Traditional Chinese medicine composition for treating chronic kidney diseases as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating chronic kidney diseases and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts by weight: 15 to 45 parts of radix astragali seu hedysari, 10 to 30 parts of fructus rosae laevigatae, 5 to 15 parts of herba artemisiae anomalae, 10 to 30 parts of herba taraxaci, 5 to 12 parts of rhizoma sparganii, 3 to 10 parts of semen persicae, 5 to 15 parts of herba lycopi and 10 to 20 parts of caulis perillae. The traditional Chinese medicine composition provided by the invention strengthens the body resistance to eliminate pathogenic factors, treats both symptoms and root causes, comprehensively regulates qi and blood and viscera functions of an organism through multi-medicine compatibility, enables blood stasis to be converted, qi and blood to be smooth and viscera to be normal, and is suitable for various diseases with blood stasis and different pathological expressions. After the traditional Chinese medicine composition is used for treatment, the renal function is remarkably improved, and the development process of chronic kidney diseases can be successfully intervened. The traditional Chinese medicine composition has the advantages of definite clinical curative effect, high safety, simple preparation method, low cost and easily available raw materials, and has an application prospect in the field of chronic kidney disease treatment.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chronic kidney disease, and a preparation method and application thereof. Background Art

[0002] Chronic kidney disease (CKD) is a progressive disease, particularly common in patients with diabetes and hypertension. Currently, there is no cure. Dietary adjustments and medications are primarily used to protect kidney function and slow progression to end-stage renal disease. While Western medicine can directly control risk factors such as blood pressure, blood sugar, and lipids, it also has limitations such as significant side effects and relatively limited treatment options. Traditional Chinese medicine, with its multi-component, multi-target mechanism of action, holds great promise for the treatment of CKD, particularly in reducing the adverse reactions of Western medications.

[0003] Numerous clinical trials have demonstrated the significant advantages of traditional Chinese medicine in the treatment of chronic kidney disease and renal fibrosis. The combined use of traditional Chinese and Western medicine in the treatment of chronic kidney disease and renal fibrosis has demonstrated efficacy, effectively delaying the progression of chronic kidney disease to end-stage renal disease, improving clinical symptoms, and enhancing patient survival and quality of life. Therefore, there is an urgent need to identify effective, reliably effective, and highly safe traditional Chinese medicine combinations for the prevention and treatment of chronic kidney disease. Summary of the Invention

[0004] The present invention aims to overcome the problem in the prior art of lack of clinical medication with good efficacy and small side effects, and provides a Chinese medicine composition for treating chronic kidney disease and its preparation method and application to overcome the above-mentioned defects.

[0005] To achieve the above-mentioned purpose, the present invention is implemented through the following technical solutions: The invention discloses a traditional Chinese medicine composition for treating chronic kidney disease. The traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 15-45 parts of astragalus, 10-30 parts of rose laevigata, 5-15 parts of aconite, 10-30 parts of dandelion, 5-12 parts of trigonosciadium japonicum, 3-10 parts of peach kernel, 5-15 parts of zedoaria, and 10-20 parts of perilla stem.

[0006] The properties, taste, meridians and effects of each Chinese herbal medicine in the Chinese herbal composition of the present invention are as follows: Astragalus: Sweet, slightly warm. It enters the Lung and Spleen meridians. It tonifies Qi and raises Yang, strengthens the exterior and stops sweating, promotes diuresis and reduces swelling, promotes fluid production and nourishes blood, promotes circulation and clears cancer, expels toxins and pus, and heals sores and promotes tissue regeneration. It is used for Qi deficiency and fatigue, poor appetite and loose stools, sinking Qi in the middle, chronic diarrhea and prolapse of the anus, bloody stool and metrorrhagia, spontaneous sweating due to exterior deficiency, edema due to Qi deficiency, internal heat and thirst, sallow complexion due to blood deficiency, hemiplegia, pain and numbness, and persistent carbuncles and ulcers.

[0007] Rosa Laevigata: Sour, sweet, astringent, neutral. Enters the kidney, bladder, and large intestine meridians. Strengthens semen, reduces urination, stops metrorrhagia and leukorrhea, and astringes the intestines to stop diarrhea. Used for spermatorrhea, nocturnal emission, frequent urination, metrorrhagia, leukorrhea, and chronic diarrhea and dysentery.

[0008] Liu Ji Nu: Pungent, slightly bitter, and warm in nature. It enters the Heart, Liver, and Spleen meridians. It dissolves blood stasis and promotes menstruation, stops bleeding and reduces swelling, and helps eliminate food stagnation. It is used to treat amenorrhea, dysmenorrhea, postpartum abdominal pain, lochia retention, bruises, injuries from falls, bleeding from wounds, rheumatic pain, blood in the stool, blood in the urine, carbuncles, swellings, burns, abdominal pain from food stagnation, and diarrhea and dysentery.

[0009] Dandelion: Bitter, sweet, and cold. Enters the Liver and Stomach meridians. Clears heat and detoxifies, reduces swelling and resolves stagnation, and promotes diuresis and relieving stranguria. Used for carbuncle swelling, breast abscess, scrofula, conjunctivitis, sore throat, lung abscess, intestinal abscess, damp-heat jaundice, and painful stranguria caused by heat.

[0010] Trigonosciadium japonicum: Pungent, bitter, neutral. Enters the Liver and Spleen meridians. Promotes blood circulation and qi circulation, eliminates stagnation and relieves pain. Used for fatigue, lumps, dysmenorrhea, amenorrhea, chest pain, and pain from food stagnation.

[0011] Peach kernel: Bitter, sweet, neutral. Entries the Heart, Liver, and Large Intestine meridians. Promotes blood circulation, removes blood stasis, moistens the intestines and promotes bowel movements, relieves cough and asthma. Used for amenorrhea, dysmenorrhea, fatigue, abdominal distension, lung and intestinal abscesses, injuries from falls, constipation due to dry intestines, and cough and asthma.

[0012] Ze Lan: Bitter, pungent, slightly warm. Enters the Liver and Spleen meridians. Promotes blood circulation and regulates menstruation, removes blood stasis and resolves carbuncles, and promotes diuresis and reduces swelling. Used for menstrual irregularities, amenorrhea, dysmenorrhea, postpartum bleeding and abdominal pain, sores, carbuncles, swelling, and edema.

[0013] Perilla stem: Pungent, warm. Enters the Lung and Spleen meridians. Regulates Qi, relieves fullness, relieves pain, and stabilizes the fetus. Used for chest tightness, epigastric pain, vomiting, and fetal restlessness.

[0014] Chronic kidney disease is characterized by deficiency of Qi and blood stasis as the root, and damp-heat and blood stasis as the symptoms, which is a syndrome of deficiency of the root and excess of the symptoms. Treatment should be based on tonifying Qi and activating blood circulation to consolidate the root, removing blood stasis and unblocking the meridians to promote the flow of Qi and blood, clearing away heat and removing dampness to eliminate the symptoms, and regulating the spleen and kidney and regulating the Qi. The Chinese medicine composition of the present invention focuses on using Astragalus to tonify Qi and raise Yang, benefit the Deficiency and consolidate the exterior; Trigonosciadium japonicum to break up blood circulation and promote Qi circulation, eliminate symptoms and disperse nodules. The two medicines, one to tonify and the other to promote circulation, play a leading therapeutic role in the core pathogenesis of Qi deficiency and blood stasis. Zedoariae, peach kernel, and Achyranthes bidentata are used as auxiliary herbs to strengthen the power of activating blood circulation and removing blood stasis, and Zedoariae can also promote diuresis and reduce swelling; peach kernel can moisten the intestines and promote bowel movements; Achyranthes bidentata can disperse blood stasis and relieve pain, synergistically improving the circulation of Qi and blood. The three medicines help the main medicine to eliminate blood stasis, dampness, and Qi stagnation. Qi and blood are closely related. Qi is the leader of blood and can promote blood circulation. After Astragalus replenishes Qi, the three auxiliary herbs, Zedoariae Radix, Peach Kernel, and Achyranthes bidentata, exert their stasis-resolving properties, leveraging Qi to dissipate stagnant blood and prevent it from blocking Qi and blood circulation. This reinforces Astragalus's ability to promote the smooth flow of Qi and blood, achieving mutual nourishment. Dandelion is added to clear heat and detoxify, promote dampness and relieve stranguria; Rosa rugosa consolidates essence and promotes urination, astringes the intestines and stops diarrhea; and Perilla stems regulate Qi and alleviate fullness. These three herbs complement the formula, respectively, by clearing heat and dampness, tonifying the kidneys and consolidating essence, and regulating Qi and harmonizing the middle. The formula strengthens the body's vital energy, dispels pathogenic factors, and addresses both the symptoms and the root cause. Through its multi-herb combination, it comprehensively regulates the body's Qi and blood, as well as the function of the internal organs, enabling the dissolution of stagnant blood, the smooth flow of Qi and blood, and the restoration of normal internal organs. It is suitable for a variety of conditions characterized by blood stasis and various pathological manifestations.

[0015] The above components are scientifically matched and, through multi-drug compatibility, can fully regulate the body's Qi and blood, and the function of the internal organs, so that blood stasis can be eliminated, Qi and blood can flow freely, and the internal organs can be restored to normal. It is suitable for a variety of diseases with blood stasis and different pathological manifestations. The best therapeutic effect can be achieved within the above dosage range. Excessive or insufficient drug dosage will cause the primary and secondary pathological mechanisms of the prescription to change.

[0016] Furthermore, the Chinese medicine composition includes the following Chinese medicinal raw materials in parts by weight: 30 parts of Astragalus, 15 parts of Rosa laevigata, 10 parts of Achyranthes bidentata, 20 parts of Taraxacum mongolicum, 8 parts of Trillium, 6 parts of Peach Kernel, 10 parts of Zedoariae, and 15 parts of Perilla stem.

[0017] Furthermore, the traditional Chinese medicine composition also includes pharmaceutically acceptable excipients.

[0018] Furthermore, the Chinese medicine composition is an oral preparation.

[0019] Furthermore, the oral preparation includes capsules, granules, powders, pills, tablets, oral liquids or decoctions.

[0020] On the other hand, the present invention also discloses a method for preparing a traditional Chinese medicine composition for treating chronic kidney disease, which is characterized by comprising the following steps: S1. Weigh out the Chinese medicinal materials according to the ratio and mix them evenly; S2. Extracting the uniformly mixed Chinese medicinal materials with a solvent to prepare a Chinese medicinal extract; concentrating the prepared Chinese medicinal extract to prepare the above-mentioned Chinese medicinal composition for treating chronic kidney disease.

[0021] Furthermore, the extraction solvent of the Chinese medicinal materials is water, ethanol or ethanol-water solution.

[0022] Furthermore, in step S1, the peach kernel is first crushed and then mixed with other Chinese medicinal materials.

[0023] Furthermore, in step S2, the Chinese medicinal materials are extracted in two steps. In practice, the preferred extraction method is as follows: the first extraction time is 1 hour, and the amount of water added is 8-10 times (the appropriate amount of water is determined based on the degree of immersion); the second extraction time is 0.5 hours, and the amount of water added is 6-8 times. The medicinal juice is filtered out and combined with the medicinal juice extracted in the first step.

[0024] On the other hand, the present invention discloses the use of the above-mentioned traditional Chinese medicine composition for treating chronic kidney disease in the preparation of a medicine for treating chronic kidney disease stages 1-4.

[0025] Therefore, the present invention has the following beneficial effects: The Chinese medicine composition of the present invention strengthens the body's vital energy and eliminates pathogenic factors, treating both the symptoms and the root cause. Through a multi-drug combination, it comprehensively regulates the body's qi and blood, as well as the function of the internal organs, promoting the elimination of blood stasis, the smooth flow of qi and blood, and the restoration of normal internal organs. It is suitable for a variety of conditions characterized by blood stasis and various pathological manifestations. Treatment with the Chinese medicine composition of the present invention significantly improves renal function, successfully intervening in the progression of chronic kidney disease. The Chinese medicine composition of the present invention has definite clinical efficacy, high safety, a simple and low-cost preparation method, and readily available raw materials, and has promising application prospects in the treatment of chronic kidney disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the KM survival curve in survival analysis.

[0027] Figure 2 Forest plot for subgroup analysis

[0028] Figure 3 Analyze network graphs for association rules.

[0029] Figure 4 Grouping matrix diagram for association rule analysis.

[0030] Figure 5 This is a cluster analysis diagram of high-frequency medicinal flavors.

[0031] Figure 6 This is a frequency distribution diagram of the dosage of core prescription drug flavors.

[0032] Figure 7 This is a schematic diagram comparing the blood creatinine levels of each group in the rat efficacy experiment.

[0033] Figure 8 This is a schematic diagram comparing the urea nitrogen levels of each group in the rat efficacy experiment.

[0034] Figure 9 This is a schematic diagram comparing the HE staining results of each group in the rat efficacy experiment.

[0035] Figure 10 This is a schematic diagram comparing the Masson staining results of each group in the rat efficacy experiment. DETAILED DESCRIPTION

[0036] The present invention will be further described below with reference to specific embodiments. Those skilled in the art will be able to implement the present invention based on these descriptions. Furthermore, the embodiments of the present invention described below generally represent only a portion of the present invention, rather than all of the embodiments. Therefore, all other embodiments derived by those skilled in the art based on the embodiments of the present invention without inventive effort should fall within the scope of protection of the present invention.

[0037] Example 1: A traditional Chinese medicine composition for treating chronic kidney disease is prepared from the following raw materials: 30g of astragalus, 15g of Rosa laevigata fruit, 10g of Achyranthes bidentata, 20g of Taraxacum mongolicum, 8g of Trigonum multiflorum, 6g of Peach kernel, 10g of Zedoariae rhizome, and 15g of Perilla stem.

[0038] Preparation of Chinese medicine composition: Pre-treatment: First, weigh out each Chinese herbal medicine according to the ratio of raw materials, take peach kernels, crush them through a 0.8cm baffle, and set aside; Extraction: Mix all pre-treated herbs evenly and boil in water. The first extraction is performed for 1 hour with 8 times the total weight of the herbs added, until all the herbs are submerged and some light materials float. The second extraction is performed for 0.5 hour with 6 times the total weight of the herbs added, until all the herbs are submerged and the liquid surface is visible. Combine the extracts from the two extractions to obtain the final product.

[0039] Example 2: A traditional Chinese medicine composition for treating chronic kidney disease is prepared from the following raw materials: 15g of astragalus, 10g of Rosa laevigata fruit, 5g of Achyranthes bidentata, 10g of Taraxacum mongolicum, 5g of Trigonum multiflorum, 3g of Peach kernel, 5g of Zedoariae rhizome, and 10g of Perilla stem.

[0040] Preparation of Chinese medicine composition: Pre-treatment: First, weigh out each Chinese herbal medicine according to the ratio of raw materials, take peach kernels, crush them through a 0.8cm baffle, and set aside; Extraction: Mix all pre-treated herbs evenly and boil in water. The first extraction is performed for 1 hour with 8 times the total weight of the herbs added, until all the herbs are submerged and some light materials float. The second extraction is performed for 0.5 hour with 6 times the total weight of the herbs added, until all the herbs are submerged and the liquid surface is visible. Combine the extracts from the two extractions to obtain the final product.

[0041] Example 3: A traditional Chinese medicine composition for treating chronic kidney disease is prepared from the following raw materials: 45g of astragalus, 30g of Rosa laevigata fruit, 15g of Achyranthes bidentata, 30g of Taraxacum mongolicum, 12g of Trigonum multiflorum, 10g of Peach kernel, 15g of Zedoariae rhizome, and 20g of Perilla stem.

[0042] Preparation of Chinese medicine composition: Pre-treatment: First, weigh out each Chinese herbal medicine according to the ratio of raw materials, take peach kernels, crush them through a 0.8cm baffle, and set aside; Extraction: Mix all pre-treated herbs evenly and boil in water. The first extraction is performed for 1 hour with 8 times the total weight of the herbs added, until all the herbs are submerged and some light materials float. The second extraction is performed for 0.5 hour with 6 times the total weight of the herbs added, until all the herbs are submerged and the liquid surface is visible. Combine the extracts from the two extractions to obtain the final product.

[0043] The beneficial effects of the Chinese medicine composition provided by the present invention are further illustrated below in combination with specific clinical trials and animal pharmacodynamic experiments.

[0044] 1. Clinical Efficacy Verification of Traditional Chinese Medicine in Treating CKD

[0045] 1. Study Design (1) Data source: Patients with CKD stages 1-4 who visited the First Affiliated Hospital, Zhejiang University School of Medicine between October 2021 and December 2024. The study was approved by the Review Board and Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (Zhejiang University First Hospital Ethics Review 2025 No. 0121-Fast), which was granted on February 3, 2025.

[0046] (2) Grouping: Exposed group (n=116): basic Western medicine treatment + individualized Chinese herbal decoction with non-fixed formula (physician differentiates and treats based on syndrome differentiation, and the prescription ingredients are not fixed); non-exposed group (n=148): only basic Western medicine treatment.

[0047] (3) Inclusion criteria: ① Patients with CKD 1-4 stage as the main diagnosis of Western medicine; ② Patients aged 18-80 years old, regardless of gender; ③ Patients using Chinese herbal decoction for more than 3 months continuously or more than 6 months intermittently. Exclusion criteria: ① Patients who have received dialysis treatment or kidney transplantation; ② Patients with other serious underlying diseases (such as hematological malignancies, malignant tumors, etc.); ③ Patients with less than 3 visits in a year; ④ Patients using Chinese patent medicine for a long time. All included patients had no record of taking Chinese herbal decoction within the first three months of baseline. In order to avoid the interference of the components of Chinese patent medicine on the evaluation of clinical efficacy and the excavation of core prescriptions, patients who were not suitable for this study were excluded.

[0048] 2. Results of efficacy evaluation: (1) Patient baseline characteristics: 334 patients who met the inclusion criteria and had no record of taking Chinese herbal decoction within the first three months of baseline were screened from the electronic medical record system, and 2202 prescriptions were visited. In order to avoid the influence of Chinese patent medicine on the statistical results of efficacy, patients who were not suitable for this study were excluded. Finally, 264 patients had complete demographic, diagnostic and medication records, and laboratory examination records, and the number of visit prescriptions was 1718. The patient baseline table is shown in Table 1, of which 116 patients were in the exposure group and 148 patients were in the non-exposure group. There was no significant difference in demographic data (age, gender, occupation) between the two groups of patients, and the patients in the exposure group and the non-exposure group had no preference for the use of traditional Chinese medicine. There were significant differences in CKD stage (p = 0.025) and duration of diagnosis (p = 0.026) between the two groups. In the comparison of comorbidities and concomitant medications (Table 2), there was a significant difference in the use of antihypertensive drugs (p = 0.039) between the two groups, and there was no significant difference in other aspects. For the indicators with significant differences between the groups, further subgroup analysis will be conducted.

[0049] Table 1. Patient baseline table

[0050] Table 2. Patient comorbidities and concomitant medications

[0051] (2) Survival analysis: Survival analysis was performed on 264 patients, and the endpoint event was the proportion of patients with a 10% decrease in eGFR compared with baseline in half a year. Among them, 95 cases (35.9%) reached the endpoint. Among them, 116 cases in the exposure group, 32 cases (27.5%) had outcome events; 148 cases in the non-exposure group, 63 cases (42.5%) had outcome events. Kaplan-Meier curve showed that the survival probability of the exposure group was higher than that of the non-exposure group, and the difference was significant (p = 0.0118) (see Figure 1). Figure 1In the univariate Cox regression, five variables showed significant differences: group (p = 0.0134), hypertension (p = 0.0280), glomerular filtration rate (p = 0.0041), serum creatinine (p = 0.0010), and urea (p = 0.0012). Two multivariate Cox regression models were constructed (Table 3). All variables in each model met the proportional hazards assumption. Model 1 (AIC: 1009.95) included all variables with significant differences in the univariate Cox analysis, and Model 2 (AIC: 1006.59) included the variables retained after eliminating them using the backward stepwise regression method based on Model 1. The HRs for the exposure group in Model 1 and Model 2 were 0.542 (95% CI: 0.351-0.836, p = 0.0056) and 0.533 (95% CI: 0.346-0.822, p = 0.0044), respectively. These results suggest that taking traditional Chinese medicine is an independent protective factor against the long-term decline in glomerular filtration rate in patients with CKD.

[0052] Table 3. Cox regression results

[0053] (3) Subgroup analysis: Variables with significant differences in the baseline table (CKD stage, diagnosis time, and antihypertensive drugs) and variables with significant differences in the Cox regression of survival analysis (hypertension, median SCr, and median BUN) were selected for subgroup analysis and forest plots were drawn (see Appendix Figure 2 ). The results showed that in the subgroup analysis, except for the subgroup of diagnosis time, there was an interaction effect (p = 0.04), while there was no interaction effect in other subgroups (p > 0.05). Among patients with a diagnosis time of ≤5 years, the risk of the exposed group was significantly increased (HR=2.52, 95% CI 1.41-4.49, P=0.002), suggesting that patients diagnosed in the short term are more sensitive to treatment with traditional Chinese medicine; for patients diagnosed for more than 5 years, the HR was not statistically significant.

[0054] (4) Changes in the slopes of eGFR, SCr, and PRO: During the 6-, 9-, and 12-month follow-up periods, the exposed group showed significant differences in the slope changes of glomerular filtration rate (eGFR) and serum creatinine (SCr) compared with the non-exposed group (P < 0.001) (see Table 4). The rate of decline of eGFR in the exposed group was significantly slower, while the rate of decline of SCr was significantly faster, indicating that the renal function of the exposed group improved more significantly. In addition, the slope of proteinuria (PRO) showed no significant difference between the two groups at 6 and 9 months, but was significantly higher in the exposed group than in the non-exposed group at 12 months (P = 0.035), indicating that proteinuria was reduced after long-term treatment. These results indicate that the exposed group had more significant improvements in renal function and proteinuria indicators than the non-exposed group, and this improvement remained stable during the follow-up period.

[0055] Table 4. Changes in eGFR, SCr, and PRO Slopes

[0056] The results of the study showed that the use of non-fixed Chinese medicine formulas can significantly delay the deterioration of renal function, but the optimal formula is unknown.

[0057] 2. Determination of core prescriptions based on data mining

[0058] 1. Prescription data source: 776 valid TCM prescriptions (involving 207 TCM ingredients) were extracted from the exposure group for the clinical efficacy verification of TCM for CKD. After removing duplicate prescriptions, 688 prescriptions remained, involving a total of 207 medicinal ingredients. All prescriptions have shown efficacy in clinical verification.

[0059] 2. Core prescription mining process:

[0060] Step 1 Prescription data cleaning: To ensure the accuracy of the research data analysis results, the names of traditional Chinese medicines are standardized with reference to the 2020 edition of the Chinese Pharmacopoeia.

[0061] Step 2: Efficacy Category Statistics and Nature, Flavor, and Meridian Analysis: TCM efficacy category statistics revealed that tonics, heat-clearing drugs, and blood-activating and stasis-removing drugs were the top three most frequently used categories. Medicinal property analysis revealed that cold-natured drugs (37.26%) were the most commonly used, followed by warm-natured drugs (29.72%). Medicinal flavor analysis revealed that sweet (34.19%) and bitter (31.29%) flavors were commonly used with similar frequency, followed by pungent (23.23%). Meridian analysis revealed that the most commonly used TCMs for chronic kidney disease were primarily categorized as belonging to the liver meridian (20.50%), spleen meridian (15.86%), lung meridian (14.70%), and kidney meridian (12.19%).

[0062] Step 3: Screening of high-frequency medicinal flavors: A frequency analysis was performed on the 207 medicinal flavors, and the 55 Chinese medicinal herbs with the top 10% usage frequency were defined as high-frequency medicinal flavors.

[0063] Step 4: Association rule analysis: 55 frequently occurring medicinal flavors were analyzed using the Apriori algorithm. Minimum support and confidence levels were set to 0.2 and 0.8, respectively, and lift > 1. A total of 45 frequent itemsets were detected. The association rule drug pairs were sorted from highest to lowest support. The top 10 drug pairs with the highest co-occurrence frequency are shown in Table 5. The top two drug pairs with the highest confidence levels were Peach Kernel-Eupatorium Radix and Rosa Laevigatae-Astragalus Radix, indicating the strongest associations. The top two drug pairs with the highest lift levels were Perilla Stem-Eupatorium Radix and Peach Kernel-Eupatorium Radix, demonstrating high reliability.

[0064] Table 5 Analysis of the compatibility relationship of high-frequency Chinese medicine pairs

[0065] Draw the 45 frequent item sets into a network diagram (see Appendix Figure 3 ), it can be concluded from the figure that Astragalus, Zedoaria and Tripterygium wilfordii are the core Chinese medicines for treating chronic kidney disease. Among them, Astragalus is a tonic, while Zedoaria and Tripterygium wilfordii are blood-activating and blood-stasis-removing medicines, reflecting the combined effects of CKD treatment on replenishing qi and activating blood circulation. Use the grouping matrix diagram to cluster the association rule results (see Appendix Figure 4 ), combined with the size of support, the degree of lift and the number of associations, it was determined that the combined use of peach kernel, dandelion, Liu Ji Nu and Ze Lan, Trillium and Astragalus was closer.

[0066] Step 5 Cluster analysis: Use Ward.D method to perform hierarchical cluster analysis on high-frequency medicinal flavors (see Appendix Figure 5 ), the first category focuses on warming and nourishing the spleen and kidneys, while also clearing heat and dampness and strengthening the body; the second category emphasizes strengthening the spleen and removing dampness, supplemented by clearing heat and detoxifying, and nourishing yin; the third category focuses on simultaneously invigorating qi and strengthening the spleen, promoting blood circulation and promoting diuresis; and the fourth category emphasizes the combined use of promoting blood circulation and removing stasis, while also clearing dampness and heat. These four categories, when used in appropriate combinations, can comprehensively regulate the body's yin and yang balance, qi and blood circulation, and visceral function. Astragalus and Trigonosciadium japonicum appeared together in 44.3% of prescriptions, with at least one of them appearing in 84.6% of prescriptions, forming an inseparable monarch-drug pair.

[0067] Step 6: Dose optimization and formula determination: Combine clinical efficacy indicators to screen for patients with eGFR slope > 0 and SCr slope < 0 within 6 months of treatment, corresponding to a total of 459 treatment prescriptions. On this basis, screen for prescriptions containing both Huangqi and Sanleng as the two monarch herbs and with the proportion of core medicinal ingredients > 50%, a total of 145 prescriptions. By statistically analyzing the frequency of use of the dose of each medicinal ingredient, select the highest frequency of clinical use as the optimal dose of the core prescription, wherein Huangqi 30g, Jinyingzi 15g, Liujinuo 10g, Pugongying 20g, Sanleng 8g, Taoren 6g, Zelan 10g, and Zixugeng 15g (see Appendix Figure 6 ).

[0068] III. Preparation of the core formula extract Concentration: The extract obtained in Example 1 was concentrated in a machine-concentration tank (200L) (liquid temperature 60-75℃, vacuum degree ≤-0.08MPa) to a volume of 13.4L, and then transferred to a rotary evaporator (20L) for further concentration (water bath temperature 70℃, vacuum degree ≤-0.092MPa) to a relative density of 1.350 (60℃).

[0069] Drying: All the concentrated liquids were subjected to reduced-pressure drying (temperature 70℃, vacuum degree ≤-0.08MPa, with moderate addition of phosphorus pentoxide to assist drying).

[0070] Pulverization: After drying, the extract was pulverized and passed through a 50-mesh sieve to obtain a traditional Chinese medicine lyophilized powder.

[0071] IV. Pharmacological experiment of traditional Chinese medicine for treating chronic kidney disease in rats The present application uses an adenine-induced chronic kidney disease (CKD) rat model for experiments. The adenine-induced CKD model has the characteristics of being simple, high success rate, long and stable duration of kidney function abnormalities, and similar pathological changes to human CKD. By gavage with adenine, pathological changes such as renal tubular injury, interstitial fibrosis, and glomerular sclerosis can be caused in rats, which have high similarity to the pathological process of human chronic kidney disease. Therefore, the present application uses an adenine-induced CKD rat model to investigate whether the traditional Chinese medicine formula can improve the decline in kidney function and renal fibrosis caused by CKD.

[0072] 1. Experimental method Experimental Animals: Forty-eight SPF male Sprague-Dawley rats, weighing 200 ± 20 g, were provided by Hangzhou Medical College (Quality Certificate No. SCXK (Zhejiang) 2024-0037). The rats were group-housed in an environment maintained at 24 ± 1°C, 50 ± 10% humidity, and a 12-h light / dark cycle. They were allowed to acclimate for 6 days before the experiment. All animal experimental protocols were approved by the Animal Experimentation Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (No. 2025 Shidong No. 117). This approval was granted on April 25, 2025.

[0073] Experimental drugs: The test drug was the lyophilized powder of the Chinese medicine composition prepared in Example 1, and the positive control drug was Urea Clearing Granules, a commonly used Chinese patent medicine for the clinical treatment of chronic kidney disease.

[0074] Animal Model Establishment: After 7 days of adaptive feeding, rats were randomly assigned to six groups (n = 8 per group): a blank control group (CON), a model control group (CKD), a positive drug group (UCG), a low-dose Chinese medicine group (L), a medium-dose Chinese medicine group (M), and a high-dose Chinese medicine group (H). Body weights were measured every other day. Every morning, except for the blank control group, all rats were gavaged with adenine suspension (200 mg / kg / day, prepared and used fresh daily) using 0.5% sodium carboxymethylcellulose (CMC-Na). The control group received an equivalent dose of 0.5% CMC-Na.

[0075] Dosing regimen: Every afternoon (at least 6 hours after modeling), the freeze-dried powder of the traditional Chinese medicine composition and the Niaoduqing granules were dissolved in pure water. The dosages of the crude Chinese medicines were 5.13 g / kg, 10.26 g / kg, and 20.52 g / kg, respectively. The middle dose is the clinically equivalent dose. The Niaoduqing granules were administered at a dose of 5 g / kg. The model and blank control groups were gavaged with an equal volume of pure water.

[0076] 2. Sample collection and indicator testing Four weeks after administration, blood was collected and serum creatinine (SCr) and blood urea nitrogen (BUN) were measured using an automatic biochemical analyzer. Kidneys were fixed with 4% paraformaldehyde and subsequently analyzed by HE and Masson staining.

[0077] 3. Statistical methods Graphpad Prism 10.1.2 software was used for data processing. The measurement data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among multiple groups, and t-test was used for pairwise comparison between groups. P < 0.05 was considered statistically significant.

[0078] 4. Experimental Results (1) Effects on blood creatinine and urea nitrogen in rats Compared with the normal control group, the serum creatinine and urea nitrogen of the rats in the model group increased significantly, indicating that the renal function of the rats was significantly damaged after the modeling. Compared with the model control group, the serum creatinine and urea nitrogen of the Chinese medicine in each dose group were significantly reduced. Among them, the effects of the medium and high dose groups of Chinese medicine on improving the serum creatinine and urea nitrogen were comparable, showing a significant protective effect on the renal function of the rats. The positive drug group also showed a significant improvement effect (see Appendix Figure 7 、 8 ). Figure 7 Compared with the normal control group, *P<0.05, **P<0.01, ***P<0.001; compared with the model control group, #P<0.05, ##P<0.01, ###P<0.001. Figure 8 Compared with the normal control group, * P<0.05, ** P<0.01, *** P<0.001; compared with the model control group, # P<0.05, ## P<0.01, ### P<0.001.

[0079] (2) Pathological changes in rat kidneys HE staining results showed that in the model group, glomerular atrophy, tubular lumen enlargement, epithelial cell damage, inflammatory cell infiltration and a large number of adenine crystal deposition were observed. Different doses of Chinese medicine improved these pathologies. The size of renal tubular epithelial cells was uniform, the glomerular morphology was regular, and the degree of inflammatory cell infiltration was mild. The positive drug group also showed significant improvement (see Appendix). Figure 9 Masson staining revealed extensive renal pathological changes in the adenine group, including focal tubular atrophy and dilation, infiltration of inflammatory cells and myofibroblasts, tubular interstitial fibrosis, and significant collagen deposition. Different doses of Chinese herbal medicine effectively alleviated these pathological abnormalities. The positive drug group also showed significant pathological improvement, with a decrease in the degree of fibrosis (see Appendix). Figure 10 ).

[0080] In summary, the present invention provides a traditional Chinese medicine composition for treating chronic kidney disease and a preparation method thereof. The effective ingredients are extracted from the traditional Chinese medicine and their optimal weight ratio is studied. Experimental results show that the traditional Chinese medicine composition can significantly delay the progression of CKD and improve renal function.

[0081] The above embodiments and experiments are only used to illustrate the technical solutions of the present application, but not limit the present application; although the present application is described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions recorded in the above embodiments can be modified, or some or all of the technical features can be replaced by equivalent replacements; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A Chinese medicine composition for treating chronic kidney disease, characterized in that: The traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 15-45 parts of astragalus, 10-30 parts of rose laevigata, 5-15 parts of aconite, 10-30 parts of dandelion, 5-12 parts of trigonosciadium japonicum, 3-10 parts of peach kernel, 5-15 parts of zedoaria, and 10-20 parts of perilla stem.

2. A Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 30 parts of astragalus, 15 parts of rose laevigata, 10 parts of lilyturf, 20 parts of dandelion, 8 parts of trigonosciadium japonicum, 6 parts of peach kernel, 10 parts of zedoaria, and 15 parts of perilla stem.

3. A Chinese medicine composition for treating chronic kidney disease according to claim 1 or 2, characterized in that: The traditional Chinese medicine composition also includes pharmaceutically acceptable excipients.

4. A Chinese medicine composition for treating chronic kidney disease according to claim 3, characterized in that: The traditional Chinese medicine composition is an oral preparation.

5. A Chinese medicine composition for treating chronic kidney disease according to claim 4, characterized in that: The oral preparations include capsules, granules, powders, pills, tablets, oral liquids or decoctions.

6. A method for preparing a traditional Chinese medicine composition for treating chronic kidney disease, characterized in that: The steps include: S1. Weigh out the Chinese medicinal materials according to the proportion and mix them evenly; S2. Extracting the uniformly mixed Chinese medicinal materials with a solvent to prepare a Chinese medicinal extract; concentrating the prepared Chinese medicinal extract to prepare a Chinese medicinal composition for treating chronic kidney disease as claimed in claim 1 or 2.

7. The method for preparing a traditional Chinese medicine composition for treating chronic kidney disease according to claim 6, characterized in that: The extraction solvent of the Chinese medicinal materials is water, ethanol or ethanol-water solution.

8. The method for preparing a traditional Chinese medicine composition for treating chronic kidney disease according to claim 7, characterized in that: In step S1, the peach kernel is first crushed and then mixed with other Chinese medicinal materials.

9. The method for preparing a traditional Chinese medicine composition for treating chronic kidney disease according to claim 8, characterized in that: In step S2, the Chinese medicinal materials are extracted twice.

10. Use of the traditional Chinese medicine composition for treating chronic kidney disease according to claim 1 or 2 in the preparation of a medicament for treating chronic kidney disease stages 1 to 4.

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