A uric acid-lowering pharmaceutical composition and its preparation method, application and product

Abstract

The present invention provides a uric acid-lowering pharmaceutical composition and its preparation method, application and product, belonging to the field of medicine. The uric acid-lowering pharmaceutical composition is composed of component A and component B, wherein component A is composed of 5 parts of Tripterygium wilfordii, 30 parts of Smilax glabra, 15 parts of Viscum album, 15 parts of Astragalus membranaceus, 15 parts of Salvia miltiorrhiza, 30 parts of Coix seeds and 10 parts of Gentiana macrophylla; component B is a xanthine oxidase inhibitor, and the xanthine oxidase inhibitor is allopurinol or febuxostat. The present invention adopts xanthine oxidase inhibitor and Chinese medicine components Tripterygium wilfordii, Smilax glabra, Viscum album, Astragalus membranaceus, Salvia miltiorrhiza, Coix seeds and Gentiana macrophylla to act together, and multiple components work together to significantly reduce blood uric acid levels, can be used to treat hyperuricemia, can improve renal function and pathology at the same time, reduce side effects, and provide a basis for the clinical use of Chinese medicine compositions and xanthine oxidase inhibitors.

Description

Technical Field

[0001] The present invention belongs to the field of medicine and relates to a uric acid-lowering pharmaceutical composition, and specifically relates to a uric acid-lowering pharmaceutical composition and a preparation method, application and product thereof. Background Art

[0002] Hyperuricemia is a metabolic syndrome caused by purine metabolism disorders. Regardless of whether it is a man or a woman, if the blood uric acid level exceeds 420 µmol / L (7 mg / dL) twice on different days, it can be diagnosed as hyperuricemia. Hyperuricemia without gout attacks is called asymptomatic hyperuricemia. In recent years, with the rapid economic development and changes in lifestyle, the incidence of hyperuricemia has increased significantly and is becoming younger. Hyperuricemia is not only a key risk factor for gout, but is also closely related to kidney disease, hypertension, diabetes, cardiovascular disease, etc., which seriously threatens human health.

[0003] Effectively lowering uric acid levels is the key to reducing the risk of gout and preventing the development of complications. Modern medicine has many drugs for treating hyperuricemia, such as Febuxostat and Allopurinol, which inhibit uric acid production; Benzbromarone, which promotes uric acid excretion, etc. However, long-term use has multiple side effects such as gastrointestinal discomfort, rash, bone marrow suppression, liver and kidney damage, etc.

[0004] Chinese patent application CN102309705B discloses the use of a Chinese medicine composition to reduce blood uric acid. The test results show that the Chinese medicine composition has a regulatory effect on blood lipids and lipid metabolism disorders in the liver of hyperlipidemia rats, can protect liver cells and inhibit fatty degeneration, and has a good clinical effect on patients with hyperuricemia or combined hyperlipidemia, but its uric acid-lowering effect needs to be further improved.

[0005] Due to the above problems, the uric acid-lowering effect of drugs currently used to treat hyperuricemia still needs to be further improved, and there is still a phenomenon in clinical practice that patients are not sensitive to drug treatment. Therefore, actively seeking safe, cheap, and effective drugs to prevent and treat elevated uric acid and improve the rate of uric acid reaching the target has important clinical value and public health significance. Summary of the invention

[0006] The present invention aims at the problems existing in the prior art and provides a uric acid-lowering pharmaceutical composition and its preparation method, application and product. The present invention adopts a Chinese medicine composition and a xanthine oxidase inhibitor to act together, which can significantly reduce serum uric acid levels, improve kidney function and pathology, and reduce side effects, providing a basis for the clinical use of a Chinese medicine composition and a xanthine oxidase inhibitor.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] In a first aspect, the present invention provides a uric acid-lowering pharmaceutical composition, which is composed of component A and component B, wherein component A is composed of 5 parts of Trillium gracile, 30 parts of Smilax glabra, 15 parts of Morus alba, 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Coix seeds and 10 parts of Gentiana macrophylla;

[0009] The component B is a xanthine oxidase inhibitor, and the xanthine oxidase inhibitor is allopurinol or febuxostat;

[0010] When the xanthine oxidase inhibitor in the component B is allopurinol, the mass ratio of the component A to allopurinol is 1000:0.1-0.4;

[0011] When the xanthine oxidase inhibitor in the component B is febuxostat, the mass ratio of the component A to febuxostat is 1000:0.02-0.1.

[0012] Preferably, the xanthine oxidase inhibitor in the component B is allopurinol, and the mass ratio of the component A to allopurinol is 1000:1.2.

[0013] Preferably, the xanthine oxidase inhibitor in the component B is febuxostat, and the mass ratio of the component A to febuxostat is 1000:0.24.

[0014] In the pharmaceutical composition, the xanthine oxidase inhibitor and the traditional Chinese medicine components Trillium gracile, Smilax glabra, Viscum album, Astragalus membranaceus, Salvia miltiorrhiza, Coix seeds, and Gentiana macrophylla work together to treat hyperuricemia and improve the liver and kidney function damage caused by hyperuricemia.

[0015] In a second aspect, the present invention provides a method for preparing the pharmaceutical composition according to the above technical solution, comprising the following steps:

[0016] 1) decocting component A in water to obtain a decoction, concentrating and drying the decoction to obtain a dry paste powder;

[0017] 2) Mixing the obtained dry paste powder with component B to obtain a pharmaceutical composition.

[0018] Step 1) specifically comprises: decocting component A in water to obtain a decoction; the number of decoctions is 1-4 times, preferably 2 times; the time of each decoction is 1-3 hours, preferably 1.5 hours; then concentrating the decoction, the density of the concentrated decoction is 1.1-1.3, to obtain a clear paste, and drying the clear paste to obtain a dry paste powder.

[0019] In one embodiment, component A is first soaked in water for 1-3 hours, preferably 1 hour, and then boiled in water to obtain a decoction; the number of water decoctions is 1-4 times, preferably 2 times; the time of each water decoction is 1-3 hours, preferably 1.5 hours; then the decoction is concentrated, and the density of the concentrated decoction is 1.1-1.3 to obtain a clear paste, and the clear paste is dried and crushed to obtain a dry paste powder.

[0020] Step 2) specifically comprises: mixing the obtained dry paste powder with component B to obtain a pharmaceutical composition.

[0021] Preferably, the xanthine oxidase inhibitor in component B is allopurinol, and the mass ratio of dry cream powder to allopurinol is 1000:0.6-1.8, preferably 1000:1.2.

[0022] Preferably, the xanthine oxidase inhibitor in component B is febuxostat, and the mass ratio of dry cream powder to febuxostat is 1000:0.12-0.48, preferably 1000:0.24.

[0023] In a third aspect, the present invention provides an application of the pharmaceutical composition described in the above technical scheme or the pharmaceutical composition prepared by the preparation method described in the above technical scheme in the preparation of drugs for lowering blood uric acid and / or improving liver and kidney function. Preferably, the improvement of liver and kidney function is to improve liver and kidney inflammation or liver and kidney fibrosis.

[0024] In a fourth aspect, the present invention provides a drug, comprising the drug composition described in the above technical solution or the drug composition prepared by the preparation method described in the above technical solution, and excipients.

[0025] The excipients are any one or more pharmaceutical excipients commonly used in the technical field and are not limited here.

[0026] The drug may be in any dosage form, including but not limited to: powder, granules, capsules, tablets, pills, injections or oral solutions.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The invention adopts the xanthine oxidase inhibitor and the Chinese medicinal components Trillium gracile, Smilax glabra, Morus alba, Astragalus, Salvia miltiorrhiza, Coix seeds and Gentiana macrophylla to work together, and the multi-components work synergistically, can significantly reduce the blood uric acid level, can be used to treat hyperuricemia, can improve kidney function and pathology, and reduce side effects, and provide a basis for the clinical use of the Chinese medicinal composition and the xanthine oxidase inhibitor in combination. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 H&E stained mouse kidney pathology. DETAILED DESCRIPTION

[0030] It is worth noting that, unless otherwise specified, the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0031] The following sources of raw materials are provided for illustrative purposes:

[0032] Allopurinol: Allopurinol tablets, white tablets, specification: 0.1 g / tablet, batch number: 20230106, purchased from Hefei Jiulian Pharmaceutical Co., Ltd.

[0033] Febuxostat: Febuxostat tablets, white tablets, specification: 0.04 g / tablet, batch number: 624057012, purchased from Jiangsu Wanbang Biochemical Pharmaceutical Group Co., Ltd.

[0034] Basic Example 1

[0035] Preparation of dry paste powder

[0036] Prescription for component A: 5 parts of Trillium gracile, 30 parts of Smilax glabra, 15 parts of Viscum album, 15 parts of raw Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Coix seeds, and 10 parts of Gentiana macrophylla.

[0037] Preparation method of dry paste powder: according to the prescription ratio, take 120kg of component A, add 10 times the amount of water, decoct twice, soak for 1 hour before decoction, decoct for 1.5 hours for the first time, and decoct for 1.5 hours for the second time, collect the two decoctions, centrifuge, centrifuge speed 3000rpm, centrifuge time 20min; take the centrifuge and concentrate it to a clear paste with a relative density of 1.1-1.3 (60℃). Take the clear paste, vacuum dry, crush, and get the first batch of dry paste powder 25kg (extraction rate is about 21%). Prepare 5 batches of dry paste powder according to the above method, mix them, and get dry paste powder.

[0038] Example 1

[0039] 33.6 g of the dry powder prepared in Basic Example 1 was taken and mixed evenly with 20 mg of allopurinol to obtain a pharmaceutical composition.

[0040] Example 2

[0041] 33.6 g of the dry powder prepared in Basic Example 1 was taken and mixed evenly with 40 mg of allopurinol to obtain a pharmaceutical composition.

[0042] Example 3

[0043] 33.6 g of the dry powder prepared in Basic Example 1 was taken and mixed evenly with 60 mg of allopurinol to obtain a pharmaceutical composition.

[0044] Example 4

[0045] 33.6 g of the dry powder prepared in Basic Example 1 was taken and mixed evenly with 4 mg of febuxostat to obtain a pharmaceutical composition.

[0046] Example 5

[0047] 33.6 g of the dry powder prepared in Basic Example 1 was taken and mixed evenly with 8 mg of febuxostat to obtain a pharmaceutical composition.

[0048] Example 6

[0049] 33.6 g of the dry powder prepared in Basic Example 1 was taken and mixed evenly with 16 mg of febuxostat to obtain a pharmaceutical composition.

[0050] Test Example 1

[0051] Uric acid lowering effect of pharmaceutical composition

[0052] 1. Experimental methods

[0053] 1.1 Cell lines

[0054] Rat renal tubular epithelial NRK-52E cells were purchased from the Cell Resource Center of Shanghai Institute for Biological Sciences, Chinese Academy of Sciences.

[0055] 1.2 Reagents

[0056] Penicillin was purchased from BBI Life Science; streptomycin and trypsin were purchased from Amresco; DMEM culture medium and fetal bovine serum were purchased from Gibco; CCK-8 kit was purchased from Dojindo; UA was purchased from Sigma, USA.

[0057] 1.3 CCK-8 assay to detect cell proliferation activity in each group

[0058] 100 μL of cells in logarithmic growth phase were inoculated into 96-well cell culture plates per well. After culturing the cells for 48 h, serum-free culture medium was replaced and starved for 12 h, and the culture medium was discarded. A blank control group, a Chinese medicine composition group (500 μg / mL), allopurinol 1-3 groups (allopurinol group 1: 0.3 μg / mL, allopurinol group 2: 0.6 μg / mL, allopurinol group 3: 0.9 μg / mL), febuxostat 1-3 groups (febuxostat group 1: 0.06 μg / mL, febuxostat group 2: 0.12 μg / mL, febuxostat group 3: 0.24 μg / mL), and Example 1-6 groups (all 500 μg / mL) were set up, and the culture medium of the corresponding drugs was given respectively, with 6 replicates in each group. After culturing for 24 h, the culture medium was discarded, the absorbance (A) value of each group of cells at a wavelength of 450 nm was detected, and the cell proliferation activity of each group was calculated.

[0059] 1.4 Establishment of adenosine-induced hyperuricemia cell model

[0060] The cells in logarithmic growth phase were inoculated in a 24-well cell culture plate and cultured for 24 h. They were divided into a blank control group, a Chinese medicine composition group (500 μg / mL), allopurinol 1-3 groups (allopurinol group 1: 0.3 μg / mL, allopurinol group 2: 0.6 μg / mL, allopurinol group 3: 0.9 μg / mL), febuxostat 1-3 groups (febuxostat group 1: 0.06 μg / mL, febuxostat group 2: 0.12 μg / mL, febuxostat group 3: 0.24 μg / mL), and Example 1-6 groups (all 500 μg / mL), serum starvation for 24 h, and pre-medication was performed at the same time. The cells in the blank control group and model group were replaced with serum-free culture medium containing 2.5 μmol / L adenosine, and the cells in the drug-treated group were replaced with serum-free culture medium containing 2.5 μmol / L adenosine and corresponding drugs. After 24 hours, 1 μL of 5U / mL XO was added to each well of the cells in each group except the blank control group. After 6 hours, the supernatant of the cells in each group was collected for detection.

[0061] 1.5 Detection of UA levels in cells of each group by HPLC

[0062] Accurately weigh 1.00 mg of the reference substance UA, add 0.02 mol / L NaOH to dissolve and dilute to 1 mL to prepare a 1 g / L UA reference solution, mix well, and filter through a 0.45 μm microporous filter. Dilute with ultrapure water to 7 concentrations of 100.0000, 50.0000, 25.0000, 12.5000, 6.2500, 3.1250 and 1.5625 mg / L, and detect by HPLC, with UA concentration as the horizontal axis and peak area as the vertical axis, draw a standard curve, and perform linear regression. Collect the cell culture supernatant of each group, centrifuge at 4°C and 12000g for 15 minutes, and then take the supernatant for testing.

[0063] 1.6 Determination of synergistic index

[0064] Uric acid inhibition rate = (blood uric acid value of model group - blood uric acid value of drug administration group) / blood uric acid value of model group

[0065] Synergy index q = A / (B + C - B*C)

[0066] Calculate the index change rate and synergistic index q value: A represents the numerical change rate of the detection index of Example 1-6, that is, the actual combined effect; (B + C-B*C) represents the expected combined effect, and q value>1, indicating that the combined drug effect is better than single drug use, and the two drugs have a synergistic effect. B represents the numerical change rate of the detection index of the Chinese medicine combination group, and C represents the numerical change rate of the detection index of the allopurinol group or the febuxostat group.

[0067] 1.7 Statistical methods

[0068] SPSS 19.0 software was used for statistical analysis, and all data were expressed as mean ± standard deviation ( ) indicated that the ANOVA analysis of variance was used to evaluate the test results for quantitative data, and the LSD test was used to compare the two groups.

[0069] 2. Experimental results

[0070] 2.1 Cell proliferation activity in each group

[0071] After NRK-52E cells were treated with drugs, there was no statistical difference in cell proliferation activity between the drug-treated groups compared with the blank control group ( P >0.05), the specific results are shown in Table 1.

[0072] Table 1 Cell proliferation activity in each group

[0073]

[0074] 2.2 UA levels in cells of each group

[0075] The regression equation of the uric acid standard curve is y=30.635x+0.0317 (R 2 =0.999), indicating that uric acid has a good relationship with the range of 0.0015625-0.100 0000 mg / mL. The specific results are shown in Table 2. Compared with the blank control group, the UA level in the model group cells was significantly increased ( ## P <0. 01). Compared with the model control group, the UA levels in the cells of each drug-treated group were significantly reduced ( * P <0.05 or ** P <0.01).

[0076] Among them, the synergistic index q values ​​of the uric acid levels in the groups of Examples 1-6 were all greater than 1, indicating that the Chinese medicine composition and allopurinol / febuxostat in Examples 1-6 can synergistically reduce uric acid levels.

[0077] Among the groups of Examples 1-3, the synergistic index q value of the group of Example 2 was the largest, indicating that the mass ratio of dry cream powder to allopurinol was 1000:1.2, which had a higher synergistic index and better uric acid lowering effect.

[0078] Among the groups of Examples 4-6, the synergistic index q value of the group of Example 5 was the largest, indicating that under the condition that the mass ratio of dry cream powder and febuxostat was 1000:0.24, it had a higher synergistic index and better uric acid lowering effect.

[0079] Table 2 Uric acid levels in cells of each group

[0080]

[0081] Note: Compared with the blank group, the model group # P <0.05; ## P <0.01. Compared with the model control group, * P <0.05; ** P <0.01.

[0082] Test Example 2

[0083] The therapeutic effect of the drug combination on Uox-KO mice

[0084] 1. Experimental methods

[0085] 1.1 Experimental animals

[0086] Uox-KO mice, grade: SPF grade; gender: male; age: 7-8 weeks; production unit: Jiangsu Jicui Pharmaceutical Biotechnology Co., Ltd., production license number is SCXK (Su) 2023-0009.

[0087] This study used Uox knockout (Uox-KO) mice, in which uricase synthesis was blocked and a hyperuricemia phenotype spontaneously developed.

[0088] C57BL / 6 (wild type) mice, grade: SPF grade; gender: male; age: 7-8 weeks; production unit: Jiangsu Jicui Pharmaceutical Biotechnology Co., Ltd., production license number is SCXK (Su) 2023-0009.

[0089] 1.2 Experimental drugs and reagents

[0090] UA test kit batch number: 230727101, Meikang Biotechnology Co., Ltd.;

[0091] CREA test kit, R&D company;

[0092] Eosin stain: batch number: 121886, Epredia, USA;

[0093] Hematoxylin stain: Batch number: 123196, Epredia, USA.

[0094] 1.3 Grouping and Dosing

[0095] 60 Uox-KO mice were taken, and after 2 weeks of adaptation, they were evenly stratified and grouped according to serum UA, and divided into G1-G6 groups, which were model control group (20 mL / kg / d pure water), Chinese medicine composition group (dry paste powder of basic example 1, 33.6 g / kg / d), allopurinol group (allopurinol 40 mg / kg / d), febuxostat group (febuxostat 8 mg / kg / d), Example 2 group and Example 5 group (all 33.6 g / kg / d), and each group was given corresponding drugs or pure water every day for 6 consecutive weeks. In addition, 10 C57BL / 6 (wild type) male mice of the same age were taken as the normal control group G0, and the corresponding volume of pure water was given every day.

[0096] 1.4 Blood biochemical index detection

[0097] Blood samples were collected before administration and 2, 4, and 6 weeks after administration to measure serum uric acid, and renal function (CREA level, BUN level) and liver function (ALT level, AST level) were measured 6 weeks after administration.

[0098] 1.5 Renal histopathological examination

[0099] After 6 weeks of administration, the kidneys of the mice were observed and weighed, and H&E staining was performed to observe the condition and extent of kidney lesions.

[0100] (1) Preparation of paraffin sections of renal tissue

[0101] 1) Flushing: The fixed renal tissue was placed in a plastic embedding box and rinsed with running water for 4 h; 2) Dehydration: The specimens were dehydrated in 70% and 80% ethanol for 1.5 h, 90% ethanol for 1 h, 95% ethanol I and II for 1.5 h, and anhydrous ethanol I and II for 2 h, respectively, in a gradient manner; 3) Transparentization: The specimens were placed in xylene I and II solutions for transparentization for 20 min and 30 min, respectively; 4) Wax immersion: The specimens were placed in pre-warmed dissolved paraffin I for 1 h, paraffin II for 2 h, and paraffin III for 2 h, and then the tissue blocks were embedded in paraffin; 5) Sectioning: The paraffin-embedded tissue blocks were sliced ​​continuously with a thickness of 4 μm, and the dehydration, transparentization, and wax immersion processes were completed by a fully automatic tissue dehydrator.

[0102] (2) HE staining

[0103] Arrange the slices in order, bake in a 60℃ oven for 2 h; dewax in xylene I and II for 15 min each; dexylene in anhydrous ethanol I and II for 10 min each; 95% ethanol, 80% ethanol, and 70% ethanol for 2 min each; rinse with tap water for 1 min; stain with hematoxylin for 5 min; rinse with running water for 2 min; differentiate with 0.5% hydrochloric acid alcohol for 5 s; rinse with running water for 1 min; blue with 0.5% dilute ammonia for 20 s; rinse with running water for 3 min; stain with 0.5% eosin for 2 min; rinse with running water for 1 min; 80% ethanol and 95% ethanol for 30 s each; anhydrous ethanol I and II for 2 min each; xylene I and II transparent for 5 min each; finally seal the slides with neutral gum for preservation.

[0104] (3) Scoring criteria

[0105] The renal tissue pathology evaluation items in this experiment include: 1) glomerular injury; 2) tubular dilatation; 3) tubular atrophy; 4) tubular epithelial injury (degeneration, necrosis); 5) interstitial inflammatory cell infiltration; 6) interstitial fibrosis. No lesions in each item are scored as 0 points, lesions less than 15% are scored as 1 point, 16%-30% are scored as 2 points, 31%-50% are scored as 3 points, and more than 50% are scored as 4 points. The maximum cumulative score for renal lesions is 24 points.

[0106] 1.6 Determination of synergistic index

[0107] Same as Section 1.6 of Test Example 1.

[0108] 1.7 Data Processing

[0109] SPSS 19.0 software was used for statistical analysis, and all data were expressed as mean ± standard deviation ( ) indicated that the ANOVA analysis of variance was used to evaluate the test results for quantitative data, and the LSD test was used to compare the two groups.

[0110] 2. Experimental results

[0111] 2.1 Changes of serum uric acid in each group of mice

[0112] The specific results are shown in Table 3. The results showed that compared with the normal control group, the serum uric acid levels of the mice in the model control group were significantly increased at 0, 2, 4, and 6 weeks of administration; compared with the model control group, the uric acid levels of the mice in each medication group were significantly decreased at 2 weeks of administration ( ** P <0.01, * P <0.05); After 4 and 6 weeks of administration, the serum uric acid of mice in the allopurinol group, febuxostat group, Example 2 group, and Example 5 group was significantly reduced ( ** P <0.01,* P <0.05); the TCM combination group showed a certain downward trend after 4 weeks of administration, and decreased significantly after 6 weeks of administration ( * P <0.05). After calculation, the synergistic index q of Example 2 and Example 5 groups was both>1, indicating that the Chinese medicine composition in Example 2 and Example 5 groups combined with the xanthine oxidase inhibitor can enhance the effect of reducing serum uric acid in mice, and is better than the simple addition of the two drugs.

[0113] Table 3 Changes of serum uric acid in each group of mice

[0114]

[0115] Note: Compared with the normal group, the model group # P <0.05; ## P <0.01. Compared with the model control group, * P <0.05; ** P <0.01.

[0116] 2.2 Changes in liver and kidney function of mice in each group

[0117] The results are shown in Table 4. The results showed that compared with the normal control group, the serum ALT and AST levels of mice in the model control group decreased significantly after 6 weeks of administration ( ## P <0.01), serum BUN and CREA increased significantly ( ## P <0.01). Compared with the model control group, there was no significant statistical change in ALT and AST in each drug-treated group; BUN in each drug-treated group showed a downward trend but no significant statistical difference ( P> 0.05); serum CREA of mice in Example 2 and Example 5 groups decreased significantly ( * P <0.05).

[0118] Table 4 Changes of liver and kidney function indicators in each group of mice

[0119]

[0120] Note: Compared with the normal group, the model group ## P <0.01. Compared with the model control group, * P <0.05.

[0121] 2.3 Observation of renal pathology in each group of mice

[0122] The results are shown in Table 5 and Figure 1 .

[0123] Figure 1 The cortical and medullary structures of the renal tissue of mice in the normal control group were clear, the volume of the glomeruli did not increase or decrease significantly, there was no obvious inflammatory cell infiltration in the interstitium, and no fibrous tissue proliferation. The renal pathological observation of mice in the model control group showed that at 6 weeks of administration, the renal tissue structure was disordered, a large number of cortical glomeruli were atrophied and reduced in number, the glomerular capsule was edematous, the mesangial matrix was proliferated, the renal tubules and renal pelvis were extremely dilated, a large number of renal tubular epithelial vacuolar and granular degenerations were observed, a large number of epithelial necrosis and shedding were observed, and shedding epithelial cells were observed in the lumen. The brush border was missing, a small amount of vascular hyalinization was observed, and the renal interstitial inflammatory cells were diffusely infiltrated, accompanied by a small amount of bleeding, obvious edema, and diffuse proliferation of fibrous cords.

[0124] The results in Table 5 show that compared with the normal control group, the scores of glomerular injury, tubular dilatation, tubular atrophy, tubular epithelial injury, interstitial inflammation, interstitial fibrosis and their total scores in the model control group were significantly increased ( ## P <0.01). Compared with the model control group, the scores of interstitial inflammation and interstitial fibrosis in mice in Example 2 and Example 5 were significantly reduced ( * P <0.05, ** P <0.01). Therefore, compared with the model control group, the mice in the Example 2 group were administered with the Chinese medicine components and allopurinol, and the mice in the Example 5 group were administered with the Chinese medicine components and febuxostat. The renal pathology of the mice was slightly improved, the infiltration of renal interstitial inflammatory cells was alleviated, and the renal pathology was improved to a certain extent.

[0125] Table 5 Renal histopathological scores of each group ( )

[0126]

[0127] Note: Compared with the normal control group, # P <0.05, ## P <0.01; compared with the model control group, * P <0.05, ** P <0.01.

[0128] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition for lowering uric acid, characterized in that: The invention is composed of component A and component B, wherein component A is composed of 5 parts of Tripterygium wilfordii, 30 parts of Smilax glabra, 15 parts of Morus alba, 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Coix seeds and 10 parts of Gentiana macrophylla; The component B is a xanthine oxidase inhibitor, and the xanthine oxidase inhibitor is allopurinol or febuxostat; When the xanthine oxidase inhibitor in component B is allopurinol, the mass ratio of component A to allopurinol is 1000:0.25; When the xanthine oxidase inhibitor in the component B is febuxostat, the mass ratio of component A to febuxostat is 1000:0.

05.

2. The method for preparing the pharmaceutical composition according to claim 1, characterized in that: The following steps are involved: 1) decocting component A in water to obtain a decoction, concentrating and drying the decoction to obtain a dry paste powder; 2) Mixing the obtained dry paste powder with component B to obtain a pharmaceutical composition.

3. The preparation method according to claim 2, characterized in that: The xanthine oxidase inhibitor in component B is allopurinol, and the mass ratio of the dry cream powder to allopurinol is 1000:0.6-1.8; The xanthine oxidase inhibitor in the component B is febuxostat, and the mass ratio of the dry cream powder to febuxostat is 1000:0.12-0.

48.

4. The preparation method according to claim 2, characterized in that: The xanthine oxidase inhibitor in the component B is allopurinol, and the mass ratio of component A to allopurinol is 1000:1.

2.

5. The preparation method according to claim 2, characterized in that: The xanthine oxidase inhibitor in the component B is febuxostat, and the mass ratio of the component A to febuxostat is 1000:0.

24.

6. The preparation method according to claim 2, characterized in that: In the step 1), the water decoction is performed 1-4 times; the water decoction time is 1-3 hours each time; and the density of the concentrated decoction is 1.1-1.

3.

7. Use of the pharmaceutical composition according to claim 1 or the pharmaceutical composition prepared by the preparation method according to any one of claims 2 to 6 in the preparation of drugs for lowering blood uric acid and / or improving liver and kidney function.

8. A drug, characterized in that The invention comprises the pharmaceutical composition according to claim 1 or the pharmaceutical composition prepared by the preparation method according to any one of claims 2 to 6, and excipients.

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