Application of Traditional Chinese Medicine Composition in Preparation of Medicine for Preventing and Treating Hyperuricemia

Abstract

The present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating hyperuricemia; the traditional Chinese medicine composition comprises the following active ingredients: bupleurum, ganoderma lucidum, salvia miltiorrhiza, and schizandra chinensis. The present invention verifies through animal experiments that the above traditional Chinese medicine composition can reduce the contents of uric acid and urea nitrogen in the serum of hyperuricemic rats, and at the same time can reduce the level of xanthine oxidase in the serum of rats, improve the kidney injury of hyperuricemic rats, and proves that the above traditional Chinese medicine composition can prevent and treat hyperuricemia, improve the excretion of uric acid, and at the same time can also improve kidney function.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly to the application of a traditional Chinese medicine composition in the preparation of a medicament for preventing and treating hyperuricemia. Background Art

[0002] Hyperuricemia is a chronic disease caused by purine metabolism disorder and abnormal uric acid excretion in the body. Excessive production or insufficient excretion of uric acid in the body can lead to hyperuricemia, and then form gout and other diseases, which is extremely harmful to human health.

[0003] Xanthine oxidase (XOD) is a very important enzyme in the body's uric acid metabolism. It catalyzes the oxidation of hypoxanthine to xanthine, and further catalyzes the oxidation of xanthine to uric acid. When the uric acid concentration is too high, it will lead to hyperuricemia. Therefore, inhibiting the activity of XOD can, to a certain extent, inhibit the occurrence of hyperuricemia.

[0004] Currently, the most commonly used western medicine preparations for reducing uric acid are divided into two categories: one is to inhibit uric acid production, and the other is to promote uric acid excretion. Although these western medicine preparations can effectively reduce the serum uric acid level, they have certain limitations and side effects. Long-term use will cause abnormal conditions such as bone marrow suppression, renal toxicity and hypersensitivity syndrome in patients. Therefore, it is necessary to find a safer and more effective drug for the treatment of hyperuricemia. Summary of the Invention

[0005] In view of this, the technical problem to be solved by the present invention is to provide the application of a traditional Chinese medicine composition in the preparation of a medicament for preventing and treating hyperuricemia, providing a new treatment approach for hyperuricemia.

[0006] The present invention provides the application of a traditional Chinese medicine composition in the preparation of a medicament for preventing and treating hyperuricemia;

[0007] The traditional Chinese medicine composition comprises the following active ingredients: Bupleurum chinense, Ganoderma lucidum, Salvia miltiorrhiza, Schisandra chinensis.

[0008] The preferred ratio of each component of the above active components is as follows:

[0009] 200 - 350 parts by weight of Bupleurum chinense; 150 - 200 parts by weight of Ganoderma lucidum; 300 - 400 parts by weight of Salvia miltiorrhiza; 300 - 400 parts by weight of Schisandra chinensis.

[0010] Further preferably, the ratio of each component of the above active components is preferably as follows:

[0011] 340 - 350 parts by weight of Bupleurum chinense, 170 - 180 parts by weight of Ganoderma lucidum, 340 - 350 parts by weight of Salvia miltiorrhiza, 340 - 350 parts by weight of Schisandra chinensis.

[0012] In some specific embodiments of the present invention, the ratio of each component of the above active components is preferably as follows:

[0013] 342 parts by weight of Bupleurum chinense, 173 parts by weight of Ganoderma lucidum, 342 parts by weight of Salvia miltiorrhiza, and 342 parts by weight of Schisandra chinensis.

[0014] The present invention has no special limitation on the dosage form of the above traditional Chinese medicine composition, including but not limited to conventional applicable dosage forms in the art such as tablets, pills, capsules, powders, oral liquids, etc.

[0015] Optionally, the traditional Chinese medicine composition is Wuling Capsule.

[0016] Optionally, the prevention and treatment include inhibiting the activity of xanthine oxidase.

[0017] Optionally, the inhibition of xanthine oxidase activity includes inhibiting the activity of xanthine oxidase in serum.

[0018] Optionally, the prevention and treatment include reducing the levels of uric acid and / or urea nitrogen.

[0019] Optionally, the prevention and treatment include improving the kidney damage of patients with hyperuricemia.

[0020] Optionally, the improvement of the kidney damage of patients with hyperuricemia includes reducing the dilation of renal tubule lumen and / or edema.

[0021] Compared with the prior art, the present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating hyperuricemia; the traditional Chinese medicine composition includes the following active ingredients: Bupleurum chinense, Ganoderma lucidum, Salvia miltiorrhiza, and Schisandra chinensis. The present invention verifies through animal experiments that the above traditional Chinese medicine composition can reduce the contents of uric acid and urea nitrogen in the serum of rats with hyperuricemia, and at the same time can reduce the level of xanthine oxidase in the serum of rats, and improve the kidney damage of rats with hyperuricemia, confirming that the above traditional Chinese medicine composition can prevent and treat hyperuricemia, improve the excretion of uric acid, and at the same time can also improve kidney function. Description of the Drawings

[0022] Figure 1 Effect of Wuling Capsule on the body weight and organ index of rats with hyperuricemia (n = 6);

[0023] Figure 2 Effect of Wuling Capsule on uric acid, urea nitrogen, and xanthine oxidase in rats with hyperuricemia (n = 4);

[0024] Figure 3 Effect of Wuling Capsule on the liver and kidney tissue pathology of rats with hyperuricemia (n = 3). Detailed Embodiments

[0025] To further illustrate the present invention, the application of the traditional Chinese medicine composition provided by the present invention in the preparation of a drug for preventing and treating gouty arthritis will be described in detail below in conjunction with embodiments.

[0026] Example 1 Evaluation of the Effect of Wuling Capsules on Rats with Hyperuricemia

[0027] 1 Materials

[0028] 1.1 Test Drugs

[0029] Wuling Capsule powder (batch number: 220812), Qinghua Deren Xi'an Xingfu Pharmaceutical Co., Ltd. 36 clean-grade male SD rats, weighing (220±20) g, were all purchased from Chengdu Dashuo Experimental Animal Co., Ltd.

[0030] 1.2 Reagents

[0031] Hypoxanthine (product number: S18025-100g), potassium oxonate (product number: S17112-100g), Shanghai Yuanye Bio-Technology Co., Ltd. Uric acid test kit, urea nitrogen test kit, xanthine oxidase determination kit (product numbers: C012-2-01, C013-2-1, A002-1-1) were all purchased from Nanjing Jiancheng Bioengineering Research Institute. Absolute ethanol, xylene, neutral gum (batch numbers: 100092683, 10023418, 10004160), Sinopharm Chemical Reagent Co., Ltd. HE staining solution set (batch number: G1003), Servicebio Company.

[0032] 1.3 Instruments

[0033] Thermo an GO 1510 full-wavelength microplate reader, Micro17R micro refrigerated centrifuge, Thermo Scientific Forma 900 Series -80°C ultra-low temperature freezer, Thermo Fisher Scientific; IX73 inverted microscope, Olympus Microscopy Technologies; ME204 / 02 electronic balance, Leica CM1860UV cryostat, Leica Biosysterms Nussloch GmbH; UXFSTPRP-64 high-speed centrifugal grinder, Eppendorf.

[0034] 2 Methods

[0035] 2.1 Establishment of a Rat Model of Hyperuricemia and Administration

[0036] Establishment of a hyperuricemia rat model. There were six rats in each group. After seven days of adaptive feeding, the rats in the blank group and the model group were intragastrically administered normal saline every afternoon, while the rats in the intervention group were intragastrically administered the corresponding drugs. Wuling Capsule was administered at a clinical dosage of 5.5 g / 70 kg. Converted to the dosage for rats, the low-dose group of Wuling Capsule was (0.25 g / kg), the medium-dose group was (0.5 g / kg), the high-dose group was (1.0 g / kg), and the allopurinol group was (27 mg / kg). After seven days of pre-protection, 500 mg / kg of hypoxanthine was intragastrically administered every morning for seven consecutive days, with the solvent being 5% CMC-Na solution. Potassium oxonate solution at 100 mg / kg was intraperitoneally injected, and 0.9% normal saline was used. On the 14th day, the liver, spleen, and kidneys were taken for weighing analysis, and blood was taken from the abdominal aorta, centrifuged, and the serum was stored at -80°C for later use.

[0037] 2.2 Effects of Wuling Capsule on the body weight and organ indices of hyperuricemia rats

[0038] On the 7th day of modeling, the animals in each group were euthanized 4 h after the last intraperitoneal injection for modeling, and then blood was taken from the abdominal aorta. The liver, kidney, and spleen tissues were dissected and weighed.

[0039] 2.3 Effects of Wuling Capsule on uric acid, urea nitrogen, and xanthine oxidase in hyperuricemia rats

[0040] After taking the blood of the rats, the serum was obtained by centrifugation. The centrifugation speed was 3000 revolutions for 10 minutes. The contents of uric acid, urea nitrogen, and xanthine oxidase in the rat serum were detected according to the kits of Nanjing Jiancheng Bioengineering Institute.

[0041] 2.4 Effects of Wuling Capsule on the liver and kidney tissue pathology of hyperuricemia rats

[0042] After taking out the liver and kidneys of the rats, the right kidney and liver of the rats were fixed in paraformaldehyde for animal tissue section analysis. The rat kidney and liver tissues were cleaned, embedded in paraffin, sectioned with a microtome, dewaxed with xylene I and xylene II for 15 min respectively, and rehydrated with gradient ethanol from high to low for 5 min each. Then the sections were stained with hematoxylin solution for 3 - 5 min, rinsed with pure water, differentiated with the differentiating solution, rinsed with pure water and then stained with eosin for 4 min, blued with the bluing solution, rinsed, dehydrated with gradient ethanol from low to high, and finally cleared with xylene and sealed with neutral resin. The pathological changes of the rat joints were observed under a light microscope, and images were collected for analysis.

[0043] 2.5 Statistical methods

[0044] All data are presented as the mean ± SD of at least three independent experiments. One-way analysis of variance (ANOVA) was used for comparison of means. The results were statistically analyzed using GraphPad Prism Version 9. P < 0.05 was considered statistically significant.

[0045] 3 Results

[0046] 3.1 Effects of Wuling Capsule on body weight and organ indices of hyperuricemia rats

[0047] The study found that there were no significant differences in liver indices among groups ( Figure 1 A); compared with the control group, the kidney index and spleen index of the model group were significantly increased, and there was a certain improvement after administration of medium-dose Wuling Capsule ( Figure 1 B, 1C); there were no significant differences in the body weight changes of rats among groups during the experimental period ( Figure 1 D). Figure 1 In, compared with the blank group: ## P < 0.01, compared with the model group; * P < 0.05, ** P < 0.01.

[0048] 3.2 Effects of Wuling Capsule on levels of uric acid, urea nitrogen, and xanthine oxidase in serum of hyperuricemia rats

[0049] As Figure 2 shown, compared with the control group, the levels of uric acid, urea nitrogen, and xanthine oxidase in the serum of rats in the model group were significantly increased. Administration of each dose of Wuling Capsule could significantly reduce the levels of uric acid and urea nitrogen and inhibit the activity of xanthine oxidase. These results indicate that Wuling Capsule has a certain uric acid-lowering effect. Figure 2 In, compared with the blank group: ### P < 0.001, compared with the model group; * P < 0.05, ** P < 0.01 ** , P < 0.001.

[0050] 3.3 Effects of Wuling Capsule on liver and kidney tissue pathology of hyperuricemia rats

[0051] In this study, HE staining was performed on the liver and kidney tissues of hyperuricemia rats. The results of histopathological analysis showed that there were no obvious changes in the liver tissues of the blank group, model group, and each administration group, indicating that this model did not cause obvious damage to the liver ( Figure 3 A). As Figure 3As shown in Figure B, pathological observation of kidney tissues found that, compared with the blank group, the aggregated secretions in the renal tubules of rats in the model group increased, with a lighter color, obvious local lumen dilation of the renal tubules, accompanied by local edema. After treatment with different doses of Wuling Capsule, the lumen dilation and edema of the renal tubules decreased. This result indicates that Wuling Capsule has a certain ameliorating effect on kidney injury in hyperuricemia rats.

[0052] 4 Summary

[0053] The above experimental results show that Wuling Capsule has a certain inhibitory effect on the uric acid and blood urea nitrogen levels in hyperuricemia rats, an inhibitory effect on the activity of xanthine oxidase, and a certain ameliorating effect on kidney injury, preliminarily confirming that Wuling Capsule has a certain uric acid-lowering effect on hyperuricemia rats.

[0054] The description of the above embodiments is only used to help understand the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating hyperuricemia, wherein the traditional Chinese medicine composition is composed of the following active ingredients: 342 parts by weight of Bupleurum chinense DC., 173 parts by weight of Ganoderma lucidum, 342 parts by weight of Salvia miltiorrhiza Bunge, 342 parts by weight of Schisandra chinensis (Turcz.) Baill.

2. The application according to claim 1, wherein The dosage form of the traditional Chinese medicine composition is tablet, pill, capsule, powder, oral liquid.

3. The application according to claim 2, characterized in that, The traditional Chinese medicine composition is Wuling Capsule.

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