Mongolian medicine compound for treating anaphylactoid purpura nephritis

Abstract

The invention discloses a Mongolian medicine compound for treating anaphylactoid purpura nephritis, and belongs to the technical field of traditional Chinese medicine. The Mongolian medicine compound for treating the anaphylactoid purpura nephritis is prepared from the following raw materials in parts by mass: 50 parts of flos carthami, 50 parts of bear gall, 40 parts of cockscomb, 3 parts of humifuse euphorbia herb, 35 parts of red sandalwood, 35 parts of blackberry lily, 25 parts of vermilion and 25 parts of semen momordicae. The Mongolian medicine compound designed by the invention shows an excellent and stable technical effect in the aspect of treating HSPN, can effectively relieve proteinuria of an HSPN model, improve renal functions and relieve pathological injury of kidney tissues through the action of multiple targets and multiple links, and has a good overall curative effect. The compound provides a potential drug choice which is clear in curative effect and relatively low in side effect risk for treating the anaphylactoid purpura nephritis, and has good application value.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a Mongolian medicine compound for treating allergic purpuric nephritis. Background Technology

[0002] Henoch-Schönlein purpura (HSP), also known as immunoglobulin A (IgA) vasculitis, is a systemic small vessel vasculitis. Its main clinical features include non-thrombocytopenic purpura, arthritis, and abdominal pain, and it can affect the kidneys, developing into Henoch-Schönlein purpura nephritis (HSPN). Epidemiological data shows that HSP is more common in children, with a significantly higher incidence than in adults. Studies have shown that HSPN accounts for 61%–73% of secondary glomerulonephritis in children, making it one of the most common secondary kidney diseases. With increasing age, later age of onset, more frequent relapses, and increased body mass index all increase the risk of kidney involvement. Adult patients are also more prone to severe chronic kidney disease. Approximately 10% of adult HSPN patients reach end-stage renal disease within 15 years, and their long-term prognosis is not to be underestimated.

[0003] Currently, the clinical treatment of Henoch-Schönlein purpura nephritis (HSP) mainly relies on a comprehensive approach using immunosuppressants, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARBs), and hormones. However, long-term use of these hormones can easily lead to numerous adverse reactions, including metabolic disorders, increased risk of infection, and osteoporosis, with some patients exhibiting hormone resistance. Immunosuppressants also carry potential risks such as bone marrow suppression, liver and kidney damage, and secondary infections. Therefore, while current Western medicine treatments can control the disease to some extent, they still face problems such as insufficient efficacy and significant side effects. Mongolian medicine, as an important part of traditional medicine, has shown potential in the treatment of HSP and HSPPN through clinical observation, possessing advantages such as abundant natural drug resources, holistic regulation, and relatively few side effects. However, its mechanism of action, dosage form optimization, and systemic efficacy evaluation still require further in-depth research. Against this backdrop, developing a Mongolian medicine compound with significant efficacy, few side effects, and strong targeting has become an urgent clinical need. Summary of the Invention

[0004] The purpose of this invention is to provide a Mongolian medicine compound for treating Henoch-Schönlein purpura nephritis (HSPN), thereby addressing the aforementioned problems in the background art. The Mongolian medicine compound designed in this invention exhibits excellent and stable technical effects in treating HSPN, effectively reducing proteinuria, improving renal function, and alleviating pathological damage to kidney tissue in HSPN models through multi-target and multi-process action, demonstrating good overall efficacy. This compound provides a potential drug option for treating HSPN with clear efficacy and relatively lower side effect risks, and has significant application value.

[0005] To achieve the above objectives, the present invention provides the following technical solution: One of the technical solutions of this invention is to provide a Mongolian medicine compound for treating allergic purpuric nephritis, the raw materials of which include safflower, bear bile, cockscomb flower, euphorbia humifusa, sandalwood, belamcanda chinensis, cinnabar and momordica cochinchinensis.

[0006] Preferably, the amount of the raw material added, by weight, is: 50 parts safflower, 50 parts bear bile, 40 parts cockscomb flower, 3 parts creeping privet, 35 parts sandalwood, 35 parts belamcanda, 25 parts cinnabar and 25 parts momordica cochinchinensis.

[0007] Preferably, the *Momordica cochinchinensis* seed is a roasted *Momordica cochinchinensis* kernel.

[0008] Preferably, the Mongolian medicine compound also contains pharmaceutically acceptable excipients.

[0009] Preferably, the dosage form of the Mongolian medicine compound includes decoction, granules, tablets, capsules, pills, oral liquid, drop pills, or ointment.

[0010] The second technical solution of the present invention provides a method for preparing the above-mentioned Mongolian medicine compound for treating allergic purpuric nephritis, comprising the following steps: The ingredients are mixed to obtain the Mongolian medicine compound used to treat allergic purpuric nephritis.

[0011] The third technical solution of the present invention provides the application of the above-mentioned Mongolian medicine compound for treating allergic purpuric nephritis in the preparation of a drug for treating allergic purpura.

[0012] Preferably, the application is in the preparation of a medicament for treating Henoch-Schönlein purpura nephritis.

[0013] The beneficial technical effects of the present invention are as follows: The Mongolian medicine compound provided by this invention demonstrates excellent and stable technical efficacy in treating Henoch-Schönlein purpura nephritis (HSPN). After testing with a rat model of HSPN induced by a combination of bovine serum albumin, lipopolysaccharide, and carbon tetrachloride, it was found that the Mongolian medicine compound exhibited significant renal protective effects at low, medium, and high doses. Its core efficacy is reflected in the following aspects: First, in terms of renal function indicators, the compound significantly reduced urinary protein quantification, blood urea nitrogen, and serum creatinine levels, with statistically significant differences compared to the model group, indicating that it can effectively improve glomerular filtration function and reduce protein leakage. Second, in terms of renal pathological morphology, HE staining results showed that, compared with the model group, the pathological changes such as glomerular mesangial cell proliferation and mesangial matrix expansion in the treated rats were effectively alleviated, and the renal tubular structure tended to be normal. Furthermore, further immunofluorescence and Western blot (WB) analysis showed that the compound may exert its therapeutic effect by regulating the expression of key proteins related to coagulation and inflammation in the kidney.

[0014] In summary, the Mongolian medicine compound designed in this invention can effectively reduce proteinuria, improve renal function, and alleviate pathological damage to kidney tissue in the HSPN model through multi-target and multi-process action, demonstrating good overall efficacy. This compound provides a potential drug option for the treatment of Henoch-Schönlein purpura nephritis with a clear therapeutic effect and relatively lower risk of side effects, and has significant application value. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 The results show the 24-hour proteinuria quantification for the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0017] Figure 2 The results are for blood urea nitrogen (UREA) tests in the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0018] Figure 3 The results are for serum creatinine (CRE) levels in the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0019] Figure 4 HE staining results of kidney tissues from the normal group, model group, low-dose group, medium-dose group, high-dose group, and losartan group at different magnifications.

[0020] Figure 5 The results show the expression levels of thrombomodulin in the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group. Detailed Implementation

[0021] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0022] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0023] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. It should be noted that any aspects of this invention not described in detail are conventional practices in the art and are not the focus of this invention.

[0024] The terms “comprising,” “including,” “having,” “containing,” etc., used in this invention are all open-ended terms, meaning that they include but are not limited to.

[0025] All raw materials used in the following embodiments and comparative examples of the present invention are commercially available products.

[0026] Example 1 A Mongolian medicine compound for treating Henoch-Schönlein purpura nephritis, comprising the following ingredients by weight: 50 parts safflower, 50 parts bear bile, 40 parts cockscomb flower, 3 parts creeping euphorbia, 35 parts sandalwood, 35 parts belamcanda, 25 parts cinnabar, and 25 parts stir-fried ginkgo seeds.

[0027] The preparation method of sand-fried Momordica cochinchinensis kernel is as follows: Place clean river sand in a pot and heat it to 300°C over high heat. Add clean Momordica cochinchinensis kernels. After adding the medicine, keep the sand temperature stable at 280-300°C and stir constantly. Fry until the surface bulges and a fragrant aroma is released (frying time is about 3 minutes). Remove the sand, sift out the river sand, let it cool, peel off the outer shell, and scrape off the green seed coat to obtain sand-fried Momordica cochinchinensis kernels.

[0028] The preparation method of this Mongolian medicine compound is as follows: Grind the remaining 6 medicinal materials (excluding safflower and bear bile) into a fine powder (pass through an 80-mesh sieve). Then grind the safflower and bear bile separately and pass them through an 80-mesh sieve. Finally, mix all the ingredients together to obtain the final product.

[0029] Effect verification 1. To verify the efficacy of the Mongolian medicine compound of Example 1 of the present invention on allergic purpuric nephritis, an animal model of "allergic purpuric nephritis" was constructed, and the improvement effect of the compound on allergic purpuric nephritis was studied by serum biochemistry, histopathology and other indicators.

[0030] (a) Laboratory animals and grouping Healthy SD rats were randomly divided into two groups: a normal group (n=10, blank control) and a model group (n=50).

[0031] (b) Model building The animal model of "allergic purpuric nephritis" was constructed using a combination of bovine serum albumin (BSA), lipopolysaccharide (LPS), carbon tetrachloride (CCl4), and dried ginger to create a hemorrhagic fever model of HSPN, as detailed below: BSA was prepared with physiological saline to a concentration of 40 mg / mL, and the dose was 10 mL / kg. SD rats were administered BSA by gavage every other day for 8 weeks. At the same time, 0.5 mL of castor oil and 0.2 mL of CCl4 were subcutaneously injected every Monday for 8 weeks. At weeks 6, 8, 10 and 12, 1 mL of LPS (prepared with sterile physiological saline to a concentration of 0.05 mg / mL) was injected via the tail vein. From week 9 to the end of week 12, 25% dried ginger aqueous solution (10 mL / kg) was administered by gavage every other day.

[0032] (c) Model Evaluation All rats underwent initial screening for urinary protein before modeling. After modeling (end of week 12), 24-hour urinary protein quantification was measured, and three rats from each of the normal group and the model group were randomly selected for kidney tissue collection and HE staining to observe renal pathological changes and confirm successful model establishment.

[0033] (d) Experimental design and drug administration After successful modeling, the 50 rats in the model group were randomly divided into 5 groups of 10 each: Model group (without any treatment; in) Figure 1-4 (referred to as model group) Positive drug control group (losartan potassium tablets, 3.93 mg / kg); Figure 1-3 The middle group was designated as the positive group. Figure 4 (referred to as losartan group) The low-dose group of the Mongolian medicine compound in Example 1 of this invention (0.8 g / kg); Figure 1-4 (The middle group is designated as the low-dose group) The medium-dose group of the Mongolian medicine compound in Example 1 of this invention (1.2 g / kg); Figure 1-4 (This is referred to as the medium-dose group) The high-dose group of the Mongolian medicine compound in Example 1 of this invention (1.6 g / kg); Figure 1-4 (The middle group is designated as the high-dose group) All groups were treated with the prescribed dosage, and other test conditions were conducted in accordance with standard procedures in the field to systematically evaluate the therapeutic effect of the Mongolian medicine compound on HSPN.

[0034] The test results are shown below: (1) 24-hour proteinuria levels in rats of each group (x±s, n=8) Figure 1 The results show the 24-hour proteinuria quantification for the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0035] Depend on Figure 1 It can be seen that the urinary protein content of rats in the low-dose group, medium-dose group and high-dose group was significantly reduced 24 hours after treatment compared with the model group.

[0036] (2) Blood urea nitrogen levels in rats in each group (x±s, n=8) Figure 2 The results are for blood urea nitrogen (UREA) tests in the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0037] (3) Serum creatinine levels in each group of rats (x±s, n=8) Figure 3 The results are for serum creatinine (CRE) levels in the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0038] In this invention, the statistical significance of all data is indicated by an asterisk (*). Mark: This indicates that P < 0.05. This indicates that P < 0.01. This indicates that P < 0.001.

[0039] (4) HE staining of rats in each group Figure 4 HE staining results of kidney tissues from the normal group, model group, low-dose group, medium-dose group, high-dose group, and losartan group at different magnifications.

[0040] Figure 4The “×200” and “×400” refer to the specific magnification factor of the relevant data.

[0041] Figure 4 The results showed that the glomeruli in the normal group rats had normal structure, morphology, and size; the ratio of the glomerulus to the glomerular capsule was normal; and the wall thickness and lumen size of the proximal and distal tubules were normal. In the model group rats, varying degrees of mesangial cell proliferation and mesangial matrix changes were observed in the kidney tissue. The low-dose, medium-dose, high-dose, and losartan groups showed alleviating effects compared to the model group. This demonstrates that the Mongolian medicine compound of Example 1 of this invention can significantly alleviate the pathological changes in kidney tissue.

[0042] Figure 5 The results show the expression levels of thrombomodulin in the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group.

[0043] Figure 5 In the diagram, CN, M, PC, ZXBW-L, ZXBW-M, and ZXBW-H represent the normal group, model group, positive group, low-dose group, medium-dose group, and high-dose group, respectively.

[0044] To explore the mechanism of action of the Mongolian medicine compound in Example 1 of this invention from the molecular level, Western blotting (WB) was used for detection. The results showed that the compound could significantly regulate the expression level of renal thromboprotein.

[0045] 2. The efficacy of the Mongolian medicine compound of Example 1 of the present invention on allergic purpuric nephritis was characterized by clinical cases.

[0046] Case 1 Patient: Male, 16 years old, from Ordos City, Inner Mongolia Autonomous Region.

[0047] Present Illness: Five months ago, the patient developed symmetrical purpura on both lower extremities without any obvious cause; the purpura did not blanch upon pressure. The patient presented to our hospital, where laboratory tests showed positive for proteinuria and hematuria (3+). The 24-hour urine protein quantification was 0.20 g / 24h. The clinical diagnosis was Henoch-Schönlein purpura nephritis.

[0048] Treatment and outcome: The patient was given Zhixue Bawei San (a traditional Chinese medicine formula), 3 g each time, twice daily orally. Follow-up examination after treatment showed that 24-hour urine protein quantification decreased to 0.09 g / 24h, urine protein became negative, and purpura on both lower extremities significantly subsided.

[0049] Case 2 Patient: Male, 29 years old, from Keerqin District, Tongliao City, Inner Mongolia.

[0050] History of present illness: The patient developed symmetric purpura on both lower extremities without obvious inducement one month ago, which did not fade when pressed. The patient visited our hospital, and the 24-hour urinary protein quantification was 0.336 g / 24h. The clinical diagnosis was Henoch-Schönlein purpura nephritis.

[0051] Treatment and outcome: The patient was given Bawei Zhixue Powder, 3 g each time, orally twice a day. After continuous treatment for one month, the 24-hour urinary protein quantification decreased to 0.099 g / 24h, the urinary protein turned negative, and the purpura on both lower extremities significantly subsided.

[0052] Case 3 Patient: Male, 57 years old, from Horqin District, Tongliao City, Inner Mongolia.

[0053] History of present illness: The patient developed symmetric purpura around the ankles of both lower extremities without obvious inducement three months ago, which did not fade when pressed, and the rash was sometimes mild and sometimes severe. In the recent one month, the patient developed fatigue, so he visited our hospital. Laboratory tests showed that the morphology of urinary red blood cells was renal origin deformed red blood cells, urinary occult blood (3+), and urinary protein (2+). The patient reported that the rash worsened after eating oranges.

[0054] Treatment and outcome: The patient was instructed to avoid foods that could induce disease exacerbation such as oranges and spicy and stimulating foods, and was given Bawei Zhixue Powder, 3 g each time, orally twice a day. After one week of treatment, the reexamination showed urinary occult blood (±), urinary protein (1+), and the rash improved significantly; after half a month of treatment, the reexamination showed urinary occult blood (+), urinary protein (1+), and the rash on both lower extremities basically subsided.

[0055] Case 4 Patient: Male, 57 years old, from Horqin Left Wing Middle Banner, Tongliao City, Inner Mongolia.

[0056] History of present illness: The patient developed symmetric scattered purpura below the knees of both lower extremities without obvious inducement three months ago, which did not fade when pressed. The patient visited a local hospital, and the routine urine test showed urinary protein (2+) (the specific report was not seen). Then the patient visited our hospital, and the reexamination of the routine urine test showed urinary protein (2+) and urinary occult blood (3+).

[0057] Treatment and outcome: The patient was instructed to avoid spicy and stimulating foods and fatigue, and was given Bawei Zhixue Powder, 3 g each time, orally twice a day. After treatment, the rash on both lower extremities subsided and the urinary protein decreased. Then, Bawei Zhixue Powder was taken orally for one month every season, 3 g each time, twice a day, to consolidate the curative effect. The reexamination of the routine urine test showed urinary protein (1+) and urinary occult blood (-).

[0058] The embodiments described above are only descriptions of the preferred modes of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A Mongolian medicine compound for treating allergic purpuric nephritis, characterized in that, The ingredients include safflower, bear bile, cockscomb flower, creeping privet, sandalwood, belamcanda chinensis, cinnabar, and momordica cochinchinensis.

2. The Mongolian medicine compound for treating allergic purpuric nephritis according to claim 1, characterized in that, The amount of the raw material added, by weight, is: 50 parts safflower, 50 parts bear bile, 40 parts cockscomb flower, 3 parts creeping privet, 35 parts sandalwood, 35 parts belamcanda, 25 parts cinnabar and 25 parts momordica.

3. The Mongolian medicine compound for treating allergic purpuric nephritis according to claim 1, characterized in that, The *Momordica cochinchinensis* mentioned is the kernel of *Momordica cochinchinensis* that has been stir-fried with sand.

4. The Mongolian medicine compound for treating allergic purpuric nephritis according to claim 1, characterized in that, The Mongolian medicine compound also contains pharmaceutically acceptable excipients.

5. The Mongolian medicine compound for treating allergic purpuric nephritis according to claim 1, characterized in that, The dosage forms of the Mongolian medicine compound include decoctions, granules, tablets, capsules, pills, oral liquids, drop pills, or ointments.

6. A method for preparing a Mongolian medicine compound for treating allergic purpuric nephritis according to any one of claims 1-5, characterized in that, Includes the following steps: The ingredients are mixed to obtain the Mongolian medicine compound used to treat allergic purpuric nephritis.

7. The use of the Mongolian medicine compound for treating allergic purpuric nephritis as described in any one of claims 1-5 in the preparation of a medicament for treating allergic purpura.

8. The application according to claim 7, characterized in that, The application is in the preparation of a drug for treating Henoch-Schönlein purpura nephritis.

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