Nanoscale targeted health intervention nutritional ingredient embedding method

Abstract

The invention relates to a nanoscale targeted health intervention nutritional ingredient embedding method, and belongs to the technical field of ingredient embedding. The specific embedding method comprises the following steps: preparing 1-[(tert-butoxy) methyl]-4-iodobenzene by utilizing iodobenzene methanol or tert-butyldimethylsilyl chloride solution; adding selenium powder, a first catalyst and alkali, and reacting to obtain 1-[(t-butoxy) methyl]-4-({4-[(t-butoxy) methyl] phenyl} disilyl) benzene; trifluoroacetic acid is added for a reaction, and bis (4, 1-hydroxy benzyl) diselenide is obtained; dissolving the mixed solution, EGCG and a second catalyst in an organic solvent to obtain a mixed solution containing EGCG; dropwise adding an oxalyl chloride solution into the mixed solution containing EGCG for reaction to obtain a SeOE polymer; the preparation method comprises the following steps: emulsifying and homogenizing a SeOE polymer solution and a polyvinyl alcohol solution, centrifuging and freeze-drying to obtain the SeOE polymer nanoparticles. According to the invention, by introducing an ROS sensitive chemical part, the ROS removal capability of the targeted delivery polymer and the oxidation stability of EGCG are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of ingredient encapsulation, and in particular to a method for encapsulating nano-level targeted health intervention nutritional ingredients. Background Art

[0002] Inflammatory bowel disease (IBD) is a chronic inflammation of the intestinal mucosa, which has become a global health problem and its incidence has been continuously increasing in recent years. IBD often causes diarrhea, abdominal pain, bloody stools, and weight loss, seriously affecting the quality of life of patients. Although the etiology of IBD has not been fully understood, it is generally believed that the etiology of IBD is related to the combined effects of environmental factors, genetic factors, immune-related factors, and bacterial factors. Recently, some drugs, including aminosalicylic acid, corticosteroids, and immunosuppressants, have been reported to be used to relieve the symptoms of IBD. However, the therapeutic effects of these drugs are not ideal, and even adverse reactions occur due to their poor stability, low solubility, and side effects caused by systemic absorption. In order to reduce potential systemic toxicity and improve the therapeutic effect, compared with systemic administration, targeted drug delivery is a promising precise IBD treatment strategy. Many studies have confirmed that there is an excess of reactive oxygen species (ROS) in the intestinal mucosa of IBD patients. Excess ROS is considered a signaling molecule that regulates the oxidative balance in the body. In addition, using the microenvironment rich in reactive oxygen species, a variety of ROS-responsive drug delivery systems for targeted drug delivery have been increasingly favored by researchers. For example, organic selenium compounds can be oxidized from divalent to tetravalent, making them attractive ROS scavengers. The ROS oxidation of monoselenium compounds may lead to a phase change from hydrophobic to hydrophilic, which can be utilized when constructing ROS-responsive drug carriers.

[0003] In recent years, natural products extracted from many plants, fruits, and herbs, such as curcumin, quercetin, berberine, resveratrol, and polysaccharides, have been considered promising drugs for the treatment of IBD. Epigallocatechin gallate (EGCG, (-)-Epigallocatechin gallate) is a polyphenol abundant in green tea. EGCG has antioxidant, anti-inflammatory, anti-proliferative, and anti-apoptotic effects. However, due to the low solubility and stability of EGCG, its use is limited. Some researchers have developed EGCG encapsulation systems to improve these problems. For example, EGCG is combined with layered montmorillonite under the action of double hydrogen bonds and electrostatic adsorption to form a sustained-release EGCG nanoparticle carrier. However, these systems still cannot meet the ROS-responsive requirements mentioned above. Summary of the Invention

[0004] To solve the above technical problems, the present invention provides a method for encapsulating nano-level targeted health intervention nutritional ingredients.

[0005] The present invention provides a method for encapsulating nano-scale targeted health intervention nutritional components, comprising the following steps: (1) Add a catalyst containing isobutene to an iodobenzyl alcohol or tert-butyldimethylchlorosilane (TBDSCl) solution, and react to obtain 1-[(tert-butoxy)methyl]-4-iodobenzene; under an inert atmosphere, add selenium powder, a first catalyst, and a base to the 1-[(tert-butoxy)methyl]-4-iodobenzene solution, and react to obtain 1-[((tert-butoxy)methyl]-4-({4-[((tert-butoxy]methyl]phenyl}disilyl)benzene. Dissolve the product in an organic solvent, and add TFA and react at room temperature for 1 h - 8 h to obtain bis(4,1-hydroxybenzyl) diselenide; (2) Dissolve the bis(4,1-hydroxybenzyl) diselenide, epigallocatechin gallate, and a second catalyst in an organic solvent to obtain a mixed solution containing epigallocatechin gallate; under an inert atmosphere, stir, dropwise add an oxalyl chloride solution to the mixed solution containing epigallocatechin gallate, and react at 0°C - 25°C for 6 - 24 h to obtain a SeOE polymer; (3) Emulsify and homogenize using the SeOE polymer solution and a polyvinyl alcohol solution, centrifuge, and freeze-dry to obtain the SeOE polymer nanoparticles; The present invention utilizes the nucleophilic reaction of oxalyl chloride with epigallocatechin gallate (EGCG) and diselenide to form a peroxyoxalate bond, connecting EGCG and diselenide, promoting the polymerization reaction, and forming a SeOE polymer.

[0006] The structural formula of the SeOE polymer is: , wherein, m and n are the number of repeating units, i.e., the degree of polymerization. m is the number of repetitions of EGCG connected to the peroxyoxalate bond in the SeOE polymer, and n is the number of repetitions of diselenide connected to the peroxyoxalate bond in the SeOE polymer.

[0007] In some embodiments of the present invention, in step (1), the catalyst containing isobutene further includes concentrated sulfuric acid; the reaction temperature for preparing 1-[(tert-butoxy)methyl]-4-iodobenzene is 0°C - 25°C, and the reaction time is 12 - 72 h; The inert gas in the inert atmosphere includes nitrogen and / or argon; The first catalyst includes one or more of CuO, MnO2, Fe2O3, and Co3O4; The base includes one or more of KOH, Ca(OH)2, Mg(OH)2, and Na2CO3.

[0008] In some embodiments of the present invention, in step (1), the mass ratio of iodobenzyl alcohol to isobutene is (0.01 - 0.1):(0.1 - 0.5). In some embodiments of the present invention, in step (1), the mass ratio of 1-[(tert-butoxy)methyl]-4-iodobenzene, selenium powder, the first catalyst, and the base is (0.02 - 0.1):(0.1 - 0.5):(0.01 - 0.1):(0.1 - 0.5).

[0009] In some embodiments of the present invention, in step (1), the reaction conditions for preparing 1-[(tert-butoxy)methyl]-4-({4-[(tert-butoxy)methyl]phenyl}disilanyl)benzene are: the temperature is 50 - 100 °C, and the time is 12 - 48 hours; The organic solvent includes DCM.

[0010] In some embodiments of the present invention, in step (2), the mass ratio of bis(4,1-hydroxybenzyl) diselenide, epigallocatechin gallate, the second catalyst, and oxalyl chloride is (0.01 - 0.1):(0.01 - 0.1):(0.01 - 0.1):(0.01 - 0.1).

[0011] In some embodiments of the present invention, the structural formula of bis(4,1-hydroxybenzyl) diselenide is .

[0012] In some embodiments of the present invention, in step (2), the organic solvent includes tetrahydrofuran; the second catalyst is selected from one or more of triethylamine, pyridine, or pyridine derivatives, which can improve the reaction rate and efficiency, and it has basicity and can adjust the acidity and basicity of the reaction system. Specifically, it can be triethylamine or pyridine, 2-pyridinemethanol, etc. These substances also have a catalytic effect and can adjust the acidity and basicity of the reaction environment; The non-reactive gas in the inert atmosphere includes nitrogen and / or argon.

[0013] In some embodiments of the present invention, in step (3), the concentration of the SeOE polymer solution is 1 - 1000 mg / mL. Exemplarily, it can be 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 mg / mL, etc.

[0014] In some embodiments of the present invention, in step (3), the concentration of the polyvinyl alcohol solution is 0.1-10 wt%, and exemplarily, it can be 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 wt%.

[0015] In some embodiments of the present invention, in step (3), the emulsification time is 1-30 minutes; the homogenization time is 1-30 minutes.

[0016] In some embodiments of the present invention, the structural formula of epigallocatechin gallate (EGCG) is ; The above technical solutions of the present invention have the following advantages compared with the prior art: The present invention adopts a brand-new synthesis method to synthesize polydiselenide-oxalate-EGCG with a ROS-sensitive chemical structure, and uses the nanoprecipitation technique to further emulsify the SeOE polymer to obtain ROS-responsive SeOE nanoparticles (SeOE-NP). By introducing a ROS-sensitive chemical moiety, the present invention improves the ROS scavenging ability of the targeted delivery polymer and the oxidation stability of EGCG. Description of the Drawings

[0017] In order to make the content of the present invention easier to be clearly understood, the following further details the present invention according to the specific embodiments of the present invention and in combination with the drawings, wherein, Figure 1 is the 1H NMR spectrum of EGCG, bis(4,1-hydroxybenzyl) diselenide and SeOE polymer obtained in Example 1 of the present invention.

[0018] Figure 2 is the infrared spectrum of SeOE-NP and EGCG obtained in Example 1 of the present invention.

[0019] Figure 3 is the TEM image of SeOE-NP obtained in Example 1 of the present invention.

[0020] Figure 4 is the particle size distribution curve of SeOE-NP obtained in Example 1 of the present invention.

[0021] Figure 5 is the ultraviolet absorption spectrum of EGCG obtained in Example 1 of the present invention.

[0022] Figure 6 is the standard curve of EGCG of the present invention.

[0023] Figure 7 is the stability of EGCG of the present invention.

[0024] Figure 8 It is the release curve diagram of EGCG under different pH conditions of the present invention.

[0025] Figure 9 It is the release curve of EGCG in SeOE-NP by different concentrations of H2O2 in PBS of the present invention. Detailed implementation manners

[0026] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the specific embodiments cited are not intended to limit the present invention.

[0027] Example 1 This example provides the synthesis and characterization of nanoparticles (SeOE-NPs). I. Synthesis of nanoparticles (SeOE-NPs) 1. Synthesis of bis(4,1-hydroxybenzyl) diselenide Weigh 0.0234 g of p-iodobenzyl alcohol and dissolve it in DCM. Cool the temperature to 0 °C, add 100 μL of DCM solution containing 0.2806 g of isobutene and 200 μL of concentrated sulfuric acid as a catalyst, and react at room temperature for 48 hours. Wash the reaction solution with sodium bicarbonate solution, dry the organic phase with anhydrous sodium sulfate, filter, and concentrate to obtain compound B (1-[(tert-butoxy)methyl]-4-iodobenzene). Under nitrogen protection, weigh 0.0290 g of compound B and dissolve it in DMSO, add 0.1974 g of selenium powder, 0.008 g of CuO and 0.1403 g of KOH, react at 90 °C for 20 hours, add saturated NaCl solution, extract the organic phase with ethyl acetate, wash the organic phase with water, dry, filter, and concentrate to obtain the crude product of compound C (1-[(tert-butoxy)methyl]-4-({4-[(tert-butoxy]methyl]phenyl}disilanyl)benzene). The obtained crude product of compound C is dissolved in DCM, add TFA and react for 3 hours, concentrate, and purify by column chromatography to obtain compound D (bis(4,1-hydroxybenzyl) diselenide). The obtained compound D is subjected to structure characterization, and the results are shown in Figure 1 .

[0028] 2. Preparation of poly(diselenide-oxalate-EGCG) (SeOE) Weigh 0.0138 g of epigallocatechin gallate (EGCG), 0.0486 g of bis(4,1-hydroxybenzyl) diselenide, and 0.0253 g of pyridine and dissolve them in dry tetrahydrofuran (40 mL). Stir the mixture at 4 °C under a nitrogen atmosphere to obtain a mixed solution containing EGCG. Then, weigh 0.0406 g of oxalyl chloride and dissolve it in 20 mL of dry tetrahydrofuran. Slowly add the solution dropwise to the above-mentioned mixed solution containing EGCG and react for 6 h. After the reaction, dissolve it in DCM, extract it with saturated sodium chloride solution, dry it with anhydrous sodium sulfate, filter it, precipitate it with n-hexane at -20 °C overnight, filter it, and rotary evaporate the filtrate to obtain the SeOE polymer.

[0029] 3. Synthesis of nanoparticles (SeOE-NPs) Dissolve the SeOE polymer in tetrahydrofuran at a concentration of 150 mg / mL. Drop 700 μL of the SeOE polymer into 10 mL of polyvinyl alcohol (5 wt%) and ultrasonically emulsify it for 2 minutes to obtain an emulsion containing the SeOE polymer. Add the obtained emulsion to 10 mL of polyvinyl alcohol (0.5 wt%) and homogenize it for 2 minutes to form the final emulsion. Then, centrifuge it at 1500 g for 5 min. Finally, wash it twice with deionized water, centrifuge it at 15000 rpm for 10 min, and freeze-dry it to obtain SeOE-NPs nanoparticles.

[0030] II. Characterization 1. Qualitative analysis of the chemical structure of the synthesized SeOE polymer - nuclear magnetic resonance hydrogen spectrum, and the results are shown in Figure 1 . It can be seen from Figure 1 that the appearance of the absorption peak at 4.71 ppm is attributed to the methylene proton adjacent to the oxalate bond in EGCG, and the appearance of the absorption peak at 2.31 ppm is attributed to the methylene proton adjacent to the oxalate bond in the diselenide. Through the nuclear magnetic spectrum data, it can be determined that the product structure is correct and it is the target product, the SeOE polymer.

[0031] 2. Qualitative analysis of the chemical structure of the synthesized SeOE polymer - infrared spectrum, and the results are shown in Figure 2 . It can be seen from Figure 2 that in SeOE, the absorption peak at 2855 cm -1 is the stretching vibration of the methyl group, and the characteristic absorption peak appearing at 17333 cm -1 is caused by the stretching vibration of C=O of the oxalate ester bond. In EGCG, the absorption peak of C=O is located at 1694 cm -1 , and SeOE has a red shift. At 1594 cm -1The absorption peak that appears is caused by the C=C skeletal vibration of the benzene ring in EGCG and the diselenide compound. The above infrared spectroscopy analysis shows that EGCG and bis(4,1-hydroxybenzyl) diselenide react with oxalyl chloride to form peroxyoxalate bonds, proving the successful synthesis of the SeOE polymer.

[0032] 3. Structural characterization was performed on the synthesized SeOE-NPs nanoparticles, and the results are shown in Figure 3 (TEM image) and Figure 4 (particle size distribution curve). As Figure 3 can be seen, the synthesized SeOE-NP was confirmed by TEM, showing that the nanoparticles are spherical and of uniform size, and are individually dispersed. In addition, in the presence of H2O2 (5 mM), the spherical morphology of SeOE-NP ruptured. This is because the stimulation of H2O2 causes the peroxyoxalate bond to break, and SeOE-NP hydrolyzes, resulting in the rupture of SeOE-NP.

[0033] As Figure 4 can be seen, the SeOE-NP measured by DLS is irregularly spherical, with a particle size of 217.7 nm. The nanoparticles swell in aqueous solution, and the nanoparticle size is uniform and evenly dispersed. In addition, the particle size of SeOE-NP in PBS is 297 nm, which is larger than that of SeOE-NP in water, and the nanoparticles are relatively uniform. This is because SeOE-NP has poor stability in PBS (pH = 7.4). The particle size distribution in H2O2 shows two peaks, at 403.7 nm and 5419 nm respectively. This is because the stimulation of H2O2 destroys the bond structure of diselenate and peroxyoxalate, disrupts the hydrophilic-hydrophobic balance of SeOE-NP, resulting in the generation of hydrophobic EGCG in the medium, increasing its diameter, further indicating that SeOE-NP has ROS responsiveness.

[0034] 4. The ultraviolet absorption spectrum of EGCG was detected, and the results are shown in Figure 5 and Figure 6 . Figure 5 is the ultraviolet absorption spectrum of EGCG. From the data in the figure, it can be seen that the absorbance value of EGCG at 272 nm increases with the increase of the solution concentration; as Figure 6 of the standard curve shows, the correlation coefficient between the absorbance value of EGCG and its corresponding solution concentration curve is 0.9993, indicating that its correlation meets the requirements.

[0035] Performance Test 1. The stability of free EGCG and SeOE polymers under oxidative conditions was evaluated and compared by incubating them in a medium containing H2O2 (100 mM). Experimental procedure: 100 μL of EGCG solution (EGCG dissolved in DMSO at a concentration of 200 μg / mL) or SeOE-NP (equivalent to 200 μg / mL of EGCG) was added to 1 mL of PBS (0.01 M, pH = 7.4), and H2O2 was added to a final concentration of 100 mM. The mixture was incubated in a thermostatic shaker (37 °C, 120 rpm). Samples of 500 μL were taken at 0, 10, 20, and 30 minutes, and 500 μL of fresh PBS was added. According to the pre-established standard curve, the content of EGCG in the collected samples was measured using a UV spectrophotometer (Shimadzu, UV1800), and the measurement was monitored at 272 nm. The experimental results are shown in Figure 7 . As can be seen from the figure, the amount of free EGCG in the medium containing H2O2 decreased to 27.24 ± 3.36% within 30 minutes, indicating that free EGCG could be rapidly degraded. The content of EGCG in SeOE-NP only decreased to 83.39 ± 3.15%. The degradation amount of EGCG in SeOE-NP in the oxidative environment was significantly lower than that of free EGCG, and the stability of EGCG in SeOE-NP was higher than that of free EGCG, indicating that SeOE-NP could effectively protect EGCG from oxidative degradation.

[0036] 2. In vitro release of EGCG from SeOE-NP Specific experimental steps: 100 μL of SeOE-NP (equivalent to 200 μg / mL of EGCG) was added to 1 mL of PBS (at pH = 3.0, 5.0, and 7.4, respectively, 0.01 M), and the mixture was incubated in a thermostatic shaker (37 °C, 120 rpm). Samples of 500 μL were taken at 1, 2, 4, 8, 12, 18, and 24 hours, and 500 μL of fresh PBS was added. The content of EGCG was measured using a UV spectrophotometer. The experimental results are shown in Figure 8 . As Figure 8As shown, after incubation of SeOE-NP in PBS (pH = 3.0) for 24 h, the release amount of EGCG from SeOE-NP was 28.39 ± 0.64%. After incubation in PBS (pH = 5.0) for 24 h, the release amount of EGCG from SeOE-NP was 41.24 ± 0.17%. After treatment in PBS (pH = 7.4) for 1 h and 24 h, the release amounts of EGCG from SeOE-NP reached 33.12 ± 0.66% and 81.97 ± 2.06% respectively. It can be seen that SeOE-NP showed good stability under acidic conditions, but poor stability at pH = 7.4, which may be due to water promoting the hydrolysis degradation of the diperoxalate bond and the release of EGCG, and then the further degradation of EGCG under alkaline conditions.

[0037] 3. Release curves of EGCG from SeOE-NP in PBS with different concentrations of H2O2 To evaluate the controlled release behavior of EGCG in SeOE-NP, a dialysis solution containing 0.5 wt% Tween 80 and 4 mL of PBS with different concentrations (0, 1, 5 or 10 mM) of H2O2 was prepared. A dialysis bag (1000D, Φ10 mm) containing 1 mL of the sample (1 mg / mL SeOE-NP) was immersed in the dialysis solution. 500 μL of the release medium was sampled at 1, 2, 4, 6, 8, 10, 12 and 24 hours, and 500 μL of fresh release medium was added. The content of EGCG in the release medium was determined by ultraviolet spectrophotometer according to the above method. The experimental results are as Figure 9 shown. In the absence of H2O2, the cumulative release amount of EGCG was 35.09 ± 0.29%. After stimulation with 5 mM and 10 mM of H2O2 for 24 h, SeOE-NP released 85.75 ± 1.35% and 95.46 ± 1.58% of EGCG respectively. The increase in the release amount of EGCG was attributed to the oxidation of the diselenide and diperoxalate bonds by H2O2, resulting in the disintegration of SeOE-NP and the release of EGCG. In summary, these results indicate that SeOE-NP is an effective ROS-responsive drug release system.

[0038] Obviously, the above embodiments are only examples for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. A method for encapsulating nanoscale targeted health intervention nutritional components, characterized in that, It includes the following steps: (1) Add a catalyst containing isobutene to the iodobenzyl alcohol or tert-butyldimethylchlorosilane solution, and react to obtain 1-[(tert-butoxy)methyl]-4-iodobenzene; under an inert atmosphere, add selenium powder, a first catalyst, and a base to the 1-[(tert-butoxy)methyl]-4-iodobenzene solution, and react to obtain 1-[(tert-butoxy)methyl]-4-({4-[(tert-butoxy)methyl]phenyl}disilanyl)benzene. Dissolve the product in an organic solvent, and add trifluoroacetic acid to react to obtain bis(4,1-hydroxybenzyl) diselenide; (2) Dissolve the bis(4,1-hydroxybenzyl) diselenide, epigallocatechin gallate, and a second catalyst in an organic solvent to obtain a mixed solution containing epigallocatechin gallate; under an inert atmosphere, stir, and dropwise add an oxalyl chloride solution to the mixed solution containing epigallocatechin gallate to react to obtain a SeOE polymer; (3) Emulsify and homogenize the SeOE polymer solution and the polyvinyl alcohol solution, centrifuge and freeze-dry to obtain the SeOE polymer nanoparticles; The structural formula of the SeOE polymer is as follows: .

2. The nano-level targeted health intervention nutrient encapsulation method according to claim 1, characterized in that In step (1), the catalyst containing isobutene further includes concentrated sulfuric acid; The reaction temperature for preparing 1-[(tert-butoxy)methyl]-4-iodobenzene is 0°C - 25°C, and the reaction time is 12 - 72 h; The inert gas in the inert atmosphere includes nitrogen and / or argon; The first catalyst is selected from one or more of CuO, MnO2, Fe2O3, and Co3O4; The base is selected from one or more of KOH, Ca(OH)2, Mg(OH)2, and Na2CO3.

3. The nano-level targeted health intervention nutrient encapsulation method according to claim 1, characterized in that, In step (1), the mass ratio of iodobenzyl alcohol to isobutene is (0.01 - 0.1):(0.1 - 0.5).

4. The nano-level targeted health intervention nutritional ingredient embedding method according to claim 1, wherein In step (1), the mass ratio of 1-[(tert-butoxy)methyl]-4-iodobenzene, selenium powder, the first catalyst, and the base is (0.02 - 0.1):(0.1 - 0.5):(0.01 - 0.1):(0.1 - 0.5).

5. The nano-level targeted health intervention nutrient encapsulation method according to claim 1, wherein In step (1), the reaction conditions for preparing 1-[(tert-butoxy)methyl]-4-({4-[(tert-butoxy)methyl]phenyl}disilanyl)benzene are: the temperature is 50 - 100°C, and the time is 12 - 48 hours.

6. The nano-level targeted health intervention nutrient encapsulation method according to claim 1, characterized in that, In step (2), the mass ratio of bis(4,1-hydroxybenzyl) diselenide, epigallocatechin gallate, the second catalyst, and oxalyl chloride is (0.01 - 0.1):(0.01 - 0.1):(0.01 - 0.1):(0.01 - 0.1).

7. The nano-level targeted health intervention nutrient encapsulation method according to claim 1, characterized in that, In step (2), the reaction temperature is 0°C - 25°C, and the reaction time is 6 - 24 h; The second catalyst includes one or more of triethylamine, pyridine, or pyridine derivatives; The inert gas in the inert atmosphere includes nitrogen and / or argon.

8. The nano-level targeted health intervention nutrient encapsulation method according to claim 1, wherein In step (3), the concentration of the SeOE polymer solution is 1 - 1000 mg / mL.

9. The nano-level targeted health intervention nutritional ingredient embedding method according to claim 1, wherein In step (3), the concentration of the polyvinyl alcohol solution is 0.1 - 10 wt%.

10. The nano-level targeted health intervention nutritional ingredient embedding method according to claim 1, wherein In step (3), the emulsification time is 1 - 30 minutes; the homogenization time is 1 - 30 minutes.

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