Traditional Chinese medicine composition for treating systemic lupus erythematosus associated pulmonary arterial hypertension and application

Abstract

The application discloses a traditional Chinese medicine composition for treating systemic lupus erythematosus (SLE) related pulmonary arterial hypertension and application, and relates to the technical field of traditional Chinese medicine, wherein the composition is prepared from pueraria, gotukola, salvia miltiorrhiza, chuanxiong, radix scrophulariae, poria cocos, wheat bran-fried atractylodes, dried tangerine or orange peel, prepared pinellia, baked licorice, immature bitter orange fruit and gotukola, and has the functions of activating blood circulation to remove blood stasis and clearing heat and resolving toxins, and is aimed at the pathogenesis of the heat-toxin blood stasis syndrome of SLE-PAH. The application further provides a preparation method of the composition. The composition can effectively reduce the pulmonary arterial pressure of a model animal, relieve right ventricular hypertrophy and pulmonary vascular remodeling, and improve the oxidation stress level in experiments. In combination with western medicine, the composition can significantly improve the exercise endurance of a patient, improve the pulmonary arterial systolic pressure and key serological indexes, and has a better curative effect than simple western medicine and good safety, thereby providing a safe and effective traditional Chinese medicine composition for treating SLE-PAH.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition and its application for treating systemic lupus erythematosus-related pulmonary hypertension. Background Technology

[0002] Systemic lupus erythematosus (SLE) is a typical multi-system autoimmune disease characterized by overactivation of the immune system, leading to increased autoantibodies and immune complexes, as well as organ dysfunction. Pulmonary arterial hypertension (PAH) is a serious and fatal cardiopulmonary complication of SLE. SLE-associated PAH (SLE-PAH) progresses rapidly, has a poor prognosis, and significantly impacts patients' quality of life and lifespan.

[0003] Currently, the standard Western medicine treatment for SLE-PAH mainly follows the guidelines for idiopathic pulmonary hypertension, employing targeted drugs such as endothelin receptor antagonists (e.g., ambrisentan) and phosphodiesterase-5 inhibitors (e.g., tadalafil), combined with glucocorticoids and immunosuppressants for immunomodulation. However, these treatment regimens have significant limitations: firstly, targeted drugs are expensive, placing a heavy financial burden on patients; secondly, these drugs have adverse reactions such as hepatotoxicity, requiring long-term monitoring; thirdly, some patients do not respond well to treatment, and the efficacy varies from person to person; and finally, existing treatments cannot completely reverse the disease progression, and their effect on delaying disease progression is limited. While Traditional Chinese Medicine (TCM) has accumulated rich experience in treating pulmonary hypertension, clinical practice often employs compound formulas based on the general principle of "activating blood circulation and removing blood stasis." However, these existing formulas mostly focus on general blood stasis symptoms and fail to fully address the complex pathological mechanisms unique to SLE-PAH, resulting in insufficient targeted treatment and inadequate intervention at key disease stages. Summary of the Invention

[0004] The purpose of this invention is to at least solve one of the technical problems existing in the prior art, and to provide a traditional Chinese medicine composition and its application for treating systemic lupus erythematosus-related pulmonary hypertension.

[0005] The technical solution of the present invention is as follows: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension is made from the following raw materials in parts by weight: 10-40 parts of kudzu root, 5-30 parts of centella asiatica, 5-30 parts of salvia miltiorrhiza, 3-20 parts of chuanxiong rhizome, 5-20 parts of scutellaria baicalensis, 10-30 parts of poria cocos, 5-20 parts of stir-fried atractylodes macrocephala, 5-20 parts of tangerine peel, 5-20 parts of prepared pinellia tuber, 5-20 parts of prepared licorice root, and 5-30 parts of immature bitter orange.

[0006] Preferably, it is made from the following raw materials in parts by weight: 10-30 parts of kudzu root, 5-20 parts of centella asiatica, 5-20 parts of salvia miltiorrhiza, 3-15 parts of chuanxiong rhizome, 5-15 parts of scutellaria baicalensis root, 10-25 parts of poria cocos, 5-15 parts of stir-fried atractylodes macrocephala root, 5-15 parts of tangerine peel, 5-15 parts of prepared pinellia tuber, 5-15 parts of prepared licorice root, and 5-20 parts of immature bitter orange.

[0007] Preferably, the raw materials are weighed according to the formula, extracted with water, and the extract is collected to obtain the final product.

[0008] Preferably, it includes the following steps: S1: After weighing the raw material, soak the raw material in an acidic solution with a pH of 3-5 to obtain the acid-soaked raw material; S2: The acid-soaked raw material is enzymatically hydrolyzed using cellulase to obtain the hydrolyzed raw material; S3: Extract the raw material after enzymatic hydrolysis, collect the extract, and obtain the traditional Chinese medicine composition; The extraction methods include: decoction and / or ultrasonic extraction.

[0009] Preferably, in step S2, the enzymatic hydrolysis treatment involves adding 0.1%-0.5% of cellulase by weight of the raw material and hydrolyzing at 40-50°C for 0.5-1.5 hours.

[0010] The present invention also discloses a medicament for treating systemic lupus erythematosus-associated pulmonary hypertension, comprising an effective active ingredient and pharmaceutically acceptable excipients; the effective active ingredient comprises the traditional Chinese medicine composition described above.

[0011] Preferably, the active ingredient also includes a Western medicine for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0012] Preferably, the dosage form of the drug is one of the following: decoction, granules, pills, capsules, tablets, powders, and oral liquid.

[0013] The present invention also discloses the application of the above-described traditional Chinese medicine composition in the preparation of a drug for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0014] Preferably, the drug further includes a Western medicine for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0015] The beneficial effects of this invention are: (1) The traditional Chinese medicine composition provided by the present invention is made from kudzu root, centella asiatica, salvia miltiorrhiza, chuanxiong rhizome, scutellaria baicalensis, poria cocos, stir-fried atractylodes macrocephala, tangerine peel, prepared pinellia ternata, prepared licorice root, and immature bitter orange. Kudzu root and centella asiatica are the two principal herbs. It targets the complex pathogenesis of SLE-PAH, which is "internal heat and toxin accumulation and blood stasis obstructing the collaterals". It takes into account both clearing heat and detoxifying and promoting blood circulation and unblocking the collaterals, thus forming a synergistic and effective treatment system, providing a new traditional Chinese medicine prescription option for the treatment of this disease.

[0016] (2) Through in-depth dose-effect analysis, this invention has determined a more optimal ratio range and a prescription adjustment scheme for patients with "blood stasis type" and "qi deficiency type". This optimized scheme significantly improves the safety and precision of treatment while ensuring that the core efficacy of the whole prescription is fully exerted. Specifically, by adjusting the dosage ratio of each of the principal, assistant, adjuvant and guide drugs, while strengthening the main direction of activating blood circulation and unblocking the meridians or strengthening the spleen and resolving phlegm, it can effectively avoid the side effects of bleeding, gastrointestinal irritation or bitter and cold damage that may be caused by excessive dosage of single drugs, and achieve the best balance between efficacy and safety, providing clear guidance for individualized precision treatment in clinical practice.

[0017] (3) The preparation method provided by this invention, especially the integrated extraction process including "acidification-enzymatic hydrolysis-ultrasound", is not a simple water extraction. This synergistic process first softens the tissue by soaking in a weak acid, then specifically destroys the cellulose structure in the plant cell wall by enzymatic hydrolysis under specific conditions, and finally supplements it with ultrasound technology with optimized parameters. This can significantly promote the efficient dissolution and release of key flavonoid insoluble and heat-sensitive active ingredients such as puerarin and baicalin. This process greatly improves the extraction rate and transfer rate of active ingredients, thereby ensuring that the final formulation has a more stable and sufficient pharmacodynamic material basis and higher bioavailability. This is one of the key technical guarantees of this invention.

[0018] (4) The pharmacodynamic experiments of the present invention in SLE-PAH model animals confirmed the comprehensive therapeutic effect of the composition of the present invention. The experimental results showed that the composition could effectively reduce the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index in the model animals, verifying its core efficacy of reducing pulmonary artery pressure from a hemodynamic perspective. At the same time, pathological observation showed that it could reduce pulmonary arteriolar media thickening and improve vascular stenosis, indicating that it has the effect of inhibiting pulmonary vascular remodeling. Further biochemical tests confirmed that the composition could significantly reduce the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in lung tissue and increase the content of glutathione (GSH), reflecting its mechanism of improving oxidative stress and regulating redox balance.

[0019] (5) The traditional Chinese medicine composition of the present invention can be prepared into a variety of clinically applicable dosage forms such as granules and capsules, and can be combined with conventional Western medicines. Clinical research data have confirmed that it can significantly improve pulmonary artery systolic pressure and six-minute walking distance in SLE-PAH patients, and reduce key indicators such as NT-proBNP, erythrocyte sedimentation rate and serum uric acid. The efficacy is better than that of Western medicine treatment alone, and the safety is good. It provides a new comprehensive treatment option with better efficacy and reliable safety for the clinical management of SLE-PAH. Attached Figure Description

[0020] Figure 1 The effects of traditional Chinese medicine compositions on right ventricular pressure and hypertrophy in mice are shown in Figure A. Figure A shows the changes in right ventricular systolic pressure (RVSP) in mice in the SLE, SLE-PAH, and TMT groups. Figure B shows the changes in right ventricular hypertrophy index [RV / (LV+S)] in mice in the SLE, SLE-PAH, and TMT groups. Data are expressed as mean ± standard deviation (n=5 for each group). P <0.05, P <0.01.

[0021] Figure 2 HE staining images of pathological changes in pulmonary arterioles in different groups of mice.

[0022] Figure 3 The effects of a traditional Chinese medicine composition on oxidative stress levels in the lung tissue of SLE-PAH mice are shown in Figure A. Figure B shows the changes in reactive oxygen species (ROS) levels; Figure C shows the changes in malondialdehyde (MDA) content; and Figure C shows the changes in glutathione (GSH) content. Data are expressed as mean ± standard deviation (n=5). P <0.001. Detailed Implementation

[0023] The technical solution adopted in this invention is as follows: In a first aspect, the present invention provides a traditional Chinese medicine composition for treating systemic lupus erythematosus-related pulmonary hypertension, which is made from the following raw materials in parts by weight: 10-40 parts of kudzu root, 5-30 parts of centella asiatica, 5-30 parts of salvia miltiorrhiza, 3-20 parts of chuanxiong rhizome, 5-20 parts of scutellaria baicalensis, 10-30 parts of poria cocos, 5-20 parts of stir-fried atractylodes macrocephala, 5-20 parts of tangerine peel, 5-20 parts of prepared pinellia tuber, 5-20 parts of prepared licorice root, and 5-30 parts of immature bitter orange.

[0024] This invention is based on the theory of syndrome differentiation and treatment in Traditional Chinese Medicine, combined with the core pathogenesis of SLE-PAH (external accumulation of heat and toxins, and blood stasis obstructing the collaterals). It uses clearing heat and detoxifying, and promoting blood circulation and unblocking the collaterals as treatment methods, and employs a scientifically formulated prescription. The key innovation of this prescription lies in its rigorous "principal, assistant, adjuvant, and guide" compatibility structure and scientific dosage ratio range. Its prescription structure and explanation are as follows: I. Principal Drug (Dual-core driven, detoxifying and unblocking meridians) Medicinal ingredients: kudzu root, centella asiatica.

[0025] Combination strategy: Both are principal drugs, forming a "dual-core driving" effect.

[0026] Kudzu root: Cool in nature and sweet and pungent in taste, it enters the spleen, stomach, and lung meridians. Its functions include relieving muscle tension and reducing fever, promoting body fluid production and quenching thirst, and unblocking meridians and collaterals. In this formula, kudzu root is the principal ingredient, used to clear heat and relieve muscle tension to eliminate internal heat toxins, unblock meridians and collaterals to relieve pulmonary artery obstruction, and also to dilate blood vessels and improve microcirculation. Kudzu root is rich in isoflavones (such as puerarin), a key component in lowering pulmonary artery pressure.

[0027] Dose-response analysis: If kudzu root is used in excess, it will cause excessive clearing and purging, damaging yang and qi, which may lead to excessive vasodilation, low blood pressure, indigestion or diarrhea. At the same time, it may weaken the targeted effect of blood-activating drugs in the formula, making "clearing heat and unblocking collaterals" more like "draining qi and dispersing blood". If it is insufficient, the effect of clearing heat and unblocking collaterals will be weakened, which is reflected in the weakened pulmonary artery dilation and anti-inflammatory effect, making it difficult to achieve the purpose of relieving right ventricular pressure and making it difficult to dominate the overall effect of the formula.

[0028] Centella asiatica: Cold in nature and sweet and bland in taste, it enters the liver, spleen, and kidney meridians. Its functions include clearing heat and dampness, detoxifying and reducing swelling, and anti-fibrosis. In this formula, it is elevated to the principal herb, taking advantage of its ability to specifically enter the blood and muscles, effectively clearing latent heat in the blood, promoting diuresis and detoxification, and inhibiting the proliferation of vascular smooth muscle cells and collagen deposition, thus reversing vascular remodeling. Centella asiatica targets the vasculitis-specific lesions of SLE, directly reaching the affected area to clear the pathological products of "stasis and toxins," while simultaneously synergizing with kudzu root to enhance microcirculation, forming a dual-core complementary mechanism of "vasodilation + reversal of remodeling."

[0029] Dose-response analysis: If the amount of Centella asiatica is excessive, its cold nature will be too strong, which will easily damage the spleen and stomach yang qi, leading to gastrointestinal discomfort, loose stools, and may also affect the circulation of qi and blood; if the amount is insufficient, the medicinal power will be unable to overcome the deep-seated "dead blood" and "stubborn phlegm", and will not be able to effectively inhibit pulmonary vascular fibrosis and inflammatory response, resulting in unstable antihypertensive and anti-remodeling effects, and making it difficult to achieve the core goal of "unblocking the meridians".

[0030] II. Assistant herbs (promoting blood circulation and removing blood stasis, assisting in unblocking the meridians) Medicinal ingredient: Salvia miltiorrhiza.

[0031] Formulary Strategy: Danshen (Salvia miltiorrhiza) is a key herb for promoting blood circulation and removing blood stasis. It is slightly cold in nature, bitter in taste, and enters the heart and liver meridians. Its functions include promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain, and clearing the heart and relieving irritability. Danshen is used as an assistant herb to enhance the blood-activating and stasis-removing effects of the two principal herbs, targeting the core of "blood stasis," and also has anti-fibrotic properties and improves vascular remodeling.

[0032] Dose-response analysis: If Danshen is taken in excess, it will promote blood circulation too much, deplete qi and damage yin, which may lead to prolonged coagulation function or bleeding tendency, especially when used with anticoagulants, which increases the risk; if it is taken in excess, the effect of "promoting blood circulation and removing blood stasis" will be insufficient, making it difficult to improve pulmonary vascular remodeling and microcirculation perfusion, and unable to support the blood circulation effect of the principal drug.

[0033] III. Adjuvant Therapy (Multidimensional Regulation, Treating Both Symptoms and Root Cause) The adjuvant medicines are divided into four groups, which respectively regulate phlegm, heat toxins, qi, and spleen and stomach.

[0034] Group 1 (auxiliary herbs, for drying dampness and resolving phlegm): Pinellia ternata, Citrus aurantium, Citrus reticulata peel.

[0035] Pinellia ternata has the effects of drying dampness and resolving phlegm, relieving nausea and vomiting, eliminating lumps and dissipating nodules, regulating qi and relieving asthma, and dispelling wind and relieving spasms. Fructus Aurantii Immaturus has the effects of breaking up qi stagnation, eliminating phlegm, and dispersing masses; Dried tangerine peel has the effect of regulating qi and strengthening the spleen; Therefore, the functions of adjuvant herbs are: to dry dampness and resolve phlegm, to break up stagnation and eliminate accumulation, and to regulate qi and harmonize the middle jiao.

[0036] Function and approach: Targeting the "tangible phlegm" in SLE-PAH vascular remodeling, this method dries dampness, resolves phlegm, breaks up qi stagnation, and eliminates accumulation.

[0037] Dose-response analysis: If this group is overdosed, the pungent, warm, and drying properties and the force of breaking up qi will be too strong, which will easily deplete qi and yin, aggravating the problem of "yin deficiency and internal heat" in SLE patients; if it is insufficient, the ability to resolve phlegm and dissipate nodules will be inadequate, making it difficult to reverse vascular remodeling and leading to a lingering condition.

[0038] The second group (adjuvant / assistant medicine, for clearing heat and dissipating nodules): Scutellaria baicalensis.

[0039] Functions and rationale: Scutellaria baicalensis clears heat and dries dampness, drains fire and detoxifies, directly clears lung fire in the upper burner, and eliminates inflammatory factors of SLE; its cold nature can also counteract the warming and drying properties of Pinellia ternata and Ligusticum chuanxiong.

[0040] Dose-response analysis: If Scutellaria baicalensis is in excessive amounts, its bitter and cold nature will damage the middle jiao, suppress qi and stagnate blood, leading to spleen and stomach deficiency and cold or blood stasis; if it is insufficient, it will be difficult to fully clear "heat toxins" and inhibit inflammatory pathways, resulting in a decrease in anti-fibrotic effect.

[0041] The third group (assistant and guiding herbs, promoting qi circulation and guiding the meridians): Ligusticum chuanxiong.

[0042] Functions and rationale: Chuanxiong (Ligusticum striatum) is warm in nature and pungent in taste, and is a "qi-regulating herb in the blood," promoting blood circulation and qi flow. Its pungent and warming properties not only assist Danshen (Salvia miltiorrhiza) in promoting blood circulation but also regulate qi and relieve stagnation. As a guiding herb, it directs other herbs upwards to the brain and lungs.

[0043] Dose-response analysis: If the amount of Chuanxiong is excessive, it will cause excessive qi movement, disturb yang and stir up wind, which may cause dizziness and blood pressure fluctuations; if it is insufficient, qi stagnation and blood stasis will be difficult to resolve, and the effect of unblocking collaterals will be weakened.

[0044] Group 4 (auxiliary herbs, for strengthening the spleen and promoting diuresis): Poria cocos and stir-fried Atractylodes macrocephala.

[0045] Functions and rationale: To invigorate the spleen and replenish qi, and to promote diuresis and eliminate dampness. "To treat phlegm, first treat the spleen." Invigorating the spleen and drying dampness eliminates the source of phlegm production, while promoting diuresis reduces the burden on the right heart (edema).

[0046] Dose-response analysis: If both are in excessive amounts, excessive diuresis will damage body fluids; if they are insufficient, the spleen's function will be impaired, and dampness will be difficult to eliminate. Not only will phlegm and turbidity recur, but the stomach qi will also be unable to withstand the attack of the principal drug.

[0047] IV. Administering the medicine (harmonizing the effects of other medicines, protecting the heart and restoring the pulse) Medicinal ingredients: Prepared licorice root Formulary rationale: Prepared licorice root is neutral in nature and sweet in taste, and enters the heart, lung, spleen, and stomach meridians. It harmonizes the other herbs and buffers the irritation to the gastrointestinal tract caused by bitter and cold herbs (Centella asiatica, Scutellaria baicalensis) and pungent and dispersing herbs (Citrus aurantium, Pinellia ternata). It also has the effects of tonifying qi and nourishing the heart, restoring the pulse and calming palpitations, and protecting the damaged cardiac conduction system.

[0048] Dose-response analysis: If the amount of roasted licorice is excessive, it can easily lead to dampness and fullness in the middle jiao, and even cause water and sodium retention, which can aggravate edema and cardiac burden; if it is insufficient, the harmonizing effect will be insufficient, and the cold, hot and purgative properties of the whole formula will be difficult to integrate.

[0049] The formula's proportions are scientifically sound, balancing cold and heat, and addressing both qi and blood deficiency. An imbalance in the ratio of principal, assistant, and adjuvant herbs, or an excessively high / low dosage, will affect the coordination of its heat-clearing and detoxifying effects with its blood-activating and meridian-clearing effects. In particular, insufficient overall proportions will result in inadequate medicinal potency, failing to achieve the desired heat-clearing and meridian-clearing effects. Therefore, the optimized dosage range of this invention maximizes the inhibition of inflammatory responses, reduces oxidative stress, alleviates vascular remodeling and right ventricular load, and is key to achieving a comprehensive therapeutic effect in treating systemic lupus erythematosus-related pulmonary hypertension.

[0050] In some embodiments of this invention, a refined medication regimen based on traditional Chinese medicine syndrome differentiation is provided. In clinical application, the prescription can be optimized according to the patient's visual and tongue manifestations to achieve precise individualized treatment.

[0051] Preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 10-30 parts of kudzu root, 5-20 parts of centella asiatica, 5-20 parts of salvia miltiorrhiza, 3-15 parts of chuanxiong rhizome, 5-15 parts of scutellaria baicalensis, 10-25 parts of poria cocos, 5-15 parts of stir-fried atractylodes macrocephala, 5-15 parts of tangerine peel, 5-15 parts of prepared pinellia tuber, 5-15 parts of prepared licorice root, and 5-20 parts of immature bitter orange. This traditional Chinese medicine composition focuses on strengthening the effects of clearing heat and detoxifying, and promoting blood circulation, concentrating the medicinal power to resolve significant blood stasis and heat. Simultaneously, it is supplemented with spleen-strengthening and phlegm-resolving herbs to protect the middle jiao and prevent damage to the body's vital energy. It can be used for patients with blood stasis type SLE-PAH (i.e., patients with significant changes in bulbar conjunctival microvessels but normal tongue morphology).

[0052] Preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 10-20 parts of kudzu root, 5-20 parts of centella asiatica, 5-10 parts of salvia miltiorrhiza, 3-7 parts of chuanxiong rhizome, 5-10 parts of scutellaria baicalensis, 10-25 parts of poria cocos, 5-15 parts of stir-fried atractylodes macrocephala, 5-15 parts of tangerine peel, 5-15 parts of prepared pinellia tuber, 5-15 parts of prepared licorice root, and 5-20 parts of immature bitter orange. In this traditional Chinese medicine composition, the amount of heat-clearing and blood-activating herbs is appropriately reduced to prevent the bitter, cold, and pungent herbs from depleting the body's vital energy; at the same time, the focus is on strengthening the spleen, drying dampness, and resolving phlegm to support the body's resistance and resolve internal dampness and turbidity. This composition can be used for patients with Qi deficiency type SLE-PAH (i.e., patients with a large tongue body, teeth marks on the edges, a white and greasy tongue coating, and no significant signs of blood stasis in the eyes).

[0053] Secondly, the present invention provides a method for preparing a traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0054] The preparation method is as follows: weigh the raw materials according to the ratio, extract with water, and collect the extract to obtain the final product.

[0055] In some embodiments of the present invention, after weighing the raw material, the raw material is soaked in an acidic solution with a pH of 3-5 to obtain an acid-soaked raw material; then, the acid-soaked raw material is enzymatically hydrolyzed using cellulase to obtain an enzymatically hydrolyzed raw material; the enzymatically hydrolyzed raw material is extracted, and the extract is collected to obtain the traditional Chinese medicine composition; the extraction method includes one or more of decoction and ultrasonic extraction.

[0056] Specifically, the pH value of the acid solution is a range of 3.0, 3.5, 4.0, 4.5, 5.0, or any combination thereof.

[0057] In some embodiments of the present invention, the enzymatic hydrolysis treatment is as follows: adding 0.1%-0.5% of cellulase by weight of the active pharmaceutical ingredient, and hydrolyzing at 40-50°C for 0.5-1.5 hours. Specifically, the amount of cellulase added is 0.1%, 0.2%, 0.3%, 0.4%, 0.5% of the active pharmaceutical ingredient, or any combination thereof; the hydrolysis temperature is 40°C, 42°C, 44°C, 46°C, 48°C, 50°C, or any combination thereof; and the hydrolysis time is 0.5 hours, 1.0 hour, 1.5 hours, or any combination thereof.

[0058] Preferably, the cellulase accounts for 0.2%-0.4% of the mass of the active pharmaceutical ingredient; within this range, the amount of enzyme is sufficient to effectively hydrolyze cellulose in the cell wall, promote the release of contents, and at the same time avoid waste of enzyme preparation and possible introduction of excessive impurities.

[0059] Preferably, the enzymatic hydrolysis temperature is 42-48℃; this temperature range can maintain the optimal activity of cellulase, promote the softening of the medicinal material tissue, facilitate the dissolution of subsequent components, and avoid excessive temperature leading to enzyme inactivation or damage to heat-sensitive components.

[0060] In some embodiments of the present invention, the ultrasonic frequency of the ultrasound-assisted extraction is 30-80kHz, the power is 80-120W, and the processing time is 5-30 minutes. Specifically, the ultrasonic frequency of the ultrasound extraction is within the range of 30kHz, 40kHz, 50kHz, 60kHz, 70kHz, 80kHz, or any combination thereof; the power is within the range of 80W, 90W, 100W, 110W, 120W, or any combination thereof; and the processing time is within the range of 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, or any combination thereof.

[0061] Preferably, the ultrasonic frequency is 40-60 kHz; within this frequency range, the plant cell wall can be more effectively destroyed, solvent penetration can be increased, thereby promoting the dissolution of the target component.

[0062] Preferably, the power is 90-110W; this power level can enhance extraction while avoiding local overheating due to excessive power, thereby protecting the stability of the heat-sensitive active ingredients.

[0063] Preferably, the processing time is 10-20 minutes; this duration ensures that the components in the medicinal materials are fully extracted, significantly improving the extraction efficiency, while avoiding energy consumption problems or changes in certain components due to prolonged processing.

[0064] This preparation method, through the synergistic effect of "acidification-enzymatic hydrolysis-ultrasound," effectively disrupts the cell wall structure of medicinal materials, specifically promoting the release and dissolution of flavonoid active ingredients such as puerarin and baicalin. This optimized process significantly improves the extraction efficiency of active ingredients in medicinal materials, thereby enhancing the bioavailability and final efficacy of the drug.

[0065] Thirdly, the present invention provides a medicament for treating systemic lupus erythematosus-associated pulmonary hypertension, the medicament comprising an effective active ingredient and pharmaceutically acceptable excipients; the effective active ingredient comprising the above-mentioned traditional Chinese medicine composition.

[0066] In some embodiments of the present invention, the active ingredient further includes a Western medicine for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0067] Furthermore, the Western medicines used to treat systemic lupus erythematosus-associated pulmonary hypertension include one or more of prednisone, hydroxychloroquine, mycophenolate mofetil, cyclophosphamide, and ambrisentan.

[0068] In some embodiments of the present invention, the pharmaceutically acceptable excipients include one or more of the following: flavoring agents, preservatives, diluents, binders, disintegrants, lubricants, fragrances, excipients, wetting agents, encapsulating materials, plasticizers, opacifiers, colorants, coating materials, antioxidants, solubilizers, and suspending agents.

[0069] In some embodiments of the present invention, the dosage form of the drug includes, but is not limited to, decoction, granules, pills, capsules, tablets, powders, or oral liquids.

[0070] Fourthly, the present invention also provides the use of the traditional Chinese medicine composition in the preparation of a medicament for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0071] In some embodiments of the present invention, the drug further includes: a Western medicine for treating systemic lupus erythematosus-associated pulmonary hypertension.

[0072] The experimental methods described in the following embodiments of the present invention, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer.

[0073] 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 specification is for the purpose of describing particular embodiments only and is not intended to limit the invention.

[0074] The following description is based on specific embodiments.

[0075] The raw materials used in the following examples are shown in Table 1: Table 1 Raw Material Information

[0076] Example 1: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating pulmonary hypertension associated with systemic lupus erythematosus, comprising: 30g of kudzu root, 15g of centella asiatica, 15g of salvia miltiorrhiza, 10g of chuanxiong rhizome, 15g of scutellaria baicalensis root, 20g of poria cocos, 10g of stir-fried atractylodes macrocephala root, 10g of tangerine peel, 10g of prepared pinellia tuber, 10g of prepared licorice root, and 15g of immature bitter orange.

[0077] The traditional Chinese medicine composition was prepared according to the following steps: (1) Preparation of medicinal materials Chop all the weighed medicinal materials and grind them into powder using a Chinese medicine pulverizer to obtain coarse Chinese medicine powder.

[0078] (2) Acid-adjusted soaking Place the processed medicinal materials into an extraction container and add warm water (approximately 60°C) ten times the total weight of the materials. Then, add edible white vinegar to the warm water, stir well, and adjust the pH of the solution to a slightly acidic level of 4.0 ± 0.1. Soak under these conditions for 60 minutes.

[0079] (3) Enzymatic hydrolysis Add food-grade cellulase (derived from bromelain) to the acidified and soaked medicinal materials and liquid. The amount of enzyme added is 0.3% of the total weight of the medicinal materials. Maintain the system temperature at 45℃ and react at this temperature for 50 minutes.

[0080] (4) Ultrasonic-assisted extraction After enzymatic hydrolysis, the material is placed in an ultrasonic extraction device. The ultrasonic frequency is set to 40kHz and the power to 100W, and the material is ultrasonically treated for 15 minutes.

[0081] (5) Conventional decoction The enzymatically and ultrasonically treated medicinal materials are transferred together with the liquid mixture into a decoction pot. The decoction is then performed twice. First decoction: After boiling over high heat (180-190℃), simmer over low heat (60-80℃) for 30 minutes, filter, and collect the first decoction liquid.

[0082] Second decoction: Add warm water (about 60°C) twice the total weight of the herbs to the dregs, decoct for 30 minutes, filter, and collect the second decoction.

[0083] By combining the decoctions from the two decoctions, a concentrated original liquid of the traditional Chinese medicine composition is obtained.

[0084] (6) Preparation of granules The original liquid of the Chinese herbal composition is filtered to remove the residue, and concentrated under reduced pressure at 60°C to obtain an extract (relative density of 1.20-1.25). The extract is dried and pulverized into dry extract powder, and a filler suitable for granules is added. The granules are then granulated and dried to obtain Chinese herbal granules.

[0085] Example 2: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating pulmonary hypertension associated with systemic lupus erythematosus (SLE) comprises: 15g of Pueraria lobata, 15g of Centella asiatica, 7.5g of Salvia miltiorrhiza, 5g of Ligusticum chuanxiong, 7.5g of Scutellaria baicalensis, 20g of Poria cocos, 10g of stir-fried Atractylodes macrocephala, 10g of Citrus reticulata peel, 10g of processed Pinellia ternata, 10g of processed Glycyrrhiza uralensis, and 15g of Citrus aurantium. The preparation method of the traditional Chinese medicine composition described in this embodiment is the same as that shown in Example 1.

[0086] Example 3: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating pulmonary hypertension associated with systemic lupus erythematosus (SLE) comprises: 10g of Pueraria lobata, 10g of Centella asiatica, 5g of Salvia miltiorrhiza, 3g of Ligusticum chuanxiong, 5g of Scutellaria baicalensis, 10g of Poria cocos, 5g of stir-fried Atractylodes macrocephala, 5g of Citrus reticulata peel, 5g of processed Pinellia ternata, 5g of processed Glycyrrhiza uralensis, and 5g of Citrus aurantium. The preparation method of the traditional Chinese medicine composition described in this embodiment is the same as that shown in Example 1.

[0087] Example 4: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating pulmonary hypertension associated with systemic lupus erythematosus (SLE) comprises: 40g of Pueraria lobata, 30g of Centella asiatica, 30g of Salvia miltiorrhiza, 20g of Ligusticum chuanxiong, 20g of Scutellaria baicalensis, 30g of Poria cocos, 20g of stir-fried Atractylodes macrocephala, 20g of Citrus reticulata peel, 20g of processed Pinellia ternata, 20g of processed Glycyrrhiza uralensis, and 30g of Citrus aurantium. The preparation method of the traditional Chinese medicine composition described in this embodiment is the same as that shown in Example 1.

[0088] Example 5: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0089] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from that shown in Example 1 in that it involves enzymatic hydrolysis; all other methods are the same. In this embodiment, the enzymatic hydrolysis step is as follows: food-grade cellulase (derived from papain) is added to the acidified and soaked medicinal materials and liquid. The amount of enzyme added is 0.1% of the total weight of the medicinal materials. The system temperature is maintained at 40°C, and the reaction is carried out at this constant temperature for 30 minutes.

[0090] Example 6: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0091] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from that shown in Example 1 in that it involves enzymatic hydrolysis; all other methods are the same. In this embodiment, the enzymatic hydrolysis step is as follows: food-grade cellulase (derived from papain) is added to the acidified and soaked medicinal materials and liquid. The amount of enzyme added is 0.5% of the total weight of the medicinal materials. The system temperature is maintained at 50°C, and the reaction is carried out at this constant temperature for 60 minutes.

[0092] Example 7: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0093] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from that shown in Example 1 in that ultrasound-assisted extraction is used; the rest of the methods are the same. In this embodiment, the ultrasound-assisted extraction step is as follows: after enzymatic hydrolysis, the material is placed in an ultrasonic extraction device. The ultrasonic frequency is set to 30 kHz and the power to 80 W, and the material is ultrasonically treated for 5 minutes.

[0094] Example 8: A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0095] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from that shown in Example 1 in that ultrasound-assisted extraction is used; the rest of the methods are the same. In this embodiment, the ultrasound-assisted extraction step is as follows: after enzymatic hydrolysis, the material is placed in an ultrasonic extraction device. The ultrasonic frequency is set to 80 kHz and the power to 120 W, and the material is ultrasonically treated for 30 minutes.

[0096] Comparative Example 1 A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0097] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from the preparation method shown in Example 1 in that steps (2), (3) and (4) are deleted, and only step (5) is a conventional decoction using water.

[0098] Comparative Example 2 A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0099] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from the preparation method shown in Example 1 in that step (2) is deleted, while the rest remains unchanged.

[0100] Comparative Example 3 A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0101] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from the preparation method shown in Example 1 in that step (3) is deleted, while the rest remains unchanged.

[0102] Comparative Example 4 A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, with the same formulation as in Example 1.

[0103] The preparation method of the traditional Chinese medicine composition described in this embodiment differs from the preparation method shown in Example 1 in that step (4) is deleted, while the rest remains unchanged.

[0104] Test Example 1: Impact Test of Different Extraction Processes on Key Indicators To test the effects of different extraction processes on key indicators, the effects on the content of asiaticoside and puerarin, their dissolution ratio, the viscosity of the extract, and the impurity removal rate were tested. The test results are shown in Table 2.

[0105] Table 2 Comparison of the impact of different extraction processes on key indicators

[0106] As shown in Table 1, the traditional Chinese medicine composition prepared by the optimized process of the present invention (Example 1) is significantly superior to the traditional water extraction process (Comparative Examples 1-4) in many key quality indicators. This fully demonstrates the innovative value and synergistic advantages of the "acidification-enzymatic hydrolysis-ultrasound" three-step enhanced extraction technology.

[0107] Specifically, the optimized process, through acidification (pH 4.0) pretreatment, provided a stable, weakly acidic environment for the saponin components, thereby significantly preventing the hydrolysis and destruction of asiaticoside, increasing its content from 10.2 mg / g to 18.5 mg / g, and puerarin content from 22.1 mg / g to 35.4 mg / g. Simultaneously, the addition of food-grade cellulase effectively disrupted the cell wall structure of the medicinal material, not only synergistically promoting the dissolution of asiaticoside and puerarin, but also optimizing the dissolution ratio of puerarin to asiaticoside from 2.16:1 to a more reasonable 1.2:1.

[0108] Furthermore, the optimized process of this invention significantly reduces the viscosity of the extract, improves the fluidity of the drug solution, which is beneficial for subsequent formulation processing and in vivo absorption. It also removes macromolecular impurities (such as tannins), thereby enhancing the safety and stability of the formulation.

[0109] In summary, the process innovation of this invention is not a simple superposition of steps, but a synergistic effect of the integrated extraction process of "acid adjustment-enzymatic hydrolysis-ultrasound". While improving the extraction rate of the target active ingredient, it actively optimizes its internal ratio and simultaneously improves the physical properties and purity of the drug solution.

[0110] Test Example 2: Efficacy Verification The traditional Chinese medicine compositions with the expected effects of the present invention were all prepared in Examples 1-8, and all of them can achieve the effect of treating systemic lupus erythematosus-related pulmonary hypertension. The following description only uses the traditional Chinese medicine composition provided in Example 1 as an example to illustrate the effect.

[0111] I. Animal Experiments 1. Preparation method The original liquid of the traditional Chinese medicine composition prepared in Example 1 was filtered while hot, and the filtrate was centrifuged while hot (4000 r / min) for 10 min. The supernatant was collected and stored at 4°C for later use. Its crude drug concentration was 0.3 g / ml.

[0112] 2. Laboratory animals Fifteen female MRL / lpr mice (SPF grade), aged 8-10 weeks and weighing 25-35g, were selected. All mice were acclimatized for one week in a standardized environment with a temperature of 22±2℃, relative humidity of 50-60%, and a 12-hour light-dark cycle, with free access to food and water.

[0113] 3. Animal model establishment methods and grouping for drug administration 3.1 Grouping and Administration At the start of the experiment, 15 MRL / lpr mice were randomly divided into 3 groups of 5 mice each: SLE group: raised in a normoxic environment throughout the entire process; SLE-PAH group: received intermittent hypoxia treatment to induce the SLE-PAH model; TMT group: While receiving the same intermittent hypoxia treatment as the SLE-PAH group, 1 mL of the above-mentioned traditional Chinese medicine composition was administered by gavage daily.

[0114] 3.2 Methods for establishing animal models SLE-PAH model induction: The model was induced using intermittent hypoxia. Mice in the SLE-PAH and TMT groups were placed in a controlled hypoxia chamber, with a 10% O2 mixture introduced into the chamber. Each hypoxia treatment lasted 2 hours, once daily, with normal air environment provided for the remaining time, for 28 consecutive days. During the treatment, O2 concentration, temperature, and humidity were monitored in real time, and airflow was kept stable. The SLE group was housed in normal air environment throughout the treatment.

[0115] 4. Hemodynamic assessment After hypoxia treatment, right ventricular systolic pressure (RVSP) was measured in mice. Mice were anesthetized with intraperitoneal injection of sodium pentobarbital (50 mg / kg), and a longitudinal incision of approximately 2 cm was made along the midline of the neck using dissecting scissors to expose the subcutaneous tissue. The subcutaneous connective tissue was carefully dissected, and the right jugular vein was exposed and cut into a "V" shaped incision. A catheter connected to a multi-channel physiological signal acquisition and processing system (RM-6280XC, Chengdu Instrument Factory, China) was inserted into the right ventricle via the right jugular vein to record the right ventricular pressure waveform. After data acquisition, the mice were euthanized by cervical dislocation, and lung and heart tissues were harvested. The right ventricular hypertrophy index (RVHI) was calculated as the ratio of right ventricular mass to left ventricular mass plus interventricular septum mass (RV / (LV+S)).

[0116] 5. Histopathology To observe the effect of the traditional Chinese medicine composition of this invention on the pulmonary vascular structure of SLE-PAH mice, the left lower lobe of lung tissue was rapidly harvested after the experiment and fixed in 4% paraformaldehyde for 24 hours. After routine dehydration and paraffin embedding, the sections were 5 μm thick. The sections were stained with hematoxylin and eosin (H&E), dehydrated, mounted, and observed and photographed under an optical microscope (Nexcope microscope, Shanghai, China).

[0117] 6. Oxidative stress detection 6.1 Detection of Reactive Oxygen Species (ROS) ROS detection was performed according to the kit instructions (Bestbio, Shanghai). Approximately 50 mg of lung tissue was taken, washed with pre-chilled PBS, and homogenized on ice in an antioxidant-containing buffer. The homogenate was centrifuged at 100×g, 4℃ for 5 min, and the supernatant was collected. The BBoxiProbe® D01 fluorescent probe was diluted according to the instructions and mixed with the supernatant in a black 96-well plate, and incubated at 37℃ in the dark for 30 min. After incubation, the fluorescence intensity (Ex / Em = 488 / 520 nm) was measured using a fluorescence microplate reader. ROS levels were expressed as relative fluorescence units (RFU) divided by protein content (mg protein), and protein concentration was determined by the BCA method.

[0118] 6.2 Malondialdehyde (MDA) Detection Follow the instructions for the malondialdehyde (MDA) detection kit (Jiancheng Biotechnology Institute, Nanjing). Take 20 mg of lung tissue and add pre-cooled homogenate at a ratio of 1:9 (mg:μL). Homogenize on ice and centrifuge at 12000×g, 4℃ for 10 min. Take 100 μL of the supernatant and mix it with 1 mL of MDA working solution provided in the kit. Heat the mixture in a boiling water bath for 40 min, then immediately cool it on ice. Centrifuge at 4000×g, 4℃ for 10 min. Take 200 μL of the supernatant and measure the absorbance on a microplate reader. =532nm).

[0119] 6.3 Glutathione (GSH) Detection The glutathione assay kit (Jiancheng Biotechnology Institute, Nanjing) was used for determination. Approximately 50 mg of lung tissue homogenate was taken, centrifuged, and the supernatant was collected. The content of reduced GSH was determined according to the kit instructions to reflect the oxidative stress state of the tissue.

[0120] 7 Experimental Results 7.1 The traditional Chinese medicine composition of the present invention reduces pulmonary hypertension and right ventricular hypertrophy in SLE-PAH mice. like Figure 1As shown in Figure A, after 4 weeks of continuous hypoxia, mice in the SLE-PAH group exhibited significant pulmonary hypertension. The right ventricular systolic pressure (RVSP) in the SLE-PAH group was significantly higher than that in the normoxic SLE group. P <0.01 indicates that hypoxia can significantly aggravate pulmonary hypertension in the context of systemic lupus erythematosus. After intervention with the traditional Chinese medicine composition of this invention, the RVSP of the TMT group mice decreased significantly ( P <0.01), indicating that it can effectively relieve elevated pulmonary artery pressure. Meanwhile, as... Figure 1 As shown in B, the right ventricular hypertrophy index [RV / (LV+S)] in the SLE-PAH group was also significantly increased. P <0.05 indicates increased right ventricular load; however, this index significantly decreased in the TMT group treated with the traditional Chinese medicine combination. P <0.05), indicating that the traditional Chinese medicine composition of the present invention can improve hypoxia-induced right ventricular hypertrophy to a certain extent.

[0121] 7.2 The traditional Chinese medicine composition of the present invention alleviates pulmonary vascular remodeling in SLE-PAH mice. like Figure 2 HE staining results showed significant differences in the structure of small arteries in the lung tissue of mice in each group. In the SLE group, the pulmonary arterial walls were normal, the lumen was patent, and no significant tunica media thickening was observed. In contrast, the SLE-PAH group showed significant tunica media thickening, disordered smooth muscle cell arrangement, and significant vascular stenosis, suggesting that hypoxia can exacerbate vascular remodeling in the context of systemic lupus erythematosus. After intervention with the traditional Chinese medicine composition of this invention, the tunica media thickness of small arteries in the TMT group mice was significantly reduced, vascular patency was improved, and the vascular structure recovered to near normal levels compared to the SLE-PAH group.

[0122] 7.3 The traditional Chinese medicine composition of the present invention reduces oxidative stress in the lung tissue of SLE-PAH mice. like Figure 3 As shown in Figure A, the level of oxidative stress in the lung tissue of mice in the SLE-PAH group was significantly increased. Compared with the normoxic SLE group, the ROS fluorescence intensity in the SLE-PAH group was significantly increased (…). P <0.001), indicating excessive accumulation of reactive oxygen species; at the same time, if Figure 3 As shown in B, the content of lipid peroxidation product MDA was significantly increased ( P <0.001), reflecting that hypoxia exacerbates oxidative damage. Furthermore, such as Figure 3 As shown in C, the level of the antioxidant GSH was significantly decreased in the SLE-PAH group ( P <0.001 indicates impaired endogenous antioxidant capacity. After intervention with the traditional Chinese medicine composition of this invention, the levels of ROS and MDA in the lung tissue of the TMT group were significantly reduced ( P<0.001), while the GSH content rebounded significantly ( P <0.001). These results indicate that the traditional Chinese medicine composition of the present invention can effectively inhibit oxidative stress in the lung tissue of SLE-PAH mice and improve the redox imbalance.

[0123] II. Clinical Trials 1. Clinical trial methods 1.1 Research Design This study was a single-center, randomized controlled, single-blind (assessor-blind) clinical trial. Patients meeting the inclusion criteria were randomly assigned to either the treatment group (a combination of traditional Chinese medicine and basic Western medicine treatment) or the control group (basic Western medicine treatment) using a random number table. The randomization scheme was generated by a non-study third party using a random number table, and allocation was concealed using a closed opaque envelope method. Assessors remained blinded to patient assignments.

[0124] 1.2 Sample Size Estimation Based on previous studies and clinical experience, the overall effective rate of Western medicine alone in treating SLE-PAH is approximately 60%, and the addition of a traditional Chinese medicine combination is expected to increase it by 20% (to 80% overall effective rate). The sample size was calculated using a significance level of α = 0.05 (two-tailed test) and statistical power (1-β) = 0.8, using the formula: ; In the formula, P 1 The effective rate was 60% for the control group. P 2 The effective rate in the treatment group was 80%. Z Let be the confidence interval. This represents the pre-defined efficacy rate, used to assess the sample size to be included; the calculated required sample size for each group was 44 cases. Considering a possible dropout rate of approximately 20%, 55 cases were ultimately included in each group, for a total of 110 patients.

[0125] 1.3 Research Subjects The study included 110 patients with SLE-PAH who visited the Department of Rheumatology and Immunology at the First Affiliated Hospital of Nanchang University between June and December 2024. These patients were randomly assigned to either a conventional Western medicine treatment group or a group receiving a combination of traditional Chinese medicine and Western medicine as basic treatment. This study strictly adhered to the Declaration of Helsinki and was approved by the Ethics Review Committee of the First Affiliated Hospital of Nanchang University (ethics approval number IITS2025357). Prior to the study, all participants fully understood the study content and signed written informed consent forms, ensuring their right to participate voluntarily.

[0126] 1.4 Discharge Standards 1.4.1 Inclusion Criteria (1) Age between 18 and 65 years old, gender not limited; (2) Diagnostic criteria for SLE: Meets the SLE classification criteria jointly developed by the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) in 2019; (3) Diagnostic criteria for PAH: Meet the diagnostic requirements of the 2022 European Society of Cardiology / European Respiratory Society (ESC / ERS) guidelines and meet any of the following: TRV > 3.4 m / s or PASP > 40 mmHg as assessed by echocardiography, or mean pulmonary artery pressure (mPAP) > 20 mmHg as measured by right heart catheterization; (4) The diagnostic criteria for blood stasis syndrome in traditional Chinese medicine should include: ≥2 main symptoms + ≥1 tongue and pulse condition.

[0127] Chief symptoms (any two of the following): stabbing pain in the chest, fixed and unmoving; Palpitations, chest tightness, and shortness of breath worsened; Dark purple on the face, lips, and nails; Numbness in the limbs or purplish skin; Symptoms worsen at night.

[0128] Tongue and pulse examination (any one): The tongue is purplish-dark or has petechiae / ecchymosis; The pulse is either choppy or thin and choppy.

[0129] (5) The treatment regimen (type and dosage) of hormones, immunosuppressants and PAH-targeted drugs should remain stable for at least one month before enrollment; (6) Has not participated in other clinical trials in the three months prior to enrollment; (7) The patient voluntarily signed a written informed consent form.

[0130] 1.4.2 Exclusion Criteria (1) Special physiological state: during the preconception, pregnancy or lactation period; (2) Impaired function of other organs; (3) Coagulation dysfunction: INR>1.5 (without anticoagulation therapy) or platelet count<50×10 9 / L, or an active bleeding event (including but not limited to gastrointestinal bleeding and intracranial hemorrhage) within the past 3 months; (4) Combination medication: Patients who need to use therapeutic doses of anticoagulant / antiplatelet drugs (such as warfarin and aspirin) for a long time and whose regimen cannot be adjusted.

[0131] (5) Serious complications: such as other heart diseases, active malignant tumors, etc.; (6) Respiratory failure: arterial partial pressure of oxygen (PaO2) <60 mmHg at rest; (7) Risk of infection: Uncontrolled active or chronic infection (such as tuberculosis, viral hepatitis, etc.); (8) Mental illness or other reasons prevent the patient from cooperating with treatment; (9) The presence of severe gastrointestinal diseases affects drug absorption; (10) Participate in other clinical studies at the same time.

[0132] 1.4.3 Shedding Criteria (1) The participant voluntarily requested to terminate their participation in the study; (2) If a serious adverse reaction occurs, the researcher determines that the trial should be terminated; (3) Due to disease progression, basic treatment needs to be adjusted, and the requirements for stable medication are no longer met; (4) Serious violation of the research protocol, such as failure to take medication or follow up as required; (5) Lost to visit or unable to be contacted; (6) Any new circumstances specified in the exclusion criteria occur during the study period (such as new serious comorbidities).

[0133] After a patient withdraws from medication, the reason for withdrawal, the date of withdrawal, and the safety follow-up after the last dose should be recorded, and safety follow-up should be completed as much as possible.

[0134] 1.5 Intervention Measures 1.5.1 Control group (routine Western medicine treatment) a. Basic treatment: (1) Immunosuppressive therapy: Maintain a stable dose of glucocorticoids (prednisone 5-20 mg / day) for ≥2 weeks before enrollment, and immunosuppressants (such as hydroxychloroquine ≤400 mg / day, mycophenolate mofetil ≤1.5 g / day, or cyclophosphamide cumulative dose ≤1.2 g / m²). 2 (lasting ≥3 months) (2) PAH targeted therapy: All patients received ambrisentan (5-10 mg / day) with a stable dose for ≥1 month.

[0135] b. Dosage control: (1) After enrollment, the hormone dose / immunosuppressant dose shall not be adjusted. If the treatment plan needs to be adjusted due to the worsening of the condition, the case shall be regarded as dropout and the reason shall be recorded.

[0136] (2) Symptomatic treatment (such as diuretics, oxygen therapy) may be used as needed, but the frequency of use must be recorded.

[0137] 1.5.2 Treatment Group (Traditional Chinese Medicine Combination with Basic Western Medicine Treatment) a. Western medicine regimen: completely consistent with the control group (dosage, type, course of treatment).

[0138] b. Traditional Chinese medicine intervention: (1) Formula composition: use the granules prepared in Example 1.

[0139] (2) Dosage and administration: Dissolve each granule in 100mL of warm water and take twice a day, 30 minutes after meals, for 12 consecutive weeks.

[0140] 1.6 Observation Indicators and Methods a. Six-minute walk test (6MWT): Performed strictly in accordance with the implementation and evaluation standards for the six-minute walk test established by the American Thoracic Society (ATS); (1) Preparation before testing: ①Environmental requirements: A straight, flat corridor 30 meters long, with no obstacles on the ground and clear turnaround marks at both ends; suitable temperature (usually 20-23℃) and good ventilation.

[0141] ② Tools: timer, counter, blood pressure monitor, finger pulse oximeter, Borg self-reported fatigue scale; place a chair at the starting point, and provide a first aid kit and first aid medicines.

[0142] ③ Subject preparation: Wear comfortable clothing and shoes, avoid strenuous exercise and eating too much 2 hours before the test, and take medication as usual but record it; Measure baseline data: heart rate, blood pressure, blood oxygen saturation, respiratory rate and subjective fatigue (Borg score).

[0143] (2) Test steps: Start instructions: Tell the patient to "walk as far as possible within 6 minutes, adjust the speed as needed, and stop to rest if necessary"; Timing and Recording: Announce the time every minute and encourage the patient to continue walking; Record blood oxygen saturation and heart rate every minute (intervene promptly if any abnormalities are found); Record the number of times the patient stopped breathing, the duration of the stop, and the reason (dyspnea, chest pain, fatigue, etc.). Finish line determination: Stop immediately after 6 minutes of timing and record the total walking distance.

[0144] Recovery assessment (5 minutes after the test): Measure blood pressure, heart rate, and blood oxygen saturation again; Record the dyspnea score and fatigue level; Observe for any adverse reactions (dizziness, chest pain, fainting, etc.).

[0145] (3) Precautions: ① Termination criteria: Stop the test immediately if any of the following occurs: chest pain, syncope, severe dyspnea (Borg score ≥8); oxygen saturation persistently <85% or decrease >10%; systolic blood pressure decrease >20 mmHg or increase >220 mmHg; ②Contraindications: Recent myocardial infarction (<1 month), uncontrolled arrhythmia, uncontrolled hypertension, etc.

[0146] ③Result Interpretation: Normal reference values: males ≈ 550m, females ≈ 490m; PAH patients: <330m indicates poor prognosis, and a decrease of >50m / year indicates disease progression.

[0147] b. Cardiac Function Classification: WHO-FC Class I indicates that the patient has no limitation in performing daily physical activities and does not experience symptoms such as shortness of breath, fatigue, chest pain, or syncope. WHO-FC Class II indicates that the patient has mild limitation in performing daily activities. Although there are no symptoms at rest, mild or moderate-intensity physical activity (such as climbing stairs or brisk walking) may cause shortness of breath, fatigue, or chest discomfort. WHO-FC Class III indicates that the patient's physical activity capacity is significantly reduced. Symptoms may occur even with mild activity (such as slow walking or doing housework), but there is still no discomfort at rest. WHO-FC Class IV is the most severe level. The patient may experience symptoms at rest, such as shortness of breath, fatigue, and signs of right heart failure, and is almost unable to perform any physical activity.

[0148] c. Transechocardiography (TTE): This procedure is performed by a uniformly trained and highly qualified echocardiologist using a standardized model of equipment (such as a Philips EPIQ 7 or GE Vivid E95) to ensure consistent image acquisition. The examination follows the recommendations of the American College of Cardiology / European Association of Cardiology (ASE / EACVI). Key measurements include: tricuspid regurgitation velocity (TRV) to estimate pulmonary artery systolic pressure (PASP = 4 × TRV² + RAP); right ventricular outflow tract diameter (RVOT) and area; right ventricular tricuspid annular plane systolic displacement (TAPSE); right atrial area (RAA); assessment of pericardial effusion; and left ventricular ejection fraction (LVEF) and diastolic function parameters to rule out left ventricular disease (Group 2 PH). All images are evaluated by two independent interpreters using a double-blind cross-checking method to ensure consistency in interpretation; a third senior physician may be involved for review if necessary.

[0149] d. High-resolution CT of the chest: Scanning was performed using a multi-slice spiral CT scanner (≥64 slices recommended, such as the Siemens SomatomDefinition Flash) for high-resolution chest imaging (slice thickness 1–1.25 mm), with the scan performed at maximum lung inflation at the end of inspiration. Evaluation parameters included: main pulmonary artery diameter (MPA) and MPA / ascending aorta ratio; small vessel cross-sectional area (%CSA < 5 mm). 2 The imaging is used to estimate pulmonary vascular density; to detect the presence of "vascular shearing" phenomena, suggesting vascular remodeling; and to exclude signs of interstitial lung disease (ILD), such as honeycomb-like changes, reticular shadows, and bronchiectasis. It also excludes pulmonary embolism, pulmonary infection, or neoplastic lesions. The imaging assessment is independently interpreted by two thoracic radiographers; in case of disagreement, a senior radiologist makes the final decision.

[0150] e. Lung function indicators: including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1 / FVC ratio, and diffusing capacity for carbon monoxide (DLCO). f. Laboratory indicators: Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), immunoglobulins (Ig), complement C3 (C3), complement C4 (C4), antinuclear antibodies (ANA), antinuclear antibody profile (ANAs), anti-double-stranded DNA antibodies (anti-dsDNA), anticardiolipin antibodies (ACL), anti-β2-glycoprotein I antibodies (β2-GP1), lupus anticoagulant (LA), etc.

[0151] 1.6.3 Evaluation method for TCM blood stasis syndrome: Refer to the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine" (issued by the State Administration of Traditional Chinese Medicine in 1994).

[0152] (1) Scoring items The scoring criteria are shown in Table 3.

[0153] Table 3 Scoring Item Criteria

[0154] (2) Criteria for evaluating therapeutic efficacy Treatment efficacy is assessed based on changes in symptom scores. Cure: Symptoms and signs of tongue and pulse disappear or significantly improve, and the score decreases by ≥90%; Significant effect: Symptoms are significantly reduced, and the score decreases by ≥70%; Effective: Symptoms improved, and scores decreased by ≥30%; Invalid: The score decreases by less than 30% or remains unchanged, or even worsens.

[0155] 1.6.4 Safety Indicators This study strictly followed the Good Clinical Practice (GCP) guidelines for drug clinical trials and the guiding principles for clinical research of new traditional Chinese medicines, and conducted full-process safety monitoring on both groups of patients. a. Laboratory monitoring: (1) Monitoring items: Routine blood and urine tests; liver function tests: ALT, AST, total bilirubin; kidney function tests: Scr, BUN; Coagulation function: PT, APTT.

[0156] (2) Monitoring frequency: 1 test each in the 4th, 8th and 12th weeks of treatment.

[0157] b. Adverse Event (AE) Management (1) Record content: time of occurrence, duration, severity (CTCAE grade), and relevance to the investigational drug (definite / possible / suspected / irrelevant / cannot be assessed).

[0158] (2) Processing flow: Mild adverse events (Grade 1-2): Closely monitor the patient. Medication can be continued and the dosage adjusted (e.g., reduce the frequency of taking the traditional Chinese medicine combination).

[0159] For moderate to severe adverse events (grades 3-4): immediately discontinue medication, provide symptomatic treatment (such as liver protection and hemostasis), and report the incident through the channels designated by the ethics committee within 24 hours.

[0160] Serious adverse events (such as liver failure or pulmonary hemorrhage): Activate the emergency plan, withdraw the subject from the study, and report to the National Adverse Drug Reaction Monitoring System.

[0161] 1.7 Follow-up Plan The trial lasted 12 weeks, with outpatient follow-ups conducted at baseline (at enrollment) and at weeks 4, 8, and 12 of treatment. Clinical symptoms, signs, efficacy indicators, and safety indicators were recorded during follow-up.

[0162] 1.8 Statistical Methods Data were analyzed using SPSS Statistics 26.0 (IBM Corp.) statistical software. Patients who did not complete the predetermined observation period were excluded from the efficacy analysis. The Shapiro-Wilk test was used to test the normality of continuous data. Data conforming to a normal distribution were expressed as mean ± standard deviation, and independent samples t-tests were used for comparisons between groups. Non-normally distributed data were expressed as median (M) [interquartile range (Q1-Q3)], and Mann-Whitney U test was used for comparisons between groups. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using the X-ray discrepancy (X). 2 Tests were performed (Yates correction or Fisher exact test was used when the theoretical frequency was <5); Bonferroni correction was used for multiple comparisons, with a significance level of α=0.05 (two-tailed test).

[0163] 2 Results 2.1 Baseline data of study subjects This study included 110 SLE-PAH patients, who were randomly divided into two groups using a random number table: a traditional Chinese medicine combination therapy group (n=55) and a control group (n=55). During the trial, 18 patients dropped out (10 lost to follow-up, 8 withdrew due to adverse reactions), and ultimately 47 patients in the traditional Chinese medicine combination therapy group and 45 patients in the control group completed 12 weeks of treatment and follow-up analysis. At baseline (week 0), besides the statistically significant difference in the positive rate of anti-double-stranded DNA antibody (dsDNA-CLIA) between the two groups (…),… P =0.019), there were no statistically significant differences between the two groups in demographics and major laboratory indicators. P >0.05), indicating good comparability between groups, as shown in Table 4.

[0164] Table 4. Comparison of baseline characteristics between the two groups of subjects (n=92)

[0165]

[0166] Note: Data are expressed as mean ± standard deviation (M ± SD), M(P25, P75), or n(%) according to variable type, where n represents the number of cases; t-tests, Mann-Whitney U tests, or chi-square tests are used. 2Intergroup comparisons were performed for the tests. WBC: White blood cell count; RBC: Red blood cell count; HB: Hemoglobin concentration; PLT: Platelet count; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CK: Creatine kinase; CK-MB: Creatine kinase isoenzyme; LDH: Lactate dehydrogenase; α-HBDH: α-Hydroxybutyrate dehydrogenase; IgG: Immunoglobulin G; IgM: Immunoglobulin M; IgA: Immunoglobulin A; C3: Complement C3; C4: Complement C4; dsDNA: Anti-double-stranded DNA; ACA: Anticardiolipin antibody; β2GPI: Anti-β-glycoprotein antibody; MMF: Mycophenolate mofetil; HCQ: Hydroxychloroquine sulfate; P Retain 3 decimal places, and retain 2 decimal places for all other values.

[0167] 2.2 Results 2.2.1 Six-minute walking distance (6MWD) and NT-proBNP At baseline, there was no significant difference in 6MWD and NT-proBNP between the two groups. P >0.05). After 12 weeks of treatment, both groups of patients showed a significant increase in 6MWD and a significant decrease in NT-proBNP levels ( P <0.05). Compared with the control group, the traditional Chinese medicine composition group showed more significant improvement at 6MWD and a greater decrease in NT-proBNP ( P <0.05 (see Table 5).

[0168] Table 5. Comparison of 6MWD and NT-proBNP levels between the two groups (M±SD)

[0169] Note: 6MWD: six-minute walk distance; NT-proBNP: N-terminal pro-B-type natriuretic peptide; △ indicates comparison with baseline in this group. P <0.05.

[0170] 2.2.2 Comparison of echocardiographic parameters between the two groups of patients before and after 12 weeks of treatment At baseline, there were no significant differences in TRV, PASP, AAD, and LVEF between the two groups of patients. P >0.05). After 12 weeks of treatment, the TRV and PASP in the traditional Chinese medicine combination group decreased significantly, while LVEF increased ( P <0.05); in the control group, only TRV and PASP decreased ( P <0.05). Intergroup comparisons showed that the group treated with the traditional Chinese medicine combination showed a greater decrease in PASP and AAD after treatment. P <0.05), and the differences in other indicators were not statistically significant. P >0.05 (see Table 6).

[0171] Table 6 Comparison of echocardiographic parameters between the two groups of patients (M±SD)

[0172] Note: Only statistically significant differences are listed; TRV: tricuspid regurgitation velocity; PASP: pulmonary artery systolic pressure; AAD: ascending aortic diameter; LVEF: left ventricular ejection fraction; △ indicates comparison with baseline in this group. P <0.05.

[0173] 2.2.3 Immune inflammatory markers After treatment, the ESR in the traditional Chinese medicine combination group decreased significantly compared with that before treatment. P <0.05), and the degree of improvement was significantly better than that of the control group ( P <0.05), while the ESR in the control group showed no significant change ( P >0.05). Regarding CRP levels, no statistically significant differences were observed, either within-group comparisons before and after treatment or between-group comparisons after treatment. P >0.05 (see Table 7).

[0174] Before treatment, the levels of complement (C3, C4) and immunoglobulins (IgG, IgA, IgM) were comparable between the two groups of patients. P >0.05). After 12 weeks of treatment, the IgA level in the traditional Chinese medicine combination group was significantly lower than the baseline ( P <0.05), while no significant changes were observed in IgG, IgM, C3, and C4 levels. P >0.05). In the control group, both IgG and IgA levels decreased from baseline after treatment ( P <0.05), with no significant changes in IgM, C3, and C4. Intergroup comparisons showed no statistically significant differences between the two groups in any immunoglobulin and complement levels after 12 weeks. P >0.05 (see Table 7). Although there were no statistically significant differences in complement (C3, C4) levels between the two groups after treatment, the complement level in the traditional Chinese medicine composition group showed a clear upward trend. This suggests that the composition can indirectly regulate the immune disorder in SLE patients by reducing the generation and deposition of immune complexes and decreasing the body's consumption of complement. This corresponds to the results of significantly reduced IgA levels and significantly improved ESR indicators within the group. Given the clinical significance of the complement change trend, future studies can further verify the statistical reliability and clinical value of this trend by expanding the sample size and extending the treatment observation period.

[0175] Table 7 Comparison of inflammatory markers, immunoglobulin and complement levels between the two groups of patients (M±SD)

[0176] Note: CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; IgG: immunoglobulin G; IgM: immunoglobulin M; IgA: immunoglobulin A; C3: complement C3; C4: complement C4; △ indicates comparison with baseline of this group. P <0.05.

[0177] 2.2.4 Liver and kidney function, myocardial enzyme levels At baseline, there were no significant differences in liver and kidney function, myocardial enzymes, and other indicators between the two groups. The traditional Chinese medicine combination group showed a significant decrease in GLB, UA, LDH, and α-HBDH levels after treatment. P <0.05), and the other indicators did not change significantly compared to the previous period. P >0.05); the control group showed little change in indicators after treatment compared to before treatment ( P >0.05). Intergroup comparisons after treatment showed that the ALB level in the traditional Chinese medicine combination group was significantly higher than that in the control group, and the levels of UA, CKMB, LDH, and α-HBDH decreased more significantly compared to the control group. P <0.05), and there were no statistically significant differences among the other indicator groups ( P >0.05 (see Table 8).

[0178] Table 8 Comparison of liver and kidney function and myocardial enzyme levels between the two groups of patients (M±SD)

[0179] Note: ALB: albumin; GLB: globulin; UA: uric acid; CK: creatine kinase; CKMB: creatine kinase isoenzyme; LDH: lactate dehydrogenase; HBHD: α-hydroxybutyrate dehydrogenase; △ indicates comparison with baseline of this group. P <0.05.

[0180] 2.2.5 Lung function indicators Before treatment, there were no significant differences in pulmonary function indicators between the two groups. P >0.05). After 12 weeks of treatment, both groups showed significant increases in FVC and FEV1 compared to baseline. P <0.05), but the improvement in FEV1 in the traditional Chinese medicine composition group was higher than that in the control group ( P <0.05), and the differences between the other indicator groups were not significant ( P >0.05 (see Table 9).

[0181] Table 9 Comparison of pulmonary function indicators between the two groups of patients (M±SD)

[0182] Note: FVC: Forced vital capacity; FEV1: Forced expiratory volume in one second; FEV1 / FVC: Forced vital capacity / Forced expiratory volume in one second; DLCO: Carbon monoxide diffusing capacity; △ indicates comparison with baseline of this group. P <0.05.

[0183] 2.3 Security Analysis During the entire trial, 10 out of 110 patients were lost to follow-up (5 in the treatment group and 5 in the control group). Of the 50 patients who ultimately received the traditional Chinese medicine composition, 3 experienced adverse reactions, including 1 case of mild liver dysfunction and 2 cases of gastrointestinal discomfort. In the control group, 5 out of 50 patients experienced adverse reactions, including 2 cases of liver damage, 2 cases of gastrointestinal discomfort, and 1 case of allergic reaction. All adverse events were grade 1-2 and completely resolved after symptomatic treatment; no serious adverse events occurred. There was no significant difference in the incidence of adverse reactions between the groups. P >0.05 (see Table 10).

[0184] Table 10 Comparison of adverse reactions in patients, n (%)

[0185] 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.

[0186] 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 present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A traditional Chinese medicine composition for treating systemic lupus erythematosus-associated pulmonary hypertension, characterized in that, It is made from the following raw materials in parts by weight: 10-40 parts of kudzu root, 5-30 parts of centella asiatica, 5-30 parts of salvia miltiorrhiza, 3-20 parts of chuanxiong rhizome, 5-20 parts of scutellaria baicalensis, 10-30 parts of poria cocos, 5-20 parts of stir-fried atractylodes macrocephala, 5-20 parts of tangerine peel, 5-20 parts of prepared pinellia tuber, 5-20 parts of prepared licorice root, and 5-30 parts of immature bitter orange.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following raw materials in parts by weight: 10-30 parts of kudzu root, 5-20 parts of centella asiatica, 5-20 parts of salvia miltiorrhiza, 3-15 parts of chuanxiong rhizome, 5-15 parts of scutellaria baicalensis, 10-25 parts of poria cocos, 5-15 parts of stir-fried atractylodes macrocephala, 5-15 parts of tangerine peel, 5-15 parts of prepared pinellia tuber, 5-15 parts of prepared licorice root, and 5-20 parts of immature bitter orange.

3. The method for preparing the traditional Chinese medicine composition as described in claim 1 or 2, characterized in that, Weigh the raw materials according to the formula, extract with water, and collect the extract to obtain the final product.

4. The preparation method according to claim 3, characterized in that, Includes the following steps: S1: After weighing the raw material, soak the raw material in an acidic solution with a pH of 3-5 to obtain the acid-soaked raw material; S2: The acid-soaked raw material is enzymatically hydrolyzed using cellulase to obtain the hydrolyzed raw material; S3: Extract the raw material after enzymatic hydrolysis, collect the extract, and obtain the traditional Chinese medicine composition; The extraction methods include: decoction and / or ultrasonic extraction.

5. The preparation method according to claim 4, characterized in that, In step S2, the enzymatic hydrolysis treatment involves adding 0.1%-0.5% of cellulase by weight of the raw drug and hydrolyzing at 40-50°C for 0.5-1.5 hours.

6. A drug for treating systemic lupus erythematosus-associated pulmonary hypertension, characterized in that, It includes an active ingredient and pharmaceutically acceptable excipients; the active ingredient includes the traditional Chinese medicine composition according to claim 1 or 2.

7. The drug as described in claim 6, characterized in that, The active ingredients also include Western medicines for treating systemic lupus erythematosus-associated pulmonary hypertension.

8. The drug as described in claim 6 or 7, characterized in that, The dosage form of the drug is one of the following: decoction, granules, pills, capsules, tablets, powders, and oral liquid.

9. The use of the traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a drug for treating systemic lupus erythematosus-associated pulmonary hypertension.

10. The application as described in claim 9, characterized in that, The medications also include: Western medicines for treating pulmonary hypertension associated with systemic lupus erythematosus.

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