Application of collateral dredging preparation in preparation of medicine for treating pulmonary embolism

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to application of a traditional Chinese medicine composition in preparation of pulmonary embolism treatment substances, and the traditional Chinese medicine composition is mainly prepared from astragalus membranaceus, honeysuckle, golden cypress, rhizoma atractylodis, coix seeds, radix scrophulariae, angelica sinensis, radix paeoniae alba, liquorice, leech, centipede and scorpio. All the medicines in the traditional Chinese medicine composition conform to the principle of compatibility of monarch, minister, assistant and guide, compatibility is scientific, the traditional Chinese medicine composition is suitable for clinical cases, pharmacodynamic tests show that the composition can relieve inflammatory injury of rats suffering from acute pulmonary embolism, and clinical tests prove that the composition can effectively relieve symptoms of patients suffering from pulmonary embolism and is low in toxic and side effect, good in safety and wide in market prospect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine and relates to a new pharmaceutical use of the Mailuoshutong preparation, specifically the application of the Mailuoshutong preparation in the preparation of drugs for treating pulmonary embolism. Background Technology

[0002] Pulmonary embolism (PE), also known as pulmonary thromboembolism, is a clinical and pathophysiological syndrome caused by the blockage of the main pulmonary artery or its branches by endogenous or exogenous emboli, resulting in pulmonary circulatory disturbances. If pulmonary hemorrhage or necrosis further develops on this basis, it is called pulmonary infarction. Clinically, the two are sometimes difficult to distinguish.

[0003] Pulmonary embolism (PE) can be caused by various emboli that break off from the systemic circulation, with thrombi being the most common type. This condition is also known as pulmonary thromboembolism. Clinically, patients often present with sudden, unexplained collapse, pallor, profuse sweating, dyspnea, chest pain, and cough, which may be accompanied by symptoms of insufficient cerebral oxygen supply, such as intense anxiety, fatigue, nausea, convulsions, and even loss of consciousness. In recent years, the incidence of pulmonary embolism in my country has shown a significant upward trend. Its pathogenesis involves a complex interaction between genetic factors and acquired risk factors. The elderly population is at higher risk, and population aging further increases the accumulation of acquired risk factors, leading not only to an increased incidence but also a significant increase in the absolute number of patients. In addition, unhealthy lifestyle habits such as smoking, obesity, unhealthy diet, and lack of exercise are also important contributing factors to the development of this disease.

[0004] Acute pulmonary embolism (APE) is a critical illness with a high clinical mortality rate. It can trigger a systemic inflammatory response, vascular endothelial cell damage, and a hypercoagulable state, further leading to a series of pathophysiological changes such as increased pulmonary vascular resistance and elevated pulmonary artery pressure, significantly increasing the risk of death and disability in patients. Therefore, early diagnosis and effective intervention are crucial for improving patient prognosis.

[0005] Currently, the treatment of acute thrombotic embolism (APE) primarily relies on low-molecular-weight heparin anticoagulation. While this therapy effectively prevents further thrombus formation, it has limitations such as a high risk of bleeding, limited effectiveness in dissolving existing thrombi, and inability to effectively alleviate post-embolism inflammatory responses and vascular endothelial damage. In recent years, Traditional Chinese Medicine (TCM) has demonstrated unique advantages in multi-target, holistic regulation of thrombotic diseases. Mailuoshutong Pills / Granules, a marketed TCM compound preparation, possesses the effects of clearing heat and detoxifying, resolving blood stasis and unblocking collaterals, and eliminating dampness and reducing swelling. It is widely used clinically for vascular diseases such as thrombophlebitis. Its formula contains ingredients such as leeches and scorpions, which have been proven to have potent anticoagulant activity, while honeysuckle and phellodendron bark have anti-inflammatory effects. Theoretically, this drug may exert a comprehensive effect of antithrombosis, anti-inflammation, and vascular endothelial protection through multiple pathways. However, to date, there have been no public reports or indications regarding the application of Mailuoshutong pills / granules in the preparation of drugs for the treatment of pulmonary embolism. Its therapeutic effects and mechanisms of action on pulmonary embolism are unknown, which greatly limits the clinical application and development of this preparation in the important disease field of pulmonary embolism. Summary of the Invention

[0006] The inventors would like to clarify that the use of the Mailuoshutong preparation in the preparation of drugs for treating pulmonary embolism in this invention is based on feedback from the clinical use of Mailuoshutong preparations (granules / pills). Some clinicians have tried using Mailuoshutong pills in combination with conventional treatment methods and found that the treatment effect is better and the cure rate is higher than that of conventional treatment methods.

[0007] In view of the shortcomings of existing technologies, and based on clinical application feedback of the marketed product "Mailuoshutong", this invention provides a new use for Mailuoshutong preparations. Pharmacological tests have confirmed that Mailuoshutong preparations have significant efficacy in treating pulmonary embolism, with few side effects and a low recurrence rate. Furthermore, its production cost is lower than that of existing technologies, and it has already achieved industrial-scale production, demonstrating significant commercial value.

[0008] One of the objectives of this invention is to provide a new pharmaceutical use for the pulmonox preparation, namely, its use in the preparation of drugs for the prevention and / or treatment of pulmonary embolism. The use described in this invention was discovered during the clinical application of the drug and subsequently confirmed by relevant pharmacodynamic tests.

[0009] In some embodiments, the pulmonary embolism is selected from one or more of acute pulmonary embolism and subacute pulmonary embolism.

[0010] In some embodiments, the application includes one or more of the following: dissolving pulmonary vascular thrombi, inhibiting new thrombus formation, improving pulmonary circulation, reducing pulmonary hypertension, and improving respiratory function.

[0011] The blood vessel smoothing preparations described in this invention include, but are not limited to, blood vessel smoothing granules and blood vessel smoothing pills.

[0012] The meridian-clearing preparation is made from 12 medicinal materials: Astragalus membranaceus, honeysuckle, Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, Glycyrrhiza uralensis, leech, centipede, and scorpion.

[0013] In some embodiments, the vascular lubricant preparation comprises the following components in parts by weight:

[0014] Astragalus membranaceus 400-900 parts by weight, Lonicera japonica 400-900 parts by weight, Phellodendron chinense 200-500 parts by weight

[0015] Atractylodes lancea 200-500 parts by weight, Coix lacryma-jobi 400-900 parts by weight, Scrophularia ningpoensis 400-900 parts by weight

[0016] Angelica sinensis 200-500 parts by weight, Paeonia lactiflora 200-500 parts by weight, Glycyrrhiza uralensis 50-150 parts by weight

[0017] Leeches 200-500 parts by weight, centipedes 15-40 parts by weight, and whole scorpions 50-150 parts by weight.

[0018] In a preferred embodiment, the vascular relaxation preparation comprises the following components in parts by weight:

[0019] Astragalus membranaceus 833 parts by weight, Lonicera japonica 833 parts by weight, Phellodendron chinense 417 parts by weight

[0020] Atractylodes lancea 417 parts by weight, Coix lacryma-jobi 833 parts by weight, Scrophularia ningpoensis 833 parts by weight

[0021] Angelica sinensis 417 parts by weight, Paeonia lactiflora 417 parts by weight, Glycyrrhiza uralensis 138 parts by weight

[0022] Leech 417 parts by weight, centipede 33 parts by weight, whole scorpion 138 parts by weight.

[0023] In a preferred embodiment, the vascular relaxation preparation comprises the following components in parts by weight:

[0024] Astragalus membranaceus 500 parts by weight, honeysuckle 500 parts by weight, and phellodendron chinense 250 parts by weight

[0025] Atractylodes lancea 250 parts by weight, Coix lacryma-jobi 500 parts by weight, Scrophularia ningpoensis 500 parts by weight

[0026] Angelica sinensis 250 parts by weight, Paeonia lactiflora 250 parts by weight, Glycyrrhiza uralensis 83 parts by weight

[0027] Leech 250 parts by weight, centipede 20 parts by weight, whole scorpion 83 parts by weight.

[0028] Another object of the present invention is to provide a method for preparing the aforementioned vasodilator:

[0029] The raw medicinal materials of Astragalus membranaceus, Lonicera japonica, Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, and Glycyrrhiza uralensis, along with half the prescription amount of leeches, centipedes, and scorpions, were extracted by steam distillation, decoction, and ethanol reflux to obtain an extract. After drying and pulverizing, the extract was mixed with the remaining half of the prescription amount of finely powdered leeches, centipedes, and scorpions, and pharmaceutically acceptable excipients were added to prepare a clinically acceptable dosage form.

[0030] In a more preferred embodiment, the method for preparing the meridian-relieving preparation is as follows:

[0031] A. Weigh out the prescribed amounts of honeysuckle, atractylodes, scrophularia, angelica, and white peony root slices, add water and distill for 6-8 hours, collect the volatile oil, and set aside the distilled aqueous solution and residue.

[0032] B. Weigh out the prescribed amounts of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, Glycyrrhiza uralensis, and 1 / 2 of the prescribed amounts of Hirudo medicinalis, Scolopendra subspinipes, and Buthus martensii. Combine these with the dregs obtained in step A, add 6-12 times the amount of water, and decoct 2-3 times, 1-3 hours each time. Combine the decoctions, filter, and set aside.

[0033] C. Combine the aqueous solution after distillation in step A with the decoction in step B, concentrate to obtain a concentrated solution, add ethanol to make the alcohol content reach 60%-70%, let stand for 24-36 hours to allow it to fully precipitate, collect the supernatant, filter, concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and pulverize it into a dry powder.

[0034] D. Grind the remaining 1 / 2 of the prescription amount of leeches, centipedes, and scorpions into fine powder and set aside; E. Mix the fine powder of medicinal materials obtained in step D and the dry powder obtained in step C, add the volatile oil from step A, and prepare a clinically acceptable dosage form by directly or by adding pharmaceutically acceptable excipients through conventional processes.

[0035] In a more preferred embodiment, a clinically acceptable dosage form is one of granules, tablets, pellets, microcapsules, or capsules.

[0036] The main benefits of this invention are as follows:

[0037] (1) Pharmacodynamic tests showed that the composition of the present invention significantly improved the overall condition of mice with pulmonary embolism, specifically by reducing mean pulmonary artery pressure (mPAP) and right ventricular pressure (RVP), thus alleviating pulmonary hypertension and preventing thrombosis. Simultaneously, the composition reduced pulmonary edema, improved lung function, and decreased serum levels of inflammatory factors TNF-α and IL-1β, effectively inhibiting the inflammatory response. Furthermore, studies also showed that the composition of the present invention inhibited platelet activation and aggregation, thereby further protecting lung tissue structure and function.

[0038] (2) Clinical trials have verified that the Vein Relief Preparation of this invention exhibits significant comprehensive therapeutic effects in the treatment of pulmonary embolism. It effectively relieves major clinical symptoms such as dyspnea and chest pain, and promotes the recovery of blood gas parameters and pulmonary perfusion function. Simultaneously, this product has the effects of inhibiting inflammatory response and regulating coagulation function, which helps control thrombus development and reduce lung tissue damage. Clinical observations show that its combined use on the basis of conventional treatment can further enhance efficacy, promote patient recovery, and has good safety.

[0039] (3) In the formulation of this invention, Astragalus membranaceus replenishes qi and nourishes blood, Lonicera japonica clears heat and detoxifies, Scrophularia ningpoensis nourishes yin and reduces fire, Coix lacryma-jobi promotes diuresis and reduces swelling, and Scorpion and Hirudo dredge the meridians. The various Chinese medicine components complement each other, integrating qi replenishment, yin nourishment, blood dredging and meridian clearing, and heat detoxification into one, demonstrating the characteristics of Chinese medicine components that emphasize the whole, dynamic adjustment, yin-yang harmony, and enhanced efficacy and reduced toxicity, thereby improving the effectiveness and safety of the drug. Attached Figure Description

[0040] Figure 1 The level of TNF-α in the serum of mice in each group (compared to the control group) was measured. * P<0.05, compared with the APE group, # P<0.05, compared with the LMWH group, @P<0.05).

[0041] Figure 2 The level of IL-1β in the serum of mice in each group (compared to the control group) * P<0.05, compared with the APE group, # P<0.05, compared with the LMWH group, @P<0.05).

[0042] Figure 3 The levels of IL-10 in the serum of mice in each group (compared to the control group) * P<0.05, compared with the APE group, # P<0.05, compared with the LMWH group, @P<0.05). Detailed Implementation

[0043] Example 1: Commercially available Mailuoshutong granules (National Drug Approval Number Z19991025)

[0044] Components:

[0045] Astragalus membranaceus 500 parts by weight, honeysuckle 500 parts by weight, and phellodendron chinense 250 parts by weight

[0046] Atractylodes lancea 250 parts by weight, Coix lacryma-jobi 500 parts by weight, Scrophularia ningpoensis 500 parts by weight

[0047] Angelica sinensis 250 parts by weight, Paeonia lactiflora 250 parts by weight, Glycyrrhiza uralensis 83 parts by weight

[0048] Leech 250 parts by weight, centipede 20 parts by weight, whole scorpion 83 parts by weight.

[0049] Preparation method:

[0050] A. Take leeches, centipedes, and scorpions, and crush them to a particle size of less than 100μm;

[0051] B. Phellodendron bark, coix seed, scrophularia root, and white peony root were extracted with ethanol, then extracted with water. After recovering the ethanol from the ethanol extract, the extract was concentrated into an ethanol extract paste, and the water extract was filtered for later use.

[0052] C. Extract the volatile oil from honeysuckle, atractylodes, angelica, astragalus, and licorice with water. Add half the prescription amount of leeches, centipedes, and scorpions to the remaining liquid and residue, decoct in water, filter, and concentrate the filtrate with the water extract from step B to form an extract.

[0053] D. Mix the remaining 1 / 2 of the prescription amount of leeches, centipedes, and scorpions with the alcohol extract from step B and the water extract from step C, and then prepare granules directly or by adding pharmaceutically acceptable excipients through conventional procedures.

[0054] Example 2: Commercially available Mailuoshutong granules (National Drug Approval Number Z20090636)

[0055] Components:

[0056] Astragalus membranaceus 833 parts by weight, Lonicera japonica 833 parts by weight, Phellodendron chinense 417 parts by weight

[0057] Atractylodes lancea 417 parts by weight, Coix lacryma-jobi 833 parts by weight, Scrophularia ningpoensis 833 parts by weight

[0058] Angelica sinensis 417 parts by weight, Paeonia lactiflora 417 parts by weight, Glycyrrhiza uralensis 138 parts by weight

[0059] Leech 417 parts by weight, centipede 33 parts by weight, whole scorpion 138 parts by weight.

[0060] Preparation method:

[0061] A. Take leeches, centipedes, and scorpions, and crush them to a particle size of less than 100μm;

[0062] B. Phellodendron bark, coix seed, scrophularia root, and white peony root were extracted with ethanol, then extracted with water. After recovering the ethanol from the ethanol extract, the extract was concentrated into an ethanol extract paste, and the water extract was filtered for later use.

[0063] C. Extract the volatile oil from honeysuckle, atractylodes, angelica, astragalus, and licorice with water. Add half the prescription amount of leeches, centipedes, and scorpions to the remaining liquid and residue, decoct in water, filter, and concentrate the filtrate with the water extract from step B to form an extract.

[0064] D. Mix the remaining 1 / 2 of the prescription amount of leeches, centipedes, and scorpions with the alcohol extract from step B and the water extract from step C, and then prepare pills directly or by adding pharmaceutically acceptable excipients through conventional procedures.

[0065] Example 3: Meridian-Soothing Pills

[0066] Components:

[0067] Astragalus membranaceus 900 parts by weight, honeysuckle 900 parts by weight, and phellodendron chinense 500 parts by weight

[0068] Atractylodes lancea 500 parts by weight, Coix lacryma-jobi 900 parts by weight, Scrophularia ningpoensis 900 parts by weight

[0069] Angelica sinensis 500 parts by weight, Paeonia lactiflora 500 parts by weight, Glycyrrhiza uralensis 150 parts by weight

[0070] Leech 500 parts by weight, centipede 40 parts by weight, whole scorpion 150 parts by weight.

[0071] Preparation method: Same as in Example 2

[0072] Example 4: Meridian-Soothing Granules

[0073] Components:

[0074] Astragalus membranaceus 400 parts by weight, honeysuckle 400 parts by weight, and phellodendron chinense 200 parts by weight

[0075] Atractylodes lancea 200 parts by weight, Coix lacryma-jobi 400 parts by weight, Scrophularia ningpoensis 400 parts by weight

[0076] Angelica sinensis 200 parts by weight, Paeonia lactiflora 200 parts by weight, Glycyrrhiza uralensis 50 parts by weight, Hirudo medicinalis 200 parts by weight, Scolopendra subspinipes 15 parts by weight, Scorpion 50 parts by weight.

[0077] Preparation method: Same as in Example 2

[0078] Comparative Example 1: Meridian-Soothing Pills

[0079] Components:

[0080] Astragalus membranaceus 350 parts by weight, honeysuckle 350 parts by weight, and phellodendron chinense 600 parts by weight

[0081] Atractylodes lancea 600 parts by weight, Coix lacryma-jobi 350 parts by weight, Scrophularia ningpoensis 350 parts by weight, Angelica sinensis 600 parts by weight, Paeonia lactiflora 600 parts by weight, Glycyrrhiza uralensis 200 parts by weight, Hirudo medicinalis 150 parts by weight, Scolopendra subspinipes 50 parts by weight, and Scorpion 30 parts by weight.

[0082] Preparation method: Same as in Example 2

[0083] Comparative Example 2: Meridian Relaxing Granules

[0084] Components:

[0085] Astragalus membranaceus 500 parts by weight, honeysuckle 500 parts by weight, and phellodendron chinense 250 parts by weight

[0086] Atractylodes lancea 250 parts by weight, Coix lacryma-jobi 500 parts by weight, Scrophularia ningpoensis 500 parts by weight

[0087] Angelica sinensis 250 parts by weight, Paeonia lactiflora 250 parts by weight, Glycyrrhiza uralensis 83 parts by weight, Pheretima aspergillum 250 parts by weight, Bombyx mori 20 parts by weight, Salvia miltiorrhiza 500 parts by weight. Preparation method: Same as in Example 1.

[0088] Comparative Example 3: Meridian-Soothing Pills

[0089] Astragalus membranaceus 833 parts by weight, Lonicera japonica 833 parts by weight, Phellodendron chinense 417 parts by weight, Atractylodes lancea 417 parts by weight, Coix lacryma-jobi 833 parts by weight, Scrophularia ningpoensis 833 parts by weight, Angelica sinensis 417 parts by weight, Paeonia lactiflora 417 parts by weight, Glycyrrhiza uralensis 138 parts by weight, Prunus persica 417 parts by weight, Scolopendra subspinipes 33 parts by weight, Pheretima aspergillum 138 parts by weight.

[0090] Preparation process: Same as in Example 2

[0091] Comparative Example 4: Meridian Relaxing Granules

[0092] Components:

[0093] Astragalus membranaceus 500 parts by weight, resveratrol 500 parts by weight, Phellodendron chinense 250 parts by weight, Atractylodes lancea 250 parts by weight, Coix lacryma-jobi 500 parts by weight, Scrophularia ningpoensis 500 parts by weight, Angelica sinensis 250 parts by weight, Paeonia lactiflora 250 parts by weight, Glycyrrhiza uralensis 83 parts by weight, Hirudo medicinalis 250 parts by weight, Scolopendra subspinipes 20 parts by weight, Buthus martensii 83 parts by weight. Preparation method: Same as in Example 1.

[0094] Comparative Example 5: Meridian Soothing Granules

[0095] Components:

[0096] Astragalus membranaceus 833 parts by weight, Lonicera japonica 833 parts by weight, Phellodendron chinense 417 parts by weight

[0097] Atractylodes lancea 417 parts by weight, Coix lacryma-jobi 833 parts by weight, Scrophularia ningpoensis 833 parts by weight

[0098] Angelica sinensis 417 parts by weight, Paeonia lactiflora 417 parts by weight, Glycyrrhiza uralensis 138 parts by weight

[0099] Leech 417 parts by weight, centipede 33 parts by weight, whole scorpion 138 parts by weight.

[0100] Preparation method:

[0101] A. Pre-processing of medicinal materials: Take all twelve medicinal materials (Astragalus membranaceus, Lonicera japonica, Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, Glycyrrhiza uralensis, Hirudo medicinalis, Scolopendra subspinipes, and Buthus martensii), grind them into coarse powder (particle size less than 100μm), and mix them evenly.

[0102] B. Unified extraction: Decoct the above mixed medicinal powder twice with water. First time: Add 10 times the amount of water and decoct for 1.5 hours, filter, and reserve the filtrate. Second time: Add 8 times the amount of water to the medicinal residues and decoct for 1 hour, then filter.

[0103] C. Concentration and pill making: Combine the two filtrates, concentrate under reduced pressure to a relative density of an appropriate concentration, and obtain a clear extract with a relative density of 1.35 at 60°C. Make this clear extract into pills through conventional procedures, either directly or by adding an appropriate amount of pharmaceutically acceptable excipients.

[0104] I. Experimental Example 1: Experimental study on the inhibitory effect of Mailuoshutong preparation on inflammation in rats with acute pulmonary embolism

[0105] To verify the efficacy of the Mailuoshutong preparation in treating pulmonary embolism in this invention, the inventor carried out a pharmacodynamic experiment study. It should be noted that the drugs selected for the pharmacodynamic experiment of this invention are the drugs obtained from the representative formula and its preparation method of this invention. Due to space limitations, the experiments and results of the drugs obtained from other formulas and preparation methods included in this invention are not listed one by one here.

[0106] 1. Experimental materials

[0107] I.1 Experimental animals

[0108] SD rats, male, 8 weeks old, SPF grade, body weight 200 ± 20 g, 8 individuals, provided by Lunan Pharmaceutical Group Co., Ltd. Certificate number: SYXK(Lu)20230023. The feeding conditions are an environment with a 12h / 12h light-dark cycle, a temperature of 20°C - 26°C, and a humidity of 50% - 70%. They are allowed to drink water and eat freely, and are adaptively fed for one week before the start of the experiment.

[0109] [[ID=2​​​​​​​​​​​First, collect 1 ml of rat tail vein blood and allow it to coagulate. Heat the coagulated blood at 70°C for 10 minutes, then cut the coagulated blood into small thrombus particles with a diameter of approximately 0.5 mm. Anesthetize the rats, prepare and disinfect the neck area, separate the right jugular vein, mix about 30 thrombus particles into 1 ml of 0.9% sodium chloride solution, inject the thrombus into the jugular vein through a syringe, and push the thrombus along the direction of venous return for about 5 minutes. Suture the wound. Four hours later, measure the rats' mean pulmonary artery pressure (mPAP) and right ventricular pressure (RVP). When the rats show a significant increase in mPAP and exhibit deeper and faster breathing, and diffuse dry and wet rales in both lungs, the modeling is considered successful.

[0114] 2.2 Experimental Grouping

[0115] Eighty rats were randomly divided into a control group, an APE group, a low molecular weight heparin group (LMWH group), a low-dose MLST-L group, a medium-dose MLST-M group, and a high-dose MLST-H group, with 4 control groups and 5 control groups, and 10 rats in each group. Except for the control group, the APE rat model was established in all other groups using the above method. The control group was infused with an equal volume of physiological saline through the right common carotid artery using the same method, and other procedures were the same as before.

[0116] Low molecular weight heparin group: 1 mg / kg subcutaneously;

[0117] Control group and APE group: Intraperitoneal injection of equal volume of normal saline;

[0118] The low, medium, and high dose groups of the vascular lubricant (0.84g / kg, 1.68g / kg, and 3.36g / kg).

[0119] 2.3 Observation Indicators and Measurements

[0120] 2.3.1 Pulmonary artery pressure (mPAP) and right ventricular pressure (RVP) measurement

[0121] Two hours after modeling, the right jugular vein was separated, and a polystyrene tube was inserted, which was then passed through the right atrium, right ventricle, and pulmonary artery in sequence. The mPAP and RVP of each group of rats were measured and recorded.

[0122] 2.3.2 Lung tissue wet / dry weight ratio (W / D)

[0123] Right lung tissue was harvested, weighed, and dried in an 80℃ constant temperature oven for 24 hours, then weighed again. Lung W / D ratio was used to evaluate tissue edema.

[0124] 2.3.3 Detection of inflammatory factor levels

[0125] Blood was drawn from the heart and the collected blood was placed in a sterile stoppered test tube without anticoagulation. The blood was centrifuged at 3000 rpm for 10 min to separate the serum, which was then processed and stored at -40°C. TNF-α, IL-10, and IL-1β levels were measured using serum stored at -40°C and detected using an enzyme-linked immunosorbent assay (ELISA) kit. The procedure was strictly followed according to the instructions. The optical density was measured at 570 nm using an ELISA reader, and the levels of TNF-α, IL-10, and IL-1β in the serum were calculated based on the established standard curve.

[0126] 2.3.4 Platelet activation index detection

[0127] The serum obtained above was used to detect the serum CD62P, CD63, and TXA2 levels using an ELISA kit.

[0128] 2.4 Statistical Analysis

[0129] Data results are expressed as mean ± standard deviation. The analysis software used was SPSS 22.0 statistical software package. One-way ANOVA was used to compare data between groups, and P < 0.05 was considered statistically significant.

[0130] 3 Results

[0131] 3.1 Effects on pulmonary artery pressure (mPAP) and right ventricular pressure (RVP)

[0132] As shown in Table 1, compared with the control group, the mPAP and RVP levels in the APE group were significantly increased (P < 0.05); compared with the APE group, the mPAP and RVP levels in the LMWH, MLST-L, M, and H groups were significantly decreased (P < 0.05). Among them, the MLST-H and LMWH groups showed comparable effects, and the effects of each dose group of the pulmonoxone were superior to those of the control group. The elevated mPAP and RVP levels in the body due to APE may be related to the large accumulation of inflammatory factors in the body, causing thrombotic arterial hypertension. Lowering the mPAP and RVP levels can reduce pulmonary artery pressure and prevent pulmonary hemodynamic disorders. In this invention, the pulmonoxone can reduce the mPAP and RVP levels, indicating that it can reduce pulmonary artery pressure and prevent thrombosis.

[0133] 3.2 Effects on W / D of Lung Tissue in Each Group

[0134] As shown in Table 1, compared with the control group, the lung tissue W / D ratio was significantly increased in the APE group (P < 0.05); compared with the APE group, the lung tissue W / D ratio was significantly decreased in the LMWH, MLST-L, M, and H groups in that order (P < 0.05). Among them, the MLST-H and LMWH groups showed comparable effects, and the effects of each dose group of the pulmonol were better than those of the control group. This indicates that the pulmonol reduces pulmonary edema, improves lung function, inhibits inflammatory response, and protects against lung damage.

[0135] Table 1. mPAP, RVP, and lung tissue W / D levels in each group

[0136]

[0137] Compared with the control group, * P<0.05, compared with the APE group, # P<0.05, compared with the LMWH group, @P<0.05.

[0138] 3.3 Effects on inflammatory factors

[0139] The levels of inflammatory factors in each group of mice are shown in the figure. Figure 1 , Figure 2 and Figure 3 . Figure 1 , Figure 2 and Figure 3 It can be seen that, compared with the control group, the APE group showed significantly increased levels of TNF-α and IL-1β, and significantly decreased levels of IL-10 (P < 0.05). Compared with the APE group, the LMWH, MLST-L, M, and H groups showed significantly decreased levels of TNF-α and IL-1β, and significantly increased levels of IL-10 (P < 0.05). Among them, the MLST-H and LMWH groups showed comparable effects, while the comparative groups showed poor effects compared with each dose group of the pulmonase. The inflammatory response triggered by emboli entering the pulmonary artery is a key element in the pathogenesis of APE. TNF-α and IL-1β are inflammatory factors released by pro-inflammatory alveolar macrophages, promoting the inflammatory response, while the anti-inflammatory mediator IL-10 released by anti-inflammatory macrophages can alleviate the inflammatory response. The pulmonase of this invention can reduce TNF-α and IL-1β levels, alleviate the inflammatory response of APE, thereby improving pulmonary hemodynamics and gas exchange function, reducing the release of inflammatory factors, alleviating the inflammatory response, and thus protecting against inflammatory lung injury caused by APE.

[0140] 3.4 Effects of platelet activation indices on different groups

[0141] Table 2 shows that compared with the control group, the levels of CD62P, CD63, and TXA2 in the APE group were significantly increased (P < 0.05); compared with the APE group, the levels of CD62P, CD63, and TXA2 in the LMWH, MLST-L, M, and H groups were significantly decreased (P < 0.05), with the MLST-H and LMWH groups showing comparable effects. Platelet activation and aggregation are also key factors in the pathogenesis of APE. Inhibiting the expression of D62P and CD63 can reduce platelet aggregation in APE model rats, and TXA2 can be used to reflect the degree of platelet activation and protect against lung tissue damage. The results indicate that the vascular endothelial prophylaxis can inhibit platelet activation and aggregation and protect lung tissue.

[0142] Table 2. Platelet activation index levels in each group

[0143] Grouping CD62P (ng / ml) CD63 (ng / ml) TXA2 (ng / ml) control group 15.72±1.43 35.98±2.04 36.14±2.43 APE group <![CDATA[43.82±1.16 * ]]> <![CDATA[88.35±3.12 * ]]> <![CDATA[90.76±3.56 * ]]> LMWH Group <![CDATA[17.45±1.32 # ]]> <![CDATA[39.85±1.34 # ]]> <![CDATA[45.47±2.94 # ]]> MLST-L <![CDATA[30.49±1.74 *#@ ]]> <![CDATA[58.33±2.62 *#@ ]]> <![CDATA[60.25±3.47 *# ]]> MLST-M <![CDATA[25.56±1.96 *# ]]> <![CDATA[51.58±1.96 *# ]]> <![CDATA[55.06±2.25 *# ]]> MLST-H <![CDATA[20.12±1.70 # ]]> <![CDATA[45.43±1.92 *# ]]> <![CDATA[50.13±2.17 *# ]]> Comparative Example 4 Groups <![CDATA[33.15±1.12 *#@ ]]> <![CDATA[78.92±3.73 *@ ]]> <![CDATA[65.33±3.12 *#@ ]]> Comparative Example 5 Groups <![CDATA[36.12±1.43 *@ ]]> <![CDATA[66.43±2.56 *#@ ]]> <![CDATA[78.21±4.43 *@ ]]>

[0144] Compared with the control group, * P<0.05, compared with the APE group, # P<0.05, compared with the LMWH group, @P<0.05.

[0145] II. Clinical Data

[0146] 1. General Information

[0147] Three hundred patients with pulmonary embolism were selected and randomly divided into two groups: a treatment group and a control group.

[0148] Case screening criteria:

[0149] (1) Those with chest tightness and difficulty breathing that cannot be explained by other diseases;

[0150] (2) Blood gas analysis showed low PaO2, low PaCO2, and high pH.

[0151] (3) Radionuclide examination showed perfusion defects distributed in lung segments;

[0152] (4) Spiral CT showed pulmonary embolism.

[0153] 2. Treatment methods

[0154] 300 patients with pulmonary embolism within 2 weeks of onset were given 5000U of low molecular weight heparin daily. The treatment group also took Mailuoshutong pills orally according to the instructions.

[0155] 3. Criteria for Evaluating Therapeutic Effect

[0156] Cure: Symptoms such as difficulty breathing disappear; the number of defective lung segments on radionuclide lung perfusion imaging completely disappears or less than one remains; blood gas analysis shows that PaO2 and PaCO2 return to normal.

[0157] Significant effect: Dyspnea disappears or is significantly reduced, blood gas analysis shows that PaO2 and PaCO2 have basically returned to normal, and the number of defective lung segments is reduced by 7-9 on repeat radionuclide lung perfusion imaging or more than 70% of the lung lobes and segments that have recovered perfusion on repeat lung perfusion / ventilation.

[0158] Effective: Dyspnea is significantly reduced, blood gas analysis shows significant improvement in PaO2 and PaCO2, and the number of defective lung segments is reduced by 1-6 on radionuclide lung perfusion imaging, or the number of lobes or segments with restored lung perfusion / ventilation is less than 70% on follow-up examination;

[0159] Ineffective: No significant improvement in symptoms or death.

[0160] 4. Results

[0161] Control group: 109 cases were cured, 16 cases showed significant improvement, 21 cases showed improvement, and 4 cases were ineffective.

[0162] Treatment group: 128 cases were cured, 11 cases showed significant improvement, 10 cases showed improvement, and 1 case showed no improvement;

[0163] 5. Typical Cases

[0164] Ms. Yang, 63 years old, presented with symptoms including shortness of breath and chest pain, with a course of illness of one year. She began taking the Velocitrate Relief Granules of this invention in September 2020. After three courses of treatment, she experienced significant relief from shortness of breath, reduced chest pain, and smoother breathing. After two more courses of treatment, all symptoms completely disappeared, achieving clinical cure, and she discontinued medication. Follow-up to date has shown no recurrence.

[0165] Ms. Teng, 55 years old, had a six-month history of illness, presenting with shortness of breath, cyanosis of the lips, and moist rales on lung auscultation, occasionally accompanied by pulmonary vascular murmurs. She began taking the Pulse-Soothing Pills of this invention in December 2023. After three courses of treatment, the cyanosis subsided, the lung rales and murmurs significantly decreased, and her breathing became more stable. After continuing medication for another three courses, her clinical symptoms completely disappeared, and she has not relapsed to date.

Claims

1. The use of a vasodilator in the preparation of a drug for treating pulmonary embolism, characterized in that, The aforementioned meridian-soothing preparation is mainly made from Astragalus membranaceus, Lonicera japonica, Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, Glycyrrhiza uralensis, Hirudo medicinalis, Scolopendra subspinipes, and Scorpion.

2. The use as described in claim 1, characterized in that, The aforementioned meridian-clearing preparation is made from the following traditional Chinese medicines in the indicated weight ratios: Astragalus membranaceus 400-900 parts by weight, Lonicera japonica 400-900 parts by weight, Phellodendron chinense 200-500 parts by weight Atractylodes lancea 200-500 parts by weight, Coix lacryma-jobi 400-900 parts by weight, Scrophularia ningpoensis 400-900 parts by weight Angelica sinensis 200-500 parts by weight, Paeonia lactiflora 200-500 parts by weight, Glycyrrhiza uralensis 50-150 parts by weight Leeches 200-500 parts by weight, centipedes 15-40 parts by weight, and whole scorpions 50-150 parts by weight.

3. The use according to claim 2, characterized in that, The aforementioned meridian-clearing preparation is made from the following traditional Chinese medicines in the indicated weight ratios: Astragalus membranaceus 833 parts by weight, Lonicera japonica 833 parts by weight, Phellodendron chinense 417 parts by weight Atractylodes lancea 417 parts by weight, Coix lacryma-jobi 833 parts by weight, Scrophularia ningpoensis 833 parts by weight Angelica sinensis 417 parts by weight, Paeonia lactiflora 417 parts by weight, Glycyrrhiza uralensis 138 parts by weight Leech 417 parts by weight, centipede 33 parts by weight, whole scorpion 138 parts by weight.

4. The use according to claim 2, characterized in that, The aforementioned meridian-clearing preparation is made from the following traditional Chinese medicines in the indicated weight ratios: Astragalus membranaceus 500 parts by weight, honeysuckle 500 parts by weight, and phellodendron chinense 250 parts by weight Atractylodes lancea 250 parts by weight, Coix lacryma-jobi 500 parts by weight, Scrophularia ningpoensis 500 parts by weight Angelica sinensis 250 parts by weight, Paeonia lactiflora 250 parts by weight, Glycyrrhiza uralensis 83 parts by weight Leech 250 parts by weight, centipede 20 parts by weight, whole scorpion 83 parts by weight.

5. The use according to claim 1, characterized in that, The pulmonary embolism is selected from one or more of acute pulmonary embolism and subacute pulmonary embolism.

6. The use according to any one of claims 1-5, characterized in that, The applications include one or more of the following: dissolving pulmonary vascular thrombi, inhibiting new thrombus formation, improving pulmonary circulation, reducing pulmonary hypertension, and improving respiratory function.

7. The use according to any one of claims 1-6, characterized in that, The aforementioned meridian-soothing preparation is prepared using the following method: Astragalus membranaceus, Lonicera japonica, Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, Glycyrrhiza uralensis raw medicinal materials, along with 1 / 2 of the prescription amount of leeches, centipedes, and scorpions, are extracted by steam distillation, decoction in water, and ethanol reflux to obtain an extract. After drying and pulverizing, the extract is mixed with the remaining 1 / 2 of the prescription amount of finely powdered leeches, centipedes, and scorpions, and pharmaceutically acceptable excipients are added to prepare a clinically acceptable dosage form.

8. The use according to claim 7, characterized in that, The meridian-relieving preparation is prepared using the following method: A. Weigh out the prescribed amounts of honeysuckle, atractylodes, scrophularia, angelica, and white peony root slices, add water and distill for 6-8 hours, collect the volatile oil, and set aside the distilled aqueous solution and residue. B. Weigh out the prescribed amounts of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, Glycyrrhiza uralensis, and 1 / 2 of the prescribed amounts of Hirudo medicinalis, Scolopendra subspinipes, and Buthus martensii. Combine these with the dregs obtained in step A, add 6-12 times the amount of water, and decoct 2-3 times, 1-3 hours each time. Combine the decoctions, filter, and set aside. C. Combine the aqueous solution after distillation in step A with the decoction in step B, concentrate to obtain a concentrated solution, add ethanol to make the alcohol content reach 60%-70%, let stand for 24-36 hours to allow it to fully precipitate, collect the supernatant, filter, concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and pulverize it into a dry powder. D. Grind the remaining 1 / 2 of the prescription amount of leeches, centipedes, and scorpions into fine powder and set aside; E. Mix the fine powder of medicinal materials obtained in step D and the dry powder obtained in step C, add the volatile oil from step A, and prepare a clinically acceptable dosage form by directly or by adding pharmaceutically acceptable excipients through conventional processes.

9. The use according to claim 8, characterized in that, The clinically acceptable dosage form is one of granules, tablets, pellets, micro-pellets, or capsules.

10. The use as described in any one of claims 1-9, characterized in that, The aforementioned preparations for promoting blood circulation include, but are not limited to, blood circulation granules and blood circulation pills.

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