Traditional Chinese medicine composition for treating uric acid nephropathy as well as preparation and application thereof

Abstract

The invention relates to the field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating uric acid nephropathy, which is prepared from 9-60 parts of astragalus membranaceus, 9-30 parts of rhizoma polygonati, 6-18 parts of rhizoma cibotii, 6-18 parts of teasel root, 15-30 parts of polygonum cuspidatum, 15-30 parts of caulis spatholobi, 6-12 parts of angelica sinensis and 6-12 parts of safflower carthamus. The invention further provides a traditional Chinese medicine compound preparation for treating uric acid nephropathy and application of the traditional Chinese medicine compound preparation.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicines, and in particular, relates to a traditional Chinese medicine composition for treating uric acid nephropathy, and a preparation and application thereof. Background Art

[0002] Uric acid nephropathy is also known as gout kidney and hyperuricemia renal damage. It is a renal disease caused directly or indirectly by excessive production of uric acid in the blood due to purine metabolism disorders in the body, or accumulation of uric acid in the blood due to renal excretion dysfunction, and deposition of urate crystals in the distal tubules or collecting duct lumen. Clinically, common manifestations include tubular damage, renal interstitial fibrosis, and glomerular sclerosis, and gradually develop into chronic renal failure (CRF) as the disease progresses. Studies have shown that as of 2023, the prevalence of hyperuricemia (HUA) in my country is 14.10%, and among HUA patients, about 16.10% may be combined with chronic kidney disease (CKD). Studies have confirmed that HUA is an independent risk factor for CKD, and HUA alone can cause renal dysfunction. At present, modern medical treatment for uric acid nephropathy is mainly symptomatic treatment for HUA, starting with lowering uric acid levels, and lacks treatment for kidney damage. Although the patient's blood uric acid level improved after treatment, there was no significant improvement in renal function. Therefore, the development of drugs for the treatment of uric acid nephropathy is still the focus and difficulty of current research. Summary of the invention

[0003] The purpose of the present invention is to provide a Chinese medicine composition for treating uric acid nephropathy and its preparation and application.

[0004] The first aspect of the present invention provides a traditional Chinese medicine composition for treating uric acid nephropathy, which is prepared from the following raw materials in parts by weight: 9-60 parts of Astragalus, 9-30 parts of Polygonatum, 6-18 parts of Cibotium barometz, 6-18 parts of Dipsacus asper, 15-30 parts of Polygonum cuspidatum, 15-30 parts of Millettia reticulata, 6-12 parts of Angelica sinensis, and 6-12 parts of Carthamus tinctorius.

[0005] In a preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 15-45 parts of Astragalus, 15-18 parts of Polygonatum, 9-12 parts of Cibotium barometz, 9-12 parts of Dipsacus asper, 15-30 parts of Polygonum cuspidatum, 15-30 parts of Millettia reticulata, 6-12 parts of Angelica sinensis, and 6-12 parts of Carthamus tinctorius.

[0006] In another preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 30 parts of Astragalus, 18 parts of Polygonatum, 12 parts of Cibotium barometz, 12 parts of Dipsacus asper, 15 parts of Polygonum cuspidatum, 30 parts of Millettia reticulata, 12 parts of Angelica sinensis, and 6 parts of Carthamus tinctorius.

[0007] The second aspect of the present invention is to provide a Chinese medicine compound preparation for treating uric acid nephropathy, wherein the Chinese medicine compound preparation is a decoction, granules, powder, capsule, tablet or oral liquid with the above-mentioned Chinese medicine composition as the active ingredient.

[0008] In a preferred embodiment, the Chinese medicine compound preparation is a decoction.

[0009] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition in preparing medicine for treating uric acid nephropathy.

[0010] The details of various aspects of the present invention will be described in detail in the following sections. The features, objectives and advantages of the present invention will become more apparent through the following description and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 The Chinese medicine composition significantly improved the renal compensatory state of rats; (a) normal group, (b) model group, (c) low-dose group of the Chinese medicine composition, (d) medium-dose group of the Chinese medicine composition, and (e) high-dose group of the Chinese medicine composition.

[0012] Figure 2 Comparison results of left kidney weight; ns, p>0.05; *, p<0.05; **, p<0.01; ***, p<0.001, ****, p<0.0001.

[0013] Figure 3 The Chinese medicine composition significantly improves the renal function of rats; (a) comparison results of blood creatinine levels of rats in each group, (b) comparison results of blood urea nitrogen levels of rats in each group, (c) comparison results of blood uric acid levels of rats in each group; ns is p>0.05; * is p<0.05; ** is p<0.01; *** is p<0.001, **** is p<0.0001.

[0014] Figure 4 The Chinese medicine composition significantly reduces renal tubular dilatation, renal fibrosis and inflammatory cell infiltration in rats; (a) normal group, (b) model group, (c) low-dose group of the Chinese medicine composition, (d) medium-dose group of the Chinese medicine composition, (e) high-dose group of the Chinese medicine composition.

[0015] Figure 5 The Chinese medicine composition significantly improved the renal function of rats compared with the literature prescription; (a) comparison results of blood creatinine levels of rats in each group, (b) comparison results of blood urea nitrogen levels of rats in each group, (c) comparison results of blood uric acid levels of rats in each group; ns is p>0.05; * is p<0.05; ** is p<0.01; *** is p<0.001, **** is p<0.0001.

[0016] Figure 6 The Chinese medicine combination significantly improved the renal function of rats compared with the separated prescription groups; (a) comparison results of blood creatinine levels of rats in each group, (b) comparison results of blood urea nitrogen levels of rats in each group, (c) comparison results of blood uric acid levels of rats in each group; ns is p>0.05; * is p<0.05; ** is p<0.01; *** is p<0.001, **** is p<0.0001. DETAILED DESCRIPTION

[0017] The Chinese medicinal materials used by the inventors in the process of preparing the Chinese medicine composition of the present invention have the following sources:

[0018] Astragalus is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the Leguminosae family. Polygonatum is the dried rhizome of Polygonatum kingianum Coll. et Hemsl., Polygonatum sibiricum Red. or Polygonatum cyrtonema Hua of the Liliaceae family. Cibotium barometz (L.) J. Sm. is the dried rhizome of Cibotium barometz (L.) J. Sm. of the Pteridaceae family. Dipsacus asper is the dried root of Dipsacus asper Wall. ex Henry. of the Dipsacus family. Polygonum cuspidatum is the dried rhizome and root of Polygonum cuspidatum Sieb. et Zucc. of the Polygonaceae family. Millettia reticulata is the dried vine stem of Spatholobus suberectus Dunn. of Leguminosae. Angelica sinensis is the dried root of Angelica sinensis (Oliv.) Diels. of Apiaceae. Safflower is the dried flower of Carthamus tinctorius L. of Asteraceae.

[0019] Based on many years of clinical practice experience, the inventor believes that the pathogenesis of uric acid nephropathy is always due to deficiency of the root and excess of the side, with deficiency and excess mixed. The root deficiency can be blamed on the spleen and kidney, and the excess of the side is mainly pathological products such as blood stasis, dampness, damp heat, and turbidity. It is emphasized that turbidity and blood stasis block the kidney network is the unique pathogenesis of uric acid nephropathy, which runs through the disease. Then, the Chinese medicine composition of the present invention contains eight Chinese medicines in total. Astragalus is sweet and warm in nature, focusing on replenishing qi, and qi can produce blood, absorb blood, promote blood circulation, and promote body fluid. It can relieve blood stasis caused by qi deficiency. It is used for numbness of limbs, hemiplegia or arthralgia caused by qi deficiency and blood stasis. Polygonatum is sweet and flat in nature, mainly enters the kidney meridian, replenishes qi and nourishes yin, strengthens the spleen, moistens the lungs, and benefits the kidneys. This product has a moist texture and a mild effect, and enters the lungs, spleen, and kidney meridians. It can not only moisten the lungs and nourish kidney yin, but also benefit the spleen qi, replenish spleen yin, and benefit kidney qi and kidney essence. It belongs to a medicine for both qi and yin supplementation and lung, spleen, and kidney treatment. The two medicines are used together, and the effect of replenishing qi is particularly strong, so they are used together as the main medicine. Dog spine is bitter, sweet and warm in nature, and enters the liver and kidney meridians. Bitterness can dry dampness, sweetness can benefit blood and relieve urgency, and warmth can nourish the kidney and nourish qi. It is good at removing rheumatism, nourishing the liver and kidney, and strengthening the waist and knees. It is mainly used to treat rheumatism, soreness of the waist and knees, weakness of the lower limbs, and enuresis. "Ben Cao Qiu Zhen" says that it is a "drug that can replenish and move". In addition to replenishing, it can also warm and consolidate. Combined with Chuanduan, the effect of replenishing the liver and kidney and strengthening the tendons and bones is doubled, and they are all ministers. Combined with the main medicine, it has the effect of replenishing qi and strengthening the waist and knees. Chuanduan tastes bitter, pungent, sweet and slightly warm. It enters the liver and kidney meridians. It tastes sweet and slightly warm, enters the liver and kidney meridians, can replenish the liver and kidney, strengthen the tendons and bones, and is bitter and pungent, which can promote blood circulation. It is a commonly used medicine for treating liver and kidney deficiency, soreness of the waist and knees due to poor blood circulation, weakness of the feet and knees, or wind-cold dampness arthralgia, and muscle and bone cramps. "Southern Yunnan Materia Medica" says: "Replenish the liver, strengthen the tendons and bones. Circulate the meridians and stop the pain during menstruation." Polygonum cuspidatum is bitter and cold, enters the liver meridian blood, is good at purging blood stasis, can activate blood circulation and remove blood stasis, and has the effects of dredging menstruation, relieving pain, healing wounds, and eliminating symptoms. "Supplement to Materia Medica" calls it "the main wind in the joints and blood stasis." It can activate blood circulation and relieve pain. Because of its bitter and cold nature, it can clear away heat and dampness, so it is especially suitable for damp-heat arthritis. Millettia reticulata tastes bitter, sweet and warm, and belongs to the liver and kidney meridians. It is bitter and sweet, warm and unblocked. It is bitter but not dry, warm but not strong, and has a mild nature. It can remove blood stasis and generate new blood. It has the functions of activating blood circulation and replenishing blood, relaxing tendons and activating collaterals. It is a commonly used medicine for treating obstructed meridians and disharmony of collaterals. It is combined with Dipsacus asper and Cibotium barometz to nourish the liver and kidney, strengthen tendons and bones, and treat rheumatic arthritis. Qi and blood deficiency, stagnation of blood vessels, and poor flexion and extension of limbs can be combined with safflower to replenish qi, activate blood circulation and dredge collaterals. Combined with Polygonum cuspidatum, it is an adjuvant drug, which has the effect of promoting blood circulation and removing blood stasis. Angelica sinensis is sweet, pungent, warm and moist in nature. It enters the liver, heart and spleen meridians. It is sweet and moist to nourish blood, and pungent and warm to promote blood circulation. It has good blood-tonifying, blood-activating and analgesic effects. "Jingyue Complete Book·Compendium of Materia Medica" says: "Its taste is sweet and heavy, so it can only nourish blood; its qi is light and pungent, so it can also promote blood circulation. It has the effect of promoting blood circulation, moving while nourishing, and promoting blood circulation while nourishing. It is truly a blood-qi medicine and a blood-sacred medicine." Because of its blood-activating, analgesic, warm and dispersing cold stagnation, it can be effective for symptoms such as abdominal pain due to deficiency and cold, rheumatic arthralgia, traumatic injury, carbuncle and ulcer. Safflower is pungent in taste and warm in nature. It enters the heart and liver meridians. It has the effect of promoting blood circulation and menstruation, dispersing blood stasis and relieving pain. It is a commonly used medicine for treating blood stasis syndrome. It is good at promoting blood circulation and meridians, and is a blood-qi medicine. It can purge and nourish. It is used as an adjuvant drug to treat the tingling of qi and blood all over the body. This is its function of promoting blood circulation. Combined with Angelica sinensis, it is a guide drug.Qi is the leader of blood. Qi deficiency cannot circulate blood, blood stasis will stagnate, and blood stasis will hinder the Qi. Therefore, it is necessary to replenish Qi to activate blood. Blood stasis blocks the kidney collaterals. If blood stasis is not removed, new blood will not be generated. Simply replenishing Qi may not be effective. Therefore, the combination of blood-activating and stasis-removing products, tonifying and purging, tonifying the kidney and replenishing Qi, removing blood stasis and generating new blood, can eliminate all symptoms. The whole prescription is well matched, tonifying and purging, taking into account both the positive and negative, treating the symptoms and the root causes, and hitting the pathogenesis of kidney deficiency and blood stasis in uric acid nephropathy. The method of tonifying the kidney and activating blood circulation is adopted, and the prescription of replenishing Qi and removing blood stasis is applied, which has the effect of collateral unblocking and kidney health.

[0020] All the Chinese medicine compositions of the present invention are prepared from Chinese medicine pieces prepared by the Chinese medicine pharmacy of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine. The pharmaceutical composition of the present invention can be prepared according to conventional methods in the art, such as adding 8 times and 6 times the amount of water to eight herbs such as Astragalus, respectively, decocting twice, each time for 1 hour, filtering, combining the filtrate, and concentrating into an extract with a relative density of 1.15-1.2 (80-85° C.) for standby use.

[0021] The Chinese medicine composition of the present invention is easy to use, has a definite curative effect, has little side effects, is low in cost, can be taken for a long time, and has good clinical curative effect on treating uric acid nephropathy of different degrees. In view of the high incidence of uric acid nephropathy and the great physical and mental pain it brings to patients, the current treatment effects of uricosuric drugs, non-steroidal anti-inflammatory drugs, etc. are different, and there are limitations such as easy recurrence and large side effects. Therefore, the Chinese medicine composition of the present invention has good clinical application prospects.

[0022] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually performed under normal conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0023] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the methods of the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only.

[0024] The above features mentioned in the present invention or the features mentioned in the embodiments can be combined in any way. All the features disclosed in this patent specification can be used in combination with any combination form, and each feature disclosed in the specification can be replaced by any alternative feature that can provide the same, equal or similar purpose. Therefore, unless otherwise specified, the disclosed features are only general examples of equal or similar features.

[0025] Embodiment 1

[0026] Take 9g of Astragalus, 9g of Polygonatum, 6g of Cibotium barometz, 6g of Dipsacus asper, 15g of Polygonum cuspidatum, 15g of Millettia reticulata, 6g of Angelica sinensis, and 6g of Carthamus tinctorius.

[0027] The preparation method is as follows:

[0028] Add 8 times and 6 times the amount of water to the eight herbs respectively, boil twice, each time for 1 hour, filter, combine the filtrate, and concentrate it into an extract with a relative density of 1.15-1.2 (80-85℃) for later use.

[0029] The administration method is as follows: heat in a water bath and then administer orally.

[0030] Embodiment 2

[0031] Take 15g of Astragalus, 15g of Polygonatum, 9g of Cibotium barometz, 9g of Dipsacus asper, 30g of Polygonum cuspidatum, 30g of Millettia reticulata, 9g of Angelica sinensis, and 9g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0032] Embodiment 3

[0033] Take 18g of Astragalus, 18g of Polygonatum, 12g of Cibotium barometz, 12g of Dipsacus asper, 15g of Polygonum cuspidatum, 15g of Millettia reticulata, 12g of Angelica sinensis, and 12g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0034] Embodiment 4

[0035] Take 30g of Astragalus, 30g of Polygonatum, 15g of Cibotium barometz, 15g of Dipsacus asper, 15g of Polygonum cuspidatum, 15g of Millettia reticulata, 6g of Angelica sinensis, and 6g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0036] Embodiment 5

[0037] Take 45g of Astragalus, 18g of Polygonatum, 18g of Cibotium barometz, 18g of Dipsacus asper, 30g of Polygonum cuspidatum, 30g of Millettia reticulata, 12g of Angelica sinensis, and 12g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0038] Embodiment 6

[0039] Take 60g of Astragalus, 30g of Polygonatum, 18g of Cibotium barometz, 18g of Dipsacus asper, 30g of Polygonum cuspidatum, 30g of Millettia reticulata, 12g of Angelica sinensis, and 12g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0040] Embodiment 7

[0041] Take 30g of Astragalus, 18g of Polygonatum, 12g of Cibotium barometz, 12g of Dipsacus asper, 15g of Polygonum cuspidatum, 30g of Millettia reticulata, 12g of Angelica sinensis, and 6g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0042] Embodiment 8

[0043] Take 30g of Astragalus, 15g of Polygonatum, 12g of Cibotium barometz, 12g of Dipsacus asper, 30g of Polygonum cuspidatum, 30g of Millettia reticulata, 12g of Angelica sinensis, and 6g of Carthamus tinctorius. The preparation method and administration method are the same as those in Example 1.

[0044] Example 9 Animal Experiment on Treatment of Uric Acid Nephropathy with Chinese Medicine Composition

[0045] Experimental animals: SD rats

[0046] Experimental drugs: Chinese medicine composition prepared according to Example 7

[0047] Experimental methods: Male SD rats weighing 180-200g were used as model animals. After one week of adaptive feeding, they were randomly divided into a normal group, a model group, and a medication group. The model group and the medication group were induced by potassium oxonate combined with adenine to construct a rat model of uric acid nephropathy. The medication group was given a Chinese medicine composition intervention 4 weeks after modeling, and the model group and the normal group were given an equal volume of normal saline. The dose for rats was 6.3 times the human dose. The rats were gavaged at a dose of 1ml / 100g per day for a total of 8 weeks of intervention. The next day, the experimental rats in each group were treated, the residual kidney weight was recorded, photos were taken, and the embedded sections were stained. The pathological changes in the renal tissue were observed using an upright white light camera microscope to evaluate the therapeutic effect of the Chinese medicine composition on uric acid nephropathy.

[0048] Statistical methods: IBM SPSS Statistics 25.0 statistical software was used for statistical analysis. Renal function indicators include creatinine, urea nitrogen and urine protein, which are all quantitative data. The quantitative data were tested for normal distribution using the Shapiro-Wilk (SW) method. The differences in means among multiple groups were tested by one-way analysis of variance, and the LSD test method was used for pairwise comparison. If it did not conform to the normal distribution, the rank sum test Kruskal-Wallis H statistical analysis method was used. P < 0.05 was used as the criterion for statistical significance, and the test level α = 0.05 (two-tailed).

[0049] Experimental results: Compared with the normal group Figure 1 (a) Compared with the model group Figure 1 (b) Compensatory hypertrophy of the kidneys of rats, which was drum-shaped, with a lighter surface color. The cross-section showed thickening of the renal cortex, which was lighter in color, and a heavier residual kidney mass. Figure 1 (c)~ Figure 1 (e) The renal compensation of rats was significantly improved, and the kidneys were dark red, shiny, and smooth. The remaining kidney mass was reduced compared with the model group ( Figure 2), and the medium-dose and high-dose groups were significantly relieved. As shown in Figures 3(a) to 3(c), by testing various renal function indicators, it was found that compared with the normal group, the levels of blood creatinine, urea nitrogen, and blood uric acid in the model group rats were significantly increased; compared with the model group, the Chinese medicine composition can significantly reduce the levels of blood creatinine, urea nitrogen, and blood uric acid, with statistical differences (p < 0.01). Figure 4 As shown in (a) to 4(e), pathological observation and fibrosis analysis of kidney tissues in different treatment groups were performed by HE staining. Figure 4 (a) (normal group) shows that the glomerular structure is intact, the capillary loops are clear, the renal tubules are not dilated, and there is no obvious inflammatory infiltration or fibrosis in the interstitium; Figure 4 (b) (model group) showed dilation of the renal tubule lumen, blurred brush borders of some proximal tubules, and shedding, dark-stained particles (suspected to be urate crystals) in some tubule lumens, accompanied by inflammatory cell infiltration, widened interstitium, decreased cell density, and mild signs of fibrosis; Figure 4 (c) (low-dose group) showed crystal salt deposition in the lumen of renal tubules, the renal tubules were still significantly dilated, interstitial inflammation was significantly alleviated, and the degree of fibrosis was reduced compared with the model group; Figure 4 (d) (medium dose group) and Figure 4 (e) (High-dose group) The dilatation of renal tubules was alleviated, the proximal tubule structure was relatively intact, no significant crystal deposition was observed in the tubular lumen, interstitial inflammatory infiltration was less, there was no obvious abnormality in the interstitial structure, and the degree of fibrosis was lighter.

[0050] Example 10 Comparative study of Chinese medicine composition and literature prescription (Kidney-Nourishing and Blood-Activating Prescription)

[0051] Experimental animals: SD rats

[0052] Experimental drugs: Chinese medicine composition prepared according to Example 7

[0053] Literature prescription: Astragalus 45g, Polygonatum 20g, Chuanduan 12g, Cibotium barometz 12g, Angelica sinensis 12g, Polygonum cuspidatum 15g, Carthamus tinctorius 9g, Trichosanthes kirilowii 15g, Serissa 30g, Epimedium brevicornum 15g, prepared according to the method disclosed in the literature (Wang Yuan, Deng Yueyi. Observation on the efficacy of kidney-tonifying and blood-activating method in the treatment of gouty nephropathy [J]. Journal of Clinical Nephrology, 2014(6):374-375.).

[0054] Experimental methods: Six-week-old SPF male SD rats were used as model animals. After one week of adaptive feeding, they were randomly divided into a normal group, a model group, a Chinese medicine combination group, and a literature group. The experimental rats in the model group, the Chinese medicine combination group, and the literature group were all induced by potassium oxonate combined with adenine to establish a rat model of uric acid nephropathy. The Chinese medicine combination and the literature group were given intervention the next day after the successful modeling, and the model group and the normal group were given an equal volume of normal saline. The dosage of rats was 6.3 times that of the human body. The rats were gavaged at a dose of 1ml / 100g per day. After 8 weeks of intervention, the animals in each group were treated the next day, and the abdominal aorta blood was taken for blood creatinine, urea nitrogen, and blood uric acid to evaluate the therapeutic effects of the Chinese medicine combination and the literature group on rats with uric acid nephropathy.

[0055] Statistical methods: IBM SPSS Statistics 25.0 statistical software was used for statistical analysis. The Shapiro-Wilk (SW) method was used to test the normal distribution of the measurement data. The differences in means among multiple groups were tested by one-way analysis of variance, and the LSD test method was used for pairwise comparison. If it did not conform to the normal distribution, the rank sum test Kruskal-Wallis H statistical analysis method was used, and P < 0.05 was used as the criterion for statistical difference.

[0056] Experimental results: The improvement of uric acid nephropathy was evaluated based on the renal function indicators of serum creatinine, urea nitrogen, and blood uric acid. As shown in Figure 5(a) to Figure 5(c), compared with the model group, the Chinese medicine composition and the literature prescription can significantly improve the renal function of rats with uric acid nephropathy and delay the progression of the disease, with statistical differences (p < 0.01), and the Chinese medicine composition medium dose group is significantly better than the literature prescription (p < 0.05).

[0057] Example 11 Comparative study of Chinese medicine combination and separated prescriptions

[0058] Experimental animals: SD rats

[0059] Experimental drugs: Chinese medicine composition prepared according to Example 7

[0060] The composition of prescription 1: Polygonatum 18g, Cibotium barometz 12g, Dipsacus asper 12g, Polygonum cuspidatum 15g, Millettia reticulata 30g, Angelica sinensis 12g, and Safflower 6g.

[0061] The composition of prescription 2: 30g of Astragalus, 12g of Cibotium barometz, 12g of Dipsacus asper, 15g of Polygonum cuspidatum, 30g of Millettia reticulata, 12g of Angelica sinensis, and 6g of Carthamus tinctorius.

[0062] The composition of prescription 3: 30g Astragalus, 18g Polygonatum, 12g Dipsacus asper, 15g Polygonum cuspidatum, 30g Millettia reticulata, 12g Angelica sinensis, and 6g Carthamus tinctorius.

[0063] The composition of prescription 4: 30g of Astragalus, 18g of Polygonatum, 12g of Cibotium barometz, 15g of Polygonum cuspidatum, 30g of Millettia reticulata, 12g of Angelica sinensis, and 6g of Carthamus tinctorius.

[0064] The composition of prescription 5: 30g of Astragalus, 18g of Polygonatum, 12g of Cibotium barometz, 12g of Dipsacus asper, 30g of Millettia reticulata, 12g of Angelica sinensis, and 6g of Carthamus tinctorius.

[0065] The composition of prescription 6: 30g of Astragalus, 18g of Polygonatum, 12g of Cibotium barometz, 12g of Dipsacus asper, 15g of Polygonum cuspidatum, 12g of Angelica sinensis, and 6g of Carthamus tinctorius.

[0066] The composition of prescription 7: 30g Astragalus, 18g Polygonatum, 12g Cibotium barometz, 12g Dipsacus asper, 15g Polygonum cuspidatum, 30g Millettia reticulata, and 6g Carthamus tinctorius.

[0067] The composition of prescription 8: 30g Astragalus, 18g Polygonatum, 12g Cibotium barometz, 12g Dipsacus asper, 15g Polygonum cuspidatum, 30g Millettia reticulata, and 12g Angelica sinensis.

[0068] Preparation method of the split prescription medicine: prepare it according to the method of Example 1.

[0069] Experimental methods: Six-week-old male SD rats were used as model animals. After one week of adaptive feeding, they were randomly divided into a blank group, a model group, a Chinese medicine combination group, and each disassembled prescription group (disassembled prescription 1, disassembled prescription 2, disassembled prescription 3, disassembled prescription 4, disassembled prescription 5, disassembled prescription 6, disassembled prescription 7, and disassembled prescription 8). The model group, the Chinese medicine combination group, and the disassembled prescription groups were all induced by potassium oxonate combined with adenine to establish a rat model of uric acid nephropathy. The Chinese medicine combination and each disassembled prescription were given intervention the next day after the successful modeling, and the model group and the normal group were given an equal volume of normal saline. The dosage of rats was 6.3 times that of human use. The rats were gavaged at a dose of 1 ml / 100 g per day. After 8 weeks of intervention, the animals in each group were treated the next day, and the blood creatinine, urea nitrogen, and blood uric acid in the abdominal aorta were detected to evaluate the therapeutic effects of the Chinese medicine combination and each disassembled prescription on uric acid nephropathy.

[0070] Statistical methods: IBM SPSS Statistics 25.0 statistical software was used for statistical analysis. The Shapiro-Wilk (SW) method was used to test the normal distribution of the measurement data. The differences in means among multiple groups were tested by one-way analysis of variance, and the LSD test method was used for pairwise comparison. If it did not conform to the normal distribution, the rank sum test Kruskal-Wallis H statistical analysis method was used, and P < 0.05 was used as the criterion for statistical difference.

[0071] Experimental results: The improvement of uric acid nephropathy was evaluated based on the renal function indicators of blood creatinine, urea nitrogen, and blood uric acid. As shown in Figure 6 (a) to Figure 6 (c), compared with the model group, the Chinese medicine combination and each separated prescription can significantly improve the renal function of rats with uric acid nephropathy, with statistical differences (*, compared with the normal group, P < 0.05; #, compared with the model group, P < 0.05). However, the therapeutic effect of any separated prescription with one less medicine is not as good as that of the Chinese medicine combination, and there is a statistical difference (△, compared with the Chinese medicine combination group, P < 0.05).

[0072] Example 12 Clinical comparative study of Chinese medicine composition and Febuxostat tablets

[0073] 1. Clinical Data and Methods

[0074] 1.1 Research subjects

[0075] All patients with uric acid nephropathy who visited the outpatient and inpatient departments of the Nephrology Department of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine.

[0076] 1.2 Diagnostic criteria

[0077] 1.2.1 Western medicine diagnostic criteria

[0078] It was formulated with reference to the fourth edition of "Nephrology" edited by Wang Haiyan and the "Diagnosis, Syndrome Differentiation and Therapeutic Effect Evaluation of Uric Acid Nephropathy (Trial Program)" formulated by the Nephrology Branch of the Chinese Association of Traditional Chinese Medicine in 2008.

[0079] 1.2.2 Diagnostic criteria of TCM syndrome types:

[0080] The diagnostic criteria for spleen-kidney qi deficiency and blood stasis syndrome were formulated in accordance with the 2008 "Diagnosis, Syndrome Differentiation and Therapeutic Effect Evaluation of Uric Acid Nephropathy (Trial Program)".

[0081] 1.2.3 Inclusion criteria:

[0082] ① Those who meet the above-mentioned diagnostic criteria of traditional Chinese medicine and Western medicine; ② Aged 18-85 years old, regardless of gender; ③ Subjects give informed consent and sign a letter of commitment; ④ Those who have not participated in other clinical observations within 1 year;

[0083] 1.2.4 Exclusion criteria:

[0084] ① Patients with hyperuricemia caused by tumor lysis syndrome, blood system diseases, other kidney diseases or drug use; ② Pregnant or lactating women; ③ Patients with severe primary diseases such as heart, brain, liver and hematopoietic system; ④ Patients with chronic kidney disease who have started renal replacement therapy; ⑤ Patients with mental illness who cannot cooperate with treatment; ⑥ Patients who are known to be allergic to the drug components in the regimen;

[0085] 1.2.5 Sample size estimation

[0086] Refer to the relevant content of the 6th edition of "Medical Statistics" and use the calculation formula for comparing the means of two samples:

[0087]

[0088] Where n r 、n c are the sample contents required for the Chinese medicine group and the control group respectively; μ r is the mean of the Chinese medicine group, μ c is the mean of the control group, Δ is the superiority margin, σ is the standard deviation (assuming that the standard deviations of the two groups are equal), type I error α (take 0.025 on one side); type II error β (take 0.10 on one side); the ratio K of the Chinese medicine group to the control group is 1. After looking up the table, Z 1-α =1.960, Z 1-β =1.282. According to the preliminary experimental results, μ r =63.36ml / (min·1.73m 2 ), μ c =44.56ml / (min·1.73m 2 ), σ=13.28ml / (min·1.73m 2 ), Δ takes 1 / 2 standard deviation as 6.64 ml / (min·1.73 m 2 ), and n is calculated r =n c ≈26 cases. Considering the dropout effect, the dropout rate is calculated as 20%. The total sample size is N=n / (1-20%)=32.5. 33 cases are taken, and a total of 66 cases need to be included.

[0089] 1.2.6 Ethical Review

[0090] This study has been reviewed by the Ethics Committee of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine and obtained the ethics number: 2023-034-1.

[0091] 1.3 Drug treatment

[0092] Conventional treatment: ① Healthy diet: avoid high-purine diet, drink plenty of water, 2000ml / d; ② Moderate exercise: exercise according to your own situation. For example, moderate intensity exercise for more than 30 minutes a day, such as walking, yoga and other aerobic exercises; ③ Weight control: obese people should lose weight and control BIM <24; ④ Quit smoking and limit alcohol; ⑤ For those with more severe renal function impairment, limit protein intake; control blood pressure, correct water and electrolyte, acid-base imbalance, and symptomatic treatment of various other complications.

[0093] Control group: On the basis of conventional treatment, 20 mg of Febuxostat (trade name: Youlitong, produced by Jiangsu Wanbang Biochemical Pharmaceutical Group Co., Ltd.) was taken orally every day. The dosage can be adjusted according to the actual situation of the patient.

[0094] Chinese medicine group: on the basis of the control group, the Chinese medicine composition of the present invention was administered daily.

[0095] The Chinese medicine composition was prepared according to the dosage of Example 7. All Chinese medicine pieces were decocted in water to 200 ml and taken orally twice a day, morning and evening. Both groups were treated for 12 weeks.

[0096] 1.4 Observation indicators

[0097] The renal function (eGFR, serum creatinine Scr, serum uric acid HUA) and TCM syndrome score of each group of patients were recorded before and after treatment.

[0098] The efficacy was evaluated based on the total effective rate, which was calculated as follows: total effective rate = (markedly effective + effective + stable) ÷ total number of cases × 100%.

[0099] ① Markedly effective: eGFR increased by ≥20%, and TCM syndrome score decreased by ≥60%; ② Effective: eGFR increased by ≥10%, and TCM syndrome score decreased by ≥30%; ③ Stable: eGFR increased by <10%, and TCM syndrome score decreased by <30%; ④ Ineffective: eGFR decreased, and TCM syndrome score did not improve or worsened.

[0100] Statistical methods: SPSS 25.0 version was used for statistical analysis. Measurement data that conformed to normal distribution were expressed as mean ± standard deviation (x ± s), and those that did not conform were expressed as [M (P25, P75)]. Paired t-test was used for the difference between the data before and after treatment in the same group that conformed to normal distribution; independent sample t-test was used for the data between groups that conformed to normal distribution and homogeneity of variance; non-parametric tests were used for data that were not normally distributed or had unequal variances. Chi-square test was used for count data, and rank sum test was used for rank data. P < 0.05 was considered statistically different, and P < 0.01 indicated that the statistical difference was significant.

[0101] 2. Results

[0102] As shown in Table 1, a total of 66 patients with uric acid nephropathy were included in this study, with 33 cases in the Chinese medicine group and 33 cases in the control group, and all completed the treatment. The total effective rate of the Chinese medicine group was 87.88%, and the total effective rate of the control group was 63.64%. Compared with the control group, the total effective rate of the Chinese medicine group was significantly improved, with statistical difference (P < 0.05). And through follow-up, it was found that no adverse reactions occurred in both groups. It can be seen that the Chinese medicine combination combined with Febuxostat has a significant effect in the treatment of uric acid nephropathy.

[0103] Table 1 Comparison of clinical efficacy between the two groups

[0104] Group n Significant effect efficient Stablize invalid Total Effectiveness Chinese Medicine Group 33 16 7 6 4 87.88％ Control group 33 8 5 8 12 63.64％

[0105] The various aspects of the present invention have been described above. However, it should be understood that, without departing from the spirit of the present invention, equivalent changes and modifications may be made by those skilled in the art, and the changes and modifications also fall within the scope of the appended claims of the present application.

Claims

1. A Chinese medicine composition for treating uric acid nephropathy, which is made from the following raw materials in parts by weight: 9-60 parts of Astragalus, 9-30 parts of Polygonatum, 6-18 parts of Cibotium barometz, 6-18 parts of Dipsacus asper, 15-30 parts of Polygonum cuspidatum, 15-30 parts of Millettia reticulata, 6-12 parts of Angelica sinensis, and 6-12 parts of Carthamus tinctorius.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 15-45 parts of astragalus, 15-18 parts of polygonatum, 9-12 parts of cibotium barometz, 9-12 parts of dipsaccharum officinale, 15-30 parts of polygonatum cuspidatum, 15-30 parts of millettia reticulata, 6-12 parts of angelica sinensis and 6-12 parts of safflower.

3. The Chinese medicine composition according to claim 2, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30 parts of astragalus, 18 parts of polygonatum, 12 parts of cibotium barometz, 12 parts of dipsaccharum officinale, 15 parts of polygonum cuspidatum, 30 parts of millettia reticulata, 12 parts of angelica sinensis and 6 parts of safflower.

4. A Chinese medicinal compound preparation for treating uric acid nephropathy, characterized in that: The Chinese medicine compound preparation is a decoction, granule, powder, capsule, tablet or oral liquid with the Chinese medicine composition described in claim 1, 2 or 3 as the active ingredient.

5. The Chinese medicinal compound preparation according to claim 4, characterized in that: The Chinese medicine compound preparation is a decoction.

6. Use of the Chinese medicine composition as claimed in claim 1, 2 or 3 in the preparation of a medicament for treating uric acid nephropathy.

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