A composition for lowering uric acid, its preparation method and application

Abstract

This invention provides a uric acid-lowering composition comprising the following raw materials in weight percentages: 10-20% sea buckthorn extract, 20-35% marine fish oligopeptides, 5-12% tart cherry extract, 5-10% Poria cocos extract, 20-35% food-medicine homologous components, and 5-10% lecithin. This invention also provides a method for preparing the above-mentioned uric acid-lowering composition and its applications. This invention constructs a three-dimensional regulatory mechanism of "'inhibition' synergy + 'excretion' synergy + 'protection' synergy," realizing a three-dimensional uric acid-lowering network of "liver-kidney-intestinal tract," with multi-target synergistic effects and significant uric acid-lowering effects. The peptide molecules of this invention can self-assemble with phospholipid molecules through hydrophobic interactions to form "peptide-phospholipid micelles," which can effectively encapsulate poorly soluble components such as sea buckthorn flavonoids and tart cherry anthocyanins to form nanocomplexes, enabling them to form stable micelles in the gastrointestinal tract, significantly improving solubility and transmembrane absorption rate. This invention belongs to the fields of functional foods, health products, and pharmaceutical technology.

Description

Technical Field

[0001] This invention relates to the fields of functional foods, health products and pharmaceuticals, specifically to a composition for lowering uric acid, its preparation method and application. Background Technology

[0002] Hyperuricemia (HUA) is a metabolic disease caused by purine metabolism disorders or reduced uric acid excretion, leading to elevated blood uric acid levels. It is a significant contributing factor to gout, chronic kidney disease, and cardiovascular disease. Currently available medications for treating hyperuricemia, such as allopurinol and febuxostat, while effective, often come with side effects such as liver and kidney damage, allergic reactions, and gastrointestinal discomfort. Furthermore, long-term use can easily lead to drug resistance. Therefore, developing safe, effective, and low-side-effect natural products or functional food alternatives has become a research hotspot.

[0003] In existing technologies, there are various natural product or functional food formulations used to assist in lowering uric acid, such as compositions containing medicinal and edible ingredients like chicory and gardenia. However, some natural products generally suffer from poor solubility, low bioavailability, and difficulty in achieving effective concentrations in the body. Furthermore, single ingredients often target only one aspect of uric acid metabolism (such as inhibiting xanthine oxidase or promoting excretion), making it difficult to achieve multi-target regulation of uric acid metabolism, resulting in limited uric acid-lowering effects.

[0004] Therefore, developing a composition that can synergistically lower uric acid at multiple targets and improve bioavailability is a current focus of research on hyperuricemia. Summary of the Invention

[0005] The purpose of this invention is to provide a composition for lowering uric acid, its preparation method and application, in order to solve the technical problems of low bioavailability and single target of action of existing natural products or functional food formulations for lowering uric acid.

[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: to provide a composition for lowering uric acid, comprising the following raw materials in weight percentage: 10-20% sea buckthorn extract, 20-35% marine fish oligopeptides, 5-12% sour cherry extract, 5-10% poria cocos extract, 20-35% food and medicine homologous components, and 5-10% lecithin.

[0007] Preferably, the total flavonoid content of the sea buckthorn extract is ≥40%, the molecular weight of the marine fish oligopeptide is 500-1000 Da, the anthocyanin content of the sour cherry extract is ≥25%, the content of poria cocos polysaccharide in the poria cocos extract is ≥30%, and the content of phosphatidylcholine in the lecithin is ≥60%.

[0008] Preferably, the medicinal and edible components include any one or a combination of at least two of chicory, gardenia, corn silk, and coix seed; the lecithin includes any one or a combination of two of soybean lecithin and egg yolk lecithin.

[0009] Preferably, the composition is a nanoparticle composition with a self-assembled marine fish oligopeptide and lecithin as a carrier, the composition having an average particle size of 100-200 nm and an encapsulation efficiency of 70-85%.

[0010] Preferably, the mass ratio of the marine fish oligopeptide to the lecithin is 3:1-5:1.

[0011] A second aspect of the present invention provides a method for preparing the uric acid-lowering composition according to any one of the above claims, comprising the following steps: (1) Add marine fish oligopeptides to purified water, stir to dissolve, and obtain a peptide solution; then add lecithin, stir to disperse, and obtain a homogeneous emulsion A; (2) Dissolve sea buckthorn extract and sour cherry extract in ethanol to obtain solution B; (3) Under stirring, solution B is slowly added dropwise to emulsion A. After the addition is complete, stirring is continued to obtain a mixture. The mixture is then subjected to high-pressure homogenization to obtain a nanocomposite emulsion. (4) The nanocomposite emulsion was concentrated under reduced pressure to recover ethanol, and a concentrated aqueous nano suspension was obtained. (5) Mix the aqueous nano suspension with the food-medicine homology components and Poria cocos extract evenly to obtain a mixed slurry; (6) Spray dry the mixed slurry to obtain a uric acid-lowering composition.

[0012] Preferably, in step (1), a peptide solution with a mass concentration of 5-10% is obtained; lecithin is in powder or granule form and is dispersed by stirring at 60-70°C; in step (2), the volume fraction of ethanol is 70-95%.

[0013] Preferably, in step (3), the homogenization pressure is 20-40 MPa, the number of cycles is 2-3, and a nanocomposite emulsion with a particle size of 100-200 nm is obtained; in step (4), the temperature of vacuum concentration is 40-50℃, and the vacuum degree is -0.08 to -0.1 MPa.

[0014] Preferably, in step (5), the medicinal and edible homologous components are in powder or granule form; in step (6), before spray drying, an anti-caking agent accounting for 1-3% of the total weight of the mixed slurry is added, wherein the anti-caking agent includes any one or a combination of two of silica and microcrystalline cellulose; during spray drying, the inlet air temperature is 160-180℃ and the outlet air temperature is 80-90℃.

[0015] A third aspect of the present invention provides the use of the uric acid-lowering composition described in any one of the above claims in the preparation of functional foods, health products or pharmaceuticals that lower uric acid and protect kidney function.

[0016] This invention provides a uric acid-lowering composition, its preparation method, and its application. Compared with the prior art, the beneficial effects of this invention are: (1) This invention provides a composition for lowering uric acid, wherein the raw materials have a synergistic effect: ① Sour cherry extract is rich in anthocyanins and flavonoids, while sea buckthorn extract is rich in flavonoids. The two work synergistically to inhibit the activity of xanthine oxidase in the liver, thereby blocking the uric acid production pathway at its source and reducing uric acid production, thus creating an "inhibition" synergy.

[0017] ② Marine fish oligopeptides can specifically regulate the expression of uric acid transporters URAT1 / GLUT9 in the proximal convoluted tubule of the kidney, promoting uric acid excretion from the kidney; Poria cocos polysaccharide in Poria cocos extract can regulate the intestinal epithelial transporter ABCG2, promoting uric acid excretion from the intestine and reducing the burden on the kidney; the two work synergistically to form a dual-channel excretion mechanism of "kidney + intestine", constructing a "excretion" synergy and solving the bottleneck of kidney damage caused by relying solely on kidney excretion.

[0018] ③ The phosphatidylcholine in lecithin can repair damaged renal tubular epithelial cells; the antioxidant effects of Poria cocos extract combined with sea buckthorn extract and sour cherry extract can reduce the inflammatory response of the kidneys caused by high uric acid; the medicinal and edible components (chicory, gardenia, corn silk, coix seed) have diuretic, anti-inflammatory and liver-protective effects; the three work synergistically to form an "antioxidant + anti-inflammatory + kidney protection" mechanism, thus constructing a "protective" synergy.

[0019] This invention constructs a three-dimensional regulatory mechanism of "'inhibition' synergy + 'excretion' synergy + 'protection' synergy", realizing a three-dimensional uric acid-lowering network of "liver-kidney-intestine", with multi-target synergistic effect and significant uric acid-lowering effect.

[0020] (2) This invention provides a method for preparing a composition for lowering uric acid, using marine fish oligopeptides (500-1000 Da) as a natural carrier. The peptide molecules can self-assemble with phospholipid molecules through hydrophobic interactions to form "peptide-phospholipid micelles". The internal part of the micelle is a hydrophobic core, which can effectively encapsulate poorly soluble components such as sea buckthorn flavonoids and tart cherry anthocyanins to form nanocomplexes, making them stable micelles in the gastrointestinal tract, significantly improving solubility and transmembrane absorption rate; the external part is a hydrophilic shell, which increases the dispersibility of the nanocomplexes in water. When the nanocomplexes enter the intestine, the phospholipids and peptides can open the tight junctions of intestinal epithelial cells or be directly transported through endocytosis, greatly increasing the blood concentration of active ingredients and improving bioavailability.

[0021] (3) The raw materials of the present invention are all food-grade or medicinal materials. They have no toxic side effects when consumed for a long time, have high safety, overcome the side effects and drug resistance of chemical drugs, and are suitable for a wide range of people. Detailed Implementation

[0022] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative of this application and are not intended to limit this application. Unless otherwise specified, the methods used in this invention are conventional methods; the raw materials and apparatus used, unless otherwise specified, are conventional commercially available products.

[0023] To verify the reliability of the effectiveness of the present invention, the present invention will be described below with reference to Examples 1-5, and compared with Comparative Examples 1-8.

[0024] Example 1 This embodiment provides a composition for lowering uric acid, comprising the following raw materials by weight: 120g of sea buckthorn extract (total flavonoid content 45%), 300g of marine fish oligopeptides (molecular weight 800 Da), 80g of sour cherry extract (anthocyanin content 28%), 60g of Poria cocos extract (Poria cocos polysaccharide content 40%), 180g of chicory (powder), 80g of gardenia (powder), 40g of corn silk (powder), 40g of coix seed (powder), and 100g of soybean lecithin (powder, phosphatidylcholine PC content 65%).

[0025] This embodiment also provides a method for preparing the above-mentioned uric acid-lowering composition, including the following steps: (1) Preparation of carrier solution: Weigh 300g of marine fish oligopeptide, add it to 5L of purified water, stir until completely dissolved to obtain a peptide solution with a mass concentration of 6%; add 100g of soybean lecithin, and shear and stir at 5000rpm / min at 65℃ for 20min to obtain a homogeneous emulsion A.

[0026] (2) Dissolution of active ingredients: Weigh 120g of sea buckthorn extract and 80g of sour cherry extract, add 1L of 95% edible ethanol, stir until completely dissolved, and obtain solution B.

[0027] (3) High-pressure homogenization and encapsulation: Under continuous stirring, solution B is slowly added dropwise to emulsion A. After the addition is complete, continue to keep warm and stir for 30 minutes to obtain a mixture. The mixture is then passed through a high-pressure homogenizer and homogenized twice under a pressure of 30 MPa to obtain a nanocomposite emulsion.

[0028] (4) Vacuum concentration: The nanocomposite emulsion was concentrated under reduced pressure to recover ethanol. The temperature of the vacuum concentration was 45℃ and the vacuum degree was -0.1MPa, and the concentrated aqueous nano suspension was obtained.

[0029] (5) Mixing: Weigh 180g of chicory, 80g of gardenia, 40g of corn silk, 40g of coix seed and 60g of poria extract, add them to the aqueous nano suspension, stir and mix evenly to obtain a mixed slurry.

[0030] (6) Drying: Add 70g of microcrystalline cellulose to the mixed slurry, stir evenly, and then spray dry. Set the air inlet temperature to 170℃ and the air outlet temperature to 85℃. Collect the dried powder, pass it through an 80-mesh sieve, and obtain a light yellow powder, which is the composition for lowering uric acid.

[0031] Example 2 The difference between this embodiment and Embodiment 1 is that the uric acid-lowering composition includes the following raw materials by weight: 100g of sea buckthorn extract (total flavonoid content 45%), 350g of marine fish oligopeptides (molecular weight 600 Da), 80g of sour cherry extract (anthocyanin content 30%), 80g of Poria cocos extract (Poria cocos polysaccharide content 40%), 210g of chicory (powder), 100g of gardenia (powder), and 80g of soybean lecithin (powder, phosphatidylcholine PC content 65%); the remaining operations are the same, and the uric acid-lowering composition is finally obtained.

[0032] Example 3 The difference between this embodiment and Embodiment 1 is that the uric acid-lowering composition includes the following raw materials by weight: 160g of sea buckthorn extract (total flavonoid content 45%), 250g of marine fish oligopeptides (molecular weight 950 Da), 60g of sour cherry extract (anthocyanin content 30%), 100g of Poria cocos extract (Poria cocos polysaccharide content 40%), 230g of gardenia (powder), 120g of corn silk (powder), and 80g of soybean lecithin (powder, phosphatidylcholine PC content 65%); the remaining operations are the same, and the uric acid-lowering composition is finally obtained.

[0033] Example 4 The difference between this embodiment and Embodiment 1 is that the uric acid-lowering composition includes the following raw materials by weight: 180g of sea buckthorn extract (total flavonoid content 45%), 270g of marine fish oligopeptides (molecular weight 800 Da), 120g of sour cherry extract (anthocyanin content 30%), 90g of Poria cocos extract (Poria cocos polysaccharide content 40%), 150g of corn silk (powder), 130g of coix seed (powder), and 60g of soybean lecithin (powder, phosphatidylcholine PC content 65%); the remaining operations are the same, and the uric acid-lowering composition is finally obtained.

[0034] Example 5 The difference between this embodiment and Embodiment 1 is that the uric acid-lowering composition includes the following raw materials by weight: 200g of sea buckthorn extract (total flavonoid content 45%), 220g of marine fish oligopeptides (molecular weight 800 Da), 110g of sour cherry extract (anthocyanin content 30%), 100g of Poria cocos extract (Poria cocos polysaccharide content 40%), 170g of chicory (powder), 70g of gardenia (powder), 30g of corn silk (powder), 30g of coix seed (powder), and 70g of soybean lecithin (powder, phosphatidylcholine PC content 65%); the remaining operations are the same, and the uric acid-lowering composition is finally obtained.

[0035] Comparative Example 1 The difference between this comparative example and Example 1 is that no sour cherry extract was added to the uric acid-lowering composition; the rest of the operations were the same, and the final uric acid-lowering composition was obtained.

[0036] Comparative Example 2 The difference between this comparative example and Example 1 is that no sea buckthorn extract was added to the uric acid-lowering composition; the rest of the operations were the same, and the final uric acid-lowering composition was obtained.

[0037] Comparative Example 3 The difference between this comparative example and Example 1 is that the uric acid-lowering composition does not contain sour cherry extract and sea buckthorn extract, while the rest of the operations are the same, and the final uric acid-lowering composition is obtained.

[0038] Comparative Example 4 The difference between this comparative example and Example 1 is that marine fish oligopeptides are not added to the uric acid-lowering composition, but the rest of the operations are the same, and the final uric acid-lowering composition is obtained.

[0039] Comparative Example 5 The difference between this comparative example and Example 1 is that Poria cocos extract was not added to the uric acid-lowering composition, but the other operations were the same, and the final uric acid-lowering composition was obtained.

[0040] Comparative Example 6 The difference between this comparative example and Example 1 is that marine fish oligopeptides and Poria cocos extract were not added to the uric acid-lowering composition. The rest of the operations were the same, and the final uric acid-lowering composition was obtained.

[0041] Comparative Example 7 The difference between this comparative example and Example 1 is that no soy lecithin was added to the uric acid-lowering composition. The rest of the operations were the same, and the final uric acid-lowering composition was obtained.

[0042] Comparative Example 8 The difference between this comparative example and Example 1 is that all raw materials were directly put into a V-type mixer and mixed for 30 minutes to obtain a uric acid-lowering composition.

[0043] In Examples 1-5 and Comparative Examples 1-8 above, the sea buckthorn extract, marine fish oligopeptides, sour cherry extract, poria cocos extract, medicinal and edible components (chicory, gardenia, corn silk, coix seed), lecithin (soybean lecithin), and microcrystalline cellulose are all conventional commercially available products that can be purchased directly from the market. Sea buckthorn extract, marine fish oligopeptides, sour cherry extract, and poria cocos extract can also be prepared in-house using the following methods: Sea buckthorn extract: Crush dried sea buckthorn raw material, extract with 60-80% ethanol under reflux, recover the solvent, concentrate and dry to obtain the final product. Marine fish oligopeptides: Mince fish meat, add water, add protease, hydrolyze at a suitable temperature for several hours, inactivate the enzyme, centrifuge, collect the supernatant, and spray dry to obtain the final product. Sour cherry extract: Pulp sour cherry pulp, extract with ethanol solution containing citric acid at low temperature in the dark, concentrate and dry the filtrate to obtain the final product. Poria cocos extract: Crush poria cocos, decoct with water to extract, add ethanol to the concentrated solution to precipitate polysaccharides, collect the precipitate and dry to obtain the final product. The total flavonoid content of sea buckthorn extract is ≥40%, the molecular weight of marine fish oligopeptides is 500-1000 Da, the anthocyanin content of sour cherry extract is ≥25%, the content of poria cocos polysaccharide in poria cocos extract is ≥30%, and the phosphatidylcholine content of lecithin is ≥60%. The medicinal and edible components include any one or a combination of at least two of chicory, gardenia, corn silk, and coix seed. The lecithin includes any one or a combination of two of soybean lecithin and egg yolk lecithin. The mass ratio of marine fish oligopeptides to lecithin is 3:1-5:1. As long as the above parameters are within the range, they can be adjusted according to the specific situation in actual production.

[0044] In the above Examples 1-5 and Comparative Examples 1-8, in step (1), the mass concentration of the peptide solution is 5-10%, and the lecithin is in powder or granule form, and is stirred and dispersed at 60-70℃; in step (2), the volume fraction of ethanol is 70-95%; in step (3), the homogenization pressure is 20-40MPa, the number of cycles is 2-3, and a nanocomposite emulsion with a particle size of 100-200nm is obtained; in step (4), the temperature of vacuum concentration is 40-50℃, and the vacuum degree is -0.08 to -0.1MPa; in step (6), the anti-caking agent includes any one or a combination of two of silica and microcrystalline cellulose, and the anti-caking agent accounts for 1-3% of the total weight of the mixture; during spray drying, the inlet air temperature is 160-180℃, and the outlet air temperature is 80-90℃; the above parameters are acceptable as long as they are within the range, and can be adjusted according to specific circumstances in actual production.

[0045] To verify the effectiveness of the present invention, the uric acid-lowering compositions of Examples 1-5 and Comparative Examples 1-8 were tested and their effects were verified below.

[0046] (a) Detection of particle size, zeta potential and encapsulation efficiency ① Particle size and Zeta potential: Take an appropriate amount of sample and disperse it in purified water to prepare a 1 mg / mL dispersion. Use a Malvern laser particle size analyzer to determine the average particle size, polydispersity index (PDI) and Zeta potential.

[0047] ② Encapsulation efficiency test: Take the nanocomposite emulsion (or reconstituted solution) from step (3) of Examples 1-5 and Comparative Examples 1-7, and centrifuge at 12000 rpm / min for 30 min. Take the supernatant and determine the content of free sea buckthorn flavonoids (calculated as quercetin) and tart cherry anthocyanins in the supernatant using high performance liquid chromatography (HPLC). Calculate the encapsulation efficiency according to the following formula: Encapsulation efficiency (%) = (Total added - Free amount) / Total added × 100%.

[0048] Comparative Example 8 was prepared as a suspension directly using purified water without any encapsulation.

[0049] The specific results are shown in Table 1.

[0050] Table 1. Average particle size, polydispersity index, zeta potential, and encapsulation efficiency of the uric acid-lowering compositions.

[0051] As can be seen from Table 1, The uric acid-lowering compositions in Examples 1-5 all had particle sizes controlled between 100-200 nm and were uniformly distributed (PDI<0.25), exhibiting high Zeta potentials (absolute potential value>30), indicating good system stability and high encapsulation efficiency.

[0052] The uric acid-lowering compositions in Comparative Examples 1-3 lack some active ingredients (sour cherry extract, sea buckthorn extract), but because they contain a core carrier (marine fish oligopeptides + lecithin), they can still form a nanosystem with a high encapsulation rate of the existing components.

[0053] The uric acid-lowering compositions in Comparative Examples 4 and 6 lacked marine fish oligopeptides, thus failing to form nanocarriers, resulting in large particle sizes and extremely low encapsulation rates.

[0054] The uric acid-lowering composition in Comparative Example 7 lacked soybean lecithin, resulting in decreased emulsifying ability, increased particle size, and significantly reduced encapsulation efficiency.

[0055] The uric acid-lowering composition of Comparative Example 8 was a physical mixture with no nano-sized features and an encapsulation rate close to 0.

[0056] Comparative Examples 4, 6, and 7 show that the combination of marine fish oligopeptides and lecithin is key to the formation of nanocarrier systems.

[0057] (ii) Bioavailability testing (1) Experimental animals: healthy SD rats, weighing 180-220g. The rats were randomly divided into 13 groups, with 10 rats in each group.

[0058] (2) Test substances: the uric acid-lowering compositions of Examples 1-5 (referred to as test groups 1-5); the uric acid-lowering compositions of Comparative Examples 1-8 (referred to as control groups 1-8). The test substances were prepared into suspensions with distilled water.

[0059] (3) Experimental method: After fasting for 12 hours, rats were given the uric acid-lowering compositions of Examples 1-5 and Comparative Examples 1-8 by gavage, with a dosage of 50 mg / kg (calculated as sea buckthorn flavonoids).

[0060] Blood samples were collected from the orbital rim before administration (0 h) and at 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, and 8 h after administration. Plasma concentrations of isorhamnetin and anthocyanin-3-glucoside were determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS), and pharmacokinetic parameters were calculated.

[0061] Relative bioavailability calculation: The bioavailability of other groups relative to control group 8 (comparative example 8, physical mixture) was calculated with the AUC value of control group 8 (comparative example 8, physical mixture) as 100%.

[0062] The pharmacokinetic model was fitted using DAS 2.0 software, and the data were analyzed using SPSS 22.0 software. A p-value < 0.05 was considered statistically significant. Experimental data are expressed as mean ± standard deviation (x ± s), and the specific results are shown in Table 2.

[0063] Table 2. Relative bioavailability of rats in each group (x±s, n=10)

[0064] Note: In Table 2, ** indicates P<0.01 compared with control group 8; * indicates P<0.05 compared with control group 8; unmarked indicates P>0.05 compared with control group 8.

[0065] As shown in Table 2, In experimental groups 1-5 (Examples 1-5), the relative bioavailability of isorhamnetin and anthocyanin-3-glucoside were all between 280% and 320%, which was nearly three times higher than that of control group 8 (Comparative Example 8, physically mixed). This indicates that the "marine fish oligopeptide-soybean lecithin" composite nanocarrier system of the present invention can significantly improve the oral absorption of poorly soluble active ingredients.

[0066] In control group 4 (comparative example 4, without marine fish oligopeptides) and control group 6 (comparative example 6, without marine fish oligopeptides and Poria cocos extract), the bioavailability of isorhamnetin and anthocyanin-3-glucoside both decreased sharply to around 110%-115%, showing no significant difference from control group 8 (comparative example 8, physically mixed) (P>0.05). This indicates that marine fish oligopeptides are not only nutritional components but also essential raw materials for forming nanocarriers and improving bioavailability. Without marine fish oligopeptides, soybean lecithin alone cannot form a stable nanostructure, thus failing to achieve a breakthrough in bioavailability.

[0067] In control group 7 (comparative example 7, without soy lecithin), the bioavailability of isorhamnetin and anthocyanin-3-glucoside was significantly lower than that of experimental groups 1-5 (Examples 1-5), but still higher than that of control group 8 (comparative example 8, physically mixed). This indicates that soy lecithin can assist in emulsification, but the key to improving bioavailability lies in the combination of marine fish oligopeptides and soy lecithin to form a nanocarrier.

[0068] (III) Validation of the efficacy of the hyperuricemia mouse model (1) Experimental animals: SPF-grade male ICR mice, weighing 18-22g. The mice were randomly divided into 16 groups, with 10 mice in each group.

[0069] (2) Test substances: the uric acid-lowering compositions of Examples 1-5 (referred to as test groups 1-5); the uric acid-lowering compositions of Comparative Examples 1-8 (referred to as control groups 1-8); distilled water (referred to as model control group); allopurinol (referred to as positive control group). In test groups 1-5 and control groups 1-8, the uric acid-lowering compositions were prepared into suspensions with distilled water; in the positive control group, allopurinol tablets were prepared into solutions.

[0070] (3) Modeling method: After one week of adaptive feeding, except for the blank control group, the other mice were injected intraperitoneally with potassium oxonate (250mg / kg / d) daily to induce the hyperuricemia model. At the same time, the corresponding drugs were administered by gavage once a day for 7 consecutive days. The blank control group and the model control group were administered the same amount of distilled water by gavage.

[0071] The specifics are shown in Table 3.

[0072] Table 3. Grouping of hyperuricemic mice (n=10)

[0073] (4) Test results Testing indicators: ① Serum uric acid (SUA): Blood was collected from the orbital cavity 1 hour after the last administration, serum was separated, and the serum uric acid content was determined by the phosphotungstic acid method.

[0074] ② Hepatic xanthine oxidase (XOD) activity: One hour after the last administration, the animals were sacrificed, and liver tissue was collected to prepare homogenates. XOD activity was measured by spectrophotometry.

[0075] ③ URAT1 protein expression in the kidneys (relative expression level): One hour after the last administration, the animals were sacrificed, and kidney tissue was collected. The relative expression level of URAT1 protein was determined by Western blotting.

[0076] ④ Renal function indicators: serum blood urea nitrogen (BUN): blood was collected 1 hour after the last administration, serum was separated, and serum urea nitrogen content was determined by urease method.

[0077] Experimental data are expressed as mean ± standard deviation (x ± s). One-way ANOVA was performed using SPSS 22.0 software. The LSD method was used for comparisons between groups, and P < 0.05 was considered statistically significant. The specific results are shown in Table 4.

[0078] Table 4. Serum uric acid and renal function indicators of mice in each group (x±s, n=10)

[0079] Note: In Table 4, ## indicates P<0.01 compared with the blank control group; ** indicates P<0.01 compared with the model control group; * indicates P<0.05 compared with the model control group; unmarked indicates P>0.05 compared with the model control group.

[0080] As shown in Table 4, ① Overall analysis of uric acid lowering effect The SUA and XOD activities, relative expression of URAT1 protein, and BUN in the model control group mice were significantly higher than those in the blank control group (P<0.01), indicating that the model was successfully established.

[0081] Compared with the model control group, the SUA and XOD activities, relative expression of URAT1 protein, and BUN in experimental groups 1-5 (Examples 1-5) were significantly lower than those in the model control group (P<0.01), and significantly better than those in control groups 1-8 (Comparative Examples 1-8), and close to those in the positive control group. This indicates that the uric acid-lowering compositions prepared in Examples 1-5 have a significant effect on reducing blood uric acid levels.

[0082] ② Analysis of the synergistic effect of "inhibition" (control groups 1-3) The SUA and XOD activities, relative URAT1 protein expression, and BUN levels in control group 3 (comparative example 3, without acid cherry extract and sea buckthorn extract) were significantly higher than those in control group 1 (comparative example 1, without acid cherry extract) and control group 2 (comparative example 2, without sea buckthorn extract). This indicates that acid cherry extract and sea buckthorn extract have a synergistic effect in lowering blood uric acid levels. While a single component can play a certain role, the combination of both is necessary to demonstrate a superior synergistic "inhibitory" effect.

[0083] ③ Analysis of the synergistic effect of "excretion" (control group 4-6) The SUA and XOD activities, relative URAT1 protein expression, and BUN levels in control group 6 (comparative example 6, without marine fish oligopeptides and Poria cocos extract) were slightly higher than those in control group 4 (comparative example 4, without marine fish oligopeptides), and significantly higher than those in control group 5 (comparative example 5, without Poria cocos extract). This indicates that marine fish oligopeptides and Poria cocos extract have a synergistic effect in lowering blood uric acid levels. The absence of either component weakens the synergistic effect of "excretion".

[0084] Control group 4 (comparative example 4, without marine fish oligopeptides) and control group 6 (comparative example 6, without marine fish oligopeptides and Poria cocos extract) lacked marine fish oligopeptides and could not form nanocarriers, resulting in extremely low bioavailability. Consequently, the improvement of SUA and XOD was not significant, and URAT1 expression was not significantly downregulated. This illustrates the dual importance of peptides in both their carrier function and uric acid-lowering function.

[0085] ④ Effect analysis of the nanocarrier system (control groups 4, 6-8) All indicators of the control group 7 (comparative example 7, without soybean lecithin) were worse than those of the experimental groups 1-5 (examples 1-5), which indicates that lecithin-assisted nano-sizing is crucial for improving efficacy.

[0086] All indicators of Comparative Example 8 (Comparative Example 8, physical mixing) were worse than those of Experimental Groups 1-5 (Examples 1-5), which indicates that the preparation process (composite nanocarrier system) of the present invention plays a key role in improving drug efficacy.

[0087] Comparative Examples 4, 6, 7, and 8 show that the "marine fish oligopeptide-soybean lecithin" composite nanocarrier system is crucial for improving drug efficacy.

[0088] In summary, the uric acid-lowering composition provided by this invention achieves multi-target synergistic uric acid reduction through specific component combinations and ratios, and a unique nano-preparation process. Compared to comparative compositions that involve simple physical mixing or lack key components, the uric acid-lowering composition of this invention has smaller particle size and higher bioavailability, significantly inhibiting XOD activity and downregulating URAT1 expression, thereby effectively reducing blood uric acid and protecting kidney function. This provides experimental evidence for the development of functional foods.

[0089] The present invention also provides the application of the uric acid-lowering compositions prepared in Examples 1-5 in the preparation of functional foods, health products or drugs that lower uric acid and protect kidney function.

[0090] This invention provides a uric acid-lowering composition, its preparation method, and its application, compared with the prior art: (1) This invention provides a composition for lowering uric acid, wherein the raw materials have a synergistic effect: ① Sour cherry extract is rich in anthocyanins and flavonoids, while sea buckthorn extract is rich in flavonoids. The two work synergistically to inhibit the activity of xanthine oxidase in the liver, thereby blocking the uric acid production pathway at its source and reducing uric acid production, thus creating an "inhibition" synergy.

[0091] ② Marine fish oligopeptides can specifically regulate the expression of uric acid transporters URAT1 / GLUT9 in the proximal convoluted tubule of the kidney, promoting uric acid excretion from the kidney; Poria cocos polysaccharide in Poria cocos extract can regulate the intestinal epithelial transporter ABCG2, promoting uric acid excretion from the intestine and reducing the burden on the kidney; the two work synergistically to form a dual-channel excretion mechanism of "kidney + intestine", constructing a "excretion" synergy and solving the bottleneck of kidney damage caused by relying solely on kidney excretion.

[0092] ③ Phosphatidylcholine in lecithin can repair damaged renal tubular epithelial cells; the antioxidant effects of Poria cocos extract combined with sea buckthorn extract and sour cherry extract can reduce the inflammatory response of the kidneys caused by high uric acid; the medicinal and edible components (chicory, gardenia, corn silk, coix seed) have diuretic, anti-inflammatory and liver-protective effects; the three work synergistically to form an "antioxidant + anti-inflammatory + kidney protection" mechanism, thus constructing a "protective" synergy.

[0093] This invention constructs a three-dimensional regulatory mechanism of "'inhibition' synergy + 'excretion' synergy + 'protection' synergy", realizing a three-dimensional uric acid-lowering network of "liver-kidney-intestine", with multi-target synergistic effect and significant uric acid-lowering effect.

[0094] (2) This invention provides a method for preparing a composition for lowering uric acid, using marine fish oligopeptides (500-1000 Da) as a natural carrier. The peptide molecules can self-assemble with phospholipid molecules through hydrophobic interactions to form "peptide-phospholipid micelles". The internal part of the micelle is a hydrophobic core, which can effectively encapsulate poorly soluble components such as sea buckthorn flavonoids and tart cherry anthocyanins to form nanocomplexes, making them stable micelles in the gastrointestinal tract, significantly improving solubility and transmembrane absorption rate; the external part is a hydrophilic shell, which increases the dispersibility of the nanocomplexes in water. When the nanocomplexes enter the intestine, the phospholipids and peptides can open the tight junctions of intestinal epithelial cells or be directly transported through endocytosis, greatly increasing the blood concentration of active ingredients and improving bioavailability.

[0095] (3) The raw materials of the present invention are all food-grade or medicinal materials. They have no toxic side effects when consumed for a long time, have high safety, overcome the side effects and drug resistance of chemical drugs, and are suitable for a wide range of people.

[0096] The above-described embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application, and should all be included within the protection scope of this application.

Claims

1. A composition for lowering uric acid, characterized in that, The ingredients include the following ingredients by weight percentage: 10-20% sea buckthorn extract, 20-35% marine fish oligopeptides, 5-12% sour cherry extract, 5-10% poria cocos extract, 20-35% food and medicinal components, and 5-10% lecithin.

2. The uric acid-lowering composition according to claim 1, characterized in that, The sea buckthorn extract contains ≥40% total flavonoids, the marine fish oligopeptide has a molecular weight of 500-1000 Da, the sour cherry extract contains ≥25% anthocyanins, the poria cocos extract contains ≥30% poria cocos polysaccharides, and the lecithin contains ≥60% phosphatidylcholine.

3. The uric acid-lowering composition according to claim 1, characterized in that, The medicinal and edible components include any one or a combination of at least two of chicory, gardenia, corn silk, and coix seed; the lecithin includes any one or a combination of two of soybean lecithin and egg yolk lecithin.

4. The uric acid-lowering composition according to claim 1, characterized in that, The composition is a nanoparticle composition with a self-assembled marine fish oligopeptide and lecithin as a carrier, and the average particle size of the composition is 100-200 nm with an encapsulation efficiency of 70-85%.

5. The uric acid-lowering composition according to claim 4, characterized in that, The mass ratio of the marine fish oligopeptide to the lecithin is 3:1-5:

1.

6. A method for preparing a uric acid-lowering composition as described in any one of claims 1-5, characterized in that, Includes the following steps: (1) Add marine fish oligopeptides to purified water, stir to dissolve, and obtain a peptide solution; then add lecithin, stir to disperse, and obtain a homogeneous emulsion A; (2) Dissolve sea buckthorn extract and sour cherry extract in ethanol to obtain solution B; (3) Under stirring, solution B is slowly added dropwise to emulsion A. After the addition is complete, stirring is continued to obtain a mixture. The mixture is then subjected to high-pressure homogenization to obtain a nanocomposite emulsion. (4) The nanocomposite emulsion was concentrated under reduced pressure to recover ethanol, and a concentrated aqueous nano suspension was obtained. (5) Mix the aqueous nano suspension with the food-medicine homology components and Poria cocos extract evenly to obtain a mixed slurry; (6) Spray dry the mixed slurry to obtain a uric acid-lowering composition.

7. The method for preparing the uric acid-lowering composition according to claim 6, characterized in that, In step (1), a peptide solution with a mass concentration of 5-10% is obtained; lecithin is in powder or granule form and is dispersed by stirring at 60-70℃; in step (2), the volume fraction of ethanol is 70-95%.

8. The method for preparing the uric acid-lowering composition according to claim 6, characterized in that, In step (3), the homogenization pressure is 20-40 MPa, the number of cycles is 2-3, and a nanocomposite emulsion with a particle size of 100-200 nm is obtained; in step (4), the temperature of vacuum concentration is 40-50℃, and the vacuum degree is -0.08 to -0.1 MPa.

9. The method for preparing the uric acid-lowering composition according to claim 6, characterized in that, In step (5), the medicinal and edible components are in powder or granule form; in step (6), before spray drying, an anti-caking agent accounting for 1-3% of the total weight of the mixed slurry is added, wherein the anti-caking agent includes any one or a combination of two of silica and microcrystalline cellulose; during spray drying, the inlet air temperature is 160-180℃ and the outlet air temperature is 80-90℃.

10. The use of a uric acid-lowering composition as described in any one of claims 1-5 in the preparation of functional foods, health products, or medicines that lower uric acid and protect kidney function.

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