Use of kynurenic acid in resisting hyperuricemia and structural analog thereof in preparing XOD inhibitor

Abstract

Provided is use of kynurenic acid in resisting hyperuricemia and a structural analog thereof in preparing an XOD inhibitor, wherein kynurenic acid and the structural analog have good inhibitory activity on xanthine oxidase (XOD). Kynurenic acid has no significant influence on the growth and body weight of mice, and the oral administration of kynurenic acid at a low dose, medium dose, or high dose can significantly reduce the serum levels of creatinine and blood urea nitrogen in mice and effectively inhibit the activity of XOD in the liver of mice, thus reducing the level of uric acid in the livers in a concentration-dependent manner. Kynurenic acid, whether administered at a low dose, medium, or high dose, can effectively reduce the enzymatic activity of adenosine deaminase (ADA) in the serum of mice with hyperuricemia and limit the generation of uric acid precursors. Therefore, kynurenic acid can be used as a medicament for alleviating or treating hyperuricemia.

Description

Application of Kynuric Acid in Treating Hyperuricemia and Its Structural Analogs in the Preparation of XOD Inhibitors Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to application of kynurenic acid in treating hyperuricemia and its structural analogs in preparing XOD inhibitors. Background Art

[0002] Uric acid (UA) is the end product of purine metabolism in the liver, muscles, and intestines, primarily formed by the breakdown of adenylate and guanine. Under normal circumstances, uric acid production and excretion in the human body maintain a dynamic balance, with 70% excreted through the kidneys and 30% excreted through the intestines. Hyperuricemia (HUA) is a metabolic disease caused by abnormal purine metabolism, resulting in excessive uric acid production and / or decreased excretion, leading to elevated serum uric acid levels. Due to the lack of urate oxidase in the human body, hypoxanthine is metabolized by xanthine oxidase (XOD) to form uric acid as the final product. Xanthine oxidase, which promotes uric acid synthesis, is most highly expressed in the liver and intestines. In recent years, with rapid economic development and changes in lifestyle, the incidence of hyperuricemia has increased significantly worldwide, with a younger age group. Hyperuricemia is not only a key risk factor for gout but is also closely associated with kidney disease, hypertension, diabetes, cardiovascular disease, and other conditions. Timely and effective uric acid-lowering treatment is the key to reducing urate deposition in the body, lowering the risk of gout, alleviating kidney damage, and reducing the occurrence of other complications.

[0003] Allopurinol, a purine analog, selectively inhibits xanthine oxidase, thereby reducing uric acid production. However, long-term use of allopurinol can cause side effects such as allergic rashes and liver and kidney failure. Therefore, there is an urgent need for safe and effective functional foods or medications to mitigate the harmful effects of hyperuricemia.

[0004] Summary of the Invention

[0005] The present invention aims to solve, at least to some extent, one of the technical problems in the related art. To this end, one object of the present invention is to provide a use of kynurenic acid and its structural analogs in the preparation of xanthine oxidase inhibitors, wherein the structural formula of the kynurenic acid is as follows:

[0006] The general structural formula of the kynurenic acid structural analogue is as follows:

[0007] wherein R3 is ethyl carboxylate, R4 is hydroxyl, and R6 is methoxy; or R3 is ethyl carboxylate, R4 is hydroxyl, and R8 is methoxy; or R3 is ethyl carboxylate, R4 is hydroxyl; or R3 is carboxylic acid, R4 is hydroxyl; or R3 is carboxylic acid, R6 is hydroxyl; or R4 is hydroxyl; or R2 is ethyl carboxylate, R4 is hydroxyl; or R2 is carboxylic acid, R4 is hydroxyl, and R8 is hydroxyl; or R2 is carboxylic acid, R5 is hydroxyl; or R2 is hydroxyl, R4 is carboxylic acid; or R2 is carboxylic acid; or R2 is carboxylic acid, R3 is hydroxyl; or R2 is carboxylic acid, R8 is hydroxyl; or R6 is carboxylic acid, R8 is hydroxyl; or R7 is carboxylic acid, R8 is hydroxyl; or R4 is hydroxyl, and R7 is carboxylic acid.

[0008] Optionally, the kynurenic acid structural analogue is 4-hydroxy-6-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxy-8-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid, 6-hydroxyquinoline-3-carboxylic acid, 4-hydroxyquinoline, 4-hydroxyquinoline-2-carboxylic acid ethyl ester, xanthuric acid, 5-hydroxy-2-quinolinecarboxylic acid, 2-hydroxy-4-quinolinecarboxylic acid, 2-carboxyquinoline, 3-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-6-quinolinecarboxylic acid, 8-hydroxy-7-quinolinecarboxylic acid or 4-hydroxy-7-quinolinecarboxylic acid.

[0009] According to the application of the embodiment of the present invention, the results of the in vitro xanthine oxidase inhibitory activity test showed that 6-Hydroxyqui noline-3-carboxylic acid had the best in vitro xanthine oxidase inhibitory activity, IC 50 3-Hydroxyquinoline-2-carboxylic acid, 2-Hydroxyquinoline-4-carboxylic acid and Kynurenic acid all showed good xanthine oxidase inhibitory activity, with IC 50 They are: 0.97±0.05mM, 1.61±0.07mM and 1.99±0.26mM respectively.

[0010] In a second aspect of the present invention, embodiments of the present invention provide use of kynurenic acid in the preparation of a medicament for improving or treating hyperuricemia.

[0011] According to the application of the embodiments of the present invention, the intake of kynurenic acid has no significant effect on the growth status and body weight of mice. Oral administration of low-dose (7mM / kg / day), medium-dose (35mM / kg / day), or high-dose (70mM / kg / day) kynurenic acid can significantly reduce the levels of serum creatinine (CRE) and blood urea nitrogen (BUN) in mice, and can effectively inhibit the activity of XOD enzyme in the liver of mice, thereby reducing liver uric acid levels, and in a concentration-dependent manner. In the experimental groups, low-dose, medium-dose, or high-dose kynurenic acid can effectively reduce the activity of ADA enzyme in the serum of hyperuricemic mice, limiting the production of uric acid precursors.

[0012] In a third aspect of the present invention, an embodiment of the present invention provides a drug for improving or treating hyperuricemia, comprising kynurenic acid and a pharmaceutically acceptable carrier.

[0013] According to the drug of the embodiment of the present invention, the ingestion of kynurenic acid had no significant effect on the growth status and body weight of mice. Oral administration of low-dose (7mM / kg / day), medium-dose (35mM / kg / day), or high-dose (70mM / kg / day) kynurenic acid significantly reduced the levels of serum creatinine (CRE) and blood urea nitrogen (BUN) in mice, and effectively inhibited the activity of XOD enzyme in the liver of mice, thereby reducing liver uric acid levels in a concentration-dependent manner. In the experimental groups, low-dose, medium-dose, or high-dose kynurenic acid effectively reduced the activity of ADA enzyme in the serum of hyperuricemic mice, limiting the production of uric acid precursors.

[0014] In the fourth aspect of the present invention, an embodiment of the present invention provides a drug for improving or treating hyperuricemia, which comprises a kynurenic acid structural analogue and a pharmaceutically acceptable carrier, wherein the kynurenic acid structural analogue is 4-hydroxy-6-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxy-8-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid, 6-hydroxyquinoline-3-carboxylic acid, 4-hydroxyquinoline, 4-hydroxyquinoline-2-carboxylic acid ethyl ester, xanthuric acid, 5-hydroxy-2-quinolinecarboxylic acid, 2-hydroxy-4-quinolinecarboxylic acid, 2-carboxyquinoline, 3-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-6-quinolinecarboxylic acid, 8-hydroxy-7-quinolinecarboxylic acid or 4-hydroxy-7-quinolinecarboxylic acid.

[0015] According to the drug of the embodiment of the present invention, the results of the in vitro xanthine oxidase inhibitory activity test showed that 6-Hydroxyquinoline-3-carboxylic acid had the best in vitro xanthine oxidase inhibitory activity, IC 503-Hydroxyquinoline-2-carboxylic acid, 2-Hydroxyquinoline-4-carboxylic acid and Kynurenic acid all showed good xanthine oxidase inhibitory activity, with IC 50 The concentrations of kynurenic acid in the serum of patients with hyperuricemia were 0.97±0.05mM, 1.61±0.07mM and 1.99±0.26mM, respectively. Therefore, kynurenic acid structural analogs can be used as drugs to improve or treat hyperuricemia.

[0016] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG1 is a chemical structure of kynurenic acid according to an embodiment of the present invention;

[0018] FIG2 shows the weight changes of mice at different times according to an embodiment of the present invention;

[0019] FIG3 shows changes in serum uric acid levels in mice according to an embodiment of the present invention;

[0020] FIG4 shows changes in serum XOD enzyme activity in mice according to an embodiment of the present invention;

[0021] FIG5 shows changes in serum creatinine (CRE) levels in mice according to an embodiment of the present invention;

[0022] FIG6 shows changes in urea nitrogen (BUN) levels in mice according to an embodiment of the present invention;

[0023] FIG7 shows changes in XOD enzyme activity in mouse liver according to an embodiment of the present invention;

[0024] FIG8 shows changes in uric acid levels in mouse livers according to an embodiment of the present invention;

[0025] FIG9 shows changes in serum adenosine deaminase activity (ADA) in mice according to an embodiment of the present invention;

[0026] FIG10 shows the xanthine oxidase inhibitory activity of quinoline structural analogs at various concentrations according to an embodiment of the present invention;

[0027] FIG11 shows the XOD inhibitory activity of KA and its structural analogs at a concentration of 1 mM according to an example of the present invention. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is described below through specific examples. It should be understood that the one or more method steps mentioned in the present invention do not exclude the presence of other method steps before and after the combination step or the insertion of other method steps between these explicitly mentioned steps; it should also be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the order of arrangement of each method step or to define the scope of the present invention. Changes or adjustments in their relative relationships, without substantially changing the technical content, should also be regarded as the scope of the present invention.

[0029] In order to better understand the above technical solutions, exemplary embodiments of the present invention are described in more detail below. Although exemplary embodiments of the present invention are shown, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0030] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0031] Kynuric acid structural analogs may be as follows:

[0032] (1) 4-hydroxy-6-methoxyquinoline-3-carboxylate

[0033] Wherein: R3 is ethyl carboxylate, R4 is hydroxyl, R6 is methoxy

[0034] (2) Ethyl 4-hydroxy-8-methoxyquinoline-3-carboxylate

[0035] Wherein: R3 is carboxyethyl ester, R4 is hydroxyl, R8 is methoxy

[0036] (3) 4-Hydroxyquinoline-3-carboxylic acid ethyl ester

[0037] Wherein: R3 is ethyl carboxylate, R4 is hydroxyl

[0038] (4) 4-hydroxyquinoline-3-carboxylic acid

[0039] Wherein: R3 is carboxylic acid, R4 is hydroxyl

[0040] (5) 6-Hydroxyquinoline-3-carboxylic acid

[0041] Wherein: R3 is carboxylic acid, R6 is hydroxyl

[0042] (6) 4-Hydroxyquinoline

[0043] Wherein: R4 is hydroxyl

[0044] (7) Ethyl 4-hydroxyquinoline-2-carboxylate

[0045] Wherein: R2 is ethyl carboxylate, R4 is hydroxyl

[0046] (8) Xanthurenic acid

[0047] Wherein: R2 is carboxylic acid, R4 is hydroxyl, R8 is hydroxyl

[0048] (9) 5-hydroxyquinoline-2-carboxylic acid

[0049] Wherein: R2 is carboxylic acid, R5 is hydroxyl

[0050] (10) 2-hydroxyquinoline-4-carboxylic acid

[0051] Wherein: R2 is hydroxyl, R4 is carboxylic acid

[0052] (11) Quinoline-2-carboxylic acid

[0053] Wherein: R2 is carboxylic acid

[0054] (12) 3-Hydroxyquinoline-2-carboxylic acid

[0055] Wherein: R2 is carboxylic acid, R3 is hydroxyl

[0056] (13) 8-Hydroxyquinoline-2-carboxylic acid

[0057] Wherein: R2 is carboxylic acid, R8 is hydroxyl

[0058] (14) 8-Hydroxyquinoline-6-carboxylic acid

[0059] Wherein: R6 is carboxylic acid, R8 is hydroxyl

[0060] (15)8-Hydroxyquinoline-7-carboxylic acid

[0061] Wherein: R7 is carboxylic acid, R8 is hydroxyl

[0062] (16) 4-Hydroxyquinoline-7-carboxylic acid

[0063] Wherein: R4 is hydroxyl, R7 is carboxylic acid

[0064] The present invention is described below with reference to specific examples. It should be noted that these examples are merely illustrative and do not limit the present invention in any way.

[0065] Example 1 Effect of Kynuric Acid on Body Weight in Hyperuricemia Mice

[0066] Kynurenic acid (KA), whose chemical structure is shown in Figure 1, was obtained from Sigma-Aldrich (Shanghai) Trading Co., Ltd.

[0067] SPF male Kunming mice (8 weeks old), 35 ± 5 g, were purchased from Changzhou Cavens Laboratory Animal Co., Ltd. The animal quality was tested by Suzhou Xishan Biotechnology Co., Ltd.

[0068] Experimental mice were housed in a clean animal housing unit and handled according to the standards of the Animal Laboratory Center. The animal housing unit and operating table were cleaned and disinfected daily. All experimental mice were housed in a comfortable environment (temperature: 25±2°C, humidity: 40%-70%, 12-hour day / night cycle) with good ventilation and provided with daily feed and drinking water.

[0069] Thirty-six relatively uniform, healthy, SPF-grade male Kunming mice were randomly divided into a normal control group, a model group, a positive control group, a low-dose kynurenic acid group (KA-L), a medium-dose kynurenic acid group (KA-M), and a high-dose kynurenic acid group (KA-H), with six mice in each group. The normal control group received an equal volume of CMC-Na solution and an equal volume of saline daily by oral gavage. The other groups received 500 mg / kg hypoxanthine (HX) and 300 mg / kg potassium oxonate (PO) by intraperitoneal gavage. The positive control group received 35 mM / kg allopurinol daily by oral gavage. The other experimental groups received 7 mM / kg KA (KA-L), 35 mM / kg KA (KA-M), and 70 mM / kg KA (KA-H), respectively. Oral administration was continued for 21 days. SPSS 23.0 software was used to analyze the correlation and significance of the data. One-way analysis of variance was used to compare the differences between the groups. *p<0.05 indicated a significant difference, **p<0.01 indicated an extremely significant difference. express.

[0070] After 21 days of feeding, the weight of mice in each group was measured at different time points, and the results are shown in Figure 2. On the seventh day of intervention, there was no significant difference in the weight of mice in each group. On the 21st day of intervention, the weight of mice in the model group increased compared to the other groups, but there was no significant difference compared to the weight of mice in the other groups (p>0.05). These results indicate that oral administration of KA to mice did not affect their growth status or weight.

[0071] Example 2 Effect of Kynuric Acid on Serum Uric Acid in Hyperuricemic Mice

[0072] At the end of the experiment on day 21, the mice in each group of Example 1 were fasted and deprived of water for 12 h, and then blood was collected from the mice's eyeballs. After collecting sufficient blood samples, they were allowed to stand at room temperature for 30 min and then centrifuged (3500 rpm, 10 min). The supernatant was taken and stored at -20°C for later use.

[0073] A uric acid (UA) test kit was used to measure the serum uric acid levels of the target mice. Serum uric acid levels are an important evaluation indicator for the improvement of hyperuricemia by drugs. As shown in Figure 3, the serum uric acid levels of mice in the blank control group were significantly lower than those in the model group (p < 0.01). The positive control group (allopurinol) significantly inhibited the increase in serum uric acid levels in mice (p < 0.01). All three KA dose groups significantly reduced the serum uric acid levels of mice (p < 0.01), with KA-H having the most pronounced inhibitory effect on the serum uric acid levels in mice.

[0074] Example 3 Effect of Kynuric Acid on Serum XOD Activity in Hyperuricemic Mice

[0075] The serum samples of Example 2 were taken, and the Xanthine Oxidase (XOD) enzyme activity level in the mouse serum samples was determined using a Xanthine Oxidase (XOD) assay kit (colorimetric method). The experimental procedures and data calculations were performed strictly in accordance with the kit instructions.

[0076] As shown in Figure 4, the XOD enzyme activity level in the model group mice remained at a higher level compared with the blank control group. The positive control group significantly reduced the serum XOD enzyme activity level in hyperuricemia mice (p < 0.01). KA-L, KA-M, and KA-H all reduced the serum XOD enzyme activity in hyperuricemia mice to varying degrees (p < 0.01), and the activity was positively correlated with the KA concentration.

[0077] Example 4 Effect of Kynuric Acid on Serum Creatinine and Urea Nitrogen in Hyperuricemic Mice

[0078] The serum samples in Example 2 were taken and the CRE content of the mouse serum samples was detected using a creatinine (CRE) assay kit (sarcosine oxidation method). The experimental procedures and data calculations were performed strictly in accordance with the kit instructions.

[0079] The serum samples in Example 2 were taken and the BUN content in the mouse serum samples was detected using a urea nitrogen (BUN) assay kit (urease method). The experimental procedures and data calculations were performed strictly in accordance with the kit instructions.

[0080] Creatinine (CRE) and blood urea nitrogen (BUN) are important indicators of renal function. As shown in Figures 5 and 6, the serum CRE and BUN of mice in the model group were significantly increased compared with those in the blank control group (p < 0.01), indicating that administration of PO, HX, and 10% fructose to mice resulted in renal damage. Compared with the model group, KA was able to significantly reduce the serum CRE and BUN of mice (p < 0.01), and showed a good concentration-dependent effect. Moreover, compared with the positive control group, KA-M and KA-H were able to more significantly reduce the BUN levels of mice (p < 0.01). This indicates that KA can improve renal dysfunction in mice by reducing the serum CRE and BUN of hyperuricemic mice.

[0081] Example 5 Effect of Kynurenic Acid on Uric Acid and Xanthine Oxidase (XOD) in the Liver of Hyperuricemic Mice

[0082] On day 21, after fasting and depriving the mice in each group of Example 1 for 12 hours, the mice were quickly killed by cervical dislocation, and the livers were harvested, weighed, and aliquoted. A 100 mg mouse liver sample was ground in physiological saline and centrifuged at 3500 rpm at 4°C for 15 minutes. The supernatant homogenate was stored at -20°C until use. The uric acid level in the mouse liver homogenate sample was measured using the method described in Example 2. The XOD enzyme activity level in the mouse liver homogenate sample was measured using the method described in Example 3.

[0083] The XOD enzyme activity in the mouse liver was measured, and the results are shown in Figure 7. Compared with the blank control group and the positive control group, the XOD enzyme activity in the model group was significantly increased (p < 0.01). Furthermore, after administration of KA, the XOD enzyme activity in the mouse liver was significantly decreased (p < 0.01) and positively correlated with the KA concentration.

[0084] Uric acid levels in mouse livers were measured, and the results are shown in Figure 8. Compared to the blank control group, the positive control group significantly reduced uric acid levels in the mouse livers (p < 0.01), reaching a level comparable to that of the blank control group. Following administration of different concentrations of KA, uric acid levels in the mouse livers decreased gradually (p < 0.01). These results demonstrate that KA can effectively inhibit XOD enzyme activity in mouse livers, thereby reducing liver uric acid levels.

[0085] Example 6 Effect of Kynuric Acid on Serum Adenosine Deaminase Activity (ADA) in Hyperuricemic Mice

[0086] The serum samples in Example 2 were taken, and the ADA enzyme activity level in the mouse serum samples was determined using an ADA assay kit (peroxidase method).

[0087] As shown in Figure 9, compared with the blank and positive control groups, the serum ADA enzyme activity levels in the model group were significantly increased (p < 0.01). After KA administration, the serum ADA enzyme activity levels in the mice were significantly reduced, reaching levels comparable to those in the blank and positive control groups (p < 0.01). KA-H had the most significant inhibitory effect on the serum ADA enzyme activity levels in mice. This suggests that KA can effectively reduce the serum ADA enzyme activity in hyperuricemic mice, thereby limiting the production of uric acid precursors.

[0088] Example 7 Inhibitory Effects of Kynuric Acid and Its Structural Analogs on XOD Enzyme Activity in Vitro

[0089] After the inhibitor and XOD reacted for 10 minutes, a certain concentration of xanthine, a reaction substrate, was added. The amount of uric acid generated was detected at 290 nm to evaluate the inhibitory effect of the quinoline analogue on XOD. Using allopurinol as a positive control, the inhibitory activity of the quinoline analogue on XOD is shown in Figure 10. The xanthine oxidase inhibitory activity of the 17 targets tested increased with increasing concentration. The xanthine oxidase inhibitory activity of the positive control allopurinol also showed concentration dependence in this system, and its IC 50 Compared with other compounds, compounds 5, 7, 11, 13 and KA have better inhibitory effects on XOD, IC 50 The XOD inhibitory activity of compounds 5 and 13 at 1 mM was 0.50±0.13, 5.65±0.10, 1.61±0.07, 0.97±0.05, and 1.99±0.26, respectively (Table 1). Compound 5 exhibited significantly higher XOD inhibitory activity than the other compounds (p<0.05). Furthermore, by comparing the xanthine oxidase inhibitory activity of the compounds at the same concentration, the influence of their structure on XOD inhibitory activity was analyzed. As shown in Figure 11, at a compound concentration of 1 mM, compounds 5 and 13 exhibited xanthine oxidase inhibitory activity exceeding 50%. The xanthine oxidase inhibitory activity of both compounds at this concentration was significantly higher than that of the other compounds (p<0.05).

[0090] Table 1 XOD inhibitory activity (XOI) of kynurenic acid and its structural analogs

[0091] Note: XOI (xanthine oxidase inhibitory) activity of allopurinol: IC 50 :0.004±0.001 (mM). Capital letters indicate significant differences in XOD inhibitory activity of compounds (p<0.05).

[0092] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms should not be understood as necessarily referring to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification.

[0093] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. Use of kynurenic acid and its structural analogs in the preparation of xanthine oxidase inhibitors, wherein the structural formula of the kynurenic acid is as follows: The general structural formula of the kynurenic acid structural analog is as follows: in, R3 is ethyl carboxylate, R4 is hydroxyl, and R6 is methoxy; or R3 is ethyl carboxylate, R4 is hydroxyl, and R8 is methoxy; or R3 is ethyl carboxylate, R4 is hydroxyl; or R3 is carboxylic acid, R4 is hydroxyl; or R3 is carboxylic acid, R6 is hydroxyl; or R4 is hydroxyl; or R2 is ethyl carboxylate, R4 is hydroxyl; or R2 is carboxylic acid, R4 is hydroxyl, and R8 is hydroxyl; or R2 is carboxylic acid, R5 is hydroxyl; or R2 is hydroxyl, R4 is carboxylic acid; or R2 is carboxylic acid; or R2 is carboxylic acid, R3 is hydroxyl; or R2 is carboxylic acid, R8 is hydroxyl; or R6 is carboxylic acid, R8 is hydroxyl; or R7 is carboxylic acid, R8 is hydroxyl; or R4 is hydroxyl, R7 is carboxylic acid.

2. The use according to claim 1, characterized in that The kynurenic acid structural analogue is 4-hydroxy-6-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxy-8-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid, 6-hydroxyquinoline-3-carboxylic acid, 4-hydroxyquinoline, 4-hydroxyquinoline-2-carboxylic acid ethyl ester, xanthurenic acid, 5-hydroxy-2-quinolinecarboxylic acid, 2-hydroxy-4-quinolinecarboxylic acid, 2-carboxylic acid quinoline, 3-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-6-quinolinecarboxylic acid, 8-hydroxy-7-quinolinecarboxylic acid or 4-hydroxy-7-quinolinecarboxylic acid.

3. Use of kynurenic acid in the preparation of drugs for improving or treating hyperuricemia.

4. A drug for improving or treating hyperuricemia, characterized in that: The invention comprises kynurenic acid and a pharmaceutically acceptable carrier.

5. A drug for improving or treating hyperuricemia, characterized in that: The invention comprises a kynurenic acid structural analogue and a pharmaceutically acceptable carrier, wherein the kynurenic acid structural analogue is 4-hydroxy-6-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxy-8-methoxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid ethyl ester, 4-hydroxyquinoline-3-carboxylic acid, 6-hydroxyquinoline-3-carboxylic acid, 4-hydroxyquinoline, 4-hydroxyquinoline-2-carboxylic acid ethyl ester, xanthurenic acid, 5-hydroxy-2-quinolinecarboxylic acid, 2-hydroxy-4-quinolinecarboxylic acid, 2-carboxylic acid quinoline, 3-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-2-quinolinecarboxylic acid, 8-hydroxy-6-quinolinecarboxylic acid, 8-hydroxy-7-quinolinecarboxylic acid or 4-hydroxy-7-quinolinecarboxylic acid.

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