Composition for reducing uric acid and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a uric acid reducing composition and a preparation method thereof. The uric acid reducing composition is prepared from 35 to 45 parts of a cyclodextrin inclusion compound, 25 to 35 parts of nano-liposome, 20 to 30 parts of a chicory extract-phospholipid compound and 5 to 8 parts of an antioxidant compound, the preparation method of the cyclodextrin inclusion compound comprises the following steps: step 1, adding beta-cyclodextrin into water, stirring and dissolving, adding a radix puerariae extract, and drying after inclusion reaction to obtain an inclusion compound a; 2, hydroxypropyl-gamma-cyclodextrin is added into water, stirring is performed, the mulberry leaf extract is added, drying is performed after inclusion, and an inclusion compound b is obtained; and step 3, mixing the clathrate compound a and the clathrate compound b to obtain the compound. The uric acid reducing composition provided by the invention can be used for more comprehensively and efficiently reducing the blood uric acid level, and is high in safety, strong in stability and high in bioavailability. The preparation method is simple, convenient, easy to industrialize and beneficial to large-scale industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a uric acid-lowering composition and a preparation method thereof. Background Art

[0002] Hyperuricemia is a metabolic disease caused by elevated uric acid levels in the blood due to disrupted purine metabolism or decreased uric acid excretion. With lifestyle changes, particularly increased intake of high-purine diets and lack of exercise, the incidence of hyperuricemia has been increasing year by year, and is becoming younger.

[0003] Hyperuricemia not only triggers gouty arthritis, leading to joint swelling, pain, and deformity, severely impacting patients' quality of life, but also damages the kidneys and cardiovascular system, increasing the risk of kidney stones, chronic renal failure, hypertension, and coronary heart disease. Therefore, effectively lowering blood uric acid levels is crucial for the prevention and treatment of hyperuricemia and its associated complications.

[0004] Currently, commonly used uric acid-lowering drugs in clinical practice mainly include drugs that inhibit uric acid production (such as allopurinol and febuxostat) and drugs that promote uric acid excretion (such as benzbromarone). However, these chemical drugs often have certain side effects during use. For example, allopurinol may cause severe skin allergic reactions, febuxostat may pose cardiovascular risks, and benzbromarone may cause liver damage. In addition, some patients have poor tolerance to these drugs, which limits their widespread clinical application.

[0005] Given the limitations of chemical drugs, natural products have attracted widespread attention for their safety and minimal side effects in the field of uric acid lowering. Studies have shown that extracts from natural plants, such as kudzu root, mulberry leaf, chicory, corn silk, and gardenia, contain a variety of active ingredients with uric acid-lowering properties. For example, puerarin from kudzu root, flavonoids from mulberry leaf, and chicoric acid from chicory have all been reported to regulate purine metabolism and promote uric acid excretion.

[0006] However, the active ingredients in natural extracts are often unstable and easily degraded by environmental factors such as light, temperature, and humidity, resulting in reduced biological activity. Furthermore, some natural extracts have poor water solubility and low bioavailability, which limits their full uric acid-lowering effect. Furthermore, a single natural extract often struggles to achieve the desired uric acid-lowering effect, requiring the synergistic action of multiple active ingredients. The question of how to rationally combine these multiple active ingredients and improve their stability and bioavailability remains a pressing issue in the field of natural product uric acid-lowering research.

[0007] The patent with the publication number CN102309705B discloses a medicine for reducing blood uric acid and a preparation method and use thereof. The medicine is prepared from the following proportion of medicinal materials: 5-15 parts of sedge, 10-60 parts of smilax glabra, 6-30 parts of taxillus, 9-45 parts of astragalus, 10-30 parts of salvia miltiorrhiza, 10-60 parts of semen coicis, and 9-20 parts of gentiana macrophylla. The medicinal materials are subjected to decoction, concentration, impurity removal, and drying processes to obtain an effective part for reducing blood uric acid. The effective part can be made into different dosage forms accepted by clinics according to the conventional method. The medicine can be used in medicines for reducing blood uric acid, reducing blood lipids, and protecting liver and kidney. The gentiana macrophylla extract has certain toxicity, and the dosage needs to be controlled according to the actual situation during clinical use. The sedge resource is not easy to obtain, and the ability of the medicine to reduce blood uric acid needs to be further improved.

[0008] Therefore, it is of great significance and application value to develop a uric acid reducing composition composed of natural active ingredients, which has remarkable uric acid reducing effect, good stability, high bioavailability, and good safety. SUMMARY

[0009] To solve the above problems, the present application provides a uric acid reducing composition. The natural plant ingredients such as pueraria extract, mulberry leaf extract, corn silk extract, gardenia extract, and chicory extract are used to form a synergistic effect, which can more comprehensively and efficiently reduce blood uric acid level, and has high safety, strong stability, and high bioavailability. The preparation method of the present application is simple and easy to industrialize, and the preparation process steps of each component are clear and controllable, which is beneficial to large-scale industrial production.

[0010] The technical scheme adopted by the present application to achieve the above-mentioned purposes is as follows: A uric acid reducing composition, including cyclodextrin inclusion compound 35-45 parts, nano-liposome 25-35 parts, chicory extract-phospholipid complex 20-30 parts, and antioxidant complex 5-8 parts by weight; The preparation method of the cyclodextrin inclusion compound includes the following steps: Step 1, β-cyclodextrin is added to water at 60-65℃, stirred at 300-400rpm for 20-30min, and pueraria extract is added. The inclusion reaction is carried out at 55-65℃ and a stirring speed of 300-400rpm for 1.5-2.5h to obtain solution a. Then, solution a is spray dried to obtain inclusion compound a; Step 2, hydroxypropyl-γ-cyclodextrin is added to water at 45-50℃, stirred at 250-350rpm for 15-25min, and mulberry leaf extract is added. The inclusion reaction is carried out at 43-48℃ and a stirring speed of 250-350rpm for 1.0-1.5h to obtain solution b. Then, solution b is spray dried to obtain inclusion compound b; Step 3, mixing inclusion compound a and inclusion compound b in a weight ratio of 1:1-1.5 to obtain.

[0011] Preferably, in step 1, the mass ratio of the kudzu root extract to β-cyclodextrin is 1:1.8-2.2, and the amount of water used is 6-7 times the weight of β-cyclodextrin.

[0012] Preferably, in step 2, the mass ratio of the mulberry leaf extract to hydroxypropyl-γ-cyclodextrin is 1:1.5-2.0, and the amount of water used is 10-12 times the weight of hydroxypropyl-γ-cyclodextrin.

[0013] Preferably, the method for preparing the nanoliposomes comprises the following steps: Step S1, dissolving phospholipids, cholesterol, corn silk extract, and gardenia extract in a mixed solvent of chloroform and methanol, and rotary evaporating at 40-45° C. to form a lipid film; Step S2, adding PBS buffer with a pH of 7.4 and containing vitamin E at 55-58° C., and stirring at 200-250 rpm for 30-40 minutes; Step S3, primary homogenization: pressure 700-800 bar, cycle 3-5 times, then secondary homogenization: pressure 800-1000 bar, cycle 5-7 times; Step S4, freeze-drying, to obtain.

[0014] Preferably, in step S1, the weight ratio of the corn silk extract, gardenia extract, phospholipids, and cholesterol is 0.7-1.0:0.3-0.6:3.5-4.5:0.8-1.2, the mass volume ratio of the corn silk extract to the mixed solvent is 0.8 g:18-32 mL, and the volume ratio of chloroform and methanol in the mixed solvent is 1.8-2.2:1; in step S2, the amount of vitamin E is 0.3-0.5% of the weight of the phospholipids, and the volume of the PBS buffer is 2.5-3 times the volume of the mixed solvent.

[0015] Preferably, the preparation method of the chicory extract-phospholipid complex is: Add chicory extract, phospholipids and sodium ascorbate to anhydrous ethanol, stir at a constant temperature of 58-62°C and a rotation speed of 250-350 rpm, react for 3.0-3.5 hours, rotary evaporate at 45-50°C to a colloidal state, and vacuum dry at 30-40°C to obtain a block, which is crushed to obtain composite particles.

[0016] Preferably, the weight ratio of the chicory extract, phospholipids and sodium ascorbate is 1:2.5-3.5:0.15-0.25, and the weight-to-volume ratio of the chicory extract to ethanol is 4-5 g:100 ml.

[0017] Preferably, the preparation method of the antioxidant complex is: mixing sodium ascorbate, vitamin E, and tea polyphenols evenly, and then spraying the mixture for coating, specifically: inlet air temperature 50-55°C, atomization pressure 0.9-1.1 bar, spray rate 2-4g / min, and material temperature 35-40°C.

[0018] Preferably, the mass ratio of sodium ascorbate, vitamin E, and tea polyphenols is 42-48:28-32:22-28, the coating solution is a 6-7% hydroxypropyl methylcellulose aqueous solution, the coating solution also contains 0.05% BHT, and the weight-to-volume ratio of sodium ascorbate to the coating solution is 10g:13-16ml.

[0019] The preparation method of the above-mentioned uric acid-lowering composition is specifically as follows: cyclodextrin inclusion compound, nanoliposome, chicory extract-phospholipid complex, and antioxidant complex are mixed uniformly according to parts by weight.

[0020] The present invention has the following beneficial effects: The uric acid-lowering composition of the present invention utilizes natural plant-based ingredients, including kudzu root extract, mulberry leaf extract, corn silk extract, gardenia extract, and chicory extract, all of which are highly safe and avoid the potential toxic side effects of chemical drugs. Furthermore, these natural ingredients each have distinct uric acid-lowering mechanisms. For example, kudzu root extract and mulberry leaf extract can regulate purine metabolism, corn silk extract and gardenia extract can promote uric acid excretion, and chicory extract helps inhibit uric acid production. These ingredients work together to form a synergistic effect, effectively and comprehensively lowering blood uric acid levels.

[0021] Furthermore, the present invention adopts a variety of processing techniques to improve performance. The preparation of cyclodextrin inclusion complex utilizes β-cyclodextrin and hydroxypropyl-γ-cyclodextrin to include Pueraria extract and mulberry leaf extract. With the help of the cavity structure of cyclodextrin, the stability and water solubility of the active ingredients in the extract are effectively improved, and the degradation loss during storage and in vivo transport is reduced. At the same time, in the cyclodextrin inclusion complex, puerarin inhibits xanthine oxidase and reduces the rate of uric acid synthesis. β-cyclodextrin forms a rigid inclusion cavity, which can be instantly solubilized in the stomach, greatly improving its bioavailability. Mulberry leaf extract blocks purine nucleoside phosphorylase and reduces the generation of uric acid precursors. Hydroxypropyl-γ-cyclodextrin has a larger cavity and better water solubility, protecting DNJ from gastric acid damage and slowly releasing mulberry leaf flavonoids in the weakly alkaline environment of the intestine. The combination of the two realizes a "fast stomach-slow intestine" gradient release, synergistically inhibits xanthine oxidase, and reduces uric acid production.

[0022] Nanoliposomes are prepared by encapsulating corn silk extract and gardenia extract within liposomes. Leveraging the nanoparticle size, these ingredients enhance their targeting and bioavailability, allowing them to more precisely target sites involved in uric acid metabolism and improve uric acid-lowering efficacy. Corn silk flavonoids increase renal excretion of uric acid, while gardenia aglycone inhibits uric acid reabsorption by renal proximal tubular cells and promotes uric acid excretion, lowering uric acid levels. These two ingredients synergize with cholesterol to enhance liposome membrane stability. The chicory extract-phospholipid complex is prepared by combining it with phospholipids to further improve the chicory extract's lipid solubility and absorption. For the antioxidant complex, sodium ascorbate, vitamin E, and tea polyphenols are mixed and spray-coated. The coating material, hydroxypropyl methylcellulose, and the BHT it contains, effectively protect the antioxidant components from environmental influences, reducing their oxidative decomposition and extending the shelf life of the composition. Furthermore, these antioxidant components scavenge free radicals in the body, alleviating oxidative stress damage caused by hyperuricemia. They work synergistically with the uric acid-lowering components, enhancing the overall efficacy of the composition. The uric acid-lowering composition of the present invention utilizes a cyclodextrin inclusion complex for rapid onset of action and nanoliposomes for sustained release. The nanoliposomes and cyclodextrin inclusion complex form a dual pathway for "extrahepatic circulation + intestinal release," significantly improving renal targeting and bioavailability. The phospholipid complex enhances membrane permeability. Furthermore, the cyclodextrin backbone adsorbs antioxidants, while the lyophilized liposome particles are dispersed within the chicory extract-phospholipid complex. The coated antioxidant complex provides antioxidant protection, extending the stability of the composition.

[0023] In addition, the preparation method of the present invention is simple and easy to industrialize, and the preparation process steps of each component are clear and controllable, which is conducive to large-scale industrial production. DETAILED DESCRIPTION

[0024] The following will be combined with the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the embodiments described are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments of the present application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0025] All raw materials used in the following examples are commercially available products. Lecithin, soybean lecithin, 99% active ingredient content, Xi'an Hongyao Pharmaceutical Excipients Co., Ltd.; corn silk extract, 10:1, Lianfeng Biotechnology; gardenia extract, fine brown powder, Snot Biotechnology; vitamin E, white powder, 99% active ingredient content, Xi'an Musen Biotechnology Co., Ltd.

[0026] Example 1 A uric acid-lowering composition comprising, by weight, 40 parts of a cyclodextrin inclusion compound, 30 parts of nanoliposomes, 25 parts of a chicory extract-phospholipid complex, and 6 parts of an antioxidant complex; The preparation method of the cyclodextrin inclusion compound comprises the following steps: Step 1, inclusion of kudzu root extract: β-cyclodextrin was added to water at 63°C, stirred at 350 rpm for 25 minutes, kudzu root extract was added, and the inclusion reaction was carried out at 60°C and 350 rpm for 2 hours to obtain solution a, and solution a was spray-dried at an inlet air temperature of 160°C, an outlet air temperature of 75°C, and an atomization pressure of 0.20±0.02 MPa to obtain inclusion compound a, wherein the mass ratio of kudzu root extract to β-cyclodextrin was 1:2, and the amount of water was 6.5 times the weight of β-cyclodextrin; Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 47°C, stir at 300 rpm for 20 min, add mulberry leaf extract, and carry out inclusion complexation at 45°C and 300 rpm for 1.2 h to obtain solution b, and spray dry solution b at an inlet air temperature of 123°C, an outlet air temperature of 63°C, and an atomization pressure of 0.15±0.03 MPa to obtain inclusion compound b, wherein the mass ratio of the mulberry leaf extract to the hydroxypropyl-γ-cyclodextrin is 1:1.8, and the amount of water is 11 times the weight of the hydroxypropyl-γ-cyclodextrin; Step 3: crush inclusion complex a and inclusion complex b to D90 ≤ 50 μm (to avoid stratification due to particle size difference), and mix the crushed inclusion complex a and inclusion complex b in a weight ratio of 1:1.2 in a three-dimensional mixer filled with nitrogen at 24 rpm for 30 minutes to obtain the product.

[0027] The preparation method of the nanoliposome comprises the following steps: Step S1, preparing an organic phase: dissolving phospholipids, cholesterol, corn silk extract, and gardenia extract in a mixed solvent of chloroform and methanol, and rotary evaporating at -0.085 to -0.095 MPa and 42° C. to form a lipid film, wherein the weight ratio of the corn silk extract, gardenia extract, phospholipids, and cholesterol is 0.8:0.4:4:1, the mass volume ratio of the corn silk extract to the mixed solvent is 0.8 g:24 mL, and the volume ratio of chloroform to methanol in the mixed solvent is 2:1; Step S2, hydration: adding 55°C PBS buffer containing vitamin E at pH 7.4 to the lipid film, stirring at 220 rpm for 35 min, wherein the amount of vitamin E is 0.4% of the weight of the phospholipids and the volume of the PBS buffer is 2.8 times the volume of the mixed solvent; Step S3, the reaction solution obtained in step S2 is subjected to primary homogenization: at a pressure of 750 bar, for 4 cycles, and then to secondary homogenization: at a pressure of 900 bar, for 6 cycles; Step S4, freeze-drying: add 6% trehalose to the reaction solution homogenized in step S3, pre-freeze at -48°C for 4 hours, dry at 0.10 mbar and -38°C for 24 hours, and then dry at 25°C for 8 hours to obtain the product.

[0028] The preparation method of the chicory extract-phospholipid complex is as follows: Chicory extract, phospholipids and sodium ascorbate were added to anhydrous ethanol, stirred at a constant temperature of 60°C and a speed of 300 rpm, reacted for 3.2 hours, rotary evaporated at -0.075 to -0.085 MPa and 47°C to a colloidal state, and vacuum dried at 35°C until the ethanol residue was ≤0.1% to obtain a lump. The dried lump was preliminarily crushed to particles with a particle size of ≤2 mm by a jaw crusher, and then pulverized by low-temperature ball milling at a ball milling temperature of -25°C (continuous injection of liquid nitrogen), 250 rpm, 15 minutes, and a ball-to-material ratio of 8:1 (zirconia balls). The product particle size: D90 ≤20 μm; wherein, the weight ratio of chicory extract, phospholipids and sodium ascorbate is 1:3:0.2, and the weight-to-volume ratio of chicory extract to ethanol is 4.5 g:100 ml.

[0029] The preparation method of the antioxidant complex comprises: passing sodium ascorbate, vitamin E, and tea polyphenols through a 90-mesh sieve respectively and mixing them evenly, and then spray-coating the mixture on the bottom of a fluidized bed, wherein the coating solution is a 6.5% hydroxypropyl methylcellulose aqueous solution, and the coating solution also contains 0.05% BHT, with an inlet air temperature of 53°C, an atomization pressure of 1.0 bar, a spray rate of 3g / min, and a material temperature of 38°C; wherein the mass ratio of the sodium ascorbate, vitamin E, and tea polyphenols is 45:30:25.

[0030] The preparation method of the above-mentioned uric acid-lowering composition comprises the following steps: Step a, mixing the cyclodextrin inclusion compound and the antioxidant complex using a three-dimensional mixer at a speed of 18-22 rpm for 15 minutes to uniformly disperse the antioxidant in the cyclodextrin framework and enhance the stability of the hydrophilic phase, thereby obtaining material 1; Step b, chicory extract-phospholipid complex and 50% of nanoliposomes were mixed in a V-type mixer at a speed of 12-15 rpm for 10 minutes, and then the remaining 50% of nanoliposomes were added and stirred for 10 minutes. The mixing process was protected by nitrogen to obtain material 2; Step c: Mix material a and material b in a three-dimensional mixer at a speed of 25 rpm for 35 minutes.

[0031] In this preparation method, nanoliposomes were added in two batches (50% + 50%) to avoid aggregation of phospholipid complexes due to overload, and the three-dimensional mixer was mixed at a low speed of 24 rpm to reduce mechanical damage to the nanoparticles.

[0032] Example 2 A uric acid-lowering composition comprising 35 parts by weight of a cyclodextrin inclusion compound, 35 parts by weight of a nano-liposome, 30 parts by weight of a chicory extract-phospholipid complex, and 8 parts by weight of an antioxidant complex; The preparation method of the cyclodextrin inclusion compound comprises the following steps: Step 1, inclusion of pueraria extract: β-cyclodextrin is added to water at 60°C, stirred at 400 rpm for 20 min, and pueraria extract is added. The inclusion reaction is carried out at 55°C with a stirring speed of 400 rpm for 2.5 h to obtain solution a. Solution a is spray dried at an inlet temperature of 158°C, an outlet temperature of 72°C, and an atomization pressure of 0.20±0.02 MPa to obtain inclusion compound a. The mass ratio of the pueraria extract to β-cyclodextrin is 1:1.8, and the water usage is 7 times the weight of β-cyclodextrin. Step 2, hydroxypropyl-γ-cyclodextrin is added to water at 45°C, stirred at 350 rpm for 25 min, and mulberry leaf extract is added. The inclusion reaction is carried out at 43°C with a stirring speed of 350 rpm for 1.5 h to obtain solution b. Solution b is spray dried at an inlet temperature of 120°C, an outlet temperature of 60°C, and an atomization pressure of 0.15±0.03 MPa to obtain inclusion compound b. The mass ratio of the mulberry leaf extract to hydroxypropyl-γ-cyclodextrin is 1:2.0, and the water usage is 10 times the weight of hydroxypropyl-γ-cyclodextrin. Step 3, the weight ratio of inclusion compound a and inclusion compound b is 1:1, and the rest is the same as in Example 1.

[0033] The preparation method of the nano-liposome comprises the following steps: Step S1, organic phase preparation: phospholipid, cholesterol, corn silk extract, and gardenia extract are dissolved in a mixed solvent of chloroform and methanol. The lipid film is formed by rotary evaporation at -0.085 to -0.095 MPa and 40°C. The weight ratio of the corn silk extract, gardenia extract, phospholipid, and cholesterol is 1.0:0.3:4.5:0.8. The mass-volume ratio of the corn silk extract to the mixed solvent is 0.8g:32mL. In the mixed solvent, the volume ratio of chloroform to methanol is 1.8:1. Step S2, hydration: the above lipid film is added with 55°C PBS buffer solution containing vitamin E with a pH of 7.4, and stirred at 200 rpm for 40 min. The dosage of vitamin E is 0.3% of the weight of phospholipid, and the volume dosage of the PBS buffer solution is 2.5 times the volume of the mixed solvent. Steps S3 and S4 are the same as in Example 1.

[0034] In the preparation method of the chicory extract-phospholipid complex, the weight ratio of chicory extract, phospholipid, and sodium ascorbate is 1:2.5:0.25, and the weight-volume ratio of chicory extract to ethanol is 4g:100ml. The rest is the same as in Example 1.

[0035] The preparation method of the antioxidant complex comprises: passing sodium ascorbate, vitamin E, and tea polyphenols through a 100-mesh sieve respectively and then mixing them uniformly; then spray coating the mixture on the bottom of a fluidized bed; the coating solution is a 6% hydroxypropyl methylcellulose aqueous solution, the coating solution also contains 0.05% BHT, the inlet air temperature is 55°C, the atomization pressure is 0.9 bar, the spray rate is 4g / min, and the material temperature is 35°C; wherein the mass ratio of the sodium ascorbate, vitamin E, and tea polyphenols is 48:28:28.

[0036] The preparation method of the above-mentioned uric acid-lowering composition is the same as that in Example 1.

[0037] Example 3 A uric acid-lowering composition comprising, by weight, 45 parts of a cyclodextrin inclusion compound, 25 parts of nanoliposomes, 20 parts of a chicory extract-phospholipid complex, and 5 parts of an antioxidant complex; The preparation method of the cyclodextrin inclusion compound comprises the following steps: Step 1, inclusion of Pueraria extract: β-cyclodextrin was added to water at 65°C, stirred at 300 rpm for 30 minutes, Pueraria extract was added, and the inclusion reaction was carried out at 65°C and 300 rpm for 1.5 hours to obtain solution a, and solution a was spray-dried at an inlet air temperature of 162°C, an outlet air temperature of 77°C, and an atomization pressure of 0.20±0.02 MPa to obtain inclusion compound a, wherein the mass ratio of Pueraria extract to β-cyclodextrin was 1:2.2, and the amount of water was 6 times the weight of β-cyclodextrin; Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 50°C, stir at 250 rpm for 15 minutes, add mulberry leaf extract, and carry out inclusion complexation at 48°C and 250 rpm for 1.0 hour to obtain solution b, spray-dry solution b at an inlet air temperature of 125°C, an outlet air temperature of 65°C, and an atomization pressure of 0.15±0.03 MPa to obtain inclusion compound b, wherein the mass ratio of the mulberry leaf extract to the hydroxypropyl-γ-cyclodextrin is 1:1.5, and the amount of water is 12 times the weight of the hydroxypropyl-γ-cyclodextrin; In step 3, the weight ratio of inclusion compound a to inclusion compound b is 1:1.5, and the rest is the same as in Example 1.

[0038] The preparation method of the nanoliposome comprises the following steps: Step S1, preparing an organic phase: dissolving phospholipids, cholesterol, corn silk extract, and gardenia extract in a mixed solvent of chloroform and methanol, and rotary evaporating at -0.085 to -0.095 MPa and 45° C. to form a lipid film, wherein the weight ratio of the corn silk extract, gardenia extract, phospholipids, and cholesterol is 0.7:0.6:3.5:1.2, the mass volume ratio of the corn silk extract to the mixed solvent is 0.8 g:18 mL, and the volume ratio of chloroform to methanol in the mixed solvent is 2.2:1; Step S2, hydration: adding 56°C PBS buffer containing vitamin E at pH 7.4 to the lipid film, stirring at 250 rpm for 30 min, wherein the amount of vitamin E is 0.5% of the weight of the phospholipids and the volume of the PBS buffer is 3 times the volume of the mixed solvent; Step S3 and step S4 are the same as in Example 1.

[0039] In the preparation method of the chicory extract-phospholipid complex, the weight ratio of chicory extract, phospholipid, and sodium ascorbate is 1:3.5:0.15, the weight volume ratio of chicory extract to ethanol is 5g:100ml, and the rest is the same as in Example 1.

[0040] The preparation method of the antioxidant complex comprises: passing sodium ascorbate, vitamin E, and tea polyphenols through a 90-mesh sieve respectively and mixing them evenly, and then spraying the mixture on the bottom of a fluidized bed for coating, wherein the coating solution is a 7% hydroxypropyl methylcellulose aqueous solution, and the coating solution also contains 0.05% BHT, with an inlet air temperature of 50°C, an atomization pressure of 1.1 bar, a spray rate of 2 g / min, and a material temperature of 40°C; wherein the mass ratio of sodium ascorbate, vitamin E, and tea polyphenols is 42:32:22.

[0041] The preparation method of the above-mentioned uric acid-lowering composition is the same as that in Example 1.

[0042] Example 4 A uric acid-lowering composition comprises, by parts, 42 parts of cyclodextrin inclusion compound, 28 parts of nanoliposome, 24 parts of chicory extract-phospholipid complex, and 7 parts of antioxidant complex, with the rest being the same as in Example 1.

[0043] Comparative Example 1 A uric acid-lowering composition comprises, by weight, 13 parts of kudzu root extract, 14 parts of mulberry leaf extract, 4 parts of corn silk extract, 2 parts of gardenia extract, and 6 parts of chicory extract. The composition is prepared by directly stirring and mixing the above materials.

[0044] Comparative Example 2 A uric acid-lowering composition comprises, by weight, 13 parts of kudzu root extract, 14 parts of mulberry leaf extract, 30 parts of nanoliposomes, 25 parts of chicory extract-phospholipid complex, and 6 parts of antioxidant complex; the rest of the ingredients are the same as those in Example 1.

[0045] Comparative Example 3 A uric acid-lowering composition comprises, by weight, 40 parts of a cyclodextrin inclusion compound, 4 parts of corn silk extract, 2 parts of a gardenia extract, 25 parts of a chicory extract-phospholipid complex, and 6 parts of an antioxidant complex; the rest of the ingredients are the same as in Example 1.

[0046] Comparative Example 4 A uric acid-lowering composition comprises, by weight, 40 parts of cyclodextrin inclusion compound, 30 parts of nanoliposome, 25 parts of chicory extract-phospholipid complex, and 4.5 parts of sodium ascorbate, with the remaining ingredients being the same as those in Example 1.

[0047] Safety test: acute toxicity reaction of single administration of the composition to SD rats 1. Experimental Animals SD rats, grade: SPF grade; gender: half male and half female; age: 6-7 weeks; 2. Grouping and Dosing After adaptive feeding, SD rats were divided into 12 groups, each with 10 rats, half male and half female, and the uric acid-lowering composition of Examples 1-4 was used, and three dose groups of 30g / kg / d, 40g / kg / d, and 60g / kg / d were used, respectively. Each group of rats was orally gavaged with the corresponding concentration of the uric acid-lowering composition at a dosage volume of 40mL / kg. The administration was repeated twice within 24 hours, with an interval of 6 hours between each administration, and the rats were observed for 14 days after administration. The day of administration was defined as the first day of the experiment.

[0048] 3. Observation indicators The mortality of rats in each group was observed during the experiment. The results are shown in Table 1.

[0049] Table 1 Mortality of rats in each group

[0050] As shown in Table 1, the composition showed no acute toxicity in mice at doses of 30, 40, and 60 g / kg / day, and no abnormalities were observed in the animals' behavior, body weight, or feeding habits. These test results demonstrate the safety of the composition within the selected dosage range and indicate that the ingredients of the uric acid-lowering composition of the present invention have a high safety profile.

[0051] Uric acid lowering test: SPF healthy male SD rats (200±20 g), 2 months old, were selected and, after one week of adaptive feeding, randomly divided into a blank control group, a model group, a positive drug group, Example 1-4 groups, and Comparative Examples 1-3 groups, with 10 rats in each group. Except for the blank control group, all other groups received daily oral administration of potassium oxonate (750 mg / kg / day) to establish a hyperuricemia model. The blank control and model groups received oral administration of normal saline, while the positive drug group received oral administration of allopurinol (100 mg / kg / day). The compositions of Examples 1-4 and Comparative Examples 1-3 were administered daily at a dose of 40 g / kg / day, or purified water, for 6 consecutive weeks. Following the experiment, serum uric acid (UA), xanthine oxidase (XOD) activity in liver tissue, and malondialdehyde (MDA) in kidney tissue were measured. The results are shown in Table 2.

[0052] Table 2. Uric acid lowering test results

[0053] Note: Indicates p<0.05 compared with the model group; # indicates p<0.05 compared with the positive group As shown in Table 2, the test results of Examples 1-4 of the present invention were all superior to those of Comparative Examples 1-4. Among them, Comparative Example 1 (the Pueraria root extract and mulberry leaf extract were not cyclodextrin-included) showed the lowest UA reduction, which was due to the gastric degradation of the mulberry leaf extract and the reduced absorption of puerarin. Comparative Example 2 lacked liposomes, resulting in ineffective lymphatic targeting and reduced bioavailability of geniposide. Comparative Example 3 did not undergo phospholipid complexation, resulting in slow dissolution of chicoric acid and a weakened lipid-lowering synergistic effect. Comparative Example 4 (single antioxidant) showed a significant increase in kidney MDA and exacerbated oxidative damage. Thus, the uric acid-lowering composition of the present invention, with the synergistic cooperation of the cyclodextrin inclusion complex, nanoliposomes, and chicory extract-phospholipid complex, can more comprehensively and efficiently reduce blood uric acid levels.

[0054] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.

[0055] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely exemplary and that changes can be made in detail without departing from the principles and spirit of the application. The scope of the application is therefore defined by the appended claims and their equivalents.

Claims

1. A uric acid-lowering composition, characterized in that: The components include 35-45 parts of cyclodextrin inclusion compound, 25-35 parts of nanoliposome, 20-30 parts of chicory extract-phospholipid complex, and 5-8 parts of antioxidant complex by weight; The preparation method of the cyclodextrin inclusion compound comprises the following steps: Step 1: adding β-cyclodextrin to water at 60-65° C. and stirring at 300-400 rpm for 20-30 minutes, adding Pueraria root extract, and carrying out inclusion reaction at 55-65° C. and stirring at 300-400 rpm for 1.5-2.5 hours to obtain solution a, and then spray drying solution a to obtain inclusion compound a; Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 45-50° C., stir at 250-350 rpm for 15-25 min, add mulberry leaf extract, and carry out inclusion complexation at 43-48° C. and 250-350 rpm for 1.0-1.5 h to obtain solution b, and spray dry solution b to obtain inclusion compound b; Step 3, mixing inclusion compound a and inclusion compound b in a weight ratio of 1:1-1.5 to obtain.

2. The uric acid-lowering composition according to claim 1, characterized in that In step 1, the mass ratio of the kudzu root extract to β-cyclodextrin is 1:1.8-2.2, and the amount of water used is 6-7 times the weight of β-cyclodextrin.

3. The uric acid-lowering composition according to claim 1, characterized in that In step 2, the mass ratio of the mulberry leaf extract to hydroxypropyl-γ-cyclodextrin is 1:1.5-2.0, and the amount of water used is 10-12 times the weight of hydroxypropyl-γ-cyclodextrin.

4. The uric acid-lowering composition according to claim 1, characterized in that The preparation method of the nanoliposome comprises the following steps: Step S1, dissolving phospholipids, cholesterol, corn silk extract, and gardenia extract in a mixed solvent of chloroform and methanol, and rotary evaporating at 40-45° C. to form a lipid film; Step S2, adding PBS buffer with a pH of 7.4 and containing vitamin E at 55-58° C., and stirring at 200-250 rpm for 30-40 minutes; Step S3, primary homogenization: pressure 700-800 bar, cycle 3-5 times, then secondary homogenization: pressure 800-1000 bar, cycle 5-7 times; Step S4, freeze-drying, to obtain.

5. The uric acid-lowering composition according to claim 4, characterized in that In step S1, the weight ratio of the corn silk extract, gardenia extract, phospholipids, and cholesterol is 0.7-1.0:0.3-0.6:3.5-4.5:0.8-1.2, the mass volume ratio of the corn silk extract to the mixed solvent is 0.8 g:18-32 mL, and the volume ratio of chloroform and methanol in the mixed solvent is 1.8-2.2:1; in step S2, the amount of vitamin E is 0.3-0.5% of the weight of the phospholipids, and the volume of the PBS buffer is 2.5-3 times the volume of the mixed solvent.

6. The uric acid-lowering composition according to claim 4, characterized in that The preparation method of the chicory extract-phospholipid complex is as follows: Add chicory extract, phospholipids and sodium ascorbate to anhydrous ethanol, stir at a constant temperature of 58-62°C and a rotation speed of 250-350 rpm, react for 3.0-3.5 hours, rotary evaporate at 45-50°C to a colloidal state, and vacuum dry at 30-40°C to obtain a block, which is crushed to obtain composite particles.

7. The uric acid-lowering composition according to claim 6, characterized in that The weight ratio of the chicory extract, phospholipid and sodium ascorbate is 1:2.5-3.5:0.15-0.25, and the weight volume ratio of the chicory extract to ethanol is 4-5g:100ml.

8. The uric acid-lowering composition according to claim 1, characterized in that The preparation method of the antioxidant complex is: sodium ascorbate, vitamin E, and tea polyphenols are mixed evenly, and then the mixture is sprayed on the coating, specifically: inlet air temperature 50-55°C, atomization pressure 0.9-1.1 bar, spray rate 2-4g / min, and material temperature 35-40°C.

9. The uric acid-lowering composition according to claim 8, wherein The mass ratio of sodium ascorbate, vitamin E, and tea polyphenols is 42-48:28-32:22-28. The coating solution is a 6-7% hydroxypropyl methylcellulose aqueous solution. The coating solution also contains 0.05% BHT. The weight-to-volume ratio of sodium ascorbate to the coating solution is 10g:13-16ml.

10. The method for preparing the uric acid-lowering composition according to any one of claims 1 to 9, wherein: The cyclodextrin inclusion compound, nanoliposome, chicory extract-phospholipid complex and antioxidant complex are mixed evenly according to weight proportions to obtain the product.

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