A traditional Chinese medicine composition for treating chronic kidney disease, and a preparation method and use thereof

Abstract

The application provides a traditional Chinese medicine composition for treating chronic kidney disease and a preparation method and application thereof, and belongs to the field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from raw medicinal materials in the following weight ratio: 16-24 parts of Astragalus membranaceus, 24-36 parts of Poria cocos, 24-36 parts of Motherwort, 16-24 parts of Cornus officinalis, 24-36 parts of Agrimonia pilosa, 24-36 parts of Ledum palustre, 16-24 parts of Silene conica, 16-24 parts of Malva sylvestris, and 6.4-9.6 parts of Saururus chinensis. The application also provides a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition can safely and effectively improve the kidney function of patients with the syndrome of qi deficiency and blood stasis and internal retention of dampness, relieve clinical symptoms, and delay disease progression, and provides a traditional Chinese medicine scheme with definite curative effect for the clinical treatment of the disease.

Description

TECHNICAL FIELD

[0001] The application relates to a traditional Chinese medicine composition for treating chronic kidney disease and belongs to the field of traditional Chinese medicines. BACKGROUND

[0002] Chronic kidney disease (CKD) refers to kidney damage and (or) GFR reduction [<60ml / (min·1.73m 2 )] for more than 3 months. Kidney damage refers to abnormality of kidney structure and function, including abnormality of blood and (or) urine components and abnormality in imaging examination, and pathological morphological changes in kidney tissue. The progression of CKD is a continuous process, and different stages and types can manifest as renal insufficiency (decreased kidney filtration function), chronic renal failure (a severe stage of renal insufficiency), and nephrotic syndrome (massive proteinuria, hypoproteinemia, high edema, and hyperlipidemia) with specific clinical manifestations.

[0003] In the Adult Chronic Kidney Disease Diet Guide (2024 Edition) issued by the National Health Commission, the classification of chronic kidney disease in traditional Chinese medicine mainly includes two categories of root deficiency syndrome (such as qi deficiency syndrome, blood deficiency syndrome, yin deficiency syndrome, and yang deficiency syndrome) and branch excess syndrome (such as dampness syndrome, heat syndrome, and blood stasis syndrome). CKD has a long course and poor prognosis, and can eventually develop into end-stage renal disease. In traditional Chinese medicine theory, the occurrence and development of CKD are closely related to "deficiency, stasis, dampness, and turbidity". If the kidney qi is insufficient, the gasification will be out of control, the clear will not rise and cannot be utilized, and the turbid will stay in the body and cause harm. The deficiency of spleen and kidney qi is the root, leading to internal retention of water and dampness; prolonged disease into the collaterals, and deficiency of qi unable to promote blood flow, resulting in blood stasis. Dampness and stasis are mutually intertwined, further hindering the movement of qi, damaging the kidney, and forming a vicious cycle.

[0004] In the research and clinical practice of traditional Chinese medicine, "qi deficiency and blood stasis, dampness and turbidity" as a complex syndrome is a pathological state of root deficiency and branch excess in patients with chronic kidney disease in the middle and late stages, especially on the basis of spleen and kidney deficiency, unsmooth blood circulation, and internal retention of dampness and turbidity. It is a common and key syndrome in the middle and late stages of CKD.

[0005] The existing treatment means, such as ACEI / ARB drugs, hormones or immunosuppressants of western medicine. Although ACEI / ARB drugs have certain effects in reducing proteinuria and delaying the progression of CKD, but part of the patients still have persistent proteinuria after treatment, and the curative effect is not ideal. Long-term use may cause adverse reactions such as hyperkalemia, acute kidney injury (AKI) and symptomatic hypotension, especially in patients with severely impaired renal function, the risk is higher, although the combination of ACEI and ARB can enhance the efficacy in theory, but clinical studies show that this combination therapy increases the risk of adverse reactions, such as worsening renal function and hyperkalemia. Hormones and immunosuppressants are often used to treat some types of CKD (such as glomerular disease), but they have many side effects, including increased risk of infection, bone marrow suppression, liver and kidney damage, metabolic disorders, etc. The use should be controlled and reduced as much as possible.

[0006] The existing Chinese medicine compound for treating CKD, or focuses on tonifying (such as tonifying kidney qi), or focuses on attacking evil (such as dredging the bowels and reducing turbidity, mainly clearing heat and promoting diuresis), the tonifying Chinese medicine usually takes effect slowly, for the patients with rapidly progressing disease or severely impaired renal function, it is difficult to effectively control the disease in a short time. And the attacking evil Chinese medicine containing rhubarb and other drugs causes adverse reactions such as diarrhea and electrolyte imbalance (such as hypokalemia) when used for a long time or in excess, especially in patients with renal insufficiency, which aggravates the burden on the kidney. For the complex pathogenesis of "qi deficiency" and "blood stasis" and "dampness and turbidity", it is often difficult to balance or attack too much. Simple tonification may "close the door and leave the enemy", and aggravate dampness; too much attack may also damage the healthy qi and aggravate qi deficiency. Therefore, there is an urgent need in the art for a Chinese medicine composition that can achieve "tonifying qi and supporting healthy qi" and "promoting blood circulation and removing dampness" at the same time, treating both the symptoms and the root causes, and is specially used for CKD with qi deficiency, blood stasis and internal dampness. SUMMARY

[0007] The present application provides a kind of Chinese medicine composition for treating chronic kidney disease, the present application also provides the preparation method and purpose of the Chinese medicine composition.

[0008] The present application provides a kind of Chinese medicine composition for treating chronic kidney disease, which is prepared from the following raw materials in the following weight ratio:

[0009] Radix Astragali 16-24 parts, Poria cocos 24-36 parts, Motherwort 24-36 parts, Cornus officinalis 16-24 parts, Agrimonia 24-36 parts, Dwarf tea 24-36 parts, Yarrow 16-24 parts, Winter holly fruit 16-24 parts, and Saururus 6.4-9.6 parts.

[0010] Preferably, it is prepared from the following raw materials in the following weight ratio:

[0011] Radix Astragali 16-24 parts, Poria cocos 24-36 parts, Motherwort 24-36 parts, Cornus officinalis 16-24 parts, Agrimonia 24-36 parts, Dwarf tea 24-36 parts, Yarrow 16-24 parts, Winter holly fruit 16-24 parts, and Saururus 6.4-9.6 parts.

[0012] The Chinese medicine composition in the present application is prepared by using the raw medicine powder, water or organic solvent extract as the active ingredient, and adding pharmaceutically acceptable adjuvants or auxiliary ingredients to prepare the commonly used pharmaceutical preparations.

[0013] The preparation is tablet, capsule, pill, granule or oral liquid.

[0014] The present application also provides a preparation method of the Chinese medicine composition for treating chronic kidney disease, which comprises the following steps:

[0015] a. weighing the raw medicine according to the weight ratio;

[0016] b. powdering the raw medicine, or extracting with water or organic solvent, and then adding pharmaceutically acceptable adjuvants or auxiliary ingredients to prepare the commonly used pharmaceutical preparations.

[0017] The present application also provides the use of the Chinese medicine composition in the preparation of a medicine for treating chronic kidney disease.

[0018] The medicine is a medicine for treating chronic kidney disease with the symptoms of deficiency of vital energy and blood stasis, and internal retention of dampness.

[0019] Preferably, the medicine is a medicine for treating chronic kidney disease in the 3-4 stages.

[0020] The present application also provides the use of the Chinese medicine composition in the preparation of a medicine for treating renal insufficiency, renal failure or nephrotic syndrome.

[0021] In the Chinese medicine composition of the present application, the Pyrola herb is the dried whole plant of Pyrola calliantha H. Andres or Pyrola decorata H. Andres of the Pyrola herb family. It has the effects of dispelling wind and dampness, and strengthening bones and muscles.

[0022] The agrimony is the dried aboveground part of Agrimonia pilosa Ledeb. of the Rosaceae family. It has the effects of detoxification and deficiency.

[0023] The dwarf tea is the dried whole plant of Ardisia japonica (Thunb.) Blume of the Ardisia family. It has the effects of clearing damp heat and promoting blood circulation.

[0024] The winter holly fruit is the dried mature fruit of Malva verticillata L. of the Malvaceae family. It has the effects of clearing heat and promoting diuresis, and eliminating swelling.

[0025] Poria cocos is the dried sclerotium of Poria cocos (Schw.) Wolf. It has the effects of promoting water diuresis, moistening, invigorating the spleen and calming the heart.

[0026] Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. It has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting water diuresis and swelling, producing fluid and nourishing blood, removing stagnation and relieving arthralgia.

[0027] Leonurus japonicus Houtt. It has the effects of activating blood and regulating menstruation, promoting water diuresis and swelling, clearing heat and detoxifying.

[0028] Dianthus chinensis L. It has the effects of promoting water diuresis and relieving stranguria, activating blood and regulating menstruation.

[0029] Tetrapanax papyrifer (Hook.) K. Koch. It has the effects of clearing heat and promoting water diuresis.

[0030] The Su Wen · Reversed Transmission Theory' states: "The kidney is the water organ, and it controls body fluids." If the kidney qi is insufficient, the qi transformation is out of order, then the clear one cannot be raised and utilized, and the turbid one cannot be lowered and stays in the body to cause harm. Professor Zhiyou ZHU, a famous TCM doctor in Sichuan Province, created the present invention medicine according to this theory. The medicine is composed of Leonurus japonicus Houtt. as the core drug combination. The Leonurus japonicus Houtt. has the effects of activating blood and promoting water diuresis. The Pyrola rotundifolia Druce has the effects of warming the kidney and dredging collaterals, and the Camellia grijsii Lévl. has the effects of clearing damp heat. The Pyrola rotundifolia Druce can increase the effects of activating blood and promoting water diuresis of the Leonurus japonicus Houtt., and can strengthen the effects of clearing damp heat and removing blood stasis of the Camellia grijsii Lévl.. The Camellia grijsii Lévl. and the Leonurus japonicus Houtt. complement each other, and the effects of promoting water diuresis, removing dampness and activating blood are significantly improved. The three drugs are used together, and the effects of warming the kidney, activating blood and clearing damp heat are all performed, and the kidney activity is efficiently stimulated. Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao and Poria cocos can tonify qi, and the Herba Galium verum can tonify deficiency and detoxify. The three drugs can tonify the kidney and strengthen the body resistance, and are used as the ministerial drugs. Dianthus chinensis L. and Malva sylvestris L. can promote water diuresis and relieve stranguria, and can help the kidney to remove turbidity from the body, and are used as the auxiliary drugs. Tetrapanax papyrifer (Hook.) K. Koch. has the effect of promoting water diuresis, and is used as the ministerial drug.

[0031] The traditional Chinese medicine composition of the present application is used for treating the following symptoms caused by deficiency of vital energy and blood stasis and internal retention of dampness: milky or rice gruel-like urine with floating oil, deposition, abdominal distension, urine pain and incomplete urination, lumbar and back pain, edema, fatigue, lumbar and back pain, frequent urination or nocturia. The composition is used for treating chronic kidney disease, renal insufficiency, renal failure and nephrotic syndrome. DETAILED DESCRIPTION

[0032] Example 1 Preparation of the traditional Chinese medicine composition of the present application

[0033] [Prescription] Radix Astragali 277.24 g, Poria cocos 415.86 g, Motherwort 415.86 g, Cornus officinalis 277.24 g, Artemisia scoparia 415.86 g, Potentilla discolor 415.86 g, Winter melon fruit 277.24 g, and Tetrapanax papyriferus 110.90 g.

[0034] [Preparation method] The above nine ingredients are decocted twice, the first time for 45 minutes and the second time for 30 minutes. The decoction is filtered, combined, concentrated to an appropriate amount, and then spray-dried to obtain extract powder. The extract powder is mixed with dextrin and stevioside, granulated, dried, and then tableted to obtain 1000 g of tablets.

[0035] Example 2 Preparation of the traditional Chinese medicine composition of the present application

[0036] Radix Astragali 16 g, Poria cocos 24 g, Motherwort 24 g, Cornus officinalis 16 g, Artemisia scoparia 24 g, Potentilla discolor 24 g, Winter melon fruit 16 g, and Tetrapanax papyriferus 6.4 g are prepared into extract powder according to the extraction method of Example 1, and then tableted to obtain tablets.

[0037] Example 3 Preparation of the traditional Chinese medicine composition of the present application

[0038] Radix Astragali 24 g, Poria cocos 36 g, Motherwort 36 g, Cornus officinalis 24 g, Artemisia scoparia 36 g, Potentilla discolor 36 g, Winter melon fruit 24 g, and Tetrapanax papyriferus 9.6 g.

[0039] The raw materials are mixed and powdered to prepare a powder.

[0040] The beneficial effects of the present application are proved by the following clinical trials.

[0041] Example 1 Clinical trial of the traditional Chinese medicine composition of the present application

[0042] The present application is proved by clinical practice that the combination of the present application and conventional western medicine can further improve the symptoms of CKD, protect residual renal function, delay the progression of early and middle stage renal failure, and further improve the quality of life of patients with CKD.

[0043] 1. Research object

[0044] (1) Case source

[0045] 70 cases who met the conditions and visited Chengdu Shuangliu District Hospital of Traditional Chinese Medicine were selected as research objects, regardless of gender, and were evenly divided into the test group and the control group according to the random number table method. Among them, 5 cases were lost due to patient loss and hospital transfer, of which 2 cases were in the treatment group and 3 cases were in the control group. A total of 65 cases were completed, and the situation of the control group and the treatment group is shown in Table 1. Statistical analysis showed that there was no statistically significant difference in gender, age, and disease duration between the two groups (P>0.05), which was comparable.

[0046] Table 1 Case situation

[0047]

[0048] (2) Case selection criteria

[0049] ① Western medicine diagnostic criteria:

[0050] Patients diagnosed as CKD 3-4 stage according to eGFR.

[0051] The above renal function staging method is recommended by the 2012 International KDIGO CKD Assessment and Management Clinical Practice Guidelines based on GFR staging. According to the eGFR level, CKD is divided into 5 stages.

[0052] ② TCM syndrome differentiation criteria:

[0053] Reference Lin Mei, ed. Internal Medicine of Traditional Chinese Medicine (China Press of Traditional Chinese Medicine, 2018.07).

[0054] Main symptoms: ointment (chyluria)

[0055] Secondary symptoms: lumbar and cervical pain, or edema, fatigue, lumbar and cervical pain, frequent urination or nocturia.

[0056] Pale red tongue, white and greasy or yellow and greasy fur, and slow or slippery pulse.

[0057] At the same time, 2 or more main symptoms and secondary symptoms, combined with tongue and pulse manifestations, are identified as qi deficiency and blood stasis, and internal retention of dampness.

[0058] (3) Inclusion criteria

[0059] ① Meet the above diagnostic criteria, regardless of gender and age;

[0060] ② TCM syndrome differentiation is qi deficiency and blood stasis, and internal retention of dampness;

[0061] ③ Agree to participate in this study voluntarily.

[0062] (3) Exclusion criteria

[0063] ① There are urinary system deformity or history of urinary system operation;

[0064] ② Pregnant or lactating women;

[0065] ③ Combined with severe primary diseases of heart, liver, kidney and hematopoietic system;

[0066] ④ Combined with other urinary system diseases;

[0067] ⑤ With severe psychological and emotional disorders;

[0068] ⑥ The researchers judge that it is not suitable for participating in the study.

[0069] (4) Treatment method

[0070] ① Basic treatment: the control group and the test group patients maintain the standard treatment of western medicine (including controlling primary disease, nutrition and lifestyle guidance, controlling risk factors such as hypertension and hyperglycemia, inhibiting excessive activation of renin-angiotensin system, preventing and treating complications, etc.).

[0071] ② Test group treatment: the test group patients take the kidney turbidity formula (Huangqi 20g, Fuling 30g, Yimucao 30g, Luanhancao 20g, Xianhecao 30g, Aitidi 30g, Qumei 20g, Dongkui 20g, Tongcao 8g) on the basis of the above treatment. Water decoction, 4 days per dose, 3 times a day.

[0072] ③ Treatment cycle: the patients in both groups are treated for 60 days continuously according to the above method.

[0073] (5) Observation index

[0074] ① Main index: renal function [serum creatinine (Scr), estimated glomerular filtration rate (eGFR)], 24h urine protein quantification.

[0075] ② Secondary index: TCM syndrome score.

[0076] ③ Safety index: adverse event record.

[0077] (6) Efficacy determination standard

[0078] Marked effect: Scr is significantly reduced (≥20%), eGFR is significantly improved (≥20%), and the TCM syndrome total score reduction rate is ≥70%.

[0079] Effective: Scr is reduced (≥10% but <20%), eGFR is improved (≥10% but <20%), and the TCM syndrome total score reduction rate is ≥30%.

[0080] Invalid: Scr and eGFR have no improvement or deterioration, and / or TCM syndrome total score reduction rate <30%.

[0081] Total effective rate=(number of cases of marked effectiveness + number of cases of effectiveness) / total number of cases x 100%.

[0082] (7) Statistical methods:

[0083] Statistical analysis was performed by SPSS 22.0 software. The description form of count data was percentage, and χ2 test was used for comparison; the description form of measurement data was (x±s), and t test was used for comparison. P<0.05 was considered statistically significant. 2

[0084] 2. Results:

[0085] 2.1 Comparison of renal function indexes between the two groups of patients

[0086] Before treatment, there was no statistically significant difference in Scr and eGFR indexes between the two groups of patients (P>0.05). After treatment, the levels of Scr and eGFR were significantly improved in both groups, and the improvement effect of each index level in the test group was significantly better than that in the control group (P<0.001), as shown in Table 2.

[0087] Table 2 Comparison of renal function indexes between the two groups of patients before and after treatment

[0088]

[0089] 2.2 Comparison of 24h urinary protein quantitative levels between the two groups of patients

[0090] Before treatment, there was no statistically significant difference in 24h urinary protein quantitative level between the two groups of patients (P>0.05). After treatment, the 24h urinary protein quantitative level was significantly decreased in both groups, and the test group was significantly lower than the control group (P<0.001), as shown in Table 3.

[0091] Table 3 Comparison of 24h urinary protein quantitative levels between the two groups of patients before and after treatment

[0092]

[0093] 2.3 Comparison of TCM syndrome scores between patients

[0094] According to the TCM syndrome score formulated according to the inclusion criteria, after treatment, the scores of all core symptoms and total scores in both groups were significantly decreased, and the test group was significantly lower than the control group (P<0.001), as shown in Tables 4 and 5.

[0095] Table 4 TCM syndrome score standard​​​​

[0096]

[0097] Table 5 Comparison of TCM syndrome scores in two groups of patients after treatment )

[0098]

[0099] 2.4 Comprehensive efficacy analysis

[0100] According to the efficacy evaluation criteria, the total effective rate of the test group was 96.97%, which was significantly higher than that of the control group (75.00%), and the difference was statistically significant (P<0.05), as shown in Table 6.

[0101] Table 6 Comprehensive efficacy analysis of patients

[0102]

[0103] 2.5 Safety evaluation

[0104] During the study, no serious adverse events related to the test drug or treatment regimen occurred in the test group and the control group. The vital signs of the patients in the two groups were stable, and there were no clinically significant abnormal changes in safety indicators such as blood routine and liver function.

[0105] 3. Results and discussion

[0106] This study used a randomized controlled design to scientifically evaluate the clinical value of Shentu Decoction for patients with CKD 3-4 stage with qi deficiency and blood stasis and internal retention of dampness. The results showed that conventional western medicine standard treatment (control group) could partially improve the renal function and clinical symptoms of patients, but the test group combined with Shentu Decoction showed a significant advantage in the improvement of various indicators. Shentu Decoction combined with western medicine standard treatment can more effectively delay the decline of renal function in patients with CKD 3-4 stage, reduce proteinuria, and significantly improve TCM clinical syndromes, with a total effective rate of 96.97%, and good safety. The efficacy advantage may be due to the overall regulation of multiple components and multiple targets of traditional Chinese medicine, which complements the advantages of western medicine treatment.

[0107] In summary, the traditional Chinese medicine composition in the present application can safely and effectively improve the renal function of patients with chronic kidney disease with qi deficiency and blood stasis, relieve clinical symptoms, and delay disease progression, providing a traditional Chinese medicine regimen with definite efficacy for the clinical treatment of the disease, and having important clinical popularization value and industrialization prospects.

Claims

1. A traditional Chinese medicine composition for treating chronic kidney disease, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: Astragalus membranaceus 16-24 parts, Poria cocos 24-36 parts, Leonurus japonicus 24-36 parts, Pyrola rotundifolia 16-24 parts, Agrimonia pilosa 24-36 parts, Lysimachia christinae 24-36 parts, Dianthus superbus 16-24 parts, Malva verticillata fruit 16-24 parts, Tetrapanax papyriferus 6.4-9.6 parts; The aforementioned traditional Chinese medicine composition is a drug for treating stage 3-4 chronic kidney disease, specifically for the syndrome of qi deficiency, blood stasis, and internal dampness accumulation in chronic kidney disease.

2. The traditional Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: Astragalus membranaceus 20 parts, Poria cocos 30 parts, Leonurus japonicus 30 parts, Pyrola rotundifolia 20 parts, Agrimonia pilosa 30 parts, Dianthus superbus 20 parts, Malva verticillata fruit 20 parts, Tetrapanax papyriferus 8 parts.

3. The traditional Chinese medicine composition for treating chronic kidney disease according to claim 1 or 2, characterized in that: It is a pharmaceutically commonly used formulation prepared by adding pharmaceutically acceptable excipients or auxiliary ingredients to the active ingredient, which is the original drug powder, water or organic solvent extract of the active pharmaceutical ingredient.

4. The traditional Chinese medicine composition for treating chronic kidney disease according to claim 3, characterized in that: The preparations mentioned are tablets, capsules, pills, granules, and oral liquids.

5. A method for preparing a traditional Chinese medicine composition for treating chronic kidney disease according to any one of claims 1-4, characterized in that: It includes the following steps: a. Weigh the raw materials according to the specified weight ratio; b. The active pharmaceutical ingredient is powdered, or extracted with water or organic solvents, and then pharmaceutically acceptable excipients or auxiliary ingredients are added to prepare commonly used pharmaceutical preparations.

6. The use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating chronic kidney disease, wherein the medicament is for treating stage 3-4 chronic kidney disease and is for the syndrome of qi deficiency and blood stasis with internal dampness and turbidity in chronic kidney disease.

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