Formula of Shuliguguan drink for treating chronic kidney diseases from liver and preparation method of Shuliguguan drink

Abstract

The invention relates to a formula and a preparation method of a Shuliguguan drink for treating chronic kidney diseases from liver, and belongs to the field of traditional Chinese medicine preparations for treating chronic kidney diseases. In view of the fact that the current commercially available Chinese patent medicine for treating the CKD cannot comprehensively cover the pathogenesis of liver depression, spleen deficiency and pathogen accumulation in triple jiao, the invention provides the Chinese patent medicine which is prepared from 30g of raw astragalus membranaceus, 15g of roasted rhizoma atractylodis macrocephalae, 10g of radix bupleuri, 15g of poria cocos, 15g of cistanche, 15g of oriental wormwood, 10g of rhizoma alismatis, 15g of serissa serissoide, 15g of salvia miltiorrhiza and 10g of raw rhubarb, has the effects of strengthening body resistance, removing toxicity and dredging triple jiao, and is high in total effective rate in clinical tests for treating CKD patients with liver depression and spleen deficiency. Serum creatinine and urea nitrogen can be reduced, and urine protein excretion can be reduced; malnutrition of a patient is improved, the immune function is improved, and the kidney microinflammation state is relieved; the residual renal function is protected, and the renal fibrosis progress is delayed; compared with western medicine basic treatment, the medicine can slow down the decline rate of the glomerular filtration rate, and achieves the effects of delaying renal hypofunction and delaying dialysis starting time.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparations for the treatment of chronic kidney disease, specifically relating to a formula for Shuli Guange Decoction for treating chronic kidney disease from the perspective of liver function and its preparation method. Background Technology

[0002] Chronic kidney disease (CKD) refers to a clinical syndrome characterized by persistent damage to the structure or function of the kidneys for more than three months, resulting in edema, proteinuria, hematuria, impaired renal function, and pathological abnormalities. This disease is prevalent worldwide, with a complex pathogenesis, a long course, and an increasing prevalence and mortality rate.

[0003] Modern medicine has not yet fully elucidated the pathogenesis of CKD, but it may be related to renal fibrosis, nephron loss, microinflammatory states, lipid metabolism disorders, and secondary hyperparathyroidism. Western medicine primarily focuses on conservative treatment for patients with chronic kidney disease that has not yet reached end-stage renal disease. For primary chronic kidney disease, this often involves hormones, immunosuppressants, and conventional kidney-protective drugs, as well as measures to prevent complications and treat comorbidities. For patients with secondary chronic kidney disease, treatment focuses on actively controlling secondary factors, effectively lowering blood sugar and blood pressure, and regulating metabolic abnormalities. However, these approaches face challenges such as numerous drug side effects, heavy financial burdens, and unsatisfactory efficacy. Therefore, the use of traditional Chinese medicine or a combination of traditional Chinese medicine and Western medicine for symptomatic treatment is crucial for the treatment of CKD patients.

[0004] In recent years, traditional Chinese medicine has accumulated rich experience in the treatment of CKD. Through the combination of Chinese medicine, appropriate modifications are made according to the symptoms, thereby achieving the optimization of clinical efficacy. Chinese patent medicines have the advantages of being easy to carry, store, and take, and are one of the important means of TCM prevention and treatment of CKD. Although different TCM doctors have different views on the etiology, pathogenesis and treatment of CKD, they have generally reached a consensus, namely, "deficiency of vital energy and excess of pathogenic factors, impaired qi transformation, and internal accumulation of blood stasis and toxins in the three jiaos". However, the Chinese patent medicines currently used in clinical practice have not covered this basic pathogenesis, specifically: (1) treating CKD with deficiency of both lung and kidney. Such as Jinshuibao and Bailing capsules, which mainly tonify the deficiency of lung and kidney; (2) treating CKD with damp-heat syndrome. Such as Shenkang granules and Huangkui capsules. Shenkang granules mainly resolve dampness and eliminate turbidity, while Huangkui capsules mainly clear damp-heat; (3) treating CKD with damp-turbidity and blood stasis syndrome. Such as Shenkang injection and Shenkang suppositories; (4) treating CKD with damp-turbidity syndrome. Such as Haikun Shenxi capsules. Shenkang Injection, Shenkang Suppository, and Haikun Shenxi Capsules are all mainly used to remove blood stasis, eliminate turbidity, and detoxify. (5) Treatment of CKD with spleen deficiency, dampness, turbidity, and blood stasis syndrome. Such as Shenshui Ning Tablets and Uremic Clearing Granules; mainly used to treat spleen deficiency with dampness and turbidity syndrome and spleen deficiency with blood stasis syndrome. (6) Treatment of CKD with qi and yin deficiency and turbidity syndrome. Such as Shenwu Yishen Tablets; mainly used to treat qi and yin deficiency and turbidity syndrome.

[0005] None of the aforementioned traditional Chinese medicine preparations cover the syndrome of liver stagnation and spleen deficiency. Traditional Chinese medicine believes that if the Shaoyang Sanjiao (Triple Energizer) mechanism is impaired, the qi transformation function is obstructed, leading to dysfunction of the lungs, spleen, and kidneys, abnormal ascending and descending functions of the internal organs, and impaired water metabolism. This results in a series of pathological changes, including poor distribution and excretion, indiscriminate separation of clear and dirty fluids, water retention, leakage of essential substances, and sluggish blood circulation. Therefore, treatment should focus on leveraging the overall regulating and dredging function of the Shaoyang Sanjiao, by supporting the body's resistance and eliminating toxins, and by clearing the Sanjiao, allowing the qi mechanism to function properly, expelling dampness, turbidity, and stagnant toxins from the body, coordinating the functions of the internal organs, and restoring the dynamic balance of the body's internal environment, ultimately achieving the therapeutic effect for CKD (Chronic Chronic Disease). Summary of the Invention

[0006] Given that currently available commercially available traditional Chinese medicine (TCM) treatments for CKD fail to fully encompass the pathogenesis of liver stagnation and spleen deficiency, and the accumulation of pathogenic factors in the triple burner, the purpose of this invention is to propose a formula for treating chronic kidney disease from the perspective of liver function, namely, Shuli Guange Yin, which has the effects of strengthening the body's resistance, eliminating toxins, and regulating the triple burner, and is used to treat patients with CKD exhibiting liver stagnation and spleen deficiency. This Shuli Guange Yin can comprehensively cover the basic pathogenesis of CKD, enriching and improving TCM treatments for CKD and meeting clinical needs.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] A formula for treating chronic kidney disease from the perspective of liver function, called Shuli Guange Decoction, includes the following Chinese herbs by weight: Astragalus membranaceus 20-40g, Atractylodes macrocephala (fried) 10-20g, Bupleurum chinense 5-15g, Poria cocos 10-20g, Cistanche deserticola 10-20g, Artemisia capillaris 10-20g, Alisma plantago-aquatica 5-15g, Serissa japonica 10-20g, Salvia miltiorrhiza 10-20g, and Rheum palmatum 5-15g.

[0009] The explanations of each Chinese herbal medicine in the formula are as follows:

[0010] (1) Raw Astragalus: It is sweet in taste and slightly warm in nature. It has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting tissue regeneration and healing sores, and reducing swelling and promoting diuresis. Experimental studies have found that Astragalus can improve renal hemodynamics, reduce glomerular hyperfiltration, reduce the occurrence of glomerular sclerosis and renal interstitial fibrosis, resist free radicals, and improve the body's immunity, thereby promoting the recovery of damaged glomerular capillaries and renal tubules, preventing further deterioration of the function of remaining nephrons, and improving renal function.

[0011] (2) Stir-fried Atractylodes macrocephala: It tastes bitter and sweet, and is warm in nature. It has the effects of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. Experimental studies have found that Atractylodes macrocephala has the functions of regulating immunity, anti-inflammation, antibacterial, improving gastrointestinal function, lowering blood sugar, diuresis, anti-cancer, and protecting nerves.

[0012] (3) Bupleurum: It is pungent and bitter in taste and slightly cold in nature. It has the effects of dispersing and reducing fever, soothing the liver and relieving depression, and raising yang qi. Experimental studies have found that the main active ingredient of Bupleurum is saikosaponin, which can reduce proteinuria, lower blood lipids, reduce the proliferation of glomerular mesangial cells and the expansion of extracellular matrix in various nephritis models.

[0013] (4) Poria cocos: It is sweet and bland in taste and neutral in nature. It has the effects of promoting diuresis and reducing swelling, eliminating dampness, strengthening the spleen and calming the mind. Experimental studies have found that the water extract of Poria cocos has an effect on the renal function of male rats with kidney yang deficiency and lower limb edema. It also reduces the levels of creatinine, protein, urea nitrogen, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in rats to varying degrees.

[0014] (5) Cistanche deserticola: It is sweet and salty in taste and warm in nature. It has the effects of tonifying kidney yang, nourishing essence and blood, and moistening the intestines to relieve constipation. Experimental studies have found that the water extract of Cistanche deserticola can induce ileal contraction in mice, enhance intestinal peristalsis, and shorten defecation time; enhance cellular and humoral immunity in mice, promote metabolism and enhance physical strength, resist oxidative aging, and promote endocrine function; in addition, it also has the effects of protecting the liver, resisting myocardial ischemia, resisting arteriosclerosis, lowering blood pressure, promoting urination, and reducing blood urea nitrogen content, without toxic side effects.

[0015] (6) Artemisia capillaris: It is bitter and cold in nature, and has the effects of clearing heat and dampness, promoting bile secretion and relieving jaundice. Experimental studies have found that it has multiple effects such as inhibiting renal inflammatory response and cell apoptosis, improving oxidative stress, anti-fibrosis, and protecting cells.

[0016] (7) Alisma plantago-aquatica: It is sweet and bland in taste and cold in nature. It has the effects of promoting diuresis and removing dampness, clearing heat, resolving turbidity and lowering lipids. Experimental studies have found that in addition to its many pharmacological effects such as diuresis, anti-inflammation, hypoglycemia, lipid reduction, immune regulation, inhibition of kidney stones, and anti-tumor, Alisma plantago-aquatica also has the effect of strengthening the spleen.

[0017] (8) Serissa japonica: It has a bland and slightly spicy taste and is cool in nature. It has the effects of dispelling wind and relieving exterior syndrome, clearing heat and promoting diuresis, and relaxing muscles and tendons. Experimental studies have found that Serissa japonica has a protective effect on the kidneys of diabetic nephropathy model rats. It can improve renal function, reduce proteinuria, and alleviate pathological changes in the kidneys. Its mechanism of action may be related to the decrease in the expression of TGF-β1 and IL-6 in renal tissue, thereby inhibiting renal inflammatory response and oxidative stress, and achieving the effect of protecting the kidneys.

[0018] (9) Salvia miltiorrhiza: It is bitter and slightly cold in nature. It has the effects of promoting blood circulation and regulating menstruation, removing blood stasis and relieving pain, cooling blood and eliminating carbuncles, and relieving irritability and calming the mind. Experimental studies have found that Salvia miltiorrhiza can significantly inhibit the apoptosis of renal tubular epithelial cells induced by aristolochic acid and can significantly protect renal tubular epithelial cells; it can significantly improve the anemia state of rats, reduce Scr, and reduce the excretion of 24-hour urinary protein. It has a certain renal protective effect on the rat model of chronic aristolochic acid nephropathy; it can reduce the serum IL-6 and TNF content in CRF patients and has the effect of protecting renal function.

[0019] (10) Raw rhubarb: It is bitter and cold in nature, and has the effects of purging accumulation, clearing heat and purging fire, cooling blood and detoxifying, and removing blood stasis and promoting menstruation. Experimental studies have found that rhubarb can partially clear metabolic waste in the digestive tract of CRF patients, improve the barrier function of the digestive tract mucosa, prevent serum endotoxin (ETX) from entering the blood, and reduce the activity of nitric oxide enzyme (NOS) due to the decrease in ETX level, thus reducing NO production; at the same time, it can reduce the levels of serum BUN and Scr.

[0020] Astragalus membranaceus (Huangqi) is sweet and warm, and its functions include tonifying qi and strengthening the spleen, promoting diuresis and reducing swelling, generating fluids and nourishing blood, and effectively regulating the qi of the three jiaos. Bupleurum chinense (Chaihu) is bitter and pungent, and its functions include soothing the liver and relieving stagnation, promoting qi and blood circulation, and raising clear yang, and effectively regulating the qi of the three jiaos. Artemisia capillaris (Yinchen) is bitter, pungent, and slightly cold, and it enters the liver, gallbladder, spleen, and stomach meridians, effectively clearing stagnant heat in the liver and gallbladder and clearing damp heat in the spleen and stomach. Poria cocos (Fuling) is sweet and bland, promotes diuresis, strengthens the spleen and tonifies the middle jiao. The combination of stir-fried Atractylodes macrocephala (Baizhu) and Poria cocos, one tonifying and one diuretic, one drying and one moistening, allows for the elimination of dampness and promotes the healthy functioning of the spleen. Alisma plantago-aquatica (Zexie) promotes diuresis and eliminates dampness, expelling dampness from the three jiaos. Serissa japonica (Liuyue Xue) is bitter and slightly sweet, and it enters the lung, spleen, liver, and stomach meridians, and can dispel wind and dampness, clear heat and detoxify. Cistanche deserticola (Roucongrong) warms and tonifies kidney yang, benefits essence and nourishes blood, and also moistens the intestines and promotes bowel movements. Salvia miltiorrhiza (Danshen) invigorates blood and removes blood stasis; when combined with Astragalus membranaceus, it tonifies qi and invigorates blood, ensuring smooth flow of qi and blood. Raw rhubarb is cold in nature and bitter in taste. It is effective in purging and eliminating stagnation, clearing heat and fire, and removing blood stasis and detoxifying. The whole formula is mild in nature, detoxifies and removes blood stasis, unblocks the three jiaos (upper, middle, and lower burners), and expels pathogens. It reflects the holistic view of traditional Chinese medicine that regulates the liver and spleen and treats both the root cause and the symptoms. Based on syndrome differentiation, it can be modified according to the symptoms and can effectively improve kidney function.

[0021] As a preferred technical solution of the present invention, the Shuli Guange Decoction formula includes the following Chinese medicinal herbs by weight: 30g of raw Astragalus membranaceus, 15g of stir-fried Atractylodes macrocephala, 10g of Bupleurum chinense, 15g of Poria cocos, 15g of Cistanche deserticola, 15g of Artemisia capillaris, 10g of Alisma plantago-aquatica, 15g of Serissa japonica, 15g of Salvia miltiorrhiza, and 10g of raw Rheum palmatum. The 10 herbs are decocted with water to extract the extract, the extracts are combined, filtered, and allowed to stand to obtain the supernatant, which is then used to prepare a decoction. Alternatively, the supernatant can be concentrated to a fluid extract with a specific gravity of 1.10, then dextrin is added as a base, and the mixture is spray-dried to granulate, yielding granules.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] The main functions of this Shuli Guange Decoction are to strengthen the body's resistance and eliminate toxins, regulate the triple burner, and treat CKD with liver stagnation and spleen deficiency. Clinical trial results show that it has a high overall effective rate in treating CKD, can reduce serum creatinine and blood urea nitrogen, reduce urinary protein excretion, improve malnutrition, enhance immune function, and alleviate renal micro-inflammatory states; protect residual renal function and delay the progression of renal fibrosis; compared with basic Western medicine treatment, it can slow the rate of decline in glomerular filtration rate (GFR), thereby delaying the decline in renal function and postponing the start of dialysis. Meanwhile, no significant adverse reactions were observed during the clinical trials, indicating its safety. Attached Figure Description

[0024] Figure 1 The results are the renal pathology results (HE staining ×400) for each group. Among them, (a) corresponds to the normal group, (b) corresponds to the model group, (c) corresponds to the high-dose group of Shuliguan Geyin, (d) corresponds to the medium-dose group of Shuliguan Geyin, and (e) corresponds to the low-dose group of Shuliguan Geyin.

[0025] Figure 2 The results are the renal pathology results (Masson staining ×400) for each group. Among them, (a) corresponds to the normal group, (b) corresponds to the model group, (c) corresponds to the high-dose group of Shuliguan Geyin, (d) corresponds to the medium-dose group of Shuliguan Geyin, and (e) corresponds to the low-dose group of Shuliguan Geyin. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings.

[0027] Example 1: Preparation of Shuli Guange Decoction:

[0028] The formula for Shuli Guange Decoction includes the following Chinese herbs by weight: 30g raw Astragalus membranaceus, 15g stir-fried Atractylodes macrocephala, 10g Bupleurum chinense, 15g Poria cocos, 15g Cistanche deserticola, 15g Artemisia capillaris, 10g Alisma plantago-aquatica, 15g Serissa japonica, 15g Salvia miltiorrhiza, and 10g raw Rheum palmatum.

[0029] Boil 10 herbs in 10 times their volume of water to extract the extract, yielding 150mL of decoction. Let it cool to a warm temperature before taking the single dose. Take twice daily. For the second dose, boil the dregs from the previous decoction in 10 times their volume of water again to extract the extract, yielding 150mL of decoction. Let it cool to a warm temperature before taking.

[0030] Example 2: Preparation of Shuliguan Geyin Granules:

[0031] The formula for Shuli Guange Decoction includes the following Chinese herbs by weight: Astragalus membranaceus 25g, Atractylodes macrocephala 14g, Bupleurum chinense 8g, Poria cocos 16g, Cistanche deserticola 14g, Artemisia capillaris 12g, Alisma plantago-aquatica 8g, Serissa japonica 16g, Salvia miltiorrhiza 16g, and Rheum palmatum 8g.

[0032] Ten herbs were decocted three times with water. For the first decoction, 10 times the amount of water was added, and the decoction was carried out for 1.5 hours. For the second and third decoctions, 8 times the amount of water was added, and the decoctions were carried out for 1 hour each. The extracts were combined, filtered, and allowed to settle for 48 hours. The supernatant was collected, concentrated under reduced pressure to a specific gravity of 1.10, dextrin was added as a base material, and the mixture was spray-dried at below 80°C. The mixture was then granulated and sized (upper sieve 10 mesh, lower sieve 60 mesh) to obtain granules. These granules were then packaged in 10g packets, sent for testing, and stored.

[0033] Example 3: Clinical Trial

[0034] I. Research Subjects and Methods

[0035] All study subjects were from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, and the study period was from October 2023 to October 2024.

[0036] Sixty patients with CKD stages 3-5 (non-dialysis stage) were selected according to the inclusion criteria and randomly divided into an experimental group (n=30) and a control group (n=30). Inclusion criteria: ① Age 18-70 years; ② Meeting the diagnostic criteria for CKD stages 3-5; ③ Blood pressure <140 / 90 mmHg, serum potassium <5.5 mmol / L, hemoglobin ≥80 g / L at enrollment, infection under control, and stable condition for more than 2 weeks; ④ No use of traditional Chinese medicine for CKD treatment within 2 weeks prior to enrollment, or those who had used traditional Chinese medicine but had completed a 2-week washout period; ⑤ Approval by the hospital's ethics committee.

[0037] The control group received basic Western medicine treatment (including dietary nutrition, blood pressure control, anemia correction, prevention and treatment of mineral and bone metabolism abnormalities, and regulation of water, electrolyte, and acid-base balance). The experimental group received basic Western medicine treatment plus oral administration of Shuli Guange Decoction (prepared according to the method in Example 1, 150 mL twice daily). The treatment course for both groups was 12 weeks.

[0038] There were no statistically significant differences in gender, age, disease duration, primary disease, and CKD stage between the experimental and control groups, making them comparable. See Table 1.

[0039] Table 1 Comparison of general patient information

[0040] Group control group experimental group Number of cases N 30 30 male 18 16 female 12 14 Age / years 55.1±11.6 52.6±13.2 Course of illness / month 19.2±12.7 21.5±15.3 Primary disease - chronic nephritis 13 16 Primary disease - Diabetic nephropathy 7 6 Primary disease - Hypertensive nephropathy 6 5 Primary disease - other 4 3 CKD Installment Plan - 3 Phases 7 10 CKD Installment Plan - 4 Phases 14 12 CKD Installment Plan - 5 Phases 9 8

[0041] II. Results of clinical trials:

[0042] (1) Comparative evaluation of TCM syndrome efficacy

[0043] The TCM syndrome differentiation and efficacy evaluation criteria are revised based on the "Syndrome Differentiation and Efficacy Judgment Criteria for Chronic Renal Failure" in the 2002 "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)". The efficacy is mainly determined by scoring the symptoms of liver stagnation and spleen-kidney deficiency syndrome, such as epigastric or hypochondriac distending pain, nausea, vomiting, abdominal distension, poor appetite, depression or irritability, dry mouth, bitter taste, and abdominal distension.

[0044] ① Significant effect: Syndrome score decreases by ≥70%. ② Effective: Syndrome score decreases by ≥30%. ③ Ineffective: No significant improvement in TCM clinical symptoms and signs, or even worsening of symptoms, and syndrome score decreases by <30%.

[0045] Calculation formula: [(Pre-treatment score - Post-treatment score) ÷ Pre-treatment score] × 100%

[0046] Effective rate of TCM syndrome improvement = (Number of effective cases / Total number of cases) × 100%

[0047] Results: The total effective rate of TCM syndrome scores in the control group was 53.33%, while that in the experimental group was 76.67% (P < 0.05). This indicates that the experimental group was more effective than the control group in improving TCM syndromes. See Table 2.

[0048] Table 2 Comparison of TCM syndrome efficacy evaluation

[0049] Group Number of examples Effective efficient invalid Overall efficiency control group 30 3 13 14 53.33% experimental group 30 6 17 7 <![CDATA[76.67% ＃ ]]>

[0050] Note: Comparison between two groups ＃ P < 0.05.

[0051] (2) Evaluation of disease treatment efficacy

[0052] The criteria for evaluating the efficacy of treatment for chronic renal failure were revised with reference to the "Criteria for Judging the Efficacy of Treatment for Chronic Renal Failure" in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine (Trial)" issued in 2002.

[0053] ① Effective: Estimated glomerular filtration rate (eGFR) increases by ≥10%. ② Stable: eGFR does not decrease, or increases by <10%. ③ Ineffective: eGFR decreases.

[0054] Effective rate of renal function improvement = (Number of effective cases + Number of stable cases) / Total number of cases × 100%

[0055] Results: The total effective rate of the disease treatment in the experimental group was 80.00%, which was significantly better than that in the control group (66.67%), P<0.05 (see Table 3).

[0056] Table 3 Comparison of Disease Treatment Efficacy Evaluation

[0057] Group Number of examples efficient Stablize invalid Overall efficiency control group 30 5 15 10 66.67% experimental group 30 8 16 6 <![CDATA[80.00% ＃ ]]>

[0058] Note: Comparison between two groups＃ P < 0.05.

[0059] (3) Comparison of renal function (serum creatinine, blood urea nitrogen, serum uric acid, estimated glomerular filtration rate) among patients in each group.

[0060] In the control group, blood urea nitrogen and serum uric acid levels were significantly lower after 12 weeks of treatment compared with those before treatment (P<0.05), while serum creatinine and estimated glomerular filtration rate (eGFR) did not change significantly before and after treatment (P>0.05).

[0061] After 12 weeks of treatment, the levels of serum creatinine, blood urea nitrogen, and serum uric acid in the experimental group were significantly lower than before treatment, while the level of eGFR was significantly higher (P < 0.05). Among these, the experimental group was significantly better than the control group in reducing serum creatinine and improving eGFR (P < 0.05). See Table 4.

[0062] Table 4 Comparison of renal function among groups

[0063] project Before treatment (control group) After 12 weeks of treatment (control group) Before treatment (experimental group) After 12 weeks of treatment (experimental group) Serum creatinine (μmol / L) 320.24±101.11 309.13±110.77 314.03±104.02 <![CDATA[275.13±90.09 ＃* ]]> eGFR (ml / min) 26.09±14.17 27.00±14.17 29.46±16.42 <![CDATA[38.10±19.06 ＃* ]]> Blood urea nitrogen (mmol / L) 14.12±5.21 <![CDATA[12.78±5.42 ＃ ]]> 13.80±4.95 <![CDATA[10.32±4.13 ＃ ]]> Serum uric acid (μmol / L) 424.00±76.85 <![CDATA[419.50±73.17 ＃ ]]> 439.19±133.86 <![CDATA[404.84±91.94 ＃ ]]>

[0064] Note: Compared with the group before treatment. ＃ P < 0.05; compared with the control group at the same time point, * P < 0.05.

[0065] (4) Comparison of hemoglobin, plasma albumin, blood lipids, and 24-hour urinary protein levels among the patients in each group.

[0066] In the control group, hemoglobin levels were significantly higher after 12 weeks of treatment compared to pre-treatment levels. In the experimental group, hemoglobin and plasma albumin levels were significantly higher after 12 weeks of treatment compared to pre-treatment levels, while serum cholesterol and 24-hour urinary protein levels were significantly lower (P < 0.05). The experimental group showed a significantly better effect on reducing 24-hour urinary protein levels than the control group (P < 0.05). See Table 5.

[0067] Table 5 Comparison of blood biochemical indicators among groups

[0068] project Before treatment (control group) After 12 weeks of treatment (control group) Before treatment (experimental group) After 12 weeks of treatment (experimental group) Hemoglobin (g / L) 95.34±20.13 <![CDATA[103.06±17.09 ＃ ]]> 95.09±19.34 <![CDATA[108.09±20.17 ＃ ]]> Plasma albumin (g / L) 35.57±6.72 37.40±4.32 37.89±5.42 39.78±4.78 Blood cholesterol (mmol / L) 5.07±1.31 4.76±1.19 5.39±1.81 <![CDATA[4.80±1.74 ＃ ]]> Triglycerides (mmol / L) 1.75±0.80 1.71±0.70 2.05±0.89 1.38±0.60 Low-density lipoprotein (mmol / L) 2.09±0.78 2.01±0.56 2.13±0.45 2.01±1.45 High-density lipoprotein (mmol / L) 1.12±0.54 1.15±0.56 1.13±0.33 1.19±0.98 24-hour urine protein quantification (g / 24h) 3.63±1.08 2.94±1.25 3.54±1.23 <![CDATA[2.32±1.00 ＃* ]]>

[0069] Note: Compared with the group before treatment. ＃ P < 0.05; compared with the control group at the same time point, * P < 0.05.

[0070] (5) Quality of life assessment

[0071] KDQOL-SF after 12 weeks of treatment in the experimental group TM1.3 The total score of the scale and its constituent SF-36 and KDTA scale scores were significantly improved compared with those before treatment (P<0.05); among them, the scores of the Physical Health (PCS) and Mental Health (MCS) components of the SF-36 scale, as well as the scores of the Symptoms and Discomfort (SPL), Kidney Disease Burden (BKD), Work Status (WS), Cognitive Function (CF), Sleep (SLEEP), Healthcare Staff Encouragement (DSF), Patient Satisfaction (PS), and Overall Health Assessment (OH) dimensions of the KDTA scale were significantly higher than those before treatment (P<0.05).

[0072] The control group had KDQOL-SF levels before and after treatment. TM 1.3 There was no significant improvement in the total score of the scale or its constituent SF-36 and KDTA scales (P > 0.05). Improvements were only observed in the Physical Health Assessment (PCS) score, Symptoms and Discomfort (SPL), Sleep, and Healthcare Staff Encouragement (DSF) dimensions. The experimental group showed significantly greater improvement than the control group in the SF-36 scale score and its constituent Mental Health Assessment (MCS) score, as well as in the Symptoms and Discomfort (SPL), Patient Satisfaction (PS), and Overall Health Assessment (OH) dimensions of the KDTA scale (P < 0.05). See Table 6.

[0073] Table 6 Comparison of Quality of Life Scores

[0074] The various dimensions of the scale Before treatment (control group) After 12 weeks of treatment (control group) Before treatment (experimental group) After 12 weeks of treatment (experimental group) SF-36 scale score 54.11±15.67 57.32±16.19 53.43±16.45 <![CDATA[61.29±18.83 ＃* ]]> Overall Physical Health Assessment (PCS) 51.78±14.32 <![CDATA[56.10±14.61 ＃ ]]> 51.56±17.18 <![CDATA[58.15±17.30 ＃ ]]> Mental Health Overall Score (MCS) 56.44±17.03 58.53±17.76 55.30±15.71 <![CDATA[64.43±20.37 ＃* ]]> Physiological function (PF) 72.11±13.23 <![CDATA[77.35±12.22 ＃ ]]> 74.71±12.11 <![CDATA[80.15±17.46 ＃ ]]> Functional role (RP) 41.52±14.15 <![CDATA[51.16±17.35 ＃ ]]> 38.35±22.15 <![CDATA[47.21±21.36 ＃ ]]> Physical discomfort (BP) 58.35±17.15 62.74±17.37 59.23±22.05 <![CDATA[66.84±17.23 ＃ ]]> Energy (VT) 35.13±12.74 33.14±11.51 33.93±12.41 <![CDATA[38.41±13.13 ＃* ]]> Social function (SF) 52.89±15.48 <![CDATA[60.06±20.05 ＃ ]]> 49.57±14.19 <![CDATA[67.13±22.64 ＃* ]]> Emotional Function (RE) 62.05±16.27 60.44±18.35 58.31±15.86 <![CDATA[65.02±20.21 ＃ ]]> Mental Health (MH) 52.37±19.05 53.16±15.22 53.16±17.47 55.26±16.66 Health changes (HT) 58.44±17.30 60.47±17.43 60.15±15.33 <![CDATA[70.31±21.96 ＃ *]]> KDTA scale score 58.16±17.69 61.05±18.91 56.86±17.38 <![CDATA[63.05±19.93 ＃ ]]> Symptoms and discomfort (SPL) 74.24±17.47 <![CDATA[80.56±22.55 ＃ ]]> 77.28±12.23 <![CDATA[85.92±22.35 ＃* ]]> The impact of kidney disease on daily life (EKD) 61.95±18.79 62.73±16.73 62.39±17.54 65.61±17.19 Kidney disease (BKD) can be a burden on daily life. 42.12±19.42 44.08±20.19 40.35±17.18 <![CDATA[46.67±17.23 ＃ ]]> Work Status (WS) 42.19±18.03 46.51±17.22 42.19±15.37 <![CDATA[48.63±21.23 ＃ ]]> Cognitive function (CF) 63.05±15.31 66.16±19.06 61.47±18.33 <![CDATA[69.34±20.20 ＃ ]]> Social Quality (QSI) 66.67±15.95 71.31±16.16 63.17±17.29 65.83±19.53 Sexual function (SEXF) 44.58±19.93 46.27±14.10 41.24±17.41 43.34±14.61 Sleep 61.55±18.69 <![CDATA[67.37±16.37 ＃ ]]> 58.39±19.45 <![CDATA[67.73±21.07 ＃ <!-- 6 -->]]> Social Support (SOS) 62.11±21.33 66.13±20.52 60.93±20.37 66.84±20.52 Healthcare workers encourage (DSF) 62.87±17.31 <![CDATA[67.46±21.85 ＃ ]]> 59.72±21.15 <![CDATA[71.57±22.83 ＃ ]]> Patient satisfaction (PS) 61.25±16.35 62.86±22.64 61.84±18.64 <![CDATA[68.77±20.93 ＃* ]]> Overall Health Assessment (OH) 55.34±13.69 57.11±19.51 53.29±13.55 <![CDATA[63.35±21.48 ＃* ]]> <![CDATA[KDQOL-SF TM 1.3 Total score of the scale]]> 56.54±16.88 59.65±17.82 55.48±17.00 <![CDATA[62.70±19.49 ＃ ]]>

[0075] Note: Compared with the group before treatment. ＃ P < 0.05; compared with the control group at the same time point, * P < 0.05.

[0076] (6) Safety indicators and adverse event observation

[0077] For the sake of objectivity and safety, this study monitored patients' routine blood tests, liver function (ALT, AST) and electrocardiograms before and after the start of the study, closely observing changes in patients' conditions. No significant adverse changes were found in any safety indicators throughout the process, and no adverse events such as allergies, rashes or even death occurred.

[0078] III. Clinical trial conclusions:

[0079] ① The experimental group patients who took Shuliguan Geyin experienced significant improvement in clinical symptoms and quality of life. The total effective rate of the treatment of the syndrome and the total effective rate of the treatment of the disease were significantly better than those of the control group.

[0080] ②Shuliguan Geyin can significantly reduce serum creatinine and blood urea nitrogen levels and improve renal function; it can also effectively improve patients' anemia and nutritional status.

[0081] ③The safety profile of Shuli Guange Drink is good.

[0082] Example 4: Animal Experiment

[0083] I. Research Subjects and Methods:

[0084] Fifty SPF-grade male SD rats were randomly divided into five groups: normal group, model group, high-dose Shuliguan Geyin group, medium-dose Shuliguan Geyin group, and low-dose Shuliguan Geyin group, with 10 rats in each group.

[0085] Except for the normal group, rats in the other groups were given an adenine-induced renal fibrosis rat model. The modeling method was as follows: rats were given adenine suspension (250 mg / kg·d) by gavage once a day for 3 consecutive weeks.

[0086] Rats in each group were fed a fixed animal diet. The three dose groups of traditional Chinese medicine were administered Shuli Guange Decoction by gavage at doses of 4.0 g crude drug / kg·d, 8.0 g crude drug / kg·d, and 16.0 g crude drug / kg·d, respectively. The converted results are: the three dose groups of traditional Chinese medicine were administered Shuli Guange Decoction at doses of 4 mL / kg·d, 8 mL / kg·d, and 16.0 mL / kg·d, respectively (taken from 150 mL of decoction prepared according to the method in Example 1).

[0087] Rats in the normal group and model group were administered 3 mL of distilled water by gavage for 8 consecutive weeks.

[0088] Serum creatinine (Scr), 24-hour urinary protein (24hUpro), and the activities of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) in renal tissue were detected by enzyme-linked immunosorbent assay (ELISA). DNA-binding activity of NF-κB p65 in renal tissue was measured by gel migration assay (EMSA). The expression of E-cadherin and α-smooth muscle actin (α-SMA) in renal tissue was detected by immunohistochemistry. The protein expression of NF-κB p65, p-IκBα, IκKα, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in renal tissue was detected by Western blot. The mRNA expression of fibronectin (FN) and type I and IV collagen (Col-I and IV) in renal tissue was detected by RT-PCR. Pathological changes in the kidneys were observed by HE and Masson staining.

[0089] II. Results of animal experiments:

[0090] After the experiment, 6 rats died (caused by improper gavage), leaving 44 rats, including 10 in the normal group, 9 in the model group, 8 in the high-dose group of Shuliguan Geyin, 9 in the medium-dose group of Shuliguan Geyin, and 8 in the low-dose group of Shuliguan Geyin.

[0091] (1) Comparison of serum creatinine and 24-hour urinary protein quantification in rats of different groups (ELISA method)

[0092] Compared with the normal group, the serum creatinine and 24-hour urinary protein levels in the model group rats were significantly increased, with statistically significant differences (P < 0.01). Compared with the model group, the serum creatinine and 24-hour urinary protein levels in the high, medium, and low dose groups of Shuliguan Geyin were significantly lower than those in the model group (P < 0.01); the high dose group of Shuliguan Geyin showed the best performance. See Table 7.

[0093] Table 7 Comparison of serum creatinine and 24-hour urinary protein quantification in rats of different groups

[0094] Group N Serum creatinine (μmol / L) 24-hour urine protein quantification (mg / 24h) normal group 10 46.41±3.17 1.47±0.36 Model group 9 <![CDATA[109.14±12.55 ＃ ]]> <![CDATA[3.81±1.13 ＃ ]]> Shuliguan Geyin low-dose group 8 <![CDATA[90.06±8.27 * ]]> <![CDATA[2.91±1.04 * ]]> Shuliguan Geyin medium dose group 9 <![CDATA[86.57±9.52 * ]]> <![CDATA[1.97±0.76 * ]]> High-dose group of Shuliguan Geyin 8 <![CDATA[81.20±9.02 * ]]> <![CDATA[2.06±0.60 * ]]>

[0095] Note: Compared with the normal group: ＃ P < 0.05; compared with the model group: * P < 0.05.

[0096] (2) Renal pathological manifestations of rats in each group (HE, Masson staining)

[0097] HE and Masson staining of rat kidneys in each group: In the normal group, no glomerular atrophy was observed, and the renal tubules were large and regular in size, exhibiting an imbricate distribution. No obvious inflammatory cell infiltration was observed in the renal interstitium. In the model group, the renal tissue showed incomplete glomerular structure, sclerosis of some glomeruli, dilation of the renal tubule lumen, and vacuolar degeneration, even atrophy, necrosis, and detachment of epithelial cells. The renal interstitial region was widened, with extensive fibrosis and inflammatory cell infiltration. The fibrotic areas showed a distribution of blue-stained collagen fibers. Compared with the model group, the above pathological changes were alleviated in all dose groups of Shuliguan Geyin. The degree of fibrosis gradually decreased, and the blue-stained collagen fibers and inflammatory cell infiltration decreased. Some renal tubules showed detachment and necrosis. The high-dose group of Shuliguan Geyin showed the least damage. See Figure 1 and Figure 2 .

[0098] (3) Comparison of fibronectin (FN) and type I and IV collagen (Col-I, IV) mRNA expression in the kidney tissues of rats in each group (RT-PCR)

[0099] Compared with the normal group, the expression levels of FN, Col-I, and Col-IV mRNA in the kidneys of rats in the model group were significantly increased (P < 0.01). Compared with the model group, the expression levels of FN, Col-I, and Col-IV mRNA in the high, medium, and low dose groups of Shuliguan Geyin were significantly decreased (P < 0.01 or P < 0.05); among them, the expression levels of FN and Col-I mRNA in the high dose group of Shuliguan Geyin were significantly lower than those in the low dose group (P < 0.05). See Table 8.

[0100] Table 8 Comparison of FN, Col-I, and Col-IV mRNA expression levels in rat kidney tissues of different groups

[0101] Group N FN Col-Ⅰ Col-Ⅳ normal group 10 1.00±0.05 1.00±0.07 1.00±0.06 Model group 9 <![CDATA[3.18±0.35 ＃ ]]> <![CDATA[3.91±0.49 ＃ ]]> <![CDATA[4.35±0.34 ＃ ]]> Shuliguan Geyin low-dose group 8 <![CDATA[2.59±0.51 * ]]> <![CDATA[3.02±0.62 * ]]> <![CDATA[4.07±0.73 * ]]> Shuliguan Geyin medium dose group 9 <![CDATA[2.22±0.43 * ]]> <![CDATA[2.71±0.40 * ]]> <![CDATA[3.78±0.62 * ]]> High-dose group of Shuliguan Geyin 8 <![CDATA[2.01±0.47 *△ ]]> <![CDATA[2.55±0.44 *△ ]]> <![CDATA[3.64±0.51 * ]]>

[0102] Note: Compared with the normal group: ＃ P < 0.05; compared with the model group: * P < 0.05; compared with the medium-dose group of Shuliguan Geyin: △ P < 0.05.

[0103] (4) Comparison of E-cadherin and α-smooth muscle actin (α-SMA) expression in the kidney tissues of rats in each group (immunohistochemistry)

[0104] Compared with the normal group, the expression of E-cadherin in the kidney tissue of rats in the model group was lower than that in the normal group, while the expression of α-SMA was higher than that in the normal group, and the differences were statistically significant (P < 0.01). Compared with the model group, the expression of E-cadherin in the kidney tissue of rats in the high, medium, and low dose groups of Shuliguan Geyin was higher than that in the model group, while the expression of α-SMA was lower than that in the model group, and the differences were statistically significant (P < 0.01). Among them, the high dose group of Shuliguan Geyin had the highest expression of E-cadherin and the lowest expression of α-SMA. See Table 9.

[0105] Table 9. Comparison of immunohistochemical expression of E-cadherin and α-SMA in rats of different groups

[0106] Group N field of vision E-cadherin α-SMA normal group 10 20 0.354±0.032 0.096±0.017 Model group 9 20 <![CDATA[0.172±0.026 ＃ ]]> <![CDATA[0.214±0.041 ＃ ]]> Shuliguan Geyin low-dose group 8 20 <![CDATA[0.202±0.047 * ]]> <![CDATA[0.173±0.031 * ]]> Shuliguan Geyin medium dose group 9 20 <![CDATA[0.229±0.056 * ]]> <![CDATA[0.151±0.020 * ]]> High-dose group of Shuliguan Geyin 8 20 <![CDATA[0.255±0.070 *△ ]]> <![CDATA[0.137±0.015 *△ ]]>

[0107] Note: Compared with the normal group: ＃ P < 0.05; compared with the model group: * P < 0.05; compared with the medium-dose group of Shuliguan Geyin: △ P < 0.05.

[0108] III. Conclusions of animal experiments:

[0109] Shuliguange Decoction can significantly reduce the pathological damage to the kidneys of UUO rats. Its mechanism is related to its ability to inhibit the NF-κB-mediated inflammatory response in the kidney tissue of UUO rats through its antioxidant stress effect, thereby inhibiting the renal tubular epithelial cell transdifferentiation (EMT) process and exerting an anti-renal fibrosis effect.

[0110] In summary, this invention innovatively proposes that the basic pathogenesis of CKD (non-dialysis period) is liver stagnation and spleen deficiency, with pathogenic factors accumulating in the triple burner. Given that currently used Chinese patent medicines for CKD in China do not address liver stagnation and spleen deficiency, this invention proposes a Chinese herbal preparation, Shuli Guange Yin, which has the effects of strengthening the body's resistance, eliminating toxins, and regulating the triple burner, and can be used to treat liver stagnation and spleen deficiency in CKD. Compared with other Chinese patent medicines, its composition and efficacy are more comprehensive. This preparation has the effects of strengthening the body's resistance, eliminating toxins, and regulating the triple burner, while also addressing liver stagnation and spleen / kidney deficiency, which aligns with the pathogenesis characteristics of CKD patients.

Claims

1. A formula for a liver-based treatment of chronic kidney disease, characterized by: The following Chinese herbs are included in the following weights: Astragalus membranaceus 20-40g, Atractylodes macrocephala (fried) 10-20g, Bupleurum chinense 5-15g, Poria cocos 10-20g, Cistanche deserticola 10-20g, Artemisia capillaris 10-20g, Alisma plantago-aquatica 5-15g, Serissa japonica 10-20g, Salvia miltiorrhiza 10-20g, and Rheum palmatum 5-15g.

2. The formula for Shuli Guange Drink as described in claim 1, characterized in that, The following Chinese herbs are included in the following weights: raw Astragalus membranaceus 30g, stir-fried Atractylodes macrocephala 15g, Bupleurum chinense 10g, Poria cocos 15g, Cistanche deserticola 15g, Artemisia capillaris 15g, Alisma plantago-aquatica 10g, Serissa japonica 15g, Salvia miltiorrhiza 15g, and raw Rheum palmatum 10g.

3. A method for preparing the Shuli Guange Yin formula as described in claim 1 or 2, characterized in that, Ten herbs were boiled in water to extract the extract. The extract was filtered, allowed to stand, and the supernatant was collected to make a decoction.

4. A method for preparing the Shuli Guange Yin formula as described in claim 1 or 2, characterized in that, Ten herbs were decocted with water three times to extract the extracts. The extracts were combined, filtered, and allowed to stand. The supernatant was concentrated to a fluid extract with a specific gravity of 1.

10. Dextrin was then added as a base material, and the extracts were spray-dried to granulate the extract. The granules were then dissolved in warm water and taken orally.

5. The application of the Shuli Guange Decoction formula as described in claim 1 or 2 in the preparation of medicines for chronic kidney disease with liver stagnation and spleen deficiency.

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