A spleen-invigorating and dampness-dispelling composition and use thereof in treating hyperuricemia

Abstract

The present application relates to the technical field of traditional Chinese medicine composition, and disclose a kind of application of spleen-strengthening and dampness-removing composition in treating hyperuricemia, spleen-strengthening and dampness-removing composition includes 12-18 weight parts of wilsonia, 15-25 weight parts of astragalus, 12-20 weight parts of bletilla striata, 25-38 weight parts of coix seed, 14-20 weight parts of giant knotweed.The uric acid-lowering effect of giant knotweed is related to the metabolism of 18 potential biomarkers related to hyperuricemia, and can also reduce the renal interstitial fibrosis area of hyperuricemia rats, and has a certain protective effect on the kidneys of hyperuricemia rats, thereby achieving the effects of anti-uric acid and anti-inflammatory.The spleen-strengthening and dampness-removing prescription can improve the clinical symptoms and inflammatory response of hyperuricemia patients, improve the clinical efficacy, and has good safety, and is worthy of clinical promotion.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine composition, in particular to a spleen-strengthening and dampness-removing composition and application thereof in treating hyperuricemia. BACKGROUND

[0002] Hyperuricemia is a common metabolic disease, which seriously threatens people's health. The incidence of hyperuricemia in China is on the rise, especially in some coastal areas and economically developed cities, the incidence has reached 5% to 23.5%, close to the incidence in some developed countries. In addition, hyperuricemia is an independent risk factor for complications of cardiovascular disease, chronic kidney disease, etc. Western medicine treatment drugs mainly promote uric acid excretion and inhibit uric acid synthesis, but long-term application has a greater impact on liver and kidney function, often accompanied by adverse reactions such as gastrointestinal tract adverse reactions, dermatitis, etc., which restricts the expected effect of hyperuricemia treatment. For simple hyperuricemia without any clinical symptoms, it is classified as "disease" category.

[0003] Sheng Hui-ming described that Wuling-san is the main drug for gout, and is suitable for both upper and lower parts. Wuling-san is also called the special drug for gout and stubborn arthralgia in "Medicine Nature and Application". Pharmacological studies have shown that Wuling-san can significantly reduce blood uric acid, and can effectively protect the kidney due to its strong anti-inflammatory effect, and treat kidney disease caused by high uric acid. The present application aims to scientifically compound Wuling-san, Huangqi, Chao Baishu, Fuling, etc. to obtain a spleen-strengthening and dampness-removing composition for treating hyperuricemia. SUMMARY

[0004] (I) Technical problem solved

[0005] The present application provides a spleen-strengthening and dampness-removing composition with the effect of treating hyperuricemia.

[0006] (II) Technical scheme

[0007] A spleen-strengthening and dampness-removing composition, which is composed of the following components: Wuling-san 12-18 parts by weight, Huangqi 15-25 parts by weight, Chao Baishu 10-20 parts by weight, Fuling 10-18 parts by weight, Bixie 12-20 parts by weight, Yiyiren 25-38 parts by weight, Zexie 12-20 parts by weight, Zhuling 13-16 parts by weight, Tufuling 12-16 parts by weight, Heye 13-18 parts by weight, Dongguapi 14-22 parts by weight, and Hu Zhang 14-20 parts by weight.

[0008] Preferably, the spleen-strengthening and dampness-removing composition is prepared by the following method:

[0009] Mixing 15-25 parts by weight of Huangqi, 10-20 parts by weight of Fried Baizhu, 10-18 parts by weight of Fuling, 25-38 parts by weight of Yiyiren, 12-20 parts by weight of Zexie, 13-16 parts by weight of Gualing, 12-16 parts by weight of Tufuling, 13-18 parts by weight of Heye, 14-22 parts by weight of Dongguapi and 14-20 parts by weight of Huozhang to obtain a composition, then adding the composition into distilled water, heating to boiling, cooling after decoction, removing the filter residue, adding Wilingxian extract and Bixie extract to the filtrate, and mixing to obtain a spleen-strengthening and dampness-eliminating prescription.

[0010] Preferably, the fire is adjusted during decoction, and the decoction time is controlled to be 40-60 min. The total volume of the solution after decoction is controlled to be reduced by 70-75%.

[0011] Preferably, the ratio of the composition and distilled water is 1g:(4-6)mL.

[0012] Preferably, the spleen-strengthening and dampness-eliminating prescription is used in the treatment of hyperuricemia.

[0013] Beneficial technical effects:

[0014] The present application is scientifically matched, and Wilingxian, Bixie, Huangqi, Fried Baizhu, Fuling, Yiyiren, Zexie, Gualing, Tufuling, Heye, Dongguapi and Huozhang are compounded to obtain a spleen-strengthening and dampness-eliminating composition and a spleen-strengthening and dampness-eliminating prescription. The uric acid-lowering effect of Huozhang is related to the regulation of the metabolism of eighteen potential biomarkers related to hyperuricemia, and can also reduce the renal interstitial fibrosis area of hyperuricemia rats, and has a certain protective effect on the kidneys of hyperuricemia rats, thereby achieving the effects of anti-uric acid and anti-inflammation. In the prescription, Baizhu, Yiyiren and Tufuling strengthen the spleen and eliminate dampness, Wilingxian benefits the kidney, eliminates dampness and unblocks the meridians, Huozhang clears heat and dampness, Chishao and Dilong eliminate dampness, activate blood and unblock the meridians. The uric acid-lowering mechanism of Tufuling may be to increase the expression of ABcG2 transporter protein and promote uric acid excretion. The uric acid excretion mechanism of Tufuling may be related to the down-regulation of mRNA expression of rat kidney genes. Wilingxian is pungent, salty and warm, and can eliminate wind and dampness and unblock the meridians. Materia Medica describes Wilingxian as a medicine for gout, which is suitable for both upper and lower parts, and Wilingxian is also called a medicine for gout and stubborn arthralgia in Medicine Nature and Application. Pharmacological studies have shown that Wilingxian can significantly reduce blood uric acid, and because Wilingxian has a strong anti-inflammatory effect, it can effectively protect the kidneys and treat kidney disease caused by high uric acid. Pharmacopoeia records that Bixie can eliminate dampness and turbidity, dispel wind and relieve arthralgia, and is used for treating oedema, leucorrhoea, excessive wind and dampness, arthralgia, joint stiffness and lumbago. The spleen-strengthening and dampness-eliminating prescription can improve the clinical symptoms and inflammatory response of hyperuricemia patients, improve the clinical curative effect, and has good safety, and is worthy of clinical promotion. DETAILED DESCRIPTION

[0015] The technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of the present application.

[0016] Embodiment 1

[0017] 15 g of Weilingxian, 20 g of Bixie, 15 g of Huangqi, 18 g of Fried Baizhu, 10 g of Fuling, 25 g of Yiyiren, 20 g of Zexie, 13 g of Gualou, 16 g of Tufuling, 15 g of Heye, 18 g of Dongguapi and 15 g of Huzhang are uniformly mixed to obtain a composition, the composition is then added into 700 mL of distilled water, and the mixture is decocted on a small fire for 40 min, the total volume reduction of the solution after decoction is controlled to be 70%, and the solution is cooled after decoction, and the filter residue is removed to obtain a spleen-strengthening and dampness-removing prescription.

[0018] Embodiment 2

[0019] 20 g of Weilingxian, 12 g of Bixie, 25 g of Huangqi, 10 g of Fried Baizhu, 12 g of Fuling, 38 g of Yiyiren, 15 g of Zexie, 15 g of Gualou, 12 g of Tufuling, 13 g of Heye, 20 g of Dongguapi and 14 g of Huzhang are uniformly mixed to obtain a composition, the composition is then added into 1000 mL of distilled water, and the mixture is decocted on a small fire for 60 min, the total volume reduction of the solution after decoction is controlled to be 75%, and the solution is cooled after decoction, and the filter residue is removed to obtain a spleen-strengthening and dampness-removing prescription.

[0020] Embodiment 3

[0021] 18 g of Weilingxian, 15 g of Bixie, 20 g of Huangqi, 20 g of Fried Baizhu, 18 g of Fuling, 30 g of Yiyiren, 12 g of Zexie, 16 g of Gualou, 15 g of Tufuling, 18 g of Heye, 14 g of Dongguapi and 20 g of Huzhang are uniformly mixed to obtain a composition, the composition is then added into 1000 mL of distilled water, and the mixture is decocted on a small fire for 60 min, the total volume reduction of the solution after decoction is controlled to be 75%, and the solution is cooled after decoction, and the filter residue is removed to obtain a spleen-strengthening and dampness-removing prescription.

[0022] Embodiment 4

[0023] 15 g of Weilingxian, 15 g of Bixie, 20 g of Huangqi, 15 g of Fried Baizhu, 15 g of Fuling, 30 g of Yiyiren, 15 g of Zexie, 15 g of Gualou, 15 g of Tufuling, 15 g of Heye, 20 g of Dongguapi and 15 g of Huzhang are uniformly mixed to obtain a composition, the composition is then added into 900 mL of distilled water, and the mixture is decocted on a small fire for 60 min, the total volume reduction of the solution after decoction is controlled to be 75%, and the solution is cooled after decoction, and the filter residue is removed to obtain a spleen-strengthening and dampness-removing prescription.

[0024] A total of 168 patients with hyperuricemia admitted to the outpatient and inpatient department of the First Central Hospital of Tianjin from January 2019 to October 2020 were selected as the research objects. They were divided into the experimental group (n=84) and the control group (n=84) by random number table method.

[0025] Inclusion criteria: In line with the China Hyperuricemia Related Diseases Diagnosis and Treatment Multidisciplinary Expert Consensus (2017).

[0026] Diagnosis: (1) Fasting blood uric acid level more than 420 μmol / L for two times on different days; (2) Age > 18 years; (3) Normal liver and kidney function.

[0027] Exclusion criteria: Secondary gout caused by kidney disease, blood disease, drug use, tumor radiotherapy, etc.; in the acute attack period of gouty arthritis; combined with serious lung, cardiovascular, blood and hematopoietic system, central nervous system or other system diseases; combined with malignant tumor; pregnant, lactating women or those with pregnancy plan; allergic to the test drug or physically weak, allergic constitution. There was no statistically significant difference in gender, age, body mass index, blood uric acid level between the two groups (P>0.05), which was comparable. This study was approved by the hospital ethics committee, and the patients and their families signed the informed consent form.

[0028] Treatment: Both the experimental group and the control group were given low purine diet, alcohol prohibition, daily water intake >2000 ml, reasonable rest, appropriate exercise and other basic treatment.

[0029] Group A (traditional Chinese medicine test group): Patients were treated with Spleen-Strengthening and Damp-Expelling Prescription (prepared by Example 4), which was orally taken once a day, twice a day.

[0030] Group B (febuxostat control group): Patients in the control group were treated with febuxostat, 40 mg orally after breakfast every day. No other drugs or other treatment methods that affect the efficacy of hyperuricemia treatment were added during the treatment observation. Febuxostat (Jiangsu Wanbang Biochemical Pharmaceutical Co., Ltd. National Drug Code: H20130058; 40 mg, oral. 1 time / d. Course of treatment 12 weeks.

[0031] Observation index and efficacy evaluation criteria:

[0032] Peripheral venous blood was drawn before and after treatment to detect blood uric acid 12 weeks before and after treatment, and IL-1β and TNF levels were detected by enzyme-linked immunosorbent assay. The occurrence of adverse reactions in patients in the two groups was recorded, including nausea, abdominal discomfort, skin rash, liver and kidney function abnormalities, etc.

[0033] The clinical efficacy of the two groups of patients was compared, and the patients were evaluated according to the "Guidelines for the Diagnosis and Treatment of Primary Gout". The patient's clinical symptoms and signs improved significantly, and the blood uric acid level was reduced by at least 60% compared with before treatment; the patient's clinical symptoms and signs improved, and the blood uric acid level was reduced by 20%-60% compared with before treatment; the patient's clinical symptoms and signs did not improve, and the blood uric acid level was reduced by less than 20% compared with before treatment. The total effective rate = (number of cases with significant effect + number of cases with effective) / total number of cases x 100%. Effective rate = (significant effect + effective) / total number of cases x 100%.

[0034] Statistical methods were analyzed by SPSS25.0 software, and the measurement data conforming to normal distribution were expressed as mean ± standard deviation (x ± s), and the comparison between the two groups used independent sample t test, P<0.05 was statistically significant. See Table 1.

[0035] Table 1 Comparison of TNF-α, IL-1β and uric acid levels in patients in the two groups (x ± s)

[0036]

[0037]

[0038] The clinical efficacy of the two groups of patients was compared after treatment, and the effective rate of group A was 96.4% (81 / 84), and that of group B was 95.2% (80 / 84), with no significant difference (P>0.05). See Table 2.

[0039] Table 2 Comparison of clinical efficacy of the two groups of patients (percentage / %)

[0040] Group Markedly effective (cases) Effective (cases) Ineffective (cases) Effective rate (%) Group A 44 37 3 96.4 Group B 40 40 4 95.2 x value - - - 0.149 p value - - - 0.669

[0041] The total incidence of adverse reactions in the two groups of patients was compared, and there was no significant difference (P>0.05). See Table 3.

[0042] Table 3 Comparison of adverse reactions in the two groups of patients (percentage / %)

[0043] Group Nausea Abdominal discomfort Rash Abnormal liver and kidney function Total incidence (%) Group A 4 3 2 2 13.1 Group B 5 3 2 2 14.3

[0044] Gout is caused by purine metabolism disorder leading to elevated uric acid and deposition in joints and surrounding tissues causing inflammatory damage, with the characteristics of repeated attacks, prolonged and difficult to heal, and severe cases can cause disability and deformity.

[0045] TCM believes that "spleen deficiency and internal obstruction of dampness and turbidity" is the key to the onset of gout, and "dampness, phlegm, turbidity and blood stasis" is the main pathological basis. The root cause is that the constitution of spleen deficiency and dampness is the internal basis, and the external cold, damp and hot evil is the external cause. "Phlegm and dampness obstruction, abdominal distension and heat accumulation, and blood stasis" are consistent. Huangqi and Yiyiren in the recipe of invigorating the spleen and removing dampness can invigorate the spleen and remove dampness and turbidity, restore the transportation and transformation function of the spleen, and promote the rise of clear and the fall of turbid, so they are the monarch drugs. Fuzhuan and Fuling and Biejiu are the minister drugs.

[0046] Febuxostat is a new non-purine inhibitor that can bind to the active center of xanthine oxidase to inhibit the activity of xanthine oxidase, thereby inhibiting the generation of uric acid from purine. TNF-α and IL-1β are involved in and mediate and regulate the inflammatory response caused by uric acid deposition. Therefore, TNF-α and IL-1β were chosen as indicators for evaluating the inflammatory response of gout. The results showed that after treatment, the levels of uric acid, TNF-α and IL-1β in the two groups were lower than before treatment, and there was no statistical difference in the levels of uric acid, TNF-α and IL-1β between the two groups after treatment (P>0.05), indicating that the recipe of invigorating the spleen and removing dampness can improve the levels of uric acid and inflammatory factors in patients with hyperuricemia.

[0047] The analysis of the reasons shows that modern Chinese medicine theory believes that the uric acid-lowering effect of rhubarb is related to the regulation of the metabolism of 18 potential biomarkers related to hyperuricemia, and can reduce the area of renal interstitial fibrosis in rats with hyperuricemia, and has a certain protective effect on the kidneys of rats with hyperuricemia, thereby achieving the effects of anti-uric acid and anti-inflammatory. Atractylodes rhizome, yiyi and tuber fomes can invigorate the spleen and remove dampness, and Wilingxian can benefit the kidney and remove dampness and unblock the collaterals. Rhubarb can clear dampness and heat. Chishao and dilong can remove dampness and promote blood circulation and unblock the collaterals. The mechanism of the uric acid-lowering effect of tuber fomes may be to increase the expression of ABcG2 transporter protein and promote the excretion of uric acid. The mechanism of tuber fomes in promoting uric acid excretion may be related to the down-regulation of mRNA expression of rat kidney genes. Wilingxian is pungent, salty and warm, and can dispel wind and dampness and unblock the meridians. Bencao Gangmu describes Wilingxian as a medicine for gout, which is suitable for both upper and lower parts, and Yaushe Yong also calls Wilingxian a special medicine for gout and stubborn arthralgia. Pharmacological studies have shown that Wilingxian can significantly reduce blood uric acid, and because of its strong anti-inflammatory effect, it can effectively protect the kidneys and treat kidney disease caused by high uric acid. The Pharmacopoeia records that Biejiu can remove dampness and turbidity, dispel wind and relieve arthralgia, and is used for treating clamydia, leukorrhea, excessive leukorrhea, arthralgia caused by wind and dampness, and pain in the waist and knees.

[0048] The study found that there was no significant difference in the total incidence of adverse reactions between the two groups. In summary, the recipe of invigorating the spleen and removing dampness can improve the clinical symptoms and inflammatory response of patients with hyperuricemia, improve the clinical efficacy, and has good safety, which is worthy of clinical promotion.

[0049] It will be apparent to those skilled in the art that the application is not limited to the details of the above-exemplified embodiments and that the present application can be implemented in other particular forms without departing from the spirit or essential characteristics of the present application. The embodiments should therefore be considered in all respects as illustrative and not restrictive, the scope of the application being indicated by the appended claims rather than by the above description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims

1. A spleen-strengthening and dampness-removing composition, characterized in that, The spleen-strengthening and dampness-removing composition comprises the following components: Clematis chinensis 12-18 parts by weight, Astragalus membranaceus 15-25 parts by weight, stir-fried Atractylodes macrocephala 10-20 parts by weight, Poria cocos 10-18 parts by weight, Dioscorea hypoglauca 12-20 parts by weight, Coix lacryma-jobi 25-38 parts by weight, Alisma plantago-aquatica 12-20 parts by weight, Polyporus umbellatus 13-16 parts by weight, Smilax glabra 12-16 parts by weight, Nelumbo nucifera leaf 13-18 parts by weight, Benincasa hispida peel 14-22 parts by weight, and Polygonum cuspidatum 14-20 parts by weight.

2. A method for preparing the spleen-strengthening and dampness-removing composition as described in claim 1, characterized in that, The method for preparing the spleen-strengthening and dampness-removing formula is as follows: 15-25 parts by weight of Astragalus membranaceus, 10-20 parts by weight of stir-fried Atractylodes macrocephala, 10-18 parts by weight of Poria cocos, 25-38 parts by weight of Coix lacryma-jobi, 12-20 parts by weight of Alisma plantago-aquatica, 13-16 parts by weight of Polyporus umbellatus, 12-16 parts by weight of Smilax glabra, 13-18 parts by weight of Nelumbo nucifera leaf, 14-22 parts by weight of Benincasa hispida peel, and 14-20 parts by weight of Polygonum cuspidatum are mixed to obtain a composition. Then, the composition is added to distilled water, heated until the solution boils, decocted, cooled, filtered to remove the residue, and Clematis chinensis extract and Dioscorea hypoglauca extract are added to the filtrate and mixed to obtain the spleen-strengthening and dampness-removing composition.

3. The method for preparing the spleen-strengthening and dampness-removing composition according to claim 2, characterized in that, The heat should be adjusted during the decoction process, and the decoction time should be controlled to be 40-60 minutes; and the reduction in the total volume of the solution after decoction should be controlled to be 70-75%.

4. The preparation method of the spleen-strengthening and dampness-removing composition according to claim 2, characterized in that, The ratio of the composition to distilled water is 1 g:(4-6) mL.

5. The use of a spleen-strengthening and dampness-removing composition obtained by any one of claims 2-4 in the preparation of a drug for treating hyperuricemia.

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