Hydrophilic tocotrienol nanoparticles as well as preparation method and application thereof

Abstract

The invention belongs to the field of hydrophilic nano-particles, and discloses hydrophilic tocotrienol nano-particles as well as a preparation method and application thereof. The hydrophilic type tocotrienol nano particles comprise tocotrienol and a water-soluble carrier, and the tocotrienol is loaded on the water-soluble carrier. The water-soluble carrier is one or a combination of beta-lactoglobulin (beta-LG) and carboxymethyl chitosan (CMS). According to the invention, beta-LG and / or CMS are / is used as a carrier, so that the water solubility, the stability and the biological accessibility of tocotrienols are greatly improved. Oily tocotrienols can be converted into solid tocotrienols to be stored, the redissolving effect is good, and the material storage and transportation convenience is greatly improved.

Description

Technical Field

[0001] This invention belongs to the field of hydrophilic nanoparticles, and specifically relates to a hydrophilic tocotrienol nanoparticle, its preparation method, and its application. Background Technology

[0002] Vitamin E comprises tocopherol (TOC) and tocotrienol (T3), both existing in four configurations: α, β, γ, and δ. T3 is primarily derived from palm oil, rice bran oil, annatto seed oil, barley, and wheat germ, and possesses a variety of biological activities. Compared to TOC, T3 exhibits stronger antioxidant, anti-inflammatory, and anticancer activities. However, its poor water solubility, instability, and low bioavailability limit its application in functional foods. Traditional delivery systems are mainly oil-in-water emulsions, often relying on large amounts of surfactants, resulting in inconsistent stability and difficulty in effectively addressing the numerous challenges of preserving and using liquid products. Therefore, developing a nanoparticle preparation technology to enhance the performance of T3 is of great significance. Summary of the Invention

[0003] In order to overcome the shortcomings and deficiencies of the prior art, the primary objective of this invention is to provide a hydrophilic tocotrienol nanoparticle, which has high loading capacity, good stability, and can transform tocotrienol from an oily liquid to a solid powder form, thereby improving its convenience for storage and transportation.

[0004] Another objective of this invention is to provide hydrophilic tocotrienol nanoparticles prepared by the above method.

[0005] Another object of the present invention is to provide the application of the above-mentioned hydrophilic tocotrienol nanoparticles.

[0006] The objective of this invention is achieved through the following solution: A hydrophilic tocotrienol nanoparticle comprising tocotrienol and a water-soluble carrier, wherein the tocotrienol is loaded onto the water-soluble carrier.

[0007] The tocotrienol is at least one of α-tocotrienol, β-tocotrienol, γ-tocotrienol, or δ-tocotrienol.

[0008] The mass ratio of the tocotrienol to the water-soluble carrier is 1:(2.5~20), more preferably 1:(2.5~10).

[0009] The water-soluble carrier is one or a combination of β-lactoglobulin (β-LG) and carboxymethyl chitosan (CMS), preferably β-lactoglobulin (β-LG).

[0010] A method for preparing the above-mentioned hydrophilic tocotrienol nanoparticles includes the following steps: First, tocotrienol is dissolved in anhydrous ethanol to obtain a tocotrienol alcohol solution. The carrier is dissolved in water to obtain a carrier aqueous solution. Then, using the antisolvent precipitation method, the tocotrienol alcohol solution is added to the carrier aqueous solution under stirring conditions, and the reaction is continued to be stirred. The ethanol is then removed by vacuum evaporation to prepare a hydrophilic tocotrienol nanoparticle dispersion. Solid nanoparticle powder can be obtained by freeze drying.

[0011] The concentration of the tocotrienol solution is 5~40 mg / mL; The concentration of the carrier aqueous solution is 5~20 mg / mL; The volume ratio of the tocotrienol solution to the carrier aqueous solution is (1~2.5):10; The stirring reaction refers to a stirring reaction at room temperature for 5 to 30 minutes, more preferably 5 to 10 minutes. Stirring is only to ensure sufficient contact between the raw materials, therefore the stirring speed is not limited.

[0012] The above-mentioned hydrophilic tocotrienol nanoparticles are used in the preparation of health foods or medicines.

[0013] Compared with the prior art, the present invention has the following advantages and beneficial effects: 1. This invention utilizes β-LG and / or CMS as carriers, which greatly improves the water solubility, stability and bioavailability of tocotrienols.

[0014] 2. This invention can convert oily tocotrienols into solid form for storage, and has a good resolubility effect, which greatly improves the convenience of material storage and transportation.

[0015] 3. The preparation method of the present invention involves a simple and safe production process, which is suitable for mass production. Attached Figure Description

[0016] Figure 1 This is an atomic force microscope image of β-LG and tocotrienol nanoparticles (TBNPs) from Example 1. Figure 2 The appearance (A), particle size distribution (B), and zeta potential (C) of the tocotrienol nanoparticles (TBNPs) of Example 1 under different pH conditions are shown. Figure 3 The appearance (A), particle size distribution (B), and zeta potential (C) of the tocotrienol nanoparticles (TBNPs) of Example 1 in NaCl solutions of different concentrations are shown. Figure 4The changes in appearance (A), particle size distribution (B), and zeta potential (C) of the tocotrienol nanoparticles (TBNPs) of Example 1 during long-term storage are shown. Figure 5 The bioavailability (A), particle size distribution (B), and zeta potential (C) of the tocotrienol nanoparticles (TBNPs) of Example 1 during a simulated digestion process are shown. Figure 6 These are comparative images of the appearance of tocotrienol nanoparticles TBNPs (Example 1), TCNPs (Example 5), and TNPs (Example 6) after freeze-drying and rehydration.

[0017] Figure 7 These are comparative images showing the appearance of tocotrienol dispersions before and after centrifugation using the blank carrier and different hydrophilic carriers. A, C: Blank carrier before and after centrifugation; B, D: Mixed dispersion samples before and after centrifugation; a: β-lactoglobulin; b: chitosan; c: carboxymethyl chitosan; d: β-cyclodextrin; e: methyl-β-cyclodextrin; f: pectin; g: whey protein. Detailed Implementation

[0018] The present invention will be further described in detail below with reference to embodiments and accompanying drawings, but the embodiments of the present invention are not limited thereto. Unless otherwise specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products.

[0019] The terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product, or device that includes a series of steps is not limited to the steps or modules listed, but may optionally include steps not listed, or may optionally include other steps inherent to such process, method, product, or device.

[0020] In this invention, "multiple" refers to two or more. "And / or" describes the relationship between related objects, indicating that there can be three relationships. For example, A and / or B can represent three situations: A exists alone, A and B exist simultaneously, and B exists alone.

[0021] Example 1: Preparation of Tocotrienol Nanoparticles (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add β-LG (Shanghai Aladdin Biochemical Technology Co., Ltd.) to deionized water at a concentration of 10 mg / mL, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the β-LG solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain a dispersion of tocotrienol-loaded β-LG nanoparticles (TBNPs). After freeze-drying, TBNPs solid powder was obtained.

[0022] The tocotrienol nanoparticles (TBNPs) were characterized as follows: (1) Analysis of drug loading Accurately weigh 10 mg of TBNPs solid powder, add it to 2 mL of anhydrous ethanol, sonicate for 10 min, centrifuge, take the supernatant, remove the ethanol using a nitrogen blower, add an equivalent amount of n-hexane, filter through a membrane, and determine the content of tocotrienols in TBNPs by ultra-high performance liquid chromatography.

[0023] The results showed that the average drug loading of tocotrienols in TBNPs was 17.49%. Higher drug loading can reduce the use of large amounts of excipients and control costs.

[0024] (2) Determination of particle size, polydispersity index (PDI) and zeta potential The particle size distribution and zeta potential of the TBNPs were analyzed using a Malvern Nano ZS particle size analyzer at 25°C, with each sample measured in triplicate.

[0025] The average particle size of TBNPs in the TBNPs dispersion obtained in this example is 158.63 nm, and the PDI is 0.16, indicating that the particle size distribution of the TBNPs is relatively concentrated; the Zeta potential is -35.83 mV, and the high absolute value of the potential indicates that the sample has good physical stability.

[0026] (3) Observation by atomic force microscopy The morphology of TBNPs was observed using atomic force microscopy. The freshly prepared particle dispersion was diluted with deionized water to a β-LG concentration of 10 μg / mL (1000-fold dilution). A 5 μL sample was deposited on the surface of freshly split mica sheets and then air-dried at room temperature. Tests were performed at room temperature using a tapping mode.

[0027] The results are as follows Figure 1 As shown, atomic force microscopy reveals that β-LG forms heterogeneous, aggregated particles with relatively large particle size and height. TBNPs, on the other hand, are spherical, well-dispersed, and have smaller particle size and height.

[0028] (4) Stability analysis of TBNPs in physiological pH environment The samples (i.e., the tocotrienol nanoparticle dispersion prepared in step (3)) were adjusted to different pH values ​​(1.5 and 7.0) using hydrochloric acid (1.5 or 0.1 M) or sodium hydroxide (1.5 or 0.1 M). After the samples were stored at 4 °C for 24 h, the appearance of all samples was observed and recorded, and their particle size distribution and zeta potential were analyzed.

[0029] The results are as follows Figure 2 As shown, TBNPs remained stable at physiological pH, appearing as a milky-white homogeneous dispersion with no significant changes in appearance. The particle size distribution remained largely unchanged. With pH adjustment to 1.5, the potential significantly increased to a positive value (35.10 mV), while no significant change was observed at pH 7. This indicates that the sample is stable in a physiological pH environment.

[0030] (5) Stability analysis of TBNPs at different salt ion concentrations In this embodiment, different amounts of NaCl powder were added to the TBNPs dispersion to obtain TBNPs solutions with different sodium chloride mass concentrations (0.5%, 1%, 2%, and 3%). After the solutions were stored at 4°C for 24 h, the appearance of all samples was observed and recorded, and their particle size distribution and zeta potential were analyzed.

[0031] The results are as follows Figure 3 As shown, the appearance, particle size distribution, and potential of TBNPs did not change significantly. This indicates that the salt ions have good stability and did not disrupt the original state.

[0032] (6) Storage stability analysis of TBNPs The TBNPs dispersion obtained in this example was stored at 4°C for 30 days to determine its storage stability. The appearance of the samples was recorded, and their particle size distribution and zeta potential were analyzed.

[0033] The results are as follows Figure 4 As shown in the figure. According to the particle size distribution diagram, overall, the particle size distribution curve of TBNPs did not change much during storage at 4℃, while the potential decreased slightly. This indicates that TBNPs can remain stable during long-term storage.

[0034] (7) Biological accessibility of TBNPs The bioavailability of TBNPs during digestion was evaluated using in vitro simulated digestion. During digestion, an equal amount of tocotrienols was added to water as a control for free tocotrienols. The simulated digestion experiment was conducted as follows.

[0035] Gastric digestion: Take 5 mL of the freshly prepared TBNPs dispersion from step (3), adjust the pH to 1.5 with 1 M HCl, and then mix with 5 mL of simulated gastric juice SGF (2.0 mg / mL NaCl, 3.2 mg / mL pepsin, pH 1.5). Incubate at 37°C in a shaker (100 rpm) for 1 h. For the control group, use 5 mL of an aqueous dispersion containing an equivalent amount of tocotrienols as the free T3 group.

[0036] Small intestinal digestion: After gastric digestion, 5 mL of the digested sample was removed and immediately adjusted to pH 7.0 with 4 M NaOH. It was then mixed with an equal volume of simulated intestinal fluid SIF (8.8 mg / mL NaCl, 6.8 mg / mL KH₂PO₄, 5 mg / mL bile salts, 2 mg / mL trypsin, pH 7.0). The mixture was incubated at 37 °C and 100 rpm for 2 h.

[0037] The bioavailability of TBNPs and free tocotrienols was investigated during digestion. After digestion, the samples were centrifuged, and the micelle phase was mixed with 9 volumes of anhydrous ethanol. Then, 2 volumes of n-hexane were added, and the mixture was vortexed for 2 min. After centrifugation, the upper n-hexane phase was collected and its content was determined by high-performance liquid chromatography (HPLC). Bioavailability was calculated using the following formula: Biological accessibility (%) = ms / mi × 100 (Equation 1) Where ms and mi represent the mass of tocotrienols in the micelle phase after small intestinal digestion and the initial mass of tocotrienols in the entire system.

[0038] The results are as follows Figure 5 As shown, the bioavailability of free tocotrienols is only 0.44%, while that of TBNPs is as high as 60%, indicating that TBNPs can significantly improve the bioavailability of tocotrienols. During gastric digestion, the particle size distribution of TBNPs changes little, and the potential change is positive, corresponding to pH 1.5; while during small intestinal digestion, due to the presence of bile salt micelles, the particle size shows a bimodal distribution. The first peak, less than 100 nm, corresponds to micellar particles, and the second peak corresponds to particles that have not entered the micellar structure.

[0039] Example 2: Preparation of Tocotrienol Nanoparticles (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 10 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add β-LG to deionized water at a concentration of 10 mg / mL, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the β-LG solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain a dispersion of tocotrienol-loaded β-LG nanoparticles (TBNPs). After freeze-drying, TBNPs solid powder was obtained.

[0040] The average drug loading of the TBNPs obtained in this embodiment was 8.91%; the average particle size was 143.1 nm; the PDI value was 0.17; and the Zeta potential was -32.33 mV. The TBNPs exhibited high stability: the particle size potential distribution was relatively stable under pH 1.5 and pH 7.0 conditions, in NaCl solution (0.5%–3%), and after being placed at 4°C for 1 month. No stratification, deterioration, or precipitation was observed in the solution.

[0041] Example 3: Preparation of Tocotrienol Nanoparticles (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 30 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add β-LG to deionized water at a concentration of 10 mg / mL, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the β-LG solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain a dispersion of tocotrienol-loaded β-LG nanoparticles (TBNPs). After freeze-drying, TBNPs solid powder was obtained.

[0042] The average drug loading of the TBNPs obtained in this embodiment was 21.25%; the average particle size was 187.3 nm; the PDI value was 0.17; and the Zeta potential was -40.13 mV. The TBNPs exhibited high stability: the particle size potential distribution remained relatively stable under pH 1.5 and pH 7.0 conditions, in NaCl solution (0.5%–3%), and after being placed at 4°C for one month. No stratification, deterioration, or precipitation was observed in the solution.

[0043] Example 4: Preparation of Tocotrienol Nanoparticles (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 40 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add β-LG to deionized water at a concentration of 10 mg / mL, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the β-LG solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain a dispersion of tocotrienol-loaded β-LG nanoparticles (TBNPs). After freeze-drying, TBNPs solid powder was obtained.

[0044] The TBNPs obtained in this embodiment had an average drug loading of 25.08%, an average particle size of 198.6 nm, a PDI value of 0.21, and a Zeta potential of -43.7 mV. The TBNPs exhibited high stability: the particle size potential distribution remained relatively stable under pH 1.5 and pH 7.0 conditions, in NaCl solution (0.5%–3%), and after being placed at 4°C for one month. No stratification, deterioration, or precipitation was observed in the solution.

[0045] Example 5: Preparation of Tocotrienol Nanoparticles (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add carboxymethyl chitosan (CMS) at a concentration of 10 mg / mL to deionized water, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the CMS solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain a dispersion of tocotrienol-loaded CMS nanoparticles (TCNPs). After freeze-drying, TCNPs solid powder was obtained.

[0046] The average drug loading of the TCNPs obtained in this example was 16.02%; the average particle size was 435.47 nm, the PDI value was 0.34, and the Zeta potential was -63.77 mV. The drug loading of TCNPs was close to that of TBNPs (including Examples 1-4), but the stability was slightly worse. Significant precipitation occurred under pH 1.5 and pH 7.0 conditions. After being placed in NaCl solution (0.5% to 3%), the particle size potential distribution was relatively stable, and no layering, deterioration, or precipitation was observed in the solution. After being placed at 4°C for 1 month, the particle size distribution shifted significantly to the right, and the particle size increased.

[0047] Example 6: Preparation of Tocotrienol Nanoparticles (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Under stirring conditions, the tocotrienol alcohol solution from step (1) was added to deionized water at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain a carrier-free tocotrienol nanoparticle (TNPs) dispersion.

[0048] The TNPs obtained in this embodiment had an average particle size of 184.7 nm, a PDI value of 0.22, and a Zeta potential of -25.3 mV. The particle size of the TNPs was similar to that of TBNPs (including Examples 1-4), but their stability was poor. Large particles formed under pH 1.5 conditions, and precipitation occurred after centrifugation. In 0.5% NaCl solution, the particle size distribution shifted significantly to the right, while in 1%–3% NaCl solutions, the milky white color disappeared, and a small amount of oil droplets appeared, indicating particle breakage and disappearance. After being placed at 4°C for one month, the particle size distribution shifted significantly to the right. Furthermore, due to the absence of a carrier, obvious oil droplets were visible precipitating on the water surface of the TNPs. Figure 6 As shown, TNPs revert to oily droplets after freeze-drying and cannot be reconstituted with water (reconstitution refers to reconstitution to the volume before freeze-drying), making it difficult to preserve in solid form. In contrast, TBNPs and TCNPs can both form solid powders after freeze-drying, with good reconstitution effect (10 mg / mL), which greatly improves the convenience of storage and transportation of tocotrienols.

[0049] Comparative Example 1: Preparation of Tocotrienol Dispersion (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Chitosan (CS) was added to 1% acetic acid aqueous solution at a concentration of 10 mg / mL and stirred to dissolve, thus preparing a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the CS solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain the tocotrienol-CS dispersion (TCSD). The state of the dispersion before and after centrifugation (8000g, 10 min) was observed.

[0050] The TCSD state obtained in this comparative example is relatively stable, such as Figure 7 row A and column b Figure 7 As shown in row C and column b, CS is a colorless, transparent, and clear solution before and after centrifugation. After adding tocotrienol, it forms a white emulsion. Figure 7 (row B, column b), a small number of oil droplets were visible adhering to the bottle wall. After centrifugation, a small amount of sediment and slight stratification were produced. Figure 7Therefore, a uniform nanoparticle dispersion cannot be formed due to the (D row, b column) of the carbon dioxide. Furthermore, the dissolution of chitosan requires an acidic solution, and the preparation process involves pH changes, making it quite complex.

[0051] Comparative Example 2: Preparation of Tocotrienol Dispersion (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add β-cyclodextrin (BCD) to deionized water at a concentration of 10 mg / mL, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the BCD solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain the tocotrienol-BCD dispersion (TBD). The state of the dispersion before and after centrifugation (8000g, 10 min) was observed.

[0052] The TBD state obtained in this comparative example is not stable, such as Figure 7 As shown in row A, column d and row C, columns d and d, BCD are colorless, transparent, and clear solutions before and after centrifugation. After adding tocotrienol, they form a white emulsion. Figure 7 (row B, column d), obvious white deposits were visible on the bottle wall. After centrifugation, a large amount of precipitate was produced ( Figure 7 (D rows and d columns), therefore a uniform nanoparticle dispersion cannot be formed.

[0053] Comparative Example 3: Preparation of Tocotrienol Dispersion (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add 10 mg / mL of methyl-β-Cyclodextrin (MBCD) to deionized water, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the MBCD solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain the tocotrienol-MBCD dispersion (TMBD). The state of the dispersion before and after centrifugation (8000g, 10 min) was observed.

[0054] The TMBD state obtained in this comparative example is not stable, such as Figure 7As shown in row A, column e and row C, column e, MBCD is a colorless, transparent, and clear solution before and after centrifugation. After adding tocotrienol, it forms a white emulsion. Figure 7 (in row B and column e), a small number of oil droplets are visible adhering to the bottle wall. After centrifugation, precipitation and stratification occur. Figure 7 (D rows and e columns), therefore a uniform nanoparticle dispersion cannot be formed.

[0055] Comparative Example 4: Preparation of Tocotrienol Dispersion (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add citrus pectin at 10 mg / mL to deionized water, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol solution from step (1) was added to the pectin solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain the tocotrienol-pectin dispersion (TPD). The state of the dispersion before and after centrifugation (8000 g, 10 min) was observed.

[0056] The TPD state obtained in this comparative example is not stable, such as Figure 7 As shown in row A and column f, pectin appears as a yellowish-brown turbid liquid, with a small amount of precipitate after centrifugation. Figure 7 The solution in row C, column f is a yellow, transparent solution. After adding tocotrienol, it becomes a yellow emulsion. Figure 7 (in row B, column f), turbidity increases, and a large number of oil droplets are visible adhering to the bottle wall. After centrifugation, precipitation and stratification occur. Figure 7 Therefore, a uniform nanoparticle dispersion cannot be formed due to the D row and f column.

[0057] Comparative Example 5: Preparation of Tocotrienol Dispersion (1) Dissolve δ-tocotrienol in anhydrous ethanol at a concentration of 20 mg / mL to prepare an ethanol solution of tocotrienol; (2) Add whey protein at a concentration of 10 mg / mL to deionized water, stir to dissolve, and prepare a carrier solution; (3) Under stirring conditions, the tocotrienol alcohol solution from step (1) was added to the pectin solution from step (2) at a volume ratio of 1:10. After stirring for 10 min at room temperature, the ethanol was removed by vacuum evaporation to obtain the tocotrienol-Whey protein dispersion (TWPD). The state of the dispersion before and after centrifugation (8000 g, 10 min) was observed.

[0058] The TWPD state obtained in this comparative example is not stable, such as Figure 7 As shown in row A and column g, whey protein appears as a white emulsion, and after centrifugation, a significant amount of precipitate forms. Figure 7 (C row g column), after adding tocotrienol, a white emulsion was formed ( Figure 7 (row B, column g), turbidity increases, and after centrifugation, more precipitate is produced ( Figure 7 The main reason for the poor solubility of whey protein is that it cannot form a uniform nanoparticle dispersion.

[0059] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A hydrophilic tocotrienol nanoparticle, characterized in that... It includes tocotrienols and a water-soluble carrier, with the tocotrienols loaded onto the water-soluble carrier.

2. The hydrophilic tocotrienol nanoparticles according to claim 1, characterized in that: The tocotrienol is at least one of α-tocotrienol, β-tocotrienol, γ-tocotrienol, or δ-tocotrienol.

3. The hydrophilic tocotrienol nanoparticles according to claim 1, characterized in that: The tocotrienol is at least one of α-tocotrienol, β-tocotrienol, γ-tocotrienol or δ-tocotrienol; The water-soluble carrier is one or a combination of β-lactoglobulin and carboxymethyl chitosan, preferably β-lactoglobulin.

4. The hydrophilic tocotrienol nanoparticles according to claim 1, characterized in that: The mass ratio of the tocotrienol to the water-soluble carrier is 1:(2.5~20), more preferably 1:(2.5~10).

5. A method for preparing hydrophilic tocotrienol nanoparticles according to any one of claims 1-4, characterized in that... Includes the following steps: First, tocotrienol is dissolved in anhydrous ethanol to obtain a tocotrienol alcohol solution. The carrier is dissolved in water to obtain a carrier aqueous solution. Then, using the antisolvent precipitation method, the tocotrienol alcohol solution is added to the carrier aqueous solution under stirring conditions, and the reaction is continued to be stirred. The ethanol is then removed by vacuum evaporation to prepare a hydrophilic tocotrienol nanoparticle dispersion. Solid nanoparticle powder can be obtained by freeze drying.

6. The method for preparing hydrophilic tocotrienol nanoparticles according to claim 5, characterized in that: The concentration of the tocotrienol solution is 5~40 mg / mL.

7. The method for preparing hydrophilic tocotrienol nanoparticles according to claim 5, characterized in that: The concentration of the carrier aqueous solution is 5~20 mg / mL.

8. The method for preparing hydrophilic tocotrienol nanoparticles according to claim 5, characterized in that: The volume ratio of the tocotrienol solution to the carrier aqueous solution is (1~2.5):

10.

9. The method for preparing hydrophilic tocotrienol nanoparticles according to claim 5, characterized in that: The stirring reaction refers to a stirring reaction at room temperature for 5 to 30 minutes, more preferably 5 to 10 minutes.

10. The application of the hydrophilic tocotrienol nanoparticles according to any one of claims 1-4 in the preparation of health foods or pharmaceuticals.

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