Preparation method of uric acid reducing medicine based on steam-exploded dry pteridium aquilinum

Abstract

The invention relates to a preparation method of a uric acid reducing medicine based on steam-exploded dry pteridium aquilinum, and belongs to the technical field of traditional Chinese medicine preparation. The method comprises the following operation steps: (1) carrying out steam explosion on chopped dry pteridium aquilinum with the water content of 8-13% to obtain steam-exploded dry pteridium aquilinum; (2) adding water into the steam-exploded dry pteridium aquilinum, performing reflux extraction, filtering, performing vacuum concentration, and performing spray drying to obtain brown powdery steam-exploded dry pteridium aquilinum water extract; the steam-exploded dry pteridium aquilinum water extract contains the following components in percentage by mass: 17.8-44.9% of pteridium aquilinum polysaccharide, 4.1-8.8% of protein and small molecule polypeptide; and (3) uniformly mixing the steam-exploded dry pteridium aquilinum water extract, an excipient, a disintegrating agent and a lubricant, adding a proper amount of water, preparing granules by a granulating machine, and tabletting by a tabletting machine to obtain the uric acid-reducing tablets. The mass of each tablet is 0.40 g, and the mass content of the steam-exploded dry pteridium aquilinum water extract is 80-88%; according to the uric acid reducing medicine, 67 mg of the steam-exploded dry pteridium aquilinum water extract is taken every day according to each kilogram of body weight, and the remarkable uric acid reducing effect is achieved.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a preparation method of a uric acid-lowering medicine based on steam-exploded dried bracken. Background Art

[0002] Uric acid is the end product of human purine metabolism, which is produced by hypoxanthine and xanthine under the action of xanthine oxidase (XO). Due to the lack of urate oxidase in the human body, it cannot be further broken down into soluble allantoin, making humans very prone to hyperuricemia. Any cause of increased uric acid production or decreased excretion can lead to hyperuricemia. Hyperuricemia is usually considered a sign of gout. According to statistics, about 5%-12% of hyperuricemia can eventually develop into gout. Studies have shown that hyperuricemia is not only the most important biochemical basis of gout, but also closely related to the occurrence of hypertension, hyperlipidemia, atherosclerosis, obesity, and insulin resistance. It has become a serious metabolic disease that threatens human health.

[0003] At present, the methods to relieve gout symptoms mainly start from two aspects: reducing uric acid production and increasing uric acid excretion, including the use of purine oxidase inhibitors such as allopurinol and febuxostat to reduce uric acid production, or the use of probenecid, benzbromarone and other drugs to inhibit uric acid reabsorption in the renal tubules, increase uric acid excretion to relieve gout symptoms, or use colchicine to neutralize and inhibit uric acid; however, allopurinol and febuxostat are very likely to cause allergic reactions or liver and kidney damage, probenecid cannot be used for patients with renal insufficiency, and colchicine has clear cytotoxicity. In recent years, drugs such as rasburicase, pegloticase, rasburicase and peglotidase have emerged to catalyze the conversion of uric acid into allantoin, but these drugs have great toxic side effects and are often intolerant to patients, which limits their use to a certain extent. Therefore, finding highly effective and low-toxic uric acid-lowering drugs is still a difficulty in the current development of new uric acid-lowering drugs. Summary of the invention

[0004] In order to reduce toxic side effects and achieve safe tolerance in patients with hyperuricemia, the present invention provides a method for preparing a uric acid-lowering drug based on steam-exploded dried bracken.

[0005] The preparation steps of a uric acid-lowering drug based on steam-exploded dried bracken are as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash, boil or steam to kill the green, and dry to a water content of 8-13% to obtain dried bracken; cut the dried bracken into 1-5 cm pieces; The fresh bracken is a plant of the genus Pteridaceae, Pteridaceae ( Pteridium aquilinum (L.) Kuhn var. a little wider(Desv.) Underw. ex Heller) young leaves; (2) Steam explosion treatment The chopped dried bracken is subjected to steam explosion and pressure-maintaining treatment for 3-60 seconds in a steam explosion chamber under a pressure of 0.5-2.0 MPa to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dried bracken added is not less than 1 / 3 of the steam explosion chamber; (3) Preparation of steam-exploded dried bracken water extract The steam-exploded dried bracken is extracted by reflux with water, the amount of water added is 10-20 times the weight of the dried bracken, the extraction water temperature is 50°C-100°C, and the extraction time is 2-5 hours; filtering to obtain a filtrate; concentrating the filtrate under reduced pressure, the concentration temperature does not exceed 90°C, to obtain a concentrated solution; spray drying the concentrated solution to obtain a brown powdery steam-exploded dried bracken water extract; The steam-exploded dried bracken water extract contains: 17.8-44.9% by weight of bracken polysaccharide, 4.1-8.8% by weight of protein and small molecule polypeptide; (4) Preparation of uric acid-lowering tablets 80-88% steam-exploded dried bracken water extract, 10-15% excipient, 1.5-3% disintegrant and 0.5-2% lubricant are mixed evenly, an appropriate amount of water is added, granules are obtained by a granulator, and tablets are pressed by a tablet press to obtain uric acid-lowering tablets; The mass of each tablet is 0.40 g, and the mass content of steam-exploded dried bracken water extract in each tablet is 80-88%; The uric acid lowering drug, at a daily dosage of 67 mg of steam-exploded dried bracken water extract per kilogram of body weight, achieves a significant uric acid lowering effect.

[0006] The technical solution is further defined as follows: In step (1), the fresh bracken is young bracken leaves picked in April-May each year at the tender leaf curling stage, specifically, young bracken leaves with petioles that grow 15-25 cm above the ground.

[0007] In step (1), the water boiling and killing is carried out at a temperature of 80-100° C. and a time of 1-5 minutes.

[0008] In step (1), the steam killing is carried out at a temperature of 100-130° C. and a time of 3-7 minutes.

[0009] In step (2), the excipient is microcrystalline cellulose.

[0010] In step (2), the disintegrant is two of cross-linked sodium carboxymethyl starch, sodium starch glycolate, and cross-linked sodium carboxymethyl cellulose.

[0011] In step (2), the lubricant is one or two of talc, stearic acid, and polyethylene glycol.

[0012] In step (2), the extract, excipient, disintegrant and lubricant are mixed uniformly according to the formula to prepare granules or capsules.

[0013] The uric acid lowering drug based on steam-exploded dried bracken has a daily dosage of 67 mg of steam-exploded dried bracken water extract per kilogram of body weight, achieving a significant uric acid lowering effect.

[0014] The beneficial technical effects of the present invention are embodied in the following aspects: 1. The steam-exploded dried bracken water extract has the effect of significantly reducing the uric acid level of rats with high uric acid. The steam-exploded dried bracken water extract is used to steam-explode the dried bracken and then extract it with water to obtain the steam-exploded dried bracken water extract. The steam-exploded dried bracken water extract has a good uric acid-lowering effect and is used to prepare a uric acid-lowering drug with little toxicity and side effects and safe tolerance by patients.

[0015] The essence of steam explosion technology is to release the compressed gas that has penetrated into the plant tissue in a short period of time, with the purpose of decomposing the raw materials according to the purpose with less energy. The steam explosion machine suspends the raw materials in the container in the form of explosion in the atmosphere within milliseconds. Due to its short action time, high and concentrated energy density, steam molecules can penetrate between macromolecules such as cellulose and lignin, and can fully decompose the materials at the macromolecular level. At the same time, under the environment of high temperature, high pressure and water, the material molecules react to a certain extent, and the composition and material form change to a certain extent, creating basic conditions for later material processing. The use of this steam explosion principle and technology to process dried bracken solves the problem of slow dissolution of effective ingredients in dried bracken and low total dissolution. See Figure 1 The HPLC-DAD test results of the water extract of dried bracken before and after steam explosion showed that the HPLC fingerprints of dried bracken before and after steam explosion were very different. After the dried bracken was treated with high temperature and high pressure steam explosion, the types and quantities of small polar components in the water extract were significantly reduced. The types and quantities of small polar components in the water extract of dried bracken that had not been treated with high temperature and high pressure steam explosion were relatively large, indicating that steam explosion had a significant effect on the composition of the water extract of dried bracken. Steam explosion changed the composition of dried bracken, and this change was conducive to the formation of the uric acid-lowering effect of steam-exploded dried bracken water extract.

[0016] 2. The results of the acute toxicity test of steam-exploded dried bracken water extract prove that the steam-exploded dried bracken water extract of the present invention is non-toxic. The results of the animal test of steam-exploded dried bracken water extract tablets for lowering uric acid prove that the steam-exploded dried bracken water extract tablets of the present invention have similar uric acid lowering activity. (For details, see the subsequent acute toxicity test of steam-exploded dried bracken water extract and the animal test of steam-exploded dried bracken water extract tablets for lowering uric acid.) 3. The clinical trial results of steam-exploded dried bracken water extract tablets for lowering uric acid showed that taking 67 mg of steam-exploded dried bracken water extract per kilogram of body weight per day can achieve a significant effect of lowering uric acid. The specific experimental results are as follows: 21 patients with hyperuricemia were treated clinically; 19 males with an average age of 50 years old took 4-7 tablets three times a day for 10 consecutive days, and their uric acid levels were normal or basically normal. 2 females with an average age of 51 years old took 4-7 tablets three times a day for 10 consecutive days, and their uric acid levels were normal or basically normal. The acute toxicity test of steam-exploded dried bracken water extract is as follows:

[0017] 1 Materials and methods 1.1 Animals Kunming mice, weighing (20±2) g, half male and half female, were purchased from the Medical Experimental Animal Center of Nanjing Medical University and were kept in the laboratory for one week for adaptation.

[0018] 1.2 Preparation of steam-exploded dried bracken extract A method for preparing a steam-exploded dried bracken water extract according to the method of the following Example 1 is used to prepare a concentrated solution, and the concentrated solution is spray-dried to obtain a brown powdery steam-exploded dried bracken water extract.

[0019] 1.3 Animal experiment Forty mice weighing (20±2) g, half male and half female, were randomly divided into 4 groups according to Horn's method, which were respectively given 2.15, 4.64, 10.00 and 21.50 g / kg of steam-exploded dried bracken water extract groups; the mice were fasted but not watered for 16 h before gavage, and were given 40 ml / kg of steam-exploded dried bracken water extract of different concentrations by gavage according to the groups; after gavage, the mice's activity, diet, hair, defecation and urination and death were observed for 7 consecutive days. For the dead mice, the tissue changes of their main organs such as heart, liver, spleen, lung and kidney were observed by dissection; the mice that did not die were killed on the 8th day of the experiment, and the tissue changes of their main organs such as heart, liver, spleen, lung and kidney were observed by dissection.

[0020] 1.4 Statistical methods The data of each group were expressed as x±s, and the differences among the means of each group were analyzed by variance analysis using statistical software.

[0021] 2 Results 2.1 Effects on general physical signs of mice Four groups of mice were gavaged with steam-exploded dried bracken water extract at 2.15, 4.64, 10.00 and 21.50 g / kg, respectively. Within 10 minutes after gavage, the mice showed poor mental state and reduced activity. Ten minutes later, the mice were active again, which was considered to be due to the effects of gavage. After 7 consecutive days of observation, all the test mice had smooth fur, normal diet, activity and defecation, no abnormal secretions from the nose, eyes and mouth, and no adverse conditions occurred.

[0022] 2.2 Effects on the body weight of mice before and after administration As shown in Table 1, the steam-exploded dried bracken water extract groups had no effect on the body weight of mice ( P >0.05).

[0023]

[0024] 2.3 Death of mice Seven days after oral administration, the mice in each group appeared normal and no death was observed.

[0025] 2.4 Effects on the heart, liver, spleen, lungs, kidneys and other organs All mice were killed and after autopsy, no abnormal changes were found in the heart, liver, spleen, lungs, kidneys and stomach and other major organs of the mice in the steam-exploded bracken water extract groups.

[0026] From the above, it can be seen that the steam-exploded dried bracken water extract 2.15, 4.64, 10.00 and 21.5 g / kg oral administration of mice showed no abnormal symptoms, indicating that the steam-exploded dried bracken water extract has a LD50-fold increase in mice. 50 >21.50 g / kg, therefore, the steam-exploded dried bracken water extract is non-toxic.

[0027] Similarly, the concentrated solution was prepared by the method of the following Examples 2 to 8, and the concentrated solution was spray-dried to obtain a brown powdery steam-exploded bracken water extract. The acute toxicity test of the steam-exploded bracken water extract was carried out. The results showed that the dry bracken water extracts obtained in Examples 2 to 8 had an LD of 1.04 to 1.05 on mice. 50 >21.50 g / kg, therefore, the steam-exploded dried bracken water extract is non-toxic. Animal experiments on lowering uric acid using water extract tablets of dried bracken before and after steam explosion are as follows:

[0028] The steam-exploded dried bracken water extract tablets obtained in the following Example 1 were used in an animal experiment on the effect of lowering uric acid. The results showed that the steam-exploded dried bracken water extract tablets had a significant effect of lowering uric acid. The dried bracken obtained in the following Example 1 was cut into sections but not steam-exploded, and directly extracted with water to obtain a dried bracken water extract. The steam-exploded dried bracken water extract tablets were prepared according to the method of Example 1 and used in an animal experiment on the effect of lowering uric acid. The results showed that the unexploded dried bracken water extract tablets had no significant effect of lowering uric acid. The experimental process and conclusions are as follows:

[0029] 1 Materials and methods 1.1 Animals Rats Clean grade adult male Kunming rats were purchased from the Medical Experimental Animal Center of Nanjing Medical University.

[0030] 1.2 Instruments and reagents High-speed refrigerated centrifuge (Beckman, USA), ultra-low temperature refrigerator (Thermo, USA), electric constant temperature water thermostat (Shanghai Boxun Industrial Co., Ltd.), UV2100 ultraviolet-visible spectrophotometer (Beijing Rayleigh Analytical Instrument Co., Ltd.), uric acid test kit (Nanjing Jiancheng Bioengineering Institute), high yeast feed, adenine (SIGMA), allopurinol tablets (produced by Shanghai Xinyi Wanxiang Pharmaceutical Co., Ltd.); water was double-distilled water, homemade.

[0031] 1.3 Steam-exploded dried bracken water extract tablets The steam-exploded dried bracken water extract tablets obtained in Example 1 were crushed and dissolved in water for oral administration to rats.

[0032] 1.4 Non-steam-exploded dried bracken water extract tablets are prepared according to the above-mentioned “steam-exploded dried bracken water extract tablets”, except that the dried bracken is not steam-exploded.

[0033] 1.5 Experimental methods Rats were randomly divided into 9 groups, including blank control group, hyperuricemia group (model group), allopurinol group (positive drug group), steam-exploded bracken water extract tablets high, medium and low dose groups, and non-steam-exploded bracken water extract tablets high, medium and low dose groups. The model group was fed with 10% high yeast feed and given intragastric administration of adenine solution to prepare a hyperuricemia model; the control group was fed with ordinary rat pellet feed and given intragastric administration of the same volume of distilled water. The treatment group was given high-purine feed and adenine by intragastric administration, and was given high, medium and low doses of steam-exploded bracken water extract tablets and high, medium and low doses of non-steam-exploded bracken water extract tablets by intragastric administration. The dosage was the amount of dry bracken water extract in steam-exploded bracken water extract tablets and non-steam-exploded bracken water extract tablets. The high, medium and low doses were 0.8 g·kg -1 , 0.4g·kg -1 , 0.2g·kg -1 The experimental time was 30 days. Blood samples were collected from rats in each group 1 hour after administration of the corresponding drugs on the 10th, 20th and 30th days, and the blood samples were centrifuged (3000 r·min -1 , 10 min), take the supernatant and determine the uric acid content according to the instructions of the kit.

[0034] 1.6 Statistical methods The data of each group were expressed as x±s, and the differences among the means of each group were analyzed by variance analysis using statistical software.

[0035] 2 Experimental Results The results of blood sample analysis on days 10, 20, and 30 are shown in Table 2.

[0036]

[0037] As can be seen from Table 2, the high and medium dose groups of steam-exploded dried bracken water extract tablets administered for 10, 20, and 30 days had an excellent inhibitory effect on hyperuricemia in rats, and uric acid dropped to the level of uric acid in the blank control group ( P >0.05); the low-dose group had no significant inhibitory effect on hyperuricemia in rats after administration for 10, 20, and 30 days. Overall, there was a dose-effect relationship. The high, medium, and low-dose groups of non-steam-exploded dried bracken water extract tablets had no inhibitory effect on hyperuricemia in rats and no significant uric acid-lowering effect.

[0038] Similarly, the steam-exploded dried bracken water extract tablets obtained in the following Examples 2 to 8 were used in animal experiments on the anti-hyperuricemia effect in rats. The results showed that the steam-exploded dried bracken water extract tablets obtained in Examples 2 to 8 all had similar uric acid-lowering activity as the steam-exploded dried bracken water extract tablets obtained in Example 1. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 HPLC-DAD test results of water extract of dried bracken before and after steam explosion. DETAILED DESCRIPTION

[0040] The present invention will be described in further detail below in conjunction with the embodiments.

[0041] The fresh bracken used in the following examples is a plant of the genus Pteridaceae, Pteridaceae ( Pteridium aquilinum (L.) Kuhnvar. a little wider (Desv.) Underw. ex Heller) young leaves. Example 1

[0042] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash, and boil in water for 5 minutes at 80°C, and dry until the water content is 8.0% to obtain dried bracken; cut the dried bracken into 1 cm pieces.

[0043] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment in a steam explosion chamber at a pressure of 0.5 MPa for 60 seconds to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0044] Preparation of steam-exploded dried bracken extract 400 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 50° C. for 5 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 9.1 kg of brown powdered steam-exploded dried bracken water extract.

[0045] The water extract of steam-exploded dried bracken contains: 17.8% bracken polysaccharide by mass, 8.8% protein and small molecule peptides by mass, as well as a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0046] (4) Preparation of uric acid-lowering tablets Take 850g of steam-exploded dried bracken water extract, 110g of microcrystalline cellulose, 10g of cross-linked sodium carboxymethyl starch, 10g of sodium starch glycolate and 20g of talc, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator; and obtain granules.

[0047] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the mass of each tablet is 0.40 g, and the mass content of the steam-exploded dried bracken water extract in each tablet is 85%. Example 2

[0048] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash, and boil in water for 1 minute at 100°C, and dry until the water content is 13.0% to obtain dried bracken; cut the dried bracken into 5 cm pieces.

[0049] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment for 3 seconds in a steam explosion chamber under a pressure of 2.0 MPa to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0050] (3) Preparation of steam-exploded dried bracken water extract 400 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 50° C. for 5 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 12.3 kg of brown powdered steam-exploded dried bracken water extract.

[0051] The water extract of steam-exploded dried bracken contains: 21.9% bracken polysaccharide by mass, 7.9% protein and small molecule peptides by mass, and a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0052] (4) Preparation of uric acid-lowering tablets Take 800g of steam-exploded dried bracken water extract, 150g of microcrystalline cellulose, 10g of cross-linked sodium carboxymethyl starch, 20g of sodium starch glycolate and 20g of polyethylene glycol, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator to obtain granules.

[0053] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the weight of each tablet is 0.40 g, and the weight content of the steam-exploded dried bracken water extract in each tablet is 80%, and the tablets are packaged to prepare finished products. Example 3

[0054] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash it, and steam it for 7 minutes at a steam temperature of 100°C, and dry it to a moisture content of 9.5% to obtain dried bracken; cut the dried bracken into 4 cm pieces.

[0055] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment for 6 seconds in a steam explosion chamber under a pressure of 1.5 MPa to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0056] (3) Preparation of steam-exploded dried bracken water extract 800 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 100° C. for 2 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 10.5 kg of brown powdered steam-exploded dried bracken water extract.

[0057] The water extract of steam-exploded dried bracken contains: 31.1% bracken polysaccharide by mass, 5.1% protein and small molecule peptides by mass, and a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0058] (4) Preparation of uric acid-lowering tablets Take 880g of steam-exploded dried bracken water extract, 100g of microcrystalline cellulose, 5g of cross-linked sodium carboxymethyl starch, 10g of cross-linked sodium carboxymethyl cellulose and 5g of stearic acid, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator; and obtain granules.

[0059] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the mass of each tablet is 0.40 g, and the mass content of the steam-exploded dried bracken water extract in each tablet is 88%, and the tablets are packaged to prepare finished products. Example 4

[0060] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash it, and steam it for 3 minutes at a steam temperature of 130°C, and dry it to a water content of 10.2% to obtain dried bracken; cut the dried bracken into 3 cm pieces.

[0061] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment in a steam explosion chamber at a pressure of 2.0 MPa for 10 seconds to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0062] (3) Preparation of steam-exploded dried bracken water extract 600 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 50° C. for 5 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 9.6 kg of brown powdered steam-exploded dried bracken water extract.

[0063] The water extract of steam-exploded dried bracken contains: 37.3% bracken polysaccharide by mass, 5.6% protein and small molecule peptides by mass, and a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0064] (4) Preparation of uric acid-lowering tablets Take 880g of steam-exploded dried bracken water extract, 100g of microcrystalline cellulose, 5g of cross-linked sodium carboxymethyl starch, 10g of cross-linked sodium carboxymethyl cellulose, 2g of talc and 3g of stearic acid, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator to obtain granules.

[0065] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the mass of each tablet is 0.40 g, and the mass content of the steam-exploded dried bracken water extract in each tablet is 88%, and the tablets are packaged to prepare finished products. Example 5

[0066] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash, and boil in water for 4 minutes at 80°C, and dry to a water content of 8.1% to obtain dried bracken; cut the dried bracken into 2 cm pieces.

[0067] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment in a steam explosion chamber at a pressure of 1.0 MPa for 50 seconds to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0068] (3) Preparation of steam-exploded dried bracken water extract 600 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 60° C. for 4 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 11.2 kg of brown powdered steam-exploded dried bracken water extract.

[0069] The water extract of steam-exploded dried bracken contains: 39.9% bracken polysaccharide by mass, 4.3% protein and small molecule peptides by mass, and a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0070] (4) Preparation of uric acid-lowering tablets Take 800g of steam-exploded dried bracken water extract, 150g of microcrystalline cellulose, 20g of sodium starch glycolate, 10g of cross-linked sodium carboxymethyl cellulose, 10g of polyethylene glycol, and 10g of talc, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator to obtain granules.

[0071] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the weight of each tablet is 0.40 g, and the weight content of the steam-exploded dried bracken water extract in each tablet is 80%, and the tablets are packaged to prepare finished products. Example 6

[0072] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash, and boil in water for 3 minutes at 100°C, and dry to a water content of 11.9% to obtain dried bracken; cut the dried bracken into 5 cm pieces.

[0073] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment in a steam explosion chamber at a pressure of 1.5 MPa for 40 seconds to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0074] (3) Preparation of steam-exploded dried bracken water extract 800 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 100° C. for 3 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 13.2 kg of brown powdered steam-exploded dried bracken water extract.

[0075] The water extract of steam-exploded dried bracken contains: 29.4% bracken polysaccharide by mass, 8.5% protein and small molecule peptides by mass, and a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0076] (4) Preparation of uric acid-lowering tablets Take 850g of steam-exploded dried bracken water extract, 110g of microcrystalline cellulose, 10g of sodium starch glycolate, 10g of cross-linked sodium carboxymethyl starch and 20g of talc, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator; and obtain granules.

[0077] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the weight of each tablet is 0.40 g, and the weight content of the steam-exploded dried bracken water extract in each tablet is 85%, and the tablets are packaged to prepare finished products. Example 7

[0078] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash it, and steam-sterilize it at 130°C for 5 minutes, then dry it to a moisture content of 8.8% to obtain dried bracken; cut the dried bracken into 4 cm pieces.

[0079] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment in a steam explosion chamber at a pressure of 1.0 MPa for 30 seconds to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0080] (3) Preparation of steam-exploded dried bracken water extract 400 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 70° C. for 4 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 9.9 kg of brown powdered steam-exploded dried bracken water extract.

[0081] The water extract of steam-exploded dried bracken contains: 44.5% bracken polysaccharide by mass, 5.8% protein and small molecule peptides by mass, as well as a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0082] (4) Preparation of uric acid-lowering tablets Take 880g of bracken water extract, 100g of microcrystalline cellulose, 5g of cross-linked sodium carboxymethyl starch, 10g of cross-linked sodium carboxymethyl starch, 2g of polyethylene glycol and 3g of stearic acid, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator to obtain granules.

[0083] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the mass of each tablet is 0.40 g, and the mass content of bracken water extract in each tablet is 88%, and the tablets are packaged to prepare finished products. Example 8

[0084] The preparation of the uric acid-lowering drug based on the steam-exploded dried bracken water extract is as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash it, and steam-sterilize it at 100°C for 6 minutes, then dry it to a moisture content of 12.1% to obtain dried bracken; cut the dried bracken into 3 cm pieces.

[0085] (2) Steam explosion treatment 40 kg of chopped dried bracken was subjected to steam explosion and pressure-maintaining treatment in a steam explosion chamber at a pressure of 1.0 MPa for 60 seconds to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dry bracken added is not less than 1 / 3 of the steam explosion chamber.

[0086] (3) Preparation of steam-exploded dried bracken water extract 600 kg of water was added to 40 kg of steam-exploded dried bracken, and the mixture was refluxed and extracted at 100° C. for 3 hours. The filtrate was filtered, concentrated under reduced pressure, and spray-dried to obtain 8.1 kg of brown powdered steam-exploded dried bracken water extract.

[0087] The water extract of steam-exploded dried bracken contains: 44.9% bracken polysaccharide by mass, 4.8% protein and small molecule peptide by mass, and a certain amount of small molecule substances such as cryptochlorogenic acid, costus lactone, citric acid, shikimic acid, dextrorotatory quinic acid, neochlorogenic acid, and protocatechuic aldehyde.

[0088] (4) Preparation of uric acid-lowering tablets Take 800g of bracken water extract, 150g of microcrystalline cellulose, 20g of sodium starch glycolate, 10g of cross-linked sodium carboxymethyl cellulose and 20g of polyethylene glycol, mix them evenly; add appropriate amount of water to granulate; granulate with a granulator; and obtain granules.

[0089] The granules are compressed by a tablet press to prepare uric acid lowering tablets; the weight of each tablet is 0.40 g, and the weight content of the steam-exploded dried bracken water extract in each tablet is 80%, and the tablets are packaged to prepare finished products.

[0090] It is easy for those skilled in the art to understand that the above embodiments 1-8 are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a uric acid-lowering drug based on steam-exploded dried bracken, characterized in that: The steps are as follows: (1) Pretreatment of fresh bracken Remove yellow leaves and impurities from the fresh bracken, wash, boil or steam to kill the green, and dry to a water content of 8-13% to obtain dried bracken; cut the dried bracken into 1-5 cm pieces; The fresh bracken is a plant of the genus Pteridaceae, Pteridaceae ( Pteridium aquilinum (L.) Kuhn var. latiusculum (Desv.) Underw. ex Heller) young leaves; (2) Steam explosion treatment The chopped dried bracken is subjected to steam explosion and pressure-maintaining treatment for 3-60 seconds in a steam explosion chamber under a pressure of 0.5-2.0 MPa to obtain steam-exploded dried bracken; In the steam explosion chamber, the amount of chopped dried bracken added is not less than 1 / 3 of the steam explosion chamber; (3) Preparation of steam-exploded dried bracken water extract The steam-exploded dried bracken is refluxed with water, the amount of water added is 10-20 times the weight of the dried bracken, the extraction water temperature is 50°C-100°C, and the extraction time is 2-5 hours; Filter to obtain a filtrate; concentrate the filtrate under reduced pressure at a concentration temperature not exceeding 90° C. to obtain a concentrated solution; spray dry the concentrated solution to obtain a brown powdery steam-exploded dried bracken water extract; The steam-exploded dried bracken water extract contains: 17.8-44.9% by weight of bracken polysaccharide, 4.1-8.8% by weight of protein and small molecule peptides; (4) Preparation of uric acid-lowering tablets 80-88% steam-exploded dried bracken water extract, 10-15% excipient, 1.5-3% disintegrant and 0.5-2% lubricant are mixed evenly, an appropriate amount of water is added, granules are obtained by a granulator, and tablets are pressed by a tablet press to obtain uric acid-lowering tablets; The mass of each tablet is 0.40 g, and the mass content of steam-exploded dried bracken water extract in each tablet is 80-88%; The uric acid lowering drug, at a daily dosage of 67 mg of steam-exploded dried bracken water extract per kilogram of body weight, achieves a significant uric acid lowering effect.

2. A method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (1), the fresh bracken is young leaves of a fern in the tender leaf curling period picked in April or May each year, specifically, young leaves of a fern with petioles that grow 15 to 25 cm above the ground.

3. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (1), the water boiling and killing is carried out at a temperature of 80-100° C. and a time of 1-5 minutes.

4. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (1), the steam killing is carried out at a temperature of 100-130° C. and a time of 3-7 minutes.

5. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (2), the excipient is microcrystalline cellulose.

6. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (2), the disintegrant is two of cross-linked sodium carboxymethyl starch, sodium starch glycolate, and cross-linked sodium carboxymethyl cellulose.

7. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (2), the lubricant is one or two of talc, stearic acid, and polyethylene glycol.

8. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: In step (2), the extract, excipient, disintegrant and lubricant are mixed uniformly according to the formula to prepare granules or capsules.

9. The method for preparing a uric acid-lowering drug based on steam-exploded dried bracken according to claim 1, characterized in that: The uric acid lowering drug based on steam-exploded dried bracken has a daily dosage of 67 mg of steam-exploded dried bracken water extract per kilogram of body weight, achieving a significant uric acid lowering effect.

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