A uric acid-lowering pharmaceutical composition, its preparation method and use

Abstract

The present invention relates to the field of biomedical technologies, and particularly relates to a drug composition for reducing uric acid, a preparation method thereof, and an application thereof. The drug composition, calculated by weight parts, mainly comprises the following raw materials: 35-45 parts of Poria cocos, 20-25 parts of Alisma orientale, 20-25 parts of Atractylodes lancea, and 20-25 parts of Pueraria lobata. Using this drug composition can reduce the uric acid content in the serum of hyperuricemia mice, increase the uric acid excretion amount of hyperuricemia mice, improve the renal function of hyperuricemia mice, and inhibit kidney inflammation.

Description

Technical Field

[0001] The present invention relates to the field of biological medicine technology, and particularly relates to a uric acid-lowering pharmaceutical composition, a preparation method thereof, and an application thereof. Background Art

[0002] Uric acid is the end product of purine metabolism in the human body, and its excessive accumulation in the body will lead to hyperuricemia. Uric acid (UA), with the chemical name of 2,6,8-trioxypurine and the molecular formula of C5H4N4O3, is mainly synthesized in the liver, intestine, and endothelial cells. The sources of uric acid are divided into endogenous (nucleic acids and purine nucleotides) and exogenous (purines in the diet). There are two ways for the production of nucleotides: the de novo synthesis pathway for newly produced purines and the salvage pathway for reusing purines. This kind of nucleotide is metabolized into xanthine and finally converted into uric acid through the action of xanthine oxidase (XOD). Through this process, about 700 milligrams of uric acid are produced every day. The kidneys play a leading role in uric acid excretion, and 70% of the daily-produced UA is excreted through the kidneys, and the remaining 30% is excreted from the intestine.

[0003] Clinically, hyperuricemia is defined as the serum UA level ≥ 7 mg / dL in men and postmenopausal women, and the serum UA level ≥ 6 mg / dL in premenopausal women. The prevalence of hyperuricemia in men is higher than that in women. Hyperuricemia can cause various diseases, such as gout and urinary tract stones. The increase in UA level is also closely related to diabetes, cardiovascular, and kidney diseases. Hyperuricemia is divided into "UA overproduction type", "UA excretion deficiency type", and "combined type", and their proportions in the incidence of hyperuricemia are 10%, 60%, and 30% respectively.

[0004] Uric acid is mainly excreted into the urine after three stages of reabsorption, secretion, and reabsorption in the proximal tubule of the kidney, and a small part is excreted through the intestine. The glucose transporter 9 (GLUT9) encoded by the SLC2A9 gene mediates the reabsorption of uric acid across the basolateral membrane of renal tubular epithelial cells, and GLUT9 is located on the outer side of the basolateral membrane of the proximal tubule of the kidney. Studies have found that GLUT9 not only participates in the transport of glucose but is also a urate transporter. OAT1 is located on the basolateral membrane of renal tubular epithelial cells and is responsible for transporting uric acid from renal tubular capillaries to the proximal tubule, playing a role in excreting uric acid into the urine in the kidney. ABCG2 is located in the proximal tubule of the kidney and is responsible for transporting uric acid from the proximal tubule to the urine in the kidney.

[0005] The excessive accumulation of uric acid will lead to kidney dysfunction and inflammation. Relevant studies have shown that abnormally increased uric acid content will cause the overexpression of the JAK2 / STAT3 signaling pathway and the activation of the inflammasome NLRP3 in the kidney.

[0006] Traditional Chinese medicine believes that hyperuricemia is closely related to the functions of "the kidney governing water metabolism and the spleen governing transportation and transformation". It is mentioned in "Complete Works of Jingyue" that "Blood is essentially a refined substance, and the kidney governs the five fluids". It is believed that the kidney is mainly involved in maintaining the dynamic balance of nutrient components and metabolites in blood and urine. Once the kidney function is damaged, its function of metabolizing uric acid will surely be affected. "Spiritual Pivot - Determination of Qi" records that "The middle jiao receives qi and extracts essence, transforms and turns it red, and this is called blood". Blood is generated by the spleen and stomach transporting and transforming the essence of water and grains. If a large amount of high-purine foods are ingested in the diet, it will lead to abnormal functions of the spleen and stomach, and thus affect the blood components. "Spiritual Pivot - Basic Spirit" mentions that "The liver stores blood, and blood houses the soul". The liver is the sea of blood, governing dispersion and discharge, and liking smoothness. The regulation of water metabolism by the liver is mainly reflected in regulating the qi movement of the triple energizer, maintaining the smoothness of the triple energizer water passages, and facilitating the flow of water and fluid.

[0007] In the prior art, there is a lack of a pharmaceutical composition that can reduce uric acid and improve kidney damage caused by hyperuricemia. Summary of the Invention

[0008] The present invention provides a pharmaceutical composition for reducing uric acid, its preparation method and application, aiming to solve the defect in the prior art that there is a lack of a pharmaceutical composition that can reduce uric acid and improve kidney damage caused by hyperuricemia, reduce the uric acid content in serum, increase the urine output, and improve kidney damage caused by hyperuricemia.

[0009] The present invention provides a pharmaceutical composition. Calculated by weight, its main raw materials are: 35 - 45 parts of Poria cocos, 20 - 25 parts of Alisma orientale, 20 - 25 parts of Atractylodes lancea, and 20 - 25 parts of Pueraria lobata.

[0010] The present invention clears heat and promotes diuresis, removes stasis and discharges turbidity, and restores the normal flow of the body's water metabolism from the aspects of strengthening the spleen and tonifying the kidney, and promoting diuresis and discharging turbidity, so as to achieve the purpose of improving hyperuricemia. Experimental results prove that this pharmaceutical composition can reduce the uric acid content in the serum of hyperuricemic mice, increase the uric acid excretion of hyperuricemic mice, improve the kidney function of hyperuricemic mice, and inhibit kidney inflammation.

[0011] The raw materials of the pharmaceutical composition of the present invention are simple and can be prepared into dosage forms such as aqueous solutions and pills.

[0012] Preferably, the pharmaceutical composition includes: 39 - 41 parts of Poria cocos, 23 - 25 parts of Alisma orientale, 23 - 25 parts of Atractylodes lancea, and 23 - 25 parts of Pueraria lobata.

[0013] Preferably, the pharmaceutical composition includes: 40 parts of Poria cocos, 25 parts of Alisma orientale, 25 parts of Atractylodes lancea, and 25 parts of Pueraria lobata.

[0014] The main identified components of the aqueous extract of the pharmaceutical composition are: puerarin, daidzin, puerarin glycoside, formononetin glycoside, alisol A, alisol C, alisol F, polysaccharides, etc., and derivatives of these components.

[0015] The present invention also provides a method for preparing the pharmaceutical composition, which extracts the raw materials with water.

[0016] According to the present invention, the method for preparing the pharmaceutical composition includes the following steps:

[0017] 1) Extract the raw materials with water to obtain a decoction, and the mass-volume ratio of the raw materials to water is 1 g: 8-12 ml.

[0018] 2) Separate the decoction obtained in step 1) from the medicinal materials, add water to the medicinal materials and decoct again to obtain a medicinal liquid; the mass ratio of the decoction to water is 1: 6-10.

[0019] 3) Combine the decoction obtained in step 1) and the medicinal liquid obtained in step 2) to obtain a mixed liquid.

[0020] According to the present invention, the method for preparing the pharmaceutical composition further includes evaporating and concentrating the mixed liquid in step 3).

[0021] Preferably, the preparation method includes: taking 40 parts of Poria cocos, 25 parts of Alisma orientale, 25 parts of Atractylodes lancea, 25 parts of Pueraria lobata, adding 10 times the volume of distilled water and decocting for one hour, then pouring out the decoction, adding 8 times the volume of distilled water and decocting for 1 hour, combining the two medicinal liquids, and concentrating with a rotary evaporator. Finally, obtain a decoction and store it at -20 °C for standby.

[0022] The present invention provides the application of the pharmaceutical composition in any one of the following:

[0023] 1) Preparing a drug for reducing uric acid.

[0024] 2) Preparing a drug for improving kidney injury.

[0025] 3) Preparing a drug for improving nephritis.

[0026] The present invention provides the application of the pharmaceutical composition in any one of the following:

[0027] 1) Preparing a drug for treating hyperuricemia.

[0028] 2) Preparing a drug for treating kidney injury caused by hyperuricemia.

[0029] 3) Preparing a drug for treating nephritis caused by hyperuricemia.

[0030] The present invention provides the application of the pharmaceutical composition in preparing a drug for reducing the uric acid content in serum and / or increasing the urinary excretion of uric acid.

[0031] The present invention provides the application of the pharmaceutical composition in preparing a drug for reducing xanthine oxidase.

[0032] Preferably, preparing a drug for reducing the content of xanthine oxidase in serum.

[0033] The present invention provides the use of the said pharmaceutical composition in the preparation of a medicament for improving the content of urate transporter.

[0034] Preferably, it improves the content of urate transporter in the kidney of hyperuricemic patients.

[0035] The present invention provides the use of the said pharmaceutical composition in the preparation of a medicament for inhibiting the JAK2 / STAT3 signaling pathway and / or inhibiting the NLRP3 inflammasome.

[0036] The present invention provides the use of the said pharmaceutical composition in the preparation of a medicament for improving renal inflammation by inhibiting the JAK2 / STAT3 signaling pathway and the NLRP3 inflammasome.

[0037] The present invention provides the use of the said pharmaceutical composition in the preparation of a medicament for improving one or more of the creatinine content, blood urea nitrogen content, urine protein content, and urine protein / urine creatinine ratio.

[0038] The pharmaceutical composition of the present invention has the following pharmacological effects:

[0039] 1. The water decoction of the pharmaceutical composition of the present invention can reduce the uric acid content in the serum of hyperuricemic mice and increase the urinary excretion of uric acid.

[0040] 2. The water decoction of the pharmaceutical composition of the present invention can improve the kidney injury of hyperuricemic mice.

[0041] 3. The water decoction of the pharmaceutical composition of the present invention can reduce the content of xanthine oxidase in the serum of hyperuricemic mice.

[0042] 4. The water decoction of the pharmaceutical composition of the present invention can improve the content of urate transporter in the kidney of hyperuricemic mice.

[0043] 5. The pharmaceutical composition of the present invention is made of Poria cocos, Pueraria lobata, Alisma orientale, and Atractylodes lancea according to the method of "clearing heat and promoting diuresis, removing stasis and discharging turbidity". From the perspective of strengthening the spleen, tonifying the kidney, promoting diuresis and discharging turbidity, it restores the body's water metabolism and circulation, thereby improving hyperuricemia.

[0044] 6. The inventors used immunoblotting to detect the effects of the water decoction of the drug combination on the JAK2 / STAT3 protein pathway and the NLRP3 inflammasome in the kidneys of hyperuricemic mice. Using techniques such as HPLC-MS coupling, a variety of compounds were identified from the water decoction of the drug combination, mainly including terpenoids, flavonoids, polysaccharides such as puerarin, daidzin, puerarin glycoside, formononetin glycoside, alisol A, alisol C, alisol F, polysaccharides, and derivatives of these components. The water decoction of the pharmaceutical composition of the present invention and its main components have the effects of reducing uric acid and resisting kidney inflammation caused by hyperuricemia, and their effects are related to the regulation of the JAK2 / STAT3 pathway and the NLRP3 inflammasome.

[0045] 7. The pharmaceutical composition of the present invention has good application effects in clinical practice, can reduce uric acid, treat hyperuricemia, and treat kidney damage caused by hyperuricemia. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention.

[0047] Figure 1 It is a schematic diagram of the effect of the uric acid-lowering and anti-hyperuricemic nephritis drug combination of the present invention on the serum uric acid content and urine uric acid content in hyperuricemic mice. # indicates statistical significance compared with the normal control group mice (p < 0.05), and * indicates statistical significance compared with the hyperuricemic group mice (p < 0.05). (The same applies to the following figures);

[0048] Among them, A is the serum uric acid content; B is the urine uric acid content.

[0049] Figure 2 It is a schematic diagram of the effect of the uric acid-lowering and anti-hyperuricemic nephritis drug combination of the present invention on the activity of xanthine oxidase (XOD) in the serum of hyperuricemic mice.

[0050] Figure 3 It is a schematic diagram of the effect of the uric acid-lowering and anti-hyperuricemic nephritis drug combination of the present invention on the renal function-related indexes in hyperuricemic mice;

[0051] Among them, A is the kidney weight / body weight; B is the creatinine content in the serum; C is the blood urea nitrogen content in the serum; D is the urine protein content; E is the urine creatinine content; F is the urine protein / creatinine.

[0052] Figure 4 It is a schematic diagram of the effect of the uric acid-lowering and anti-hyperuricemic nephritis drug combination of the present invention on the content of urate transporter in hyperuricemic mice;

[0053] Among them, A is the content of OAT1 protein in the kidneys of mice; B is the content of GLUT9 protein in the kidneys of mice; C is the content of ABCG2 protein in the kidneys of mice.

[0054] Figure 5 It is a schematic diagram of the effect of the uric acid-lowering and anti-hyperuricemic nephritis drug combination of the present invention on the JAK2 / STAT3 signaling pathway in the kidneys of hyperuricemic mice;

[0055] A is the content of interleukin-6 (IL-6) in mouse serum; B is the content of p-JAK2 in mouse kidneys; C is the content of p-STAT3 in mouse kidneys; D is the content of SOCS3 in mouse kidneys.

[0056] Figure 6 It is a schematic diagram of the effect of the drug combination for reducing uric acid and anti-hyperuricemic nephritis of the present invention on the inflammasome NLRP3 in the kidneys of hyperuricemic mice;

[0057] A is the content of interleukin-1-β (IL-1β) in mouse serum; B is the content of inflammasome NLRP3 in mouse kidneys; C is the content of ASC in mouse kidneys; D is the content of cleaved-Casp-1 in mouse kidneys. Detailed implementation manners

[0058] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts fall within the scope of protection of the present invention.

[0059] Please refer to Figures 1 to 6 , the present invention provides a drug composition for reducing uric acid, mainly including the drug combination flavor compatibility and its main active monomer components such as puerarin, daidzin, puerarin glycoside, formononetin glycoside, alisol A, alisol C, alisol F, polysaccharide, etc. and derivatives of these components.

[0060] Example 1

[0061] This example provides a drug composition, and the drug composition includes the following raw materials in parts by weight: 40 parts of Poria cocos, 25 parts of Alisma orientale, 25 parts of Atractylodes lancea, and 25 parts of Pueraria lobata.

[0062] Example 2

[0063] This example provides a drug composition, and the drug composition includes the following raw materials in parts by weight: 35 parts of Poria cocos, 20 parts of Alisma orientale, 20 parts of Atractylodes lancea, and 25 parts of Pueraria lobata.

[0064] Example 3

[0065] This example provides a drug composition, and the drug composition includes the following raw materials in parts by weight: 45 parts of Poria cocos, 20 parts of Alisma orientale, 25 parts of Atractylodes lancea, and 20 parts of Pueraria lobata.

[0066] Example 4

[0067] This example provides a preparation method of a pharmaceutical composition. The preparation method includes: taking 40 parts of Poria cocos, 25 parts of Alisma orientale, 25 parts of Atractylodes lancea, and 25 parts of Pueraria lobata, adding 10 times the volume of distilled water, decocting for 1 hour, pouring out the decoction, then adding 8 times the volume of distilled water and decocting for 1 hour, combining the two decoctions, and concentrating with a rotary evaporator. Finally, the decoction is obtained and stored at -20°C for later use.

[0068] Example 5

[0069] Study the components of the decoction prepared in Research Example 4, and determine the effects of the decoction on the uric acid content in the serum and urine of hyperuricemia mice, xanthine oxidase in the serum, renal function, and the content of urate transporter proteins.

[0070] The research method includes the following steps:

[0071] The obtained decoction is filtered and the effective components are explored by HPLC-MS coupling technology, and other components are determined by liquid chromatography combined with standard substance control or liquid chromatography-mass spectrometry technology.

[0072] An acute hyperuricemia mouse model is constructed by oral gavage of hypoxanthine (300 mg / kg) combined with intraperitoneal injection of potassium oxonate (500 mg / kg). Allopurinol (5 mg / kg) is used as a positive control drug, and the low dose of 7500 mg / kg, medium dose of 15000 mg / kg, and high dose of 30000 mg / kg of the decoction of this drug combination are given by oral gavage.

[0073] Collect the serum, urine, and kidneys of mice, use kits to detect uric acid and related biochemical indexes in the serum and urine, and use Western blot method to determine the expression of JAK2 / STAT3 and inflammasome NLRP3 in the kidney tissues of each group of mice.

[0074] In summary, the results are as follows:

[0075] 1. The compounds analyzed by HPLC-MS liquid mass spectrometry of the decoction are shown in Table 1:

[0076] Table 1

[0077]

[0078]

[0079]

[0080]

[0081] 2. The effects of the decoction of this drug combination on the urine content in the serum and urine of hyperuricemia mice.

[0082] The uric acid contents in the sera and urine of each group of mice are shown in Figure 1 .

[0083] As Figure 1 shown in A of Figure 1 , compared with the normal control group of mice, the uric acid content in the sera of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the positive drug group and each dose group of this drug combination significantly decreased the uric acid content in the sera of hyperuricemic mice (p < 0.05). As

[0084] shown in B of

[0085] , compared with the normal control group of mice, the uric acid content in the urine of the hyperuricemia group of mice was significantly decreased (p < 0.05). Compared with the hyperuricemia group of mice, the uric acid content in the urine of the positive drug group, the low-dose group and the high-dose group of this drug combination was significantly increased (p < 0.05), and there was an increasing trend in the medium-dose group of this drug combination but no significant difference. This indicates that the water decoction of this drug combination can reduce the uric acid content in the blood of hyperuricemic mice and increase the uric acid excretion in urine.

[0084] 3. Effect of the water decoction of this drug combination on the xanthine oxidase content in the sera of hyperuricemic mice.

[0085] The xanthine oxidase contents in the sera of each group of mice are shown in Figure 2 . As Figure 2 shown, compared with the normal control group of mice, the xanthine oxidase content in the sera of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the positive drug group and each dose group of this drug combination significantly decreased the xanthine oxidase content in the sera of hyperuricemic mice (p < 0.05). This indicates that the water decoction of this drug combination can reduce the xanthine oxidase content in the sera of hyperuricemic mice.

[0086] 4. Effect of the water decoction of this drug combination on the renal function of hyperuricemic mice.

[0087] The kidney weight / body weight of each group of mice is shown in Figure 3 A of Figure 3 , as shown in A of

[0088] , compared with the normal control group of mice, the kidney weight / body weight of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, there was a decreasing trend in the kidney weight / body weight of the low-dose group of the water decoction of this drug combination, but no obvious difference, and the kidney weight / body weight of the medium-dose and high-dose groups of the water decoction of this drug combination was significantly decreased (p < 0.05).

[0088] The creatinine contents in the sera of each group of mice are shown in Figure 3 B of Figure 3As shown in Figure B, compared with the normal control group of mice, the creatinine content in the serum of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the serum creatinine content of the low-dose group of the water decoction of the drug combination showed a decreasing trend, but there was no significant difference. The serum creatinine content of the medium- and high-dose groups of the drug combination was significantly decreased (p < 0.05).

[0089] The urea nitrogen content in the serum of each group of mice is shown in Figure 3 Figure C, as Figure 3 shown in Figure C, compared with the normal control group of mice, the urea nitrogen content in the serum of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the urea nitrogen content in the serum of each dose group of the water decoction of the drug combination was significantly decreased (p < 0.05).

[0090] The urine protein, urine creatinine and urine protein / creatinine of each group of mice are shown in Figures D, E and F. As shown in Figure F, compared with the normal control group of mice, the urine protein / urine creatinine of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the urine protein / urine creatinine of each dose group of the water decoction of the drug combination was significantly decreased (p < 0.05). This indicates that the water decoction of the drug combination can significantly improve the renal function of hyperuricemia mice.

[0091] 5. Effect of the water decoction of the drug combination on the content of urate transporters in hyperuricemia mice.

[0092] According to the above indexes, western blot detection was performed on the normal control group, hyperuricemia group, low-dose group and medium-dose group of the drug combination of mice to explore the mechanism of the water decoction of the drug combination in reducing the uric acid content in the serum.

[0093] The OAT1 protein content in the kidneys of each group of mice is shown in Figure 4 Figure A. Compared with the normal control group of mice, the OAT1 content of the hyperuricemia group of mice was significantly decreased (p < 0.05). Compared with the hyperuricemia group of mice, the OAT1 content of the low-dose group of the water decoction of the drug combination showed an increasing trend but no significant difference, and the OAT1 content of the medium-dose group of the drug combination was significantly increased (p < 0.05). The GLUT9 protein content in the kidneys of each group of mice is shown in Figure 4 Figure B. Compared with the normal control group of mice, the GLUT9 content of the hyperuricemia group of mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the GLUT9 content of the low- and medium-dose groups of the water decoction of the drug combination was significantly decreased (p < 0.05). The ABCG2 protein content in the kidneys of each group of mice is shown in Figure 4In C, compared with the normal control group of mice, the content of ABCG2 in hyperuricemia mice decreased significantly (p<0.05). Compared with the hyperuricemia group of mice, there was an upward trend but no significant difference in the low-dose group of the decoction of this drug combination. The content of ABCG2 in the middle-dose group of the drug combination in mice increased significantly (p<0.05). This indicates that the decoction of this drug combination can improve the content of urate transporters in the kidneys of hyperuricemic mice.

[0094] 6. Effects of the decoction of this drug combination on the JAK2 / STAT3 signaling pathway in the kidneys of hyperuricemia mice.

[0095] The content of interleukin 6 (IL-6) in the sera of mice in each group is shown in Figure 5 In A, compared with the normal control group of mice, the content of IL-6 in the sera of hyperuricemia group of mice increased significantly (p<0.05). Compared with the hyperuricemia group of mice, there was a downward trend but no significant difference in the content of IL-6 in the sera of the low-dose and high-dose groups of this drug combination. The content of IL-6 in the sera of the middle-dose group of the drug combination in mice decreased significantly (p<0.05).

[0096] According to the above indicators, western blot detection was performed on mice in the normal control group, hyperuricemia group, low-dose group and middle-dose group of this drug combination to explore the mechanism by which this drug combination improves kidney inflammation.

[0097] The content of p-JAK2 in the kidneys of mice in each group is shown in Figure 5 In B, compared with the normal control group of mice, the content of p-JAK2 in the kidneys of the hyperuricemia mouse group increased significantly (p<0.05). Compared with the hyperuricemia group of mice, the content of p-JAK2 in the kidneys of the low-dose and middle-dose groups of this drug combination in mice decreased significantly (low dose: p<0.05, middle dose: p<0.01). The content of p-STAT3 in the kidneys of mice in each group is shown in Figure 5 In C, compared with the normal control group of mice, the content of p-STAT3 in the kidneys of hyperuricemia mice increased significantly (p<0.01). Compared with the hyperuricemia group of mice, there was a downward trend but no significant difference in the content of p-STAT3 in the kidneys of the low-dose group of this drug combination. The ratio in the middle-dose group of the drug combination decreased significantly (p<0.01). The content of SOCS3 in the kidneys of mice in each group is shown in Figure 5 In D, compared with the normal control group of mice, the content of SOCS3 in the kidneys of hyperuricemia mice increased significantly (p<0.01). Compared with the hyperuricemia group of mice, the content of SOCS3 in the kidneys of the low-dose and middle-dose groups of this drug combination in mice decreased significantly (low dose: p<0.01, middle dose: p<0.05). This indicates that the decoction of this drug combination can inhibit the JAK2 / STAT3 inflammatory signaling pathway in the kidneys of hyperuricemic mice.

[0098] 7. Effects of the water decoction of the drug combination on NLRP3 inflammasome in the kidneys of hyperuricemia mice.

[0099] The content of interleukin-1β (IL-1β) in the sera of mice in each group is shown in Figure 6 Figure A. Compared with the normal control group of mice, the content of IL-1β in the sera of hyperuricemia group mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the content of IL-1β in the sera of the high-dose group of the drug combination had a decreasing trend but no significant difference, and the content of IL-1β in the sera of the low-dose and medium-dose groups of the drug combination was significantly decreased (p < 0.01).

[0100] According to the above indexes, western blot detection was performed on the mice in the normal control group, hyperuricemia group, low-dose and medium-dose groups of the drug combination to explore the mechanism of the drug combination in improving renal inflammation.

[0101] The content of NLRP3 inflammasome in the kidneys of mice in each group is shown in Figure 6 Figure B. Compared with the normal control group of mice, the content of NLRP3 in the kidneys of hyperuricemia group mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the content of NLRP3 in the kidneys of the low-dose group of the drug combination had a decreasing trend but no significant difference, and the content of NLRP3 in the kidneys of the medium-dose group of the drug combination was significantly decreased (p < 0.01). The content of ASC in the kidneys of mice in each group is shown in Figure 6 Figure C. Compared with the normal control group of mice, the content of ASC in the kidneys of hyperuricemia mice was significantly increased. Compared with the hyperuricemia group of mice, the content of ASC in the kidneys of the low-dose and medium-dose groups of the drug combination was significantly decreased (low dose: p < 0.05, medium dose: p < 0.01). The content of cleaved-Casp-1 in the kidneys of mice in each group is shown in Figure 6 Figure D. Compared with the normal control group of mice, the content of cleaved-Casp-1 in the kidneys of hyperuricemia mice was significantly increased (p < 0.05). Compared with the hyperuricemia group of mice, the content of cleaved-Casp-1 in the kidneys of the low-dose and medium-dose groups of the drug combination was significantly decreased (low dose: p < 0.05, medium dose: p < 0.01). This indicates that the water decoction of the drug combination can inhibit the expression of NLRP3 inflammasome in the kidneys of hyperuricemic mice.

[0102] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features. These modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A pharmaceutical composition for treating hyperuricemia, characterized in that, By weight, its raw materials are: 35-45 parts of Poria cocos, 20-25 parts of Alisma orientale, 20-25 parts of Atractylodes lancea, and 20-25 parts of Pueraria lobata.

2. The preparation method of the pharmaceutical composition according to claim 1, characterized in that, Extract the said raw materials with water.

3. The preparation method of the pharmaceutical composition according to claim 2, characterized in that, It includes the following steps: 1) Extract the said raw materials with water to obtain a decoction, and the mass-volume ratio of the raw materials to water is 1 g: 8-12 ml; 2) Separate the decoction obtained in step 1) from the medicinal materials, add water to the medicinal materials and decoct again to obtain a medicinal liquid; the mass ratio of the decoction to water is 1: 6-10; 3) Combine the decoction obtained in step 1) and the medicinal liquid obtained in step 2) to obtain a mixture.

4. The preparation method of the pharmaceutical composition according to claim 3, characterized in that, It also includes evaporating and concentrating the mixture in step 3).

5. Use of the pharmaceutical composition according to claim 1 in the preparation of a medicament for treating hyperuricemia.

6. Use of the pharmaceutical composition according to claim 1 in the preparation of a medicament for treating kidney injury caused by hyperuricemia.

7. Use of the pharmaceutical composition according to claim 1 in the preparation of a medicament for treating nephritis caused by hyperuricemia.

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