A solid lipid nanoparticle encapsulating hydroxytyrosol, and a preparation method and use thereof

Abstract

The application belongs to the technical field of preparation, and particularly relates to solid lipid nanoparticles for wrapping hydroxytyrosol and a preparation method and application thereof. The application realizes that the hydroxytyrosol is dissolved in oil by adjusting the pH value to create an acid environment, and further provides the possibility of wrapping the hydroxytyrosol by oil. The hydroxytyrosol is wrapped by solid oil, and further, the solid lipid nanoparticle emulsion is prepared, so that the stability of the hydroxytyrosol is significantly improved.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a solid lipid nanoparticle encapsulating hydroxytyrosol, its preparation method, and its uses. Background Technology

[0002] Hydroxytyrosol is a highly active plant monomer commonly used in food, cosmetics, and health products. Hydroxytyrosol itself possesses various pharmacological effects, such as benefiting bone growth and development, aiding in mineral absorption, improving endocrine system function, promoting metabolism, accelerating wound healing, eliminating free radicals, restoring the health of internal organs, preventing brain aging, delaying aging, and maintaining youthful vitality. Hydroxytyrosol can also intervene in lung cancer, breast cancer, uterine cancer, and prostate cancer, promoting late-stage cancer recovery and enhancing chemotherapy effectiveness; prevent and treat various diseases caused by smoking; and has preventive and therapeutic effects on arteriosclerosis, hypertension, heart disease, and cerebral hemorrhage. In cosmetics, hydroxytyrosol effectively enhances skin elasticity and hydration, and has antioxidant, wrinkle-reducing, and anti-aging effects.

[0003] However, hydroxytyrosol, a type of polyphenol, exhibits many beneficial physiological properties but also suffers from instability and discoloration during application. Therefore, it is worth considering preparing hydroxytyrosol into liposomes to address its instability through encapsulation technology. For example, Chinese patent application CN114557963A discloses a nano-hydroxytyrosol liposome and its preparation method, which includes steps such as preparing a transparent lecithin film, preparing a hydroxytyrosol emulsion, and preparing hydroxytyrosol liposomes. However, this method uses conventional raw materials such as lecithin, follows a conventional liposome preparation process, and is very complex, thus failing to address the instability of hydroxytyrosol. Chinese patent application CN114099357A discloses an oil-encapsulated polyol nanoemulsion containing hydroxytyrosol, its preparation method, and its application, including hydroxytyrosol, polyol, emulsifier, and oil. This application claims that...

[0004] An oil-in-oil polyol emulsion containing hydroxytyrosol was prepared. Compared to conventional oil-in-water or water-in-oil systems, this oil-in-oil polyol combination effectively inhibited the oxidation and discoloration of hydroxytyrosol. However, whether the polyol was successfully encapsulated in the oil in this patent application remains to be verified, and the reason why encapsulating the polyol in the oil can improve the stability of hydroxytyrosol has not been investigated.

[0005] In typical oil-in-water emulsions, hydroxytyrosol is largely soluble in water due to its excellent water solubility and poor oil solubility. In experiments, the inventors discovered that adding hydroxytyrosol directly to conventional oils resulted in almost no dissolution. However, they unexpectedly found that hydroxytyrosol aggregated at the bottom of the oil and remained unchanged for a month at a high temperature (45°C). This suggests that the oil might prevent oxygen from oxidizing the hydroxytyrosol. Therefore, the inventors attempted to use oil to encapsulate and protect the hydroxytyrosol.

[0006] In addition, the inventors discovered a pattern during the detection of hydroxytyrosol degradation: the lower the relative content of hydroxytyrosol, the easier it is to degrade. For example, the stability of 1% hydroxytyrosol in aqueous solution is significantly better than that of 0.1%. The encapsulation of solid lipid nanoparticles can cause hydroxytyrosol to aggregate in local space. The lipid particle size is at the nanoscale, which significantly improves the stability of hydroxytyrosol compared to ordinary emulsions that exist in the state of water molecules.

[0007] The inventors hypothesize that if hydroxytyrosol can be dissolved in oils, solid lipid nanoparticles will create a larger encapsulation space, increasing the relative content of hydroxytyrosol in the local space and thus improving its stability. In ordinary emulsions, hydroxytyrosol is uniformly dispersed in the aqueous phase at a molecular size. In oil-in-water emulsions, the aqueous phase containing hydroxytyrosol encapsulates the oil phase. Factors such as oxygen and light can easily affect the stability of hydroxytyrosol in the aqueous phase. At the same time, in ordinary oil-in-water emulsions, the oil phase does not dissolve hydroxytyrosol and does not play any protective role.

[0008] Based on the above research results, the inventors provide a new method for preparing solid lipid nanoparticles encapsulating hydroxytyrosol. This method improves the solubility of hydroxytyrosol in oils and successfully enhances the stability of hydroxytyrosol during application by encapsulating it with solid oil particles of nanoparticle size. Summary of the Invention

[0009] To address the shortcomings and deficiencies in existing technologies, this invention provides solid lipid nanoparticles encapsulating hydroxytyrosol, along with their preparation method and applications. This invention creates an acidic environment by adjusting the pH value, enabling hydroxytyrosol to dissolve in oils, thus providing the possibility for oils to encapsulate hydroxytyrosol. By encapsulating hydroxytyrosol with solid oils, a solid lipid nanoparticle emulsion is prepared, significantly improving the stability of hydroxytyrosol.

[0010] Specifically, the present invention is achieved through the following technical solutions:

[0011] In a first aspect, the present invention provides a method for preparing solid lipid nanoparticles encapsulating hydroxytyrosol, the method comprising the following steps:

[0012] (1) Use 0.01-0.5 g of weak acid as a pH adjuster, add 0.1-1 g of hydroxytyrosol to 5-15 g of oil, stir in a water bath at 30-60℃ for 30-60 min, so that the hydroxytyrosol is fully dissolved in the oil to form solution A.

[0013] (2) Dissolve 0-5 grams of wax and 2-8 grams of emulsifier in 50-100 grams of water, and use a water bath at 70-90℃ to fully dissolve the wax and emulsifier to form solution B;

[0014] (3) Dissolve solution A and solution B completely at 70-90℃ to form solution C. Use a homogenizer to homogenize at 8000-9000 rpm for 20-40 seconds to form a homogeneous emulsion of solution C.

[0015] (4) Keep the solution C after homogenization in step (3) at 70-90℃, and then use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 200-400W, the ultrasonic time is 5-8min, and the ultrasonic is stopped for 2s every 3s.

[0016] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain solid lipid nanoparticles encapsulating hydroxytyrosol.

[0017] Alternatively, in the above preparation method, in step (1), the weak acid is acetic acid or formic acid, and the oil is selected from one or more of the following: caprylic / capric triglyceride, isopropyl myristate, cetyl alcohol, pentaerythritol tetracocoate, jojoba oil, squalane, or grape seed oil.

[0018] Alternatively, in the above preparation method, in step (2), the wax is beeswax, candelilla wax or mineral wax, and the emulsifier is cetyl glucoside, glyceryl stearate or PEG-100 stearate.

[0019] Alternatively, in the above preparation method, the preparation method includes the following steps:

[0020] (1) 0.05-0.1 g of acetic acid as pH adjuster, add 0.5 g of hydroxytyrosol to 8-10 g of pentaerythritol tetracocoate, stir in a water bath at 40-50℃ for 45 min, so that hydroxytyrosol is fully dissolved in pentaerythritol tetracocoate to form solution A.

[0021] (2) Dissolve 4-5 grams of cetyl glucoside in 80 grams of water, and then use an 80°C water bath to fully dissolve the cetyl glucoside to form solution B.

[0022] (3) Dissolve solution A and solution B at 80°C to form solution C. Homogenize solution C for 30 seconds at 8000-9000 rpm using a homogenizer to form a homogeneous emulsion.

[0023] (4) Keep the solution C after homogenization in step (3) at 80°C and use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 200-400W and the ultrasonic time is 5-8min. Stop for 2s every 3s of ultrasonication.

[0024] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain monolayer solid lipid nanoparticles encapsulating hydroxytyrosol.

[0025] Alternatively, in the above preparation method, the preparation method includes the following steps:

[0026] (1) 0.05-0.1 g of acetic acid as a pH adjuster, add 0.5 g of hydroxytyrosol to 1-2 g of pentaerythritol tetracocoate, stir in a water bath at 40-50°C for 45 min, so that hydroxytyrosol is fully dissolved in pentaerythritol tetracocoate to form solution A.

[0027] (2) Dissolve 1-3 grams of beeswax and 4-5 grams of cetyl glucoside in 80 grams of water, and then use a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B.

[0028] (3) Dissolve solution A and solution B completely at 90°C to form solution C. Use a homogenizer to homogenize solution C at 8000-9000 rpm for 1 min to form a homogeneous emulsion.

[0029] (4) Keep the solution C after homogenization in step (3) at 90°C and use an ultrasonic cell disruptor to further ultrasonically disrupt the solution C. The ultrasonic power is 200-400W and the ultrasonic time is 5-8min. Stop for 2s every 3s of ultrasonication.

[0030] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain solid-solid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

[0031] Alternatively, in the above preparation method, the preparation method includes the following steps:

[0032] (1) 0.05-0.1 g of acetic acid as a pH adjuster, add 0.5 g of hydroxytyrosol to 1-2 g of caprylic / capric triglyceride, stir in a water bath at 40-50°C for 45 min, so that the hydroxytyrosol is fully dissolved in pentaerythritol tetracocoate to form solution A.

[0033] (2) Dissolve 1-3 grams of beeswax and 4-5 grams of cetyl glucoside in 80 grams of water, and then use a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B.

[0034] (3) Dissolve solution A and solution B completely at 90°C to form solution C. Use a homogenizer to homogenize solution C at 8000-9000 rpm for 1 min to form a homogeneous emulsion.

[0035] (4) Keep the solution C after homogenization in step (3) at 90°C and use an ultrasonic cell disruptor to further ultrasonically disrupt the solution C. The ultrasonic power is 200-400W and the ultrasonic time is 5-8min. Stop for 2s every 3s of ultrasonication.

[0036] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain solid-liquid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

[0037] In a second aspect, the present invention provides solid lipid nanoparticles encapsulating hydroxytyrosol prepared by the preparation method described in the first aspect above.

[0038] Alternatively, in the above-mentioned solid lipid nanoparticles, the particle size of the solid lipid nanoparticles is 150-250 nm, and the encapsulation efficiency of the solid lipid nanoparticles is greater than 50%.

[0039] In a third aspect, the present invention provides the use of the solid lipid nanoparticles described in the second aspect above in the preparation of cosmetics, wherein the amount of the solid lipid nanoparticles added to the cosmetic is 0.01-20% of the total weight of the cosmetic.

[0040] Alternatively, in the above-described uses, the cosmetic product may be one or more of the following: lotion, serum, cream, mask, and gel.

[0041] Compared with the prior art, the present invention has the following advantages:

[0042] (1) The present invention uses acetic acid to adjust the pH value of the solution and improves the solubility of hydroxytyrosol in oils.

[0043] (2) The present invention encapsulates hydroxytyrosol with solid fats and oils to prepare solid lipid nanoparticle emulsion, which significantly improves the stability of hydroxytyrosol.

[0044] (3) This invention prepares different types of solid lipid nanoparticles, such as solid oil single-layer encapsulation, solid-liquid oil double-layer encapsulation, and solid-solid oil double-layer encapsulation, by compounding different types of oils. Attached Figure Description

[0045] Figure 1Photos showing the color changes of Examples 5 and 2 after being placed in a heat-resistant environment.

[0046] Figure 2 Photographs of the solid lipid nanoemulsions prepared in Examples 2, 3, and 4. From left to right in the figures are Examples 2, 3, and 4. Detailed Implementation

[0047] In the above description of the invention and specific embodiments, as well as in the claims, specific features of the invention have been mentioned. It should be understood that the specification of this invention discloses all possible combinations including these specific features. For example, when a specific feature is disclosed in a particular aspect or embodiment of the invention or in a particular claim, that feature may also be used as much as possible and / or in combination with other specific aspects and embodiments of the invention.

[0048] The present invention will be further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the invention.

[0049] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0050] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods. Unless otherwise specified, the experimental materials used in the following embodiments are commercially available products.

[0051] Example:

[0052] Example 1: Improved oil solubility of hydroxytyrosol

[0053] Hydroxytyrosol is highly water-soluble but poorly oil-soluble. Due to its high reactivity, it easily discolors during use. Experiments have shown that hydroxytyrosol discolors quickly when dissolved in water, but remains colorless for a long time when dispersed in oil. Based on this, the inventors investigated the solubility of hydroxytyrosol in different solid oil formulations (see Table 1) to explore methods for improving the oil solubility of hydroxytyrosol and achieving its encapsulation in solid lipid nanoparticles.

[0054] Table 1: Solubility Study of Hydroxytyrosol in Different Solid Oil Formulations

[0055] Hydroxytyrosol Fats + 0.2g acetic acid Can it dissolve? 0.5 g hydroxytyrosol 5g caprylic / capric triglyceride Can 0.5 g hydroxytyrosol 5 grams of isopropyl myristate Can 0.5 g hydroxytyrosol 5 grams of cetyl alcohol Can 0.5 g hydroxytyrosol 5 grams of pentaerythritol tetracocoate Can 0.5 g hydroxytyrosol 5 grams of beeswax Can't

[0056] The experimental results are shown in Table 1. Most oils contain varying numbers of hydroxyl or carboxyl groups, so most oils can undergo esterification and etherification reactions with hydroxytyrosol under acidic conditions, allowing hydroxytyrosol to dissolve in the oil. However, some complex waxes, such as beeswax, may not react. Utilizing the relatively stable nature of beeswax, it can be used as a solid oil to encapsulate hydroxytyrosol.

[0057] Example 2: Pentaerythritol tetracocoate as a solid fat for monolayer encapsulation of hydroxytyrosol

[0058] The specific preparation method of pentaerythritol tetracocoate as a solid fat to monolayer encapsulate hydroxytyrosol to prepare solid lipid nanoemulsions is as follows:

[0059] (1) 0.1 g of acetic acid was used as a pH adjuster. 0.5 g of hydroxytyrosol was added to 8 g of pentaerythritol tetracocoate. The mixture was stirred in a water bath at 50°C for 45 min to fully dissolve the hydroxytyrosol in the pentaerythritol tetracocoate to form solution A.

[0060] (2) Dissolve 4 g of cetyl glucoside in 80 g of water, and then use an 80°C water bath to fully dissolve the cetyl glucoside to form solution B.

[0061] (3) Dissolve solution A and solution B completely at 80°C to form solution C. Use a homogenizer to homogenize solution C at 8000 rpm for 30 seconds to form a homogeneous emulsion.

[0062] (4) Keep the solution C after homogenization in step (3) at 80°C and use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 300W and the ultrasonic time is 5min. Stop for 2s every 3s of ultrasonication.

[0063] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain monolayer solid lipid nanoparticles encapsulating hydroxytyrosol.

[0064] Example 3: Beeswax and pentaerythritol tetracoedate as solid fats for solid-solid bilayer encapsulation of hydroxytyrosol

[0065] The specific preparation method of solid lipid nanoemulsions encapsulating hydroxytyrosol by solid-solid bilayer encapsulation of hydroxytyrosol using beeswax and pentaerythritol tetracoedate as solid fats is shown below:

[0066] (1) 0.1 g of acetic acid was used as a pH adjuster. 0.5 g of hydroxytyrosol was added to 2 g of pentaerythritol tetracocoate. The mixture was stirred in a water bath at 50°C for 45 min to fully dissolve the hydroxytyrosol in the pentaerythritol tetracocoate to form solution A.

[0067] (2) Dissolve 1 gram of beeswax and 4 grams of cetyl glucoside in 80 grams of water, and then use a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B.

[0068] (3) Dissolve solution A and solution B completely at 90°C to form solution C. Homogenize solution C for 1 min at 8000 rpm using a homogenizer to form a homogeneous emulsion.

[0069] (4) Keep the solution C after homogenization in step (3) at 90°C and use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 300W and the ultrasonic time is 5min. Stop for 2s every 3s of ultrasonication.

[0070] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain solid-solid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

[0071] Example 4: Beeswax as a solid oil and caprylic / capric triglyceride as a liquid oil for solid-liquid double-layer encapsulation of hydroxytyrosol

[0072] The specific preparation method for preparing a solid lipid nanoemulsion encapsulating hydroxytyrosol by solid-liquid bilayer encapsulation of hydroxytyrosol using beeswax as a solid oil and caprylic / capric triglyceride as a liquid oil is shown below:

[0073] (1) 0.1 g of acetic acid was used as a pH adjuster. 0.5 g of hydroxytyrosol was added to 2 g of caprylic / capric triglyceride. The mixture was stirred in a water bath at 50°C for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A.

[0074] (2) Dissolve 1 gram of beeswax and 4 grams of cetyl glucoside in 80 grams of water, and then use a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B.

[0075] (3) Dissolve solution A and solution B completely at 90°C to form solution C. Homogenize solution C for 1 min at 8000 rpm using a homogenizer to form a homogeneous emulsion.

[0076] (4) Keep the solution C after homogenization in step (3) at 90°C and use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 300W and the ultrasonic time is 5min. Stop for 2s every 3s of ultrasonication.

[0077] (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain solid-liquid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

[0078] Example 5: Preparation of ordinary emulsion samples compared with Example 2

[0079] (1) Add 0.5 g of hydroxytyrosol to the solution and stir in a 50°C water bath for 5 min to fully dissolve the hydroxytyrosol in the water to form solution A.

[0080] (2) Dissolve 8 g pentaerythritol tetracocoate and 4 g cetyl glucoside in 80 g of water, and then use an 80°C water bath to fully dissolve the cetyl glucoside to form solution B.

[0081] (3) Dissolve solution A and solution B at 80°C to form solution C. Use a homogenizer to homogenize solution C at 8000 rpm for 30 seconds to form a homogeneous emulsion.

[0082] Example 6: Particle size test of solid lipid nanoparticle samples

[0083] (1) Images of the solid lipid nanoemulsions prepared in Examples 2, 3 and 4 are shown below. Figure 2 As shown. 0.1 mL of samples prepared in Examples 2, 3, and 4 were taken as test samples, and the average particle size of the samples was measured using a laser particle size analyzer.

[0084] (2) Dilute with pure water to 0.5 mL and put into the sample cell. The number of cycles is the system default. The detection temperature is 25℃. The refractive index and viscosity are selected as the values ​​of water as the medium.

[0085] (3) Each sample was measured three times;

[0086] (4) The results showed that the particle size of the solid lipid nanoparticles was within 300 nm, and the appearance of the samples was uniform and stable, with no obvious large particles. The specific experimental results are shown in Table 2.

[0087] Table 2: Particle size of solid lipid nanoparticle samples from Examples 2, 3, and 4

[0088] Example 2 Example 3 Example 4 Particle size / nm 187 206 232

[0089] Example 7: Encapsulation efficiency test of solid lipid nanoparticle samples

[0090] (1) A Shimadzu LC-20A high performance liquid chromatograph was used with a Waters Symmetry C18 column (5 μm, 250 mm × 4.6 mm); the mobile phase was methanol (A): 0.1% formic acid aqueous solution (B) = 40:60 (V / V); the flow rate was 0.7 mL / min; a 2998PDA diode array detector was used with a detection wavelength of 280 nm, a column temperature of 35 °C, and an injection volume of 10 μL.

[0091] (2) According to the preparation method of Example 2, the prepared solid lipid nanoparticle sample was divided into two equal parts; one part of the solution was taken, and the volume was adjusted to the same volume with liquid methanol. The emulsion was broken by sonication for 60 seconds using a cell disruptor, and the concentration was measured as X by liquid chromatography.

[0092] (3) The encapsulation efficiency of another solid lipid nanoparticle sample was determined by ultrafiltration. The molecular weight of the ultrafiltration tube was 30 kDa, and the centrifugation speed was 10,000 rpm for 20 min. The hydroxytyrosol content of the lower layer of the ultrafiltration tube was also determined by liquid chromatography and denoted as X'.

[0093] EE (Encapsulation Efficiency)=(X-X') / X×100%

[0094] (4) The encapsulation efficiency was determined using the same methods as in Example 2 for Examples 3 and 4. The specific experimental results are shown in Table 3.

[0095] Table 3: Encapsulation efficiency of solid lipid nanoparticle samples from Examples 2, 3, and 4

[0096] Example 2 Example 3 Example 4 Encapsulation rate / % 53 58 60

[0097] Example 8: Stability of solid lipid nanoparticle samples

[0098] The performance test results of the samples obtained in Examples 2, 3, 4, and 5 are shown in Table 4 below.

[0099] Table 4: Stability of solid lipid nanoparticle samples from Examples 2, 3, and 4

[0100]

[0101] As can be seen from the data in the table above, the solid lipid nanoparticle samples prepared in Examples 2, 3, and 4 have a uniform and stable appearance and remain stable under high and low temperature conditions, without any layering, clumping, discoloration, or other phenomena. The emulsion sample prepared in Example 5 shows obvious discoloration when placed in a heat-resistant environment. It can be seen that the discoloration is more significant in a high-temperature environment when hydroxytyrosol is dissolved in water. Figure 1 From left to right, these are the color changes of Examples 5 and 2 after being placed in a heat-resistant environment. The samples prepared at the beginning were all white emulsions, while the emulsion of Example 2 had a bluish sheen.

[0102] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for preparing solid lipid nanoparticles encapsulating hydroxytyrosol, characterized in that: The preparation method includes the following steps: (1) 0.05-0.1 g of acetic acid as pH adjuster, add 0.5 g of hydroxytyrosol to 8-10 g of pentaerythritol tetracocoate, stir in a water bath at 40-50℃ for 45 min, so that hydroxytyrosol is fully dissolved in pentaerythritol tetracocoate to form solution A. (2) Dissolve 4-5 grams of cetyl glucoside in 80 grams of water, and then use an 80°C water bath to fully dissolve the cetyl glucoside to form solution B; (3) Dissolve solution A and solution B at 80°C to form solution C. Homogenize solution C for 30 seconds at 8000-9000 rpm using a homogenizer to form a homogeneous emulsion. (4) Keep the solution C after homogenization in step (3) at 80°C and then use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 200-400W and the ultrasonic time is 5-8 min. Stop for 2s every 3s of ultrasonication. (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain monolayer solid lipid nanoparticles encapsulating hydroxytyrosol.

2. A method for preparing solid lipid nanoparticles encapsulating hydroxytyrosol, characterized in that: The preparation method includes the following steps: (1) 0.05-0.1 g of acetic acid as pH adjuster, add 0.5 g of hydroxytyrosol to 1-2 g of pentaerythritol tetracocoate, stir in a water bath at 40-50℃ for 45 min, so that hydroxytyrosol is fully dissolved in pentaerythritol tetracocoate to form solution A. (2) Dissolve 1-3 grams of beeswax and 4-5 grams of cetyl glucoside in 80 grams of water, and then use a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B. (3) Dissolve solution A and solution B at 90°C to form solution C. Homogenize solution C for 1 min at 8000-9000 rpm using a homogenizer to form a homogeneous emulsion. (4) Keep the solution C after homogenization in step (3) at 90°C and then use an ultrasonic cell disruptor to ultrasonically disrupt the solution C again. The ultrasonic power is 200-400W and the ultrasonic time is 5-8 min. Stop for 2s every 3s of ultrasonication. (5) The solution C after ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down, so as to obtain solid-solid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

3. Solid lipid nanoparticles encapsulating hydroxytyrosol prepared by the preparation method described in claim 1 or claim 2.

4. The solid lipid nanoparticles according to claim 3, characterized in that: The solid lipid nanoparticles have a particle size of 150-250 nm and an encapsulation efficiency of greater than 50%.

5. The use of the solid lipid nanoparticles according to claim 3 or claim 4 in the preparation of cosmetics, characterized in that: The amount of the solid lipid nanoparticles added to the cosmetic is 0.01-20% of the total weight of the cosmetic.

6. The use according to claim 5, characterized in that: The cosmetic product is one or more of the following: toner, serum, cream, mask, and gel.

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