Application of traditional Chinese medicine composition in preparation of medicine for treating pulmonary arterial hypertension

Abstract

The invention discloses application of a traditional Chinese medicine composition in preparation of a medicine for treating pulmonary arterial hypertension, and relates to the technical field of traditional Chinese medicines. The invention provides a traditional Chinese medicine composition Jinshui ten-component decoction in a medicine for treating pulmonary arterial hypertension. The traditional Chinese medicine composition comprises the following components in parts by weight: 20-50 parts of raw astragalus membranaceus, 10-30 parts of codonopsis pilosula, 10-25 parts of salvia miltiorrhiza, 8-20 parts of safflower carthamus, 10-25 parts of herba lycopi, 6-15 parts of winged euonymus twig, 10-20 parts of semen lepidii, 10-25 parts of poria cocos, 3-10 parts of white mulberry root-bark and 10-25 parts of semen plantaginis. The traditional Chinese medicine compound is based on the treatment principle of tonifying qi, activating blood and inducing diuresis to alleviate edema of traditional Chinese medicine, realizes multi-target regulation and control, effectively reduces pulmonary arterial pressure, improves right heart function and reverses pulmonary vascular remodeling through synergistic compatibility of multiple traditional Chinese medicines, has the advantages of high safety, low price and suitability for long-term administration, and provides a new effective choice for treatment of pulmonary arterial hypertension.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to the application of a traditional Chinese medicine composition in the preparation of a drug for treating pulmonary arterial hypertension. Background Technology

[0002] Pulmonary hypertension (PH) is a group of serious cardiovascular diseases characterized by progressively increasing pulmonary artery pressure and persistently increasing pulmonary vascular resistance. Its pathogenesis is complex, involving multiple key aspects such as pulmonary endothelial dysfunction, pulmonary inflammation, pulmonary vasoconstriction, pulmonary vascular wall remodeling, and an imbalance between smooth muscle cell proliferation and apoptosis. Disease progression leads to increased right ventricular afterload, ultimately causing right heart failure, posing a serious threat to the patient's life.

[0003] Currently, commonly used clinical treatments mainly include endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostacyclin drugs. However, these drugs have significant limitations: limited long-term efficacy, making it difficult to reverse the core pathological process of pulmonary vascular remodeling; numerous adverse reactions, poor tolerance in some patients; and high cost, imposing a heavy economic burden on patients. Furthermore, while some single-component traditional Chinese medicines (such as sophoridine) have been shown in existing studies to improve pulmonary hypertension through single mechanisms such as anti-oxidative stress, they suffer from single-target effects and incomplete efficacy coverage, failing to meet the clinical demand for safe, effective, and multi-target-regulated treatments.

[0004] Traditional Chinese medicine (TCM) categorizes pulmonary hypertension under the terms "lung distension," "asthma," and "edema," considering its core pathogenesis to be qi deficiency, blood stasis, and internal retention of dampness. Qi deficiency leads to impaired lung function and insufficient nourishment of the heart vessels, resulting in weak blood circulation; blood stasis causes obstruction of the lung collaterals, hindering the flow of qi and blood; and internal retention of dampness overflows into the skin and obstructs the airways. These three factors intertwine to form a vicious cycle, exacerbating the condition. Existing research on TCM herbs largely focuses on single effects (such as simply promoting blood circulation or simply promoting diuresis), lacking the precise synergistic application of compound formulas that combine qi-tonifying, blood-activating, and diuretic effects, thus failing to develop a comprehensive treatment plan targeting this core pathogenesis. Summary of the Invention

[0005] The purpose of this invention is to provide an application of a traditional Chinese medicine composition in the preparation of drugs for treating pulmonary hypertension, thereby addressing the problems existing in the prior art. This invention provides an application of the traditional Chinese medicine composition Jinshui Shiwei Decoction in the preparation of drugs for treating pulmonary hypertension. This traditional Chinese medicine compound is based on the TCM treatment principle of "tonifying qi and promoting blood circulation, promoting diuresis and reducing swelling." Through the synergistic combination of multiple traditional Chinese medicines, it achieves multi-target regulation, effectively reducing pulmonary artery pressure, improving right ventricular function, and reversing pulmonary vascular remodeling. It also possesses the advantages of high safety, low price, and suitability for long-term use, providing a new and effective option for the treatment of pulmonary hypertension.

[0006] To achieve the above objectives, the present invention provides the following solution:

[0007] This invention provides a traditional Chinese medicine composition for treating pulmonary hypertension, comprising the following components in parts by weight:

[0008] Raw Astragalus 20-50 parts, Codonopsis pilosula 10-30 parts, Salvia miltiorrhiza 10-25 parts, Carthamus tinctorius 8-20 parts, Lycopus lucidus 10-25 parts, Euonymus alatus 6-15 parts, Lepidium apetalum 10-20 parts, Poria cocos 10-25 parts, Morus alba root bark 3-10 parts, and Plantago asiatica 10-25 parts.

[0009] Preferably, the components include the following parts by weight:

[0010] 30 parts raw Astragalus membranaceus, 15 parts Codonopsis pilosula, 15 parts Salvia miltiorrhiza, 10 parts Carthamus tinctorius, 15 parts Lycopus lucidus, 12 parts Euonymus alatus, 15 parts Lepidium apetalum, 15 parts Poria cocos, 6 parts Morus alba root bark, and 15 parts Plantago asiatica.

[0011] The present invention also provides the application of the aforementioned traditional Chinese medicine composition in the preparation of drugs for treating pulmonary hypertension.

[0012] Preferably, the pulmonary hypertension is a type of pulmonary hypertension characterized by qi deficiency and blood stasis, and internal retention of dampness.

[0013] The present invention also provides a medicament for treating pulmonary hypertension, the medicament comprising the aforementioned traditional Chinese medicine composition and pharmaceutically acceptable adjuvants.

[0014] Preferably, the dosage form of the drug includes any one of decoction, extract, powder, granules, pills, tablets and soft capsules.

[0015] Preferably, the preparation method of the decoction includes: mixing and pulverizing all components of the traditional Chinese medicine composition except for plantain seeds, mixing them with wrapped plantain seeds, soaking them in water for 20-30 minutes; then boiling them over high heat and simmering them over low heat for 20-30 minutes, filtering out the liquid; adding water to the dregs and simmering them again, filtering out the liquid, combining the two liquids, and concentrating them into a clear paste to obtain the decoction.

[0016] Preferably, the concentration of the decoction is 0.5 g crude drug / mL.

[0017] Preferably, the method for preparing the granules includes: further drying and pulverizing the decoction, and adding pharmaceutically acceptable excipients to obtain the granules.

[0018] Preferably, the additives include binders, disintegrants, fillers, stabilizers, preservatives, coating materials, and / or fragrances.

[0019] The present invention discloses the following technical effects:

[0020] (1) The traditional Chinese medicine composition Jinshui Shiwei Decoction of the present invention is divided into three categories according to its efficacy: raw astragalus and codonopsis belong to the qi-tonifying category (strengthening the foundation and nourishing the source); salvia miltiorrhiza, safflower, eupatorium and euonymus belong to the blood-activating category (unblocking the meridians and removing blood stasis); lepidium seed, poria cocos, mulberry bark and plantain seed belong to the diuretic category (reducing swelling and eliminating pathogens). In the formula, raw astragalus is the chief ingredient, which greatly tonifies the original qi, benefits the lungs and strengthens the spleen, and also promotes diuresis and reduces swelling; codonopsis is the assistant ingredient, which assists astragalus in tonifying qi and strengthening the spleen, and enhances the qi-tonifying effect. The two are used together to achieve the effect of tonifying qi and strengthening the foundation. The formula uses four blood-activating herbs—Salvia miltiorrhiza, Carthamus tinctorius, Lycopus lucidus, and Euonymus alatus—as assistant herbs. Salvia miltiorrhiza activates blood circulation, removes blood stasis, unblocks menstruation, and relieves pain; Carthamus tinctorius activates blood circulation, unblocks menstruation, disperses blood stasis, and relieves pain; Lycopus lucidus activates blood circulation, regulates menstruation, promotes diuresis, and reduces swelling; Euonymus alatus breaks up blood stasis, unblocks menstruation, detoxifies, and reduces swelling. These four herbs work synergistically to clear the lung channels and improve blood stasis. The formula also uses four diuretic herbs—Lepidium apetalum, Poria cocos, Morus alba root bark, and Plantago asiatica—as adjuvant herbs. Lepidium apetalum drains the lungs, relieves asthma, promotes diuresis, and reduces swelling; Poria cocos promotes diuresis, eliminates dampness, strengthens the spleen, and calms the mind; Morus alba root bark drains the lungs, relieves asthma, promotes diuresis, and reduces swelling; Plantago asiatica promotes diuresis, clears the lungs, and resolves phlegm (wrapped in a decocted container to retain the active ingredients). These four herbs work together to promote diuresis, reduce swelling, drain the lungs, and relieve asthma. The entire formula works to invigorate qi, activate blood circulation, promote diuresis, and reduce swelling, closely addressing the core pathogenesis of pulmonary hypertension: "qi deficiency and blood stasis, internal retention of dampness."

[0021] (2) Synergistic Mechanism of Formula. **Qi-tonifying as the core:** Astragalus membranaceus greatly tonifies vital energy, benefits the lungs and spleen, and promotes diuresis and reduces swelling. Codonopsis pilosula assists Astragalus membranaceus in enhancing its qi-tonifying effect. Both provide impetus for blood circulation and diuresis, addressing the problems of "weak blood flow" and "difficulty in eliminating dampness." **Blood circulation as the key:** Salvia miltiorrhiza, Carthamus tinctorius, Lycopus lucidus, and Euonymus alatus work synergistically to invigorate blood circulation, remove blood stasis, relieve pain, and clear the lung channels, improving blood stasis and opening channels for dampness excretion. **Dampness promotion as an auxiliary:** Lepidium apetalum, Poria cocos, Morus alba root bark, and Plantago asiatica work together to purge the lungs, relieve asthma, promote diuresis and reduce swelling, quickly eliminate pathogens, and reduce the burden on the lungs and heart, creating conditions for the qi-tonifying and blood-circulating effects to be realized. The synergistic effect of these three herbs forms a virtuous cycle of "sufficient qi leads to blood circulation, smooth blood flow leads to water elimination, and water elimination leads to smooth qi flow," comprehensively targeting the multiple pathological aspects of pulmonary hypertension.

[0022] (3) Core therapeutic effects. Reduce pulmonary artery pressure: Significantly reduces the mean pulmonary artery pressure (mPAP) in pulmonary hypertension model animals and improves hemodynamic disturbances; Protect right heart function: Reduces the right ventricular hypertrophy index (RVHI) and lung index, alleviates right ventricular hypertrophy, and improves right heart function; Reverse pulmonary vascular remodeling: Reduces the percentage of pulmonary arteriolar wall thickness to vessel outer diameter (WT%) and the percentage of vessel wall area to total vessel area (WA%).

[0023] (4) The present invention provides a multi-effect synergistic drug for treating pulmonary hypertension, which differs from single-effect traditional Chinese medicine or single-drug formulations. It achieves synergistic effects through three categories: invigorating qi, promoting blood circulation, and promoting diuresis, covering multiple pathological aspects of pulmonary hypertension, resulting in a more comprehensive therapeutic effect. It is highly safe, as the traditional Chinese medicines used are all commonly used clinical materials, widely available, mild in nature, and without significant toxic side effects, making them suitable for long-term use. It offers high cost-effectiveness, with inexpensive medicinal materials and a simple preparation process that requires no complex equipment, reducing treatment costs. It is available in various dosage forms, including decoctions, granules, and capsules, making it convenient to take and meeting the medication needs of different patients. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 The graph shows the results of mean pulmonary artery pressure (mPAP) in each group of rats; Con: normal control group; Mod: model control group; 0.5 g / kg: low-dose group of Jinshui Shiwei Decoction; 1.0 g / kg: medium-dose group of Jinshui Shiwei Decoction; 2.0 g / kg: high-dose group of Jinshui Shiwei Decoction; Sildenafil: positive control group;

[0026] Figure 2 The graph shows the results of right ventricular systolic pressure (RVSP) detection, a hemodynamic parameter in rats of each group; Con: normal control group; Mod: model control group; 0.5 g / kg: low-dose group of Jinshui Shiwei Decoction; 1.0 g / kg: medium-dose group of Jinshui Shiwei Decoction; 2.0 g / kg: high-dose group of Jinshui Shiwei Decoction; Sildenafil: positive control group;

[0027] Figure 3 The graph shows the results of right ventricular hypertrophy index (RVHI) detection in rats of each group; Con: normal control group; Mod: model control group; 0.5g / kg: low-dose group of Jinshui Shiwei Decoction; 1.0g / kg: medium-dose group of Jinshui Shiwei Decoction; 2.0g / kg: high-dose group of Jinshui Shiwei Decoction; Sildenafil: positive control group;

[0028] Figure 4 The results of lung index detection in rats in each group are shown in the figure; Con: normal control group; Mod: model control group; 0.5g / kg: low-dose group of Jinshui Shiwei Decoction; 1.0g / kg: medium-dose group of Jinshui Shiwei Decoction; 2.0g / kg: high-dose group of Jinshui Shiwei Decoction; Sildenafil: positive control group;

[0029] Figure 5HE-stained sections of pulmonary arterioles from different groups (400× field of view); A: Normal control group; B: Model control group; C: Low-dose Jinshui Shiwei Decoction group; D: Medium-dose Jinshui Shiwei Decoction group; E: High-dose Jinshui Shiwei Decoction group; F: Sildenafil positive control group;

[0030] Figure 6 Statistical results of pulmonary arteriole wall thickness in different groups; WT%: percentage of wall thickness to vessel outer diameter; Con: normal control group; Mod: model control group; 0.5g / kg: low-dose group of Jinshui Shiwei Decoction; 1.0g / kg: medium-dose group of Jinshui Shiwei Decoction; 2.0g / kg: high-dose group of Jinshui Shiwei Decoction; sildenafil: positive control group;

[0031] Figure 7 Graph showing the statistical results of pulmonary arteriolar wall area in different groups; WA%: percentage of wall area to total vascular area; Con: normal control group; Mod: model control group; 0.5g / kg: low-dose group of Jinshui Shiwei Decoction; 1.0g / kg: medium-dose group of Jinshui Shiwei Decoction; 2.0g / kg: high-dose group of Jinshui Shiwei Decoction; sildenafil: positive control group;

[0032] Compared with the control group: ##P<0.01; compared with the model group: *P<0.05, **P<0.01. Detailed Implementation

[0033] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0034] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0035] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0036] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be obvious to those skilled in the art. This specification and embodiments are merely exemplary.

[0037] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0038] The traditional Chinese medicine composition for treating pulmonary hypertension provided by this invention comprises 10 kinds of traditional Chinese medicine raw materials, namely, raw Astragalus membranaceus, Codonopsis pilosula, Salvia miltiorrhiza, Carthamus tinctorius, Lycopus lucidus, Euonymus alatus, Lepidium apetalum, Poria cocos, Morus alba root bark, and Plantago asiatica seed. The traditional Chinese medicine composition composed of these 10 kinds of traditional Chinese medicine is briefly referred to as "Jinshui Ten-Flavor Decoction" in this invention.

[0039] Example 1

[0040] A traditional Chinese medicine composition for treating pulmonary hypertension, Jinshui Shiwei Decoction, is composed of the following ingredients:

[0041] Raw Astragalus 30g, Codonopsis pilosula 15g, Salvia miltiorrhiza 15g, Carthamus tinctorius 10g, Lycopus lucidus 15g, Euonymus alatus 12g, Lepidium apetalum 15g, Poria cocos 15g, Morus alba root bark 6g, Plantago asiatica 15g (wrapped and decocted to retain active ingredients).

[0042] Example 2

[0043] A traditional Chinese medicine composition for treating pulmonary hypertension, Jinshui Shiwei Decoction, is composed of the following ingredients:

[0044] Raw Astragalus 20g, Codonopsis 10g, Salvia miltiorrhiza 10g, Carthamus tinctorius 8g, Lycopus lucidus 10g, Euonymus alatus 6g, Lepidium apetalum 10g, Poria cocos 10g, Morus alba root bark 3g, Plantago asiatica 10g (wrapped and decocted to retain active ingredients).

[0045] Example 3

[0046] A traditional Chinese medicine composition for treating pulmonary hypertension, Jinshui Shiwei Decoction, is composed of the following ingredients:

[0047] Raw Astragalus 50g, Codonopsis pilosula 30g, Salvia miltiorrhiza 25g, Carthamus tinctorius 20g, Lycopus lucidus 25g, Euonymus alatus 15g, Lepidium apetalum 20g, Poria cocos 25g, Morus alba root bark 10g, Plantago asiatica 25g (wrapped and decocted to retain active ingredients).

[0048] Example 4: Preparation method of Jinshui Shiwei Decoction

[0049] A method for preparing a decoction of Jinshui Shiwei Decoction, a traditional Chinese medicine composition for treating pulmonary hypertension, includes the following steps:

[0050] 1. Raw material pretreatment: Weigh the Chinese herbal raw materials according to the weight proportions shown in any one of the Chinese herbal composition formulas in Examples 1-3. Except for Plantago seed which is wrapped in gauze (for decoction), wash and dry the other herbs and grind them into coarse powder (pass through a 20-mesh sieve).

[0051] 2. Decoction and Extraction: Place all medicinal materials (including the plantain seeds wrapped for decoction) in a decoction pot, add 8-10 times the amount of distilled water (in this example, 8 times the mass of distilled water is added), and soak for 30 minutes; bring to a boil over high heat, then simmer over low heat for 30 minutes, filter and collect the first decoction; add 6-8 times the amount of distilled water to the dregs (in this example, 6 times the mass of distilled water is added), bring to a boil over high heat, then simmer over low heat for 20 minutes, filter and collect the second decoction;

[0052] 3. Formulation of the preparation: Combine the two decoctions and concentrate them under reduced pressure to a clear paste with a relative density of 1.10-1.20 (60℃) (in this example, the concentration is 1.10) to obtain the decoction.

[0053] A method for preparing granules of a traditional Chinese medicine composition for treating pulmonary hypertension—Jinshui Shiwei Decoction—comprising the following steps:

[0054] 1. Raw material pretreatment: Weigh the Chinese herbal raw materials according to the weight proportions shown in any one of the Chinese herbal composition formulas in Examples 1-3. Except for Plantago seed which is wrapped in gauze (for decoction), wash and dry the other herbs and grind them into coarse powder (pass through a 20-mesh sieve).

[0055] 2. Decoction and Extraction: Place all medicinal materials (including the plantain seeds wrapped for decoction) in a decoction pot, add 8-10 times the amount of distilled water (in this example, 8 times the mass of distilled water is added), and soak for 30 minutes; bring to a boil over high heat, then simmer over low heat for 30 minutes, filter and collect the first decoction; add 6-8 times the amount of distilled water to the dregs (in this example, 6 times the mass of distilled water is added), bring to a boil over high heat, then simmer over low heat for 20 minutes, filter and collect the second decoction;

[0056] 3. Formulation: Combine the two decoctions, concentrate under reduced pressure, add dextrin as an excipient, and then process into granules using conventional methods.

[0057] Example 5: Application of Jinshui Shiwei Decoction in the Treatment of Pulmonary Hypertension

[0058] The Jinshui Shiwei Decoction and its preparations can be used to prepare drugs for the treatment of pulmonary hypertension, especially suitable for patients with pulmonary hypertension of the type caused by qi deficiency and blood stasis and internal retention of dampness.

[0059] 1. Experimental materials

[0060] 1.1 Animals: SPF grade SD rats, male, weighing 180-220g, were purchased from the Experimental Animal Center of Ningxia Medical University, Animal Production License No.: SCXK-2021-0001; the feeding conditions were standard feed, tap water, room temperature (21±2)℃, humidity 50-60%, and 12 hours of light and dark time per day. They were acclimatized for 7 days before the experiment.

[0061] 1.2 Drugs: Jinshui Shiwei Decoction (prepared according to the traditional Chinese medicine composition formula in Example 1 and the decoction preparation method of Jinshui Shiwei Decoction in Example 4, with a concentration of 0.5g crude drug / mL); Positive control drug: Sildenafil tablets (25mg / tablet), dissolved in physiological saline to prepare the required concentration;

[0062] 1.3 Reagent: Lilium alkaloid (MCT, purchased from Sigma);

[0063] 1.4 Instruments: Small animal echocardiography system (GE VIVID7), invasive blood pressure monitoring system (MPA cardiac function analyzer), pathological slicer, enzyme-linked immunosorbent assay (ELISA) reader (Thermo Fisher 1510), electronic balance, etc.

[0064] 2. Experimental Methods

[0065] 2.1 Establishment of a pulmonary hypertension model

[0066] Rats were induced to develop the model by subcutaneous injection of lily alkaloid solution (60 mg / kg) into the neck and back. The specific procedure was as follows: 300 mg MCT was first dissolved in 1.8 mL of 1 mol / L HCl, 3-4 mL of double-distilled water was added, the pH was adjusted to 7.4 with 1 mol / L NaOH, and the double-distilled water was added to a final volume of 15 mL. The solution was injected at a rate of 0.1 mL / 10 g body weight. The normal control group was injected subcutaneously into the neck and back of rats with an equal volume of physiological saline. The model was confirmed to be successful 21 days after initiation.

[0067] 2.2 Grouping and Dosing

[0068] Rats that successfully developed the model were randomly divided into 5 groups of 10 rats each, with an additional 10 rats serving as a normal control group.

[0069] Normal control group: Gavage with an equal volume of normal saline once daily for 21 consecutive days;

[0070] Model control group: Administered an equal volume of physiological saline by gavage once daily for 21 consecutive days;

[0071] Low-dose group of Jinshui Shiwei Decoction: 0.5g raw Jinshui Shiwei Decoction was administered by gavage once a day for 21 consecutive days;

[0072] Medium-dose group of Jinshui Shiwei Decoction: 1.0g raw herb / kg of Jinshui Shiwei Decoction was administered by gavage once a day for 21 consecutive days;

[0073] High-dose group of Jinshui Shiwei Decoction: 2.0g raw herbs / kg of Jinshui Shiwei Decoction were administered by gavage once a day for 21 consecutive days;

[0074] Positive control group: Sildenafil 30 mg / kg was administered by gavage once daily for 21 consecutive days.

[0075] 2.3 Testing Indicators and Procedures

[0076] (1) Hemodynamic testing

[0077] After administration, the rats were weighed and anesthetized with an intraperitoneal injection of 1 mL / 100g of 20% urethane. Once respiration was even and stable, the rats were fixed on the operating table. The MPA cardiac function analyzer was turned on, and the right external jugular vein was carefully dissected. A silk suture was tied at the distal end of the right external jugular vein. Using forceps handles supported under the vessel, ophthalmic scissors were used to make an oblique incision at a 45° angle, cutting 1 / 3 of the vessel diameter 4 mm proximal to the suture ligation point. The catheter was quickly inserted into the vessel along this incision direction. Another ligature was used to ligate the catheter (the ligation should be moderately tight, ensuring no bleeding at the incision site while allowing the catheter to pass through). (To ensure smooth insertion) Slowly advance the catheter forward. If resistance is encountered, do not force it; instead, slowly rotate and adjust the catheter to change the direction of its tip. Once it is in the correct position, determine the location of the catheter opening based on the pressure value on the pressure waveform curve and the length of the catheter inserted. Enter the common jugular vein, superior vena cava, right atrium, and right ventricle sequentially. When a typical right ventricular waveform appears, stabilize for a moment and then measure and record the right ventricular systolic pressure (RVSP). Next, advance the catheter into the pulmonary artery. When a typical pulmonary artery waveform appears, stabilize for a moment and then record the mean pulmonary artery pressure (mPAP). After measurement, withdraw the catheter from the pulmonary artery. Results are shown below. Figure 1 and Figure 2 .

[0078] (2) Right ventricular function and organ index testing

[0079] After hemodynamic testing, rats were euthanized, and their heart and lung tissues were removed. The right ventricle (RV) and left ventricle + interventricular septum (LV+S) were separated. Surface moisture was absorbed with filter paper, and the rats were weighed. The right ventricular hypertrophy index (RVHI = RV weight / (LV+S) weight × 100%) and lung index (lung tissue weight / body weight × 100%) were calculated. Results are shown below. Figure 3 and Figure 4 .

[0080] (3) Echocardiography

[0081] After weighing, the rats were anesthetized by intraperitoneal injection of 1ml / 100g of 10% chloral hydrate. Once their breathing was even and stable, their chests were shaved and they were fixed on the operating table. Using a GEVIVID7 echocardiogram, the pulmonary artery acceleration time (PAAT) and pulmonary artery deceleration rate (PAD) were measured sequentially. The results are shown in Table 1.

[0082] (4) Detection of pulmonary vascular remodeling

[0083] After the hemodynamic parameters were tested, the complete heart and lungs were removed, the lower lobe of the right lung was separated, and the residual blood was slowly rinsed with 6-8 ml of 14% paraformaldehyde. The tissue was then fixed in 4% paraformaldehyde for 48 hours. Hematoxylin-eosin staining (HE staining): Paraffin sections were baked in a 65°C oven for 20 min. Then, the slides were sequentially immersed in xylene I (10 min), xylene II (5 min), anhydrous ethanol I (1 min), anhydrous ethanol II (1 min), 95% ethanol (30 s), 80% ethanol (30 s), and 70% ethanol (30 s), and washed three times with water. Then, they were immersed in hematoxylin for 5 min, washed three times with water, immersed in 1% hydrochloric acid alcohol solution for 20 s, washed three times with water, immersed in eosin solution for 2 min, and washed quickly with water. Then, the paraffin sections were continuously immersed in 80% ethanol (30 s), 95% ethanol (30 s), anhydrous ethanol I (1 min), anhydrous ethanol II (3 min), xylene I (2 min), and xylene II (2 min). Finally, the slides were mounted with neutral resin. After HE staining of paraffin sections of lung tissue from each group of rats, the sections were observed under a microscope at a magnification of 400× per field (results are shown in [link to results]). Figure 5 For each slice, 20 relatively round blood vessels were photographed and recorded. Pulmonary arterioles with diameters ranging from 50 to 300 μm were selected, and the percentage of vessel wall thickness to outer diameter (WT%) was calculated using a microscope-specific micrometer. The results are shown below. Figure 6 And the percentage of vessel wall area to total vessel area (WA%). Results are shown in […]. Figure 6 and Figure 7 .

[0084] 2.4 Statistical Analysis

[0085] All data were analyzed using SPSS 22.0 statistical software and expressed as (x±s). One-way ANOVA was used for comparisons between groups, and P<0.05 was considered statistically significant.

[0086] 3. Experimental Results and Analysis

[0087] 3.1 By Figure 1 , Figure 2 It was found that after pulmonary hypertension model group rats, hemodynamic parameters such as mPAP and RVSP were significantly increased compared with control group. After continuous gavage treatment with Jinshui Shiwei Decoction, mPAP and RVSP decreased, and the effect increased with increasing dose, with the strongest protective effect at 2.0 g / kg (P<0.01 compared with model group). The experiment also included a positive control group of sildenafil (30 mg / kg). It is suggested that Jinshui Shiwei Decoction (0.5 g / kg, 1.0 g / kg, 2.0 g / kg) can alleviate pulmonary hypertension induced by lily alkaloid in rats, and the protective effect against pulmonary hypertension in rats is dose-dependent.

[0088] 3.2 By Figure 3 , Figure 4 It was found that the RVHI and lung index of rats in the pulmonary hypertension model group were significantly higher than those in the control group after modeling. After continuous gavage treatment with Jinshui Shiwei Decoction, both RVHI and lung index decreased. The effect increased with increasing dose, reaching its strongest protective effect at 2.0 g / kg (P < 0.05 compared to the model group). A positive control group was also included in the experiment using sildenafil (30 mg / kg). This suggests that Jinshui Shiwei Decoction (0.5 g / kg, 1.0 g / kg, 2.0 g / kg) can alleviate right ventricular hypertrophy in rats with pulmonary hypertension induced by lily alkaloids, and its protective effect against right ventricular hypertrophy in rats with pulmonary hypertension is dose-dependent.

[0089] 3.3 As shown in Table 1, the hemodynamic parameters such as PAAT and PAD in the pulmonary hypertension model group were significantly increased compared with the control group after modeling. After continuous gavage administration of Jinshui Shiwei Decoction, PAAT and PAD decreased, with the effect increasing with increasing dose, reaching its strongest protective effect at 2.0 g / kg (P<0.05, P<0.01 compared with the model group). A positive control group was also included in the experiment using sildenafil (30 mg / kg). This suggests that Jinshui Shiwei Decoction (0.5 g / kg, 1.0 g / kg, 2.0 g / kg) can alleviate pulmonary hypertension induced by lily alkaloids in rats, and its protective effect against pulmonary hypertension in rats is dose-dependent.

[0090] Table 1. Effects of Jinshui Shiwei Decoction on echocardiographic parameters in rats with purpuric alkaloid-induced pulmonary hypertension (x±s)

[0091]

[0092] (Compared with the control group: #P<0.05, ##P<0.01; Compared with the model group: *P<0.05, **P<0.01)

[0093] 3.4 such as Figure 5 , Figure 6 , Figure 7 As shown, the WT% and WA% of rats in the pulmonary hypertension model group were significantly higher than those in the control group after modeling. Compared with the model group, the pathological changes of pulmonary arteriolar hypertrophy in the rat lung tissue of the strychnine-treated group were reduced with increasing dose, and the WT% and WA% decreased (P<0.05, P<0.01 compared with the model group). The experiment also included a sildenafil (30mg / kg) positive control group, suggesting that Jinshui Shiwei Decoction (0.5g / kg, 1.0g / kg, 2.0g / kg) has the effect of reducing pulmonary arteriolar hypertrophy in the lung tissue of rats with strychnine-induced pulmonary hypertension.

[0094] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating pulmonary hypertension, characterized in that, The components include the following parts by weight: Raw Astragalus 20-50 parts, Codonopsis pilosula 10-30 parts, Salvia miltiorrhiza 10-25 parts, Carthamus tinctorius 8-20 parts, Lycopus lucidus 10-25 parts, Euonymus alatus 6-15 parts, Lepidium apetalum 10-20 parts, Poria cocos 10-25 parts, Morus alba root bark 3-10 parts, and Plantago asiatica 10-25 parts.

2. A traditional Chinese medicine composition for treating pulmonary hypertension, characterized in that, The components include the following parts by weight: 30 parts raw Astragalus membranaceus, 15 parts Codonopsis pilosula, 15 parts Salvia miltiorrhiza, 10 parts Carthamus tinctorius, 15 parts Lycopus lucidus, 12 parts Euonymus alatus, 15 parts Lepidium apetalum, 15 parts Poria cocos, 6 parts Morus alba root bark, and 15 parts Plantago asiatica.

3. The use of the traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a drug for treating pulmonary hypertension.

4. The application as described in claim 3, characterized in that, The pulmonary hypertension mentioned is a type of pulmonary hypertension caused by qi deficiency and blood stasis, and internal retention of dampness.

5. A drug for treating pulmonary hypertension, characterized in that, The drug contains the traditional Chinese medicine composition as described in claim 1 or 2, as well as pharmaceutically acceptable adjuvants.

6. The drug as described in claim 5, characterized in that, The dosage form of the drug includes any one of decoction, extract, powder, granule, pill, tablet and soft capsule.

7. The drug as described in claim 6, characterized in that, The preparation method of the decoction includes: mixing and pulverizing all components of the traditional Chinese medicine composition except for plantain seeds, mixing them with wrapped plantain seeds, soaking them in water for 20-30 minutes; then boiling them over high heat and simmering them over low heat for 20-30 minutes, filtering out the liquid; adding water to the dregs and simmering them again, filtering out the liquid, combining the two liquids, and concentrating them into a clear paste to obtain the decoction.

8. The drug as described in claim 7, characterized in that, The concentration of the decoction is 0.5g crude drug / mL.

9. The drug as described in claim 6, characterized in that, The method for preparing the granules includes: further drying and pulverizing the decoction, and adding pharmaceutically acceptable excipients to obtain the granules.

10. The drug as described in claim 5, characterized in that, The additives include binders, disintegrants, fillers, stabilizers, preservatives, coating materials, and / or fragrances.

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