A Chinese medicine composition for treating cor pulmonale

Abstract

The invention relates to a traditional Chinese medicine composition for treating cor pulmonale. The active ingredients of the traditional Chinese medicine composition comprise the following raw materials in parts by weight: 8-12 parts of ginseng, 12-18 parts of poria, 4-10 parts of atractylodes macrocephala, 5-10 parts of cinnamon twig, 7-11 parts of roasted liquorice root, 9-15 parts of scutellaria baicalensis seeds, 2-8 parts of jujube, 3-8 parts of peach kernel, 12-18 parts of salvia miltiorrhiza and 7-15 parts of pinellia tuber. The traditional Chinese medicine composition follows the medication principle of "monarch, minister, assistant and messenger" of traditional Chinese medicine, replenishes heart qi, unblocks heart meridians, descends lung qi and resolves phlegm, and has a good therapeutic effect on cor pulmonale.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and more specifically, to a traditional Chinese medicine composition for treating cor pulmonale. Background Art

[0002] Chronic pulmonary heart disease (CPHD) has become an increasingly serious public problem, threatening the health and quality of life of people around the world. The disease has a high incidence rate and is on the rise. The condition is serious, prone to recurrence, and has a poor prognosis, which increases the economic burden on patients. Epidemiological surveys show that about 330 million patients in China suffer from cardiovascular diseases, of which 5 million are CPHD patients.

[0003] The World Health Organization defines CPHD as a disease that causes right ventricular hypertrophy and may further lead to heart failure due to diseases that affect lung function or structure. Its main pathological mechanism is pulmonary hypertension (PAH) caused by respiratory diseases or hypoxia. From the perspective of disease progression, hypoxia can cause pulmonary vasoconstriction and pulmonary vascular remodeling, leading to PAH. PAH can also react on the vascular wall, promoting compensatory hypertrophy and proliferation of vascular-related cells, thereby further aggravating pulmonary vascular remodeling, forming a vicious cycle, and ultimately leading to the occurrence and development of CPHD. Surveys and studies have shown that the incidence of CPHD patients in China is around 0.46%, and the probability of PAH developing into CPHD and death in the late stage is as high as 50%. From this point of view, CPHD is becoming one of the most important public health issues in my country today.

[0004] Currently, Western medicine treatment for CPHD mainly focuses on symptomatic supportive treatment such as controlling infection, maintaining airway patency, improving respiratory function, correcting hypoxia and carbon dioxide retention, controlling respiratory failure and heart failure, and preventing and treating complications. However, Western medicine treatment alone has problems such as serious side effects, drug resistance, and superinfection.

[0005] In recent years, although significant progress has been made in the treatment of PAH, which has improved the prognosis of PAH patients, there is still a lack of specific methods for the treatment of CPHD. The anti-PAH drugs currently used in clinical practice mainly include prostacyclin analogs, prostacyclin receptor agonists, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and soluble guanylate cyclase receptor activators, but all of them have certain problems. In recent years, clinical diagnosis and treatment of PH have made certain progress, and drug development is also ongoing, but there is still an urgent need for low-cost, clear-target, and effective drugs. Summary of the invention

[0006] Based on the above technical problems existing in the prior art, the present invention provides a traditional Chinese medicine composition for treating cor pulmonale, which can replenish heart qi, unclog heart meridians, reduce lung qi and resolve phlegm, and has a good therapeutic effect on cor pulmonale.

[0007] In order to achieve the above object, the technical solution of the present invention is as follows:

[0008] A traditional Chinese medicine composition for treating cor pulmonale, wherein the active ingredients include the following raw materials in parts by weight: 8-12 parts of ginseng, 12-18 parts of poria, 4-10 parts of atractylodes macrocephala, 5-10 parts of cinnamon twig, 7-11 parts of roasted liquorice, 9-15 parts of scutellaria baicalensis seeds, 2-8 parts of jujube, 3-8 parts of peach kernel, 12-18 parts of salvia miltiorrhiza and 7-15 parts of pinellia ternata.

[0009] In some embodiments, the active ingredients of the traditional Chinese medicine composition include the following raw materials in parts by weight: 9 parts of ginseng, 15 parts of Poria cocos, 9 parts of Atractylodes macrocephala, 6 parts of cinnamon twig, 9 parts of roasted liquorice, 12 parts of Lemongrass seeds, 5 parts of jujube, 6 parts of peach kernel, 15 parts of Salvia miltiorrhiza and 9 parts of Pinellia ternata.

[0010] In some embodiments, the active ingredients of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 8-12 parts of ginseng, 12-18 parts of Poria cocos, 4-10 parts of Atractylodes macrocephala, 5-10 parts of cinnamon twig, 7-11 parts of roasted licorice, 9-15 parts of Lemongrass seeds, 2-8 parts of jujube, 3-8 parts of peach kernel, 12-18 parts of Salvia miltiorrhiza and 7-15 parts of Pinellia ternata.

[0011] In some embodiments, the active ingredients of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 9 parts of ginseng, 15 parts of Poria cocos, 9 parts of Atractylodes macrocephala, 6 parts of cinnamon twig, 9 parts of roasted liquorice, 12 parts of Lemongrass seeds, 5 parts of jujube, 6 parts of peach kernel, 15 parts of Salvia miltiorrhiza and 9 parts of Pinellia ternata.

[0012] In some embodiments, the traditional Chinese medicine composition is a preparation made from the powder of the raw material drug, the water or organic solvent extract of the raw material drug in the weight ratio as the active ingredient, and pharmaceutically acceptable excipients.

[0013] In some embodiments, the Chinese medicine composition is a decoction, granules, pills, tablets or capsules.

[0014] In some embodiments, the cor pulmonale is chronic cor pulmonale.

[0015] The pharmacological effects of the present invention are as follows:

[0016] Ginseng: sweet, slightly bitter, neutral, enters the spleen, lung, and heart meridians. It greatly replenishes vital energy, restores the pulse and consolidates the body, nourishes the spleen and lungs, promotes the production of body fluids, and calms the mind. It is used for physical weakness and fainting, cold limbs and weak pulse, spleen deficiency and poor appetite, lung deficiency and wheezing and coughing, thirst due to loss of body fluids, internal heat and thirst, long-term illness and weakness, palpitations and insomnia, impotence and cold uterus; heart failure, cardiogenic shock.

[0017] Atractylodes macrocephala: bitter, sweet, warm, enters the spleen and stomach meridians. Strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating, and stabilizes the fetus. Used for spleen deficiency, poor appetite, abdominal distension and diarrhea, phlegm and fluid, dizziness and palpitations, edema, spontaneous sweating, and restless fetus.

[0018] Cinnamon twig: pungent, sweet, warm, enters the heart, lung, and bladder meridians. It induces sweating and relieves muscle tension, warms and dredges the meridians, helps yang and transforms qi, and balances and descends qi. It is used for colds, cold pain in the abdomen, amenorrhea due to cold blood, joint pain, phlegm and fluid retention, edema, palpitations, and running pig.

[0019] Tinglizi: pungent, bitter, extremely cold, enters the lung and bladder meridians. It can relieve lung and asthma, promote water circulation and reduce swelling. It is used for phlegm blocking the lung, asthma, cough and sputum, chest and flank distension, inability to lie flat, chest and abdominal edema, urinary difficulty; edema caused by cor pulmonale.

[0020] Poria: sweet, light, neutral, enters the heart, lung, spleen, and kidney meridians. It promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind. It is used for edema, oliguria, phlegm and fluid, palpitations, spleen deficiency, poor appetite, loose stools, restlessness, palpitations, and insomnia.

[0021] Roasted Licorice: sweet, neutral, enters the heart, lung, spleen, and stomach meridians. Nourishes the spleen and stomach, replenishes qi and restores pulse. Used for spleen and stomach weakness, fatigue, palpitations, and irregular pulse.

[0022] Jujube: sweet, warm, enters the spleen and stomach meridians. It replenishes the middle qi, nourishes the blood and calms the mind. It is used for spleen deficiency, poor appetite, fatigue, loose stools, and irritability in women.

[0023] Danshen: bitter, slightly cold, enters the heart and liver meridians. Removes blood stasis and relieves pain, promotes blood circulation and menstruation, clears the heart and relieves restlessness. Used for irregular menstruation, amenorrhea, dysmenorrhea, accumulation of masses, stabbing pain in the chest and abdomen, pain caused by heat arthralgia, swelling and pain of sores, restlessness and insomnia; hepatosplenomegaly, angina pectoris.

[0024] Peach kernel: bitter, sweet, neutral, enters the heart, liver, and large intestine meridians. It promotes blood circulation and removes blood stasis, moistens the intestines and promotes bowel movements. It is used for amenorrhea, dysmenorrhea, lumps and masses, injuries from falls, and constipation due to dry intestines.

[0025] Banxia: pungent, warm. Enters the spleen, stomach, and lung meridians. Drys dampness and resolves phlegm. Used for cough and asthma due to excessive phlegm, dizziness and palpitations due to phlegm, dizziness due to wind phlegm, and headache due to phlegm.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The Chinese medicine composition of the present invention follows the medication principle of "monarch, minister, assistant and envoy" of Chinese medicine. The ginseng and white atractylodes in the prescription are sweet and warm, and are used together to nourish the heart, spleen and lung qi, and are the monarch medicine; cinnamon twig enters the heart, warms and unblocks the heart yang, makes the heart meridian unobstructed to prevent blood stasis, so that the heart qi is unobstructed and palpitations are relieved; scutellaria baicalensis enters the lung, purges turbid qi, opens knots and promotes diuresis, so that the lung qi is unobstructed and descends, and both phlegm and water are discharged, so that wheezing can be relieved and swelling can be reduced, and they are the minister medicine; tuckahoe is used to penetrate dampness and strengthen the spleen, pinellia tuber is used to dry dampness and resolve phlegm, roasted liquorice root helps heart fire and strengthens the spleen and replenishes qi, jujube is sweet and warm to calm the middle and moderate the power of the medicine, so that the evil is expelled without hurting the body, salvia miltiorrhiza and peach kernel enter the heart meridian, warm and unblock the heart meridian, promote blood circulation and promote diuresis, and are the adjuvant medicines; the combination of the medicines can play the effects of nourishing the heart qi and unblocking the heart meridian, descending the lung qi and resolving phlegm, and has a good therapeutic effect on the treatment of chronic pulmonary heart disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the test result of the effect of Feixin Decoction on the echocardiographic indexes of rats in each group;

[0029] Figure 2 This is the test result of the effect of Feixin decoction on the hemodynamics of rats in each group;

[0030] Figure 3 These are the test results of the effect of Feixin Decoction on the heart and pulmonary vascular remodeling of each group of rats. DETAILED DESCRIPTION

[0031] Many specific details are set forth in the following description to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar modifications without violating the connotation of the present invention, so the present invention is not limited to the specific implementation disclosed below.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0033] Example 1

[0034] A Chinese medicine composition for treating cor pulmonale, comprising the following raw materials:

[0035] Ginseng 9g, Poria 15g, Atractylodes macrocephala 9g, Cinnamon twig 6g, Roasted Licorice root 9g, Lemongrass seed 12g, Jujube 5g, Peach kernel 6g, Salvia miltiorrhiza 15g, Pinellia ternata 9g;

[0036] According to the prescription, ginseng, Poria, Atractylodes, cinnamon twig, roasted liquorice, scutellaria baicalensis, jujube, peach kernel, salvia miltiorrhiza and pinellia ternata were weighed respectively, combined, and water was added and decocted twice. Once, 10 times the amount of water was added, soaked for 0.5 h, and decocted for 1 h (kept slightly boiling for 1 h). The second time, 8 times the amount of water was added, decocted for 1 h (kept slightly boiling for 1 h), the decoctions were combined, filtered, the filtrate was concentrated, and cooled to room temperature to prepare an extract containing 0.77 g / mL of crude drug to obtain a traditional Chinese medicine composition.

[0037] Example 2

[0038] A Chinese medicine composition for treating cor pulmonale, comprising the following raw materials:

[0039] Ginseng 10g, Poria 12g, Atractylodes macrocephala 5g, Cinnamon twig 8g, Radix Glycyrrhizae Radix 10g, Semen Lepidii 15g, Jujube 8g, Semen Pruni 5g, Salvia miltiorrhiza 12g, and Pinellia ternata 12g;

[0040] According to the prescription, ginseng, Poria, Atractylodes macrocephala, cinnamon twig, roasted liquorice, scutellaria baicalensis, jujube, peach kernel, salvia miltiorrhiza and pinellia ternata were weighed respectively, combined, and water was added and decocted twice. Once, 10 times the amount of water was added, soaked for 0.5 h, and decocted for 1 h (kept slightly boiling for 1 h). The second time, 8 times the amount of water was added, decocted for 1 h (kept slightly boiling for 1 h), the decoctions were combined, filtered, the filtrate was concentrated, and cooled to room temperature to prepare an extract containing 0.78 g / mL of crude drug to obtain a traditional Chinese medicine composition.

[0041] Example 3

[0042] A Chinese medicine composition for treating cor pulmonale, comprising the following raw materials:

[0043] Ginseng 9kg, Poria 15kg, Atractylodes macrocephala 9kg, Cinnamon twig 6kg, Roasted Licorice root 9kg, Lemongrass seed 12kg, Jujube 5kg, Peach kernel 6kg, Salvia miltiorrhiza 15kg, Pinellia ternata 9kg;

[0044] Weigh ginseng, Poria, Atractylodes macrocephala, cinnamon twig, roasted liquorice, scutellaria baicalensis, jujube, peach kernel, salvia miltiorrhiza and pinellia ternata respectively according to the prescription, add water and boil twice, add 10 times the amount of water once, soak for 0.5h, boil for 1h (keep slightly boiling for 1h), add 8 times the amount of water for the second time, boil for 1h (keep slightly boiling for 1h), combine the decoctions, filter, concentrate the filtrate, concentrate the filtrate to a relative density of 1.15 (80℃, thermal measurement), cool to room temperature, and obtain a thick paste;

[0045] Take 45 kg of white sugar powder (passed through 80 mesh), add the thick paste, mix well, granulate, pass through a 16-mesh sieve, bake the granules under the sieve at 80°C for 4 hours, sieve the granules (passed through a 16-mesh sieve) to obtain granules, and pack the granules in 12 g bags to obtain granules.

[0046] Example 4

[0047] A Chinese medicine composition for treating cor pulmonale, comprising the following raw materials:

[0048] Ginseng 9kg, Poria 15kg, Atractylodes macrocephala 9kg, Cinnamon twig 6kg, Roasted Licorice root 9kg, Lemongrass seed 12kg, Jujube 5kg, Peach kernel 6kg, Salvia miltiorrhiza 15kg, Pinellia ternata 9kg;

[0049] Weigh ginseng, Poria, Atractylodes macrocephala, cinnamon twig, roasted liquorice, scutellaria baicalensis, jujube, peach kernel, salvia miltiorrhiza and pinellia ternata respectively according to the prescription, add water and boil twice, add 10 times the amount of water once, soak for 0.5h, boil for 1h (keep slightly boiling for 1h), add 8 times the amount of water for the second time, boil for 1h (keep slightly boiling for 1h), combine the decoctions, filter, concentrate the filtrate, concentrate the filtrate to a relative density of 1.15 (80℃, thermal measurement), cool to room temperature, and obtain a thick paste;

[0050] Take 40 kg of white sugar powder (passed through 80 mesh), add the thick paste, mix well, granulate, pass through a 16-mesh sieve, bake the granules under the sieve at 80°C for 4 hours, granulate (pass through a 16-mesh sieve) to obtain granules, and press the granules into tablets (each tablet weighs 0.5 g) to obtain tablets.

[0051] Comparative Example 1

[0052] The prescription with patent application number ZL201210192453.X is: 6 parts of scutellaria baicalensis, 20 parts of water centipede, 10 parts of ophiopogon japonicus, 12 parts of cinnamon twig, 6 parts of schisandra chinensis, 6 parts of orange peel, 10 parts of white peony root, 10 parts of perilla root, 10 parts of light soya bean sprouts, 10 parts of aconite root, 10 parts of poria, 5 parts of atractylodes macrocephala, 6 parts of liquorice, 10 parts of ginseng, and 4 parts of jujube.

[0053] A 0.78 g / mL drug solution was prepared according to the method of Example 1.

[0054] Pharmacological experiments

[0055] In order to further evaluate the efficacy of the Chinese medicine composition of the present application, pharmacological experiments were conducted on the drugs of Example 1 and Comparative Example 1, as follows:

[0056] 1. Materials and Methods

[0057] 1.1 Animals

[0058] 60 SPF male SD rats (200 ± 20 g) were purchased from Hunan Slake Experimental Animal Technology Company (SCXK (Xiang) 2019-0004). All animals were kept in the Animal Experiment Center of the First Affiliated Hospital of Hunan University of Chinese Medicine (experimental unit license: SYXK (Xiang) 2020-0010) for one week at a temperature of 25 °C and a humidity of 40% to 60%. Rats were free to eat and drink.

[0059] 1.2 Drugs

[0060] Comparative patent prescription (Comparative Example 1), Junren Bufei Yixin Fang (Example 1, hereinafter referred to as Feixin Fang FXD) decoction pieces were purchased from the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine;

[0061] Sildenafil citrate tablets (National Medicine Standard No. Z10960063, 0.1 g / tablet, Pfizer, USA) were prepared with distilled water into a 2.5 mg·mL-1 solution and refrigerated for later use.

[0062] 1.3 Model replication

[0063] 60 rats were randomly divided into a normal group (10 rats, NC) and a model group (50 rats). The model group rats were treated with chronic hypoxia (intermittent hypoxia, 10% O2, 4 weeks), and the model rats were randomly divided into a model group (HX), a sildenafil group (XDNF), a low-dose Feixinfang group (FXD1 / 2), a medium-dose Feixinfang group (FXD) and a high-dose Feixinfang group (FXD2), and a patent prescription group (ZLDBF) were compared, with 10 rats in each group.

[0064] 1.4 Administration

[0065] The animal dosage was calculated based on the ratio of 70kg human body surface area. The rats in the low, medium and high dose groups of Feixin Decoction were given intragastric administration of Feixin Decoction liquid equivalent to 1 / 2, 1 and 2 times of adult dose (3.87g·kg-1, 7.74g·kg-1 and 15.48g·kg-1, respectively), compared with the patent prescription liquid equivalent to 1 times of adult dose (11.00g·kg-1). The rats in the sildenafil group were given intragastric administration of sildenafil liquid equivalent to adult dose (0.025g·kg-1).

[0066] The model group was given an equal volume of distilled water (the intragastric volume was 10 mL kg-1).

[0067] The drugs were administered by gavage 1 hour after model establishment, once a day, for 28 consecutive days.

[0068] 1.5 Sampling and index testing

[0069] 1.5.1 Echocardiographic index detection

[0070] One hour after the last intragastric administration, the rats were anesthetized by isoflurane inhalation. The pulmonary artery acceleration time (PAT), pulmonary artery ejection time (PET), tricuspid valve annular systolic displacement (TAPSE), and right ventricular anterior wall thickness at end diastole (RVAWT) were measured by small animal B-ultrasound machine.

[0071] 1.5.2 Hemodynamic testing

[0072] After completing the echocardiographic test, the rat right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were measured by right heart catheterization through the external jugular vein. The multichannel physiology instrument was pre-adjusted, the pressure channel was selected, the PE-50 catheter was connected and the equipment was adjusted to zero. The external jugular vein was separated and the distal end was ligated. The catheter was pre-flushed with heparin saline, a "V"-shaped incision was made from the external jugular vein, and the catheter was slowly inserted into the right ventricle through the superior vena cava and then to the pulmonary artery. The physiological recorder recorded the experimental results and measured RVSP and mPAP.

[0073] 1.5.3 Detection of right ventricular and pulmonary vascular remodeling indicators

[0074] Right ventricular hypertrophy index (RVHI): The rats were killed and the hearts were separated. The masses of the right ventricle (RV) and left ventricle (LV) plus the septum (S) were weighed. RVHI = RV / (LV+S).

[0075] Pulmonary arteriolar wall thickness as a percentage of vessel outer diameter (WT%): The left lung of each group of rats was taken for HE staining, and the morphological changes of pulmonary arterioles were observed under an optical microscope (×400). Pulmonary arterioles with a diameter of 50-100 μm were selected for observation and photography, and WT% was calculated using Image Pro Plus 6.0 software: WT% = 2×inner wall thickness / vessel diameter×%.

[0076] 1.6 Statistical analysis

[0077] All data were expressed as `x±S, and SPSS25.0 software was used for statistical analysis. One-way ANOVA was used for inter-group comparisons when variance was equal, and Tukey's multiple comparison analysis was used for unequal variance. Tamhane's T2 test was used for unequal variance.

[0078] 2 Results

[0079] 2.1 Effects of Feixin Decoction on echocardiographic parameters of rats in each group

[0080] like Figure 1 As shown in the data, compared with the normal group, the PAT / PET and TAPSE in the model group were significantly decreased (P < 0.01), and the RVAWT was significantly increased (P < 0.001); compared with the model group, the PAT / PET and TAPSE in the sildenafil group, the control patent prescription group, and the low, medium, and high dose groups of the Feixin prescription were increased (P < 0.01), and the RVAWT in the medium dose group of the Feixin prescription was significantly decreased (P < 0.01); compared with the high, medium, and low dose groups of the Feixin prescription, the medium dose group had the best therapeutic effect.

[0081] 2.2 Effects of Feixinfang on hemodynamics of rats in each group

[0082] like Figure 2As shown in the figure, compared with the normal group, the RVHI and WT% in the model group increased significantly (P < 0.01). Compared with the model group, the RVHI and WT% in the sildenafil group, the control patent prescription group, and the low, medium, and high dose groups of Feixin Decoction decreased significantly (P < 0.05, P < 0.01), and there was no difference in the high, medium, and low dose groups.

[0083] 2.3 Effects of Feixin Decoction on cardiac and pulmonary vascular remodeling in rats of each group

[0084] like Figure 3 As shown in the figure, compared with the normal group, the RVHI and WT of the model group were significantly increased (P < 0.01). Compared with the model group, the RVHI and WT of the sildenafil group, the control patent prescription group, and the low, medium, and high dose groups of Feixin Decoction were significantly reduced (P < 0.05, P < 0.01); compared with the high, medium, and low dose groups, the medium dose group could significantly improve WT (P < 0.01).

[0085] 3. Conclusion

[0086] Feixin decoction can improve hemodynamics, right heart function, right ventricular and pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension, and the medium-dose group has the best therapeutic effect.

[0087] Clinical Research

[0088] 1 Materials and methods

[0089] 1.1 Design Method

[0090] Single-center, randomized controlled clinical trial method. All cases were selected from 600 outpatients and inpatients of the Department of Respiratory Medicine of the First Affiliated Hospital of Hunan University of Chinese Medicine, and 59 cases were randomly selected and arranged in a 1:1 ratio as the observation group and the control group.

[0091] 1.2 Case selection and withdrawal

[0092] a) Western medicine diagnostic standards

[0093] With reference to the "2018 Primary Diagnosis and Treatment Guidelines for Chronic Pulmonary Heart Disease" and "Clinical Diagnosis and Treatment Guidelines·Respiratory Diseases" (edited by the Chinese Medical Association, People's Medical Publishing House), chronic pulmonary heart disease is divided into the compensated cor pulmonale stage, the decompensated cor pulmonale stage, and the right heart failure stage.

[0094] b) Diagnostic criteria for lung qi deficiency, phlegm, stasis and water retention

[0095] With reference to the document "GB / T16751.1-1997" TCM clinical diagnosis and treatment terminology and the textbooks of higher medical colleges "Chinese Medicine Diagnosis", "Chronic Cor Pulmonary Heart Disease TCM Syndrome Diagnostic Criteria (2012 Edition)", "Chronic Cor Pulmonary Heart Disease TCM Diagnosis and Treatment Guidelines (2014 Edition)", and combined with the functions and indications of Feixin Granule, it was formulated. Main symptoms: cough, expectoration, shortness of breath, blue lips and nails; secondary symptoms: fatigue, palpitations, spontaneous sweating, fear of wind, chest tightness, edema; tongue and pulse: pale purple or dark purple tongue or with spots and ecchymosis, thick and greasy fur, thin and stringy pulse, and tortuous and rough sublingual collaterals.

[0096] c) Inclusion criteria

[0097] ① Aged between 40 and 80, and with the ability to move independently; ② Meet the Western medical diagnostic criteria for chronic cor pulmonale; ③ Meet the TCM diagnostic criteria for lung qi deficiency and phlegm and blood stasis; ④ 6MWD baseline ≥100m and <450m;

[0098] d) Exclusion criteria

[0099] ①. Serious primary diseases of important organs; ②. Receiving systemic (e.g., oral, intravenous or intramuscular) corticosteroids or antibiotics (including macrolide antibiotics) treatment in the previous 8 weeks; ③. Pregnant or lactating women; patients with malignant tumors, mental or physical disabilities; suspected or confirmed history of alcohol or drug abuse; ④. Diagnosed with cancer, diabetes, infectious diseases, renal or liver dysfunction, gastrointestinal diseases in the past 8 weeks.

[0100] e) Case exclusion criteria

[0101] ① Subjects who did not receive treatment after randomization; ② Subjects who dropped out or were lost to follow-up after randomization, and no data was collected. ③ Subjects who experienced drug-related adverse reactions after taking the medicine, and the researchers believed that the subjects were not suitable for further research. ④ Subjects who did not strictly follow the treatment plan, such as increasing or reducing the number of medications on their own. ⑤ After the case was selected, the researchers found that the subject did not meet the inclusion criteria.

[0102] 1.3 Administration

[0103] a) Name and specification of the investigational drug

[0104] Test drug: Feixin granules (Example 3), specification: 12 g / bag.

[0105] b) Method of administration and course of treatment

[0106] Dosage: Experimental group: On the basis of western medicine treatment, use Feixin granules, 3 times a day, 1 pack each time. Control group: Western medicine basic treatment. Treatment course: Total treatment course is 8 weeks. Follow-up of the number of patients in the two groups who were re-hospitalized 3 months after the end of treatment (times).

[0107] 1.4 Measurement indicators and efficacy evaluation

[0108] a) Demographic information: gender, age, height, weight, fertility status, etc.

[0109] b) Efficacy observation

[0110] ① Pulmonary artery systolic pressure: an echocardiogram was performed at the time of enrollment, 1 month, and 2 months respectively to measure and record the pulmonary artery systolic pressure. The measurement method was as follows: the patient was in the left lateral position and breathed calmly. The probe was placed at the left edge of the sternum between the 2nd and 3rd ribs for scanning, and if necessary, under the xiphoid process. The pulmonary artery pressure was estimated by the tricuspid regurgitation area, and the stenosis of the right ventricular outflow system was excluded. The pulmonary artery systolic pressure = right ventricular systolic pressure;

[0111] ② Arterial blood gas analysis indicators: blood was collected at three time points: at the time of enrollment, 1 month, and 2 months later. Blood was collected in the morning from the radial artery without oxygen inhalation. A fully automatic blood gas analyzer was used to detect and record arterial oxygen partial pressure, carbon dioxide partial pressure, and oxygen saturation indicators (electrode method).

[0112] ③ Pulmonary function test: Pulmonary function classification is based on the standards of the 2020 version of GOLD-Global Initiative. The lung function of patients was counted at three time points: at enrollment, 1 month, and 2 months, including: FEV1, FVC, and FEV1%.

[0113] ④ Six-minute walk test (6MWT): Refer to the guidelines of the American Thoracic Society and conduct it in a 30m long straight corridor, with a chair placed at both ends and in the middle for marking and resting. Before the test, let the subjects familiarize themselves with the test process and environment, and then walk back and forth in the corridor to avoid external interference, and ask the patients to walk as far as possible and complete the longest distance they can within six minutes. During the test, if the subjects have obvious symptoms such as dizziness and shortness of breath, the test will be stopped immediately. At the end of the test, the six-minute walking distance of the subjects and the changes in blood oxygen saturation before and after the test were measured and recorded. Considering the pain caused to patients by repeated blood oxygen saturation tests, the observation index of this experiment only takes the six-minute walking distance.

[0114] ⑤ Comparison of TCM syndrome scores: TCM syndrome scores of the two groups of patients were collected at three time points: at enrollment, 1 month, and 2 months, before and after treatment, and statistical analysis was performed. TCM syndrome efficacy evaluation criteria: The nimodipine method was used for clinical efficacy evaluation, and the calculation formula was:

[0115] Syndrome efficacy rate (score before treatment minus score after treatment) / score before treatment Clinical control: after treatment, symptoms and signs basically disappear, and the patient can participate in normal activities and work;

[0116] Markedly effective: symptoms, signs and auxiliary examination results are significantly improved after treatment;

[0117] Effective: Symptoms, signs and auxiliary examination results improved after treatment.

[0118] Ineffective: Symptoms, signs and auxiliary examination results after treatment were not improved compared with those before treatment.

[0119] c) Safety indicators

[0120] Blood was drawn at the time of enrollment, 1 month, and 2 months later, and routine blood test, urine test, stool test, liver function test (ALT, AST), kidney function test (Cr, BUN), electrocardiogram, and adverse events were performed.

[0121] 1.5 Statistical analysis

[0122] SPSS 22.0 statistical software was used for statistical analysis. All quantitative data were expressed as mean ± standard deviation. The mean of multiple samples was compared by one-way analysis of variance, and Fisher's analysis of variance was used when the variance was equal, and the approximate F test Welch method was used when the variance was unequal; the SNK-q test was used for pairwise comparison of the means of multiple samples when the variance was equal, and Dunnett's T3 test was used when the variance was unequal. The count data were expressed as constituent ratios, and the chi-square test was used for comparison of constituent ratios of multiple samples. The Pearson correlation analysis method was used for correlation analysis. P<0.05 was considered statistically significant.

[0123] 2 Research results

[0124] 2.1 Clinical Data

[0125] A total of 59 patients with cor pulmonale who met the above inclusion criteria were enrolled. As shown in Table 1, in the treatment group, there were 19 males and 10 females; aged 45-80 years; the average course of disease was (15.66±4.29) years, and 19 patients had a history of smoking; in the control group, there were 18 males and 12 females; aged 45-80 years, the average course of disease was (70.2±4.1) years, and 21 patients had a history of smoking. There was no significant difference in age, gender, smoking history, and course of disease between the two groups (P>0.05), and the two groups were comparable.

[0126] Table 1 Comparison of baseline data between the two groups

[0127]

[0128] 2.2 Efficacy indicators

[0129] (1) Comparison of pulmonary artery pressure between the two groups before and after treatment

[0130] As shown in Table 2, after 1 month of treatment, the pulmonary artery pressure of both the treatment group and the control group decreased compared with that before treatment, but there was no statistical difference compared with that before treatment (P>0.05). After 2 months of treatment, the pulmonary artery pressure of the two groups of patients decreased significantly compared with that before treatment (p<0.05), and there was also statistical significance between the two groups (P<0.05). This suggests that Feixin Decoction has a good effect on reducing pulmonary artery pressure in elderly patients with COPD and PAH in the stable stage.

[0131] Table 2 Comparison of pulmonary artery pressure between the two groups before and after treatment ( mmHg)

[0132]

[0133] Note: Compared with before treatment, t1=2.475, t2=2.597, *P<0.05; compared with the two groups after 2 months of treatment, t=2.343, # P<0.05.

[0134] (2) Comparison of blood gas analysis between the two groups before and after treatment

[0135] As shown in Table 3. After 1 month of treatment, the PaO2 (mmHg) and Pa CO2 (mmHg) of the treatment group and the control group were improved compared with those before treatment, but there was no statistical difference compared with those before treatment (P>0.05). After 2 months of treatment, there were statistical differences in PaO2 (mmHg) and Pa CO2 (mmHg) between the two groups before and after treatment (p<0.05), and there was also statistical significance between the two groups (P<0.05). This suggests that Feixinfang granules have a good effect on improving blood oxygen saturation in elderly patients with COPD and PAH in the stable stage.

[0136] Table 3 Comparison of blood gas analysis between the two groups before and after treatment

[0137]

[0138] Note: Compared with before treatment *P<0.05; Comparison between the two groups after 2 months of treatment # P<0.05.

[0139] (3) Comparison of lung function between the two groups before and after treatment

[0140] As shown in Table 4, after 1 month of treatment, FEV1(L) and FEV1 / FVC(%) of the treatment group and the control group increased compared with those before treatment, but there was no statistical difference compared with those before treatment (P>0.05); after 2 months of treatment, there were statistical differences in FEV1(L) and FEV1 / FVC(%) between the two groups before and after treatment (P<0.05), and there was also statistical significance between the two groups (P<0.05). This suggests that Feixinfang granules have a good effect on improving lung function in elderly patients with COPD and PAH in stable stage.

[0141] Table 4 Comparison of lung function between the two groups before and after treatment

[0142]

[0143] Note: Compared with before treatment *P<0.05; Comparison between the two groups after 2 months of treatment # P<0.05.

[0144] (4) Comparison of 6MWT distance between the two groups before and after treatment

[0145] As shown in Table 5, after one month of treatment, the six-minute walk distance of the two groups of patients increased, but there was no statistical difference compared with before treatment (P>0.05). After two months of treatment, the six-minute walk distance of the two groups of patients increased, and there was a statistical difference compared with before treatment (P<0.05). After two months of treatment, there was a statistical difference between the two groups (P<0.05), indicating that Guben Wenfei Huoxue Recipe has a good effect on improving the cardiopulmonary function of elderly patients with COPD and PAH in the stable stage.

[0146] Table 5 Comparison of six-minute walk test distance between the two groups before and after treatment ( m)

[0147]

[0148] Note: Compared with before treatment, t1=2.139, t2=2.374, *P<0.05; compared with the two groups after 2 months of treatment, t=2.654, # P<0.05.

[0149] (5) Comparison of TCM efficacy

[0150] A) Comparison of TCM syndrome efficacy

[0151] As shown in Table 6. After 2 months of treatment, the efficacy of TCM syndrome in the two groups was compared. The effective rate (markedly effective) of the Feixin Decoction group was 62.07%, and the effective rate of the control group was 26.67%. The chi-square test showed that there was a significant statistical difference in the effective rate between the two groups (P < 0.01), and the Feixin Decoction group was significantly better than the control group.

[0152] Table 6 Comparison of TCM syndrome efficacy between the two groups

[0153]

[0154]

[0155] B) Comparison of TCM symptom scores between the two groups before and after treatment

[0156] As shown in Table 7. After 1 month of treatment, the TCM symptom scores of the two groups of patients decreased, which was statistically different from before treatment (P < 0.05); after 2 months of treatment, the TCM symptom scores of the two groups of patients decreased, which was significantly different from before treatment (P < 0.05), and the changes in TCM symptom scores between the two groups were also statistically significant (P < 0.05), indicating that Feixin Decoction has a good effect on improving clinical symptoms in elderly patients with COPD and PAH in the stable stage.

[0157] Table 7 Comparison of TCM symptom scores between the two groups before and after treatment ( point)

[0158]

[0159] Note: Compared with before treatment, t1=2.235, t2=2.347, *p<0.05, t1=2.015, t2=1.975, **p<0.01; t=2.446, t2=2.347, **p<0.01 compared with before treatment; t=2.015, t2=1.975, **p<0.01 compared with before treatment; t=2.446, # p<0.05.

[0160] 2.3 Safety evaluation

[0161] During the study, urine and stool routine tests and liver and kidney function tests were performed on patients before treatment, 1 month after treatment, and 2 months after treatment. The chi-square test showed no statistically significant differences in urine and stool routine tests and liver and kidney function related indicators between the two groups before and after treatment (P>0.05). It can be seen that there were no obvious adverse reactions during the treatment of the two groups, and the clinical application was safe.

[0162] 3 Conclusion

[0163] During the entire observation process, no obvious adverse reactions or allergic reactions occurred in the patients in the Feixin Decoction group, indicating that the clinical use of Feixin Decoction is safe and effective.

[0164] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0165] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A Chinese medicine composition for treating cor pulmonale, characterized in that: The active ingredients are prepared from the following raw materials in parts by weight: 8-12 parts of ginseng, 12-18 parts of poria, 4-10 parts of atractylodes, 5-10 parts of cinnamon twig, 7-11 parts of roasted liquorice, 9-15 parts of scutellaria baicalensis seeds, 2-8 parts of jujube, 3-8 parts of peach kernel, 12-18 parts of salvia miltiorrhiza and 7-15 parts of pinellia.

2. The Chinese medicine composition for treating cor pulmonale according to claim 1, characterized in that: The active ingredients are prepared from the following raw materials in parts by weight: 9 parts of ginseng, 15 parts of tuckahoe, 9 parts of atractylodes macrocephala, 6 parts of cinnamon twig, 9 parts of roasted liquorice, 12 parts of scutellaria baicalensis seeds, 5 parts of jujube, 6 parts of peach kernel, 15 parts of salvia miltiorrhiza and 9 parts of pinellia ternata.

3. The Chinese medicine composition for treating cor pulmonale according to any one of claims 1 to 2, characterized in that: The Chinese medicine composition is a preparation made of the powder of the raw material medicine and the water or organic solvent extract of the raw material medicine in the weight ratio as active ingredients, and pharmaceutically acceptable excipients.

4. The Chinese medicine composition for treating cor pulmonale according to claim 3, characterized in that: The Chinese medicine composition is in the form of decoction, granules, pills, tablets or capsules.

5. The Chinese medicine composition for treating cor pulmonale according to any one of claims 1 to 4, characterized in that: The cor pulmonale is a chronic cor pulmonale.

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