Application of ginsenoside in preparation of medicine for improving kidney inflammation and enhancing uric acid excretion

Abstract

The invention relates to the technical field of medicines, in particular to application of ginsenoside in preparation of medicines for improving kidney inflammation and enhancing uric acid excretion. It is found for the first time that ginsenoside Rg2 can reduce systematic and kidney inflammatory reactions by reducing expression levels of inflammatory factors LPS, TNF-alpha and IL-1beta; by down-regulating the expression level of fibrosis marker molecules alpha-SMA and Smad3, the effect of improving HUA-related kidney inflammation and fibrosis is achieved; by up-regulating the expression levels of uric acid transporters OAT1, OAT3 and ABCG2, the active transport and excretion ability of the kidney to uric acid is enhanced. The discovery can generate great influence on research and treatment of relieving hyperuricemia, and has clinical practical value.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly to the application of ginsenosides in the preparation of drugs for improving renal inflammation and enhancing uric acid excretion. Background Art

[0002] Hyperuricemia (HUA) is a metabolic disease, and its typical feature is the disorder of purine metabolism and the abnormal increase in the level of serum uric acid (UA). The formation of uric acid involves adenosine deaminase (ADA), which can catalyze the deamination of adenosine to inosine; nucleoside phosphorylase (PNP), which catalyzes the formation of hypoxanthine; and mainly xanthine oxidase (XOD), which catalyzes the conversion of hypoxanthine to xanthine and then to UA. Therefore, excessive intake of purine and the unrestricted catalytic action of XOD will lead to the excessive production of UA.

[0003] In the state of renal inflammation, the infiltration of inflammatory cells and the change of glomerular basement membrane will affect its filtration function, making the uric acid that should have been filtered unable to effectively enter the primary urine, thus leading to an increase in blood uric acid level. At the same time, the excretion of uric acid in the kidneys and intestines depends on various uric acid transporters, including glucose transporter 9 (GLUT9), urate transporter 1 (URAT1), organic anion transporters 1 (OAT1, OAT3), and ATP-binding cassette transporter (ABCG2).

[0004] As a natural active ingredient, ginsenosides have a wide range of pharmacological effects such as anti-cancer, anti-inflammatory, anti-allergic, antibacterial, treatment of leukemia, antiviral, hypoglycemic, and prevention and treatment of cardiovascular and cerebrovascular diseases, but there is no report on improving renal inflammation and enhancing uric acid excretion.

[0005] The inventors explored the mechanism of action of ginsenosides in the development of HUA, and evaluated the effect of ginsenosides on hyperuricemic rats through indicators such as serum uric acid, creatinine, blood urea nitrogen levels, renal phenotype and index, etc., providing an experimental basis for the application of ginsenosides in the clinical treatment of HUA, and at the same time providing new ideas for the development of traditional Chinese medicine monomers for the treatment and prevention of hyperuricemia. Summary of the Invention

[0006] Aiming at the above technical deficiencies, the inventors took ginsenoside Rg2 as the research object and conducted a bioactivity study on it, and found that it can reduce the levels of serum uric acid, creatinine, and blood urea nitrogen in hyperuricemic rats, reverse the weight loss, reduce the kidney index, and restore the normal appearance of the kidneys, thereby reducing kidney damage and effectively reducing uric acid.

[0007] One of the purposes of the present invention is to provide the application of ginsenoside Rg2 in the preparation of drugs for improving renal inflammation.

[0008] Another object of the present invention is to provide the use of ginsenoside Rg2 in the preparation of a drug for enhancing uric acid excretion.

[0009] The following uses are also within the protection scope of the present invention:

[0010] Further, the mechanism of action of the drug is manifested as down-regulating the expression levels of inflammatory factors LPS, TNF-α, and IL-1β;

[0011] Further, the mechanism of action of the drug is manifested as down-regulating the expression levels of fibrosis marker molecules α-SMA and Smad3;

[0012] Further, the mechanism of action of the drug is manifested as up-regulating the expression levels of uric acid transporters OAT1, OAT3, and ABCG2.

[0013] A third object of the present invention is to provide a drug for improving kidney inflammation and enhancing uric acid excretion, comprising an active ingredient and a pharmaceutically acceptable excipient; the active ingredient is ginsenoside Rg2 or its derivative, or its precursor metabolite, or its pharmaceutically acceptable salt.

[0014] Further, the amount of the active ingredient is 0.001-90 wt% relative to the total weight of the drug; or, 0.02-50 wt%; or 0.1-20%; or 0.005-5%.

[0015] In some specific embodiments, the amount of the active ingredient can be selected as 0.01%, 0.05%, 0.1%, 0.5%, 2%, 5%, 10%, 30%, 40%, 50%, 80% relative to the total weight of the drug;

[0016] Further, the drug for improving kidney inflammation and enhancing uric acid excretion provided by the present invention can be used in combination with other components having anti-inflammatory activity.

[0017] It is well understood by those skilled in the art that the pharmaceutically acceptable carrier is generally recognized for this purpose and serves as an inactive ingredient of the medicament.

[0018] The excipients include solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, antiadhesives, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickeners, clathrates, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, and release retardants.

[0019] Among them, the diluent can be one or more of mannitol, sucrose, lactose, sorbitol, xylitol, polyethylene glycol, propylene glycol, vegetable oil, and mineral oil; the disintegrant can be one or more of croscarmellose sodium, colloidal silicon dioxide, and citric acid; the binder can be one or more of starch paste, ethanol, water, and polyvinylpyrrolidone solution; the preservative can be one or more of ethyl p-hydroxybenzoate, propyl hydroxybenzoate, sorbic acid, potassium sorbate, calcium propionate, sodium dehydroacetate, sodium diacetate, and sodium lactate; the antioxidant can be one or more of ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate, dibutylhydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid, and sodium metabisulfite; the flavoring agent can be one or more of aspartame, sucrose, xylitol, stevioside, sodium cyclamate, sorbitol, cocoa, pure vanilla, vanillin, ethyl vanillin, chocolate, malt, and mint; the suspending agent can be one or more of xanthan gum, polyvinylpyrrolidone, sodium alginate, aluminum stearate, and hydrogenated vegetable oil; the emulsifier can be one or more of alkyl sulfates, soaps, dodecylbenzenesulfonates, lactate esters, sulfosuccinates, monoglyceride sulfonates, phosphate esters, siloxanes, and taurates.

[0020] Among them, the drug exists in the form of tablets, capsules, pills, powders, granules, syrups, solutions, emulsions, injections, sprays, aerosols, and patches.

[0021] Among them, the drug is administered through gastrointestinal and non-gastrointestinal administration routes.

[0022] In particular, the non-gastrointestinal administration route is selected from injection administration, respiratory administration, cutaneous administration, mucosal administration, or cavity administration.

[0023] Among them, the non-gastrointestinal administration preparations are selected from injections, sprays, aerosols, patches, etc.

[0024] In particular, the gastrointestinal administration preparations are selected from tablets, capsules, powders, granules, pills, solutions, emulsions, or syrups, etc.

[0025] The pharmaceutical composition of the present invention contains 0.1 - 90% by weight of the active ingredient.

[0026] The pharmaceutical composition can be prepared according to methods known in the art. For this purpose, if necessary, the active ingredient can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to form a suitable administration form or dosage form for human use.

[0027] In addition, if necessary, colorants, preservatives, fragrances, flavor correctors, sweeteners, or other materials can also be added to the pharmaceutical preparation.

[0028] The dosage of the pharmaceutical composition of the present invention depends on many factors, such as the sex, age, weight and individual response of the patient or animal, the route of administration and the frequency of administration, etc. The above dosage can be administered in a single dose form or divided into several, for example, two, three or four dose forms. The dosage level must be selected according to the specific route of administration, the severity of the condition being treated and the condition and medical history of the patient to be treated, etc. However, the practice in the art is to start with a dosage lower than the level required to obtain the desired therapeutic effect and gradually increase the dosage until the desired effect is obtained.

[0029] It should be recognized that the total daily dosage of the pharmaceutical composition of the present invention must be determined by the attending physician within the scope of sound medical judgment. For any particular patient, the specific therapeutically effective dosage level will depend on a variety of factors, including the disorder being treated and the severity of that disorder; the specific composition employed; the age, weight, general health, sex and diet of the patient; the time of administration, the route of administration and the rate of excretion; the duration of the treatment; drugs used in combination with or concurrently with; and similar factors well known in the medical arts. For example, the practice in the art is to start with a dosage lower than the level required to obtain the desired therapeutic effect and gradually increase the dosage until the desired effect is obtained.

[0030] Generally speaking, the dosage of the pharmaceutical composition of the present invention calculated based on the active ingredient for mammals, especially humans, can be between 1 - 1000 mg / kg body weight / day, for example, between 1 - 500 mg / kg body weight / day, for example, between 50 - 500 mg / kg body weight / day, or 100 - 500 mg / kg, or 150 - 500 mg / kg, or 200 - 500 mg / kg, or 250 - 500 mg / kg.

[0031] This protocol discussed the effect of ginsenoside Rg2 on improving the renal function of hyperuricemia rats induced by high-purine diet constructed by gastric yeast extract and adenine combined with potassium oxonate from the phenomenon to the mechanism through animal and molecular biology experiments.

[0032] The present invention first discovered that ginsenoside Rg2 can reduce systemic and renal inflammatory responses by downregulating the expression levels of inflammatory factors LPS, TNF-α and IL-1β; achieve the effect of improving HUA-related renal inflammation and fibrosis by downregulating the expression levels of fibrosis marker molecules α-SMA and Smad3; enhance the active transport and excretion ability of the kidney to uric acid by upregulating the expression levels of uric acid transporters OAT1, OAT3 and ABCG2. This discovery will have a significant impact on the research and treatment of alleviating hyperuricemia and has clinical practical value. Description of the Drawings

[0033] Figure 1Effect of ginsenoside Rg2 on the kidney tissue of HUA rats;

[0034] Figure 2 Effect of ginsenoside Rg2 on uric acid excretion in HUA rats; 2A shows the change in urine uric acid content; 2B shows the change in the content of total urine uric acid / serum uric acid; 2C shows the change in urine creatinine content; 2D shows the change in urine urea nitrogen content; *P < 0.05, **P < 0.01, ***P < 0.001;

[0035] Figure 3 Effect of ginsenoside Rg2 on kidney inflammation-related proteins in HUA rats; 3A shows the expression level of LPS in serum; 3B shows the expression level of TNF-α in serum; 3C shows the expression level of IL-1β in serum; 3D shows the expression level of LPS in the kidney; 3E shows the expression level of TNF-α in the kidney; 3F shows the expression level of IL-1β in the kidney; *P < 0.05, **P < 0.01, ***P < 0.001;

[0036] Figure 4 Effect of ginsenoside Rg2 on kidney fibrosis proteins in HUA rats; 4A shows the expression level of α-SMA mRNA in the kidney; 4B shows the expression level of Smad3 mRNA in the kidney; *P < 0.05, **P < 0.01, ***P < 0.001;

[0037] Figure 5 Effect of ginsenoside Rg2 on kidney uric acid transport-related proteins in HUA rats; 5A shows the expression level of kidney URAT1 mRNA; 5B shows the expression level of kidney GLUT9 mRNA; 5C shows the expression level of kidney OAT3 mRNA; 5D shows the expression level of kidney OAT1 mRNA; 5E shows the expression level of kidney ABCG2 mRNA; 5F shows the expression level of kidney OAT1 protein; 5G shows the expression level of kidney ABCG2 protein; 5H shows the Western blot of kidney OAT1 and ABCG2 proteins; *P < 0.05, **P < 0.01, ***P < 0.001. Detailed implementation methods

[0038] To enable those skilled in the art to better understand the technical solutions of the present invention, the present invention will be described in detail below in conjunction with specific embodiments. For the experimental methods without specific conditions noted in the following examples, they are generally carried out under conventional conditions or according to the conditions recommended by the manufacturer. The test materials used in the following examples are all obtained from regular biochemical reagent stores unless otherwise specified. Unless otherwise stated, percentages and parts are calculated by weight. Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred implementation methods and materials described herein are for illustrative purposes only.

[0039] The technical solutions of the present invention will be further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following examples are only used to explain the present invention and are not used to limit the present invention.

[0040] Data was analyzed and graphed using Graphpad prism 9.4.0 software, and the results were expressed in the form of mean ± standard error (means ± SEM). The t-test (student’s t-test) was used for data comparison and analysis of two or more groups, and one-way ANOVA was used for data comparison and analysis of two or more groups. The multi-variable analysis was performed using the cloud platform of Meiji Biopharmaceutical Technology Co., Ltd.; unless otherwise specified in the legend, when P < 0.05, the results were considered to be statistically significant. The bivariate correlation was calculated using the Pearson r coefficient.

[0041] Experimental animals: 24 male Sprague Dawley rats, with a body weight of 180 - 220 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (SPF level), and the animal license number is SCXK (Jing) 2021 - 0011.

[0042] Experimental grouping: It included a blank control group (Control), a model control group (HUA), a ginsenoside group (G-Rg2), and a positive control group (BEN), with 6 rats in each group, and there was no significant difference in the average body weight of the rats in each group.

[0043] Experimental method: The animals were housed in a thermostatic environment (24 ± 1°C, 12 h light-dark cycle), and were allowed free access to food (AIN-93M basal diet, purchased from Shanghai Nantong Trolife Feed Technology Co., Ltd.) for 1 week. Except for the blank control group, the other two groups were induced to establish a hyperuricemia model with a high-purine diet. Specifically: They were gavaged with 10 g / (kg·bw) yeast extract and 100 mg / (kg·bw) adenine solution twice a day for 18 days. During this period, the CON group was intraperitoneally injected with normal saline every two days, and the other groups were intraperitoneally injected with an equal volume of 300 mg / (kg·bw) potassium oxonate solution (PO) to establish a HUA rat model. After successful model replication, the G-Rg2 group was gavaged with 200 mg / kg G-Rg2, the BEN group was gavaged with 50 mg / (kg·bw) benzbromarone, and the blank control group and the model group were given the same volume of 0.9% normal saline.

[0044] Example 1: To investigate the effect of ginsenoside Rg2 on the kidney tissues of HUA rats

[0045] After the experiment, the rats were dissected, and kidney samples were taken, rinsed with PBS, preserved with 4% (V / V) paraformaldehyde, embedded in paraffin and sectioned. The section thickness was 4 μm, and they were stored in an oven at 65°C for 6 hours, and then stained with hematoxylin and eosin (H&E). Images were captured using an Olympus CX43 microscope and CellSens Entry software (see Figure 1 ).

[0046] As can be seen from Figure 1 , in the HUA group, obvious inflammatory cell infiltration occurred in the renal tissues of the rats, the renal tubule lumen was significantly dilated, and brownish-yellow urate crystal deposits could also be seen in some renal tubule lumens. These pathological changes indicated that hyperuricemia caused obvious kidney damage. In contrast, after Rg2 intervention, the degree of pathological changes in the renal tissues of the rats was significantly reduced, the inflammatory cell infiltration decreased, the renal tubule structure tended to be complete, and the urate deposition in the lumen was also significantly reduced, and the overall tissue morphology was closer to the normal state.

[0047] Example 2: To investigate the effect of ginsenoside Rg2 on uric acid excretion in HUA rats

[0048] After the experiment, 24-hour urine of the rats was collected, the animals were euthanized, and then samples such as blood, kidneys, livers, and intestines were collected; the blood samples were placed at room temperature for 1 hour, and then centrifuged at 3000 r / min for 10 minutes to obtain serum, and uric acid, creatinine, and urea nitrogen in the serum and urine were detected (see Figure 2 ).

[0049] Figure 2As shown in A-2B, compared with the CON group, the urinary uric acid excretion of rats in the HUA group was significantly decreased, indicating that under the state of hyperuricemia, the ability of the kidney to excrete uric acid was inhibited (P<0.001), while the uric acid excretion in the G-Rg2 group was significantly increased (P<0.05), suggesting that ginsenoside Rg2 restored the function of the kidney to excrete uric acid to a certain extent. At the same time, the urinary creatinine excretion level in the HUA group was significantly lower than that in the CON group (P<0.001), reflecting that hyperuricemia might damage the glomerular filtration function or the tubular excretion ability, while the urinary creatinine excretion in the G-Rg2 group increased significantly (P<0.01), indicating that the protective effect of ginsenoside Rg2 on renal function was not limited to uric acid metabolism but also involved the regulation of creatinine excretion( Figure 2 C). It is worth noting that significant fluctuations also occurred in the urinary urea nitrogen level( Figure 2 D). The urinary urea nitrogen level in the HUA group was significantly higher than that in the CON group (P<0.01), suggesting that after renal function was damaged, the excretion of urea nitrogen was affected, while the urea nitrogen level in the G-Rg2 group was effectively decreased (P<0.05), further indicating that ginsenoside Rg2 had a certain repair and improvement effect on renal function.

[0050] Example 3 investigated the effect of ginsenoside Rg2 on kidney inflammation in HUA rats

[0051] Take 30 mg of mouse kidney tissue, homogenize it on ice, then centrifuge it at 5000 g for 10 min at 4°C to extract the supernatant; take the mouse blood sample and let it stand at room temperature for 1 hour, then centrifuge it at 3000 r / min for 10 minutes to obtain the serum. Use an ELISA kit (Enzyme-linked Biotechnology Co., Ltd., Shanghai, China) to detect the expression levels of IL-1β, LPS, and TNF-α in the supernatant and serum (see Figure 3 ).

[0052] Figure 3 As shown in A-3C, compared with the CON group, the levels of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the serum of the HUA group were all significantly increased, indicating that the systemic inflammatory response was significantly aggravated, while in the G-Rg2 group, the levels of these inflammatory factors were all significantly decreased, indicating that ginsenoside Rg2 had a certain inhibitory effect on the systemic inflammation. As Figure 3 shown in D-3F, the same change trend also appeared in the kidney tissue. The levels of LPS, TNF-α, and IL-1β in the kidneys of rats in the HUA group were all significantly higher than those in the CON group, indicating that the local inflammatory response was also significantly activated, while the intervention of ginsenoside Rg2 could effectively down-regulate the expression levels of these inflammatory factors, indicating that ginsenoside Rg2 also had a certain improvement effect on local kidney inflammation.

[0053] Example 4: Investigation of the effect of ginsenoside Rg2 on kidney fibrosis in HUA

[0054] Total RNA of kidney tissues was extracted using TaKaRa MiniBEST Universal RNA Extraction Kit (TaKaRa, Japan), and reverse transcription was performed using PrimeScript TM RT reagent Kit with gDNA Eraser (Perfect RealTime). According to the Premix Ex Taq TM II (Tli RNaseH Plus) kit instructions, the mRNA levels of genes were analyzed using 480 System (Roche Diagnostics). GAPDH was used as an internal reference gene to calibrate the relative expression of target mRNA. According to the CT values of the samples, the results were calculated using the 2-ΔΔ C t method, and the experimental results are shown in Figure 4 Figure. The specific primer sequences are shown in Table 1.

[0055] Table 1

[0056]

[0057] Figure 4 The results showed that compared with the CON group, the expressions of α-SMA and Smad3 mRNA in the HUA group were significantly up-regulated, indicating that the kidney fibrosis process has been initiated in the HUA state. In the G-Rg2 group, the expressions of these two fibrosis marker molecules were significantly down-regulated, indicating that Rg2 also played a positive role in anti-fibrosis.

[0058] Example 5: Investigation of the effect of ginsenoside Rg2 on kidney urate transporters in HUA

[0059] Using the same method as in Example 4, total RNA of kidney tissues was extracted and reverse transcribed into cDNA. Using the prepared cDNA as a template, RT-qPCR amplification was performed, and the experimental results are shown in Figure 5 Figure. The specific primer sequences are shown in Table 2.

[0060] Table 2

[0061]

[0062]

[0063] Figure 5A-5B showed that ginsenoside Rg2 did not significantly affect the expression of solute carrier family 22 member 12 (URAT1) and glucose transporter 9 (GLUT9) transporters. As Figure 5 Shown in C-5E, compared with the HUA group, the expression levels of OAT3 mRNA, OAT1 mRNA, and ABCG2 mRNA in the kidneys of rats in the G-Rg2 group were significantly up-regulated, indicating that ginsenoside Rg2 may improve the renal uric acid transport function by regulating the gene transcription of transporters.

[0064] Further verification was performed by Western blot assay as follows: Total renal proteins were extracted with RIPA lysis buffer containing 2% protease. Proteins (30 μg) were separated by 10% SDS-PAGE and transferred to a 0.45 μm PVDF membrane. The PVDF membrane was blocked with 5% non-fat milk and 5% BSA for 1 hour. Then the PVDF membrane was incubated overnight at 4°C with primary antibodies against ABCG2 (1:1000), GLUT9 (1:1000) (purchased from Abclonal Biotechnology Co., Ltd., Wuhan, China), OAT1 (1:500), and GAPDH (1:5000) (Proteintech Biotechnology Co., Ltd., Wuhan, China). Then, the membrane was incubated with a horseradish peroxidase (HRP)-conjugated secondary antibody (1:2000) for 2 hours at room temperature. Protein bands were detected using an enhanced chemiluminescence (ECL) detection kit, and the protein bands were captured and exposed for imaging. The protein bands were quantified using ImageJ software.

[0065] Figure 5 As shown in F-5H, compared with the CON group, the protein expression levels of OAT1 and ABCG2 in the HUA group were significantly down-regulated, indicating that the uric acid transport function of HUA rats was impaired under hyperuricemic conditions, while the expression of these two transporters in the G-Rg2 group significantly rebounded and approached normal levels. It can be seen that ginsenoside Rg2 can enhance the active transport and excretion ability of the kidneys to uric acid by up-regulating the expression of OAT3, OAT1, and ABCG2.

[0066] Finally, it should be noted that the above description is only the preferred embodiment of the present invention. Those skilled in the art can make various similar representations under the inspiration of the present invention without departing from the purpose and claims of the present invention, and such transformations all fall within the protection scope of the present invention.

Claims

1. Use of ginsenoside Rg2 in the preparation of a drug for improving kidney inflammation.

2. Use of ginsenoside Rg2 in the preparation of a drug for enhancing uric acid excretion.

3. The application according to claim 1, wherein The mechanism of action of the drug is shown as: a. Down-regulating the expression levels of inflammatory factors LPS, TNF-α and IL-1β; and / or, b. Down-regulating the expression levels of fibrosis marker molecules α-SMA and Smad3.

4. The application according to claim 2, wherein The mechanism of action of the drug is shown as: up-regulating the expression levels of uric acid transporters OAT1, OAT3 and ABCG2.

5. The application according to any one of claims 1-4, characterized in that: The drug uses ginsenoside Rg2 or its derivatives, or its precursor metabolites, or its pharmaceutically acceptable salts as active ingredients and is made into a pharmaceutically acceptable dosage form with pharmaceutically acceptable excipients.

6. The application according to any one of claims 1-4, characterized in that: The drug is administered through gastrointestinal and non-gastrointestinal administration routes.

7. A drug for improving kidney inflammation and enhancing uric acid excretion, characterized in that, It includes active ingredients and pharmaceutically acceptable excipients; the active ingredients are ginsenoside Rg2 or its derivatives, or its precursor metabolites, or its pharmaceutically acceptable salts.

8. The medicament according to claim 7, characterized in that, The drug is administered through gastrointestinal and non-gastrointestinal administration routes.

9. The drug according to claim 7, wherein The mechanism of action of the drug is shown as: a. Down-regulating the expression levels of inflammatory factors LPS, TNF-α and IL-1β; and / or, b. Down-regulating the expression levels of fibrosis marker molecules α-SMA and Smad3 mRNA; and / or, c. Up-regulating the expression levels of uric acid transporters OAT1, OAT3 and ABCG2.

10. The drug according to claim 7, characterized in that, The amount of the active ingredient is 0.001-90 wt% relative to the total weight of the drug; or, 0.02-50 wt%; or 0.1-20%; or 0.005-5%.

Images