Active matter deep eutectic solvent liposome cream and method of making same

Abstract

The application provides an active substance eutectic solvent liposome cream and a preparation method thereof, which is based on active substance eutectic solvent technology and supramolecular liposome technology. Phospholipid, cholesterin and emulsifier are dissolved at a water bath temperature of 50-75 DEG C, and then the obtained oil-soluble active substance eutectic solvent is added and stirred and mixed to obtain an oil phase. A stabilizer, a humectant and pure water are dissolved at a water bath temperature of 50-75 DEG C, and then the water-soluble active substance eutectic solvent is added and stirred and mixed to obtain an aqueous phase. The aqueous phase is slowly added to the oil phase under shearing, and then high-pressure homogenization treatment is carried out to obtain the active substance eutectic solvent liposome cream. The active substance eutectic solvent liposome cream has high stability, small cream particle size, delicate and refreshing skin feeling, simple preparation method and is beneficial to scale-up production.

Description

Technical Field

[0001] This invention belongs to the field of cosmetic technology, specifically relating to an active ingredient eutectic solvent liposome face cream and its preparation method. Background Technology

[0002] Face creams occupy a significant share of the cosmetics industry, primarily composed of water-in-oil (W / O) and oil-in-water (O / W) systems. Face creams exhibit uneven particle size distribution, ranging from hundreds of nanometers to tens of micrometers, resulting in inconsistent skin texture and poor skin absorption. Due to their physicochemical characteristics, most active ingredients are blocked by the skin barrier outside the stratum corneum, making it difficult for them to penetrate deeper into the skin to exert their effects. Furthermore, some active ingredients are highly susceptible to external environmental influences, such as transition metal ions, light, pH, temperature, and high concentrations of oxygen, causing them to lose their original efficacy.

[0003] Deep eutectic solvents (DESs) are eutectic mixtures formed under specific conditions by hydrogen bond acceptors and hydrogen bond donors in a certain stoichiometric ratio. DESs offer advantages such as environmental friendliness, high biodegradability, non-flammability, low cost, and ease of preparation. Natural deep eutectic solvents (NDESs) are composed of natural products. NDESs are significantly less toxic than DESs, and from both economic and environmental perspectives, NDESs are superior to DESs in terms of biodegradability, sustainability, and preparation cost.

[0004] Liposome technology refers to the encapsulation of bioactive substances within closed vesicles formed by amphiphilic lipid molecules within a phospholipid bilayer structure. Similar to cell membranes, these vesicles are primarily composed of phospholipids and cholesterol and are also known as artificial biomembranes. Liposomes can effectively address issues related to the solubility, stability, irritation, odor, formulation difficulties, and bioavailability of bioactive substances. Currently, the cosmetic industry almost exclusively uses this technology for the development of active ingredients, rather than for finished cosmetic formulations. While this technology significantly improves the stability and transdermal absorption of cosmetic active ingredients, when applied to cosmetic production, these products are susceptible to the influence of manufacturing processes and the physicochemical properties of the product, such as shear stress, excessive metal ions, production temperature, and product pH, which can damage their structure and affect the transdermal absorption and stability of the active ingredients. Summary of the Invention

[0005] To address the problems in the prior art, this invention provides an active ingredient low eutectic solvent liposome face cream and its preparation method. It does not add preservatives and applies supramolecular liposome technology to the finished cosmetic formulation, effectively increasing the retention of various active ingredients in the skin, promoting the penetration of functional components, reducing the impact of environmental factors on active ingredients, and improving the overall skin feel of the face cream system.

[0006] The technical problem solved by this invention is achieved by the following technical solution:

[0007] The first objective of this invention is to provide a method for preparing an active ingredient eutectic solvent liposome face cream, characterized by comprising the following steps:

[0008] 1) Preparation of the eutectic solvent for the active ingredient:

[0009] The active ingredient and its ligands are precisely weighed and heated to dissolve at 40-100℃. The mixture is stirred and mixed evenly, and then cooled to room temperature to form a low eutectic solvent for the active ingredient. The low eutectic solvent for the active ingredient includes an oil-soluble low eutectic solvent for the active ingredient and a water-soluble low eutectic solvent for the active ingredient, which are respectively prepared as oil-soluble low eutectic solvent for the active ingredient and water-soluble low eutectic solvent for the active ingredient.

[0010] 2) Preparation of the oil phase:

[0011] Phospholipids, cholesterol, and emulsifiers are dissolved in a water bath at 50-75°C, magnetically stirred and mixed, and then the oil-soluble active material eutectic solvent obtained in step 1) is added and stirred to obtain the oil phase.

[0012] 3) Preparation of the aqueous phase:

[0013] The stabilizer, humectant and pure water are dissolved in a water bath at 50-75℃, and the mixture is stirred magnetically. The water-soluble active ingredient eutectic solvent obtained in step 1) is added and stirred until homogeneous to obtain the aqueous phase.

[0014] 4) Preparation of face cream:

[0015] The aqueous phase was slowly added to the oil phase under shear conditions to obtain the pre-emulsion; then the pre-emulsion was subjected to high-pressure homogenization and cyclicated 4 to 16 times; cooled to 35 to 60°C, a pH adjuster was added and stirred evenly, and then cooled to room temperature to obtain the active ingredient eutectic solvent liposome face cream.

[0016] Furthermore, the molar ratio of the active ingredient to the ligand is 1:3 to 3:1.

[0017] Preferably, the molar ratio of the active ingredient to the ligand is 1:2-3:2.

[0018] Furthermore, the shearing conditions are: shearing speed of 5000-10000 rpm; shearing temperature of 50-75℃; and shearing time of 3-8 min.

[0019] Furthermore, the conditions for high-pressure homogenization are a homogenization pressure of 500-1000 bar and a homogenization temperature of 50-75℃.

[0020] A second objective of this invention is to provide an active ingredient eutectic solvent liposome face cream prepared by the above method, characterized in that it comprises the following components by mass percentage:

[0021] Eutectic solvent for active ingredient: 1.5-12.0%

[0022] Phospholipids: 1.0-5.0%

[0023] Emulsifier: 1.0-3.0%

[0024] Cholesterol: 0.1-0.5%

[0025] Moisturizer: 5.0-15.1%

[0026] Stabilizer: 0.2-0.8%

[0027] pH adjuster: 0-0.5%

[0028] Pure water: Balance;

[0029] The eutectic solvent for the active ingredient includes oil-soluble eutectic solvents and water-soluble eutectic solvents.

[0030] Furthermore, the eutectic solvent of the active ingredient is selected from at least one of the following: idebenone menthol, coenzyme Q10 menthol, nicotinamide xylitol, nicotinamide propylene glycol, nicotinamide fructose, and nicotinamide citric acid.

[0031] Furthermore, the phospholipid is selected from at least one of soybean lecithin, hydrogenated lecithin, lysophosphatidylcholine, and egg yolk lecithin.

[0032] Furthermore, the emulsifier is selected from at least one of PEG-100 stearate, polysorbate-20, polysorbate-60, polysorbate-80, polyglycerol-10-laurate, polyglycerol-10-oleate, polyglycerol-10-myristate, glyceryl stearate, stearyl alcohol polyether-21, and cetearyl glucoside.

[0033] Furthermore, the moisturizer is selected from at least one of glycerin, 1,3-propanediol, glyceryl glucoside, sodium hyaluronate, 1,3-butanediol, 1,2-pentanediol, 1,2-hexanediol, ethylhexylglycerin, dipropylene glycol, and glyceryl glucoside.

[0034] Furthermore, the stabilizer is selected from at least one of EDTA-2Na, sodium metabisulfite, tocopherol, ethyl tocopherol, carbomer, and polyacrylate crosspolymer-6.

[0035] Furthermore, when the stabilizer is tocopherol or ethyl tocopherol, it is mixed with phospholipids, cholesterol, and emulsifiers to prepare the oil phase.

[0036] Furthermore, the pH adjuster is selected from at least one of sodium hydroxide, potassium hydroxide, triethanolamine, arginine, lactic acid, and citric acid.

[0037] Compared with the prior art, the beneficial technical effects of the present invention are as follows:

[0038] This invention combines active ingredients with ligands to form a low-melting-point solvent for the active ingredient, which is then co-loaded with liposomes to prepare a low-melting-point solvent liposome face cream. Using these liposomes in the finished face cream results in a liposome face cream with high stability, small particle size, and a delicate, refreshing texture. This invention is entirely green and safe, with no added preservatives; it significantly promotes transdermal absorption of the active ingredient and reduces the impact of environmental factors on the active ingredient. The face cream preparation method of this invention is simple, facilitating industrial-scale application in cosmetics, and has broad application value.

[0039] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, and in order to make the above and other objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention are described below. Attached Figure Description

[0040] Figure 1 This is a comparison of the appearance of Example 1 and Comparative Example 1 in the preparation method of a face cream based on supramolecular liposome technology of the present invention.

[0041] Figure 2 This is a comparison diagram of the water dispersion of Example 1 and Comparative Example 1 in the preparation method of a face cream based on supramolecular liposome technology of the present invention.

[0042] Figure 3 This is a transmission electron microscope image of Example 1 of the face cream and its preparation method based on supramolecular liposome technology of the present invention.

[0043] Figures 4-11 The particle size distribution of samples from various embodiments and comparative examples of a face cream and its preparation method based on supramolecular liposome technology according to the present invention is shown in the figure.

[0044] Figure 12 The images show the appearance and stability of various embodiments of a face cream and its preparation method based on supramolecular liposome technology according to the present invention.

[0045] Figure 13 This is a particle size stability diagram of Example 1 in the preparation method of a face cream based on supramolecular liposome technology of the present invention.

[0046] Figure 14 This is a stability diagram of the encapsulation rate in Example 1 of the preparation method of a face cream using supramolecular liposome technology according to the present invention.

[0047] Figure 15-17 This is a comparison chart showing the stability of active ingredient content in Example 1, Comparative Example 1, Example 2, Comparative Example 2, and Example 3, and Comparative Example 3, in the preparation method of a face cream using supramolecular liposome technology according to the present invention.

[0048] Figure 18 This is a comparison chart of the cumulative skin retention of active ingredients in Example 1, Comparative Example 1, Example 2, Comparative Example 2, and Example 3, Comparative Example 3, in the preparation method of a face cream using supramolecular liposome technology according to the present invention.

[0049] Figure 19 This is a comparison chart of the skin feel evaluation of Example 1 and Comparative Example 1 in the preparation method of a face cream based on supramolecular liposome technology of the present invention.

[0050] Figure 20 The images show skin elasticity diagrams of Example 1 and Comparative Example 1 in the preparation method of a face cream using supramolecular liposome technology according to the present invention.

[0051] Figure 21 The images show the skin firmness of Example 1 and Comparative Example 1 in the preparation method of a face cream based on supramolecular liposome technology of the present invention.

[0052] Figure 22 The images show skin roughness test results for Example 1 and Comparative Example 1 in the preparation method of a face cream based on supramolecular liposome technology of the present invention. Detailed Implementation

[0053] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0054] In addition, unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be obtained by purchasing them from the market or prepared by existing methods.

[0055] Example 1: 0.5% Idebenone Eutectic Solvent Liposome Face Cream

[0056] The preparation method is as follows:

[0057] (1) Preparation of idebenone active ingredient eutectic solvent: Accurately weigh idebenone and menthol in a molar ratio of 1:2, heat to dissolve at 55°C, stir and mix evenly, cool to room temperature to form idebenone menthol eutectic solvent;

[0058] (2) Preparation of oil phase: Dissolve 4.0g hydrogenated lecithin, 0.2g cholesterol, 2.0g PEG-100 stearate and glyceryl stearate in a water bath at 75℃, stir magnetically to mix, add 1.5g idebenone menthol eutectic solvent obtained above and stir magnetically to mix to obtain oil phase for later use.

[0059] (3) Preparation of aqueous phase: Dissolve 0.2g carbomer, 0.1g EDTA-2Na, 0.1g sodium hyaluronate, 5g glycerol, 5g 1,2-pentanediol, 5g dipropylene glycol and 76.6g pure water in a water bath at 50℃, stir magnetically to mix well, and heat to 75℃ for later use.

[0060] (4) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 5000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the primary emulsion.

[0061] (5) High-pressure homogenization: The colostrum was homogenized under high pressure at a pressure of 500 bar and a temperature of 75°C for 5 cycles. After cooling to 60°C, 0.3 g of triethanolamine was added, stirred evenly, and cooled to room temperature to obtain 0.5% idebenone eutectic solvent liposome face cream.

[0062] Example 2: 0.5% Coenzyme Q10 Eutectic Solvent Liposome Face Cream

[0063] The preparation method is as follows:

[0064] (1) Preparation of coenzyme Q10 eutectic solvent: accurately weigh coenzyme Q10 and menthol in a molar ratio of 1:2, heat to dissolve at 50°C, stir and mix evenly, cool to room temperature to form coenzyme Q10 menthol eutectic solvent.

[0065] (2) Preparation of oil phase: Dissolve 1.0g hydrogenated lecithin, 0.1g cholesterol and 1.0g polyglycerol-10-laurate in a water bath at 75℃, stir magnetically to mix well, add the above 1.5g coenzyme Q10 menthol eutectic solvent and stir magnetically to mix well to obtain oil phase for later use.

[0066] (2) Preparation of aqueous phase: Dissolve 0.2g carbomer, 0.1g EDTA-2Na, 0.1g sodium hyaluronate, 5.0g glyceryl glucoside, 5g 1,2-pentanediol and 85.9g pure water in a water bath at 50℃, stir magnetically to mix well, and heat to 75℃ for later use.

[0067] (3) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 5000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the primary emulsion.

[0068] (4) High-pressure homogenization: The colostrum is homogenized under high pressure at a pressure of 500 bar and a temperature of 75°C for 10 cycles. After cooling to 60°C, 0.1 g of sodium hydroxide is added, stirred evenly, and cooled to room temperature to obtain 0.5% coenzyme Q10 eutectic solvent liposome face cream.

[0069] Example 3: 5% Niacinamide Active Ingredient Eutectic Solvent Liposome Face Cream

[0070] The preparation method is as follows:

[0071] (1) Preparation of nicotinamide eutectic solvent: Accurately weigh nicotinamide and xylitol with a molar ratio of 1:1, heat and dissolve them at 100°C, stir and mix evenly, and cool to room temperature to form nicotinamide eutectic solvent;

[0072] (2) Preparation of oil phase: Dissolve 4.0g hydrogenated lecithin, 0.2g cholesterol and 1g cetearyl glucoside in a water bath at 75℃, stir magnetically to mix well, and prepare oil phase for later use;

[0073] (3) Preparation of aqueous phase: Dissolve 0.15g carbomer, 0.05g EDTA-2Na, 0.1g sodium hyaluronate, 5g glycerol, 5g 1,2-pentanediol and 74g pure water in a water bath at 50℃, then add 10g nicotinamide eutectic solvent and stir magnetically to mix well to obtain aqueous phase;

[0074] (4) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 10,000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the primary emulsion.

[0075] (5) High-pressure homogenization: The colostrum is homogenized under high pressure at a pressure of 600 bar and a temperature of 75°C for 10 cycles. After cooling to 60°C, 0.5 g of triethanolamine is added and stirred evenly. The mixture is then cooled to room temperature to obtain a 5% nicotinamide eutectic solvent liposome face cream.

[0076] Example 4: 4% Niacinamide Eutectic Solvent Liposome Face Cream

[0077] The preparation method is as follows:

[0078] (1) Preparation of nicotinamide fructose eutectic solvent: Accurately weigh nicotinamide and fructose with a molar ratio of 1:2, heat and dissolve them at 100°C, stir and mix evenly, and cool to room temperature to form nicotinamide fructose eutectic solvent;

[0079] (2) Preparation of oil phase: Dissolve 4.0g hydrogenated lecithin, 0.2g cholesterol, 0.5% tocopheryl ethyl acetate, 1g stearyl alcohol polyether-21, and 2g cetearyl glucoside in a water bath at 75°C, stir magnetically to mix, add the above-obtained mixed solution and stir magnetically to mix, and prepare the oil phase for later use.

[0080] (3) Preparation of aqueous phase: Dissolve 0.2g polyacrylate crosslinker-6, 0.1g EDTA-2Na, 5g 1,2-pentanediol and 75g pure water in a water bath at 50℃, stir magnetically to mix well, then add 12g nicotinamide fructose eutectic solvent, stir to mix evenly to obtain aqueous phase;

[0081] (4) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 5000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the primary emulsion.

[0082] (5) High pressure homogenization: The colostrum is homogenized under high pressure at a pressure of 800 bar and a temperature of 75°C for 8 cycles. After cooling to room temperature, a 4% nicotinamide eutectic solvent liposome cream is obtained.

[0083] Example 5: 3% Niacinamide Eutectic Solvent Liposome Face Cream

[0084] The preparation method is as follows:

[0085] (1) Preparation of nicotinamide citric acid eutectic solvent: Accurately weigh nicotinamide and citric acid with a molar ratio of 1:1, heat and dissolve them at 100°C, stir and mix evenly, and cool to room temperature to form nicotinamide citric acid eutectic solvent;

[0086] (2) Preparation of oil phase: Dissolve 5.0g hydrogenated lecithin, 0.5g cholesterol and 2g polysorbate-80 in a water bath at 75℃, stir magnetically to mix well, and prepare oil phase for later use;

[0087] (3) Preparation of aqueous phase: 0.2g carbomer, 0.05g EDTA-2Na, 0.1g sodium hyaluronate, 5g glyceryl glucoside, 6g propylene glycol, 4g 1,2-pentanediol and 67.97g pure water were dissolved in a water bath at 50℃, magnetically stirred and mixed, and 9g nicotinamide citric acid eutectic solvent was added and stirred and mixed evenly to obtain the aqueous phase;

[0088] (4) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 10,000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the primary emulsion.

[0089] (5) High-pressure homogenization: The colostrum was homogenized under high pressure at a pressure of 700 bar and a temperature of 70°C for 8 cycles. After cooling to 60°C, 0.18 g of triethanolamine was added and stirred evenly. The mixture was then cooled to room temperature to obtain a 3% nicotinamide eutectic solvent liposome face cream.

[0090] Comparative Example 1: 0.5% Idebenone Cream

[0091] The preparation method is as follows:

[0092] (1) Preparation of oil phase: Dissolve 0.5g idebenone, 2.0g PEG-100 stearate and glyceryl stearate in a water bath at 75℃, stir magnetically until well mixed, and set aside;

[0093] (2) Preparation of aqueous phase: Dissolve 0.2g carbomer, 0.1g EDTA-2Na, 0.5g p-hydroxyacetophenone, 0.1g sodium hyaluronate, 5.0g glycerol and 91.1g pure water in a water bath at 50℃, stir magnetically to mix well, and heat to 75℃ for later use.

[0094] (3) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 5000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min.

[0095] (4) Cool to 60°C, add 0.3g of triethanolamine and stir well; cool to 45°C, add 0.5% 1,2-hexanediol and stir well, then cool to room temperature to obtain 0.5% idebenone face cream.

[0096] Comparative Example 2: 0.5% Coenzyme Q10 Face Cream

[0097] The preparation method is as follows:

[0098] (1) Preparation of oil phase: Dissolve 0.5g coenzyme Q10, 1.0g polyglycerol-10-laurate and 0.1g propylparaben in a water bath at 75℃, stir magnetically until well mixed, and set aside.

[0099] (2) Preparation of aqueous phase: Dissolve 0.2g carbomer, 0.1g EDTA-2Na, 0.2g methylparaben, 0.1g sodium hyaluronate, 5.0g glycerol and 92.7g pure water in a water bath at 50℃, stir magnetically to mix well, and heat to 75℃ for later use.

[0100] (3) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 5000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the initial emulsion. After cooling to 60℃, 0.1 g of sodium hydroxide is added, stirred evenly, and cooled to room temperature to obtain 0.5% coenzyme Q10 face cream.

[0101] Comparative Example 3:5% Niacinamide Face Cream

[0102] The preparation method is as follows:

[0103] (1) Preparation of oil phase: Dissolve 1g stearyl alcohol polyether-21 and 2g cetearyl glucoside in a water bath at 75°C, stir magnetically until well mixed, and set aside.

[0104] (2) Preparation of aqueous phase: Dissolve 5g nicotinamide, 0.2g carbomer, 0.1g EDTA-2Na, 0.1g sodium hyaluronate, 5.0g 1,3-butanediol and 85.6g pure water in a water bath at 50℃, stir magnetically to mix well, and heat to 75℃ for later use.

[0105] (3) High-speed shearing: The aqueous phase is slowly added to the oil phase under shearing conditions. The shearing speed is 5000 rpm, the shearing temperature is 75℃, and the shearing time is 3 min to obtain the initial emulsion. Cool to 60℃, add 0.5g of triethanolamine, and stir evenly. Cool to 45℃, add 0.5g of phenoxyethanol, stir evenly, and continue to cool to room temperature to obtain 0.1% niacinamide face cream.

[0106] Experimental example:

[0107] 1. Appearance Comparison

[0108] The appearance of the active ingredient eutectic solvent liposome face cream obtained in Example 1 of this invention and the conventional face cream obtained in Comparative Example 2 were observed, as shown in the attached figure. Figure 1 As shown, the active ingredient eutectic solvent liposome face cream prepared in Example 1 of the present invention has a more delicate and radiant appearance.

[0109] 2. Comparison of water dispersibility

[0110] The face creams obtained in Example 1 and Comparative Example 1 of this invention were diluted with water to the same ratio, and their dispersion was observed. (See Appendix) Figure 2 It can be seen that the active ingredient eutectic solvent liposome face cream of Example 1 of the present invention is easier to disperse than conventional face cream, and has a transparent appearance with a light blue opalescence.

[0111] 3. Observation by transmission electron microscopy

[0112] The eutectic solvent liposome face cream obtained in Example 1 was diluted with distilled water. The sample was then pipetted onto a grid using a capillary tube, stained, washed, and dried. It was then observed using a transmission electron microscope and photographed. (See Appendix) Figure 3 As can be seen, the active ingredient eutectic solvent liposome face cream has small and uniform particle size.

[0113] 4. Particle size stability

[0114] The active ingredient eutectic solvent liposome face creams prepared in each example and the ordinary face creams prepared in each comparative example were diluted and their particle size was determined using a nanoparticle size zeta potential analyzer (Anton Paar Co., Ltd., Litesizer 500).

[0115] See appendix Figure 4-11 As shown in Table 1, the active ingredient low eutectic solvent liposome face cream of the present invention has uniform particle size and a PDI index of less than 0.22. The active ingredient low eutectic solvent liposome face cream obtained in Example 5 has a PDI index of 0.025, indicating good particle size uniformity. In contrast, the face creams obtained in the comparative examples all have PDI indices greater than 0.3. Figure 9-11 It can also be seen that the particle size distribution range of the face cream is wide. The liposome face cream of the present invention has a small particle size, with an average particle size between 100 and 300 nm. The liposome face cream obtained in Example 1 has a particle size of 122.52 nm; while the average particle size of the ordinary face creams prepared in each comparative example is greater than 1000 nm.

[0116] Table 1. Results of particle size determination

[0117] Sample Name Particle size (nm) PDI Example 1 122.52 0.189 Example 2 181.90 0.070 Example 3 151.31 0.133 Example 4 201.2 0.228 Example 5 249.1 0.025 Comparative Example 1 3980 0.324 Comparative Example 2 1217.2 0.318 Comparative Example 3 1052.4 0.325

[0118] The idebenone active ingredient eutectic solvent liposome face cream prepared in Example 1 was placed under conditions of 4°C, 45°C, room temperature light exposure (RT), and -8°C. The average particle size was measured on the day of preparation (0), 7 days, 14 days, 30 days, 60 days, and 90 days, respectively, to generate particle size stability curves. (See Appendix). Figure 13 It can be seen that the eutectic solvent liposome face cream of the present invention exhibits good stability over time.

[0119] 5. Appearance stability

[0120] The active ingredient eutectic solvent liposome face creams prepared in each example were stored at 4°C, under normal temperature and light (RT), 45°C, and -8°C, respectively. Appearance changes were photographed and recorded on the day of preparation (0 indicates 0) and 30 days later. (See Appendix) Figure 12 As can be seen, the active ingredient eutectic solvent liposome face creams obtained in each embodiment showed almost no change in appearance after 30 days compared to the freshly prepared face cream, indicating that they have good appearance stability.

[0121] 6. Encapsulation efficiency stability

[0122] The encapsulation efficiency of the idebenone active ingredient eutectic solvent liposome face cream prepared in Example 1 was measured at 4°C, 45°C, room temperature light irradiation (RT), and -8°C on the day of preparation (0), 7 days, 14 days, 30 days, 60 days, and 90 days.

[0123] Encapsulation efficiency was tested using ultracentrifugation: the sample was diluted 10-fold and ultracentrifuged at 20,000 r / min for 30 minutes. The supernatant was collected, and the content of idebenone (W) was determined by HPLC. 测 Then, the total content W of idebenone in the sample was determined. 总 According to W 测 *10 / W 总 *100% is used to calculate the encapsulation rate.

[0124] See appendix Figure 14 It can be seen that the encapsulation efficiency of the idebenone active ingredient eutectic solvent liposome face cream decreased under high temperature conditions of 45℃, while the encapsulation efficiency of the liposome face cream was relatively stable under other temperature conditions. Overall, the active ingredient eutectic solvent liposome face cream of the present invention has good encapsulation efficiency stability over three months.

[0125] 7. Skin retention

[0126] The face creams prepared in Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3 were placed under conditions of 4°C, 45°C, room temperature light (RT), and -8°C, respectively, and the content of active ingredients in each example and comparative example was measured on day 90.

[0127] The test results are attached. Figure 15 , 16 As shown in Figure 17, the results show that after 90 days, the active ingredient content in the eutectic solvent liposome face cream is significantly higher than that in the free active ingredient face cream. The supramolecular liposome technology can effectively protect the active ingredients and reduce the impact of the environment on them.

[0128] The transdermal retention of the face creams prepared in Examples 1, 2, and 3 and Comparative Examples 1, 2, and 3 was measured.

[0129] Before the experiment, a pigskin model with a thickness of 300±50 μm was prepared using a skin grafting scalpel. This model was then cut into small circular pieces the size of the receiving pool and placed in physiological saline for later use. Phosphate-buffered saline (pH=7.4) was used as the receiving medium. During the experiment, the skin model was fixed between the release pool and the receiving pool, with the stratum corneum side facing the release pool and the dermis side facing the receiving pool, ensuring close contact between the skin and the receiving solution, and preventing air bubbles from forming. Subsequently, a certain amount of the eutectic solvent liposome creams containing the active ingredients obtained in Examples 1, 2, and 3 were added to the skin surface. The temperature of the receiving pool was maintained at 32±0.5℃, and a magnetic magnet was placed inside the receiving pool, rotating at 300 rpm throughout the experiment. The control group in this experiment used the free active ingredient creams obtained in Comparative Examples 1, 2, and 3. Both the control and experimental groups had three replicates.

[0130] Eight hours after the in vitro transdermal treatment, the skin was removed, and the residual solution on the surface was cleaned with pure water. The skin from the transdermal site was taken, cut into small pieces, and 1.5 ml of extraction solution was added (ethanol was used as the extraction solution in Examples 1-2 and Comparative Examples 1-2, and pure water was used as the extraction solution in Examples 3 and Comparative Examples 3). The mixture was homogenized and sonicated for 1 hour to extract the active ingredients from the skin. The homogenate was transferred to a centrifuge tube, vortexed, and centrifuged at 12000 rpm / min for 10 min. The residue was extracted again with 1 ml of the corresponding extraction solution. The supernatants from the two extractions were combined, mixed, and the supernatant was filtered through a 0.22 μm filter membrane. The sample was analyzed by high performance liquid chromatography as described above. This yielded the transdermal retention amount of the active ingredient eutectic solvent liposome cream and the free active ingredient cream.

[0131] Test results are as follows Figure 18 As shown in the results, the active ingredient eutectic solvent liposome face creams prepared in each embodiment have a significantly greater skin retention rate than the ordinary face creams prepared in the comparative examples. The skin retention rate of idebenone in Example 1 is 3.02 times that of Comparative Example 1; the skin retention rate of coenzyme Q10 in Example 2 is 2.91 times that of Comparative Example 2; and the skin retention rate of niacinamide in Example 3 is 2.44 times that of Comparative Example 3. This indicates that the active ingredient eutectic solvent liposome face cream of the present invention can effectively promote the skin penetration of the active ingredients.

[0132] 8. Human skin patch test

[0133] Patch tests were conducted on the samples from Example 1 and Comparative Example 1. A total of 33 volunteers aged 18-40 years were selected, including 12 males and 21 females. The experiments were conducted according to the "Cosmetic Safety Technical Specifications" (2015 edition), and the results were recorded according to the skin reaction grading standards in Table 2.

[0134] Table 2. Grading Criteria for Skin Reaction in Closed Patch Tests

[0135]

[0136] The volunteers' skin was tested simultaneously with samples from Example 1 and Comparative Example 1. After observation, all volunteers using the sample from Example 1 of this invention had a negative reaction of grade 0, while 2 volunteers using the sample from Comparative Example 1 had a grade 1 reaction. It can be seen that the active ingredient eutectic solvent liposome face cream obtained by this invention is more skin-friendly and has no obvious allergic irritation.

[0137] 9. Skin feel evaluation

[0138] Thirty-three volunteers aged 18-40 were randomly selected, including 14 males and 19 females. The cosmetics were evaluated based on five dimensions: spreadability, absorption, thickness, stickiness, and oiliness, by comparing and contrasting Example 1(A) and Comparative Example 1(B). Scores were assigned as follows: 0-3 for poor, 3-5 for average, 5-7 for good, 7-9 for excellent, and 9-10 for outstanding. The overall scores are as follows: Figure 19 As shown.

[0139] The results showed that the sample obtained in Example 1 was superior to Comparative Example 1 in all five dimensions: spreadability, absorbency, thickness, stickiness, and smoothness. This indicates that the active ingredient eutectic solvent liposome face cream of the present invention has a significantly better skin feel than the traditional face cream system.

[0140] 10. Evaluation of the body's firming effect

[0141] Thirty-three healthy Chinese male and female subjects, aged 18–60 years, with loose facial skin, fine lines or wrinkles, and crow's feet wrinkles graded 2–5, were selected. Subjects were divided into two groups and used the samples from Example 1 and Comparative Example 1. After 28 days of continuous use, skin elasticity and firmness were measured using a Customereter dual MPA580 skin elasticity tester, employing a before-and-after control method. Subjective assessments were conducted, and full-face photographs were taken. The experimental results were compared using statistical tests to determine statistical significance, obtaining R² data for skin elasticity and F4 data for skin firmness.

[0142] See appendix Figure 20 The results showed that after 28 consecutive days of use of samples from Example 1 and Comparative Example 1, the subjects experienced a significant increase in skin elasticity (R²) compared to baseline, with Example 1 showing a higher increase than Comparative Example 1. This indicates that Example 1 has a significant effect on improving skin elasticity.

[0143] See appendix Figure 21 Therefore, it can be seen that after subjects used the samples of Example 1 and Comparative Example 1 continuously for 28 days, the skin firmness F4 of both samples decreased significantly compared with the baseline value, and the decrease rate of Example 1 was higher than that of Comparative Example 1. This indicates that Example 1 has a significant effect on improving skin firmness.

[0144] 11. Evaluation of anti-aging effects on the human body

[0145] Thirty-three healthy Chinese male and female subjects, aged 18–60 years, with loose facial skin, fine lines or wrinkles, and crow's feet wrinkles graded 2–5, were selected. Subjects were divided into two groups and used samples from Example 1 and Comparative Example 1. Skin roughness Sa was measured using the PRIMOS rapid optical imaging system on days 0 and 28. A before-and-after control method was used, measuring skin roughness, conducting subjective assessments, and taking full-face photographs. Experimental results were compared using statistical tests to determine statistical differences, obtaining skin roughness Sa data.

[0146] See appendix Figure 22 The results showed that after 28 consecutive days of use of samples from Example 1 and Comparative Example 1, the skin roughness Sa of the subjects significantly decreased compared to the baseline value, and the decrease rate of Example 1 was higher than that of Comparative Example 1. This indicates that Example 1 has a significant effect on improving skin roughness.

[0147] The sequence numbers of the above embodiments of the present invention are for descriptive purposes only and do not represent the superiority or inferiority of the embodiments.

[0148] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A method for preparing a eutectic solvent liposome face cream containing active ingredients, characterized in that, Includes the following steps: 1) Preparation of the eutectic solvent for the active ingredient: The active ingredient and its ligand are accurately weighed and dissolved by heating at 40-100℃, stirred and mixed evenly, and cooled to room temperature to form a eutectic solvent for the active ingredient. The eutectic solvent for the active ingredient is selected from: idebenone menthol eutectic solvent, coenzyme Q10 menthol eutectic solvent, nicotinamide xylitol eutectic solvent, nicotinamide fructose eutectic solvent, and nicotinamide citric acid eutectic solvent. 2) Preparation of the oil phase: Phospholipids, cholesterol, and emulsifiers are dissolved in a water bath at 50-75°C, and after being magnetically stirred and mixed, the oil-soluble active material eutectic solvent obtained in step 1) is added and stirred to obtain the oil phase. 3) Preparation of the aqueous phase: The stabilizer, humectant and pure water are dissolved in a water bath at 50-75℃, and the mixture is stirred magnetically. The water-soluble active ingredient eutectic solvent obtained in step 1) is added and stirred until homogeneous to obtain the aqueous phase. 3) Preparation of face cream: The aqueous phase was slowly added to the oil phase under shear conditions to obtain the primary emulsion; then the primary emulsion was subjected to high-pressure homogenization and cyclicated 4 to 16 times; cooled to 35 to 60°C, a pH adjuster was added and stirred evenly, and then cooled to room temperature to obtain the active ingredient eutectic solvent liposome face cream.

2. The method for preparing an active ingredient eutectic solvent liposome face cream as described in claim 1, characterized in that: The molar ratio of the active ingredient to the ligand is 1:3 to 3:

1.

3. The method for preparing an active ingredient eutectic solvent liposome face cream as described in claim 1, characterized in that: The shearing conditions are: shearing speed of 5000-10000 rpm; shearing temperature of 50-75℃; and shearing time of 3-8 min.

4. A eutectic solvent liposome face cream containing active ingredients prepared according to the method of any one of claims 1-3, characterized in that, Includes the following components by mass percentage: Eutectic solvent for active ingredient: 1.5-12.0% Phospholipids: 1.0-5.0% Emulsifier: 1.0-3.0% Cholesterol: 0.1-0.5% Moisturizer: 5.0-15.1% Stabilizer: 0.2-0.8% pH adjuster: 0-0.5% Pure water: Balance.

5. The active ingredient eutectic solvent liposome face cream as described in claim 4, characterized in that: The phospholipid is selected from at least one of soybean lecithin, hydrogenated lecithin, lysophosphatidylcholine, and egg yolk lecithin.

6. The active ingredient eutectic solvent liposome face cream as described in claim 4, characterized in that: The emulsifier is selected from at least one of PEG-100 stearate, polysorbate-20, polysorbate-60, polysorbate-80, polyglycerol-10-laurate, polyglycerol-10-oleate, polyglycerol-10-myristate, glyceryl stearate, stearyl alcohol polyether-21, and cetearyl glucoside.

7. The active ingredient eutectic solvent liposome face cream as described in claim 4, characterized in that: The moisturizer is selected from at least one of glycerin, 1,3-propanediol, glyceryl glucoside, sodium hyaluronate, 1,3-butanediol, 1,2-pentanediol, 1,2-hexanediol, ethylhexylglycerin, dipropylene glycol, and glyceryl glucoside.

8. The active ingredient eutectic solvent liposome face cream as described in claim 4, characterized in that: The stabilizer is selected from at least one of EDTA-2Na, sodium metabisulfite, tocopherol, ethyl tocopherol, carbomer, and polyacrylate crosspolymer-6.

9. The active ingredient eutectic solvent liposome face cream as described in claim 4, characterized in that: The pH adjuster is selected from at least one of sodium hydroxide, potassium hydroxide, triethanolamine, arginine, lactic acid, and citric acid.

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