Application of white ginseng mushroom in preparation of medicine for treating hyperuricemia

Abstract

The application discloses application of white ginseng mushroom in preparation of a medicine for treating hyperuricemia, and belongs to the technical field of deep processing of edible mushrooms. The white ginseng mushroom is vacuum freeze-dried, ground into powder, other traditional Chinese medicine ingredients are extracted, concentrated, and spray-dried into powder; the white ginseng mushroom powder is mixed with sodium carboxymethyl cellulose and guar gum solution to form a mushroom suspension colloid, the microcapsules are collected after being dropped into a calcium-containing aqueous solution; the microcapsules are immersed in a high polymer compound solution for treatment, finally mixed with a stabilizer paste, and then filled after being treated by a high-pressure homogenizer and sterilized. Compared with the prior art, the medicine has good stability in simulated gastric juice, can be quickly released in simulated intestinal juice, significantly improves the bioavailability and curative effect of the medicine, can effectively reduce the serum uric acid level, improve liver and kidney functions, and regulate the intestinal flora structure, and has a significant uric acid-lowering effect and multi-target synergistic effect.

Description

Technical Field

[0001] This invention relates to the field of edible fungi deep processing technology, and in particular to the application of a type of white ginseng fungus in the preparation of drugs for treating hyperuricemia. Background Technology

[0002] Hyperuricemia (HUA) is a metabolic disease characterized by abnormally elevated serum uric acid (UA) levels and has become a global public health problem. Epidemiological data show that the prevalence of hyperuricemia is high and closely related to serious complications such as gout, chronic kidney disease, and cardiovascular disease. Current clinical treatments mainly rely on xanthine oxidase inhibitors (such as allopurinol and febuxostat) and uricosuric agents (such as benzbromarone). Although these drugs can effectively lower uric acid levels, long-term use may lead to liver and kidney damage, allergic reactions, and drug resistance. In addition, single-target intervention strategies are insufficient to comprehensively regulate the imbalance of uric acid metabolism (excessive production and impaired excretion) and its associated inflammatory and oxidative stress damage. Therefore, exploring multi-target, low-toxicity natural drugs has become an important research direction in the treatment of hyperuricemia.

[0003] In recent years, the role of gut microbiota in metabolic diseases has received increasing attention. The gut microbiota is a complex ecosystem in the human gut, containing thousands of bacterial species, mainly distributed among phyla such as Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. Studies have confirmed that the gut microbiota directly affects the pathogenesis of hyperuricemia by regulating the catabolism of purines and uric acid. Approximately 70% of uric acid is excreted through the kidneys, while the remaining 30% is metabolized by the gut microbiota. Hyperuricemia can lead to gut microbiota dysbiosis, manifested as reduced species richness and diversity, thereby exacerbating disease progression. For example, increased abundance of harmful bacteria such as Desulfovibrionaceae and Desulfovibrion promotes inflammatory responses, while decreased abundance of beneficial bacteria such as Lactobacillus and Lactobacillus reuteri weakens uric acid breakdown. Animal experiments have shown that abnormal changes in the Firmicutes / Bacteroidetes ratio (F / B) in the gut microbiota of hyperuricemic rat models, with a significantly increased abundance of Parasutterella, are directly related to elevated hypoxanthine levels and increased uric acid synthesis.

[0004] Traditional Chinese medicines, often used both as food and medicine, have shown potential in improving hyperuricemia due to their multi-target and low-toxicity advantages. *Schizophyllum commune*, a rare fungus used for both food and medicine, is rich in active ingredients such as polysaccharides, triterpenoids, and adenosine, and possesses effects such as lowering uric acid, regulating immunity, and antioxidation. Existing research indicates that *Schizophyllum commune* polysaccharides can lower uric acid levels by altering the gut microbiota structure in obese mouse models and shrimp (e.g., increasing Bacteroidetes abundance and decreasing Firmicutes abundance). However, existing technologies mainly focus on the modification and application of *Schizophyllum commune* polysaccharides. For example, Chinese patent application CN114957507A discloses a composite modification method to enhance the bioactivity of *Schizophyllum commune* polysaccharides. This method improves polysaccharide solubility and α-amylase inhibitory activity through enzymatic hydrolysis, irradiation, and carboxymethylation treatment, but its application is limited to health supplements and does not involve the treatment of hyperuricemia. Furthermore, this method fails to address the instability of the active ingredients of *Syngonium oxyphylla* in the acidic environment of the stomach, resulting in low oral bioavailability and a lack of delivery systems targeting the regulation of the gut microbiota. Therefore, developing a direct drug delivery strategy based on *Syngonium oxyphylla*, combined with microencapsulation technology to improve intestinal targeting and sustained-release performance, is of great significance for achieving efficient and safe treatment of hypertrophic inflammatory bowel disease (HUA). Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention aims to provide a multi-component synergistic drug based on microencapsulation of *Panax ginseng*, which achieves gastric protection and targeted intestinal release through a calcium lactate-low-ester pectin sustained-release system, significantly improving the efficacy of uric acid reduction and alleviating liver and kidney damage.

[0006] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0007] Application of white ginseng fungus in the preparation of drugs for treating hyperuricemia.

[0008] Specifically, the preparation method of the drug for treating hyperuricemia includes the following steps:

[0009] Step 1: Vacuum freeze-dry the white ginseng fungus and grind it into powder; extract the chicory, kudzu root, Ganoderma lucidum and purslane separately with ethanol aqueous solution using countercurrent extraction, concentrate and spray dry them into powder; juice the celery, concentrate and spray dry it into powder.

[0010] Step 2: Dissolve sodium carboxymethyl cellulose in deionized water and mix with guar gum solution. Add white ginseng mycelium powder to form a mycelium suspension. Drop the suspension into a calcium-containing aqueous solution and collect the microcapsules. Rinse to obtain wet microcapsules. Add a polymer compound to an acetic acid aqueous solution and stir until clear. Immerse the wet microcapsules in the polymer compound solution and filter to collect the microcapsules. Immerse the microcapsules again in a calcium-containing aqueous solution and collect the microcapsules. Rinse and freeze-dry under vacuum to obtain white ginseng mycelium microcapsule powder.

[0011] Step 3: Disperse microcrystalline cellulose and xanthan gum in deionized water to swell and then cool. Add Tween-80, potassium sorbate, and xylitol and stir to dissolve to obtain a stabilizer slurry. Gradually add white ginseng microcapsule powder, chicory powder, kudzu root powder, Ganoderma lucidum powder, purslane powder, and celery powder to the stabilizer slurry. After shearing, process the mixture with a high-pressure homogenizer, add deionized water, sterilize, and fill to obtain the drug.

[0012] Preferably, the preparation method of the drug for treating hyperuricemia is as follows, in parts by weight:

[0013] Step 1: Vacuum freeze-dry the white ginseng fungus, grind it through a 150-300 mesh sieve to obtain white ginseng fungus powder; extract chicory, kudzu root, Ganoderma lucidum and purslane respectively using 50wt%-70wt% ethanol aqueous solution countercurrently, and juice celery using cold water at 5-15℃ for 10-30 minutes. Concentrate the juice separately and spray dry it into powder to obtain powder of each substance.

[0014] Step 2: Dissolve 15-25 parts of sodium carboxymethyl cellulose in 800-1200 parts of deionized water and stir magnetically at room temperature for 1-3 hours to obtain a sodium carboxymethyl cellulose solution; dissolve 15-25 parts of guar gum in 800-1200 parts of deionized water and stir magnetically at room temperature for 2 hours to obtain a guar gum solution; mix the sodium carboxymethyl cellulose solution and the guar gum solution, add 30-50 parts of white ginseng powder, and stir magnetically for 10-30 minutes to form a uniform bacterial suspension. Drop the bacterial suspension into 1800-2200 parts of a 0.1-0.5 mol / L calcium-containing aqueous solution and treat for 20-50 minutes. Collect the microparticles using a filter. The capsules were washed twice with PBS buffer to obtain wet microcapsules. 5-15 parts of the polymer compound were added to 800-1200 parts of 0.5-2wt% acetic acid aqueous solution and stirred until clear. The wet microcapsules were immersed in the polymer compound solution and magnetically stirred for 20-60 minutes. The microcapsules were collected by filtration and then immersed in 1800-2200 parts of 0.1-0.5mol / L calcium-containing aqueous solution for 5-15 minutes. The microcapsules were collected by filtration, washed twice with PBS buffer, and freeze-dried under vacuum at -15~-30℃ for 10-48 hours at a vacuum degree of 15-30Pa to obtain white ginseng microcapsule powder.

[0015] Step 3: Disperse 10-20 parts microcrystalline cellulose and 1-3 parts xanthan gum in 400-600 parts deionized water, stir in a 60-90℃ water bath until completely swollen, cool to room temperature, add 0.5-2 parts Tween-80, 0.3-0.8 parts potassium sorbate, and 5-15 parts xylitol, stir to dissolve, and obtain a stabilizer slurry. Gradually add 30-50 parts of white ginseng microcapsule powder, 15-25 parts of chicory powder, 10-20 parts of kudzu root powder, 5-15 parts of Ganoderma lucidum powder, 5-15 parts of purslane powder, and 10-20 parts of celery powder to the stabilizer slurry, shear in an ice-water bath at 20000-30000 rpm for 10-30 minutes, then process by a high-pressure homogenizer, add deionized water to 800-1200 mL, sterilize, and fill into brown glass bottles to obtain the drug.

[0016] In step 1, the vacuum freeze-drying conditions for the white ginseng fungus are -30~-40℃ for 10-48 hours, with a vacuum degree of 15-30Pa.

[0017] The countercurrent extraction conditions in step 1 are 30-50℃ for 50-100 minutes.

[0018] In step 1, the controlled particle size of the spray-dried powder is less than 50-150 μm.

[0019] In step 3, the parameters for the high-pressure homogenizer are: flow rate 80-120 mL / min, pressure 15000-25000 psi, 5-15 cycles, and temperature control at 3-8℃.

[0020] The sterilization in step 3 is performed at 115-130℃ for 5-30 minutes.

[0021] The calcium-containing aqueous solution is at least one of calcium lactate aqueous solution, calcium gluconate aqueous solution, and calcium aspartate aqueous solution.

[0022] The polymeric compound is at least one of pullulan, low-ester pectin, and konjac polysaccharide.

[0023] The roles of each substance in drug preparation are as follows:

[0024] The core active ingredient in white ginseng mycelium powder is to lower blood uric acid levels by regulating intestinal flora and inhibiting uric acid synthesis.

[0025] Chicory powder promotes uric acid excretion and relieves hyperuricemia.

[0026] Kudzu root powder protects liver function and lowers serum ALT / AST levels.

[0027] Reishi powder regulates immunity and provides antioxidant benefits, synergistically improving kidney function.

[0028] Purslane powder promotes diuresis and eliminates uric acid, helping to lower serum uric acid levels.

[0029] Celery powder contains flavonoids, which inhibit xanthine oxidase activity and reduce uric acid production.

[0030] Sodium carboxymethyl cellulose and guar gum form a primary gel network, which encapsulates the white ginseng powder to form a bacterial suspension.

[0031] Calcium lactate and pectin form an "egg carton structure" to construct acid-resistant microcapsules.

[0032] Low-ester pectin is a pH-responsive coating material that is stable in the gastric acid environment and dissociates to release drugs in the neutral intestinal environment.

[0033] Microcrystalline cellulose and xanthan gum thicken and stabilize the gel, ensuring the uniformity of the suspension.

[0034] Tween-80 is a surfactant that improves the dispersion of hydrophobic components.

[0035] Potassium sorbate acts as a preservative and antibacterial agent, extending the shelf life of the preparation.

[0036] Xylitol, as a flavoring agent and stabilizer, improves oral palatability.

[0037] Compared with existing technologies, it has the following advantages:

[0038] 1) This invention significantly improves the sustained-release performance of drugs by constructing microcapsule structures using calcium lactate aqueous solution and low-ester pectin. In simulated gastric juice, the drug can effectively resist gastric acid erosion, while in simulated intestinal juice, it can be rapidly released, achieving precise targeted release, prolonging the duration of drug action, reducing the frequency of administration, and improving patient medication compliance.

[0039] 2) The microcapsule structure of this invention effectively protects the active ingredients in the drug, preventing them from being degraded by gastric acid and digestive enzymes, thereby improving the bioavailability of the drug. Simultaneously, the optimized preparation process ensures uniform release of the drug in the intestine, further enhancing the absorption efficiency and therapeutic effect.

[0040] 3) This invention ingeniously combines *Gynostemma pentaphyllum* with various traditional Chinese medicine ingredients such as chicory, kudzu root, Ganoderma lucidum, purslane, and celery, fully leveraging the synergistic effects of each ingredient. The uric acid-lowering activity of *Gynostemma pentaphyllum* synergistically complements the metabolic regulatory functions of chicory, kudzu root, and other ingredients, significantly improving not only the overall efficacy of the drug but also enhancing the comprehensive improvement effect on metabolic disorders related to hyperuricemia, achieving a multi-target, all-round therapeutic effect. Detailed Implementation

[0041] Main source of materials:

[0042] White ginseng mycelium, a commercially available product, produced in Dafang County, Guizhou Province.

[0043] Chicory, a commercially available product, is produced in Hinggan League, Inner Mongolia.

[0044] Kudzu root, a commercially available product, is produced in Rongjiang County, Guizhou Province.

[0045] Lingzhi, a commercially available product, is produced in Nyingchi City, Tibet.

[0046] Purslane, a commercially available product, is produced in Lanzhou, Gansu Province.

[0047] Celery, a commercially available product, is produced in Qingdao, Shandong.

[0048] Microcrystalline cellulose, grade: pharmaceutical grade, conforms to standard: 20th edition of Pharmacopoeia, model: 102, Xi'an Jinxiang Pharmaceutical Excipients Co., Ltd.

[0049] Sodium carboxymethyl cellulose, product grade: food grade, model: FH9 low viscosity, Henan Rude Food Ingredients Co., Ltd.

[0050] Guar gum, product grade: food grade, item number: 6686681097, Anhui Weimao Biotechnology Co., Ltd.

[0051] Low-ester pectin, product grade: food grade, item number: 101, Guangzhou Bloomage Biotechnology Co., Ltd.

[0052] PBS buffer, specification PBS buffer 1X (pH 7.4), Changde Bickman Biotechnology Co., Ltd.

[0053] Xanthan gum, product number: hyj, product grade: food grade, Henan Qinuo Food Ingredients Co., Ltd.

[0054] All other raw materials used in the embodiments and comparative examples of this invention are commercially available products.

[0055] Example 1

[0056] The preparation method of drugs for treating hyperuricemia is as follows:

[0057] Step 1: Freeze-dry the white ginseng fungus at -35℃ for 24 hours under vacuum of 20 Pa, grind it through a 200-mesh sieve to obtain white ginseng fungus powder; extract chicory, kudzu root, Ganoderma lucidum and purslane separately with 60wt% ethanol aqueous solution at 40℃ countercurrent for 80 minutes, and juice celery with cold water at 10℃ for 20 minutes. Concentrate the juice separately and spray dry it into powder, controlling the particle size to be less than 100μm to obtain powder of each substance;

[0058] Step 2: Dissolve 20g of sodium carboxymethyl cellulose in 1000g of deionized water and stir magnetically for 2 hours at room temperature to obtain a sodium carboxymethyl cellulose solution; dissolve 20g of guar gum in 1000g of deionized water and stir magnetically for 2 hours at room temperature to obtain a guar gum solution; mix the sodium carboxymethyl cellulose solution and guar gum solution, add 40g of white ginseng powder, and stir magnetically for 20 minutes to form a uniform bacterial suspension. Drop the bacterial suspension into 2000g of 0.3mol / L calcium lactate aqueous solution for 30 minutes, collect the microcapsules through a filter, and wash twice with PBS buffer to obtain wet microcapsules; add 10g of low-ester pectin to 1000g of 1wt% acetic acid aqueous solution and stir until clear; immerse the wet microcapsules in the low-ester pectin solution, stir magnetically for 40 minutes, filter to collect the microcapsules, and then immerse them in 2000g of... Microcapsules were collected by filtering with a 0.3 mol / L calcium lactate aqueous solution for 10 minutes, washed twice with PBS buffer, and then freeze-dried under vacuum at -20°C for 24 hours at a vacuum degree of 20 Pa to obtain white ginseng microcapsule powder.

[0059] Step 3: Disperse 15g microcrystalline cellulose and 2g xanthan gum in 500g deionized water, stir in an 80℃ water bath until completely swollen, cool to room temperature, add 1g Tween-80, 0.5g potassium sorbate, and 10g xylitol, stir to dissolve, and obtain a stabilizer slurry. Gradually add 40g white ginseng microcapsule powder, 20g chicory powder, 15g kudzu root powder, 10g Ganoderma lucidum powder, 10g purslane powder, and 15g celery powder to the stabilizer slurry, shear in an ice-water bath at 22000rpm for 20 minutes, then process by a high-pressure homogenizer at a flow rate of 100mL / min, a pressure of 20000psi, 10 cycles, and a temperature of 5℃. Add deionized water to 1000mL, sterilize at 121℃ for 15 minutes, and fill into brown glass bottles to obtain the drug.

[0060] Example 2

[0061] The preparation method of the drug for treating hyperuricemia is basically the same as that in Example 1, except that the calcium lactate aqueous solution in step 2 is replaced with an equal amount and concentration of calcium aspartate aqueous solution.

[0062] Example 3

[0063] The preparation method of the drug for treating hyperuricemia is basically the same as that in Example 1, except that the calcium lactate aqueous solution in step 2 is replaced with an equal amount and concentration of calcium gluconate aqueous solution.

[0064] Example 4

[0065] The preparation method of the drug for treating hyperuricemia is basically the same as that in Example 1, except that the low-ester pectin mentioned in step 2 is replaced with an equal amount of konjac polysaccharide.

[0066] Example 5

[0067] The preparation method of the drug for treating hyperuricemia is basically the same as that in Example 1, except that the low-ester pectin mentioned in step 2 is replaced with an equal amount of pullulan.

[0068] Comparative Example 1

[0069] The preparation method of the drug for treating hyperuricemia is basically the same as that in Example 1, except that the calcium lactate aqueous solution in step 2 is replaced with an equal amount and concentration of calcium chloride aqueous solution.

[0070] Comparative Example 2

[0071] The preparation method of the drug for treating hyperuricemia is basically the same as that in Example 1, except that the low-ester pectin mentioned in step 2 is replaced with an equal amount of chitosan.

[0072] Comparative Example 3

[0073] The preparation method of drugs for treating hyperuricemia is as follows:

[0074] Step 1: Freeze-dry the white ginseng fungus at -35℃ for 24 hours under vacuum of 20 Pa, grind it through a 200-mesh sieve to obtain white ginseng fungus powder; extract chicory, kudzu root, Ganoderma lucidum and purslane separately with 60wt% ethanol aqueous solution at 40℃ countercurrent for 80 minutes, and juice celery with cold water at 10℃ for 20 minutes. Concentrate the juice separately and spray dry it into powder, controlling the particle size to be less than 100μm to obtain powder of each substance;

[0075] Step 2: Disperse 15g microcrystalline cellulose and 2g xanthan gum in 500g deionized water, stir in an 80℃ water bath until completely swollen, cool to room temperature, add 1g Tween-80, 0.5g potassium sorbate, and 10g xylitol, stir to dissolve, and obtain a stabilizer slurry. Gradually add 40g white ginseng powder, 20g chicory powder, 15g kudzu root powder, 10g Ganoderma lucidum powder, 10g purslane powder, and 15g celery powder to the stabilizer slurry, shear in an ice-water bath at 22000rpm for 20 minutes, then process by a high-pressure homogenizer at a flow rate of 100mL / min, a pressure of 20000psi, 10 cycles, and a temperature of 5℃. Add deionized water to 1000mL, sterilize at 121℃ for 15 minutes, and fill into brown glass bottles to obtain the drug.

[0076] Test Example 1

[0077] Treatment test for hyperuricemia

[0078] I. Laboratory Animals and Group Design

[0079] 1. The animals selected were SPF - level male SD rats, weighing 160 - 220 g, provided by the Guangdong Provincial Medical Laboratory Animal Center. The production license number of the laboratory animals is SCXK (Guangdong) 2022 - 0002.

[0080] Number of groups: 80 rats, divided into 10 groups by stratified random method (n = 8 / group);

[0081] Control group: Intragastric administration of normal saline;

[0082] Model group: HUA model establishment + intragastric administration of normal saline;

[0083] The other 8 groups were experimental groups, with intragastric administration of drugs at 324 mg / kg of each example or comparative example after HUA model establishment.

[0084] II. Establishment of HUA model

[0085] 1. Modeling reagents: Potassium oxonate (uricase inhibitor): 100 mg / kg, intraperitoneal injection; Hypoxanthine suspension (100 mg / mL): 500 mg / kg, intragastric administration;

[0086] 2. Modeling cycle

[0087] Modeling was performed once a day for 21 consecutive days (days 1 - 21);

[0088] III. Drug administration intervention plan

[0089] Starting time: On the 4th day of modeling, intragastric administration (0.5 hours after modeling); Days 4 - 21 (a total of 18 days).

[0090] IV. Detection indexes and methods

[0091] 1. Basic physiological indexes

[0092] Body weight monitoring: Record the body weight on the last day of intragastric administration to observe the effect of HUA on metabolism.

[0093] 2. Serum biochemical indexes

[0094] Sampling: Fast on the 17th day of treatment, collect blood from the abdominal aorta on the 18th day → centrifuge at 4℃ (3000 rpm × 15 min) to obtain serum. Test the indexes of UA, Cr, BUN, ALT, and AST.

[0095] The sources of each reagent are as follows:

[0096] Hypoxanthine (Shanghai Maclean Biochemical Technology Co., Ltd., batch number: H811076), Potassium oxazine (Shanghai Maclean Biochemical Technology Co., Ltd., batch number: P831461), Blood Urea Nitrogen (BUN) Test Kit (Nanjing Jiancheng Bioengineering Institute, batch number: C013-2-1), Aspartate Aminotransferase (AST / GOT) Test Kit (Nanjing Jiancheng Bioengineering Institute, batch number: C010-2-1), Uric Acid (UA) Test Kit (Nanjing Jiancheng Bioengineering Institute, batch number: C012-2-1), Creatinine (Cr) Assay Kit (Nanjing Jiancheng Bioengineering Institute, batch number: C011-2-1), Alanine Aminotransferase (ALT / GPT) Test Kit (Nanjing Jiancheng Bioengineering Institute, batch number: C009-2-1)

[0097] The following is a brief explanation of each test indicator and its meaning:

[0098] 1. UA (uric acid): The final product of purine metabolism in the human body. Elevated levels of UA can lead to hyperuricemia and gout.

[0099] 2. Cr (creatinine): A chemical substance produced by muscle metabolism, mainly excreted through the kidneys, and is a core indicator for assessing glomerular filtration function.

[0100] 3. BUN (Bureaumic Urea Nitrogen): The end product of protein metabolism, reflecting the kidney's ability to excrete nitrogenous waste and used to assess renal filtration function.

[0101] 4. ALT / AST: These are alanine aminotransferase (ALT) and aspartate aminotransferase (AST), respectively. They are released into the blood when hepatocellular cells are damaged and are key enzymes for evaluating the degree of hepatocellular damage.

[0102] Table 1

[0103]

[0104] Test Example 2

[0105] Drug sustained-release performance testing:

[0106] Preparation of simulated gastric juice: Weigh 2g of sodium chloride and 3.2g of pepsin, add them to 1L of distilled water, and then adjust the pH of the solution to 2.0 using hydrochloric acid to prepare simulated gastric juice.

[0107] Preparation of simulated intestinal fluid: Add potassium dihydrogen phosphate (0.65% by mass), 1g trypsin, and 18g ox bile salt to 1L of distilled water, and then adjust the pH to 7.4 with sodium hydroxide solution to obtain simulated intestinal fluid.

[0108] Drug response experiment:

[0109] Take 1g of the drug prepared in the embodiments and comparative examples of the present invention, add it to 10mL of simulated gastric fluid, and carry out the reaction for 2h at 37℃ and 50r / min.

[0110] In addition, 1g of the drug prepared in this invention was added to 10mL of simulated gastric fluid, placed in a shaker, and reacted for 2h at 37℃ and 50r / min. After centrifugation, 10mL of simulated intestinal fluid was added, and the reaction was continued for 3h.

[0111] The drug release rate is calculated using the following formula:

[0112] Release rate (%) = (Wt - W0) / Wt × 100%

[0113] In the formula, Wt is the initial solid weight of the drug (g); W0 is the solid weight of the drug after treatment (g).

[0114] The test results are shown in Table 2.

[0115] Table 2

[0116]

[0117] Example 1 demonstrates the superior efficacy of calcium lactate, likely due to the synergistic effect of its cross-linking properties and bioactivity. As an organic calcium salt, calcium lactate constructs a dense and stable capsule wall structure through a mild and controllable cross-linking reaction during microcapsule formation, effectively isolating it from gastric acid erosion. Simultaneously, the released lactate ions inhibit xanthine oxidase activity, directly blocking the uric acid synthesis pathway. In contrast, calcium aspartate exhibits slow capsule wall dissociation and reduced intestinal release efficiency due to the strong chelation of intramolecular calcium ions. Calcium chloride, on the other hand, suffers from excessively rapid cross-linking, resulting in a structurally uneven capsule wall and significantly weakened gastric acid protection. This dual advantage of structural stability and bioactivity makes the calcium lactate system more effective in maintaining stable blood drug concentrations and targeted delivery, thereby enhancing its uric acid-lowering efficacy.

[0118] The low-ester pectin used in Example 1 forms a dense and stable cross-linked network with calcium ions in its molecular chain, effectively resisting pepsin attack and ensuring the integrity of the active ingredients. In the neutral environment of the intestine, the carboxyl groups dissociate, and the cross-linked network rapidly disintegrates, achieving targeted release. In contrast, konjac polysaccharide leaks prematurely into the stomach due to its loose molecular gel network, pullulan lacks pH-responsive carboxyl groups, resulting in delayed release, and chitosan undergoes protonation and dissolution in gastric acid, compromising its structural stability. This intelligent responsiveness allows for precise drug release in the intestine, synergistically enhancing the uric acid-lowering activity of *Scutellaria baicalensis* and the excretion-promoting effects of components such as chicory, thereby significantly optimizing the therapeutic effect.

Claims

1. The application of *Scutellaria baicalensis* in the preparation of drugs for treating hyperuricemia, characterized in that: The method for preparing the drug for treating hyperuricemia includes the following steps, in parts by weight: Step 1: Vacuum freeze-dry the white ginseng fungus and grind it into powder; extract the chicory, kudzu root, Ganoderma lucidum and purslane separately with 50wt%-70wt% ethanol aqueous solution countercurrently, concentrate and spray dry them into powder; juice the celery and concentrate and spray dry it into powder. Step 2: Dissolve 15-25 parts of sodium carboxymethyl cellulose in 800-1200 parts of deionized water and mix with guar gum solution. The guar gum solution is obtained by dissolving 15-25 parts of guar gum in 800-1200 parts of deionized water and stirring magnetically at room temperature. Add 30-50 parts of white ginseng mycelium powder to form a bacterial suspension, and drop it into 1800-2200 parts of 0.1-0.5 mol / L calcium-containing aqueous solution for treatment. Collect the microcapsules and rinse to obtain wet microcapsules. Add 5-15 parts of polymer compound to 800-1200 parts of 0.5-2 wt% acetic acid aqueous solution and stir until clear. Immerse the wet microcapsules in the polymer compound solution, filter and collect the microcapsules. Then immerse them in 1800-2200 parts of 0.1-0.5 mol / L calcium-containing aqueous solution for treatment, collect the microcapsules, rinse and freeze-dry under vacuum to obtain white ginseng mycelium microcapsule powder. Step 3: Disperse 10-20 parts of microcrystalline cellulose and 1-3 parts of xanthan gum in 400-600 parts of deionized water until swollen, then cool. Add 0.5-2 parts of Tween-80, 0.3-0.8 parts of potassium sorbate, and 5-15 parts of xylitol and stir to dissolve to obtain a stabilizer slurry. Gradually add 30-50 parts of white ginseng microcapsule powder, 15-25 parts of chicory powder, 10-20 parts of kudzu root powder, 5-15 parts of Ganoderma lucidum powder, 5-15 parts of purslane powder, and 10-20 parts of celery powder to the stabilizer slurry. After shearing, process the mixture using a high-pressure homogenizer, add deionized water, sterilize, and fill to obtain the drug. The calcium-containing aqueous solution is a calcium lactate aqueous solution; The polymer compound is low-ester pectin.

2. The application as described in claim 1, characterized in that, The method for preparing the drug for treating hyperuricemia using *Panax ginseng* is as follows, by weight: Step 1: Vacuum freeze-dry the white ginseng fungus, grind it through a 150-300 mesh sieve to obtain white ginseng fungus powder; extract chicory, kudzu root, Ganoderma lucidum and purslane respectively using 50wt%-70wt% ethanol aqueous solution countercurrently, and juice celery using cold water at 5-15℃ for 10-30 minutes. Concentrate the juice separately and spray dry it into powder to obtain powder of each substance. Step 2: Dissolve 15-25 parts of sodium carboxymethyl cellulose in 800-1200 parts of deionized water and stir magnetically at room temperature for 1-3 hours to obtain a sodium carboxymethyl cellulose solution; dissolve 15-25 parts of guar gum in 800-1200 parts of deionized water and stir magnetically at room temperature for 2 hours to obtain a guar gum solution; mix the sodium carboxymethyl cellulose solution and the guar gum solution, add 30-50 parts of white ginseng powder, and stir magnetically for 10-30 minutes to form a uniform bacterial suspension; drop the bacterial suspension into 1800-2200 parts of 0.1-0.5 mol / L calcium-containing aqueous solution and treat for 20-50 minutes; collect the microcapsules with a filter screen, wash twice with PBS buffer to obtain wet microcapsules; add 5-15 parts of the polymer compound to 800-1200 parts of 0.5-2 wt% acetic acid aqueous solution and stir until clear; The wet microcapsules were immersed in a polymer compound solution and magnetically stirred for 20-60 minutes. The microcapsules were collected by filtration and then immersed in 1800-2200 parts of 0.1-0.5 mol / L calcium-containing aqueous solution for 5-15 minutes. The microcapsules were collected by filtration, washed twice with PBS buffer, and freeze-dried under vacuum at -15 to -30℃ for 10-48 hours at a vacuum degree of 15-30 Pa to obtain white ginseng microcapsule powder. Step 3: Disperse 10-20 parts microcrystalline cellulose and 1-3 parts xanthan gum in 400-600 parts deionized water, stir in a 60-90℃ water bath until completely swollen, cool to room temperature, add 0.5-2 parts Tween-80, 0.3-0.8 parts potassium sorbate, and 5-15 parts xylitol, stir to dissolve, and obtain a stabilizer slurry. Gradually add 30-50 parts of white ginseng microcapsule powder, 15-25 parts of chicory powder, 10-20 parts of kudzu root powder, 5-15 parts of Ganoderma lucidum powder, 5-15 parts of purslane powder, and 10-20 parts of celery powder to the stabilizer slurry, shear in an ice-water bath at 20000-30000 rpm for 10-30 minutes, then process by a high-pressure homogenizer, add deionized water to 800-1200 mL, sterilize, and fill into brown glass bottles to obtain the drug.

3. The application as described in claim 1 or 2, characterized in that, In step 1, the vacuum freeze-drying conditions for the white ginseng fungus are -30~-40℃ for 10-48 hours, with a vacuum degree of 15-30Pa.

4. The application as described in claim 1 or 2, characterized in that, The countercurrent extraction conditions in step 1 are 30-50℃ for 50-100 minutes.

5. The application as described in claim 1 or 2, characterized in that, In step 1, the controlled particle size of the spray-dried powder is less than 50-150 μm.

6. The application as described in claim 1 or 2, characterized in that, In step 3, the parameters for the high-pressure homogenizer are: flow rate 80-120 mL / min, pressure 15000-25000 psi, 5-15 cycles, and temperature control at 3-8℃.

7. The application as described in claim 1 or 2, characterized in that, The sterilization in step 3 is performed at 115-130℃ for 5-30 minutes.

Images