Lycopene and resveratrol microbeads and a preparation method thereof

Abstract

The present application relates to a kind of lycopene and resveratrol microbead and preparation method thereof, to provide a kind of lycopene and resveratrol microbead capable of stable package, not only improve the solubility of two, and have significant antioxidant effect, can make active ingredient stable storage before use, belong to the skin care product technical field.

Description

Technical Field

[0001] This invention discloses a skin care product, specifically a lycopene and resveratrol microgel skin care product and its preparation method, belonging to the field of skin care product technology. Background Technology

[0002] With the continuous improvement of my country's economic development level and the ongoing progress and development of society, people's material needs have been met, their living standards have been greatly improved, and their demand for beauty has been constantly increasing, leading to a booming beauty and skincare market. Against this backdrop, my country's cosmetics industry is flourishing.

[0003] Lycopene and resveratrol both possess antioxidant properties and are preferred bioactive substances for scavenging free radicals. Existing research indicates that lycopene and resveratrol also have anti-inflammatory, antibacterial, and tumor cell proliferation-inhibiting functions, making them highly promising functional factors for application in the cosmetics field. However, their stability is poor, resulting in significant losses during production. Therefore, maximizing the preservation of the bioactivity of lycopene and resveratrol is a crucial issue that urgently needs to be addressed. Consequently, the microencapsulation of lycopene and resveratrol has attracted increasing attention. Beads are an effective method for improving the stability of bioactive compounds sensitive to environmental factors such as temperature, light, and oxygen. They can effectively protect lycopene from adverse environmental conditions while enhancing physical stability, improving bioavailability, and facilitating handling and storage. They offer advantages such as high specialization and low cost, thus strengthening the in-depth application of lycopene and resveratrol in the cosmetics field. They possess high market value and development prospects and should be vigorously developed.

[0004] A search revealed that patent CN113413333A discloses a nano-bead and its preparation method, as well as an essence prepared from the nano-beads, and patent CN109106681B discloses a micro-bead whitening essence and its preparation method. This invention's patent application differs significantly from the aforementioned patents. This invention, for the first time, uses semi-interpenetrating polymer network technology to encapsulate natural active ingredients such as lycopene and resveratrol within the beads. It also employs solid dispersion technology to address the poor solubility of lycopene and, for the first time, combines solid dispersion technology with nano-formulations to achieve highly efficient encapsulation of lycopene and resveratrol, delivering them directly to the skin through application to achieve antioxidant, anti-aging, and whitening effects. Summary of the Invention

[0005] Lycopene and resveratrol both possess powerful antioxidant and free radical scavenging abilities, making them highly promising natural active substances. However, due to their inherent instability and poor solubility, this invention provides a method for preparing lycopene and resveratrol microspheres. For the first time, resveratrol and lycopene are co-encapsulated, demonstrating their superior synergistic antioxidant capacity. Because lycopene has extremely poor solubility, this invention prepares it as a solid dispersion, improving its solubility. Furthermore, for the first time, the solid dispersion is combined with nanoemulsions to dissolve resveratrol in the oil phase, achieving co-encapsulation of the two. However, due to the poor stability and susceptibility to oxidation of lycopene and resveratrol, this invention also employs semi-interpenetrating polymer network technology to encapsulate the active ingredients within the microspheres, further enhancing their stability and providing antioxidant, anti-aging, and whitening effects, thus solving the problems of poor solubility and stability of lycopene and resveratrol.

[0006] The purpose of this invention is to provide a method for preparing lycopene and resveratrol microspheres, which consists of an outer phase solution and an inner phase nanoemulsion containing lycopene and resveratrol, with a mass ratio of 1~5:5~1.

[0007] The first technical solution adopted in this invention is: the outer phase solution should be agar or agarose, combined with one or more of the following: sodium alginate, carrageenan, chitosan, gelatin, xanthan gum, gum arabic and gellan gum. The mass ratio of agar, agarose and other compound solutions should be 1~10:1~10.

[0008] The second technical solution adopted in this invention is: a lycopene and resveratrol microsphere inner phase nanoemulsion, the raw material components and weight parts of which are: 0.1-5 parts of lycopene solid dispersion, 0.1-5 parts of resveratrol, 0-10 parts of 1,3-propanediol, 0-10 parts of 1,2-hexanediol, 0-10 parts of 1,2-pentanediol, 0-5 parts of ethoxydiethylene glycol, 0-10 parts of PEG-40 hydrogenated castor oil, and deionized water to make up to 100 parts.

[0009] The third technical solution adopted in this invention is as follows: A certain amount of lycopene and poloxamer 188 are placed in a round-bottom flask, a certain amount of organic solvent is added, and the mixture is sonicated to dissolve them. The round-bottom flask is then placed in a rotary evaporator, and the solvent is recovered by rotary evaporation under reduced pressure for several minutes, forming a thin film. The round-bottom flask is then removed and placed in a vacuum drying oven for overnight drying to obtain the lycopene solid dispersion.

[0010] The fourth technical solution adopted in this invention is: a method for preparing lycopene and resveratrol microbeads, comprising the following preparation steps:

[0011] (1) Prepare an oil phase by heating and stirring 1,3-propanediol, 1,2-hexanediol, 1,2-pentanediol, ethoxydiethylene glycol, and PEG-40 hydrogenated castor oil, and then add resveratrol to it and stir until completely dissolved.

[0012] (2) Add a certain concentration of lycopene solid dispersion to the aqueous phase and stir until completely dissolved.

[0013] (3) Slowly add the oil phase from step (1) to step (2) and stir for 1-2 hours to obtain lycopene and resveratrol inner phase nanoemulsion.

[0014] (4) Dissolve agar or agarose in preheated ultrapure water and cool it to 45°C. Then, dissolve the compound solution in the agar or agarose aqueous solution.

[0015] (5) Add the lycopene and resveratrol inner phase nanoemulsion to the above solution and stir until fully miscible.

[0016] (6) The above solution containing lycopene and resveratrol inner phase nanoemulsion is injected into cold oil through a single-channel micro-injection pump.

[0017] (7) Wash the obtained microbeads with ultrapure water 3 to 4 times.

[0018] (8) Immerse the washed microbeads in the cross-linking solution under gentle stirring to achieve full cross-linking.

[0019] (9) Wash the obtained microbeads with ultrapure water 3-4 times to obtain lycopene and resveratrol microbeads.

[0020] The invention is further characterized by:

[0021] In step (2) of technical solution 3, the mass ratio of lycopene and resveratrol is 1~3:1~3.

[0022] The preheating temperature in step (4) is 70~90℃.

[0023] In step (6), the cold oil should be one of polydimethylsiloxane, liquid paraffin, squalane, or olive oil.

[0024] In step (8), the crosslinking solution should be one of calcium chloride, magnesium sulfate, sodium sulfate, sodium carbonate, or calcium carbonate.

[0025] Based on the microbeads described in technical solutions one to three above, this invention is applicable to skincare products.

[0026] Compared with the prior art, the beneficial effects of the present invention are:

[0027] I. This invention prepares lycopene and resveratrol microspheres, combining lycopene and resveratrol as natural antioxidants, and co-encapsulating them. The free radical scavenging rate of the compound is much higher than that of the single substance, which proves its synergistic antioxidant effect, improves the antioxidant capacity of this invention, and enhances the anti-aging efficacy of this invention to a certain extent.

[0028] Second, this invention prepares lycopene into a solid dispersion, which solves the problem of its low solubility and makes it more suitable for use in skin care products.

[0029] Third, this invention is the first to combine solid dispersions with nanoemulsions, dissolving resveratrol in the oil phase and lycopene solid dispersions in the aqueous phase, achieving co-encapsulation of the two and improving their stability and addressing issues such as poor bioavailability.

[0030] Fourth, in response to the problems of lycopene and resveratrol being sensitive to environmental factors such as temperature, light and oxygen and having poor stability, this invention is the first to use semi-interpenetrating polymer network technology to encapsulate the active ingredients in the beads, which further improves stability, makes them easy to apply and absorb, and the micro beads are light pink in color, which improves the appearance and makes them more popular with consumers. Attached Figure Description

[0031] Figure 1 The image shows lycopene and resveratrol microbeads from Example 2, where the microbeads are pink in color.

[0032] Figure 2 The image shows an optical microscope image of the lycopene and resveratrol microbeads from Example 3. The microbeads have smooth surfaces and clear edges.

[0033] Figure 3 The image shows an optical microscope image of the lycopene and resveratrol microbeads from Example 4. The microbeads have a smooth surface and clear edges.

[0034] Figure 4 The particle size diagram is shown for the internal phase nanoemulsion prepared in Example 5.

[0035] Figure 5 The particle size diagram of the internal phase nanoemulsion prepared in Comparative Example 2 is shown.

[0036] Figure 6 The image shown is a field emission transmission electron microscope (FESTEM) image of the internal phase nanoemulsion from Example 5. It can be seen that the internal phase nanoemulsions are all uniformly spherical and closely related to the attached... Figure 3 The measured particle sizes were consistent.

[0037] Figure 7 The images show isoradiometric analysis of lycopene and resveratrol in different proportions in Examples 6-8, demonstrating that Examples 6-8 possess superior synergistic antioxidant capabilities. Detailed Implementation

[0038] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the embodiments. The illustrative embodiments and descriptions of this invention are only used to explain this invention and are not intended to limit this invention.

[0039] Comparative Example 1: Prepare a 25 mg / mL sodium alginate solution, add 2 mg / mL lycopene and resveratrol to the solution, and add 5 mg / mL lecithin. Inject the solution into cold oil using a single-channel microinjection pump. Then, immerse the filtered microbeads in a calcium chloride solution and allow them to solidify for 20 minutes.

[0040] Comparative Example 2: 6.5 parts of 1,3-propanediol, 7 parts of 1,2-hexanediol, 10 parts of 1,2-pentanediol, 6.5 parts of ethoxydiethylene glycol, and 20 parts of PEG-40 hydrogenated castor oil were stirred evenly, and then resveratrol was added. An aqueous solution containing lycopene solid dispersion was then slowly added dropwise to the oil mixture. After stirring for 1 hour, a lycopene and resveratrol nanoemulsion was prepared. A 25 mg / mL agarose solution was then prepared, and the two were mixed evenly in a 1:1 ratio. The mixture was then injected into cold oil using a single-channel micro-injection pump and washed 3-4 times to obtain the final product.

[0041] Comparative Example 3: A lycopene solution with a concentration of 1 mg / mL was prepared using ethyl acetate, and the lycopene solution was diluted with ethyl acetate to 1 μg / mL, 5 μg / mL, 10 μg / mL, 25 μg / mL, and 50 μg / mL.

[0042] Comparative Example 4: A resveratrol solution with a concentration of 1 mg / mL was prepared using ethyl acetate, and the resveratrol solution was diluted with ethyl acetate to 1 μg / mL, 5 μg / mL, 10 μg / mL, 25 μg / mL, and 50 μg / mL.

[0043] Comparative Example 5: A vitamin E solution with a concentration of 1 mg / mL was prepared using ethyl acetate, and the vitamin E solution was diluted with ethyl acetate to 1 μg / mL, 5 μg / mL, 10 μg / mL, 25 μg / mL, and 50 μg / mL.

[0044] In Example 1, 2 parts of 1,3-propanediol, 3.5 parts of 1,2-hexanediol, 3 parts of 1,2-pentanediol, 4 parts of ethoxydiethylene glycol, and 7.5 parts of PEG-40 hydrogenated castor oil were stirred until homogeneous. Resveratrol was then added, and an aqueous solution containing a lycopene solid dispersion was slowly added dropwise to the oil. The mixture was stirred for 1 hour to prepare a lycopene and resveratrol nanoemulsion. An external phase coating solution was then prepared, containing 10 mg / mL agarose, 5 mg / mL gelatin, and 1 mg / mL chitosan. The nanoemulsion containing 1 mg / mL lycopene and 1 mg / mL resveratrol was mixed homogeneously with the external phase coating solution and injected into cold oil using a single-channel microinjection pump. The filtered microbeads were then immersed in a calcium chloride solution and cured for 20 minutes to obtain the final product.

[0045] In Example 2, 2 parts of 1,3-propylene glycol, 3.5 parts of 1,2-hexanediol, 3 parts of 1,2-pentanediol, 4 parts of ethoxydiethylene glycol, and 7.5 parts of PEG-40 hydrogenated castor oil were stirred until homogeneous. Resveratrol was then added, and an aqueous solution containing a lycopene solid dispersion was slowly added dropwise to the oil. The mixture was stirred for 1 hour to prepare a lycopene and resveratrol nanoemulsion. An external phase coating solution was then prepared, containing 5 mg / mL agarose and 5 mg / mL sodium alginate. The nanoemulsion containing 1 mg / mL lycopene and 2 mg / mL resveratrol was mixed homogeneously with the external phase coating solution. This solution was then injected into cold oil using a single-channel microinjection pump. The filtered microbeads were then immersed in a calcium chloride solution and solidified for 20 minutes to obtain the final product.

[0046] In Example 3, 2 parts of 1,3-propanediol, 3.5 parts of 1,2-hexanediol, 3 parts of 1,2-pentanediol, 4 parts of ethoxydiethylene glycol, and 7.5 parts of PEG-40 hydrogenated castor oil were stirred until homogeneous. Resveratrol was then added, and an aqueous solution containing a lycopene solid dispersion was slowly added dropwise to the oil. The mixture was stirred for 1 hour to prepare a lycopene and resveratrol nanoemulsion. An external phase coating solution was then prepared, containing 6 mg / mL agarose, 2 mg / mL carrageenan, and 1 mg / mL xanthan gum. The nanoemulsion containing 1 mg / mL lycopene and 1.5 mg / mL resveratrol was mixed homogeneously with the external phase coating solution. This solution was then injected into cold oil using a single-channel microinjection pump. The filtered microbeads were then immersed in a calcium chloride solution and cured for 20 minutes to obtain the final product.

[0047] Example 4: 2 parts 1,3-propanediol, 3.5 parts 1,2-hexanediol, 3 parts 1,2-pentanediol, 4 parts ethoxydiethylene glycol, and 7.5 parts PEG-40 hydrogenated castor oil were stirred until homogeneous. Resveratrol was then added, and an aqueous solution containing a lycopene solid dispersion was slowly added dropwise to the oil. The mixture was stirred for 1 hour to prepare a lycopene and resveratrol nanoemulsion. An external phase coating solution was then prepared, containing 7 mg / mL agarose and 3 mg / mL gum arabic. The nanoemulsion containing 1 mg / mL lycopene and 1.2 mg / mL resveratrol was then mixed homogeneously with the external phase coating solution. This solution was injected into cold oil using a single-channel micro-injection pump. The filtered microbeads were then immersed in a magnesium sulfate solution and cured for 20 minutes to obtain the final product. (See attached image) Figure 1 .

[0048] Example 5: 2 parts 1,3-propanediol, 3.5 parts 1,2-hexanediol, 3 parts 1,2-pentanediol, 4 parts ethoxydiethylene glycol, and 7.5 parts PEG-40 hydrogenated castor oil were stirred until homogeneous. Resveratrol was then added, and an aqueous solution containing a lycopene solid dispersion was slowly added dropwise to the oil. The mixture was stirred for 1 hour to prepare a lycopene and resveratrol nanoemulsion. An external phase coating solution was then prepared, containing 8 mg / mL agarose, 4 mg / mL gellan gum, and 2 mg / mL sodium alginate. The nanoemulsion containing 1 mg / mL lycopene and 1 mg / mL resveratrol was mixed homogeneously with the external phase coating solution. This solution was then injected into cold oil using a single-channel micro-injection pump. The filtered microspheres were then immersed in a calcium carbonate solution and cured for 20 minutes to obtain the final product. (See attached image). Figure 2 .

[0049] In Example 6, a 1:1 solution of lycopene and resveratrol was prepared using ethyl acetate, and then diluted with ethyl acetate to form a series of gradients as shown in Table 7.

[0050] In Example 7, a 1:2 solution of lycopene and resveratrol was prepared using ethyl acetate, and then diluted with ethyl acetate to form a series of gradients as shown in Table 7.

[0051] In Example 8, a 1:3 solution of lycopene and resveratrol was prepared using ethyl acetate, and then diluted with ethyl acetate to form a series of gradients as shown in Table 7.

[0052] Experiment Example 1 Stability Test

[0053] Experimental methods: For Examples 1 to 3, the stability of the samples in Comparative Example 1 was tested under light, heat, and room temperature conditions.

[0054] Illumination: The test samples of Examples 1-3 and Comparative Example 1 were placed in a light source and the changes of the samples on days 0, 1, 3 and 7 were observed. Table 1 shows the test results of the samples under light conditions.

[0055] Table 1. Stability test results of samples under illumination conditions

[0056]

[0057] As can be seen from the table, after one week, Examples 1-3 remained stable under light conditions without any change in state. The beads prepared by the method in Comparative Example 1 agglomerated and had uneven color, exhibiting an agglomerated state, indicating instability in the system.

[0058] Heat resistance: The test samples of Examples 1-3 and Comparative Example 1 were placed in a 50-degree oven and the changes of the samples were observed on days 0, 1, 3 and 7. Table 2 shows the test results of the samples under high temperature conditions.

[0059] Table 2. Stability test results of samples under high temperature conditions

[0060]

[0061] As can be seen from the table, after one week, Examples 1-3 remained stable under high-temperature conditions without any change in state. The agglomerated samples prepared by the method in Comparative Example 1 agglomerated and had uneven color, exhibiting an agglomerated state, indicating an unstable system.

[0062] Room temperature: The test samples of Examples 1-3 and Comparative Example 1 were placed at room temperature, and the changes of the samples on days 0, 1, 3 and 7 were observed. Table 3 shows the test results of the samples under room temperature conditions.

[0063] Table 3. Stability test results of samples under normal temperature conditions

[0064]

[0065] As can be seen from the table, after one week, Examples 1-3 remained stable at room temperature without any change in state. The agglomerated samples prepared by the method in Comparative Example 1 agglomerated and exhibited uneven coloring, showing a clumped and unstable system.

[0066] Experimental Example 2: Measurement of the Particle Size of Intraphase Nanoemulsions in Microbeads

[0067] Experimental Methods: The internal phase nanoemulsion prepared in Example 5 was diluted 10 times with the internal phase nanoemulsion obtained in Comparative Example 2. The particle size of the nanoemulsion was measured using a Malvern particle size analyzer. The results are shown in Tables 4 and 5. The particle size distribution is shown in the appendix. Figure 4 , 5.

[0068] Table 4. Particle size and PDI measurement results of the internal phase nanoemulsion in Example 5 (n=3)

[0069]

[0070] Table 5. Comparative Example 2: Particle size and PDI measurement results of the internal phase nanoemulsion (n=3)

[0071]

[0072] As can be seen from Tables 4 and 5, the internal phase nanoemulsion obtained in Example 5 has a smaller particle size and PDI compared to the nanoemulsion obtained in Comparative Example 2, and the internal phase nanoemulsion is also more stable.

[0073] Experimental Example 3: Field Emission Transmission Electron Microscopy Observation of Inner Phase Nanoemulsions

[0074] Experimental Method: The internal phase nanoemulsion prepared in Example 5 was diluted 10 times and dropped onto the surface of a copper mesh. It was negatively stained with 2% phosphotungstic acid solution for 2 minutes. Excess liquid was absorbed with filter paper, and the nanoemulsion was allowed to air dry. The microstructure of the nanoemulsion was observed using a field emission transmission electron microscope (FET). (See attached figure) Figure 6 .

[0075] Experimental Example 4: Synergistic Antioxidant Activity of Lycopene and Resveratrol (Isoradiometric Analysis)

[0076] DPPH radicals are synthetic, stable, nitrogen-centered paramagnetic compounds with a single electron. In the presence of a radical scavenger, a DPPH radical accepts an electron or a hydrogen atom to form a stable DPPH-H compound, causing its methanol (or ethanol) solution to change from deep purple to yellow. The degree of color change is quantitatively related to the number of electrons accepted (radical scavenging activity), allowing for rapid quantitative analysis using a spectrophotometer. Therefore, this invention evaluates its efficacy by measuring the DPPH radical scavenging results.

[0077] Solution preparation:

[0078] Weigh 2 mg of DPPH free radical powder into a 50 mL volumetric flask, dissolve it in anhydrous ethanol, dilute to volume, and shake well to obtain a 0.04 mg / mL DPPH solution.

[0079] Take a 96-well plate, add 100 μL of DPPH solution, and then add 100 μL of solutions diluted at different ratios. Mix well and react in the dark at room temperature for 20 min. Measure the UV absorbance at 517 nm and calculate the DPPH scavenging rate. The results are shown in Table 4.

[0080] Table 6. Experimental results of DPPH free radical scavenging rate

[0081]

[0082] As shown in Table 6, the IC50 of Comparative Example 2 for scavenging free radicals... 50 The value was 5.123 μg / mL, and the IC50 of Comparative Example 3 was... 50 The value was 41.214 μg / mL.

[0083] Isobologram (isoradiometric analysis) is used to analyze drug interactions by comparing theoretical IC50 values. 50add IC obtained from experiments 50mix The type and strength of synergistic effects between the two can be determined by the differences between them and the magnitude of their interaction index (γ). IC 50 Table 6 shows the concentration at which the sample achieves a 50% free radical scavenging rate. The IC50 for Comparative Example 3, which scavenges free radicals, is also shown in Table 6. 50 The IC50 for scavenging free radicals in Comparative Example 4 was 5.123 μg / mL. 50 The concentration was 41.214 μg / mL. The IC50 values ​​for Examples 6, 7, and 8 were calculated using the following formula. 50add The results of the comparison with γ are shown in Tables 7, 8, and 9, and appendix. Figure 7 As shown.

[0084]

[0085] Where R is the efficacy ratio of antioxidants A and B when used alone, i.e., R = IC50A / IC50B; P1 is the proportion of antioxidant A in the compound group; P2 is the proportion of antioxidant B in the compound group;

[0086] Table 7. Experimental results of DPPH free radical scavenging rate in Examples 6-8

[0087]

[0088] As shown in Tables 6 and 7, the DPPH scavenging rates of Examples 6, 7, and 8 after different ratios of compounding were much higher than the scavenging rates of Comparative Examples 3, 4, and 5 as a single substance, indicating their superior synergistic effect.

[0089] Table 8. ICs for scavenging free radicals in Examples 6-8 50 value

[0090]

[0091] As shown in Table 8, the free radical scavenging ICs of Examples 6, 7, and 8... 50 The values ​​are all lower than the IC50 values ​​of the two active substances themselves. 50 value.

[0092] Table 9. Statistical analysis results of Examples 6-8

[0093]

[0094] As shown in Table 9, the γ values ​​of Examples 6, 7, and 8 are all less than 1, indicating that Examples 6, 7, and 8 have a synergistic antioxidant effect, and IC 50 A smaller γ value indicates a stronger synergistic effect.

[0095] Although embodiments of the invention have been disclosed for illustrative purposes, those skilled in the art will understand that various substitutions, variations, and modifications are possible without departing from the spirit and scope of the invention and the appended claims. Therefore, the scope of the invention is not limited to the contents disclosed in the embodiments.

Claims

1. A type of lycopene and resveratrol microbeads, characterized in that, The microbeads have a semi-interpenetrating polymer network structure and are formed by cross-linking and curing of an inner phase nanoemulsion and an outer phase encapsulation solution. First, a lycopene solid dispersion needs to be prepared. The preparation method is as follows: a certain amount of lycopene and poloxamer are placed in a round-bottom flask, a certain amount of organic solvent is injected and ultrasonically dissolved, then the round-bottom flask is placed in a rotary evaporator and the solvent is recovered by rotary evaporation under reduced pressure for several minutes to form a thin film. The round-bottom flask is then removed and placed in a vacuum drying oven and dried overnight to obtain the lycopene solid dispersion. The internal phase nanoemulsion is composed of lycopene solid dispersion, resveratrol, 1,3-propanediol, 1,2-hexanediol, 1,2-pentanediol, ethoxydiethylene glycol, PEG-40 hydrogenated castor oil, and deionized water. The outer phase coating solution is agarose, which is combined with one or more of the following: sodium alginate, carrageenan, chitosan, gelatin, xanthan gum, gum arabic, and gellan gum. The mass ratio of agarose to the other compound solutions is 1-10:1-10. Furthermore, in the microspheres, the mass ratio of the outer phase encapsulation solution to the inner phase nanoemulsion is 1–5:5–1.

2. The method for preparing lycopene and resveratrol microbeads according to claim 1, characterized in that... The preparation process includes the following steps: (1) Add 1,3-propanediol, 1,2-hexanediol, 1,2-pentanediol, ethoxydiethylene glycol, and PEG-40 hydrogenated castor oil, heat and stir to prepare an oil phase, and then add resveratrol and stir until completely dissolved. (2) Add a certain concentration of lycopene solid dispersion to the aqueous phase and stir until completely dissolved; (3) Slowly add the oil phase from step (1) to the aqueous phase from step (2) and stir for 1-2 hours to obtain lycopene and resveratrol nanoemulsion. (4) Dissolve agarose in preheated ultrapure water, cool to 45°C, and then dissolve the compound solution in the agarose aqueous solution to obtain an external phase encapsulation solution. (5) Mix a certain concentration of lycopene and resveratrol inner phase nanoemulsion with the above outer phase coating solution, stir until fully miscible, and then inject it into cold oil through a single-channel micro-injection pump. (6) Wash the obtained microbeads with ultrapure water 3 to 4 times; (7) Immerse the washed microbeads in the crosslinking solution under gentle stirring to fully solidify and crosslink; (8) Wash the obtained microbeads with ultrapure water 3 to 4 times to obtain lycopene and resveratrol microbeads.

3. The method for preparing lycopene and resveratrol microbeads according to claim 2, characterized in that, The preheating temperature in step (4) is 70-90℃.

4. The method for preparing lycopene and resveratrol microbeads according to claim 2, characterized in that, The cross-linking solution mentioned in step (7) is one of calcium chloride solution, magnesium sulfate solution, and calcium carbonate solution.

5. The application of lycopene and resveratrol microbeads according to claim 1 in the preparation of skin care products.

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