A composition for alleviating hyperuricemia and a method for preparing the same

Abstract

The application discloses a composition for relieving hyperuricemia and a preparation method and application thereof. The method comprises the following steps: firstly, extracting active ingredients from a traditional Chinese medicine mixture composed of chrysanthemum, spirea, sophora flower, corn silk and honeysuckle; and then, using PSBMA-glycyrrhetinic acid compound and diphenylalanine dipeptide-beta-cyclodextrin compound in sequence to load and prepare the composition. The composition is loaded with active ingredients through a cage-type interpenetrating structure, has temperature / pH dual response release characteristics, can be released in the intestinal tract, can efficiently inhibit xanthine oxidase, can significantly reduce serum uric acid, urea nitrogen and creatinine levels of hyperuricemia mice, can improve kidney function and can play an anti-inflammatory role. The application can be used for preparing granules, tablets and other medicines, and has a good application prospect in relieving hyperuricemia products.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine, and particularly relates to a composition for relieving hyperuricemia and a preparation method thereof. BACKGROUND

[0002] At present, drugs for treating hyperuricemia include uracil drugs and xanthine oxidase (XOD) inhibitors. Benpropyl and benzbromarone are examples of uracil drugs. However, after treatment with such drugs, excreted urate crystals often accumulate in the urinary tract, causing renal colic and renal insufficiency. Allopurinol and febuxostat are XOD inhibitor drugs, however, it has been reported that they are harmful to the gastrointestinal tract, heart and liver function. The concept of food as medicine has a history of more than 3,000 years in China, and can provide essential nutrients and prevent and treat a variety of diseases.

[0003] At present, there is some progress in the treatment of hyperuricemia with medicinal food, mainly focusing on single traditional Chinese medicine or the mechanism of traditional prescriptions. The research on compositions for relieving hyperuricemia is still shallow, and the active ingredients contained in the compositions will be protonated and precipitated in the low pH environment of the patient's stomach during the digestion stage; the enzymatic action of pepsin will degrade active peptide components; the hydrolysis reaction catalyzed by gastric acid will destroy the ester bond or glycosidic bond contained in some active components (such as flavonoid glycosides), greatly affecting the effect of relieving hyperuricemia. Therefore, new ideas are needed for the treatment of hyperuricemia. SUMMARY

[0004] The technical problem to be solved is that, in view of the above technical problems, the purpose of the present application is to disclose a composition for relieving hyperuricemia and a preparation method and application thereof. The method first extracts active ingredients from a traditional Chinese medicine mixture composed of chrysanthemum, honeysuckle, sophora flower, corn silk and honeysuckle, and then uses PSBMA-glycyrrhetic acid complex and diphenylalanine dipeptide-β-cyclodextrin complex to load and prepare the composition. The composition loads active ingredients through a cage-type interpenetrating structure, has temperature / pH dual response release characteristics, releases in the intestinal tract, can efficiently inhibit xanthine oxidase, significantly reduces the serum uric acid, urea nitrogen and creatinine levels of hyperuricemia mice, improves kidney function and plays an anti-inflammatory role. The present application can be used for preparing granules, tablets and other drugs, and has good application prospect in products for relieving hyperuricemia.

[0005] Technical solution: A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0006] S1. Weigh chrysanthemum, honeysuckle, sophora flower, corn silk and honeysuckle, and mix them with water to prepare a slurry, and then use subcritical extraction technology, rotary evaporation concentration and vacuum freeze drying to obtain an extract freeze-dried powder;

[0007] S2. Dissolve β-cyclodextrin in buffer to obtain a β-cyclodextrin solution with a concentration of 10-15 g / mL, then add 4-8 g of diphenylalanine dipeptide, ultrasonic treatment at room temperature, and stand at 0-4℃ for 8-12 h, centrifugal collection of the precipitate, freeze-drying to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0008] S3. Dissolve poly (sulfobetaine methacrylate) in ultrapure water to obtain a poly (sulfobetaine methacrylate) solution with a concentration of 8-12 g / mL, dissolve glycyrrhetinic acid in ethanol to obtain a glycyrrhetinic acid solution with a mass fraction of 0.5-1.5 wt%, mix the poly (sulfobetaine methacrylate) solution and the glycyrrhetinic acid solution at room temperature under magnetic stirring at 250-500 rpm for 2-5 h, freeze-drying after dialysis to obtain a PSBMA-glycyrrhetinic acid complex;

[0009] S4. Add the extract freeze-dried powder to the PSBMA-glycyrrhetinic acid complex solution and homogenize, then add 1-1.5 wt% of genipin for cross-linking treatment for 30-60 min, centrifugal collection of the precipitate at 10000-12000 rpm for 10-25 min, freeze-drying to obtain extract microspheres; then mix the extract microspheres with the diphenylalanine dipeptide-β-cyclodextrin complex solution, drop the calcium chloride solution with a mass concentration of 1.5-2.5 wt% at a uniform speed, and stir at 200-300 rpm for 10-30 min, freeze-drying after centrifugation to obtain the composition.

[0010] Preferably, the mass ratio of chrysanthemum, honeysuckle, radix astragali, corn silk, and honeysuckle in S1 is (1-3):(1.5-3):(1-2.5):(1-3):(1.5-2.5).

[0011] Preferably, the subcritical extraction conditions in S1 are an extraction temperature of 120-140℃, a solid-liquid ratio of 1g:(15-30)mL, an extraction pressure of 0.5-1.5 MPa, and an extraction time of 20-60 min.

[0012] Preferably, the ultrasonic treatment conditions in S2 are an ultrasonic power of 200-400 W and an ultrasonic time of 3-6 h.

[0013] Preferably, the ratio of the extract freeze-dried powder to the PSBMA-glycyrrhetinic acid complex solution in step S4 is 1g:(1-4 mL), and the concentration of the NAGA-glycyrrhetinic acid complex solution is 7.5-10 g / mL.

[0014] Preferably, the ratio of the extract microspheres and the solution of the diphenylalanine dipeptide-β-cyclodextrin complex in step S4 is 1 g: (1-3.5) mL; and the concentration of the solution of the diphenylalanine dipeptide-β-cyclodextrin complex is 5-10 g / mL.

[0015] The composition prepared by the method of any one of the above.

[0016] Preferably, the composition is used in the preparation of a product for relieving hyperuricemia.

[0017] Preferably, the product is a medicine.

[0018] Preferably, the dosage form of the medicine includes granular preparation, tablet, and liquid preparation.

[0019] Beneficial effects:

[0020] 1. The present application adopts diphenylalanine dipeptide-β-cyclodextrin complex and poly (sulfobetaine methacrylate) -glycyrrhetinic acid complex to form a cage-type interpenetrating structure, load the active ingredients in the composition, and improve the stability of the active ingredients in the body; on the one hand, the hydrophobic cavity of β-cyclodextrin encloses the aromatic structure unit of diphenylalanine dipeptide, and forms a stable complex through the size matching of the cavity and the hydrogen bond of the port hydroxyl group, and the peptide bond unit in the diphenylalanine dipeptide molecule further self-assembles into a fibrous aggregate through intermolecular hydrogen bond, which provides a basic structural unit for network construction as a "cage-type" building unit; on the other hand, the hydrocarbon fragment of the PSBMA backbone combines with the triterpenoid skeleton of glycyrrhetinic acid through hydrophobic interaction, and the quaternary ammonium cation group of its side chain forms electrostatic interaction with the carboxyl anion group of glycyrrhetinic acid, forming a PSBMA-glycyrrhetinic acid complex, which forms a dynamic reversible physical crosslinking network through the multiple interactions of the main chain and the side chain, and the carboxyl group and other polar groups contained in the glycyrrhetinic acid group form hydrogen bonds with the port hydroxyl group of β-CD, becoming a "molecular bridge" connecting the host-guest complex and the polymer network, and additionally interweaving with the diphenylalanine dipeptide-β-cyclodextrin complex through hydrogen bond and hydrophobic interaction, forming an interpenetrating network around the "cage-type" building unit, thereby forming a stable cage-type interpenetrating structure and embedding the composition.

[0021] 2. The prepared composition of the present application releases the efficacy component in the body based on temperature / pH dual response. On the one hand, in the strong acidic environment of the stomach, the β-cyclodextrin terminal hydroxyl group forms a dense hydrogen bond network with the diphenylalanine dipeptide fiber, and the carboxyl group of glycyrrhetic acid is completely protonated to form a strong electrostatic interaction with the sulfonic acid group of PSBMA, ensuring the stability of the efficacy component; on the other hand, when the composition enters the intestine under neutral or alkaline conditions, the carboxyl group of glycyrrhetic acid is deprotonated, and the electrostatic interaction of PSBMA disappears, at the same time, the hydrogen bond between β-CD and diphenylalanine dipeptide is destroyed by the weak alkaline environment of the intestine, and the diphenylalanine dipeptide fibrous aggregate is disassembled, in addition, the temperature-sensitive response of PSBMA triggers the loosening of the hydrogen bond network, improves the porosity of the cage structure, and promotes the release of the efficacy component in the intestine, avoiding stomach irritation and improving intestinal absorption efficiency.

[0022] 3. The prepared composition of the present application can efficiently inhibit the activity of the key enzyme xanthine oxidase (XOD) of hyperuricemia, can significantly reduce the levels of uric acid (UA), urea nitrogen (BUN) and creatinine (CRE) in the serum of hyperuricemia mice, inhibit the activity of XOD in the liver of mice, improve the kidney function of hyperuricemia mice and has anti-inflammatory function. The method of the present application can improve the stability and bioavailability of the efficacy component of food and drug homologous materials, the preparation method is simple and feasible, suitable for industrial production, and has wide market application prospect. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 The in vitro simulated digestion stability of the compositions prepared in Example 5 and Comparative Examples 1-4;

[0024] Figure 2 The serum biochemical indicators and kidney inflammatory cytokine levels of the mice in each group in Example 10, wherein A represents uric acid (UA), B represents urea nitrogen (BUN), C represents creatinine (CRE), D represents interleukin-1β (IL-1β), and E represents tumor necrosis factor-α (TNF-α);

[0025] Figure 3 The liver XOD activity of the mice in each group in Example 10;

[0026] Figure 4 The kidney H&E staining chart of the mice in each group in Example 10;

[0027] wherein Figure 2 and Figure 3 in * indicates p <0.05, *** indicates p <0.001; # indicates p <0.05, ## indicates p <0.01, ### indicates p<0.001; Figure 4 The black arrow indicates glomerular atrophy, the red arrow indicates tubular epithelial cell edema and degeneration, the blue arrow indicates cast, the green arrow indicates dilation and hyperemia, and the yellow arrow indicates lymphocytes. DETAILED DESCRIPTION

[0028] The application will be further described in conjunction with the following examples, which are illustrative of the application but not limitative of the application: Example 1

[0029] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0030] S1. 20 g of chrysanthemum, 20 g of spirea, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, and then subcritical extraction was performed at 120℃ and 1 MPa for 40 min, and the filtrate after filtration was concentrated to about 200 mL at 60℃ using a rotary evaporator, and vacuum freeze-drying was performed to obtain an extract freeze-dried powder;

[0031] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, 6 g of diphenylalanine dipeptide was added, ultrasonic treatment was performed at room temperature and 300 W for 4 h, and then the mixture was placed at 4℃ for 12 h, the precipitate was collected by centrifugation, and freeze-drying was performed to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0032] S3. 10 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL, 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0wt%, 75 mL of the glycyrrhetic acid solution was slowly added to 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed, magnetic stirring was performed at room temperature and 400 rpm for 3 h, dialysis was performed, and then freeze-drying was performed to obtain a PSBMA-glycyrrhetic acid complex;

[0033] S4. 50 g of the extract freeze-dried powder was added to the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, 1.0wt% of genipin was added for crosslinking for 30 min, centrifugation was performed at 10000 rpm for 10 min to obtain a precipitate, and freeze-drying was performed to obtain extract microspheres; 50 g of the extract microspheres was added to 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, a calcium chloride solution with a mass concentration of 2.0wt% was added at a constant speed, stirring was performed at 300 rpm for 30 min, and then freeze-drying was performed after centrifugation to obtain the composition.

[0034] Example 2

[0035] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0036] S1. Take 10 g of chrysanthemum, 30 g of spirea, 10 g of sophora flower, 30 g of corn silk, and 20 g of honeysuckle, and mix them with 2000 mL of water to make a slurry. Extract the slurry under subcritical conditions at 130°C and 1 MPa for 40 min. Concentrate the filtered filtrate to about 200 mL at 60°C using a rotary evaporator. Freeze-dry the extract to obtain an extract freeze-dried powder.

[0037] S2. Dissolve 12 g of β-cyclodextrin in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL. Add 6 g of diphenylalanine dipeptide, and ultrasonically treat it at room temperature and 300 W for 4 h. Let it stand at 4°C for 12 h. Collect the precipitate by centrifugation, and freeze-dry it to obtain a diphenylalanine dipeptide-β-cyclodextrin complex.

[0038] S3. Dissolve 10 g of poly(methacrylic acid sulfobetaine) in 100 mL of ultrapure water to obtain a poly(methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL. Dissolve 1 g of glycyrrhetic acid in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%. Slowly add 75 mL of the glycyrrhetic acid solution to 50 mL of the poly(methacrylic acid sulfobetaine) solution, and mix them at room temperature and 400 rpm for 3 h of magnetic stirring. Freeze-dry the dialyzed solution to obtain a PSBMA-glycyrrhetic acid complex.

[0039] S4. Add 50 g of the extract freeze-dried powder to 100 mL of the PSBMA-glycyrrhetic acid complex solution, and homogenize it at 3500 rpm for 20 min. Add 1.0 wt% of genipin for crosslinking, and let it stand for 30 min. Centrifuge it at 10000 rpm for 10 min to obtain a precipitate. Freeze-dry the precipitate to obtain extract microspheres. Mix 50 g of the extract microspheres with 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution. Slowly drop the mixture into a calcium chloride solution with a mass concentration of 2.0 wt%, and stir it at 300 rpm for 30 min. Freeze-dry the centrifuged mixture to obtain the composition. Example 3

[0040] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0041] S1. Take 20 g of chrysanthemum, 20 g of spirea, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle, and mix them with 2500 mL of water to make a slurry. Extract the slurry under subcritical conditions at 120°C and 1 MPa for 40 min. Concentrate the filtered filtrate to about 200 mL at 60°C using a rotary evaporator. Freeze-dry the extract to obtain an extract freeze-dried powder.

[0042] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, 6 g of diphenylalanine dipeptide was added, ultrasonic treatment was carried out at room temperature and 300 W for 4 h, and standing was carried out at 4℃ for 12 h, the precipitate was collected by centrifugation, and freeze-drying was carried out to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0043] S3. 10 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL, 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%, 75 mL of the glycyrrhetic acid solution was slowly added to 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed, magnetic stirring was carried out at room temperature and 400 rpm for 3 h, freeze-drying was carried out after dialysis to obtain a PSBMA-glycyrrhetic acid complex;

[0044] S4. 50 g of the extract freeze-dried powder was added to the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, 1.0 wt% of genipin was added for crosslinking for 30 min, the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and freeze-drying was carried out to obtain extract microspheres; 50 g of the extract microspheres was added to 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, a calcium chloride solution with a mass concentration of 2.0 wt% was added at a constant speed, stirring was carried out at 300 rpm for 30 min, and freeze-drying was carried out after centrifugation to obtain the composition. Example 4

[0045] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0046] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, subcritical extraction was carried out at 120℃ and 1 MPa for 40 min, the filtrate after filtration was concentrated to about 200 mL at 60℃ using a rotary evaporator, and vacuum freeze-drying was carried out to obtain an extract freeze-dried powder;

[0047] S2. 10 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 10 g / mL, 6 g of diphenylalanine dipeptide was added, ultrasonic treatment was carried out at room temperature and 400 W for 5 h, and standing was carried out at 4℃ for 10 h, the precipitate was collected by centrifugation, and freeze-drying was carried out to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0048] S3. 10 g of poly (sulfobetaine methacrylate) was dissolved in 100 mL of ultrapure water to obtain a poly (sulfobetaine methacrylate) solution with a concentration of 10 g / mL, 1 g of glycyrrhetinic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetinic acid solution with a mass fraction of 1.0 wt%, 75 mL of the glycyrrhetinic acid solution was slowly added to 50 mL of the poly (sulfobetaine methacrylate) solution and mixed at room temperature, 400 rpm, and magnetic stirring for 3 h, and after dialysis, freeze-drying was performed to obtain a PSBMA-glycyrrhetinic acid complex;

[0049] S4. 50 g of the extract freeze-dried powder was added to the PSBMA-glycyrrhetinic acid complex solution and homogenized at 3500 rpm for 20 min, then 1.0 wt% of genipin was added for cross-linking for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and freeze-drying was performed to obtain extract microspheres; 50 g of the extract microspheres was added to 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, a calcium chloride solution with a mass concentration of 2.0 wt% was added at a constant speed, and stirring was performed at 300 rpm for 30 min, and freeze-drying was performed after centrifugation to obtain the composition. Example 5

[0050] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0051] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, subcritical extraction was performed at 120℃ and 1 MPa for 40 min, the filtrate after filtration was concentrated to about 200 mL using a rotary evaporator at 60℃, and vacuum freeze-drying was performed to obtain an extract freeze-dried powder;

[0052] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, 8 g of diphenylalanine dipeptide was added, ultrasonic treatment was performed at room temperature and 300 W for 5 h, and the precipitate was collected by centrifugation after standing at 4℃ for 12 h, and freeze-drying was performed to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0053] S3. 10 g of poly (sulfobetaine methacrylate) was dissolved in 100 mL of ultrapure water to obtain a poly (sulfobetaine methacrylate) solution with a concentration of 10 g / mL, 1 g of glycyrrhetinic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetinic acid solution with a mass fraction of 1.0 wt%, 75 mL of the glycyrrhetinic acid solution was slowly added to 50 mL of the poly (sulfobetaine methacrylate) solution and mixed at room temperature, 500 rpm, and magnetic stirring for 3 h, and after dialysis, freeze-drying was performed to obtain a PSBMA-glycyrrhetinic acid complex;

[0054] S4. 50 g of the extract lyophilized powder was added into the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, then 1.0 wt% genipin was added and cross-linked for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and then freeze-dried to obtain the extract microspheres; 50 g of the extract microspheres was added into 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, and then a 2.0 wt% calcium chloride solution was added at a constant speed, and stirred at 300 rpm for 30 min, and then freeze-dried after centrifugation to obtain the composition. Example 6

[0055] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0056] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, and then subcritical extraction was performed at 120°C and 1 MPa for 40 min, and the filtrate after filtration was concentrated to about 200 mL by a rotary evaporator at 60°C, and then vacuum freeze-dried to obtain an extract lyophilized powder;

[0057] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, and then 6 g of diphenylalanine dipeptide was added, and ultrasonic treatment was performed at room temperature and 300 W for 4 h, and then the mixture was placed at 4°C for 12 h, and then the precipitate was collected by centrifugation, and then freeze-dried to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0058] S3. 12 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 12 g / mL, and 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%, and then 75 mL of the glycyrrhetic acid solution was slowly added into 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed, and then magnetic stirring was performed at room temperature and 400 rpm for 3 h, and then the mixture was dialyzed and freeze-dried to obtain a PSBMA-glycyrrhetic acid complex;

[0059] S4. 50 g of the extract lyophilized powder was added into the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, then 1.0 wt% genipin was added and cross-linked for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and then freeze-dried to obtain the extract microspheres; 50 g of the extract microspheres was added into 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, and then a 2.0 wt% calcium chloride solution was added at a constant speed, and stirred at 300 rpm for 30 min, and then freeze-dried after centrifugation to obtain the composition. Example 7

[0060] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0061] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, and then subcritical extraction was performed at 120℃ and 1 MPa for 40 min, and the filtrate after filtration was concentrated to about 200 mL by a rotary evaporator at 60℃, and then vacuum freeze-drying was performed to obtain an extract lyophilized powder;

[0062] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, and then 6 g of diphenylalanine dipeptide was added, and ultrasonic treatment was performed at room temperature and 400 W for 5 h, and then the solution was placed at 4℃ for 12 h, and then the precipitate was collected by centrifugation, and then freeze-drying was performed to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0063] S3. 10 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL, 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.5 wt%, and then 75 mL of the glycyrrhetic acid solution was slowly added into 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed, and then magnetic stirring was performed at room temperature and 400 rpm for 3 h, and then freeze-drying was performed after dialysis to obtain a PSBMA-glycyrrhetic acid complex;

[0064] S4. 50 g of the extract lyophilized powder was added into the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, then 1.0 wt% genipin was added and cross-linked for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and then freeze-dried to obtain the extract microspheres; 50 g of the extract microspheres was added into 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, and then a 2.0 wt% calcium chloride solution was added at a constant speed, and stirred at 300 rpm for 30 min, and then freeze-dried after centrifugation to obtain the composition. Example 8

[0065] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0066] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, and then subcritical extraction was performed at 120°C and 1 MPa for 40 min, and the filtrate after filtration was concentrated to about 200 mL by a rotary evaporator at 60°C, and then vacuum freeze-dried to obtain an extract lyophilized powder;

[0067] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, and then 6 g of diphenylalanine dipeptide was added, and ultrasonic treatment was performed at room temperature and 300 W for 4 h, and then the mixture was placed at 4°C for 12 h, and then the precipitate was collected by centrifugation, and then freeze-dried to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0068] S3. 10 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL, and 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%, and then 75 mL of the glycyrrhetic acid solution was slowly added into 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed, and then magnetic stirring was performed at room temperature and 400 rpm for 3 h, and then dialysis was performed and freeze-dried to obtain a PSBMA-glycyrrhetic acid complex;

[0069] S4. 50 g of the extract lyophilized powder was added into the PSBMA-glycyrrhetic acid complex solution and homogenized at 4000 rpm for 20 min, then 1.0 wt% genipin was added and cross-linked for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and then freeze-dried to obtain the extract microspheres; 50 g of the extract microspheres was added into 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, and then a 2.0 wt% calcium chloride solution was added at a constant speed, and stirred at 300 rpm for 30 min, and then freeze-dried after centrifugation to obtain the composition. Example 9

[0070] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0071] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, and then subcritical extraction was performed at 120°C and 1 MPa for 40 min, and the filtrate after filtration was concentrated to about 200 mL by a rotary evaporator at 60°C, and then vacuum freeze-drying was performed to obtain an extract lyophilized powder;

[0072] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, and then 6 g of diphenylalanine dipeptide was added, and ultrasonic treatment was performed at room temperature and 300 W for 4 h, and then the solution was placed at 4°C for 12 h, and then the precipitate was collected by centrifugation, and then freeze-drying was performed to obtain a diphenylalanine dipeptide-β-cyclodextrin complex;

[0073] S3. 10 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL, 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%, and then 75 mL of the glycyrrhetic acid solution was slowly added into 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed, and then magnetic stirring was performed at room temperature and 400 rpm for 3 h, and then freeze-drying was performed after dialysis to obtain a PSBMA-glycyrrhetic acid complex;

[0074] S4. 50 g of the extract lyophilized powder was added into the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, then 1.0 wt% genipin was added and cross-linked for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and then freeze-dried to obtain the extract microspheres; 50 g of the extract microspheres was added into 150 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly, and then a calcium chloride solution with a mass concentration of 2.0 wt% was added at a constant speed, and stirred at 300 rpm for 30 min, and then freeze-dried after centrifugation to obtain the composition. Comparative Example 1

[0075] The difference between this comparative example and Example 5 is that only the diphenylalanine dipeptide-β-cyclodextrin complex is used for embedding.

[0076] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0077] S1. 20 g of chrysanthemum, 20 g of honeysuckle, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle were weighed and mixed with 2000 mL of water to prepare a slurry, and then subcritical extraction was performed at 120℃ and 1 MPa for 40 min, and the filtrate after filtration was concentrated to about 200 mL by a rotary evaporator at 60℃, and then vacuum freeze-drying was performed to obtain an extract lyophilized powder;

[0078] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, and then 8 g of diphenylalanine dipeptide was added, and ultrasonic treatment was performed at room temperature and 300 W for 5 h, and then the mixture was placed at 4℃ for 12 h, and then the precipitate was collected by centrifugation, and then freeze-drying was performed to obtain a diphenylalanine dipeptide-β-cyclodextrin complex.

[0079] S3. 50 g of the extract lyophilized powder was added into the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min, then 1.0 wt% genipin was added and cross-linked for 30 min, and the precipitate was obtained by centrifugation at 10000 rpm for 10 min, and then freeze-dried to obtain the composition. Comparative Example 2

[0080] The difference between this comparative example and Example 5 is that only the PSBMA-glycyrrhetic acid complex is used for embedding.

[0081] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0082] S1. Take 20 g of chrysanthemum, 20 g of spirea, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle, and add 2000 mL of water to mix into a slurry. Subcritical extraction is carried out at 120°C and 1 MPa for 40 min. The filtrate after filtration is concentrated to about 200 mL at 60°C using a rotary evaporator, and vacuum freeze-drying is performed to obtain an extract freeze-dried powder.

[0083] S2. 10 g of poly (methacrylic acid sulfobetaine) is dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL. 1 g of glycyrrhetic acid is dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%. 75 mL of the glycyrrhetic acid solution is slowly added to 50 mL of the poly (methacrylic acid sulfobetaine) solution and mixed at room temperature under magnetic stirring at 500 rpm for 3 h. After dialysis, freeze-drying is performed to obtain a PSBMA-glycyrrhetic acid complex.

[0084] S3. 50 g of the extract freeze-dried powder is added to 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly. A calcium chloride solution with a mass concentration of 2.0 wt% is added at a constant speed, and stirring is performed at 300 rpm for 30 min. After centrifugation, freeze-drying is performed to obtain a composition. Comparative Example 3

[0085] The difference between this comparative example and Example 5 is that no diphenylalanine dipeptide-β-cyclodextrin complex and PSBMA-glycyrrhetic acid complex are used for embedding.

[0086] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0087] S1. Take 20 g of chrysanthemum, 20 g of spirea, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle, and add 2000 mL of water to mix into a slurry. Subcritical extraction is carried out at 120°C and 1 MPa for 40 min. The filtrate after filtration is concentrated to about 200 mL at 60°C using a rotary evaporator, and vacuum freeze-drying is performed to obtain an extract freeze-dried powder. Comparative Example 4

[0088] The difference between this comparative example and Example 5 is that subcritical extraction is replaced by hot water extraction.

[0089] A preparation method of a composition for relieving hyperuricemia, comprising the following steps:

[0090] S1. Take 20 g of chrysanthemum, 20 g of spirea, 20 g of sophora flower, 20 g of corn silk, and 20 g of honeysuckle, and add 2000 mL of water to mix into a slurry. Subcritical extraction is carried out at 120°C and 1 MPa for 40 min. The filtrate after filtration is concentrated to about 200 mL at 60°C using a rotary evaporator, and vacuum freeze-drying is performed to obtain an extract freeze-dried powder.

[0091] S2. 12 g of β-cyclodextrin was dissolved in 100 mL of PBS buffer to obtain a β-cyclodextrin solution with a concentration of 12 g / mL, and 8 g of diphenylalanine dipeptide was added. The mixture was ultrasonically treated at room temperature for 5 h at 300 W, and then was left to stand at 4°C for 12 h. The precipitate was collected by centrifugation and freeze-dried to obtain a diphenylalanine dipeptide-β-cyclodextrin complex.

[0092] S3. 10 g of poly (methacrylic acid sulfobetaine) was dissolved in 100 mL of ultrapure water to obtain a poly (methacrylic acid sulfobetaine) solution with a concentration of 10 g / mL. 1 g of glycyrrhetic acid was dissolved in 100 mL of ethanol to obtain a glycyrrhetic acid solution with a mass fraction of 1.0 wt%. 75 mL of the glycyrrhetic acid solution was slowly added to 50 mL of the poly (methacrylic acid sulfobetaine) solution, and the mixture was magnetically stirred at room temperature at 500 rpm for 3 h. After dialysis, the PSBMA-glycyrrhetic acid complex was obtained by freeze-drying.

[0093] S4. 50 g of the extract freeze-dried powder was added to the PSBMA-glycyrrhetic acid complex solution and homogenized at 3500 rpm for 20 min. Then, 1.0 wt% of genipin was added for cross-linking for 30 min. The precipitate was obtained by centrifugation at 10000 rpm for 10 min, and was freeze-dried to obtain extract microspheres. Then, 50 g of the extract microspheres was added to 100 mL of the diphenylalanine dipeptide-β-cyclodextrin complex solution and mixed uniformly. The mixture was dropped into a calcium chloride solution with a mass concentration of 2.0 wt% at a constant speed, and was stirred at 300 rpm for 30 min. The composition was obtained by freeze-drying after centrifugation.

[0094] Performance test

[0095] (1) Particle size

[0096] After the composition was diluted 100 times with water, the average particle size of the sample was analyzed by a laser particle size analyzer.

[0097] (2) Embedding rate

[0098] The embedding rate was determined by the total polyphenol content and the total flavonoid content. 5 g of the sample solution was placed in 100 mL of PBS buffer (pH 7.4) and reacted at 40°C for 1 h. The supernatant was removed by centrifugation. The total polyphenol content was determined by the Folin-phenol method, and the total flavonoid content was determined by the sodium nitrite-aluminum nitrate colorimetric method. The embedding rate was analyzed by the ratio of the total polyphenol content (or the total flavonoid content) of the extract freeze-dried powder obtained by the preparation method S1 to the total polyphenol content (or the total flavonoid content) in the supernatant after treatment.

[0099] (3) Xanthine oxidase inhibition rate

[0100] The composition or allopurinol, XOD solution, PBS was prepared into a reaction mixture, incubated at 25°C for 15 min, then 40 μL of 0.2 mg / mL xanthine solution was added to the system at 35°C to initiate the reaction for 10 min, the composition and allopurinol were dissolved in PBS, the negative control DMSO and the positive control allopurinol were run at the same time, each sample was repeated 3 times, xanthine was catalyzed by XOD to generate uric acid; the xanthine oxidase inhibition rate was analyzed by measuring the content of uric acid at 295 nm using a UV spectrophotometer. The reagent addition of each group is shown in Table 1.

[0101] Table 1 Reagent composition of each group in the test The calculation formula of XOD inhibition rate is as follows:

[0102] Inhibition rate (%) = (A-B-C+D) / A x 100 , wherein A represents the XOD activity without the test solution, B represents the sample without XOD or the test solution, C represents the XOD and the test solution, and D represents the test solution without XOD.

[0103] Table 2 Particle size, embedding rate and XOD inhibition rate of the compositions prepared in Examples 1-9 and Comparative Examples 1-4

[0104] As can be seen from Table 1, the average particle size of the compositions prepared in Examples 1-9 is smaller than that of Comparative Examples 1-4, but the embedding rate and XOD inhibition rate are higher than those of Comparative Examples 1-4, especially the embedding efficiency and XOD inhibition rate of Example 5 are the highest, which shows that the freeze-dried powder of the extract loaded by the diphenylalanine dipeptide-β-cyclodextrin complex and the poly (sulfobetaine methacrylate) -glycyrrhetic acid complex is used in the present application, the host-guest recognition of β-cyclodextrin and diphenylalanine dipeptide forms a "cage type" building unit, and the dynamic reversible physical crosslinking network is formed by the hydrophobic interaction of PSBMA and glycyrrhetic acid, which is connected as a "molecular bridge" by the hydrogen bond between the carboxyl group of glycyrrhetic acid and the hydroxyl group at the end of β-CD, and an interpenetrating network structure is constructed around the "cage type" unit; this multi-level assembly system effectively limits the particle growth through the steric hindrance effect, realizes the controllability of the particle size, and the embedding stability is synergistically enhanced by the multiple hydrogen bonds and hydrophobic interaction, which significantly improves the embedding rate and XOD inhibition rate of the composition.

[0105] (4) In vitro simulated digestion

[0106] The artificial simulated gastric juice (pH 1.5) and the artificial simulated intestinal juice (pH 6.8) were purchased from Tianjin Maiji Biological Technology Co., Ltd.

[0107] ① Simulated gastric digestion: Weigh 3g of sample, dissolve it in 25mL of simulated gastric digestion solution, and shake at 40℃ for 60min. After the reaction is completed, inactivate the enzyme in the sample at 80℃ for 15min, and then centrifuge at 5000r / min for 15min to collect the supernatant, which is the gastric digestion solution. Freeze-dry at -80℃ for storage.

[0108] ② Simulated intestinal digestion: Take gastric digestion fluid, adjust the pH of the solution to 6.8 with 1 mol / L NaHCO3 solution, add 25 mL of simulated intestinal digestion fluid, then add 2 mL of 1 mol / L NaCl solution and 2 mL of 1 mol / L KCl solution respectively, and shake at 37℃ for 120 min. After the reaction is completed, inactivate the enzyme at 80℃ for 15 min, then centrifuge at 5000 r / min for 15 min and collect the supernatant to obtain the intestinal digestion fluid. Freeze-dry at -80℃ for later use.

[0109] ③ The gastrointestinal stability of the compositions described in Example 5 and Comparative Examples 1-4 was analyzed according to the test method for xanthine oxidase inhibition rate described in (3).

[0110] Depend on Figure 1 It can be seen that during the gastric digestion stage, the XOD inhibition rate of Example 5 was significantly lower than that of Comparative Examples 1-4. However, during the intestinal digestion stage, the XOD inhibition rate of Example 5 was significantly higher than that of Comparative Examples 1-4. This indicates that the composition prepared in this invention has a dual temperature / pH response. In the acidic environment simulating the stomach, the diphenylalanine dipeptide-β-cyclodextrin complex can exist stably and protect the internal extract from gastric acid degradation. When it enters the neutral or slightly alkaline environment simulating the intestine, the composition undergoes a structural change and releases the internal extract, thereby exerting its inhibitory effect on xanthine oxidase. This dual-response characteristic enables the composition prepared in this invention to exist stably and be effectively released in the gastrointestinal tract, improving its bioavailability and therapeutic effect.

[0111] Example 10

[0112] The efficacy of the composition prepared in Example 5 in relieving hyperuricemia was verified by an experimental test.

[0113] ① Male KM / 6 mice (18-22g) were randomly divided into 6 groups. The administration methods and dosages for each group are shown in Table 3.

[0114] Table 3. Administration methods and dosages for the six groups.

[0115] HUA, ALL, SL, SM and SH mice were administered PO and HX suspended in 0.5% sodium carboxymethyl cellulose by gavage from 8:00 to 8:30 every day. After 2 hours of treatment, the corresponding group of mice were administered ALL by gavage and homogenized in water. The mixture was centrifuged at 2400 rpm for 10 minutes at 4°C, and the supernatant was retained to determine the level of XOD active protein.

[0116] Histopathological analysis of mouse kidney tissue: Kidney tissue was fixed in 4% paraformaldehyde solution (4% PFA solution) for 48 h, then dehydrated with graded ethanol, cleared, embedded in paraffin, paraffin-embedded (5 μm), stained with hematoxylin and eosin (HE staining), and then observed with a regular optical microscope with a 20x magnification. Images were also acquired using an image acquisition system.

[0117] Depend on Figure 2 As shown in A, B, and C, UA is a key indicator of HUA. Chronic hyperuricemia damages the kidneys, further leading to insufficient renal uric acid excretion. The UA level in the model group (HUA group) mice was significantly higher than that in the control group (NC). p <0.001 indicates that the hyperuricemia model was successfully established; simultaneous administration of the formulation at doses of 100, 150, and 200 mg / kg significantly reduced serum UA levels ( p <0.001 indicates that the composition prepared in Example 5 can significantly alleviate hyperuricemia in mice. Furthermore, compared with the control group (NC), the important indicators of renal dysfunction, CRE and BUN, were significantly elevated in the model group (HUA group) mice. p <0.001); The levels of BUN and CRE in the urine of mice in the model group (HUA group) were significantly reduced ( p <0.01). By Figure 2 As shown in D and E, the levels of TNF-α and IL-1β in the kidney tissue of mice in the HUA group were significantly higher than those in the control group. p <0.001), in addition, the SL group, SM group, SH group and ALL group can significantly reverse the increase of TNF-α and IL-1β levels in the kidney tissue of hyperuricemic mice, indicating that the composition prepared in Example 5 can inhibit the secretion of renal inflammatory cytokines.

[0118] like Figure 3 As shown, the level of XOD in the liver of mice in the HUA group was significantly higher than that in the control group ( p <0.001), the XOD levels in the livers of mice in the ALL, SL, SM, and SH groups were significantly lower than those in the control group, indicating that the composition prepared in Example 5 can inhibit XOD activity in the liver. Figure 4As shown, the kidney tissue of the NC group mice showed normal histological structure of glomerulus and renal medullary tubule without signs of inflammation, but the kidney tissue staining sections of the HUA group mice showed severe morphological lesions, the cytoplasm of renal tubular epithelial cells was loose and edematous, moderate edema degeneration, irregular arrangement, part of the renal tubular epithelial cells were exfoliated in the lumen, part of the renal tubular lumen could see cast, renal interstitial blood vessels were dilated and hyperemic, and inflammatory cells were infiltrated in the renal interstitium; the kidney tissue staining sections of the ALL group, the SL group, the SM group and the SH group mice showed obvious alleviation of the severe morphological lesions of the kidney tissue of the HUA mice, so it was proved that the composition prepared in Example 5 could effectively alleviate the pathological changes of the kidney of the hyperuricemia mice.

[0119] The above merely describes preferred embodiments of the present application, but does not limit the present application in any form. Any person skilled in the art can make many possible changes and modifications to the technical solutions of the present application, or modify equivalent embodiments, without departing from the spirit and technical solutions of the present application, by using the disclosed methods and technical contents. Therefore, any simple modification, equivalent replacement, equivalent change and modification made to the above embodiments according to the technical essence of the present application, without departing from the technical solutions of the present application, still falls within the protection scope of the technical solutions of the present application.

Claims

1. A method for preparing a composition for relieving hyperuricemia, characterized in that, Includes the following steps: S1. Weigh chrysanthemum, prunella vulgaris, sophora japonica, corn silk, and honeysuckle, add water and mix to make a slurry. Use subcritical extraction technology, rotary evaporation concentration, and vacuum freeze-drying to obtain freeze-dried extract powder; the mass ratio of chrysanthemum, prunella vulgaris, sophora japonica, corn silk, and honeysuckle is (1-3):(1.5-3):(1-2.5):(1-3):(1.5-2.5). S2. Dissolve β-cyclodextrin in buffer solution to obtain a β-cyclodextrin solution with a concentration of 10-15 g / mL, then add 4-8 g of diphenylalanine dipeptide, sonicate at room temperature, and let stand at 0-4℃ for 8-12 h. Centrifuge to collect the precipitate, and freeze dry to obtain the diphenylalanine dipeptide-β-cyclodextrin complex. S3. Poly(sulfonated betaine methacrylate) was dissolved in ultrapure water to obtain a poly(sulfonated betaine methacrylate) solution with a concentration of 8-12 g / mL. Glycyrrhetinic acid was dissolved in ethanol to obtain a glycyrrhetinic acid solution with a mass fraction of 0.5-1.5 wt%. The poly(sulfonated betaine methacrylate) solution and the glycyrrhetinic acid solution were mixed and magnetically stirred at room temperature and 250-500 rpm for 2-5 h. After dialyzing, the mixture was freeze-dried to obtain the PSBMA-glycyrrhetinic acid complex. S4. Add the freeze-dried extract powder to the PSBMA-glycyrrhetinic acid complex solution for homogenization, then add 1-1.5wt% genipin for cross-linking treatment for 30-60 min, centrifuge at 10000-12000 rpm for 10-25 min to obtain a precipitate, and freeze-dry to obtain extract microspheres; then add the extract microspheres to the diphenylalanine dipeptide-β-cyclodextrin complex solution and mix evenly, then add the mixture dropwise to a calcium chloride solution with a mass concentration of 1.5-2.5wt% at a uniform rate, stir at 200-300 rpm for 10-30 min, centrifuge, and freeze-dry to obtain the composition.

2. The method for preparing a composition for relieving hyperuricemia according to claim 1, characterized in that: The subcritical extraction conditions in S1 are: extraction temperature 120-140℃, solid-liquid ratio 1g:(15-30)mL, extraction pressure 0.5-1.5MPa, and extraction time 20-60min.

3. The method for preparing a composition for relieving hyperuricemia according to claim 1, characterized in that: The conditions for ultrasonic treatment in S2 are ultrasonic power of 200-400W and ultrasonic time of 3-6h.

4. A method for preparing a composition for relieving hyperuricemia according to claim 1, characterized in that, In step S4, the ratio of the freeze-dried extract powder to the PSBMA-glycyrrhetinic acid complex solution is 1 g: (1-4 mL); the concentration of the NAGA-glycyrrhetinic acid complex solution is 7.5-10 g / mL.

5. A method for preparing a composition for relieving hyperuricemia according to claim 1, characterized in that, In step S4, the ratio of the extract microspheres to the diphenylalanine dipeptide-β-cyclodextrin complex solution is 1 g: (1-3.5) mL; the concentration of the diphenylalanine dipeptide-β-cyclodextrin complex solution is 5-10 g / mL.

6. The composition prepared by the method according to any one of claims 1-5.

7. The use of the composition according to claim 6 in the preparation of a product for relieving hyperuricemia.

8. The application according to claim 7, characterized in that: The product is a medicine.

9. The application according to claim 8, characterized in that: The dosage forms of the drug include granules, tablets, and liquids.

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