Application of 5-O-methylvisamminol glycoside in the preparation of products for treating hyperuricemia

Abstract

The present invention belongs to the field of biomedicine, and particularly relates to the application of 5-O-methylvisamminol glycoside in the preparation of products for treating hyperuricemia. The present invention has detected that 5-O-methylvisamminol glycoside, a new inhibitor of CNT2, can reduce the absorption of dietary purine nucleosides in the intestine by inhibiting CNT2, thereby exerting a uric acid-lowering effect and protecting against uric acid-related diseases. At the cellular level, 5-O-methylvisamminol glycoside can competitively bind to CNT2 and inhibit adenosine transport. At the animal level, the uric acid concentration in mice treated with 5-O-methylvisamminol glycoside is more stable and can return to the initial uric acid range more quickly. It can relieve liver and kidney injuries caused by hyperuricemia and improve intestinal permeability at the same time. The solution of the present invention provides a design idea for the design, synthesis and development of novel intestinal purine absorption inhibitors, and provides a new target for the clinical treatment of hyperuricemia.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to the application of 5-O-methylvisamminol glycoside in the preparation of products for treating hyperuricemia. Background Art

[0002] Hyperuricemia (HUA) and gout are both chronic metabolic diseases caused by purine metabolism disorders that lead to elevated uric acid in the serum. However, currently, the drugs used clinically mainly target the liver and kidneys, and there is no uric acid-lowering drug that acts on the intestinal dietary purine absorption pathway. A large number of epidemiological studies have shown that the common causes of elevated uric acid are excessive consumption of alcohol and purine-rich foods (such as meat and seafood). At the same time, experiments have proven that a low-purine diet can reduce the serum uric acid level in patients with hyperuricemia. Therefore, it can be seen that an increase in purine intake can elevate the blood uric acid level, and inhibiting its gastrointestinal absorption can be a link in the prevention and treatment of hyperuricemia.

[0003] Purine is a substance in the human body, mainly existing in the form of purine nucleotides. The main site of its gastrointestinal absorption is the small intestine, and the main form of absorption is nucleoside. The transmembrane transport of nucleoside depends on nucleoside transporters. There are mainly two types of nucleoside transporters in the human body: equilibrative nucleoside transporters (ENTs or SLC29) and concentrative nucleoside transporters (CNTs or SLC28). ENTs transport pyrimidine and purine substances by facilitated diffusion and are mainly distributed on the basolateral membrane of intestinal epithelial cells. CNT is a Na+-dependent enriched nucleoside transporter, which is an active transporter that can transport extracellular nucleosides into cells against the concentration gradient. It is mainly distributed on the apical membrane of intestinal epithelial cells, transports purine nucleosides and uridine, and has the highest expression in the human digestive system.

[0004] In recent years, CNT2 has been considered the core transporter for intestinal purine nucleoside absorption. Not only does it mainly enrich purine nucleosides in function, but it also has a relatively high expression level in the intestine, mainly distributed in organs such as the stomach, duodenum, jejunum, and ileum. Existing studies have found that the intestinal CNT2 expression is significantly increased in hyperuricemia model animals. However, the research on the application of CNT2 inhibitors in hyperuricemia only comes from the compounds KGO-2142 and KGO-2173 discovered in Japan. These compounds have confirmed that inhibiting the CNT2 nucleoside transporter can effectively reduce intestinal dietary purine absorption and lower serum uric acid, but the toxic and side effects on important organs such as the liver and kidneys have not been verified, which is not conducive to clinical development. Therefore, it is particularly urgent and important to search for and develop new uric acid-lowering drug targets or drugs.

[0005] Currently, there are mainly three categories of drugs for reducing uric acid in clinical applications: The first category is to inhibit xanthine oxidase to reduce uric acid synthesis, and the representative drugs are allopurinol and febuxostat, both of which are first-line drugs in clinical practice. Allopurinol has related severe skin adverse reactions, and long-term use can cause gastrointestinal discomfort, abnormal liver function, blood system damage, and an increased risk of death; febuxostat has relatively large toxic and side effects on the heart and kidneys. The second category is to inhibit the reabsorption of urate in the renal tubules, and the representative drug is benzbromarone. Benzbromarone can cause severe liver damage. The third category is drugs that promote uric acid dissolution, and the representative drug is rasburicase, which belongs to recombinant uricase. It is expensive and is mainly used for patients with hyperuricemia caused by chemotherapy. The safety of this drug still needs to be further verified. Clinically, the drugs mainly target the liver and kidneys, but HUA and gout are both chronic metabolic diseases caused by purine metabolism disorders leading to elevated uric acid in the serum. Currently, there is no drug for reducing uric acid that acts on the intestinal purine absorption pathway in clinical practice.

[0006] 5-O-methylvisammioside (hereinafter referred to as AM) is a natural and effective active ingredient from Saposhnikovia divaricata, and has various pharmacological activities such as anti-tumor and anti-depressant effects. In recent years, more and more studies have found the pharmacological effects of 5-O-methylvisammioside, such as analgesic, anti-inflammatory, and effects on energy metabolism. However, no study has yet found the relationship between 5-O-methylvisammioside and uric acid-related diseases. Summary of the Invention

[0007] The purpose of the first aspect of the present invention is to provide an application.

[0008] The purpose of the second aspect of the present invention is to provide a method.

[0009] In order to achieve the above purposes of the present invention, the technical solutions adopted by the present invention are as follows:

[0010] In the first aspect of the present invention, there is provided an application of 5-O-methylvisammioside or its derivative in a1) to a3):

[0011] a1) Preparation of a CNT2 inhibitor;

[0012] a2) Preparation of a product for inhibiting the absorption of purine nucleosides;

[0013] a3) Preparation of a product for treating uric acid-related diseases.

[0014] Preferably, the derivative includes one of a halogenated product, a nitrated product, a sulfonated product, an esterified product, or an alcoholate.

[0015] Preferably, the alcoholate includes a salt formed by 5-O-methylvisammioside and a metal ion.

[0016] Preferably, the uric acid-related disease refers to a disease associated with abnormal uric acid levels in an organism.

[0017] Preferably, the uric acid-related disease includes at least one of uric acid nephropathy, hyperuricemia, gout, uric acid arthritis, and kidney stones.

[0018] Preferably, the CNT2 is nucleoside transporter CNT2 (Official Symbol: SLC28A2, NCBI, GeneID: 9153).

[0019] Preferably, the product includes at least one of a drug and a health product.

[0020] Preferably, the product includes pharmaceutically acceptable excipients.

[0021] Preferably, the pharmaceutically acceptable excipients include at least one of a solvent, a propellant, a solubilizer, a cosolvent, an emulsifier, a colorant, a binder, a disintegrant, a filler, a lubricant, a wetting agent, an osmotic pressure regulator, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an aromatic agent, an antiadhesive, a chelating agent, a penetration enhancer, a pH regulator, a buffer, a plasticizer, a surfactant, a foaming agent, a defoaming agent, a thickening agent, an inclusion agent, a humectant, an absorbent, a diluent, a flocculant and a deflocculant, a filter aid, a release retardant, and a carrier.

[0022] Furthermore, for the convenience of administration, the active ingredient 5-O-methylvisammioside can be processed into a specific dosage form with any one or several pharmaceutically acceptable excipients. These excipients can be diluents (such as starch, pregelatinized starch, dextrin, sucrose, lactose, mannitol, and microcrystalline cellulose, etc.), absorbents (such as calcium sulfate, calcium hydrogen phosphate, light magnesium oxide, and calcium carbonate, etc.), wetting agents (such as water and ethanol, etc.), binders (such as hydroxypropyl methylcellulose, povidone, starch paste, and syrup, etc.), disintegrants (such as dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, effervescent disintegrants, and crospovidone, etc.), lubricants (such as magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol, and colloidal silica, etc.), colorants (such as titanium dioxide, sunset yellow, methylene blue, and medicinal iron oxide, etc.), coating materials (such as acrylic resin, hydroxypropyl methylcellulose, and povidone, etc.), solvents (such as water for injection, ethanol, propylene glycol, and glycerol, etc.), acid-base regulators (such as hydrochloric acid, lactic acid, sodium hydroxide, tartaric acid, and sodium tartrate, etc.), antioxidants (such as sodium sulfite, sodium metabisulfite, and sodium thiosulfate, etc.), bacteriostatic agents (such as phenol, benzyl alcohol, and thimerosal, etc.), or isotonicity regulators (such as sodium chloride and glucose, etc.).

[0023] Preferably, the dosage form of the product includes a gastrointestinal dosage form or a parenteral dosage form.

[0024] Preferably, the gastrointestinal dosage form includes at least one of powder, tablet, granule, capsule, sustained-release preparation, solution, dry suspension, effervescent tablet, emulsion, suspension, syrup, drops, chewable tablet.

[0025] Furthermore, the gastrointestinal dosage form includes, but is not limited to, enteric-coated tablets, coated tablets, film-coated tablets, sugar-coated tablets, dispersible tablets, sucking tablets, chewable tablets, effervescent tablets, scored tablets, sustained-release controlled-release dosage forms such as sustained-release tablets, sustained-release coated tablets, controlled-release tablets, orally disintegrating tablets, lozenges, oral patches, etc.

[0026] Preferably, the parenteral dosage form includes at least one of injection dosage form, respiratory tract dosage form, skin dosage form, mucosal dosage form, cavity dosage form.

[0027] Furthermore, the injection dosage form includes, but is not limited to, injection solution, injection solution for injection, injection for intravenous drip, injection suspension, sterile powder for injection, intravenous injection, aqueous injection, emulsion for injection, powder for injection, injection, sterile powder for injection, lyophilized powder for injection, etc.

[0028] In a second aspect of the present invention, a method for inhibiting the activity of CNT2 in vitro for non-therapeutic purposes is provided, including the step of treating cells with 5-O-methylvisamminol glycoside.

[0029] The beneficial effects of the present invention are as follows:

[0030] The present invention detects a new inhibitor of CNT2, 5-O-methylvisamminol glycoside, which can reduce the absorption of dietary purine nucleosides in the intestine by inhibiting CNT2, thereby exerting a uric acid-lowering effect and protecting against uric acid-related diseases. At the cellular level, 5-O-methylvisamminol glycoside can competitively bind to CNT2 and inhibit adenosine transport. At the animal level, the uric acid concentration in 5-O-methylvisamminol glycoside-treated mice is more stable and can return to the initial uric acid range faster. It can relieve liver and kidney damage caused by hyperuricemia and improve intestinal permeability at the same time. The solution of the present invention provides a design idea for designing, synthesizing and developing new intestinal purine absorption inhibitors, and provides a new target for the treatment of clinical hyperuricemia. Description of the Drawings

[0031] Figure 1 For molecular docking of adenosine (A), 5-O-methylvisamminol glycoside (B), and positive control inhibitor (C) and 3 H adenosine uptake experiment (D), docking score results of each group (E).

[0032] Figure 2Effect diagram of single-dose 5-O-methylvisamminol glycoside on serum uric acid in hyperuricemia diet mice.

[0033] Figure 3 Uric acid-lowering effect of 5-O-methylvisamminol glycoside on chronic hyperuricemia mice.

[0034] Figure 4 Protective effect of 5-O-methylvisamminol glycoside on important organs of chronic hyperuricemia mice; A-B are HE pathological staining diagrams of the liver and kidney, and C is the result of the intestinal permeability experiment.

[0035] Reference signs: **** indicates P < 0.001 compared with the NC group; # indicates P < 0.05 compared with the OE-CNT2 group; # indicates P < 0.0001 compared with the HUA group. Detailed implementation mode

[0036] The concept and technical effects of the present invention will be clearly and completely described below in combination with the embodiments to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative efforts shall fall within the scope of protection of the present invention.

[0037] The reagent materials used in the embodiments of the present invention are all commercially available or can be prepared. The reagents used in the following embodiments are as follows: yeast extract, CAS NO.: 8013-01-2; potassium oxonate, CAS NO.: 2207-75-2; 5-O-methylvisamminol glycoside, CAS NO.: 84272-85-5; CNT2 inhibitor, CAS NO.: 880155-70-4; adenosine, CAS NO.: 58-61-7.

[0038] Example 1 Compound molecular docking with CNT2 protein as the receptor

[0039] 1) Virtual screening and flexible docking

[0040] Screening for potential binding compounds using CNT2 protein (Official Symbol: SLC28A2, NCBI, Gene ID: 9153). Two databases were selected: one was conducted in the internal natural product database (PMID: 38669781, 34775203), which contains 205 herbs and 811 natural products; the other was the saccharide and glycoside compound library, purchased from Kasima Mall (Saccharide and Glycoside Natural Product Library, 345 natural products). Using the CNT2 protein as the docking conformation, potential CNT2 inhibitors were identified through 3D shape similarity screening, and the top 8 compounds with the highest similarity values were selected for further study. One of the 8 compounds, 5-O-methylvisammioside, is a natural compound extracted from Saposhnikovia divaricata, which has obvious antipyretic, analgesic and anti-inflammatory effects. The results are as Figure 1 shown in A - C, E in

[0041] By docking with the CNT2 protein, 5-O-methylvisammioside can bind to CNT2, and its docking score is higher than that of adenosine and the known CNT2 inhibitor ( Figure 1 shown in E in Figure 1 ). In addition, docking analysis shows that there is partial overlap between the conformations of 5-O-methylvisammioside and adenosine, indicating their structural similarity, suggesting that it may inhibit the adenosine transport effect and play a uric acid-lowering role by competing for the adenosine binding site (

[0042] Example 2 In vitro inhibitory effect of 5-O-methylvisammioside on CNT2

[0043] 1) Coating a 96-well plate with poly-D-lysine (PDL)

[0044] Coat a 96-well plate with 0.1 mg / mL poly-D-lysine for 24 h, then discard the poly-D-lysine and dry it in an oven at 37 °C for 12 h for later use.

[0045] 2) Cell transfection

[0046] When the human embryonic kidney cells (HEK293T cells) grow and fuse to 90%, inoculate the HEK293T cells into a 96-well plate coated with PDL, place it in an incubator at 37 °C with 5% CO2, and culture for 18 h to 24 h. After the cell fusion rate is about 70% to 80%, perform transient transfection of the CNT2 plasmid. The CNT2 plasmid is designed by Tsingke Biotechnology Co., Ltd. Select pcDNA3.1(+) as the expression vector. The active fragment of the target gene sequence is the full length of CNT2 (Gene ID: 9153), and the gene is labeled with 3xFlag.

[0047] The specific transfection steps are as follows: Add 25 μL of serum-free medium (Opti-MEM, glibco, 31985070) to two 1.5 mL EP tubes (tube 1 and tube 2) respectively, and then add 500 ng of the plasmid in (1) and 1 μL of P3000 TM (Thermo fisher, L3000015) to tube 1 and mix well; add 0.75 μL of Lipo 3000 TM to tube 2. Vortex the above sample tubes for 10 seconds and let stand for 5 min; then mix the liquids in the two tubes, vortex for 10 seconds, let stand for 25 min, and evenly drop them into the wells containing 500 μL / well of fresh medium at a volume of 10 μL / well. Place it in an incubator at 37 °C with 5% CO2 and culture for 24 h.

[0048] 3) 3 3H adenosine uptake experiment

[0049] (1) Prepare Na + uptake buffer: The formula is: 140 mM NaCl, 2 mM KCl, 1 mM MgCl2, 2 mM CaCl2, 10 mM HEPES, 5 mM Tris, 5 mM D-glucose. After preparation, adjust the pH to about 7.4 with 0.1 M NaOH, and then filter it with a 0.22 μm microporous filter membrane and store it at 4 °C for later use.

[0050] (2) Prepare drug-containing uptake buffer: Dissolve 5-O-methylvisamminol glycoside powder with DMSO to obtain a 50 mM stock solution; dilute it with Na + uptake buffer to obtain the required concentration of 10 μM. It is advisable to prepare and use it immediately.

[0051] (3) Prepare the uptake solution containing both 3 3H adenosine and 5-O-methylvisamminol glycoside: Prepare a 100 μM solution of + with Na 3H-adenosine solution, and then mixed with an equal volume of 5-O-methylvisamminol glycoside solution dissolved in (2) uptake buffer, finally obtaining an uptake mixed solution of H-adenosine and 10 μM 5-O-methylvisamminol glycoside with a final concentration of 50 μM. 3 The uptake mixed solution of H-adenosine and 10 μM 5-O-methylvisamminol glycoside.

[0052] (4) 3 Specific steps of the H-adenosine uptake experiment: Discard the medium in HEK293T cells transfected with CNT2, wash the cells 3 times with 200 μL of uptake buffer each time. Add 245 μL of uptake buffer containing 5-O-methylvisamminol glycoside (10 μM) respectively for pre-incubation for 15 min. After the pre-incubation, add the uptake buffer containing both the drug and adenosine. Immediately discard the liquid in the wells after incubation for 15 min, add ice-cold DPBS buffer to wash the cells 3 times with 200 μL each time. Finally, add 150 μL of 0.1 M NaOH to lyse the cells for 10 min, add 800 μL of liquid scintillation fluid (Revvity, 6013329), and transfer to a liquid scintillation counter to record the change in radioactivity value.

[0053] Figure 1 In D, it shows the uptake of H-adenosine under 5-O-methylvisamminol glycoside and CNT2 overexpression (OE-CNT2), indicating that 5-O-methylvisamminol glycoside can competitively bind to CNT2 and inhibit adenosine transport. 3 The uptake of H-adenosine, suggesting that 5-O-methylvisamminol glycoside can competitively bind to CNT2 and inhibit adenosine transport.

[0054] Example 3 Effect of single-dose 5-O-methylvisamminol glycoside on serum uric acid in hyperuricemic diet mice

[0055] 1) Grouping of experimental animals

[0056] Select SPF-grade male C57 mice at 6 weeks of age with a body weight of 22 ± 2 g, divide them into 3 groups according to the average body weight, and group them according to Table 1 below. The temperature for all animals is controlled at 24 °C - 26 °C, and the relative humidity is controlled at 40% - 60%, with 8 animals in each cage. After 1 week of adaptive feeding, the experiment is carried out. The relevant animal experiments have obtained the consent of the ethics review committee and obtained the relevant permits.

[0057] 2) Effect of single-dose administration on uric acid

[0058] Before administration, orbital blood collection was performed on each group of mice to detect the uric acid value of each mouse before administration. Each group of mice was intraperitoneally injected with 300 mg / kg of potassium oxonate solution and gavaged with 15 mg / kg of yeast extract solution (the solvent was 0.5wt% CMC-Na). Among them, in the administration group, low-dose (the final concentration of 5-O-methylvisammioside was 10 mg / kg) and high-dose (the final concentration of 5-O-methylvisammioside was 20 mg / kg) 5-O-methylvisammioside were mixed with the yeast extract solution and administered simultaneously.

[0059] After administration, blood samples of each group of mice were collected by orbital blood collection at 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, and 8 h. After standing at room temperature for 30 min, centrifugation was performed at 3000 rpm at 4 °C for 15 min, the upper serum was taken, and the uric acid level in the serum was measured using a uric acid test kit (Nanjing Jiancheng Bioengineering Institute, C012-2-1).

[0060] Table 1 Grouping and gavage conditions of mice in the in vivo uric acid-lowering activity test of single-dose 5-O-methylvisammioside

[0061]

[0062] The drug preparations and concentrations of each group were as follows: 0.5wt% sodium carboxymethylcellulose was used as the drug solvent, potassium oxonate (36 mg / mL), yeast extract (1.8 g / mL), low-dose group of 5-O-methylvisammioside (1.2 mg / mL), and high-dose of 5-O-methylvisammioside (2.4 mg / mL). All injections were administered at a volume of 100 μL / 12 g.

[0063] Figure 2 It is the serum uric acid effect diagram of single-dose 5-O-methylvisammioside on mice with high-purine diet, indicating that the uric acid concentration of mice treated with 5-O-methylvisammioside is more stable and returns to the initial uric acid range faster.

[0064] Example 4 Protective effect of 5-O-methylvisammioside on important organs in a mouse model of chronic hyperuricemia

[0065] 1) Grouping of experimental animals

[0066] SPF-grade male C57 mice at 6 weeks of age with a body weight of 22 ± 2 g were selected, divided into 4 groups according to the average body weight, and grouped according to Table 2 below. The feeding temperature of all animals was controlled at 24 °C to 26 °C, the relative humidity was controlled at 40% to 60%, and 8 animals were placed in each cage. The experiment was carried out after 1 week of adaptive feeding. The relevant animal experiments obtained the consent of the Ethics Review Committee and obtained the relevant permits.

[0067] 2) Establishment of a chronic hyperuricemia model

[0068] During the experiment, the mice ate and drank normally. Except for the blank group, mice in each group were intraperitoneally injected with 300 mg / kg potassium oxonate solution and gavaged with 15 mg / kg yeast extract solution (the solvent was 0.5 wt% CMC-Na) at 9:30 every day. In the administration group, low-dose (final concentration of 5-O-methylvisamminol glycoside was 10 mg / kg) and high-dose (final concentration of 5-O-methylvisamminol glycoside was 20 mg / kg) 5-O-methylvisamminol glycoside were mixed with the yeast extract solution and administered simultaneously. The blank control group was gavaged and injected with the same volume of 0.5 wt% sodium carboxymethylcellulose. This experiment lasted for 21 days in total. After the administration ended on the 21st day, blood was collected and the mice were sacrificed. When sacrificed, a part of the kidney, liver, and intestinal tissue (duodenum, jejunum, ileum) samples were immersed in paraformaldehyde fixative, and a part was stored at -80 °C.

[0069] Table 2 Grouping and gavage conditions of mice in the experiment on the protection of important organs of mice with chronic hyperuricemia by 5-O-methylvisamminol glycoside

[0070]

[0071] The drug preparations and concentrations of each group were as follows: 0.5 wt% sodium carboxymethylcellulose was used as the drug solvent, potassium oxonate (36 mg / mL), yeast extract (1.8 g / mL), low-dose group of 5-O-methylvisamminol glycoside (1.2 mg / mL), and high-dose of 5-O-methylvisamminol glycoside (2.4 mg / mL). The injection was administered at a volume of 100 μL / 12 g.

[0072] 3) Intestinal permeability FITC experiment

[0073] The mice were treated in the same way as described in 2) above to establish chronic hyperuricemia model mice. On the 21st day after modeling, the in vivo permeability was measured using FITC-labeled dextran (4 kD, Sigma, 46944) method to evaluate the barrier function. After the mice were fasted for 4 h, they were gavaged with 400 mg / kg FITC-labeled dextran. After 4 h, the mice were anesthetized, blood was collected by enucleation of the eyeballs, and after standing for 30 min, the serum was obtained by centrifugation at 4 °C, 3000 rpm for 15 min. The intestinal permeability of each group of mice was obtained by measuring the fluorescence intensity of each sample (excitation wavelength 490 nm; emission wavelength 520 nm; the concentration of FITC-dextran was determined by the standard curve generated by continuous dilution of FITC-dextran).

[0074] 4) Sample processing and determination

[0075] Blood: After leaving approximately 500 μL of blood standing at room temperature for 30 min, centrifuge it at 3000 rpm at 4°C for 15 min, collect the serum, and store it at -20°C. Use a uric acid test kit (Uric Acid Test Kit C012-2-1, Nanjing Jiancheng Bioengineering Institute) to measure the uric acid (UA) in the serum.

[0076] Kidney: After sacrificing the mice, quickly isolate the kidney tissues, remove the renal capsule, take pictures of both kidneys against a white background, and then place the right kidney in paraformaldehyde fixative for preservation for HE staining.

[0077] Liver: After sacrificing the mice, quickly isolate the liver tissues, take pictures of the whole liver against a white background, and then uniformly remove the left lobe of the mice and place it in paraformaldehyde fixative for preservation for HE staining.

[0078] Intestine: After sacrificing the mice, remove the duodenum, jejunum, and ileum respectively. Place a part of them in paraformaldehyde fixative for preservation for HE staining, and place the other part at -80°C for preservation.

[0079] Figure 3 The uric acid-lowering effect of 5-O-methylvisamminol glycoside on mice with chronic hyperuricemia. A yeast extract of high-purine diet was given by gavage combined with intraperitoneal injection of the uricase inhibitor oxonic acid potassium, and the drug was administered daily for 4 weeks to establish a chronic hyperuricemia mouse model. The blood collection results after 4 weeks showed that the serum uric acid of the mice treated with 5-O-methylvisamminol glycoside was significantly lower than that of the HUA model group, indicating that it could achieve the uric acid-lowering effect.

[0080] Figure 4 The protective effect of 5-O-methylvisamminol glycoside on important organs of mice with chronic hyperuricemia: A-B are the HE pathological staining pictures of the liver and kidney, and C is the result of the intestinal permeability experiment. In the chronic hyperuricemia mouse model, it was found that after using 5-O-methylvisamminol glycoside, it could relieve the liver and kidney injuries caused by hyperuricemia and improve the intestinal permeability at the same time. This shows that 5-O-methylvisamminol glycoside can not only play a role in lowering uric acid, but also improve the pathological changes of organs caused by hyperuricemia.

Claims

Application of 1.5-O-methylvisaminol glycoside in the preparation of products for treating gout. Application of 2.5-O-methylvisaminol glycoside in the preparation of products for treating uric acid nephropathy, hyperuricemia or uric acid arthritis.

3. The use according to claim 1 or 2, characterized in that: The product described is a drug.

4. The use according to claim 3, characterized in that: The product includes pharmaceutically acceptable excipients.

5. The use according to claim 4, characterized in that: The pharmaceutically acceptable excipients include at least one of solvents, propellants, cosolvents, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesive agents, penetration enhancers, pH regulators, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

6. The use according to claim 5, characterized in that: The dosage form of the product includes a dosage form for gastrointestinal administration or a dosage form for parenteral administration.

7. The use according to claim 6, characterized in that: The dosage form for administration through the gastrointestinal tract is powder, tablet, granule, capsule, sustained-release agent, solution, emulsion, suspension, syrup, or drops.

8. The use according to claim 6, characterized in that: The parenteral administration dosage form is an injection dosage form, a skin administration dosage form, or a mucosal administration dosage form.

9. The use according to claim 3, characterized in that: The product is administered to mammals.

10. The use according to claim 3, characterized in that: The product is administered to humans.

11. The use according to claim 9, characterized in that: The mammal is a mouse, a cat, a dog, a rabbit, a pig, a cow, or a sheep.

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