Application of deep-sea butyrolactone compound in preparation of product for preventing and / or treating hyperuricemia and / or uric acid nephropathy

Abstract

The invention belongs to the technical field of biological medicines, and discloses application of a deep-sea butyrolactone compound in preparation of a product for preventing and / or treating hyperuricemia and / or uric acid nephropathy. The butyrolactone compound disclosed by the invention is specifically 5-acetyl-3-hydroxy-4-(4-hydroxyphenyl)-5-[4-methyl-3-(3-methylbutyl-2-ene-1-yl) benzyl] furan-2 (5H)-ketone, and the structural formula of the butyrolactone compound is shown in the description. It is proved for the first time that the butyrolactone compound has the capacity of remarkably improving hyperuricemia and uric acid nephropathy, and the blood uric acid level, the serum creatinine level and the blood urea nitrogen level of hyperuricemia mice induced by oteracil potassium and hypoxanthine and uricase knockout mice are remarkably improved; the compound can be applied to preparation of products for preventing and / or treating the hyperuricemia and / or the uric acid nephropathy, a new product is provided for prevention and treatment of the hyperuricemia and the uric acid nephropathy, and therefore the compound has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and specifically relates to the application of a deep-sea butyrolactone compound in the preparation of products for the prevention and / or treatment of hyperuricemia and / or uric acid nephropathy. Background Technology

[0002] Uric acid is the final product of purine metabolism in the body. Hyperuricemia (HUA) is a chronic metabolic disease caused by purine metabolism disorders, and can be divided into primary and secondary types. Primary hyperuricemia is mainly caused by decreased uric acid excretion or increased uric acid production, while secondary hyperuricemia is caused by certain systemic diseases or the use of certain drugs that inhibit uric acid excretion. In addition, consuming too much food high in purines may also induce the onset of hyperuricemia. Its main clinical symptom is elevated blood uric acid. Sustained elevation of uric acid levels can easily lead to renal tubular damage, interstitial fibrosis, glomerular sclerosis, and urate crystal deposition, ultimately leading to hyperuricemic nephropathy (HN) caused by hyperuricemia. It can also cause gout, induce and aggravate hypertension, diabetes, acute coronary syndrome, renal failure, stroke, non-alcoholic fatty liver disease, and other diseases, and has become a major health problem that urgently needs to be addressed.

[0003] Currently, the first-line drugs for lowering uric acid used in clinical practice mainly include allopurinol, benzbromarone, and febuxostat. These drugs have significant uric acid-lowering effects. However, since gout and other diseases caused by hyperuricemia are chronic diseases, long-term use of these drugs can cause liver and kidney damage. In addition, there are some health products that lower uric acid, but their effects and side effects need further clarification. Therefore, it is still very important to find a product or drug that has a significant uric acid-lowering effect and few side effects. Summary of the Invention

[0004] In order to overcome the shortcomings and deficiencies of the prior art, the primary objective of this invention is to provide the use of deep-sea butyrolactone compounds or their derivatives or pharmaceutically acceptable salts in the preparation of products for the prevention and / or treatment of hyperuricemia and / or uric acid nephropathy.

[0005] The objective of this invention is achieved through the following solution:

[0006] The use of butyrolactone compounds or their derivatives or pharmaceutically acceptable salts in the preparation of one of the following products:

[0007] (a) Prevention and / or treatment of hyperuricemia;

[0008] (ii) Prevention and / or treatment of uric acid nephropathy.

[0009] Furthermore, the butyrolactone compound is specifically 5-acetyl-3-hydroxy-4-(4-hydroxyphenyl)-5-[4-methyl-3-(3-methylbut-2-en-1-yl)benzyl]furan-2(5H)-one, having the structure shown in the following formula:

[0010] .

[0011] Furthermore, the butyrolactone compound may have the structure shown in the following formula:

[0012] .

[0013] Furthermore, one or more hydrogen atoms on the molecular chain of the butyrolactone compound may be replaced by conventional groups such as halogen atoms, C1-C20 straight / branched / cyclic alkyl groups, C1-C20 haloalkyl groups, C2-C10 alkenyl groups, C2-C10 alkynyl groups, C1-C20 alkoxy groups, C1-C10 hydroxyalkyl groups, hydroxyl groups, C1-C20 carbonyl groups, carboxyl groups, cyano groups, nitro groups, amino groups, phenyl groups, C1-C20 ester groups, and C6-C20 aryl groups.

[0014] Furthermore, the products, whether identical or different, include therapeutically effective amounts of butyrolactone compounds or their derivatives or pharmaceutically acceptable salts thereof.

[0015] Furthermore, the same or different products can be made into various pharmaceutical dosage forms using conventional methods. These dosage forms include: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, powders, pills, elixirs, suspensions, tinctures, drops, and other oral dosage forms, as well as non-oral dosage forms such as injections.

[0016] Furthermore, the products, whether identical or different, may also contain one or more pharmaceutically acceptable carriers or excipients.

[0017] Furthermore, the carrier or excipient may include diluents, adhesives, surfactants, humectants, adsorbents, lubricants, fillers, disintegrants, preservatives, etc.

[0018] The present invention also provides a product composition for the prevention or treatment of hyperuricemia and / or uric acid nephropathy, comprising the said butyrolactone compound or a derivative thereof or a pharmaceutically acceptable salt thereof.

[0019] This invention demonstrates for the first time that butyrolactone compounds can significantly improve serum uric acid levels in hyperuricemic mice, and significantly improve body weight, kidney index, serum creatinine, and blood urea nitrogen in mice with hyperuricemia induced by hypoxanthine combined with potassium oxonate and uricase gene knockout mice. The effect is comparable to that of the positive control drug benzbromarone / allopurinol, providing a new product for the treatment of hyperuricemia and uric acid nephropathy, and therefore has broad application prospects. Attached Figure Description

[0020] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0021] Figures 1-4 The effects of butyrolactone compounds on body weight, kidney index, and serum uric acid in mice with PO+HX-induced acute hyperuricemia were investigated.

[0022] Figures 5-6 The effects of butyrolactone compounds on renal function in mice with PO+HX-induced acute hyperuricemia.

[0023] Figure 7 This is a pathological section of kidney tissue from mice with acute hyperuricemia induced by butyrolactone compounds and PO+HX.

[0024] Figures 8-12 The effects of butyrolactone compounds on uric acid and renal function in uricase gene knockout (Uox - / -) mice.

[0025] Figures 13-14 The effects of butyrolactone compounds on uric acid transporters in the kidneys of mice with PO+HX-induced acute hyperuricemia. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto. Unless otherwise specified, all materials involved in the following embodiments are commercially available. Unless otherwise specified, all methods described are conventional methods.

[0027] One embodiment involves the use of butyrolactone compounds or their derivatives or pharmaceutically acceptable salts in the preparation of products for the prevention and / or treatment of hyperuricemia and / or uric acid nephropathy.

[0028] In a specific embodiment of the present invention, the butyrolactone compound is specifically 5-acetyl-3-hydroxy-4-(4-hydroxyphenyl)-5-[4-methyl-3-(3-methylbut-2-en-1-yl)benzyl]furan-2(5H)-one, having the structure shown in the following formula:

[0029] .

[0030] In a specific embodiment of the present invention, the butyrolactone compound, named BTL-MK, has the structure shown in the following formula:

[0031] .

[0032] In a specific embodiment of the present invention, one or more hydrogen atoms on the molecular chain of the butyrolactone compound may be replaced by conventional groups such as halogen atoms, C1-C20 straight / branched / cyclic alkyl groups, C1-C20 haloalkyl groups, C2-C10 alkenyl groups, C2-C10 alkynyl groups, C1-C20 alkoxy groups, C1-C10 hydroxyalkyl groups, hydroxyl groups, C1-C20 carbonyl groups, carboxyl groups, cyano groups, nitro groups, amino groups, phenyl groups, C1-C20 ester groups, and C6-C20 aryl groups.

[0033] In specific embodiments of the present invention, the products, whether identical or different, comprise therapeutically effective amounts of butyrolactone compounds or their derivatives or pharmaceutically acceptable salts.

[0034] In another embodiment, a product composition for treating hyperuricemia and / or uric acid nephropathy comprises the said butyrolactone compound or a derivative thereof or a pharmaceutically acceptable thereof.

[0035] In specific embodiments of the present invention, the dosage of the product or product composition of the present invention can be varied depending on factors such as the formulation method, manner, patient's age, weight, gender, condition, diet, time, route, excretion rate, and responsiveness.

[0036] In specific embodiments of the present invention, the therapeutically effective amount refers to an amount that can produce a therapeutic effect on humans and / or animals and is acceptable to humans and / or animals. For example, a therapeutically or pharmaceutically effective amount refers to the amount of drug required to produce the desired therapeutic effect, which can be reflected by the results of clinical trials, animal model studies, and / or in vitro studies. A pharmaceutically effective amount depends on several factors, including but not limited to: the characteristics of the treatment subject (such as the height, weight, sex, age, and medication history of the treatment subject), and the severity of the disease.

[0037] In a specific embodiment of the present invention, the therapeutically effective amount refers to an amount that can produce a therapeutic effect on patients with hyperuricemia and / or uric acid nephropathy and is acceptable to the patients.

[0038] In specific embodiments of the present invention, the administration methods of the drug or drug composition include, but are not limited to: oral administration, non-gastrointestinal administration, administration via inhalation spray, topical administration, rectal administration, nasal administration, buccal administration, vaginal administration, or administration via an implanted drug storage device. Oral administration or injection is preferred.

[0039] In specific embodiments of the present invention, any orally acceptable dosage form may be used, including but not limited to capsules (hard capsules, soft capsules), tablets (sugar-coated tablets, film-coated tablets, enteric-coated tablets), aqueous suspensions, or solutions.

[0040] In specific embodiments of the present invention, liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs.

[0041] In specific embodiments of the present invention, solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.

[0042] In specific embodiments of the invention, the drug or pharmaceutical composition further includes one or more pharmaceutically acceptable carriers or excipients. The pharmaceutically acceptable carriers or excipients may contain inert components that do not unduly inhibit the biological activity of the compound. The pharmaceutically acceptable carriers or excipients should be biocompatible, for example, non-toxic, non-inflammatory, non-immunogenic, or free from other undesirable reactions or side effects when administered to a subject. Standard pharmaceutical formulation techniques can be used.

[0043] In specific embodiments of the invention, pharmaceutically acceptable carriers or excipients include, but are not limited to, diluents, binders, surfactants, humectants, adsorbents, lubricants, fillers, disintegrants, preservatives, etc. These substances are used as needed to aid in the stability of the formulation or to contribute to its activity or bioavailability, or to produce an acceptable taste or odor when taken orally. Formulations that can be used in such pharmaceutical compositions may be in the form of the original compound itself or optionally in the form of its pharmaceutically acceptable salts. Such formulated pharmaceutical compositions may be administered in any suitable manner known to those skilled in the art as needed.

[0044] In specific embodiments of the present invention, the diluent includes, but is not limited to, lactose, sodium chloride, glucose, urea, starch, and water.

[0045] In specific embodiments of the present invention, the adhesive includes, but is not limited to, starch, pregelatinized starch, dextrin, maltodextrin, sucrose, gum arabic, gelatin, methylcellulose, carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, alginate and alginates, xanthan gum, hydroxypropylcellulose and hydroxypropylmethylcellulose.

[0046] In specific embodiments of the present invention, the surfactants include, but are not limited to, polyethylene oxide sorbitan fatty acid ester, sodium lauryl sulfate, glyceryl monostearate, and hexadecyl alcohol.

[0047] In specific embodiments of the present invention, the humectant includes, but is not limited to, glycerin and starch.

[0048] In specific embodiments of the present invention, the adsorption carrier includes, but is not limited to, starch, lactose, bentonite, silica gel, kaolin, and bentonite.

[0049] In specific embodiments of the present invention, the lubricant includes, but is not limited to, zinc stearate, glyceryl monostearate, polyethylene glycol, talc, calcium and magnesium stearate, polyethylene glycol, boric acid powder, hydrogenated vegetable oil, sodium stearate fumarate, polyoxyethylene monostearate, monolauric sucrose ester, sodium lauryl sulfate, magnesium lauryl sulfate, and magnesium dodecyl sulfate.

[0050] In specific embodiments of the present invention, the fillers include, but are not limited to, mannitol (granular or powdered), xylitol, sorbitol, maltose, erythrose, microcrystalline cellulose, polysaccharides, coupled sugars, glucose, lactose, sucrose, dextrin, starch, sodium alginate, kelp polysaccharide powder, agar powder, calcium carbonate, and sodium bicarbonate.

[0051] In specific embodiments of the present invention, the disintegrants include, but are not limited to, crosylvinylpyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropylmethyl, crosylcarboxymethyl cellulose sodium, and soybean polysaccharides.

[0052] In specific embodiments of the present invention, the drug or drug composition further includes other drugs for treating hyperuricemia and / or uric acid nephropathy, i.e., the butyrolactone compound or its derivative or its pharmaceutically acceptable salt may be used in combination with other compounds that can be used to treat hyperuricemia and / or uric acid nephropathy.

[0053] Example 1: Uric acid-lowering effect of butyrolactone compounds on mice with acute hyperuricemia

[0054] (1) Potassium oxazine and hypoxanthine induce hyperuricemia model in mice

[0055] Forty healthy male SPF-grade KM mice were randomly divided into five groups of eight each: control group (CON), disease model group (HUA, i.e., PO+HX), low-dose butyrolactone group (HUA+BTL-L, 20 mg / kg), high-dose butyrolactone group (HUA+BTL-H, 40 mg / kg), and benzbromarone group (HUA+Ben, 5 mg / kg). Mice had free access to water. Except for the control group, the other groups received daily intraperitoneal injections of potassium oxonate (PO, 300 mg / kg) and intragastric administration of hypoxanthine (HX, 300 mg / kg). The control group received an equal volume of saline in the same manner. One hour later, the mice were administered BTL-MK and benzbromarone via intragastric administration. The entire cycle lasted two weeks.

[0056] (2) Serum uric acid and kidney indicators detection.

[0057] After inducing a hyperuricemia model with PO+HX, 0.2 mL of blood was collected from the fundus venous plexus, centrifuged at 4500 r / min for 10 min, and the serum was collected to detect the levels of uric acid (UA), creatinine (Scr), and blood urea nitrogen (BUN) in the serum.

[0058] (3) Mouse euthanasia and tissue collection

[0059] Two weeks after the above-mentioned drug administration, the mice were weighed and anesthetized. After cardiac perfusion, liver, kidney and other tissues were harvested, weighed and soaked in formalin for cryopreservation for subsequent experiments.

[0060] (4) The uric acid-lowering and renal function-protective effects of BTL-MK on mice with PO+HX-induced acute hyperuricemia.

[0061] like Figure 1 As shown, the kidneys of the control group mice were normal, the kidneys of the model group mice showed obvious paleness and edema, and the kidneys of the mice in the drug-treated group showed significant improvement. Figure 2 and Figure 3 As shown, at day 14, compared with the control group, the model group mice exhibited a slight stagnation or decline in weight gain, while the treatment group showed a slight improvement. Furthermore, the kidney weight ratio (kidney weight / mouse weight × 100%) in the model group mice was significantly different from that in the control group (p < 0.05), indicating significant kidney enlargement in the model group mice. After administration of the test drug BTL-MK (BTL-L, 20 mg / kg, gavage), the kidney index showed a significant difference compared with the model group (p < 0.05), while after administration of the test drug BTL-MK (BTL-H, 40 mg / kg, gavage), the kidney index showed a highly significant difference compared with the model group (p < 0.01), indicating that this drug has a protective effect on the kidneys of mice with HX+PO-induced acute hyperuricemia.

[0062] The results are shown in Table 1 and Figures 4-6 As shown, the serum uric acid, blood urea nitrogen (BUN), and serum creatinine (Cr) levels in the model group mice were 796.25±264.25 μM, 7.81±1.74 mM, and 42±14.2 μM, respectively, showing highly significant differences compared to the control group (p<0.01). After administration of the positive control drug benzbromarone 5 mg / kg, the serum uric acid, BUN, and creatinine levels in hyperuricemic mice decreased by 83.9%, 43.3%, and 65.4%, respectively, showing significant differences compared to the model group (p<0.05, p<0.01). However, administration of the test substance BTL-MK (BTL-L, 20 mg / kg) resulted in a significant decrease in these levels. After administration of the test substance BTL-MK (BTL-H, 40 mg / kg), the serum uric acid, blood urea nitrogen, and serum creatinine in hyperuricemia model mice decreased by 72.7%, 48.0%, and 57.1%, respectively, showing significant differences compared with the model group (p<0.05). After administration of the test substance BTL-MK (BTL-H, 40 mg / kg), the serum uric acid, blood urea nitrogen, and serum creatinine in hyperuricemia model mice decreased by 82.7%, 46.7%, and 63.8%, respectively, showing extremely significant differences compared with the model group (p<0.05, p<0.01).

[0063] Table 1 Effects of BTL-MK on serum uric acid and renal function index in PO+HX-induced hyperuricemia mice ( ±s)

[0064] Compared with the control group, #p<0.05 indicates a significant difference, and ###p<0.001 indicates a significant difference; compared with the model group, *p<0.05 indicates a significant difference; **p<0.01 indicates a significant difference, and ***p<0.001 indicates an extremely significant difference.

[0065] (4) BTL-MK can improve kidney damage induced by hyperuricemia and kidney fibrosis induced by hyperuricemia.

[0066] The kidneys of mice in each group were embedded in paraffin, sectioned after embedding, and then stained according to the instructions of the HE staining kit and Masson staining kit.

[0067] like Figure 7 As shown, the kidneys of mice in the model group showed damage such as neutrophil and monocyte aggregation, renal tubular dilation, and interstitial fibrosis. Mice in the benzbromarone group also showed the same mild kidney damage. In contrast, the kidneys of mice in the BTL-MK treatment group (BTL-L, 20 mg / kg; BTL-H, 40 mg / kg) showed significant reduction in hyperuricemia-induced kidney damage and renal interstitial fibrosis.

[0068] Example 2: Uric acid-lowering effect of butyrolactone compounds on uricase knockout mice

[0069] (1) Construction of uricase gene knockout mice (Uox- / -)

[0070] The Uox- / - mouse model was constructed by the Experimental Animal Center of Xiamen University. Cas9 mRNA and single-stranded guide RNA were synthesized in vitro via transcription and then co-injected into C57BL / 6J mouse embryos during the pronuclear stage. Uox- / - mice carrying a 172 bp deletion mutation were ultimately obtained. The knockout efficiency was verified using PCR and Western blotting, and serum uric acid levels were measured. A significant increase in serum uric acid levels was observed, indicating successful construction of the Uox- / - mouse model. See Am J Physiol Endocrinol Metab 320:E1031-E1043, 2021 for details.

[0071] (2) Drug treatment of wild-type (WT) mice and uricase gene knockout mice (Uox- / -)

[0072] Thirty age-matched SPF-grade C57BL / 6J WT and Uox- / - mice were randomly divided into five groups: WT group, Uox- / - group, low-dose butyrolactone group (BTL-L, 20 mg / kg), medium-dose butyrolactone group (BTL-M, 30 mg / kg), and allopurinol group (AP). The treatment groups received BTL-MK (BTL-L, 20 mg / kg; BTL-M, 30 mg / kg, by gavage) and allopurinol (AP, average 70 mg / kg, by drinking water), while the non-treatment groups received an equal volume of physiological saline by gavage. Treatment continued for four weeks. Serum uric acid and serum creatinine were measured weekly after the end of each treatment period.

[0073] (2) Protective effect of BTL-MK on Uox- / - mice

[0074] The results are shown in Table 2 and Figures 8-12As shown, the kidneys of the control group mice were normal, while the kidneys of the model group mice showed significant shrinkage, and the kidneys of the drug-treated group mice showed significant improvement. On day 28, compared with the control group, the model group mice showed a slight stagnation or decline in weight gain, while the low-dose treatment group and the allopurinol group showed slight improvement. The serum uric acid, blood urea nitrogen, and serum creatinine levels of the model group mice were 538.4±42.70 μM, 14.07±1.030 mM, and 38.44±4.274 μM, respectively, showing highly significant differences compared with the control group (p<0.0001). After administration of the positive control drug allopurinol, the serum uric acid, blood urea nitrogen, and serum creatinine levels of the uricase gene knockout mice decreased by 64.82%, 48.21%, and 40.48%, respectively, showing significant differences compared with the model group (p<0.0001). After administration of the test substance BTL-MK (BTL-L, 20 mg / kg), serum uric acid, blood urea nitrogen, and serum creatinine in uricase knockout mice decreased by 43.82%, 54.66%, and 46.83%, respectively, showing highly significant differences compared with the model group (p<0.0001). After administration of the test substance BTL-MK (BTL-M, 30 mg / kg), serum uric acid, blood urea nitrogen, and serum creatinine in uricase knockout mice decreased by 48.18%, 51.13%, and 35.33%, respectively, showing highly significant differences compared with the model group (p<0.0001).

[0075] Table 2 Effects of BTL-MK on serum uric acid and renal function index in uricase gene knockout mice ( ± s)

[0076] Compared with the control group, p < 0.0001 indicates a significant difference; compared with the model group, p < 0.0001 indicates a significant difference.

[0077] Example 3: Effect of BTL-MK on uric acid transport channel proteins

[0078] 1. BTL-MK lowers uric acid levels by acting on uric acid transport channel proteins in renal tubular epithelial cells.

[0079] (1) Weigh the kidneys of mice with acute hyperuricemia induced by HX+PO as described above. Add 20 μL of RIPA lysis buffer and 0.1 μL of protease inhibitor and phosphatase inhibitor per 1 mg of tissue, grind thoroughly, and add protease inhibitor again after grinding. Centrifuge at 12000 rpm for 20 min at 4 °C, take the supernatant, add 5× loading buffer to the protein at a ratio of 4:1, incubate at 100 °C for 5 min to denature the protein, cool rapidly on ice, and store at -20 °C.

[0080] (2) Western blot was used to detect uric acid transport-related proteins such as ABCG2 and GLUT9. The results are as follows: Figure 13 As shown, the expression levels of ABCG2 protein in mice in the BTL-MK treatment groups (low-dose butyrolactone group BTL-L, 20 mg / kg and high-dose butyrolactone group BTL-H, 40 mg / kg) were significantly different from those in the model group (HUA) mice (p < 0.0001). BTL-MK significantly increased the ABCG2 channel protein in mice with acute hyperuricemia. ABCG2 is a uric acid excretion protein, and increased expression levels help reduce uric acid levels. Figure 14 As shown, the expression level of GLUT9 protein in mice in the BTL-MK treatment group (BTL-L, 20 mg / kg) was significantly different from that in mice in the model group (HUA) (p < 0.01), while the expression level of GLUT9 protein in mice in the BTL-MK treatment group (BTL-H, 40 mg / kg) and the benzbromarone group was extremely significantly different from that in mice in the model group (p < 0.001). This indicates that BTL-MK can significantly reduce the GLUT9 channel protein in mice with acute hyperuricemia. GLUT9 is a uric acid reabsorption protein, and its reduced expression level helps uric acid excretion.

[0081] The above experimental results all indicate that the BTL-MK of the present invention can reduce uric acid in hyperuricemic mice by upregulating the expression level of ABCG2 protein and reducing the expression level of GLUT9 channel transport protein.

[0082] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. The use of butyrolactone compounds or their derivatives or pharmaceutically acceptable salts in the preparation of one of the following drugs: (a) Prevention and / or treatment of hyperuricemia; (ii) Prevention and / or treatment of uric acid nephropathy.

2. Use according to claim 1, characterized in that The butyrolactone compound is specifically 5-acetyl-3-hydroxy-4-(4-hydroxyphenyl)-5-[4-methyl-3-(3-methylbut-2-en-1-yl)benzyl]furan-2(5H)-one, having the structure shown in the following formula: 。 3. Use according to claim 1, characterized in that The butyrolactone compounds have the structure shown in the following formula: 。 4. The application according to claim 2 or 3, characterized in that... The butyrolactone compounds have one or more hydrogen atoms on their molecular chains substituted with halogen atoms, C1-C20 straight / branched / cyclic alkyl groups, C1-C20 haloalkyl groups, C2-C10 alkenyl groups, C2-C10 alkynyl groups, C1-C20 alkoxy groups, C1-C10 hydroxyalkyl groups, hydroxyl groups, C1-C20 carbonyl groups, carboxyl groups, cyano groups, nitro groups, amino groups, phenyl groups, C1-C20 ester groups, or C6-C20 aryl groups.

5. The application according to claim 1, characterized in that... The drug comprises a therapeutically effective amount of a butyrolactone compound or a derivative thereof or a pharmaceutically acceptable salt thereof.

6. The application according to claim 1, characterized in that... The product is manufactured into various dosage forms using conventional methods, including: tablets, capsules, oral liquids, lozenges, granules, pills, elixirs, suspensions, tinctures, drops, and injections for oral administration.

7. The application according to claim 1, characterized in that... The product is manufactured into various dosage forms using conventional methods, including: sugar-coated tablets, film-coated tablets, enteric-coated tablets, hard capsules, soft capsules, oral liquids, lozenges, granules, pills, boluses, suspensions, tinctures, drops, and injections for oral administration.

8. The application according to claim 1, characterized in that: The product also contains one or more pharmaceutically acceptable carriers or excipients.

9. The application according to claim 8, characterized in that: The carrier or excipient includes at least one of diluent, adhesive, surfactant, humectant, adsorbent carrier, lubricant, filler, disintegrant and preservative.

10. A product composition for the prevention and treatment of hyperuricemia and / or uric acid nephropathy, characterized in that... It comprises any butyrolactone compound or its derivative or a pharmaceutically acceptable salt thereof as described in any one of claims 1-9.

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