A method for preparing double-layered microspheres embedding fat-soluble nutrients

Abstract

This invention discloses a continuous method for preparing double-layered encapsulated fat-soluble nutrient microparticles, comprising the following steps: (1) emulsifying the fat-soluble nutrient core material to form a nano-sized nutrient emulsion; (2) sending hydrophobic excipients into a granulation tower via hot air flow, where they are suspended under the action of a blower and induced draft system to form an excipient aerosol; atomizing the nutrient emulsion into fine droplets via a centrifugal spray device and spraying them into the excipient aerosol, where a layer of hydrophobic excipients is adsorbed on the surface of the droplets, dried and shaped to form double-layered encapsulated fat-soluble nutrient microparticles; (3) the double-layered encapsulated fat-soluble nutrient microparticles and some of the hydrophobic excipients fall from the granulation tower into a built-in fluidized bed for drying. The excipients are separated by a cyclone sieve and further dried in a vibrating fluidized bed and a vertical fluidized bed. Simultaneously, the excipients are separated and recovered by an induced draft system. This method simplifies the product preparation process, reduces equipment requirements and energy consumption, achieves continuous automated production, and enhances industrial advantages.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a method for preparing double-layer-encapsulated fat-soluble nutrient microparticles. Background Technology

[0002] Fat-soluble nutrients mainly refer to fat-soluble vitamins and carotenoids. These are micronutrients that humans and animals must obtain from food or feed to maintain normal physiological functions. They play a vital role in growth, metabolism, and development, and also enhance animal fertility and immunity. Furthermore, they possess various physiological functions such as antioxidation, coloring, and strengthening intercellular connections. However, fat-soluble nutrients are generally susceptible to external environmental factors (temperature, light, oxygen, etc.), processing and storage conditions, and the digestive tract environment (pH, enzymes, other substances), leading to content loss and poor stability, making them unsuitable for direct addition to feed, food, or pharmaceuticals. Additionally, their water insolubility limits their application areas, restricts in vivo absorption, and results in low bioavailability. Therefore, formulation is necessary. On one hand, protective wall materials are used to encapsulate them to resist oxidation and reduce processing and storage losses, thereby improving their stability and bioavailability. On the other hand, water-soluble formulations are created, where the active ingredients are in a finely dispersed form, expanding their application range in various fields.

[0003] Microcapsules have become an important technology for drug encapsulation and delivery in the pharmaceutical industry. Microcapsules refer to tiny spheres or spheroids formed by dissolving or dispersing the target drug within a polymer material, with particle sizes typically ranging from 1 to 250 μm. The principle is to physically encapsulate or adsorb the drug within the polymer; the stability of the polymer ensures drug delivery and sustained-release effects. Current nutrient formulation technology typically involves simply mixing nutrients and preservatives to complete the encapsulation, followed by drying to produce a powder for use in production. For example, patent document CN111109552A discloses a method for preparing deodorized and debittered oyster complete nutritional powder. However, the product obtained after processing nutrients using this method has a low encapsulation rate, cannot effectively reduce mutual degradation, and does not guarantee the stability of the nutrient preparation in formulated foods. Patent documents CN118045540A and CN113785987A both use single-layer encapsulation technology. Products encapsulated using this method generally suffer from low stability and limited application scenarios. US patent US5364563 discloses a method for preparing carotenoid powder preparations, which involves mixing, dissolving, emulsifying, and drying carotenoids and vegetable oils using steam at temperatures up to 200°C. However, the high-temperature heating process causes a significant loss of carotenoid content and affects the all-trans content of the product. Furthermore, high temperature and high pressure require expensive equipment, the equipment operation requirements are high, the process is complex, and the production efficiency is low. The patent document with publication number CN111134332A discloses a method and product for preparing probiotic microcapsules by fluidized bed spray granulation. The method involves layer-by-layer encapsulation of microcapsules by fluidized bed spray granulation, with different wall materials used for each encapsulation. This method cannot prove a positive correlation between the number of encapsulations and the integrity, and it is difficult to achieve continuous production. In addition, the range of applicable core materials is limited.

[0004] Current encapsulation technologies suffer from numerous problems, including low encapsulation depth, poor application stability, significant product content loss, low preparation efficiency, high equipment requirements, and low level of automation. These issues fail to meet current market demands and lack industrialization advantages. Summary of the Invention

[0005] To address the above shortcomings, this invention provides a method for preparing double-layer encapsulated fat-soluble nutrient microparticles. On one hand, it systematically integrates emulsion preparation, spray granulation, fluidized bed drying, and separation and recovery equipment, with an integrated process design that reduces material handling, simplifies operation, facilitates large-scale automated production, and enhances industrialization advantages. On the other hand, it solves the problems of easy degradation, poor stability, and difficulty in application during the processing and storage of fat-soluble nutrients in existing technologies. Unlike single-layer encapsulation methods such as mixed encapsulation and liquid encapsulation, or staged encapsulation methods that first form single-layer microcapsule particles and then encapsulate them layer by layer, the double-layer encapsulated microparticles of this invention undergo double-layer encapsulation simultaneously with granulation and drying in a granulation tower, forming microparticles with a core-shell structure (see...). Figure 3 This structure boasts excellent sealing and integrity, resulting in high drug loading and encapsulation efficiency. It effectively protects the drug / active ingredient from direct contact with air, oxygen, and heat, preventing content loss due to processing and storage methods and improving the bioavailability of the drug / active ingredient. It also allows for control of the drug release rate and mode, achieving targeted, timed, and quantitative drug release, reducing adverse drug reactions and minimizing gastrointestinal irritation. Furthermore, the entire production process maintains a high-temperature sterilization and antimicrobial environment, effectively mitigating microbial risks and ensuring safe application in infant formula and pharmaceuticals with stringent microbiological requirements.

[0006] The present invention provides a method for preparing double-layer-encapsulated fat-soluble nutrient microparticles through the following technical solution:

[0007] (1) Emulsify or uniformly and stably suspend the fat-soluble nutrient core material in the liquefied wall material to form a nano-sized nutrient emulsion, wherein the nano-sized refers to the average particle size of the liquid microspheres being 10nm-500nm.

[0008] (2) The hydrophobic excipients are fed into the granulation tower under the action of hot air flow to form excipient aerosol; then the nutrient emulsion obtained in step (1) is atomized into fine droplets by centrifugal spray and sprayed into the excipient aerosol. The droplets adsorb the hydrophobic excipients and shrink and wrap them, dry and shape them to form double-layer embedded fat-soluble nutrient microparticles.

[0009] (3) The double-layer-encapsulated fat-soluble nutrient microparticles fall from the granulation tower into the built-in fluidized bed for drying. After hydrophobic excipients are separated by a cyclone screen, the microparticles enter a vibrating fluidized bed and a vertical fluidized bed for further drying and excipient separation. The hydrophobic excipients are recovered through an induced draft system and then sent to the excipient silo for recycling after drying in the intermediate bed.

[0010] (4) Finally, the double-layer encapsulated fat-soluble nutrient microparticles are sieved through a double-layer vibrating screen to obtain the finished product, which is then packaged in the packaging system.

[0011] The technical solution is basically as follows: Figure 1 As shown.

[0012] In one embodiment, the preparation of the nanoscale nutrient emulsion in step (1) is performed as follows: a fat-soluble nutrient is dissolved in an organic solvent to prepare an oil phase; an emulsifier / stabilizer is dissolved in water to prepare an aqueous phase; the aqueous and oil phases are mixed and emulsified to obtain an emulsion; the emulsion is homogenized under high pressure, desolventized, and dehydrated to obtain a fine emulsion; an embedding wall material is added to the fine emulsion, and the mixture is emulsified and homogenized again to obtain the nanoscale nutrient emulsion. Preferably, the organic solvent is an organic solvent permitted by the FDA for use in drug production, such as dichloromethane.

[0013] The fat-soluble nutrients mentioned in step (1) above are substances selected from the group consisting of: vitamin A, vitamin A acetate, vitamin A palmitate, vitamin E, vitamin E acetate, vitamin E palmitate, β-carotene, astaxanthin, lycopene, canthaxanthin, lutein, apoester, coenzyme Q10, and one or more of them.

[0014] The wall material described in step (1) is selected from the group consisting of: lignin sulfonate, gelatin, fish gelatin, gum arabic, shellac, CMC-Na, gelling sugar, xanthan gum, β-carrageenan, cellulose acetate acetate, sodium caseinate, sodium octenyl succinate starch, soy protein, maltodextrin, xanthodextrin, resistant dextrin, β-cyclodextrin, sorbitol, mannitol, sucrose, glucose, fructose, trehalose, lactose, dextran, corn syrup, pectin, gum arabic, chitosan, modified soy lecithin, acetylated mono- and diglycerides of fatty acids, konjac gum, carrageenan, waxes, and one or more of the following;

[0015] The emulsifier / stabilizer used in step (1) is a substance selected from the group consisting of: vitamin C palmitate, sorbitol glycerol ester, mono- and diglycerides, citrate, sucrose fatty acid ester, polyglycerol stearate, propylene glycol fatty acid ester, Tween 60, Tween 80, or one or more of them.

[0016] The hydrophobic excipients mentioned in steps (2) and (3) are substances selected from the group consisting of starch, silicon dioxide, tricalcium phosphate, calcium silicate, magnesium stearate, or one or more of these.

[0017] In one embodiment, the viscosity of the nano-sized nutrient emulsion in step (1) is 100-2000 CP, preferably 200-1000 CP; the temperature of the nano-sized nutrient emulsion is above 45°C, preferably 45-65°C.

[0018] Preferably, in step (2) above, the nano-sized nutrient emulsion described in step (1) is sprayed into the excipient aerogel using a centrifugal sprayer to complete the double-layer encapsulation.

[0019] The air intake of the granulation tower is hot air, preferably at a temperature of 100–130°C.

[0020] Preferably, the rotational speed of the centrifugal sprayer is 1500–2500 r / min;

[0021] Preferably, the spray ring orifice diameter of the centrifugal sprayer is 0.25 to 0.35 mm.

[0022] In one embodiment, the double-layer-encapsulated fat-soluble nutrient microparticles in step (3) fall from the granulation tower into the built-in fluidized bed for drying. After hydrophobic excipients are separated by a cyclone sieve, the microparticles enter a vibrating fluidized bed and a vertical fluidized bed for further drying and excipient separation.

[0023] In step (3) above, the excess hydrophobic auxiliary materials separated from the granulation tower, cyclone screen, vibrating fluidized bed and vertical fluidized bed by the induced draft system enter the intermediate bed for drying and are then sent to the auxiliary material silo for recycling.

[0024] In one embodiment, the double-layered encapsulated fat-soluble nutrient microparticles in step (4) are sieved through a double-layer vibrating screen to obtain a finished product with a particle size between 20 mesh and 120 mesh. Finally, the finished product enters the packaging system for packaging.

[0025] The advantage of this invention is that it provides a method for preparing double-layer encapsulated fat-soluble nutrient microparticles, which can be prepared by the method described above to obtain double-layer encapsulated fat-soluble nutrient microparticles with good encapsulation effect and high stability.

[0026] Preferably, the above-mentioned particulate products have two or more of the following characteristics, more preferably three or more, and more preferably four: A. The moisture content of fat-soluble nutrients is ≤5.0%; B. Under environmental conditions of 40℃±2.0℃ and 75%±5% RH, the core material content retention rate is ≥95% in the 6-month accelerated stability test; C. The microbial content of the product meets the following standards: total bacterial count ≤1000cfu / g, mold and yeast ≤100cfu / g; D. The particle size of the product meets the following indicators: 100% passing through a 20-mesh sieve, ≥85% passing through a 40-mesh sieve, and ≤15% passing through a 100-mesh sieve.

[0027] Furthermore, the particulate products are spherical with good flowability; they have effects such as masking taste, preventing oxidation, and slow release, and are suitable for various processing and application methods such as tableting; they have good water solubility and can be widely used in the pharmaceutical, food, and feed additive industries.

[0028] Compared with existing inventions, this invention features an integrated process, high production efficiency (more than three times the capacity of intermittent production), a rational and highly intelligent production flow, reducing material handling and labor costs, recycling auxiliary materials to save production costs, and continuous automated production, resulting in at least 60% cost savings compared to intermittent production. This significantly improves economic benefits, meets market demands, and possesses industrialization advantages. The produced double-layer encapsulated microcapsules offer advantages such as high encapsulation degree, minimal content loss, good stability, and wide applicability. Attached Figure Description

[0029] Figure 1 This is a process flow diagram of the present invention.

[0030] Figure 2 This is a 1000x magnified photomicrograph of the double-layered encapsulated fat-soluble nutrient microparticles prepared in Example 1.

[0031] Figure 3 The images show cross-sectional views of the double-layered encapsulated lipophilic microcapsule product prepared in Example 1 and a single double-layered encapsulated microparticle. The left image shows the actual product, and the right image is a schematic diagram of the microcapsule structure. Detailed Implementation

[0032] In this invention, unless otherwise stated, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the laboratory procedures described herein are all standard procedures widely used in the relevant fields.

[0033] The term "continuous" refers to (automated) continuous granulation, continuous drying, and continuous recovery. This differs from the intermittent spray drying / fluidization process used in the production of similar products, which involves sequentially forming single-layer and double-layer microcapsule particles.

[0034] In this article, for the sake of convenience, the term "double-layered fat-soluble nutrient microparticles" can be abbreviated as "double-layered fat-soluble nutrient microparticles," "double-layered microparticles," or simply "microparticles." They all have the same meaning and can be used interchangeably.

[0035] In the embodiments described herein, unless otherwise specified, the operating temperature generally refers to room temperature (15-35°C).

[0036] Raw materials and reagents: The raw materials and reagents used in the embodiments of this invention are all pharmaceutical grade and were purchased from Aladdin Shanghai Co., Ltd. or Sinopharm Group.

[0037] Example

[0038] The present invention is further illustrated below by way of examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the invention. Various changes or modifications made by those skilled in the art based on the concept of the present invention should fall within the protection scope of the present invention.

[0039] Figure 1 The production process of the double-layer encapsulated fat-soluble nutrient microparticles of the present invention is illustrated. Some of the production equipment used in the embodiments includes:

[0040] The manufacturer of the high-pressure homogenizer is Jinzhu Machinery Equipment Co., Ltd., and the model number is JZH2000.

[0041] The pipeline emulsification pump manufacturer is Ningbo Delishi Pump Industry Co., Ltd., and the model number is DHX2.

[0042] The centrifugal sprayer manufacturer is Wuxi Modern Spray Drying Equipment Co., Ltd., and the model is 350kg / h.

[0043] The granulation tower (including the built-in fluidized bed) is manufactured by Wuxi Modern Spray Drying Equipment Co., Ltd., and the model is WLG-350.

[0044] The vertical fluidized bed manufacturer is Yisite Company, and the model number is φ1600*φ1200;

[0045] The vibrating fluidized bed manufacturer is Est. Company, and the model is 350kg / h.

[0046] Example 1

[0047] 24 kg of cantharidin crystals, 4 kg of dl-α-tocopherol, and 360 kg of dichloromethane were stirred and mixed evenly in a reactor at room temperature and then heated to 60°C. After complete dissolution, an oil phase was prepared. 3 kg of vitamin C palmitate, 0.3 kg of sodium hydroxide, and 300 kg of water were dissolved in a reactor and then cooled to 35°C to obtain an aqueous solution.

[0048] The oil phase matrix of cantharidin solution and the aqueous phase matrix of colloidal solution were mixed and emulsified using a pipeline emulsification pump, and then homogenized under high pressure homogenization at 60 MPa to obtain a primary crude emulsion. The primary crude emulsion was then dehydrated and concentrated using a thin-film evaporator to remove dichloromethane organic solvent. 85 kg of lignin sulfonate and 55 kg of maltodextrin were added and fully dissolved. The resulting cantharidin mixed solution was then mixed and emulsified again using a pipeline emulsification pump, and then homogenized and nano-dispersed under high pressure homogenization at 60 MPa to obtain a cantharidin emulsion with a viscosity of 100 cp. The cantharidin emulsion was then sprayed using a centrifugal sprayer and granulated in a starch aerogel-containing granulation tower with an inlet air temperature of 100℃ and an atomizer speed of 1500 r / min. A layer of dry starch was adsorbed onto the surface of the microdroplets, and the granules were shaped and dried. The inlet air temperature was 100℃ and the atomizer speed was 1500 r / min. The starch-containing cantharidin granules were subsequently dried again in a fluidized bed to separate the outer excipient (starch). Finally, the product was sieved to collect cantharidin microcapsule products with a particle size of 20-120 mesh, yielding approximately 200 kg of cantharidin microparticles.

[0049] Moisture content of the cantharidin microparticles was 3.2% after moisture testing. Accelerated stability testing (40℃±2.0℃, 75%RH±5%RH) showed a retention rate of 96.3% (accelerated product mass content / initial product mass content) as determined by HPLC. Microbiological testing showed a total bacterial count <100 CFU / g and mold and yeast count <10 CFU / g. Particle size distribution: 100% passing through a 20-mesh sieve, 96% passing through a 40-mesh sieve, and 2% passing through a 100-mesh sieve.

[0050] Example 2

[0051] 24 kg of astaxanthin crystals, 4 kg of dl-α-tocopherol, and 340 kg of dichloromethane were stirred and mixed evenly in a reactor at room temperature and then heated to 60°C. After complete dissolution, an oil phase was prepared. 3 kg of sorbitol glycerol ester and 300 kg of water were dissolved in a reactor and then cooled to 35°C to obtain an aqueous phase solution.

[0052] The astaxanthin solution (oil phase) and colloidal solution (aqueous phase) were mixed and emulsified using a pipeline emulsification pump, and then homogenized under high pressure at 30 MPa to obtain a primary crude emulsion. The primary crude emulsion was then concentrated by desolvation and solvent removal using a thin-film evaporator, followed by the addition of 45 kg gelatin, 40 kg dextrin, 40 kg glucose, and 12 kg sorbitol, which were thoroughly dissolved. The resulting astaxanthin mixture was then emulsified a second time using a pipeline emulsification pump, and further homogenized and nano-dispersed under high pressure at 30 MPa to obtain an astaxanthin emulsion with a viscosity of 300 cp. Astaxanthin emulsion was sprayed using a centrifugal sprayer and granulated in a granulation tower containing silica aerogel at an inlet air temperature of 120℃ and an atomizer speed of 2000 r / min. A layer of silica was adsorbed onto the surface of the microdroplets, forming and drying them. The silica-containing astaxanthin particles were then further dried in a subsequent fluidized bed to separate the outer excipient (silica). Finally, the product was sieved, and astaxanthin microcapsules with a particle size of 20–120 mesh were collected, yielding approximately 210 kg of astaxanthin microparticles.

[0053] Moisture content of the astaxanthin microparticles was 3.1% after moisture testing. Accelerated stability testing (40℃±2.0℃, 75%RH±5%RH) showed a 95.5% retention rate (accelerated product content / initial product content) as measured by HPLC. Microbiological testing showed a total bacterial count <100 CFU / g and mold and yeast count <10 CFU / g. Particle size distribution was 100% passing through a 20-mesh sieve, 95% through a 40-mesh sieve, and 1.5% through a 100-mesh sieve.

[0054] Example 3

[0055] 24 kg of apocyanide crystals, 4 kg of dl-α-tocopherol, and 340 kg of dichloromethane were stirred and mixed evenly in a reactor at room temperature and then heated to 60 °C. After complete dissolution, an oil phase was prepared. 3 kg of mono- and diglycerides and 300 kg of water were dissolved in a reactor and then cooled to 35 °C to obtain an aqueous solution.

[0056] The oil phase matrix of apoester solution and the aqueous phase matrix of colloidal solution were mixed and emulsified using a pipeline emulsification pump, and then homogenized under high pressure at 60 MPa to obtain a primary crude emulsion. The primary crude emulsion was then desolventized and concentrated using a thin-film evaporator to remove organic solvents, and then 30 kg of sodium caseinate, 15 kg of soy protein, 70 kg of resistant dextrin, and 22 kg of mannitol were added and fully dissolved. The resulting apoester mixed solution was then emulsified again using a pipeline emulsification pump, and then homogenized and nano-dispersed under high pressure at 60 MPa to obtain an apoester emulsion with a viscosity of 500 cp. Apocyanate emulsion was sprayed using a centrifugal sprayer and granulated in a granulation tower containing tricalcium phosphate aerogel at an inlet air temperature of 120°C and an atomizer speed of 2500 r / min. A layer of tricalcium phosphate was adsorbed onto the surface of the microdroplets, forming and drying them. The tricalcium phosphate-containing apocyanate particles were then further dried in a subsequent fluidized bed to separate the outer excipient (tricalcium phosphate). Finally, the product was sieved, and apocyanate microcapsules with a particle size of 20–120 mesh were collected, yielding approximately 205 kg of apocyanate microparticles.

[0057] Moisture content of the apoester microparticles was 2.9% after moisture testing. Accelerated stability testing (40℃±2.0℃, 75%RH±5%RH) showed a content retention rate (accelerated product mass content / initial product mass content) of 97.8% as determined by HPLC. Microbiological testing showed a total bacterial count <100 CFU / g and mold and yeast count <10 CFU / g. Particle size distribution was 100% passing through a 20-mesh sieve, 96% through a 40-mesh sieve, and 1.6% through a 100-mesh sieve.

[0058] Example 4

[0059] 25 kg of β-carotene crystals, 4 kg of dl-α-tocopherol, and 450 kg of dichloromethane were stirred and mixed evenly in a reactor at room temperature, and then heated to 60 °C. After complete dissolution, an oil phase was prepared. 3 kg of vitamin C palmitate, 0.3 kg of sodium hydroxide, and 300 kg of water were dissolved in a reactor and then cooled to 35 °C to obtain an aqueous solution.

[0060] The oil phase matrix of the β-carotene solution and the aqueous phase matrix of the colloidal solution were mixed and emulsified using a pipeline emulsification pump, and then homogenized under high pressure at 50 MPa to obtain a primary crude emulsion. The primary crude emulsion was then dehydrated and concentrated using a thin-film evaporator to remove dichloromethane organic solvent. 115 kg of sodium octenyl succinate starch and 36 kg of sucrose were added and dissolved thoroughly. The resulting β-carotene mixed solution was then emulsified again using a pipeline emulsification pump, and then homogenized and nano-dispersed under high pressure at 50 MPa to obtain a β-carotene emulsion with a viscosity of 800 cp. β-carotene emulsion was sprayed using a centrifugal sprayer and granulated in a granulation tower containing calcium silicate aerogel at an inlet air temperature of 130℃ and an atomizer speed of 1800 r / min. A layer of calcium silicate was adsorbed onto the surface of the microdroplets, forming and drying them. The calcium silicate-containing β-carotene granules were then further dried in a subsequent fluidized bed, achieving separation of the outer excipient (calcium silicate). Finally, the product was sieved, and β-carotene microcapsules with a particle size of 20–120 mesh were collected, yielding approximately 200 kg of β-carotene microparticles.

[0061] Moisture content of the β-carotene microparticles was 2.8% after moisture testing. Accelerated stability testing (40℃±2.0℃, 75%RH±5%RH) showed a 99.2% retention rate (accelerated product mass content / initial product mass content) as determined by HPLC. Microbiological testing revealed a total bacterial count <100 CFU / g and mold and yeast count <10 CFU / g. Particle size distribution was 100% passing through a 20-mesh sieve, 97% through a 40-mesh sieve, and 2.3% through a 100-mesh sieve.

[0062] Example 5

[0063] 25 kg of lycopene crystals, 4 kg of dl-α-tocopherol, and 460 kg of dichloromethane were stirred and mixed evenly in a reactor at room temperature and then heated to 60°C. After complete dissolution, an oil phase was prepared. 3 kg of citrate ester and 300 kg of water were dissolved in a reactor and then cooled to 35°C to obtain an aqueous solution.

[0064] The oil phase matrix of lycopene solution and the aqueous phase matrix of colloidal solution were mixed and emulsified using a pipeline emulsification pump, and then homogenized under high pressure at 45 MPa to obtain a primary crude emulsion. The primary crude emulsion was then dehydrated and concentrated using a thin-film evaporator to remove dichloromethane organic solvent. 115 kg of sodium octenyl succinate starch, 23 kg of fructose, and 13 kg of trehalose were added and fully dissolved. The resulting lycopene mixed solution was then emulsified again using a pipeline emulsification pump, and then homogenized and nano-dispersed under high pressure at 45 MPa to obtain a lycopene emulsion with a viscosity of 2000 cp. Lycopene emulsion was atomized using a centrifugal sprayer in a granulation tower containing a starch and silica mixed aerogel at an inlet air temperature of 120℃ and an atomizer speed of 12000 r / min. A layer of starch and silica mixed powder was adsorbed onto the surface of the microdroplets, forming and drying them. The lycopene granules containing the starch and silica mixed powder were then further dried in a subsequent fluidized bed, achieving separation of the outer excipient (starch and silica mixed powder). Finally, the product was sieved, and lycopene microcapsules with a particle size of 20–120 mesh were collected, yielding approximately 205 kg of lycopene microparticles.

[0065] The product's moisture content was 2.5% according to moisture testing. After a 6-month accelerated stability study (test conditions: 40℃±2.0℃, 75%RH±5%RH), the lycopene microparticles showed a retention rate of 98.6% (accelerated product mass content / initial product mass content) as determined by HPLC. Microbiological testing showed a total bacterial count <100 CFU / g and mold and yeast count <10 CFU / g. Particle size distribution: 100% passing through a 20-mesh sieve, 95% passing through a 40-mesh sieve, and 1.2% passing through a 100-mesh sieve.

[0066] Example 6

[0067] 25 kg of lutein crystals, 4 kg of dl-α-tocopherol, and 300 kg of dichloromethane were stirred and mixed evenly in a reactor at room temperature and then heated to 60°C. After complete dissolution, an oil phase was prepared. 3 kg of vitamin C palmitate, 0.3 kg of sodium hydroxide, and 300 kg of water were dissolved in a reactor and then cooled to 35°C to obtain an aqueous phase solution.

[0068] The oil phase matrix of lutein solution and the aqueous phase matrix of colloidal solution were mixed and emulsified using a pipeline emulsification pump, and then homogenized under high pressure at 40 MPa to obtain a primary crude emulsion. The primary crude emulsion was then dehydrated and concentrated using a thin-film evaporator to remove dichloromethane organic solvent. 113 kg of sodium octenyl succinate starch and 28 kg of sucrose were added and dissolved thoroughly. The resulting lutein mixture was then emulsified again using a pipeline emulsification pump, and then homogenized and nano-dispersed under high pressure at 40 MPa to obtain a lutein emulsion with a viscosity of 1500 cp. Lutein emulsion was sprayed using a centrifugal atomizer and granulated in a granulation tower containing starch and tricalcium phosphate aerogel at an inlet air temperature of 120℃ and an atomizer speed of 2200 r / min. A layer of starch and tricalcium phosphate mixed powder was adsorbed onto the surface of the microdroplets, forming and drying them. The lutein granules containing the starch and tricalcium phosphate mixed powder were then dried again in a subsequent fluidized bed to separate the outer excipients (starch and tricalcium phosphate mixed powder). Finally, the product was sieved, and lutein microcapsules with a particle size of 20–120 mesh were collected, yielding approximately 185 kg of lutein microparticles.

[0069] Moisture content of the lutein microparticles was 3.3% after moisture testing. Accelerated stability testing (40℃±2.0℃, 75%RH±5%RH) showed a 95.7% retention rate (accelerated product content / initial product content) as determined by HPLC. Microbiological testing showed a total bacterial count <100 CFU / g and mold and yeast count <10 CFU / g. Particle size distribution was 100% passing through a 20-mesh sieve, 94% through a 40-mesh sieve, and 0.8% through a 100-mesh sieve.

[0070] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing double-layered microencapsulated fat-soluble nutrient microparticles, characterized by, Includes the following steps: (1) Emulsify or uniformly suspend fat-soluble nutrient core material in liquefied wall material to form nano-sized nutrient emulsion; (2) The hydrophobic excipients are sent into the granulation tower through hot air flow and suspended to form excipient aerosol under the action of air supply and exhaust system; then the nutrient emulsion obtained in step (1) is atomized into micro droplets through centrifugal spray device, and a layer of hydrophobic excipients is adsorbed on the surface of the droplets, dried and shaped to form double-layer encapsulated fat-soluble nutrient microparticles. (3) The double-layer-encapsulated fat-soluble nutrient microparticles and some hydrophobic excipients fall from the granulation tower into the built-in fluidized bed for primary drying; the excipients are separated by a cyclone screen and then enter a vibrating fluidized bed and a vertical fluidized bed for further drying; at the same time, the excipients are separated and recovered by an exhaust system. (4) Finally, the double-layer encapsulated fat-soluble nutrient microparticles are sieved through a double-layer vibrating screen to obtain the finished product, which is then packaged in the packaging system.

2. The production method according to claim 1, characterized by, The preparation of the nano-sized nutrient emulsion in step (1) is as follows: the fat-soluble nutrients are dissolved in an organic solvent to prepare an oil phase; the emulsifier / stabilizer is dissolved in water to prepare an aqueous phase; the aqueous phase and the oil phase are mixed and emulsified to obtain an emulsion; the emulsion is homogenized under high pressure, desolventized and dehydrated to obtain a fine emulsion; the embedding wall material is added to the fine emulsion and emulsified and homogenized again to obtain the nano-sized nutrient emulsion.

3. The preparation method according to claim 1, characterized in that, The fat-soluble nutrients mentioned in step (1) are substances selected from the group consisting of: vitamin A, vitamin A acetate, vitamin A palmitate, vitamin E, vitamin E acetate, vitamin E palmitate, β-carotene, astaxanthin, lycopene, canthaxanthin, lutein, apoester, coenzyme Q10, or one or more of these. The wall material described in step (1) is selected from the group consisting of: lignin sulfonate, gelatin, fish gelatin, gum arabic, shellac, CMC-Na, gelling sugar, xanthan gum, β-carrageenan, cellulose acetate acetate, sodium caseinate, sodium octenyl succinate starch, soy protein, maltodextrin, xanthodextrin, resistant dextrin, β-cyclodextrin, sorbitol, mannitol, sucrose, glucose, fructose, trehalose, lactose, dextran, corn syrup, pectin, gum arabic, chitosan, modified soy lecithin, acetylated mono- and diglycerides of fatty acids, konjac gum, carrageenan, waxes, and one or more of the following; The emulsifier / stabilizer used in step (1) is a substance selected from the group consisting of: vitamin C palmitate, sorbitol glycerol ester, mono- and diglycerides, citrate, sucrose fatty acid ester, polyglycerol stearate, propylene glycol fatty acid ester, Tween 60, Tween 80, or one or more of them.

4. The production method according to claim 1, characterized by, The hydrophobic excipients mentioned in steps (2) and (3) are substances selected from the group consisting of starch, silicon dioxide, tricalcium phosphate, calcium silicate, magnesium stearate, or one or a mixture thereof.

5. The method of claim 1, wherein, In step (1), the viscosity of the nano-sized nutrient emulsion is 100-2000 CP, preferably 200-1000 CP; the temperature of the nano-sized nutrient emulsion is above 45℃, preferably 45-65℃.

6. The method of claim 1, wherein, In step (2), the nano-sized nutrient emulsion is sprayed into the aerogel of the auxiliary material in the granulation tower by a centrifugal sprayer to complete the double-layer encapsulation.

7. The preparation method according to claim 1, characterized in that, In step (3), the double-layer-encapsulated fat-soluble nutrient microparticles and excipients fall from the granulation tower into the built-in fluidized bed for primary drying. After the excipients are separated by a cyclone screen, the microparticles enter the vibrating fluidized bed and the vertical fluidized bed for secondary and tertiary drying.

8. The method of claim 1, wherein, In step (3), the auxiliary materials separated from the granulation tower, cyclone screen, vibrating fluidized bed and vertical fluidized bed induced draft system enter the intermediate bed for drying and are then recycled to the auxiliary material silo for reuse.

9. The method of claim 1, wherein, In step (4), the double-layer encapsulated fat-soluble nutrient microparticles are sieved through a double-layer vibrating screen to obtain finished products with a particle size between 20 mesh and 120 mesh. Finally, the finished products are packaged in the packaging system.

10. Double-layered microgranules embedding a fat-soluble nutrient, characterized in that, It is prepared by the preparation method according to any one of claims 1-9.

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