A Zhuang medicine composition, medicine and application for treating IgA nephropathy

Abstract

The present invention discloses a Zhuang medicine composition, medicine, and application for treating IgA nephropathy, belonging to the field of medical technology. The Zhuang medicine composition of the present invention is formulated based on the theory of pharynx-kidney correlation and the therapeutic concept of "symptoms in the nasopharynx, root in the spleen and kidneys." It utilizes radix scutellariae, hollyhock, liriodendron, dwarf ...

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a Zhuang medicine composition, a medicine and an application thereof for treating IgA nephropathy. Background Art

[0002] IgA nephropathy (IgAN) is a glomerulonephritis characterized by the deposition of IgA-based immune complexes in the mesangial region. Clinically, it presents with recurrent gross hematuria and varying degrees of proteinuria. It is a common primary glomerular disease worldwide. The incidence of IgAN accounts for approximately 30% to 40% of primary glomerular diseases abroad and 45% to 50% in my country. Approximately 15% to 20% of IgAN patients progress to end-stage renal disease (ESRD) after 10 years of follow-up. IgAN is currently a major cause of ESRD in my country, severely impacting patients' quality of life and placing a significant economic burden on society and families. Therefore, early prevention of IgAN progression is crucial for improving patients' quality of life and survival.

[0003] The pathogenesis of IgAN remains unclear. Current research suggests it is primarily linked to genetic inheritance and mucosal immune abnormalities. Clinical treatment primarily involves immunosuppression, reducing proteinuria, controlling blood pressure, and slowing renal function. Specific therapies are currently unavailable, leading to the ongoing research focus on preventing and treating the onset and progression of IgAN. Traditional Chinese Medicine, with over two thousand years of development, has accumulated extensive experience in the diagnosis and treatment of diseases. Exploring this knowledge could offer a promising path to resolving this clinical challenge. Summary of the Invention

[0004] The purpose of the present invention is to provide a strong medicine composition, medicine and application for treating IgA nephropathy, which can eliminate the symptoms of edema and fatigue caused by kidney disease, and has the effects of nourishing the kidney and removing dampness, strengthening the spleen and replenishing qi, promoting diuresis and reducing swelling, thereby improving the quality of life of patients. It is a good medicine for treating IgA nephropathy.

[0005] The invention provides a Zhuang medicine composition for treating IgA nephropathy, comprising the following crude drugs: gypsophila chinensis, hollyhock, liriodendron chinense, dog shit wood, golden bamboo leaf, astragalus, codonopsis pilosula, magnolia flower, asarum, platycodon and cimicifuga.

[0006] Preferably, the following crude drugs are included in parts by weight: 1.5-2.5 parts of Tianxingmu, 0.5-1.5 parts of Maoyixiong, 1.5-2.5 parts of Liuerling, 2.5-3.5 parts of Dog Shit Wood, 0.5-1.5 parts of Jinzhuye, 1.5-2.5 parts of Astragalus, 0.5-1.5 parts of Codonopsis, 0.5-1.5 parts of Magnolia Flower, 0.5-1.5 parts of Asarum, 0.5-1.5 parts of Platycodon and 0.5-1.5 parts of Cimicifuga.

[0007] Preferably, the herbal medicine comprises the following parts by weight: 2 parts of Tianxingmu, 1 part of Maoyijing, 2 parts of Liuerling, 3 parts of Dog Shit Wood, 1 part of Jinzhuye, 2 parts of Astragalus, 1 part of Codonopsis, 1 part of Magnolia Flos, 1 part of Asarum, 1 part of Platycodon and 1 part of Cimicifuga.

[0008] Preferably, the dosage form of the Zhuang medicine composition includes an oral dosage form.

[0009] Preferably, the oral dosage form includes tablets, dispersions, soft capsules, granules, pills, drop pills, gels or oral liquid preparations.

[0010] The present invention also provides the use of the Zhuang medicine composition in preparing a medicine for treating IgA nephropathy.

[0011] The present invention also provides a medicine for treating IgA nephropathy, which contains the Zhuang medicine composition as an effective ingredient and further comprises pharmaceutically acceptable excipients.

[0012] Preferably, the dosage form of the drug is an oral dosage form.

[0013] Beneficial effects: The present invention provides a Zhuang medicine composition for treating IgA nephropathy, which is formulated based on the pharynx-kidney correlation theory and the treatment idea of "the symptoms are in the nasopharynx, the root is in the spleen and kidney", and uses Tianxingmu, Maoyi, Liuerling, Dog Shit Wood, Jinzhuye, Astragalus, Codonopsis, Magnolia Flower, Asarum, Platycodon and Cimicifuga for blending. It is confirmed by the examples that the therapeutic effect of combining the Zhuang medicine composition with the basic treatment regimen is better than the effect of combining the basic treatment regimen with dipyridamole, and the composition has the effects of eliminating edema and fatigue symptoms of kidney disease, and has the effects of tonifying the kidney and removing dampness, strengthening the spleen and replenishing qi, and promoting diuresis and reducing swelling, thereby improving the quality of life of patients. The composition is a good medicine for treating IgA nephropathy. DETAILED DESCRIPTION

[0014] The invention provides a Zhuang medicine composition for treating IgA nephropathy, comprising the following crude drugs: gypsophila chinensis, hollyhock, liriodendron chinense, dog shit wood, golden bamboo leaf, astragalus, codonopsis pilosula, magnolia flower, asarum, platycodon and cimicifuga.

[0015] The traditional Zhuang medicine composition of the present invention preferably comprises the following crude drugs in parts by weight: 1.5 - 2.5 parts of Ilex asprella, 0.5 - 1.5 parts of Ilex pubescens, 1.5 - 2.5 parts of Blumea lacera, 2.5 - 3.5 parts of Dichroa febrifuga, 0.5 - 1.5 parts of Phyllostachys nigra var. henonis, 1.5 - 2.5 parts of Astragalus membranaceus, 0.5 - 1.5 parts of Codonopsis pilosula, 0.5 - 1.5 parts of Magnolia liliflora Desr., 0.5 - 1.5 parts of Asarum sieboldii Miq., 0.5 - 1.5 parts of Platycodon grandiflorus and 0.5 - 1.5 parts of Cimicifuga foetida; more preferably, it comprises the following crude drugs in parts by weight: 2 parts of Ilex asprella, 1 part of Ilex pubescens, 2 parts of Blumea lacera, 3 parts of Dichroa febrifuga, 1 part of Phyllostachys nigra var. henonis, 2 parts of Astragalus membranaceus, 1 part of Codonopsis pilosula, 1 part of Magnolia liliflora Desr., 1 part of Asarum sieboldii Miq., 1 part of Platycodon grandiflorus and 1 part of Cimicifuga foetida. The crude drugs referred to in the present invention mean natural and unprocessed or simply processed Chinese herbal medicines of plant, animal and mineral categories.

[0016] The characteristics of the crude drugs comprised in the traditional Zhuang medicine composition of the present invention:

[0017] Ilex asprella: It is called Ilex asprella in Flora Reipublicae Popularis Sinicae. The roots and leaves of this species are used as medicine, having the effects of clearing heat and detoxifying, promoting the production of body fluid to quench thirst, and dissipating swelling and stasis. Radix Ilicis Asprellae: (Radix Ilicis Asprellae, Ilex asprella Champ. ex Benth.) Bitter, sweet, cold. Acting on the lung, liver and large intestine meridians. The main effects are: clearing heat and detoxifying, promoting the production of body fluid to quench thirst, and activating blood circulation to heal wounds. Modern pharmacological research finds that Ilex asprella contains triterpenoid saponins, phenolic acids, steroids and monoterpenes, etc., having the effects of anti - inflammation, anti - virus, anti - tumor, regulating lipid metabolism, etc. It is commonly used for colds, high fever with restlessness and thirst, tonsillitis, pharyngitis, tracheitis, pertussis, enteritis, dysentery, etc.

[0018] Ilex pubescens: Bitter, flat. Activating blood circulation to dredge meridians, detumescence and relieving pain, clearing heat and detoxifying. It is used for treating central retinitis, tonsillitis, pharyngitis, angina pectoris, myocardial infarction, thromboangiitis obliterans, infantile pneumonia, chilblains, periodontitis, pustular dermatosis. It has antibacterial effect, relieving cough and expelling phlegm, anti - inflammation, having preventive effect on acute renal failure in rats, increasing urine volume, reducing pathological changes of the kidney, decreasing the urine protein volume of experimental animals, accelerating the absorption of immune complexes in glomeruli, and improving pathological tissue damage.

[0019] Blumea lacera: (Also known as Blumea megacephala (Randeria) Chang) Pungent and flat, expelling pathogenic wind, removing damp - toxicity, dredging the "dragon meridian" and "fire meridian", relieving pain. It is mainly used for treating rheumatic pain after parturition, bone pain, headache, etc. For oral administration, 30 - 60 g, decocted in water and taken with wine. For external use, appropriate amount, mashed for application or decocted in water for external washing.

[0020] Dichroa febrifuga (in the book: Dichroa febrifuga Lour.): Sweet, bitter, flat, slightly poisonous, clearing heat and detoxifying, dredging the digestive tract, promoting granulation. It is mainly used for treating carbuncles, furuncles, contusions and strains, dermatitis, traumatic hemorrhage. For oral administration, 6 - 12 g, for external use, appropriate amount, mashed for application, or ground into powder for dressing or decocted in water for washing.

[0021] Astragalus: Sweet in flavor and slightly warm in nature. It enters the lung, spleen, liver, and kidney meridians. It tonifies qi and strengthens the exterior, supports sores and promotes tissue regeneration. It is primarily used to treat chronic nephritis, spontaneous sweating due to physical weakness, chronic diarrhea, rectal prolapse, uterine prolapse, edema due to physical weakness, chronic ulcers, and persistent wounds. It is also used to treat spleen and stomach deficiency, loss of appetite, loose stools, fatigue, and weakness. It is often used with Codonopsis pilosula, Atractylodes macrocephala, and Chinese yam.

[0022] Codonopsis: Neutral in nature, sweet and slightly sour in flavor. It enters the spleen and lung meridians. It tonifies the middle qi, strengthens the spleen and benefits the lungs. It is used for spleen and lung deficiency, shortness of breath, palpitations, loss of appetite, loose stools, asthenia and cough, and internal heat and thirst.

[0023] Magnolia flower: neutral in nature, pungent and warm in flavor. Enters the Lung and Stomach meridians. Dispels wind and cold, and clears the nasal passages. Used for wind-cold headaches, nasal congestion, sinusitis, and runny nose.

[0024] Asarum: pungent, warm, slightly toxic. Meridians: Lung, Heart, Kidney. It is recorded in Tangye Bencao as the guiding medicine of the Hand Shaoyin Kidney Meridian. Efficacy and indications: 1. Dispel wind, dispel cold, relieve pain, treat headache, arthralgia, abdominal pain, toothache. 2. Dispel cold and relieve exterior symptoms, treat wind-cold exterior symptoms; 3. Warm the lungs and transform fluid, treat phlegm and cough; 4. Open the orifices, treat sinusitis, orifice obstruction, and coma.

[0025] Platycodon grandiflorum: Bitter and pungent in flavor, neutral in nature. Enters the Lung Meridian. Benefits: Nourishes the lungs, relieves sore throat, eliminates phlegm, and discharges pus.

[0026] Cimicifuga: Pungent, slightly sweet, and slightly cold. It enters the Lung, Spleen, Stomach, and Large Intestine meridians. It clears away heat and toxic substances, and boosts Yang Qi. It is used for wind-heat headaches, toothaches, mouth sores, sore throats, measles that haven't cleared up, and rash caused by Yang toxicity; it also treats rectal prolapse and uterine prolapse.

[0027] The dosage form of the Zhuang medicine composition of the present invention preferably includes an oral preparation, and the oral preparation preferably includes tablets, dispersants, soft capsules, granules, pills, drop pills, gels or oral liquid preparations. The present invention does not specifically limit the preparation method of the oral preparation, and it can be prepared using conventional methods in the art.

[0028] The present invention also provides the use of the Zhuang medicine composition in preparing a medicine for treating IgA nephropathy.

[0029] In the embodiment of the present invention, the basic treatment regimen + Zhuang medicine composition capsule group was used as the treatment group, and the basic treatment regimen + dipyridamole was used as the control group. The effective rates of the two groups were compared, and the effective rate of the treatment group was 44.40%; the effective rate of the control group was 37.14%. The treatment group increased significantly, and the difference was statistically significant (P = 0.04); before treatment, the symptom scores of the two groups of patients were compared, and the difference was not statistically significant (P = 0.50); after treatment, the symptom scores of the treatment group were significantly reduced compared with those of the control group, and the difference was statistically significant (P < 0.001). Intra-group comparison: Compared with before treatment, the symptom scores of the two groups of patients after treatment were significantly reduced, and the differences were statistically significant; before treatment, the BUN, Scr, and 24h urine protein quantification of the two groups of patients were not statistically significant (P> 0.05); after treatment, the BUN, Scr, and 24h urine protein quantification of the treatment group were significantly improved compared with those of the control group, and the differences were statistically significant (P < 0.05). It is confirmed that the Zhuang medicine composition can eliminate the symptoms of edema and fatigue caused by kidney disease, has the effects of nourishing the kidney and removing dampness, strengthening the spleen and replenishing qi, promoting diuresis and reducing swelling, improves the quality of life of patients, and has a good therapeutic effect on IgA nephropathy.

[0030] The present invention also provides a medicine for treating IgA nephropathy, which contains the Zhuang medicine composition as an effective ingredient and further comprises pharmaceutically acceptable excipients.

[0031] The dosage form of the drug of the present invention is preferably an oral dosage form. When the oral dosage form is a liquid preparation, it is preferred to take each raw material according to the above ratio, crush the coarse medicinal materials into coarse powder or flakes, blocks, or silk and mix them evenly, put them into a medicinal composite film bag, add water to each dose of medicine to 450-500mL, and take 150-165mL each time, orally twice a day. The oral dosage form of the present invention can also be other dosage forms, and there is no special limitation on the preparation method. It can be prepared by adding corresponding excipients according to conventional methods in the field.

[0032] To further illustrate the present invention, the following describes in detail a Zhuang medicine composition, medicine and application for treating IgA nephropathy provided by the present invention in conjunction with examples, but they should not be construed as limiting the scope of protection of the present invention.

[0033] Example 1

[0034] 1.1 Case selection

[0035] A total of 151 patients with IgAN who were hospitalized in the Nephrology Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2019 to October 2020 were selected. This study was approved by the Ethics Committee of our hospital, and the subjects signed informed consent when they were conscious. Inclusion and exclusion criteria were as follows:

[0036] Inclusion criteria: IgAN confirmed by renal biopsy and clinical examination, in line with the criteria of the "Evidence-Based Guidelines for the Diagnosis and Treatment of Primary IgA Nephropathy 2016"; Lee grade I to III; informed consent for this study.

[0037] Exclusion criteria: Exclusion criteria: Hepatitis B-related nephritis, purpuric nephritis, lupus nephritis; cardiovascular and cerebrovascular diseases, infectious diseases, autoimmune diseases; history of glucocorticoid and immunosuppressant treatment in the past 3 months.

[0038] 1.2 Case Grouping

[0039] In this example, all 151 patients who were selected for observation met the selection criteria. According to the randomized control principle of clinical prospective studies, the patients were numbered in the order of their inclusion as treatment subjects and randomly grouped using statistical software. The random number number of each group of patients did not change or adjust during the entire study process.

[0040] All subjects were randomly divided into two groups, with 77 cases in the treatment group receiving Zhuang medicine treatment and 74 cases in the control group receiving dipyridamole treatment. During the study, 9 cases were excluded due to loss of follow-up or withdrawal, including 5 cases in the treatment group and 4 cases in the control group. Therefore, a total of 142 cases were actually included (treatment group, n=72, control group, n=70).

[0041] 1.3 Treatment options

[0042] 1.3.1 Basic treatment plan

[0043] According to the patient's condition, routine symptomatic treatment such as diuresis, blood pressure control, lipid lowering and anticoagulation are given, and a high-quality protein, low-salt, low-fat diet is given.

[0044] 1.3.2 Control Group Scheme

[0045] In addition to the “basic treatment plan”, dipyridamole (Henan Shengjia Pharmaceutical Co., Ltd., national medicine approval number H41020918) was added for treatment, taken orally, 3 times / d, 50 mg / time, for 3 consecutive months.

[0046] 1.3.3 Treatment Group

[0047] In addition to the “basic treatment plan”, Zhuang medicine prescriptions are used: the preparation is made by the central pharmacy of the First Affiliated Hospital of Guangxi University of Chinese Medicine.

[0048] The drug composition and dosage are as follows: 30g of Tianxingmu, 15g of Ilex pubescens, 30g of Ligusticum wallichii, 45g of Dog Shitwood, 15g of Jinzhuye, 30g of Astragalus membranaceus, 15g of Codonopsis pilosula, 15g of Magnolia flower, 15g of Asarum, 15g of Platycodon grandiflorum, and 15g of Cimicifuga heracleifolia. This is a custom-made Traditional Chinese Medicine / Zhuang medicine granule (Jiangyin Tianjiang Pharmaceutical Co., Ltd.). Take one dose daily with 250mL of water.

[0049] Both groups of patients were re-examined and the efficacy was evaluated after 3 consecutive months of treatment.

[0050] 1.4 Observation indicators

[0051] 1.4.1 General Items

[0052] Before the start of the clinical trial, the general information of all research subjects is collected, mainly including basic information such as name, gender, ethnicity, weight, age, occupation, height; and treatment conditions, such as family history, medical history, allergy history and medication history.

[0053] 1.4.2 Efficacy indicators

[0054] (1) All subjects were scored using syndrome scores before and after treatment to observe the improvement of their symptoms.

[0055] (2) The BUN, Scr, and 24-hour urine protein levels of the two groups were compared before and after treatment.

[0056] (3) The DBP and SBP of the two groups of patients were compared before and after treatment.

[0057] 1.4.3 Symptom Rating Criteria

[0058] According to the Stanghellini criteria, symptoms are divided into four levels according to their severity: 0: no symptoms; 1: occasional symptoms but not obvious, not affecting daily work and life; 2: relatively common symptoms, slightly affecting daily work and life; 3: severe symptoms, frequent occurrence, and affecting work and life.

[0059] 1.4.4 TCM syndrome efficacy evaluation criteria

[0060] Syndrome efficacy rate = (total score before treatment - total score after treatment) / total score before treatment × 100%. Clinical control: syndrome efficacy rate after treatment ≥ 90%; marked effect: syndrome efficacy rate after treatment ≥ 70% but < 90%; effective: syndrome efficacy rate after treatment ≥ 30% but < 70%; ineffective: syndrome efficacy rate after treatment < 30%.

[0061] 1.5 Criteria for evaluating efficacy

[0062] A negative urine red blood cell count and a negative or >75% decrease in 24-hour urine protein count are considered markedly effective. A ≥50% decrease in urine red blood cell count and a 50%-75% decrease in 24-hour urine protein count are considered effective. Anything other than these criteria is considered ineffective. Total effectiveness = effective + markedly effective.

[0063] 1.6 Statistical methods

[0064] Data The data were analyzed using SPSS 23.0 statistical software, and the independent t test and χ 2 The differences between the groups were calculated and P < 0.05 was considered significant. PCA statistics of endogenous metabolites in bile were performed using SIMCA software to import the relative peak area data of metabolites and observe the distribution of samples in the PCA model after standardization.

[0065] 2 Results

[0066] 2.1 Comparison of general information between the two groups of patients at admission

[0067] The results are shown in Table 1. There were no significant differences in gender, age, body mass index, disease course, and TCM symptom score between the two groups before treatment (P = 0.32, P = 0.73, P = 0.46, P = 0.48, P = 0.50), and the two groups were comparable.

[0068] Table 1 Comparison of general information of the two groups of patients at admission

[0069]

[0070]

[0071] 2.2 Comparison of efficacy between the two groups of patients

[0072] Comparison of the effective rates between the two groups is shown in Table 2. The effective rate in the treatment group was 44.40%, while that in the control group was 37.14%. The effective rate in the treatment group was significantly higher, with a statistically significant difference (P=0.04).

[0073] Table 2 Comparison of treatment effects between the two groups of patients

[0074]

[0075] Note: There is statistically significant difference compared with the control group, ●P<0.05.

[0076] 2.3 Comparison of syndrome scores before and after treatment between the two groups of patients

[0077] The results of intergroup comparisons are shown in Table 3: Before treatment, there was no statistically significant difference in the symptom scores between the two groups (P = 0.50); after treatment, the symptom scores of the treatment group decreased significantly compared with those of the control group, and the difference was statistically significant (P < 0.001). Intragroup comparisons: Compared with before treatment, the symptom scores of both groups decreased significantly after treatment, and the differences were statistically significant (P < 0.001).

[0078] Table 3 Comparison of scores between the two groups before and after treatment

[0079]

[0080] Note: There is a statistically significant difference compared with before treatment, ●●P<0.001; there is a statistically significant difference compared with the control group, ★★P<0.001.

[0081] 2.4 BUN, Scr, and 24-hour urine protein in the two groups before and after treatment

[0082] The results are shown in Table 4. Before treatment, there was no statistically significant difference in BUN, Scr, and 24-hour urine protein between the two groups (P>0.05). After treatment, BUN, Scr, and 24-hour urine protein in the treatment group improved significantly compared with the control group (P<0.05).

[0083] Table 4 Comparison of BUN, Scr and 24h urine protein between the two groups

[0084]

[0085] Note: There is statistically significant difference compared with the control group, ★P<0.05.

[0086] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A medicinal composition for treating IgA nephropathy, characterized in that: The invention is prepared from the following crude drugs in parts by weight: 2 parts of gypsophila, 1 part of holly, 2 parts of lilacinus, 3 parts of dog shit wood, 1 part of golden bamboo leaf, 2 parts of astragalus, 1 part of codonopsis, 1 part of magnolia flower, 1 part of asarum, 1 part of platycodon and 1 part of cimicifuga.

2. Use of the Zhuang medicine composition according to claim 1 in the preparation of a medicament for treating IgA nephropathy.

3. A drug for treating IgA nephropathy, characterized in that: The medicine contains the Zhuang medicine composition according to claim 1 as an active ingredient and further comprises pharmaceutically acceptable excipients.

4. The drug according to claim 3, characterized in that The dosage form of the drug is oral dosage.

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