A composition for reducing uric acid and a method for preparing the same

Abstract

The application 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 comprises 35-45 parts of a cyclodextrin inclusion compound, 25-35 parts of nano-liposomes, 20-30 parts of a chicory extract-phospholipid complex and 5-8 parts of an antioxidant complex; the preparation method of the cyclodextrin inclusion compound comprises the following steps: step 1, adding beta-cyclodextrin into water, stirring and dissolving, adding pueraria extract, drying after inclusion reaction, and obtaining inclusion compound a; step 2, adding hydroxypropyl-gamma-cyclodextrin into water, stirring, adding mulberry leaf extract, drying after inclusion, and obtaining inclusion compound b; and step 3, mixing the inclusion compound a and the inclusion compound b, and obtaining the product. The uric acid reducing composition can more comprehensively and efficiently reduce blood uric acid level, and has high safety, high stability and high bioavailability. The preparation method is simple, easy to industrialize and beneficial to large-scale industrial production.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a uric acid-lowering composition and its preparation method. Background Technology

[0002] Hyperuricemia is a metabolic disease caused by disordered purine metabolism or reduced uric acid excretion, leading to elevated uric acid levels in the blood. With changes in lifestyle, especially increased intake of high-purine foods and lack of exercise, the incidence of hyperuricemia is rising year by year and showing a trend towards affecting younger people.

[0003] Hyperuricemia not only triggers gouty arthritis, causing joint redness, swelling, pain, and deformity, severely impacting patients' quality of life, but it 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 related 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 received widespread attention in the research and application of uric acid-lowering drugs due to their high safety and fewer side effects. Existing studies have shown that extracts from natural plants such as kudzu root, mulberry leaves, chicory, corn silk, and gardenia contain various active ingredients that have certain uric acid-lowering effects. For example, puerarin in kudzu root, flavonoids in mulberry leaves, and chicoric acid in 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, leading to reduced bioactivity. Simultaneously, some natural extracts have poor water solubility and low bioavailability, hindering their full uric acid-lowering effect. Furthermore, single natural extracts often fail to achieve ideal uric acid-lowering effects, requiring the synergistic effect of multiple active ingredients. Therefore, how to rationally combine multiple active ingredients and improve their stability and bioavailability is a pressing issue in the field of natural product-based uric acid-lowering research.

[0007] Patent CN102309705B discloses a drug for lowering blood uric acid, its preparation method, and its uses. The drug is prepared from the following medicinal materials in the indicated weight ratios: 5-15 parts of *Cremastra appendiculata*, 10-60 parts of *Smilax glabra*, 6-30 parts of *Taxillus chinensis*, 9-45 parts of raw *Astragalus membranaceus*, 10-30 parts of *Salvia miltiorrhiza*, 10-60 parts of *Coix lacryma-jobi*, and 9-20 parts of *Gentiana macrophylla*. The medicinal materials are processed through decoction, concentration, impurity removal, and drying to obtain the effective fraction for lowering blood uric acid. This effective fraction can be conventionally formulated into different clinically acceptable dosage forms. This invention can be used in drugs that lower blood uric acid, lower blood lipids, and protect the liver and kidneys. However, the *Gentiana macrophylla* extract has certain toxicity, and the dosage needs to be controlled according to the actual situation during clinical use. *Cremastra appendiculata* resources are not readily available, and the drug's ability to lower blood uric acid needs further improvement.

[0008] Therefore, developing a uric acid-lowering composition composed of natural active ingredients, with significant uric acid-lowering effects, good stability, high bioavailability, and excellent safety is of great significance and application value. Summary of the Invention

[0009] To address the aforementioned problems, this invention provides a uric acid-lowering composition. It utilizes natural plant ingredients such as kudzu root extract, mulberry leaf extract, corn silk extract, gardenia extract, and chicory extract, which work synergistically to comprehensively and efficiently lower blood uric acid levels. Furthermore, it exhibits high safety, strong stability, and high bioavailability. The preparation method of this invention is simple and easily industrialized; the preparation steps for each component are clear and controllable, facilitating large-scale industrial production.

[0010] The technical solution adopted by the present invention to achieve the above objectives is as follows:

[0011] A uric acid-lowering composition comprising, by weight, 35-45 parts of cyclodextrin inclusion complex, 25-35 parts of nanoliposomes, 20-30 parts of chicory extract-phospholipid complex, and 5-8 parts of antioxidant complex;

[0012] The preparation method of the cyclodextrin inclusion complex includes the following steps:

[0013] Step 1: Add β-cyclodextrin to water at 60-65℃ and stir at 300-400 rpm for 20-30 min. Add kudzu root extract and react at 55-65℃ and stirring speed of 300-400 rpm for 1.5-2.5 h to obtain solution a. Then spray dry solution a to obtain inclusion complex a.

[0014] Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 45-50℃ and stir at 250-350 rpm for 15-25 min. Add mulberry leaf extract and incorporate at 43-48℃ and stirring speed of 250-350 rpm for 1.0-1.5 h to obtain solution b. Spray dry solution b to obtain inclusion complex b.

[0015] Step 3: Mix inclusion complex a and inclusion complex b in a weight ratio of 1:1-1.5 to obtain the final product.

[0016] Preferably, in step 1, the mass ratio of 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.

[0017] Preferably, in step 2, the mass ratio of 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.

[0018] Preferably, the method for preparing the nanoliposomes includes the following steps:

[0019] Step S1: Dissolve phospholipids, cholesterol, corn silk extract, and gardenia extract in a mixed solvent of chloroform and methanol, and rotary evaporate at 40-45°C to form a lipid film.

[0020] Step S2: Add PBS buffer (pH 7.4, containing vitamin E) at 55-58℃, and stir at 200-250 rpm for 30-40 min.

[0021] Step S3, primary homogenization: 3-5 cycles at a pressure of 700-800 bar, then secondary homogenization: 5-7 cycles at a pressure of 800-1000 bar.

[0022] Step S4: Freeze-dry to obtain the final product.

[0023] Preferably, in step S1, the weight ratio of 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-to-volume ratio of corn silk extract to mixed solvent is 0.8g:18-32mL, and the volume ratio of chloroform to methanol in the mixed solvent is 1.8-2.2:1; in step S2, the amount of vitamin E used is 0.3-0.5% of the weight of phospholipids, and the volume of PBS buffer used is 2.5-3 times the volume of the mixed solvent.

[0024] Preferably, the preparation method of the chicory extract-phospholipid complex is as follows:

[0025] Chicory extract, phospholipids, and sodium ascorbate were added to anhydrous ethanol and stirred at a constant temperature of 58-62℃ and a speed of 250-350 rpm for 3.0-3.5 h. The mixture was then rotary evaporated at 45-50℃ to a colloidal state and vacuum dried at 30-40℃ to obtain a block. The block was then pulverized to obtain composite particles.

[0026] Preferably, the weight ratio of chicory extract, phospholipids, and sodium ascorbate is 1:2.5-3.5:0.15-0.25, and the weight-volume ratio of chicory extract to ethanol is 4-5g:100ml.

[0027] Preferably, the method for preparing the antioxidant complex is as follows: sodium ascorbate, vitamin E, and tea polyphenols are mixed evenly, and then the mixture is spray-coated, specifically: the inlet air temperature is 50-55℃, the atomization pressure is 0.9-1.1 bar, the spraying rate is 2-4 g / min, and the material temperature is 35-40℃.

[0028] 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 coating solution is 10g:13-16ml.

[0029] The preparation method of the above-mentioned uric acid-lowering composition is as follows: the cyclodextrin inclusion complex, nanoliposomes, chicory extract-phospholipid complex and antioxidant complex are mixed in parts by weight to obtain the composition.

[0030] The present invention has the following beneficial effects:

[0031] The uric acid-lowering composition of this invention utilizes natural plant ingredients such as kudzu root extract, mulberry leaf extract, corn silk extract, gardenia extract, and chicory extract, ensuring high safety and avoiding the potential toxic side effects of chemical drugs. Furthermore, these natural ingredients each have their own focus in lowering uric acid; 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 components work synergistically to more comprehensively and effectively reduce blood uric acid levels.

[0032] Furthermore, this invention employs multiple processing techniques to enhance performance. The preparation of cyclodextrin inclusion complexes utilizes β-cyclodextrin and hydroxypropyl-γ-cyclodextrin to encapsulate kudzu root extract and mulberry leaf extract. The hollow structure of cyclodextrin effectively improves the stability and water solubility of the active ingredients in the extracts, reducing degradation losses during storage and in vivo transport. Simultaneously, within the cyclodextrin inclusion complex, puerarin inhibits xanthine oxidase, reducing the rate of uric acid synthesis; β-cyclodextrin forms a rigid inclusion cavity, allowing for instantaneous solubilization in the stomach, significantly improving bioavailability; mulberry leaf extract blocks purine nucleoside phosphorylase, reducing uric acid precursor formation; and hydroxypropyl-γ-cyclodextrin, with its larger cavity and better water solubility, protects DNJ from gastric acid degradation and slowly releases mulberry leaf flavonoids in the weakly alkaline intestinal environment. The combination of these two components achieves a "fast stomach, slow intestine" gradient release, synergistically inhibiting xanthine oxidase and reducing uric acid production.

[0033] The preparation of nanoliposomes involves encapsulating corn silk extract and gardenia extract onto liposomes. Utilizing the nanoscale particle size, the targeting and bioavailability of the components are enhanced, allowing them to act more precisely on sites related to uric acid metabolism and improve uric acid-lowering efficiency. Specifically, corn silk flavonoids increase renal uric acid excretion, while geniposide inhibits the reabsorption of uric acid by renal proximal tubular cells and promotes uric acid excretion, thus lowering uric acid levels. Both also synergistically enhance liposome membrane stability with cholesterol. The preparation of the chicory extract-phospholipid complex further improves the liposoluble and absorption properties of chicory extract by binding it with phospholipids. For the antioxidant complex, sodium ascorbate, vitamin E, and tea polyphenols are mixed and spray-coated. The coating material, hydroxypropyl methylcellulose, and its BHT content effectively protect the antioxidant components from external environmental influences, reducing their oxidative decomposition and extending the shelf life of the composition. Simultaneously, these antioxidant components can scavenge free radicals in the body, alleviate oxidative stress damage caused by hyperuricemia, and work synergistically with the uric acid-lowering components to enhance the overall efficacy of the composition. The uric acid-lowering composition of this invention features a cyclodextrin inclusion complex that provides rapid onset of action, and nanoliposomes that offer long-lasting sustained release. The nanoliposomes and the cyclodextrin inclusion complex form a dual pathway of "extrahepatic circulation + intestinal release," significantly improving renal targeting and bioavailability. A phospholipid complex enhances membrane permeability. Simultaneously, the cyclodextrin backbone adsorbs antioxidants, and the lyophilized liposome particles are dispersed within the chicory extract-phospholipid complex. This coating of antioxidant complex provides antioxidant protection, thus prolonging the stability of the composition system.

[0034] Furthermore, 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 Implementation

[0035] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the embodiments of this application. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0036] All raw materials used in the following examples are commercially available products. Phospholipids, specifically soybean phospholipids with an active ingredient content of 99%, are from Xi'an Hongyao Pharmaceutical Excipients Co., Ltd.; corn silk extract, 10:1 specification, is from Lianfeng Biotechnology; gardenia extract, a fine brownish-yellow powder, is from Snowt Biotechnology; vitamin E, a white powder with an active ingredient content of 99%, is from Xi'an Musen Bioengineering Co., Ltd.

[0037] Example 1

[0038] A uric acid-lowering composition comprising, by weight, 40 parts of cyclodextrin inclusion complex, 30 parts of nanoliposomes, 25 parts of chicory extract-phospholipid complex, and 6 parts of antioxidant complex;

[0039] The preparation method of the cyclodextrin inclusion complex includes the following steps:

[0040] Step 1, Inclusion of kudzu root extract: β-cyclodextrin was added to water at 63°C and stirred at 350 rpm for 25 min. Kudzu root extract was added, and the inclusion reaction was carried out at 60°C and 350 rpm for 2 h to obtain solution a. 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. The mass ratio of kudzu root extract to β-cyclodextrin was 1:2, and the amount of water used was 6.5 times the weight of β-cyclodextrin.

[0041] Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 47°C, stir at 300 rpm for 20 min, add mulberry leaf extract, and incorporate at 45°C and 300 rpm for 1.2 h to obtain solution b. Spray dry solution b with 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 complex b. The mass ratio of mulberry leaf extract to hydroxypropyl-γ-cyclodextrin is 1:1.8, and the amount of water used is 11 times the weight of hydroxypropyl-γ-cyclodextrin.

[0042] Step 3: Crush inclusion complex a and inclusion complex b to D90≤50μm (to avoid stratification caused by particle size difference). Mix the crushed inclusion complex a and inclusion complex b at a weight ratio of 1:1.2 in a three-dimensional mixer under nitrogen atmosphere at 24 rpm for 30 min to obtain the final product.

[0043] The method for preparing the nanoliposomes includes the following steps:

[0044] Step S1, Organic phase preparation: Phospholipids, cholesterol, corn silk extract, and gardenia extract are dissolved in a mixed solvent of chloroform and methanol, and rotary evaporated at -0.085 to -0.095 MPa and 42°C to form a lipid film. The weight ratio of corn silk extract, gardenia extract, phospholipids, and cholesterol is 0.8:0.4:4:1, the mass-to-volume ratio of 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.

[0045] Step S2, hydration: Add PBS buffer containing vitamin E at pH 7.4 at 55°C to the above lipid membrane, stir at 220 rpm for 35 min, the amount of vitamin E is 0.4% of the weight of phospholipid, and the volume of PBS buffer is 2.8 times the volume of the mixed solvent;

[0046] Step S3: The reaction solution obtained in step S2 is subjected to primary homogenization: 4 cycles at a pressure of 750 bar, and then secondary homogenization: 6 cycles at a pressure of 900 bar.

[0047] Step S4, freeze drying: Add 6% trehalose to the homogenized reaction solution in step S3, pre-freeze at -48℃ for 4 hours, dry at 0.10 mbar and -38℃ for 24 hours, and then dry at 25℃ for 8 hours to obtain the product.

[0048] The preparation method of the chicory extract-phospholipid complex is as follows:

[0049] Chicory extract, phospholipids, and sodium ascorbate were added to anhydrous ethanol and stirred at 60°C and 300 rpm for 3.2 h. The mixture was then rotary evaporated at -0.075 to -0.085 MPa and 47°C until it reached a colloidal state. Finally, it was vacuum dried at 35°C until the ethanol residue was ≤0.1%, yielding a blocky substance. The dried blocky substance was initially crushed to particles with a diameter ≤2 mm using a jaw crusher, and then further pulverized using a low-temperature ball mill at -25°C (with continuous liquid nitrogen injection), 250 rpm, for 15 min, with a ball-to-material ratio of 8:1 (zirconia balls). The product particle size was D90 ≤20 μm. The weight ratio of chicory extract, phospholipids, and sodium ascorbate was 1:3:0.2, and the weight-to-volume ratio of chicory extract to ethanol was 4.5 g:100 ml.

[0050] The antioxidant complex is prepared as follows: sodium ascorbate, vitamin E, and tea polyphenols are passed through a 90-mesh sieve and mixed evenly. The mixture is then sprayed onto the bottom of a fluidized bed for coating. The coating solution is a 6.5% hydroxypropyl methylcellulose aqueous solution, which also contains 0.05% BHT. The inlet air temperature is 53°C, the atomization pressure is 1.0 bar, the spray rate is 3 g / min, and the material temperature is 38°C. The mass ratio of sodium ascorbate, vitamin E, and tea polyphenols is 45:30:25.

[0051] The preparation method of the above-mentioned uric acid-lowering composition includes the following steps:

[0052] Step a: The cyclodextrin inclusion complex and the antioxidant complex are mixed in a three-dimensional mixer at a speed of 18-22 rpm for 15 min to ensure that the antioxidant is uniformly dispersed in the cyclodextrin skeleton and to enhance the stability of the hydrophilic phase, thus obtaining material 1.

[0053] Step b: Chicory extract-phospholipid complex and 50% nanoliposomes are mixed in a V-type mixer at 12-15 rpm for 10 min. Then the remaining 50% nanoliposomes are added and the mixture is stirred for another 10 min. Nitrogen gas is used for protection during the mixing process to obtain material 2.

[0054] Step c: Place material a and material b in a three-dimensional mixer and mix at 25 rpm for 35 minutes.

[0055] In this preparation method, the nanoliposomes are added in two stages (50%+50%) to avoid the aggregation of phospholipid complex due to overload. The three-dimensional mixer is used for low-speed mixing at 24 rpm to reduce mechanical damage to the nanoparticles.

[0056] Example 2

[0057] A uric acid-lowering composition comprising, by weight, 35 parts of cyclodextrin inclusion complex, 35 parts of nanoliposomes, 30 parts of chicory extract-phospholipid complex, and 8 parts of antioxidant complex;

[0058] The preparation method of the cyclodextrin inclusion complex includes the following steps:

[0059] Step 1, Inclusion of kudzu root extract: β-cyclodextrin was added to water at 60°C and stirred at 400 rpm for 20 min. Kudzu root extract was added, and the inclusion reaction was carried out at 55°C and 400 rpm for 2.5 h to obtain solution a. Solution a was spray-dried at an inlet air temperature of 158°C, an outlet air temperature of 72°C, and an atomization pressure of 0.20 ± 0.02 MPa to obtain inclusion compound a. The mass ratio of kudzu root extract to β-cyclodextrin was 1:1.8, and the amount of water was 7 times the weight of β-cyclodextrin.

[0060] Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 45°C, stir at 350 rpm for 25 min, add mulberry leaf extract, and incorporate at 43°C and 350 rpm for 1.5 h to obtain solution b. Spray dry solution b with an inlet air temperature of 120°C, an outlet air temperature of 60°C, and an atomization pressure of 0.15 ± 0.03 MPa to obtain inclusion complex b. The mass ratio of mulberry leaf extract to hydroxypropyl-γ-cyclodextrin is 1:2.0, and the amount of water used is 10 times the weight of hydroxypropyl-γ-cyclodextrin.

[0061] 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.

[0062] The method for preparing the nanoliposomes includes the following steps:

[0063] Step S1, Organic phase preparation: Phospholipids, cholesterol, corn silk extract, and gardenia extract are dissolved in a mixed solvent of chloroform and methanol, and rotary evaporated at -0.085 to -0.095 MPa and 40°C to form a lipid film. The weight ratio of corn silk extract, gardenia extract, phospholipids, and cholesterol is 1.0:0.3:4.5:0.8, the mass-to-volume ratio of corn silk extract to the mixed solvent is 0.8 g:32 mL, and the volume ratio of chloroform to methanol in the mixed solvent is 1.8:1.

[0064] Step S2, hydration: Add PBS buffer containing vitamin E at pH 7.4 and heated to 55°C to the above lipid membrane, stir at 200 rpm for 40 min, the amount of vitamin E is 0.3% of the weight of phospholipid, and the volume of PBS buffer is 2.5 times the volume of the mixed solvent;

[0065] Steps S3 and S4 are the same as in Example 1.

[0066] 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.

[0067] The method for preparing the antioxidant complex is as follows: sodium ascorbate, vitamin E, and tea polyphenols are each passed through a 100-mesh sieve and then mixed evenly. The mixture is then sprayed onto the bottom of a fluidized bed for coating. The coating solution is a 6% hydroxypropyl methylcellulose aqueous solution, which also contains 0.05% BHT. The inlet air temperature is 55°C, the atomization pressure is 0.9 bar, the spray rate is 4 g / min, and the material temperature is 35°C. The mass ratio of sodium ascorbate, vitamin E, and tea polyphenols is 48:28:28.

[0068] The preparation method of the above-mentioned uric acid-lowering composition is the same as that in Example 1.

[0069] Example 3

[0070] A uric acid-lowering composition comprising, by weight, 45 parts of cyclodextrin inclusion complex, 25 parts of nanoliposomes, 20 parts of chicory extract-phospholipid complex, and 5 parts of antioxidant complex;

[0071] The preparation method of the cyclodextrin inclusion complex includes the following steps:

[0072] Step 1, Inclusion of kudzu root extract: β-cyclodextrin was added to water at 65°C and stirred at 300 rpm for 30 min. Kudzu root extract was added, and the inclusion reaction was carried out at 65°C and 300 rpm for 1.5 h to obtain solution a. 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. The mass ratio of kudzu root extract to β-cyclodextrin was 1:2.2, and the amount of water was 6 times the weight of β-cyclodextrin.

[0073] Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 50°C, stir at 250 rpm for 15 min, add mulberry leaf extract, and incorporate at 48°C and 250 rpm for 1.0 h to obtain solution b. Spray dry solution b with 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 complex b. The mass ratio of mulberry leaf extract to hydroxypropyl-γ-cyclodextrin is 1:1.5, and the amount of water used is 12 times the weight of hydroxypropyl-γ-cyclodextrin.

[0074] 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.

[0075] The method for preparing the nanoliposomes includes the following steps:

[0076] Step S1, Organic phase preparation: Phospholipids, cholesterol, corn silk extract, and gardenia extract are dissolved in a mixed solvent of chloroform and methanol, and rotary evaporated at -0.085 to -0.095 MPa and 45°C to form a lipid film. The weight ratio of corn silk extract, gardenia extract, phospholipids, and cholesterol is 0.7:0.6:3.5:1.2, the mass-to-volume ratio of 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.

[0077] Step S2, hydration: Add PBS buffer containing vitamin E at pH 7.4 and 56°C to the above lipid membrane, stir at 250 rpm for 30 min, the amount of vitamin E is 0.5% of the weight of phospholipid, and the volume of PBS buffer is 3 times the volume of the mixed solvent;

[0078] Steps S3 and S4 are the same as in Example 1.

[0079] 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.

[0080] The antioxidant complex is prepared as follows: sodium ascorbate, vitamin E, and tea polyphenols are passed through a 90-mesh sieve and mixed evenly. The mixture is then sprayed onto the bottom of a fluidized bed for coating. The coating solution is a 7% hydroxypropyl methylcellulose aqueous solution, which also contains 0.05% BHT. The inlet air temperature is 50°C, the atomization pressure is 1.1 bar, the spray rate is 2 g / min, and the material temperature is 40°C. The mass ratio of sodium ascorbate, vitamin E, and tea polyphenols is 42:32:22.

[0081] The preparation method of the above-mentioned uric acid-lowering composition is the same as that in Example 1.

[0082] Example 4

[0083] A uric acid-lowering composition comprises, by parts, 42 parts of cyclodextrin inclusion complex, 28 parts of nanoliposomes, 24 parts of chicory extract-phospholipid complex, 7 parts of antioxidant complex, and the remainder being the same as in Example 1.

[0084] Comparative Example 1

[0085] A uric acid-lowering composition comprises, by weight, 13 parts kudzu root extract, 14 parts mulberry leaf extract, 4 parts corn silk extract, 2 parts gardenia extract, and 6 parts chicory extract. The above materials are directly stirred and mixed to obtain the final product.

[0086] Comparative Example 2

[0087] 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 remainder is the same as in Example 1.

[0088] Comparative Example 3

[0089] A uric acid-lowering composition comprises, by weight, 40 parts of cyclodextrin inclusion complex, 4 parts of corn silk extract, 2 parts of gardenia extract, 25 parts of chicory extract-phospholipid complex, and 6 parts of antioxidant complex; the remainder is the same as in Example 1.

[0090] Comparative Example 4

[0091] A uric acid-lowering composition comprises, by weight, 40 parts of cyclodextrin inclusion complex, 30 parts of nanoliposomes, 25 parts of chicory extract-phospholipid complex, 4.5 parts of sodium ascorbate, and the remainder being the same as in Example 1.

[0092] Safety studies: Acute toxicity of the composition in SD rats after a single administration

[0093] 1. Laboratory animals

[0094] SD rats, grade: SPF; sex: half male and half female; age: 6-7 weeks;

[0095] 2. Grouping and drug administration

[0096] After acclimatization, SD rats were divided into 12 groups of 10 rats each (half male and half female). The rats were administered the uric acid-lowering compositions described in Examples 1-4, at doses of 30 g / kg / day, 40 g / kg / day, and 60 g / kg / day. Each group was administered the corresponding concentration of the uric acid-lowering composition orally via gavage at a volume of 40 mL / kg. The administration was repeated twice within 24 hours, with a 6-hour interval between administrations. Rats were observed for 14 days after administration. The day of administration was defined as day 1 of the experiment.

[0097] 3. Observation indicators

[0098] The mortality of rats in each group was observed during the experiment, and the results are shown in Table 1.

[0099] Table 1 Mortality rate of rats in each group

[0100]

[0101] Table 1 shows that the composition used did not cause acute toxicity in mice at doses of 30, 40, and 60 g / kg / d, and there were no abnormalities in animal behavior, weight, or feeding. These results demonstrate the safety of the composition within the selected dosage range, and also indicate that the raw materials of the uric acid-lowering composition of this invention have high safety.

[0102] Uric acid lowering test:

[0103] Healthy male SD rats (200±20 g) aged 2 months were selected and, after one week of acclimatization, were randomly divided into a blank control group, a model group, a positive drug group, groups of Examples 1-4, and groups of Comparative Examples 1-3, with 10 rats in each group. Except for the blank control group, the other groups were administered potassium oxonate (750 mg / (kg·d)) daily by gavage to establish a rat model of hyperuricemia. Simultaneously, the blank control group and the model group were administered physiological saline by gavage, while the positive drug group was administered allopurinol (100 mg / (kg·d)) by gavage. The combinations of Examples 1-4 and Comparative Examples 1-3 were administered at a dose lower than 40 g / kg / d. Each group was given the corresponding drug or pure water daily for 6 consecutive weeks. After 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.

[0104] Table 2. Results of uric acid reduction test

[0105]

[0106] Note: # indicates p < 0.05 compared to the model group; # indicates p < 0.05 compared to the positive group.

[0107] As shown in Table 2, the detection results of Examples 1-4 of the present invention are all superior to those of Comparative Examples 1-4. Among them, Comparative Example 1 (without cyclodextrin inclusion complex in kudzu root extract and mulberry leaf extract) showed the lowest UA reduction, which is due to the reduced gastric degradation of mulberry leaf extract and decreased absorption of puerarin. Comparative Example 2 (without liposomes) showed ineffective lymphatic targeting and reduced bioavailability of geniposide. Comparative Example 3 (without phospholipid complex) showed slow dissolution of chicoric acid and weakened lipid-lowering synergistic effect. Comparative Example 4 (single antioxidant) showed a significant increase in renal MDA and aggravated oxidative damage. It is evident that the uric acid-lowering composition of the present invention, with the synergistic effect of cyclodextrin inclusion complex, nanoliposomes, and chicor extract-phospholipid complex, can more comprehensively and efficiently reduce blood uric acid levels.

[0108] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0109] Although embodiments of this application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of this application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A uric acid-lowering composition, characterized in that, Composed of the following raw materials in parts by weight: 35-45 parts of cyclodextrin inclusion complex, 25-35 parts of nanoliposomes, 20-30 parts of chicory extract-phospholipid complex, and 5-8 parts of antioxidant complex; The preparation method of the cyclodextrin inclusion complex includes the following steps: Step 1: Add β-cyclodextrin to water at 60-65℃ and stir at 300-400 rpm for 20-30 min. Add kudzu root extract and react at 55-65℃ and stirring speed of 300-400 rpm for 1.5-2.5 h to obtain solution a. Then spray dry solution a to obtain inclusion complex a. Step 2: Add hydroxypropyl-γ-cyclodextrin to water at 45-50℃ and stir at 250-350 rpm for 15-25 min. Add mulberry leaf extract and incorporate at 43-48℃ and stirring speed of 250-350 rpm for 1.0-1.5 h to obtain solution b. Spray dry solution b to obtain inclusion complex b. Step 3: Mix inclusion complex a and inclusion complex b in a weight ratio of 1:1-1.5 to obtain the final product. The method for preparing the nanoliposomes includes the following steps: Step S1: Dissolve phospholipids, cholesterol, corn silk extract, and gardenia extract in a mixed solvent of chloroform and methanol, and rotary evaporate at 40-45°C to form a lipid film. Step S2: Add PBS buffer (pH 7.4, containing vitamin E) at 55-58℃, and stir at 200-250 rpm for 30-40 min. Step S3, primary homogenization: 3-5 cycles at a pressure of 700-800 bar, then secondary homogenization: 5-7 cycles at a pressure of 800-1000 bar. Step S4: Freeze-dry to obtain the product; The preparation method of the chicory extract-phospholipid complex is as follows: Chicory extract, phospholipids, and sodium ascorbate were added to anhydrous ethanol and stirred at a constant temperature of 58-62℃ and a speed of 250-350 rpm for 3.0-3.5 h. The mixture was then rotary evaporated at 45-50℃ to a colloidal state and vacuum dried at 30-40℃ to obtain a block. The block was then pulverized to obtain composite particles.

2. The uric acid-lowering composition according to claim 1, characterized in that, In step 1, the mass ratio of 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 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, In step S1, the weight ratio of 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-to-volume ratio of corn silk extract to mixed solvent is 0.8g:18-32mL, and the volume ratio of chloroform to methanol in the mixed solvent is 1.8-2.2:

1. In step S2, the amount of vitamin E used is 0.3-0.5% of the weight of phospholipids, and the volume of PBS buffer used is 2.5-3 times the volume of the mixed solvent.

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

6. The uric acid-lowering composition according to claim 1, characterized in that, The method for preparing the antioxidant complex is as follows: sodium ascorbate, vitamin E, and tea polyphenols are mixed evenly, and then the mixture is spray-coated, specifically: air inlet temperature 50-55℃, atomization pressure 0.9-1.1 bar, spray rate 2-4 g / min, and material temperature 35-40℃.

7. The uric acid-lowering composition according to claim 6, characterized in that, 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% aqueous solution of hydroxypropyl methylcellulose, and the coating solution also contains 0.05% BHT. The weight-volume ratio of sodium ascorbate to coating solution is 10g:13-16ml.

8. The method for preparing the uric acid-lowering composition according to any one of claims 1-7, characterized in that, The steps are as follows: Step a: The cyclodextrin inclusion complex and the antioxidant complex are mixed in a three-dimensional mixer at a speed of 18-22 rpm for 15 min to ensure that the antioxidant is uniformly dispersed in the cyclodextrin skeleton and to enhance the stability of the hydrophilic phase, thus obtaining material 1. Step b: Chicory extract-phospholipid complex and 50% nanoliposomes are mixed in a V-type mixer at 12-15 rpm for 10 min. Then the remaining 50% nanoliposomes are added and the mixture is stirred for another 10 min. Nitrogen gas is used for protection during the mixing process to obtain material 2. Step c: Place material a and material b in a three-dimensional mixer and mix at 25 rpm for 35 minutes.

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