A Chinese medicine preparation for treating hyperuricemia and gout

Abstract

The present invention provides a Chinese medicine preparation for treating hyperuricemia and gout, and relates to the technical field of Chinese medicine pharmaceutical manufacturing. The Chinese medicine preparation is composed of papaya, stir-fried coix seeds, rose, angelica, stir-fried burdock seeds, thistle, dandelion, flat chrysanthemum Panax notoginseng, rattan tea, tangerine peel, ginseng, and jujube, which are the main ingredients. Each Chinese medicine composition is reasonably compatible according to the principle of Chinese medicine dialectical treatment, and each medicine is synergistically enhanced, with the effects of clearing away heat and dampness, promoting blood circulation and detoxifying, invigorating the spleen and replenishing qi, and eliminating pain and purging turbidity. The Chinese medicine preparation of the present invention has a significant uric acid-lowering effect, significantly reduces the organ index of the kidney, reduces the SCr, BUN, SUA levels in serum, and the XOD and ADA activities in liver homogenate, improves the pathological morphology of kidney tissue, and has a significant improvement effect on gouty nephropathy. At the same time, it can significantly improve the clinical symptoms of patients, alleviate the pain of patients, and has a more obvious uric acid-lowering effect.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine pharmaceutical preparations, and in particular to a traditional Chinese medicine preparation for treating hyperuricemia and gout. Background Art

[0002] In recent years, people's living standards have improved, and they have consumed more high-purine foods in their daily diet, resulting in an increasing incidence of hyperuricemia at a younger age. The prevention and treatment of primary hyperuricemia has become a public health issue of global concern. Under a normal purine diet, if the fasting blood uric acid level is >420μmol / L for men and >360μmol / L for women on two different days, hyperuricemia can be diagnosed. Hyperuricemia can cause gout, affect joint health, and can also lead to kidney disease, kidney stones, and renal failure, increasing the risk of cardiovascular and cerebrovascular diseases, diabetes and other diseases. Treating and reducing the occurrence of hyperuricemia is an important problem that needs to be solved urgently.

[0003] Gout is a well-known difficult and complicated disease due to its high incidence, difficulty in cure, high recurrence rate after recovery, and multiple complications. Common gout treatment drugs include the following categories: (1) drugs that promote uric acid excretion, such as probenecid and benzbromarone; (2) drugs that inhibit uric acid production, such as allopurinol; (3) drugs that inhibit granulocyte infiltration, such as colchicine; (4) non-steroidal anti-inflammatory drugs, such as acetaminophen; (5) adrenocortical hormones, such as prednisone; (6) drugs that alkalinize urine, such as sodium bicarbonate. The above drugs are effective in the treatment of gout and can achieve significant results in a short period of time, but they usually have large side effects, which are common in gastrointestinal disorders, liver and kidney damage, rashes, dermatitis, etc., especially after stopping the drug, it is easy to relapse, so it is not a fundamental solution.

[0004] With the development of traditional Chinese medicine, people have gradually come to know that traditional Chinese medicine has a series of advantages, such as multiple pathways, multiple targets, variable formulations, low product cost, and few toxic and side effects. In recent years, many studies have confirmed that traditional Chinese medicine plays a significant role in the treatment of hyperuricemia. Hyperuricemia is a disease name in Western medicine, and there is no such thing as hyperuricemia in traditional Chinese medicine. The ancients classified it into the categories of Lijie, Bizheng, Linzheng, and edema in traditional Chinese medicine based on the arthritis or kidney damage caused by it, and the subsequent symptoms such as joint pain, urinary tract stones, and edema. Traditional Chinese medicine believes that the spleen is responsible for transporting and transforming water and dampness. If the spleen is deficient and fails to transport, dampness will be generated endogenously, and dampness will turn into heat or gather phlegm. After a long time, it will enter the collaterals and become stasis, leading to dampness, heat, phlegm, and stasis, or blood stasis or stagnation of meridians and joints to induce this disease and gout. Therefore, traditional Chinese medicine believes that the disease is located in the tendons and bones, and the root of the disease is the spleen and kidney. The pathogenesis is a mixture of deficiency and excess, with spleen and kidney deficiency as the basis, dampness, heat, phlegm and blood stasis as the symptoms, and improper diet, emotional frustration, and excessive work and rest as the inducement. The main treatment principles are to tonify the kidney and spleen, clear away heat and dampness, and remove phlegm and blood stasis. At present, many traditional Chinese medicine preparations for the treatment of hyperuricemia and gout have been reported, but they often have problems such as complex formulas, high costs, and uncertain efficacy. Summary of the invention

[0005] 1. Technical issues to be solved

[0006] In view of the deficiencies in the prior art, the present invention provides a traditional Chinese medicine preparation for treating hyperuricemia and gout, which has significant therapeutic effects, treats both the symptoms and the root causes, and has the effects of clearing away heat and dampness, promoting blood circulation and detoxifying, strengthening the spleen and replenishing qi, and relieving pain and purging turbidity.

[0007] (II) Technical solution

[0008] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0009] On the one hand, the present invention provides a traditional Chinese medicine preparation for treating hyperuricemia and gout, wherein the traditional Chinese medicine preparation is composed of the following components by weight: 10-30g of papaya, 10-30g of fried coix seed, 5-25g of rose, 5-25g of angelica, 10-30g of fried burdock fruit, 10-30g of chicory, 5-25g of dandelion, 3-15g of chrysanthemum notoginseng, 5-15g of rattan tea, 5-20g of tangerine peel, 5-15g of ginseng, and 5-25g of jujube.

[0010] Furthermore, the Chinese medicine preparation is composed of the following components by weight: 15-25g papaya, 15-25g fried coix seed, 10-20g rose, 10-20g angelica, 15-25g fried burdock fruit, 15-25g thistle, 10-20g dandelion, 3-10g flat chrysanthemum Panax notoginseng, 5-10g rattan tea, 5-15g tangerine peel, 5-10g ginseng, and 10-20g jujube.

[0011] Furthermore, the Chinese medicine preparation is composed of the following components by weight: 20g papaya, 20g fried coix seed, 15g rose, 15g angelica, 20g fried burdock fruit, 20g thistle, 15g dandelion, 6g chrysanthemum notoginseng, 5g rattan tea, 10g tangerine peel, 5g ginseng, and 15g jujube.

[0012] The above-mentioned Chinese medicine preparations are prepared into any drug form acceptable to the human body according to conventional methods, including but not limited to oral liquid, granules, capsules, decoctions, and freeze-dried powders.

[0013] Pharmacological effects of the Chinese medicinal materials involved in the Chinese medicine preparation of the present invention:

[0014] Papaya: sour in taste, warm in nature, and enters the liver and spleen meridians; it has the effects of relaxing muscles and tendons, harmonizing the stomach and eliminating dampness; it is used to treat dampness, stiffness, soreness and pain in the waist and knee joints, cramps, gastric ulcers, asthma and other diseases; papaya contains a variety of natural active ingredients such as polyphenols, polysaccharides, flavonoids, organic acids, vitamins, etc.; it has multiple physiological functions such as antibacterial, antioxidant, anti-inflammatory and analgesic.

[0015] Fried coix seed: sweet, light in taste, cool in nature, and enters the spleen, stomach, and lung meridians; it has the effects of promoting diuresis, penetrating dampness, strengthening the spleen and stopping diarrhea, detoxifying and dispersing nodules; it is used to treat edema, dysuria, spleen deficiency diarrhea, dampness and cramps, lung abscess, intestinal abscess and other diseases; coix seed contains fatty acids and esters, polysaccharides, flavonoids, triterpenes, alkaloids, sterols, lactams, starch and other compounds, which have the effects of inhibiting skeletal muscle contraction, relieving fever, analgesia, anti-inflammatory, anti-tumor and enhancing immune function.

[0016] Rose: slightly bitter in taste, warm in nature; enters the liver and spleen meridians; promotes qi and relieves depression, harmonizes blood and disperses blood stasis; used for liver and stomach pain, new and long-term rheumatism, vomiting blood and hemoptysis, irregular menstruation, leucorrhea, dysentery, breast abscess, and swelling; rose mainly contains flavonoids, volatile oils and aromatics, polysaccharides, polyphenols, fatty acids and other effective ingredients, which have antioxidant, antibacterial, lipid-lowering, blood sugar-lowering, and anti-tumor pharmacological effects.

[0017] Angelica: sweet and spicy in taste, neutral in nature, enters the liver, heart and spleen meridians, has the effects of nourishing blood and activating blood circulation, regulating menstruation and relieving pain, moistening the intestines and promoting bowel movements; often used for blood deficiency and sallow complexion, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatism and pain, injuries from falls, carbuncles, ulcers, dry intestines and constipation and other symptoms; Angelica mainly contains volatile oils, organic acids, polysaccharides, flavonoids, amino acids, and various trace elements and other effective ingredients, has antioxidant, liver protection, anti-inflammatory, hematopoietic promotion, liver protection and kidney strengthening effects and other effects.

[0018] Fried burdock seeds: spicy and bitter in taste, cold in nature, and enter the lung and stomach meridians; it has the effects of dispersing wind-heat, promoting lung function and relieving sore throat, detoxifying and clearing rashes, reducing swelling and treating sores; it is used for wind-heat colds, the initial stage of febrile diseases, measles that does not break out, carbuncles, sores and other symptoms; the main ingredients in burdock seeds include lignans, volatile oils, fatty oils and terpenes. Modern research shows that burdock seeds have antibacterial, anti-inflammatory, antiviral, anti-tumor, and blood sugar-lowering pharmacological effects.

[0019] Thistle: sweet and bitter in taste, cool in nature, enters the heart and liver meridians; has the effects of cooling blood and stopping bleeding, dispersing blood stasis, detoxifying and eliminating carbuncle; used for epistaxis, hematemesis, hematuria, hematuria, bloody stool, metrorrhagia, traumatic bleeding, carbuncle, sore and other symptoms; Thistle mainly contains chemical components such as flavonoids, lignans, triterpenes and steroids, volatile oils, long-chain alkyne enol and aldehyde alkaloids and organic acid compounds; it has pharmacological effects such as hemostasis and coagulation, antibacterial and anti-inflammatory, and anti-cancer.

[0020] Dandelion: bitter and sweet, cold in nature, enters the liver and stomach meridians; has the effects of clearing away heat and detoxifying, reducing swelling and dispersing knots, diuresis and relieving stranguria; used for carbuncle, breast abscess, scrofula, red eyes, sore throat, lung abscess, intestinal abscess, damp-heat jaundice, hot stranguria and other diseases; it contains flavonoids, coumarins, phenolic acids, terpenes, sterols and polysaccharides and other effective ingredients. Clinical studies have shown that it has antibacterial, antioxidant, anti-inflammatory, anti-tumor gastrointestinal protection and other pharmacological effects

[0021] Flat Chrysanthemum Panax Notoginseng: Sweet and mild in taste, neutral in nature, can promote blood circulation, relieve inflammation and cough, dissipate blood stasis and reduce swelling, and promote blood circulation and tissue regeneration. It can be used for cooking or medicinal purposes, and has the effects of lowering blood lipids, blood pressure, and blood sugar. It can supplement calcium, resist influenza and hepatitis B virus, resist colds, and improve human immunity. It has good effects on herpes zoster, various dermatitis, scalds, burns, and unknown swelling and pain when used externally. It can also stop bleeding, relieve pain, relieve itching, protect skin and moisturize, and resist aging.

[0022] Rattan tea: sweet and light in taste, cool in nature; has the effects of clearing away heat and detoxifying, calming the liver and lowering blood pressure, promoting blood circulation and dredge channels; used to treat icteric hepatitis, wind-heat cold, sore throat and other symptoms; rattan tea mainly contains flavonoids, phenols, steroids and terpenes, volatile components, etc.; modern pharmacological research shows that rattan tea has anti-inflammatory and analgesic, antibacterial, antioxidant, anti-tumor, liver protection, lipid-lowering, blood sugar-lowering, and immunity-enhancing effects.

[0023] Tangerine peel: bitter and spicy in taste, warm in nature, and enters the lung and spleen meridians; it has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm; it is used to treat symptoms such as abdominal distension, loss of appetite, vomiting and diarrhea, cough and excessive sputum; tangerine peel mainly contains volatile oils, flavonoids, organic amines and trace elements; it has pharmacological effects such as insecticidal and inhibition of microbial activity, anti-aging and antioxidant.

[0024] Ginseng: warm in nature, sweet and slightly bitter in taste, enters the spleen and lung meridians; has the effects of greatly replenishing vital energy, restoring the pulse and strengthening the body, nourishing the spleen and lungs, promoting body fluid, and calming the mind; used for physical weakness and collapse, cold limbs and weak pulse, spleen deficiency and poor appetite, lung deficiency and wheezing and coughing, and thirst due to loss of body fluid; its main physiologically active ingredients are triterpenoid saponins, flavonoids, phenols and polysaccharide compounds; has pharmacological effects such as anti-fatigue, enhancing the body's immunity, promoting hematopoietic function, anti-inflammatory, anti-allergic, and anti-tumor.

[0025] Jujube: sweet in taste, warm in nature, and enters the spleen and stomach meridians; it has the effects of tonifying the spleen and stomach, replenishing Qi and promoting body fluid, regulating the Ying and Wei, and detoxifying; it is used to treat stomach deficiency, poor appetite, weak spleen and loose stools, insufficient Qi and blood, disharmony between the Ying and Wei, palpitations and other symptoms; jujube is rich in nutrients, including amino acids, sugars, vitamins and various trace elements, and contains a large amount of nucleotide derivatives. Jujube has a good auxiliary therapeutic effect on diseases such as tumors, hypertension, hypercholesterolemia, and has the effects of delaying aging, anti-oxidation, improving immunity, protecting the liver, etc.

[0026] (III) Beneficial effects

[0027] The invention provides a Chinese medicine preparation for treating hyperuricemia and gout. The Chinese medicine preparation is composed of papaya, stir-fried coix seeds, rose, angelica, stir-fried burdock seeds, thistle, dandelion, flat chrysanthemum sanqi, rattan tea, tangerine peel, ginseng, and jujube, which are the main ingredients. The Chinese medicine preparation is reasonably matched according to the principle of Chinese medicine dialectical treatment, and the drugs are synergistic. In the prescription, papaya, stir-fried coix seeds, rose, and angelica are the main drugs, which can play the effects of removing dampness and purging turbidity, promoting blood circulation and relaxing muscles. Stir-fried burdock seeds, thistle, dandelion, flat chrysanthemum sanqi, and rattan tea are the assistant drugs, which have the functions of clearing heat and detoxifying, removing dampness and lowering turbidity. Tangerine peel, ginseng, and jujube are used as adjuvant drugs, which have the functions of regulating qi and strengthening the spleen. The drugs are used together to play the functions of clearing heat and removing dampness, promoting blood circulation and detoxifying, strengthening the spleen and replenishing qi, and eliminating pain and purging turbidity. Animal experiments have well verified that the Chinese medicine preparation of the present invention has a significant uric acid-lowering effect on the animal model of gouty nephropathy, can significantly improve the coat color and mental state of the model mice, significantly reduce the organ index of the kidney, reduce the levels of SCr, BUN, SUA in serum and the activity of XOD and ADA in liver homogenate, and improve the pathological morphology of kidney tissue. The above results show that the Chinese medicine preparation of the present invention has a significant improvement effect on gouty nephropathy. At the same time, the Chinese medicine preparation of the present invention can significantly improve the clinical symptoms of patients, relieve the pain of patients, and has a more obvious uric acid-lowering effect. The Chinese medicine preparation of the present invention provides a new treatment plan for hyperuricemia and gout, and has a good application prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The diagrams are the tissue case status of mice in each group, wherein a is a blank group; b is a model group; c is a Tongfengshu tablet group; d is a low-dose group of the Chinese medicine preparation of the present invention; and e is a high-dose group of the Chinese medicine preparation of the present invention. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Example 1

[0031] A traditional Chinese medicine preparation for treating hyperuricemia and gout, the traditional Chinese medicine preparation is composed of the following components by weight: 10g of papaya, 10g of stir-fried coix seeds, 5g of rose, 5g of angelica, 10g of stir-fried burdock seeds, 10g of chicory, 5g of dandelion, 3g of chrysanthemum notoginseng, 5g of rattan tea, 5g of tangerine peel, 5g of ginseng, and 5g of jujube.

[0032] The above-mentioned Chinese medicine preparations are prepared into any drug form acceptable to the human body according to conventional methods, including but not limited to oral liquid, granules, capsules, decoctions, and freeze-dried powders.

[0033] Example 2

[0034] The difference between this embodiment and embodiment 1 is that:

[0035] The Chinese medicine preparation is composed of the following components by weight: 30g papaya, 30g fried coix seed, 25g rose, 25g angelica, 30g fried burdock fruit, 30g thistle, 25g dandelion, 15g flat chrysanthemum Panax notoginseng, 15g rattan tea, 20g tangerine peel, 15g ginseng, and 25g jujube.

[0036] Example 3

[0037] The difference between this embodiment and embodiment 1 is that:

[0038] The Chinese medicine preparation is composed of the following components by weight: 26g papaya, 18g fried coix seed, 22g rose, 14g angelica, 26g fried burdock fruit, 14g thistle, 8g dandelion, 12g flat chrysanthemum Panax notoginseng, 12g rattan tea, 8g tangerine peel, 12g ginseng, and 8g jujube.

[0039] Example 4

[0040] The difference between this embodiment and embodiment 1 is that:

[0041] The Chinese medicine preparation is composed of the following components by weight: 15g papaya, 15g fried coix seed, 10g rose, 10g angelica, 15g fried burdock fruit, 15g thistle, 10g dandelion, 3g flat chrysanthemum Panax notoginseng, 5g rattan tea, 5g tangerine peel, 5g ginseng, and 10g jujube.

[0042] Example 5

[0043] The difference between this embodiment and embodiment 1 is that:

[0044] The Chinese medicine preparation is composed of the following components by weight: 25g papaya, 25g fried coix seed, 20g rose, 20g angelica, 25g fried burdock fruit, 25g thistle, 20g dandelion, 10g flat chrysanthemum Panax notoginseng, 10g rattan tea, 15g tangerine peel, 10g ginseng, and 20g jujube.

[0045] Example 6

[0046] The difference between this embodiment and embodiment 1 is that:

[0047] The Chinese medicine preparation is composed of the following components by weight: 22g papaya, 18g fried coix seed, 12g rose, 18g angelica, 18g fried burdock fruit, 18g thistle, 14g dandelion, 5g chrysanthemum and notoginseng, 8g rattan tea, 9g tangerine peel, 7g ginseng, and 12g jujube.

[0048] Example 7

[0049] The difference between this embodiment and embodiment 1 is that:

[0050] 20g papaya, 20g fried coix seed, 15g rose, 15g angelica, 20g fried burdock seed, 20g chicory, 15g dandelion, 6g flat chrysanthemum and Panax notoginseng, 5g rattan tea, 10g tangerine peel, 5g ginseng, and 15g jujube.

[0051] Test Example 1

[0052] The Chinese medicine components of the present invention are reasonably matched, and the effects of each medicine are fully exerted. The medicines work together to enhance the efficacy. The composition of the Chinese medicine preparation of the present invention is adjusted many times and experiments are carried out. Here, only multiple groups of prescriptions with higher efficacy are listed and compared with the prescription of the present invention. The specific formula composition is shown in Table 1.

[0053] Table 1 Specific composition and weight of formula 1-6 (g)

[0054]

[0055]

[0056] 1 Experimental Materials

[0057] 1.1 Experimental animals: Healthy KM (Kunming) mice, male, SPF (specific pathogen free), weight 20-22g, 6-8 weeks old, provided by Shandong Jinan Pengyue Experimental Animal Breeding Co., Ltd. (License: SCXK (Lu) 20190003), Animal Certificate No.: 3370726221100429688. Laboratory Animal Use Permit: SYXK (Yu) 2021-0015, Animal Experiment Training No.: NO00826. Animals were kept in an environment of (23±1)℃, relative humidity (55±15)%, and 12h cycle light conditions, with free access to food and water.

[0058] 1.2 Experimental drugs: According to the formula of each group in Table 1, weigh the raw materials respectively, grind into powder, add 10 times (m / V) amount of distilled water to the drug, soak for 30 minutes, boil for 1 hour, get the filtrate, add 8 times amount of distilled water again and boil for 1 hour, combine the filtrate, concentrate to 220mL, make the concentration to 2.11g / mL, and put it in a 4℃ refrigerator for use.

[0059] 2 Model establishment and group processing

[0060] Healthy male Kunming mice were given potassium oxonate (450 mg / kg) by oral gavage daily for 7 consecutive days. One hour before each modeling, they were deprived of water but not food.

[0061] The experiment was set up as a blank group, a model group, a Chinese medicine control group, and experimental groups 1-6. There were 10 mice in each group. Except for the blank group, which was given the same amount of normal saline, the mice in the other groups were given potassium oxonate to construct a hyperuricemia model. The Chinese medicine control group was given Tongfengshu tablets (0.82 / kg), and the experimental groups 1-6 corresponded to the Chinese medicine stock solution of formula 1-6 (19.38g / kg) by gavage. After 5 days of administration, each group of mice was placed in a metabolic cage to collect urine for 24 hours. On the 7th day of the experiment, 2 hours after administration, the eyeballs were aseptically removed to obtain blood and kidney tissue, and the serum was separated and stored for later use.

[0062] 3. Detection indicators

[0063] The uric acid levels in the blood and urine of each group of mice were measured using an ELISA uric acid kit and a biochemical analyzer, respectively, according to the operating steps in the kit instructions.

[0064] 4 Data processing and statistics

[0065] The experimental data were analyzed using GraphPad Prism v.9.0 (GraphPad Software Inc, San Diego, CA, USA) statistical software. One-way ANOVA was used for inter-group analysis. Brown-Forsythe and Welch ANOVA tests were used for analysis of unequal variances. P < 0.05 was considered to be significantly different, and P < 0.01 was considered to be significantly different.

[0066] 5 Results

[0067] Table 2 shows the results of uric acid and urea nitrogen content determination in each group of mice. The uric acid and urea nitrogen content in the model group increased significantly compared with the blank group (P < 0.01). Compared with the model group, the uric acid and urea nitrogen content in the Chinese medicine control group and experimental groups 1-6 decreased significantly after drug treatment. Compared with the model group, the uric acid and urea nitrogen content in the experimental group 1 decreased significantly, with extremely significant differences (P < 0.01), and the uric acid and urea nitrogen content in the Chinese medicine control group also decreased significantly (P < 0.05); but the decrease in each index in the experimental group 1 was greater than that in the Chinese medicine control group. The uric acid and urea nitrogen content in the experimental groups 2-6 also decreased, but there was no significant difference between the experimental groups 2-3 and the model group, and the uric acid and urea nitrogen content in the experimental group 1 was significantly lower than that in the experimental groups 2-6. The above results indicate that the Chinese medicine preparation of the present invention has a significant effect of lowering uric acid and has obvious effects of preventing and treating gout. The various Chinese medicines in the Chinese medicine preparation are rationally combined according to the principle of Chinese medicine dialectical treatment. The various drugs have synergistic effects, and none of the ingredients in the formula can be missing.

[0068] Table 2 Results of determination of uric acid and urea nitrogen content in mice in each group

[0069]

[0070] Note: * represents P < 0.05 compared with the model group; ** represents P < 0.01 compared with the model group.

[0071] Test Example 2

[0072] 1 Experimental Materials

[0073] 1.1 Experimental animals

[0074] 108 KM (Kunming) mice, male, SPF (specific pathogen free), 20-22 g, 6-8 weeks old, provided by Shandong Jinan Pengyue Experimental Animal Breeding Co., Ltd. (License: SCXK (Lu) 20190003), Animal Certificate No.: 3370726221100429688. Laboratory Animal Use License: SYXK (Yu) 2021-0015, Animal Experiment Training No.: NO00826. Animals were kept in an environment of (23 ± 1) °C, relative humidity (55 ± 15)%, and 12 h of light cycle, with free access to food and water.

[0075] 1.2 Experimental Reagents

[0076] Serum uric acid (UA) ELISA detection kit, catalog number: E20220601A, Suzhou Calvin Biotechnology Co., Ltd., batch number: E20220601A; serum creatinine (Cr) ELISA detection kit, Suzhou Calvin Biotechnology Co., Ltd., batch number: E20220601A; adenosine dehydrogenase (ADA) ELISA detection kit, Suzhou Calvin Biotechnology Co., Ltd., batch number: E20220601A; drugs: potassium oxonate (batch number 6231021), Beijing Solebao Biotechnology Co., Ltd.; adenine (batch number 1014G051), Beijing Solebao Biotechnology Co., Ltd.

[0077] 1.3 Experimental drugs

[0078] Tongfengshu tablets (batch number 20211001), Shanxi Renyuantang Pharmaceutical Co., Ltd.

[0079] The Chinese medicine preparation of the present invention comprises: 20 grams of papaya, 20 grams of stir-fried coix seeds, 15 grams of rose, 15 grams of angelica, 20 grams of stir-fried burdock seeds, 20 grams of thistle, 15 grams of dandelion, 6 grams of flat chrysanthemum and notoginseng, 5 grams of rattan tea, 10 grams of tangerine peel, 5 grams of ginseng, and 15 grams of jujube. The Chinese herbal medicines were purchased from Henan Zhang Zhongjing Pharmacy, and the relevant Chinese herbal medicines were identified by Professor Dai Liping of Henan University of Traditional Chinese Medicine.

[0080] 1.4 Experimental instruments

[0081] AR1140 / C electronic balance (Ohaus, Shanghai); precision balance (JA1103N), Henan Zhongliang Scientific Instrument Co., Ltd.; grinder (JXFSTPRP-48), Shanghai Jingxin Industrial Development Co., Ltd.; CYT3MFVDG microplate reader (BioTekInstruments, USA); KDC-160HR high-speed refrigerated centrifuge (Hunan Xiangyi Experimental Instrument Development Co., Ltd.); adjustable pipette, Shanghai Leibo Analytical Instrument Co., Ltd.

[0082] 2 Experimental methods

[0083] 2.1 Drug preparation

[0084] Adenine (60 mg kg -1 ) and potassium oxonate (200 mg kg -1 ) were prepared according to the dosage volume of 0.2 ml / 10 g. All drugs were prepared to the required concentration using pure water as the solvent.

[0085] Weigh each Chinese medicinal material according to the weight proportions described in 1.3, add 10 times (m / V) amount of distilled water, soak for 30 min, decoct for 1 h, obtain a filtrate, add 8 times amount of distilled water again and decoct for 1 h, combine the filtrates, concentrate to 220 mL, make the concentration to 2.11 g / mL, and place in a refrigerator at 4 degrees Celsius for standby use, which is the original solution of the Chinese medicine preparation of the present invention.

[0086] 2.2 Animal grouping, modeling and drug administration

[0087] 2.2.1 Animal grouping

[0088] 108 Kunming (KM) mice, SPF (specific pathogen free) grade, male, 20-22 g, were randomly divided into 9 groups after adaptive feeding for 3 days, namely, blank group, model group, positive control group (Tongfengshu tablets group), high-dose group of the Chinese medicine preparation of the present invention, and low-dose group of the Chinese medicine preparation of the present invention, with 12 mice in each group.

[0089] 2.2.2 Establishment of animal model

[0090] During the experiment, the blank group was gavaged with an equal volume of pure water, and the mice in the other groups were given adenine (60 mg kg -1 ) and potassium oxonate (200 mg kg -1 ) The model was established by intragastric administration, with the administration volume of 0.2 ml / 10 g, once a day for 21 consecutive days to create a mouse gouty nephropathy model. After 14 consecutive days, UA, Cr, and BUN were significantly increased, indicating that the model was successfully established.

[0091] 2.2.3 Drug administration

[0092] From the 14th day of modeling, the blank group and the model group were given the same volume (solvent) of pure water, and the administration volume was 0.2ml / 10g. The remaining groups of mice were given corresponding drugs by gavage: Tongfengshu tablets group (0.45g / kg), high-dose group of the Chinese medicine preparation of the present invention (19.38g / kg), and low-dose group of the Chinese medicine preparation of the present invention (9.69g / kg) were treated. Each group was administered for a total of 14 days, and the experiment lasted for a total of 28 days. The samples were collected 1 hour after the last administration (fasting for 12 hours).

[0093] 2.3 Detection indicators

[0094] 2.3.1 Renal Index

[0095] During the experiment, all mouse kidneys were removed and weighed, and the mouse kidney index was calculated. The calculation method is as follows:

[0096] Renal index = renal treatment (mg) / body weight (g)

[0097] 2.3.2 Determination of serum biochemical indexes

[0098] One hour after the last administration, the animals were weighed and the eyeballs were removed to collect blood. The blood sample was placed in a static chamber for 30 minutes, and the serum was separated (3500rm, 4°C, 10 minutes) and stored at -40°C for testing. The levels of SUA, blood uric acid, SCr, and BUN in the serum were determined according to the kit instructions.

[0099] 2.3.3 Determination of liver tissue homogenate parameters

[0100] The abdominal cavity was opened, and the mouse liver was quickly taken out. A small part was cut and mixed with normal saline in a ratio of 1:9, and homogenized on ice. The blood sample was allowed to stand for 30 min in the blood sample chamber and centrifuged (3500 rm, 4°C, 10 min). The contents of XOD xanthine oxidase and ADA adenosine deaminase in liver tissue homogenate were measured by ELISA kit.

[0101] 2.3.4 Renal pathological morphology

[0102] The left kidney was fixed in 10% formalin solution, embedded in paraffin, sectioned, and stained using hematoxylin-eosin (HE) staining. The histomorphological changes of mice in each group were observed under an optical microscope.

[0103] 2.4 Data processing and statistics

[0104] The experimental data were analyzed using GraphPad Prism v.9.0 (GraphPad Software Inc, San Diego, CA, USA) statistical software. One-way ANOVA was used for inter-group analysis. Brown-Forsythe and Welch ANOVA tests were used for analysis of unequal variances. P < 0.05 was considered to be significantly different, and P < 0.01 was considered to be significantly different.

[0105] 3 Experimental results

[0106] 3.1 Effect of the Chinese medicine preparation of the present invention on renal index of gouty nephropathy mouse model

[0107] The organ indexes of mice in each group are shown in Table 3. The results showed that compared with the blank group, the kidney index of the model group mice increased significantly (P < 0.01), indicating that the gouty nephropathy model was successfully established. Compared with the model group, the Tongfengshu tablet group, the low-dose group of the Chinese medicine preparation of the present invention, and the high-dose group of the Chinese medicine preparation of the present invention can significantly reduce the kidney index of hyperuricemia mice (P < 0.01).

[0108] Table 3 Effects of Xiaotong Xiezhuo Decoction on renal index of hyperuricemia mice ( n=10)

[0109]

[0110] Note: * represents P < 0.05 compared with the model group; ** represents P < 0.01 compared with the model group.

[0111] 3.2 Effect of the Chinese medicine preparation of the present invention on serum BUN, SUA and Cr in mice with gouty nephropathy

[0112] Compared with the blank group, the serum BUN, SUA and SCr levels of the mice in the model group increased significantly (P < 0.05). Compared with the model group, the serum BUN, SUA and Cr levels of the mice in the Tongfengshu tablet group, the high-dose group of the Chinese medicine preparation of the present invention and the low-dose group of the Chinese medicine preparation of the present invention decreased significantly (P < 0.05). As shown in Table 4.

[0113] Table 4 Effects of the Chinese medicine preparation of the present invention on serum BUN, SUA and SCr in hyperuricemia mice ( n=10)

[0114]

[0115] Note: * represents P < 0.05 compared with the model group; ** represents P < 0.01 compared with the model group.

[0116] 3.3 Effect of the Chinese medicine preparation of the present invention on XOD and ADA in the liver of mice with gouty nephropathy

[0117] As can be seen from Table 5, compared with the blank group, the content of XOD xanthine oxidase and ADA adenosine deaminase in the liver of the model group mice increased significantly (P < 0.05). Compared with the model group, the levels of XOD and ADA in the kidney of the Tongfengshu tablet group and the high-dose group of the Chinese medicine preparation of the present invention mice decreased significantly (P < 0.05).

[0118] Table 5 Effects of the Chinese medicine preparation of the present invention on XOD and ADA in the liver of hyperuricemia mice ( n=10)

[0119]

[0120] Note: * represents P < 0.05 compared with the model group; ** represents P < 0.01 compared with the model group.

[0121] 3.4 Effect of the Chinese medicine preparation of the present invention on the renal tissue pathological morphology of mice with gouty nephropathy

[0122] According to the different morphologies of renal tissue pathology, it is divided into four grades: "-" there is no obvious change in the volume of the renal capsule cavity and glomerulus, there is no congestion and swelling of the tubular interstitium, and there is no infiltration of inflammatory cells; "+10" the renal capsule cavity is slightly narrowed, the glomerulus volume is slightly increased, there is no congestion and swelling of the tubular interstitium, and there is no infiltration of inflammatory cells; "+10" the renal capsule cavity is narrowed, the glomerulus volume is increased, there is a small amount of congestion and swelling in the tubular interstitium, and there is a small amount of inflammatory cell infiltration; "+10000" the renal capsule cavity almost disappears, the glomerulus volume is significantly increased, the tubular interstitium is congested and swollen, vacuolar degeneration, and there is a large amount of inflammatory cell infiltration.

[0123] From the results obtained, we can see that all groups have 10 mice. There are 10 mice in the blank group with "-" level, a total of 10 mice; there are 1 mouse in the model group with "+" level, 2 mice in the "+10+10" level, and 3 mice in the "+10+10" level; there are 6 mice in the Tongfengshu tablets group with "-" level, 3 mice with "+10", and 1 mouse with "+10+10"; there are 3 mice in the low-dose Xiaotong Xiezhuo prescription group with "-" level, 3 mice in the "+10" level, 2 mice in the "+10+10" level, and 2 mice in the "+10+10" level; there are 4 mice in the high-dose Xiaotong Xiezhuo prescription group with "-" level, 4 mice in the "+10" level, and 2 mice in the "+10+10" level.

[0124] The renal tissue of the blank group mice was in normal morphology, and the model group showed changes in the volume of the renal capsule cavity and glomerulus of the mice, and more than half of the mice had congestion and swelling of the tubular interstitium, vacuolar degeneration, and a large number of inflammatory cells infiltrated. The low-dose group of the Chinese medicine preparation of the present invention and the high-dose group of the Chinese medicine preparation of the present invention can improve the above phenomenon of the model group, indicating that the Chinese medicine preparation of the present invention has the effect of improving kidney damage caused by gout.

[0125] The pathological changes of the mice in each group are shown in Table 6, and the pathological changes of the mice in each group are shown in Figure 1 .

[0126] Table 6 Effect of the Chinese medicine preparation of the present invention on renal pathological tissues in hyperuricemia mice

[0127]

[0128] 4 Discussion

[0129] In this experiment, a gouty nephropathy mouse model was established by oral administration of potassium oxonate combined with adenine. By observing the changes in serum levels of the mouse model before and after administration, it was shown that the Chinese medicine preparation of the present invention had different degrees of uric acid lowering effects on the gouty nephropathy animal model. Compared with the model group, the low-dose and high-dose groups of the Chinese medicine preparation of the present invention could significantly improve the coat color and mental state of the model mice, significantly reduce the organ index of the kidney, reduce the levels of SCr, BUN, and SUA in serum, and the activity of XOD and ADA in liver homogenate, and improve the pathological morphology of kidney tissue. The above results show that the Chinese medicine preparation of the present invention has an improving effect on gouty nephropathy.

[0130] Clinical Application

[0131] 1 Clinical Data

[0132] 1.1 Diagnostic criteria: (1) Typical acute arthritis attacks that terminate on their own and enter a symptom-free interval, and hyperuricemia is confirmed; (2) Urate crystals are found in joint effusions or white blood cells; (3) Uric acid crystals are found in gout nodules. Anyone who meets any of the above three conditions can be diagnosed with gout.

[0133] 1.2 Inclusion criteria

[0134] All cases that met the diagnostic criteria in Section 1.1 were included, and the serum uric acid level was above the normal range.

[0135] 2 Treatment methods

[0136] Experimental group: The Chinese medicine decoction prepared by the formula of Example 7 was administered orally, one dose per day, for 14 days. Control group: Tongfengshu tablets, 0.3 g per tablet, orally, 2 to 4 tablets at a time, 3 times a day, for 14 days. 3. Efficacy observation and standard

[0137] Refer to the "Guidelines for Clinical Research of New Chinese Medicines". Markedly effective: clinical symptoms and signs disappear, joint function basically returns to normal, blood uric acid significantly decreases, male <350umol / L, female <300umol / L, or blood uric acid decreases by >35% compared with before treatment; effective: clinical symptoms and signs improve, joint function improves, male blood uric acid rises to 350-417umol / L, female blood uric acid drops to 300-357umol / L, or blood uric acid decreases by 220% compared with before treatment, and erythrocyte sedimentation rate decreases; ineffective: clinical symptoms and signs have no significant changes or worsening, blood uric acid does not decrease or decreases by <20%, and erythrocyte sedimentation rate has no significant changes or worsening.

[0138] 4 Treatment results

[0139] As shown in Table 7, the Chinese medicine preparation of the present invention has a high total effective rate for the treatment of gout patients, which is much higher than the control Chinese medicine Tongfengshu tablets. The Chinese medicine preparation of the present invention can significantly improve the clinical symptoms of patients, relieve the pain of patients, and has a more obvious effect of reducing blood uric acid. The Chinese medicine preparation of the present invention provides a new treatment plan for hyperuricemia and gout, and has a good application prospect.

[0140] Table 7 Clinical efficacy results

[0141] Grouping Number of observations Significant effect efficient invalid Total Effectiveness Experimental Group 70 33 31 6 91.43％ Control group 70 26 28 12 77.14％

[0142] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicine preparation for treating hyperuricemia and gout, characterized in that: The Chinese medicine preparation is composed of the following components by weight: 10-30g of papaya, 10-30g of fried coix seeds, 5-25g of rose, 5-25g of angelica, 10-30g of fried burdock seeds, 10-30g of chicory, 5-25g of dandelion, 3-15g of chrysanthemum notoginseng, 5-15g of rattan tea, 5-20g of tangerine peel, 5-15g of ginseng, and 5-25g of jujube.

2. A Chinese medicine preparation for treating hyperuricemia and gout according to claim 1, characterized in that: The Chinese medicine preparation is composed of the following components by weight: 15-25g of papaya, 15-25g of fried coix seeds, 10-20g of rose, 10-20g of angelica, 15-25g of fried burdock seeds, 15-25g of chicory, 10-20g of dandelion, 3-10g of flat chrysanthemum and Panax notoginseng, 5-10g of rattan tea, 5-15g of tangerine peel, 5-10g of ginseng, and 10-20g of jujube.

3. A Chinese medicine preparation for treating hyperuricemia and gout according to claim 1, characterized in that: The Chinese medicine preparation is composed of the following components by weight: 20g papaya, 20g fried coix seed, 15g rose, 15g angelica, 20g fried burdock fruit, 20g thistle, 15g dandelion, 6g flat chrysanthemum and Panax notoginseng, 5g rattan tea, 10g tangerine peel, 5g ginseng, and 15g jujube.

4. A Chinese medicine preparation for treating hyperuricemia and gout as claimed in any one of claims 1 to 3, characterized in that: The above-mentioned Chinese medicine preparations are prepared into any drug form acceptable to the human body according to conventional methods, including but not limited to oral liquid, granules, capsules, decoctions, and freeze-dried powders.

Images