Solid lipid nanoparticles wrapping hydroxytyrosol as well as preparation method and application of solid lipid nanoparticles

Abstract

The invention belongs to the technical field of preparations, and particularly relates to solid lipid nanoparticles wrapping hydroxytyrosol as well as a preparation method and application of the solid lipid nanoparticles. According to the method, an acid environment is created by adjusting the pH value, hydroxytyrosol is dissolved in grease, and then possibility is provided for wrapping hydroxytyrosol by the grease; hydroxytyrosol is wrapped by solid grease, then the solid lipid nanoparticle emulsion is prepared, and the stability of hydroxytyrosol is remarkably improved.

Description

Technical Field

[0001] The invention belongs to the technical field of preparations, and particularly relates to solid lipid nanoparticles encapsulating hydroxytyrosol, and a preparation method and application thereof. Background Art

[0002] Hydroxytyrosol is a plant monomer with rich activity, which is often used in food, cosmetics and health products. Hydroxytyrosol raw materials themselves have a variety of pharmacological effects. For example, it is beneficial to bone growth and function, helps the body absorb minerals, and has the effects of improving the function of the endocrine system, promoting metabolism, promoting wound healing, eliminating free radicals in the body, restoring the health of human organs, preventing brain failure, delaying aging, and maintaining youthful vitality; Hydroxytyrosol can also intervene in lung cancer, breast cancer, uterine cancer, prostate cancer, etc., promote the recovery of cancer in the later stage and improve the effect of chemotherapy; prevent and treat various diseases caused by smoking; and have preventive and therapeutic effects on arteriosclerosis, hypertension, heart disease, cerebral hemorrhage, etc. Hydroxytyrosol is used in cosmetics to effectively enhance skin elasticity and moisturizing, and has antioxidant and anti-wrinkle and anti-aging effects.

[0003] However, hydroxytyrosol belongs to a kind of polyphenol substance. While it shows many beneficial properties physiologically, it itself has disadvantages such as instability and easy discoloration during the application process. Therefore, it can be considered to make hydroxytyrosol into liposomes, in order to solve the problem of hydroxytyrosol instability through encapsulation technology. For example, Chinese patent application CN114557963A discloses a nano hydroxytyrosol liposome and a preparation method thereof, which comprises the steps of preparing a transparent lecithin film, preparing a hydroxytyrosol emulsion and preparing a hydroxytyrosol liposome. However, the raw materials of this method use conventional raw materials such as lecithin, which belongs to a conventional liposome preparation process and the preparation process is very complicated, and actually does not solve the disadvantage of hydroxytyrosol instability. Chinese patent application CN114099357A discloses a hydroxytyrosol-containing oil-in-polyol nanoemulsion and a preparation method and application, including hydroxytyrosol, a polyol, an emulsifier and oil. The application claims that it

[0004] The oil-in-polyol method is used to prepare an emulsion containing hydroxytyrosol. Compared with conventional oil-in-water or water-in-oil systems, the oil-in-polyol combination can effectively inhibit the oxidation and discoloration of hydroxytyrosol. However, whether the polyol in the patent application is successfully encapsulated in oil remains to be verified, and the reason why the polyol encapsulation in oil can improve the stability of hydroxytyrosol has not been explored.

[0005] In common water-in-oil emulsions, hydroxytyrosol is basically dissolved in water because it is highly soluble in water but poorly soluble in oil. The inventors found in experiments that if hydroxytyrosol is directly added to conventional oils and fats, there is almost no dissolution, but unexpectedly found that hydroxytyrosol can be kept at a high temperature (45°C) for one month without discoloration when it is gathered at the bottom of the oils and fats. Analysis suggests that the oils and fats may block the oxidation of hydroxytyrosol by oxygen, so the inventors tried to use oils and fats to wrap hydroxytyrosol to protect it.

[0006] In addition, the inventors discovered a rule in the process of detecting the degradation of hydroxytyrosol, that is, 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 0.1%. The encapsulation of solid lipid nanoparticles will aggregate hydroxytyrosol in local space, and the oil particle size is at the nanometer level. Compared with ordinary emulsions stored in the state of water molecules, the stability of hydroxytyrosol is significantly improved.

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

[0008] Based on the results of the above research, the inventors provide a new method for preparing solid lipid nanoparticles encapsulating hydroxytyrosol, which improves the solubility of hydroxytyrosol in oils and fats. By encapsulating hydroxytyrosol with solid oils of nanoparticle size, the stability of hydroxytyrosol during application is successfully improved. Summary of the invention

[0009] In order to solve the defects and deficiencies in the prior art, the present invention provides a solid lipid nanoparticle encapsulating hydroxytyrosol and a preparation method and use thereof. The present invention adjusts the pH value to create an acidic environment, thereby achieving the dissolution of hydroxytyrosol in oil and fat, thereby providing the possibility of oil and fat encapsulating hydroxytyrosol; hydroxytyrosol is encapsulated by solid oil and fat, thereby preparing a solid lipid nanoparticle emulsion, which significantly improves the stability of hydroxytyrosol.

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

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

[0012] (1) 0.01-0.5 g of a weak acid as a pH adjuster, 0.1-1 g of hydroxytyrosol is added to 5-15 g of oil, and the mixture is stirred in a water bath at 30-60° C. for 30-60 min to fully dissolve the hydroxytyrosol in the oil to form a solution A;

[0013] (2) dissolving 0-5 g of wax material and 2-8 g of emulsifier in 50-100 g of water, and placing in a water bath at 70-90° C. to fully dissolve the wax material and emulsifier to form solution B;

[0014] (3) Solution A and Solution B are fully dissolved at 70-90° C. to form Solution C, and solution C is homogenized at 8000-9000 rpm for 20-40 seconds using a homogenizer to form a uniform emulsion;

[0015] (4) keeping the solution C homogenized in step (3) at 70-90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s;

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

[0017] As an optional manner, 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] As an optional manner, in the above preparation method, in step (2), the wax substance is beeswax, candelilla wax or mineral wax, and the emulsifier is cetyl glucoside, glyceryl stearate or PEG-100 stearate.

[0019] As an optional mode, in the above preparation method, the preparation method comprises the following steps:

[0020] (1) 0.05-0.1 g of acetic acid as a pH adjuster, 0.5 g of hydroxytyrosol is added to 8-10 g of pentaerythritol tetracocoate, and the mixture is stirred in a water bath at 40-50° C. for 45 min to fully dissolve the hydroxytyrosol in the pentaerythritol tetracocoate to form solution A;

[0021] (2) dissolving 4-5 g of cetyl glucoside in 80 g of water in a water bath at 80° C. to fully dissolve the cetyl glucoside to form solution B;

[0022] (3) Solution A and Solution B were fully dissolved at 80° C. to form Solution C, and solution C was homogenized at 8000-9000 rpm for 30 s to form a uniform emulsion;

[0023] (4) keeping the solution C homogenized in step (3) at 80° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s;

[0024] (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down to obtain a single-layer solid lipid nanoparticle encapsulating hydroxytyrosol.

[0025] As an optional mode, in the above preparation method, the preparation method comprises the following steps:

[0026] (1) 0.05-0.1 g of acetic acid as a pH adjuster, 0.5 g of hydroxytyrosol is added to 1-2 g of pentaerythritol tetracocoate, and the mixture is stirred in a water bath at 40-50° C. for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A;

[0027] (2) 1-3 g of beeswax and 4-5 g of cetyl glucoside are dissolved in 80 g of water and placed in a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B;

[0028] (3) Solution A and Solution B were fully dissolved at 90° C. to form Solution C, and solution C was homogenized at 8000-9000 rpm for 1 min using a homogenizer to form a uniform emulsion;

[0029] (4) keeping the solution C homogenized in step (3) at 90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s;

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

[0031] As an optional mode, in the above preparation method, the preparation method comprises the following steps:

[0032] (1) 0.05-0.1 g of acetic acid as a pH adjuster, 0.5 g of hydroxytyrosol is added to 1-2 g of caprylic acid and capric acid triglyceride, and the mixture is stirred in a water bath at 40-50° C. for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A;

[0033] (2) 1-3 g of beeswax and 4-5 g of cetyl glucoside are dissolved in 80 g of water and placed in a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B;

[0034] (3) Solution A and Solution B were fully dissolved at 90° C. to form Solution C, and solution C was homogenized at 8000-9000 rpm for 1 min using a homogenizer to form a uniform emulsion;

[0035] (4) keeping the solution C homogenized in step (3) at 90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s;

[0036] (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down 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.

[0038] As an optional mode, 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 use of the solid lipid nanoparticles described in the second aspect in preparing cosmetics, wherein the amount of the solid lipid nanoparticles added to the cosmetics is 0.01-20% of the total weight of the cosmetics.

[0040] As an optional mode, in the above-mentioned use, the cosmetics are one or more of lotion, essence, cream, mask, and gel.

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

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

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

[0044] (3) The present invention prepares different types of solid lipid nanoparticles such as solid lipid single-layer encapsulation, solid-liquid lipid double-layer encapsulation, and solid-solid lipid double-layer encapsulation by compounding different types of lipids. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0046] Figure 2 : Photos of the solid lipid nanoemulsions prepared in Example 2, Example 3 and Example 4. From left to right in the figure are Example 2, Example 3 and Example 4. DETAILED DESCRIPTION

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

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

[0049] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0050] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0051] Example:

[0052] Example 1: Improving the oil solubility of hydroxytyrosol

[0053] Hydroxytyrosol raw material itself is very water-soluble, but oil-soluble. Because of its own strong active characteristics, it is easy to change color during use. It is found by experiment that hydroxytyrosol is soluble in water and changes color in a short time, but it can be kept unchanged for a long time when dispersed in oil. Based on this, the inventor has investigated the solubility of hydroxytyrosol in different solid oil formulas (see Table 1), to explore the method for improving the oil solubility of hydroxytyrosol, and realize the encapsulation in solid lipid nanoparticles.

[0054] Table 1: Study on the solubility of hydroxytyrosol in different solid oil formulations

[0055] Hydroxytyrosol Oil + 0.2 g acetic acid Is it soluble? 0.5 g hydroxytyrosol 5 g caprylic capric triglyceride Can 0.5 g hydroxytyrosol 5 g isopropyl myristate Can 0.5 g hydroxytyrosol 5 g Cetyl Alcohol Can 0.5 g hydroxytyrosol 5 g Pentaerythritol Tetracocoate Can 0.5 g hydroxytyrosol 5 g beeswax Can't

[0056] The experimental results are shown in Table 1. Most oils contain different numbers of hydroxyl groups or carboxyl groups, so most oils can undergo esterification and etherification reactions with hydroxytyrosol in an acidic environment, making hydroxytyrosol soluble in oil. However, some wax substances with complex ingredients may not react, such as beeswax. Taking advantage of its relatively stable characteristics, beeswax can be used as a solid oil to encapsulate hydroxytyrosol.

[0057] Example 2: Pentaerythritol tetracocoate as solid oil to encapsulate hydroxytyrosol in a single layer

[0058] The specific preparation method of using pentaerythritol tetracocoate as solid oil to monolayer encapsulate hydroxytyrosol to prepare solid lipid nanoemulsion encapsulating hydroxytyrosol 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, and the mixture was stirred in a 50° C. water bath for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A;

[0060] (2) dissolving 4 g of cetyl glucoside in 80 g of water in a water bath at 80° C. to fully dissolve the cetyl glucoside to form solution B;

[0061] (3) Solution A and Solution B were fully dissolved at 80° C. to form Solution C, and solution C was homogenized at 8000 rpm for 30 s to form a uniform emulsion;

[0062] (4) keeping the solution C homogenized in step (3) at 80° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 300 W and an ultrasonic time of 5 min, with ultrasonication for 3 s and rest for 2 s;

[0063] (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down to obtain a single-layer solid lipid nanoparticle encapsulating hydroxytyrosol.

[0064] Example 3: Beeswax and pentaerythritol tetracocoate as solid fats for solid-solid double-layer encapsulation of hydroxytyrosol

[0065] The specific preparation method of using beeswax and pentaerythritol tetracocoate as solid fats to solid-solid double-layer encapsulate hydroxytyrosol to prepare a solid lipid nanoemulsion encapsulating hydroxytyrosol is as follows:

[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, and the mixture was stirred in a 50° C. water bath for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A;

[0067] (2) 1 g of beeswax and 4 g of cetyl glucoside were dissolved in 80 g of water and the solution was formed by fully dissolving the beeswax and cetyl glucoside in a 90°C water bath;

[0068] (3) Solution A and Solution B were fully dissolved at 90° C. to form Solution C, and solution C was homogenized at 8000 rpm for 1 min using a homogenizer to form a uniform emulsion;

[0069] (4) keeping the solution C homogenized in step (3) at 90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 300 W and an ultrasonic time of 5 min, with ultrasonication for 3 s and rest for 2 s;

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

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

[0072] The specific preparation method of using beeswax as solid fat and caprylic capric triglyceride as liquid fat to solid-liquid double-layer encapsulate hydroxytyrosol to prepare a solid lipid nanoemulsion encapsulating hydroxytyrosol is as follows:

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

[0074] (2) 1 g of beeswax and 4 g of cetyl glucoside were dissolved in 80 g of water and the solution was formed by fully dissolving the beeswax and cetyl glucoside in a 90°C water bath;

[0075] (3) Solution A and Solution B were fully dissolved at 90° C. to form Solution C, and solution C was homogenized at 8000 rpm for 1 min using a homogenizer to form a uniform emulsion;

[0076] (4) keeping the solution C homogenized in step (3) at 90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 300 W and an ultrasonic time of 5 min, with ultrasonication for 3 s and rest for 2 s;

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

[0078] Example 5: Preparation of a common emulsion sample in Comparative Example 2

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

[0080] (2) 8 g of pentaerythritol tetracocoate and 4 g of cetyl glucoside were dissolved in 80 g of water and the solution was formed by fully dissolving the cetyl glucoside in a water bath at 80°C;

[0081] (3) Solution A and solution B were fully dissolved at 80° C. to form solution C, and solution C was homogenized at 8000 rpm for 30 s to form a uniform emulsion.

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

[0083] (1) The solid lipid nanoemulsions prepared in Example 2, Example 3 and Example 4 are shown in the following figure. Figure 2 Take 0.1 mL of the samples prepared in Example 2, Example 3, and Example 4 respectively as the samples to be tested, and use a laser particle size analyzer to test the average particle size of the samples;

[0084] (2) Dilute with pure water to 0.5 mL and place in the sample pool. The number of measurement cycles is the system default, the detection temperature is 25 °C, and the refractive index and viscosity are selected based on the water medium;

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

[0086] (4) The results show that the particle size of the solid lipid nanoparticle samples is within 300 nm, the sample appearance is uniform and stable, and there is no obvious large particle phenomenon. The specific experimental results are shown in Table 2.

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

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

[0089] Example 7: Solid lipid nanoparticle sample encapsulation efficiency test

[0090] (1) A Shimadzu LC-20A high performance liquid chromatograph and a Waters Symmetry C18 column (5 μm, 250 mm×4.6 mm) were used; 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 2998 PDA diode array detector was used, the detection wavelength was 280 nm, the column temperature was 35°C, and the injection volume was 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, and then the emulsion was broken by ultrasonication in a cell disruptor for 60 seconds, and the concentration was measured by liquid phase to be X;

[0092] (3) Another solid lipid nanoparticle sample was tested for encapsulation efficiency using ultrafiltration. The molecular weight of the ultrafiltration tube was 30 kDa, the centrifugal speed was 10,000 rpm, and the centrifugation was performed for 20 min. The lower layer of the ultrafiltration tube was taken and the hydroxytyrosol content was also tested using liquid phase, which was recorded as X'.

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

[0094] (4) The encapsulation efficiency determination method of Example 3 and Example 4 is the same as that of Example 2. The specific experimental results are shown in Table 3.

[0095] Table 3: Encapsulation efficiency of solid lipid nanoparticle samples of Example 2, Example 3, and Example 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 Example 2, Example 3, Example 4 and Example 5 are shown in Table 4 below.

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

[0100]

[0101] It can be seen from the data in the above table that the solid lipid nanoparticle samples prepared in Example 2, Example 3, and Example 4 have a uniform and stable appearance and remain stable under high and low temperature conditions without any stratification, agglomeration, discoloration, etc.; the emulsion sample prepared in Example 5 changes color significantly when placed in a heat-resistant environment. It can be seen that when hydroxytyrosol is dissolved in water, the color change in a high temperature environment is more significant. Figure 1 From left to right are the color changes of Example 5 and Example 2 after being placed in a heat-resistant environment. The samples prepared at the beginning are all in the form of white emulsions, and the emulsion of Example 2 has a blue glow.

[0102] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A method for preparing solid lipid nanoparticles encapsulating hydroxytyrosol, characterized in that: The preparation method comprises the following steps: (1) 0.01-0.5 g of a weak acid as a pH adjuster, 0.1-1 g of hydroxytyrosol is added to 5-15 g of oil, and the mixture is stirred in a water bath at 30-60° C. for 30-60 min to fully dissolve the hydroxytyrosol in the oil to form a solution A; (2) dissolving 0-5 g of wax material and 2-8 g of emulsifier in 50-100 g of water, and placing in a water bath at 70-90° C. to fully dissolve the wax material and emulsifier to form solution B; (3) Solution A and Solution B are fully dissolved at 70-90° C. to form Solution C, and solution C is homogenized at 8000-9000 rpm for 20-40 s to form a uniform emulsion; (4) keeping the solution C homogenized in step (3) at 70-90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s; (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down to obtain solid lipid nanoparticles encapsulating hydroxytyrosol.

2. The preparation method according to claim 1, characterized in that: 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.

3. The preparation method according to claim 1, characterized in that: In step (2), the wax substance is beeswax, candelilla wax or mineral wax, and the emulsifier is cetyl glucoside, glyceryl stearate or PEG-100 stearate.

4. The preparation method according to claim 1, characterized in that: The preparation method comprises the following steps: (1) 0.05-0.1 g of acetic acid as a pH adjuster, 0.5 g of hydroxytyrosol is added to 8-10 g of pentaerythritol tetracocoate, and the mixture is stirred in a water bath at 40-50° C. for 45 min to fully dissolve the hydroxytyrosol in the pentaerythritol tetracocoate to form solution A; (2) dissolving 4-5 g of cetyl glucoside in 80 g of water in a water bath at 80° C. to fully dissolve the cetyl glucoside to form solution B; (3) Solution A and Solution B were fully dissolved at 80° C. to form Solution C, and solution C was homogenized at 8000-9000 rpm for 30 s to form a uniform emulsion; (4) keeping the solution C homogenized in step (3) at 80° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s; (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down to obtain a single-layer solid lipid nanoparticle encapsulating hydroxytyrosol.

5. The preparation method according to claim 1, characterized in that: The preparation method comprises the following steps: (1) 0.05-0.1 g of acetic acid as a pH adjuster, 0.5 g of hydroxytyrosol is added to 1-2 g of pentaerythritol tetracocoate, and the mixture is stirred in a water bath at 40-50° C. for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A; (2) 1-3 g of beeswax and 4-5 g of cetyl glucoside are dissolved in 80 g of water and placed in a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B; (3) Solution A and Solution B were fully dissolved at 90° C. to form Solution C, and solution C was homogenized at 8000-9000 rpm for 1 min using a homogenizer to form a uniform emulsion; (4) keeping the solution C homogenized in step (3) at 90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s; (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down to obtain solid-solid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

6. The preparation method according to claim 1, characterized in that: The preparation method comprises the following steps: (1) 0.05-0.1 g of acetic acid as a pH adjuster, 0.5 g of hydroxytyrosol is added to 1-2 g of caprylic acid and capric acid triglyceride, and the mixture is stirred in a water bath at 40-50° C. for 45 min to fully dissolve the hydroxytyrosol in pentaerythritol tetracocoate to form solution A; (2) 1-3 g of beeswax and 4-5 g of cetyl glucoside are dissolved in 80 g of water and placed in a 90°C water bath to fully dissolve the beeswax and cetyl glucoside to form solution B; (3) Solution A and Solution B were fully dissolved at 90° C. to form Solution C, and solution C was homogenized at 8000-9000 rpm for 1 min using a homogenizer to form a uniform emulsion; (4) keeping the solution C homogenized in step (3) at 90° C., and ultrasonically pulverizing the solution C again using an ultrasonic cell pulverizer, with an ultrasonic power of 200-400 W and an ultrasonic time of 5-8 min, with ultrasonication for 3 s and rest for 2 s; (5) The solution C after the ultrasonic treatment in step (4) is quickly placed in an ice bath to cool down to obtain solid-liquid bilayer solid lipid nanoparticles encapsulating hydroxytyrosol.

7. Solid lipid nanoparticles encapsulating hydroxytyrosol prepared by the preparation method according to any one of claims 1 to 6.

8. The solid lipid nanoparticle according to claim 7, characterized in that: The particle size of the solid lipid nanoparticles is 150-250nm, and the encapsulation rate of the solid lipid nanoparticles is greater than 50%.

9. Use of the solid lipid nanoparticles according to claim 7 or claim 8 in preparing cosmetics, characterized in that: The solid lipid nanoparticles are added in an amount of 0.01-20% of the total weight of the cosmetics.

10. The use according to claim 9, characterized in that: The cosmetics are one or more of lotion, essence, cream, mask and gel.

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