A traditional Chinese medicine composition for treating diabetic nephropathy and application thereof

Abstract

The application provides a traditional Chinese medicine composition for treating diabetic nephropathy and an application, and relates to the technical field of traditional Chinese medicine pharmacy.The traditional Chinese medicine composition is composed of Nanhaiteng, Tianhuafen, Xia' erxiancao, Heilu, Luohua'zi, Gegen, Corn silk, Gansui, Zhushenfen, Huangqi and Danshen.The traditional Chinese medicine composition can significantly improve blood glucose, blood lipid indexes and kidney function indexes of diabetic nephropathy rats, regulate the internal environment of the body, improve insulin resistance, and protect the kidney function of the rats.In addition, the traditional Chinese medicine composition can reduce the FPG, 2hPBG, HbA1c, Scr, BUN and UAER levels of diabetic nephropathy patients, regulate the sugar metabolism pathway of the body, reduce the blood glucose level of the patients, improve the kidney function of the patients, reduce the related TCM syndrome score of the patients, relieve clinical symptoms, and provide a scheme with remarkable effect and high safety for the treatment of diabetic nephropathy.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating diabetic kidney disease and application thereof. BACKGROUND

[0002] Diabetic kidney disease (DKD) is a chronic kidney disease caused by diabetes, which can involve the whole kidney (including glomerulus, renal tubule, renal interstitium, and renal blood vessels). It is also one of the common microvascular complications of diabetes. Its pathogenesis is very complex, involving genetic, abnormal renal hemodynamics, metabolic changes caused by high blood sugar, hypertension, and abnormal metabolism of vasoactive substances (such as angiotensin, endothelin, prostaglandin, and growth factor). Many factors are involved. The main clinical manifestations are edema, foamy urine, nausea and vomiting, fatigue, and other symptoms, accompanied by progressive renal damage. At present, the incidence of chronic kidney disease caused by diabetes is increasing rapidly, which has become the main cause of chronic kidney disease. In 2021, China has become the country with the largest number of diabetes patients, among these patients, diabetic kidney disease patients account for 20%-60%. Diabetic kidney disease not only affects the quality of life of patients, but also leads to decreased filtration and excretion function of the kidney, causing proteinuria, edema, and other symptoms, and can even cause renal failure.

[0003] At present, angiotensin-converting enzyme inhibitors, calcium antagonists, vasodilators, and antihypertensive drugs that act on the sympathetic nervous system are commonly used in clinical treatment of diabetic kidney disease. Although these western medicines can delay the further development of the disease, they cannot cure the disease itself. In addition, long-term use of these drugs during treatment may lead to drug dependence, and can cause urinary tract and reproductive system infections, liver and kidney function damage, and other adverse reactions. Compared with modern medicine, traditional Chinese medicine and its prescriptions show certain curative effect in this disease. Traditional Chinese medicine focuses on individualized treatment according to the specific condition of the patient, and uses traditional Chinese medicine prescriptions to adjust and restore the balance of the body, so as to slow down the development of the disease and improve the quality of life of the patient.

[0004] In traditional Chinese medicine theory, diabetes belongs to the category of "consumption", and diabetic kidney disease is a secondary disease of consumption disease, which is usually caused by long-term consumption, yin deficiency, and kidney yin involvement. The core pathogenesis is deficiency of both qi and yin. There are various methods for treating diabetic kidney disease in traditional Chinese medicine. According to the specific condition and constitution of the patient, the treatment principles of nourishing yin and tonifying kidney, tonifying qi and strengthening body resistance, regulating and smoothing the qi movement of triple energizer, and dredging and permeating the membrane origin are adopted. However, the pathophysiological process of diabetic kidney disease is complex, and a single or a few kinds of traditional Chinese medicinal materials cannot meet the comprehensive treatment requirements. Moreover, the existing traditional Chinese medicine prescriptions are mostly traditional prescriptions, which have been verified for thousands of years, but often lack systematic scientific research support, so it is urgent to develop a traditional Chinese medicine composition with significant therapeutic effect and good safety for treating diabetic kidney disease. SUMMARY

[0005] The technical problems solved by the present application

[0006] In view of the deficiencies of the prior art, the present application provides a traditional Chinese medicine composition for treating diabetic nephropathy and application thereof.

[0007] The technical scheme (II)

[0008] To achieve the above object, the present application is implemented by the following technical scheme:

[0009] The present application provides a traditional Chinese medicine composition for treating diabetic nephropathy, which is composed of the following raw materials in parts by weight: Nanhaiteng 20-40 parts, Tianhuafen 5-25 parts, Xiaoxiancao 5-25 parts, Guchuang 5-25 parts, Luohangzi 5-25 parts, Gegen 5-25 parts, Yushu 20-40 parts, Gansui 0.1-0.8 parts, Zhunkenfen 15-35 parts, Huangqi 1-20 parts, Danshen 1-18 parts.

[0010] Further, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Nanhaiteng 25-35 parts, Tianhuafen 10-20 parts, Xiaoxiancao 10-20 parts, Guchuang 10-20 parts, Luohangzi 10-20 parts, Gegen 10-20 parts, Yushu 25-35 parts, Gansui 0.1-0.4 parts, Zhunkenfen 20-30 parts, Huangqi 5-15 parts, Danshen 3-13 parts.

[0011] Further, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Nanhaiteng 30 parts, Tianhuafen 15 parts, Xiaoxiancao 15 parts, Guchuang 15 parts, Luohangzi 15 parts, Gegen 15 parts, Yushu 30 parts, Gansui 0.2 parts, Zhunkenfen 25 parts, Huangqi 10 parts, Danshen 8 parts.

[0012] The present application provides a preparation method of the traditional Chinese medicine composition for treating diabetic nephropathy, characterized in that the traditional Chinese medicine composition is prepared into any oral dosage form acceptable to human body by using conventional pharmaceutical methods and medical acceptable excipients, including pills, powders, granules, oral liquids, water decoction, tablets.

[0013] Further, the preparation method of the traditional Chinese medicine water decoction for treating diabetic nephropathy comprises the following steps:

[0014] (1) Gansui is weighed according to the above weight parts, washed, uniformly mixed with vinegar, placed in a pot and fried with a small amount of water on a low heat until it is slightly dry, then taken out and dried to obtain vinegar gansui, 3-5 parts of vinegar is used for every 10 parts of gansui;

[0015] (2) the remaining raw materials and vinegar gansui are weighed according to the above weight parts, washed, dried and crushed into coarse powder, and the coarse powder of medicinal materials is placed in a sand pot and soaked in water for 30 min;

[0016] (3) after soaking, the medicinal material is boiled with large fire and then is transferred to small fire to slowly decoct for 30 min, filtration is conducted, the filtrate is taken, the filter residue is added with water again to decoct for 30 min, filtration is conducted, the filtrates of two times are combined, the filtrate is concentrated to 200 mL under reduced pressure, and thus the traditional Chinese medicine decoction of the application is obtained.

[0017] The application provides application of the traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating diabetic nephropathy.

[0018] The pharmacological effects of the traditional Chinese medicine components in the traditional Chinese medicine composition are as follows:

[0019] Nanhaifeng: sweet in taste, neutral in nature, and entering kidney and lung meridians; it has the effects of tonifying deficiency, moistening lung, strengthening tendon and activating collateral; it is used for treating lumbar muscle strain, rheumatic arthritis, pulmonary tuberculosis, chronic bronchitis, chronic hepatitis, spermatorrhea and leukorrhea.

[0020] Tianhuafen: sweet and slightly bitter in taste, slightly cold in nature, and entering lung and stomach meridians; it has the effects of clearing heat and purging fire, generating fluid to relieve thirst, eliminating swelling and discharging pus; it is used for treating heatiness with polydipsia, lung heat with dry cough, internal heat with diabetes, sore and toxic swelling.

[0021] Xiaoerxiancao: bitter in taste, cool in nature, and entering lung, large intestine and bladder meridians; it has the effects of relieving cough and asthma, clearing heat and dampness, regulating menstruation and promoting blood circulation; it is used for treating cough and asthma, dysentery, dysuria, irregular menstruation and contusion and injury.

[0022] Caltrops: pungent and bitter in taste, slightly warm in nature; it enters liver meridian; it has the effects of soothing liver and relieving depression, promoting blood circulation and expelling wind, improving eyesight and relieving itching; it is used for treating headache and dizziness, chest and hypochondrium distending pain, breast abscess, red eyes with nebula, wind dermatosis and itching.

[0023] Luohuazi: also known as pongamia fruit, sweet in taste, neutral in nature, and entering stomach, large intestine and small intestine meridians; it has the effects of harmonizing stomach and promoting digestion, detoxification and insect killing; it is used for treating regurgitation and food vomiting, intestinal obstruction, hernia pain and infantile head abscess.

[0024] Gegen: sweet and pungent in taste, cool in nature, and entering spleen, stomach and lung meridians; it has the effects of relieving muscle and reducing fever, generating fluid to relieve thirst, promoting rash, ascending yang to stop diarrhea, promoting channels and activating collaterals, and relieving alcoholism; it is used for treating external heat with fever and headache, neck and back pain, polydipsia, diabetes, measles without rash, dysentery, diarrhea, dizziness and headache, hemiplegia due to stroke, chest pain and alcoholism.

[0025] Corn silk: sweet and bland in taste, neutral in nature, and entering kidney, stomach, liver and gallbladder meridians; it has the effects of diuresis, eliminating swelling, heat elimination, liver soothing and gallbladder benefiting; it is used for treating nephritis with edema, beriberi, jaundice hepatitis, hypertension, cholecystitis, cholelithiasis, diabetes, hematemesis and metrorrhagia, nasal catarrh and mastitis.

[0026] Gansui: bitter in taste, cold in nature, and entering lung, kidney and large intestine meridians; it has the effects of purging water and fluid, eliminating swelling and resolving mass; it is used for treating edema and distension, chest and abdominal water retention, phlegm retention, adverse qi with cough and asthma, difficulty in urination and defecation, wind-phlegm epilepsy and abscess and sore.

[0027] Pig kidney powder: salty, flat, liver and kidney; has the effect of tonifying kidney and benefiting yang, and promoting water; for kidney deficiency, lumbago, edema, spermatorrhea, night sweats, deafness in the elderly.

[0028] Radix Astragali: sweet, slightly warm, lung and spleen meridians; has the effect of tonifying qi and ascending yang, consolidating the exterior and stopping sweating, promoting water and reducing swelling, producing fluid and nourishing blood, removing stagnation and relieving pain, removing toxins and draining pus, and astringing and generating muscle; for qi deficiency and weakness, poor appetite and loose stools, middle qi collapse, chronic diarrhea and prolapse, blood and metrorrhagia, sweating due to deficiency, edema due to deficiency, internal heat and diabetes, blood deficiency and emaciation, hemiplegia, arthralgia and numbness, and carbuncle and ulcer.

[0029] Salvia miltiorrhiza: bitter, cold, heart and liver meridians; has the effect of promoting blood circulation and removing blood stasis, dredging channels and relieving pain, clearing heart and relieving restlessness, cooling blood and resolving abscess; for chest pain, abdominal pain, accumulation of masses, heat and pain, restlessness and insomnia, irregular menstruation, dysmenorrhea, and abscess.

[0030] (III) beneficial effects

[0031] The application provides a traditional Chinese medicine composition for treating diabetic nephropathy and application, the traditional Chinese medicine composition is composed of south sea rattan, radix trichosanthis, small two fairy grass, tribulus terrestris, ro haozi, radix puerariae, corn silk, kansasan, pig kidney powder, radix astragali, salvia miltiorrhiza, the traditional Chinese medicine composition takes south sea rattan and pig kidney powder as monarch drug, south sea rattan tonifies deficiency and moistens lung, strengthens tendon and activates collateral, can improve glomerular microcirculation, delays renal fibrosis, pig kidney powder tonifies kidney qi and benefits essence-blood, is rich in active peptide and trace element, can regulate kidney metabolism microenvironment, both are used together to jointly play the effects of spleen and kidney tonification and essence-trace element conservation, which is in line with the core pathogenesis of diabetic nephropathy "spleen and kidney deficiency and essence-trace element excretion".

[0032] The traditional Chinese medicine composition can significantly improve blood glucose, blood lipid indexes and kidney function indexes of a diabetic nephropathy model rat, has the effects of regulating sugar and lipid metabolism, improving and protecting kidney function.

[0033] The traditional Chinese medicine composition of the present application significantly improves the total effective rate of clinical treatment of diabetic nephropathy, significantly reduces the fasting blood glucose (FPG), 2h postprandial blood glucose (2hPBG) and glycosylated hemoglobin (HbA1c) levels of diabetic nephropathy patients, has the effect of regulating sugar metabolism of the body; can also significantly reduce the levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary protein excretion rate (UAER), and achieve the effect of improving the kidney function of the patient; in addition, the traditional Chinese medicine composition of the present application can significantly reduce the TCM syndrome score of the patient and improve the clinical symptoms of the patient, and the traditional Chinese medicine composition of the present application can be further developed and applied as a drug for treating diabetic nephropathy. DETAILED DESCRIPTION

[0034] To make the objectives, technical solutions, and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described below in connection with the embodiments of the present application. Obviously, the described embodiments are only some 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 of ordinary skill in the art without creative work fall within the scope of protection of the present application.

[0035] Embodiment 1

[0036] A traditional Chinese medicine composition for treating diabetic nephropathy, which is composed of the following raw materials in parts by weight: Nanhaiteng 30 parts, Tianhuafen 15 parts, Xiaoxiancao 15 parts, Guchuang 15 parts, Luohangzi 15 parts, Gegen 15 parts, Yushu 30 parts, Gansui 0.2 parts, Zhushenfen 25 parts, Huangqi 10 parts, Danshen 8 parts.

[0037] Embodiment 2

[0038] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Nanhaiteng 20 parts, Tianhuafen 5 parts, Xiaoxiancao 5 parts, Guchuang 5 parts, Luohangzi 5 parts, Gegen 5 parts, Yushu 20 parts, Gansui 0.1 part, Zhushenfen 15 parts, Huangqi 1 part, Danshen 1 part.

[0039] Embodiment 3

[0040] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Nanhaiteng 37 parts, Tianhuafen 23 parts, Xiaoxiancao 23 parts, Guchuang 23 parts, Luohangzi 23 parts, Gegen 23 parts, Yushu 37 parts, Gansui 0.7 part, Zhushenfen 32 parts, Huangqi 17 parts, Danshen 16 parts.

[0041] Example 4

[0042] The difference between this example and Example 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Gynura japonica 22 parts, Radix Trichosanthis 7 parts, small two fairy grass 7 parts, Tribulus terrestris 7 parts, Lonicera japonica 7 parts, Pueraria lobata 7 parts, corn silk 22 parts, Kansuia 0.2 parts, pig kidney powder 17 parts, Astragalus 3 parts, Salvia miltiorrhiza 2 parts.

[0043] Example 5

[0044] The difference between this example and Example 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Gynura japonica 40 parts, Radix Trichosanthis 25 parts, small two fairy grass 25 parts, Tribulus terrestris 25 parts, Lonicera japonica 25 parts, Pueraria lobata 25 parts, corn silk 40 parts, Kansuia 0.8 parts, pig kidney powder 35 parts, Astragalus 20 parts, Salvia miltiorrhiza 18 parts.

[0045] Example 6

[0046] The difference between this example and Example 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Gynura japonica 28 parts, Radix Trichosanthis 12 parts, small two fairy grass 12 parts, Tribulus terrestris 12 parts, Lonicera japonica 12 parts, Pueraria lobata 12 parts, corn silk 28 parts, Kansuia 0.5 parts, pig kidney powder 22 parts, Astragalus 5 parts, Salvia miltiorrhiza 4 parts.

[0047] Example 7

[0048] The difference between this example and Example 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Gynura japonica 25 parts, Radix Trichosanthis 9 parts, small two fairy grass 9 parts, Tribulus terrestris 9 parts, Lonicera japonica 9 parts, Pueraria lobata 9 parts, corn silk 25 parts, Kansuia 0.4 parts, pig kidney powder 20 parts, Astragalus 3 parts, Salvia miltiorrhiza 2 parts.

[0049] Example 8

[0050] The difference between this example and Example 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Gynura japonica 35 parts, Radix Trichosanthis 20 parts, small two fairy grass 20 parts, Tribulus terrestris 20 parts, Lonicera japonica 20 parts, Pueraria lobata 20 parts, corn silk 35 parts, Kansuia 0.7 parts, pig kidney powder 30 parts, Astragalus 14 parts, Salvia miltiorrhiza 12 parts.

[0051] Example 9

[0052] The difference between this example and Example 1 is that the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: Gynura japonica 32 parts, Radix Trichosanthis 18 parts, small two fairy grass 18 parts, Tribulus terrestris 18 parts, Lonicera japonica 18 parts, Pueraria lobata 18 parts, corn silk 32 parts, Kansuia 0.6 parts, pig kidney powder 27 parts, Astragalus 17 parts, Salvia miltiorrhiza 15 parts.

[0053] Test Example 1

[0054] 1 Materials and Methods

[0055] 1.1 Experimental Animals

[0056] 120 male SPF SD rats, weighing (200±20) g, 28-30 days old, were purchased from Beijing Huafukang Biotechnology Co., Ltd. and were raised in accordance with the requirements of the laboratory, at a constant temperature of about 25℃, in a 12h light / 12h dark environment, with sufficient drinking water.

[0057] 1.2 Test Drugs

[0058] The traditional Chinese medicine extract in the present application comprises 30 parts of Nanhaiteng, 15 parts of Tianhuafen, 15 parts of Xiaerxiancao, 15 parts of Gucheng, 15 parts of Luohangzi, 30 parts of Corn Silk, 0.2 parts of Gansui, 25 parts of Pig Kidney Powder, 10 parts of Huangqi, and 8 parts of Danshen. Each raw material is weighed according to the above weight ratio, washed, and boiled in 8 times the amount of water for 30 minutes. The filtrate is obtained by filtration, and the process is repeated twice. The two filtrates are combined and concentrated to a crude drug content of 1 g / mL, and stored at 4℃ for use. When used, it is diluted into a high dose of 200 mg / mL and a low dose of 50 mg / mL.

[0059] Sirolimus (rapamycin) oral solution, 50mL: 50mg / bottle, which is used to prepare a 0.05mg / mL solution with drinking water.

[0060] Jinkui Shenqi Pill, which is used to prepare a solution with a drug concentration of 200mg / mL with warm water.

[0061] 1.3 Rat Modeling and Feeding

[0062] The 120 SD rats were randomly divided into a normal control group (n=20) and a diabetic nephropathy modeling group (n=100). The rats in the diabetic nephropathy modeling group were fed with high-sugar high-fat feed for one month, and were injected with streptozotocin twice. The streptozotocin was prepared into an 8mg / mL solution with sterile citric acid buffer (0.1mol / L, pH=4.5). The first injection amount was 30mg / kg of body weight. After the injection, the state of the rats was observed, and the blood glucose was measured by taking the tail blood. One week later, the rats were injected with streptozotocin again at an amount of 35mg / kg of body weight. The modeling standard was that the fasting blood glucose (FPG) was >16.7mmol / L (measured by taking the tail blood every day) 72 hours after the injection. The rats in the normal control group were fed with conventional feed for one month, and were injected with citric acid-sodium citrate buffer (0.1mol / L, pH=4.5) with an injection amount equivalent to that of the modeling group. After the modeling of the diabetic nephropathy rats was successful, all the rats in the normal control group and the diabetic nephropathy modeling group were continued to be fed with conventional feed.

[0063] 1.4 Grouping and Drug Administration

[0064] 100 rats with successful modeling of diabetic nephropathy were randomly divided into 5 groups, namely the model group, the high-dose group of the traditional Chinese medicine composition of the present application (referred to as the high-dose group), the low-dose group of the traditional Chinese medicine composition of the present application (referred to as the low-dose group), the western medicine control group, and the traditional Chinese medicine control group, 20 rats in each group. The high-dose group (200 mg / mL) and the low-dose group (50 mg / mL) were respectively given the traditional Chinese medicine extract of the present application by gavage, with the dose being 25.56 g / kg of body weight and 6.39 g / kg of body weight; the western medicine control group was given rapamycin 0.05 mg / mL solution by gavage, with the dose being 0.5 mg / kg of body weight; the traditional Chinese medicine control group was given 200 mg / mL of Jingu Qiqiwan solution by gavage, with the dose being 12.78 g / kg of body weight; the model group and the normal control group were not given drugs, and were given the same amount of drinking water by gavage; the drug treatment was started on the day of successful modeling, and the continuous administration lasted for 12 weeks.

[0065] 1.5 Determination of biochemical indicators of rats in each group

[0066] Blood test: The blood biochemical indicators were determined by using a fully automatic blood biochemical analyzer. The whole blood was taken from the angular vein on the last day after administration, and the serum was obtained after centrifugation at 3500 rpm at room temperature. The serum of rats in each group was placed on the biochemical analyzer to determine the levels of blood glucose (FPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triacylglycerol (TG), blood urea nitrogen (BUN), serum creatinine (Scr), and albumin (Alb).

[0067] Urine test: 24 h urine was collected by using a metabolic cage after the end of the last administration, and the 24 h urine albumin quantification (24hUAlb) was determined.

[0068] 1.6 Light microscopy of rat kidney tissues

[0069] Hematoxylin-eosin (HE) staining light microscopy: fresh kidney tissues were fixed in 4% paraformaldehyde, paraffin-embedded sections were cut, and the pathological changes of kidney tissues were observed under an optical microscope. The pathological changes of kidney tissues of rats in each group were observed.

[0070] 1.7 Statistical method

[0071] Graphpad Prism 8.0 software was used for data statistical analysis and plotting. The results were expressed as mean ± standard deviation (Mean ± SD). Single factor variance test was used for comparison of differences between groups. P<0.05 was considered to have statistical significance.

[0072] 2 Results

[0073] 2.1 Comparison of blood glucose and lipid indicators of rats in each group

[0074] From Table 1, compared with the normal control group, the FPG, HbA1c, TC and TG levels of the model group rats were significantly increased (P<0.01), indicating that the modeling was successful; compared with the model group, the FPG, HbA1c, TC and TG levels of each administration group were decreased, among which the decrease of the western medicine control group was the most significant (P<0.05, P<0.01), followed by the low-dose group and the traditional Chinese medicine control group (P<0.05), however, the decrease of the high-dose group was relatively small, and the difference was not statistically significant (P>0.05), indicating that the traditional Chinese medicine composition of the application can significantly improve the blood glucose and blood lipid levels of diabetic nephropathy rats, and the effect is the best when the administration dose is 6.39 g / kg.

[0075] Table 1 FPG, HbA1c, TC and TG detection results of rats in each group

[0076]

[0077] Note: compared with the normal control group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01

[0078] 2.2 Comparison of kidney function indexes of rats in each group

[0079] From Table 2, compared with the normal control group, the BUN, Scr and 24hUAlb levels of the model group rats were significantly increased (P<0.01), and the Alb level was significantly decreased (P<0.01), indicating that the modeling was successful, and the kidney function of the rats was impaired; compared with the model group, the BUN, Scr and 24hUAlb levels of each administration group were decreased, and the Alb level was increased, among which the western medicine control group had the most significant improvement effect on the kidney function indexes (P<0.01), followed by the high-dose group and the traditional Chinese medicine control group (P<0.05, P<0.01), and the improvement effect of the low-dose group on the kidney function indexes of rats was relatively small, and the difference was not statistically significant (P>0.05), the above results showed that the traditional Chinese medicine composition of the application had obvious protective effect on the kidney function of diabetic nephropathy rats, and the protective effect was more significant with the increase of the administration dose.

[0080] Table 2 BUN, Scr, Alb and 24hUAlb detection results of rats in each group

[0081] Group BUN(mmol / L) Scr(μmol / L) Alb(g / L) 24hUAlb(mg / L) Normal control group 5.68±0.45 28.67±3.20 40.40±0.68 139.43±25.96 Model group 10.98 ± 0.83 ## ]] 58.69 ± 9.43 ## ]] 29.92 ± 1.23 ## ]] 864.97 ± 240.60 ## ]] Low-dose group 9.56±1.30 43.13 ± 5.54 * ]] 32.88±2.56 405.11 ± 71.27 ** ]] High-dose group 8.87 ± 0.60 * ]] 37.24 ± 3.21 ** ]] 35.16 ± 2.03 * ]] 340.54 ± 68.34 ** ]] Western medicine control group 8.02 ± 0.94 ** ]] 35.71 ± 2.81 ** ]] 36.25 ± 2.04 ** ]] 323.97 ± 70.19 ** ]] Traditional Chinese medicine control group 9.03 ± 0.45 * ]] 39.56 ± 4.73 ** ]] 34.28 ± 1.49 * ]] 363.18 ± 78.99 ** ]]

[0082] Note: compared with the normal control group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05,** P<0.01

[0083] 3Conclusion

[0084] The above test results show that the traditional Chinese medicine composition can significantly improve the blood glucose and blood lipid indicators of diabetic nephropathy rats, reduce the levels of FPG, HbA1c, TC and TG; in addition, the traditional Chinese medicine composition can also significantly improve the renal function indicators of diabetic nephropathy rats, reduce the levels of BUN, Scr and 24hUAlb, and increase the level of Alb, and has a protective effect on the renal function of diabetic nephropathy rats, providing a new idea and method for the treatment of diabetic nephropathy.

[0085] Test Example 2

[0086] Clinical test

[0087] 1Materials and methods

[0088] 1.1General information

[0089] 100 cases of DKD patients were selected as the research objects, and divided into observation group and control group according to random number table method, 50 cases in each group. In the observation group, there were 26 males and 24 females, with an average age of (52.87±6.94) years, an average course of diabetes of (4.97±3.06) years, and an average course of DKD of (12.33±2.16) months. In the control group, there were 27 males and 23 females, with an average age of (54.23±4.88) years, an average course of diabetes of (5.29±2.78) years, and an average course of DKD of (13.57±3.04) months. There was no statistically significant difference in general data between the two groups (P>0.05), which was comparable.

[0090] 1.2Diagnostic criteria

[0091] 1.2.1Diagnosis of diabetes

[0092] According to the diagnostic criteria of type II diabetes in Chinese Type II Diabetes Prevention Guidelines (2017 Edition). That is, there are typical symptoms of diabetes and random blood glucose is ≥11.1mmol / L, or fasting blood glucose (FPG) is ≥7.0mmol / L, or oral glucose tolerance test (OGTT) 2h postprandial blood glucose (2hPG) is ≥11.1mmol / L.

[0093] 1.2.2Diagnosis of DKD

[0094] According to the diagnosis of DKD in American Kidney Foundation Kidney Disease Prognosis Quality Initiative (NKF-K / DOQI) Guidelines and Expert Consensus on Prevention and Treatment of Diabetic Kidney (2014 Edition), the disease stage is stage III, with persistent microalbuminuria, urinary albumin excretion rate (UAER) 20-200μg / min or 30-300mg / 24h.

[0095] 1.2.3 Inclusion Criteria

[0096] Meet the above diagnostic criteria; age 30-70 years old, DKD stage Ⅲ; patients voluntarily participate in this study and sign the informed consent form, approved by the medical ethics committee.

[0097] 1.2.4 Exclusion Criteria

[0098] Recent history of surgery or infection; combined with other kidney disease or urological disease; DKD patients with severe disease requiring dialysis treatment; patients with severe cardiovascular and cerebrovascular diseases or liver function abnormalities; pregnant and lactating women.

[0099] 1.3 Treatment Method

[0100] Control group: conventional western medicine treatment such as hypoglycemic and hypotensive drugs including Glimepiride (GMP, H20057672) and Lutin New (H20030514), etc. Among them, Glimepiride 2mg / time, 1 time / d; Lutin New 5-10mg / time, 1 time / d, during the treatment, symptomatic treatment can be carried out according to the patient's condition.

[0101] Observation group: on the basis of the treatment of the control group, the patients in the observation group orally take the water decoction of the traditional Chinese medicine composition described in Example 1, decocted with water to 200mL, taken twice a day, morning and evening each time, 1 dose / d.

[0102] The treatment course of both groups is 2 months.

[0103] 1.4 Observation Index

[0104] 1.4.1 Blood glucose

[0105] Compare the changes of blood glucose index of patients in two groups before and after treatment, including fasting blood glucose (FPG), 2h postprandial blood glucose (2hPBG) and glycosylated hemoglobin (HbA1c).

[0106] 1.4.2 Renal function

[0107] Compare the changes of blood creatinine (Scr), blood urea nitrogen (BUN) and urinary protein excretion rate (UAER) of patients in two groups before and after treatment.

[0108] 1.4.3 TCM syndrome score

[0109] The changes of TCM symptom scores of the patients in the two groups before and after treatment were compared. The scoring criteria were formulated according to the relevant contents in the "Guidelines for Clinical Research on New Drugs of Traditional Chinese Medicine (Trial)", including fatigue, shortness of breath, lazy speech, soreness of waist and knees, fixed and unmovable waist pain, poor appetite, sticky mouth, heavy limbs, obesity, facial swelling, and limb numbness. According to the severity of the symptoms, 0, 1, 2, and 3 points were scored respectively, and the higher the score, the more severe the symptoms.

[0110] 1.5 Therapeutic criteria

[0111] Marked effect: the symptoms and signs of the patient disappeared, and the UAER decreased by more than 40% compared with before treatment.

[0112] Effectiveness: the symptoms and signs of the patient were alleviated, and the UAER decreased by less than 40% compared with before treatment.

[0113] Ineffectiveness: the symptoms and signs of the patient were not improved or worsened.

[0114] 1.6 Statistical method

[0115] The SPSS 18.0 statistical software was used to represent the measurement data as mean ± standard deviation, the non-independent sample t-test was used between groups, the paired sample t-test was used within groups, the percentage was used to represent the count data, the χ2 test was used for comparison between groups, and P<0.05 was considered to have statistical significance. 2

[0116] 2 Results

[0117] 2.1 Comparison of blood glucose levels of the patients in the two groups before and after treatment

[0118] As shown in Table 3, there was no significant difference in the FPG, 2hPBG, and HbA1c levels of the patients in the control group and the observation group before treatment (P>0.05). After treatment, the FPG, 2hPBG, and HbA1c of the patients in the control group and the observation group were significantly decreased (P<0.05, P<0.01), and the FPG and 2hPBG of the patients in the observation group were significantly lower than those in the control group (P<0.05), and there was no significant difference in HbAlc (P>0.05), indicating that the traditional Chinese medicine composition may effectively improve the blood glucose level of the patients with diabetic nephropathy by regulating the sugar metabolism pathway of the body.

[0119] Table 3 Comparison of blood glucose levels of the two groups

[0120]

[0121] Note: compared with the treatment group, * P<0.05, ** P<0.01; compared with the control group after treatment, # P<0.05, ## P<0.01.​

[0122] 2.2 Two groups of renal function indicators

[0123] From table 4, the BUN, Scr, UAER levels of patients in the control group and the observation group have no significant difference before treatment (P>0.05); after treatment, the BUN, Scr, UAER levels of patients in the control group and the observation group are obviously decreased (P<0.05), and the Scr, UAER levels of patients in the observation group are obviously lower than those in the control group (P<0.05), and the BUN level has no significant difference (P>0.05), which indicates that the traditional Chinese medicine composition can effectively improve the renal function of patients with diabetic nephropathy by reducing the BUN, Scr, UAER levels of patients.

[0124] Table 4 Comparison of renal function indicators of two groups

[0125]

[0126] Note: compared with the treatment group, * P<0.05, ** P<0.01; compared with the control group after treatment, # P<0.05, ## P<0.01.

[0127] 2.3 Comparison of changes of TCM syndrome score of two groups before and after treatment

[0128] From table 5, the TCM syndrome scores of patients in the control group and the observation group have no significant difference before treatment (P>0.05); after treatment, the TCM syndrome scores of patients in the control group and the observation group are obviously lower than those before treatment (P<0.05), and the TCM syndrome score of patients in the observation group is obviously lower than that in the control group (P<0.05), which indicates that the traditional Chinese medicine composition can obviously relieve the clinical symptoms of patients with diabetic nephropathy, and further verifies the effectiveness of the traditional Chinese medicine composition in treating diabetic nephropathy.

[0129] Table 5 TCM syndrome scores of two groups before and after treatment

[0130]

[0131] Note: compared with the treatment group, * P<0.05, ** P<0.01; compared with the control group after treatment, # P<0.05, ## P<0.01.

[0132] 2.4 Comparison of clinical curative effects of two groups

[0133] As shown in Table 6, the total clinical effective rate of the control group is 72%, and the total clinical effective rate of the observation group is 92%, which is significantly higher than that of the control group (P<0.05). In addition, no obvious adverse reactions are observed in the patients during the treatment, indicating that the traditional Chinese medicine composition has a significant clinical effect on the treatment of diabetic nephropathy, and has good tolerability and safety.

[0134] Table 6 Comparison of clinical effects of two groups

[0135]

[0136] 3 Conclusion

[0137] The above test results show that the traditional Chinese medicine composition significantly improves the total clinical effective rate of the treatment of diabetic nephropathy, significantly reduces the fasting blood glucose (FPG), 2h postprandial blood glucose (2hPBG) and glycosylated hemoglobin (HbA1c) levels of the patients with diabetic nephropathy, and has the effect of regulating the body's glucose metabolism; can also significantly reduce the levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary protein excretion rate (UAER), and achieve the effect of improving the renal function of the patients; in addition, the traditional Chinese medicine composition can significantly reduce the TCM syndrome score of the patients and improve the clinical symptoms of the patients, and the traditional Chinese medicine composition can be further developed and applied as a drug for the treatment of diabetic nephropathy.

[0138] The above examples are only used to illustrate the technical solutions of the present application, but not to limit it; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that; the technical solutions recorded in the foregoing examples can be modified, or some technical features can be replaced by equivalents; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A traditional Chinese medicine composition for treating diabetic nephropathy, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 30 parts of *Nanhaiteng*, 15 parts of *Tianhuafen*, 15 parts of *Xiao Erxiancao*, 15 parts of *Jili*, 15 parts of *Luohuangzi*, 15 parts of *Gegen*, 30 parts of corn silk, 0.2 parts of *Gansui*, 25 parts of pig kidney powder, 10 parts of *Huangqi*, and 8 parts of *Danshen*.

2. The method for preparing a traditional Chinese medicine composition for treating diabetic nephropathy as described in claim 1, characterized in that, The traditional Chinese medicine composition is prepared into pills, powders, granules, oral liquids, decoctions, and tablets by conventional pharmaceutical methods and with medically acceptable excipients.

3. The use of the traditional Chinese medicine composition as described in claim 1 in the preparation of a medicament for treating diabetic nephropathy.

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