Medicinal and edible composition for treating gout as well as preparation method and application thereof

Abstract

The invention discloses a medicinal and edible composition for treating gout as well as a preparation method and application of the medicinal and edible composition, and belongs to the technical field of biological medicines. Comprising the following raw materials in parts by weight: 5-10 parts of honeysuckle, 5-10 parts of endive, 5-10 parts of galangal, 5-10 parts of bamboo fungus, 5-10 parts of alfalfa, 5-10 parts of gardenia, 5-10 parts of platycodon grandiflorum, 5-10 parts of sunflower seeds, 3-5 parts of cherries, 3-5 parts of blueberries, 3-5 parts of waxberries, 3-5 parts of Chinese wolfberry fruits, 2-3 parts of chrysanthemum, 2-3 parts of celery seeds, 2-3 parts of tricholoma matsutake, 2-3 parts of sparassis crispa, 2-3 parts of lotus leaves, 2-3 parts of hawthorn, 2-3 parts of dendrobium officinale and 2-3 parts of lucid ganoderma. Through reasonable compatibility of food-borne materials, the traditional Chinese medicine composition can well reduce the blood uric acid level, improve related inflammation indexes and relieve gout pain after being taken for a long time.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a medicine-food homologous composition for treating gout, and a preparation method and application thereof. Background Art

[0002] Uric acid is the end product of purine metabolism. Under normal circumstances, the production and excretion of uric acid in the human body are in a dynamic equilibrium. When uric acid is produced too much or excreted less, it will lead to hyperuricemia. When blood uric acid is >420μmol / L, urate crystals are easily formed, causing gouty arthritis (such as redness and swelling of the big toe), kidney stones, chronic kidney disease, and is closely related to hypertension, atherosclerosis, metabolic syndrome (hyperglycemia, hyperlipidemia, obesity), etc. Studies have shown that for every 1mg / dL increase in uric acid, the risk of hypertension increases by 13%, especially in young people and women. There is a vicious cycle between hyperuricemia and kidney damage: uric acid crystal deposition can cause interstitial nephritis, renal fibrosis and glomerular sclerosis, and decreased renal function further aggravates uric acid excretion disorders.

[0003] In recent years, studies have found that uric acid transporters play an important role in uric acid metabolism. Uric acid transporters mainly include uric acid reabsorption transporters (such as URAT1 and GLUT9) and uric acid secretion transporters (such as ABCG2 and MRP4). By regulating the activity of these transporters, blood uric acid levels can be effectively regulated and the damage of hyperuricemia to the kidneys can be reduced.

[0004] At present, the commonly used uric acid-lowering drugs in clinical practice mainly include allopurinol and febuxostat, which inhibit the production of uric acid, and benzbromarone and probenecid, which promote the excretion of uric acid. However, these drugs have certain side effects. For example, allopurinol may cause severe allergic reactions, and febuxostat may increase the risk of cardiac death, especially for patients with cardiovascular and cerebrovascular diseases, coronary heart disease or heart failure. Benzbromarone has a weakened efficacy when the glomerular filtration rate (GFR) is <30mL / min, which may increase the burden on the kidneys. Propanesulfonic acid may aggravate renal insufficiency and cause nausea and diarrhea, etc., and has gradually withdrawn from the market.

[0005] The combination of medicine and food reflects the traditional Chinese medicine wisdom of "preventive treatment of disease" and "overall conditioning" in the treatment of hyperuricemia. Its natural, safe and multi-target characteristics provide an important supplement for the management of hyperuricemia. Substances that combine medicine and food are derived from natural foods or Chinese medicinal materials. After long-term consumption verification, they are highly safe, have few side effects, and are suitable for long-term use. Compared with chemically synthesized drugs, substances that combine medicine and food are more easily accepted by the human body, especially suitable for patients with impaired liver and kidney function and those sensitive to chemical drugs. Substances that combine medicine and food usually contain a variety of active ingredients and can play a role in reducing uric acid through multiple pathways. For example, chicoric acid in chicory can inhibit the activity of xanthine oxidase and reduce uric acid production. Geniposide in gardenia can inhibit the activity of URAT1 transporter and promote uric acid excretion. Chlorogenic acid in honeysuckle, lycium barbarum polysaccharide in wolfberry, etc. have antioxidant and anti-inflammatory effects, can reduce oxidative stress and inflammatory responses caused by hyperuricemia, and protect the kidneys. Secondly, substances that combine medicine and food are widely sourced, relatively inexpensive, and easily accessible, which can reduce the economic burden on patients. Therefore, it is crucial to provide a medicine-food homologous composition with the effect of reducing uric acid. Summary of the Invention

[0006] An object of the present invention is to provide a medicine-food homologous composition for treating gout, its preparation method and application to solve the problems existing in the above-mentioned prior art. Based on the regulation mechanism of uric acid transporter proteins and combined with the uric acid-lowering effect of natural plant extracts, the present invention provides a composition for reducing uric acid and protecting the kidneys and its preparation method. This composition effectively reduces the blood uric acid level by synergistically inhibiting the activities of URAT1 and GLUT9 transporter proteins and enhancing the activities of uric acid ABCG2 and OAT1 excretion proteins, while reducing oxidative stress damage to the kidneys, providing a new treatment option for patients with hyperuricemia accompanied by kidney injury.

[0007] To achieve the above object, the present invention provides the following solutions:

[0008] One of the technical solutions of the present invention is a medicine-food homologous composition for treating gout, comprising the following raw materials in parts by weight: 5-10 parts of honeysuckle, 5-10 parts of chicory, 5-10 parts of galangal, 5-10 parts of dictyophora indusiata, 5-10 parts of alfalfa, 5-10 parts of gardenia, 5-10 parts of platycodon grandiflorum, 5-10 parts of sunflower seeds, 3-5 parts of cherries, 3-5 parts of blueberries, 3-5 parts of waxberries, 3-5 parts of wolfberries, 2-3 parts of chrysanthemums, 2-3 parts of celery seeds, 2-3 parts of matsutake, 2-3 parts of Sparassis crispa, 2-3 parts of lotus leaves, 2-3 parts of hawthorns, 2-3 parts of dendrobium officinale, 2-3 parts of ganoderma lucidum.

[0009] Another technical solution of the present invention is the preparation method of the medicine-food homologous composition, comprising the following steps:

[0010] (1) Weigh the raw materials according to the ratio and pulverize them to obtain powder;

[0011] (2) Add water to the obtained powder for extraction, collect the extract, filter and concentrate to obtain a concentrated solution;

[0012] (3) Add erythritol and maltodextrin to the concentrated solution for granulation and drying to obtain a particulate agent of the anti-gout food-derived composition.

[0013] For the third technical solution of the present invention, an application of the medicine-food homologous composition in the preparation of a drug for treating hyperuricemia.

[0014] For the fourth technical solution of the present invention, an application of the medicine-food homologous composition in the preparation of a drug for reducing IL-1β and TNF-α.

[0015] For the fifth technical solution of the present invention, an application of the medicine-food homologous composition in the preparation of a drug for regulating the peroxidation level.

[0016] For the sixth technical solution of the present invention, an application of the medicine-food homologous composition in the preparation of a drug for reducing ALT, AST, BUN and SCr.

[0017] Based on the above technical solutions, the present invention has the following technical effects:

[0018] (1) The anti-gout composition prepared by the present invention can achieve a good anti-gout effect. Through the reasonable compatibility of food-derived materials such as honeysuckle, chicory, galangal, dictyophora indusiata, alfalfa, gardenia, platycodon grandiflorum, sunflower seeds, cherries, blueberries, waxberries, wolfberries, chrysanthemums, celery seeds, matsutake, Sparassis crispa, lotus leaves, hawthorns, dendrobium officinale, ganoderma lucidum, etc., taking it for a long time can well reduce the blood uric acid level, improve related inflammatory indexes and relieve the pain of gout.

[0019] (2) The traditional Chinese medicine composition for reducing blood uric acid of the present invention uses traditional Chinese medicine of medicine-food homology as the main raw material, has high safety, no toxic and side effects, can be taken for a long time, effectively avoids the risk of liver damage that may be brought by the common use of multiple traditional Chinese medicine components, and solves the problem that most of the existing drugs for anti-gout are western medicines with large side effects. It improves the safety of the drug and the compliance of the patient.

[0020] (3) The preparation method of the anti-gout composition provided by the present invention is simple and inexpensive. Description of the Drawings

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0022] Figure 1The uric acid-lowering effect of the drug of the present invention on hyperuricemia model rats.

[0023] Figure 2 The effect of the drug of the present invention on the level of related inflammatory factor TNF-α in hyperuricemia model. ##: Compared with the blank control group, p < 0.01; **: Compared with the hyperuricemia model group, p < 0.01; ▲▲: Compared with the positive control group, p < 0.01.

[0024] Figure 3 The effect of the drug of the present invention on the level of related inflammatory factor IL-1β in hyperuricemia model. ##: Compared with the blank control group, p < 0.01; **: Compared with the hyperuricemia model group, p < 0.01; ▲▲: Compared with the positive control group, p < 0.01.

[0025] Figure 4 The effect of the drug of the present invention on the serum SOD level in hyperuricemia model.

[0026] Figure 5 The effect of the drug of the present invention on the serum MDA level in hyperuricemia model.

[0027] Figure 6 The effect of the drug of the present invention on the serum ALT level, a liver function index, in hyperuricemia model.

[0028] Figure 7 The effect of the drug of the present invention on the serum AST level, a liver function index, in hyperuricemia model.

[0029] Figure 8 The effect of the drug of the present invention on the serum BUN level, a kidney function index, in hyperuricemia model.

[0030] Figure 9 The effect of the drug of the present invention on the serum SCr level, a kidney function index, in hyperuricemia model.

[0031] Figure 10 The HE detection results of the liver in hyperuricemia model by the drug of the present invention.

[0032] Figure 11 The HE detection results of the kidney in hyperuricemia model by the drug of the present invention.

[0033] Figure 12 The analgesic effect of the drug of the present invention on the hot plate analgesia method rat model. ##: Compared with the blank control group, p < 0.01; **: Compared with the hyperuricemia model group, p < 0.01; ▲▲: Compared with the positive control group, p < 0.01.

[0034] Figure 13WB results of OAT1, ABCG2, URATI, and GLUT9 and relative expression levels of the target proteins. Among them, A shows the WB results of OAT1, ABCG2, URATI, and GLUT9, B shows the relative content of OAT1 protein, C shows the relative content of ABCG2 protein, D shows the relative content of URATI protein, and E shows the relative content of GLUT9 protein. #: p < 0.01 compared with the blank control group; **: p < 0.01 compared with the hyperuricemia model group; ▲▲: p < 0.01 compared with the positive control group. Detailed implementation manners

[0035] The various exemplary implementation manners of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, characteristics, and implementation schemes of the present invention.

[0036] It should be understood that the terms used in the present invention are only for describing specific implementation manners and are not used to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0037] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0038] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific implementation manners of the present invention specification, which are obvious to those skilled in the art. Other implementation manners obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of this application are merely exemplary.

[0039] Regarding the terms "comprising", "including", "having", "containing", etc. used herein, they are all open-ended terms, meaning including but not limited to.

[0040] The technical solutions of the present invention, unless otherwise specified, are all conventional solutions in the art. The reagents or raw materials used, unless otherwise specified, are all purchased from commercial channels or have been publicly disclosed.

[0041] An embodiment of the present invention provides a medicine and food homologous composition for treating gout, comprising the following raw materials in parts by weight: 5-10 parts of honeysuckle, 5-10 parts of chicory, 5-10 parts of galangal, 5-10 parts of dictyophora indusiata, 5-10 parts of alfalfa, 5-10 parts of gardenia, 5-10 parts of platycodon grandiflorum, 5-10 parts of sunflower seeds, 3-5 parts of cherries, 3-5 parts of blueberries, 3-5 parts of waxberries, 3-5 parts of wolfberries, 2-3 parts of chrysanthemums, 2-3 parts of celery seeds, 2-3 parts of matsutake, 2-3 parts of Sparassis crispa, 2-3 parts of lotus leaves, 2-3 parts of hawthorns, 2-3 parts of dendrobium officinale, and 2-3 parts of ganoderma lucidum.

[0042] In some specific embodiments, it comprises the following raw materials in parts by weight: 10 parts of honeysuckle, 10 parts of chicory, 10 parts of galangal, 10 parts of dictyophora indusiata, 10 parts of alfalfa, 10 parts of gardenia, 10 parts of platycodon grandiflorum, 10 parts of sunflower seeds, 5 parts of cherries, 5 parts of blueberries, 5 parts of waxberries, 5 parts of wolfberries, 3 parts of chrysanthemums, 3 parts of celery seeds, 3 parts of matsutake, 3 parts of Sparassis crispa, 3 parts of lotus leaves, 3 parts of hawthorns, 3 parts of dendrobium officinale, and 3 parts of ganoderma lucidum.

[0043] An embodiment of the present invention also provides a preparation method of the medicine and food homologous composition, comprising the following steps:

[0044] (1) Weigh the raw materials according to the ratio and crush them to obtain powder;

[0045] (2) Add water to the obtained powder for extraction, collect the extract, filter and concentrate to obtain a concentrated solution;

[0046] (3) Add erythritol and maltodextrin to the concentrated solution for granulation and drying to obtain a granular anti-gout food-derived composition.

[0047] In some specific embodiments, the mass ratio of the powder to water is 1:(6-12); the extraction conditions are: extraction at 95-98°C for 3 h, and the number of extraction times is 2-3 times.

[0048] In some specific embodiments, by weight, the erythritol is 40-50 parts and the maltodextrin is 3-5 parts.

[0049] In some specific embodiments, the granulation conditions are: slow stirring for 3-5 min, cutting for 1-2 min; fast stirring for 1-2 min, cutting for 0.5-1 min;

[0050] The drying conditions are: the inlet air temperature is 50-60°C, the drying time is 4 hours, and the material is turned over once every 1 hour.

[0051] An embodiment of the present invention also provides the application of the medicine and food homologous composition in the preparation of a drug for treating hyperuricemia.

[0052] The embodiments of the present invention also provide the application of the medicine and food homologous composition in the preparation of a drug for reducing IL-1β and TNF-α.

[0053] The embodiments of the present invention also provide the application of the medicine and food homologous composition in the preparation of a drug for regulating the peroxidation level.

[0054] The embodiments of the present invention also provide the application of the medicine and food homologous composition in the preparation of a drug for reducing ALT, AST, BUN and SCr.

[0055] The medicine and food homologous composition provided by the present invention comprises honeysuckle, chicory, galangal, dictyophora indusiata, alfalfa, gardenia, platycodon grandiflorum, sunflower seeds, cherries, blueberries, waxberries, wolfberries, chrysanthemums, celery seeds, matsutake, Sparassis crispa, lotus leaves, hawthorns, dendrobium officinale, ganoderma lucidum, erythritol and maltodextrin. Granules are prepared by technologies such as super extraction, concentration and granulation. It can synergistically inhibit the activities of URAT1 and GLUT9 transporter proteins and enhance the activities of uric acid ABCG2 and OAT1 excretion proteins. Experiments show that this composition can reduce the serum uric acid level by 42% - 93%, and at the same time, the content of MDA, a marker of renal oxidative stress injury, decreases by 34% - 82%, and the content of SOD decreases by 11% - 40%. The present invention overcomes the defect of large liver and kidney toxicity of existing anti-gout drugs, and provides a new treatment option for patients with hyperuricemia accompanied by kidney injury.

[0056] The content of flavonoids in the honeysuckle of the present invention is ≥5%; the content of flavonoids in the chicory is ≥3%.

[0057] Example 1

[0058] An anti-gout composition and its preparation method, comprising the following steps:

[0059] Weigh raw materials by weight parts: 10 parts of honeysuckle, 10 parts of chicory, 10 parts of galangal, 10 parts of dictyophora indusiata, 10 parts of alfalfa, 10 parts of gardenia, 10 parts of platycodon grandiflorum, 10 parts of sunflower seeds, 5 parts of cherries, 5 parts of blueberries, 5 parts of waxberries, 5 parts of wolfberries, 3 parts of chrysanthemums, 3 parts of celery seeds, 3 parts of matsutake, 3 parts of Sparassis crispa, 3 parts of lotus leaves, 3 parts of hawthorns, 3 parts of dendrobium officinale and 3 parts of ganoderma lucidum.

[0060] Pour into a pulverizer and pulverize to powder. The obtained powder and water are heated to 98°C in a weight ratio of 1:12 and extracted for 3 h, repeated 2 times. Collect the extract, filter and concentrate. 50 parts of erythritol and 5 parts of maltodextrin are added to the concentrated solution, and granulation is carried out using a one-step granulator (slow stirring for 3 - 5 min, cutting for 1 - 2 min; fast stirring for 1 - 2 min, cutting for 0.5 - 1 min), and drying (inlet air temperature is 50 - 60°C, drying time is 4 hours, and the tray is turned over every 1 hour) to obtain anti-gout food-derived composition granules.

[0061] Example 2

[0062] Rat hyperuricemia model

[0063] Experimental animals: 60 male rats at SPF level, weighing 200±20 g.

[0064] Experimental grouping: The preparations obtained from Example 1 of the present invention were injected at different doses to form low, medium, and high dose groups, a positive control group: febuxostat, a model group, and a blank group.

[0065] Model establishment: The rats were intragastrically administered with hypoxanthine emulsion (10 mL / kg, 50 mg / mL, suspended in CMC-Na), and intraperitoneally injected with potassium oxonate solution (10 mL / kg, 25 mg / mL, in warm water solution).

[0066] One hour after model establishment, the solid beverages at doses of 100, 200, and 300 mg / kg were intragastrically administered as the low, medium, and high dose groups, and 20 mg / kg of febuxostat was intragastrically administered as the positive control. The blank group and the hyperuricemia model group were only intragastrically administered with normal saline. Four hours after administration, according to animal ethics, the rats were sacrificed by taking blood from the fundus vein of the eyes, and the livers and kidneys of the rats were stored in formalin for standby, and the levels of related factors were measured.

[0067] The results are as Figure 1 shown. The serum uric acid level of the rats in the hyperuricemia model group should be significantly higher than that of the blank control group, and more than twice the normal value, proving that the model establishment was successful. Compared with the model group, the uric acid levels of the rats in the hyperuricemia model group could be significantly reduced by the drugs of the present invention at doses of 100, 200, and 300 mg / kg and the positive drug febuxostat. Among them, the anti-gout composition of the present invention achieved the uric acid-lowering effect of the existing products under the premise of the same dose or low dose.

[0068] Example 3

[0069] ELISA detection of IL-1β and TNF-α includes the following steps:

[0070] After serum collection, it needs to be centrifuged at 3000 rpm for 10 minutes at 4°C, and the supernatant is taken. Tissue samples are added with PBS for homogenization, and the supernatant is taken after centrifugation. It is dissolved with deionized water or the dilution solution provided by the kit and serially diluted (such as the highest concentration of IL-1β is 2000 pg / ml, and the highest concentration of TNF-α is 500 pg / ml) as the standard product. The detection antibodies are diluted according to the instructions (such as 1:100), prepared immediately before use, and avoid long-term placement. The 20× concentrate is diluted with distilled water to 1× for washing the plate.

[0071] Add 100 μL of each of the standard product and the sample to a pre-coated 96-well plate, and incubate at 37 °C for 2 hours (IL-1β) or 1.5 hours (TNF-α). After discarding the liquid, add 300 μl of washing solution to each well, soak for 1 minute, repeat 3 times, and pat dry. Add biotinylated detection antibody (100 μL / well), and incubate at 37 °C for 1 hour (IL-1β) or 30 minutes (TNF-α). Add streptavidin-HRP (100 μL / well), and incubate at 37 °C for 1 hour. Add TMB substrate (90 μL / well), and develop color in the dark for 15 - 30 minutes (IL-1β) or 10 - 20 minutes (TNF-α). Immediately add stop solution (50 μL / well) after color development is completed. Read the OD value at a wavelength of 450 nm, and zero the blank well.

[0072] As Figure 2 , 3 shown, in the rat hyperuricemia model constructed in Example 2, the contents of IL-1β and TNF-α in the serum were significantly increased compared with the blank control group, and the difference was statistically significant (p < 0.01); both the positive drug group (febuxostat) and the solid beverage treatment group could reduce the contents of IL-1β and TNF-α in the rat serum, and the difference was statistically significant (p < 0.01); while the contents of IL-1β and TNF-α in the medium and high solid beverage groups were significantly lower than those in the positive drug group, and the difference was statistically significant (p < 0.01); it shows that the solid beverage group has a good anti-inflammatory effect.

[0073] Example 4

[0074] ELISA detection of SOD and MDA includes the following steps:

[0075] After centrifuging the serum, take the supernatant. Add tissue to PBS for homogenization at a ratio of 1:9, and take the supernatant after centrifugation. Dilute the standard product in gradients (such as 0 - 100 U / ml), and the detection antibody and enzyme-labeled secondary antibody need to be diluted according to the instructions. Add 50 μL of each of the standard product and the sample to the pre-coated plate, and incubate at 37 °C for 1 hour. Wash according to the above general steps, and repeat 5 times. Add TMB substrate to develop color for 15 minutes, and read the value after termination.

[0076] The results are as Figure 4 , 5 shown, the hyperuricemia model can cause a significant decrease in the SOD value of rats (p < 0.01) and a significant increase in the MDA value (p < 0.01), resulting in abnormal levels of free radicals in the body and making the body in a state of peroxidation; compared with the positive drug group, the medium and high-dose solid beverage groups can better increase the content of SOD and reduce the content of MDA (p < 0.01), indicating that the solid beverage can regulate the peroxidation level in the body to reduce the peroxidation damage caused by hyperuricemia.

[0077] Example 5

[0078] ELISA tests for ALT and AST include the following steps:

[0079] Centrifuge the serum at 400×g for 5 minutes at 4°C and take the supernatant. Homogenize the liver tissue with physiological saline at a ratio of 1:9 and take the supernatant after centrifugation. Add 100μL of the standard and sample to the pre-coated plate and incubate at 37°C for 1 hour. After color development, read the OD value at 505nm (ALT) or 450nm (AST).

[0080] like Figure 6 , 7 As shown, the ALT and ASTP content in the serum of the rat hyperuricemia model constructed by Example 2 was significantly increased compared with the blank control group, and the difference was statistically significant (p < 0.01); the positive drug group and the high, medium and low dose groups of solid beverages can reduce the ALT and AST content in the rat serum, and the difference is statistically significant (p < 0.01); and the concentrations of ALT and AST in the medium and high dose groups of solid beverages are lower than those in the positive drug group, and the difference is statistically significant (p < 0.01). Therefore, solid beverages show better liver protection.

[0081] Example 6

[0082] ELISA for BUN and SCr detection includes the following steps:

[0083] Blood samples need to be centrifuged at 3000rpm for 10 minutes and the supernatant is taken. Urine is collected for 24 hours and the supernatant is taken after centrifugation. 50μl of each standard and sample are added to the pre-coated plate and incubated at 37℃ for 30 minutes. After color development, stop solution is added and the OD value is read.

[0084] The results are as follows Figure 8 , 9 As shown, the BUN content in the serum of the rat hyperuricemia model constructed by Example 2 was significantly increased compared with the blank control group, and the difference was statistically significant (p < 0.01); the positive drug group and the high, medium and low dose groups of solid beverages can reduce the BUN content in rat serum, and the difference is statistically significant (p < 0.01); and the BUN content in the medium and high dose solid beverage groups is significantly lower than that in the positive drug group, and the difference is statistically significant (p < 0.01). The SCr content in its serum was significantly increased compared with the blank control group, and the difference was statistically significant (p < 0.01); the positive drug group (febuxostat) and the high, medium and low dose groups of solid beverages can reduce the SCr content in rat serum, and the difference is statistically significant (p < 0.01); and the SCr content in the medium and high dose solid beverage groups is significantly lower than that in the positive drug group, and the difference is statistically significant (p < 0.01). Therefore, solid beverages show better kidney protection.

[0085] Example 7

[0086] The liver of the hyperuricemia model was detected by HE method, including the following steps:

[0087] After sacrificing the hyperuricemia model animals in Example 2, the liver tissue was quickly removed to avoid tissue autolysis. Cut it into small pieces with a uniform thickness (about 5 mm 3 ) using a sharp blade. Immediately immerse the tissue in 4% paraformaldehyde and fix for 24 hours to keep the cell structure intact. After fixation, rinse with running water for 1 hour to remove the residual fixative and avoid affecting subsequent staining. Dehydrate sequentially through 70%, 80%, 95%, and 100% ethanol gradients, soak in each grade for 1 - 2 hours to completely replace the tissue moisture. Use xylene to replace ethanol and clarify twice, 30 minutes each time, to make the tissue transparent for paraffin penetration. Immerse the tissue in melted paraffin (65 °C) for 4 hours, then embed it into a wax block, and trim it into a regular shape after cooling. Use a microtome to prepare continuous sections with a thickness of 4 - 5 μm to ensure that the sections are complete and without wrinkles. Float the sections on a 40 °C warm water bath to flatten them, attach them to glass slides, and dry them in an oven at 60 °C for 2 hours.

[0088] The HE staining process is as follows: Dewax with xylene twice, 5 - 10 minutes each time. Hydrate with gradient ethanol (100% → 70%), 2 minutes for each grade, and finally soak in distilled water. Immerse in hematoxylin staining solution for 5 - 15 minutes, and the cell nuclei are stained dark blue. Differentiate with 1% hydrochloric acid ethanol for several seconds to remove non-specific staining, and control under the microscope until the cell nuclei are clear and the cytoplasm is colorless. Rinse with running water for 15 - 30 minutes, or alkalize with 0.75% ammonium chloride solution to restore the blue color of the cell nuclei. Stain with 0.1% - 0.5% eosin staining solution for 1 - 5 minutes, and the cytoplasm and collagen fibers are stained pink. Dehydrate with gradient ethanol (70% → 100%), 2 - 3 minutes for each grade. Clarify with xylene twice, 5 minutes each time, to improve the transparency of the sections. Drop neutral gum, cover with a coverslip, avoid air bubbles, and store after drying in a fume hood.

[0089] The results are as Figure 10 shown. The liver cells of the rats in the hyperuric acid model group were significantly damaged. The main damages were obvious cell edema of the liver cells, obvious damage to the cell membrane and cell nucleus, obvious bleeding phenomena and infiltration of inflammatory cells in the cells; the liver cells of the rats in the positive drug group and the solid beverage group had varying degrees of repair effects, among which the repair effect of the solid beverage group was more significant and the damage to the liver cells was smaller.

[0090] Example 8

[0091] The kidney of the hyperuricemia model was detected by HE method, including the following steps:

[0092] After sacrificing the hyperuricemia model animals in Example 2, the kidneys were quickly removed and immersed in 4% paraformaldehyde for 7 days to maintain the tissue structure. The thickness of the tissue block was not more than 2 - 3 mm to ensure sufficient penetration of the fixative. Ethanol (80%, 95%, 100%) and xylene were used successively to remove water and lipids, followed by impregnation with wax (60 °C) and embedding into wax blocks. After trimming the wax blocks, 3 - 5 μm thin sections were cut using a microtome and attached to glass slides. The wax was removed twice with xylene, 15 minutes each time. Hydration was carried out with gradient ethanol (100% → 80%), 2 minutes for each step, and finally immersed in distilled water. Immersed in hematoxylin stain for 15 minutes, differentiated with 1% hydrochloric acid ethanol for 1 - 3 seconds and then rinsed with running water and added with bluing solution. Stained with 0.5% eosin stain for 3 minutes, and the cytoplasm and collagen fibers were stained pink. Dehydration was carried out with gradient ethanol (80% → 100%), 2 - 3 minutes for each step. Transparency was carried out twice with xylene, 5 minutes each time, to improve the transparency of the sections. A drop of neutral gum was added, covered with a coverslip, avoiding air bubbles, and stored after drying in a fume hood.

[0093] The results are shown in Figure 11 , the renal cell damage in the hyperuricemia model group of rats was obvious. The main damage was that some renal cell membranes and nuclei were significantly damaged, and there were obvious bleeding phenomena and infiltration of inflammatory cells in the cells; the renal cells of rats in the positive drug group and the solid beverage group had varying degrees of repair effects, among which the repair effect of the solid beverage group was more significant and the damage to renal cells was smaller.

[0094] Example 9

[0095] Effect on the analgesic experiment model of rats by the hot plate method

[0096] Experimental animals: 60 male rats of SPF grade, weighing 200 ± 20 g.

[0097] Experimental grouping: The preparation group prepared in Example 1 of the present invention, positive control group: allopurinol, blank group.

[0098] Model establishment: Mice with pain responses within 30 s were preselected. The mice were placed in a hot plate apparatus at a temperature of 55 ± 0.5 °C, and the pain threshold of the mice was measured 2 times, at intervals of 5 min. Licking the hind paw of the mouse was used as the observation index. The pain threshold was measured 20 min after administration. If the mouse had no pain response within 60 s, it was immediately taken out and calculated as 60 s.

[0099] The results are shown in Figure 12, In the rat hyperuricemia model, the time that the rat toes were placed on the hot plate was significantly reduced compared with the blank control group, and the difference was statistically significant (p < 0.01); both the positive drug group and the solid group could increase the time that the rat toes were placed on the hot plate, and the difference was statistically significant (p < 0.01); moreover, the time that the toes of the high-dose solid beverage group were placed on the hot plate was higher than that of the positive drug group, and the difference was statistically significant (p < 0.01). It shows that the solid beverage group has a better analgesic effect.

[0100] Example 10

[0101] Western blot was used to detect OAT1, ABCG2, URATI and GLUT9, including the following steps:

[0102] Lyse cell or tissue samples with RIPA lysis buffer (containing protease inhibitor), and fully disrupt them by ultrasound or mechanical homogenization. Determine the protein concentration by the BCA method, adjust it to 1 - 2.5 μg / μL, and ensure equal loading (30 μg / well). Add SDS-PAGE loading buffer (containing DTT) at a ratio of 1:4, and heat at 95 °C for 10 minutes to denature the protein. Prepare separating gel and stacking gel (12%) with appropriate concentrations according to the protein molecular weight. Add the sample into the gel well, and at the same time add a prestained protein Marker. Perform electrophoresis at 100 - 120 V until the dye reaches the bottom of the gel. Prepare a membrane transfer device, and soak the gel and PVDF or NC membrane in the membrane transfer buffer. Transfer the membrane at 100 V for 1 - 2 hours to ensure that the protein is transferred from the gel to the membrane. Block with 5% BSA at room temperature for 1 hour to reduce non-specific binding. Dilute the primary antibodies against OAT1, ABCG2, URAT1 and GLUT9 according to the instructions for primary antibody dilution. Incubate the membrane with the primary antibody overnight at 4 °C. Wash the membrane 3 times with TBST buffer, 10 minutes each time. Dilute the HRP-labeled secondary antibody according to the instructions. Incubate the membrane with the secondary antibody at room temperature for 1 hour. Wash the membrane 3 times with TBST buffer, 10 minutes each time. Use ECL chemiluminescence reagent to expose the X-ray film in the dark room or use a chemiluminescence imaging system to detect the signal. Analyze the band intensity through software such as ImageJ, and calculate the relative expression level of the target protein.

[0103] It can be seen from Figure 13 that the expressions of OAT1 and ABCG2 in the experimental group were significantly up-regulated (p < 0.01), and the expressions of URAT1 and GLUT9 were significantly down-regulated (p < 0.01). It shows that the composition of the present invention may promote uric acid excretion by up-regulating OAT1 and ABCG2, and at the same time inhibit uric acid reabsorption by down-regulating URAT1 and GLUT9, thereby playing a role in reducing uric acid and protecting the kidney.

[0104] The composition provided by the present invention has a reasonable compatibility and is a new traditional Chinese medicine composition with both medicinal and edible properties. It can effectively reduce the level of blood uric acid, improve relevant inflammatory indicators, relieve the pain of gout, and is safe for long-term use without side effects. The preparation method of the anti-gout composition provided by the present invention is simple and inexpensive, solving the problem that most of the existing anti-gout drugs are Western medicines with large side effects.

[0105] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limiting the implementation manners of the present invention. For those of ordinary skill in the art, based on the above description, other different forms of changes or modifications can be made. It is not necessary and impossible to list all the implementation manners here. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included in the protection scope of the claims of the present invention.

Claims

1. A medicinal and edible composition for treating gout, characterized in that: The invention comprises the following raw materials in parts by weight: 5-10 parts of honeysuckle, 5-10 parts of chicory, 5-10 parts of galangal, 5-10 parts of bamboo fungus, 5-10 parts of alfalfa, 5-10 parts of gardenia, 5-10 parts of platycodon, 5-10 parts of sunflower seeds, 3-5 parts of cherries, 3-5 parts of blueberries, 3-5 parts of bayberries, 3-5 parts of wolfberries, 2-3 parts of chrysanthemums, 2-3 parts of celery seeds, 2-3 parts of matsutake mushrooms, 2-3 parts of hydrangea mushrooms, 2-3 parts of lotus leaves, 2-3 parts of hawthorn, 2-3 parts of dendrobium officinale and 2-3 parts of ganoderma lucidum.

2. The medicine-food composition according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 10 parts of honeysuckle, 10 parts of chicory, 10 parts of galangal, 10 parts of bamboo fungus, 10 parts of alfalfa, 10 parts of gardenia, 10 parts of platycodon, 10 parts of sunflower seeds, 5 parts of cherry, 5 parts of blueberry, 5 parts of bayberry, 5 parts of wolfberry, 3 parts of chrysanthemum, 3 parts of celery seed, 3 parts of matsutake, 3 parts of hydrangea, 3 parts of lotus leaf, 3 parts of hawthorn, 3 parts of dendrobium officinale and 3 parts of ganoderma lucidum.

3. The method for preparing the edible-medicinal composition according to claim 1 or 2, characterized in that: The following steps are involved: (1) weighing raw materials according to proportions and crushing them into powder; (2) adding water to the obtained powder for extraction, collecting the extract, filtering and concentrating to obtain a concentrated solution; (3) Adding erythritol and maltodextrin to the concentrated solution for granulation and drying to obtain anti-gout food-derived composition granules.

4. The preparation method according to claim 3, characterized in that: The mass ratio of the powder to water is 1:(6-12); the extraction conditions are: extraction at 95-98° C. for 3 hours, and the number of extractions is 2-3 times.

5. The preparation method according to claim 3, characterized in that: In terms of weight, the erythritol is 40 to 50 parts, and the maltodextrin is 3 to 5 parts.

6. The preparation method according to claim 3, characterized in that: The granulation conditions are: slow stirring for 3 to 5 minutes, cutting for 1 to 2 minutes; fast stirring for 1 to 2 minutes, cutting for 0.5 to 1 minute; The drying conditions are as follows: the air inlet temperature is 50-60° C., the drying time is 4 hours, and the pan is turned over once every hour.

7. Use of the medicine-food composition as claimed in claim 1 or 2 in the preparation of a medicament for treating hyperuricemia.

8. Use of the edible-medicinal composition as claimed in claim 1 or 2 in the preparation of a drug for reducing IL-1β and TNF-α.

9. Use of the edible-medicinal composition as claimed in claim 1 or 2 in the preparation of a drug for regulating peroxidation levels.

10. Use of the medicine-food composition as claimed in claim 1 or 2 in the preparation of a drug for reducing ALT, AST, BUN and SCr.

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