Pharmaceutical composition for reducing uric acid and preparation method thereof

Abstract

The invention provides a pharmaceutical composition for reducing uric acid and a preparation method thereof, and belongs to the technical field of biological pharmacy, and the active ingredients of the pharmaceutical composition comprise an okra seed extract, a carrot leaf extract, a red sword bean extract, quercetin and resveratrol. The abelmoschus esculentus seed extract is prepared by performing compound enzymolysis on abelmoschus esculentus seeds by cellulase, pectinase and xylanase, fermenting the abelmoschus esculentus seeds by rhizopus oryzae to obtain an extracting solution, and purifying the extracting solution by a D101 macroporous adsorption resin column and a polyamide chromatographic column. The carrot leaf extract is a component which is obtained by extracting carrot leaves with an ethanol water solution and is less than 10kDa. The red sword bean extract is prepared by the following steps: degreasing red sword bean seeds, carrying out compound enzymolysis on the degreased red sword bean seeds by using neutral protease and beta-glucosidase, fermenting the degreased red sword bean seeds by using lactobacillus plantarum to obtain an extracting solution, and processing the extracting solution by using a Sephadex G25 gel column. All the components are compatible to construct a multi-component, multi-target and multi-channel action system, and good acid reduction is realized by inhibiting uric acid to generate key enzyme and regulating purine metabolism.

Description

Technical Field

[0001] This invention pertains to the field of biopharmaceutical technology, specifically relating to a uric acid-lowering drug composition and its preparation method. Background Technology

[0002] Hyperuricemia and gout are metabolic diseases caused by purine metabolism disorders and uric acid excretion disorders. Sustained high blood uric acid levels can induce joint inflammation, kidney damage, urinary system stones and cardiovascular complications, and have become common chronic metabolic diseases.

[0003] Currently available uric acid-lowering drugs are mainly chemical drugs, divided into three categories: those that inhibit uric acid production, those that promote excretion, and those that break down uric acid. Allopurinol, febuxostat, and benzbromarone are representative drugs. Although they can rapidly lower blood uric acid, they have serious safety and applicability limitations. Allopurinol is prone to causing gene-related severe drug eruptions in Asian populations; febuxostat carries cardiovascular risks; and benzbromarone has a clear liver damage side effect. Furthermore, single-drug Western medicines have a single target, and long-term use easily leads to drug tolerance and large fluctuations in blood uric acid. Use is limited in patients with concomitant liver or kidney dysfunction or cardiovascular disease. Conventional combination therapy can lead to cumulative adverse reactions, and long-term use for metabolic regulation has poor safety.

[0004] In recent years, research on natural drugs and traditional Chinese medicine extracts in the field of uric acid reduction has become increasingly in-depth. The flavonoids, triterpenoids, and alkaloids in extracts of herbs such as Smilax glabra, Dioscorea hypoglauca, Plantago asiatica, Polygonum cuspidatum, and Pueraria lobata can exert a mild uric acid-lowering effect through multiple pathways, including inhibiting xanthine oxidase activity, downregulating uric acid transporter expression, anti-inflammatory and kidney-protective effects, and improving purine metabolism. These extracts also possess advantages such as low toxicity and side effects, multiple target mechanisms, and the ability to balance anti-inflammation and organ protection, thus overcoming the shortcomings of single-target chemical drugs and their significant adverse reactions. However, single traditional Chinese medicine extracts suffer from slow onset of action, uneven content of active ingredients, insufficient uric acid-lowering strength, and difficulty in achieving rapid uric acid reduction when used alone, making them unable to meet the demand for rapid uric acid reduction on their own.

[0005] In summary, both existing chemical drugs and traditional Chinese medicine extracts have their own technical limitations, and single formulations cannot simultaneously address issues such as uric acid reduction, multiple regulatory functions, and synergistic effects. Therefore, it is necessary to develop safe and effective drugs with rationally combined synergistic effects, utilizing synergistic mechanisms such as inhibiting uric acid production, promoting uric acid excretion, and anti-inflammatory and kidney-protective effects to improve the overall uric acid-lowering effect and address the pain points of existing traditional Chinese medicines such as slow onset of action, significant side effects of Western medicines, and poor compatibility. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a uric acid-lowering drug composition and its preparation method. It is prepared using a targeted process with natural plant extracts from okra seeds, carrot leaves, and red sword beans, and precisely formulated with quercetin and resveratrol. Based on the triple pathological mechanism of hyperuricemia—excessive uric acid production, impaired excretion, and amplified inflammatory oxidative stress—a multi-component, multi-target, and multi-pathway system of action is constructed. This system effectively lowers uric acid by inhibiting key enzymes in uric acid production and regulating purine metabolism. The specific technical solution is as follows: A uric acid-lowering drug composition, wherein the active pharmaceutical ingredients include okra seed extract, carrot leaf extract, red sword bean extract, quercetin and resveratrol in a mass ratio of (9-11):(3-5):(6-8):(1.2-1.8):(1.0-1.5); The okra seed extract is obtained by dissolving okra seed powder in 6 to 8 times its weight of deionized water, adjusting the pH to 4.8 to 5.2, followed by enzymatic hydrolysis with 0.8% to 1.5% (by weight of seed powder) of cellulase, pectinase, and xylanase at 48℃ to 52℃ for 2.5 to 3.5 hours. Glucose and ammonium sulfate are then added to adjust the pH to 5.0 to 5.5. 5% to 8% (by weight of seed powder) of Rhizopus oryzae Went et Prinsen-Geerligs activation solution is added, and the mixture is fermented at 25℃ to 30℃ under aerobic conditions for 52 to 60 hours to obtain the fermentation broth. After reflux extraction with ethanol, the broth is purified sequentially using a D101 macroporous adsorption resin column and a polyamide chromatography column to obtain the powder extract. The carrot leaf extract is a component with a content of less than 10 kDa obtained by extracting carrot leaves with an ethanol aqueous solution. The red sword bean extract is obtained by adjusting the pH of defatted red sword bean seed powder to 6.8-7.2 in 8-12 times its weight of deionized water, followed by enzymatic hydrolysis with 0.8%-1.5% (by weight of defatted red sword bean powder) of neutral protease and β-glucosidase at 45-50℃ for 3-4 hours. After enzyme inactivation, yeast extract is added, the pH is adjusted to 6.0-6.5, and 7%-9% (by weight of defatted red sword bean powder) of Lactobacillus plantarum activation solution is added. The mixture is then fermented anaerobicly at 35-40℃ for 38-42 hours to obtain the fermentation broth. After reflux extraction with ethanol, the extract is further processed through a Sephadex G25 gel column to obtain the powder extract.

[0007] The preparation method of the okra seed extract in the above-mentioned drug includes the following steps: okra seeds are crushed into seed powder, deionized water is added at a material-to-liquid mass ratio of 1:(6-8), the pH is adjusted to 4.8-5.2, 0.8%-1.5% (by weight of seed powder) of cellulase, pectinase, and xylanase are added, and the mixture is enzymatically hydrolyzed at 48℃-52℃ for 2.5-3.5 hours. The enzymes are then inactivated to obtain the enzymatic hydrolysate. Glucose and ammonium sulfate are added, the pH is adjusted to 5.0-5.5, and 5%-8% (by weight of seed powder) of Rhizopus oryzae activation solution is added. The mixture is then fermented at 25℃-30℃ with aeration for 52-60 hours to obtain the final product. The fermentation broth was refluxed with ethanol for extraction, concentrated under reduced pressure, centrifuged, and the supernatant was collected and loaded onto a D101 macroporous adsorption resin column. The column was first eluted with purified water for 3-4 BV to remove impurities, then eluted with 55-65 vol% ethanol aqueous solution for 5-7 BV. The eluent was collected, concentrated under reduced pressure, and loaded onto a polyamide chromatography column. The column was first eluted with 15-25 vol% ethanol aqueous solution for 2-3 BV to remove impurities, then eluted with 50-60 vol% ethanol aqueous solution for 4-6 BV. The eluent was collected, concentrated under reduced pressure, and freeze-dried to obtain okra seed extract.

[0008] In the above method for preparing okra seed extract, the stirring speed during enzymatic hydrolysis is 100 r / min to 150 r / min; the enzyme inactivation is performed at 85℃ to 90℃ for 10 to 15 minutes, followed by cooling to room temperature; the amount of glucose added is 0.5% to 0.8% of the seed powder mass; the amount of ammonium sulfate added is 0.1% to 0.3% of the seed powder mass; and the bacterial concentration of the Rhizopus oryzae activation solution is 0.8 × 10⁻⁶. 7 CFU / mL ~1.2×10 7 CFU / mL.

[0009] In the above method for preparing okra seed extract, the amount of ethanol added is 2 to 3 times the volume of the fermentation liquid; the reflux extraction is performed at 65℃ to 75℃ for 2 to 3 hours; and the centrifugation is performed at 5000 r / min to 6000 r / min for 15 to 20 minutes.

[0010] The preparation method of the carrot leaf extract in the above-mentioned drug includes the following steps: carrot leaves are made into powder, ethanol aqueous solution is added, reflux extraction is performed, vacuum concentration is performed, centrifugation is performed, the supernatant is taken, ultrafiltration is performed, the fraction with less than 10 kDa is taken, and freeze drying is performed to obtain carrot leaf extract.

[0011] In the above method for preparing carrot leaf extract, the carrot leaves are chopped, dried to a moisture content of less than 5 wt%, and pulverized through a 60-80 mesh sieve to obtain powder; the amount of ethanol aqueous solution added is 12-15 times the mass of the powder; the concentration of the ethanol aqueous solution is 60 vol%-70 vol%; the reflux extraction is performed at 65-75℃ for 3-5 hours; the vacuum concentration is performed at 60-65℃ to 15-20% of the volume; the centrifugation is performed at 5000-6000 r / min for 15-20 minutes; and the ultrafiltration uses an ultrafiltration membrane with a molecular weight cutoff of 10 kDa.

[0012] The preparation method of the red sword bean extract in the above-mentioned drug includes the following steps: red sword bean seeds are crushed into bean flour, hexane is added, ultrasonic defatting is performed, and hexane is removed by vacuum evaporation to obtain defatted bean flour. Deionized water is added to the defatted bean flour at a material-to-liquid mass ratio of 1:(8-12), and the pH is adjusted to 6.8-7.2. Neutral protease and β-glucosidase, each at 0.8%-1.5% of the defatted bean flour mass, are added, and enzymatic hydrolysis is performed at 45℃-50℃ for 3-4 hours. The enzymes are then inactivated. Yeast extract is added, and the pH is adjusted to 6.0-6.5. Lactobacillus plantarum activation solution, at 7%-9% of the defatted bean flour mass, is added. Anaerobic fermentation is performed at 35℃-40℃ for 38-42 hours to obtain the fermentation broth. Ethanol is added, and the mixture is refluxed for extraction, concentrated under reduced pressure, centrifuged, and the supernatant is collected and loaded onto Sephadex. G25 gel column was used to elute 3 BV to 5 BV with 25 vol% to 35 vol% aqueous ethanol solution. The eluent was collected, concentrated under reduced pressure, and freeze-dried to obtain red sword bean extract.

[0013] In the above method for preparing red sword bean extract, the amount of n-hexane added is 8 to 12 times the mass of the bean flour; the ultrasonic defatting is performed at 45°C to 50°C for 30 to 50 minutes; the stirring speed for enzymatic hydrolysis is 100 to 150 r / min; the enzyme inactivation is performed at 85°C to 90°C for 10 to 15 minutes, followed by cooling to room temperature; the amount of yeast extract added is 0.15% to 0.25% of the mass of defatted bean flour; and the bacterial concentration of the *Lactobacillus plantarum* activation solution is 1.0 × 10⁻⁶. 8 CFU / mL ~1.5×10 8 CFU / mL.

[0014] In the above method for preparing red sword bean extract, the amount of ethanol added is 2 to 3 times the volume of the fermentation liquid; the reflux extraction is performed at 65℃ to 75℃ for 2 to 3 hours; and the centrifugation is performed at 5000 r / min to 6000 r / min for 15 to 20 minutes.

[0015] The preparation method of the above-mentioned uric acid-lowering drug composition includes the following steps: According to the mass ratio of the components, okra seed extract, carrot leaf extract, red sword bean extract, quercetin and resveratrol are mixed evenly to obtain a pharmaceutical composition.

[0016] The above-mentioned pharmaceutical composition is used to prepare a pharmaceutical preparation with pharmaceutically usable excipients.

[0017] The present invention provides a uric acid-lowering drug composition and its preparation method, the beneficial effects of which include: I. The uric acid-lowering drug composition of this invention is prepared through a targeted process using natural plant extracts and is precisely formulated with quercetin and resveratrol. Based on the triple pathological mechanism of hyperuricemia—excessive uric acid production, impaired excretion, and amplified inflammatory oxidative stress—it constructs a multi-component, multi-target, and multi-pathway system of action. It achieves effective uric acid reduction by inhibiting key enzymes in uric acid production and regulating purine metabolism, while also blocking the pathological amplification cycle of hyperuricemia through anti-inflammatory, antioxidant, and free radical scavenging effects. At the same time, it achieves high biocompatibility by relying on the low toxicity of natural plant extracts and precise process control.

[0018] II. In the preparation of okra seed extract, a targeted process involving enzymatic hydrolysis, aerobic fermentation by Rhizopus oryzae, and dual-column purification, along with precise parameter control, was employed to achieve the activation and efficient enrichment of active ingredients: The combined enzymatic hydrolysis using cellulase, pectinase, and xylanase broke down plant cell walls, releasing bound active ingredients; aerobic fermentation by Rhizopus oryzae hydrolyzed flavonoid glycosides and triterpenoid esters into highly active free aglycones and terpenoids, improving bioavailability; stepwise purification using D101 macroporous adsorption resin and polyamide chromatography selectively enriched flavonoids, polyphenols, peptides, and other uric acid-lowering active ingredients, while removing impurities such as polysaccharides and proteins, reducing toxicity. The extract can bind to the XOD active site and is the main active ingredient in the drug composition that inhibits uric acid production.

[0019] III. In the preparation of carrot leaf extract, the process and parameters of ethanol reflux extraction and 10kDa ultrafiltration are controlled to retain small molecule flavonoids and polyphenols, remove large molecule sensitizing impurities, achieve a balance between low toxicity and activity, and play a role in DPPH free radical scavenging.

[0020] IV. In the preparation of red sword bean extract, a targeted process and precise parameter control, including defatting, double enzymatic hydrolysis, anaerobic fermentation with *Lactobacillus plantarum*, and gel purification, are employed to achieve the biotransformation and enrichment of active ingredients: ultrasonic defatting removes lipid-soluble impurities; a complex enzyme of neutral protease and β-glucosidase decomposes and amplifies molecular proteins; *Lactobacillus plantarum* fermentation hydrolyzes these proteins into small-molecule active peptides and alkaloids, while simultaneously producing functional organic acids; Sephadex G25 gel purification precisely retains small-molecule active ingredients and removes large-molecule impurities. The extract regulates upstream enzymes in purine metabolism, reduces uric acid production substrates, and also possesses anti-inflammatory and kidney-protective effects, making it a dual-effect component in pharmaceutical compositions for lowering uric acid and reducing inflammation.

[0021] Fifth, the rational combination of each component balances the core uric acid-lowering effect of okra seed extract, the antioxidant activity of carrot leaf extract, the uric acid-lowering and anti-inflammatory effects of red sword bean extract, the enhanced XOD inhibition and anti-inflammatory effects of quercetin, and the regulatory and antioxidant effects of resveratrol on purine metabolism. This avoids the toxicity risk caused by excessive concentrations of a single component or the insufficient activity caused by insufficient concentrations, achieving precise synergy among the components in the four major pathways of uric acid production inhibition, uric acid excretion promotion, inflammation suppression, and oxidative stress clearance, maximizing the multi-target effects.

[0022] In summary, the flavonoids and polyphenols in okra seed extract bind to the XOD active site, quercetin enhances the XOD inhibitory effect, resveratrol regulates upstream enzymes of purine metabolism to reduce uric acid production substrates, and small molecule peptides / alkaloids in red sword bean extract assist in inhibiting key enzymes in uric acid production, forming a dual blockade of enzyme activity inhibition and substrate reduction, significantly improving the efficiency of uric acid production inhibition and achieving good uric acid reduction. The functional organic acids in red sword bean extract, the anti-inflammatory pathway inhibition of quercetin, and the free radical scavenging effect of resveratrol, synergistically with the polyphenols and flavonoids in the three plant extracts, block the pathological amplification cycle of high uric acid, oxidative stress, inflammation, and further increase in uric acid production, reducing the risk of acute gout attacks. Detailed Implementation

[0023] The present invention will be further described below with reference to specific implementation examples, but the present invention is not limited to these embodiments.

[0024] Example 1 A uric acid-lowering drug composition comprising okra seed extract, carrot leaf extract, red sword bean extract, quercetin, and resveratrol in a mass ratio of 10:4:7:1.5:1.3.

[0025] The preparation method of the okra seed extract includes the following steps: okra seeds are pulverized into seed powder that passes through an 80-mesh sieve; deionized water is added at a material-to-liquid mass ratio of 1:7; the pH is adjusted to 5.0; 1.2% (by weight) of cellulase, pectinase, and xylanase are added to the seed powder; enzymatic hydrolysis is carried out at 48℃~52℃ and 120r / min for 3 hours; enzyme inactivation is performed at 88℃ for 12 minutes; the mixture is then cooled to room temperature to obtain the enzymatic hydrolysate; 0.7% (by weight) of glucose and 0.2% (by weight) of ammonium sulfate are added to the seed powder; the pH is adjusted to 5.2; and 6.5% (by weight) of Rhizopus oryzae activation solution (concentration 1.0×10⁻⁶) is added to the seed powder. 7Fermentation was carried out at 25℃~30℃ with 1.0 vvm aeration for 56 h to obtain the fermentation broth. 2.5 times the volume of ethanol was added, and the mixture was refluxed at 65℃~75℃ for 2.5 h. The ethanol was removed by vacuum concentration at 60℃~65℃ to a relative density of 1.15 g / mL. The mixture was centrifuged at 5500 r / min for 18 min, and the supernatant was collected. The supernatant was loaded onto a D101 macroporous adsorption resin column (column diameter to height ratio 1:8) at a flow rate of 2.0 BV / h, and first washed with purified water for 3.5 B... After removing impurities, the sample was eluted with 60 vol% ethanol aqueous solution for 6 BV, and the eluent was collected. The eluent was then concentrated under reduced pressure at 60℃~65℃ to remove ethanol. The eluent was then loaded onto a polyamide chromatography column (column diameter to height ratio 1:10) at a flow rate of 1.5 BV / h. After elution with 20 vol% ethanol aqueous solution for 2.5 BV, the eluent was eluted with 55 vol% ethanol aqueous solution for 5 BV, and the eluent was collected. The eluent was then concentrated under reduced pressure at 60℃~65℃ to remove ethanol. After sterilization by filtering through a 0.22 μm microporous membrane, the extract was freeze-dried to obtain okra seed extract.

[0026] The preparation method of the carrot leaf extract includes the following steps: carrot leaves are chopped, dried to a moisture content of 4.5 wt%, pulverized through a 60-mesh sieve to obtain powder, 65 vol% ethanol aqueous solution is added at a material-to-liquid mass ratio of 1:13, refluxed at 65℃~75℃ for 4 h, concentrated under reduced pressure at 60℃~65℃ to 18% of volume, centrifuged at 5500 r / min for 18 min, the supernatant is collected, ultrafiltered through a 10 kDa ultrafiltration membrane, the fraction with a mass below 10 kDa is collected, and freeze-dried to obtain the carrot leaf extract.

[0027] The preparation method of the red sword bean extract includes the following steps: Red sword bean seeds are taken, pulverized through a 60-mesh sieve to obtain bean flour. Hexane is added to the bean flour at a material-to-liquid mass ratio of 1:10. The mixture is ultrasonically defatted at 45℃~50℃ for 40 min, and then evaporated under reduced pressure at 40℃~45℃ to remove the hexane, obtaining defatted bean flour. Deionized water is added to the defatted bean flour at a material-to-liquid mass ratio of 1:10 to adjust the pH to 7.0. Neutral protease and β-glucosidase, each at 1.2% of the defatted bean flour mass, are added. Enzymatic hydrolysis is performed at 45℃~50℃ and 120 r / min for 3.5 h, followed by enzyme inactivation at 88℃ for 12 min. The mixture is then cooled to room temperature. Yeast extract at 0.20% of the defatted bean flour mass is added, and the pH is adjusted to 6.2. Lactobacillus plantarum activation solution (concentration 1.2 × 10⁻⁶) at 8% of the defatted bean flour mass is added. 8The red sword bean extract was obtained by anaerobic fermentation at 35℃~40℃ for 40h (CFU / mL). 2.5 times the volume of ethanol was added to the fermentation broth, and the mixture was refluxed at 65℃~75℃ for 2.5h. The extract was then concentrated under reduced pressure at 60℃~65℃ to remove ethanol and achieve a relative density of 1.10 g / mL. The extract was centrifuged at 5500 r / min for 18 min, and the supernatant was collected and loaded onto a Sephadex G25 gel column (column diameter to height ratio 1:10). The column was eluted with 30 vol% ethanol aqueous solution at a flow rate of 0.8 BV / h for 4 BV. The eluent was collected, concentrated under reduced pressure to remove ethanol, sterilized by filtration through a 0.22 μm microporous membrane, and freeze-dried to obtain the red sword bean extract.

[0028] Example 2 A uric acid-lowering drug composition comprising okra seed extract, carrot leaf extract, red sword bean extract, quercetin, and resveratrol in a mass ratio of 9:5:6:1.8:1.0.

[0029] The preparation method of the okra seed extract includes the following steps: okra seeds are pulverized into seed powder that passes through a 100-mesh sieve; deionized water is added at a material-to-liquid mass ratio of 1:6; the pH is adjusted to 5.2; 0.8% (by weight) of cellulase, pectinase, and xylanase are added to the seed powder; enzymatic hydrolysis is carried out at 48℃~52℃ and 150r / min for 2.5h; enzyme inactivation is performed at 90℃ for 10min; the solution is then cooled to room temperature to obtain the enzymatic hydrolysate; 0.8% (by weight) of glucose and 0.1% (by weight) of ammonium sulfate are added to the seed powder; the pH is adjusted to 5.5; and 5% (by weight) of Rhizopus oryzae activation solution (concentration 1.2×10⁻⁶) is added to the seed powder. 7 Fermentation was carried out at 25℃~30℃ with 0.8 vvm aeration for 60 h to obtain the fermentation broth. Twice the volume of ethanol was added to the fermentation broth, and the mixture was refluxed at 65℃~75℃ for 3 h. The ethanol was then removed by vacuum concentration at 60℃~65℃ to a relative density of 1.10 g / mL. The mixture was centrifuged at 6000 r / min for 15 min, and the supernatant was collected. The supernatant was loaded onto a D101 macroporous adsorption resin column (column diameter to height ratio 1:8) at a flow rate of 2.5 BV / h. The column was first washed with 4 BV of purified water to remove impurities. The extract was eluted with 55 vol% ethanol aqueous solution for 7 BV, and the eluent was collected. The eluent was concentrated under reduced pressure at 60℃~65℃ to remove ethanol. The eluent was then loaded onto a polyamide chromatography column (column diameter to height ratio 1:10) at a flow rate of 1.2 BV / h. The column was first eluted with 15 vol% ethanol aqueous solution for 3 BV to remove impurities, and then eluted with 50 vol% ethanol aqueous solution for 6 BV. The eluent was collected and concentrated under reduced pressure at 60℃~65℃ to remove ethanol. The eluent was then sterilized by filtering through a 0.22 μm microporous membrane and freeze-dried to obtain okra seed extract.

[0030] The preparation method of the carrot leaf extract includes the following steps: carrot leaves are chopped, dried to a moisture content of 4wt%, pulverized through an 80-mesh sieve to obtain powder, 70 vol% ethanol aqueous solution is added at a material-to-liquid mass ratio of 1:12, refluxed at 65℃~75℃ for 3 hours, concentrated under reduced pressure at 60℃~65℃ to 20% of the volume, centrifuged at 5000 r / min for 20 min, the supernatant is collected, ultrafiltered through a 10 kDa ultrafiltration membrane, the fraction with a mass below 10 kDa is collected, and freeze-dried to obtain the carrot leaf extract.

[0031] The preparation method of the red sword bean extract includes the following steps: Red sword bean seeds are taken, pulverized through a 60-mesh sieve to obtain bean flour. Hexane is added to the bean flour at a material-to-liquid mass ratio of 1:12. The mixture is ultrasonically defatted at 45℃~50℃ for 30 minutes, and then evaporated under reduced pressure at 40℃~45℃ to remove the hexane, obtaining defatted bean flour. Deionized water is added to the defatted bean flour at a material-to-liquid mass ratio of 1:12 to adjust the pH to 6.8. Neutral protease and β-glucosidase, each at 1.5% of the defatted bean flour mass, are added. Enzymatic hydrolysis is performed at 45℃~50℃ and 100 r / min for 4 hours, followed by enzyme inactivation at 85℃ for 15 minutes. The mixture is then cooled to room temperature. Yeast extract at 0.15% of the defatted bean flour mass is added, and the pH is adjusted to 6.5. Finally, Lactobacillus plantarum activation solution (concentration 1.5 × 10⁻⁶) at 7% of the defatted bean flour mass is added. 8 The red sword bean extract was obtained by anaerobic fermentation at 35℃~40℃ for 38 h to obtain the fermentation broth. Two volumes of ethanol were added to the fermentation broth, and the mixture was refluxed at 65℃~75℃ for 3 h. The extract was then concentrated under reduced pressure at 60℃~65℃ to remove ethanol and achieve a relative density of 1.05 g / mL. The mixture was centrifuged at 6000 r / min for 15 min, and the supernatant was collected and loaded onto a Sephadex G25 gel column (column diameter to height ratio 1:10). The column was eluted with 35 vol% ethanol aqueous solution at a flow rate of 0.6 BV / h for 5 BV. The eluent was collected, concentrated under reduced pressure to remove ethanol, sterilized by filtration through a 0.22 μm microporous membrane, and freeze-dried to obtain the red sword bean extract.

[0032] Example 3 A uric acid-lowering drug composition comprising okra seed extract, carrot leaf extract, red sword bean extract, quercetin, and resveratrol in a mass ratio of 11:3:8:1.2:1.5.

[0033] The preparation method of the okra seed extract includes the following steps: okra seeds are pulverized into seed powder that passes through an 80-mesh sieve; deionized water is added at a material-to-liquid mass ratio of 1:8; the pH is adjusted to 4.8; 1.5% (by weight) of cellulase, pectinase, and xylanase are added to the seed powder; enzymatic hydrolysis is carried out at 48℃~52℃ and 100r / min for 3.5h; enzyme inactivation is performed at 85℃ for 15min; the solution is then cooled to room temperature to obtain the enzymatic hydrolysate; 0.5% (by weight) of glucose and 0.3% (by weight) of ammonium sulfate are added to the seed powder; the pH is adjusted to 5.0; and 8% (by weight) of Rhizopus oryzae activation solution (concentration 0.8×10⁻⁶) is added to the seed powder. 7 Fermentation was carried out at 25℃~30℃ with 1.2vvm oxygen for 52h to obtain the fermentation broth. Three times the volume of ethanol was added to the fermentation broth, and the mixture was refluxed at 65℃~75℃ for 2h. The ethanol was removed by vacuum concentration at 60℃~65℃ to a relative density of 1.20g / mL. The mixture was centrifuged at 5000r / min for 20min, and the supernatant was collected. The supernatant was loaded onto a D101 macroporous adsorption resin column (column diameter to height ratio 1:10) at a flow rate of 1.5BV / h. The column was first washed with 3BV of purified water. After removing impurities, the sample was eluted with 65 vol% ethanol aqueous solution for 5 BV. The eluent was collected and concentrated under reduced pressure at 60℃~65℃ to remove ethanol. The eluent was then loaded onto a polyamide chromatography column (column diameter to height ratio 1:8) at a flow rate of 1.8 BV / h. The sample was first eluted with 25 vol% ethanol aqueous solution for 2 BV to remove impurities, and then eluted with 60 vol% ethanol aqueous solution for 4 BV. The eluent was collected and concentrated under reduced pressure at 60℃~65℃ to remove ethanol. The sample was then sterilized by filtering through a 0.22 μm microporous membrane and freeze-dried to obtain okra seed extract.

[0034] The preparation method of the carrot leaf extract includes the following steps: carrot leaves are chopped, dried to a moisture content of 5 wt%, pulverized through a 60-mesh sieve to obtain powder, and 60 vol% ethanol aqueous solution is added at a material-to-liquid mass ratio of 1:15. The mixture is refluxed at 65℃~75℃ for 5 h, concentrated under reduced pressure at 60℃~65℃ to 15% of its volume, centrifuged at 6000 r / min for 15 min, and the supernatant is collected. The supernatant is then ultrafiltered through a 10 kDa ultrafiltration membrane, and the fraction with a supernatant content below 10 kDa is collected and freeze-dried to obtain the carrot leaf extract.

[0035] The preparation method of the red sword bean extract includes the following steps: Red sword bean seeds are taken, pulverized through an 80-mesh sieve to obtain bean flour. Hexane is added to the bean flour at a material-to-liquid mass ratio of 1:8. The mixture is ultrasonically defatted at 45℃~50℃ for 50 min, and then evaporated under reduced pressure at 40℃~45℃ to remove the hexane, obtaining defatted bean flour. Deionized water is added to the defatted bean flour at a material-to-liquid mass ratio of 1:8, and the pH is adjusted to 7.2. Neutral protease and β-glucosidase, each at 0.8% of the defatted bean flour mass, are added. Enzymatic hydrolysis is performed at 45℃~50℃ and 150 r / min for 3 h, followed by enzyme inactivation at 90℃ for 10 min. The mixture is then cooled to room temperature. Yeast extract at 0.25% of the defatted bean flour mass is added, and the pH is adjusted to 6.0. Finally, Lactobacillus plantarum activation solution (concentration 1.0 × 10⁻⁶) at 9% of the defatted bean flour mass is added. 8 The red sword bean extract was obtained by anaerobic fermentation at 35℃~40℃ for 42 h to obtain the fermentation broth. Three times the volume of ethanol was added to the fermentation broth, and the mixture was refluxed at 65℃~75℃ for 2 h. The ethanol was removed by vacuum concentration at 60℃~65℃ and the relative density was reduced to 1.15 g / mL. The mixture was centrifuged at 5000 r / min for 20 min, and the supernatant was collected and loaded onto a Sephadex G25 gel column (column diameter to height ratio 1:8). The column was eluted with 25 vol% ethanol aqueous solution at a flow rate of 1.0 BV / h for 3 BV. The eluent was collected, concentrated under reduced pressure to remove the ethanol, sterilized by filtering through a 0.22 μm microporous membrane, and freeze-dried to obtain the red sword bean extract.

[0036] The preparation methods of the pharmaceutical compositions in the above embodiments include the following steps: Okra seed extract, carrot leaf extract, red sword bean extract, quercetin, and resveratrol were mixed evenly according to the component mass ratio to obtain a pharmaceutical composition. The pharmaceutical composition was then used with pharmaceutically acceptable excipients to prepare a drug formulation.

[0037] Comparative Example 1 The difference from Example 1 is that the mass ratio of okra seed extract, carrot leaf extract, red sword bean extract, quercetin and resveratrol is 4:10:7:1.5:1.3.

[0038] Comparative Example 2 The difference from Example 1 is that the mass ratio of okra seed extract, carrot leaf extract, red sword bean extract, quercetin and resveratrol is 10:9:2:1.5:1.3.

[0039] Comparative Example 3 The difference from Example 1 is that no carrot leaf extract was added.

[0040] Comparative Example 4 The difference from Example 1 is that in the preparation of okra seed extract, Rhizopus oryzae is replaced by Lactobacillus plantarum for anaerobic fermentation.

[0041] Comparative Example 5 The difference from Example 1 is that in the preparation of okra seed extract, D101 macroporous adsorption resin is replaced with AB-8 macroporous adsorption resin.

[0042] Comparative Example 6 The difference from Example 1 is that polyamide chromatography column purification is not used in the preparation of okra seed extract.

[0043] Comparative Example 7 The difference from Example 1 is that Lactobacillus plantarum fermentation is not used in the preparation of the red sword bean extract.

[0044] Comparative Example 8 The difference from Example 1 is that in the preparation of red sword bean extract, Sephadex G25 gel is replaced with Sephadex G50.

[0045] The raw materials used in the above embodiments and comparative examples were sourced as follows: Quercetin was sourced from Shaanxi Shuoyang Biotechnology Co., Ltd., anhydrous quercetin. Resveratrol was sourced from Shaanxi Huikang Bioengineering Co., Ltd. Okra seeds were sourced from Xingning Qingfeng Yingke Seed Co., Ltd. Cellulase was sourced from Claylan (Shaanxi) Biotechnology Co., Ltd., with an enzyme activity of 20,000 U / g. Pectinase was sourced from Zhengzhou Huafeng Food Technology Co., Ltd., with an enzyme activity of 30,000 U / g. Xylanase was sourced from Zhengzhou Huafeng Food Technology Co., Ltd., with an enzyme activity of 10,000 U / g. Rhizopus oryzae Went et Prinsen-Geerligs was sourced from Shanghai Xuanke Biotechnology Co., Ltd., ATCC 24861. D101 macroporous adsorption resin, AB-8 macroporous adsorption resin, Sephadex G25, and Sephadex G50 were all sourced from Shanghai Mairui Biochemical Technology Co., Ltd. Polyamide was sourced from Shanghai Chuangsai Technology Co., Ltd., 30-60 mesh. Carrot leaves were obtained from Hongsen carrots. Red sword bean seeds were sourced from Bozhou Dapeng Pharmaceutical Co., Ltd. Hexane purity ≥ 99%. Neutral protease sourced from Wuhan Dingxintong Pharmaceutical Co., Ltd., enzyme activity 20,000 U / g. β-glucosidase sourced from Shanghai Mairui Biochemical Technology Co., Ltd., enzyme activity 10,000 U / g. Yeast extract sourced from Wuhan Jiyesheng Chemical Co., Ltd., for microbial culture medium. Lactobacillus plantarum sourced from Shanghai Fuxiang Biotechnology Co., Ltd., ACCC 11095.

[0046] I. Cytotoxicity test: Sample preparation: Take the drug composition powders from each example and comparative example, prepare a stock solution of 10 mg / mL with DMSO, and filter it through a 0.22 μm filter membrane for sterilization. Dilute the drug solution to 200 μg / mL with high-glucose DMEM complete medium containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin, with a final DMSO concentration of <0.1%.

[0047] Detection method: NIH / 3T3 mouse embryonic fibroblasts were analyzed at a density of 5 × 10⁶ cells per well. 3 Cells were seeded at a density of [number] cells per well in 96-well plates and cultured at 37°C with 5% CO2 for 24 h. The original culture medium was discarded, and 100 μL of drug solution was added to each well to create the drug group. A blank group (culture medium only, no cells) and a negative control group (complete culture medium of 0.1% DMSO) were also included. Each group had 5 replicates. After culturing for another 24 h, 10 μL of CCK-8 solution was added to each well, and the cells were incubated at 37°C in the dark for 2 h. The OD value was measured at 450 nm using a microplate reader. Cell viability (%) = [(OD drug group - OD blank group) / (OD negative control group - OD blank group)] × 100%.

[0048] II. Hemolytic test: Sample preparation: Take the drug composition powders from each example and comparative example, prepare a 10 mg / mL stock solution with DMSO, and filter it through a 0.22 μm filter membrane for sterilization. Dilute the stock solution with physiological saline to 200 μg / mL to obtain the drug solution.

[0049] Detection Method: Whole blood from healthy New Zealand white rabbits was anticoagulated with sodium citrate. Red blood cells were washed three times with physiological saline (centrifuged at 1500 rpm for 10 min) to prepare a 2% (v / v) red blood cell suspension. In a 96-well plate, 100 μL of the drug solution and 100 μL of the red blood cell suspension were added to each well (drug group). A negative control (100 μL physiological saline + 100 μL red blood cell suspension) and a positive control (100 μL distilled water + 100 μL red blood cell suspension) were set up. Each group had three replicates. After incubation at 37℃ for 3 h, the plates were centrifuged at 1500 rpm for 10 min, and the supernatant was measured at 540 nm. Hemolysis rate (%) = [(OD drug group - OD negative control group) / (OD positive control group - OD negative control group)] × 100%.

[0050] III. Detection of xanthine oxidase (XOD) inhibitory activity: Sample preparation: Take the drug composition powders from each example and comparative example, prepare a 10 mg / mL stock solution with DMSO, and filter it through a 0.22 μm filter membrane for sterilization. Dilute with 50 mM potassium phosphate buffer (pH 7.5) to a 10 μg / mL drug solution.

[0051] Detection method: In a 96-well quartz plate, add 140 μL of potassium phosphate buffer, 20 μL of drug solution, and 20 μL of XOD solution (0.04 U / mL) sequentially, and incubate at 25°C for 5 min. Add 20 μL of xanthine substrate solution (0.15 mM, prepared in 0.1 M NaOH) to initiate the reaction. After reacting at 25°C for 30 min, add 20 μL of 1 M HCl to terminate the reaction. Set up a blank group (without enzyme solution, using buffer solution instead) and a control group (without drug, using buffer solution instead). Each group has 3 replicates. Measure the OD value at 295 nm. XOD inhibition rate (%) = [(OD control group - OD drug group) / (OD control group - OD blank group)] × 100%.

[0052] IV. Uric acid production inhibition test: Sample preparation: Take the drug composition powders from each example and comparative example, prepare a 10 mg / mL stock solution with DMSO, and filter it through a 0.22 μm filter membrane for sterilization. Dilute with 0.1 M PBS (pH 7.4) to a drug solution of 10 μg / mL.

[0053] Detection method: The reaction system contained XOD (0.2 U / mL), hypoxanthine (2 mM), and drug solution (10 μg / mL), and was made up to 300 μL with 0.1 M PBS. A model group (without drug) and a blank group (without XOD) were set up. Each group had 5 replicates. The reaction was stopped at 37℃ for 60 min, followed by heating in a boiling water bath for 5 min. The mixture was centrifuged at 12000 rpm for 10 min, and the supernatant was collected. Uric acid was detected using a uric acid assay kit, and the OD value was measured at 520 nm. The uric acid concentration was calculated from the standard curve. Uric acid production inhibition rate (%) = [(model group uric acid concentration - drug group uric acid concentration) / model group uric acid concentration] × 100%. The blank group eliminated background uric acid interference.

[0054] V. Anti-inflammatory activity test: Sample preparation: Take the drug composition powders from each example and comparative example, prepare a stock solution of 10 mg / mL with DMSO, and sterilize by filtration through a 0.22 μm filter membrane. Dilute with complete culture medium to a drug solution of 10 μg / mL.

[0055] Detection method: RAW264.7 mouse mononuclear macrophages were cultured at a density of 1 × 10⁶ cells per well. 5Cells were seeded at a density of [number] cells per well in 96-well plates and cultured for 12 h. The cells were pretreated with the drug solution for 2 h, followed by stimulation with LPS (final concentration 1 μg / mL) for 24 h. A blank control group (no LPS or drug) and a model group (LPS only, no drug) were set up. Each group had 5 replicates. After stimulation, the cell supernatant was collected. The concentrations of TNF-α and IL-1β in the supernatant were detected using an ELISA kit for TNF-α and IL-1β. Inflammatory factor inhibition rate (%) = [(model group factor content - drug group factor content) / model group factor content] × 100%.

[0056] VI. Antioxidant Activity Testing: Sample preparation: Take the drug composition powder of each example and comparative example, prepare a 1 mg / mL stock solution with anhydrous methanol, and then dilute it with methanol to a 20 μg / mL drug solution.

[0057] Detection method: Add 100 μL of drug solution and 100 μL of 0.1 mM DPPH methanol solution to a 96-well plate, mix well, and react at room temperature in the dark for 30 min. A blank control (100 μL methanol + 100 μL DPPH solution) was set up. Each group had 3 replicates. The OD value was measured at a wavelength of 517 nm. DPPH free radical scavenging rate (%) = [1 - (OD drug group / OD blank control group)] × 100%.

[0058] Table 1. Test Results (Average Values)

[0059] The above data: * P < 0.03.

[0060] The performance advantages of the uric acid-lowering drug compositions in the above embodiments stem from the dual effects of multi-component, multi-target synergy and targeted enrichment, achieving a four-dimensional synergy of inhibiting uric acid production, promoting uric acid excretion, anti-inflammatory and antioxidant effects, and organ protection. Furthermore, the optimized process and formulation result in formulations with both high activity and high safety. The flavonoids, polyphenols, and peptides enriched from okra seed extract after enzymatic hydrolysis and Rhizopus oryzae fermentation bind to the XOD active site. Red sword bean extract, quercetin, and okra seed extract enhance XOD inhibition to varying degrees. Resveratrol regulates upstream enzymes in purine metabolism, reducing substrates, forming a dual blockade of enzyme inhibition and metabolic regulation, effectively reducing uric acid production. Quercetin and resveratrol inhibit pathways, reducing the release of pro-inflammatory factors. The polyphenols, flavonoids, and small molecule peptides from various plant extracts scavenge free radicals, reduce lipid peroxidation, and have anti-inflammatory effects, blocking the amplified cycle of high uric acid, oxidative stress, and inflammation, thus reducing the risk of acute gout attacks. The process involves enzymatic hydrolysis, fermentation, D101 resin, and polyamide chromatography to purify okra seeds, selectively enriching active ingredients such as flavonoids and polyphenols while removing impurities like polysaccharides and proteins. Carrot leaves undergo ethanol reflux and 10kDa ultrafiltration to retain small-molecule active components, remove large-molecule sensitizing impurities, and enhance DPPH free radical scavenging. Red sword beans are defatted, undergo double enzymatic hydrolysis, fermented with *Lactobacillus plantarum*, and then fractionated with Sephadex G25 gel electrophoresis to enrich small-molecule peptides and alkaloids. Precise impurity control in this process increases the concentration of active ingredients while maintaining low toxicity and high bioavailability. The examples focus on optimizing the core mass ratio, balancing the roles of each component in inhibiting uric acid production, promoting excretion, and providing anti-inflammatory and antioxidant effects. This avoids the toxicity risks caused by excessively high concentrations of a single component or the insufficient activity caused by excessively low concentrations, achieving a balance between potent uric acid reduction and high biocompatibility.

[0061] Comparative Examples 1 to 3 disrupted the core compatibility balance of the formula, significantly reduced the proportion of key components, or directly lacked core auxiliary components, resulting in a significant weakening of the multi-target synergistic effect between the components and a significant reduction in the overall uric acid-lowering, anti-inflammatory, and antioxidant effects. At the same time, the improper excessive proportion of some components not only failed to make up for the gap in the function of the core components, but also caused slight safety risks due to the excessive introduction of impurities and component redundancy, leading to the appearance of side effects.

[0062] In Comparative Example 4, aerobic fermentation by *Rhizopus oryzae* hydrolyzed bound flavonoids and triterpenoids in okra seeds into highly active free aglycones and terpenoids via extracellular oxidases and glycosidases. In contrast, anaerobic fermentation by *Lactobacillus plantarum* primarily involved acid production and protein hydrolysis, failing to activate flavonoids and triterpenoids, resulting in low bioavailability. Furthermore, the altered product profile of anaerobic fermentation reduced the enrichment efficiency of subsequent resin purification, further decreasing the concentration of active ingredients, and the byproducts of anaerobic fermentation slightly affected cell membrane stability.

[0063] In Comparative Example 5, D101 is a non-polar mesoporous resin that exhibits highly specific adsorption selectivity for moderately polar flavonoids, polyphenols, and triterpenoids in okra seeds, effectively enriching the active ingredients. In contrast, AB-8 is a weakly polar resin with a wider pore size distribution, which enhances the adsorption of polar impurities and reduces the selectivity for target active ingredients, resulting in a decrease in the loading and purity of active ingredients, while increasing the proportion of impurities.

[0064] In Comparative Example 6, polyamide chromatography exhibits hydrogen-bonded specific adsorption of flavonoids and phenolic acids. This step is crucial for fine impurity removal and secondary enrichment after crude purification with D101 resin, eliminating ineffective impurities such as polysaccharides, pigments, and lipid-soluble substances, thereby increasing the relative concentration of active ingredients. Eliminating this step significantly increases the proportion of impurities in the extract, diluting the active ingredients and directly leading to a decrease in various activity indicators. Simultaneously, large-molecule polysaccharides and lipids easily bind non-specifically to cell membranes.

[0065] In Comparative Example 7, fermentation with Lactobacillus plantarum is the core step in the biotransformation and enhancement of the active ingredients in red sword beans. It hydrolyzes large molecular proteins into small molecular active peptides and produces functional organic acids to enhance anti-inflammatory and metabolic regulation capabilities. Without fermentation, the effective ingredients of red sword beans are difficult to release, the bioavailability is extremely low, and the anti-inflammatory, antioxidant, and purine metabolism regulation capabilities are almost lost.

[0066] In Comparative Example 8, the exclusion limit of Sephadex G25 was highly matched with the molecular weight of the target active ingredients such as small molecule peptides, alkaloids, and flavonoids after red bean fermentation, accurately retaining the active ingredients and removing large molecule proteins and polysaccharide impurities. In contrast, Sephadex G50 had a higher exclusion limit, allowing more large molecule impurities to enter the elution fraction, resulting in dilution of the target active ingredients, decreased purity, and a significant reduction in bioactivity per unit mass. Simultaneously, the increased amount of large molecule impurities caused slight irritation to the cell membrane.

Claims

1. A uric acid-lowering drug composition, characterized in that, The active pharmaceutical ingredients include okra seed extract, carrot leaf extract, red sword bean extract, quercetin, and resveratrol in a mass ratio of (9–11):(3–5):(6–8):(1.2–1.8):(1.0–1.5). The okra seed extract is obtained by dissolving okra seed powder in 6 to 8 times its weight of deionized water, adjusting the pH to 4.8 to 5.2, followed by enzymatic hydrolysis with 0.8% to 1.5% (by weight of seed powder) of cellulase, pectinase, and xylanase at 48℃ to 52℃ for 2.5 to 3.5 hours. Glucose and ammonium sulfate are then added to adjust the pH to 5.0 to 5.

5. 5% to 8% (by weight of seed powder) of Rhizopus oryzae Went et Prinsen-Geerligs activation solution is added, and the mixture is fermented at 25℃ to 30℃ under aerobic conditions for 52 to 60 hours to obtain the fermentation broth. After reflux extraction with ethanol, the broth is purified sequentially using a D101 macroporous adsorption resin column and a polyamide chromatography column to obtain the powder extract. The carrot leaf extract is a component with a content of less than 10 kDa obtained by extracting carrot leaves with an ethanol aqueous solution. The red sword bean extract is obtained by adjusting the pH of defatted red sword bean seed powder to 6.8-7.2 in 8-12 times its weight of deionized water, followed by enzymatic hydrolysis with 0.8%-1.5% (by weight of defatted red sword bean powder) of neutral protease and β-glucosidase at 45-50℃ for 3-4 hours. After enzyme inactivation, yeast extract is added, the pH is adjusted to 6.0-6.5, and 7%-9% (by weight of defatted red sword bean powder) of Lactobacillus plantarum activation solution is added. The mixture is then fermented anaerobicly at 35-40℃ for 38-42 hours to obtain the fermentation broth. After reflux extraction with ethanol, the extract is further processed through a Sephadex G25 gel column to obtain the powder extract.

2. The uric acid-lowering drug composition according to claim 1, characterized in that, The preparation method of the okra seed extract includes the following steps: okra seeds are crushed into seed powder, deionized water is added at a material-to-liquid mass ratio of 1:(6-8), the pH is adjusted to 4.8-5.2, and 0.8%-1.5% (by weight) of cellulase, pectinase, and xylanase are added. Enzymatic hydrolysis is carried out at 48℃-52℃ for 2.5-3.5 hours, the enzymes are inactivated, and an enzymatic hydrolysate is obtained. Glucose and ammonium sulfate are added, the pH is adjusted to 5.0-5.5, and 5%-8% (by weight) of Rhizopus oryzae activation solution is added. Aerobic fermentation is carried out at 25℃-30℃ for 52-60 hours to obtain the fermentation broth. Ethanol was added, and the mixture was refluxed for extraction. The extract was concentrated under reduced pressure, centrifuged, and the supernatant was collected. The supernatant was then loaded onto a D101 macroporous adsorption resin column. The column was first eluted with purified water for 3-4 BV to remove impurities, and then eluted with 55-65 vol% ethanol aqueous solution for 5-7 BV. The eluent was collected, concentrated under reduced pressure, and loaded onto a polyamide chromatography column. The column was first eluted with 15-25 vol% ethanol aqueous solution for 2-3 BV to remove impurities, and then eluted with 50-60 vol% ethanol aqueous solution for 4-6 BV. The eluent was collected, concentrated under reduced pressure, and freeze-dried to obtain okra seed extract.

3. The uric acid-lowering drug composition according to claim 2, characterized in that, The stirring speed for enzymatic hydrolysis is 100 r / min to 150 r / min; the enzyme inactivation is performed at 85℃ to 90℃ for 10 to 15 minutes, followed by cooling to room temperature; the amount of glucose added is 0.5% to 0.8% of the seed flour mass; the amount of ammonium sulfate added is 0.1% to 0.3% of the seed flour mass; the bacterial concentration of the Rhizopus oryzae activation solution is 0.8 × 10⁻⁶. 7 CFU / mL ~1.2×10 7 CFU / mL.

4. The uric acid-lowering drug composition according to claim 2, characterized in that, The amount of ethanol added is 2 to 3 times the volume of the fermentation liquid; the reflux extraction is carried out at 65℃ to 75℃ for 2 to 3 hours; the centrifugation is carried out at 5000 r / min to 6000 r / min for 15 to 20 minutes.

5. The uric acid-lowering drug composition according to claim 1, characterized in that, The preparation method of the carrot leaf extract includes the following steps: carrot leaves are made into powder, ethanol aqueous solution is added, reflux extraction is performed, vacuum concentration is performed, centrifugation is performed, the supernatant is collected, ultrafiltration is performed, the fraction with less than 10 kDa is collected, and freeze drying is performed to obtain carrot leaf extract.

6. The uric acid-lowering drug composition according to claim 5, characterized in that, The carrot leaves are chopped, dried to a moisture content of less than 5 wt%, and pulverized through a 60-80 mesh sieve to obtain powder. The amount of ethanol aqueous solution added is 12 to 15 times the mass of the powder. The concentration of the ethanol aqueous solution is 60 vol% to 70 vol%. The reflux extraction is performed at 65℃ to 75℃ for 3 to 5 hours. The vacuum concentration is performed at 60℃ to 65℃ to 15% to 20% of the volume. The centrifugation is performed at 5000 r / min to 6000 r / min for 15 to 20 minutes. The ultrafiltration uses an ultrafiltration membrane with a molecular weight cutoff of 10 kDa.

7. The uric acid-lowering drug composition according to claim 1, characterized in that, The preparation method of the red sword bean extract includes the following steps: red sword bean seeds are crushed into bean flour, hexane is added, and the mixture is ultrasonically defatted and evaporated under reduced pressure to remove the hexane, resulting in defatted bean flour. The defatted bean flour is added to deionized water at a material-to-liquid mass ratio of 1:(8-12), and the pH is adjusted to 6.8-7.

2. Neutral protease and β-glucosidase, each at 0.8%-1.5% of the defatted bean flour mass, are added, and the mixture is enzymatically hydrolyzed at 45℃-50℃ for 3-4 hours to inactivate the enzymes. Yeast extract is added, and the pH is adjusted to 6.0-6.

5. Lactobacillus plantarum activation solution, at 7%-9% of the defatted bean flour mass, is added, and the mixture is anaerobic fermented at 35℃-40℃ for 38-42 hours to obtain the fermentation broth. Ethanol is added, and the mixture is refluxed for extraction, concentrated under reduced pressure, centrifuged, and the supernatant is collected and loaded onto a Sephadex G25 gel column. The column is eluted with 25vol%-35vol% ethanol aqueous solution for 3-5 BV, and the eluent is collected, concentrated under reduced pressure, and freeze-dried to obtain the red sword bean extract.

8. The uric acid-lowering drug composition according to claim 1, characterized in that, The amount of hexane added is 8 to 12 times the mass of the soybean flour; the ultrasonic defatting is performed at 45°C to 50°C for 30 to 50 minutes; the stirring speed for enzymatic hydrolysis is 100 to 150 rpm; the enzyme inactivation is performed at 85°C to 90°C for 10 to 15 minutes, followed by cooling to room temperature; the amount of yeast extract added is 0.15% to 0.25% of the mass of defatted soybean flour; the bacterial concentration of the *Lactobacillus plantarum* activation solution is 1.0 × 10⁻⁶. 8 CFU / mL ~1.5×10 8 CFU / mL.

9. The uric acid-lowering drug composition according to claim 1, characterized in that, The amount of ethanol added is 2 to 3 times the volume of the fermentation liquid; the reflux extraction is carried out at 65℃ to 75℃ for 2 to 3 hours; the centrifugation is carried out at 5000 r / min to 6000 r / min for 15 to 20 minutes.

10. The method for preparing the uric acid-lowering drug composition according to claim 1, characterized in that, Includes the following steps: According to the mass ratio of the components, okra seed extract, carrot leaf extract, red sword bean extract, quercetin and resveratrol are mixed evenly to obtain a pharmaceutical composition.

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