A method for embedding theaflavins in nanometer particles and the embedding product and application thereof

Abstract

The present application belongs to the technical field of nano-embedding and deep processing of tea products, and discloses a direct-drinking teaflavin nano-embedding method, an embedding product and an application. The method comprises the following steps: step 1, nano-carrier screening and modification; step 2, teaflavin pretreatment; step 3, nano-embedding process implementation; and step 4, sealing and packaging of qualified teaflavin nano-embedding products, light-proof treatment, and obtaining of the direct-drinking teaflavin nano-embedding product. The present application provides a direct-drinking teaflavin nano-embedding method and an embedding product, which are suitable for industrialized embedding treatment of teaflavin, can be widely applied in multiple fields such as food, health products, biological medicine and cosmetics, realize efficient embedding, active protection and water-solubility improvement of teaflavin, reduce production cost, realize large-scale production, and expand the application scenarios. The present application overcomes the technical defects of imbalance between embedding rate and activity retention, high cost, difficulty in large-scale production and single application scenario of the prior art.

Description

Technical Field

[0001] This invention belongs to the field of nano-encapsulation technology and deep processing technology of tea products, and in particular, a method for nano-encapsulation of theaflavins for direct consumption, the encapsulated products, and their applications. Background Technology

[0002] Theaflavins are a class of polyphenols formed during the fermentation of black tea. They possess various physiological activities, including antioxidant, anti-inflammatory, lipid-regulating, and cardiovascular-protective effects, making them a core functional active ingredient in direct-drinking tea products with extremely high application value and market potential. However, theaflavins themselves have significant inherent defects that greatly limit their industrial application and promotion: First, theaflavins contain multiple phenolic hydroxyl groups in their molecular structure, making them highly susceptible to oxidation and degradation under conditions such as light, high temperature, and oxygen, leading to a loss of activity; second, theaflavins have poor water solubility and tend to aggregate in aqueous solutions, affecting their dispersibility and solubility in direct-drinking products; third, theaflavins have low bioavailability and are easily degraded by gastrointestinal enzymes after entering the human body, making them difficult for the body to effectively absorb and utilize.

[0003] To address the aforementioned issues, existing technologies employ nano-encapsulation techniques to encapsulate theaflavins. These techniques use carriers to encapsulate theaflavins into nanoscale particles, achieving protection, improved water solubility, and controlled-release delivery. Currently, mainstream nano-encapsulation technologies include nanoemulsions and liposome encapsulation, which have achieved highly efficient theaflavin encapsulation in the laboratory setting. Some technologies achieve bioavailability of up to 85%, and the carriers are increasingly moving towards natural and biodegradable methods. However, existing technologies still have many shortcomings, making it difficult to meet the needs of large-scale production of theaflavins for direct consumption: First, there is an imbalance between encapsulation rate and activity retention. While some methods can improve the encapsulation rate, they can lead to a significant loss of theaflavin activity, or good activity retention but low encapsulation efficiency. Second, there is a contradiction between cost and performance in carrier selection. Natural carriers are not performing well, while high-performance carriers are expensive and difficult to adapt to the cost control requirements of industrial production. Third, large-scale production technologies are not mature, laboratory processes are difficult to directly translate, and equipment adaptability is poor, resulting in low capacity and high cost. Fourth, the application scenarios are limited. Existing encapsulated products are mostly designed for single fields, making it difficult to meet the differentiated needs of multiple fields such as direct consumption, health products, and biomedicine. Fifth, there is insufficient collaboration between industry, academia, and research, resulting in low technology transfer efficiency and a lack of a sound quality control system and industrialization linkage plan.

[0004] Therefore, developing a direct-drinking theaflavins nano-encapsulation technology that can balance encapsulation efficiency and activity retention, controllable cost, scalable production, and adaptable to multiple application scenarios, and addressing the pain points of existing technologies, is of great significance for promoting the industrial application of theaflavins and helping the tea industry transform into a high-value-added industry. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a method for direct-drinking theaflavins nano-encapsulation, the encapsulation product, and its applications.

[0006] The technical solution adopted by this invention to solve its technical problem is: A method for nano-encapsulating theaflavins for direct consumption includes the following steps: Step 1: Screening and Modification of Nanocarriers Based on the application scenario, suitable nanocarriers are selected, and the selected carriers are modified to obtain modified nanocarriers. Step 2: Theaflavins Pretreatment Select direct-drinking theaflavins raw materials with a purity of not less than 80%, wherein the mass ratio of theaflavins-3-gallate to theaflavins-3'-gallate is 1:0.8-1.2. After pulverizing, pass through an 80-100 mesh sieve, add deionized water, and prepare a theaflavins aqueous solution with a mass concentration of 5-10 mg / mL. After stirring evenly, the pretreated theaflavins aqueous solution is obtained and stored at 4℃ for later use to avoid oxidation and degradation of theaflavins. Step 3: Implementation of the nano-embedding process The pretreated theaflavins aqueous solution was mixed with the modified nanocarrier at a core-to-wall ratio of 1:2-1:4. The pH of the system was adjusted to 5.0-7.0, the emulsification temperature was controlled at 28-32℃, the ultrasonic power was 40%, the ultrasonic frequency was 20-40kHz, and the emulsification was carried out for 20-30 minutes to obtain theaflavins nano-embedded emulsion. The emulsion was then dried by spray freeze-drying at a temperature controlled at -25℃ to obtain theaflavins nano-embedded powder. Step 4: Seal and package the qualified theaflavins nano-encapsulated products and protect them from light to obtain the direct-drinking theaflavins nano-encapsulated products; return unqualified products to step 3 for re-encapsulation.

[0007] Furthermore, in step 1, suitable nanocarriers are selected according to the application scenario and divided into three categories: food-grade carriers are selected from one or a mixture of chitosan and modified wheat gliadin; pharmaceutical-grade carriers are selected from one or a mixture of liposomes and porous platinum-based nanoparticles; and cosmetic-grade carriers are selected from one or a mixture of nanoemulsions and nanomicelles. The modified carriers after screening were specifically modified as follows: chitosan was modified by carboxymethylation or quaternization, and liposomes were modified by surface modification. After modification, the carrier ratio was optimized to reduce particle aggregation and improve the water solubility, dispersibility and encapsulation performance of the carriers. Among them, porous platinum-based nanoparticles were synthesized using liposomes as templates. Specifically, the nanoparticles were rotary evaporated in a chloroform organic phase containing DPPC and cholesterol until a thin film was formed. An aqueous solution of α-ascorbic acid was added, and the mixture was sonicated until clear. Then, a chloroplatinic acid solution was added and reacted until the solution turned black. The porous platinum-based nanoparticles were obtained by solid-liquid separation. The concentration of DPPC was 0.5~1 mg / mL, the concentration of cholesterol was 0.1~0.5 mg / mL, the concentration of α-ascorbic acid aqueous solution was 52.8 mg / mL, and the concentration of chloroplatinic acid was 10~20 mM. Alternatively, in step 3, the corresponding preparation method can be selected according to the carrier type: for food grade, ultrasonic emulsification-spray freeze drying is used; for pharmaceutical grade, thin film dispersion-ultrasound is used; and for cosmetic grade, high-pressure homogenization-nano emulsification is used. Among them, when encapsulating theaflavins in pharmaceutical grade porous platinum-based nanoparticles, the porous platinum-based nanoparticles are first carboxylated, dissolved in ethanol, and reacted with lipoic acid for 10-15 hours. After washing and purification, they are dissolved in water, and theaflavins are added and stirred for 10-15 hours to achieve the encapsulation of theaflavins. The mass of lipoic acid is 8-12 times that of the porous platinum-based nanoparticles.

[0008] Furthermore, the method also includes the following steps: Step 4: Process Optimization and Quality Inspection The encapsulation process parameters were optimized using response surface methodology to control the particle size distribution of the encapsulated product: 50-200 nm for food grade and 110-120 nm for pharmaceutical grade, with a coefficient of variation ≤15%. Theaflavin activity was detected by HPLC, particle size distribution by laser particle size analyzer, and carrier residue by HPLC-MS to ensure that the encapsulation rate met the corresponding standards: ≥80% for food grade, ≥85% for pharmaceutical grade, and ≥82% for cosmetic grade, with an activity retention rate ≥90%. Unqualified products were returned to step 3 for re-encapsulation. Step 5: Integration of Storage and Industrialization The qualified theaflavins nano-encapsulated products are sealed and packaged, and protected from light. Food-grade products can be stored and transported at room temperature, while pharmaceutical and cosmetic-grade products must be refrigerated and transported below 4°C. The industrial production equipment consists of an ultrasonic emulsifier (JS-1000, 1000W), a high-pressure homogenizer (GJB-2000), a spray freeze dryer (SLFD-500), and a PLC control system (S7-1200). The production capacity target is 200 kg / day for pilot production and 500-1000 kg / day (food grade) for large-scale production. By purchasing raw materials in bulk, optimizing process parameters, and recycling waste materials, the unit cost of food-grade encapsulated products is controlled to ≤35 yuan / kg.

[0009] Furthermore, the method includes the following precise, controllable, and hierarchically adaptable steps: Step 1: Hierarchical nanocarrier directional screening and in-situ modification treatment Based on the three major application scenarios of food, medicine and cosmetics, we grade and screen food-grade, pharmaceutical-grade and cosmetic-grade nanocarriers that meet the corresponding national standards, pharmacopoeia and cosmetic safety specifications. We then perform targeted in-situ modification on different carriers, and simultaneously optimize the carrier molecular weight, degree of substitution and hydrophilic-lipophilic balance ratio. The entire process is protected by low temperature inert gas, i.e. nitrogen with a purity of ≥99.99%, to prevent carrier particle agglomeration, oxidative degradation and cross-linking inactivation. Step 2: Targeted pretreatment and stabilization of high-purity direct-drinking theaflavins High-purity direct-drinking theaflavins raw materials with a total purity of ≥80% are selected. Through targeted impurity removal, desalting, and dephenolization refining processes, the ratio of characteristic monomers is controlled to prepare a constant-temperature stabilized theaflavins aqueous solution. The entire process is carried out in the dark and at low temperature to inhibit the oxidation and degradation of theaflavins and ensure the stability of the core material activity. Step 3: Precision fabrication process of hierarchical and adaptive nano-embedding Stabilized theaflavins aqueous solution and modified nanocarriers were precisely fed at a core-to-wall mass ratio of 1:2 to 1:4, tailored to specific application scenarios. A differentiated encapsulation preparation process adapted one-to-one with the application scenario was adopted. Temperature and power were controlled throughout the process for ultrasonic emulsification and homogenization to complete the in-situ encapsulation of theaflavins. Subsequently, gradient temperature controlled spray freeze-drying was used to obtain direct-drinking theaflavins nano-encapsulated powder with no agglomeration and excellent dispersibility. Step 4: Multi-dimensional process closed-loop optimization and comprehensive quality control Real-time online control of particle size distribution and particle size variation coefficient of encapsulated products; establishment of comprehensive quality control standards; simultaneous detection of encapsulation rate, theaflavin activity retention rate, carrier residue, heavy metal and microbial limits using dedicated detection methods; closed-loop recovery and re-encapsulation of unqualified products to eliminate batch differences. Step 5: Connecting Stabilized Storage with Full-Process Industrialization Qualified encapsulated products are packaged in light-proof, oxygen-proof, and moisture-proof special packaging. They are matched with corresponding low-temperature light-proof storage and transportation specifications according to the application level, and are simultaneously adapted to continuous industrial production equipment. Process connection parameters are optimized to achieve seamless connection from pilot production to large-scale mass production, and to strictly control mass production costs and product stability.

[0010] Furthermore, in step 1, the selection of the graded carrier and the specific in-situ modification process are as follows: (1) Food-grade carrier: Select one or two of high-purity chitosan with a deacetylation degree ≥90% and modified wheat gliadin, with a mass ratio of 1:1 to 1:1.5. After compounding, add 0.3% to 0.5% nano-SiO2 as an anti-agglomeration regulator. The modification method is low-temperature temperature-controlled carboxymethylation modification and quaternization grafting modification. The modification temperature is 35 to 40℃, the pH is controlled at 5.0 to 5.5, the degree of carboxymethyl substitution is controlled at 0.6 to 0.8, and the degree of quaternization substitution is controlled at 0.5 to 0.7. After modification, the carrier potential is adjusted to +25 to +35mV. Large particulate impurities are removed by filtration through a 0.1μm filter membrane to prevent particle agglomeration from the source, which is different from the conventional single carrier compounding process. (2) Pharmaceutical-grade carrier: one or two of targeted liposomes and porous platinum-based nanoparticles are selected. The porous platinum-based nanoparticles are synthesized in situ using monolayer liposomes as soft templates. After synthesis, the surface is modified by carboxymethylation. After modification, the carrier potential is controlled at -10~+10mV. It has blood compatibility, passive targeting, and no cytotoxicity. (3) Cosmetic-grade carrier: Select one or two of nanoemulsions and pH-responsive nanomicelles, and add modified silk fibroin, activated soybean seed polysaccharide and pH-responsive self-assembled short peptides in situ after compounding. Form a three-dimensional interpenetrating network carrier through non-covalent cross-linking. The network pore size is controlled at 20~50nm. Simultaneously add 0.1%~0.2% hyaluronic acid derivative as a transdermal promoter to achieve slow controlled release of theaflavins and improve transdermal efficiency by more than 25%. Unlike the conventional three-dimensional network carrier preparation process without transdermal promoters, and avoiding the technical solutions of theaflavin compounded with coenzyme Q10, selenocysteine ​​and other similar whitening patents, theaflavin is compounded with 2-o-ethyl ascorbic acid and eugenol to form a unique whitening synergistic system, further reducing the risk of overlap with existing whitening theaflavin-related patents.

[0011] Furthermore, in step 1, the preparation method of pharmaceutical-grade porous platinum-based nanoparticles differs from conventional liposome drug delivery methods. The specific steps and precise parameters are as follows: (1) Film preparation: DPPC and cholesterol were completely dissolved in a chloroform-methanol mixed organic phase according to the concentration ratio of 3:1. The mixture was evaporated under reduced pressure for 30 min in a constant temperature water bath at 40℃ and a rotation speed of 60 r / min until a uniform, pinhole-free monolayer lipid film was formed on the inner wall of the round bottom flask. The film was then dried under reduced pressure for 15 min to completely remove the organic solvent residue. (2) Hydration and dispersion: Nitrogen gas was introduced into the dried lipid film to remove the air in the bottle, and α-ascorbic acid aqueous solution preheated to 30°C was added. The mixture was kept at a constant temperature for 20 min to hydrate. Then, the mixture was sonicated under ice bath conditions with a probe at 30% power and 40 kHz frequency for 10 min until the system was completely clear and without stratification, thus obtaining a monolayer liposome template solution. (3) In-situ reduction synthesis: Chloroplatinic acid solution was slowly added dropwise to the clear liposome template solution. The reaction was carried out under nitrogen protection and at a constant temperature of 30°C for 60 min until the solution changed from light yellow to uniform black. The reaction was then stopped. (4) Purification and refining: Transfer the reaction solution into an ultrafiltration centrifuge tube, centrifuge at 10000 r / min for 15 min at low temperature, discard the supernatant free metal ions and unreacted reagents, resuspend and wash 3 times with ultrapure water, and finally obtain a porous platinum-based nanoparticle suspension, which is stored at 4℃ for later use. The final concentration parameters of the system were as follows: DPPC final concentration 0.5~1 mg / mL, cholesterol final concentration 0.1~0.5 mg / mL, α-ascorbic acid aqueous solution final concentration 52.8 mg / mL, and chloroplatinic acid final concentration 10~20 mM; the particle size of the prepared particles was 110~120 nm, the coefficient of variation was ≤10%, and the specific surface area was ≥15 m². 2 / g, with high drug loading porosity.

[0012] Alternatively, the method for preparing the theaflavins through targeted pretreatment and stabilization in step 2 differs from the conventional direct dissolution method, specifically as follows: (1) Raw material refining: Select direct drinking theaflavins raw materials with a total purity of ≥80% and remove impurities, desalinate and remove free phenolic impurities through a 3000Da ultrafiltration membrane. After refining, control the ratio of characteristic monomers: the mass ratio of theaflavins-3-gallate to theaflavins-3'-gallate is strictly controlled at 1:0.8~1.2 to prevent differences in encapsulation stability caused by fluctuations in monomer ratio; (2) Stabilization and dissolution: The refined theaflavins raw material is added to a citrate-sodium citrate buffer solution preheated to 25°C and pH 6.0~6.5, and stirred at low speed until completely dissolved to prepare an aqueous solution of theaflavins with a mass concentration of 5~10 mg / mL. The entire process is protected from light and nitrogen. After dissolution, the solution is immediately filtered through a 0.22 μm sterile filter membrane and stored at 4°C in the dark for later use. The storage time should not exceed 2 hours to avoid oxidation and deactivation of the core material. Alternatively, in step 3, the three-level scenario-specific one-to-one embedding preparation method, with each level of the process supplemented with complete operation steps and closed-loop precise parameters, is significantly different from conventional general processes, specifically as follows: (1) Food grade: Ultrasonic emulsification-gradient spray freeze drying exclusive process 1) Feeding and emulsification: The modified chitosan / alcohol-soluble protein carrier solution is mixed with the theaflavins aqueous solution at a core-to-wall ratio of 1:2.5 to 1:4. The mixture is premixed by stirring at a constant temperature of 30°C for 10 minutes, and then transferred to the probe ultrasonic reactor. 2) Ultrasonic homogenization: The ultrasonic power is fixed at 40%, the frequency is 25~35kHz, the ice bath temperature is controlled at 28~32℃, and the ultrasonic emulsification is carried out for 20~30 minutes. The ultrasonic mode is intermittent ultrasonication with 3 seconds on and 2 seconds off to avoid local overheating and degradation of theaflavins, so as to obtain a uniform nanoemulsion. 3) Gradient drying: The emulsion is filtered through a 0.22μm filter membrane to remove agglomerated particles, and then fed into a spray freeze dryer at a feed rate of 5~8mL / min, atomization pressure of 0.2~0.3MPa, and cold trap temperature of -55℃. The material drying temperature gradient is controlled as follows: first, it is kept at -25℃ for 120min, then at -10℃ for 30min, and finally, it is desorbed and dried at room temperature for 20min to obtain a free-flowing, non-agglomerated nano-embedded powder. (2) Pharmaceutical grade: Thin film dispersion-targeted drug delivery ultrasonic method exclusive process 1) Carrier film formation: Liposomes / porous platinum-based nanocarriers are dissolved in an organic phase in a certain proportion, and the film is formed by rotary evaporation at 40°C and then dried under reduced pressure to remove the organic solvent; 2) Drug loading hydration: Add theaflavins aqueous solution, keep at a constant temperature of 30℃ for 25 minutes to allow the carrier to fully swell and simultaneously adsorb and encapsulate the theaflavins core material; 3) Homogenization and size control: The probe is ultrasonically controlled under ice bath conditions at 35% power and 40kHz frequency for 15-20 minutes in intermittent ultrasonic mode. Then, it is extruded through a 100nm polycarbonate film three times to precisely control the uniformity of particle size and obtain a nano suspension. The suspension is then freeze-dried at low temperature to obtain a pharmaceutical-grade encapsulated powder.

[0013] (3) Cosmetic grade: High-pressure homogenization-controlled release nano-emulsification exclusive process 1) Preparation of colostrum: The three-dimensional network carrier solution was mixed with theaflavins aqueous solution and sheared at 30°C for 10 min to prepare crude emulsion; 2) High-pressure homogenization: The crude emulsion is transferred to a high-pressure homogenizer, with a first-stage pressure of 80MPa and a second-stage pressure of 40MPa. The homogenization is repeated 5 times, and the temperature is controlled at ≤30℃ throughout the process to obtain nano-emulsion with uniform particle size. 3) Low-temperature drying: Low-temperature spray freeze drying is adopted, with a feed rate of 6~10mL / min and a drying temperature of -25℃, to obtain cosmetic-grade encapsulation powder with good water solubility and strong transdermal properties; The core parameters for this step are universal: ultrasonic power 40%, frequency 20-40kHz, emulsification temperature 28-32℃, and drying core temperature -25℃. Alternatively, in step 4, the graded quality control standards and closed-loop optimization methods are specifically as follows: (1) Precise particle size control: food-grade products have a particle size of 50-200nm, pharmaceutical-grade products have a particle size of 110-120nm, cosmetic-grade products have a particle size of 80-150nm, and the particle size variation coefficient of all grades of products is ≤15%; (2) Performance quality control thresholds: food grade encapsulation rate ≥80%, pharmaceutical grade encapsulation rate ≥85%, cosmetic grade encapsulation rate ≥82%, the theaflavins activity retention rate of all grades of products ≥90%, carrier organic solvent residue ≤0.1%, meeting the corresponding safety standards; (3) Dedicated detection methods: High performance liquid chromatography (HPLC) is used to quantitatively detect the content, encapsulation rate, and activity retention rate of theaflavins. Laser dynamic light scattering instrument is used to detect particle size and distribution. HPLC-MS is used to detect carrier residues and impurities. Unqualified products are reconstituted at low temperature and re-homogenized and encapsulated to achieve closed-loop recovery without wasting raw materials. Alternatively, in step 5, the industrial-scale continuous production process and capacity cost control specifically include: (1) Adaptable to industrial equipment: The whole set adopts customized continuous production equipment, including 1000W JS-1000 CNC ultrasonic emulsifier (equipped with online temperature control and power feedback module, which can adjust the ultrasonic intermittent cycle in real time), GJB-2000 high pressure homogenizer (with pressure closed-loop regulation system, pressure fluctuation ≤1MPa), SLFD-500 spray freeze dryer (equipped with gradient temperature control and automatic feed flow rate adjustment device, drying uniformity ≥95%), Siemens S7-1200 PLC fully automatic control system, which integrates feeding metering, emulsification parameter monitoring, drying effect detection and automatic packaging functions, realizes full-process automated closed-loop control, equipment linkage error ≤2%, and can record production data in real time for traceability; (2) Graded production capacity target: The pilot production capacity is stable at 200kg / day (fluctuation ≤5%), and the food-grade mass production capacity is 500-1000kg / day, which can be flexibly adjusted according to order demand (adjustment range 500-1000kg / day, adjustment response time ≤2h); the process scale-up adopts the "gradient scale-up method", from small-scale test (100g / batch), pilot test (50kg / batch) to mass production (200kg / batch), with particle size and encapsulation rate fluctuations ≤3% and no batch differences; during mass production, a continuous feeding mode is adopted, with a single feeding amount ≥50kg, equipped with a raw material pretreatment buffer tank, which shortens the production cycle while ensuring product uniformity, and the single batch production cycle ≤8h; (3) Mass production cost control: Through carrier compounding optimization (compounding chitosan and wheat gliadin, adding nano SiO2 anti-agglomeration regulator, the cost is reduced by 12% compared with single chitosan carrier) and energy-saving control of process parameters (ultrasonic intermittent mode saves 15% energy, gradient drying saves 20% energy, equipment linkage saves 8% energy), the unit comprehensive production cost of food-grade mass production products is ≤35 yuan / kg, of which the carrier cost accounts for ≤40%, energy consumption cost accounts for ≤25%, and raw material loss accounts for ≤5%, which is suitable for large-scale application in the food processing industry. The cost is reduced by more than 10% compared with conventional nano-embedding process, and the shelf life of mass production products is extended to 12 months; it is different from the mass production process of single carrier or no anti-agglomeration regulator in the existing technology, and avoids the technical defects of "fixed capacity that cannot be adjusted" in the existing theaflavins encapsulation industrialization. The new capacity can be flexibly adjusted and the cost can be precisely controlled, further reducing the overlap with existing patents; Furthermore, it also includes targeted modification and synergistic post-processing, which differs from conventional simple mixed modification, specifically: (1) After the pharmaceutical-grade encapsulated product was freeze-dried, it was first subjected to vacuum degassing (vacuum degree -0.095MPa, temperature 25℃, time 15min) to remove residual air in the pores of the product. Then it was placed in a pH 7.0 phosphate buffer system, and an EDC / NHS catalytic system was added (EDC to NHS molar ratio 1.2:1, both concentrations 50mM, the amount of catalytic system added was 8% of the product mass). The reaction was carried out at 37℃ and 120r / min for 2h with constant temperature shaking. The nanoparticles encapsulating theaflavins were directionally covalently linked to bone-targeting alendronate through amide bond reaction. After the reaction, it was purified by ultrafiltration centrifugation (12000r / min, 10min, ultrafiltration membrane pore size 50nm) to remove residual air. Unreacted reagents and small molecule impurities were then freeze-dried at low temperature (-40℃, 2h) to obtain bone-targeting drug-loaded nanoparticles. The enrichment rate of these particles at the lesion site was increased by more than 40% compared with unmodified particles, the in vitro sustained-release period was extended to 48h, the blood half-life was extended by 2.5 times compared with unmodified particles, and there was no hemolytic toxicity. Unlike the "theaflavins-metal-organic framework complex" encapsulation modification method in the existing technology, this method abandons the metal-organic framework carrier and adopts porous platinum-based nanoparticles and liposome composite carriers combined with alendronate for targeted modification to form a unique targeted drug delivery system. This effectively avoids the overlap of existing anti-aging and targeted encapsulation related patents, while enhancing bone-targeting specificity, forming a significant technical difference from existing theaflavins anti-aging related patents. (2) During the emulsification stage, 2% to 5% by mass of 2-o-ethyl ascorbic acid and 0.5% to 1% eugenol are added simultaneously to the cosmetic-grade encapsulation product as synergistic ingredients. They are combined with theaflavins to enhance the whitening, antioxidant, anti-inflammatory and soothing effects without affecting the encapsulation stability and particle size distribution. The whitening activity of the product is increased by more than 35% compared with the single theaflavin encapsulation product.

[0014] The theaflavins nano-encapsulated products prepared by the method described above have a core-shell structure, with theaflavins as the core (i.e., highly stable theaflavins for direct consumption) and modified functionalized nanocarriers as the shell. These products exhibit uniform particle size distribution, a coefficient of variation ≤15%, encapsulation rate ≥80%, activity retention rate ≥90%, water solubility increased by more than 30% compared to unencapsulated theaflavins, bioavailability ≥85%, and light-protected room-temperature stability increased by more than 6 months compared to unencapsulated raw materials. Based on application scenarios, these products are categorized into three types: food-grade, pharmaceutical-grade, and cosmetic-grade. Pharmaceutical-grade products can be further linked with alendronate for osteoporosis treatment; cosmetic-grade products can be supplemented with 2-o-ethyl ascorbic acid and eugenol to achieve synergistic whitening and moisturizing effects; and food-grade products can be used for meat product preservation, beverage and baking product processing. Unlike the product structure of "theaflavins-metal-organic framework complex" in existing technologies, this product uses a hierarchically modified nanocarrier to form a core-shell structure, without metal-organic framework components, and has specific functions for different scenarios (food-grade anti-agglomeration, pharmaceutical-grade bone targeting, cosmetic-grade transdermal whitening), forming a significant structural and functional difference from existing theaflavins-related encapsulated products.

[0015] As mentioned above, the theaflavins nano-encapsulated products for direct consumption have applications in the food, pharmaceutical, and cosmetic fields.

[0016] The products are categorized into three types based on their application scenarios: food-grade, pharmaceutical-grade, and cosmetic-grade, with clearly defined functions and application scenarios. (1) Food-grade products: Excellent water solubility and strong antioxidant properties. They can be directly used for antioxidant preservation of meat products, addition of functional beverages, and processing of baked goods. They have no odor and do not affect the sensory properties of the products. (2) Pharmaceutical grade products: They have bone-targeting properties, good biocompatibility, and excellent sustained-release properties, and can be used as adjunctive treatment for osteoporosis and in the development of related drug formulations; (3) Cosmetic grade products: They have strong transdermal absorption properties and, when combined with other ingredients, have whitening, brightening, antioxidant, moisturizing, anti-inflammatory, and soothing effects. They can be used in the development of skin care products and functional cosmetic formulations.

[0017] The advantages and positive effects of this invention are as follows: 1. This invention provides a method for direct-drinking theaflavins nano-encapsulation and the encapsulated product, suitable for the industrial encapsulation of theaflavins. It can be widely applied in multiple fields such as food, health products, biomedicine, and cosmetics, achieving efficient encapsulation, activity protection, and improved water solubility of theaflavins, while reducing production costs, enabling large-scale production, and expanding its application scenarios. It overcomes the technical shortcomings of existing theaflavin nano-encapsulation technologies, such as an imbalance between encapsulation rate and activity retention, high cost, difficulty in scaling up, and limited application scenarios.

[0018] 2. This invention achieves efficient encapsulation, activity protection, and controlled-release delivery of theaflavins by screening food-grade, pharmaceutical-grade, and cosmetic-grade nanocarriers suitable for different application scenarios, modifying and optimizing these carriers, and combining this with targeted encapsulation process parameter control. The method includes four core steps: nanocarrier screening and modification, theaflavin encapsulation, process optimization, and quality testing. The encapsulated product exhibits uniform particle size distribution and strong stability, with an encapsulation rate exceeding 80% and an activity retention rate of no less than 90%. It can be mass-produced and widely applied in food, health products, biopharmaceuticals, and cosmetics, contributing to the high-value-added transformation of the tea industry and demonstrating significant economic benefits and application value. This invention solves the technical challenges of existing theaflavins, such as easy oxidation, poor water solubility, low bioavailability, difficulty in large-scale application of encapsulation technology, and an imbalance between encapsulation rate and activity retention.

[0019] 3. This invention addresses the pain point of imbalance between the encapsulation rate and activity retention of theaflavins. Through carrier modification and optimization and precise control of process parameters, while ensuring the encapsulation rate (≥80%), the activity retention rate of theaflavins is achieved at ≥90%, effectively protecting the physiological activity of theaflavins and preventing their oxidative degradation. 4. This invention improves the water solubility and dispersibility of theaflavins. The water solubility of the encapsulated product is increased by more than 30% compared with that of unencapsulated theaflavins, solving the problem of easy aggregation and poor solubility of theaflavins in direct-drinking tea, and improving the taste and quality of direct-drinking products.

[0020] 5. This invention achieves multi-scenario adaptation. By selecting suitable carriers and optimizing processes according to different application needs, three types of products are prepared: food-grade, pharmaceutical-grade, and cosmetic-grade. These products can be applied to direct drinking beverages, health products, biomedicine (osteoporosis treatment, etc.), cosmetics, etc., respectively, expanding the application scope of theaflavins and exploring their diverse values.

[0021] 6. This invention enables large-scale production, optimizes the industrialization linkage scheme, determines suitable industrial equipment and production capacity targets, and controls the unit cost of food-grade products to below 35 yuan / kg through cost control measures, thereby reducing production costs and enhancing the market competitiveness of the products.

[0022] 7. This invention establishes a comprehensive quality control system, clarifies the testing methods and core indicators, and ensures the stability and consistency of the encapsulated products. At the same time, the carrier is made of natural and biodegradable materials, which are highly safe and meet the safety standards of the food, pharmaceutical and cosmetic fields. Furthermore, some carrier modifications and preparation processes can effectively improve the targeting and sustained-release performance of the encapsulated products, further enhancing the product value. Attached Figure Description

[0023] Figure 1 The process flow diagram is shown for the general direct-drinking theaflavins nano-encapsulation method of Embodiments 1-3 of the present invention; Figure 2The particle size distribution curves of theaflavins encapsulated in different carriers in Examples 1-3 of the present invention are shown (the horizontal axis is particle size / nm, and the vertical axis is the percentage of particle size distribution / %). Figure 3 This is a comparison chart of the oxidative stability of the encapsulated product and the unencapsulated theaflavins in Example 1 of this invention (horizontal axis is storage time / d, vertical axis is activity retention rate / %). Figure 4 This is a schematic diagram of the direct drinking theaflavins nano-encapsulation method and the in vitro release curve of the encapsulated product in Example 2 of the present invention (the horizontal axis is the release time / h, and the vertical axis is the release rate / %). Detailed Implementation

[0024] The present invention will be further described below with reference to the embodiments. The following embodiments are descriptive and not limiting, and should not be used to limit the scope of protection of the present invention.

[0025] The various experimental operations involved in the specific embodiments are all conventional techniques in the field. For parts not specifically annotated in this document, those skilled in the art can refer to various commonly used reference books, scientific and technological documents or related instructions and manuals prior to the filing date of this invention to carry out the operations.

[0026] A method for nano-encapsulating theaflavins for direct consumption includes the following steps: Step 1: Screening and Modification of Nanocarriers Based on the application scenario, suitable nanocarriers are selected, and the selected carriers are modified to obtain modified nanocarriers. Step 2: Theaflavins Pretreatment Select direct-drinking theaflavins raw materials with a purity of not less than 80%, wherein the mass ratio of theaflavins-3-gallate to theaflavins-3'-gallate is 1:0.8-1.2. After pulverizing, pass through an 80-100 mesh sieve, add deionized water, and prepare a theaflavins aqueous solution with a mass concentration of 5-10 mg / mL. After stirring evenly, the pretreated theaflavins aqueous solution is obtained and stored at 4℃ for later use to avoid oxidation and degradation of theaflavins. Step 3: Implementation of the nano-embedding process The pretreated theaflavins aqueous solution was mixed with the modified nanocarrier at a core-to-wall ratio of 1:2-1:4. The pH of the system was adjusted to 5.0-7.0, the emulsification temperature was controlled at 28-32℃, the ultrasonic power was 40%, the ultrasonic frequency was 20-40kHz, and the emulsification was carried out for 20-30 minutes to obtain theaflavins nano-embedded emulsion. The emulsion was then dried by spray freeze-drying at a temperature controlled at -25℃ to obtain theaflavins nano-embedded powder. Step 4: Seal and package the qualified theaflavins nano-encapsulated products and protect them from light to obtain the direct-drinking theaflavins nano-encapsulated products; return unqualified products to step 3 for re-encapsulation.

[0027] Furthermore, in step 1, suitable nanocarriers are selected according to the application scenario and divided into three categories: food-grade carriers are selected from one or a mixture of chitosan and modified wheat gliadin; pharmaceutical-grade carriers are selected from one or a mixture of liposomes and porous platinum-based nanoparticles; and cosmetic-grade carriers are selected from one or a mixture of nanoemulsions and nanomicelles. The modified carriers after screening were specifically modified as follows: chitosan was modified by carboxymethylation or quaternization, and liposomes were modified by surface modification. After modification, the carrier ratio was optimized to reduce particle aggregation and improve the water solubility, dispersibility and encapsulation performance of the carriers. Among them, porous platinum-based nanoparticles were synthesized using liposomes as templates. Specifically, the nanoparticles were rotary evaporated in a chloroform organic phase containing DPPC and cholesterol until a thin film was formed. An aqueous solution of α-ascorbic acid was added, and the mixture was sonicated until clear. Then, a chloroplatinic acid solution was added and reacted until the solution turned black. The porous platinum-based nanoparticles were obtained by solid-liquid separation. The concentration of DPPC was 0.5~1 mg / mL, the concentration of cholesterol was 0.1~0.5 mg / mL, the concentration of α-ascorbic acid aqueous solution was 52.8 mg / mL, and the concentration of chloroplatinic acid was 10~20 mM. Alternatively, in step 3, the corresponding preparation method can be selected according to the carrier type: for food grade, ultrasonic emulsification-spray freeze drying is used; for pharmaceutical grade, thin film dispersion-ultrasound is used; and for cosmetic grade, high-pressure homogenization-nano emulsification is used. Among them, when encapsulating theaflavins in pharmaceutical grade porous platinum-based nanoparticles, the porous platinum-based nanoparticles are first carboxylated, dissolved in ethanol, and reacted with lipoic acid for 10-15 hours. After washing and purification, they are dissolved in water, and theaflavins are added and stirred for 10-15 hours to achieve the encapsulation of theaflavins. The mass of lipoic acid is 8-12 times that of the porous platinum-based nanoparticles.

[0028] Furthermore, the method also includes the following steps: Step 4: Process Optimization and Quality Inspection The encapsulation process parameters were optimized using response surface methodology to control the particle size distribution of the encapsulated product: 50-200 nm for food grade and 110-120 nm for pharmaceutical grade, with a coefficient of variation ≤15%. Theaflavin activity was detected by HPLC, particle size distribution by laser particle size analyzer, and carrier residue by HPLC-MS to ensure that the encapsulation rate met the corresponding standards: ≥80% for food grade, ≥85% for pharmaceutical grade, and ≥82% for cosmetic grade, with an activity retention rate ≥90%. Unqualified products were returned to step 3 for re-encapsulation. Step 5: Integration of Storage and Industrialization The qualified theaflavins nano-encapsulated products are sealed and packaged, and protected from light. Food-grade products can be stored and transported at room temperature, while pharmaceutical and cosmetic-grade products must be refrigerated and transported below 4°C. The industrial production equipment consists of an ultrasonic emulsifier (JS-1000, 1000W), a high-pressure homogenizer (GJB-2000), a spray freeze dryer (SLFD-500), and a PLC control system (S7-1200). The production capacity target is 200 kg / day for pilot production and 500-1000 kg / day (food grade) for large-scale production. By purchasing raw materials in bulk, optimizing process parameters, and recycling waste materials, the unit cost of food-grade encapsulated products is controlled to ≤35 yuan / kg.

[0029] Furthermore, the method includes the following precise, controllable, and hierarchically adaptable steps: Step 1: Hierarchical nanocarrier directional screening and in-situ modification treatment Based on the three major application scenarios of food, medicine and cosmetics, we grade and screen food-grade, pharmaceutical-grade and cosmetic-grade nanocarriers that meet the corresponding national standards, pharmacopoeia and cosmetic safety specifications. We then perform targeted in-situ modification on different carriers, and simultaneously optimize the carrier molecular weight, degree of substitution and hydrophilic-lipophilic balance ratio. The entire process is protected by low temperature inert gas, i.e. nitrogen with a purity of ≥99.99%, to prevent carrier particle agglomeration, oxidative degradation and cross-linking inactivation. Step 2: Targeted pretreatment and stabilization of high-purity direct-drinking theaflavins High-purity direct-drinking theaflavins raw materials with a total purity of ≥80% are selected. Through targeted impurity removal, desalting, and dephenolization refining processes, the ratio of characteristic monomers is controlled to prepare a constant-temperature stabilized theaflavins aqueous solution. The entire process is carried out in the dark and at low temperature to inhibit the oxidation and degradation of theaflavins and ensure the stability of the core material activity. Step 3: Precision fabrication process of hierarchical and adaptive nano-embedding Stabilized theaflavins aqueous solution and modified nanocarriers were precisely fed at a core-to-wall mass ratio of 1:2 to 1:4, tailored to specific application scenarios. A differentiated encapsulation preparation process adapted one-to-one with the application scenario was adopted. Temperature and power were controlled throughout the process for ultrasonic emulsification and homogenization to complete the in-situ encapsulation of theaflavins. Subsequently, gradient temperature controlled spray freeze-drying was used to obtain direct-drinking theaflavins nano-encapsulated powder with no agglomeration and excellent dispersibility. Step 4: Multi-dimensional process closed-loop optimization and comprehensive quality control Real-time online control of particle size distribution and particle size variation coefficient of encapsulated products; establishment of comprehensive quality control standards; simultaneous detection of encapsulation rate, theaflavin activity retention rate, carrier residue, heavy metal and microbial limits using dedicated detection methods; closed-loop recovery and re-encapsulation of unqualified products to eliminate batch differences. Step 5: Connecting Stabilized Storage with Full-Process Industrialization Qualified encapsulated products are packaged in light-proof, oxygen-proof, and moisture-proof special packaging. They are matched with corresponding low-temperature light-proof storage and transportation specifications according to the application level, and are simultaneously adapted to continuous industrial production equipment. Process connection parameters are optimized to achieve seamless connection from pilot production to large-scale mass production, and to strictly control mass production costs and product stability.

[0030] Furthermore, in step 1, the selection of the graded carrier and the specific in-situ modification process are as follows: (1) Food-grade carrier: Select one or two of high-purity chitosan with a deacetylation degree ≥90% and modified wheat gliadin, with a mass ratio of 1:1 to 1:1.5. After compounding, add 0.3% to 0.5% nano-SiO2 as an anti-agglomeration regulator. The modification method is low-temperature temperature-controlled carboxymethylation modification and quaternization grafting modification. The modification temperature is 35 to 40℃, the pH is controlled at 5.0 to 5.5, the degree of carboxymethyl substitution is controlled at 0.6 to 0.8, and the degree of quaternization substitution is controlled at 0.5 to 0.7. After modification, the carrier potential is adjusted to +25 to +35mV. Large particulate impurities are removed by filtration through a 0.1μm filter membrane to prevent particle agglomeration from the source, which is different from the conventional single carrier compounding process. (2) Pharmaceutical-grade carrier: one or two of targeted liposomes and porous platinum-based nanoparticles are selected. The porous platinum-based nanoparticles are synthesized in situ using monolayer liposomes as soft templates. After synthesis, the surface is modified by carboxymethylation. After modification, the carrier potential is controlled at -10~+10mV. It has blood compatibility, passive targeting, and no cytotoxicity. (3) Cosmetic-grade carrier: Select one or two of nanoemulsions and pH-responsive nanomicelles, and add modified silk fibroin, activated soybean seed polysaccharide and pH-responsive self-assembled short peptides in situ after compounding. Form a three-dimensional interpenetrating network carrier through non-covalent cross-linking. The network pore size is controlled at 20~50nm. Simultaneously add 0.1%~0.2% hyaluronic acid derivative as a transdermal promoter to achieve slow controlled release of theaflavins and improve transdermal efficiency by more than 25%. Unlike the conventional three-dimensional network carrier preparation process without transdermal promoters, and avoiding the technical solutions of theaflavin compounded with coenzyme Q10, selenocysteine ​​and other similar whitening patents, theaflavin is compounded with 2-o-ethyl ascorbic acid and eugenol to form a unique whitening synergistic system, further reducing the risk of overlap with existing whitening theaflavin-related patents.

[0031] Furthermore, in step 1, the preparation method of pharmaceutical-grade porous platinum-based nanoparticles differs from conventional liposome drug delivery methods. The specific steps and precise parameters are as follows: (1) Film preparation: DPPC and cholesterol were completely dissolved in a chloroform-methanol mixed organic phase according to the concentration ratio of 3:1. The mixture was evaporated under reduced pressure for 30 min in a constant temperature water bath at 40℃ and a rotation speed of 60 r / min until a uniform, pinhole-free monolayer lipid film was formed on the inner wall of the round bottom flask. The film was then dried under reduced pressure for 15 min to completely remove the organic solvent residue. (2) Hydration and dispersion: Nitrogen gas was introduced into the dried lipid film to remove the air in the bottle, and α-ascorbic acid aqueous solution preheated to 30°C was added. The mixture was kept at a constant temperature for 20 min to hydrate. Then, the mixture was sonicated under ice bath conditions with a probe at 30% power and 40 kHz frequency for 10 min until the system was completely clear and without stratification, thus obtaining a monolayer liposome template solution. (3) In-situ reduction synthesis: Chloroplatinic acid solution was slowly added dropwise to the clear liposome template solution. The reaction was carried out under nitrogen protection and at a constant temperature of 30°C for 60 min until the solution changed from light yellow to uniform black. The reaction was then stopped. (4) Purification and refining: Transfer the reaction solution into an ultrafiltration centrifuge tube, centrifuge at 10000 r / min for 15 min at low temperature, discard the supernatant free metal ions and unreacted reagents, resuspend and wash 3 times with ultrapure water, and finally obtain a porous platinum-based nanoparticle suspension, which is stored at 4℃ for later use. The final concentration parameters of the system were as follows: DPPC final concentration 0.5~1 mg / mL, cholesterol final concentration 0.1~0.5 mg / mL, α-ascorbic acid aqueous solution final concentration 52.8 mg / mL, and chloroplatinic acid final concentration 10~20 mM; the particle size of the prepared particles was 110~120 nm, the coefficient of variation was ≤10%, and the specific surface area was ≥15 m². 2 / g, with high drug loading porosity.

[0032] Alternatively, the method for preparing the theaflavins through targeted pretreatment and stabilization in step 2 differs from the conventional direct dissolution method, specifically as follows: (1) Raw material refining: Select direct drinking theaflavins raw materials with a total purity of ≥80% and remove impurities, desalinate and remove free phenolic impurities through a 3000Da ultrafiltration membrane. After refining, control the ratio of characteristic monomers: the mass ratio of theaflavins-3-gallate to theaflavins-3'-gallate is strictly controlled at 1:0.8~1.2 to prevent differences in encapsulation stability caused by fluctuations in monomer ratio; (2) Stabilization and dissolution: The refined theaflavins raw material is added to a citrate-sodium citrate buffer solution preheated to 25°C and pH 6.0~6.5, and stirred at low speed until completely dissolved to prepare an aqueous solution of theaflavins with a mass concentration of 5~10 mg / mL. The entire process is protected from light and nitrogen. After dissolution, the solution is immediately filtered through a 0.22 μm sterile filter membrane and stored at 4°C in the dark for later use. The storage time should not exceed 2 hours to avoid oxidation and deactivation of the core material. Alternatively, in step 3, the three-level scenario-specific one-to-one embedding preparation method, with each level of the process supplemented with complete operation steps and closed-loop precise parameters, is significantly different from conventional general processes, specifically as follows: (1) Food grade: Ultrasonic emulsification-gradient spray freeze drying exclusive process 1) Feeding and emulsification: The modified chitosan / alcohol-soluble protein carrier solution is mixed with the theaflavins aqueous solution at a core-to-wall ratio of 1:2.5 to 1:4. The mixture is premixed by stirring at a constant temperature of 30°C for 10 minutes, and then transferred to the probe ultrasonic reactor. 2) Ultrasonic homogenization: The ultrasonic power is fixed at 40%, the frequency is 25~35kHz, the ice bath temperature is controlled at 28~32℃, and the ultrasonic emulsification is carried out for 20~30 minutes. The ultrasonic mode is intermittent ultrasonication with 3 seconds on and 2 seconds off to avoid local overheating and degradation of theaflavins, so as to obtain a uniform nanoemulsion. 3) Gradient drying: The emulsion is filtered through a 0.22μm filter membrane to remove agglomerated particles, and then fed into a spray freeze dryer at a feed rate of 5~8mL / min, atomization pressure of 0.2~0.3MPa, and cold trap temperature of -55℃. The material drying temperature gradient is controlled as follows: first, it is kept at -25℃ for 120min, then at -10℃ for 30min, and finally, it is desorbed and dried at room temperature for 20min to obtain a free-flowing, non-agglomerated nano-embedded powder. (2) Pharmaceutical grade: Thin film dispersion-targeted drug delivery ultrasonic method exclusive process 1) Carrier film formation: Liposomes / porous platinum-based nanocarriers are dissolved in an organic phase in a certain proportion, and the film is formed by rotary evaporation at 40°C and then dried under reduced pressure to remove the organic solvent; 2) Drug loading hydration: Add theaflavins aqueous solution, keep at a constant temperature of 30℃ for 25 minutes to allow the carrier to fully swell and simultaneously adsorb and encapsulate the theaflavins core material; 3) Homogenization and size control: The probe is ultrasonically controlled under ice bath conditions at 35% power and 40kHz frequency for 15-20 minutes in intermittent ultrasonic mode. Then, it is extruded through a 100nm polycarbonate film three times to precisely control the uniformity of particle size and obtain a nano suspension. The suspension is then freeze-dried at low temperature to obtain a pharmaceutical-grade encapsulated powder.

[0033] (3) Cosmetic grade: High-pressure homogenization-controlled release nano-emulsification exclusive process 1) Preparation of colostrum: The three-dimensional network carrier solution was mixed with theaflavins aqueous solution and sheared at 30°C for 10 min to prepare crude emulsion; 2) High-pressure homogenization: The crude emulsion is transferred to a high-pressure homogenizer, with a first-stage pressure of 80MPa and a second-stage pressure of 40MPa. The homogenization is repeated 5 times, and the temperature is controlled at ≤30℃ throughout the process to obtain nano-emulsion with uniform particle size. 3) Low-temperature drying: Low-temperature spray freeze drying is adopted, with a feed rate of 6~10mL / min and a drying temperature of -25℃, to obtain cosmetic-grade encapsulation powder with good water solubility and strong transdermal properties; The core parameters for this step are universal: ultrasonic power 40%, frequency 20-40kHz, emulsification temperature 28-32℃, and drying core temperature -25℃. Alternatively, in step 4, the graded quality control standards and closed-loop optimization methods are specifically as follows: (1) Precise particle size control: food-grade products have a particle size of 50-200nm, pharmaceutical-grade products have a particle size of 110-120nm, cosmetic-grade products have a particle size of 80-150nm, and the particle size variation coefficient of all grades of products is ≤15%; (2) Performance quality control thresholds: food grade encapsulation rate ≥80%, pharmaceutical grade encapsulation rate ≥85%, cosmetic grade encapsulation rate ≥82%, the theaflavins activity retention rate of all grades of products ≥90%, carrier organic solvent residue ≤0.1%, meeting the corresponding safety standards; (3) Dedicated detection methods: High performance liquid chromatography (HPLC) is used to quantitatively detect the content, encapsulation rate, and activity retention rate of theaflavins. Laser dynamic light scattering instrument is used to detect particle size and distribution. HPLC-MS is used to detect carrier residues and impurities. Unqualified products are reconstituted at low temperature and re-homogenized and encapsulated to achieve closed-loop recovery without wasting raw materials. Alternatively, in step 5, the industrial-scale continuous production process and capacity cost control specifically include: (1) Adaptable to industrial equipment: The whole set adopts customized continuous production equipment, including 1000W JS-1000 CNC ultrasonic emulsifier (equipped with online temperature control and power feedback module, which can adjust the ultrasonic intermittent cycle in real time), GJB-2000 high pressure homogenizer (with pressure closed-loop regulation system, pressure fluctuation ≤1MPa), SLFD-500 spray freeze dryer (equipped with gradient temperature control and automatic feed flow rate adjustment device, drying uniformity ≥95%), Siemens S7-1200 PLC fully automatic control system, which integrates feeding metering, emulsification parameter monitoring, drying effect detection and automatic packaging functions, realizes full-process automated closed-loop control, equipment linkage error ≤2%, and can record production data in real time for traceability; (2) Graded production capacity target: The pilot production capacity is stable at 200kg / day (fluctuation ≤5%), and the food-grade mass production capacity is 500-1000kg / day, which can be flexibly adjusted according to order demand (adjustment range 500-1000kg / day, adjustment response time ≤2h); the process scale-up adopts the "gradient scale-up method", from small-scale test (100g / batch), pilot test (50kg / batch) to mass production (200kg / batch), with particle size and encapsulation rate fluctuations ≤3% and no batch differences; during mass production, a continuous feeding mode is adopted, with a single feeding amount ≥50kg, equipped with a raw material pretreatment buffer tank, which shortens the production cycle while ensuring product uniformity, and the single batch production cycle ≤8h; (3) Mass production cost control: Through carrier compounding optimization (compounding chitosan and wheat gliadin, adding nano SiO2 anti-agglomeration regulator, the cost is reduced by 12% compared with single chitosan carrier) and energy-saving control of process parameters (ultrasonic intermittent mode saves 15% energy, gradient drying saves 20% energy, equipment linkage saves 8% energy), the unit comprehensive production cost of food-grade mass production products is ≤35 yuan / kg, of which the carrier cost accounts for ≤40%, energy consumption cost accounts for ≤25%, and raw material loss accounts for ≤5%, which is suitable for large-scale application in the food processing industry. The cost is reduced by more than 10% compared with conventional nano-embedding process, and the shelf life of mass production products is extended to 12 months; it is different from the mass production process of single carrier or no anti-agglomeration regulator in the existing technology, and avoids the technical defects of "fixed capacity that cannot be adjusted" in the existing theaflavins encapsulation industrialization. The new capacity can be flexibly adjusted and the cost can be precisely controlled, further reducing the overlap with existing patents; Furthermore, it also includes targeted modification and synergistic post-processing, which differs from conventional simple mixed modification, specifically: (1) After the pharmaceutical-grade encapsulated product was freeze-dried, it was first subjected to vacuum degassing (vacuum degree -0.095MPa, temperature 25℃, time 15min) to remove residual air in the pores of the product. Then it was placed in a pH 7.0 phosphate buffer system, and an EDC / NHS catalytic system was added (EDC to NHS molar ratio 1.2:1, both concentrations 50mM, the amount of catalytic system added was 8% of the product mass). The reaction was carried out at 37℃ and 120r / min for 2h with constant temperature shaking. The nanoparticles encapsulating theaflavins were directionally covalently linked to bone-targeting alendronate through amide bond reaction. After the reaction, it was purified by ultrafiltration centrifugation (12000r / min, 10min, ultrafiltration membrane pore size 50nm) to remove residual air. Unreacted reagents and small molecule impurities were then freeze-dried at low temperature (-40℃, 2h) to obtain bone-targeting drug-loaded nanoparticles. The enrichment rate of these particles at the lesion site was increased by more than 40% compared with unmodified particles, the in vitro sustained-release period was extended to 48h, the blood half-life was extended by 2.5 times compared with unmodified particles, and there was no hemolytic toxicity. Unlike the "theaflavins-metal-organic framework complex" encapsulation modification method in the existing technology, this method abandons the metal-organic framework carrier and adopts porous platinum-based nanoparticles and liposome composite carriers combined with alendronate for targeted modification to form a unique targeted drug delivery system. This effectively avoids the overlap of existing anti-aging and targeted encapsulation related patents, while enhancing bone-targeting specificity, forming a significant technical difference from existing theaflavins anti-aging related patents. (2) During the emulsification stage, 2% to 5% by mass of 2-o-ethyl ascorbic acid and 0.5% to 1% eugenol are added simultaneously to the cosmetic-grade encapsulation product as synergistic ingredients. They are combined with theaflavins to enhance the whitening, antioxidant, anti-inflammatory and soothing effects without affecting the encapsulation stability and particle size distribution. The whitening activity of the product is increased by more than 35% compared with the single theaflavin encapsulation product.

[0034] The theaflavins nano-encapsulated products prepared by the method described above have a core-shell structure, with theaflavins as the core (i.e., highly stable theaflavins for direct consumption) and modified functionalized nanocarriers as the shell. These products exhibit uniform particle size distribution, a coefficient of variation ≤15%, encapsulation rate ≥80%, activity retention rate ≥90%, water solubility increased by more than 30% compared to unencapsulated theaflavins, bioavailability ≥85%, and light-protected room-temperature stability increased by more than 6 months compared to unencapsulated raw materials. Based on application scenarios, these products are categorized into three types: food-grade, pharmaceutical-grade, and cosmetic-grade. Pharmaceutical-grade products can be further linked with alendronate for osteoporosis treatment; cosmetic-grade products can be supplemented with 2-o-ethyl ascorbic acid and eugenol to achieve synergistic whitening and moisturizing effects; and food-grade products can be used for meat product preservation, beverage and baking product processing. Unlike the product structure of "theaflavins-metal-organic framework complex" in existing technologies, this product uses a hierarchically modified nanocarrier to form a core-shell structure, without metal-organic framework components, and has specific functions for different scenarios (food-grade anti-agglomeration, pharmaceutical-grade bone targeting, cosmetic-grade transdermal whitening), forming a significant structural and functional difference from existing theaflavins-related encapsulated products.

[0035] As mentioned above, the theaflavins nano-encapsulated products for direct consumption have applications in the food, pharmaceutical, and cosmetic fields.

[0036] The products are categorized into three types based on their application scenarios: food-grade, pharmaceutical-grade, and cosmetic-grade, with clearly defined functions and application scenarios. (1) Food-grade products: Excellent water solubility and strong antioxidant properties. They can be directly used for antioxidant preservation of meat products, addition of functional beverages, and processing of baked goods. They have no odor and do not affect the sensory properties of the products. (2) Pharmaceutical grade products: They have bone-targeting properties, good biocompatibility, and excellent sustained-release properties, and can be used as adjunctive treatment for osteoporosis and in the development of related drug formulations; (3) Cosmetic grade products: They have strong transdermal absorption properties and, when combined with other ingredients, have whitening, brightening, antioxidant, moisturizing, anti-inflammatory, and soothing effects. They can be used in the development of skin care products and functional cosmetic formulations.

[0037] Specifically, the relevant preparation and testing methods are as follows: Example 1: Preparation of food-grade direct-drinking theaflavins nano-encapsulated products, which can be achieved as follows: Figure 1 As shown: Step 1: Screening and Modification of Nanocarriers 20g of high-purity chitosan with a deacetylation degree of 90% was selected as a food-grade carrier. Carboxymethylation modification was performed by dissolving the chitosan in 1000ml of 1% acetic acid solution and adding 15g of chloroacetic acid. The reaction was carried out at 60℃ with stirring for 4 hours. After the reaction, the pH of the system was adjusted to 7.0 with sodium hydroxide solution. The mixture was filtered, washed three times with deionized water, and vacuum dried at 60℃ to obtain the unoptimized carboxymethylated chitosan. The carrier ratio was optimized by adding 10g of modified wheat gliadin at a mass ratio of 2:1. Simultaneously, 0.4% of nano-SiO2 was added as an anti-agglomeration regulator to the total mass of the compounded system. The mixture was thoroughly stirred to reduce particle agglomeration, resulting in the carboxymethylated chitosan.

[0038] The modified wheat gliadin was prepared using a conventional enzymatic hydrolysis modification process, specifically: natural wheat gliadin was taken, and neutral protease (enzyme activity 10000U / g) was added. The amount of enzyme added was 0.5% of the protein mass. The mixture was enzymatically hydrolyzed at 45℃ and pH 7.0 for 2 hours. After inactivation, filtration, and freeze-drying, the modified wheat gliadin was obtained. This modification process is a conventional and publicly disclosed process in the field and does not require further description.

[0039] Step 2: Theaflavins Pretreatment Theaflavin with a purity of 85% (food-grade commercial raw material, conforming to GB 2760 standard, with a mass ratio of theaflavin-3-gallate to theaflavin-3'-gallate of 1:1.0, a commercially available conventional formulation) was selected. The theaflavin-3-gallate to theaflavin-3'-gallate mass ratio was 1:1.0. After being pulverized, the theaflavin was passed through a 90-mesh sieve and deionized water was added to prepare an aqueous solution with a mass concentration of 8 mg / mL. After stirring evenly, the pretreated theaflavin aqueous solution was obtained and stored at 4℃ for later use. The storage time should not exceed 2 hours.

[0040] Step 3: Implementation of the nano-embedding process An ultrasonic emulsification-spray freeze-drying method was used to mix pretreated theaflavins aqueous solution with carboxymethylated chitosan at a core-to-wall mass ratio of 1:3. The pH of the system was adjusted to 6.0, the emulsification temperature was controlled at 30℃, the ultrasonic power was 40% (frequency 30kHz), and ultrasonic emulsification was carried out for 25 min to obtain theaflavins nano-embedded emulsion. The emulsion was then dried by spray freeze-drying at a temperature controlled at -25℃ to obtain theaflavins nano-embedded powder.

[0041] Step 4: Process Optimization and Quality Inspection The Box-Behnken response surface methodology was employed, with particle size variation coefficient, encapsulation efficiency, and activity retention rate as the core evaluation indicators. Ultrasonic time, ultrasonic power, core-to-wall ratio, and drying temperature were selected as independent variables for a four-factor, three-level response surface optimization experiment (experimental factors and levels are shown in Table 1). The optimal process parameters were finally obtained: core-to-wall ratio 1:3, ultrasonic power 40%, ultrasonic time 25 min, and drying temperature -25℃. The particle size distribution of the encapsulated product was controlled to be 80-150 nm, with a variation coefficient of 12%. The activity and encapsulation efficiency of theaflavins were detected by HPLC, particle size distribution and variation coefficient were detected by laser particle size analyzer, and organic residues and impurities of the carrier were detected by HPLC-MS. The average value of three parallel experiments was taken: encapsulation efficiency 83%, activity retention rate 92%, carrier residue <5 mg / kg, and water solubility improvement rate 35%. All indicators met the quality standards for food-grade encapsulated products, and the qualified product is a food-grade direct-drinking theaflavins nano-encapsulated product.

[0042] Table 1. Response Surface Experiment Factors and Levels Design Table

[0043] Based on the aforementioned four-factor, three-level design, a total of 29 response surface methodology (RSM) experiments were designed. The evaluation criteria included a smaller particle size variation coefficient, higher encapsulation rate, and higher activity retention rate. Randomized sequential experiments were conducted, and the test results for each group were recorded. A quadratic polynomial regression model was established between the three indicators and the four factors through regression fitting. Analysis of variance verified that the model P < 0.01, indicating extreme significance and no significant lack of fit. The experimental data were reliable, the model fit was good, and it could accurately predict the correspondence between process parameters and product performance. Through response surface model prediction and multiple repeated experiments, the optimal process parameters for the nano-encapsulation of food-grade direct-drinking theaflavins were determined to be: core-to-wall mass ratio 1:3, ultrasonic emulsification power 40%, ultrasonic emulsification time 25 min, and spray freeze-drying temperature -25℃. Under these optimal process conditions, the particle size of the food-grade encapsulated product could be precisely controlled to a stable distribution of 80–150 nm, with a particle size variation coefficient as low as 12%. The particles were uniformly dispersed without significant agglomeration, and the powder uniformity was significantly better than that of products produced by conventional processes.

[0044] To verify the stability and reliability of the optimal process, this invention conducted three parallel verification experiments on the optimal process parameters and carried out comprehensive performance testing using industry-authoritative standard testing methods: the theaflavins encapsulation rate and activity retention rate were accurately detected by high performance liquid chromatography (HPLC), the particle size distribution and coefficient of variation of the product were determined by laser dynamic light scattering instrument, and organic residues and trace impurities of the carrier were detected by HPLC-MS. The results of the parallel experiments are shown in Table 2 below.

[0045] Table 2 Results of parallel verification tests of the optimal process (n=3)

[0046] As shown in Table 2, the parallel verification data of the three sets of repeated test data exhibited extremely small deviations and high stability, proving that the optimized process parameters obtained by this invention have good repeatability and strong mass production feasibility. The final average test results show that the encapsulation rate of the food-grade theaflavins nano-encapsulated product of this invention can reach 83%, the theaflavins activity retention rate is as high as 92%, and the carrier organic residue is <5mg / kg. Compared with unencapsulated theaflavins raw materials, the overall water solubility is improved by 35%, and all performance indicators strictly meet the safety and quality standards for food-grade nano-functional raw materials.

[0047] The above test results correspond to the present invention. Figure 2 , Figure 3 :in Figure 2 The particle size distribution of the product corresponding to this optimal process is shown in the spectrum. The spectrum shows that the product particle size distribution is concentrated, there is no large particle agglomeration, and the single peak is symmetrical, which is completely consistent with the particle size and coefficient of variation data in this table. Figure 3 The results of long-term oxidative stability testing of the products from this process confirm that the products prepared by the optimal process can significantly improve the storage stability of theaflavins.

[0048] This invention solves the defects of existing processes, such as imbalance between encapsulation rate and activity retention, poor product uniformity, high residue, and insufficient improvement in water solubility, through precise optimization of response surface methodology. It balances high encapsulation rate, high activity retention, high dispersion uniformity, and high safety. The qualified product is a food-grade theaflavins nano-encapsulated product with high stability, high activity, and high solubility.

[0049] Step 5: Integration of Storage and Industrialization The qualified encapsulated powder is packaged in light-proof, oxygen-proof, and moisture-proof aluminum foil and stored and transported in a cool, dry place at room temperature. An industrial production line is composed of a JS-1000 ultrasonic emulsifier, a GJB-2000 high-pressure homogenizer, an SLFD-500 spray freeze dryer, and an S7-1200 PLC fully automatic control system. The pilot production capacity has reached a stable 200 kg / day, and the mass production capacity can reach 800 kg / day. According to cost accounting, the unit comprehensive production cost of the product in this embodiment is 32 yuan / kg, which is lower than the preset cost threshold of 35 yuan / kg, making it suitable for large-scale food processing applications.

[0050] 1.1 Detection Results and Application Examples of Example 1 1.1.1 Summary of Core Detection Results The food-grade theaflavins nano-encapsulated powder for direct consumption prepared in Example 1 was subjected to comprehensive performance testing, and the specific results are shown in Table 3 below.

[0051] Table 3

[0052] As shown in Table 3, the food-grade encapsulated product prepared in Example 1 exhibits all performance indicators superior to industry standard thresholds. Existing conventional theaflavins nano-encapsulation technologies generally have shortcomings, such as an encapsulation rate of only 70%~78% for single chitosan encapsulation products, an activity retention rate of less than 85%, and particle size variation coefficients often exceeding 18%, resulting in severe particle agglomeration and a water solubility improvement of less than 20%. Compared to existing technologies, this invention, through a modified chitosan and modified wheat gliadin composite carrier combined with a nano-SiO2 anti-agglomeration system, controls the product variation coefficient to 12%, significantly improving particle dispersion uniformity; simultaneously achieving both encapsulation rate and activity retention rate targets, completely solving the core pain point of imbalance between encapsulation rate and activity in existing technologies. Water solubility is increased by 35% compared to unencapsulated raw materials, fully meeting the requirements for clear, sediment-free direct-drinking beverages. Room temperature storage stability is significantly better than existing ordinary encapsulated products, possessing strong advantages in the food industry. 1.1.2 Application Examples Example 1-1: Application of Direct-Drinking Beverages The food-grade encapsulated powder prepared in Example 1 was added to deionized water at a ratio of 0.5 g / 100 mL. It dissolved completely after stirring for 5 minutes without precipitation or agglomeration. The beverage had a uniform pale yellow color and a refreshing taste without bitterness. In contrast, the control group, using an equal amount of unencapsulated theaflavins with 85% purity from step 2 of Example 1, showed a small amount of precipitation after stirring for 15 minutes, and distinct stratification occurred after standing for 10 minutes. After storing the beverage at room temperature and under light for 30 days, the theaflavins activity retention rate was 88%, while the activity retention rate of the unencapsulated theaflavins beverage was only 42%. This demonstrates a significant reduction in oxidative degradation rate, effectively extending the shelf life of the direct-drinking tea beverage and solving the problems of short shelf life, turbidity, and poor taste in existing theaflavins beverages.

[0053] To further verify the advantages of the food-grade theaflavins nano-encapsulated product of this invention in direct-drink beverages, a comparative experiment was conducted under the same conditions to examine the solubility, appearance, taste, and long-term storage antioxidant stability of the nano-encapsulated product and the unencapsulated theaflavins raw material. Experimental group: The food-grade theaflavins nano-encapsulated powder prepared by the optimal process in Example 1 was uniformly added to room-temperature deionized water at a ratio of 0.5 g / 100 mL. After stirring at room temperature for 5 minutes, the system completely dissolved, resulting in a clear and transparent solution without visible particles or agglomeration. The overall color was uniformly translucent pale yellow, and the taste was refreshing, without the bitterness or astringency inherent in traditional theaflavins, demonstrating excellent sensory quality. Control group: Under identical water quality, temperature, and dosage conditions, an equal amount of 85% pure unencapsulated theaflavins from step 2 of Example 1 was added. After continuous stirring for 15 minutes, the system still exhibited significant fine insoluble precipitates and extremely poor dispersibility. After standing for 10 minutes, the system showed significant solid-liquid stratification, turbidity, and sedimentation, failing to meet the quality requirements for clear and transparent direct-drink beverages. Furthermore, it had a prominent bitter taste and a poor sensory experience. The results of the room temperature and light storage stability test showed that after continuous storage of both groups of prepared theaflavins beverages under room temperature and natural light for 30 days, the theaflavins activity retention rate of the nano-encapsulated theaflavins beverage of this invention reached 88%, with extremely low activity loss. In contrast, the activity retention rate of the unencapsulated theaflavins control group beverage was only 42%, with more than half of the active ingredients degrading and becoming ineffective due to light and oxidation. Comparative experiments fully demonstrate that the present invention, through its nano-core-shell encapsulation structure, can significantly shield the theaflavins from external light and oxygen oxidation, greatly reducing the rate of theaflavins' oxidative degradation. This effectively solves the industry's technical pain points regarding traditional theaflavins in beverages, such as poor solubility, easy turbidity and layering, strong bitterness, easy oxidation under light, and short shelf life. To quantify the performance differences between the two groups of samples, solidify the experimental data, and corroborate the beneficial effects of the technology, the comparative test results for beverage applications are summarized in the table below, with differences in appearance and stability corresponding to... Figure 3 Oxidative stability comparison curves.

[0054] Table 4 Comparison of application performance of the encapsulated product and the unencapsulated theaflavins in beverages according to the present invention

[0055] Combining the quantitative data in Table 4 with Figure 3Stability curves show that unencapsulated theaflavins, due to their poor water solubility and strong photosensitive oxidizing properties, cannot directly meet the industrial application requirements of direct-drinking beverages, exhibiting numerous defects such as difficulty in dissolution, poor finished product appearance, unpleasant taste, and extremely short shelf life. In contrast, the nano-encapsulated theaflavins prepared in this invention, relying on a dense core-shell protective structure constructed from a modified composite carrier, not only fundamentally improves the water solubility and dispersibility of theaflavins, achieving rapid dissolution and a clear, transparent beverage, but also effectively isolates them from oxidative damage caused by light and oxygen, greatly enhancing the storage stability of theaflavins. This invention's technical solution can significantly optimize the sensory quality and shelf stability of direct-drinking tea beverages while ensuring the functional activity of theaflavins, effectively extending the shelf life of tea products. It is fully adaptable to the large-scale production and market promotion of functional direct-drinking tea beverages, possessing outstanding industrial value and technological advancement.

[0056] Example 1-2: Application in meat product preservation The food-grade encapsulated powder prepared in Example 1 was added to minced pork at a final mass concentration of 0.3%, stirred evenly, and then used to make sausages. The sausages were stored at 4°C. The peroxide value (POV) and total bacterial count of the sausages were measured at 0, 7, and 14 days of storage. The results showed that at 14 days of storage, the POV of the sausages with the encapsulated product was 0.32 meq / kg, and the total bacterial count was 3.2 × 10⁻⁶. 3 The CFU / g values ​​all met food safety standards; the control group of sausages without added encapsulated products had a POV value of 0.87 meq / kg and a total bacterial count of 8.9 × 10⁻⁶ after 14 days of storage. 4 The CFU / g level exceeds food safety standards. This indicates that the encapsulated product of this invention can effectively inhibit oxidative deterioration and microbial growth in meat products, exhibiting significant preservation effects, and its addition does not affect the taste and flavor of the sausage.

[0057] To further verify the application performance and actual preservation effect of the food-grade theaflavins nano-encapsulated product of this invention in the field of meat product preservation, a blank control preservation experiment was set up. Using pork sausage as the application carrier, under refrigerated cold chain storage conditions at 4℃, the peroxide value (POV) and total bacterial count of meat products at different storage periods were measured to systematically evaluate the inhibitory ability of the nano-encapsulated theaflavins of this invention on fat oxidation and microbial growth in meat products, and to quantitatively verify the preservation, anti-corrosion, and quality-preserving effects of the product. Experimental group: The food-grade theaflavins nano-encapsulated powder prepared by the optimal process in Example 1 was uniformly added to fresh minced pork at a final mass concentration of 0.3%. After thorough mixing, the mixture was stuffed into sausages, tied, and shaped to obtain the experimental group sausage samples, which were stored in a constant temperature refrigerated environment at 4℃ in the dark. Blank control group: Blank sausage samples were prepared under the same raw material ratio, processing technology, shaping conditions, and storage environment, without the addition of any preservatives or theaflavins, for parallel control experiments. Both groups of samples were stored at 4℃. Samples were taken at three key time points: 0 days, 7 days, and 14 days of storage. Testing was conducted according to national standards: peroxide value (POV) of meat products was tested using GB 5009.37-2016, and total bacterial count was tested using GB 4789.2-2022. According to the general food safety limits for cured and sausage meat products, the acceptable limits for peroxide value after 14 days of refrigeration are ≤0.50 meq / kg, and the acceptable limits for total bacterial count are ≤1.0×10 CFU / g. Products exceeding these limits were considered oxidative deterioration and microbial contamination, failing to meet food safety standards. Three parallel tests were conducted on each group of samples, and the average value was taken. The specific results of the preservation performance tests are shown in Table 5 below, which compares the oxidation trend with the microbial growth pattern. Figure 3 Spectrum for verifying the long-term stability of the product.

[0058] Table 5 Comparison of POV value and total bacterial count results in meat product preservation test (refrigerated at 4℃)

[0059] Table 5 shows the quantitative test results: In the initial storage period (0d), the quality of the two groups of sausage samples was basically the same, with no significant difference. As the refrigeration time increased, the fat oxidation rate of the blank group sausages was rapid, and microorganisms proliferated rapidly. After 14 days of storage, the peroxide value reached 0.87 meq / kg, far exceeding the national standard limit of 0.50 meq / kg, indicating severe rancidity of the fat; the total bacterial count reached 8.9 × 10 CFU / g, exceeding the national standard limit by nearly 9 times, indicating that the meat products had spoiled and lost their safety for consumption. In contrast, the test group with the food-grade theaflavins nano-encapsulated powder of this invention, after refrigeration at 4℃ for 14 days, had a peroxide value of only 0.32 meq / kg and a total bacterial count of only 3.2 × 10 CFU / g, with all indicators strictly meeting national food safety standards. The mechanism of this invention involves the nano-encapsulated theaflavins, which exhibit good water solubility and uniform dispersion, allowing for even distribution within meat product systems. This provides sustained and potent antioxidant effects, effectively scavenging free radicals from fat oxidation and inhibiting oil rancidity. Simultaneously, it disrupts microbial cell membrane structures and inhibits microbial metabolism and reproduction, resulting in long-lasting antibacterial and preservative effects. Sensory evaluation verified that sausages containing 0.3% of the encapsulated product of this invention showed no significant difference in color, odor, taste, or elasticity compared to fresh samples throughout the entire shelf life. They exhibited no bitter or off-flavors, no darkening of color, and no alteration of the original flavor or edible quality of the meat products. This demonstrates that the product of this invention possesses excellent antioxidant, antibacterial, and preservative properties, along with excellent food compatibility. It effectively solves the industry problems of short refrigeration periods, easy oxidation and rancidity, and easy bacterial growth in low-temperature meat products, demonstrating high application value and promising prospects in the field of meat product preservation. 1.2 Example 1: Comparative Design and Detection Results To highlight the advantages of the key raw materials (carboxymethylated chitosan and modified wheat gliadin) in this invention, two comparative examples were set up, replacing the two key raw materials with conventional raw materials respectively. Except for the replacement of raw materials, the preparation process was completely consistent with Example 1. The test results are compared with Example 1 as shown in Table 6 below.

[0060] Table 6

[0061] 1.3 Discussion of the results of Example 1 and comparative examples As shown in Table 6, Example 1 exhibits significant advantages in all performance indicators compared to the two comparative examples. The specific analysis is as follows: (1) Particle size distribution and dispersibility: The particle size distribution of Example 1 was concentrated in the range of 80-150 nm, with a coefficient of variation of only 12%, indicating that the particles were uniformly dispersed and there was no obvious agglomeration. Comparative Example 1-1 used unmodified ordinary chitosan. Due to the poor water solubility and low surface activity of ordinary chitosan, the encapsulated particles agglomerated severely, and the particle size increased to 180-320 nm, with the coefficient of variation rising to 21%, exceeding the standard requirement (≤15%). Comparative Example 1-2 used unmodified ordinary wheat gliadin, which had insufficient dispersibility, resulting in an expanded particle size distribution range and a coefficient of variation rising to 17%, which was also close to the upper limit of the standard. It can be seen that the carboxymethylated modified chitosan used in this invention can significantly improve the water solubility and dispersibility of the carrier. Combined with modified wheat gliadin, it can effectively reduce particle agglomeration and optimize the particle size distribution of the encapsulated product.

[0062] (2) Encapsulation rate and activity retention rate: The encapsulation rate of Example 1 was 83%, and the activity retention rate was 92%, both far exceeding the standard requirements; the encapsulation rate of Comparative Example 1-1 was only 68%, a decrease of 15 percentage points compared to Example 1, and the activity retention rate was 81%, a decrease of 11 percentage points. This was mainly because ordinary chitosan has weak encapsulation ability and poor affinity with theaflavins, which easily leads to the oxidation and loss of theaflavins during the encapsulation process; the encapsulation rate of Comparative Example 1-2 was 75%, a decrease of 8 percentage points compared to Example 1, and the activity retention rate was 86%, a decrease of 6 percentage points. This was because ordinary wheat gliadin could not effectively form a stable encapsulation system, resulting in some theaflavins being exposed to the external environment and undergoing oxidation. This indicates that the modified carriers (carboxymethylated chitosan and modified wheat gliadin) selected in this invention can significantly improve the encapsulation efficiency while effectively protecting the activity of theaflavins, thus solving the problem of imbalance between encapsulation rate and activity retention in the prior art.

[0063] (3) Water solubility: The water solubility improvement rate of Example 1 was 35%, which is a significant improvement compared to unencapsulated theaflavins and can meet the application requirements of direct-drinking beverages and other scenarios; the water solubility improvement rate of Comparative Example 1-1 was only 18%, a decrease of 17 percentage points compared to Example 1, because the unmodified chitosan has poor water solubility and cannot effectively improve the solubility of theaflavins; the water solubility improvement rate of Comparative Example 1-2 was 25%, a decrease of 10 percentage points compared to Example 1, because ordinary wheat gliadin has fewer hydrophilic groups and has a limited effect on improving the water solubility of theaflavins. In summary, the modified carrier combination of the present invention can effectively improve the water solubility of theaflavins and solve the problems of easy aggregation and poor solubility in direct-drinking products.

[0064] Meanwhile, by comparing Example 1, Comparative Example 1-1 and Comparative Example 1-2, it can be seen that carboxymethylated chitosan and modified wheat gliadin have a synergistic effect in the method of the present invention, which can synergistically improve the relevant properties of the prepared food-grade direct-drinking theaflavins nano-encapsulated products, such as particle size distribution, coefficient of variation, encapsulation rate, activity retention rate and water solubility improvement rate.

[0065] Example 2: Preparation of pharmaceutical-grade theaflavins nano-encapsulated products for direct consumption, which can be achieved as follows: Figure 1 As shown: Step 1: Screening and Modification of Nanocarriers Porous platinum-based nanoparticles were selected as pharmaceutical-grade carriers, and liposomes were used as templates to synthesize carboxylated porous platinum-based nanoparticles. The specific preparation process of these nanoparticles is as follows: A chloroform organic mixture containing 0.7 mg / mL DPPC and 0.3 mg / mL cholesterol was placed in a vacuum environment of 40℃ and 0.08 MPa and rotary evaporated for 30 min until the organic solvent was completely evaporated, forming a uniform and transparent film on the bottle wall. Then, 10 mL of an α-ascorbic acid aqueous solution with a concentration of 52.8 mg / mL was added to the system, and the mixture was sonicated at room temperature for 20 min until the system was completely clear and transparent. Next, 8 mL of a 15 mM chloroplatinic acid solution was slowly added dropwise to the clear system, and the mixture was stirred at room temperature in the dark for 4 h at a stirring rate of 300 r / min until the solution turned completely black, which was the endpoint of the reaction. After the reaction, the solid and liquid were separated by high-speed centrifugation at 8000 r / min for 10 min, and the precipitate was collected to obtain the crude product of porous platinum-based nanoparticles. The obtained porous platinum-based nanoparticles were dispersed in anhydrous ethanol system, and thioctic acid with a mass of 10 times that of the porous platinum-based nanoparticles was added. The mixture was stirred continuously at room temperature in the dark for 12 hours at a stirring rate of 300 r / min. After the reaction was completed, the product was washed three times each with anhydrous ethanol and deionized water to remove unreacted raw materials and impurities. After purification, carboxylated porous platinum-based nanoparticles were obtained.

[0066] Step 2: Theaflavins Pretreatment Select theaflavin raw material with a purity of 90%, crush it and pass it through a 100-mesh sieve. Add deionized water to prepare an aqueous solution with a mass concentration of 10 mg / mL. After stirring evenly, the pretreated aqueous solution of theaflavin is obtained and stored at 4℃ for later use.

[0067] Step 3: Implementation of the nano-embedding process Nanoparticle encapsulation was performed using a thin-film dispersion-ultrasonic coupling process: the prepared carboxylated porous platinum nanoparticles were dispersed in deionized water to prepare an aqueous solution of carboxylated porous platinum nanoparticles with a concentration of 2 mg / mL; according to the mass ratio of carboxylated porous platinum nanoparticles to theaflavins of 1:2, a pretreated theaflavins aqueous solution was slowly added to the above aqueous solution, and the reaction was continuously stirred at room temperature for 12 h to prepare a homogeneous and stable Pt-COOH@TF nanoparticle system.

[0068] Crosslinking activators EDC and NHS were added to the prepared Pt-COOH@TF nanoparticle system, with the added mass of EDC and NHS being 5 times the mass of the Pt-COOH@TF nanoparticles, and the total added mass being 10 times the mass of the nanoparticles. Subsequently, alendronate, with a mass 8 times the mass of the carboxylated porous platinum-based nanoparticles, was added. The reaction was carried out under ambient temperature and light-protected conditions with continuous stirring for 12 hours (i.e., 12 hours for carboxylation modification), achieving bifunctional drug loading and crosslinking modification. After the reaction, the product was purified three times by repeated centrifugation and washing with deionized water to thoroughly remove unreacted free drug, activators, and impurities. Finally, a solid powder was prepared using a spray freeze-drying process. The drying process parameters were set as follows: feed rate 5 mL / min, inlet air temperature -40℃, and system vacuum degree 50 Pa. After continuous drying for 12 hours, pharmaceutical-grade theaflavin nano-encapsulated powder was obtained.

[0069] Step 4: Process Optimization and Quality Inspection A single-factor variable method was used to systematically optimize the core process parameters of the encapsulation process. With fixed basic conditions such as raw material ratios and reaction temperature, the core evaluation indicators were the uniformity of product particle size distribution, drug encapsulation rate, and theaflavin activity retention rate. Key process parameters such as ultrasonic time, stirring rate, core-to-wall ratio, and modification reaction time were optimized one by one. After screening and verification through multiple parallel experiments, the optimal process parameters were determined to be: stirring rate 300 r / min, ultrasonic emulsification time 20 min, core-to-wall ratio 1:2, and carboxylation modification reaction time 12 h. The encapsulated product prepared based on the optimal process parameters showed a precise particle size distribution controlled within 110-120 nm, a particle variation coefficient as low as 10%, and excellent particle dispersibility and system stability.

[0070] Comprehensive quality testing was conducted on the encapsulated product prepared under optimal process conditions. The results showed that the drug encapsulation rate of the product in this embodiment reached 86%, the theaflavins bioactivity retention rate was 93%, the alendronate loading was 2.0 mg / mg of encapsulated product, and the product zeta potential was -38 mV. All performance indicators consistently met and exceeded the quality standards for pharmaceutical-grade nano-encapsulated products. The product possesses excellent bone targeting and sustained-release properties, and can be applied to the targeted treatment of osteoporosis. The product that meets the quality requirements is the final pharmaceutical-grade direct-drinking theaflavins nano-encapsulated product.

[0071] This invention addresses the stringent preparation requirements of pharmaceutical-grade targeted drug delivery systems by employing a single-factor variable method to systematically and directionally optimize the core process parameters of a porous platinum-based nanocarrier coupled with theaflavins. During the experiment, basic conditions such as raw material ratios, initial reaction temperature, solvent system, and purification method were kept constant. The core evaluation indicators were multi-dimensional, including product particle size distribution uniformity, particle variation coefficient, theaflavins encapsulation rate, theaflavins activity retention rate, functional drug loading, and system colloidal stability. The effects of four key variables—stirring rate, ultrasonic emulsification time, core-to-wall ratio, and carboxylation modification reaction time—on the final product performance were investigated. Through multiple parallel repeated experiments, data comparison and screening, and stability verification, deteriorating process combinations were eliminated, and the optimal process parameters suitable for the pharmaceutical-grade porous platinum-lipoic acid modified system of this invention were determined. Through systematic single-factor experiments and verification, the optimal preparation process for pharmaceutical-grade theaflavins nano-encapsulation was determined to be: a stirring rate of 300 r / min, an ultrasonic emulsification time of 20 min, a core-to-wall mass ratio of 1:2, and a carboxylation modification reaction time of 12 h. Under this optimal combination of process parameters, sufficient carrier modification, stable in-situ encapsulation of theaflavins, and uniform loading of bifunctional drugs can be achieved. The nanoparticle formation process can be precisely controlled, avoiding process defects such as excessive particle growth, agglomeration, drug leakage, and incomplete carrier modification. Based on the above optimal process parameters, pharmaceutical-grade theaflavins nano-encapsulated products were prepared in batches. Comprehensive and standardized quality testing was conducted on the products. All experiments were performed in triplicate, and the average value of the test results was used to ensure the data was authentic, reliable, and traceable. The testing indicators cover particle size distribution, coefficient of variation, encapsulation efficiency, activity retention rate, alendronate loading, zeta potential, bioavailability, storage stability, and in vitro sustained-release performance. Supporting testing equipment and methods include: laser dynamic light scattering (LAS) for particle size and coefficient of variation, potentiometer for zeta potential, HPLC for encapsulation efficiency and activity retention rate, HPLC-MS for drug loading, in vitro dialysis for sustained-release performance, and in vivo animal metabolism experiments for bioavailability. The results of three parallel validation experiments under optimal process conditions are shown in Table 7 below, corresponding to the changes in product particle size distribution and sustained-release performance. Figure 2 , Figure 4 Detection spectrum.

[0072] Table 7 Results of parallel validation tests of the optimal process for pharmaceutical grade (n=3)

[0073] As shown in Table 7, the parallel test data of the three sets of repeated test data have extremely small deviations and excellent repeatability, proving that the pharmaceutical-grade process parameters optimized in this invention have strong stability, good mass production feasibility, and no significant performance fluctuations during process scale-up. All indicators of the product prepared by the optimal process meet and significantly exceed the general quality standards for pharmaceutical-grade nano-drug delivery systems: the product particle size is precisely locked within the optimal drug delivery range of 110–120 nm, with a coefficient of variation of only 10.0%, uniform particle dispersion, no agglomeration, and extremely high particle size uniformity; the theaflavins encapsulation rate can reach 86.0%, and the activity retention rate is as high as 93.0%, achieving a balance between high encapsulation rate and high activity retention, completely overcoming the defects of existing pharmaceutical-grade encapsulation technologies where encapsulation rate and activity are unbalanced. Meanwhile, the alendronate product of this invention has a loading capacity of 2.00 mg / mg, far exceeding the industry standard threshold, demonstrating outstanding bifunctional drug loading capacity; the product's zeta potential is stable at -38.0 mV, within the high colloidal stability range, effectively preventing sedimentation and aggregation failure of nanoparticles during storage; the product's in vivo bioavailability reaches 92.0%, and the activity retention rate remains as high as 91.0% after 30 days of refrigeration at 4℃, exhibiting excellent low-temperature storage stability; the 24-hour in vitro drug release rate reaches 78.0%, with a stable drug release curve and no burst release phenomenon (corresponding to...). Figure 4 (Sustained-release curve) enables long-lasting and uniform drug release, effectively prolonging the duration of drug efficacy in vivo. This invention utilizes a single-factor variable method to precisely optimize and adapt a proprietary process to a porous platinum-based carrier + lipoic acid modified system. Leveraging the carrier's porous structure, surface-modified targeting sites, and stable core-shell embedding structure, the product possesses excellent bone-targeting properties, long-lasting sustained-release properties, and biocompatibility. It exhibits no cytotoxicity or hemolytic risk, allowing for precise targeting of osteoporosis lesions and significantly improving therapeutic efficacy. All testing indicators fully demonstrate that the pharmaceutical-grade product prepared by this process fully meets the stringent raw material standards, production specifications, and clinical application requirements of the biopharmaceutical field. The product meeting these quality requirements is the final pharmaceutical-grade theaflavins nano-encapsulated product.

[0074] Step 5: Integration of Storage and Industrialization Qualified theaflavin nano-encapsulated powder is packaged in aseptic, light-proof aluminum-plastic sealed packaging and stored and transported in a low-temperature, light-proof environment at 4°C. This effectively avoids the degradation of active ingredients and product inactivation caused by high temperatures and light exposure. The entire process utilizes a biopharmaceutical-grade dust-free production line, low-temperature precision reaction equipment, and fully automated spray freeze-drying equipment for industrial-scale mass production. The parameters of each process can be precisely controlled, effectively controlling unit production costs, stabilizing batch consistency and overall product quality, and fully meeting the large-scale, standardized application needs of the biopharmaceutical field.

[0075] 2.1 Detection Results and Application Examples of Example 2 2.1.1 Summary of Core Detection Results The pharmaceutical-grade theaflavins nano-encapsulated powder prepared in Example 2 was subjected to comprehensive performance testing, and the specific results are shown in Table 8 below.

[0076] Table 8

[0077] As shown in Table 8, the core performance indicators of the pharmaceutical-grade theaflavins nano-encapsulated products prepared by this invention meet and exceed the industry's pharmaceutical-grade standards, demonstrating significant innovation and technological advantages compared to existing conventional theaflavins nano-encapsulation technologies. Existing traditional theaflavins encapsulated products generally suffer from defects such as wide particle size distribution, poor powder uniformity, particle variation coefficients generally exceeding 18%, drug encapsulation rates of only 75%–80%, theaflavins activity retention rates of less than 85%, and functional drug loading levels below 1.5 mg / mg. They also exhibit numerous technical shortcomings, including poor in vitro sustained-release performance, low in vivo bioavailability, and insufficient low-temperature storage stability.

[0078] Compared to existing technologies, this invention can precisely control the product particle size to the optimal medical drug delivery range of 110-120 nm, with a particle variation coefficient of only 10%. The nanoparticles are uniformly dispersed, and the colloidal system exhibits excellent stability. The product achieves a drug encapsulation rate of up to 86%, and the theaflavins bioactivity retention rate is as high as 93%, maximizing the preservation of the core bioactivity of theaflavins. The alendronate loading reaches 2.0 mg / mg, significantly improving drug loading capacity compared to existing technologies. The product's zeta potential is stable at -38 mV, within a highly stable potential range, effectively inhibiting nanoparticle aggregation and sedimentation. Furthermore, the product exhibits an in vivo bioavailability of up to 92%, and after 30 days of refrigerated storage at 4°C, the activity retention rate remains at 91%, with a 24-hour sustained-release rate of 78%. This enables long-term, stable drug release, effectively addressing the industry pain points of existing technologies, such as easy oxidation and degradation of theaflavins, short duration of efficacy, low drug loading, and insufficient bioavailability. It fully meets the stringent application standards of the biopharmaceutical field.

[0079] 2.1.2 Application Example (Osteoporosis Treatment) Sixty female osteoporosis model rats were randomly divided into three groups of 20 each: the embedded product group (Experimental Group), the unencapsulated theaflavins + alendronate mixed group (Control Group 1), and the saline group (Blank Group). The experimental group received an intraperitoneal injection of the embedded product prepared in Example 2 at a dose of 10 mg / kg body weight. Control Group 1 received the same dose of a mixed solution of unencapsulated 90% pure direct-drinking theaflavins and alendronate, with a mass ratio of 1:2 and a total concentration of 10 mg / mL. The blank group received an equal volume of saline. The treatment was continued for 4 weeks. Femoral bone mineral density and serum alkaline phosphatase (ALP) activity were measured. The results are shown in Table 9 below.

[0080] Table 9

[0081] Results Analysis: After 4 weeks of administration, the femoral bone mineral density of rats in the experimental group increased by 29.1% compared with that before administration, and serum ALP activity decreased by 30.5%, indicating that osteoporosis symptoms were significantly improved. In the control group, the femoral bone mineral density of rats increased by only 10.4%, and serum ALP activity decreased by 18.6%, with the improvement effect being far lower than that of the experimental group. There was no significant change in the blank group. The reason is that the encapsulated product of this invention has good targeting and sustained-release properties, which can accurately deliver theaflavins and alendronate to the bone site, release them slowly, prolong the duration of action, and at the same time avoid the degradation of theaflavins in the gastrointestinal tract, thereby improving bioavailability. In contrast, in the unencapsulated mixed system, theaflavins are easily oxidized and degraded, and alendronate has no targeting, and most of it is rapidly metabolized in vivo, failing to exert its full therapeutic effect.

[0082] 2.2 Comparative Design and Test Results of Example 2 To highlight the advantages of the key raw materials (porous platinum-based nanoparticles and thioctic acid) in this invention, two comparative examples were set up, replacing the two key raw materials with conventional raw materials respectively. Except for the replacement of raw materials, the preparation process was completely consistent with Example 2. The test results are compared with those of Example 2 as shown in Table 10 below.

[0083] Table 10

[0084] 2.3 Discussion of Example 2 and Comparative Example Results As shown in Table 10, all performance indicators of Example 2 are significantly better than those of the two comparative examples. The specific analysis is as follows: (1) Particle size and dispersibility: The particle size distribution of Example 2 was precisely controlled within 110-120 nm (meeting pharmaceutical grade requirements), with a coefficient of variation of only 10%, indicating uniform particle dispersion and good stability. Comparative Example 2-1 used ordinary platinum nanoparticles without porous structure, which had a small specific surface area and could not be effectively dispersed, resulting in a particle size increase to 150-180 nm and a coefficient of variation of 16%, exceeding the standard requirements. Comparative Example 2-2 used citric acid to replace lipoic acid for carboxylation modification, but the modification effect of citric acid was poor and could not effectively optimize the surface properties of the carrier, resulting in an expanded particle size distribution range and a coefficient of variation of 13%. This indicates that the porous platinum-based nanoparticles used in this invention have a porous structure that can increase the specific surface area. Combined with lipoic acid modification, they can effectively improve the dispersibility and stability of the carrier, precisely control the particle size distribution, and meet the requirements of pharmaceutical grade products.

[0085] (2) Encapsulation efficiency and activity retention rate: The encapsulation efficiency of Example 2 was 86%, and the activity retention rate was 93%, both of which met and exceeded the pharmaceutical grade standard; the encapsulation efficiency of Comparative Example 2-1 was only 72%, a decrease of 14 percentage points compared to Example 2, and the activity retention rate was 82%, a decrease of 11 percentage points. This is because ordinary platinum nanoparticles do not have a porous structure, have limited encapsulation capacity, and cannot effectively isolate external oxygen, leading to the oxidation and loss of theaflavins; the encapsulation efficiency of Comparative Example 2-2 was 79%, a decrease of 7 percentage points compared to Example 2, and the activity retention rate was 87%, a decrease of 6 percentage points. The modification effect of citric acid was insufficient, the affinity between the carrier and theaflavins was poor, and theaflavins were easily leaked and oxidized during the encapsulation process. It can be seen that the porous platinum-based nanoparticles and lipoic acid modification scheme selected in this invention can significantly improve the encapsulation efficiency, effectively protect the activity of theaflavins, and meet the stringent requirements of the biopharmaceutical field.

[0086] (3) Loading capacity and sustained-release performance: The alendronate loading capacity of Example 2 was 2.0 mg / mg, with a 24-hour sustained-release rate of 78%, achieving precise targeting and slow release of the drug. The loading capacity of Comparative Example 2-1 was only 1.2 mg / mg, a decrease of 40% compared to Example 2, and the 24-hour sustained-release rate was 55%, a decrease of 23 percentage points. This is because ordinary platinum nanoparticles lack a porous structure, have limited loading capacity, and cannot form a stable sustained-release system. The loading capacity of Comparative Example 2-2 was 1.4 mg / mg, a decrease of 30% compared to Example 2, and the 24-hour sustained-release rate was 65%, a decrease of 13 percentage points. The surface activity of the citric acid-modified carrier was insufficient, failing to effectively bind alendronate, and the sustained-release performance was poor. This indicates that the key raw material combination of the present invention can effectively improve drug loading capacity and sustained-release performance, achieving synergistic delivery of theaflavins and alendronate, and improving the therapeutic effect of osteoporosis.

[0087] Meanwhile, by comparing Example 2, Comparative Example 2-1 and Comparative Example 2-2, it can be seen that the porous platinum-based nanoparticles and thioctic acid in the method of the present invention have a synergistic effect, which can synergistically improve the relevant properties of the prepared pharmaceutical-grade direct-drinking theaflavins nano-encapsulated products, such as particle size distribution, coefficient of variation, encapsulation rate, activity retention rate, alendronate loading and 24h sustained release rate.

[0088] Example 3: Preparation of cosmetic-grade theaflavins nano-encapsulated products for direct consumption, which can be achieved as follows: Figure 1 As shown: Step 1: Screening and Modification of Nanocarriers Food-grade cosmetic-grade nanoemulsions were selected as cosmetic-grade encapsulation carriers. The nanoemulsions underwent surface activation modification to enhance their skin compatibility and permeability. The nanoemulsion matrix was placed in a 40℃ constant-temperature water bath with stirring at 300 rpm, and a trace amount of Tween-80 was slowly added dropwise as a surface activator. Stirring was continued for 15 minutes to complete the surface activation. Subsequently, functional excipients were added sequentially to the modified nanoemulsion according to the following ratio: 100% nanoemulsion matrix, 8% modified silk fibroin protein, 5% activated soybean seed polysaccharide, and 3% pH-responsive self-assembled short peptides. Stirring was continued for 30 minutes, followed by 30kHz low-frequency ultrasonic dispersion for 10 minutes. Finally, a structurally stable three-dimensional network encapsulation carrier with moisturizing, transdermal absorption, and pH-responsive properties was prepared.

[0089] The modified silk fibroin was prepared using a conventional ethanol modification process: natural silk fibroin was dissolved in deionized water to prepare a 5% (w / w) silk fibroin aqueous solution, and anhydrous ethanol was added at a volume ratio of 1:4. The mixture was reacted at a constant temperature of 60°C for 2 hours. After the reaction, the mixture was cooled, dialyzed, and freeze-dried to obtain the modified silk fibroin. The activated soybean seed polysaccharide and pH-responsive self-assembled short peptides are both commercially available cosmetic-grade functional excipients, which are known in the field as raw materials that can be directly applied to skin care systems without the need for additional custom synthesis.

[0090] Step 2: Theaflavins Pretreatment Theaflavin raw material with a purity of 88% was selected, in which the mass ratio of theaflavin-3-gallate to theaflavin-3'-gallate was 1:1.1. After being pulverized, it was passed through an 80-mesh sieve, and deionized water was added to prepare an aqueous solution of theaflavin with a mass concentration of 6 mg / mL. After stirring evenly, the pretreated aqueous solution of theaflavin was obtained and stored at 4℃ for later use.

[0091] Step 3: Implementation of the nano-embedding process Nano-encapsulation was achieved using a high-pressure homogenization-nanoemulsification coupling process: Pretreated theaflavins aqueous solution was mixed with a modified nanoemulsion carrier at a core-to-wall ratio of 1:2.5 to obtain a mixed base solution. 2% (by weight of the theaflavins aqueous solution) of 2-o-ethyl ascorbic acid and 1.5% (by weight of the theaflavins aqueous solution) were added to the base solution as synergistic antioxidant and anti-inflammatory components. The pH of the system was adjusted to 5.5 using citrate buffer, and the emulsification temperature was kept constant at 32℃. Ultrasonic emulsification was performed for 20 minutes at 40% ultrasonic power and 40kHz ultrasonic frequency. After ultrasonication, the system was subjected to high-pressure homogenization and cycling at 80MPa for three cycles, ultimately yielding a cosmetic-grade theaflavins nano-encapsulated emulsion with excellent homogeneity and stability.

[0092] Step 4: Process Optimization and Quality Inspection Response surface methodology (RSM) was employed to perform multi-parameter synergistic optimization of the cosmetic-grade encapsulation process. Using product particle size distribution, particle size variation coefficient, drug encapsulation rate, and skin penetration rate as core evaluation indicators, key process parameters such as emulsification temperature, system pH, ultrasonic emulsification time, and high-pressure homogenization pressure were systematically optimized. Through multiple sets of RSM experiments, the optimal process parameters were determined to be: system pH 5.5, emulsification temperature 32℃, ultrasonic emulsification time 20 min, 80 MPa high-pressure homogenization cycles (3 cycles), and a core-to-wall ratio of 1:2.5. The product prepared using this optimal process exhibited a stable particle size distribution of 60-180 nm and a particle size variation coefficient of 13%, fully meeting the particle size uniformity standards for cosmetic nanomaterials.

[0093] After comprehensive performance testing, the cosmetic-grade theaflavin nano-encapsulated emulsion prepared by the optimal process can achieve an encapsulation rate of 84% and a theaflavin activity retention rate of 91%. It also has excellent water solubility, skin permeability and whitening and moisturizing activities. All performance indicators meet the quality standards of cosmetic-grade nano-functional raw materials. It can be widely used in the cosmetic field as a highly efficient whitening, moisturizing and antioxidant functional raw material. The qualified product is the final cosmetic-grade direct-drinking theaflavin nano-encapsulated product.

[0094] This invention addresses the stringent industry requirements for cosmetic-grade skincare raw materials, demanding high particle size uniformity, excellent transdermal permeability, good sensory stability, and high activity retention. It employs the Box-Behnken response surface methodology to optimize the nanoemulsion encapsulation process for cosmetic-grade theaflavins using multiple parameters. Under constant conditions, including the modified nanoemulsion carrier formulation, functional excipient ratio, initial theaflavin concentration, and reaction environment, the interaction effects of four key process parameters—emulsification temperature, system pH, ultrasonic emulsification time, and high-pressure homogenization pressure—on the final product performance were systematically investigated, using four core comprehensive evaluation indicators: product particle size distribution range, particle variation coefficient, theaflavin encapsulation rate, and 24-hour skin penetration rate. Through multiple random response surface experiments, quadratic regression model fitting, analysis of variance, and significance testing, process combinations with poor stability and deteriorating performance were eliminated, resulting in the selection of the optimal synergistic process parameters suitable for the modified nanoemulsion three-dimensional network encapsulation system of this invention. After multiple sets of repeatable response surface methodology experiments and model prediction corrections, the optimal process parameters for the nano-encapsulation of theaflavins for cosmetic-grade direct consumption were finally determined to be: system pH value 5.5, emulsification temperature 32℃, ultrasonic emulsification time 20 min, 80 MPa high-pressure homogenization and circulation treatment three times, and material core-to-wall mass ratio 1:2.5. This combination of parameters can achieve full activation of the nanoemulsion carrier, uniform loading of theaflavins, stable emulsion system, and optimal interfacial tension. It can effectively avoid common technical defects in cosmetic emulsion systems such as wide particle size distribution, particle agglomeration, inactivation of active ingredients, emulsion stratification, and poor transdermal effect, and is suitable for the production requirements of room temperature preparation, gentle processing, and non-irritating cosmetics. Based on the above optimal process parameters, cosmetic-grade theaflavins nano-encapsulated emulsions were prepared, and the products were tested for comprehensive cosmetic quality indicators. All experiments were conducted in triplicate, and the average value of the test results was taken to effectively eliminate experimental errors and ensure data accuracy, repeatability, and reliability. The assay covered particle size distribution, particle variation coefficient, encapsulation efficiency, activity retention rate, water solubility enhancement rate, 24-hour transdermal penetration rate, whitening activity (tyrosinase inhibition rate), and low-temperature storage stability. Corresponding assay chromatograms and particle size distribution patterns are attached. Figure 2 The specific results of the parallel verification experiments are shown in Table 11 below.

[0095] Table 11 Results of parallel validation tests of optimal process for cosmetic grade (n=3)

[0096] As shown in Table 11, the parallel verification data of the three sets of repeated experiments exhibited small fluctuations and extremely high stability, proving that the cosmetic-grade process parameters obtained by the multi-factor synergistic optimization of the present invention have good repeatability and strong process stability, and can stably prepare high-quality cosmetic-grade theaflavins nano-encapsulated products on a large scale. The particle size of the product prepared by the optimal process is stably controlled within 60–180 nm, with a coefficient of variation of only 13.0%. The particle size distribution is concentrated, with no obvious agglomerates, which fully meets the particle size standard of cosmetic nanomaterials that are fine, uniform, and suitable for skin absorption.

[0097] Performance testing results show that the average encapsulation rate of the cosmetic-grade encapsulated product of this invention can reach 84.0%, and the theaflavins activity retention rate is as high as 91.0%, overcoming the shortcomings of existing cosmetic-grade theaflavins encapsulation technologies, such as low encapsulation rate and easy loss of activity. The water solubility of the product is improved by 38.0% compared with the unencapsulated raw material, completely solving the problems of poor water solubility of natural theaflavins, difficulty in adapting to water-based cosmetic systems, and easy precipitation and turbidity. The core skin care performance is excellent, with a skin transdermal penetration rate of 42.0% after 24 hours, which can effectively penetrate the stratum corneum and act on the dermis to exert its effects. The tyrosinase inhibition rate is as high as 76.0%, and the whitening and antioxidant activities are outstanding. At the same time, the activity retention rate can still reach 89.0% after refrigeration at 4℃ for 30 days, with excellent low-temperature storage stability, which can meet the production requirements of long-term storage and batch stability of cosmetics.

[0098] This invention constructs a modified nanoemulsion three-dimensional interpenetrating network carrier, combined with a synergistic whitening and antioxidant system of 2-o-ethyl ascorbic acid and eugenol, and integrates a proprietary high-pressure homogenization-nanoemulsification coupling process to simultaneously achieve high encapsulation, high activity, high transdermal permeability, and high stability of theaflavins. All indicators are superior to the industry's general standards for cosmetic-grade nanofunctional raw materials. It can be widely used as a highly efficient whitening, moisturizing, and antioxidant functional raw material in various cosmetic systems such as lotions, creams, serums, and toners. The qualified product is the final cosmetic-grade direct-drinking theaflavins nanoencapsulated product.

[0099] Step 5: Integration of Storage and Industrialization Qualified encapsulated emulsions are sealed and protected from light, and stored and transported under refrigeration at temperatures below 4°C; they are adapted to cosmetic production processes to achieve large-scale supply.

[0100] 3.1 Detection Results and Application Examples of Example 3 3.1.1 Summary of Core Test Results The cosmetic-grade theaflavins nano-encapsulated emulsion prepared in Example 3 was subjected to comprehensive performance testing, and the specific results are shown in Table 12 below.

[0101] Table 12

[0102] As shown in Table 12, the cosmetic-grade theaflavin nano-encapsulated emulsion prepared by this invention exhibits superior performance indicators compared to industry cosmetic application standards, demonstrating significant technical advantages over existing theaflavin skincare raw materials and conventional encapsulation techniques. Existing conventional theaflavin skincare raw materials suffer from inherent defects such as poor water solubility, weak transdermal absorption, easy oxidation and inactivation of activity, weak whitening efficacy, and poor storage stability. Theaflavin products prepared using conventional encapsulation processes generally have an encapsulation rate below 80%, a theaflavin activity retention rate of less than 88%, a 24-hour skin penetration rate of only 25%–32%, a tyrosinase inhibition rate generally below 65%, and an activity loss rate exceeding 20% ​​after 30 days of low-temperature refrigeration, resulting in extremely poor product stability and efficacy. This invention improves the drug encapsulation rate to 84% and the theaflavins activity retention rate to 91% by constructing a modified nanoemulsion three-dimensional network encapsulation system, maximizing the preservation of the core whitening and antioxidant activities of theaflavins. Simultaneously, it increases the water solubility of the raw material by 38%, completely solving the industry problem of poor water solubility of natural theaflavins and difficulty in compounding with water-based skincare systems. The product achieves a skin penetration rate of up to 42% within 24 hours, breaking through the skin's stratum corneum barrier and effectively acting on the dermis to continuously exert skincare effects. The product exhibits a tyrosinase inhibition rate as high as 76%, demonstrating excellent whitening activity. Furthermore, after 30 days of refrigerated storage at 4°C, the product's activity retention rate still reaches 89%, significantly improving storage stability. This invention, through carrier formulation modification and process parameter optimization, synergistically balances the product's water solubility, permeability, storage stability, and skincare activity, perfectly adapting to the needs of large-scale cosmetic production, long-term storage, and end-user skincare applications, overcoming many performance shortcomings of existing theaflavins skincare raw materials. 3.1.2 Application Examples Example 3-1: Application of Whitening and Moisturizing Lotion The theaflavin nano-encapsulated emulsion prepared in Example 3 was added to a conventional basic whitening emulsion at a ratio of 10% of the volume of the basic whitening emulsion matrix. After uniform stirring, a theaflavin whitening and moisturizing emulsion was prepared and set as the experimental group. At the same time, a parallel control group was set up. The unencapsulated theaflavin raw material with a purity of 88% from step 2 of Example 3 was added to the same basic whitening emulsion matrix at a ratio equivalent to the effective theaflavin content of the experimental group to prepare an unencapsulated theaflavin whitening emulsion and set as the control group.

[0103] The trial recruited 30 healthy volunteers aged 25-35 with dull, dry, and rough skin. They were randomly divided into an experimental group and a control group, with 15 volunteers in each group. All volunteers applied the corresponding test lotion regularly after cleansing their face every morning and evening for 4 consecutive weeks. At the beginning of the trial, 2 weeks, and 4 weeks, the volunteers' skin moisture content and skin tone brightness (L-value) were measured. The results are shown in Table 7 below.

[0104] Table 13

[0105] As shown in Table 13, the volunteer trial data revealed no significant statistical differences in skin hydration and skin tone brightness between the two groups at the initial stage of the trial, indicating that their basic skin conditions were essentially the same and the experimental samples were highly comparable. After two and four weeks of continuous use, both lotions were able to improve skin dryness and dullness to some extent, but the whitening and moisturizing effects of the experimental group lotion were significantly better than those of the control group, with a significant difference between the groups.

[0106] After four weeks of continuous use, the experimental group saw an increase in skin hydration from 32.5% to 52.3%, a 60.9% improvement in skin moisturizing performance, and a 10.5 increase in skin tone brightness (L value). Dullness and roughness were significantly improved, resulting in a noticeable brightening and radiance to the skin. In contrast, after four weeks of continuous use, the control group only experienced a 10.9% increase in skin hydration and a minimal brightening effect, with skincare benefits far less pronounced than the experimental group.

[0107] The core mechanism behind this difference is as follows: The nano-encapsulated emulsion prepared in this invention, relying on a three-dimensional network nanocarrier structure, significantly enhances the water solubility and transdermal penetration of theaflavins, allowing them to quickly penetrate the skin surface and act on the dermis, exerting a long-lasting effect of anti-oxidation, melanin inhibition, and skin barrier repair. Simultaneously, the modified silk fibroin and soybean seed polysaccharides contained in the carrier possess excellent moisturizing and water-locking effects, forming a synergistic skincare system with theaflavins. In contrast, unencapsulated natural theaflavins have poor water solubility and weak transdermal penetration; most of their active ingredients remain only on the skin surface, making it difficult to penetrate and exert their effects. Furthermore, they are easily oxidized and deactivated by air, resulting in extremely low activity utilization and very limited whitening and moisturizing effects. Compared to existing cosmetic formulations that directly combine theaflavins, the nano-encapsulation technology of this invention maximizes the release of theaflavins' skincare activity, resulting in stronger efficacy and faster onset of action, possessing extremely high application value and promising prospects for promotion.

[0108] 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 method for direct-drinking theaflavins nano-encapsulation, characterized in that: Includes the following steps: Step 1: Screening and Modification of Nanocarriers Based on the application scenario, suitable nanocarriers are selected, and the selected carriers are modified to obtain modified nanocarriers. Step 2: Theaflavins Pretreatment Select direct-drinking theaflavins raw materials with a purity of not less than 80%, wherein the mass ratio of theaflavins-3-gallate to theaflavins-3'-gallate is 1:0.8-1.

2. After pulverizing, pass through an 80-100 mesh sieve, add deionized water, and prepare a theaflavins aqueous solution with a mass concentration of 5-10 mg / mL. After stirring evenly, the pretreated theaflavins aqueous solution is obtained and stored at 4℃ for later use to avoid oxidation and degradation of theaflavins. Step 3: Implementation of the nano-embedding process The pretreated theaflavins aqueous solution was mixed with the modified nanocarrier at a core-to-wall ratio of 1:2-1:

4. The pH of the system was adjusted to 5.0-7.0, the emulsification temperature was controlled at 28-32℃, the ultrasonic power was 40%, the ultrasonic frequency was 20-40kHz, and the emulsification was carried out for 20-30 minutes to obtain theaflavins nano-embedded emulsion. The emulsion was then dried by spray freeze-drying at a temperature controlled at -25℃ to obtain theaflavins nano-embedded powder. Step 4: Seal and package the qualified theaflavins nano-encapsulated products and protect them from light to obtain the theaflavins nano-encapsulated products for direct consumption. Non-conforming products are returned to step 3 for re-embedding.

2. The method according to claim 1, characterized in that: In step 1, suitable nanocarriers are selected according to the application scenario and are divided into three categories: food-grade carriers are selected from one or a mixture of chitosan and modified wheat gliadin; pharmaceutical-grade carriers are selected from one or a mixture of liposomes and porous platinum-based nanoparticles; and cosmetic-grade carriers are selected from one or a mixture of nanoemulsions and nanomicelles. The modified carriers after screening were specifically modified as follows: chitosan was modified by carboxymethylation or quaternization, and liposomes were modified by surface modification. After modification, the carrier ratio was optimized to reduce particle aggregation and improve the water solubility, dispersibility and encapsulation performance of the carriers. Among them, porous platinum-based nanoparticles were synthesized using liposomes as templates. Specifically, the nanoparticles were rotary evaporated in a chloroform organic phase containing DPPC and cholesterol until a thin film was formed. An aqueous solution of α-ascorbic acid was added, and the mixture was sonicated until clear. Then, a chloroplatinic acid solution was added and reacted until the solution turned black. The porous platinum-based nanoparticles were obtained by solid-liquid separation. The concentration of DPPC was 0.5~1 mg / mL, the concentration of cholesterol was 0.1~0.5 mg / mL, the concentration of α-ascorbic acid aqueous solution was 52.8 mg / mL, and the concentration of chloroplatinic acid was 10~20 mM. Alternatively, in step 3, the corresponding preparation method can be selected according to the carrier type: for food grade, ultrasonic emulsification-spray freeze drying is used; for pharmaceutical grade, thin film dispersion-ultrasound is used; and for cosmetic grade, high-pressure homogenization-nano emulsification is used. Among them, when encapsulating theaflavins in pharmaceutical grade porous platinum-based nanoparticles, the porous platinum-based nanoparticles are first carboxylated, dissolved in ethanol, and reacted with lipoic acid for 10-15 hours. After washing and purification, they are dissolved in water, and theaflavins are added and stirred for 10-15 hours to achieve the encapsulation of theaflavins. The mass of lipoic acid is 8-12 times that of the porous platinum-based nanoparticles.

3. The method according to claim 2, characterized in that: The method further includes the following steps: Step 4: Process Optimization and Quality Inspection The encapsulation process parameters were optimized using response surface methodology to control the particle size distribution of the encapsulated product: 50-200 nm for food grade and 110-120 nm for pharmaceutical grade, with a coefficient of variation ≤15%. Theaflavin activity was detected by HPLC, particle size distribution by laser particle size analyzer, and carrier residue by HPLC-MS to ensure that the encapsulation rate met the corresponding standards: ≥80% for food grade, ≥85% for pharmaceutical grade, and ≥82% for cosmetic grade, with an activity retention rate ≥90%. Unqualified products were returned to step 3 for re-encapsulation. Step 5: Integration of Storage and Industrialization The qualified theaflavins nano-encapsulated products are sealed and packaged, and protected from light. Food-grade products can be stored and transported at room temperature, while pharmaceutical and cosmetic-grade products must be refrigerated and transported below 4°C. The industrial production equipment consists of an ultrasonic emulsifier (JS-1000, 1000W), a high-pressure homogenizer (GJB-2000), a spray freeze dryer (SLFD-500), and a PLC control system (S7-1200). The production capacity target is 200 kg / day for pilot production and 500-1000 kg / day (food grade) for large-scale production. By purchasing raw materials in bulk, optimizing process parameters, and recycling waste materials, the unit cost of food-grade encapsulated products is controlled to ≤35 yuan / kg.

4. The method according to claim 1, characterized in that: The method includes the following precise, controllable, and hierarchically adaptable steps: Step 1: Hierarchical nanocarrier directional screening and in-situ modification treatment Based on the three major application scenarios of food, medicine and cosmetics, we grade and screen food-grade, pharmaceutical-grade and cosmetic-grade nanocarriers that meet the corresponding national standards, pharmacopoeia and cosmetic safety specifications. We then perform targeted in-situ modification on different carriers, and simultaneously optimize the carrier molecular weight, degree of substitution and hydrophilic-lipophilic balance ratio. The entire process is protected by low temperature inert gas, i.e. nitrogen with a purity of ≥99.99%, to prevent carrier particle agglomeration, oxidative degradation and cross-linking inactivation. Step 2: Targeted pretreatment and stabilization of high-purity direct-drinking theaflavins High-purity direct-drinking theaflavins raw materials with a total purity of ≥80% are selected. Through targeted impurity removal, desalting, and dephenolization refining processes, the ratio of characteristic monomers is controlled to prepare a constant-temperature stabilized theaflavins aqueous solution. The entire process is carried out in the dark and at low temperature to inhibit the oxidation and degradation of theaflavins and ensure the stability of the core material activity. Step 3: Precision fabrication process of hierarchical and adaptive nano-embedding Stabilized theaflavins aqueous solution and modified nanocarriers were precisely fed at a core-to-wall mass ratio of 1:2 to 1:4, tailored to specific application scenarios. A differentiated encapsulation preparation process adapted one-to-one with the application scenario was adopted. Temperature and power were controlled throughout the process for ultrasonic emulsification and homogenization to complete the in-situ encapsulation of theaflavins. Subsequently, gradient temperature controlled spray freeze-drying was used to obtain direct-drinking theaflavins nano-encapsulated powder with no agglomeration and excellent dispersibility. Step 4: Multi-dimensional process closed-loop optimization and comprehensive quality control Real-time online control of particle size distribution and particle size variation coefficient of encapsulated products; establishment of comprehensive quality control standards; simultaneous detection of encapsulation rate, theaflavin activity retention rate, carrier residue, heavy metal and microbial limits using dedicated detection methods; closed-loop recovery and re-encapsulation of unqualified products to eliminate batch differences. Step 5: Connecting Stabilized Storage with Full-Process Industrialization Qualified encapsulated products are packaged in light-proof, oxygen-proof, and moisture-proof special packaging. They are matched with corresponding low-temperature light-proof storage and transportation specifications according to the application level, and are simultaneously adapted to continuous industrial production equipment. Process connection parameters are optimized to achieve seamless connection from pilot production to large-scale mass production, and to strictly control mass production costs and product stability.

5. The method according to claim 4, characterized in that: In step 1, the selection of the graded carrier and the specific in-situ modification process are as follows: (1) Food-grade carrier: Select one or two of high-purity chitosan with a deacetylation degree ≥90% and modified wheat gliadin, with a mass ratio of 1:1 to 1:1.

5. After compounding, add 0.3% to 0.5% nano-SiO2 as an anti-agglomeration regulator. The modification method is low-temperature temperature-controlled carboxymethylation modification and quaternization grafting modification. The modification temperature is 35 to 40℃, the pH is controlled at 5.0 to 5.5, the degree of carboxymethyl substitution is controlled at 0.6 to 0.8, and the degree of quaternization substitution is controlled at 0.5 to 0.

7. After modification, the carrier potential is adjusted to +25 to +35mV. Large particulate impurities are removed by filtration through a 0.1μm filter membrane to prevent particle agglomeration from the source, which is different from the conventional single carrier compounding process. (2) Pharmaceutical-grade carrier: one or two of targeted liposomes and porous platinum-based nanoparticles are selected. The porous platinum-based nanoparticles are synthesized in situ using monolayer liposomes as soft templates. After synthesis, the surface is modified by carboxymethylation. After modification, the carrier potential is controlled at -10~+10mV. It has blood compatibility, passive targeting, and no cytotoxicity. (3) Cosmetic-grade carrier: Select one or two of nanoemulsions and pH-responsive nanomicelles, and add modified silk fibroin, activated soybean seed polysaccharide and pH-responsive self-assembled short peptides in situ after compounding. Form a three-dimensional interpenetrating network carrier through non-covalent cross-linking. The network pore size is controlled at 20~50nm. Simultaneously add 0.1%~0.2% hyaluronic acid derivative as a transdermal promoter to achieve slow controlled release of theaflavins and improve transdermal efficiency by more than 25%. Unlike the conventional three-dimensional network carrier preparation process without transdermal promoters, and avoiding the technical solutions of theaflavin compounded with coenzyme Q10, selenocysteine ​​and other similar whitening patents, theaflavin is compounded with 2-o-ethyl ascorbic acid and eugenol to form a unique whitening synergistic system, further reducing the risk of overlap with existing whitening theaflavin-related patents.

6. The method according to claim 4, characterized in that: In step 1, the preparation method of pharmaceutical-grade porous platinum-based nanoparticles differs from conventional liposome drug delivery methods. The specific steps and precise parameters are as follows: (1) Film preparation: DPPC and cholesterol were completely dissolved in a chloroform-methanol mixed organic phase according to the concentration ratio of 3:

1. The mixture was evaporated under reduced pressure for 30 min in a constant temperature water bath at 40℃ and a rotation speed of 60 r / min until a uniform, pinhole-free monolayer lipid film was formed on the inner wall of the round bottom flask. The film was then dried under reduced pressure for 15 min to completely remove the organic solvent residue. (2) Hydration and dispersion: Nitrogen gas was introduced into the dried lipid film to remove the air in the bottle, and α-ascorbic acid aqueous solution preheated to 30°C was added. The mixture was kept at a constant temperature for 20 min to hydrate. Then, the mixture was sonicated under ice bath conditions with a probe at 30% power and 40 kHz frequency for 10 min until the system was completely clear and without stratification, thus obtaining a monolayer liposome template solution. (3) In-situ reduction synthesis: Chloroplatinic acid solution was slowly added dropwise to the clear liposome template solution. The reaction was carried out under nitrogen protection and at a constant temperature of 30°C for 60 min until the solution changed from light yellow to uniform black. The reaction was then stopped. (4) Purification and refining: Transfer the reaction solution into an ultrafiltration centrifuge tube, centrifuge at 10000 r / min for 15 min at low temperature, discard the supernatant free metal ions and unreacted reagents, resuspend and wash 3 times with ultrapure water, and finally obtain a porous platinum-based nanoparticle suspension, which is stored at 4℃ for later use. The final concentration parameters of the system were as follows: DPPC final concentration 0.5~1 mg / mL, cholesterol final concentration 0.1~0.5 mg / mL, α-ascorbic acid aqueous solution final concentration 52.8 mg / mL, and chloroplatinic acid final concentration 10~20 mM; the particle size of the prepared particles was 110~120 nm, the coefficient of variation was ≤10%, and the specific surface area was ≥15 m². 2 / g, with high drug loading porosity. Alternatively, the method for preparing the theaflavins through targeted pretreatment and stabilization in step 2 differs from the conventional direct dissolution method, specifically as follows: (1) Raw material refining: Select direct drinking theaflavins raw materials with a total purity of ≥80% and remove impurities, desalinate and remove free phenolic impurities through a 3000Da ultrafiltration membrane. After refining, control the ratio of characteristic monomers: the mass ratio of theaflavins-3-gallate to theaflavins-3'-gallate is strictly controlled at 1:0.8~1.2 to prevent differences in encapsulation stability caused by fluctuations in monomer ratio; (2) Stabilization and dissolution: The refined theaflavins raw material is added to a citrate-sodium citrate buffer solution preheated to 25°C and pH 6.0~6.5, and stirred at low speed until completely dissolved to prepare an aqueous solution of theaflavins with a mass concentration of 5~10 mg / mL. The entire process is protected from light and nitrogen. After dissolution, the solution is immediately filtered through a 0.22 μm sterile filter membrane and stored at 4°C in the dark for later use. The storage time should not exceed 2 hours to avoid oxidation and deactivation of the core material. Alternatively, in step 3, the three-level scenario-specific one-to-one embedding preparation method, with each level of the process supplemented with complete operation steps and closed-loop precise parameters, is significantly different from conventional general processes, specifically as follows: (1) Food grade: Ultrasonic emulsification-gradient spray freeze drying exclusive process 1) Feeding and emulsification: The modified chitosan / alcohol-soluble protein carrier solution is mixed with the theaflavins aqueous solution at a core-to-wall ratio of 1:2.5 to 1:

4. The mixture is premixed by stirring at a constant temperature of 30°C for 10 minutes, and then transferred to the probe ultrasonic reactor. 2) Ultrasonic homogenization: The ultrasonic power is fixed at 40%, the frequency is 25~35kHz, the ice bath temperature is controlled at 28~32℃, and the ultrasonic emulsification is carried out for 20~30 minutes. The ultrasonic mode is intermittent ultrasonication with 3 seconds on and 2 seconds off to avoid local overheating and degradation of theaflavins, so as to obtain a uniform nanoemulsion. 3) Gradient drying: The emulsion is filtered through a 0.22μm filter membrane to remove agglomerated particles, and then fed into a spray freeze dryer at a feed rate of 5~8mL / min, atomization pressure of 0.2~0.3MPa, and cold trap temperature of -55℃. The material drying temperature gradient is controlled as follows: first, it is kept at -25℃ for 120min, then at -10℃ for 30min, and finally, it is desorbed and dried at room temperature for 20min to obtain a free-flowing, non-agglomerated nano-embedded powder. (2) Pharmaceutical grade: Thin film dispersion-targeted drug delivery ultrasonic method exclusive process 1) Carrier film formation: Liposomes / porous platinum-based nanocarriers are dissolved in an organic phase in a certain proportion, and the film is formed by rotary evaporation at 40°C and then dried under reduced pressure to remove the organic solvent; 2) Drug loading hydration: Add theaflavins aqueous solution, keep at a constant temperature of 30℃ for 25 minutes to allow the carrier to fully swell and simultaneously adsorb and encapsulate the theaflavins core material; 3) Homogenization and size control: The probe is ultrasonically controlled under ice bath conditions at 35% power and 40kHz frequency for 15-20 minutes in intermittent ultrasonic mode. Then, it is extruded through a 100nm polycarbonate film three times to precisely control the uniformity of particle size and obtain a nano suspension. The suspension is then freeze-dried at low temperature to obtain a pharmaceutical-grade encapsulated powder. (3) Cosmetic grade: High-pressure homogenization-controlled release nano-emulsification exclusive process 1) Preparation of colostrum: The three-dimensional network carrier solution was mixed with theaflavins aqueous solution and sheared at 30°C for 10 min to prepare crude emulsion; 2) High-pressure homogenization: The crude emulsion is transferred to a high-pressure homogenizer, with a first-stage pressure of 80MPa and a second-stage pressure of 40MPa. The homogenization is repeated 5 times, and the temperature is controlled at ≤30℃ throughout the process to obtain nano-emulsion with uniform particle size. 3) Low-temperature drying: Low-temperature spray freeze drying is adopted, with a feed rate of 6~10mL / min and a drying temperature of -25℃, to obtain cosmetic-grade encapsulation powder with good water solubility and strong transdermal properties; The core parameters for this step are universal: ultrasonic power 40%, frequency 20-40kHz, emulsification temperature 28-32℃, and drying core temperature -25℃. Alternatively, in step 4, the graded quality control standards and closed-loop optimization methods are specifically as follows: (1) Precise particle size control: food-grade products have a particle size of 50-200nm, pharmaceutical-grade products have a particle size of 110-120nm, cosmetic-grade products have a particle size of 80-150nm, and the particle size variation coefficient of all grades of products is ≤15%; (2) Performance quality control thresholds: food grade encapsulation rate ≥80%, pharmaceutical grade encapsulation rate ≥85%, cosmetic grade encapsulation rate ≥82%, the theaflavins activity retention rate of all grades of products ≥90%, carrier organic solvent residue ≤0.1%, meeting the corresponding safety standards; (3) Dedicated detection methods: High performance liquid chromatography (HPLC) is used to quantitatively detect the content, encapsulation rate, and activity retention rate of theaflavins. Laser dynamic light scattering instrument is used to detect particle size and distribution. HPLC-MS is used to detect carrier residues and impurities. Unqualified products are reconstituted at low temperature and re-homogenized and encapsulated to achieve closed-loop recovery without wasting raw materials. Alternatively, in step 5, the industrial-scale continuous production process and capacity cost control specifically include: (1) Adaptable to industrial equipment: The whole set adopts customized continuous production equipment, including 1000W JS-1000 CNC ultrasonic emulsifier (equipped with online temperature control and power feedback module, which can adjust the ultrasonic intermittent cycle in real time), GJB-2000 high pressure homogenizer (with pressure closed-loop regulation system, pressure fluctuation ≤1MPa), SLFD-500 spray freeze dryer (equipped with gradient temperature control and automatic feed flow rate adjustment device, drying uniformity ≥95%), Siemens S7-1200 PLC fully automatic control system, which integrates feeding metering, emulsification parameter monitoring, drying effect detection and automatic packaging functions, realizes full-process automated closed-loop control, equipment linkage error ≤2%, and can record production data in real time for traceability; (2) Graded production capacity target: The pilot production capacity is stable at 200kg / day (fluctuation ≤5%), and the food-grade mass production capacity is 500-1000kg / day, which can be flexibly adjusted according to order demand (adjustment range 500-1000kg / day, adjustment response time ≤2h); the process scale-up adopts the "gradient scale-up method", from small-scale test (100g / batch), pilot test (50kg / batch) to mass production (200kg / batch), with particle size and encapsulation rate fluctuations ≤3% and no batch differences; during mass production, a continuous feeding mode is adopted, with a single feeding amount ≥50kg, equipped with a raw material pretreatment buffer tank, which shortens the production cycle while ensuring product uniformity, and the single batch production cycle ≤8h; (3) Mass production cost control: Through carrier compounding optimization (compounding chitosan with wheat gliadin and adding nano SiO2 anti-agglomeration regulator, the cost is reduced by 12% compared with single chitosan carrier) and energy-saving control of process parameters (ultrasonic intermittent mode saves 15% energy, gradient drying saves 20% energy, and equipment linkage saves 8% energy), the unit comprehensive production cost of food-grade mass production products is ≤35 yuan / kg, of which the carrier cost accounts for ≤40%, energy consumption cost accounts for ≤25%, and raw material loss accounts for ≤5%. It is suitable for large-scale application in the food processing industry, and the cost is reduced by more than 10% compared with conventional nano-embedding process. Moreover, the shelf life of mass production products is extended to 12 months.

7. The method according to claim 4, characterized in that: It also includes targeted modification and synergistic post-processing, which differs from conventional simple hybrid modification, specifically: (1) After the pharmaceutical-grade embedded product is freeze-dried, it is first subjected to vacuum degassing treatment, i.e., vacuum degree -0.095MPa, temperature 25℃, time 15min, to remove residual air in the product pores. Then it is placed in a pH7.0 phosphate buffer system, and an EDC / NHS catalytic system is added, i.e., the molar ratio of EDC to NHS is 1.2:1, the concentration of both is 50mM, and the amount of catalytic system added is 8% of the product mass. The reaction is carried out at 37℃ and 120r / min for 2h with constant temperature shaking, through amide bond reaction. Theaflavin-encapsulated nanoparticles were covalently linked to bone-targeting alendronate. After the reaction, the nanoparticles were purified by ultrafiltration centrifugation (12000 r / min, 10 min, 50 nm pore size) to remove unreacted reagents and small molecule impurities. The nanoparticles were then lyophilized at -40℃ for 2 h to obtain bone-targeting drug-loaded nanoparticles. The enrichment rate of these nanoparticles at the lesion site was increased by more than 40% compared to the unmodified nanoparticles. The in vitro sustained-release period was extended to 48 h, the blood half-life was extended by 2.5 times compared to the unmodified nanoparticles, and there was no hemolytic toxicity. (2) During the emulsification stage, 2% to 5% by mass of 2-o-ethyl ascorbic acid and 0.5% to 1% eugenol are added simultaneously to the cosmetic-grade encapsulation product as synergistic ingredients.

8. The theaflavins nano-encapsulated product for direct consumption prepared by the method according to any one of claims 1 to 7, characterized in that: The theaflavins nano-encapsulated product for direct consumption has a core-shell structure, with theaflavins as the core and modified nanocarriers as the shell. It has a uniform particle size distribution, a coefficient of variation ≤15%, an encapsulation rate ≥80%, an activity retention rate ≥90%, water solubility more than 30% higher than unencapsulated theaflavins, bioavailability ≥85%, and light-protected room temperature stability more than 6 months higher than unencapsulated raw materials. According to the application scenario, it is divided into three categories of products: food grade, pharmaceutical grade, and cosmetic grade. The pharmaceutical grade product can be further linked with alendronate for osteoporosis treatment, the cosmetic grade product can be added with 2-o-ethyl ascorbic acid and eugenol to achieve synergistic whitening and moisturizing effects, and the food grade product can be used for meat product preservation, beverage and baking product processing.

9. The application of the theaflavins nano-encapsulated product as described in claim 8 in the fields of food, medicine, and cosmetics.

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