Use of 3-hydroxyglutaric acid in the preparation of a drug for preventing and / or treating hyperuricemia-related diseases and a preventive and therapeutic drug

Abstract

The application discloses application of 3-hydroxyglutaric acid in preparation of a medicine for preventing and / or treating a high uric acid related disease and a preventive and therapeutic medicine. The application firstly discovers and proves that 3-hydroxyglutaric acid has the activity of reducing the uric acid level in vivo, is a pioneering discovery of new use of known substances, and determines a "treatment window" which is lower than a toxicity threshold and can effectively reduce uric acid through a rigorous dose-effect relationship study. As a metabolic intermediate in vivo, the biological compatibility of 3-hydroxyglutaric acid at a low dose is expected to be better than that of a chemically synthesized medicine, and the potential side effect risk of long-term use is lower.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of 3-hydroxyglutaric acid in the preparation of drugs for the prevention and / or treatment of hyperuricemia-related diseases and related preventive and therapeutic drugs. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] Hyperuricemia (HUA), a global metabolic disease, is experiencing a rising incidence rate and affecting increasingly younger individuals. Sustained high blood uric acid levels are not only a direct cause of gout but also an independent risk factor for chronic kidney disease, cardiovascular disease, insulin resistance, and metabolic syndrome, posing a significant public health burden.

[0004] Existing first-line uric acid-lowering drugs, such as xanthine oxidase inhibitors (allopurinol, febuxostat) and uricosuric agents (benzbromarone), while showing clear efficacy, still face significant challenges in clinical application. Allopurinol may cause severe hypersensitivity syndrome and liver and kidney damage, febuxostat carries a potential risk of cardiovascular events, and benzbromarone has been reported to cause hepatotoxicity. These limitations highlight the urgent need to develop novel uric acid-lowering drugs with novel mechanisms of action, diverse targets, and, most importantly, greater safety profiles.

[0005] 3-Hydroxyglutaric acid (3-Hydroxyglutaric acid) is an endogenous organic acid, an intermediate product in the lysine and tryptophan metabolic pathways, and a hallmark molecule accumulated in rare inherited metabolic disorders such as glutaric acidemia type I. However, to date, no published literature or patents, domestic or international, have revealed any link between 3-Hydroxyglutaric acid and the regulation of uric acid metabolism, nor have there been any reports of its use in lowering uric acid. Summary of the Invention

[0006] In view of the shortcomings of the existing technology, the purpose of this invention is to provide the application of 3-hydroxyglutaric acid in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] As a first aspect of the invention, it provides the use of 3-hydroxyglutaric acid in the preparation of a medicament for the prevention and / or treatment of hyperuricemia-related diseases, said medicament having 3-hydroxyglutaric acid as the active pharmaceutical ingredient and further comprising a pharmaceutically acceptable carrier.

[0009] This invention, through in vitro and in vivo experiments, has for the first time discovered that 3-hydroxyglutaric acid exhibits significant and safe uric acid-lowering activity at physiological concentrations, opening up a completely new direction for its application in the pharmaceutical field.

[0010] In some embodiments of the present invention, the hyperuricemia-related diseases include hyperuricemia and gout.

[0011] In some embodiments of the present invention, the gout includes acute gout and chronic gout.

[0012] The study of this invention found that 3-hydroxyglutaric acid can significantly reduce the level of uric acid in the body, with an effect comparable to that of the traditional drug allopurinol; unlike traditional drugs, 3-hydroxyglutaric acid significantly reduces the content of urea in the serum and can improve kidney function.

[0013] The study of this invention found that, within a certain dosage range, 3-hydroxyglutaric acid has no significant effect on the pathological and functional indicators of the liver and kidneys. Therefore, it has a better protective effect on the liver and kidneys than traditional uric acid-lowering drugs and is suitable for long-term use.

[0014] Current research indicates that approximately two-thirds of the uric acid produced by the liver is excreted through the kidneys. As a crucial step in regulating blood uric acid levels, the URAT1 protein, located on the apical membrane side of renal tubular cells, is responsible for transporting uric acid from the primary urine into the cells; while the GLUT9 protein, located on the basement membrane side of renal tubular cells, is responsible for transporting intracellular uric acid into the bloodstream, completing the reabsorption process. Therefore, URAT1 and GLUT9 are key genes for renal uric acid reabsorption.

[0015] In some embodiments of the present invention, 3-hydroxyglutaric acid can inhibit the expression of GLUT9 or URAT1 in renal cells, suggesting that it may lower uric acid levels by inhibiting renal reabsorption of uric acid.

[0016] In some embodiments of the present invention, the hyperuricemia-related diseases also include uric acid nephropathy caused by hyperuricemia.

[0017] As a second aspect of the present invention, a drug for the prevention and treatment of hyperuricemia-related diseases is also provided, using 3-hydroxyglutaric acid as the active pharmaceutical ingredient.

[0018] In some embodiments of the present invention, the dosage form of the drug is selected from tablets, capsules, injections, pills, granules, ointments, mixtures, or suspensions.

[0019] Furthermore, the injectable agent is an injection solution or a sterile powder for injection.

[0020] In some embodiments of the present invention, 3-hydroxyglutaric acid is dissolved in sterile saline in the drug.

[0021] In some embodiments of the present invention, the dosages used in animal experiments included 20 mg / kg / day, 40 mg / kg / day, and any dosage between 20 mg / kg / day and 40 mg / kg / day, with no significant liver or kidney toxicity observed. Doses below this range are considered safe.

[0022] Compared with the prior art, the beneficial effects achieved by one or more embodiments of the present invention are as follows:

[0023] 1. This invention is the first to propose the use of the endogenous metabolite 3-hydroxyglutaric acid for the prevention and / or treatment of hyperuricemia-related diseases. This discovery breaks through the traditional understanding of those skilled in the art that 3-hydroxyglutaric acid is mainly used as a disease biomarker, and represents the exploration of a new, non-obvious use of a known substance, possessing outstanding substantive features and significant progress.

[0024] 2. The 3-hydroxyglutaric acid provided by this invention has excellent safety potential for the prevention and / or treatment of hyperuricemia-related diseases: Although it is neurotoxic at high concentrations, this invention, through rigorous dose-response studies, has identified a "therapeutic window" below the toxicity threshold that effectively lowers uric acid. As an endogenous metabolic intermediate in the human body, its biocompatibility at low doses is expected to be superior to that of chemically synthesized drugs, and the potential risk of side effects from long-term use is lower.

[0025] 3. The 3-hydroxyglutaric acid provided by this invention for the prevention and / or treatment of hyperuricemia-related diseases has a wide range of sources and diverse applications: 3-hydroxyglutaric acid can be prepared on a large scale and at low cost through chemical synthesis, microbial fermentation, or enzymatic catalysis. It can be prepared into any suitable pharmaceutical dosage form such as tablets, capsules, oral liquids, and granules. Attached Figure Description

[0026] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0027] Figure 1 The statistical results show the effect of 3-hydroxyglutaric acid on the survival rate of 293T cells.

[0028] Figure 2 The following are statistical graphs showing the effects of 3-hydroxyglutaric acid on cellular gene expression; where a represents the transcriptional level of the GLUT9 gene in 293T cells; b represents the expression level of the GLUT9 gene in 293T cells; and c represents the transcriptional level of the GLUT9 gene in HK2 cells. * indicates... p <0.05, ** indicates p <0.01.

[0029] Figure 3 Statistical graphs showing the effects of 3-hydroxyglutaric acid on body weight and serum uric acid levels in a hyperuricemia model mouse; where a is the change in body weight over time; b is the serum uric acid level on day 8; c is the serum uric acid level on day 16; and d is the serum uric acid level on day 24. * indicates comparison with the model group. p <0.05, ** indicates p <0.01, *** indicates p <0.001, **** indicates p <0.0001.

[0030] Figure 4 Statistical graphs showing the effects of 3-hydroxyglutaric acid on serum liver and kidney function indicators in hyperuricemia model mice are presented. Specifically, a represents serum urea levels; b represents serum creatinine levels; c represents serum alanine aminotransferase (ALT) levels; d represents serum aspartate aminotransferase (AST) levels; e represents serum total bilirubin levels; f represents serum alkaline phosphatase (ALP) levels; g represents serum albumin levels; and h represents serum total protein levels. * indicates comparison with the model group, and # indicates comparison with the allopurinol group. * and # indicate... p <0.05, ** and ## indicate p <0.01, *** indicates p <0.001, **** indicates p <0.0001.

[0031] Figure 5 The following is a statistical graph showing the effects of 3-hydroxyglutaric acid on the pathological damage of the liver and kidneys in a mouse model of hyperuricemia. In the graph, a represents the H&E staining of liver tissue from the control group; b represents the H&E staining of liver tissue from the model group; c represents the H&E staining of liver tissue from the allopurinol group; d represents the H&E staining of liver tissue from the low-dose 3-hydroxyglutaric acid group; e represents the H&E staining of liver tissue from the high-dose 3-hydroxyglutaric acid group; f represents the H&E staining of kidney tissue from the control group; g represents the H&E staining of kidney tissue from the model group; h represents the H&E staining of kidney tissue from the allopurinol group; i represents the H&E staining of kidney tissue from the low-dose 3-hydroxyglutaric acid group; and j represents the H&E staining of kidney tissue from the high-dose 3-hydroxyglutaric acid group.

[0032] Figure 6 The following are statistical graphs showing the effects of 3-hydroxyglutaric acid on body weight and serum uric acid levels in healthy mice; where a is the change in body weight over time; b is the serum uric acid level on day 8; c is the serum uric acid level on day 16; and d is the serum uric acid level on day 24. * indicates a comparison with the control group. p <0.05.

[0033] Figure 7 The following are statistical graphs showing the effects of 3-hydroxyglutaric acid on liver and kidney function indicators in the serum of healthy mice: a) serum creatinine level; b) serum alanine aminotransferase (ALT) level; c) serum aspartate aminotransferase (AST) level; d) serum total bilirubin level; e) serum alkaline phosphatase (ALP) level; f) serum albumin level; and g) serum total protein level.

[0034] Figure 8 The following is a statistical graph showing the effects of 3-hydroxyglutaric acid on pathological damage to the liver and kidneys of healthy mice; where a is the H&E staining image of liver tissue in the control group; b is the H&E staining image of liver tissue in the 3-hydroxyglutaric acid group; c is the H&E staining image of kidney tissue in the control group; and d is the H&E staining image of kidney tissue in the 3-hydroxyglutaric acid group.

[0035] Figure 9 This is a statistical graph showing the effect of 3-hydroxyglutaric acid on the transcription of uric acid transporter genes in the kidneys of hyperuricemic mouse models; where a represents the transcriptional level of the GLUT9 gene; and b represents the transcriptional level of the URAT1 gene. * indicates comparison with the model group. p <0.05, *** indicates p <0.001.

[0036] Figure 10 This is a statistical graph showing the effect of 3-hydroxyglutaric acid on the transcription of uric acid transporter genes in the kidneys of healthy mice; where a represents the transcriptional level of the GLUT9 gene; and b represents the transcriptional level of the URAT1 gene. * indicates comparison with the control group. p <0.05, **** indicates p <0.0001. Detailed Implementation

[0037] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0038] The present invention will be further described below with reference to the embodiments.

[0039] Example 1

[0040] Effects of 3-hydroxyglutaric acid on cell viability

[0041] 293T and HK2 cells were purchased from the Stem Cell Bank of the Chinese Academy of Sciences (https: / / www.cellbank.org.cn / ejianjie.php). In this study, 293T cells were cultured in high-glucose DMEM (Gibco) medium supplemented with 10% (v / v) fetal bovine serum and 1% (v / v) penicillin-streptomycin (Gibco). HK2 cells were cultured in DMEM / F-12 medium (Gibco) containing 10% (v / v) fetal bovine serum and 1% (v / v) penicillin-streptomycin. Cells were seeded in 96-well plates at a density of 5000 cells per well with 0.1 mL of medium. After 16 hours, cells were treated with different concentrations of 3-hydroxyglutaric acid (0, 0.1 mM, 0.4 mM, 2.0 mM, 10 mM, and 50 mM, 3-hydroxyglutaric acid dissolved in sterile physiological saline) for 12 hours. The toxicity of the drug to cells was assessed using a Cell-Counting kit (CCK8, 40203ES60, Yeasen, Shanghai, China).

[0042] As a result, the analysis results of the Cell-Counting kit (CCK8) showed that ( Figure 1 In this experiment, 0.1 mM, 0.4 mM and 2 mM concentrations of 3-hydroxyglutaric acid had no significant effect on the viability of 293T cells. After treatment with 10 mM concentration of 3-hydroxyglutaric acid, the cell survival rate was less than 80%, indicating that cytotoxicity began to be shown. At a concentration of 50 mM, cytotoxicity was obvious.

[0043] Example 2

[0044] Effects of 3-hydroxyglutaric acid on cellular gene expression

[0045] 293T and HK2 cells were seeded in 24-well plates at a density of 1 × 10⁻⁶ cells per well. 5Cells were cultured in 0.5 mL of medium. After 16 hours, cells were treated with different concentrations of 3-hydroxyglutaric acid (50 μL of drug added to each well, with final concentrations of 0, 0.4 mM, 2.0 mM, and 10 mM, 3-hydroxyglutaric acid dissolved in sterile physiological saline) for 12 hours. The culture medium was then removed, and RT-qPCR and Western blot analyses were performed. Total RNA was extracted from the cells using the SteadyPure RNA Extraction Kit (AG21017, Accurate Biology). Genomic DNA (gDNA) was removed and complementary DNA (cDNA) was synthesized using the Evo M-MLV RT Mix Kit with gDNA Clean for qPCR Ver.2 (AG11728, Accurate Biotechnology). qPCR detection: The expression of the uric acid transporter GLUT9 (solute carrier family 2, member 9, also known as SLC2A9) gene was detected using a SYBR Green kit (AG11701, Accurate Biotechnology) on a Roche LightCycler® 480II real-time quantitative PCR system. Primer sequences used for RT-qPCR are shown in Table 1. Relative expression level calculation: The relative expression level of the gene was calculated using the 2-ΔΔCt formula.

[0046] Table 1. Primer sequences used in this study

[0047]

[0048] Western blot analysis:

[0049] Total cellular protein was extracted and separated by 10% SDS-PAGE. Protein samples were transferred to activated PVDF membranes and blocked with 5% skim milk for 1 hour. The membranes were then incubated overnight at 4°C with the following primary antibodies: anti-β-actin (1:4000 dilution, AC026, ABclonal) and anti-GLUT9 (1:1000 dilution, 26486-1-AP, Proteintech). The following day, the membranes were incubated with the corresponding secondary antibodies for 1.5 hours. Protein bands were visualized using a chemiluminescence imaging system (Analytik Jena, Germany) and analyzed for grayscale using ImageJ.

[0050] Figure 2 The results of the transcription and expression levels of the GLUT9 gene in 293T cells (a and b) indicated that 3-hydroxyglutaric acid dose-dependently inhibited the transcription and expression levels of the GLUT9 gene in 293T cells. Meanwhile, Figure 2c indicates that 3-hydroxyglutaric acid inhibits the transcription level of the GLUT9 gene in HK2 cells.

[0051] Example 3

[0052] 3-Hydroxyglutaric acid intervention in hyperuricemia model mice

[0053] After one week of acclimatization, 50 male C57BL / 6JNifdc mice aged 6-8 weeks and weighing 21-24g were randomly divided into 5 groups (n=10 per group), with no significant difference in weight between the groups. The treatments for each group were as follows: (1) Control group: 0.5% sodium carboxymethyl cellulose (CMC-Na) solution was administered by gavage; (2) Model group: hypoxanthine (300 mg / kg / d, H108384, Aladdin, Shanghai) and potassium oxonate (300 mg / kg / d, A601238, Sangon Biotech, Shanghai) mixed solution was administered by gavage; (3) Allopurinol group: Allopurinol solution (10 mg / kg / d, TA09075G, Sinopharm Chemical Reagent Co., Ltd., Shanghai) was administered by gavage on the basis of the model group; (4) Low-dose 3-hydroxyglutaric acid (Hya-L group): 3-hydroxyglutaric acid (20 mg / kg / d, H915109, Maclean, Shanghai) solution was administered by gavage on the basis of the model group; (5) High-dose 3-hydroxyglutaric acid group (Hya-H group): 3-hydroxyglutaric acid (40 mg / kg / d) was administered by gavage on the basis of the model group. Drug intervention began 2 hours after administration of the modeling drug. Patients were weighed every 6-8 days, and blood was collected from the retro-orbital venous plexus after a 12-hour fast.

[0054] Mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. and housed in a standard laboratory animal barrier environment (12 h / 12 ​​h light / dark cycle, humidity 50±15%, temperature 22±2℃). All procedures followed the "Guidelines for the Household and Use of Laboratory Animals" (8th edition, ISBN-10: 0-309-15396-4). The experimental protocol was approved by the Bioethics and Biosafety Review Board (BGI-IRB) of the Jinan Microecology Biomedical Shandong Laboratory.

[0055] Figure 3 The results showed that low and high doses of 3-hydroxyglutaric acid did not significantly affect the body weight of mice with hyperuricemia. Figure 3 The serum uric acid levels on days 8 (b), 16 (c), and 24 (d) showed that on day 8, 3-hydroxyglutaric acid did not reduce the serum uric acid level in hyperuricemic mice; on days 16 and 24, both low-dose and high-dose 3-hydroxyglutaric acid significantly reduced the serum uric acid level in mice, and the effect was comparable to that of the positive control drug allopurinol (10 mg / kg / d).

[0056] Example 4

[0057] 3-Hydroxyglutaric acid intervention in healthy mice

[0058] After one week of acclimatization, 20 male C57BL / 6JNifdc mice aged 6-8 weeks and weighing 21-24g were randomly divided into two groups (n=10 per group), with no significant difference in weight between the groups. The treatments for each group were as follows: (1) Control group: administered 0.5% sodium carboxymethyl cellulose (CMC-Na) solution by gavage; (2) 3-hydroxyglutaric acid group (Hya group): administered 3-hydroxyglutaric acid (40mg / kg / d) by gavage in addition to the treatment for the control group. After the experiment, the mice were anesthetized and their serum was collected.

[0059] Figure 6 The results showed that oral administration of 40 mg / kg / d 3-hydroxyglutaric acid did not affect the body weight of healthy mice. Figure 6 Results in b and c indicated that, on days 8 and 16, gavage administration of 40 mg / kg / d 3-hydroxyglutaric acid did not affect serum uric acid levels in healthy mice. Figure 6 The results showed that continuous gavage administration of 40 mg / kg / d 3-hydroxyglutaric acid for 24 days reduced serum uric acid levels in healthy mice.

[0060] Example 5

[0061] Effects of 3-hydroxyglutaric acid on serum uric acid and other blood biochemical indicators in mice

[0062] Whole blood was collected from euthanized mice, and serum was separated by centrifugation at 3000 rpm for 15 min at 4°C. The following indicators were strictly measured according to the kit instructions: uric acid (E-BC-K016-M, Elabscience) and urea (E-BC-K183-M, Elabscience). The following indicators were measured using a Mindray BS800M blood biochemistry analyzer: alanine aminotransferase (ALT, 105-001389-00), aspartate aminotransferase (AST, 105-001390-00), alkaline phosphatase (ALP, 105-001391-00), total bilirubin (T-bil-V, 105-001401-00), creatinine (105-001404-00), albumin (ALB, 105-001397-00), and total protein (105-015580-00).

[0063] In a mouse model of hyperuricemia Figure 4 The results showed that, compared with the model group and the allopurinol group, low-dose and high-dose 3-hydroxyglutaric acid significantly reduced serum urea levels, indicating improved renal function. Figure 4 The results showed that, compared with the model group, high-dose 3-hydroxyglutaric acid significantly reduced serum creatinine levels. Figure 4The results showed that low and high doses of 3-hydroxyglutaric acid did not affect the level of alanine aminotransferase in mouse serum. Figure 4 The results showed that, compared with the model group, low-dose and high-dose 3-hydroxyglutarate significantly reduced the level of serum aspartate aminotransferase. Figure 4 The results of serum total bilirubin level (e), serum alkaline phosphatase level (f), serum albumin level (g), and serum total protein level (h) showed that low and high doses of 3-hydroxyglutaric acid did not affect the levels of total bilirubin, alkaline phosphatase, albumin, and total protein in mouse serum. These results indicate that low doses (20 mg / kg / d) and high doses (40 mg / kg / d) of 3-hydroxyglutaric acid did not cause significant liver and kidney dysfunction.

[0064] In healthy mice, such as Figure 7 The results, shown in a for example, indicate that serum creatinine levels (a), serum alanine aminotransferase levels (b), serum aspartate aminotransferase levels (c), serum total bilirubin levels (d), serum alkaline phosphatase levels (e), serum albumin levels (f), and serum total protein levels (g), demonstrate that oral administration of 40 mg / kg / d of 3-hydroxyglutaric acid did not affect the levels of serum creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, albumin, and total protein in healthy mice. This suggests that 3-hydroxyglutaric acid does not affect the function of the liver and kidneys in healthy mice.

[0065] Example 6

[0066] Histopathological analysis of mouse liver and kidney tissue sections

[0067] Liver and kidney tissues were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, stained with hematoxylin and eosin (H&E), and observed under a microscope to assess the degree of pathological damage.

[0068] In a mouse model of hyperuricemia, such as Figure 5 H&E staining images of liver tissue from control group (a), model group (b), allopurinol group (c), low-dose 3-hydroxyglutaric acid group (d), and high-dose 3-hydroxyglutaric acid group (e); H&E staining images of kidney tissue from control group (f), model group (g), allopurinol group (h), low-dose 3-hydroxyglutaric acid group (i), and high-dose 3-hydroxyglutaric acid group (j) show that low-dose (20 mg / kg / d) and high-dose (40 mg / kg / d) 3-hydroxyglutaric acid did not cause significant pathological damage to liver and kidney tissues, indicating the high safety of 3-hydroxyglutaric acid.

[0069] In healthy mice, such as Figure 8The H&E staining images of liver tissue in the control group (a), liver tissue in the L-galactose group (b), kidney tissue in the control group (c), and kidney tissue in the L-galactose group (d) show that oral administration of 40 mg / kg / d 3-hydroxyglutaric acid did not cause significant pathological damage to the liver and kidney tissues of healthy mice, indicating that 3-hydroxyglutaric acid has high safety.

[0070] Example 7

[0071] Analysis of transcriptional levels of uric acid transporter gene in mouse kidney

[0072] Kidney tissues were collected from mice, and total RNA was extracted using the SteadyPure RNA Extraction Kit (AG21017, AccurateBiology). The transcriptional differences between the uric acid transporter GLUT9 (solute carrier family 2, member 9, also known as SLC2A9) and URAT1 genes in kidney tissues were detected using RT-PCR. Primer sequences used for RT-qPCR are shown in Table 2. Relative expression levels were calculated using the 2-ΔΔCt formula.

[0073] Table 2. Primer sequences used in this study

[0074]

[0075] In a mouse model of hyperuricemia, such as Figure 9 The results of GLUT9 gene transcription level shown in a and URAT1 gene transcription level shown in b show that low dose (20 mg / kg / d) and high dose (40 mg / kg / d) of 3-hydroxyglutaric acid significantly reduced the transcription level of URAT1 gene in kidney tissue; and high dose (40 mg / kg / d) of 3-hydroxyglutaric acid significantly reduced the transcription level of GLUT9 gene in kidney.

[0076] In healthy mice, such as Figure 10 The results of GLUT9 gene transcription level shown in a and URAT1 gene transcription level shown in b show that oral administration of 40 mg / kg / d 3-hydroxyglutaric acid significantly reduced the transcription levels of GLUT9 and URAT1 genes in kidney tissue.

[0077] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

The use of 1,3-hydroxyglutaric acid in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, The drug uses 3-hydroxyglutaric acid as its active pharmaceutical ingredient and also includes a pharmaceutically acceptable carrier. The hyperuricemia-related diseases mentioned are hyperuricemia, gout, or uric acid nephropathy caused by hyperuricemia.

2. The use of 3-hydroxyglutaric acid according to claim 1 in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, The gout mentioned includes acute gout and chronic gout.

3. The use of 3-hydroxyglutaric acid according to claim 1 in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, 3-Hydroxyglutarate inhibits the expression of GLUT9 or URAT1 in the kidneys.

4. The use of 3-hydroxyglutaric acid according to claim 1 in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, 3-Hydroxyglutaric acid lowers uric acid levels by inhibiting the reabsorption of uric acid by the kidneys.

5. The use of 3-hydroxyglutaric acid according to claim 1 in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, The dosage form of the drug is selected from tablets, capsules, injections, pills, granules, ointments, mixtures, or suspensions.

6. The use of 3-hydroxyglutaric acid according to claim 5 in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, The injection is an injection solution or a sterile powder for injection.

7. The use of 3-hydroxyglutaric acid according to claim 6 in the preparation of medicaments for the prevention and / or treatment of hyperuricemia-related diseases, characterized in that, In the injection, 3-hydroxyglutaric acid is dissolved in sterile physiological saline.

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