A traditional Chinese medicine compound composition for treating hypoxic pulmonary arterial hypertension and application thereof

Abstract

The present application relates to the field of traditional Chinese medicine, in particular to a traditional Chinese medicine compound composition for treating hypoxic pulmonary arterial hypertension and application thereof, wherein the traditional Chinese medicine compound composition is composed of Danshen, Gualoupi, Xiebai and Huangqi. The traditional Chinese medicine compound composition can significantly reduce the heart mass, right ventricular hypertrophy index and the content of endothelin-1 in plasma of a hypoxic pulmonary arterial hypertension model rat, increase the content of nitric oxide in plasma, pulmonary arterial blood flow acceleration time and the ratio of pulmonary arterial blood flow acceleration time / pulmonary arterial ejection time, improve the symptoms of pulmonary arterial hypertension, and is used for treating hypoxic pulmonary arterial hypertension with definite curative effect, no toxic side effect and good safety. The traditional Chinese medicine compound composition is used for preventing and treating hypoxic pulmonary arterial hypertension with definite effect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine compound prescriptions, specifically relating to a traditional Chinese medicine compound prescription composition for the prevention and treatment of hypoxic pulmonary hypertension. Background Technology

[0002] Pulmonary hypertension is classified into five categories according to WHO international standards: Category 1 is arterial pulmonary hypertension, induced by idiopathic factors, genetic mutations, or related diseases, characterized by pulmonary vascular remodeling; Category 2 is pulmonary hypertension caused by left ventricular disease, which is the most common clinically; Category 3 is pulmonary hypertension caused by lung diseases and / or hypoxia, with hypoxic pulmonary hypertension being an important subtype, induced by chronic hypoxia, high-altitude living, COPD, etc.; Category 4 is chronic thromboembolic pulmonary hypertension; and Category 5 is caused by unknown multifactorial mechanisms. Among these, idiopathic pulmonary hypertension in Category 1 falls under the primary category, while the other categories are secondary pulmonary hypertension. Hypoxic pulmonary hypertension is a typical example of secondary pulmonary hypertension, which is prone to serious complications such as right heart failure, arrhythmia, and thromboembolism.

[0003] Hypoxic pulmonary hypertension (or hypoxic pulmonary hypertension) typically occurs at high altitudes. Prolonged hypoxia stimulates continuous pulmonary vasoconstriction and remodeling, leading to abnormally high pulmonary artery pressure and increased right ventricular load. This results in a clinical syndrome characterized by postprandial dyspnea, fatigue, chest pain, palpitations, and lower extremity edema. It is an important type of chronic mountain sickness, often referred to as a "malignant tumor of the cardiovascular system," and falls under the categories of "asthma," "pulmonary distension," "chest pain," "phlegm retention," and / or "palpitations" in Traditional Chinese Medicine. This type of pathogenesis is characterized by its insidious nature, chronicity, and multifactorial interactions. Single treatments or short-term interventions are insufficient to achieve stable improvement, highlighting the importance of regulating the body's internal environment at a holistic level.

[0004] The current basic principles of treatment mainly revolve around correcting hypoxia, dilating pulmonary vessels, inhibiting vascular remodeling, and providing symptomatic support. Conventional treatments often involve long-term oxygen therapy (limited by the setting and equipment, resulting in poor adherence), the use of targeted chemotherapy drugs such as sildenafil, bosentan, and ambrisentan (expensive, some with hepatotoxicity and nephrotoxicity, unsuitable for long-term use), or calcium channel blockers (effective only for a small number of patients with vascular reactivity). Severe cases require surgeries such as atrial septal prostomy and lung transplantation (high risk, extremely narrow applicability), characterized by long treatment cycles and high costs. Summary of the Invention

[0005] In order to overcome the shortcomings of the existing technology, the purpose of this invention is to provide a traditional Chinese medicine compound composition for treating hypoxic pulmonary hypertension that is scientifically formulated, has significant therapeutic effects, and has no obvious toxic side effects.

[0006] The traditional Chinese medicine compound composition of the present invention comprises the following traditional Chinese medicine components: principal ingredient: Trichosanthes peel and Salvia miltiorrhiza; assistant ingredient: Allium macrostemon; adjuvant ingredient: Astragalus membranaceus; guiding ingredient: Salvia miltiorrhiza.

[0007] As a preferred embodiment of the above technical solution, the mass fractions of each component are as follows: 10-30 parts of Salvia miltiorrhiza, 5-20 parts of Trichosanthes kirilowii peel, 5-20 parts of Allium macrostemon, and 20-50 parts of Astragalus membranaceus. Alternatively, as a preferred embodiment of the above technical solution, the mass fractions of the components are as follows: 15 parts of Salvia miltiorrhiza, 10 parts of Trichosanthes kirilowii peel, 10 parts of Allium macrostemon, and 30 parts of Astragalus membranaceus.

[0008] Traditional Chinese medicine (TCM) treatment of hypoxic pulmonary hypertension, based on syndrome differentiation and treatment, employs herbs with effects such as invigorating qi and promoting yang, activating blood circulation and removing blood stasis, resolving phlegm and dissipating nodules, and widening the chest and unblocking the meridians. Simultaneously, depending on the different etiologies and clinical manifestations, it also incorporates warming yang, dispersing blood stasis, resolving phlegm, and unblocking the meridians. Following the TCM treatment philosophy of "holistic regulation and syndrome differentiation and treatment," this invention selects Danshen (Salvia miltiorrhiza), Gualoupi (Trichosanthes kirilowii peel), Xiebai (Allium macrostemon), and Huangqi (Astragalus membranaceus) to form a four-herb compound composition for the treatment of secondary pulmonary hypertension, including hypoxic pulmonary hypertension. This invention innovates the formulation based on the core pathogenesis characteristics of "wheezing," "pulmonary distension," and "palpitation," with its main effects being invigorating qi and promoting yang, activating blood circulation and removing blood stasis, resolving phlegm and dissipating nodules, and widening the chest and unblocking the meridians. The synergistic effect of the herbs in the formula, with "Gualoupi resolving phlegm," "Danshen activating blood," "Xiebai promoting yang," and "Huangqi invigorating qi" as the core treatment principles, simultaneously invigorates qi and promotes yang, resolves phlegm, and unblocks the meridians, while also activating blood circulation and dissipating blood stasis without harming the body's vital energy.

[0009] The formulation of this invention embodies the overall regulatory characteristics of traditional Chinese medicine's treatment of chest pain, namely "unblocking without depletion, invigorating without harm, and warming without drying." It helps to clear stagnation in the chest meridians and resolve phlegm obstruction while simultaneously warming and tonifying Yang Qi and regulating the Qi mechanism in the chest. This provides a systematic intervention approach for the complex pathological state of hypoxic pulmonary hypertension, which presents with "wheezing," "pulmonary distension," "chest pain," and "phlegm retention." Furthermore, it is expected to provide a basis for prevention and intervention for pulmonary hypertension caused by low pressure and hypoxia at high altitudes, a special high-altitude environmental vascular disease.

[0010] In the pharmaceutical formula of the present invention, Trichosanthes kirilowii Maxim. pericarpium is sweet, cold in nature, and belongs to the lung and stomach meridians, with the effects of clearing heat and resolving phlegm, promoting qi and widening the chest, and is the monarch drug in the formula; Salvia miltiorrhiza Bunge is bitter, slightly cold in nature, and belongs to the heart and liver meridians, with the effects of promoting blood circulation to remove blood stasis, cooling blood to eliminate carbuncles, and clearing the heart to remove vexation. The two are used together as the monarch drugs, synergistically with Trichosanthes kirilowii Maxim. pericarpium to promote blood circulation and dredge the meridians, resolve phlegm and relieve chest obstruction; moreover, Salvia miltiorrhiza Bunge also serves as the adjuvant drug, which can not only lead all the drugs into the heart meridian and directly reach the location of chest obstruction disease, but also reconcile the cold and warmth in the formula, so that resolving phlegm will not cause cold coagulation, and warming and dredging will not help heat; Allium macrostemon Bunge is pungent, bitter, warm in nature, and belongs to the heart, lung, stomach, and large intestine meridians, with the effects of promoting yang and dispersing stagnation, promoting qi and guiding stagnation, and is the ministerial drug in the formula, assisting the two monarch drugs, Trichosanthes kirilowii Maxim. pericarpium and Salvia miltiorrhiza Bunge, to promote yang and open obstruction, promote qi and resolve blood stasis; Astragalus membranaceus (Fisch.) Bunge is sweet, slightly warm in nature, and belongs to the lung and spleen meridians, with the effects of tonifying qi and lifting yang, promoting fluid production and nourishing blood, and serves as the assistant drug. With its sweet and warm tonifying nature, it protects the healthy qi, provides the "basis for qi supplementation" for the drugs such as Trichosanthes kirilowii Maxim. pericarpium, Allium macrostemon Bunge, and Salvia miltiorrhiza Bunge, so as to prevent the healthy qi from being damaged by resolving phlegm and breaking blood stasis.

[0011] The four drugs in the whole formula synergistically resolve phlegm, dredge the meridians, and disperse blood stasis without damaging the healthy qi, and prevent and treat high altitude pulmonary hypertension with "tonifying qi", "promoting yang", "activating blood circulation", and "resolving phlegm". In addition, it can be added with flavors according to clinical syndrome differentiation, and can expand the effects of widening the chest and dispersing stagnation, promoting qi and dredging obstruction, strengthening the healthy qi and consolidating the root. It can overall prevent and treat the core pathogenesis of "dyspnea syndrome", "lung distension", "chest obstruction", and "retention of phlegm-fluid". Moreover, it shows significant therapeutic potential in dealing with special vascular diseases such as chest yang obstruction and phlegm-blood stasis mutual binding in the high altitude environment of low pressure and low oxygen. The raw materials of the traditional Chinese medicine compound composition and compound preparation of the present invention are simple to obtain, low in cost, convenient to prepare, and suitable for popularization and application; they have no toxic and side effects and good safety.

[0012] The present invention also relates to a traditional Chinese medicine compound preparation for treating hypoxic pulmonary hypertension, including an active component and pharmaceutically acceptable excipients, and the active component is the above-mentioned traditional Chinese medicine compound composition. An optional scheme is that the dosage form of the traditional Chinese medicine compound preparation is decoction, granule, tablet, capsule, pill, mixture or extract. An optional scheme is that the dosage of the active component in the traditional Chinese medicine compound preparation is 3.50 g / kg / d to 14.0 g / kg / d. Preferably, it is 7.0 g / kg / d to 14.0 g / kg / d.

[0013] The present invention also relates to a preparation method of the above-mentioned traditional Chinese medicine compound preparation. The method includes: Trichosanthes kirilowii Maxim. pericarpium, Allium macrostemon Bunge, and Salvia miltiorrhiza Bunge are extracted by ethanol reflux extraction method. After that, the medicinal residues are filtered, and the medicinal liquid is concentrated to obtain a concentrated liquid; Astragalus membranaceus (Fisch.) Bunge is extracted by water decoction method to obtain an Astragalus membranaceus (Fisch.) Bunge extraction liquid; the concentrated liquid and the Astragalus membranaceus (Fisch.) Bunge extraction liquid are combined and further concentrated into a decoction. Further, corresponding excipients are added to the decoction to prepare granules, tablets, extracts, capsules or pills. Description of the Drawings

[0014] Figure 1 It shows the effect of the compound of the embodiment of the present invention on the pulmonary artery blood flow acceleration time of rats with pulmonary hypertension.

[0015] Figure 2 This invention relates to the effect of the compound formula on the ratio of pulmonary artery acceleration time to ejection time in rats with pulmonary hypertension. Figure 1 and 2 In the study: Control: Normal control group; Model: Model control group; XD: Sildenafil positive control group; DL: Danlou tablet positive control group; DLXHH: High-dose compound group; DLXHM: Medium-dose compound group; DLXHL: Low-dose compound group. Compared with the blank control group at the same time point, p <0.05, p <0.01, p <0.001; compared with the model control group, # p <0.05, ## p <0.01, ### p <0.001.

[0016] Figure 3 The effect of the compound formula of this invention on the cardiac index of rats with pulmonary hypertension.

[0017] Figure 4 The effect of the compound formula of this invention on the right ventricular hypertrophy index in rats with pulmonary hypertension is shown in this embodiment. Figure 3 and Figure 4 In the study: Control: Normal control group; Model: Model control group; XD: Sildenafil positive control group; DL: Danlou tablet positive control group; DLXHH: High-dose compound group; DLXHM: Medium-dose compound group; DLXHL: Low-dose compound group. Compared with the blank control group at the same time point, p <0.05, p <0.01, p <0.001; compared with the model control group, # p <0.05, ## p <0.01, ### p <0.001.

[0018] Figure 5This figure illustrates the effect of the compound preparation of the present invention on the NO content in the plasma of rats with pulmonary hypertension. In the figure: Control: Normal control group; Model: Model control group; XD: Sildenafil positive control group; DL: Danlou tablet positive control group; DLXHH: High-dose compound preparation group; DLXHM: Medium-dose compound preparation group; DLXHL: Low-dose compound preparation group. Compared with the blank control group at the same time point, p <0.05, p <0.01,

[0019] p <0.001; compared with the model control group, # p <0.05, ## p <0.01, ### p <0.001.

[0020] Figure 6 shows the effect of the compound preparation of the present invention on the plasma ET-1 content in rats with pulmonary hypertension; in the figure: Control: normal control group; Model: model control group; XD: sildenafil positive control group; DL: Danlou tablet positive control group; DLXHH: high-dose compound preparation group; DLXHM: medium-dose compound preparation group; DLXHL: low-dose compound preparation group. Compared with the blank control group at the same time point, p <0.05, p <0.01, p <0.001; compared with the model control group, # p <0.05, ## p <0.01, ### p <0.001.

[0021] Figure 7 shows the changes in body weight of animals in each experimental group according to the embodiments of the present invention.

[0022] Figure 8 shows the changes in organ indices of animals in each experimental group according to the embodiments of the present invention, compared with the blank control group. p <0.05, p <0.01, p <0.001. Detailed Implementation

[0023] Unless otherwise specified, the scientific and technical terms used in this article are intended for understanding by those skilled in the art.

[0024] The traditional Chinese medicine compound composition of this invention can be selectively supplemented with conventional excipients and prepared into clinically acceptable formulations according to conventional processes, including decoctions, granules, tablets, pastes, capsules, pills, etc. Preferred preparation processes are as follows: Trichosanthes peel, Allium macrostemon, and Salvia miltiorrhiza were extracted by ethanol reflux extraction. After extraction, the residue was filtered and the liquid was concentrated to obtain a concentrated solution. Astragalus membranaceus was extracted by water decoction to obtain Astragalus membranaceus extract. The above concentrated solution and Astragalus membranaceus extract were combined and further concentrated into a decoction. Then, by adding appropriate excipients, it was prepared into common drug dosage forms such as granules, tablets, decoction pastes, capsules, and pills. Specifically, (1) the decoction was further concentrated into a thick extract with a relative density of 1.20 to 1.35 (measured at 80 ℃), vacuum dried, powdered, and packaged into granules. (2) The decoction is concentrated, dried, and pulverized to obtain a dry extract powder. Pharmaceutically acceptable excipients are added: lactose and starch (20% to 80% of the dry extract powder mass), hydroxypropyl methylcellulose (2% to 10% of the dry extract powder mass), croscarmellose sodium (2% to 8% of the dry extract powder mass), talc (0.5% to 2% of the dry extract powder mass), etc., and compressed into tablets or filled capsules. (3) The decoction is concentrated under reduced pressure to obtain an extract. Appropriate pharmaceutical excipients are added: honey (30% to 100% of the extract mass), etc., to make pills. Purified water is used to adjust the extract, and potassium sorbate (0.05% to 0.2% of the extract mass) etc., to make a mixture / oral liquid. Sucrose (to make the sugar content reach 60% to 70%) is used to make a syrup. (4) The decoction is concentrated into a thick paste, and appropriate amounts of honey or sucrose (30% to 100% of the mass of the extract) are added and stirred evenly to make a decoction paste.

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the embodiments. The illustrative embodiments and descriptions of this invention are only used to explain this invention and are not intended to limit this invention.

[0026] The Trichosanthes peel, Allium macrostemon, Salvia miltiorrhiza, and Astragalus membranaceus used in the following examples were purchased from Beijing Tongrentang Xi'an Pharmacy Co., Ltd. The traditional Chinese medicine compound composition in the following examples is: Salvia miltiorrhiza 15 g, Trichosanthes peel 10 g, Allium macrostemon 10 g, and Astragalus membranaceus 30 g.

[0027] Example 1: This example describes the preparation of a decoction, and the preparation method is as follows: Trichosanthes peel and Allium macrostemon were extracted twice by heating and refluxing with 10 times the amount of grain alcohol with a mass percentage concentration of 70%, each time for 1.5 h. The extracts were combined and concentrated under reduced pressure to obtain a medicinal solution with a crude drug concentration of 2.0 g / mL (the crude drug concentration is based on the total mass of crude drug and the volume of the final concentrated solution). Take Astragalus membranaceus, add 10 times the amount of water, heat and decoct twice, 1.5 hours each time. Combine the decoctions, concentrate under reduced pressure to obtain an Astragalus membranaceus extract with a crude drug concentration of 2.5 g / mL. Combine the above concentrate and the Astragalus membranaceus extract, concentrate under reduced pressure to obtain a decoction with a crude drug concentration of 2.0 g / mL.

[0028] Experimental Example 2: This embodiment aims to study the therapeutic effect of the traditional Chinese medicine compound composition of the present invention on a rat model of hypoxic pulmonary hypertension. 1. Experimental Materials 1.1 Animals: SPF-grade male SD rats, 8 weeks old, were provided by the Experimental Animal Research Center of Air Force Medical University, Shaanxi Province, Certificate No.: SCXK (Shaanxi) 2024-002; the room temperature was controlled at 22 ± 2 ℃, the relative humidity was 50 ± 5%, and the light and dark were alternated for 12 hours; after 7 days of acclimatization feeding, abnormal rats were removed, and the remaining rats were grouped for experiments.

[0029] 1.2 Medicinal Materials: Wild lily alkaloids were purchased from Chengdu Desite Biotechnology Co., Ltd. Sildenafil citrate was purchased from Qilu Pharmaceutical Co., Ltd. Danlou tablets were purchased from Jilin Kangnai'er Pharmaceutical Co., Ltd. Example 1: The prepared decoction.

[0030] 2 Methods 2.1 Establishment of experimental animal models: The traditional Chinese medicine compound composition of this invention was validated using the hypoxic pulmonary hypertension model SD rat. A hypoxic pulmonary hypertension model was established using SD rats, and the therapeutic effect of the traditional Chinese medicine compound composition on the model rats was observed.

[0031] Model building: A rat model of hypoxic pulmonary hypertension was established using exogenous administration of lily alkaloid (MCT). After 7 days of acclimatization, rats were injected intraperitoneally with 60 mg / kg of 1% MCT on day 8 to induce the model. The rats were then administered the drug via gavage for 3 weeks starting the day after model initiation. Hemodynamic results (Figures 1 and 2) confirmed successful model establishment.

[0032] 2.2 Grouping and Administration of Experimental Animals Rats were randomly divided into a blank control group, a model control group, a sildenafil citrate positive control group (5.25 mg / kg / d), a Danlou tablet group (0.48 g / kg / d), and high (14.0 g / kg / d), medium (7.0 g / kg / d), and low (3.50 g / kg / d) dose groups of the traditional Chinese medicine compound decoction prepared in Example 1 of this invention. During the 3-week administration period, each drug group was administered the drug once by gavage at fixed times starting from day 1; the blank control group and the model control group were given an equal volume of physiological saline.

[0033] 2.3 Detection of Indicators for Hypoxic Pulmonary Hypertension Rats were anesthetized 3 weeks after drug administration. After their breathing stabilized, pulmonary artery blood flow time (PAAT) and pulmonary artery ejection time (PET) were measured using a Fujifilm Visual Sonics animal ultrasound analyzer. Rats were dissected 3 weeks after drug administration to measure heart mass (Mass) and right ventricular hypertrophy index (RVHI). Blood was collected from the abdominal aorta of rats, and the levels of nitric oxide (NO) and endothelin-1 (ET-1) in rat plasma were measured by ELISA.

[0034] 2.4 Safety Evaluation The changes in rat body weight and the determination of organ index were used as the basic safety evaluation criteria for the traditional Chinese medicine compound composition of the present invention. The initial body weight of the experimental animals was recorded before administration, and the body weight of each group of experimental animals was measured regularly during the administration period. The trend of body weight change was recorded and analyzed. After administration, the experimental animals were sacrificed, and the major organs, including the heart, liver, spleen, lungs, kidneys and brain, were separated. The weight of each organ was determined, and the organ index was calculated according to the following formula: Organ index = organ weight / body weight.

[0035] 2.5 Statistical Analysis: Data analysis was performed using GraphPad Prism 8.0 software. Data from multiple experiments are reported as mean ± standard error (sem). Unless otherwise specified, t-tests were used to compare the means of two groups. p Results with a value <0.05 are considered statistically significant.

[0036] 3. Experimental Results: 3.1 Effects on pulmonary artery blood flow acceleration time and ejection time As shown in Figures 1 and 2, the pulmonary artery blood flow acceleration time (PAAT) and the PAAT / PET ratio were significantly reduced in the model group animals. The positive control drug and all dosage groups of the compound showed a significant reduction effect, exhibiting obvious dose dependence. After three weeks of continuous administration, the PAAT and PAAT / PET levels were stably regulated to near the blank control group. Compared with the strong rebound of the positive control drug, this traditional Chinese medicine compound composition showed better regulatory potential in maintaining physiological homeostasis.

[0037] Figures 3 and 4 show that the cardiac index and right ventricular hypertrophy index were significantly increased in the model control group. All treatment groups of the compound formula reduced the levels of cardiac index and right ventricular hypertrophy index to varying degrees, with the high-dose group showing the most significant improvement. Overall, this intervention effectively reduced the abnormally elevated levels of cardiac index and right ventricular hypertrophy index in the model animals and had a significant ameliorative effect on hypoxic pulmonary hypertension. Furthermore, compared to the strong inhibition of positive control drugs, this traditional Chinese medicine compound formula showed better regulatory potential in maintaining physiological homeostasis.

[0038] Figure 5 shows that in the model control group, the synthesis and release of vascular endothelial relaxing factor-NO in plasma were reduced, leading to persistent pulmonary vasoconstriction and vascular remodeling, a condition that persisted. Each administration of the compound formula increased NO levels to varying degrees. Overall, this intervention effectively increased plasma NO levels, improved pulmonary vascular remodeling, and had a good regulatory effect on hypoxic pulmonary hypertension. Furthermore, compared to the potent enhancement of the positive control drug, this traditional Chinese medicine compound composition showed better regulatory potential in maintaining physiological homeostasis.

[0039] As shown in Figure 6, the synthesis and release of endothelin-1 (ET-1), a vasoconstrictor factor, increased in the model group animals, leading to persistent pulmonary vasoconstriction, thickening of the vessel walls, and narrowing of the lumen. After drug intervention, the high-dose group of this traditional Chinese medicine compound significantly reduced the plasma ET-1 content, demonstrating a good effect of dilating pulmonary vessels and inhibiting vascular remodeling. Compared with the strong inhibition of positive control drugs, this traditional Chinese medicine compound has potential advantages in maintaining immune homeostasis.

[0040] Efficacy evaluation: This traditional Chinese medicine compound composition showed a clear and systemic therapeutic effect on hypoxic pulmonary hypertension model animals: it significantly improved pulmonary vascular resistance and right heart failure symptoms by upregulating abnormally decreased PAAT, PAAT / PET, and NO indices and downregulating abnormally increased cardiac indices, RVHI, and ET-1 indices. Its efficacy showed a clear dose-dependent effect, and after 3 weeks of administration, it showed a mild and stable potential for regulating physiological homeostasis, which was superior to the strong inhibitory and enhancing effects of positive control drugs.

[0041] This demonstrates that the herbal compound composition of this invention can effectively regulate key indicators such as pulmonary artery blood flow acceleration time, right ventricular hypertrophy index, and plasma nitric oxide and endothelin-1 levels in a hypoxic pulmonary hypertension model induced by MCT, thereby reducing abnormally elevated pulmonary vascular resistance and improving endothelial function and vascular remodeling. Furthermore, given the pathological mechanism of hypoxic pulmonary hypertension involving chronic hypoxia driving pulmonary vasoconstriction and remodeling, leading to increased pulmonary artery pressure, the above-mentioned effects indicate that the herbal compound composition of this invention has a clear intervention effect on this type of hypoxia-related high-altitude pulmonary hypertension.

[0042] From the perspective of traditional Chinese medicine pathogenesis, this compound Chinese medicine formula works synergistically to invigorate qi and promote yang, activate blood circulation and remove blood stasis, resolve phlegm and dissipate nodules, and widen the chest and unblock the meridians. It achieves overall intervention on the complex pathogenesis of "asthma", "lung distension", "chest pain", "phlegm retention" and "palpitation", clearing the obstruction of the heart and lungs, smoothing the qi of the chest and diaphragm, and regulating the flow of meridians.

[0043] The compound composition of this invention is not only applicable to hypoxic pulmonary hypertension induced by MCT, but can also be extended to pulmonary hypertension caused by other different etiologies, including hypoxic pulmonary hypertension, and has clear therapeutic effects and good clinical application prospects.

[0044] 3.2 Safety Evaluation: By comprehensively analyzing the changes in body weight and organ indices, the effects of the traditional Chinese medicine compound composition of this invention on the overall growth status and major organs of rats were preliminarily assessed. The results are shown in Figures 7 and 8.

[0045] As can be seen from Figure 7, compared with the positive drug group, the weight of rats in all treatment groups increased steadily and continuously throughout the experiment, and the overall growth trend was better than that of the blank control group and the model control group, indicating that the treatment did not have an adverse effect on the overall growth of the rats.

[0046] As shown in Figure 8, the heart, spleen, and lung indices in the model control group were significantly elevated, accompanied by organ enlargement. The spleen index in the positive drug group was significantly elevated. In contrast, the major organ indices of the rats in this traditional Chinese medicine compound composition did not show significant changes, indicating that the traditional Chinese medicine compound composition has good safety.

[0047] In summary, this traditional Chinese medicine compound composition significantly increases abnormally decreased PAAT, PAAT / PET, and NO levels, and decreases abnormally increased cardiac indices, RVHI, and ET-1 levels, improving symptoms of elevated pulmonary vascular resistance and right heart failure, exhibiting a clear dose-dependent effect. Compared to positive control drugs, this traditional Chinese medicine compound composition, while exerting targeted therapeutic effects, significantly improves cardiac, splenic, and pulmonary enlargement while maintaining normal organ indices and weight gain. It possesses significant advantages in terms of high efficiency, low toxicity, multi-target regulation, and minimal harm to the body's vital energy, demonstrating excellent prospects for clinical development.

[0048] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A traditional Chinese medicine compound composition for treating hypoxic pulmonary hypertension, characterized in that, The principal herbs in the compound traditional Chinese medicine composition are: Trichosanthes peel and Salvia miltiorrhiza; the assistant herb is Allium macrostemon; the adjuvant herb is Astragalus membranaceus; and the guiding herb is Salvia miltiorrhiza.

2. The traditional Chinese medicine compound composition according to claim 1, characterized in that, The traditional Chinese medicine compound composition consists of the following raw materials in parts by weight: 10-30 parts of Salvia miltiorrhiza, 5-20 parts of Trichosanthes kirilowii peel, 5-20 parts of Allium macrostemon, and 20-50 parts of Astragalus membranaceus.

3. The traditional Chinese medicine compound composition according to claim 1, characterized in that, The traditional Chinese medicine compound composition consists of the following raw materials in parts by weight: 15 parts of Salvia miltiorrhiza, 10 parts of Trichosanthes kirilowii peel, 10 parts of Allium macrostemon, and 30 parts of Astragalus membranaceus.

4. A traditional Chinese medicine compound preparation for treating hypoxic pulmonary hypertension, characterized in that, It includes an active ingredient and pharmaceutically acceptable excipients, wherein the active ingredient is the traditional Chinese medicine compound composition as described in claim 1 or 2.

5. The traditional Chinese medicine compound preparation according to claim 4, characterized in that, The dosage forms of the traditional Chinese medicine compound preparations are decoctions, granules, tablets, capsules, pills, mixtures, or decoction pastes.

6. The traditional Chinese medicine compound preparation according to claim 4, characterized in that, The dosage of the active ingredient in the traditional Chinese medicine compound preparation is 3.50 g / kg / d to 14.0 g / kg / d.

7. The method for preparing the traditional Chinese medicine compound preparation according to claim 5, characterized in that, The methods include: Trichosanthes peel, Allium macrostemon and Salvia miltiorrhiza were extracted by ethanol reflux extraction. After extraction, the residue was filtered and the liquid was concentrated to obtain a concentrated solution. Astragalus extract was obtained by water decoction extraction. The combined concentrate and astragalus extract were further concentrated into a decoction.

8. The method for preparing the traditional Chinese medicine compound preparation according to claim 7, characterized in that, The method also includes preparing granules, tablets, decoctions, capsules or pills by adding appropriate excipients to the decoction.

9. The use of the traditional Chinese medicine compound composition according to any one of claims 1-3 in the preparation of a medicament for treating secondary pulmonary hypertension.

10. The use of the traditional Chinese medicine compound composition according to any one of claims 1-3 in the preparation of a medicament for treating hypoxic pulmonary hypertension.

11. The application according to claim 8, characterized in that, The hypoxic pulmonary hypertension described in traditional Chinese medicine is high-altitude pulmonary hypertension with symptoms such as "wheezing", "lung distension", "chest pain", "phlegm retention" or / and "palpitation".

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