A uric acid-lowering composite raw material comprising a tart cherry-celery seed combination and bromelain

Abstract

The present invention discloses a uric acid-lowering composite raw material comprising a tart cherry-celery seed combination and bromelain, relating to the field of functional foods. The composition comprises tart cherry extract, celery seed extract, bromelain, and a lyoprotectant. Through intermolecular non-covalent bonding, the active ingredients form an ordered core-shell structure, wherein plant- derived ingredients combine into a composite core, and bromelain is adsorbed onto the outer surface to form a protein coating layer. This delivery structure is constructed entirely from the active ingredients themselves without extra synthetic polymer carriers, avoiding metabolic burden and safety risks. The components achieve functional matching through molecular-level ordered binding; the core protects liposoluble ingredients, while the shell stabilizes the structure, fully exerting synergistic effects.

Description

[0001] DESCRIPTION

[0002] A Uric Acid-Lowering Composite Raw Material Comprising a Tart Cherry-Celery Seed Combination and Bromelain Technical Field

[0003] The present invention relates to the technical field of functional foods, and specifically relates to NVTIA™ Uric Acid-Lowering Composite Raw Material comprising a tart cherry-celery seed combination and bromelain. Background Art

[0004] Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder. In recent years, its incidence has continued to rise and has shown a marked trend toward younger age groups; it has become the fourth major chronic metabolic disease after hypertension, hyperlipidemia, and hyperglycemia. Long-term abnormally elevated blood uric acid levels not only induce typical conditions such as gouty arthritis and tophus deposition, but also cause continuous organic damage to the kidneys, cardiovascular system, and endocrine system. Although commonly used clinical chemical drugs for lowering uric acid act relatively quickly, long-term administration is associated with various side effects such as hepatic and renal toxicity, allergic reactions, and gastrointestinal irritation, and patient medication compliance is generally low. Therefore, natural- source uric acid-lowering products that are safe, mild, and have fewer side effects are receiving increasing attention and have become a development focus in the fields of functional foods and natural medicines.

[0005] However, existing natural uric acid-lowering products are mostly developed based on a single component, have a single action target, and exhibit very limited practical uric acid-lowering effects. Some compound formulas are merely simple physical mixtures of different active ingredients, achieving only macroscopic component matching without structural design and ordered binding at the molecular level. Although some technologies attempt to combine active ingredients derived from tart cherry and celery seedDESCRIPTION

[0006] with protease components, they remain at the stage of direct mixing and do not optimize the structure according to the physicochemical properties of the respective components. Liposoluble plant active ingredients have poor water solubility and are difficult to fully dissolve and absorb in the gastrointestinal environment; protein enzyme preparations are readily degraded by gastric acid and digestive tract proteases, making it difficult for them to reach the action site while retaining activity. In addition, some nanodelivery technical solutions add synthetic polymer materials as carriers in order to improve the defects; such carriers have unclear metabolic pathways in vivo and potential risks of long-term accumulation. Meanwhile, simply mixed formulas cannot achieve synergistic enhancement among components, and large doses must be taken to achieve the expected effect, resulting in obvious limitations in practical application.

[0007] Summary of the Invention

[0008] The purpose of the present invention is to remedy the deficiencies of the prior art by providing NVTIA™ Uric Acid-Lowering Composite Raw Material comprising a tart cherry-celery seed combination and bromelain. In the present invention, intermolecular non-covalent bonding among different active ingredients enables the components to form an ordered core-shell structure, wherein plant-derived active ingredients combine to form a composite core, and bromelain is adsorbed onto the outer surface of the core to form a protein coating layer. The delivery structure of the whole composition is constructed entirely from the active ingredients themselves, without the addition of an extra synthetic polymer carrier, thereby avoiding metabolic burden and potential safety risks caused by an exogenous carrier. The components achieve functional matching through molecular-level ordered binding; the composite core provides delivery protection for liposoluble active ingredients, while the shell layer also stabilizes its own structure, thereby fully exerting the synergistic effects of the different components.DESCRIPTION

[0009] To solve the above technical problems, the present invention provides the following technical solutions: in one aspect, a uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain is provided, the composition comprising tart cherry extract, celery seed extract, bromelain, and a lyoprotectant;

[0010] wherein polyphenolic components in the tart cherry extract and phthalide components in the celery seed extract bind through intermolecular non-covalent bonds to form a composite core;

[0011] wherein the bromelain is adsorbed onto an outer surface of the composite core through multi-point hydrogen bonds to form a protein coating layer, and together with the composite core forms core-shell structured nanoparticles; wherein the composition is in the form of a lyophilized powder, and after reconstitution, the lyophilized powder is restored to core-shell structured nanoparticles.

[0012] Further, the polyphenolic components in the tart cherry extract are cyani din-3 -glucoside and procyanidin B2, the phthalide component in the celery seed extract is 3-n-butylphthalide, and the intermolecular non-covalent bonds include pi-pi stacking interactions and hydrophobic interactions.

[0013] Still further, the molecular surface of the bromelain comprises lysine residues and arginine residues, the multi-point hydrogen bonds are formed by interaction between active groups of the lysine residues and arginine residues and polar groups on the surface of the composite core, and the core-shell structured nanoparticles have a particle size of 80-150 nm.

[0014] Still further, the mass ratio of the tart cherry extract to the celery seed extract is 5:1-3, and the mass ratio of the bromelain to the composite core is 1:8-5.

[0015] Still further, the lyoprotectant consists of mannitol and trehalose, the mass ratio of the mannitol to the trehalose is 1:0.8-1.2, and the total mass percentage of the lyoprotectant in the composition is 3-5%.DESCRIPTION

[0016] In another aspect, a preparation method for the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain is provided, the preparation method comprising the following specific steps:

[0017] raw-material dissolution and preparation: adding tart cherry extract and celery seed extract into a buffer solution and mixing at low temperature to obtain a polyphenol-phthalide raw-material mixed solution;

[0018] low-temperature pre-assembly induction: placing the polyphenol-phthalide raw-material mixed solution in a low-temperature environment protected by an inert gas and stirring to obtain a polyphenol-phthalide composite-core precursor solution;

[0019] microfluidization-based configuration locking: mixing the polyphenol-phthalide composite-core precursor solution with bromelain at low temperature, and conveying the mixture to a low-temperature high-pressure microfluidizer for treatment to obtain a core-shell structured nanoparticle suspension;

[0020] lyophilization solidification and forming: mixing the core-shell structured nanoparticle suspension with a lyoprotectant, and subjecting the mixture to pre-freezing and freeze-drying to obtain the composition in the form of a lyophilized powder.

[0021] Still further, in the raw-material dissolution and preparation step, the temperature for low-temperature mixing is 4-8 ° C, and the whole process is conducted away from light; the buffer solution is a phosphate buffer solution containing 10% ethanol by volume, and the pH of the buffer solution is 6.5; the mass ratio of the tart cherry extract to the celery seed extract is 5:1-3; and the mixture is stirred at a rotation speed of 100-300 rpm for 15-30 min to obtain a uniform polyphenol-phthalide raw-material mixed solution.

[0022] Still further, in the low-temperature pre-assembly induction step, the temperature of the low-temperature environment is 4-8 ° C, and the wholeDESCRIPTION

[0023] process is performed in a closed environment; the inert gas is at least one of nitrogen and argon, and the inert gas is continuously introduced until the oxygen content in the reaction system is <= 0.1 mg / L; continuous stirring is carried out at a rotation speed of 50-150 rpm for 2-4 h, during which the polyphenolic components in the tart cherry extract and the phthalide components in the celery seed extract bind through pi-pi stacking interactions and hydrophobic interactions to form a polyphenol-phthalide composite-core precursor, thereby obtaining a polyphenol-phthalide composite-core precursor solution having the Tyndall effect.

[0024] Still further, in the microfluidization-based configuration locking step, the temperature for low-temperature mixing is 4-8 ° C; bromelain is first prepared into an aqueous enzyme solution having a mass concentration of 5-10%, and then the aqueous enzyme solution is slowly added into the polyphenol-phthalide composite-core precursor solution, wherein the mass ratio of the bromelain to solid components in the polyphenol-phthalide composite-core precursor is 1:8-5; pre-stirring is performed at a rotation speed of 100-200 rpm for 10-20 min, and the mixture is then conveyed to a low-temperature high-pressure microfluidizer and cyclically treated 3-5 times under a pressure of 600-800 bar; during homogenization, lysine residues and arginine residues on the molecular surface of the bromelain are adsorbed onto the outer surface of the polyphenol-phthalide composite core through multi-point hydrogen bonds to form a core-shell structure, thereby obtaining a core-shell structured nanoparticle suspension.

[0025] Still further, in the lyophilization solidification and forming step, the lyoprotectant is added within 5-10 min after completion of the homogenization treatment; the total mass concentration of the lyoprotectant in the core-shell structured nanoparticle suspension is 3-5%; stirring is performed at a rotation speed of 50-100 rpm for 5-10 min, followed byDESCRIPTION

[0026] dispensing into a freeze-drying container with a dispensing thickness of 1-2 cm; after dispensing is completed, pre-freezing is conducted at -45 ° C for 6 h, and after completion of pre-freezing, programmed freeze-drying is performed under a vacuum degree of 10-20 Pa for 24-36 h to obtain the composition in the form of a lyophilized powder.

[0027] Compared with the prior art, the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain has the following beneficial effects:

[0028] I. In the present invention, intermolecular non-covalent bonding among different active ingredients enables the components to form an ordered core-shell structure, wherein plant-derived active ingredients combine to form a composite core, and bromelain is adsorbed onto the outer surface of the core to form a protein coating layer. The delivery structure of the whole composition is constructed entirely from the active ingredients themselves, without the addition of an extra synthetic polymer carrier, thereby avoiding metabolic burden and potential safety risks caused by an exogenous carrier. The components achieve functional matching through molecular-level ordered binding; the composite core provides delivery protection for liposoluble active ingredients, while the shell layer also stabilizes its own structure, thereby fully exerting the synergistic effects of the different components.

[0029] II. Through a staged process design under low-temperature conditions throughout the entire process, the present invention first induces plant active ingredients to pre-form a composite core structure, then completes the directional adsorption and structural locking of the bromelain shell, and finally stabilizes and solidifies the structure through a lyophilization process. No additional synthetic excipients need to be introduced throughout the entireDESCRIPTION

[0030] process, and the formation process of the nanostructure can be precisely controlled, thereby avoiding structural destruction and activity loss of the active ingredients during preparation, achieving controllable and stable preparation of the structure, and ensuring that the final product can rapidly restore its original nanostructure after reconstitution, making it suitable for different application scenarios.

[0031] Other advantages, objectives, and features of the present invention will be set forth to some extent in the following description, and to some extent will be apparent to those skilled in the art based on examination and study of the following text, or may be learned from practice of the present invention.

[0032] Brief Description of the Drawings

[0033] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or in the prior art, the drawings required for describing the embodiments or the prior art are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention, and those of ordinary skill in the art may obtain other drawings based on these drawings without creative effort.

[0034] FIG. 1 is a flowchart of a preparation method for the NVTIA™ Uric Acid-Lowering Composite Raw Material comprising a tart cherry-celery seed combination and bromelain;

[0035] FIG. 2 is a framework diagram of a preparation method for the NVTIA™ Uric Acid-Lowering Composite Raw Material comprising a tart cherry-celery seed combination and bromelain;

[0036] FIG. 3 is a framework diagram of microfluidization-based configuration locking in a preparation method for the NVTIA™ Uric Acid-Lowering Composite Raw Material comprising a tart cherry-celery seed combination and bromelain.

[0037] Detailed Description of EmbodimentsDESCRIPTION

[0038] Brand Implementation (Non-Limiting)

[0039] In certain embodiments, the composition disclosed herein may be provided under the brand designation NVTIA™ as NVTIA™ uric acid-lowering composite raw material. The brand designation is used solely for commercial identification and does not constitute a technical limitation. Unless explicitly stated otherwise, the terms "composition," "uric acid-lowering composition," and "composite raw material" refer to the claimed composition irrespective of branding, labeling, packaging, or marketing materials.

[0040] To further describe the technical means and effects adopted by the present invention to achieve the intended inventive purpose, the specific embodiments, structures, features, and effects according to the present invention are described in detail below with reference to the drawings and preferred embodiments.

[0041] Embodiment 1:

[0042] In Embodiment 1, the total polyphenol content in the tart cherry extract is >= 25%, the 3-n-butylphthalide content in the celery seed extract is >= 1%, the bromelain enzymatic activity is >= 1,000,000 U / g, and both mannitol and trehalose are pharmaceutical-grade excipients.

[0043] Raw-material dissolution and preparation: 50 g of tart cherry extract and 20 g of celery seed extract are weighed and prepared at a mass ratio of 5:2; 2 L of phosphate buffer solution containing 10% ethanol by volume is prepared, the pH value of the buffer solution is adjusted to 6.5, and the buffer solution is placed in a low-temperature water bath and cooled to 6 ° C, with aluminum foil wrapping used throughout the whole process for light protection. The weighed tart cherry extract and celery seed extract are sequentially added into the low-temperature buffer solution, a digital stirrer is started, the stirring speed is controlled at 200 rpm, and stirring is continued for 20 min until theDESCRIPTION

[0044] solid raw materials are completely dissolved and the system is uniform, without layering or visible precipitation, thereby obtaining a polyphenol-phthalide raw-material mixed solution, as shown in FIG. 1, while maintaining the system temperature at 6 ° C throughout the process.

[0045] Low-temperature pre-assembly induction: The polyphenol-phthalide raw-material mixed solution is transferred to a closed jacketed glass reactor, high-purity nitrogen is continuously introduced into the reactor to expel air from the reactor, and a dissolved oxygen meter is used to monitor the oxygen content in the reaction system in real time until the oxygen content decreases to 0.08 mg / L, thereby maintaining an inert gas protective atmosphere of slight positive nitrogen pressure. The temperature inside the glass reactor is controlled and stabilized at 6 ° C by circulating coolant through the jacket. The stirring device is started, the rotation speed is adjusted to 100 rpm, and stirring is continued for 3 h. During stirring, the polyphenolic components in the tart cherry extract and the phthalide components in the celery seed extract gradually bind through pi-pi stacking interactions and hydrophobic interactions to form a polyphenol-phthalide composite-core precursor. After stirring is completed, irradiation with a laser pointer shows a clear Tyndall light path, and a polyphenol-phthalide composite-core precursor solution is obtained, as shown in FIG. 2, while the closed and low-temperature conditions are maintained throughout the process.

[0046] Microfluidization-based configuration locking: 11.7 g of bromelain is placed in a 6 ° C low-temperature environment, and pre-cooled purified water is used to prepare an aqueous enzyme solution having a mass concentration of 8% for later use. The polyphenol-phthalide composite-core precursor solution is kept at 6 ° C. According to a mass ratio of bromelain to solid components in the polyphenol-phthalide composite-core precursor of 1:6, the aqueous enzyme solution is slowly added dropwise to theDESCRIPTION

[0047] polyphenol-phthalide composite-core precursor solution at a flow rate of 1 mL / min. After the dropwise addition is completed, stirring is started, the rotation speed is controlled at 150 rpm, and pre-stirring is performed for 15 min until uniform mixing is achieved. After mixing, the mixture is conveyed to a low-temperature high-pressure microfluidizer, the feed temperature is controlled at 6 ° C, the working pressure is set at 700 bar, and cyclic treatment is performed 4 times. During homogenization, lysine residues and arginine residues on the molecular surface of the bromelain are adsorbed onto the outer surface of the polyphenol-phthalide composite core through multi-point hydrogen bonds, thereby stably forming a core-shell structure. After homogenization is completed, a core-shell structured nanoparticle suspension is obtained, as shown in FIG. 3.

[0048] Lyophilization solidification and forming: Within 8 min after completion of the microfluidization homogenization treatment, a lyoprotectant is added into the core-shell structured nanoparticle suspension. The lyoprotectant is a mixture of mannitol and trehalose mixed at a mass ratio of 1:1, and the total mass concentration of the lyoprotectant in the suspension is controlled at 4%. The stirring device is started, the rotation speed is adjusted to 80 rpm, and stirring is continued for 8 min so that the lyoprotectant is completely dissolved and uniformly mixed. The mixed suspension is dispensed into a standard freeze-drying tray with a dispensing thickness controlled at 1.5 cm, and is quickly placed in a -45 ° C freeze-dryer cold trap for pre-freezing for 6 h. After pre-freezing is completed, vacuum is started, the vacuum degree is controlled at 15 Pa, and a programmed freeze-drying process is used for drying for 30 h. After drying is completed, the material is taken out and passed through an 80-mesh sieve to obtain the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain in the form of a lyophilized powder.DESCRIPTION

[0049] Product Testing:

[0050] Nanoparticle particle size testing: 0.5 g of the uric acid-lowering composition prepared in Embodiment 1 is taken, 10 mL of purified water is added for shaking and reconstitution, and a dynamic light scattering particle size analyzer is used to detect particle parameters at a detection temperature of 25 ° C. Each sample is tested in parallel 3 times and the average value is taken. The average particle size of the core-shell structured nanoparticles is measured to be 112 nm, and the particle size distribution index PDI is 0.16.

[0051] Reconstitution performance testing: 0.5 g of the uric acid-lowering composition prepared in Embodiment 1 is taken, 10 mL of purified water at 25 ° C is added, and the mixture is shaken manually at a uniform speed. The time required for the powder to be completely dispersed without visible agglomeration is recorded as 22 s. After reconstitution, the particle size distribution is tested again and compared with the particle size distribution of the suspension before lyophilization, showing a deviation of 6.8%.

[0052] Gastric fluid tolerance testing of bromelain: Simulated gastric fluid at pH 1.2 is used, and the reconstituted sample is incubated in a 37 ° C water bath for 2 h. The Folin-phenol method is used to detect the enzymatic activity of bromelain before and after incubation, and the enzymatic activity retention rate is calculated to be 89.2%.

[0053] Apparent solubility testing of total polyphenols: An excess amount of the uric acid-lowering composition is added to purified water at 25 ° C, and after constant-temperature shaking for 24 h, centrifugation is performed and the supernatant is collected. The Folin-phenol colorimetric method is used to detect the total polyphenol content in the supernatant, and the apparent solubility is measured to be 1.57 mg / mL.

[0054] In a non-limiting commercial embodiment, the lyophilized powder obtained in Embodiment 1 may be provided as NVTIA™ uric acid-loweringDESCRIPTION

[0055] composite raw material. The uric acid-lowering composition prepared in Embodiment 1 has mild active ingredient content and excellent long-term storage stability, and is suitable for daily metabolic care for people with borderline elevated blood uric acid, as well as long-term conditioning during the intercritical period of gout.

[0056] Embodiment 2:

[0057] In Embodiment 2, the total polyphenol content in the tart cherry extract is >= 25%, the 3-n-butylphthalide content in the celery seed extract is >= 1%, the bromelain enzymatic activity is >= 1,200,000 U / g, and both mannitol and trehalose are pharmaceutical-grade excipients.

[0058] Raw-material dissolution and preparation: 50 g of tart cherry extract and 30 g of celery seed extract are weighed and prepared at a mass ratio of 5:3; 2 L of phosphate buffer solution containing 10% ethanol by volume is prepared, the pH value of the buffer solution is adjusted to 6.5, and the buffer solution is placed in a low-temperature water bath and cooled to 6 ° C, with aluminum foil wrapping used throughout the whole process for light protection. The weighed tart cherry extract and celery seed extract are sequentially added into the low-temperature buffer solution, a digital stirrer is started, the stirring speed is controlled at 200 rpm, and stirring is continued for 20 min until the solid raw materials are completely dissolved and the system is uniform, without layering or visible precipitation, thereby obtaining a polyphenol-phthalide raw-material mixed solution, while maintaining the system temperature at 6 ° C throughout the process.

[0059] Low-temperature pre-assembly induction: The polyphenol-phthalide raw-material mixed solution is transferred to a closed jacketed glass reactor, high-purity nitrogen is continuously introduced into the reactor to expel air from the reactor, and a dissolved oxygen meter is used to monitor the oxygen content in the reaction system in real time until the oxygen content decreasesDESCRIPTION

[0060] to 0.08 mg / L, thereby maintaining an inert gas protective atmosphere of slight positive nitrogen pressure. The temperature inside the reactor is controlled and stabilized at 6 ° C by circulating coolant through the jacket. The stirring device is started, the rotation speed is adjusted to 100 rpm, and stirring is continued for 3 h. After stirring is completed, irradiation with a laser pointer shows a clear Tyndall light path, and a polyphenol-phthalide composite-core precursor solution is obtained, while the closed and low-temperature conditions are maintained throughout the process.

[0061] Microfluidization-based configuration locking: 13.3 g of bromelain is weighed and placed in a 6 ° C low-temperature environment, and pre-cooled purified water is used to prepare an aqueous enzyme solution having a mass concentration of 8% for later use. The polyphenol-phthalide composite-core precursor solution is kept at 6 ° C, and the aqueous enzyme solution is slowly added dropwise to the polyphenol-phthalide composite-core precursor solution at a flow rate of 1 mL / min. After the dropwise addition is completed, stirring is started, the rotation speed is controlled at 150 rpm, and pre-stirring is performed for 15 min until uniform mixing is achieved. After mixing, the mixture is conveyed to a low-temperature high-pressure microfluidizer, the feed temperature of the low-temperature high-pressure microfluidizer is controlled at 6 ° C, the working pressure is set at 700 bar, and cyclic treatment is performed 4 times to obtain a core-shell structured nanoparticle suspension.

[0062] Lyophilization solidification and forming: Within 8 min after completion of the microfluidization homogenization treatment, a lyoprotectant is added into the core-shell structured nanoparticle suspension. The lyoprotectant is a mixture of mannitol and trehalose mixed at a mass ratio of 1:1, and the total mass concentration of the lyoprotectant in the suspension is controlled at 4%. The stirring device is started, the rotation speed is adjusted to 80 rpm, andDESCRIPTION

[0063] stirring is continued for 8 min so that the lyoprotectant is completely dissolved and uniformly mixed. After mixing, the mixture is dispensed into a standard freeze-drying tray with a dispensing thickness controlled at 1.5 cm, and is quickly placed in a -45 ° C freeze-dryer cold trap for pre-freezing for 6 h. After pre-freezing is completed, vacuum is started, the vacuum degree is controlled at 15 Pa, and a programmed freeze-drying process is used for drying for 30 h. After drying is completed, the material is taken out and passed through an 80-mesh sieve to obtain the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain in the form of a lyophilized powder.

[0064] Product Testing:

[0065] Nanoparticle particle size testing: 0.5 g of the uric acid-lowering composition prepared in Embodiment 2 is taken, 10 mL of purified water is added for shaking and reconstitution, and a dynamic light scattering particle size analyzer is used to detect particle parameters at a detection temperature of 25 ° C. Each sample is tested in parallel 3 times and the average value is taken. The average particle size of the core-shell structured nanoparticles is measured to be 128 nm, and the particle size distribution index PDI is 0.18.

[0066] Reconstitution performance testing: 0.5 g of the uric acid-lowering composition prepared in Embodiment 2 is taken, 10 mL of purified water at 25 ° C is added, and the mixture is shaken manually at a uniform speed. The time required for the powder to be completely dispersed without visible agglomeration is recorded as 25 s. After reconstitution, the particle size distribution is tested again and compared with the particle size distribution of the suspension before lyophilization, showing a deviation of 7.5%.

[0067] Gastric fluid tolerance testing of bromelain: Simulated gastric fluid at pH 1.2 is used, and the reconstituted sample is incubated in a 37 ° C water bath for 2 h. The Folin-phenol method is used to detect the enzymatic activity ofDESCRIPTION

[0068] bromelain before and after incubation, and the enzymatic activity retention rate is calculated to be 87.6%.

[0069] Apparent solubility testing of total polyphenols: An excess amount of the uric acid-lowering composition is added to purified water at 25 ° C, and after constant-temperature shaking for 24 h, centrifugation is performed and the supernatant is collected. The Folin-phenol colorimetric method is used to detect the total polyphenol content in the supernatant, and the apparent solubility is measured to be 1.82 mg / mL.

[0070] In a non-limiting commercial embodiment, the lyophilized powder obtained in Embodiment 2 may be provided as NVTIA™ intensive uric acid-lowering composite raw material. The uric acid-lowering composition prepared in Embodiment 2 has a higher active ingredient concentration and stronger enzymatic activity, and is suitable for intensive conditioning of people with significantly elevated blood uric acid levels, as well as symptom improvement after an acute gout attack.

[0071] Comparative Example:

[0072] This comparative example adopts a conventional active-component combination and physical mixing preparation process, and all raw materials meet food- grade quality standards.

[0073] 50 g of chicory extract, 30 g of gardenia extract, and 20 g of kudzu root extract are weighed and added into a three-dimensional motion mixer, and are mixed at a rotation speed of 30 rpm for 30 min to obtain preliminarily mixed raw-material powder. The raw-material powder is placed into an ultrafine pulverizer for pulverization, and after pulverization is completed, it is passed through an 80-mesh sieve to obtain a composition powder.

[0074] Product Testing:

[0075] Testing is performed using the same testing methods and conditions as those of Embodiment 1 and Embodiment 2:DESCRIPTION

[0076] Particle size testing: 0.5 g of the composition powder prepared in this comparative example is added to 10 mL of purified water and shaken for dispersion, and a dynamic light scattering particle size analyzer is used for testing. The system has no stable homogeneous nanoparticles, the average particle size is 1427 nm, and the particle size distribution index PDI is 0.78.

[0077] Reconstitution performance testing: 0.5 g of the composition powder prepared in this comparative example is added to 10 mL of purified water at 25 ° C and shaken manually at a uniform speed. The time required for the powder to be completely dispersed without visible agglomeration is recorded as 95 s. After reconstitution, the system contains obvious insoluble precipitate and has no stable nanostructure, so comparison of particle size distribution deviation cannot be performed.

[0078] Apparent solubility testing of total polyphenols: An excess amount of the composition powder prepared in this comparative example is added to purified water at 25 ° C, and after constant-temperature shaking for 24 h, centrifugation is performed and the supernatant is collected. The Folin-phenol colorimetric method is used to detect the total polyphenol content in the supernatant, and the apparent solubility is measured to be 0.19 mg / mL.

[0079] In summary, Embodiment 1 and Embodiment 2, on the one hand, adopt a unique ternary active-component combination of tart cherry, celery seed, and bromelain, thereby achieving multi-target complementary synergy in inhibiting uric acid production, promoting uric acid excretion, and degrading urate crystals; on the other hand, they construct a carrier-free core-shell nanostructure through intermolecular non-covalent bonding, without adding any synthetic polymer carrier, and the delivery system is completely constructed from the active ingredients themselves. Compared with the comparative example, a stable nanoscale structure having uniform particle size and narrow distribution can be formed, the apparent solubility of totalDESCRIPTION

[0080] polyphenols is effectively improved, and the gastric acid tolerance retention rate of the protease is effectively improved. This solves the defects of existing natural uric acid-lowering compositions, namely low absorption efficiency of liposoluble active ingredients and easy oral inactivation of proteases. Meanwhile, by adjusting the ratio of active components and enzymatic activity parameters, products of different performance gradients can be obtained, respectively suitable for differentiated application scenarios of daily metabolic care and intensive conditioning for people with high uric acid, with good process compatibility and scenario adaptability.

[0081] The above descriptions are merely preferred embodiments of the present invention and do not limit the present invention in any form. Although the present invention has been disclosed above through preferred embodiments, such embodiments are not intended to limit the present invention. Any person skilled in the art may make slight changes or modifications to the technical contents disclosed above to form equivalent embodiments without departing from the scope of the technical solution of the present invention. Any simple modifications, equivalent changes, and modifications made to the above embodiments according to the technical essence of the present invention without departing from the contents of the technical solution of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

CLAIMS1. A uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain, characterized in that the composition comprises tart cherry extract, celery seed extract, bromelain, and a lyoprotectant;wherein polyphenolic components in the tart cherry extract and phthalide components in the celery seed extract bind through intermolecular non-covalent bonds to form a composite core;wherein the bromelain is adsorbed onto an outer surface of the composite core through multi-point hydrogen bonds to form a protein coating layer, and together with the composite core forms core-shell structured nanoparticles; wherein the composition is in the form of a lyophilized powder, and after reconstitution, the lyophilized powder is restored to core-shell structured nanoparticles.

2. The uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 1, characterized in that the polyphenolic components in the tart cherry extract are cyani din-3 -glucoside and procyanidin B2, the phthalide component in the celery seed extract is 3-n-butylphthalide, and the intermolecular non-covalent bonds include pi-pi stacking interactions and hydrophobic interactions.

3. The uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 1, characterized in that the molecular surface of the bromelain comprises lysine residues and arginine residues, the multi-point hydrogen bonds are formed by interaction between active groups of the lysine residues and arginine residues and polar groups on the surface of the composite core, and the core-shell structured nanoparticles have a particle size of 80-150 nm.

4. The uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 1, characterized in that the mass ratio of the tart cherry extract to the celery seed extract is 5:1-3, and the mass ratio of the bromelain to the composite core is 1:8-5.CLAIMS5. The uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 1, characterized in that the lyoprotectant consists of mannitol and trehalose, the mass ratio of the mannitol to the trehalose is 1:0.8-1.2, and the total mass percentage of the lyoprotectant in the composition is 3-5%.

6. A preparation method for a uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain, the preparation method being applicable to the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to any one of claims 1-5, characterized in that the preparation method comprises the following specific steps:raw-material dissolution and preparation: adding tart cherry extract and celery seed extract into a buffer solution and mixing at low temperature to obtain a polyphenol-phthalide raw-material mixed solution;low-temperature pre-assembly induction: placing the polyphenol-phthalide raw-material mixed solution in a low-temperature environment protected by an inert gas and stirring to obtain a polyphenol-phthalide composite-core precursor solution;microfluidization-based configuration locking: mixing the polyphenol-phthalide composite-core precursor solution with bromelain at low temperature, and conveying the mixture to a low-temperature high-pressure microfluidizer for treatment to obtain a core-shell structured nanoparticle suspension;lyophilization solidification and forming: mixing the core-shell structured nanoparticle suspension with a lyoprotectant, and subjecting the mixture to pre-freezing and freeze-drying to obtain the composition in the form of a lyophilized powder.

7. The preparation method for the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according toCLAIMSclaim 6, characterized in that, in the raw-material dissolution and preparation step, the temperature for low-temperature mixing is 4-8 ° C, and the whole process is conducted away from light; the buffer solution is a phosphate buffer solution containing 10% ethanol by volume, and the pH of the buffer solution is 6.5; the mass ratio of the tart cherry extract to the celery seed extract is 5:1-3; and the mixture is stirred at a rotation speed of 100-300 rpm for 15-30 min to obtain a uniform polyphenol-phthalide raw-material mixed solution.

8. The preparation method for the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 6, characterized in that, in the low-temperature pre-assembly induction step, the temperature of the low-temperature environment is 4-8 ° C, and the whole process is performed in a closed environment; the inert gas is at least one of nitrogen and argon, and the inert gas is continuously introduced until the oxygen content in the reaction system is <= 0.1 mg / L; continuous stirring is carried out at a rotation speed of 50-150 rpm for 2-4 h, during which the polyphenolic components in the tart cherry extract and the phthalide components in the celery seed extract bind through pi-pi stacking interactions and hydrophobic interactions to form a polyphenol-phthalide composite-core precursor, thereby obtaining a polyphenol-phthalide composite-core precursor solution having the Tyndall effect.

9. The preparation method for the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 6, characterized in that, in the microfluidization-based configuration locking step, the temperature for low-temperature mixing is 4-8 ° C; bromelain is first prepared into an aqueous enzyme solution having a mass concentration of 5-10%, and then the aqueous enzyme solution is slowly added into the polyphenol-phthalide composite-core precursor solution, wherein the mass ratio of the bromelain to solid components in the polyphenol-phthalideCLAIMScomposite-core precursor is 1:8-5; pre-stirring is performed at a rotation speed of 100-200 rpm for 10-20 min, and the mixture is then conveyed to a low-temperature high-pressure microfluidizer and cyclically treated 3-5 times under a pressure of 600-800 bar; during homogenization, lysine residues and arginine residues on the molecular surface of the bromelain are adsorbed onto the outer surface of the polyphenol-phthalide composite core through multi-point hydrogen bonds to form a core-shell structure, thereby obtaining a core-shell structured nanoparticle suspension.

10. The preparation method for the uric acid-lowering composition comprising a tart cherry-celery seed combination and bromelain according to claim 6, characterized in that, in the lyophilization solidification and forming step, the lyoprotectant is added within 5-10 min after completion of the homogenization treatment; the total mass concentration of the lyoprotectant in the core-shell structured nanoparticle suspension is 3-5%; stirring is performed at a rotation speed of 50-100 rpm for 5-10 min, followed by dispensing into a freeze-drying container with a dispensing thickness of 1-2 cm; after dispensing is completed, pre-freezing is conducted at -45 ° C for 6 h, and after completion of pre-freezing, programmed freeze-drying is performed under a vacuum degree of 10-20 Pa for 24-36 h to obtain the composition in the form of a lyophilized powder.

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