A traditional Chinese medicine composition for treating diabetic nephropathy

Abstract

The application provides a traditional Chinese medicine composition for treating diabetic nephropathy, which is composed of Huangqi, Danshen, Shuizhi, Fangfeng, Jiegeng, Biejia, Fuzi and Dihuang. The traditional Chinese medicine composition has the effect of treating diabetic nephropathy.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition, specifically a traditional Chinese medicine composition for treating diabetic nephropathy, belonging to the field of traditional Chinese medicine. Background Technology

[0002] Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes, a leading cause of dialysis and kidney transplantation in patients with end-stage renal disease, and a significant contributor to the increased incidence and mortality of cardiovascular disease in diabetic patients. Epidemiological surveys in my country show that the prevention and control of DKD is not optimistic; approximately 21.3% of diabetic patients also have chronic kidney disease, with 24 million cases of chronic kidney disease caused by diabetes. DKD has become a major cause of chronic kidney disease in my country, placing a heavy burden on the healthcare system.

[0003] Current Western medicine strategies for treating DKD mainly focus on four aspects: controlling blood sugar, controlling blood pressure, inhibiting the renin-angiotensin system, and reducing cardiovascular risk. However, existing therapies have very limited effectiveness in preventing the progression of DKD. The exploration and optimization of DKD treatment regimens has always been a major challenge in the field of nephrology.

[0004] Traditional Chinese medicine (TCM) does not have a specific disease name for diabetic nephropathy (DKD). Based on its clinical manifestations and etiology, TCM practitioners, both ancient and modern, generally believe it is closely related to conditions such as "turbid urine," "kidney wasting," "edema," and "abdominal obstruction" that develop after prolonged diabetes. It is attributed to various factors causing dysfunction in the body's qi transformation function, preventing the proper vaporization and distribution of nutrients, thus affecting the physiological functions of the lungs, spleen, and kidneys—a condition characterized by deficiency of the root and excess of the branch. TCM treatment of DKD largely revolves around syndrome differentiation, characterized by a holistic approach and treatment based on syndrome differentiation, primarily focusing on staging and syndrome differentiation. Therefore, given the limited effectiveness of Western medicine alone in treating DKD, the application of TCM combined with Western medicine to effectively prevent and treat DKD and slow its progression has significant clinical value and social importance. Summary of the Invention

[0005] The purpose of this application is to provide a traditional Chinese medicine composition for treating diabetic nephropathy, a method for preparing the traditional Chinese medicine composition, and its application in the preparation of a drug for treating diabetic nephropathy.

[0006] Option 1:

[0007] This application provides a traditional Chinese medicine composition for treating diabetic nephropathy, the composition being made from the following raw materials: Astragalus membranaceus, Salvia miltiorrhiza, Hirudo medicinalis, Saposhnikovia divaricata, Bombyx batryticatus, Cicadae periostracum, Aconitum carmichaelii, Rehmannia glutinosa, Cornus officinalis, Rosa laevigata, Euryale ferox, Rubus idaeus, Cnidium monnieri, Achyranthes bidentata, and Dioscorea opposita.

[0008] Preferably, the traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 20-80 parts by weight, Salvia miltiorrhiza 15-60 parts by weight, Hirudo medicinalis 2-10 parts by weight, Saposhnikovia divaricata 10-40 parts by weight, Bombyx mori 7-28 parts by weight, Cicadae periostracum 7-28 parts by weight, Aconitum carmichaelii 5-20 parts by weight, Rehmannia glutinosa 10-40 parts by weight, Cornus officinalis 10-40 parts by weight, Rosa laevigata 10-40 parts by weight, Euryale ferox 15-60 parts by weight, Rubus idaeus 15-60 parts by weight, Cnidium monnieri 10-40 parts by weight, Achyranthes bidentata 15-60 parts by weight, and Dioscorea opposita 10-40 parts by weight.

[0009] More preferably, the traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 26-69 parts by weight, Salvia miltiorrhiza 18-50 parts by weight, Hirudo medicinalis 3-8.4 parts by weight, Saposhnikovia divaricata 12-32 parts by weight, Bombyx mori 9-23 parts by weight, Cicadae periostracum 9-23 parts by weight, Aconitum carmichaelii 6-16 parts by weight, Rehmannia glutinosa 12-32 parts by weight, Cornus officinalis 12-32 parts by weight, Rosa laevigata 12-32 parts by weight, Euryale ferox 18-50 parts by weight, Rubus idaeus 18-50 parts by weight, Cnidium monnieri 12-32 parts by weight, Achyranthes bidentata 18-50 parts by weight, and Dioscorea opposita 12-32 parts by weight.

[0010] More preferably, the traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 35-60 parts by weight, Salvia miltiorrhiza 23-41 parts by weight, Hirudo medicinalis 4-7.5 parts by weight, Saposhnikovia divaricata 15-27 parts by weight, Bombyx mori 11-20 parts by weight, Cicadae periostracum 11-20 parts by weight, Aconitum carmichaelii 7.5-13 parts by weight, Rehmannia glutinosa 15-27 parts by weight, Cornus officinalis 15-27 parts by weight, Rosa laevigata 15-27 parts by weight, Euryale ferox 23-41 parts by weight, Rubus idaeus 23-41 parts by weight, Cnidium monnieri 15-27 parts by weight, Achyranthes bidentata 23-41 parts by weight, and Dioscorea opposita 15-27 parts by weight.

[0011] Most preferably, the traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 45 parts by weight, Salvia miltiorrhiza 30 parts by weight, Hirudo medicinalis 6 parts by weight, Saposhnikovia divaricata 20 parts by weight, Bombyx mori 15 parts by weight, Cicadae periostracum 15 parts by weight, Aconitum carmichaelii 10 parts by weight, Rehmannia glutinosa 20 parts by weight, Cornus officinalis 20 parts by weight, Rosa laevigata 20 parts by weight, Euryale ferox 30 parts by weight, Rubus idaeus 30 parts by weight, Cnidium monnieri 20 parts by weight, Achyranthes bidentata 30 parts by weight, and Dioscorea opposita 20 parts by weight.

[0012] Alternatively, Astragalus membranaceus 41 parts by weight, Salvia miltiorrhiza 35 parts by weight, Hirudo medicinalis 5 parts by weight, Saposhnikovia divaricata 23 parts by weight, Bombyx mori 13 parts by weight, Cicadae periostracum 17 parts by weight, Aconitum carmichaelii 8.5 parts by weight, Rehmannia glutinosa 23 parts by weight, Cornus officinalis 18 parts by weight, Rosa laevigata 23 parts by weight, Euryale ferox 27 parts by weight, Rubus idaeus 35 parts by weight, Cnidium monnieri 18 parts by weight, Achyranthes bidentata 35 parts by weight, Dioscorea opposita 18 parts by weight;

[0013] Alternatively, use the following ingredients: Astragalus membranaceus 52 parts by weight, Salvia miltiorrhiza 27 parts by weight, Hirudo medicinalis 7 parts by weight, Saposhnikovia divaricata 18 parts by weight, Bombyx mori 17 parts by weight, Cicadae periostracum 13 parts by weight, Aconitum carmichaelii 11 parts by weight, Rehmannia glutinosa 18 parts by weight, Cornus officinalis 23 parts by weight, Rosa laevigata 18 parts by weight, Euryale ferox 35 parts by weight, Rubus idaeus 27 parts by weight, Cnidium monnieri 23 parts by weight, Achyranthes bidentata 27 parts by weight, and Dioscorea opposita 23 parts by weight.

[0014] In the above technical solutions, the traditional Chinese medicine composition can be any form of the above-mentioned raw materials, including: a composition formed by pulverizing the above-mentioned raw materials separately and then mixing them; or, a composition obtained by pulverizing the above-mentioned raw materials after mixing them; or, an extract obtained by extracting the above-mentioned raw materials by conventional extraction methods, and the extract is further purified to obtain the effective fraction; or the above-mentioned extract and effective fraction are further prepared into a conventional oral dosage form according to conventional preparation processes.

[0015] The conventional extraction methods mentioned above include maceration extraction, decoction extraction, reflux extraction, percolation extraction, ultrasonic extraction, and microwave extraction; the extraction solvents include water or conventional organic solvents such as ethanol, methanol, ethyl acetate, petroleum ether, and isopropanol; the purification processes include extraction, column chromatography separation, and high-performance liquid chromatography separation.

[0016] The aforementioned conventional oral dosage forms include tablets, capsules, granules, pills, powders, and oral liquids. The preparation of these dosage forms requires the addition of commonly used pharmaceutically acceptable excipients, including: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and matrices. Fillers include: starch, pregelatinized starch, lactose, mannitol, chitosan, microcrystalline cellulose, sucrose, etc.; disintegrants include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, croscarmellose, low-substituted hydroxypropyl cellulose, croscarmellose sodium, etc.; lubricants include: magnesium stearate, sodium lauryl sulfate, talc, silica, etc.; suspending agents include: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include: starch paste, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.

[0017] Option 2:

[0018] In addition to being fed in the form of raw materials, the traditional Chinese medicine composition of this invention can also be fed in the form of extracts. Therefore, as another aspect of this application, this application further provides a traditional Chinese medicine composition for treating diabetic nephropathy, said traditional Chinese medicine composition being made from the following raw materials: 20-80 parts by weight of Astragalus membranaceus extract, 15-60 parts by weight of Salvia miltiorrhiza extract, 2-10 parts by weight of Hirudo medicinalis extract, 10-40 parts by weight of Saposhnikovia divaricata extract, 7-28 parts by weight of Bombyx mori extract, 7-28 parts by weight of Cicadae periostracum extract, 5-20 parts by weight of Aconitum carmichaelii extract, 10-40 parts by weight of Rehmannia glutinosa extract, 10-40 parts by weight of Cornus officinalis extract, 10-40 parts by weight of Rosa laevigata extract, 15-60 parts by weight of Euryale ferox extract, 15-60 parts by weight of Rubus idaeus extract, 10-40 parts by weight of Cnidium monnieri extract, 15-60 parts by weight of Achyranthes bidentata extract, and 10-40 parts by weight of Dioscorea opposita extract.

[0019] Preferably, the traditional Chinese medicine composition is made from the following raw materials: 26-69 parts by weight of Astragalus membranaceus extract, 18-50 parts by weight of Salvia miltiorrhiza extract, 3-8.4 parts by weight of Hirudo medicinalis extract, 12-32 parts by weight of Saposhnikovia divaricata extract, 9-23 parts by weight of Bombyx mori extract, 9-23 parts by weight of Cicadae periostracum extract, 6-16 parts by weight of Aconitum carmichaelii extract, 12-32 parts by weight of Rehmannia glutinosa extract, 12-32 parts by weight of Cornus officinalis extract, 12-32 parts by weight of Rosa laevigata extract, 18-50 parts by weight of Euryale ferox extract, 18-50 parts by weight of Rubus idaeus extract, 12-32 parts by weight of Cnidium monnieri extract, 18-50 parts by weight of Achyranthes bidentata extract, and 12-32 parts by weight of Dioscorea opposita extract.

[0020] More preferably, the traditional Chinese medicine composition is made from the following raw materials: 35-60 parts by weight of Astragalus membranaceus extract, 23-41 parts by weight of Salvia miltiorrhiza extract, 4-7.5 parts by weight of Hirudo medicinalis extract, 15-27 parts by weight of Saposhnikovia divaricata extract, 11-20 parts by weight of Bombyx mori extract, 11-20 parts by weight of Cicadae periostracum extract, 7.5-13 parts by weight of Aconitum carmichaelii extract, 15-27 parts by weight of Rehmannia glutinosa extract, 15-27 parts by weight of Cornus officinalis extract, 15-27 parts by weight of Rosa laevigata extract, 23-41 parts by weight of Euryale ferox extract, 23-41 parts by weight of Rubus idaeus extract, 15-27 parts by weight of Cnidium monnieri extract, 23-41 parts by weight of Achyranthes bidentata extract, and 15-27 parts by weight of Dioscorea opposita extract.

[0021] Most preferably, the traditional Chinese medicine composition is made from the following raw materials: 45 parts by weight of Astragalus membranaceus extract, 30 parts by weight of Salvia miltiorrhiza extract, 6 parts by weight of Hirudo medicinalis extract, 20 parts by weight of Saposhnikovia divaricata extract, 15 parts by weight of Bombyx mori extract, 15 parts by weight of Cicadae periostracum extract, 10 parts by weight of Aconitum carmichaelii extract, 20 parts by weight of Rehmannia glutinosa extract, 20 parts by weight of Cornus officinalis extract, 20 parts by weight of Rosa laevigata extract, 30 parts by weight of Euryale ferox extract, 30 parts by weight of Rubus idaeus extract, 20 parts by weight of Cnidium monnieri extract, 30 parts by weight of Achyranthes bidentata extract, and 20 parts by weight of Dioscorea opposita extract.

[0022] The extracts are aqueous extracts of each of the active pharmaceutical ingredients.

[0023] Option 3:

[0024] In addition to being fed in the form of raw materials or extracts, the traditional Chinese medicine composition of this invention can also be fed in granule form. Therefore, as another aspect of this application, this application further provides a traditional Chinese medicine composition for treating diabetic nephropathy, said composition being made from the following raw materials: 20-80 parts by weight of Astragalus membranaceus granules, 15-60 parts by weight of Salvia miltiorrhiza granules, 2-10 parts by weight of Hirudo medicinalis granules, 10-40 parts by weight of Saposhnikovia divaricata granules, 7-28 parts by weight of Bombyx mori granules, 7-28 parts by weight of Cicadae periostracum granules, 5-20 parts by weight of Aconitum carmichaelii granules, 10-40 parts by weight of Rehmannia glutinosa granules, 10-40 parts by weight of Cornus officinalis granules, 10-40 parts by weight of Rosa laevigata granules, 15-60 parts by weight of Euryale ferox granules, 15-60 parts by weight of Rubus idaeus granules, 10-40 parts by weight of Cnidium monnieri granules, 15-60 parts by weight of Achyranthes bidentata granules, and 10-40 parts by weight of Dioscorea opposita granules.

[0025] Preferably, the traditional Chinese medicine composition is made from the following raw materials: 26-69 parts by weight of Astragalus membranaceus granules, 18-50 parts by weight of Salvia miltiorrhiza granules, 3-8.4 parts by weight of Hirudo medicinalis granules, 12-32 parts by weight of Saposhnikovia divaricata granules, 9-23 parts by weight of Bombyx mori granules, 9-23 parts by weight of Cicadae periostracum granules, 6-16 parts by weight of Aconitum carmichaelii granules, 12-32 parts by weight of Rehmannia glutinosa granules, 12-32 parts by weight of Cornus officinalis granules, 12-32 parts by weight of Rosa laevigata granules, 18-50 parts by weight of Euryale ferox granules, 18-50 parts by weight of Rubus idaeus granules, 12-32 parts by weight of Cnidium monnieri granules, 18-50 parts by weight of Achyranthes bidentata granules, and 12-32 parts by weight of Dioscorea opposita granules.

[0026] More preferably, the traditional Chinese medicine composition is made from the following raw materials: 35-60 parts by weight of Astragalus membranaceus granules, 23-41 parts by weight of Salvia miltiorrhiza granules, 4-7.5 parts by weight of Hirudo medicinalis granules, 15-27 parts by weight of Saposhnikovia divaricata granules, 11-20 parts by weight of Bombyx mori granules, 11-20 parts by weight of Cicadae periostracum granules, 7.5-13 parts by weight of Aconitum carmichaelii granules, 15-27 parts by weight of Rehmannia glutinosa granules, 15-27 parts by weight of Cornus officinalis granules, 15-27 parts by weight of Rosa laevigata granules, 23-41 parts by weight of Euryale ferox granules, 23-41 parts by weight of Rubus idaeus granules, 15-27 parts by weight of Cnidium monnieri granules, 23-41 parts by weight of Achyranthes bidentata granules, and 15-27 parts by weight of Dioscorea opposita granules.

[0027] Most preferably, the traditional Chinese medicine composition is made from the following raw materials: 45 parts by weight of Astragalus membranaceus granules, 30 parts by weight of Salvia miltiorrhiza granules, 6 parts by weight of Hirudo medicinalis granules, 20 parts by weight of Saposhnikovia divaricata granules, 15 parts by weight of Bombyx mori granules, 15 parts by weight of Cicadae periostracum granules, 10 parts by weight of Aconitum carmichaelii granules, 20 parts by weight of Rehmannia glutinosa granules, 20 parts by weight of Cornus officinalis granules, 20 parts by weight of Rosa laevigata granules, 30 parts by weight of Euryale ferox granules, 30 parts by weight of Rubus idaeus granules, 20 parts by weight of Cnidium monnieri granules, 30 parts by weight of Achyranthes bidentata granules, and 20 parts by weight of Dioscorea opposita granules.

[0028] The particles are either granules made from the water extracts of the various raw materials using conventional processes, or commercially available Chinese medicine granules.

[0029] Option 4:

[0030] As another aspect of this application, this application provides the use of the traditional Chinese medicine composition in the preparation of a medicament for treating diabetic nephropathy.

[0031] All active pharmaceutical ingredients used in this application are listed in the Chinese Pharmacopoeia (2020 edition). Among them, raw Astragalus membranaceus is preferred, raw Rehmannia glutinosa is preferred, and Achyranthes bidentata is preferred.

[0032] The beneficial effects of this application are:

[0033] This formula uses Astragalus membranaceus as the principal herb to invigorate Yang, promote diuresis, and relieve stagnation and numbness. The assistant herbs are Rehmannia glutinosa, Cornus officinalis, Rosa laevigata, Euryale ferox, Achyranthes bidentata, Dioscorea opposita, and Rubus idaeus to tonify the kidneys, consolidate essence, warm and promote circulation without harming the body's vital energy. The adjuvant herbs are Aconitum carmichaelii and Cnidium monnieri to assist in warming Yang and promoting blood circulation. The formula is combined with Salvia miltiorrhiza and Hirudo medicinalis to expel blood stasis without harming new blood. Furthermore, the formula is combined with Saposhnikovia divaricata, Bombyx mori, and Cicadae periostracum to dispel wind. These herbs are light and ascending, also targeting the upper burner, tonifying the kidneys, opening the meridians, and promoting circulation, which helps to regulate the ascending, descending, entering, and exiting of Qi throughout the body.

[0034] Animal experiments conducted in this application have shown that the traditional Chinese medicine composition can reduce fasting blood glucose in KKAy mice, improve oral glucose tolerance (OGTT), and significantly reduce the AUC of OGTT; it can also reduce the urinary albumin to creatinine ratio (ACR) in KKAy mice, and has varying degrees of improvement on renal pathology, thus delaying the progression of kidney disease. Clinical trials have shown that the traditional Chinese medicine composition of this application can significantly reduce fasting blood glucose (FBG), glycated hemoglobin (HbA1c) levels, and 24-hour urinary protein quantification (24hUTP) in patients with diabetic nephropathy. Attached Figure Description

[0035] Various other advantages and benefits will become apparent to those skilled in the art upon reading the following detailed description of preferred embodiments. The accompanying drawings are for illustrative purposes only and are not intended to limit the invention. In the drawings:

[0036] Figure 1 HE staining images (×400x) of mice in each group of Experiment 2; where A: normal group; B: model group; C: irbesartan group; D: low-dose traditional Chinese medicine group; E: medium-dose traditional Chinese medicine group; F: high-dose traditional Chinese medicine group.

[0037] Figure 2 Masson staining images (×400x) of mice in each group of Experiment 2; where A: normal group; B: model group; C: irbesartan group; D: low-dose traditional Chinese medicine group; E: medium-dose traditional Chinese medicine group; F: high-dose traditional Chinese medicine group.

[0038] Figure 3 PAS staining images (×400x) of mice in each group of Experiment 2; where A: normal group; B: model group; C: irbesartan group; D: low-dose traditional Chinese medicine group; E: medium-dose traditional Chinese medicine group; F: high-dose traditional Chinese medicine group.

[0039] Figure 4 Immunohistochemistry of PPARγ protein in the kidney tissue of mice in each group of Experiment Example 2 (×400x); where A: normal group; B: model group; C: low-dose traditional Chinese medicine group; D: medium-dose traditional Chinese medicine group; E: high-dose traditional Chinese medicine group; F: blank control.

[0040] Figure 5 Immunohistochemistry of ERK1 / 2 protein in the kidney tissue of mice in Experiment Example 2 (×400x); where A: normal group; B: model group; C: low-dose traditional Chinese medicine group; D: medium-dose traditional Chinese medicine group; E: high-dose traditional Chinese medicine group; F: blank control. Detailed Implementation

[0041] Exemplary embodiments of the invention will now be described in more detail with reference to the accompanying drawings. While exemplary embodiments of the invention are shown in the drawings, it should be understood that the invention may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0042] Example 1

[0043] Formula: Astragalus membranaceus 45g, Salvia miltiorrhiza 30g, Hirudo medicinalis 6g, Saposhnikovia divaricata 20g, Bombyx mori 15g, Cicadae periostracum 15g, Aconitum carmichaelii 10g, Rehmannia glutinosa 20g, Cornus officinalis 20g, Rosa laevigata 20g, Euryale ferox 30g, Rubus idaeus 30g, Cnidium monnieri 20g, Achyranthes bidentata 30g, Dioscorea opposita 20g;

[0044] Preparation method:

[0045] Step 1, decoction: First decoct the aconite (soak for 30 minutes, heat and decoct for 30 minutes), then add the other medicinal materials, decoct twice in total. For the first decoction, add water equal to 10 times the total weight of the medicinal materials and decoct for 2 hours; for the second decoction, add water equal to 8 times the total weight of the medicinal materials and decoct for 1 hour; filter and combine the two decoctions.

[0046] Step 2, Concentration: Concentrate the filtrate to a thick paste with a relative density of 1.30-1.33;

[0047] Step 3, vacuum drying: Place the concentrate in a vacuum drying oven and dry it.

[0048] Step 4, Grinding: Place the dried paste in a grinder to grind it, then bag it and seal it for storage.

[0049] Example 2

[0050] Formula: Astragalus membranaceus 41g, Salvia miltiorrhiza 35g, Hirudo medicinalis 5g, Saposhnikovia divaricata 23g, Bombyx mori 13g, Cicadae periostracum 17g, Aconitum carmichaelii 8.5g, Rehmannia glutinosa 23g, Cornus officinalis 18g, Rosa laevigata 23g, Euryale ferox 27g, Rubus idaeus 35g, Cnidium monnieri 18g, Achyranthes bidentata 35g, Dioscorea opposita 18g;

[0051] Example 3

[0052] Formula: Astragalus membranaceus 52g, Salvia miltiorrhiza 27g, Hirudo medicinalis 7g, Saposhnikovia divaricata 18g, Bombyx mori 17g, Cicadae periostracum 13g, Aconitum carmichaelii 11g, Rehmannia glutinosa 18g, Cornus officinalis 23g, Rosa laevigata 18g, Euryale ferox 35g, Rubus idaeus 27g, Cnidium monnieri 23g, Achyranthes bidentata 27g, Dioscorea opposita 23g.

[0053] Example 4

[0054] Formula: Astragalus membranaceus 43g, Salvia miltiorrhiza 33g, Hirudo medicinalis 5.5g, Saposhnikovia divaricata 22g, Bombyx mori 14g, Cicadae periostracum 16g, Aconitum carmichaelii 9g, Rehmannia glutinosa 22g, Cornus officinalis 19g, Rosa laevigata 22g, Euryale ferox 28g, Rubus idaeus 33g, Cnidium monnieri 19g, Achyranthes bidentata 33g, Dioscorea opposita 19g.

[0055] Example 5

[0056] Formula: Astragalus membranaceus 48g, Salvia miltiorrhiza 28g, Hirudo medicinalis 6.5g, Saposhnikovia divaricata 19g, Bombyx mori 16g, Cicadae periostracum 14g, Aconitum carmichaelii 10.5g, Rehmannia glutinosa 19g, Cornus officinalis 22g, Rosa laevigata 19g, Euryale ferox 33g, Rubus idaeus 28g, Cnidium monnieri 22g, Achyranthes bidentata 28g, Dioscorea opposita 22g.

[0057] Example 6

[0058] Formula: Astragalus membranaceus 39g, Salvia miltiorrhiza 36g, Hirudo medicinalis 4.7g, Saposhnikovia divaricata 24g, Bombyx mori 12g, Cicadae periostracum 18g, Aconitum carmichaelii 8.2g, Rehmannia glutinosa 24g, Cornus officinalis 18g, Rosa laevigata 24g, Euryale ferox 25g, Rubus idaeus 36g, Cnidium monnieri 18g, Achyranthes bidentata 36g, Dioscorea opposita 18g.

[0059] Example 7

[0060] Formula: Astragalus membranaceus 54g, Salvia miltiorrhiza 25g, Hirudo medicinalis 7g, Saposhnikovia divaricata 18g, Bombyx mori 18g, Cicadae periostracum 12g, Aconitum carmichaelii 11.5g, Rehmannia glutinosa 18g, Cornus officinalis 24g, Rosa laevigata 18g, Euryale ferox 36g, Rubus idaeus 25g, Cnidium monnieri 24g, Achyranthes bidentata 25g, Dioscorea opposita 24g.

[0061] Example 8

[0062] Formula: Astragalus membranaceus 33g, Salvia miltiorrhiza 44g, Hirudo medicinalis 3.7g, Saposhnikovia divaricata 28g, Bombyx mori 10.5g, Cicadae periostracum 21g, Aconitum carmichaelii 7g, Rehmannia glutinosa 28g, Cornus officinalis 14g, Rosa laevigata 28g, Euryale ferox 22g, Rubus idaeus 44g, Cnidium monnieri 14g, Achyranthes bidentata 44g, Dioscorea opposita 14g.

[0063] Example 9

[0064] Formula: Astragalus membranaceus 62g, Salvia miltiorrhiza 22g, Hirudo medicinalis 7.8g, Saposhnikovia divaricata 14g, Bombyx mori 21g, Cicadae periostracum 10.5g, Aconitum carmichaelii 14g, Rehmannia glutinosa 14g, Cornus officinalis 28g, Rosa laevigata 14g, Euryale ferox 44g, Rubus idaeus 22g, Cnidium monnieri 28g, Achyranthes bidentata 22g, Dioscorea opposita 28g.

[0065] Example 10

[0066] Formula: Astragalus membranaceus 29g, Salvia miltiorrhiza 47g, Hirudo medicinalis 3.3g, Saposhnikovia divaricata 30g, Bombyx mori 9.5g, Cicadae periostracum 22g, Aconitum carmichaelii 6.5g, Rehmannia glutinosa 30g, Cornus officinalis 13g, Rosa laevigata 30g, Euryale ferox 20g, Rubus idaeus 47g, Cnidium monnieri 13g, Achyranthes bidentata 47g, Dioscorea opposita 13g.

[0067] Example 11

[0068] Formula: Astragalus membranaceus 66g, Salvia miltiorrhiza 20g, Hirudo medicinalis 8g, Saposhnikovia divaricata 13g, Bombyx mori 22g, Cicadae periostracum 9.5g, Aconitum carmichaelii 15g, Rehmannia glutinosa 13g, Cornus officinalis 30g, Rosa laevigata 13g, Euryale ferox 47g, Rubus idaeus 20g, Cnidium monnieri 30g, Achyranthes bidentata 20g, Dioscorea opposita 30g.

[0069] Example 12

[0070] Formula: Astragalus membranaceus 24g, Salvia miltiorrhiza 53g, Hirudo medicinalis 2.7g, Saposhnikovia divaricata 34g, Bombyx mori 8g, Cicadae periostracum 25g, Aconitum carmichaelii 6g, Rehmannia glutinosa 34g, Cornus officinalis 11.5g, Rosa laevigata 34g, Euryale ferox 17g, Rubus idaeus 53g, Cnidium monnieri 11.5g, Achyranthes bidentata 53g, Dioscorea opposita 11.5g.

[0071] Example 13

[0072] Formula: Astragalus membranaceus 72g, Salvia miltiorrhiza 17g, Hirudo medicinalis 9g, Saposhnikovia divaricata 11.5g, Bombyx mori 25g, Cicadae periostracum 8g, Aconitum carmichaelii 17g, Rehmannia glutinosa 11.5g, Cornus officinalis 34g, Rosa laevigata 11.5g, Euryale ferox 53g, Rubus idaeus 17g, Cnidium monnieri 34g, Achyranthes bidentata 17g, Dioscorea opposita 34g.

[0073] Example 14

[0074] Formula: Astragalus membranaceus 22g, Salvia miltiorrhiza 56g, Hirudo medicinalis 2.5g, Saposhnikovia divaricata 37g, Bombyx mori 7.5g, Cicadae periostracum 26g, Aconitum carmichaelii 6g, Rehmannia glutinosa 37g, Cornus officinalis 10g, Rosa laevigata 37g, Euryale ferox 16g, Rubus idaeus 56g, Cnidium monnieri 10g, Achyranthes bidentata 56g, Dioscorea opposita 10g.

[0075] Example 15

[0076] Formula: Astragalus membranaceus 76g, Salvia miltiorrhiza 16g, Hirudo medicinalis 9.5g, Saposhnikovia divaricata 10g, Bombyx mori 26g, Cicadae periostracum 7.5g, Aconitum carmichaelii 17g, Rehmannia glutinosa 10g, Cornus officinalis 37g, Rosa laevigata 10g, Euryale ferox 56g, Rubus idaeus 16g, Cnidium monnieri 37g, Achyranthes bidentata 16g, Dioscorea opposita 37g.

[0077] The preparation methods of the compositions in Examples 2-15 are the same as those in Example 1.

[0078] Example 16

[0079] Formula: Astragalus membranaceus extract 45g, Salvia miltiorrhiza extract 30g, Hirudo medicinalis extract 6g, Saposhnikovia divaricata extract 20g, Bombyx mori extract 15g, Cicadae periostracum extract 15g, Aconitum carmichaelii extract 10g, Rehmannia glutinosa extract 20g, Cornus officinalis extract 20g, Rosa laevigata extract 20g, Euryale ferox extract 30g, Rubus idaeus extract 30g, Cnidium monnieri extract 20g, Achyranthes bidentata extract 30g, Dioscorea opposita extract 20g;

[0080] Example 17

[0081] Formula: Astragalus membranaceus extract 41g, Salvia miltiorrhiza extract 35g, Hirudo medicinalis extract 5g, Saposhnikovia divaricata extract 23g, Bombyx mori extract 13g, Cicadae periostracum extract 17g, Aconitum carmichaelii extract 8.5g, Rehmannia glutinosa extract 23g, Cornus officinalis extract 18g, Rosa laevigata extract 23g, Euryale ferox extract 27g, Rubus idaeus extract 35g, Cnidium monnieri extract 18g, Achyranthes bidentata extract 35g, Dioscorea opposita extract 18g;

[0082] Example 18

[0083] Formula: Astragalus membranaceus extract 52g, Salvia miltiorrhiza extract 27g, Hirudo medicinalis extract 7g, Saposhnikovia divaricata extract 18g, Bombyx mori extract 17g, Cicadae periostracum extract 13g, Aconitum carmichaelii extract 11g, Rehmannia glutinosa extract 18g, Cornus officinalis extract 23g, Rosa laevigata extract 18g, Euryale ferox extract 35g, Rubus idaeus extract 27g, Cnidium monnieri extract 23g, Achyranthes bidentata extract 27g, Dioscorea opposita extract 23g.

[0084] Example 19

[0085] Formula: Astragalus membranaceus extract 39g, Salvia miltiorrhiza extract 36g, Hirudo medicinalis extract 4.7g, Saposhnikovia divaricata extract 24g, Bombyx mori extract 12g, Cicadae periostracum extract 18g, Aconitum carmichaelii extract 8.2g, Rehmannia glutinosa extract 24g, Cornus officinalis extract 18g, Rosa laevigata extract 24g, Euryale ferox extract 25g, Rubus idaeus extract 36g, Cnidium monnieri extract 18g, Achyranthes bidentata extract 36g, Dioscorea opposita extract 18g.

[0086] Example 20

[0087] Formula: Astragalus membranaceus extract 54g, Salvia miltiorrhiza extract 25g, Hirudo medicinalis extract 7g, Saposhnikovia divaricata extract 18g, Bombyx mori extract 18g, Cicadae periostracum extract 12g, Aconitum carmichaelii extract 11.5g, Rehmannia glutinosa extract 18g, Cornus officinalis extract 24g, Rosa laevigata extract 18g, Euryale ferox extract 36g, Rubus idaeus extract 25g, Cnidium monnieri extract 24g, Achyranthes bidentata extract 25g, Dioscorea opposita extract 24g.

[0088] Example 21

[0089] Formula: Astragalus membranaceus extract 29g, Salvia miltiorrhiza extract 47g, Hirudo medicinalis extract 3.3g, Saposhnikovia divaricata extract 30g, Bombyx mori extract 9.5g, Cicadae periostracum extract 22g, Aconitum carmichaelii extract 6.5g, Rehmannia glutinosa extract 30g, Cornus officinalis extract 13g, Rosa laevigata extract 30g, Euryale ferox extract 20g, Rubus idaeus extract 47g, Cnidium monnieri extract 13g, Achyranthes bidentata extract 47g, Dioscorea opposita extract 13g.

[0090] Example 22

[0091] Formula: Astragalus membranaceus extract 66g, Salvia miltiorrhiza extract 20g, Hirudo medicinalis extract 8g, Saposhnikovia divaricata extract 13g, Bombyx mori extract 22g, Cicadae periostracum extract 9.5g, Aconitum carmichaelii extract 15g, Rehmannia glutinosa extract 13g, Cornus officinalis extract 30g, Rosa laevigata extract 13g, Euryale ferox extract 47g, Rubus idaeus extract 20g, Cnidium monnieri extract 30g, Achyranthes bidentata extract 20g, Dioscorea opposita extract 30g.

[0092] Example 23

[0093] Formula: Astragalus membranaceus extract 22g, Salvia miltiorrhiza extract 56g, Hirudo medicinalis extract 2.5g, Saposhnikovia divaricata extract 37g, Bombyx mori extract 7.5g, Cicadae periostracum extract 26g, Aconitum carmichaelii extract 6g, Rehmannia glutinosa extract 37g, Cornus officinalis extract 10g, Rosa laevigata extract 37g, Euryale ferox extract 16g, Rubus idaeus extract 56g, Cnidium monnieri extract 10g, Achyranthes bidentata extract 56g, Dioscorea opposita extract 10g.

[0094] Example 24

[0095] Formula: Astragalus membranaceus extract 76g, Salvia miltiorrhiza extract 16g, Hirudo medicinalis extract 9.5g, Saposhnikovia divaricata extract 10g, Bombyx mori extract 26g, Cicadae periostracum extract 7.5g, Aconitum carmichaelii extract 17g, Rehmannia glutinosa extract 10g, Cornus officinalis extract 37g, Rosa laevigata extract 10g, Euryale ferox extract 56g, Rubus idaeus extract 16g, Cnidium monnieri extract 37g, Achyranthes bidentata extract 16g, Dioscorea opposita extract 37g.

[0096] The extracts described in Examples 16-24 above are water extracts of the respective active pharmaceutical ingredients.

[0097] Example 25

[0098] Formula: Astragalus membranaceus granules 45g, Salvia miltiorrhiza granules 30g, Hirudo medicinalis granules 6g, Saposhnikovia divaricata granules 20g, Bombyx mori granules 15g, Cicadae periostracum granules 15g, Aconitum carmichaelii granules 10g, Rehmannia glutinosa granules 20g, Cornus officinalis granules 20g, Rosa laevigata granules 20g, Euryale ferox granules 30g, Rubus idaeus granules 30g, Cnidium monnieri granules 20g, Achyranthes bidentata granules 30g, Dioscorea opposita granules 20g;

[0099] Example 26

[0100] Formula: Astragalus membranaceus granules 41g, Salvia miltiorrhiza granules 35g, Hirudo medicinalis granules 5g, Saposhnikovia divaricata granules 23g, Bombyx mori granules 13g, Cicadae periostracum granules 17g, Aconitum carmichaelii granules 8.5g, Rehmannia glutinosa granules 23g, Cornus officinalis granules 18g, Rosa laevigata granules 23g, Euryale ferox granules 27g, Rubus idaeus granules 35g, Cnidium monnieri granules 18g, Achyranthes bidentata granules 35g, Dioscorea opposita granules 18g;

[0101] Example 27

[0102] Formula: Astragalus membranaceus granules 52g, Salvia miltiorrhiza granules 27g, Hirudo medicinalis granules 7g, Saposhnikovia divaricata granules 18g, Bombyx mori granules 17g, Cicadae periostracum granules 13g, Aconitum carmichaelii granules 11g, Rehmannia glutinosa granules 18g, Cornus officinalis granules 23g, Rosa laevigata granules 18g, Euryale ferox granules 35g, Rubus idaeus granules 27g, Cnidium monnieri granules 23g, Achyranthes bidentata granules 27g, Dioscorea opposita granules 23g.

[0103] Example 28

[0104] Formula: Astragalus membranaceus granules 43g, Salvia miltiorrhiza granules 33g, Hirudo medicinalis granules 5.5g, Saposhnikovia divaricata granules 22g, Bombyx batryticatus granules 14g, Cicadae periostracum granules 16g, Aconitum carmichaelii granules 9g, Rehmannia glutinosa granules 22g, Cornus officinalis granules 19g, Rosa laevigata granules 22g, Euryale ferox granules 28g, Rubus idaeus granules 33g, Cnidium monnieri granules 19g, Achyranthes bidentata granules 33g, Dioscorea opposita granules 19g.

[0105] Example 29

[0106] Formula: Astragalus membranaceus granules 48g, Salvia miltiorrhiza granules 28g, Hirudo medicinalis granules 6.5g, Saposhnikovia divaricata granules 19g, Bombyx mori granules 16g, Cicadae periostracum granules 14g, Aconitum carmichaelii granules 10.5g, Rehmannia glutinosa granules 19g, Cornus officinalis granules 22g, Rosa laevigata granules 19g, Euryale ferox granules 33g, Rubus idaeus granules 28g, Cnidium monnieri granules 22g, Achyranthes bidentata granules 28g, Dioscorea opposita granules 22g.

[0107] Example 30

[0108] Formula: Astragalus membranaceus granules 33g, Salvia miltiorrhiza granules 44g, Hirudo medicinalis granules 3.7g, Saposhnikovia divaricata granules 28g, Bombyx mori granules 10.5g, Cicadae periostracum granules 21g, Aconitum carmichaelii granules 7g, Rehmannia glutinosa granules 28g, Cornus officinalis granules 14g, Rosa laevigata granules 28g, Euryale ferox granules 22g, Rubus idaeus granules 44g, Cnidium monnieri granules 14g, Achyranthes bidentata granules 44g, Dioscorea opposita granules 14g.

[0109] Example 31

[0110] Formula: Astragalus membranaceus granules 62g, Salvia miltiorrhiza granules 22g, Hirudo medicinalis granules 7.8g, Saposhnikovia divaricata granules 14g, Bombyx mori granules 21g, Cicadae periostracum granules 10.5g, Aconitum carmichaelii granules 14g, Rehmannia glutinosa granules 14g, Cornus officinalis granules 28g, Rosa laevigata granules 14g, Euryale ferox granules 44g, Rubus idaeus granules 22g, Cnidium monnieri granules 28g, Achyranthes bidentata granules 22g, Dioscorea opposita granules 28g.

[0111] Example 32

[0112] Formula: Astragalus membranaceus granules 24g, Salvia miltiorrhiza granules 53g, Hirudo medicinalis granules 2.7g, Saposhnikovia divaricata granules 34g, Bombyx batryticatus granules 8g, Cicadae periostracum granules 25g, Aconitum carmichaelii granules 6g, Rehmannia glutinosa granules 34g, Cornus officinalis granules 11.5g, Rosa laevigata granules 34g, Euryale ferox granules 17g, Rubus idaeus granules 53g, Cnidium monnieri granules 11.5g, Achyranthes bidentata granules 53g, Dioscorea opposita granules 11.5g.

[0113] Example 33

[0114] Formula: Astragalus membranaceus granules 72g, Salvia miltiorrhiza granules 17g, Hirudo medicinalis granules 9g, Saposhnikovia divaricata granules 11.5g, Bombyx mori granules 25g, Cicadae periostracum granules 8g, Aconitum carmichaelii granules 17g, Rehmannia glutinosa granules 11.5g, Cornus officinalis granules 34g, Rosa laevigata granules 11.5g, Euryale ferox granules 53g, Rubus idaeus granules 17g, Cnidium monnieri granules 34g, Achyranthes bidentata granules 17g, Dioscorea opposita granules 34g.

[0115] The granules described in Examples 25-33 above are granules prepared by concentrating the water extracts of each raw material drug according to conventional processes.

[0116] Experimental Example 1: Formulation Screening

[0117] Based on the famous traditional Chinese medicine formula "Shenqi Dihuang Decoction", we modified the formula and investigated the effects of different modifications on diabetic nephropathy.

[0118] Modification Method 1

[0119] Formula: Codonopsis pilosula 20g, Astragalus membranaceus 20g, Rehmannia glutinosa 15g, Dioscorea opposita 30g, Cornus officinalis 12g, Salvia miltiorrhiza 20g, Rubus idaeus 30g, Euryale ferox 15g, Euryale ferox 15g, Cinnamomum cassia 10g, Rheum palmatum (processed with wine) 3g, Ligusticum chuanxiong 15g;

[0120] Efficacy: Tonifies Qi and nourishes Yin, promotes blood circulation and removes blood stasis.

[0121] Formula: This modified formula uses Codonopsis pilosula, Astragalus membranaceus, and Rehmannia glutinosa as the principal herbs to invigorate qi and nourish yin. The assistant herbs are Rubus idaeus, Dioscorea opposita, Cornus officinalis, and Euryale ferox to tonify the kidneys and astringe essence. The adjuvant herbs are Salvia miltiorrhiza, Cinnamomum cassia, Ligusticum chuanxiong, Euonymus alatus, and Rheum palmatum (processed with wine) to unblock the kidney meridians, promote blood circulation, remove blood stasis, and eliminate turbidity.

[0122] Efficacy: In a clinical trial using modified formula 1, 33 patients with diabetic nephropathy were treated. The results showed that the clinical efficacy rate of this modified formula was 48.5% (16 cases), and the total effective rate was 87.9% (29 cases). In addition, blood glucose and urine albumin / creatinine ratios were significantly improved after treatment compared with those before treatment; however, there was no significant difference in serum creatinine levels compared with those before treatment.

[0123] Modification Method 2

[0124] Formula: Astragalus membranaceus 45g, Salvia miltiorrhiza 30g, Hirudo medicinalis 6g, Saposhnikovia divaricata 20g, Bombyx mori 15g, Cicadae periostracum 15g, Aconitum carmichaelii 10g, Rehmannia glutinosa 20g, Cornus officinalis 20g, Rosa laevigata 20g, Euryale ferox 30g, Rubus idaeus 30g, Cnidium monnieri 20g, Achyranthes bidentata 30g, Dioscorea opposita 20g.

[0125] Efficacy: Tonifies the kidneys, opens the meridians and unblocks the collaterals.

[0126] Formula: Astragalus membranaceus is the chief herb in this modified formula, which promotes yang, diuresis, and relieves stagnation and pain. Rehmannia glutinosa, Cornus officinalis, Rosa laevigata, Euryale ferox, Achyranthes bidentata, Dioscorea opposita, and Rubus idaeus are used as assistant herbs to tonify the kidneys, consolidate essence, warm and promote blood circulation without harming the body's vital energy. Aconitum carmichaelii and Cnidium monnieri are added to assist in warming yang and promoting blood circulation. Salvia miltiorrhiza and Hirudo medicinalis are added to remove blood stasis without harming new blood. Saposhnikovia divaricata, Bombyx mori, and Cicadae periostracum are added to dispel wind, which is light and ascends, also targeting the upper burner, tonifying the kidneys, opening the meridians and promoting blood circulation, which is conducive to regulating the ascending, descending, entering and exiting of qi throughout the body.

[0127] Efficacy: This modified formula was used to treat 40 patients with diabetic nephropathy. The results showed that the clinical efficacy rate was 60% (24 cases), and the overall effective rate was 90% (36 cases). In addition, blood glucose, urine albumin / creatinine ratio, and serum creatinine were all significantly improved after treatment compared with before treatment.

[0128] Comparative analysis shows that Modified Formula 2 has a stronger kidney-tonifying and astringent effect than Modified Formula 1, while its diuretic effect is weaker. Modified Formula 2 adds Rosa laevigata and Achyranthes bidentata to tonify the kidneys and astringe essence, and combines them with wind-dispelling herbs such as Saposhnikovia divaricata, Bombyx mori, and Cicadae periostracum to address the upper burner and regulate Qi. Furthermore, Modified Formula 2 removes herbs with excessively strong properties and diuretic effects, such as Euonymus alatus, Cinnamomum cassia, Rheum palmatum (processed with wine), and Ligusticum chuanxiong, to avoid harming the vital energy of patients with chronic and weakened diabetic nephropathy. Clinically, Modified Formula 2 shows a significantly higher efficacy rate in treating diabetic nephropathy than Modified Formula 1. Additionally, Modified Formula 2 significantly reduces serum creatinine levels, while Modified Formula 1 does not.

[0129] Experiment Example 2: Animal Experiment

[0130] Experimental methods:

[0131] KK-Ay diabetic mice were randomly divided into four groups: a model group, a high-dose group (5.98 g / kg / d), a medium-dose group (2.99 g / kg / d), a low-dose group (1.495 g / kg / d), and an irbesartan group (19.5 mg / kg / d), with six mice in each group. Six C57BL / 6J mice were also included as a normal control group. The high-, medium-, and low-dose groups were administered the traditional Chinese medicine composition prepared in Example 1, while the irbesartan group received irbesartan. Administration was once daily for 12 weeks. 24-hour urine samples were collected before the experiment and at weeks 4, 8, and 12 during the experiment to determine the albumin-to-creatinine ratio (ACR). Fasting blood glucose (FBG) was measured at week 12, and an oral glucose tolerance test (OGTT) was performed to measure blood pressure and heart rate. At the end of the 12th week of the experiment, the animals were euthanized and their kidneys were collected for pathological examination, and the immunohistochemical staining of PPARγ and ERK1 / 2 proteins in the kidney tissue was detected.

[0132] Experimental results:

[0133] 1. Effects of the traditional Chinese medicine composition of this application on blood glucose levels in KKAy mice

[0134] The results of fasting blood glucose measurement are shown in Table 1. The results of the OGTT test are shown in Table 2. The results of blood pressure and heart rate are shown in Table 3.

[0135] Table 1. Fasting blood glucose levels in mice before and after intervention ( n = 6, mmol / L)

[0136] normal group 3.17±1.78 7.53±1.24 Model group <![CDATA[8.66±2.23 ** ]]> <![CDATA[16.88±6.23 * ]]> Western medicine group <![CDATA[8.70±2.08 ** ]]> <![CDATA[8.06±3.91 ## ]]> High-dose group of traditional Chinese medicine <![CDATA[7.08±1.82 ** ]]> <![CDATA[9.19±3.31 ## ]]> Medium-dose group of traditional Chinese medicine <![CDATA[9.38±3.56 ** ]]> <![CDATA[6.36±1.39 ## ]]> Low-dose group of traditional Chinese medicine <![CDATA[8.55±2.11 ** ]]> <![CDATA[5.63±1.14 *## ]]>

[0137] Note: * This indicates that compared with the normal group, P<0.05; ** This indicates that compared with the normal group, P < 0.01; # This indicates that compared with the model group, P < 0.05; ##This indicates that compared with the model group, P < 0.01.

[0138] Table 2. Results of OGTT and AUC of OGTT in mice of each group after 12 weeks of intervention ( n = 6, mmol / L)

[0139]

[0140]

[0141] Note: ① * indicates comparison with the normal group, P<0.05; ** indicates comparison with the normal group, P<0.01; # indicates comparison with the model group, P<0.05; ## indicates comparison with the model group, P<0.01.

[0142] ②The AUC of OGTT refers to the area under the blood glucose curve during the oral glucose tolerance test. The higher the value of this indicator, the higher the blood glucose level, and it can more accurately reflect the function of pancreatic β cells and the status of insulin resistance.

[0143] Table 3 Comparison of blood pressure and heart rate in mice of different groups after 12 weeks of intervention.

[0144] normal group 616.38±102.71 104.29±2.77 75.29±2.77 60.75±2.47 Model group <![CDATA[482.20±66.67 * ]]> 119.38±11.65 86.62±7.94 70.16±7.23 Western medicine group <![CDATA[609.50±78.05 # ]]> 109.25±9.35 89.08±9.37 <![CDATA[78.83±9.59 * ]]> High-dose group of traditional Chinese medicine 506.05±86.39 118.39±8.51 86.62±10.73 67.96±15.38 Medium-dose group of traditional Chinese medicine <![CDATA[593.69±87.57 # ]]> 111.99±7.76 <![CDATA[87.68±3.80 ** ]]> <![CDATA[75.13±4.95 ** ]]> Low-dose group of traditional Chinese medicine <![CDATA[605.88±40.13 ## ]]> 116.29±7.34 <![CDATA[92.35±4.84 ** ]]> <![CDATA[79.96±4.16 **## ]]>

[0145] Note: * indicates comparison with the normal group, P<0.05; ** indicates comparison with the normal group, P<0.01; # indicates comparison with the model group, P<0.05; ## indicates comparison with the model group, P<0.01.

[0146] The above results indicate that the herbal composition of this application can reduce fasting blood glucose in KKAy mice, improve OGTT, and significantly reduce the AUC of OGTT, but has no effect on blood pressure.

[0147] 2. Effects of the traditional Chinese medicine composition in this application on ACR in KKAy mice

[0148] The results are shown in Table 4.

[0149] Table 4 Comparison of ACR in mice at different time points ( n=6, pg / ml)

[0150]

[0151]

[0152] Note: * indicates P<0.05 compared with the normal group; ** indicates P<0.01 compared with the normal group; # indicates P<0.05 compared with the model group; ## indicates P<0.01 compared with the model group.

[0153] The above results indicate that the herbal composition of this application can reduce the ACR of KKAy mice at different intervention times, thereby delaying the progression of kidney disease.

[0154] 3. Effects of the herbal composition of this application on renal pathological changes in KKAy mice

[0155] See results Figure 1-3 .

[0156] Depend on Figure 1-3 It is evident that the herbal composition of this application has varying degrees of improvement on the renal pathology of KKAy mice.

[0157] 4. Effects of the traditional Chinese medicine composition of this application on kidney tissue proteins in KKAy mice

[0158] See results Figure 4 , 5 See Table 5.

[0159] Table 5. Effects of the traditional Chinese medicine composition in this application on kidney tissue protein in KKAy mice.

[0160] normal group 0.285±0.009 0.225±0.004 Model group <![CDATA[0.226±0.003 ** ]]> <![CDATA[0.258±0.006 ** ]]> Low-dose group of traditional Chinese medicine <![CDATA[0.279±0.016 ## ]]> <![CDATA[0.231±0.008 ## ]]> Medium-dose group of traditional Chinese medicine <![CDATA[0.267±0.007 *## ]]> <![CDATA[0.237±0.004 **## ]]> High-dose group of traditional Chinese medicine <![CDATA[0.233±0.002 **## ]]> <![CDATA[0.235±0.006 **## ]]>

[0161] Note: * indicates P<0.05 compared with the normal group; ** indicates P<0.01 compared with the normal group; # indicates P<0.05 compared with the model group; ## indicates P<0.01 compared with the model group.

[0162] Depend on Figure 4 , 5 As shown in Table 5, the traditional Chinese medicine composition of this application can increase the content of PPARγ protein in the kidney tissue of KKAy mice and decrease the content of ERK1 / 2 protein to varying degrees.

[0163] Experimental Example 3: Clinical Trial

[0164] Ninety individuals with Kidney Disease (DKD) meeting the diagnostic criteria were randomly divided into an experimental group (n=40) and a control group (n=50). Both groups received routine Western medicine treatment, including a reasonable diet, appropriate exercise, blood sugar control, blood pressure control, and blood lipid control. The experimental group received the traditional Chinese medicine decoction (prepared as a decoction according to conventional methods) in addition to the routine Western medicine treatment. One dose of the above-mentioned traditional Chinese medicine was taken daily, divided into two administrations, morning and evening, with 200ml decocted each time. The treatment course was 3 months. Changes in monitoring indicators before and after intervention were compared between the two groups.

[0165] 2. Diagnostic criteria for DKD

[0166] 2.1 Western Medicine Diagnostic Criteria

[0167] The diagnostic criteria, based on the 2019 Clinical Guidelines for the Prevention and Treatment of Diabetic Kidney Disease in China, are as follows: ① A definite history of diabetes, with a disease duration of more than 5 years; ② Repeated tests of the urinary albumin-to-creatinine ratio (ACR) within 3-6 months, with two consecutive tests showing an ACR > 30 mg / g or a urinary albumin excretion rate (UAER) > 20 μg / min; and / or an estimated glomerular filtration rate (eGFR) < 60 ml·min. -1 1.73m -2 ; the duration exceeds 3 months; ③ and other causes of increased proteinuria caused by kidney disease can be ruled out.

[0168] 2.2 Diagnostic Criteria for Traditional Chinese Medicine Syndromes

[0169] The diagnostic criteria are proposed based on the 2011 "Guidelines for the Prevention and Treatment of Diabetic Nephropathy with Traditional Chinese Medicine":

[0170] Main symptoms: fatigue, shortness of breath, reluctance to speak, spontaneous sweating, and night sweats.

[0171] Secondary symptoms: hot flashes in the palms, soles, and chest; restlessness and insomnia; frequent urination at night; thirst and a desire to drink.

[0172] Accompanying symptoms: numbness or pain in the limbs, with the pain being fixed and unmoving, and the skin being rough and dry.

[0173] Tongue and pulse: The tongue is pale red or dark purple or has ecchymosis, with little or no coating, and the sublingual veins are bluish-purple or varicose. The pulse is soft, thin, weak or deep, wiry, and hesitant.

[0174] A diagnosis can be made by combining the symptoms with at least two primary symptoms, one secondary symptom, and one concurrent symptom, along with the tongue and pulse examination.

[0175] 3. Experimental Results

[0176] 3.1 General Situation

[0177] The results are shown in Table 6. As can be seen from Table 6, there were no statistically significant differences between the two groups in terms of gender composition, age distribution, and duration of diabetes, indicating that the baseline data of the two groups were comparable.

[0178] Table 6 Baseline Information

[0179] Number of cases (male / female) 50(31 / 19) 40(25 / 15) Age (years) 57.78±9.72 59.50±12.46 DM disease duration (years) 12.28±6.03 13.70±8.73

[0180] 3.2 Blood glucose status

[0181] The results are shown in Table 7.

[0182] Table 7 Comparison of FBG and HbA1C before and after treatment.

[0183]

[0184] Note: For comparisons within the control group before and after treatment, #P < 0.05; for comparisons within the experimental group before and after treatment, * < 0.05; for comparisons between the experimental and control groups, △ < 0.05.

[0185] The results showed no statistically significant differences in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels between the two groups before treatment, indicating that the FBG and HbA1c levels were comparable. Within-group comparisons of FBG levels before and after treatment showed that the control group had significantly higher FBG levels (P < 0.05), while the experimental group had significantly lower FBG levels (P < 0.05). Between-group comparisons of FBG levels after treatment also showed a statistically significant difference (P < 0.05). Within-group comparisons of HbA1c levels before and after treatment showed that the control group had significantly higher HbA1c levels (but the difference was not statistically significant), while the experimental group had significantly lower HbA1c levels (P < 0.05). Between-group comparisons of HbA1c levels after treatment also showed no statistically significant difference.

[0186] 3.3 Kidney function status

[0187] The results are shown in Table 8.

[0188] Table 8 Comparison of Cr levels before and after treatment

[0189]

[0190] Note: For comparisons within the control group before and after treatment, #P < 0.05; for comparisons within the experimental group before and after treatment, * < 0.05; for comparisons between the experimental and control groups, △ < 0.05.

[0191] The results showed no statistically significant difference in serum creatinine (Cr) levels between the two groups before treatment, indicating that the Cr levels in the two groups were comparable. Within-group comparisons of Cr levels before and after treatment showed that Cr levels decreased in both groups, with no statistically significant difference in the control group, while a statistically significant difference was observed in the experimental group (P < 0.05).

[0192] 3.4 Results of 24-hour urine protein quantification (24hUTP) measurement

[0193] The results are shown in Table 9.

[0194] Table 9 Comparison of 24hUTP before and after treatment.

[0195]

[0196] Note: For comparisons of the control group before and after treatment, #P<0.05; for comparisons of the experimental group before and after treatment, *<0.05.

[0197] 24-hour urine protein quantification involves collecting all urine over 24 hours to measure the protein content and calculate the total protein level over 24 hours. A persistently elevated level of urine protein is not only a marker of kidney damage but also a risk factor for decreased renal function. The results showed no statistically significant difference in 24-hour UTP levels between the two groups before treatment, indicating that their 24-hour UTP levels were comparable. Within-group comparisons of 24-hour UTP levels before and after treatment showed that the control group had significantly higher 24-hour UTP levels (P < 0.05), while the experimental group had significantly lower 24-hour UTP levels (P < 0.05).

Claims

1. A traditional Chinese medicine composition for treating diabetic nephropathy, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 26-69 parts by weight, Salvia miltiorrhiza 18-50 parts by weight, Hirudo medicinalis 3-8.4 parts by weight, Saposhnikovia divaricata 12-32 parts by weight, Bombyx mori 9-23 parts by weight, Cicadae periostracum 9-23 parts by weight, Aconitum carmichaelii 6-16 parts by weight, Rehmannia glutinosa 12-32 parts by weight, Cornus officinalis 12-32 parts by weight, Rosa laevigata 12-32 parts by weight, Euryale ferox 18-50 parts by weight, Rubus idaeus 18-50 parts by weight, Cnidium monnieri 12-32 parts by weight, Achyranthes bidentata 18-50 parts by weight, and Dioscorea opposita 12-32 parts by weight.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 35-60 parts by weight, Salvia miltiorrhiza 23-41 parts by weight, Hirudo medicinalis 4-7.5 parts by weight, Saposhnikovia divaricata 15-27 parts by weight, Bombyx mori 11-20 parts by weight, Cicadae periostracum 11-20 parts by weight, Aconitum carmichaelii 7.5-13 parts by weight, Rehmannia glutinosa 15-27 parts by weight, Cornus officinalis 15-27 parts by weight, Rosa laevigata 15-27 parts by weight, Euryale ferox 23-41 parts by weight, Rubus idaeus 23-41 parts by weight, Cnidium monnieri 15-27 parts by weight, Achyranthes bidentata 23-41 parts by weight, and Dioscorea opposita 15-27 parts by weight.

3. The traditional Chinese medicine composition as described in claim 2, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: Astragalus membranaceus 45 parts by weight, Salvia miltiorrhiza 30 parts by weight, Hirudo medicinalis 6 parts by weight, Saposhnikovia divaricata 20 parts by weight, Bombyx mori 15 parts by weight, Cicadae periostracum 15 parts by weight, Aconitum carmichaelii 10 parts by weight, Rehmannia glutinosa 20 parts by weight, Cornus officinalis 20 parts by weight, Rosa laevigata 20 parts by weight, Euryale ferox 30 parts by weight, Rubus idaeus 30 parts by weight, Cnidium monnieri 20 parts by weight, Achyranthes bidentata 30 parts by weight, and Dioscorea opposita 20 parts by weight. Alternatively, Astragalus membranaceus 41 parts by weight, Salvia miltiorrhiza 35 parts by weight, Hirudo medicinalis 5 parts by weight, Saposhnikovia divaricata 23 parts by weight, Bombyx mori 13 parts by weight, Cicadae periostracum 17 parts by weight, Aconitum carmichaelii 8.5 parts by weight, Rehmannia glutinosa 23 parts by weight, Cornus officinalis 18 parts by weight, Rosa laevigata 23 parts by weight, Euryale ferox 27 parts by weight, Rubus idaeus 35 parts by weight, Cnidium monnieri 18 parts by weight, Achyranthes bidentata 35 parts by weight, Dioscorea opposita 18 parts by weight; Alternatively, use the following ingredients: Astragalus membranaceus 52 parts by weight, Salvia miltiorrhiza 27 parts by weight, Hirudo medicinalis 7 parts by weight, Saposhnikovia divaricata 18 parts by weight, Bombyx mori 17 parts by weight, Cicadae periostracum 13 parts by weight, Aconitum carmichaelii 11 parts by weight, Rehmannia glutinosa 18 parts by weight, Cornus officinalis 23 parts by weight, Rosa laevigata 18 parts by weight, Euryale ferox 35 parts by weight, Rubus idaeus 27 parts by weight, Cnidium monnieri 23 parts by weight, Achyranthes bidentata 27 parts by weight, and Dioscorea opposita 23 parts by weight.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The Astragalus membranaceus is raw Astragalus membranaceus, the Rehmannia glutinosa is raw Rehmannia glutinosa, and the Achyranthes bidentata is Huai Achyranthes bidentata.

5. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The traditional Chinese medicine composition is a composition obtained by pulverizing the above-mentioned raw materials separately and then mixing them; or, a composition obtained by pulverizing the above-mentioned raw materials after mixing them; or, an extract obtained by extracting the above-mentioned raw materials by conventional extraction methods, and the extract is further purified to obtain the effective fraction; or the above-mentioned extract and effective fraction are further prepared into a conventional oral dosage form according to conventional preparation processes.

6. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The traditional Chinese medicine composition is prepared according to the following method: First, decoct the aconite root, then add the other medicinal materials and decoct together. Filter the decoction, combine the filtrates, and concentrate them.

7. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The traditional Chinese medicine composition is prepared according to the following method: First, soak the aconite root for 30 minutes, then heat and decoct for 30 minutes. Then add the other medicinal materials and decoct twice in total. Filter the decoction, combine the two decoctions and concentrate them.

8. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for treating diabetic nephropathy.

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