Composition for reducing uric acid as well as preparation and application thereof

Abstract

The invention belongs to the technical field of food processing and medicine preparation, and particularly relates to a uric acid reducing composition and a preparation and application thereof. According to the invention, the functional active components capsaicin and quercitrin in hot pepper are found for the first time and both have prevention and improvement effects on hyperuricemia. The two medicines can inhibit activity of purine metabolism key enzyme, promote excretion of uric acid, reduce oxidative stress and inflammatory factor level of a body, delay pathological process of hyperuricemia and protect liver and kidney functions, and do not cause liver and kidney injury and other side effects after long-term use. Moreover, the uric acid reducing effect of cooperative intervention of the capsaicin and the quercitrin, the improvement effect on hyperuricemia and the molecular mechanism of the hyperuricemia are clarified from multiple aspects, and it is proved that the capsaicin and the quercitrin are compounded according to a certain proportion to achieve synergistic interaction. Capsaicin and quercitrin are taken as active ingredients and can be used for developing health care products and medicines with the uric acid reducing effect.

Description

Technical Field

[0001] This invention belongs to the field of food processing and pharmaceutical preparation technology, specifically relating to a uric acid-lowering composition, its formulation, and its application. Background Technology

[0002] Hyperuricemia (HUA) is a chronic metabolic disease characterized by abnormally high serum uric acid levels. With societal development, the prevalence of hyperuricemia has been steadily increasing, and it is now the second most prevalent metabolic disease worldwide. Hyperuricemia not only leads to urate deposition and gout, but also causes diabetes, hypertension, and atherosclerosis. The pathogenesis mainly involves excessive uric acid production and insufficient excretion. Uric acid production is primarily regulated by key enzymes in purine metabolism in the liver, while excretion mainly involves the kidneys (70%) and intestines (30%). Uric acid excretion through the kidneys is typically regulated by urate transport proteins. Increased expression of urate anion transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and decreased expression of ornithine aminotransferase (OAT) 1 and 3, lead to hyperuricemia. Studies have shown that xanthine oxidase (XOD) in the liver causes oxidative damage, which in turn activates the TLR4 / Myd88 / NF-κB signaling pathway and the NOD-like receptor thermoprotein domain 3 (NLRP3) inflammasome, leading to kidney damage and consequently reduced renal uric acid excretion.

[0003] Inhibiting xanthine oxidase activity to lower uric acid levels is a target of many chemical drugs. For example, first-line xanthine inhibitors used clinically include allopurinol and febuxostat. Intervening in xanthine oxidase in the body is an effective measure for preventing and treating hyperuricemia. Although these drugs are effective in lowering uric acid levels, they have significant side effects, easily damaging kidney function, and long-term use may cause gastrointestinal, liver, and kidney damage. Therefore, a new method for lowering uric acid is urgently needed to overcome this problem. Summary of the Invention

[0004] The purpose of this invention is to provide a uric acid-lowering composition, its formulation, and its application, which inhibits the activity of key enzymes in purine metabolism, promotes uric acid excretion, reduces oxidative stress and inflammation levels in the body, slows the pathological progression of hyperuricemia, and protects liver and kidney function.

[0005] This invention provides the use of capsaicin and / or quercetin in one or more of the following: (1) Preparation of uric acid-lowering products; said products include health products or pharmaceuticals; (2) Prepare drugs for the prevention and / or treatment of hyperuricemia.

[0006] The present invention provides a uric acid-lowering composition comprising capsaicin and quercetin; wherein the mass ratio of capsaicin to quercetin is (1~7):1.

[0007] This invention provides the application of the uric acid-lowering composition described above in one or more of the following: (1) Preparation of uric acid-lowering products; said products include health products or pharmaceuticals; (2) Prepare drugs for the prevention and / or treatment of hyperuricemia.

[0008] Preferably, the dosage form of the product or drug includes tablets, capsules, powders, or granules.

[0009] This invention provides a uric acid-lowering product, including uric acid-lowering health supplements and / or uric acid-lowering drugs, wherein the uric acid-lowering health supplements include the uric acid-lowering composition described in the above technical solution and food-grade acceptable excipients; The uric acid-lowering drug includes the uric acid-lowering composition described in the above technical solution and pharmaceutically acceptable excipients.

[0010] The present invention provides a uric acid-lowering tablet comprising the uric acid-lowering composition described above, a lubricant, and a binder.

[0011] Preferably, the uric acid-lowering tablets comprise 50-70% uric acid-lowering composition, 5-15% lubricant, and 20-40% binder, by weight percentage.

[0012] Preferably, the lubricant comprises magnesium stearate.

[0013] Preferably, the adhesive comprises maltodextrin.

[0014] The present invention provides a method for preparing uric acid-lowering tablets as described above, wherein the uric acid-lowering composition, lubricant and binder are mixed, compressed into tablets, and coated to obtain uric acid-lowering tablets.

[0015] Beneficial effects: This invention is the first to discover that capsaicin and quercetin, the functional active ingredients in chili peppers, both have preventive and ameliorative effects on hyperuricemia. Both can inhibit the activity of key enzymes in purine metabolism, promote uric acid excretion, reduce oxidative stress and inflammatory factor levels in the body, delay the pathological progression of hyperuricemia, protect liver and kidney function, and do not cause liver or kidney damage or other side effects with long-term use. Furthermore, this invention elucidates the synergistic uric acid-lowering effect of capsaicin and quercetin, as well as their ameliorative effect on hyperuricemia and their molecular mechanisms, demonstrating that capsaicin and quercetin, when combined in a certain ratio, have a synergistic effect. Using capsaicin and quercetin as active ingredients, they can be used to develop health products and pharmaceuticals with uric acid-lowering effects. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0017] Figure 1 Results of biochemical index measurements in mice from different treatment groups; Figure 2 HE staining of liver tissue from mice in different treatment groups; Figure 3 HE staining of kidney tissue from mice in different treatment groups; Figure 4 The expression of key enzymes in purine metabolism mRNA in the liver of mice in different treatment groups; Figure 5 Results of detection of key transporter proteins excreted by the kidneys of mice in different treatment groups; Figure 6 The expression of key gene mRNAs in the kidneys of mice in different treatment groups; Among them, compared with the normal control group, * p <0.05、** p <0.01、*** p <0.001、**** p <0.0001; compared with the hyperuricemia model group, # p <0.05、 ## p <0.01、 ### p <0.001、 #### p <0.0001. Detailed Implementation

[0018] The present invention provides the use of capsaicin and / or quercetin in one or more of the following: (1) preparing uric acid-lowering products; said products include health products or pharmaceuticals; (2) preparing drugs for the prevention and / or treatment of hyperuricemia.

[0019] The present invention provides a uric acid-lowering composition comprising capsaicin and quercetin; wherein the mass ratio of capsaicin to quercetin is (1~7):1.

[0020] In one embodiment, the mass ratio of capsaicin to quercetin in this invention is 2:1. This invention can take any value within the range of (1~7):1, where capsaicin and quercetin synergistically reduce uric acid levels.

[0021] The present invention provides the application of the uric acid-lowering composition described in the above technical solution in one or more of the following: (1) preparing uric acid-lowering products; said products include health products or pharmaceuticals; (2) preparing drugs for the prevention and / or treatment of hyperuricemia.

[0022] As one implementation method, the dosage form of the product or drug of the present invention includes tablets, capsules, powders or granules.

[0023] This invention provides a uric acid-lowering product, including uric acid-lowering health supplements and / or uric acid-lowering pharmaceuticals. The uric acid-lowering health supplements include the uric acid-lowering composition described in the above technical solution and food-grade excipients. The uric acid-lowering pharmaceuticals include the uric acid-lowering composition described in the above technical solution and pharmaceutically acceptable excipients.

[0024] The present invention provides a uric acid-lowering tablet comprising the uric acid-lowering composition described above, a lubricant, and a binder.

[0025] In one embodiment, the uric acid-lowering tablets of the present invention, by weight percentage, comprise 50-70% uric acid-lowering composition, 5-15% lubricant, and 20-40% binder. In another embodiment, the uric acid-lowering tablets of the present invention, by weight percentage, comprise 60% uric acid-lowering composition, 10% lubricant, and 30% binder. In one embodiment, the lubricant comprises magnesium stearate. In another embodiment, the binder comprises maltodextrin. The present invention uses magnesium stearate as a lubricant and maltodextrin as a binder. Magnesium stearate has good lubricity, can adhere to the surface of powder particles and the inner wall of the die, reducing the frictional resistance between the powder and the punch and die orifice, ensuring a continuous and smooth tableting process, and reducing equipment wear. Maltodextrin helps the powder to form during compression and has stable chemical properties, making it less likely to interact with drugs.

[0026] This invention provides a method for preparing uric acid-lowering tablets as described above. The method involves mixing a uric acid-lowering composition, a lubricant, and a binder, compressing the mixture into tablets, and then coating them to obtain uric acid-lowering tablets. This invention does not impose strict requirements on the specific steps of tableting and coating; conventional methods in the art can be used, such as employing a tablet press. To further illustrate the present invention, a uric acid-lowering composition, its formulation, and its application are described in detail below with reference to the accompanying drawings and embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0027] Example 1 Animal experiments 1. Experimental Animals: Healthy male C57BL / 6 mice, aged 6 weeks (License: SCXK (JING) 019-0010), were purchased from Spiford (Beijing) Biotechnology Co., Ltd. They were housed in a standard laboratory animal facility at a constant temperature of (22 ± 2)℃ with a 12-hour light / 12-hour dark cycle. All mice had free access to food and water. This experiment was approved by the Experimental Animal Ethics Committee of Hebei Agricultural University (Ethics Approval Code: No. 2022126).

[0028] 2. Model construction and administration method The experimental animals were randomly divided into 6 treatment groups, with 10 mice in each group, in the following order: normal control group (CK), hyperuricemia model group (HUA), allopurinol positive control group (ALLO), capsaicin group (Cap), quercetin group (Quer), and capsaicin and quercetin 3:1 combined treatment group (Cap+Quer / 3:1). Except for the CK group, the mice in the above groups were administered potassium oxonate (200 mg / kg) combined with adenine (50 mg / kg) by gavage daily to induce hyperuricemia. One week after modeling, drug intervention was carried out according to the method in Table 1.

[0029] Table 1. Administration methods for mice in different treatment groups

[0030] Test Example 1 1. Weight and organ index testing In Example 1, mouse weight was recorded weekly. After the final weighing, mice in each treatment group were sacrificed, and their liver and kidney tissues were washed in pre-cooled 0.9% saline solution. After drying with filter paper, the wet weight of each tissue was measured, and the organ index (%) was calculated using the formula. The results are shown in Tables 2 and 3. Organ index (%) = organ wet weight (g) / final mouse weight (g) × 100%.

[0031] Table 2. Body weight of mice in each treatment group

[0032] Note: Different lowercase letters represent significant differences between different groups at the same time, and the same applies below.

[0033] As shown in Table 2, there was no significant difference in body weight among the groups of mice during the first week of the experiment. p>0.05). Starting from the second week, compared with the normal control group, the body weight of mice in the model group and each intervention group was significantly reduced ( p The value <0.05 indicates that potassium oxonate combined with adenine can induce a decrease in mouse body weight, indicating successful modeling. From the third week onwards, except for the model group, the body weight of mice in each intervention group showed a gradual upward trend. By the fourth week of the experiment, the body weight of mice in each intervention group had approached the level of the normal control group. Among them, the Cap+Quer / 3:1 group showed the most significant effect on the recovery of mouse body weight, which was superior to the single-component intervention group.

[0034] Table 3 Organ indices of mice in each treatment group

[0035] The liver and kidneys are the main organs for uric acid production and metabolism, and their organ indices change in response to the body's uric acid levels. As shown in Table 3, compared with the normal control group, the kidney and liver indices of the model group mice were significantly increased (…). p <0.05). After intervention with capsaicin and quercetin, the kidney and liver indices of mice in each treatment group were significantly reduced ( p The concentration of <0.05 indicates that these two active ingredients have a protective effect on liver and kidney tissues. The combined intervention group of capsaicin and quercetin showed significantly better improvement in kidney index than the single-ingredient intervention group, indicating that the two have a synergistic effect in alleviating kidney damage.

[0036] 2. Biochemical indicator testing Excessive accumulation of uric acid (UA) in the kidneys can induce oxidative stress, a process considered a significant risk factor for the development of chronic kidney disease. In hyperuricemia, oxidative stress markers such as superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) play crucial regulatory roles. SOD and CAT are important antioxidant enzymes in the body, while MDA levels directly reflect the degree of tissue oxidative damage. Uric acid dysfunction in the human body is primarily mediated by the kidneys, and blood urea nitrogen (BUN) and creatinine (CRE) levels are important biochemical indicators for assessing kidney function. BUN is a metabolite of protein metabolism, and CRE is a metabolite of muscle metabolism; elevations in both directly reflect the severity of kidney damage. Inflammation is one of the important pathological features of hyperuricemia, and its occurrence and development are closely related to the abnormal activation of pro-inflammatory cytokine networks.

[0037] Based on the above principles, 21 days after administration to each treatment group in Example 1, serum uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels, as well as renal superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and catalase (CAT) activity were measured using commercial kits. The results are as follows: Figure 1 As shown, (A) is serum uric acid content, (B) is malondialdehyde content, tumor necrosis factor-α content, (C) is interleukin-6 content, (D) is interleukin-1β content, (E) is blood urea nitrogen content, (F) is creatinine content, (G) is superoxide dismutase activity, (H) is malondialdehyde activity, and (I) is catalase activity.

[0038] according to Figure 1 As shown in Figure (A), compared with the normal control group (45.67 ± 10.60), the serum uric acid level in the model group mice (124.95 ± 32.11) was significantly higher. p The value <0.05 indicates that the hyperuricemia model was successfully established. After intervention with capsaicin and quercetin, the uric acid levels in mice in all treatment groups were significantly reduced. The combined capsaicin and quercetin intervention group (57.84 ± 6.18) showed a significantly better uric acid-lowering effect than the single treatment groups of capsaicin (70.40 ± 18.88) and quercetin (92.04 ± 9.67). Capsaicin and quercetin have a synergistic effect in improving uric acid metabolism.

[0039] according to Figure 1 As shown in (B) to (D), compared with the normal control group, the activities of CAT (38.14 ± 8.48) and SOD (125.43 ± 10.82) in the kidneys of mice in the model group were significantly reduced, while the level of MDA (3.98 ± 0.24) was significantly increased. p <0.05 indicates that hyperuricemia leads to significant oxidative stress damage to the kidneys. After intervention, the antioxidant indicators of each treatment group showed an improving trend. Compared with the model group, the MDA content of the capsaicin treatment group (1.57 ± 0.06), quercetin treatment group (2.05 ± 0.12), and combined treatment group (1.65 ± 0.17) was significantly reduced. Meanwhile, the SOD activity of the capsaicin treatment group (184.00 ± 7.79), quercetin treatment group (263.65 ± 9.11), and combined treatment group (285.00 ± 9.79) was significantly increased. p <0.05). Capsaicin and quercetin have a synergistic effect, which can improve renal oxidative stress by enhancing antioxidant enzyme activity and reducing lipid peroxidation damage.

[0040] according to Figure 1 As shown in Figures (E) to (F), compared with the normal control group, the serum levels of BUN (25.43 ± 1.18) and CRE (89.08 ± 15.76) in the model group mice were significantly increased. p <0.001 indicates that hyperuricemia leads to impaired renal function, consistent with previous studies. After drug intervention, renal function indicators in all treatment groups showed significant improvement. The capsaicin group (BUN 14.11 ± 0.63) and CRE 31.61 ± 2.55), the quercetin group (BUN 19.04 ± 1.35) and CRE 41.78 ± 6.61), and the combined intervention group (BUN 13.12 ± 0.60) and CRE 28.80 ± 8.10) were all significantly lower than those in the model group. p <0.05). This indicates that the combined intervention group showed the best renal function protection effect, and its indicators improved significantly better than those of the single-drug treatment group.

[0041] according to Figure 1 As shown in (G)~(H), compared with the normal control group, the expression levels of key inflammatory mediators such as TNF-α (967.60 ± 37.95 pg / mL), IL-1β (111.18 ± 3.25 pg / mL), and IL-6 (79.33 ± 1.12 pg / mL) in the serum of hyperuricemic mice were significantly upregulated. p <0.01). Notably, after intervention with capsaicin and quercetin, the levels of the above-mentioned inflammatory markers in the serum of mice in each treatment group showed a significant decreasing trend ( p <0.05), indicating that capsaicin and quercetin improve the pathological process of hyperuricemia by regulating inflammation levels.

[0042] 3. Liver histopathological examination As the main organ for uric acid production, the liver is prone to pathological changes in hyperuricemia. In Example 1, after 21 days of drug administration to each treatment group, mice were dissected, and livers were fixed, embedded, and prepared into paraffin sections and frozen sections. After staining with hematoxylin and eosin (H&E), the tissue morphology was observed using an optical microscope. The results are as follows: Figure 2 As stated above.

[0043] according to Figure 2As can be seen, compared with the normal control group, the livers of mice in the model group exhibited typical pathological features: a large number of hepatocytes showed mild edema (yellow arrows), characterized by increased cell volume and loose, pale cytoplasm. After drug intervention, the degree of hepatocyte edema improved in all treatment groups, but scattered small round vacuoles (black arrows) could still be observed in the hepatocyte cytoplasm. This indicates that the metabolic disorder has not been completely reversed. The mild disorder of hepatic cord arrangement in the model group was significantly improved in the treatment group, indicating that the drug has a positive effect on liver structure repair.

[0044] 4. Kidney histopathological examination In hyperuricemia, the kidneys are prone to both functional and organic damage. In Example 1, after 21 days of drug administration to each treatment group, mice were dissected, and kidneys were fixed, embedded, and prepared into paraffin sections and frozen sections. After staining with hematoxylin and eosin (H&E), the tissue morphology was observed using an optical microscope. The results are as follows: Figure 3 As stated above.

[0045] according to Figure 3 As can be seen, the renal cortex of the model group mice exhibited the following characteristic changes: significantly reduced glomerular volume, punctate necrosis of renal tubular epithelial cells (red arrows), swollen cells, and loose, pale cytoplasm; markedly dilated renal tubules (brown arrows), flattened epithelial cells, and necrotic cell fragments and sloughed epithelial cells visible within the lumen; and localized renal tubular atrophy (gray arrows). These pathological changes are consistent with the characteristics of renal damage such as renal tubular dilation reported in previous studies of hyperuricemia, indicating that the model was successfully established. After drug intervention, all treatment groups showed varying degrees of improvement in the pathological changes such as glomerular volume reduction, renal tubular dilation, and atrophy, but cellular edema still existed (black arrows). Notably, the combined intervention group of capsaicin and quercetin showed significantly better improvement in renal tissue structure than the single-component intervention group, suggesting that the two may have a synergistic effect in renal protection.

[0046] 5. Detection of gene expression of key enzymes in liver purine metabolism Phosphoribose pyrophosphate synthase (PRPS) is responsible for catalyzing the first step in purine nucleotide biosynthesis, namely, catalyzing the reaction of ATP and 5-phosphate ribose to produce phosphoribose pyrophosphate. PRPS activity directly affects the balance of purine levels in the body. When PRPS expression is elevated, purine biosynthesis accelerates, increasing purine levels and consequently leading to increased uric acid synthesis. Adenosine deaminase (ADA) plays a crucial role in nucleic acid catabolism, catalyzing the deamination of adenine or deoxyadenine nucleosides to generate hypoxanthine nucleosides, which are then further converted to hypoxanthine by enzymatic action. Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage synthesis pathway. This enzyme reversibly catalyzes the phosphorylation of purine nucleosides, breaking down the substrate purine nucleoside into the corresponding purine base and ribose-1-phosphate. Xanthine oxidase (XOD) is the rate-limiting enzyme in the purine nucleoside metabolic pathway and plays a leading role in the pathogenesis of hyperuricemia. It is responsible for the breakdown and metabolism of hypoxanthine and xanthine, with the final product being uric acid.

[0047] Based on the above principles, 21 days after administration to each treatment group in Example 1, total RNA was extracted using an animal tissue RNA rapid extraction kit, and the concentration and purity of the RNA were determined. Subsequently, cDNA was synthesized using FastKing one-step genomic cDNA first-strand synthesis premix reagent. Finally, real-time quantitative PCR was performed using FastReal rapid fluorescence quantitative PCR premix reagent (SYBR Green). Using 2 −ΔΔCt The method normalizes gene expression results. The results are as follows: Figure 4 As shown, (A) represents the expression of phosphoribosyl pyrophosphate synthase (PRPS) mRNA, (B) represents the expression of adenosine deaminase (ADA) mRNA, (C) represents the expression of purine nucleoside phosphorylase (PNP) mRNA, and (D) represents the expression of xanthine oxidase (XOD) mRNA.

[0048] according to Figure 4 It can be seen that, compared with the normal control group, the level of PRPS mRNA in the liver of mice in the model group was significantly increased ( p <0.0001), after intervention, the levels of PRPS mRNA in the liver of mice in each treatment group were significantly reduced, indicating that the intervention of quercetin and capsaicin was effective ( Figure 4 (A) Compared with the normal control group, the level of ADA mRNA in the liver of mice in the model group was significantly increased ( p <0.0001), after intervention, the ADA mRNA in the liver of mice in each treatment group decreased to varying degrees, indicating that quercetin and capsicum have an inhibitory effect on uric acid synthesis. Figure 4 (B) Compared with the normal control group, the level of ADA mRNA in the liver of mice in the model group was significantly increased ( p<0.01), after intervention, the ADA mRNA in the liver of mice in each treatment group decreased to varying degrees. Compared with the single treatment group, the combined treatment group of capsaicin and quercetin at a ratio of 3:1 showed better results. Figure 4 (C) Compared with the normal control group, the level of XOD mRNA in the liver of mice in the model group was significantly increased (C) p <0.01), after intervention, XOD mRNA in the liver of mice in all treatment groups decreased to varying degrees. Compared with the single treatment groups, the combined treatment group of capsaicin and quercetin at a ratio of 3:1 showed better results. Figure 4 (D)

[0049] 6. Detection of expression of key transporter proteins in uric acid excretion URAT1 and GLUT9 are reabsorption proteins, and uric acid excretion is negatively correlated with the amount of reabsorption proteins. OAT1 and OAT3 are secretion proteins, and uric acid excretion is positively correlated with the amount of secretion proteins. Based on this principle, 21 days after administration to each treatment group in Example 1, Western blotting was used to determine the expression levels of uric acid reabsorption (URAT1 and GLUT9) and secretion (OAT1 and OAT3) transporter proteins in the kidneys of six groups of mice. The specific steps are as follows: (1) After thawing mouse tissue (100 mg) on ​​ice, add 1 mL of pre-chilled RIPA lysis buffer (containing 1% PMSF, 1% protease inhibitor, and 1% phosphatase inhibitor complex) and homogenize thoroughly using a tissue homogenizer. After lysing on ice for 20 min, centrifuge at 14,000 rpm for 20 min at 4 °C and collect the supernatant as the protein sample. The protein concentration of each group of samples was determined using a BCA protein quantification kit. Take an equal amount of protein sample and mix it with 5 × SDS loading buffer, and denature in a boiling water bath for 5 min.

[0050] (2) After cooling to room temperature, the sample was loaded onto a 10% gel rapid preparation kit for electrophoresis separation (constant voltage 150 V, 60 min). The protein was then transferred to an NC membrane using a semi-dry transfer system. After transfer, the following steps were performed: a) Seal the NC membrane with 5% skim milk powder-TBST solution at room temperature for 2 h; b. Primary antibodies (GAPDH, URAT1, GLUT9, OAT1, OAT3) were incubated overnight at 4°C at the recommended dilutions in the instructions. c. After rinsing with TBST 3 times (5 min / rinse), incubate with the corresponding HRP-labeled secondary antibody at room temperature for 1 h; d. Rinse with TBST 7 times (5 min / rinse); e. Development was performed using an ultrasensitive ECL chemiluminescent substrate, and images were acquired using an imaging system. Results are as follows: Figure 5 As shown, (A) is the imaging result detected by Western blotting, (B) is the expression level of GLUT9, (C) is the expression level of URAT1, (D) is the expression level of OAT1, and (E) is the expression level of OAT3.

[0051] according to Figure 5 It can be seen that the relative expression levels of URAT1 and GLUT9 were significantly increased in the model group mice. The upregulation of these reabsorption proteins enhances the renal tubular reabsorption capacity for uric acid, leading to an abnormally high serum uric acid level. After intervention with capsaicin and quercetin, GLUT9 expression was reduced to varying degrees, and URAT1 expression was significantly reduced, indicating that capsaicin and quercetin can alleviate hyperuricemia by reducing reabsorption proteins. The relative expression levels of OAT1 and OAT3 proteins in the kidneys of the model group mice were significantly lower than those in the control group (…). p Decreased expression of OAT1 and OAT3 proteins in the kidneys (<0.0001) leads to reduced secretion of uric acid from the serum circulation into the renal tubules, thus hindering uric acid excretion and exacerbating hyperuricemia. Intervention with capsaicin and quercetin increased the expression levels of OAT1 and OAT3 proteins to varying degrees, with the 3:1 combination treatment of capsaicin and quercetin showing the best effect. This indicates that capsaicin and quercetin can alleviate hyperuricemia by increasing the secretion of these proteins.

[0052] 7. Detection of expression of key genes in the visceral inflammatory pathway Under conditions of infection and inflammation, TLR4 activates Myd88, thereby triggering NF-κB activation. The presence of uric acid crystals triggers activation of the NLRP3 inflammasome-mediated inflammatory pathway, leading to the release of pro-inflammatory cytokines. Based on this principle, 21 days after administration to each treatment group in Example 1, the expression levels of key genes in the TLR4 / Myd88 / NF-κB signaling pathway and the NLRP3 inflammasome in the kidneys of six groups of mice were analyzed using RT-qPCR. The results are as follows: Figure 6 As shown, (A) to (F) represent the expression of mRNAs of TLR4, Myd88, NF-κB, NLRP3, ASC, and Caspase 1, respectively.

[0053] according to Figure 6 It can be seen that, compared with the normal control group, the expression levels of TLR4, Myd88, and NF-κB mRNA in the kidneys of mice in the model group were significantly increased. p <0.0001 indicates that the NF-κB pathway is activated. After intervention with capsaicin and quercetin, the mRNA expression levels in all treatment groups were significantly reduced. Compared with the normal control group, the mRNA expression levels of NLRP3, ASC, and Caspase1 in the kidneys of model group mice were significantly increased.p <0.0001), after intervention with capsaicin and quercetin, the mRNA expression levels in all treatment groups were significantly reduced.

[0054] Example 2 Comparison of uric acid-lowering effects of different ratios of capsaicin and quercetin 1. An animal model of hyperuricemia was constructed according to the method in Example 1, and the drugs were administered according to the method in Table 4 below for three weeks, once a day.

[0055] Table 4. Administration methods for mice in different treatment groups

[0056] 2. After 21 days of administration to each treatment group in step 1, the serum uric acid (UA) content was detected using a commercial kit. The results are shown in Table 5.

[0057] Table 5 Serum uric acid levels in mice after drug administration in different treatment groups

[0058] As shown in Table 5, compared with the normal control group (45.67 ± 10.60), the serum uric acid level in the model group mice (124.95 ± 32.11) was significantly higher. p The value <0.05 indicates that the hyperuricemia model was successfully established. After intervention with capsaicin and quercetin, the uric acid levels in mice in all treatment groups were significantly reduced. The uric acid-lowering effect of the combination of capsaicin and quercetin in the range of (1~7:1) was significantly better than that of capsaicin (70.40 ± 18.88), the quercetin group (92.04 ± 9.67) single treatment group, and other combined treatment groups with different ratios. Furthermore, the uric acid-lowering effect was best achieved with the combined intervention of capsaicin and quercetin at a mass ratio of 3:1 (57.84 ± 6.18).

[0059] Example 3 A uric acid-lowering tablet is composed of a main ingredient and excipients. The main ingredient consists of quercetin and capsaicin, and the excipients consist of magnesium stearate and maltodextrin. The mass percentage of each component is as follows: magnesium stearate 10%, maltodextrin 30%, capsaicin 45%, and quercetin 15%.

[0060] The specific preparation method is as follows: 1. Weigh the main ingredients and auxiliary ingredients according to the proportions, and mix them evenly in a food-grade container.

[0061] 2. Disassemble the tablet press's punches (punches, die holes), hopper, and feeder. Rinse with purified water, then wipe with 75% ethanol for disinfection (to avoid contamination from residual materials from the previous batch). Reassemble after drying.

[0062] 3. Select a 12 mm die for the tablet press and adjust the pressure. Pour the direct-pressed powder into the hopper of the tablet press (Taizhou Aoyan Machinery Co., Ltd.). After confirming that everything is correct, turn on the switch to start tableting. The tableting speed is 1400 rpm, the average weight of the tablets is 0.5 g, and the weight difference is controlled within ±5%.

[0063] 4. Inspect the appearance of the tablets. They should be free of sticking, cracks, spots, and rough edges (smooth edges).

[0064] 5. The compressed tablets are sent to a temporary storage container via a tablet delivery conveyor belt. The temporary storage container must be clean and dry.

[0065] 6. Packaging is carried out using a hot press (Shanghai Yuwu Technology Co., Ltd.). The tablets are placed in a 12 mm diameter PVC aluminum-plastic pressing plate for hot pressing at a temperature of 145℃.

[0066] Example 4 A uric acid-lowering tablet similar to Example 3, with the following mass percentages of each component: magnesium stearate 10%, maltodextrin 30%, capsaicin 30%, and quercetin 30%.

[0067] Example 5 A uric acid-lowering tablet similar to Example 3, with the following mass percentages of each component: magnesium stearate 10%, maltodextrin 30%, capsaicin 40%, and quercetin 20%.

[0068] Example 6 A uric acid-lowering tablet similar to Example 3, with the following mass percentages of each component: magnesium stearate 10%, maltodextrin 30%, capsaicin 50%, and quercetin 10%.

[0069] Example 7 A uric acid-lowering tablet similar to that in Example 3 has the following mass percentages of each component: magnesium stearate 10%, maltodextrin 30%, capsaicin 52.5%, and quercetin 7.5%.

[0070] As can be seen from the above, the technical solution provided by the present invention can inhibit the activity of key enzymes in purine metabolism, promote the excretion of uric acid, reduce the body's oxidative stress, regulate the level of inflammation, improve the pathological process of hyperuricemia, and improve liver and kidney function.

[0071] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. The use of capsaicin and / or quercetin in one or more of the following: (1) Preparation of uric acid-lowering products; said products include health products or pharmaceuticals; (2) Prepare drugs for the prevention and / or treatment of hyperuricemia.

2. A uric acid-lowering composition, characterized in that, It includes capsaicin and quercetin; the mass ratio of capsaicin to quercetin is (1~7):

1.

3. The use of the uric acid-lowering composition according to claim 2 in one or more of the following: (1) Preparation of uric acid-lowering products; said products include health products or pharmaceuticals; (2) Prepare drugs for the prevention and / or treatment of hyperuricemia.

4. The application according to claim 1 or 3, characterized in that, The dosage forms of the product or drug include tablets, capsules, powders, or granules.

5. A uric acid-lowering product, comprising uric acid-lowering health supplements and / or uric acid-lowering drugs, characterized in that, The uric acid-lowering health product comprises the uric acid-lowering composition of claim 2 and food-acceptable excipients; The uric acid-lowering drug comprises the uric acid-lowering composition of claim 2 and pharmaceutically acceptable excipients.

6. A uric acid-lowering tablet, characterized in that, Includes the uric acid-lowering composition of claim 2, the lubricant, and the adhesive.

7. The uric acid-lowering tablet according to claim 6, characterized in that, The uric acid-lowering tablets, by weight percentage, comprise 50-70% uric acid-lowering composition, 5-15% lubricant, and 20-40% binder.

8. The uric acid-lowering tablet according to claim 6 or 7, characterized in that, The lubricant includes magnesium stearate.

9. The uric acid-lowering tablet according to claim 6 or 7, characterized in that, The adhesive includes maltodextrin.

10. The method for preparing uric acid-lowering tablets according to any one of claims 6 to 9, characterized in that, The uric acid-lowering composition, lubricant, and binder are mixed, compressed into tablets, and coated to obtain uric acid-lowering tablets.

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