Preparation method of diglyceride solid powder and beverage with uric acid reducing function

Abstract

The invention relates to the technical field of uric acid reducing compositions, in particular to a preparation method of diglyceride solid powder and a diglyceride beverage with a uric acid reducing function, the defects in the prior art are overcome, and the solid powder achieves the efficient uric acid reducing function through a molecular complexation-multistage assembly-interface engineering synergistic technology. The beverage is prepared by adopting a three-stage micro-fluidic emulsification technology to form a W / O / W nano-emulsion, and CO2 micro-bubble activated water phase and double-frequency ultrasonic stabilization treatment are combined. According to the invention, through the innovation of'molecular complexing synergism-mesostructure controlled release-macroscopic system delivery ', the uric acid reducing efficiency reaches 85% of that of clinical drugs, the pharmaceutical composition is free of liver and kidney toxicity, the shelf life is prolonged, and a safe and effective food-grade solution is provided for hyperuricemia patients.

Description

Technical Field

[0001] The present invention relates to the technical field of uric acid-lowering compositions, and particularly to a preparation method of diglyceride solid powder and beverage having the function of lowering uric acid. Background Art

[0002] High uric acid in the human body is a metabolic disease caused by an increase in uric acid in the blood due to metabolic disorders of a substance called purine. Clinically, the normal values are: for men, 149 - 416 μmol / L, and for women, 89 - 357 μmol / L. When the uric acid concentration is too high or in an acidic environment, uric acid can precipitate crystals and deposit in tissues such as bone joints, kidneys, and subcutaneous tissues, causing histopathological changes; the main manifestations are acute arthritis, tophus, chronic arthritis, chronic interstitial nephritis, and uric acid urinary tract stones, etc.

[0003] Currently, the commonly used means for clinical treatment of hyperuricemia mainly include drug treatment and dietary intervention. There are mainly three categories of drug treatment. One category is drugs that inhibit uric acid production, one category is drugs that promote the excretion of uric acid by the kidneys, and another category is painkillers during gout attacks. However, drugs have their toxicity and obvious side effects, such as liver and kidney function damage, severe allergic reactions, etc., and long-term use burdens the body.

[0004] Diglyceride (DAG) is the product of the esterification of glycerol and two fatty acids and is a minor component of natural oils. Diglyceride can improve the utilization of dietary fat energy, is easy to digest without accumulating body fat, and can also reduce uric acid values, improve the metabolism of postprandial blood lipids, and improve insulin levels, etc.

[0005] Patent CN 115211517 A discloses an invention of a solid beverage having the effect of lowering uric acid and its preparation method. First, weigh: erythritol, diglyceride oil powder, celery seed powder, celery juice powder, lophatherum gracile extract, corn silk extract, blueberry extract, green tea extract, marine fish oligopeptide, tart cherry fruit powder, Acer truncatum Bunge seed oil microcapsule powder, edible essence sucrose fatty acid ester, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, sucralose; through premixing and total mixing: finally, it can be filled. It can inhibit the absorption and transformation of purine in the body, promote the excretion of purine from the body with urine, and has an obvious effect on lowering uric acid and preventing gout.

[0006] Patent CN118453807A discloses an invention of an oral uric acid-lowering combination formula and its preparation method. By extracting natural active ingredients such as celery seeds, corn silk, turmeric, and monk fruit, and mixing them with other substances in the formula, an uric acid-lowering combination formula can be obtained, which can effectively inhibit the activity of xanthine oxidase, restore the balance of purine metabolism, reduce uric acid production and urate crystal deposition, and has no toxic side effects, being more beneficial to human health; it can be processed into forms such as solid beverages or oral liquids.

[0007] Although the above method for preparing hypouricemic foods or beverages has achieved certain effects, there are still some deficiencies. Merely preparing hypouricemic foods by simply mixing various natural extracts lacks scientific formula design and effective preparation process optimization, resulting in limited hypouricemic effects of the products. In addition, some products fail to fully protect the active ingredients during the preparation process, leading to their inactivation during storage and use, affecting the stability and efficacy of the products.

[0008] Therefore, we propose a method for preparing diglyceride solid powder and beverage with hypouricemic function to solve the above problems. Summary of the Invention

[0009] The purpose of the present invention is to solve the deficiencies existing in the prior art, and to propose a method for preparing diglyceride solid powder and beverage with hypouricemic function.

[0010] To achieve the above purpose, the present invention adopts the following technical solutions:

[0011] A method for preparing diglyceride solid powder with hypouricemic function, comprising the following steps: S1 Preparation of curcumin-glycyrrhizic acid metal complex: Mix curcumin extract and glycyrrhizic acid in a mass ratio of 1:1.5, add 0.05 mol / L ferric citrate solution, and perform ultrasonic treatment at 50 °C for 30 minutes to form nano-scale complex particles, obtaining curcumin-glycyrrhizic acid metal complex; S2 Sustained-release embedding of zeaxanthin: Perform molecular embedding of zeaxanthin extract and β-cyclodextrin in a mass ratio of 1:3, and adopt supercritical CO2-assisted inclusion technology to obtain embedded zeaxanthin; S3 Primary premixing: High-speed shear mix diglyceride powder and curcumin-glycyrrhizic acid metal complex in a mass ratio of 4:1 under the protection of inert gas to form a primary composite oil phase, and fluidized bed mix resistant dextrin, erythritol and embedded zeaxanthin in a mass ratio of 5:3:2 to form a secondary porous carrier matrix; S4 Dynamic assembly and molding: Put the primary composite oil phase, secondary porous carrier matrix, monk fruit powder and citrate into a three-dimensional mixer, make the materials penetrate at 200 rpm for the first 10 minutes, and promote interfacial combination at 50 rpm for the next 20 minutes. Sprinkle 0.5% sodium alginate solution at the end of mixing to form a protective hydration film, obtaining a mixed material; S5 Sub-packaging and activation: Balance the mixed material at a relative humidity of 40% and a temperature of 25 °C for 12 hours to induce the formation of microcrystalline structure of citrate, and package it with nitrogen replacement, with each package containing 5-12 g.

[0012] As a preferred technical solution:

[0013] The preparation method of the diglyceride solid powder with uric acid-lowering function as described above. In step S1, the ultrasonic treatment adopts an alternating pulse mode with a frequency of 40 kHz and a power of 300 W, and the formed nano-scale complex particles have a core-shell structure, where the turmeric extract is the core and the glycyrrhizic acid-iron complex layer is the shell layer.

[0014] The preparation method of the diglyceride solid powder with uric acid-lowering function as described above. The technical parameters of the supercritical CO2-assisted inclusion technology in step S2 are as follows: Pressure gradient control: The pressure rising rate is 3 MPa / min in the stage of rising from 0 to 20 MPa, and the maintaining time in the 20 MPa stage is 30 min; Temperature gradient control: The temperature rising rate is 1 °C / min in the stage of rising from 40 °C to 45 °C, and the maintaining time in the 45 °C stage is 20 min; The formed β-cyclodextrin inclusion has a hexagonal close-packed pore structure, and the zeaxanthin molecules are embedded in the pores in a monolayer arrangement form; The inclusion adsorbs the resistant dextrin-erythritol mixed matrix through pore capillary action in the secondary dispersion system of step S3.

[0015] The preparation method of the diglyceride solid powder with uric acid-lowering function as described above. The fluidized bed mixing in step S3 includes three-stage fluidization processes: First-stage fluidization: The gas flow rate is 0.8 m 3 / h, and the bed temperature is 35 °C to form a porous skeleton of resistant dextrin; Second-stage fluidization: The gas flow rate is 1.2 m 3 / h, and the bed temperature is 45 °C to melt and coat the surface of the skeleton with erythritol; Third-stage fluidization: The gas flow rate is 0.5 m 3 / h, and the bed temperature is 30 °C to embed the included zeaxanthin into the pores of the coating; The formed porous carrier matrix serves as a sustained-release carrier for the active ingredient in dynamic assembly.

[0016] The preparation method of the diglyceride solid powder with uric acid-lowering function as described above. The 0.5% sodium alginate solution sprayed in step S4 is subjected to the following modification treatments: Adding 0.1% nano-hydroxyapatite as a nucleating agent; Pre-emulsifying with 1% diglyceride emulsion; After spraying, the following are formed on the surface of the material: Bottom layer: Sodium alginate-hydroxyapatite composite film; Outer layer: Oriented arrangement layer of diglyceride molecules; The protective hydration film forms an airtight barrier through nitrogen replacement in step S5 packaging.

[0017] The second aspect of the present invention provides a method for preparing a diglyceride beverage with uric acid lowering function, characterized in that it comprises the following steps: S1: mixing turmeric extract and glycyrrhizic acid in a mass ratio of 1:1.5, adding 0.05 mol l / L ferric citrate solution, ultrasonically treated at 50°C for 30 minutes to form nano-scale complex particles, and obtain turmeric-glycyrrhizic acid metal complex; S2: corn silk extract and β-cyclodextrin are molecularly embedded in a mass ratio of 1:3, and supercritical CO2-assisted inclusion technology is used to obtain embedded corn silk alkali; S3: diglyceride powder, turmeric-glycyrrhizic acid metal complex and sodium stearoyl lactylate are homogenized at high speed at 60°C to form a nanoemulsion, the corn silk embedding material and citrate are dissolved in pure water, and the pH is adjusted to 6.5-7.0 to obtain an activated water phase; S4: the nanoemulsion is slowly injected into the activated water phase, the injection rate is controlled to 5mL / min, low-frequency ultrasound is applied simultaneously, 0.1% xanthan gum and 0.05% gellan gum compound stabilizer are added, and the mixture is matured at 4°C for 24 hours to obtain a diglyceride beverage.

[0018] As the preferred technical solution:

[0019] The preparation method of the diglyceride beverage with uric acid lowering function as described above, wherein the high-speed homogenization in S3 uses a microfluidic chip to perform three-stage emulsification: primary emulsification: pressure 50MPa, forming W / O colostrum; secondary emulsification: pressure 100MPa, breaking into nanoemulsion cores; tertiary emulsification: pressure 30MPa, coating the sodium stearoyl lactylate interface membrane; the nanoemulsion selectively fuses with the phospholipid bilayer of the activated water phase through the interface membrane in S4.

[0020] The method for preparing a diglyceride beverage with uric acid lowering function as described above, wherein the activated water phase in S3 is pretreated as follows: the corn silk embedding material and citrate are treated in a vacuum degassing tank for 20 minutes; a 0.01% nanobubble generator is added to generate CO2 microbubbles; gradient filtration is performed through a microporous filter membrane; the dissolved oxygen content of the treated water phase is less than 1ppm, and the emulsion dispersion is promoted by microbubble rupture when S4 is injected.

[0021] The mechanism of the present invention is as follows:

[0022] Fe 3+ Coordination chemistry is introduced into the uric acid lowering food system, and the low efficiency of traditional plant ingredients is overcome through the synergistic effect of metal-ligand; a three-level ordered structure of "core-shell complex-porous carrier-oriented membrane layer" is constructed to achieve precise controlled release of active ingredients; non-equilibrium processing technology (pulsed ultrasound / supercritical gradient / microfluidic emulsification) is developed to improve the food processing precision to the nanoscale; through molecular-mesoscopic-macroscopic multi-scale synergy, the uric acid lowering efficiency reaches 85% of the clinical drug allopurinol, without the risk of toxicity (LD50>5000mg / kg).

[0023] Beneficial effects

[0024] Diacylglycerol is scientifically formulated with natural extracts such as turmeric, glycyrrhizic acid, and corn silk to form a formula with a significant uric acid-lowering effect. This formula design not only improves the uric acid-lowering efficacy of the product but also enriches the nutritional components of the product;

[0025] The present invention adopts advanced preparation processes such as ultrasonic treatment, supercritical CO2-assisted inclusion technology, high-speed shear mixing, fluidized bed mixing, dynamic assembly of three-dimensional mixers, and nanoemulsion injection to ensure the stability and effectiveness of the active ingredients, and improve the bioavailability and uric acid-lowering effect of the product;

[0026] Through the sustained-release embedding technology of corn silk alkali, the sustained release of active ingredients is achieved, the action time of the product in vivo is prolonged, and the persistence of the uric acid-lowering effect is improved;

[0027] Spraying the modified sodium alginate solution on the surface of the product forms a protective hydrated film with an airtight barrier, effectively preventing oxidation and inactivation of the product during storage and use, and improving the stability and storage resistance of the product. Detailed implementation manners

[0028] Unless otherwise defined, all technologies and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this invention belongs. In case of conflict, the definitions in this specification shall prevail. "When a mass, concentration, temperature, time, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper preferred values and lower preferred values, it should be understood that all ranges formed by any pairing of any range upper limit or preferred value with any range lower limit or preferred value are specifically disclosed, regardless of whether the ranges are separately disclosed. For example, a range of 1-50 should be understood to include any number, combination of numbers, or sub-ranges selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, as well as all decimal values between the above integers, such as 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. Regarding sub-ranges, specifically consider the "nested sub-ranges" extending from any endpoint within the range. For example, the nested sub-ranges of the exemplary range 1-50 can include 1-10, 1-20, 1-30, and 1-40 in one direction, or 50-40, 50-30, 50-20, and 50-10 in the other direction."

[0029] The present invention will be further explained below in conjunction with specific embodiments. In the following embodiments, the experimental methods are all conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0030] A preparation method of a diglyceride solid powder with uric acid-lowering function comprises the following steps: Pretreatment of composite active ingredients:

[0031] a. Preparation of curcumin-glycyrrhizic acid metal complex:

[0032] Mix the curcumin extract and glycyrrhizic acid in a mass ratio of 1:1.5, add 0.05 mol / L ferric citrate solution, and perform ultrasonic treatment (40 kHz, 300 W) at 50 °C for 30 minutes to form nano-scale complex particles (particle size 80-150 nm);

[0033] b. Sustained-release embedding of corn silk alkali:

[0034] Perform molecular embedding on the corn silk extract and β-cyclodextrin in a mass ratio of 1:3, and adopt supercritical CO2-assisted inclusion technology (pressure 20 MPa, temperature 45 °C);

[0035] Gradient mixing process

[0036] a. Primary premixing system:

[0037] Mix the diglyceride powder and the metal complex prepared in step 1a in a mass ratio of 4:1 under the protection of inert gas by high-speed shear mixing (rotation speed 5000 rpm, time 15 minutes) to form a stable composite oil phase;

[0038] b. Secondary dispersion system:

[0039] Perform fluidized bed mixing on resistant dextrin, erythritol and the embedded corn silk alkali in step 1b in a mass ratio of 5:3:2, and control the humidity <15% to form a porous carrier matrix;

[0040] Dynamic assembly and molding

[0041] a. Three-dimensional motion mixing:

[0042] Put the primary composite oil phase (25-40 parts), the secondary porous carrier matrix (15-25 parts), Luo Han Guo powder (3-4.5 parts) and citrate (3-5 parts of potassium citrate + 2.5-3.5 parts of sodium citrate) into a three-dimensional mixer;

[0043] Adopt a variable rotation speed mixing strategy: 200 rpm for the first 10 minutes to allow the material to penetrate, and 50 rpm for the next 20 minutes to promote interfacial bonding;

[0044] b. Interface stabilization treatment:

[0045] Spray 0.5% sodium alginate solution (mass proportion in total solids is 2 - 3%) at the end of mixing to form a protective hydration film;

[0046] Sub-packaging and activation

[0047] a. Oriented crystallization control:

[0048] Equilibrate the mixed materials at a relative humidity of 40% and a temperature of 25°C for 12 hours to induce the formation of microcrystalline structure of citrate;

[0049] b. Intelligent sub-packaging system:

[0050] Use nitrogen replacement packaging (oxygen content < 0.5%), each package contains 5 - 12 g, and the proportion of active ingredients is ≥ 65%.

[0051] Among them, the ultrasonic treatment adopts an alternating pulse mode with a frequency of 40 kHz and a power of 300 W (duty cycle: 5 - second pulse / 2 - second interval), and the formed nano - scale complex particles have a core - shell structure, where the turmeric extract is the core (particle size 80 ± 5 nm), and the glycyrrhizic acid - iron complex layer is the shell layer (thickness 15 - 20 nm).

[0052] Specifically, the technical parameters of the supercritical CO2 - assisted inclusion technology in S2 are: pressure gradient control: the pressure - rising rate in the 0 - 20 MPa stage is 3 MPa / min, and the holding time in the 20 MPa stage is 30 min; temperature gradient control: the temperature - rising rate in the stage from 40°C to 45°C is 1°C / min, and the holding time in the 45°C stage is 20 min;

[0053] The formed β - cyclodextrin inclusion has a hexagonal close - packed pore structure (pore diameter 1.8 ± 0.2 nm), and the zeaxanthin molecules are embedded in the pores in a monolayer arrangement; the inclusion adsorbs the resistant dextrin - erythritol mixed matrix through pore capillary action in the S3 secondary dispersion system.

[0054] Specifically, the fluidized - bed mixing includes a three - stage fluidization process: primary fluidization: gas flow rate 0.8 m 3 / h, bed temperature 35°C, to form a porous skeleton of resistant dextrin; secondary fluidization: gas flow rate 1.2 m 3 / h, bed temperature 45°C, to melt - coat the surface of the skeleton with erythritol; tertiary fluidization: gas flow rate 0.5 m 3 / h, bed temperature 30°C, to embed the included zeaxanthin into the pores of the coating; the formed porous carrier matrix serves as a sustained - release carrier for active ingredients in dynamic assembly.

[0055] It should be noted that the sprayed 0.5% sodium alginate solution is modified as follows: adding 0.1% nano-hydroxyapatite (particle size 50 nm) as a nucleating agent; pre-emulsifying with 1% diglyceride emulsion (oil-water ratio 1:4);

[0056] After spraying, the following is formed on the surface of the material: bottom layer: sodium alginate-hydroxyapatite composite film (thickness 5 - 8 μm); outer layer: diglyceride molecular orientation layer (contact angle > 110°);

[0057] The protective hydrated film forms an airtight barrier through nitrogen replacement during packaging.

[0058] A preparation method of a diglyceride beverage with uric acid-lowering function, comprising the following steps: nanoemulsion system construction

[0059] a. Pre-emulsification of the oil phase:

[0060] Mix diglyceride powder (4 - 8 parts), the metal complex in step 1a (1 - 2 parts) and sodium stearoyl lactate (0.5 - 1.1 parts) at 60 °C by high-speed homogenization (15,000 rpm) to form a nanoemulsion (particle size < 200 nm);

[0061] b. Activation of the aqueous phase:

[0062] Dissolve the corn silk inclusion (0.1 - 0.3 parts) and citrate (0.5 - 1 part) in pure water, and adjust the pH to 6.5 - 7.0;

[0063] High-speed homogenization is carried out using a microfluidic chip (channel diameter 200 μm) for three-stage emulsification: primary emulsification: pressure 50 MPa, forming a W / O primary emulsion (particle size 2 - 5 μm); secondary emulsification: pressure 100 MPa, broken into nanoemulsion nuclei (particle size 200 ± 50 nm); tertiary emulsification: pressure 30 MPa, coating with a sodium stearoyl lactate interfacial film (thickness 10 - 15 nm); the nanoemulsion selectively fuses with the phospholipid bilayer of the activated aqueous phase through the interfacial film in S4.

[0064] The activated aqueous phase is pretreated as follows: treat the corn silk inclusion and citrate in a vacuum degassing tank (-0.08 MPa) for 20 minutes; add 0.01% nano-bubble generator to generate CO2 microbubbles (diameter 50 - 80 μm); filter through a microporous membrane (pore size 0.22 μm) in a gradient manner; the dissolved oxygen content of the treated aqueous phase < 1 ppm, and the emulsion dispersion is promoted by the rupture of microbubbles during injection in S4.

[0065] Phase interface engineering

[0066] a. Gradient mixing:

[0067] Slowly inject the nanoemulsion into the activated aqueous phase, control the injection rate at 5 mL / min, and simultaneously apply low-frequency ultrasound (28 kHz).

[0068] b. Stabilization treatment:

[0069] Add a compound stabilizer of 0.1% xanthan gum and 0.05% gellan gum, and cure at 4°C for 24 hours.

[0070] Example 1: Preparation of diglyceride solid powder

[0071] 1. Pretreatment of composite active ingredients

[0072] a. Preparation of curcumin-glycyrrhizic acid metal complex

[0073] Raw material ratio: 10 g of curcumin extract (purity ≥ 95%), 15 g of glycyrrhizic acid (pharmaceutical grade)

[0074] Process parameters:

[0075] Dissolve in 0.05 mol / L ferric citrate solution (pH = 6.0)

[0076] Ultrasonic treatment: Alternating pulses of 40 kHz frequency and 300 W power (duty cycle 5 s pulse / 2 s interval)

[0077] Temperature 50°C, time 30 minutes

[0078] Product characteristics:

[0079] Core-shell structure nanoparticles (DLS detection: core particle size 82 ± 3 nm, shell thickness 18 ± 2 nm)

[0080] Zeta potential: -28.5 mV (measured by Malvern Zetasizer Nano ZS90)

[0081] b. Sustained-release embedding of zeaxanthin

[0082] Raw material ratio: 5 g of zeaxanthin extract (total flavonoid content ≥ 50%), 15 g of β-cyclodextrin (food grade)

[0083] Supercritical CO2 process:

[0084] Pressure gradient: 0 → 20 MPa (pressure increase rate 3 MPa / min), maintained for 30 minutes

[0085] Temperature gradient: 40°C → 45°C (heating rate 1°C / min), maintained for 20 minutes

[0086] Product characteristics:

[0087] Entrapment efficiency 92.3% (determined by HPLC)

[0088] Hexagonal close-packed pore structure (BET specific surface area 23.5 m² / g, pore diameter 1.76 nm)

[0089] 2. Gradient mixing process

[0090] a. Primary premixing system

[0091] Raw material ratio: 80 g of diglyceride powder (purity ≥ 90%), 20 g of metal complex

[0092] Process parameters:

[0093] High-speed shear mixing under inert gas (N₂) protection (Fluko FA25 type, 5000 rpm × 15 min)

[0094] Temperature control ≤ 40 °C

[0095] Product characteristics:

[0096] Composite oil phase particle size D50 = 4.2 μm (detected by laser particle size analyzer)

[0097] Interface Fe 3+ Coordination bond density 3.2 groups / nm 2 (XPS analysis)

[0098] b. Secondary dispersion system Raw material ratio: 50 g of resistant dextrin, 30 g of erythritol, 20 g of embedded corn silk alkali Fluidized bed process (Glatt GPCG2 type):

[0099]

[0100] Product characteristics:

[0101] Porosity 76.8% (measured by mercury intrusion method)

[0102] Drug loading 18.2% (measured by UV-Vis spectrophotometry)

[0103] 3. Dynamic assembly and molding

[0104] Raw material ratio:

[0105] 35 parts of primary composite oil phase

[0106] 20 parts of secondary porous carrier matrix

[0107] 4 parts of Momordica grosvenori fruit powder

[0108] 4 parts of potassium citrate + 3 parts of sodium citrate

[0109] Three-dimensional mixing process (SYH-100 type three-dimensional motion mixer):

[0110] For the first 10 minutes, infiltrate and mix at 200 rpm

[0111] For the next 20 minutes, interface bonding at 50 rpm

[0112] Spray 0.5% sodium alginate solution (containing 0.1% nano-hydroxyapatite)

[0113] Product characteristics:

[0114] Hydration film thickness 6.5 μm (observed by SEM)

[0115] Contact angle 112° (measured by contact angle meter)

[0116] 4. Sub-packaging and activation

[0117] Crystallization control: Equilibrate at 25°C / RH40% for 12 hours

[0118] Sub-packaging parameters:

[0119] Replace with nitrogen and package (oxygen content 0.3%)

[0120] 10 g per pack, active ingredient proportion 68.5%

[0121] Storage stability:

[0122] Condition Time Activity retention rate 25℃ 18 months 91.2％ 40℃ 6 months 85.7％

[0123] Example 2: Preparation of diglyceride beverage

[0124] 1. Construction of nano-emulsion system

[0125] a. Raw material ratio for pre-emulsification of oil phase: 6 g of diglyceride powder, 1.5 g of metal complex, 0.8 g of sodium stearoyl lactate. Microfluidic three-stage emulsification (Dolomite μEncapsulator):

[0126] Stage Pressure (MPa) Function Product characteristics First stage 50 W / O primary emulsion formation D50 = 3.8μm Second stage 100 Nanocore fragmentation D50 = 195nm Third stage 30 Interface film coating Film thickness 12nm

[0127] b. Raw material ratio for activation of water phase: 0.25 g of corn silk embedding, 0.7 g of potassium citrate + 0.3 g of sodium citrate. Pretreatment process:

[0128] Vacuum degassing (-0.08 MPa × 20 min)

[0129] Inject nano-CO2 microbubbles (diameter 60 ± 10 μm, concentration 10 6 per mL)

[0130] Filter through 0.22 μm filter membrane

[0131] Water phase characteristics:

[0132] Dissolved oxygen content: 0.8 ppm (measured by dissolved oxygen meter)

[0133] pH = 6.8 (pH meter calibration)

[0134] 2. Phase interface engineering

[0135] a. Gradient mixing

[0136] Process parameters:

[0137] Injection rate of nanoemulsion: 5 mL / min

[0138] Dual-frequency ultrasonic treatment (28 kHz × 50 W + 132 kHz × 20 W)

[0139] Temperature: 25°C ± 1°C

[0140] Characteristics of the mixed system:

[0141] Index Value Detection method Emulsion particle size 210 ± 25nm DLS PDI 0.12 Laser particle size analyzer

[0142] b. Stabilization treatment

[0143] Addition of stabilizers: xanthan gum 0.1% + gellan gum 0.05%

[0144] Aging process:

[0145] Primary aging: Standing at 4°C for 12 hours; Dynamic aging: Heating to 25°C (rate 2°C / min) under rotating magnetic field (0.3 T); Final stabilization: Rapid cooling to 4°C

[0146] Characteristics of the final product:

[0147]

[0148]

[0149] Example 3: Comparative experiment

[0150] 1. Control group with traditional mixing process

[0151] Formulation: The same as in Example 1, but the dynamic assembly process is cancelled and a conventional V-type mixer is used for one-time mixing

[0152] Performance comparison:

[0153] Index The present invention Control group Dispersion uniformity of active ingredient (CV value) 5.2％ 23.7％ Intestinal targeting release rate 91.5％ 58.3％ 6 - month activity retention rate 89.4％ 41.6％

[0154] 2. Verification of in vitro uric acid-lowering effect

[0155] Experimental method:

[0156] Xanthine oxidase inhibition experiment (IC50 determination)

[0157] Uric Acid Adsorption Experiment (Isothermal Adsorption Model)

[0158] Results:

[0159] Sample IC50 (μg / mL) Maximum adsorption capacity (mg / g) Solid powder of the present invention 0.31 198 Commercially available uric acid - lowering products 0.89 102

[0160] Example 4: Preclinical Animal Experiment

[0161] 1. Experimental Design

[0162] Animal Model: Hyperuricemia Rats (Induced by Potassium Oxonate)

[0163] Grouping:

[0164] Blank Group (Normal Diet)

[0165] Model Group (High-Purine Diet)

[0166] Experimental Group (Model + 500 mg / kg / d of the Solid Powder of the Present Invention)

[0167] Positive Control Group (Model + Allopurinol 10 mg / kg / d)

[0168] 2. Experimental Results

[0169]

[0170] (*P<0.01 vs Model Group)

[0171] Industrial Applicability Description

[0172] Production Equipment:

[0173] Ultrasonic Treatment System: Branson UIP2000hd

[0174] Supercritical Device: Waters SFE-100

[0175] Microfluidic Emulsification System: Dolomite μEncapsulator

[0176] Quality Control Standards:

[0177] Detection item Standard Method Particle size distribution D90 < 250nm ISO 13320 Active ingredient content ≥ 90% of labeled amount HPLC Microbial limit Aerobic bacteria < 100CFU / g GB 4789.2

[0178] Summary of Technical Effects, Improvement in Uric Acid Reduction Efficiency: The inhibitory activity of xanthine oxidase is increased by 3 times (IC50 = 0.31 vs 0.89 μg / mL); Breakthrough in Stability: The shelf life is extended to 18 months (activity retention rate > 90%); Optimization of Targeting: The intestinal specific release rate reaches 91.5% (only 58.3% for the traditional process); Safety Assurance: The LD50 of the acute toxicity experiment > 5000 mg / kg, far higher than the food-grade safety standard.

[0179] Curcumin (containing β-diketone structure) and glycyrrhizic acid (containing carboxylic acid group) form a stable ternary complex (binding energy -2.8 eV) through Fe 3+ This complex exerts its effects through the following pathways:

[0180] Enhanced electron transfer: Fe 3+ As an electron mediator, it accelerates the electron transfer at the active center (molybdopterin cofactor) of xanthine oxidase, increasing the enzyme inhibition rate to 89.5% (only 52% for the traditional formulation);

[0181] Stereoselective binding: The conformation of the complex forms a complementary hydrophobic cavity (LogP = 3.2) with uric acid molecules, and the binding constant reaches 10 6 M -1 .

[0182] Under the control of supercritical CO2 gradient (pressure / temperature double gradient), β-cyclodextrin forms a hexagonal close-packed pore structure (pore diameter 1.8 nm), achieving: molecular-level arrangement: cornsilk alkaloid is embedded in the pores in a monolayer form, and the drug loading density reaches 0.35 g / cm 3 ; pH-responsive release: The alkaline environment in the intestine triggers the expansion of the pores (swelling degree > 300%), achieving a sustained release time > 8 hours.

[0183] Through the regulation of gas flow rate and temperature gradient (0.8 → 1.2 → 0.5 m 3 / h; 35 → 45 → 30 °C), a hierarchical porous structure is formed: primary skeleton: resistant dextrin forms macropores with a size of 50 - 100 μm (porosity > 70%); secondary coating: erythritol melts and fills mesopores (5 - 20 μm); tertiary drug loading: cornsilk alkaloid is embedded in micropores (< 5 μm), and the specific surface area reaches 23 m 2 / g.

[0184] As mentioned above, only the preferred specific embodiments of the present invention are described, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and should be covered by the protection scope of the present invention.

Claims

1. A method for preparing a diglyceride solid powder having a uric acid-lowering function, characterized in that: The steps include: S1 Preparation of turmeric-glycyrrhizic acid metal complex: mixing turmeric extract with glycyrrhizic acid, adding ferric citrate solution, and ultrasonic treatment to form nano-scale complex particles to obtain turmeric-glycyrrhizic acid metal complex; S2 sustained-release encapsulation of corn silk alkaloids: corn silk extract and β-cyclodextrin are molecularly encapsulated, and supercritical CO2-assisted inclusion technology is used to obtain encapsulated corn silk alkaloids; S3 primary premixing: diglyceride powder and turmeric-glycyrrhizic acid metal complex are subjected to high-speed shear mixing under the protection of inert gas to form a primary composite oil phase, and resistant dextrin, erythritol and embedded corn silk alkali are mixed in a fluidized bed to form a secondary porous carrier matrix; S4 dynamic assembly molding: the primary composite oil phase, the secondary porous carrier matrix, monk fruit powder and citrate are put into a three-dimensional mixer, and the material is infiltrated at 200 rpm for the first 10 minutes, and then at 50 rpm for the next 20 minutes to promote interface bonding. At the end of the mixing, 0.5% sodium alginate solution is sprayed to form a protective hydration film to obtain a mixed material; S5 Packaging and activation: The mixed material is balanced at a relative humidity of 40% and a temperature of 25°C for 12 hours to induce the citrate to form a microcrystalline structure, and then packaged using nitrogen displacement, with each package containing 5-12g.

2. The method for preparing the diglyceride solid powder having the function of lowering uric acid according to claim 1, characterized in that: The ultrasonic treatment in S1 adopts an alternating pulse mode of 40kHz frequency and 300W power, and the formed nano-scale complex particles have a core-shell structure, wherein the turmeric extract is the core and the glycyrrhizic acid-iron complex layer is the shell.

3. The method for preparing the diglyceride solid powder having the function of lowering uric acid according to claim 1, characterized in that: The technical parameters of supercritical CO2-assisted inclusion in S2 are: Pressure gradient control: 0-20MPa stage pressure increase rate 3MPa / min, 20MPa maintenance stage time 30min; Temperature gradient control: 40℃ to 45℃ stage heating rate 1℃ / min, 45℃ maintenance stage time 20min; The formed β-cyclodextrin embedding body has a hexagonal close-packed pore structure, and the corn silk alkaloid molecules are embedded in the pores in a single-layer arrangement; The embedding body adsorbs the resistant dextrin-erythritol mixed matrix in the S3 secondary dispersion system through pore capillary action.

4. The method for preparing the diglyceride solid powder having the function of lowering uric acid according to claim 1, characterized in that: The fluidized bed mixing in S3 includes three-stage fluidization process: First-stage fluidization: gas flow rate 0.8m 3 / h, bed temperature 35°C, so that the resistant dextrin forms a porous skeleton; Secondary fluidization: gas flow rate 1.2m 3 / h, the bed temperature is 45°C, and the erythritol is melted and coated on the skeleton surface; Three-stage fluidization: gas flow rate 0.5m 3 / h, the bed temperature is 30°C, so that the embedded corn silk alkali is embedded into the pores of the coating; The formed porous carrier matrix acts as a sustained-release carrier for active ingredients in the dynamic assembly.

5. The method for preparing the diglyceride solid powder having the function of lowering uric acid according to claim 1, characterized in that: The 0.5% sodium alginate solution sprayed in S4 is modified as follows: adding 0.1% nano-hydroxyapatite as a nucleating agent; pre-emulsifying with 1% diglyceride emulsion; After spraying, the following are formed on the surface of the material: bottom layer: sodium alginate-hydroxyapatite composite film; outer layer: diglyceride molecule oriented arrangement layer; The protective hydrated membrane forms an airtight barrier by nitrogen replacement during S5 packaging.

6. A method for preparing a diglyceride beverage having a uric acid-lowering function, characterized in that: The following steps are involved: S1: Mixing turmeric extract with glycyrrhizic acid, adding ferric citrate solution, and ultrasonic treatment to form nano-scale complex particles to obtain turmeric-glycyrrhizic acid metal complex; S2: Molecularly encapsulate corn silk extract with β-cyclodextrin, and use supercritical CO2-assisted inclusion technology to obtain encapsulated corn silk alkaloids; S3: Diglyceride powder, turmeric-glycyrrhizic acid metal complex and sodium stearoyl lactylate are homogenized at high speed at 60°C to form a nanoemulsion, corn silk embedding material and citrate are dissolved in pure water, and the pH is adjusted to 6.5-7.0 to obtain an activated water phase; S4: Slowly inject the nanoemulsion into the activated water phase, control the injection rate to 5 mL / min, apply low-frequency ultrasound simultaneously, add 0.1% xanthan gum and 0.05% gellan gum compound stabilizer, mature at 4°C for 24 hours, and obtain a diglyceride beverage.

7. The method for preparing a diglyceride beverage having a uric acid lowering function according to claim 6, characterized in that: The S3 high-speed homogenization uses a microfluidic chip for three-stage emulsification: Primary emulsification: pressure 50MPa, forming W / O colostrum; Secondary emulsification: pressure 100MPa, breaking into nanoemulsion cores; Three-stage emulsification: pressure 30MPa, coated with sodium stearoyl lactylate interface film; The nanoemulsion selectively fuses with the phospholipid bilayer of the activated water phase through the interfacial membrane in S4.

8. The method for preparing a diglyceride beverage having uric acid lowering function according to claim 6, characterized in that: The activated water phase in S3 is pretreated as follows: The corn silk embeddings were treated with citrate in a vacuum degassing tank for 20 minutes; Add 0.01% nanobubble generator to produce CO2 microbubbles; Gradient filtration through a microporous membrane; The dissolved oxygen content of the treated water phase is less than 1 ppm, and the emulsion dispersion is promoted by microbubble rupture when S4 is injected.

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