r / min. At 1, 8, 24, 48, and 72 h, 0.5 mL of the receiving solution was collected (an equal amount of physiological saline was added after each sampling). After centrifugation, the supernatant was collected, and the contents of glycyrrhizin and glycyrrhetinic acid were determined. After 24 h of sample infiltration, the pigskin was removed and rinsed with pure water. The inner diameter of the supply chamber was cut, and the pigskin was then shredded and sonicated in 3 mL of pure water for 30 min. The mixture was then filtered through a 0.22 μm filter into a sample vial to detect the contents of glycyrrhizin and glycyrrhetinic acid (comparative examples 1 and 3 did not contain glycyrrhizin and therefore did not undergo transdermal glycyrrhizin infiltration testing; comparative examples 4 and 6 did not contain glycyrrhetinic acid and therefore did not undergo transdermal glycyrrhetinic acid infiltration testing). 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 Results of transdermal glycyrrhizin penetration

[0074] As shown in Table 4, the whitening liposomes prepared using the technical solution of this disclosure in Examples 1-7 exhibit excellent transdermal permeability of glycyrrhizin, with a cumulative transdermal release of 69.13 μg / cm³ after 24 hours. 2 above.

[0075] Compared with Example 1, Comparative Examples 4, 6, 10, and 13 showed that Comparative Examples 4 and 6, which did not add glycyrrhetinic acid or replaced it with a similar component during preparation, resulted in a decrease in the transdermal release of glycyrrhizin from liposomes at all time points. Comparative Example 10, which replaced undecenoyl phenylalanine with tocopherol (vitamin E), also resulted in a decrease in the transdermal release of glycyrrhizin from liposomes at all time points. Comparative Example 13 failed to form a supramolecular eutectic gel, leading to a decrease in the release of glycyrrhizin from liposomes.

[0076] Table 5 Results of transdermal glycyrrhetinic acid permeation

[0077] As shown in Table 5, the whitening liposomes prepared using the technical solution of this disclosure in Examples 1-7 exhibit excellent transdermal permeability of glycyrrhetinic acid, with a cumulative transdermal release of 69.21 μg / cm³ after 24 hours. 2 above.

[0078] Compared with Example 1, Comparative Examples 1, 3, 10, and 13 showed that Comparative Examples 1 and 3, which did not add glycyrrhizin or replaced it with a similar component during preparation, resulted in a decrease in the transdermal release of glycyrrhetinic acid from the liposomes at all time points. In Comparative Example 10, undecenoyl phenylalanine was replaced with tocopherol (vitamin E), resulting in a decrease in the transdermal release of glycyrrhetinic acid from the liposomes at all time points. Comparative Example 13 failed to form a supramolecular eutectic gel, leading to a decrease in the glycyrrhetinic acid release from the liposomes.

[0079] Test Example 3: MC1R Targeting Effect Test

[0080] Test samples: Examples 1-7, Comparative Examples 4, 6, 10-13.

[0081] Test method:

[0082] The liposomes were modified with targeting active ingredients to enable them to bind to the MC1R of melanocytes. Palmitoyl tripeptide-8 or undecenoyl phenylalanine significantly affected the targeting efficacy of the system, thus influencing the efficacy of the liposomes. In this study, the targeting effect was detected by labeling glycyrrhizin with fluorescence. Glycyrrhizin emitted green fluorescence after Cy2 fluorescent labeling. The greater the intensity of green fluorescence emitted in the cells, the higher the amount of glycyrrhizin absorbed by the cells. By comparing the fluorescence intensity, the effect of liposomes on melanocytes was verified. Mouse melanoma cells (B16) were digested with 0.25% trypsin, centrifuged, and cultured in a cell suspension for 24±2 h. Then, 0.0005% nanoliposomes were added, and after culturing for 30 min, the fluorescence intensity was observed under a fluorescence microscope (comparative samples 1 and 3 were not measured because glycyrrhizin was not added).

[0083] Table 6 Comparison of relative fluorescence intensity

[0084] The results are shown in Table 6. The whitening liposomes prepared using the technical solution of this disclosure in Examples 1-7 can significantly target MC1R.

[0085] Compared with Example 1, Comparative Examples 4, 6, 10, 11, and 12 did not add glycyrrhetinic acid or undecenoyl phenylalanine during preparation; or replaced glycyrrhetinic acid and undecenoyl phenylalanine with similar components; or the proportions exceeded the range of this disclosure. The resulting liposomes showed significantly reduced targeting of MC1R. Comparative Example 13 did not form a supramolecular cocrystal gel, leading to a reduced MC1R targeting effect.

[0086] Test Example 4: Whitening Efficacy Test

[0087] Test samples: Examples 1-7, Comparative Examples 1, 3, 4, 6, 10-13.

[0088] Test method:

[0089] The Demalab Combo skin analyzer was used to test the skin whitening efficacy of the samples on human skin, according to the test standard "Test Method for Whitening and Spot Removing Efficacy of Cosmetics" T / ZHCA 001—2018. 1% of the sample was added to a blank aqueous solution, and the MI and ITA values ​​were compared between 30 volunteers aged 20 to 60 years before and 56 days after skin application. A lower MI value indicates less melanin in the skin, resulting in a whiter appearance. The rate of change of MI value was calculated according to formula (1); a higher absolute value indicates a better whitening effect.

[0090] MI value change rate (%) = (T MI value after 56 days of use - T MI value before use) / T MI value before use × 100% — Equation (1)

[0091] Table 7 MI Value Test Results

[0092] The results are shown in Table 7. The whitening liposomes prepared using the technical solution of this disclosure in Examples 1-7 have excellent whitening effects.

[0093] Compared with Example 1, Comparative Examples 1, 3, 4, 6, and 10-13 did not add glycyrrhizin, glycyrrhetinic acid, or undecenoyl phenylalanine during preparation; or replaced glycyrrhizin, glycyrrhetinic acid, and undecenoyl phenylalanine with similar components; or the proportions exceeded the range of this disclosure, resulting in poor whitening effects of the prepared liposomes. Comparative Example 13 did not form a supramolecular cocrystal gel, leading to poor whitening effect.

[0094] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this disclosure, and are not intended to limit them. Although this disclosure has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this disclosure. Industrial applicability

[0095] The highly efficient MC1R-targeting supramolecular cocrystal gel disclosed herein comprises the following components in parts by weight: 1-5 parts glycyrrhizin, 1-6.5 parts glycyrrhetinic acid, 3-23 parts C3-C4 alcohol, and 0.001-0.1 parts targeting active ingredient. This disclosure combines glycyrrhizin and glycyrrhetinic acid, with glycyrrhetinic acid acting as a hydrogen bond acceptor and glycyrrhizin as a hydrogen bond donor. In a small amount of C3-C4 alcohol, they can form a supramolecular cocrystal through π-π stacking and hydrogen bonding, improving the stability and skin permeability of glycyrrhizin. The targeting active ingredient exhibits a significant binding effect with MC1R, achieving a synergistic effect in promoting highly effective skin whitening. This disclosure combines supramolecular cocrystal and nanoliposome technology to obtain whitening liposomes with excellent whitening efficacy, clear target, high penetration, high utilization rate, and ease of mass production.

Claims

1. A highly efficient supramolecular cocrystal gel targeting MC1R, characterized in that, The product comprises 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 ingredient; wherein the C3-C4 alcohol is at least one of glycerol and 1,3-butanediol; wherein the targeting active ingredient is at least one of palmitoyl tripeptide-8 and undecenoyl phenylalanine; wherein the mass ratio of glycyrrhizin to glycyrrhetinic acid is glycyrrhizin: glycyrrhetinic acid = 1:(1-1.3); wherein the mass ratio of glycyrrhizin, glycyrrhetinic acid, and C3-C4 alcohol is (the sum of the masses of glycyrrhizin and glycyrrhetinic acid): C3-C4 alcohol = 1:(1.5-2).

2. The method for preparing the supramolecular eutectic gel as described in claim 1, characterized in that, The process includes the following steps: dissolving and stirring glycyrrhizin, glycyrrhetinic acid, C3-C4 alcohol and the targeting active ingredient at 70℃-75℃ until homogeneous, and then rapidly cooling to obtain the supramolecular cocrystal gel.

3. A highly efficient whitening liposome targeting MC1R, characterized in that, Includes the following components by mass percentage: The highly efficient MC1R-targeting supramolecular co-crystal gel of claim 1 comprises 5.001%-34.6% polyglycerol emulsifier, 1-3% skin-friendly lipids, 4-8% water as the balance; the polyglycerol emulsifier and skin-friendly lipids form a phospholipid bilayer structure; glycyrrhizin and glycyrrhetinic acid in the supramolecular co-crystal gel are embedded in the phospholipid bilayer structure; the targeting active ingredient in the supramolecular co-crystal gel is loaded on the surface of the phospholipid bilayer structure.

4. The highly efficient MC1R-targeting whitening liposome as described in claim 3, characterized in that, The polyglycerol emulsifier includes at least one of polyglycerol-10 oleate, polyglycerol-10 dimyristic acid ester, polyglycerol-10 stearate, polyglycerol-10 dioleate, and polyglycerol-4 oleate. And / or, the skin-friendly lipids include at least one of hydrogenated lecithin, stearic acid, phytosterols, jojoba oil, caprylic / capric triglycerides, squalane, ceramides, and cholesterol.

5. A method for preparing a highly efficient MC1R-targeting whitening liposome as described in any one of claims 3-4, characterized in that, The process includes the following steps: mixing and stirring the highly efficient MC1R-targeting supramolecular cocrystal gel, polyglycerol emulsifier, skin-friendly lipids, and water according to the mass percentage, and homogenizing to obtain the highly efficient MC1R-targeting whitening liposome.

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

7. The use of the highly efficient MC1R-targeting supramolecular eutectic gel as described in claim 1 or the highly efficient MC1R-targeting whitening liposome as described in any one of claims 3-4 in the preparation of whitening cosmetics.

8. A whitening cosmetic product, characterized in that, Includes the highly efficient MC1R-targeting supramolecular cocrystal gel as described in claim 1 or the highly efficient MC1R-targeting whitening liposome as described in any one of claims 3-4.

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