Composition for reducing uric acid as well as preparation method and application thereof

Abstract

The invention provides a uric acid reducing composition and a preparation method and application thereof, and belongs to the technical field of medicine and health care. The uric acid reducing composition provided by the invention comprises natto peptide powder, chrysanthemum extract powder and luteolin, and can effectively inhibit the activity of xanthine oxidase and reduce the blood uric acid level. Contrast experiments prove that the synergistic interaction effect of the natto peptide powder and the chrysanthemum extract powder in the composition is obvious, all the components of the composition cooperate with one another, and kidney injury is reduced while uric acid is reduced and the effect is enhanced.

Description

Technical Field

[0001] The present application relates to the field of medicine and health care technology, and specifically to a uric acid lowering composition and a preparation method and application thereof. Background Art

[0002] Hyperuricemia (HUA) is a metabolic disease caused by excessive production or blocked excretion of uric acid in the body, characterized by abnormally high uric acid levels in the blood, which can cause a variety of complications, such as chronic kidney disease, cardiovascular disease, and gout. And with the improvement of living standards and changes in living habits, the incidence of hyperuricemia and gout in my country has gradually increased, showing a trend of younger people, which seriously threatens human health.

[0003] The anti-hyperuricemia drugs currently used mainly include: allopurinol, colchicine, benzbromarone, xanthine oxidase inhibitors, etc., which have certain effects on lowering serum uric acid, but long-term use will lead to certain drug resistance and side effects. In addition, there is no effective and safe drug for asymptomatic hyperuricemia patients that can effectively prevent and treat hyperuricemia. Therefore, it is very necessary to provide a product that is safe, has no side effects, and can relieve hyperuricemia and gout. Summary of the invention

[0004] In view of this, the present application provides a uric acid lowering composition and a preparation method and application thereof, which can reduce kidney damage while lowering uric acid and increasing efficacy.

[0005] The embodiments of the present application are implemented as follows: in a first aspect, a uric acid lowering composition is provided, wherein the uric acid lowering composition comprises natto peptide powder, chrysanthemum extract powder and luteolin.

[0006] In some embodiments, the uric acid lowering composition includes 10 to 50 parts of the natto peptide powder, 10 to 40 parts of the chrysanthemum extract powder, and 1 to 3 parts of luteolin.

[0007] In some embodiments, the uric acid lowering composition includes 50 parts of the natto peptide powder, 10 parts of the chrysanthemum extract powder, and 2 parts of luteolin.

[0008] In some embodiments, the uric acid-lowering composition is a tablet, capsule, powder, granule, pill or oral liquid preparation.

[0009] In some embodiments, the uric acid lowering composition consists of the natto peptide powder, the chrysanthemum extract powder and the luteolin.

[0010] In some embodiments, the natto peptide powder is obtained by fermentation and enzymolysis of Bacillus subtilis.

[0011] In some embodiments, the Bacillus subtilis is sourced from China Center for Type Culture Collection, with the accession number being CCTCC NO: M2022132.

[0012] In some embodiments, the fermentation is liquid fermentation, and the liquid fermentation is as follows: inoculating Bacillus subtilis seed liquid into the fermentation liquid at a ratio of 1%~5%ml / 100ml; culturing for 18~24h at 20%~40% dissolved oxygen, 35~40°C, and 300~600rpm to obtain a fermentation stock solution; then centrifuging the fermentation stock solution, taking the supernatant and concentrating and drying it through a filter membrane to obtain a natto powder concentrate; using a 0.5%~1.5% pepsin solution, mixing it according to the ratio of nattokinase activity and pepsin solution 5000~10000 IU / ml, the pH value is 1.6±0.2, and enzymolysis is carried out at 37±2°C for 1~2h; after the enzymolysis is completed, the temperature is raised to above 95°C, the enzyme is inactivated for 10~15min, and then dried to obtain natto peptide powder.

[0013] In some embodiments, the fermentation is solid fermentation, and the solid fermentation is: soybeans and nutrient solution are mixed at a mass volume ratio of 1:2~1:4, soaked at 2~30°C for 6~12h and then drained; then steamed at 105°C~115°C and 0.02MPa for 30~60 minutes; after steaming and cooling, inoculated with Bacillus subtilis seed liquid at 1%~10%ml / 100g, and fermented for 24~48h under fermentation conditions of 37~41°C and humidity of 75~85%; the natto prepared by solid fermentation is crushed, pure water is added at a mass volume ratio of 10%~30%g / 100ml, mixed and stirred, and liquid enzymolysis is performed at 50°C and 180~220r / min for 2h~6h. After the enzymolysis is completed, centrifugation is performed to remove the precipitate, and the supernatant is collected and dried to obtain natto peptide powder.

[0014] In a second aspect, the present application also provides a method for preparing the above-mentioned uric acid lowering composition, comprising: weighing natto peptide powder, chrysanthemum extract powder and luteolin by weight; mixing the natto peptide powder, the chrysanthemum extract powder and the luteolin to obtain the uric acid lowering composition.

[0015] In a third aspect, the present application also provides the use of the uric acid lowering composition in uric acid lowering health foods or medicines.

[0016] The uric acid lowering composition in the present application contains natto peptide powder, chrysanthemum extract powder and luteolin. The three active ingredients are compounded in a specific proportion. Under the synergistic effect, they can effectively inhibit the activity of xanthine oxidase, and reduce kidney damage while enhancing the uric acid lowering effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0018] Figure 1 It is a schematic flow chart of an embodiment of a method for preparing a uric acid-lowering composition provided in the present application. DETAILED DESCRIPTION

[0019] The technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present application. In addition, it should be understood that the specific implementation methods described herein are only used to illustrate and explain the present application and are not used to limit the present application. In the present application, unless otherwise stated, the directional words used, such as "upper" and "lower", are specifically the directions of the drawings in the accompanying drawings. In addition, in the description of the present application, the term "including" means "including but not limited to".

[0020] Various embodiments of the present application may be presented in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity, and should not be understood as a rigid limitation on the scope of the present application; therefore, the range description should be considered to have specifically disclosed all possible sub-ranges and single numerical values ​​within the range. For example, the range description from 1 to 6 should be considered to have specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as single numbers within the range, such as 1, 2, 3, 4, 5 and 6, which apply regardless of the range. In addition, whenever a numerical range is indicated herein, it is meant to include any cited number (fractional or integer) within the indicated range.

[0021] In this application, "and / or" describes the association relationship of associated objects, indicating that there may be three types of relationships. For example, A and / or B may represent: A exists alone, A and B exist at the same time, and B exists alone. A and B may be singular or plural.

[0022] In the present application, "at least one" means one or more, and "more than one" means two or more. "At least one", "at least one of the following" or similar expressions refer to any combination of these items, including any combination of single or plural items. For example, "at least one of a, b, or c", or "at least one of a, b, and c" can all mean: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or plural, respectively.

[0023] The present application provides a uric acid lowering composition, comprising natto peptide powder, chrysanthemum extract powder and luteolin.

[0024] Specifically, the uric acid lowering composition comprises: 10-50 parts of natto peptide powder, 10-40 parts of chrysanthemum extract powder, and 1-3 parts of luteolin. Preferably, the uric acid lowering composition comprises 50 parts of natto peptide powder, 10 parts of chrysanthemum extract powder, and 2 parts of luteolin.

[0025] In a specific embodiment, the uric acid lowering composition consists of the natto peptide powder, the chrysanthemum extract powder and the luteolin.

[0026] In another specific embodiment, the uric acid lowering composition includes other auxiliary agents such as solvents, co-solvents, fillers, colorants, etc. in addition to natto peptide powder, chrysanthemum extract powder and luteolin.

[0027] The natto peptide powder is obtained by fermentation and enzymolysis of Bacillus subtilis, contains a variety of bioactive peptide substances, and has no toxic side effects. In addition to nattokinase, which has a thrombolytic effect, it also contains small molecule peptides, various amino acids, multiple vitamins and other bioactive factors, and has strong antioxidant and free radical scavenging capabilities; it also contains a variety of antibacterial and antioxidant substances produced by Bacillus subtilis, including bacteriocins, superoxides, peptides and antibacterial proteins. Natto peptide powder obtained by further enzymolysis of natto powder is rich in a variety of active peptides and has lipid-lowering, blood pressure-lowering and uric acid-lowering effects.

[0028] In one embodiment, the source of Bacillus subtilis is: China Center for Type Culture Collection, with a deposit number of CCTCC NO: M2022132. The Bacillus subtilis with a deposit number of CCTCC NO: M2022132 is deposited in the National Center for Type Culture Collection, named Bacillus subtilis ZF01, classified as Bacillus subtilis, with a deposit address of Wuhan, China, and a deposit date of February 18, 2022.

[0029] In a specific embodiment, the natto peptide powder is a natto peptide powder obtained by liquid fermentation and enzymatic hydrolysis. The natto peptide powder obtained by liquid fermentation and enzymatic hydrolysis is obtained by the following method: Inoculating Bacillus subtilis seed liquid into fermentation liquid at a ratio of 1%~5%ml / 100ml; wherein the fermentation liquid is prepared by the following steps: mixing 1%~3%g / 100ml of soy peptone, 2%~5% of glucose, 1%~3% of Na2HPO4·12H2O, 0.1%~1% of NaH2PO4·H2O, 0.01%-0.05% of MgSO4·7H2O, and 0.01%~0.05% of CaCl2 in proportion to obtain a fermentation liquid; The fermentation solution is obtained by culturing at 20%-40% dissolved oxygen, 35-40°C, and 300-600rpm for 18-24h; the fermentation solution is then centrifuged, and the supernatant is concentrated and dried through a filter membrane to obtain a natto powder concentrate; a pepsin solution with a concentration of 0.5%-1.5% is used, and the mixture is mixed according to the ratio of nattokinase activity and pepsin solution 5000-10000 IU / ml, the pH value is 1.6±0.2, and enzymolysis is performed at 37±2°C for 1-2h; after the enzymolysis is completed, the temperature is raised to above 95°C, the enzyme is inactivated for 10-15min, and then dried to obtain natto peptide powder.

[0030] In another specific embodiment, the natto peptide powder is a natto peptide powder obtained by solid fermentation and enzymolysis. The natto peptide powder obtained by solid fermentation and enzymolysis is obtained by the following method: soybeans and nutrient solution are mixed at a mass volume ratio of 1:2~1:4, soaked at 2~30°C for 6~12h and then drained; wherein the nutrient solution contains: 30g / L glucose, 8g / L disodium hydrogen phosphate dodecahydrate, 0.5g / L sodium dihydrogen phosphate monohydrate, 0.5g / L magnesium sulfate, pH 7.0; then steamed at 105°C~115°C, 0.02MPa for 30~60 minutes; steamed and After cooling, inoculate Bacillus subtilis seed liquid at 1% to 10% ml / 100g, and ferment for 24 to 48 hours under fermentation conditions of 37 to 41°C and 75 to 85% humidity; crush the natto prepared by solid fermentation, add pure water at a mass volume ratio of 10% to 30% g / 100ml, mix and stir, perform liquid enzymolysis at 50°C and 180 to 220 r / min for 2 hours to 6 hours, centrifuge to remove the precipitate after the enzymolysis is completed, collect the supernatant and dry it to obtain natto peptide powder.

[0031] Chrysanthemum extract is derived from chrysanthemum, a food and medicine substance, which is rich in flavonoids, alkaloids, anthraquinones and other chemical components, has the effects of lowering cholesterol, uric acid and blood sugar, and also has good antibacterial and antioxidant effects. Chrysanthemum extract is prepared by conventional methods in the art. In a specific embodiment, the specific preparation method is: dry and crush the dried head inflorescence of the plant, extract, filter, concentrate and dry to obtain the extract.

[0032] Luteolin (CAS: 491-70-3) is a natural flavonoid compound found in many plants. It has multiple pharmacological activities, such as anti-inflammatory, anti-allergic, uric acid-lowering, anti-tumor, antibacterial, antiviral, etc. It is mainly used clinically for cough relief, expectorant, anti-inflammatory, and uric acid-lowering.

[0033] The uric acid lowering composition in the present application contains natto peptide powder, chrysanthemum extract powder and luteolin. The three active ingredients are compounded in a specific proportion. Under the synergistic effect, they can effectively inhibit the activity of xanthine oxidase, and reduce kidney damage while enhancing the uric acid lowering effect.

[0034] Specifically, the natto peptide powder obtained by further enzymatic hydrolysis of fermented natto powder is rich in various active peptides and has a strong xanthine oxidase inhibitory effect; it also contains small molecule peptides, various amino acids, multiple vitamins and other bioactive factors, which have strong antioxidant and free radical scavenging capabilities, and play a role in alleviating hyperuricemia and improving kidney damage. Chrysanthemum total flavonoids can reduce uric acid by inhibiting the two most critical enzymes for uric acid production: adenosine deaminase and xanthine oxidase. It can also reduce uric acid reabsorption by regulating the Akt / GSK-3β pathway, and has a synergistic effect with natto peptide powder. Rhizocyanin can reduce the inflammatory response caused by hyperuricemia by downregulating or blocking the TLR / MyD88 / NF-κB pathway, and can also promote uric acid excretion by upregulating the expression level of renal uric acid secretion transporters (ABCG2, OAT1, OAT3), and synergize with natto peptide powder and chrysanthemum extract to reduce uric acid and relieve kidney damage.

[0035] The present application also provides a method for preparing a uric acid-lowering composition, see Figure 1 , Figure 1 This is a schematic flow chart of an embodiment of a method for preparing a uric acid-lowering composition provided in the present application, comprising the following steps: Step S1: weighing natto peptide powder, chrysanthemum extract powder and luteolin according to weight; Step S2: mixing the natto peptide powder, the chrysanthemum extract powder and the luteolin to obtain a uric acid-lowering composition.

[0036] In step S1, the following weight portions are weighed: 10 to 50 parts of natto peptide powder, 10 to 40 parts of chrysanthemum extract powder, and 1 to 3 parts of luteolin. Preferably, 50 parts of natto peptide powder, 10 parts of chrysanthemum extract powder, and 2 parts of luteolin. Among them, the natto peptide powder, chrysanthemum extract powder, and luteolin can refer to the relevant description of the uric acid lowering composition in this application, and will not be repeated here.

[0037] In step S2, the mixing may be dry mixing or wet mixing, and the mixing method may be one or more mixing methods known in the art such as stirring, ultrasound, and oscillation.

[0038] In one embodiment, after being evenly mixed, an oral preparation is prepared to obtain the uric acid lowering composition provided by the present application. Specifically, the uric acid lowering composition can be in the form of tablets, capsules, powders, granules, pills, oral liquid preparations, and the like.

[0039] The present application also provides an application of a uric acid-lowering composition in the preparation of a uric acid-lowering health food or medicine, so as to be applied to the treatment and health care of hyperuricemia.

[0040] In the present application, the xanthine oxidase inhibition rate and uric acid, urea nitrogen, and creatinine level tests are used to prove that the uric acid lowering composition provided in the present application can inhibit the activity of xanthine oxidase, reduce blood uric acid levels, and reduce kidney damage.

[0041] In the examples, the comparison results prove that the uric acid lowering effect of the composition is a synergistic effect of natto peptide powder and chrysanthemum extract powder.

[0042] The technical scheme and technical effects of the present application are described in detail below through specific embodiments, comparative examples and experimental examples. The following embodiments are only some embodiments of the present application and do not specifically limit the present application. The basic principles of the present invention defined in the following description can be applied to other implementation schemes, variants, improvements, equivalent schemes and other technical schemes that do not deviate from the spirit and scope of the present invention.

[0043] It can be understood that the reagents used in various embodiments, comparative examples and experimental examples are all commercially available reagents unless otherwise specified. Example 1

[0044] A uric acid lowering composition comprises the following ingredients: 10-50 parts of natto peptide powder, 10-40 parts of chrysanthemum extract powder, and 1-3 parts of luteolin. According to the following table, the components of different compositions are weighed by weight and mixed to obtain a composition, see Table 1.

[0045] Table 1 Components of different compositions and comparative compositions Grouping <![CDATA[Natto peptide powder 1 > <![CDATA[Natto peptide powder 2 > Chrysanthemum Extract Powder Luteolin Natto Powder Honeysuckle Pollen Composition 1 10 0 10 2 0 0 Composition 2 30 0 10 2 0 0 Composition 3 50 0 10 2 0 0 Composition 4 50 0 20 2 0 0 Composition 5 10 0 20 2 0 0 Composition 6 10 0 40 2 0 0 Composition 7 50 0 10 3 0 0 Composition 8 0 50 10 2 0 0 Comparative Example 1 0 0 10 2 50 0 Comparative Example 2 50 0 0 2 0 10 Comparative Example 3 50 0 0 0 0 0 Comparative Example 4 0 0 10 0 0 0 Comparative Example 5 0 0 0 2 0 0 Comparative Example 6 0 0 10 2 0 0 Comparative Example 7 50 0 0 2 0 0 Comparative Example 8 50 0 10 0 0 0 Note: “1” is natto peptide powder from liquid fermentation and enzymatic hydrolysis; “2” is natto peptide powder from solid fermentation and enzymatic hydrolysis.

[0046] The preparation method of natto peptide powder by liquid fermentation and enzymatic hydrolysis is as follows: (1) preparing fermentation liquid: 2% g / 100 ml of soybean peptone, 3% of glucose, 2% of Na2HPO4·12H2O, 0.5% of NaH2PO4·H2O, 0.02% of MgSO4·7H2O, and 0.02% of CaCl2 are mixed in proportion to prepare fermentation liquid; (2) taking frozen and stored seeds, rethawing them, and inoculating them into the liquid culture medium of the shake flask at 0.1%. The seed liquid is obtained by shaking and culturing at 180 rpm and 37°C in a shaking incubator for 16 to 18 hours. The liquid culture medium contains: 15 g / L of glucose, 15 g / L of peptone, 10 g / L of yeast extract, 5 g / L of disodium hydrogen phosphate dodecahydrate, 1 g / L of sodium dihydrogen phosphate monohydrate, 0.2 g / L of magnesium sulfate, and pH 7.0 to 7.6. The Bacillus subtilis seed liquid is inoculated into the fermentation liquid at a ratio of 3% ml / 100 ml, and the fermentation liquid is cultured at 30% dissolved oxygen, 35-40°C, and 300 rpm for 20 hours to obtain the fermentation liquid; the fermentation liquid is then centrifuged and the supernatant is concentrated through a filter membrane. (3) A 1% pepsin solution is used, and the mixture is mixed according to the ratio of nattokinase activity and pepsin solution 6000 IU / ml, with a pH value of 1.6, and enzymolysis is performed at 37°C for 1.5 hours; after the enzymolysis is completed, the temperature is raised to above 95°C, the enzyme is inactivated for 10 minutes, and the natto peptide powder is obtained by drying.

[0047] The preparation method of the solid fermentation enzymatic hydrolysis natto peptide powder is as follows: the soybeans are washed and impurities are removed, the soybeans and the nutrient solution are mixed in a mass volume ratio of 1:3, and the mixture is soaked at 8°C for 12 hours and then drained; wherein the nutrient solution contains: 30g / L glucose, 8g / L disodium hydrogen phosphate dodecahydrate, 0.5g / L sodium dihydrogen phosphate monohydrate, 0.5g / L magnesium sulfate, and the pH is 7.0. Then, the mixture is steamed at 105°C and 0.02MPa for 40 minutes. After cooking and cooling, inoculating Bacillus subtilis seed liquid at 5% ml / 100 g of the weight of the raw material, fermenting in a fermentation device for 36 hours to obtain fermented fresh natto, wherein the temperature in the fermentation device is controlled at 37-41° C. and the humidity is 75-85%; the fresh natto is crushed, pure water is added at a mass volume ratio of 20% g / 100 ml, mixed and stirred, and liquid enzymolysis is performed at 50° C. and 180-220 r / min for 4 hours. After the enzymolysis is completed, centrifugation is performed to remove the precipitate, and the supernatant is collected and dried to obtain natto peptide powder.

[0048] Natto peptide powder, chrysanthemum extract powder and luteolin are weighed according to weight, mixed and evenly prepared into an oral preparation. Example 2 Uric acid lowering activity test of the composition

[0049] The xanthine oxidase inhibition rate test experiment was used to determine the uric acid-lowering activity of each composition. Specifically, the dual enzyme method was used to determine the inhibition rate of the sample on xanthine oxidase. In the dual enzyme coupling method, xanthine is decomposed by xanthine oxidase to produce H2O2. In the process of horseradish peroxidase catalyzing H2O2, 4-aminoantipyrine and phenol form a red compound, which will produce an absorbance value at 508 nm, and the xanthine oxidase inhibition activity can be calculated.

[0050] The specific method is as follows: add 200 μL of sample solution and 50 μL of 0.5 U / mL xanthine oxidase solution to a 10 mL colorimetric tube, vortex and mix, and keep warm at 37°C for 10 min. Then add 400 μL of 2.0 mmol / L xanthine solution and 3 mL of colorimetric solution to start the reaction; keep warm at 37°C for 20 min; boil for 5 min, cool to room temperature; and measure the absorbance at 508 nm. The blank group A0 is the group without xanthine added; the positive blank group Ac is the group without sample added; the zero adjustment group is the group without xanthine oxidase added; the measurement group is As; the calculation formula is: the XOD inhibition rate of the sample (%) = (Ac-(As-A0)) / Ac*100%.

[0051] The test results are shown in Table 2.

[0052] Table 2 Uric acid lowering activity of each composition The results of compositions 1-8 showed that compositions 3 and 8 exerted the best effects, with the highest xanthine oxidase inhibition rates of 83.33% and 82.05%, and the efficacy of natto peptide powders from the two enzymatic hydrolysis processes in the composition was not much different. The results of compositions 3 and 4 showed that the inhibition rate did not increase when chrysanthemum extract was added; the results of compositions 3 and 7 showed that the inhibition rate did not increase when luteolin was added, indicating that natto peptide powder, chrysanthemum extract powder and luteolin can only exert the best synergistic effect when they are compounded in a certain proportion.

[0053] The results of Comparative Examples 3-8 and Composition 3 show that each component of the composition and the components play a role in inhibiting xanthine oxidase. The result of adding natto peptide powder and chrysanthemum extract powder (Comparative Example 8) is significantly higher than the result of natto peptide powder or chrysanthemum extract powder alone (Comparative Examples 3, 4, 6, 7). Comparison of the results of Comparative Examples 8 and 6, 7 shows that the synergistic effect of natto peptide powder and chrysanthemum extract is obvious. The results of Comparative Examples 1, 2 and Composition 3 show that the xanthine oxidase inhibition rate is significantly reduced by replacing natto peptide powder with natto powder or replacing chrysanthemum extract powder with honeysuckle powder, which has been reported to have a uric acid-lowering effect, further illustrating the importance of natto peptide powder and chrysanthemum extract powder in synergistically exerting a uric acid-lowering effect. Example 3 Animal Verification

[0054] Establishment of hyperuricemia mouse model: Adult Kunming mice were given potassium oxonate 400 mg / kg combined with hypoxanthine 500 mg / kg daily, with potassium oxonate injected intraperitoneally and hypoxanthine administered by gavage for 14 consecutive days. The serum of mice was then collected and the serum uric acid level of mice was detected using a kit. The level of uric acid in the model group was 202.15 μmol / L, which was significantly higher than that in the normal group (96.37 μmol / L), indicating that the model was successfully established.

[0055] Animal grouping and administration method: 100 adult Kunming mice were selected and randomly divided into 2 groups, 10 in the normal group, and the remaining 90 mice were randomly divided into 9 groups after the model was successfully established. The grouping is shown in Table 3, including the model group, the positive group, and the formula group (compositions 3 and 8, comparative examples 3, 4, 5, 7, and 8). Then the test samples of each experimental group were orally administered, and the normal group and the model group were given equal volumes of physiological saline by gavage; the positive group was given 50 mg / Kg of allopurinol, and the daily dose of the test samples of each formula group was 100 mg / Kg, once a day, for 28 consecutive days, and then the levels of uric acid, urea nitrogen, and creatinine in the serum of each group were measured using a kit.

[0056] Results: The results of the determination of serum uric acid, urea nitrogen and creatinine in each group of animals are shown in Tables 3 and 4.

[0057] Table 3 Results of determination of serum uric acid in animals before and after modeling Grouping Uric acid level (μmol / L) Normal group 96.37±6.21 Model Group 202.15±4.21* Table 4 Uric acid and renal function test results of each group of animals Grouping Uric acid (μmol / L) Urea nitrogen (mg / dL) Creatinine (umol / L) Normal group 91.68±8.37 11.25±2.03 41.36±4.28 Model Group 196.27±8.06* 24.58±3.24* 87.69±5.07* Positive Control <![CDATA[95.21±5.67 # ]]> <![CDATA[12.05±1.96 # ]]> <![CDATA[46.92±7.16 # ]]> Composition 3 <![CDATA[92.67±8.09 # ]]> <![CDATA[11.57±1.25 # ]]> <![CDATA[48.68±4.51 # ]]> Composition 8 <![CDATA[93.41±6.18 # ]]> <![CDATA[12.44±2.19 # ]]> <![CDATA[47.26±5.07 # ]]> Comparative Example 3 <![CDATA[121.54±7.38 # ]]> <![CDATA[16.52±2.04 # ]]> <![CDATA[62.12±6.35 # ]]> Comparative Example 4 <![CDATA[154.67±9.01 # ]]> <![CDATA[18.69±2.31 # ]]> <![CDATA[69.27±7.05 # ]]> Comparative Example 5 <![CDATA[149.64±8.33 # ]]> <![CDATA[18.90±1.58 # ]]> <![CDATA[74.58±8.14 # ]]> Comparative Example 7 <![CDATA[117.18±5.24 # ]]> <![CDATA[16.24±2.64 # ]]> <![CDATA[64.82±5.29 # ]]> Comparative Example 8 <![CDATA[109.39±6.18 # ]]> <![CDATA[14.17±2.81 # ]]> <![CDATA[58.18±6.08 # ]]> Note: *Compared with the normal group, p < 0.05. #Compared with the model group, p < 0.05.

[0058] As shown in Table 3, the modeling was successful.

[0059] As shown in Table 4, compared with the model group, the uric acid levels of compositions 3, 8 and other comparative examples all decreased. This further illustrates that each component of the composition and the components play a role in lowering uric acid. Among them, the uric acid lowering effect of compositions 3 and 8 is significantly higher than that of comparative examples 3, 4, 5, 7, and 8. And the uric acid lowering effect of compositions 3 and 8 is higher than that of the positive group.

[0060] Serum creatinine and urea nitrogen concentrations are often used to reflect renal function. The higher the value, the worse the renal function. As shown in Table 4, compared with the normal group, the serum creatinine and urea nitrogen levels of mice in the model group were significantly increased. The urea nitrogen and creatinine levels of the formula group were significantly lower than those of the model group, showing a protective effect on the kidneys. Among them, the protective effect of compositions 3 and 8 was better than that of the control group. The results showed that compositions 3 and 8 can alleviate hyperuricemia and related renal function damage.

[0061] Among them, xanthine oxidase is the rate-limiting enzyme for uric acid production, which can catalyze hypoxanthine and xanthine to eventually produce uric acid. Therefore, the level of uric acid in serum can be reduced by inhibiting the activity of xanthine oxidase.

[0062] From the above, it can be seen that the uric acid lowering composition provided by the present application can effectively inhibit the activity of xanthine oxidase and reduce the level of blood uric acid. Comparative experiments have shown that the natto peptide powder and chrysanthemum extract powder in the composition have obvious synergistic effects. The components in the composition cooperate with each other in a specific ratio, while reducing uric acid and enhancing synergy, reducing kidney damage.

[0063] The above is a detailed introduction to a uric acid-lowering composition provided in the examples of the present application, as well as its preparation method and application. Specific examples are used herein to illustrate the principles and implementation methods of the present application. The description of the above embodiments is only used to help understand the method of the present application and its core idea; at the same time, for technicians in this field, according to the ideas of the present application, there will be changes in the specific implementation methods and application scopes. In summary, the content of this specification should not be understood as a limitation on the present application.

Claims

1. A uric acid lowering composition, characterized in that: The uric acid lowering composition comprises natto peptide powder, chrysanthemum extract powder and luteolin.

2. The uric acid lowering composition according to claim 1, characterized in that The uric acid lowering composition comprises 10 to 50 parts of the natto peptide powder, 10 to 40 parts of the chrysanthemum extract powder, and 1 to 3 parts of luteolin.

3. The uric acid lowering composition according to claim 2, characterized in that: The uric acid lowering composition comprises 50 parts of the natto peptide powder, 10 parts of the chrysanthemum extract powder, and 2 parts of luteolin; and / or, The uric acid lowering composition is in the form of tablets, capsules, powders, granules, pills or oral liquid preparations.

4. The uric acid lowering composition according to any one of claims 1 to 3, characterized in that The uric acid lowering composition consists of the natto peptide powder, the chrysanthemum extract powder and the luteolin.

5. The uric acid lowering composition according to claim 1, characterized in that: The natto peptide powder is obtained by fermenting and enzymolyzing Bacillus subtilis.

6. The uric acid lowering composition according to claim 5, characterized in that: The source of the Bacillus subtilis is: China Center for Type Culture Collection, with a collection number of CCTCC NO: M2022132.

7. The uric acid lowering composition according to claim 5, characterized in that: The fermentation is liquid fermentation, and the liquid fermentation is as follows: inoculating Bacillus subtilis seed liquid into the fermentation liquid at a ratio of 1% to 5% ml / 100 ml; culturing for 18 to 24 hours at 20% to 40% dissolved oxygen, 35 to 40° C., and 300 to 600 rpm to obtain a fermentation stock solution; then centrifuging the fermentation stock solution, taking the supernatant, and concentrating and drying it through a filter membrane to obtain a natto powder concentrate; using a pepsin solution with a concentration of 0.5% to 1.5%, mixing it according to the ratio of nattokinase activity and pepsin solution 5000 to 10000 IU / ml, with a pH value of 1.6±0.2, and performing enzymolysis at 37±2° C. for 1 to 2 hours; after the enzymolysis is completed, heating to above 95° C., inactivating the enzyme for 10 to 15 minutes, and then drying to obtain natto peptide powder.

8. The uric acid lowering composition according to claim 5, characterized in that: The fermentation is solid fermentation, which comprises the following steps: mixing soybeans and nutrient solution at a mass volume ratio of 1:2 to 1:4, soaking at 2 to 30°C for 6 to 12 hours and then draining; steaming at 105 to 115°C and 0.02MPa for 30 to 60 minutes; inoculating Bacillus subtilis seed solution at 1% to 10% ml / 100g after steaming and cooling, and fermenting for 24 to 48 hours under fermentation conditions of 37 to 41°C and 75 to 85% humidity; crushing the natto prepared by solid fermentation, adding pure water at a mass volume ratio of 10% to 30% g / 100ml, mixing and stirring, performing liquid enzymolysis at 50°C and 180 to 220 r / min for 2 hours to 6 hours, centrifuging to remove precipitation after the enzymolysis is completed, collecting the supernatant and drying to obtain natto peptide powder.

9. The method for preparing the uric acid-lowering composition according to any one of claims 1 to 8, characterized in that: include: Weigh natto peptide powder, chrysanthemum extract powder and luteolin according to weight; The natto peptide powder, the chrysanthemum extract powder and the luteolin are mixed to obtain a uric acid lowering composition.

10. The use of the uric acid lowering composition according to any one of claims 1 to 8, characterized in that: Application of the uric acid lowering composition in uric acid lowering health food or medicine.

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