Nano-coated alpha-arbutin deep eutectic and preparation method and application thereof

Abstract

The invention relates to the technical field of cosmetics, in particular to a nano-coated alpha-arbutin deep eutectic and a preparation method and application thereof. The nano-coated alpha-arbutin deep eutectic is prepared from the following raw materials in parts by weight: 15 to 30 parts of soybean phospholipid, 4 to 10 parts of cholesterol, 1 to 5 parts of DSPE-PEG2000, 80 to 120 parts of choline chloride / alpha-arbutin DEA, 3 to 8 parts of trehalose and 3 to 8 parts of propylene glycol. Wherein choline chloride / alpha-arbutin DEA and alpha-arbutin form a stable deep eutectic through a hydrogen bond network by taking choline chloride as a hydrogen bond receptor, so that the problems of water solubility and photo-thermal instability of the deep eutectic are solved, and the transdermal permeation efficiency and the oxidation resistance are improved. Choline chloride / alpha-arbutin DEA is wrapped by nano-liposomes to form a physical barrier, so that external ultraviolet and high-temperature environments are avoided, the risk that the choline chloride / alpha-arbutin DEA is decomposed into hydroquinone is reduced, and the storage stability of active ingredients is prolonged.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to a nano-encapsulated α-arbutin deep eutectic, a preparation method thereof, and an application thereof. Background Art

[0002] With economic development and rising living standards, people's consumption of cosmetics has gradually increased, with whitening cosmetics experiencing the fastest growth. At the same time, consumer demand for whitening products is becoming increasingly diverse, with consumers not only focusing on the whitening effect but also on safety, mildness, and durability.

[0003] Arbutin is a whitening substance and a derivative of hydroquinone. It has attracted consumer attention for its gentleness and safety. It has two configurations, α and β. α-Arbutin (α-Arb, Alpha-Arbutin) is 10 times more effective than β-arbutin in whitening and is commonly used in high-end cosmetics. α-Arbutin achieves its whitening effect by inhibiting tyrosinase activity. However, due to its hydrophilic nature, it has poor skin permeability, resulting in low utilization. Furthermore, exposure to light or extreme pH levels can cause arbutin to decompose and produce hydroquinone, which is highly irritating to the human body. There is an urgent need to find ways to improve its stability and utilization.

[0004] Deep eutectic agents (DEAs) are eutectics formed through hydrogen bonding, consisting of a hydrogen bond donor and a hydrogen bond acceptor in a specific molar ratio. By selecting the hydrogen bond donor and hydrogen bond acceptor, functional deep eutectic mixtures can be designed on demand. Compared to the original hydrogen bond donor, the newly formed deep eutectic mixture can significantly enhance the original biological activity. Currently, these deep eutectic mixtures are used as deep eutectic agents in food preservation due to their enhanced antioxidant and antimicrobial activities.

[0005] In view of the above-mentioned related technologies, this field urgently needs to use arbutin as a hydrogen bond donor and prepare a stable and highly active deep eutectic by screening hydrogen bond acceptors, thereby improving the whitening and skin care efficacy of α-arbutin and reducing its exposure risks. Summary of the Invention

[0006] In order to improve the whitening and skin care efficacy of α-arbutin, reduce the hidden dangers of its exposure, and prolong the duration of action, the present application provides a nano-encapsulated α-arbutin deep eutectic and its preparation method and application.

[0007] In the first aspect, the present application provides a nano-encapsulated α-arbutin deep eutectic, which adopts the following technical solution: a nano-encapsulated α-arbutin deep eutectic, comprising the following raw materials in parts by weight: 15-30 parts of soybean lecithin, 4-10 parts of cholesterol, 1-5 parts of DSPE-PEG2000, 80-120 parts of choline chloride / α-arbutin DEA, 3-8 parts of trehalose, and 3-8 parts of propylene glycol.

[0008] By adopting the above solution, using safe excipients such as propylene glycol and trehalose and green processes, it meets ECOCERT organic certification standards. Soy lecithin provides an amphiphilic structure, cholesterol enhances membrane stability, and trehalose protects the structure of choline chloride / α-arbutin DEA through hydrogen bonds. The addition of propylene glycol reduces overall viscosity and promotes liposome dispersion. α-Tocopherol, a natural antioxidant, can replace traditional preservatives and improve liposome storage stability, making it suitable for sensitive skin products. α-Tocopherol and α-arbutin form a synergistic antioxidant-whitening pathway, enhancing the whitening effect by scavenging free radicals.

[0009] Preferably, the nano-encapsulated α-arbutin deep eutectic is prepared by including the following raw materials in parts by weight: 18-25 parts of soybean lecithin, 5-7 parts of cholesterol, 2-4 parts of DSPE-PEG2000, 90-110 parts of choline chloride / α-arbutin DEA, 4-6 parts of trehalose, and 4-6 parts of propylene glycol.

[0010] Preferably, the choline chloride / α-arbutin DEA adopts the following technical scheme: a certain amount of choline chloride, α-arbutin and glycerol are weighed separately, mixed and added into a reactor equipped with a mechanical stirrer, heated to 70°C-100°C, stirred until the solid mixture becomes a clear homogeneous liquid, and then the stirring is stopped to obtain a white choline chloride / α-arbutin DEA mixture, which is then purified to obtain choline chloride / α-arbutin DEA.

[0011] By adopting this scheme, choline chloride acts as a hydrogen bond acceptor, forming a stable deep eutectic with α-arbutin through a hydrogen bond network. This significantly improves the solubility of α-arbutin, resolving its water solubility and photothermal instability issues, thereby enhancing transdermal penetration efficiency and antioxidant capacity. Glycerol, as a cosolvent, reduces system viscosity and enhances compatibility with the lipid bilayer, making it more suitable for cosmetic formulations. Furthermore, the preparation and purification methods are simple, cost-effective, and convenient for large-scale industrial production. The raw materials for the preparation can all be derived from natural, green products, resulting in low raw material costs.

[0012] Preferably, in the choline chloride / α-arbutin DEA, the mass ratio of choline chloride to arbutin is 1:(1-4).

[0013] Preferably, in the choline chloride / α-arbutin DEA, the added amount of glycerol is 7-13% of the total mass of choline chloride and α-arbutin.

[0014] Preferably, the purification comprises adding ethanol to the choline chloride / α-arbutin DEA mixture, taking advantage of the low melting point of choline chloride / α-arbutin DEA at low temperatures, standing at 4°C for 12 hours to precipitate choline chloride / α-arbutin DEA, collecting the precipitate after centrifugation, and vacuum drying to ensure that the solid water content is less than 1%.

[0015] Preferably, during the purification process, the mass ratio of ethanol to the choline chloride / α-arbutin DEA mixture is (1-3):1.

[0016] Preferably, during the purification process, the purity of ethanol is 99.7%.

[0017] Preferably, during the purification process, centrifugation is performed at 6000 rpm and 4° C. for 5 min, the precipitate is collected, and dried at 40-50° C. and 0.1 mbar in vacuum for 4-6 hours to ensure that the water content of the solid is less than 1%.

[0018] In a second aspect, the present application provides a method for preparing a nano-encapsulated α-arbutin deep eutectic, which adopts the following technical solution: S1: Soy lecithin, cholesterol, and DSPE-PEG2000 were mixed, dissolved in molten α-tocopherol, and stirred thoroughly until transparent. The mixture was rotary evaporated to form a uniform film, and vacuum dried for 3 hours to remove the residual solvent. S2: Mix the pre-made choline chloride / α-arbutin DEA with trehalose and propylene glycol, preheat in a water bath, add the lipid film, and shake to hydrate; S3: probe ultrasonic treatment for 10 minutes to initially reduce the particle size; S4: Use microfluidizer to control the particle size to 50-200nm; S5: Rapid freezing for 4 hours and freeze drying for 24 hours to form loose nano-choline chloride / α-arbutin deep eutectic solid; S6: Reconstitution: Reconstitute with PBS buffer, pH 5.8, and vortex for 30 seconds.

[0019] By adopting the above scheme, choline chloride / α-arbutin DEA is encapsulated in liposomes, forming a physical barrier that prevents α-arbutin from direct contact with external ultraviolet rays and high temperature environments, reducing the risk of its decomposition into hydroquinone, and prolonging the storage stability of the active ingredient. In the weakly acidic environment of the skin, it can achieve sustained release, maintain effective concentration, and enhance the whitening effect. The 50-200nm nanoparticle size combined with surface PEG modification utilizes enhanced penetration and retention effects, preferentially enriching around melanocytes, increasing local concentration and inhibiting tyrosinase activity. The thin film dispersion method in step S2 is suitable for encapsulating hydrophilic DEA, which helps to improve the encapsulation efficiency. The re-dissolution condition uses PBS buffer at pH 5.8, which is closer to the physiological pH of the skin and reduces the risk of liposome aggregation. Through the dual protection of pH adjustment and nano-encapsulation, the hydrolysis of α-arbutin to hydroquinone is inhibited, reducing the risk of allergies.

[0020] Preferably, the melted α-tocopherol is heated to 50°C.

[0021] Preferably, the S1: rotary evaporation is at 60° C. and 150 rpm.

[0022] Preferably, in S2: preheating in a water bath at 65° C., adding the lipid film, and shaking at 200 rpm for hydration for 1 hour.

[0023] Preferably, the S3: probe ultrasound, 180W, 5 seconds pulse interval, treatment for 10 minutes, initially reducing the particle size to 400-600nm.

[0024] Preferably, the S4: using a microfluidizer with a high pressure of 600 bar and 8 cycles to control the particle size to 50-200 nm and increase the encapsulation efficiency to 25-30%.

[0025] Preferably, the S5 comprises rapid freezing at -80°C for 4 hours, and freeze-drying at -50°C and 0.5 mba for 24 hours to form a loose solid.

[0026] Preferably, in S6, PBS buffer with a pH of 5.8 is used for re-dissolution, and the mass ratio of PBS buffer to nano-choline chloride / α-arbutin deep eutectic solid is (10-20):1.

[0027] In a third aspect, the present application provides the use of the above-mentioned nano-encapsulated α-arbutin deep eutectic in the preparation of whitening functional cosmetics.

[0028] In summary, this application has the following beneficial effects: 1. The nano-encapsulated α-arbutin deep eutectic prepared in this application forms a physical barrier to avoid the risk of α-arbutin decomposing into hydroquinone in external ultraviolet rays and high temperature environments, prolonging the storage stability of the active ingredient. In the weakly acidic environment of the skin, it can achieve sustained and targeted release, increase the local effective concentration and action time, and enhance the whitening effect.

[0029] 2. The choline chloride / α-arbutin DEA prepared in this application can effectively solve the problems of α-arbutin's easy oxidation and photosensitivity, and improve transdermal penetration efficiency and antioxidant capacity; at the same time, the preparation and purification methods are simple, cost-saving, and convenient for large-scale industrial production.

[0030] 3. The nano-encapsulated α-arbutin deep eutectic prepared in this application enhances the stratum corneum penetration ability through the lipophilic phospholipid layer of the nanoliposomes, and combines with propylene glycol as a penetration enhancer to increase the epidermal deposition of choline chloride / α-arbutin DEA. At the same time, the auxiliary materials trehalose and propylene glycol synergistically enhance the water retention of the stratum corneum, alleviate the drying side effects of choline chloride / α-arbutin DEA, and form a "whitening-moisturizing" dual effect.

[0031] 4. The nano-encapsulated α-arbutin deep eutectic prepared in this application solves the industry problems of traditional α-arbutin, such as easy decomposition, poor transdermal penetration, and strong irritation, through the triple synergy of choline chloride / α-arbutin DEA construction, nano-encapsulation, and functional excipient compounding. It has both high whitening efficiency and safety, and is suitable for the development of high-end cosmetics and sensitive skin care products.

[0032] Figures in the specification Figure 1 This is the H NMR spectrum of choline chloride / α-arbutin DEA prepared in Preparation Example 1. In the figure, 3.05 ppm indicates the three methyl peaks of choline chloride attached to nitrogen, 3.39 ppm indicates the methylene peak of choline chloride attached to nitrogen, 3.59-3.9 ppm indicates the hydroxyl peak of the glycosidic bond in α-arbutin, 3.95 ppm indicates the methylene peak of choline chloride, 4.7 ppm indicates the water peak, and 6.8 ppm and 6.98 ppm are both phenyl peaks of α-arbutin. DETAILED DESCRIPTION

[0033] The technical solution of the present application is further illustrated below through specific embodiments. The specific embodiments do not limit the scope of protection of the present application; some non-essential modifications and adjustments made by others based on the concept of the present application still fall within the scope of protection of the present application.

[0034] Unless otherwise specified, the experimental methods described in the following examples are conventional methods. The reagents and materials described are all commercially available products.

[0035] The present application is further described in detail below with reference to the following examples and comparative examples.

[0036] Preparation Example Preparation Example 1-6 Preparation of Choline Chloride / α-Arbutin DEA A certain amount of choline chloride, α-arbutin, and glycerol were weighed separately, mixed, added to a reactor equipped with a mechanical stirrer, and heated. Stirring was performed until the solid mixture became a clear, homogeneous liquid. Stirring was stopped, and the mixture was cooled to room temperature. Ethanol was added and the mixture was allowed to stand at 4°C for 12 hours to precipitate the choline chloride / α-arbutin DEA mixture. The mixture was centrifuged at 4°C and 6000 rpm for 5 minutes. The precipitate was collected and dried at 40-50°C, vacuum degree 0.1 mbar, and time of 4-6 hours to ensure that the solid water content was less than 1%.

[0037] The different addition amounts of each component and the reactor heating temperature parameters of Preparation Examples 1-6 are shown in Table 1.

[0038] Table 1 Preparation Examples 1-6 Different addition amounts of each component and reactor heating temperature parameters

[0039] Examples 1-6 The embodiment provides a method for preparing a nano-encapsulated α-arbutin deep eutectic, which adopts the following technical solution: S1: Dissolve soybean lecithin, cholesterol, and DSPE-PEG2000 in 50°C molten α-tocopherol, stir thoroughly until transparent, and rotary evaporate at 60°C and 150 rpm to form a uniform film. Vacuum dry for 2 hours to remove residual solvent.

[0040] S2: The prepared choline chloride / α-arbutin DEA was mixed with trehalose and propylene glycol, preheated in a 65°C water bath, added to the lipid film, and shaken at 200 rpm for hydration for 1 hour.

[0041] S3: Probe ultrasound, 180W, 5 seconds pulse interval, treatment for 10 minutes, initial reduction of particle size to 400-600nm.

[0042] S4: Use a microfluidizer with a high pressure of 600 bar and 8 cycles to control the particle size to 50-200 nm.

[0043] S5: Rapid freezing at -80°C for 2 hours, freeze drying at -50°C, 0.5 mbar for 24 hours to form a loose solid.

[0044] S6: Before use, reconstitute with pH 5.5 PBS buffer and vortex for 30 seconds. The particle size change rate of the liposomes after reconstitution is less than 5%.

[0045] The components and addition amounts in the preparation method of nano-encapsulated α-arbutin deep eutectic are shown in Table 2.

[0046] Table 2 Components and addition amounts of Examples 1-6 (g) Example 7 The use of nano-encapsulated α-arbutin deep eutectic provided in Examples 1-6 of the present application in the preparation of whitening cream.

[0047] The whitening cream adopts the following technical solution: 5.0g glycerin, 0.2g sodium hyaluronate, 1.5g polyglycerol-3 methylglucose distearate, 0.8g behenyl alcohol, 3.0g-7.0g nano-encapsulated α-arbutin deep eutectic, 0.5g coenzyme Q10, 1.0g ceramide, 0.8g phenoxyethanol, 0.6g ethylhexylglycerin, 0.5g xanthan gum, 0.05g essence, and the balance is made up to 100mL with deionized water.

[0048] Example 8 The use of nano-encapsulated α-arbutin deep eutectic provided in Examples 1-6 of the present application in the preparation of whitening essence.

[0049] The whitening essence adopts the following technical solution: 5.0g glycerin, 5.0g propylene glycol, 0.2g dipotassium glycyrrhizate, 0.2g sodium hyaluronate, 2.0g-8.0g nano-encapsulated α-arbutin deep eutectic, 0.1g xanthan gum, 0.1g carbomer, 0.8g phenoxyethanol, 0.8g ethylhexylglycerin, 0.05g essence, and the balance is made up to 100mL with deionized water.

[0050] Example 9 The use of the nano-encapsulated α-arbutin deep eutectic provided in Examples 1-6 of the present application in the preparation of whitening and moisturizing water.

[0051] The whitening and moisturizing water adopts the following technical solution: 5.0g glycerin, 3.0g propylene glycol, 0.2g sodium hyaluronate, 1.0g-3.0g nano-encapsulated α-arbutin deep eutectic, 0.5g trehalose, 0.5g phenoxyethanol, 0.4g ethylhexylglycerin, 0.05g essence, and the balance is made up to 100mL with deionized water.

[0052] Comparative Example Comparative Example 1 The same as Example 1, except that the choline chloride / α-arbutin DEA is prepared in Preparation Example 1.

[0053] Comparative Example 2 The same as Example 1, except that the choline chloride / α-arbutin DEA is prepared in Preparation Example 2.

[0054] Comparative Example 3 The same as Example 1, except that the choline chloride / α-arbutin DEA is prepared in Preparation Example 3.

[0055] Comparative Example 4 The same as Example 1, except that the choline chloride / α-arbutin DEA is prepared in Preparation Example 4.

[0056] Comparative Example 5 The same as Example 1, except that the choline chloride / α-arbutin DEA is prepared in Preparation Example 5.

[0057] Comparative Example 6 The same as Example 1, except that the choline chloride / α-arbutin DEA is prepared in Preparation Example 6.

[0058] Comparative Example 7 The same as Example 1, except that choline chloride / α-arbutin DEA is replaced by α-arbutin.

[0059] Comparative Example 8 The same as Example 1, except that the choline chloride / α-arbutin DEA is not subjected to nano-coating treatment.

[0060] Performance testing 1. Nuclear magnetic resonance spectroscopy test and results The choline chloride / α-arbutin DEA of Example 1 was characterized by H NMR spectroscopy. The results are shown in the attached specification. Figure 1 As shown, at 3.05 ppm are the three methyl peaks of choline chloride attached to the nitrogen, at 3.39 ppm is the methylene peak of choline chloride attached to the nitrogen, at 3.95 ppm is the methylene peak of choline chloride, at 4.7 ppm is the water peak, at 3.59-3.9 ppm are the hydroxyl peaks of the glycosidic bond in α-arbutin, and at 6.8 ppm and 6.98 ppm are the phenyl peaks of α-arbutin. The phenolic hydroxyl peak of α-arbutin attached to the benzene ring disappears, indicating the formation of a hydrogen bond with choline chloride.

[0061] By adopting the above scheme, choline chloride / α-arbutin DEA is prepared. Choline chloride acts as a hydrogen bond acceptor and forms a stable DEA with α-arbutin through a hydrogen bond network. The preparation and purification methods are simple, cost-effective, and convenient for large-scale industrial production. The raw materials for the preparation can all be derived from natural green products, and the raw material cost is low.

[0062] 2. Antioxidant activity determination and test results Add 7 mL of sample solution of varying concentrations to a reaction tube, then add 3 mL of DPPH solution to each tube, shake evenly, and incubate in the dark for 30 minutes. Replace the sample solution with a mixed solvent and repeat the above steps. A control group is prepared by mixing a solvent without sample and a DPPH solution, and a blank group is prepared by mixing a solvent without sample and a solvent without DPPH. The reference group is composed of Vc and α-arbutin. Each sample is run in parallel three times, and the average value is taken. Using a UV-Vis spectrophotometer, measure the absorbance (A) at 517 nm and calculate the DPPH scavenging rate using the following formula: Where: Ao is the absorbance value of the control group (the solvent without sample is mixed with DPPH solution); Ai is the absorbance value of the sample group (the sample solution is mixed with DPPH solution); Aj is the absorbance value of the blank group (mixed solvent).

[0063] The antioxidant activity test results of the choline chloride / α-arbutin DEA prepared in Preparation Examples 1-6 and the nano-encapsulated α-arbutin deep eutectics prepared in Comparative Examples 1-6 are shown in Table 3.

[0064] Table 3 DPPH free radical scavenging rate (%) of Preparation Examples 1-6 and Comparative Examples 1-6 at different concentrations As shown in Table 3, vitamin C in the control group, a potent antioxidant, exhibited a high scavenging rate of 82.5% ± 1.2% at a low concentration of 0.2 mM. As the concentration increased, the scavenging rate approached saturation at 94.8% ± 0.5% at 1.0 mM. α-Arbutin alone had weak antioxidant activity: at a concentration of 0.2 mM, the scavenging rate was only 18.6% ± 1.5%, indicating that its free radical scavenging efficiency was limited when used alone. At a concentration of 1.0 mM, the scavenging rate rose to 63.9%, but was still significantly lower than that of Preparation Examples 1-6, indicating that the choline chloride / α-Arbutin DEA significantly enhanced its activity.

[0065] The choline chloride / α-arbutin DEA from Preparation Examples 1-6 exhibited significantly enhanced antioxidant activity: at a concentration of 0.6 mM in Preparation Example 1, the clearance rate reached 72.3% ± 1.5%, compared to only 45.2% ± 2.0% in the α-arbutin control group, confirming the synergistic effect of the hydrogen bonding network on α-arbutin. At a concentration of 1.0 mM, the clearance rate reached 89.5% ± 0.9%, approaching that of vitamin C. However, the IC50 of 0.700 mM was still approximately 0.050 mM higher than that of vitamin C, indicating that while its antioxidant capacity was strong, its efficiency was slightly inferior to that of vitamin C.

[0066] The nano-encapsulated α-arbutin deep eutectics prepared in Comparative Examples 1-6 all demonstrated superior DPPH radical scavenging rates compared to the other groups. The eutectics form a physical barrier, extending the storage stability of the active ingredient and enhancing solubility and molecular interactions. Choline chloride / α-arbutin DEA effectively addresses the oxidation and photosensitivity issues of α-arbutin, while also improving transdermal penetration efficiency and antioxidant capacity. Furthermore, the preparation and purification methods are simple, cost-effective, and convenient for large-scale industrial production.

[0067] 3. Tyrosinase activity inhibition rate L-Tyrosine was dissolved in 0.05M sodium phosphate buffer solution, pH 6.8, and after making a 0.1mg / ml solution, 0.5ml of the prepared solution was put into a test tube. 0.5ml of each of Examples 1-6 and Comparative Examples 1-8, which were adjusted to 0.7mM and dissolved in 0.05M sodium phosphate buffer solution, was added and allowed to stand in a 37°C incubator for 10 minutes. Then, 0.5ml of 200 units / mL tyrosinase was added and reacted at 37°C for 10 minutes, then placed on ice and rapidly cooled to terminate the reaction. The absorbance at a wavelength of 475nm was measured using a spectrophotometer. 0.5ml of buffer solution was used as a negative control group, and an α-arbutin solution adjusted to an appropriate concentration and dissolved in 0.05M sodium phosphate buffer solution was used as a positive control group. The inhibition rate (%) of tyrosinase was calculated according to the following formula.

[0068] Wherein: A: absorbance before reaction of the wells with added reagents; B: absorbance after reaction of the wells with added reagents; C: absorbance before reaction of the wells without added reagents; D: absorbance after reaction of the wells without added reagents.

[0069] Table 4 Tyrosinase activity inhibition rate (%) of Examples 1-6 and Comparative Examples 1-8 As shown in Table 4, compared with the α-arbutin positive control group, the inhibition rates of tyrosinase activity of Preparation Examples 1-6 and Comparative Examples 1-6 were significantly higher, while those of Comparative Examples 7 and 8 were slightly lower. Therefore, this experiment proves that Preparation Examples 1-6 and Comparative Examples 1-6 can be used to improve skin whitening.

[0070] 4. Stability determination The liposomes obtained in Preparation Example 1-9 and Comparative Example 1-8 were encapsulated with choline chloride / α-arbutin DEA and placed in a sealed container at 38-40° C. for 30 days. The properties of the samples were checked. The test results are shown in Table 5.

[0071] Table 5 Stability determination of Examples 1-9 and Comparative Examples 1-8 30-day status 30-day status Preparation Example 1 No stratification, no agglomeration Comparative Example 1 No stratification, no agglomeration Preparation Example 2 No stratification, no agglomeration Comparative Example 2 No stratification, no agglomeration Preparation Example 3 No stratification, no agglomeration Comparative Example 3 No stratification, no agglomeration Preparation Example 4 No stratification, no agglomeration Comparative Example 4 No stratification, no agglomeration Preparation Example 5 No stratification, no agglomeration Comparative Example 5 No stratification, no agglomeration Preparation Example 6 No stratification, no agglomeration Comparative Example 6 No stratification, no agglomeration Preparation Example 7 No stratification, no agglomeration Comparative Example 7 Layered, no agglomeration Preparation Example 8 No stratification, no agglomeration Comparative Example 8 No stratification or agglomeration Preparation Example 9 No stratification, no agglomeration / / The stability test results show that the samples of Examples 1-9 and Comparative Examples 1-6 did not show agglomeration and stratification after being placed for 30 days, meeting the actual application requirements. No crystallization of liposome-encapsulated choline chloride / α-arbutin DEA was found. Therefore, the liposome-encapsulated choline chloride / α-arbutin DEA provided by the present invention has good stability.

[0072] The above test results show that the present application has prepared a nano-encapsulated α-arbutin deep eutectic, forming a physical barrier to avoid the risk of α-arbutin decomposing into hydroquinone in external ultraviolet light and high temperature environments, prolonging the storage stability of the active ingredient, and achieving sustained and targeted release in the weakly acidic environment of the skin, increasing the local effective concentration and duration of action, and enhancing the whitening effect. Through the triple synergy of choline chloride / α-arbutin DEA construction-nano-encapsulation-functional excipient compounding, the industry problems of traditional α-arbutin, such as easy decomposition, poor transdermal penetration, and strong irritation, are solved. It combines high-efficiency whitening and safety, and is suitable for the development of high-end cosmetics and sensitive skin care products.

[0073] This specific embodiment is merely an explanation of the present invention and is not intended to limit the present invention. After reading this specification, those skilled in the art may make non-creative modifications to this embodiment as needed. However, as long as such modifications are within the scope of the claims of the present invention, they are protected by patent law.

Claims

1. Nano-encapsulated α-arbutin deep eutectic, characterized in that: The invention comprises the following raw materials in parts by weight: 15-30 parts of soybean lecithin, 4-10 parts of cholesterol, 1-5 parts of DSPE-PEG2000, 80-120 parts of choline chloride / α-arbutin DEA, 3-8 parts of trehalose and 3-8 parts of propylene glycol.

2. The nano-encapsulated α-arbutin deep eutectic according to claim 1, characterized in that: The choline chloride / α-arbutin DEA preparation adopts the following technical solution: a certain amount of choline chloride, α-arbutin and glycerol are respectively weighed, mixed and added into a reactor equipped with a mechanical stirrer, heated to 70°C-100°C, and stirred until the solid mixture becomes a clear homogeneous liquid. Stirring is stopped to obtain a white choline chloride / α-arbutin DEA mixture, which is then purified to obtain the choline chloride / α-arbutin DEA.

3. The nano-encapsulated α-arbutin deep eutectic according to claim 1, characterized in that: The mass ratio of the choline chloride / α-arbutin DEA to arbutin is 1:(1-4).

4. The nano-encapsulated α-arbutin deep eutectic according to claim 1, characterized in that: The added amount of the choline chloride / α-arbutin DEA and glycerol is 7-13% of the total mass of choline chloride and α-arbutin.

5. The nano-encapsulated α-arbutin deep eutectic according to claim 1, characterized in that: The purification of the choline chloride / α-arbutin DEA comprises adding ethanol to the choline chloride / α-arbutin DEA mixture, taking advantage of the low melting point of choline chloride / α-arbutin DEA at low temperatures, allowing the mixture to stand at 4°C for 12 hours to precipitate the choline chloride / α-arbutin DEA, collecting the precipitate after centrifugation, and vacuum drying to ensure that the solid water content is less than 1%.

6. The nano-encapsulated α-arbutin deep eutectic according to claim 1, characterized in that: In the purification of the choline chloride / α-arbutin DEA, the mass ratio of ethanol to the choline chloride / α-arbutin DEA mixture is (1-3):

1.

7. A method for preparing the nano-encapsulated α-arbutin deep eutectic according to any one of claims 1 to 6, characterized in that: It includes the following steps: S1: Soy lecithin, cholesterol, and DSPE-PEG2000 were mixed, dissolved in molten α-tocopherol, and stirred thoroughly until transparent. The mixture was rotary evaporated to form a uniform film, and vacuum dried for 3 hours to remove the residual solvent. S2: Mix the pre-made choline chloride / α-arbutin DEA with trehalose and propylene glycol, preheat in a water bath, add the lipid film, and shake to hydrate; S3: probe ultrasonic treatment for 10 minutes to initially reduce the particle size; S4: Use a microfluidizer to control the particle size to 50-200 nm; S5: Rapid freezing for 4 hours and freeze drying for 24 hours to form loose nano-choline chloride / α-arbutin deep eutectic solid; S6: Reconstitution: Reconstitute with PBS buffer, pH 5.8, and vortex for 30 seconds.

8. The method for preparing the nano-encapsulated α-arbutin deep eutectic according to claim 7, characterized in that: In the above S2, the lipid film was added after preheating in a water bath at 65°C, and then shaken at 200 rpm for hydration for 1 hour.

9. The method for preparing nano-encapsulated α-arbutin deep eutectic according to claim 7, characterized in that: In the S6, PBS buffer of pH 5.8 is used for re-dissolution, and the mass ratio of PBS buffer to nano-choline chloride / α-arbutin deep eutectic solid is (10-20):

1.

10. Use of the nano-encapsulated α-arbutin deep eutectic according to any one of claims 7 to 9 in the preparation of whitening cosmetics.

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