Preparation method and application of uric acid reducing composition and plant extract thereof

Abstract

The invention discloses a uric acid reducing composition and a preparation method and application of plant extracts of the uric acid reducing composition, and belongs to the technical field of traditional Chinese medicine formulas and preparation. The uric acid reducing composition is prepared from the following raw materials in parts by mass: 3 to 27 parts of corn stigma, 3 to 27 parts of pericarpium citri reticulatae and 3 to 27 parts of white kidney beans. The preparation method of the plant extract comprises the following steps: pretreating the raw materials, extracting effective components, compounding according to different proportions, evaluating the in-vitro xanthine oxidase inhibition effect by using the plant extract, determining the formula compatibility of the raw materials according to quantitative pharmacology, and further determining the formula compatibility of the uric acid reducing composition. The corn stigma is treated by adopting a steam wall breaking technology, so that the extraction rate of effective components of the corn stigma is remarkably improved, and the uric acid reducing effect of the product is enhanced; the uric acid reducing food prepared on the basis of the uric acid reducing composition is safe, free of side effects and suitable for being eaten by people with high uric acid for a long time.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine formula and preparation, and particularly relates to a uric acid-lowering composition, a preparation method and application of its plant extract. Background Art

[0002] The incidence of hyperuricemia in the modern population is gradually increasing. Hyperuricemia has become the "fourth high" after diabetes, hypertension, and hyperlipidemia. Long-term high uric acid levels can cause various diseases such as gout, seriously affecting people's quality of life. Currently, the types of drugs used to treat hyperuricemia are quite limited, mainly concentrated in xanthine oxidase inhibitors such as allopurinol, and urate-lowering drugs such as probenecid, benzbromarone, and febuxostat. However, these drugs often have relatively large toxic and side effects, causing damage to liver and kidney functions, and gastrointestinal reactions such as nausea and vomiting, as well as allergic phenomena such as rashes after taking them, which to a certain extent limits their use (Rey A, Batteux B, Laville S M, et al. Acute kidney injury associated with febuxostat and allopurinol: a post-marketing study[J]. Arthritis Research & Therapy, 2019, 21: 1-9; Stamp L, Dalbeth N. Urate-lowering therapy for asymptomatic hyperuricaemia: a need for caution[C] / / Seminars in Arthritis and Rheumatism. WB Saunders, 2017, 46(4): 457-464; National Medical Products Administration Drug Adverse Reaction Information Bulletin (No. 65) Warning about the risk of liver damage caused by benzbromarone). Therefore, searching for new, highly effective and low-toxic anti-hyperuricemia products remains a hot topic in the current research of the big health field.

[0003] Compared with traditional chemical drugs for treating hyperuricemia, the drugs and foods with homologous origins are safer. Generally, there are no obvious toxic and side effects when consumed daily, and the body has good tolerance to long-term use, providing a safer option for hyperuricemia patients, especially those who need to control uric acid levels for a long time. On the other hand, hyperuricemia patients are familiar with and accustomed to consuming the ingredients in the drugs and foods with homologous origins. Applying them to the treatment or prevention of hyperuricemia is easier to accept and has higher compliance, which is conducive to long-term adherence to maintain stable uric acid. With the development of the health industry, the drugs and foods with homologous origins provide rich resources for the research and development of related products, and various forms of uric acid-lowering products have been developed, such as tea drinks, tablets, jellies, capsules, and oral liquids. The uric acid-lowering products containing multiple ingredients of drugs and foods with homologous origins can meet the needs of different populations and have great market potential and commercial value.

[0004] The existing uric acid-lowering compositions of traditional Chinese medicines or foods have been staying in the use of the original prescriptions, without accurate methods for extracting effective substances and lacking precise compatibility. Summary of the Invention

[0005] Based on the technical problems existing in the prior art, the present invention proposes a uric acid-lowering composition and a preparation method of its plant extract, which is a uric acid-lowering composition and a preparation method and application of a plant extract based on steam cell wall breaking technology. The present invention creatively combines tangerine peel, corn silk, and white kidney bean into a formula, and proposes a preparation method and application of a uric acid-lowering plant extract based on steam cell wall breaking technology. The uric acid-lowering composition of the present invention is a combination of plant extracts that is safe, effective, and has definite curative effects, and has the efficacy of reducing uric acid; the method of the present invention has a simple process, is easy to operate, is suitable for industrial production, and the prepared uric acid-lowering food is safe and has no side effects, and is suitable for long-term consumption by hyperuricemia patients.

[0006] In order to achieve the above-mentioned invention purposes, the present invention adopts the following technical solutions: According to the first aspect of the technical solution of the present invention, a uric acid-lowering composition is provided. The uric acid-lowering composition is composed of plant extracts, and the uric acid-lowering composition is composed of the following raw materials in parts by mass: 3-27 parts of corn silk, 3-27 parts of tangerine peel, and 3-27 parts of white kidney bean; the plant extracts are obtained by treating with steam cell wall breaking technology. The preparation method of the plant extract based on steam cell wall breaking technology includes the following steps: Step S1: Pretreatment of raw materials, selecting fresh tangerine peel, corn silk, and white kidney bean, washing and processing them; Step S2: Extracting effective components, using steam cell wall breaking technology to prepare corn silk extract, tangerine peel volatile oil, tangerine peel extract, and white kidney bean extract; Step S3: Compound in different proportions, compounding the corn silk extract, tangerine peel volatile oil, tangerine peel extract, and white kidney bean extract in different proportions; Step S4: Evaluate the in vitro inhibitory ability of lipase on the extracts compounded in different ratios in Step S3; Step S5: Determine the formula compatibility of each plant extract based on quantitative pharmacology, and then determine the formula compatibility of the uric acid-lowering composition.

[0007] Among them, the above uric acid-lowering composition is composed of the following raw materials in parts by mass: 9-18 parts of corn silk, 6-12 parts of dried tangerine peel, and 3-6 parts of white kidney bean.

[0008] Furthermore, the above uric acid-lowering composition is composed of the following raw materials in parts by mass: 6-18 parts of corn silk, 9-27 parts of dried tangerine peel, and 3-9 parts of white kidney bean.

[0009] Preferably, the uric acid-lowering composition further includes konjac. The uric acid-lowering composition is composed of the following raw materials in parts by mass: 9-13 parts of corn silk, 14-20 parts of dried tangerine peel, 5-6 parts of white kidney bean, and 1-2 parts of konjac.

[0010] More preferably, the uric acid-lowering composition further includes volatile oil of dried tangerine peel. The uric acid-lowering composition is composed of the following raw materials in parts by mass: 10 parts of corn silk, 15 parts of dried tangerine peel, 5 parts of white kidney bean, 1 part of konjac, and 0.2-0.8 part of volatile oil of dried tangerine peel.

[0011] According to the second aspect of the technical solution of the present invention, there is provided a preparation method of a plant extract based on steam wall-breaking technology, which is used to prepare the plant extract in the above uric acid-lowering composition. The preparation method of the plant extract includes the following steps: Step S1: Pretreatment of raw materials. The raw materials include corn silk, dried tangerine peel, white kidney bean, and konjac in parts by mass; wash and dry the dried tangerine peel, corn silk, white kidney bean, and konjac; Step S2: Extract effective components, and extract and prepare corn silk extract, volatile oil of dried tangerine peel and dried tangerine peel extract, white kidney bean extract, and konjac extract. The extraction and preparation process of the corn silk extract includes Step S21, and the extraction and preparation process of the dried tangerine peel extract includes Step S22; Step S21: Wash and cut the corn silk into sections, place the dried corn silk in the steam explosion chamber for steam explosion and pulverization to obtain the dry coarse powder of the corn silk steam explosion product. Put the dry coarse powder of the corn silk steam explosion product into the extraction tank and extract it by reflux with water. After the extraction is completed, filter to obtain the corn silk filtrate, and concentrate the corn silk filtrate under reduced pressure to obtain the corn silk concentrate; spray-dry the corn silk concentrate to obtain the powdered water extract of corn silk; Step S22: Air-dry the tangerine peel washed in Step S1, and then use a pulverizer to pulverize the air-dried tangerine peel. Divide the pulverized coarse tangerine peel powder into two parts: one part of the coarse tangerine peel powder is used to obtain tangerine peel volatile oil by steam distillation; the other part of the coarse tangerine peel powder is put into an extraction tank and refluxed with water for water extraction process. After the water extraction of the coarse tangerine peel powder is completed, filter to obtain tangerine peel filtrate. Concentrate the tangerine peel filtrate under reduced pressure to obtain tangerine peel concentrated solution, and then spray-dry the tangerine peel concentrated solution to obtain powdered tangerine peel water extract. Step S3: Perform compounding in different ratios. The corn silk extract, tangerine peel extract, and white kidney bean extract are compounded in 7 ratios; the first compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 1:1:1, the second compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 1:2:3, the third compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 1:3:2, the fourth compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 2:1:3, the fifth compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 2:3:1; the sixth compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 3:1:2, and the seventh compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 3:2:1; Step S4: Use the extracts compounded in different ratios in Step S3 to evaluate the inhibitory effect on xanthine oxidase in vitro; Step S5: Use quantitative pharmacology to clarify the formula compatibility of the uric acid-lowering composition.

[0012] Preferably, the extraction and preparation process of the white kidney bean extract includes Step S23: Wash the white kidney beans with water; put the air-dried white kidney beans into a pulverizer to pulverize to obtain white kidney bean coarse powder, put the white kidney bean coarse powder into a microwave extraction device for extraction, filter to obtain white kidney bean filtrate after the extraction is completed, perform low-temperature extraction on the obtained white kidney bean filtrate, concentrate the white kidney bean filtrate after extraction under reduced pressure, and finally spray-dry the white kidney bean concentrated solution to obtain powdered white kidney bean water extract.

[0013] More preferably, the extraction and preparation process of the konjac extract includes Step S24: Wash the konjac with water. Put the air-dried konjac into a pulverizer to pulverize to obtain konjac coarse powder, put the konjac coarse powder into an extraction tank and reflux with water for extraction, filter to obtain konjac filtrate after the extraction is completed, concentrate the konjac filtrate under reduced pressure, and finally spray-dry the konjac concentrated solution to obtain powdered konjac water extract.

[0014] According to the third aspect of the technical solution of the present invention, a uric acid-lowering plant extract is provided, which is made of the above uric acid-lowering composition and a pharmaceutically acceptable carrier, or is made of the uric acid-lowering plant extract combination prepared by the above method for preparing a plant extract based on steam cell wall breaking technology and a pharmaceutically acceptable carrier, and the dosage form is any pharmaceutically acceptable dosage form.

[0015] Preferably, the dosage form of the above uric acid-lowering plant extract is an oral preparation, and the oral preparation is selected from tablets, capsules, granules, pills, powders, pills, syrups, oral solutions or oral suspensions.

[0016] More preferably, the above uric acid-lowering plant extract further includes adding excipients silicon dioxide and magnesium stearate to be pressed into chewable candies, or adding sweeteners and sour agents to be prepared into solid beverages or prepared into extracts.

[0017] According to the fourth aspect of the technical solution of the present invention, the above uric acid-lowering composition and the uric acid-lowering plant extract combination prepared by the above method for preparing a plant extract based on steam cell wall breaking technology are used in animals and patients with hyperuricemia.

[0018] Compared with the prior art, the uric acid-lowering composition of the present invention, its preparation method and application of the plant extract have the following beneficial technical effects: 1. The uric acid-lowering composition of the present invention can significantly inhibit the activity of xanthine oxidase and effectively promote the excretion of uric acid through the compounding of extracts such as tangerine peel, corn silk, white kidney bean and konjac. The uric acid-lowering composition also has the function of alleviating the complications caused by hyperuricemia, and regulates the uric acid metabolism level and its adverse effects of the body from multiple aspects.

[0019] 2. The uric acid-lowering composition of the present invention uses steam cell wall breaking technology to process corn silk, significantly improving the extraction rate of the effective components of corn silk and enhancing the uric acid-lowering efficacy of the product. Based on quantitative pharmacology data, the present invention clarifies the formula compatibility of water extracts such as corn silk, tangerine peel, white kidney bean, konjac, etc. and tangerine peel volatile oil, providing a new choice for the prevention and treatment of hyperuricemia population.

[0020] 3. The preparation method of the uric acid-lowering composition has a simple process and is easy to operate, suitable for industrial production. The prepared uric acid-lowering food is safe and has no side effects, and is suitable for long-term consumption by people with hyperuricemia. Description of the Drawings

[0021] Figure 1 It is a process flow chart for extracting plant extracts in the uric acid-lowering composition according to the present invention.

[0022] Figure 2It is the fitting model diagram of quantitative pharmacology for the formula ratio of plant extracts in the uric acid-lowering composition according to the present invention; in the figure, the two red curves form the dose-effect curve band of the expected additive effect, and the black curve is the actual dose-effect curve of the plant extracts of medicine and food homology. The part where the actual dose-effect curve is higher than the red curve band is "synergistic", the part that coincides with the red curve band is "additive", and the part lower than the red curve band is "antagonistic".

[0023] Figure 3 It is the diagram of the blood uric acid levels of quails at different intervention times with the plant extracts of the uric acid-lowering composition according to the present invention.

[0024] Figure 4 It is the diagram of the blood uric acid levels of rats at different intervention times with the plant extracts of the uric acid-lowering composition according to the present invention. Specific embodiments

[0025] In order to make the technical problems solved by the present invention, the technical solutions adopted and the beneficial effects obtained more clearly understood, the following further details the present invention with reference to specific embodiments. The specific embodiments described herein are only used to explain the present invention and do not constitute any limitation to the present invention. Unless otherwise defined, all terms used in the present invention have the same meaning as commonly used in the field to which the present invention belongs.

[0026] The following provides specific embodiments to help understand the present invention, but it should be understood that the embodiments and test examples listed in the present invention are only used to illustrate the present invention, but do not constitute any limitation, and the actual protection scope of the present invention is set forth in the claims.

[0027] The present invention provides a uric acid-lowering composition, a preparation method and application of plant extracts based on steam cell wall breaking technology. The present invention is based on the in-depth advancement of the research on the formula ratio of traditional Chinese medicine and the precise calculation of the compatibility ratio between multiple components based on quantitative pharmacology calculation methods. In the present invention, the quantitative pharmacology calculation method comprehensively evaluates the synergistic, additive and antagonistic effects generated by the compatibility of traditional Chinese medicine in the formula from two dimensions of mathematical logic and pharmacological principles, providing more evidence for the scientificity and effectiveness of the traditional Chinese medicine formula in the present invention. In addition, based on the dose-effect relationship in vitro xanthine oxidase inhibition data of different raw material extracts, the best formula ratio for uric acid-lowering efficacy is screened through quantitative pharmacology algorithms.

[0028] In the uric acid-lowering composition of the present invention, the preparation method and application of the plant extract based on the steam wall-breaking technology, although only the water extraction process is given in some embodiments of the present invention, the alcohol extraction process can also be used in the extraction of the plant extracts of each raw material in the present invention, and the alcohol extraction process is also within the protection scope of the present invention. In the present invention, (1) the extracts of both the water extraction and alcohol extraction processes can be used for medicines, but only the water extraction process can be used for foods; the water extraction process of the present invention makes the food free of any toxic and side effects; (2) the present invention uses tangerine peel, corn silk, and white kidney beans as the main raw materials and adds konjac to make the effect of the uric acid-lowering composition more stable; (3) the present invention uses the air explosion method (steam wall-breaking technology) to extract the active ingredients, so that the active substances are better released; (4) through quantitative pharmacology calculation in the present invention, the compatibility is more appropriate, so that the components in tangerine peel, corn silk, white kidney beans and konjac can play better roles.

[0029] The uric acid-lowering composition of the present invention is a uric acid-lowering composition composed of plant extracts. The uric acid-lowering composition includes the following traditional Chinese medicine raw material components in parts by mass: 3-27 parts of corn silk, 3-27 parts of tangerine peel, and 3-27 parts of white kidney beans; the present invention uses the steam wall-breaking technology to process corn silk, significantly improving the extraction rate of the active ingredients of corn silk and enhancing the uric acid-lowering efficacy of the product. The present invention uses the method of quantitative pharmacology to clarify the formula compatibility of the water extracts of corn silk, tangerine peel, and white kidney beans. At the same time, the preparation method of the present invention has a simple process and is easy to operate, suitable for industrial production. The prepared uric acid-lowering food is safe and has no side effects, and is suitable for long-term consumption by people with high uric acid.

[0030] Furthermore, the present invention creatively combines the traditional Chinese medicines and foods with homologous origins, such as tangerine peel, corn silk, white kidney beans, konjac, and tangerine peel volatile oil, into a formula; provides a medicine and food dual-purpose uric acid-lowering composition with good therapeutic effects, no toxic and side effects, capable of reducing blood uric acid levels, and improving the quality of life of patients with high uric acid.

[0031] In one embodiment, the uric acid-lowering composition based on the steam wall-breaking technology provided by the present invention is composed of the following raw materials in parts by mass: 9-18 parts of corn silk, 6-12 parts of tangerine peel, and 3-6 parts of white kidney beans; in another embodiment, 6-18 parts of corn silk, 9-27 parts of tangerine peel, and 3-9 parts of white kidney beans; in yet another embodiment, 9-13 parts of corn silk, 14-20 parts of tangerine peel, 5-6 parts of white kidney beans, and 1-2 parts of konjac; in the preferred embodiment, 10 parts of corn silk, 15 parts of tangerine peel, 5 parts of white kidney beans, 1 part of konjac, and 0.2-0.8 parts of tangerine peel volatile oil are used.

[0032] The present invention is based on the theory of homology of medicine and food: Corn silk contains various uric acid-lowering active ingredients such as flavonoids, saponins, polysaccharides, and sterols. Flavonoids inhibit the activity of xanthine oxidase to reduce the production of uric acid. Saponins increase urine volume and promote the excretion of uric acid with urine. Polysaccharides participate in the metabolic regulation of the body to improve the overall metabolic level. Sterols have a protective effect on the kidneys and maintain the normal structure and function of the kidneys. Corn silk has active ingredients that are difficult to fully release by traditional extraction methods. As an emerging physical treatment method, steam wall-breaking technology can effectively change the tissue structure of plant materials and improve the extraction rate of active ingredients. In addition, in terms of controlling food intake and regulating intestinal metabolism in the homology of medicine and food, white kidney beans and konjac are an effective combination. White kidney beans can reduce the absorption of purines in food and control the production of uric acid from the source. Konjac is rich in dietary fiber, which can increase satiety and regulate intestinal function.

[0033] The uric acid-lowering composition of the present invention creatively includes not only tangerine peel but also tangerine peel volatile oil; that is, tangerine peel and tangerine peel volatile oil are used simultaneously. Hyperuricemia is often related to pathological factors such as phlegm-dampness and damp-heat in the body. The tangerine peel of the present invention can restore the normal transportation and transformation function of the spleen and stomach, promote the metabolism of water-dampness, and reduce the generation of phlegm-dampness, thereby having a positive impact on the metabolism of uric acid. The tangerine peel also contains a large amount of volatile oil with anti-inflammatory properties. Hyperuricemia is often accompanied by an inflammatory reaction, especially when gout attacks, the inflammation is more obvious. Therefore, the damage of inflammation to tissues such as joints and kidneys can be reduced by the volatile oil in the tangerine peel.

[0034] The following further illustrates the uric acid-lowering composition of the present invention and the preparation method of the plant extract based on steam wall-breaking technology through multiple examples. Example 1

[0035] The following illustrates the preparation method of the plant extract based on steam wall-breaking technology of the present invention in combination with Example 1. The uric acid-lowering composition includes tangerine peel, corn silk, white kidney beans, konjac, and tangerine peel volatile oil.

[0036] As Figure 1 shown, the preparation method of the plant extract based on steam wall-breaking technology includes the following steps: Step S1: Raw material pretreatment, select fresh tangerine peel, corn silk, white kidney beans, and konjac, wash and process them; select 3-27 parts of fresh and non-mildewed corn silk, 3-27 parts of tangerine peel, 3-27 parts of white kidney beans, and 1-2 parts of konjac by mass, wash and dry them; in another embodiment, the raw materials include 9-13 parts of corn silk, 14-20 parts of tangerine peel, 5-6 parts of white kidney beans, and 1-2 parts of konjac by mass.

[0037] Step S2: Extraction of active ingredients, extracting and preparing corn silk extract, volatile oil of tangerine peel, tangerine peel extract, white kidney bean extract and konjac extract; among them, the extraction and preparation process of corn silk extract includes step S21, the extraction and preparation process of tangerine peel extract includes step S22, the extraction and preparation process of white kidney bean extract includes step S23, and the extraction and preparation process of konjac extract includes step S24.

[0038] Step S21: Extraction process of corn silk extract. Wash and cut the corn silk into sections, place the dried corn silk in a steam explosion chamber for steam explosion and pulverization to obtain dry coarse powder of corn silk steam explosion product. Put the dry coarse powder of corn silk steam explosion product into an extraction tank and extract by refluxing with water. After the extraction is completed, filter to obtain corn silk filtrate. Concentrate the corn silk filtrate under reduced pressure to obtain corn silk concentrate; spray dry the corn silk concentrate to obtain powdered water extract of corn silk. The extraction process of corn silk extract in step S21 further includes the following steps S21-1 to S21-3.

[0039] Step S21-1, drying and pulverizing corn silk step. Select 3-27 parts of fresh and non-moldy corn silk, wash, dry and cut into sections, each section not exceeding 2 mm in length. Place the dried corn silk in a steam explosion chamber for steam explosion and pulverization. In a preferred embodiment, the filling amount of corn silk is 1 / 3 to 2 / 3 of the steam explosion chamber. Pass steam into the steam explosion chamber to make the pressure in the steam explosion chamber reach 1.5 MPa - 2.5 MPa, and maintain the steam explosion pressure for any time within 60 - 120 seconds; in a preferred embodiment, the pressure reaches 2.0 MPa and the steam explosion pressure is maintained for 90 seconds, then quickly open the high-temperature and high-pressure valve, and the steam explosion chamber instantaneously releases pressure to complete the cell wall breaking of corn silk. After steam explosion, obtain corn silk steam explosion product, and dry it at 90°C to obtain dry product of corn silk steam explosion product.

[0040] Step S21-2, screening the pulverized corn silk step. Pass the dry product of pulverized corn silk steam explosion product through a 50-100 mesh sieve; preferably, in this embodiment, the corn silk extract passes through an 80 mesh sieve to obtain dry coarse powder of corn silk steam explosion product.

[0041] Step S21-3: Steps of water-extracting corn silk and filtering and concentrating corn silk. Take the sieved dry coarse powder of the steam-exploded corn silk and put it into the extraction tank according to the material-liquid ratio of 1:15 to 1:25 (g / ml). The liquid is preferably distilled water or purified water, that is, 15 to 25 ml of liquid is put into 1 g of the dry coarse powder of the steam-exploded corn silk; use the reflux extraction device to separate the effective component substances to be extracted from the soaked dry coarse powder of the steam-exploded corn silk. The reflux extraction device is preferably a high-temperature condensation reflux device, and the reflux extraction is carried out for 30 minutes to 180 minutes, preferably 1 hour, to obtain the first corn silk extract. Further, filter the soaked dry coarse powder of the steam-exploded corn silk with a traditional Chinese medicine liquid filter to remove the residue. Use a traditional Chinese medicine liquid filter with any pore size or sieve hole of 50 mesh to 100 mesh for residue filtration; preferably use a traditional Chinese medicine liquid filter with a pore size or sieve hole of 70 mesh, 80 mesh or 90 mesh for residue filtration to obtain the first corn silk extract (i.e., the filtrate) and the corn silk residue.

[0042] Soak the obtained corn silk residue in 5 to 30 times the amount of water, preferably distilled water or purified water. In another embodiment, soak the corn silk residue in 15 to 25 times the amount of water; in another preferred embodiment, soak the corn silk residue in 20 times the amount of water, and use the reflux extraction device to separate the effective component substances to be extracted from the soaked dry coarse powder of the steam-exploded corn silk. The reflux extraction device is preferably a high-temperature condensation reflux device, and the reflux extraction is carried out for 30 minutes to 180 minutes, preferably 1 hour. Obtain the second corn silk extract. Filter the two corn silk extracts (the first corn silk extract and the second corn silk extract) and merge them into the extraction liquid storage tank for standby.

[0043] Pump the filtered corn silk extract filtrate into a single-effect concentrator for concentration, control the vacuum at 0.06 to 0.08 MPa, and the concentration temperature at 50 °C to 60 °C. Concentrate the filtrate until the relative density meets the requirements for powder spraying; carry out spray drying on the corn silk extract after vacuum concentration. When spray drying, set the inlet air temperature at 150 °C - 165 °C, the outlet air temperature at 65 °C to 85 °C; set the temperature in the spray drying chamber at 75 °C to 90 °C, and the negative pressure at 10 to 18 Pa. Crush and refine the corn silk extract after spray drying through an 80-mesh sieve to remove lumps and connections to obtain the corn silk extract powder.

[0044] Step S22: Extraction process of tangerine peel extract. Air-dry the tangerine peel washed in Step S1, and use a pulverizer to pulverize the air-dried tangerine peel. The particle size of the pulverized tangerine peel is not greater than 100 mesh. Divide the pulverized coarse tangerine peel powder into two parts: One part of the coarse tangerine peel powder is used to obtain tangerine peel volatile oil by steam distillation; the other part of the coarse tangerine peel powder is put into an extraction tank and refluxed with water for water extraction process. After the water extraction is completed, filter to obtain tangerine peel filtrate. Concentrate the tangerine peel filtrate under reduced pressure to obtain tangerine peel concentrated solution. Spray-dry the tangerine peel concentrated solution to obtain powdered tangerine peel water extract. The water extraction process (water extraction process of tangerine peel extract) in Step S22 is further refined into Step S22-1, or the alcohol extraction process Step S22-1-1 is used to replace the tangerine peel water extraction process.

[0045] Step S22-1, step of extracting effective substances from tangerine peel with water. Take a part of the pulverized coarse tangerine peel powder and sieve it through a 50-100 mesh sieve. Preferably, in this embodiment, the coarse tangerine peel powder is sieved through an 80-mesh sieve. Put the tangerine peel into the extraction tank according to a material-liquid ratio of 1:8 - 1:12 (g / ml) and reflux with water for extraction. Preferably use distilled water or pure water. Use a reflux extraction device to separate the effective component substances to be extracted from the soaked coarse tangerine peel powder. The reflux extraction device preferably adopts a high-temperature condensation reflux device, and reflux for 30 minutes to 180 minutes, preferably 2 hours. Obtain the first tangerine peel extract. Further, filter the coarse tangerine peel powder with a traditional Chinese medicine liquid filter to filter out the residue. Use a traditional Chinese medicine liquid filter with any aperture or sieve hole of 50-100 mesh for residue filtration; preferably use a traditional Chinese medicine liquid filter with an aperture or sieve hole of 70 mesh, 80 mesh or 90 mesh for residue filtration to obtain the first tangerine peel extract (i.e., the filtrate) and tangerine peel residue.

[0046] Take the sieved tangerine peel residue and put it into the extraction tank according to a material-liquid ratio of 1:15 - 1:25 (g / ml), and soak the obtained tangerine peel residue with 5-30 times the amount of water. Preferably use distilled water or pure water. In another embodiment, soak the tangerine peel residue with 15-25 times the amount of water; in the preferred embodiment, soak the tangerine peel residue with 20 times the amount of water. Use a reflux extraction device to separate the effective component substances to be extracted from the soaked coarse tangerine peel powder. The reflux extraction device preferably adopts a high-temperature condensation reflux device, and reflux for 30 minutes to 180 minutes, preferably 2 hours. Obtain the second tangerine peel extract. Filter and combine the two tangerine peel extracts (the first tangerine peel extract and the second tangerine peel extract) into an extraction liquid storage tank for standby.

[0047] After extraction is completed, filtration is carried out. The filtered tangerine peel extract filtrate is pumped into a single-effect concentrator for concentration. The vacuum is controlled at 0.06 to 0.08 MPa, and the concentration temperature is 50 °C to 60 °C. The filtrate is concentrated to a relative density until it meets the requirements for powder spraying. The tangerine peel extract after vacuum concentration is subjected to spray drying. The inlet air temperature is set at 150 °C to 165 °C, the outlet air temperature is set at 65 °C - 85 °C, the temperature is set at 75 °C to 90 °C, and the negative pressure is set at 10 - 18 Pa. The tangerine peel extract after spray drying is pulverized and refined through an 80-mesh sieve to remove lumpy connections, obtaining tangerine peel extract powder.

[0048] Alternatively, the process step S22-1-1 for extracting the effective components of tangerine peel with alcohol can be used to replace the process step S22-1 for extracting the effective components of tangerine peel with water.

[0049] S22-1-1: Process for extracting the effective components of tangerine peel with alcohol. The tangerine peel washed in step S1 is dried in the air. The dried tangerine peel is pulverized using a pulverizer to obtain tangerine peel coarse powder. The tangerine peel is put into an extraction tank and extracted with ethanol assisted by ultrasonic waves. After the extraction is completed, filtration is carried out to obtain tangerine peel filtrate. The tangerine peel filtrate is concentrated under reduced pressure. Finally, the tangerine peel concentrated solution is subjected to spray drying to obtain powdered tangerine peel extract with alcohol. It includes the following steps: S22-1-1-1, Take the pulverized tangerine peel coarse powder and pass it through a 50 - 100-mesh sieve. Preferably, in this embodiment, the tangerine peel coarse powder passes through an 80-mesh sieve. The tangerine peel is put into an extraction tank according to a material-liquid ratio of 1:5 to 1:25 (g / ml) and extracted with ethanol assisted by ultrasonic waves. The ultrasonic extraction device is used to separate the effective component substances to be extracted from the soaked tangerine peel coarse powder. Ultrasonic extraction is carried out for 30 minutes to 90 minutes, preferably 60 minutes. The ultrasonic extraction temperature is 35 °C to 60 °C, preferably 50 °C. The ethanol concentration in this embodiment is preferably any concentration between 50% and 75%. In a preferred example, an ethanol concentration of 65% is used. By utilizing the cavitation effect, thermal effect, and mechanical action of ultrasonic extraction, the first tangerine peel extract is obtained. Further, the tangerine peel coarse powder is filtered through a traditional Chinese medicine liquid filter to obtain the first tangerine peel extract (i.e., the filtrate) and tangerine peel filter residue.

[0050] S22-1-1-2. Take the sieved tangerine peel filter residue and put it into the extraction tank according to the solid-liquid ratio of 1:10 to 1:15 (g / ml). Soak the obtained tangerine peel filter residue with ethanol at 10 to 15 times the amount. In another embodiment, soak the tangerine peel filter residue with ethanol at 5-25 times the amount. In the preferred embodiment, soak the tangerine peel filter residue with ethanol at 10 times the amount. Use an ultrasonic extraction device to separate the effective component substances to be extracted from the soaked tangerine peel coarse powder; perform ultrasonic extraction for 30 minutes to 90 minutes, preferably 60 minutes; obtain the second tangerine peel extract. Filter the two tangerine peel extracts (the first tangerine peel extract and the second tangerine peel extract) and combine them into the extraction liquid storage tank for standby.

[0051] S22-1-1-3. After the extraction is completed, filter. Place the filtered tangerine peel extract filtrate in a rotary evaporator for concentration. Control the vacuum at 0.06 to 0.08 MPa and the concentration temperature at 50 °C to 60 °C until the filtrate is concentrated to the relative density until it meets the requirements for powder spraying; perform spray drying on the tangerine peel extract after vacuum concentration. Set the inlet air temperature at 150 °C to 165 °C, the outlet air temperature at 65 °C - 85 °C, the temperature at 75 °C to 90 °C, and the negative pressure at 10 - 18 Pa. Crush and refine the tangerine peel extract after spray drying through an 80-mesh sieve to remove lumpy connections to obtain the tangerine peel ethanol extract powder.

[0052] The steps for extracting tangerine peel volatile oil in step S22 - S22-2 are further detailed as follows: Take another part of the crushed tangerine peel coarse powder and pass it through an 80-mesh sieve. Put the sieved tangerine peel fine powder into a distillation flask, and the tangerine peel fine powder accounts for 1 / 3 to 1 / 2 of the volume of the distillation flask. The solid-liquid weight ratio of the tangerine peel fine powder and water is in accordance with the ratio of 1:10. Add water and soak for 1 hour and stir evenly. After soaking for 1 hour, use a gentle fire to heat the soaked tangerine peel fine powder to boiling and keep it boiling for 15 minutes to 30 minutes, preferably keep it boiling for 20 minutes; the gentle fire temperature in this embodiment is preferably controlled at any temperature between 90 °C and 150 °C, and more preferably controlled at any temperature between 95 °C and 105 °C. In the preferred embodiment, use a gentle fire at 100 °C. Cool the water vapor through a condenser to condense the water vapor in the oil-water mixture into a liquid. Utilize the difference in the density of oil and water to separate the oil layer from the water layer to obtain the preliminary tangerine peel oil; use anhydrous sodium sulfate to perform dehydration and drying treatment on the preliminarily extracted tangerine peel oil to obtain the tangerine peel volatile oil.

[0053] Step S23: Extraction process of white kidney bean extract. Wash the white kidney beans with water; put the dried white kidney beans into a pulverizer to pulverize them to obtain white kidney bean coarse powder. Put the white kidney bean coarse powder into a microwave extraction device for extraction. After the extraction is completed, filter to obtain white kidney bean filtrate. Perform low-temperature extraction on the obtained white kidney bean filtrate (low temperature means below 30°C). Concentrate the white kidney bean filtrate after extraction under reduced pressure. Finally, spray-dry the white kidney bean concentrate to obtain powdered white kidney bean water extract.

[0054] Step S23-1: Wash the white kidney bean raw materials with tap water 2 times, with each amount being 2 times the amount of the white kidney bean raw materials; after the white kidney bean raw materials are dried, use a pulverizer to pulverize the raw materials to pass through a 40-80 mesh standard sieve. Preferably, in this embodiment, after the white kidney bean raw materials are dried, use a pulverizer to pulverize the raw materials to pass through a 60 mesh standard sieve to obtain white kidney bean fine powder.

[0055] Step S23-2: Put the white kidney bean fine powder into a microwave extraction device for extraction according to a solid-liquid ratio of 1:5 - 1:10 (g / ml). Preferably use distilled water or pure water. The microwave penetrates the medium to the inside of the material and is converted into heat energy to rupture the white kidney bean cells, and the active ingredients flow out and dissolve in the extraction medium. The temperature of the microwave extraction device is below 60 degrees Celsius. In a preferred embodiment, the temperature is controlled below 30°C, and the extraction time is 5 - 10 minutes. Further, filter the white kidney bean coarse powder with a traditional Chinese medicine liquid filter to filter out the residue. Use a traditional Chinese medicine liquid filter with any pore size or sieve hole between 40 mesh and 80 mesh for residue filtration; preferably use a traditional Chinese medicine liquid filter with a pore size or sieve hole of 50 mesh, 60 mesh or 70 mesh for residue filtration to obtain the first white kidney bean extract (i.e., filtrate) and white kidney bean residue.

[0056] Take the sieved white kidney bean residue and put it into an extraction tank according to a solid-liquid ratio of 1:15 - 1:25 (g / ml), and soak the obtained white kidney bean residue with 15 - 25 times the amount of water. Preferably use distilled water or pure water. In another embodiment, soak the white kidney bean residue with 15 - 25 times the amount of water. In a preferred embodiment, soak the white kidney bean residue with 20 times the amount of water. Use a microwave extraction device to separate the active component substances to be extracted from the soaked white kidney bean coarse powder. The temperature of the microwave extraction device is controlled below 30°C, and the extraction time is 5 - 10 minutes to obtain the second white kidney bean extract (i.e., filtrate) and white kidney bean residue. Filter the two white kidney bean extracts and merge them into an extraction liquid storage tank for standby.

[0057] Pump the white kidney bean extract in the storage tank into a low-temperature extraction device for low-temperature extraction (low temperature refers to below 30 °C). Pump the filtrate in the storage tank into a low-temperature reaction kettle, place the reaction kettle in a low-temperature environment, and adjust the temperature to be controlled below 60 °C. Turn on the stirrer to fully stir the white kidney bean extract under low-temperature conditions. After a period of time, observe the stratification of the mixture. After the organic layer and the water layer are clearly stratified, turn off the stirrer. Use a separating funnel to separate the organic layer and the water layer. Transfer the separated organic layer to a beaker.

[0058] Step S23-3: Pump the filtrate in the beaker into a single-effect concentrator for concentration. Control the vacuum at 0.06 - 0.08 MPa and the concentration temperature at 60 °C to 80 °C. Concentrate the filtrate to the relative density until it meets the requirements for powder spraying. The white kidney bean extract after vacuum concentration is subjected to spray drying. Set the inlet air temperature at 150 °C to 165 °C, the outlet air temperature at 65 °C - 85 °C, the temperature at 75 °C to 90 °C, and the negative pressure at 10 - 18 Pa. Crush and refine the white kidney bean extract after spray drying through an 80-mesh sieve to remove lumpy connections, and obtain white kidney bean extract powder.

[0059] Step S24: Extraction process of konjac extract. Wash the konjac with water. Put the dried konjac into a pulverizer to crush it to obtain konjac coarse powder. Put the konjac coarse powder into an extraction tank and add water for reflux extraction. After the extraction is completed, filter to obtain konjac filtrate. Concentrate the konjac filtrate under reduced pressure, and finally spray dry the konjac concentrated solution to obtain powdered konjac water extract.

[0060] The further detailed steps of Step S24 are as follows: Step S24-1: Wash the konjac raw material with tap water 2 times, with each amount being 2 times the amount of the konjac raw material. After the konjac raw material is dried, use a pulverizer to crush the konjac raw material to pass through a 10 - 100 mesh standard sieve. Preferably, in this embodiment, after the konjac raw material is dried, use a pulverizer to crush the raw material to pass through a 60-mesh sieve to obtain konjac coarse powder.

[0061] Put the konjac refined powder into a microwave extraction device according to a material-liquid ratio of 1:50 - 1:200 (g / ml) for extraction. Set the power of the microwave extraction device at 140 - 700 W. In the preferred embodiment, control the extraction power at 450 W and the extraction time at 10 - 30 minutes. Further, filter the konjac refined powder with a traditional Chinese medicine liquid filter for residue filtration, and use a traditional Chinese medicine liquid filter with any pore size or sieve hole diameter from 40 mesh to 80 mesh for residue filtration. Preferably, use a traditional Chinese medicine liquid filter with a pore size or sieve hole diameter of 60 mesh or 70 mesh for residue filtration to obtain the first konjac refined powder extract (i.e., filtrate) and konjac refined powder residue.

[0062] Take the sieved konjac refined powder residue and put it into the extraction tank according to the solid-liquid ratio of 1:80 to 1:150 (g / ml). Soak the obtained konjac refined powder residue in 80 to 150 times the amount of water, preferably distilled water or purified water. In another embodiment, soak the konjac refined powder residue in 50 to 200 times the amount of water. In the preferred embodiment, soak the konjac refined powder residue in 100 times the amount of water. Use a microwave extraction device to separate the effective component substances to be extracted from the soaked konjac refined powder. The power of the microwave extraction device is controlled at 450 W, and the extraction time is 5 to 30 minutes. In this embodiment, 25 minutes is preferred, to obtain the second konjac refined powder extract (i.e., the filtrate) and the konjac refined powder residue. Filter the two konjac refined powder extracts and merge them into the extraction liquid storage tank for standby.

[0063] Step S24-2: After extraction, filter. The filtered konjac extract filtrate is pumped into a single-effect concentrator for concentration. Control the vacuum at 0.06 - 0.08 MPa and the concentration temperature at 60 °C - 80 °C until the filtrate is concentrated to the relative density until it meets the requirements for powder spraying; the vacuum-concentrated konjac extract is spray-dried. Set the inlet air temperature at 150 °C - 165 °C, the outlet air temperature at 65 °C - 85 °C, the temperature at 75 °C - 90 °C, and the negative pressure at 10 - 18 Pa. Crush and refine the spray-dried konjac extract through an 80-mesh sieve to remove lumpy connections, to obtain the konjac extract powder.

[0064] Step S3: Compound in different ratios. The corn silk extract, tangerine peel extract, and white kidney bean extract are compounded in 7 ratios; the first compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 1:1:1; the second compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 1:2:3; the third compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 1:3:2; the fourth compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 2:1:3; the fifth compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 2:3:1; the sixth compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 3:1:2; the seventh compounding ratio is corn silk extract:tangerine peel extract:white kidney bean extract = 3:2:1.

[0065] Step S4: Use the extracts compounded in different ratios in Step S3 to evaluate the inhibitory effect on xanthine oxidase in vitro.

[0066] Xanthine oxidase can convert xanthine into uric acid, and the amount of uric acid produced directly reflects the activity level of xanthine oxidase. Uric acid has a characteristic absorption peak under the liquid phase detection conditions of 254 nm. Therefore, the change in the activity of xanthine oxidase can be reflected by the change in the chromatographic peak in the reaction system within a certain time.

[0067] In the enzyme activity assay system, add 100 μL of PBS (purchased from Beijing Solarbio, product number: P1020), 40 μL of 0.625 U / mL xanthine oxidase (purchased from Beijing Solarbio Science & Technology Co., Ltd., product number: X8020), and 20 μL of the sample working solution to a 1.5 mL Eppendorf tube, mix well, incubate at 37 °C for 15 minutes, then add 40 μL of the xanthine sample solution, mix evenly, incubate at 37 °C for 30 minutes, and add 40 μL of hydrochloric acid to terminate the reaction. The hydrochloric acid is purchased from Sinopharm Chemical Reagent Co., Ltd. (product number: 10011018). Finally, take 200 μL of the solution in the Eppendorf tube, filter through a membrane, and detect it on an Agilent 1260 high performance liquid chromatograph.

[0068] The present invention uses PBS buffer as the buffer, and its main components are Na 2 HPO 4 、KH 2 PO 4 、NaCl and KCl, which act as solvents and play a role in dissolving and protecting reagents.

[0069] In a specific embodiment, add 100 μL of PBS and 40 μL of 0.625 U / mL xanthine oxidase to a 1.5 mL Eppendorf tube, mix evenly with 20 μL of PBS and 20 μL of aqueous extracts of corn silk, tangerine peel, and white kidney bean, incubate at 37 °C for 15 minutes, then add 40 μL of 900 μM xanthine sample solution, mix evenly, incubate at 37 °C for 30 minutes, add 40 μL of 1 mol / L hydrochloric acid to terminate the reaction, take 200 μL after filtering through a membrane, and analyze it on an Agilent 1260 high performance liquid chromatograph.

[0070] The mobile phase used is a 0.02 mol / L potassium dihydrogen phosphate solution (containing 1% methanol). The chromatographic column is an Agilen XDB-C18 Column 4.6*250 mm 5 μm chromatographic column (column temperature 35 °C). The uric acid content is determined under an isocratic condition for 10 minutes at a detection wavelength of 254 nm. The series of concentrations of the uric acid standard curve are 1, 2, 5, 10, 20, 40 μg / mL. Calculate the inhibition rate, and the inhibition rate (%) = (1 - the content measured for the test sample / the content measured for the blank sample) × 100%.

[0071] In vitro xanthine oxidase activity assay showed that the compound ratio of aqueous extract of corn silk: aqueous extract of dried tangerine peel: aqueous extract of white kidney bean = 2:3:1 had the highest inhibitory rate on xanthine oxidase activity (see Table 1). Corn silk, dried tangerine peel, and white kidney bean all had the effect of inhibiting xanthine oxidase activity, and the inhibitory rate gradually increased with the increase in the concentrations of the aqueous extracts of corn silk, dried tangerine peel, and white kidney bean (see Table 2). At the ratio of aqueous extract of corn silk: aqueous extract of dried tangerine peel: aqueous extract of white kidney bean = 2:3:1, which had the highest weight in inhibiting xanthine oxidase activity, the inhibitory rate of xanthine oxidase was 6.04 - 48.80% within the measured concentration range of dried tangerine peel from 0.1875 to 12 mg / mL (see Table 3).

[0072] Table 1: Dose - effect relationship between different compound ratios of aqueous extracts of corn silk, dried tangerine peel, and white kidney bean and inhibitory rate of xanthine oxidase activity

[0073]

[0074] Table 2: Dose - effect relationship between aqueous extracts of corn silk, dried tangerine peel, white kidney bean and inhibitory rate of xanthine oxidase activity

[0075]

[0076] Table 3: Dose - effect relationship between the combination of aqueous extracts of corn silk, dried tangerine peel, white kidney bean and inhibitory rate of xanthine oxidase activity

[0077]

[0078] Step S5: According to the method of quantitative pharmacology, clarify the formulation compatibility of the uric acid - lowering composition.

[0079] According to the dose - effect relationship tables of aqueous extracts of corn silk, dried tangerine peel, white kidney bean and their combination with xanthine oxidase activity, fit the dose - effect relationship curve equation. Calculate the dose - effect data for achieving the expected additive pharmacodynamic effect under the combined use condition, and reconstruct the dose - effect curve of the combined use group and the expected additive effect and the fitted dose - effect relationship curve equation.

[0080] The calculation formula is as follows:[[]]END]] .

[0081] In the formula: Y: drug effect; f and g: respectively represent the dose - effect functions of drugs A and B; Subscript " g（Bn） ": the starting point of f(Am); Subscript "f （Am） ": the starting point of g(Bn); Bn and An: equivalent doses; Am and Bm: Equivalent doses; Lo: Low, i.e., the lowest drug dose; Hi: High, i.e., the highest drug dose; : Sorting symbol, representing the function value of the unit within the number set, which must be arranged from low to high; [ ]: Closed interval symbol.

[0082] By sequential conversion of equivalent doses, calculate each dose-effect data constituting the expected additive pharmacodynamic effect under combined use conditions. Reconstruct the dose-effect curve of the combined group dose and the expected additive effect and fit the dose-effect relationship curve equation. Compare the position relationship between the expected additive effect dose-effect curve band of the combined group and the actual dose-effect curve, and calculate relevant indicators.

[0083] Such as Figure 2 As shown, the uric acid-lowering composition of the present invention was subjected to an application test. The measured points of the combined dose were located inside or above the expected effect curve band, belonging to additive or synergistic effects. This result proves that the optimized proportion formula (corn silk: tangerine peel: white kidney bean = 2:3:1) has good synergistic and enhancing effects.

[0084] Example 2: Effects of extracts from medicinal and edible plants on serum uric acid in hyperuricemia model quails

[0085] (1) Establishment of a quail hyperuricemia model.

[0086] Purchase 60 male Defak quails, purchased from Beijing Deling Quail Farm. The quarantined qualified animals were randomly divided into a normal control group (n = 12) and a model group (n = 48) according to uric acid stratification. The normal control group was fed with ordinary feed, and the model group was fed with high-purine feed (prepared according to the ratio of ordinary feed: yeast extract powder (OXOID; batch number: 4399719-02) = 4:1, and the daily feeding amount was equivalent to 15 g / kg of yeast extract powder). On the 8th day after feeding with high-purine feed, about 0.6 mL of blood was collected from the jugular vein (fasting but not water-depriving for about 12 hours before blood collection). After separating the serum, the uric acid content was measured. The model group was significantly increased compared with the normal control group, and it was determined that the quail hyperuricemia model was successfully established.

[0087] (2) Intervention effect of uric acid-lowering plant extracts on serum uric acid in hyperuricemic model quails.

[0088] During the process of animal evolution, the gene encoding uricase is silenced and inactivated, resulting in a lack of uricase. The end product of purine metabolism in the body is mainly uric acid. Quails also lack uricase, and their purine nucleotide metabolic pathway is similar to that of humans. Given the similarities in key physiological characteristics and metabolic pathways between the two, the results of the hyperuricemia study conducted with quails as the research object have high reference value in related fields. In order to accurately evaluate the time-effect relationship of the uric acid-lowering effect of plant extracts with both medicinal and edible uses, a 4-week intervention trial for quail hyperuricemia was carried out. The plant extracts with both medicinal and edible uses were administered by oral gavage once a day. The control group and the model group were given pure water, with the same gavage frequency and cycle as the group of plant extracts with both medicinal and edible uses. The gavage volume for each group was 10 mL / kg BW, and the dosage of the plant extracts with both medicinal and edible uses was 2.5 g / kg BW. On the 7th, 14th, 21st, and 28th days after the successful establishment of the model, about 0.6 mL of blood was collected from the jugular vein 1 hour after administration in the morning (fasting overnight without water restriction for about 12 hours before blood collection). After standing at room temperature for at least 30 minutes, it was centrifuged at 5000 revolutions per minute at 4°C for 10 minutes to separate the upper serum, and a biochemical analyzer (model HITACHI 7180, produced by Hitachi, Japan) was used to measure serum uric acid (UA).

[0089] The experimental results are shown in Table 4 and Figure 3 as follows. The serum uric acid of quails in the model group showed relatively high concentration levels at different time points, with significant statistical differences compared with the control group. By comparing the serum uric acid data from week 0 to week 4, the uric acid levels of quails in each extract group (FDU1, FDU2, and FDU3) were basically at the same level as those in the model group before the intervention. After the intervention, the uric acid levels in each extract group showed significant decreases. Moreover, as the administration time continued to extend, the uric acid levels showed a gradually decreasing trend. In the first week, the uric acid levels of FDU2 and FDU3 were close and lower than that of FDU1, indicating that the tangerine peel extracted with ethanol had a better uric acid-lowering effect. In the second and third weeks, the uric acid levels of FDU1 and FDU2 were close and higher than that of FDU3, indicating that the addition of volatile oils from tangerine peel could better control uric acid. In the fourth week, there were no obvious differences in the uric acid levels of FDU1, FDU2, and FDU3. To sum up, FDU3 was better than FUD2 which was better than FDU1. That is, the tangerine peel extracted by the alcohol extraction process was better than the tangerine peel extracted by the water extraction process, and the uric acid-lowering effect in quails was more obvious after the addition of volatile oils from tangerine peel. The amplitude of uric acid reduction gradually increased with the extension of the intervention time, further proving that plant extracts with both medicinal and edible uses can not only stably control uric acid levels for a long time, but also have better long-term effects when taken for a long time.

[0090] Table 4: Effects of Uric Acid-Lowering Plant Extracts on Serum Uric Acid in Hyperuricemic Model Quails

[0091] Note: n=12 for each treatment group, *p<0.05, **p<0.01 compared with the model group.

[0092] Example 3: Effects of edible and medicinal plant extracts on serum uric acid in hyperuricemia model rats

[0093] (1) Establishment of hyperuricemia model in rats.

[0094] 40 SPF-grade SD male rats were purchased from Sibeifu Biotechnology Co., Ltd., with an age of 6-7 weeks and a body weight of 180-220g. The quarantine period was 3 days. Before the end of the quarantine, the 40 male rats were fasted for 13-14 hours, and about 0.3mL of blood was collected to determine the uric acid content. Eight male rats with uric acid and body weight around the mean were selected as the control group, and the remaining 32 were used as the modeling group. The normal control group was fed with ordinary feed, and the modeling group was fed with high-purine feed (containing 1% potassium oxonate + 0.2% adenine + 5% sucrose). On the 8th day after feeding, about 0.3mL of blood was collected from the tail vein, and the uric acid content was determined after separating the serum. The uric acid level in the model group was more than twice that in the normal control group, and it was determined that the hyperuricemia modeling of rats was successful.

[0095] (2) The intervention effect of uric acid-lowering plant extracts on the serum uric acid level in hyperuricemia model rats.

[0096] The extract of edible and medicinal plants was administered by oral gavage once a day for a period of 1 week. The control group and the model group were given pure water, and the gavage frequency and period were the same as those of the edible and medicinal plant extract group. The gavage volume of each group was 10mL / kg BW, and the dose of edible and medicinal plant extract was 2.5g / kg BW. After 1 week, about 0.5mL of blood was collected from the tail vein to determine the serum UA level. After standing at room temperature for 30 minutes, the blood was centrifuged at 5000 rpm and 4℃ for 10 minutes to separate the upper serum, and serum uric acid (UA) was determined using a biochemical analyzer (HITACHI 7180, produced by Hitachi, Japan).

[0097] The experimental results are shown in Table 5 and Figure 4As shown, the serum uric acid of the rats in the model group exceeded twice that of the normal control group during the 4-week experiment, indicating that the hyperuricemia model of rats was stable. By comparing the serum uric acid data from week 0 to week 4, the uric acid levels of the rats in each extract group (FDU1, FDU2, and FDU3) were basically the same as those in the model group before intervention. However, as the administration time continued to extend, the uric acid levels gradually decreased. In the first week, compared with the model group, the effects of FDU2 and FDU3 in reducing uric acid were obvious, with significant statistical differences, while FDU1 only had a decreasing trend without statistical differences, indicating that the tangerine peel extracted with ethanol had a better effect on reducing uric acid. From the second week to the fourth week, the average uric acid of the rats in the FDU3 group was lower than that in the FDU1 and FDU2 groups, indicating that the addition of volatile oil from tangerine peel helped to further reduce the uric acid level. To sum up, FDU3 was better than FUD2 and FDU1. That is, the tangerine peel extracted by the alcohol extraction process was better than that by the water extraction process, and the effect of reducing uric acid in rats was more obvious after adding the volatile oil from tangerine peel. This result was consistent with the conclusion of Example 2, and the effect of reducing uric acid of the plant extract of medicine and food homology was verified in two different species.

[0098] Table 5: Effects of plant extracts for reducing uric acid on serum uric acid in hyperuricemic model rats

[0099]

[0100] Note: n = 8 for each treatment group. Compared with the model group, *p < 0.05, **p < 0.01.

[0101] A uric acid-lowering composition of the present invention is composed of plant extracts, and the plant extracts are obtained by steam cell wall breaking technology. The uric acid-lowering composition of the present invention and the steam cell wall breaking technology used have extremely high creativity or innovation compared with the traditional technology. Specifically as follows: (1) The steam cell wall breaking technology of the present invention revolutionarily improves the cell wall breaking efficiency. Compared with the traditional water decoction method (80 - 100°C / 2 - 4h), the traditional water decoction method can only slowly release components through osmosis, while steam cell wall breaking (0.8 - 2.5MPa / 30 - 300s) penetrates the cell wall through high-pressure steam, and the mechanical shear force generated by instant pressure relief disintegrates the lignocellulose structure. The adopted steam cell wall breaking technology optimizes the protection mechanism of active ingredients. In the technical solution of the present invention, heat-sensitive ingredient protection is adopted. Although the steam cell wall breaking temperature reaches 160 - 230°C, the treatment time is in seconds (usually <5 minutes). Compared with traditional reflux extraction (60°C / more than 6h), the total heat exposure is reduced by 85%, significantly reducing the decomposition of heat-unstable components such as flavonoid glycosides. Using the steam cell wall breaking technology of the present invention, the molecular structures of the effective components of each component change: The patent applicant of the present invention has found that steam cell wall breaking can degrade corn silk cellulose to generate oligosaccharides (DP 2 - 6), and the antioxidant activity (DPPH scavenging rate) of these small molecule polysaccharides is increased by 42% compared with the original components.

[0102] In addition, the adopted steam cell wall breaking technology enables multi-components to have a synergistic effect, specifically manifested in: (1) Physical effect: The porosity of the cell wall is increased by 300 - 500%; (2) Chemical effect: Hemicellulose is hydrolyzed to generate synergistic components such as ferulic acid; (3) Biological effect: Promote the conversion of bound polyphenols into free forms. Experiments show that the blood sugar lowering effect (α-glucosidase inhibition rate) of the corn silk extract treated by the steam cell wall breaking technology is increased by 58%, showing a significant difference from the traditional extract (p < 0.01).

[0103] (2) Different from the existing technology that uses many different types of components and components with different component formulations, in the preferred embodiment, the uric acid lowering composition of the present invention only includes plant extracts such as tangerine peel, corn silk, white kidney bean and konjac. It mainly uses the following effects of tangerine peel, corn silk, white kidney bean and konjac.

[0104] (1) Tangerine peel: Bitter, pungent, warm in nature, entering the spleen and lung meridians. It has the effects of promoting qi circulation and strengthening the spleen, regulating the middle energizer and promoting appetite, drying dampness and resolving phlegm.

[0105] (2) Corn silk: Sweet; light; neutral in nature, entering the kidney, stomach, liver and gallbladder meridians. It has the effects of promoting diuresis and reducing swelling, clearing heat, calming the liver and promoting bile secretion.

[0106] (3) White kidney bean: Sweet, slightly warm in nature, entering the spleen and stomach meridians. It has the effects of warming the middle energizer and strengthening the spleen, regulating qi and moistening the intestine.

[0107] (4) Konjac: Pungent, cold in nature. It has the effects of detoxifying and dissipating nodules, and promoting diuresis.

[0108] (3) In the preferred embodiment of the present invention, only a small amount of konjac is added, and its proportion is extremely low. For example, konjac only accounts for about one-tenth of the corn silk component, which is different from the prior art where the proportion of konjac is extremely high or konjac is used as the main component. The core component of konjac used in the present invention is glucomannan. Approximately 70%-80% of konjac tubers is water-soluble dietary fiber, which can expand 80-100 times in volume after absorbing water to form a gel-like substance with high viscosity and strong adsorption. Konjac contains a small amount of trace elements and amino acids, such as calcium, selenium, potassium, etc. The calcium content is about 43mg / 100g, and selenium has antioxidant function; there are 16 kinds of amino acids in konjac, including 7 essential amino acids, such as lysine, tryptophan, etc. Konjac in the present invention exhibits the characteristic of low calories. Each 100 grams of konjac contains only about 7-20 kcal, and hardly contains any fat and protein.

[0109] Konjac in the present invention is used to regulate intestinal health and play the role of prebiotics. After fermentation, it produces short-chain fatty acids (such as butyric acid) to nourish the intestinal probiotic group. At the same time, it controls blood sugar and blood lipids and delays sugar absorption; the gel layer in konjac wraps food, slows down the speed of glucose entering the blood, and reduces the postprandial blood sugar peak; and it binds cholesterol, adsorbs bile acids and cholesterol, reduces lipid absorption, and helps reduce low-density lipoprotein (LDL). More importantly, konjac in the present invention can make the eater feel highly satiated. For example, the water absorption and expansion characteristics prolong the gastric emptying time, reduce hunger, and are suitable for low-calorie diet plans.

[0110] Konjac in the present invention has effects such as high-efficiency adsorption and promotion of uric acid excretion. For example, the molecular sieve effect of glucomannan: Glucomannan in konjac flour has a reticular macromolecular structure, which can adsorb uric acid, purine metabolites and toxins in the intestine, and reduce the probability of their being reabsorbed into the blood. Enhancement of intestinal uric acid excretion: Approximately 30% of human uric acid is excreted through the intestine. Konjac flour increases the volume and viscosity of feces, accelerates intestinal peristalsis, shortens the residence time of uric acid in the intestinal lumen, and indirectly improves the excretion efficiency.

[0111] In addition, konjac in the present invention has effects of metabolic regulation and inflammation alleviation. Inhibition of xanthine oxidase activity: Konjac polysaccharide has been proven to inhibit the activity of xanthine oxidase (XO) in animal experiments, which is a key link in reducing uric acid production; the selenium element and polysaccharide components in konjac can reduce the levels of pro-inflammatory factors such as serum IL-1β and TNF-α, and alleviate the local inflammatory reaction of gouty arthritis, that is, produce an anti-inflammatory synergistic effect.

[0112] The konjac in the present invention has low calories and a feeling of fullness: the calorie content of konjac flour is only 7 kcal / 100 g. After absorbing water and swelling, it occupies the space in the stomach, reducing the desire to consume high-purine foods; and it can improve insulin resistance: by regulating blood glucose fluctuations and lipid metabolism, indirectly improving insulin resistance (a common inducement of hyperuricemia), forming a comprehensive metabolic regulation.

[0113] (4) When the volatile oil of dried tangerine peel is added alone to the uric acid-lowering composition of the present invention, it is mainly used for the pharmacological mechanisms of synergistically enhancing the effects of inhibiting uric acid production and promoting uric acid excretion. Terpenoid compounds such as limonene and γ-terpinene in the volatile oil of dried tangerine peel inhibit the activity of xanthine oxidase, block the final step of purine metabolism into uric acid, and form dual-target inhibition with the mainstream uric acid-lowering components (such as allopurinol). By activating the organic anion transporters (OAT1 / OAT3), it enhances the efficiency of uric acid secretion in the renal tubules (animal experiments show that the excretion amount increases by 18.6%) and antagonizes the uric acid reabsorption transporter URAT1 to promote uric acid excretion.

[0114] Furthermore, the organic combination of dried tangerine peel and its volatile oil further exerts the function of regulating qi and strengthening the spleen to improve the metabolic basis. In addition, the penetrating property of the volatile oil enhances the trans-membrane absorption of the drug.

[0115] The homology of medicine and food is the summary of the relationship between medicine and food and their applications in traditional Chinese medicine. Since ancient times, traditional medicine has had the understanding that "medicine comes from food, food has medicinal functions, and medicine has food properties", and uses the medicinal value of food for health preservation and disease prevention and treatment, namely "food therapy" and "diet therapy". Treating insomnia with a formula composed of foods homologous to medicine and food, while exerting the characteristics of multi-pathway synergistic regulation of food compounds, has significant advantages in terms of medication safety and compliance compared with chemical drugs. The present invention uses steam wall-breaking technology to process corn silk, significantly improving the extraction rate of the effective components of corn silk and enhancing the uric acid-lowering efficacy of the product; the uric acid-lowering food prepared based on the uric acid-lowering composition of the present invention is safe and has no side effects, and is suitable for long-term consumption by people with high uric acid.

[0116] Through the uric acid-lowering formula of the present invention, the concept of the homology of medicine and food is deeply implemented. The homology of medicine and food means that it can be used both as a medicine and as a food. The combination of the foods homologous to medicine and food in the present invention can further reduce the potential safety hazards of long-term medication and improve the compliance of patients.

[0117] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention. These simple modifications all belong to the protection scope of the present invention.

[0118] It should be further noted that, in the above specific embodiments, the various specific technical features described can be combined in any way without contradiction. To avoid unnecessary repetition, the present invention does not separately describe various possible combination methods. In addition, any combination can be made among the various different embodiments of the present invention, as long as it does not violate the idea of the present invention, and it should also be regarded as the content disclosed by the present invention.

Claims

1. A uric acid lowering composition, characterized in that: The uric acid-lowering composition is composed of a plant extract, which is composed of the following raw materials by mass: 3-27 parts of corn silk, 3-27 parts of tangerine peel and 3-27 parts of white kidney bean; the plant extract is obtained by steam wall breaking technology, and the preparation method of the plant extract based on steam wall breaking technology comprises the following steps: Step S1: pre-treating the raw materials, selecting fresh tangerine peel, corn silk and white kidney beans and washing them; Step S2: extracting effective ingredients, using steam wall breaking technology to prepare corn silk extract, tangerine peel volatile oil, tangerine peel extract and white kidney bean extract; Step S3: Compounding in different proportions: corn silk extract, tangerine peel volatile oil, tangerine peel extract and white kidney bean extract in different proportions; Step S4: evaluating the in vitro lipase inhibition ability of the extracts prepared in different proportions in step S3; Step S5: Determine the composition and compatibility of each plant extract based on quantitative pharmacology, and then determine the composition and compatibility of the uric acid-lowering composition.

2. The uric acid lowering composition according to claim 1, characterized in that The uric acid lowering composition is composed of the following raw materials in parts by mass: 9-18 parts of corn silk, 6-12 parts of tangerine peel and 3-6 parts of white kidney beans.

3. The uric acid lowering composition according to claim 1, characterized in that The uric acid lowering composition is composed of the following raw materials in parts by mass: 6-18 parts of corn silk, 9-27 parts of tangerine peel and 3-9 parts of white kidney beans.

4. The uric acid lowering composition according to claim 1, characterized in that The uric acid lowering composition further includes konjac, and the uric acid lowering composition is composed of the following raw materials in parts by mass: 9-13 parts of corn silk, 14-20 parts of tangerine peel, 5-6 parts of white kidney beans and 1-2 parts of konjac.

5. The uric acid lowering composition according to claim 4, characterized in that: The uric acid lowering composition further includes tangerine peel volatile oil. The uric acid lowering composition is composed of the following raw materials in parts by mass: 10 parts of corn silk, 15 parts of tangerine peel, 5 parts of white kidney beans, 1 part of konjac and 0.2-0.8 parts of tangerine peel volatile oil.

6. A method for preparing a plant extract based on steam wall breaking technology, which is used to prepare the plant extract in the uric acid-lowering composition according to claim 1, characterized in that: The method for preparing the plant extract comprises the following steps: Step S1: pretreatment of raw materials, the raw materials comprising corn silk, tangerine peel, white kidney bean and konjac by weight; washing and drying the tangerine peel, corn silk, white kidney bean and konjac; Step S2: extracting effective ingredients, extracting and preparing corn silk extract, tangerine peel volatile oil and tangerine peel extract, white kidney bean extract and konjac extract, wherein the extraction and preparation process of corn silk extract includes step S21, and the extraction and preparation process of tangerine peel extract includes step S22; Step S21, washing and cutting corn silk into sections, placing the dried corn silk in a steam explosion chamber for steam explosion and crushing to obtain coarse powder of the steam-exploded corn silk dry product, putting the coarse powder of the steam-exploded corn silk dry product into an extraction tank, adding water and refluxing for extraction, filtering to obtain corn silk filtrate after the extraction, and concentrating the corn silk filtrate under reduced pressure to obtain corn silk concentrate; spray drying the corn silk concentrate to obtain a powdery corn silk water extract; Step S22, drying the tangerine peel washed in step S1, crushing the dried tangerine peel with a crusher, and dividing the crushed tangerine peel coarse powder into two parts: one part of the tangerine peel coarse powder is used to obtain tangerine peel volatile oil by steam distillation; the other part of the tangerine peel coarse powder is put into an extraction tank and water is added to reflux extraction to perform a water extraction process, after the tangerine peel coarse powder water extraction is completed, the tangerine peel filtrate is filtered to obtain the tangerine peel filtrate, the tangerine peel filtrate is reduced pressure concentrated to obtain the tangerine peel concentrated solution, and the tangerine peel concentrated solution is spray dried to obtain a powdery tangerine peel water extract; Step S3: compounding according to different proportions, corn silk extract, tangerine peel extract and white kidney bean extract are compounded according to 7 proportions; the first compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 1:1:1, the second compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 1:2:3, the third compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 1:3:2, the fourth compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 2:1:3, the fifth compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 2:3:1; the sixth compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 3:1:2, and the seventh compounding ratio is corn silk extract: tangerine peel extract: white kidney bean extract = 3:2:1; Step S4: using the extracts prepared in different proportions in step S3 to evaluate the xanthine oxidase inhibition effect in vitro; Step S5: Quantitative pharmacology is used to determine the composition and compatibility of the uric acid-lowering composition.

7. The method for preparing plant extracts based on steam wall breaking technology according to claim 6, characterized in that: The extraction and preparation process of the white kidney bean extract comprises step S23: washing the white kidney beans with water; putting the dried white kidney beans into a grinder to grind them to obtain white kidney bean coarse powder, putting the white kidney bean coarse powder into a microwave extraction device for extraction, filtering to obtain a white kidney bean filtrate after the extraction, performing low-temperature extraction on the obtained white kidney bean filtrate, decompressing and concentrating the extracted white kidney bean filtrate, and finally spray-drying the white kidney bean concentrate to obtain a powdery white kidney bean water extract.

8. The method for preparing plant extracts based on steam wall breaking technology according to claim 6, characterized in that: The extraction and preparation process of the konjac extract comprises step S24: washing the konjac with water, putting the dried konjac into a grinder to crush it to obtain konjac coarse powder, putting the konjac coarse powder into an extraction tank, adding water and refluxing for extraction, filtering to obtain konjac filtrate after the extraction is completed, concentrating the konjac filtrate under reduced pressure, and finally spray-drying the konjac concentrate to obtain a powdery konjac water extract.

9. A uric acid-lowering plant extract, characterized in that: It is made of the uric acid lowering composition described in any one of claims 1-5 and a food-acceptable carrier, or it is made of the plant extract combination prepared by the plant extract preparation method based on steam wall breaking technology described in any one of claims 6-8 and a food-acceptable carrier, and the dosage form is any food-acceptable dosage form.

10. The uric acid-lowering plant extract according to claim 9, characterized in that The uric acid-lowering plant extract dosage form is an oral preparation.

11. The uric acid-lowering plant extract according to claim 9, characterized in that The uric acid lowering plant extract dosage form includes adding excipients silicon dioxide and magnesium stearate to compress into tablet candy, or adding sweeteners and sour agents to prepare into solid beverage or paste.

12. Use of the uric acid lowering composition according to any one of claims 1 to 5 and the uric acid lowering plant extract combination prepared by the plant extract preparation method based on steam wall breaking technology according to any one of claims 6 to 8 in animals and patients with hyperuricemia.

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