A traditional Chinese medicine composition for treating lupus nephritis and application thereof

Abstract

The present application relates to the technical field of biological pharmacy, in particular to a traditional Chinese medicine composition for treating lupus nephritis and application thereof, which is composed of the following raw materials in parts by weight: 5-10 parts of Astragalus, 1-3 parts of Smilax glabra, 3-5 parts of Schisandra chinensis and 0.5-1.5 parts of Alisma orientale. The present application aims at the defects in the existing treatment of lupus nephritis, such as obvious side effects of western medicine, lack of speciality and potential safety risk of traditional Chinese medicine, and provides a traditional Chinese medicine composition for treating lupus nephritis and application thereof, which precisely matches the specific disease of lupus nephritis, has double effects of "kidney protection + immune regulation", and has no obvious risk of liver and kidney damage and the problem of insufficient long-term drug safety, thereby providing a better traditional Chinese medicine compound treatment scheme for the clinical treatment of LN.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, specifically to a traditional Chinese medicine composition for treating lupus nephritis and its application. Background Technology

[0002] Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus (SLE). It is an autoimmune disease caused by immune complex deposition in the kidneys due to autoimmune dysfunction, leading to inflammation, damage, and even kidney failure. Clinical statistics show that approximately 20% to 60% of SLE patients experience kidney involvement during the course of the disease. If not treated promptly and effectively, the disease can progress to chronic kidney disease and end-stage renal disease, seriously threatening the patient's life and health, and imposing a heavy medical burden on the patient's family and society.

[0003] Currently, clinical treatment for LN is primarily based on Western medicine, with core treatment regimens often involving glucocorticoids combined with immunosuppressants (such as cyclophosphamide, mycophenolate mofetil, and tacrolimus). While these treatments can suppress the immune inflammatory response and slow the progression of kidney damage to some extent, they suffer from several insurmountable technical drawbacks: First, significant side effects. Long-term, high-dose use of glucocorticoids can easily lead to adverse reactions such as osteoporosis, hyperglycemia, gastrointestinal ulcers, and increased risk of infection. Immunosuppressants may cause bone marrow suppression, liver and kidney damage, and reproductive system abnormalities, severely impacting patient adherence and quality of life. Second, the treatment efficacy is limited. Some patients are insensitive to these drugs, developing refractory LN, and the condition is prone to relapse after treatment, with continued deterioration of kidney function. Third, conventional Western medicine treatment regimens require the simultaneous use of hormones, immunosuppressants, and nephroprotective drugs to achieve the desired therapeutic effect. Patients need to take multiple medications concurrently, resulting in a heavy economic burden and decreased adherence during long-term chronic disease management.

[0004] Traditional Chinese medicine (TCM) theory categorizes lupus nephritis (LN) under the umbrella terms of "edema," "asthenia," and "kidney obstruction." Its core pathogenesis lies in the deficiency of the body's vital energy, internal accumulation of heat toxins, blood stasis, and dampness retention. The primary location of the disease is in the kidneys, but it also involves multiple organs such as the spleen and liver, resulting in a complex condition characterized by a mixture of deficiency and excess, and a combination of cold and heat patterns. Based on this understanding of the pathogenesis, TCM demonstrates unique advantages in the treatment of LN. It can not only regulate the body's overall immune function and reduce inflammatory responses, but also simultaneously strengthen the body's resistance, promote blood circulation, remove blood stasis, and eliminate dampness and toxins. It has significant potential in protecting kidney function, reducing the side effects of Western medicine, and improving treatment adherence, and has become an important component of the comprehensive treatment system for LN.

[0005] However, existing traditional Chinese medicine (TCM) treatments for lung disease (LN) still have many technical problems that limit their clinical application: First, most existing TCM formulas are general-purpose prescriptions that do not fully consider the complex pathogenesis of LN patients, characterized by "deficiency of vital energy and coexistence of heat, toxicity, and dampness," resulting in weak targeted formulation and difficulty in achieving "precise medication," leading to poor treatment outcomes for some patients; Second, existing TCM treatments are mostly used as adjuncts to Western medicine treatments, lacking specialized TCM compositions that can be used alone to significantly improve the treatment effect of LN and effectively improve kidney damage; Third, some TCMs used for LN treatment have potential risks of liver and kidney toxicity, and existing formulations do not fully consider the safety screening of medicinal materials, which may increase the burden on the liver and kidneys with long-term use, thus exacerbating kidney damage.

[0006] Therefore, in view of the above-mentioned technical defects of existing LN treatment methods (especially traditional Chinese medicine treatments), it is necessary to develop a scientifically formulated, highly targeted, effective, and safe traditional Chinese medicine composition that can inhibit kidney inflammation, improve kidney damage, and effectively regulate immune function. This is of great clinical significance and application value for improving the clinical treatment effect of LN, delaying disease progression, and improving patient prognosis, and has become a technical problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0007] To address the above problems, this invention provides a traditional Chinese medicine composition for treating lupus nephritis and its application.

[0008] This invention is achieved through the following technical solution: A traditional Chinese medicine composition for treating lupus nephritis, comprising the following raw materials in parts by weight: Astragalus membranaceus 5-10 parts, Smilax glabra 1-3 parts, Schisandra chinensis 3-5 parts and Dioscorea hypoglauca 0.5-1.5 parts.

[0009] Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Astragalus membranaceus 8 parts, Smilax glabra 2 parts, Schisandra chinensis 4 parts and Dioscorea hypoglauca 1 part.

[0010] Preferably, the traditional Chinese medicine composition is combined with pharmaceutically acceptable excipients to form a clinically acceptable formulation.

[0011] Preferably, the preparation is a decoction, pills, granules, or oral liquid.

[0012] Preferably, the preparation is a decoction.

[0013] Preferably, the preparation method of the decoction is as follows: weigh each raw material according to the specified weight proportions, mix them, add water and decoct, filter and extract the juice to obtain the decoction.

[0014] Preferably, the water is distilled water.

[0015] Preferably, the concentration of the decoction is 0.9 g / mL to 1.5 g / mL based on the total amount of raw medicinal materials.

[0016] The application of the aforementioned traditional Chinese medicine composition in the preparation of a drug for treating lupus nephritis.

[0017] Compared with the prior art, the present invention has the following beneficial effects: This invention provides a traditional Chinese medicine composition for treating lupus nephritis, comprising the following raw materials in parts by weight: Astragalus membranaceus 5-10 parts, Smilax glabra 1-3 parts, Schisandra chinensis 3-5 parts, and Dioscorea hypoglauca 0.5-1.5 parts. Addressing the core issues of existing traditional Chinese medicine formulations, such as insufficient targeted formulation, lack of specificity, and potential safety risks, this invention selects Astragalus membranaceus, Smilax glabra, Schisandra chinensis, and Dioscorea hypoglauca to construct a specific traditional Chinese medicine composition. Its core advantages precisely address the aforementioned technical pain points: firstly, it has a high degree of compatibility with the pathogenesis, and the combined use of the four herbs achieves both strengthening the body's resistance and eliminating pathogenic factors. Astragalus membranaceus replenishes qi and promotes diuresis, directly addressing the root cause of "deficiency of vital qi" and the symptoms of "excessive dampness." Smilax glabra promotes diuresis and detoxifies, Schisandra chinensis tonifies the kidneys and consolidates essence, and Dioscorea hypoglauca separates clear from turbid fluids, combining both tonifying and purging effects. The combination of these four herbs comprehensively covers the core pathogenesis of LN, solving the problem of insufficient targeting in existing treatments. Secondly, it targets the core pathogenesis of immune imbalance in LN, regulating immunity and protecting the kidneys, treating both the root cause and symptoms, with comprehensive efficacy. Thirdly, it has excellent safety, as the formula consists of commonly used low-toxicity herbs with no significant hepatotoxicity or nephrotoxicity, suitable for the long-term conditioning needs of LN patients. Fourthly, the formula is scientifically concise, economical, and convenient for research. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art 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.

[0019] Figure 1 This is a statistical graph showing the 12-hour urinary protein excretion of mice at the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); ** p <0.01, **** p <0.0001.

[0020] Figure 2 This is a statistical graph showing the serum urea nitrogen level in mice, the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); ** p <0.01, **** p <0.0001.

[0021] Figure 3This is a statistical graph showing the serum creatinine level in mice, the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); **** p <0.0001.

[0022] Figure 4 This is a statistical graph showing the serum anti-double-stranded DNA antibody levels in mice, representing the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); *** p <0.001, **** p <0.0001.

[0023] Figure 5 This is a statistical graph showing the proportion of Treg cells in spleen lymphocytes, the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); *** p <0.001, **** p <0.0001; ns indicates no statistical difference compared to the model group (MOD group); # indicates no statistical difference compared to the SBF group. p <0.01.

[0024] Figure 6 The endpoint of this invention is CD69 in spleen lymphocytes. + B cell proportion chart; Note: * indicates comparison with the model group (MOD group); **** p <0.0001; # indicates comparison with group SBF, #### p <0.0001.

[0025] Figure 7 The endpoint of this invention is CD138 in spleen lymphocytes. + Plasma cell proportion chart; Note: * indicates comparison with the model group (MOD group); **** p <0.0001.

[0026] Figure 8 This is a statistical graph of the spleen index in mice, the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); *** p <0.001, **** p <0.0001.

[0027] Figure 9 This is a statistical graph of the mouse kidney index, the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); p <0.05,** p <0.01, *** p <0.001.

[0028] Figure 10This is a statistical graph of the lung index in mice, representing the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); ** p <0.01, ns indicates no statistical difference.

[0029] Figure 11 This is a statistical graph of the mouse heart index, which is the experimental endpoint of this invention; Note: ns indicates no statistical difference compared with the model group (MOD group).

[0030] Figure 12 This is a statistical chart of mouse liver index, the experimental endpoint of this invention; Note: * indicates comparison with the model group (MOD group); p <0.05, ns indicates no statistical difference.

[0031] Figure 13 This is a diagram showing the HE staining results of mouse kidney tissue, the experimental endpoint of this invention. Figure 13 In the image, A represents the CON kidney (HE 20.0×); B represents the CON kidney (HE 40.0×); C represents the MOD kidney (HE 20.0×); D represents the MOD kidney (HE 40.0×); E represents the SBF kidney (HE 20.0×); F represents the SBF kidney (HE 40.0×); G represents the Pred kidney (HE 20.0×); and H represents the Pred kidney (HE 40.0×). The 20.0× image scale is 50 μm, and the 40.0× image scale is 25 μm. Figure 14 This is a diagram showing the HE staining results of mouse heart tissue at the experimental endpoint of this invention. Figure 14 In the image, A represents CON-HE_20.0×; B represents CON-HE_40.0×; C represents MOD-HE_20.0×; D represents MOD-HE_40.0×; E represents SBF-HE_20.0×; F represents SBF-HE_40.0×; G represents Pred-HE_20.0×; and H represents Pred-HE_40.0×. The 20.0× image scale is 50μm, and the 40.0× image scale is 25μm. Figure 15 This is a diagram showing the HE staining results of mouse lung tissue at the experimental endpoint of this invention. Figure 15 In the image, A represents the CON lung (HE_20.0×); B represents the CON lung (HE_40.0×); C represents the MOD lung (HE_20.0×); D represents the MOD lung (HE_40.0×); E represents the SBF lung (HE_20.0×); F represents the SBF lung (HE_40.0×); G represents the Pred lung (HE_20.0×); and H represents the Pred lung (HE_40.0×). The 20.0× image scale is 50 μm, and the 40.0× image scale is 25 μm. Figure 16 This is a diagram showing the HE staining results of mouse liver tissue at the experimental endpoint of this invention. Figure 16In the image, A represents a CON liver image (HE_20.0×); B represents a CON liver image (HE_40.0×); C represents a MOD liver image (HE_20.0×); D represents a MOD liver image (HE_40.0×); E represents an SBF liver image (HE_20.0×); F represents an SBF liver image (HE_40.0×); G represents a Pred liver image (HE_20.0×); and H represents a Pred liver image (HE_40.0×). The 20.0× image scale is 50 μm, and the 40.0× image scale is 25 μm. Detailed Implementation

[0032] To facilitate understanding of the present invention, a more comprehensive description is provided below, along with preferred embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the present invention.

[0033] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this invention and in its specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0034] The inventive concept of this invention is as follows: In view of the shortcomings of existing treatments for lupus nephritis, such as significant side effects of Western medicine regimens and insufficient targeted formulation, lack of specificity, and potential safety risks of traditional Chinese medicine regimens, the present invention aims to provide a traditional Chinese medicine composition and its application for treating lupus nephritis. The details are as follows:

[0035] There are three types of traditional Chinese medicine (TCM) administration regimens for treating LN: (1) Modification of classic formulas: such as Liuwei Dihuang Wan (nourishing Yin and tonifying the kidney), Taohong Siwu Tang (activating blood circulation and removing blood stasis), Zhenwu Tang (warming Yang and promoting diuresis), etc., based on the pathogenesis of LN of "deficiency, toxicity, blood stasis and dampness", and adjusting the medication according to the patient's syndrome differentiation results. (2) TCM compound preparations: such as Nephritis Recovery Tablets, Jinshuibao Capsules, Bailing Capsules, etc., which mainly focus on strengthening the body's resistance, removing dampness and detoxifying as their core effects, and are often used as adjunctive medications for Western medicine treatment in clinical practice. (3) Extracts of single Chinese herbs: such as Astragalus polysaccharides, Tripterygium wilfordii polyglycosides, etc., which use modern extraction technology to obtain effective components, and specifically inhibit immune inflammation or protect kidney tissue.

[0036] However, existing traditional Chinese medicine (TCM) treatments for lung disease (LN) still face numerous technical challenges, limiting their clinical efficacy: First, most existing TCM formulas are general prescriptions for chronic kidney disease, lacking specific targeting and failing to achieve "treatment based on disease, precise medication," resulting in poor treatment outcomes for some patients. Second, existing TCM treatments have limited efficacy, often serving as adjuncts to Western medicine treatments, lacking TCM combinations that can effectively improve kidney damage (treating the symptoms) and exert immune-regulating effects (treating the root cause) when used alone. Third, some TCM preparations used for LN treatment (such as Tripterygium wilfordii glycoside tablets) pose potential risks of hepatotoxicity or reproductive toxicity, and long-term use may increase the burden on the liver and kidneys, exacerbating kidney damage. Fourth, most existing TCM formulas for LN treatment contain numerous herbs and are complex, increasing the economic burden on patients and hindering research into their effective components and mechanisms, thus limiting the development of highly effective TCM formulas (TCM patent medicines) for LN treatment.

[0037] Therefore, in view of the above-mentioned technical defects of existing LN treatment methods (especially traditional Chinese medicine treatments), it is necessary to develop a traditional Chinese medicine composition that is scientifically simple, highly targeted, effective, safe, and capable of effectively regulating immune function, inhibiting kidney inflammation, and improving kidney damage. This is of great clinical significance and application value for improving the clinical treatment effect of LN, delaying disease progression, and improving patient prognosis, and has become a technical problem that urgently needs to be solved by those skilled in the art.

[0038] To address the core issues of existing traditional Chinese medicine (TCM) formulations, such as insufficient targetedness, lack of specificity, and potential safety risks, this invention constructs a specialized TCM composition using Astragalus membranaceus, Smilax glabra, Schisandra chinensis, and Dioscorea hypoglauca. The composition is refined, with Astragalus membranaceus as the principal herb, invigorating Qi, strengthening the spleen, and tonifying the kidneys; Smilax glabra and Schisandra chinensis as assistant herbs, the former detoxifying and eliminating dampness, clearing away turbid pathogens, and the latter tonifying the kidneys, astringing essence, and consolidating the body; and Dioscorea hypoglauca as the adjuvant herb, separating clear from turbid, eliminating dampness, and unblocking the meridians. The combined effects of these herbs invigorate Qi, detoxify and eliminate dampness, tonify the kidneys, consolidate the body, and separate clear from turbid, aligning with the pathogenesis of lupus nephritis, which is characterized by deficiency of the root and excess of the branch, and a complex interplay of deficiency and excess.

[0039] Its core advantages precisely address the aforementioned technical pain points: First, it has a high degree of alignment with the pathogenesis. The four herbs work together to simultaneously support the body's resistance and eliminate pathogenic factors. Astragalus membranaceus tonifies Qi and supports the body's resistance, directly targeting the root cause of "deficiency of vital Qi." Smilax glabra and Dioscorea hypoglauca promote diuresis, detoxify, and eliminate turbidity, targeting the symptoms of "internal retention of dampness and turbidity." Schisandra chinensis addresses both the depletion of vital Qi and the deficiency of body fluids, comprehensively covering the core pathogenesis of LN and solving the problem of insufficient targeting in existing treatments. Second, it has significant synergistic effects. The functions of each herb are complementary, which can regulate immunity, inhibit inflammation, and improve kidney damage, breaking through the limitations of existing Chinese medicines, which are mostly used as auxiliary means. Third, it has excellent safety. The formula consists of commonly used low-toxicity herbs in clinical practice, with no obvious liver and kidney toxicity, making it suitable for the long-term conditioning needs of LN patients.

[0040] The beneficial effects of the present invention will be illustrated below through specific embodiments.

[0041] In the following examples, the weight proportions of each raw material are as follows: 8 parts Astragalus membranaceus, 2 parts Smilax glabra, 4 parts Schisandra chinensis, and 1 part Dioscorea hypoglauca.

[0042] Example 1: A traditional Chinese medicine composition for treating lupus nephritis The traditional Chinese medicine composition comprises the following raw materials by weight: Astragalus membranaceus 48g, Smilax glabra 12g, Schisandra chinensis 24g, and Dioscorea hypoglauca 6g. The traditional Chinese medicine composition is prepared into a decoction, pills, granules, or oral liquid using conventional pharmaceutical methods and with medically acceptable excipients.

[0043] Example 2: A traditional Chinese medicine composition for treating lupus nephritis The traditional Chinese medicine composition comprises the following raw materials by weight: Astragalus membranaceus 60g, Smilax glabra 15g, Schisandra chinensis 30g, and Dioscorea hypoglauca 7.5g. The traditional Chinese medicine composition is prepared into a decoction, pills, granules, or oral liquid using conventional pharmaceutical methods and with medically acceptable excipients.

[0044] Example 3: A traditional Chinese medicine composition for treating lupus nephritis The traditional Chinese medicine composition comprises the following raw materials by weight: Astragalus membranaceus 36g, Smilax glabra 9g, Schisandra chinensis 18g, and Dioscorea hypoglauca 4.5g. The traditional Chinese medicine composition is prepared into a decoction, pills, granules, or oral liquid using conventional pharmaceutical methods and with medically acceptable excipients.

[0045] Example 4: A decoction of a traditional Chinese medicine composition for treating lupus nephritis The specific preparation method is as follows: Weigh the raw materials according to the proportions described in Example 1, mix them evenly, and place them in a stainless steel container. Add distilled water equivalent to 10 times the total weight of the prescription herbs and soak for 30 minutes. After soaking, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter and collect the filtrate. Then add distilled water equivalent to 8 times the total weight of the prescription herbs to the residue, bring to a boil again over high heat, then simmer over low heat for 1 hour. Filter and collect the second filtrate. Combine the two filtrates, filter, and concentrate to prepare an aqueous decoction of the traditional Chinese medicine composition with a concentration of 1.2 g / mL based on the total amount of raw herbs.

[0046] Example 5: A decoction of a traditional Chinese medicine composition for treating lupus nephritis The specific preparation method is as follows: Weigh the raw materials according to the proportions described in Example 2, mix them evenly, and place them in a stainless steel container. Add distilled water equivalent to 10 times the total weight of the prescription herbs and soak for 30 minutes. After soaking, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter and collect the filtrate. Then add distilled water equivalent to 8 times the total weight of the prescription herbs to the residue, bring to a boil again over high heat, then simmer over low heat for 1 hour. Filter and collect the second filtrate. Combine the two filtrates, filter, and concentrate to prepare an aqueous decoction of the traditional Chinese medicine composition with a concentration of 1.5 g / mL based on the total amount of raw herbs.

[0047] Example 6: A decoction of a traditional Chinese medicine composition for treating lupus nephritis The specific preparation method is as follows: Weigh the raw materials according to the proportions described in Example 3, mix them evenly, and place them in a stainless steel container. Add distilled water equivalent to 10 times the total weight of the prescription herbs and soak for 30 minutes. After soaking, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter and collect the filtrate. Then add distilled water equivalent to 8 times the total weight of the prescription herbs to the residue, bring to a boil again over high heat, then simmer over low heat for 1 hour. Filter and collect the second filtrate. Combine the two filtrates, filter, and concentrate to obtain an aqueous decoction of the traditional Chinese medicine composition with a concentration of 0.9 g / mL based on the total amount of raw herbs.

[0048] The traditional Chinese medicine composition contains 5 to 10 parts of Astragalus membranaceus, 1 to 3 parts of Smilax glabra, 3 to 5 parts of Schisandra chinensis, and 0.5 to 1.5 parts of Dioscorea hypoglauca. All of these components can be prepared into a decoction within the specified ratio range for the treatment of lupus nephritis.

[0049] Experimental Example 1 Efficacy and safety evaluation of a traditional Chinese medicine composition for treating lupus nephritis in mice with MRL / lpr lupus nephritis. 1. Laboratory animals and grouping Ten-week-old female MRL / lpr mice were selected as the lupus nephritis model animals, with normal MRL / MpJ mice in the same background serving as normal controls. The experimental animals were housed in an SPF-grade environment with free access to food and water, and were randomly assigned to groups after 7 days of acclimatization. Both the lupus nephritis model MRL / lpr mice and the normal MRL / MpJ mice in the same background were purchased from Changzhou Cavens Laboratory Animal Co., Ltd., quality certificate number No. 320730250100484263.

[0050] The experiment was divided into four groups: a normal control group (CON group), a model group (MOD group), the herbal composition administration group of this invention (SBF group), and a prednisolone acetate tablet group (Pred group), with eight animals in each group. Prednisolone acetate tablets were purchased from Changcheng Pharmacy, Vanke Store, south side of Weisi Road, Yuci District, Jinzhong City, Shanxi Province.

[0051] 2. Dosing regimen Administer medication starting at 11 weeks of age and continuing for 6 weeks until 17 weeks of age.

[0052] The normal control group consisted of normal MRL / MpJ mice administered distilled water by gavage at a volume of 0.1 mL / 10 g body weight. The model group consisted of MRL / lpr lupus nephritis model mice administered distilled water by gavage at a volume of 0.1 mL / 10 g body weight. The SBF group consisted of MRL / lpr lupus nephritis model mice administered a decoction of the traditional Chinese medicine composition prepared in Example 5 of this invention by gavage at a concentration of 1.5 g / mL, with a gavage volume of 0.1 mL / 10 g body weight, equivalent to a dose of 15 g / kg. The Pred group consisted of MRL / lpr lupus nephritis model mice administered prednisolone acetate tablet suspension by gavage at a concentration of 0.5 mg / mL, with a gavage volume of 0.1 mL / 10 g body weight, equivalent to a dose of 5 mg / kg. These doses were determined based on clinically equivalent dosage conversion. All groups were administered the medication once daily for 6 consecutive weeks.

[0053] 3. Observation indicators and detection methods 1) Kidney function indicators Urinary protein excretion was measured during the drug administration period and at the experimental endpoint. Serum was collected at the experimental endpoint to measure serum creatinine (Scr) and blood urea nitrogen (BUN) levels to evaluate renal function impairment and the effectiveness of drug intervention.

[0054] 2) Autoantibody indicators Serum was collected at the experimental endpoint to detect the level of anti-dsDNA antibody in order to evaluate lupus-related autoimmune abnormalities.

[0055] 3) Immune cell subset indicators At the experimental endpoint, splenic lymphocytes were isolated, and the proportion of regulatory T cells (Tregs) and CD69 were detected by flow cytometry. + B cell percentage and CD138 + The proportion of plasma cells is used to evaluate immune tolerance status and abnormal activation and differentiation of B cells.

[0056] 4) Organ Index At the experimental endpoint, animals were sacrificed, and the spleen, kidneys, heart, liver, and lungs were weighed. Corresponding organ indices were calculated to assess disease activity, renal involvement, and drug safety. The formula for calculating organ indices is as follows:

[0057] Organ Index = Organ Weight (mg) / Body Weight (g) 5) Pathological observation Kidney, heart, lung, and liver tissues were collected for HE pathological staining to further evaluate the efficacy and safety of the traditional Chinese medicine composition described in this invention.

[0058] 4. Statistical methods Experimental data are expressed as x̄±s. One-way ANOVA was used for inter-group comparisons, and Dunnett's test was used for multiple comparisons. P <0.05 indicates that the difference is statistically significant.

[0059] 5. Experimental Results 5.1 The herbal composition of this invention can reduce the 12-hour urinary protein excretion in 17-week-old MRL / lpr mice and improve renal function-related indicators. Compared with the normal control group, the model group mice showed a significantly increased 12-hour urinary protein excretion at 17 weeks of age, indicating significant kidney damage in the MRL / lpr mice. After 6 weeks of continuous gavage administration, the 12-hour urinary protein excretion in both the SBF and Pred groups was lower than that in the model group, with the difference in the SBF group being highly significant compared to the model group. Figure 1 As shown.

[0060] Further analysis of renal function-related biochemical indicators revealed that, compared with the normal control group, the serum urea nitrogen (BUN) and serum creatinine (Scr) levels in the model group mice were significantly elevated. After SBF intervention, the BUN and Scr levels were significantly lower than those in the model group, and the effects were similar to those in the Pred group. This indicates that the herbal composition of this invention can effectively improve renal function damage in MRL / lpr mice. Figure 2 and Figure 3 As shown.

[0061] 5.2 The traditional Chinese medicine composition of this invention can reduce anti-dsDNA antibody levels and improve lupus-related humoral immune abnormalities. Compared with the normal control group, the serum anti-dsDNA antibody level in the model group mice was significantly increased, indicating a significant lupus-related autoimmune abnormality in the model animals. After 6 weeks of continuous administration, the serum anti-dsDNA antibody levels in both the SBF group and the Pred group were significantly lower than those in the model group, showing comparable efficacy. Figure 4 As shown.

[0062] 5.3 The herbal composition of this invention can restore the proportion of Treg cells and improve immune tolerance imbalance. Compared with the normal control group, the proportion of Treg cells in the spleen lymphocytes of mice in the model group was decreased, indicating impaired immune tolerance. After SBF intervention, the proportion of Treg cells was significantly higher than that in the model group and significantly higher than that in the Pred group. This suggests that the traditional Chinese medicine composition of this invention is superior to the Pred group in restoring the proportion of Treg cells and improving the imbalance of immune tolerance. Figure 5 As shown.

[0063] 5.4 The traditional Chinese medicine composition of this invention can inhibit abnormal activation of B cells. Compared with the normal control group, CD69 in the spleen lymphocytes of the model group mice was higher. + The proportion of B cells was significantly increased, indicating that B cells were in an abnormally activated state. After intervention with SBF and Pred, CD69... + The proportion of B cells was significantly lower in the SBF group compared to the model group, while CD69 in the SBF group was also significantly lower. + The proportion of B cells was significantly lower in the group than in the Pred group, suggesting that the herbal composition of this invention is superior to the Pred group in inhibiting abnormal B cell activation. Figure 6 As shown.

[0064] 5.5 The traditional Chinese medicine composition of this invention can inhibit abnormal differentiation of plasma cells. Compared with the normal control group, CD138 in the spleen lymphocytes of the model group mice was higher. + The proportion of plasma cells was significantly increased, indicating enhanced plasma cell differentiation. After 6 weeks of continuous administration, CD138 levels were significantly increased in both the SBF and Pred groups. + The proportion of plasma cells was lower in both groups than in the model group, and the effects were similar between the two groups. This suggests that the herbal composition of this invention has a similar effect on inhibiting abnormal plasma cell differentiation as the prednisolone acetate tablet group. Figure 7 As shown.

[0065] 5.6 The traditional Chinese medicine composition of this invention can significantly improve abnormal spleen and kidney indices and, to some extent, improve abnormal lung indices. Compared with the normal control group, the spleen index of mice in the model group was significantly increased, indicating enhanced disease activity accompanied by significant proliferation of immune organs. After SBF intervention, the spleen index decreased significantly compared with the model group, and the index was comparable to that of the Pred group. This suggests that the traditional Chinese medicine composition of this invention has a similar effect on improving the spleen index to the prednisolone acetate tablet group. Figure 8 As shown.

[0066] Compared with the normal control group, the model group mice showed elevated kidney index, indicating more severe kidney involvement. After SBF intervention, the kidney index decreased significantly compared with the model group. Compared with Pred, the decrease in kidney index was more pronounced, but the difference was not statistically significant. Figure 9 As shown.

[0067] Compared with the normal control group, the lung index of mice in the model group was significantly increased, indicating some degree of lung tissue involvement. After intervention, the lung index of mice in the SBF and Pred groups showed a decreasing trend compared with the model group, but the difference was not statistically significant. This suggests that the traditional Chinese medicine composition of this invention has a certain ameliorative trend on abnormal changes in lung tissue related to lupus nephritis, but the difference did not reach statistical significance under the experimental conditions. Figure 10 As shown.

[0068] 5.7. The traditional Chinese medicine composition of this invention can improve renal pathological damage. HE staining results showed that the kidney tissue of normal control mice was structurally intact, with regular glomerular morphology, and no obvious pathological changes such as glomerular matrix hyperplasia, tubular atrophy, interstitial hyperplasia, or inflammatory cell infiltration. Figure 13 As shown.

[0069] Compared with the normal control group, the model group mice showed significant pathological damage to their kidney tissue, manifested as glomerular matrix proliferation (orange arrow), structural disorder, accompanied by a small amount of tubular atrophy (blue arrow), fibrous connective tissue proliferation (brown arrow), and extensive perivascular lymphocyte infiltration (yellow arrow). Simultaneously, a small amount of interstitial blood vessel wall thickening was observed (purple arrow), indicating significant kidney inflammation and tissue damage. Figure 13 As shown.

[0070] After 6 weeks of continuous administration, the kidney pathological damage in the SBF group mice was significantly improved, the glomerular structure was relatively intact, no obvious glomerular sclerosis or crescent formation was observed, and the renal tubular structure was basically normal, with only a small amount of inflammatory cell infiltration. This suggests that the traditional Chinese medicine composition of this invention can effectively reduce kidney inflammation and tissue damage. Figure 13 As shown.

[0071] The kidney pathological damage in the Pred group mice was also improved compared to the model group, but significant glomerular matrix proliferation (orange arrow), fibrous connective tissue proliferation (brown arrow), and inflammatory cell infiltration (yellow arrow) were still observed, with occasional crescent formation (green arrow). This suggests that although prednisolone acetate tablets can partially improve kidney pathological damage, the degree of improvement is lower than that of the traditional Chinese medicine composition of this invention. Figure 13 As shown.

[0072] 5.8 No obvious tissue toxicity damage was observed in the traditional Chinese medicine composition of this invention. HE staining of the heart showed that the myocardial fibers in the CON and SBF groups were relatively regularly arranged, and the tissue structure was well preserved. In the MOD and Pred groups, some areas showed slightly uneven myocardial fiber course and slightly irregular arrangement, accompanied by mild widening of the interstitial spaces. However, no obvious pathological damage such as myocardial necrosis, rupture, significant inflammatory cell infiltration, or hemorrhage was observed in any group. Figure 14 As shown.

[0073] HE staining of the lungs showed that the lung tissue of the normal control group mice was structurally intact, with uniform alveolar distribution, thin alveolar septa, and no obvious inflammatory cell infiltration. Compared with the normal control group, the lung tissue of the model group mice showed mild thickening of alveolar septa, increased interstitial cells, and mild inflammatory cell infiltration, suggesting a certain degree of interstitial lung inflammation, possibly related to lung involvement associated with lupus nephritis. After SBF intervention, alveolar septal thickening and inflammatory cell infiltration were reduced compared with the model group, and the lung tissue structure was improved; the Pred group also showed a similar trend of improvement. Figure 15 As shown.

[0074] HE staining of the liver showed that the overall structure of the liver tissue in all groups of mice was intact, the lobular structure was clear, and the hepatic cords were arranged relatively regularly. No obvious hepatocyte necrosis, obvious inflammatory cell infiltration, cholestasis, or obvious tissue destruction was observed. The liver tissue morphology of the SBF group was similar to that of the normal control group, and no obvious abnormal pathological changes were observed. In the Pred group, mild hepatocyte cytoplasm loosening and vacuolar changes were observed in some areas, but no obvious severe liver tissue damage was observed. Figure 16 As shown.

[0075] The above results suggest that the traditional Chinese medicine composition of the present invention did not show obvious toxic damage to the heart, lungs, and liver tissues under the experimental conditions, and has good tissue safety.

[0076] 6. Summary of Results In summary, under the conditions of this invention, after continuous oral administration of the traditional Chinese medicine composition for 6 weeks, it can significantly reduce the 12-hour urinary protein excretion, serum Scr and BUN levels in 17-week-old MRL / lpr lupus nephritis mice, and reduce serum anti-dsDNA antibody levels; at the same time, it can restore the proportion of Treg cells and inhibit CD69. + B cell aberrant activation and CD138 + The composition inhibits abnormal plasma cell differentiation and improves the abnormal trends in spleen, kidney, and lung indices. Furthermore, HE staining results show that the herbal composition of this invention can significantly reduce glomerular matrix proliferation, inflammatory cell infiltration, and renal tissue structural damage in MRL / lpr mice, suggesting that it can effectively improve pathological damage related to lupus nephritis.

[0077] Safety evaluation results showed that after intervention with the traditional Chinese medicine composition of this invention, the overall structure of the heart, liver, and lung tissues of mice remained basically intact, with no obvious tissue necrosis, severe inflammatory cell infiltration, or definite structural damage observed. HE staining of the heart showed that the myocardial fibers in the group treated with the traditional Chinese medicine composition of this invention were relatively regularly arranged, and the tissue structure was well preserved. Although slight unevenness in the course of myocardial fiber bundles and mild widening of gaps were observed in some areas of the MOD and Pred groups, no definite myocardial necrosis, myocardial fiber rupture, obvious inflammatory cell infiltration, or hemorrhage was observed in any group. Cardiac index results showed no statistically significant differences among the groups. Figure 11 As shown. HE staining of liver tissue revealed that the liver tissue morphology of the herbal composition group was generally similar to that of the normal control group, with no obvious abnormal pathological changes; the Pred group showed localized mild hepatocyte morphological changes, and its liver index was significantly lower than that of the model group, such as... Figure 12 As shown, the Pred group carries a certain risk of liver-related adverse effects. HE staining of lung tissue also revealed no obvious abnormal pathological changes. In summary, the herbal composition of this invention did not exhibit significant cardiac, hepatic, or pulmonary toxicity, demonstrating good safety.

[0078] The above results indicate that the herbal composition of this invention has good renal protective and immunomodulatory effects on lupus nephritis. Its overall efficacy is similar to that of prednisolone acetate tablets, and it shows certain advantages in some aspects of immunomodulation, improvement of renal pathology, and safety, suggesting that it has good long-term application potential. It should be noted that the decoctions prepared in Examples 4 and 6 were used in the same experiments as in Example 1. The experimental results also show that the herbal composition of this invention has significant renal protective and immunomodulatory effects on lupus nephritis, consistent with the effects in Example 5, and with good safety.

[0079] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0080] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the invention. Those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. Therefore, the scope of protection of this invention should be determined by the appended claims.

Claims

1. A traditional Chinese medicine composition for treating lupus nephritis, characterized in that, Composed of the following parts by weight of active pharmaceutical ingredient: Astragalus membranaceus 5-10 parts, Smilax glabra 1-3 parts, Schisandra chinensis 3-5 parts and Dioscorea hypoglauca 0.5-1.5 parts.

2. A traditional Chinese medicine composition for treating lupus nephritis, characterized in that, Composed of the following parts by weight of active pharmaceutical ingredient: Astragalus membranaceus 8 parts, Smilax glabra 2 parts, Schisandra chinensis 4 parts and Dioscorea hypoglauca 1 part.

3. The traditional Chinese medicine composition for treating lupus nephritis according to claim 1, characterized in that, The traditional Chinese medicine composition is combined with pharmaceutically acceptable excipients to form a clinically acceptable formulation.

4. The traditional Chinese medicine composition for treating lupus nephritis according to claim 3, characterized in that, The preparation is a decoction, pills, granules, or oral liquid.

5. The traditional Chinese medicine composition for treating lupus nephritis according to claim 4, characterized in that, The preparation is a decoction.

6. The traditional Chinese medicine composition for treating lupus nephritis according to claim 5, characterized in that, The method for preparing the decoction is as follows: weigh each raw material according to the weight proportions described in claim 1, mix them, add water and decoct, filter and extract the juice to obtain the decoction.

7. The traditional Chinese medicine composition for treating lupus nephritis according to claim 6, characterized in that, The water is distilled water.

8. The traditional Chinese medicine composition for treating lupus nephritis according to claim 6, characterized in that, The concentration of the decoction, based on the total amount of raw medicinal materials, is 0.9 g / mL to 1.5 g / mL.

9. The use of the traditional Chinese medicine composition according to any one of claims 1 to 8 in the preparation of a medicament for treating lupus nephritis.

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