A formula for invigorating Qi, warming Yang, and regulating the heart, and its preparation method.

Abstract

This application provides a formula for invigorating qi, warming yang, and regulating the heart, and its preparation method. The formula comprises the following components in parts by weight: cinnamon twig 5-10, codonopsis root 6-14, atractylodes rhizome 5-14, salvia root 6-14, poria cocos 5-14, chuanxiong rhizome 6-14, trichosanthes fruit 5-15, allium macrostemon 6-15, and red peony root 5-10. This technical solution improves exercise capacity and cardiac function.

Description

Technical Field

[0001] This application relates to the field of traditional Chinese medicine technology, and in particular to a formula for invigorating qi, warming yang, and regulating the heart, and its preparation method. Background Technology

[0002] Heart failure with reduced ejection fraction (HFrEF) is a serious clinical syndrome that occurs when various cardiovascular diseases progress to the end stage. Its main pathological manifestations are decreased myocardial contractility, ventricular remodeling, and decreased cardiac output.

[0003] Currently, modern medicine primarily treats heart failure with heart failure renal failure (HFrEF) using neuroendocrine antagonist therapy. In recent years, with continuous updates to heart failure treatment guidelines, the treatment has evolved from the original "golden triangle" to the "new quadruple therapy," and now to the "five golden flowers," which can be summarized as: angiotensin-converting enzyme inhibitors (ACE-I) / angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and diuretics. These ongoing research advancements have significantly reduced the mortality and readmission rates of heart failure. However, in extensive clinical practice, many patients still experience the following problems after receiving standardized treatment: 1. Patients still experience clinical symptoms that severely impact their quality of life, such as shortness of breath, fatigue, and decreased exercise tolerance; 2. Elderly patients often have complex conditions, including multiple underlying diseases, and long-term use of multiple Western medicines may increase the risk of adverse reactions and even lead to medication conflicts; 3. Long-term recurrent illness, high hospitalization rates, and high costs can increase patients' anxiety, uncertainty about the disease's progression, and fear of medical treatment, thus creating a vicious cycle of psychological and physiological distress. Summary of the Invention

[0004] This application provides a formula for invigorating qi, warming yang, and regulating the heart, and its preparation method, which can be used to improve exercise capacity and cardiac function.

[0005] Firstly, a formula for invigorating qi, warming yang, and regulating the heart is provided, comprising the following components in parts by weight: cinnamon twig 5-10, codonopsis pilosula 6-14, atractylodes macrocephala 5-14, salvia miltiorrhiza 6-14, poria cocos 5-14, chuanxiong rhizome 6-14, trichosanthes kirilowii fruit 5-15, allium macrostemon 6-15, and red peony root 5-10.

[0006] The above technical solution includes the following components in parts by weight: cinnamon twig 5-10, codonopsis pilosula 6-14, atractylodes macrocephala 5-14, salvia miltiorrhiza 6-14, poria cocos 5-14, chuanxiong rhizome 6-14, trichosanthes kirilowii fruit 5-15, allium macrostemon 6-15, and red peony root 5-10; which improves exercise capacity and cardiac function.

[0007] In one specific implementation scheme, the components include the following parts by weight: 6 parts cinnamon twig, 10 parts codonopsis root, 10 parts atractylodes rhizome, 10 parts salvia miltiorrhiza root, 10 parts poria cocos, 10 parts chuanxiong rhizome, 10 parts trichosanthes fruit, 10 parts allium macrostemon root, and 6 parts red peony root.

[0008] Secondly, a method for preparing a formula for invigorating qi, warming yang, and regulating the heart is provided, including the following steps:

[0009] Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 20-40 minutes. Filter and collect the filtrate. Add water to the residue, continue heating and boiling, then simmer for 15-30 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain a warming and yang-regulating heart-tonifying medicine.

[0010] In the above technical solution, cinnamon twig, codonopsis, atractylodes macrocephala, salvia miltiorrhiza, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root are boiled, then simmered for 20-40 minutes, filtered, and the filtrate is collected. Water is then added to the residue, and the mixture is heated to a boil again, then simmered for 15-30 minutes, filtered, and the filtrate is retained. The two filtrates are combined to obtain a warming and yang-regulating heart-strengthening medicine, which improves exercise capacity and cardiac function. Attached Figure Description

[0011] Figure 1 A flowchart illustrating the preparation method of the Qi-tonifying, Qi-warming, and heart-regulating formula provided in this application embodiment;

[0012] Figure 2 A flowchart illustrating another method for preparing a Qi-tonifying, Qi-warming, and heart-regulating formula provided in this application embodiment;

[0013] Figure 3 This is a schematic diagram of the granules of the Qi-tonifying and Yang-regulating formula provided in the embodiments of this application. Detailed Implementation

[0014] The present application will now be described in further detail with reference to the accompanying drawings and embodiments. Through these descriptions, the features and advantages of the present application will become clearer and more apparent.

[0015] The term “exemplary” as used herein means “serving as an example, embodiment, or illustration.” Any embodiment illustrated herein as “exemplary” is not necessarily to be construed as superior to or better than other embodiments. Although various aspects of embodiments are shown in the accompanying drawings, the drawings are not necessarily drawn to scale unless specifically indicated otherwise.

[0016] Furthermore, the technical features involved in the different embodiments of this application described below can be combined with each other as long as they do not conflict with each other.

[0017] The following detailed description, with reference to the accompanying drawings, illustrates the embodiments.

[0018] This application provides a formula for invigorating qi and warming yang, which includes the following components in parts by weight: cinnamon twig 5-10, codonopsis pilosula 6-14, atractylodes macrocephala 5-14, salvia miltiorrhiza 6-14, poria cocos 5-14, chuanxiong rhizome 6-14, trichosanthes kirilowii fruit 5-15, allium macrostemon 6-15, and red peony root 5-10.

[0019] The above technical solution includes the following components in parts by weight: cinnamon twig 5-10, codonopsis pilosula 6-14, atractylodes macrocephala 5-14, salvia miltiorrhiza 6-14, poria cocos 5-14, chuanxiong rhizome 6-14, trichosanthes kirilowii fruit 5-15, allium macrostemon 6-15, and red peony root 5-10; which improves exercise capacity and cardiac function.

[0020] In one specific implementation scheme, the components include the following parts by weight: cinnamon twig 4-9, codonopsis pilosula 7-13, atractylodes macrocephala 6-13, salvia miltiorrhiza 7-13, poria cocos 6-14, chuanxiong rhizome 7-13, trichosanthes kirilowii fruit 6-14, allium macrostemon 8-13, and red peony root 6-9.

[0021] In one specific implementation scheme, the components include the following parts by weight: cinnamon twig 5-8, codonopsis 8-12, atractylodes macrocephala 7-12, salvia miltiorrhiza 8-12, poria cocos 7-12, chuanxiong rhizome 8-12, trichosanthes fruit 7-12, allium macrostemon 9-12, and red peony root 5-8.

[0022] In one specific implementation scheme, the components include the following parts by weight: cinnamon twig 7, codonopsis 9, atractylodes macrocephala 11, salvia miltiorrhiza 9, poria cocos 11, chuanxiong rhizome 9, trichosanthes fruit 11, allium macrostemon 9, and red peony root 7.

[0023] In one specific implementation scheme, the components include the following parts by weight: 6 parts cinnamon twig, 10 parts codonopsis root, 10 parts atractylodes rhizome, 10 parts salvia miltiorrhiza root, 10 parts poria cocos, 10 parts chuanxiong rhizome, 10 parts trichosanthes fruit, 10 parts allium macrostemon root, and 6 parts red peony root.

[0024] refer to Figures 1 to 3 This application provides a method for preparing a formula for invigorating qi, warming yang, and regulating the heart, comprising the following steps:

[0025] Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 20-40 minutes. Filter and collect the filtrate. Add water to the residue, continue heating and boiling, then simmer for 15-30 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain a warming and yang-regulating heart-tonifying medicine.

[0026] In the above technical solution, cinnamon twig, codonopsis, atractylodes macrocephala, salvia miltiorrhiza, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root are boiled, then simmered for 20-40 minutes, filtered, and the filtrate is collected. Water is then added to the residue, and the mixture is heated to a boil again, then simmered for 15-30 minutes, filtered, and the filtrate is retained. The two filtrates are combined to obtain a warming and yang-regulating heart-strengthening medicine, which improves exercise capacity and cardiac function.

[0027] In one specific feasible implementation plan, take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root, boil them, then simmer for 22-38 minutes, filter, take the filtrate, add water to the residue, continue to heat to a boil, then simmer for 18-28 minutes, filter, retain the filtrate, combine the two filtrates, and obtain a warming and yang-regulating heart-tonifying medicine.

[0028] In one specific feasible implementation plan, take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root, boil them, then simmer for 30 minutes, filter, take the filtrate, add water to the residue, continue to heat to a boil, then simmer for 24 minutes, filter, retain the filtrate, combine the two filtrates, and obtain a medicine that benefits qi, warms yang, and regulates the heart.

[0029] In one specific feasible implementation, the Qi-tonifying and Yang-regulating medicine is formulated into granules.

[0030] In one specific feasible implementation, the warming and yang-tonifying medicine is made into pills.

[0031] Example 1

[0032] Take the following Chinese medicinal materials in the following proportions: Cinnamon twig 6g, Codonopsis pilosula 10g, Atractylodes macrocephala 10g, Salvia miltiorrhiza 10g, Poria cocos 10g, Ligusticum chuanxiong 10g, Trichosanthes kirilowii 10g, Allium macrostemon 10g, and Paeonia lactiflora 6g.

[0033] Each of the above portions is one gram. For example, 6 grams of cinnamon twig and 10 grams of codonopsis pilosula constitute one dose of medicine.

[0034] Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 30 minutes. Filter and collect the filtrate. Add water to the residue, continue heating to a boil, then simmer for 24 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain the Qi-invigorating and Yang-regulating Heart-Tonifying Herb. Prepare the Qi-invigorating and Yang-regulating Heart-Tonifying Herb into granules.

[0035] The verification process of the Qi-tonifying, Qi-warming, and heart-regulating formula includes:

[0036] 1. Treatment regimen for the experimental group

[0037] In addition to the treatment regimen of the control group, the experimental group was given Yiqi Wenyang Tiaoxin Formula Granules. The Yiqi Wenyang Tiaoxin Formula Granules consist of: 6g of Cinnamon Twig, 10g of Codonopsis, 10g of Atractylodes Macrocephala, 10g of Salvia Miltiorrhiza, 10g of Poria, 10g of Ligusticum Chuanxiong, 10g of Trichosanthes Fruit, 10g of Allium macrostemon, and 6g of Paeoniae Radix Rubra. The granules were taken twice a day, once in the morning and once in the evening, for a total of 2 times a day, 1 packet per dose.

[0038] 2 Observation Indicators

[0039] 2.1 General Data Collection

[0040] Basic information such as gender, weight, height, and age of all patients included in the study was collected, and clinical data such as medical history were also recorded.

[0041] 2.2 Main therapeutic indicators

[0042] The primary efficacy endpoint was NT-proBNP level. Fasting upper limb venous blood was collected before and after enrollment and detected using the Roche brain natriuretic peptide precursor assay instrument (model: cobas h232) and the matching Roche brain natriuretic peptide precursor assay kit.

[0043] 2.3 Secondary efficacy indicators include: 1. Traditional Chinese Medicine syndrome scale score; 2. Cardiopulmonary function and exercise tolerance related indicators; 3. Quality of life related indicators; 4. Six-minute walk test.

[0044] 2.4 Safety and efficacy related indicators

[0045] 3. Cardiopulmonary Exercise Test (CPET) Procedure

[0046] The cardiopulmonary exercise testing device used in this study was the Schiller SDS-104 cardiopulmonary exercise function testing device. All patients underwent cardiopulmonary exercise testing at baseline and after the intervention.

[0047] 3.1 Preparations before CPET

[0048] (1) Detailed explanation: Before the test, explain to the patient the purpose of CPET, the complete procedure, precautions and possible adverse reactions in detail so that the patient can fully understand.

[0049] (2) Signing informed consent form: After the patient fully understands, the researcher supervises the signing of a written informed consent form for cardiopulmonary exercise test.

[0050] (3) Pre-test assessment: Before the test begins, the researchers conduct a comprehensive clinical assessment of all patients to rule out contraindications to exercise and ensure that the subjects meet the test conditions and can safely and completely complete the exercise load test.

[0051] (4) Patient preparation: Instruct the patient to remain quiet for at least 15 minutes and empty their bladder beforehand to avoid interference factors affecting the test results.

[0052] (5) Operator preparation: Before the test begins, environmental parameters, capacity and gas calibration shall be performed in accordance with the instrument operation specifications.

[0053] 3.2 CPET Testing Procedure

[0054] (1) The patient sits in a standard sitting position with his back not against the chair back, and keeps his body position stable; attach the electrode pads to the corresponding parts of the chest according to the standard lead position and fix them properly, and measure the sitting resting blood pressure at the same time.

[0055] (2) Select a mask of appropriate size, connect the oxygen sensor and oxygen cylinder, and check for leaks.

[0056] (3) Provide one-on-one guidance to patients according to the standard procedure and instruct them to cooperate with the movements to complete the lung function test.

[0057] (4) The operator assists the patient to sit on the treadmill, puts on the finger pulse oximeter, sets the treadmill protocol according to the patient's basic functional status, and adopts a standardized treadmill exercise program in the testing process to systematically measure the patient's cardiopulmonary exercise reserve function.

[0058] (5) The patient’s gas exchange parameters, 12-lead electrocardiogram, blood pressure, pulse oxygen saturation and other physiological indicators are continuously monitored in real time throughout the test. The patient’s subjective symptoms and vital signs are closely observed to ensure the safety and standardization of the test process.

[0059] (6) When the patient reaches exhaustion, experiences obvious discomfort or abnormal reaction, or when the preset termination criteria are met in combination with subjective fatigue level, blood pressure, heart rate, exercise power, respiratory exchange rate (RER), etc., the test shall be terminated in a timely manner.

[0060] 4. Statistical Analysis Methods

[0061] All experimental data included in this study were statistically processed using IBM SPSS Statistics 25 software. First, a normality test was performed on all continuous data. Data conforming to a normal distribution were expressed as mean ± standard deviation (σ). Mean squared (±s) is used to represent the mean. Comparisons between two groups were performed using an independent samples t-test, and within-group comparisons were performed using a paired samples t-test. Skewed data are represented by the median (interquartile range) [M(P25,P75)], and comparisons between groups were performed using a two-sample Wilcoxon signed-rank test, while within-group comparisons were performed using a paired samples Wilcoxon test. Count data are represented by the number of cases (percentage) [n, %], and comparisons between groups were performed using a 2x2 contingency table chi-square test. The statistical significance level was set at α=0.05, meaning that a p-value < 0.05 was considered statistically significant.

[0062] 5. Research Results

[0063] This study included 72 eligible patients, with 36 in the experimental group and 36 in the control group. During the study, one patient in the control group dropped out due to loss to follow-up, and another dropped out due to refusal to return for follow-up. Two patients in the experimental group dropped out due to personal reasons. Ultimately, 68 valid patients were included.

[0064] 5.1 Baseline characteristics analysis of the two groups of patients before enrollment

[0065] 5.1.1 Comparison of gender characteristics

[0066] A comparison of the gender composition of the two groups showed that the experimental group consisted of 20 males (58.82%) and 14 females (41.18%), while the control group consisted of 19 males (55.88%) and 15 females (44.12%). There was no statistically significant difference in gender distribution between the two groups (P > 0.05), indicating that the two groups were comparable in terms of gender composition. See Table 1 for details.

[0067]

[0068] Table 1 Comparison of gender characteristics between the two groups of patients.

[0069] 5.1.2 Comparison of Age Characteristics

[0070] A comparison of the age composition of the two groups of patients showed that the mean age of the experimental group was 73.35 ± 8.01 years and the mean age of the control group was 71.79 ± 7.60 years. There was no statistically significant difference between the two groups (P > 0.05), indicating that the two groups of patients were comparable in terms of age composition. See Table 2 for details.

[0071]

[0072] Table 2 Comparison of age characteristics between the two groups of patients

[0073] 5.1.3 Comparison of Height Characteristics

[0074] The height comparison between the two groups showed that the average height of the experimental group was 167.12 ± 8.16 cm, and the average height of the control group was 164.94 ± 7.66 cm. There was no statistically significant difference between the two groups (P > 0.05), indicating that the two groups of patients were comparable in terms of age. See Table 3 for details.

[0075]

[0076] Table 3 Comparison of height characteristics between the two groups of patients

[0077] 5.1.4 Comparison of body weight characteristics

[0078] The comparison of the weight of the two groups of patients showed that the average weight of the experimental group was 70.24 ± 10.85 kg, and the average weight of the control group was 65.60 ± 11.45 kg. There was no statistically significant difference between the two groups (P > 0.05), indicating that the two groups of patients were comparable in terms of weight. See Table 4 for details.

[0079]

[0080] Table 4 Comparison of weight characteristics between the two groups of patients

[0081] 5.1.5 Comparison of Medical History Characteristics

[0082] Statistical comparison of the medical history characteristics of the two groups of patients showed that: 10 patients (29.41%) in the experimental group had a history of smoking, compared to 13 patients (38.24%) in the control group, with no statistically significant difference (P>0.05). 12 patients (35.29%) in the experimental group had a history of alcohol consumption, compared to 18 patients (52.94%) in the control group, with no statistically significant difference (P>0.05). 21 patients (61.76%) in the experimental group had hypertension, compared to 22 patients (64.71%) in the control group, with no statistically significant difference (X²=0.063, P>0.05). 14 patients (41.18%) in the experimental group had diabetes, compared to 13 patients (38.24%) in the control group, with no statistically significant difference (P>0.05). 9 patients (25.47%) in the experimental group had arrhythmia, compared to 6 patients (17.65%) in the control group, with no statistically significant difference (P>0.05). Six patients (17.65%) in the experimental group had chronic obstructive pulmonary disease (COPD), while two patients (5.88%) in the control group had it; the difference was not statistically significant (P>0.05). Thirty patients (88.24%) in the experimental group had hyperlipidemia, while 32 patients (94.12%) in the control group had it; the difference was not statistically significant (P>0.05). Twenty patients (58.82%) in the experimental group had coronary heart disease, while 26 patients (75.47%) in the control group had it; the difference was not statistically significant (P>0.05). See Table 5 for details. In summary, there were no statistically significant differences between the two groups in terms of smoking history, alcohol consumption history, hypertension, diabetes, arrhythmia, COPD, hyperlipidemia, and coronary heart disease (P>0.05), indicating that the baseline data of the two groups were comparable.

[0083]

[0084] Table 5 Comparison of medical history characteristics between the two groups of patients

[0085] 5.1.6 Pre-treatment efficacy indicators

[0086] (1) Comparison of NT-proBNP between the two groups before treatment

[0087] Before treatment, the NT-proBNP level in the control group was 759.00 (618.8, 1169.8) pg / mL, and in the experimental group it was 778.00 (675.5, 1143.0) pg / mL. There was no statistically significant difference between the two groups (P > 0.05), indicating that the NT-proBNP levels before treatment were comparable between the two groups (see Table 6 for details).

[0088]

[0089] Table 6 Comparison of NT-proBNP levels between the two groups before treatment

[0090] (2) Comparison of TCM syndrome scale scores between the two groups before treatment

[0091] Before treatment, the main symptom score of the control group was 7.56 ± 2.84 points, and that of the experimental group was 8.82 ± 3.27 points, with no statistically significant difference between the two groups (P > 0.05). The secondary symptom score of the control group was 18.00 ± 26 points, and that of the experimental group was 18.94 ± 5.30 points, with no statistically significant difference between the two groups (P > 0.05). The total score of the control group was 25.65 ± 6.07 points, and that of the experimental group was 27.76 ± 7.25 points, with no statistically significant difference between the two groups (P > 0.05). See Table 7 for details.

[0092]

[0093] Table 7 Comparison of TCM syndrome scale scores between the two groups before treatment

[0094] (3) Comparison of cardiopulmonary function and exercise tolerance-related indicators between the two groups before treatment

[0095] Table 8 shows the comparison results of cardiopulmonary exercise test-related indicators between the two groups of patients before treatment. The results indicate that the control group and the experimental group... There were no statistically significant differences in the following indicators: exercise load time, threshold power, maximum oxygen pulse, peak oxygen uptake per kilogram, dVO2 / dW, 1-minute heart rate recovery value, lower and upper limits of target heart rate for moderate-intensity exercise, and FEV1 / FVC (P>0.05).

[0096]

[0097] Table 8 Comparison of cardiopulmonary exercise test-related indicators between the two groups of patients before treatment.

[0098] (4) Comparison of C-MLHFQ quality of life scores between the two groups before treatment

[0099] Comparison of C-MLHFQ quality-of-life indicators between the two groups before treatment showed no statistically significant differences between the control and experimental groups in terms of physical dimensions, mental dimensions, other dimensions, and total score (P > 0.05), as detailed in Table 9. These results suggest that the two groups had good baseline comparability in all dimensions of quality of life and total score before treatment.

[0100]

[0101] Table 9. C-MLHFQ Quality of Life Scoring Table for Two Groups

[0102] (5) Comparison of the six-minute walk test between the two groups before treatment

[0103] A comparison of the six-minute walk test results between the two groups before treatment showed that the six-minute walk distance in the control group was 283.24 ± 41.02 m, while that in the experimental group was 179.44 ± 50.67 m. There was no statistically significant difference between the two groups (see Table 10 for details).

[0104]

[0105] Table 10 Comparison of the results of the six-minute walk test between the two groups before treatment.

[0106] 5.2 Comparison of main efficacy indicators after treatment

[0107] 5.2.1 Comparison results between the two NT-proBNP groups after treatment

[0108] The comparison of NT-proBNP levels between the experimental and control groups after treatment showed that the NT-proBNP level in the control group was 477.00 pg / mL, while that in the experimental group was 387.00 pg / mL. The difference between the two groups was statistically significant (P < 0.05), as detailed in Table 11.

[0109]

[0110] Note: Compared with the control group * P<0.05.

[0111] Table 11 Comparison results between the two NT-proBNP groups after treatment

[0112] 5.2.2 Comparison of NT-proBNP levels between the two groups before and after treatment

[0113] The comparison of NT-proBNP levels before and after treatment in the two groups showed that the NT-proBNP level in the experimental group was 778.00 pg / mL before treatment and decreased to 387.00 pg / mL after treatment, with a statistically significant difference (P<0.001); the NT-proBNP level in the control group was 759.00 pg / mL before treatment and decreased to 477.00 pg / mL after treatment, with a statistically significant difference (P<0.001). See Table 12 for details.

[0114]

[0115] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0116] Table 12 Comparison of NT-proBNP levels before and after treatment in the two groups.

[0117] 5.3 Comparison of secondary efficacy indicators after treatment

[0118] 5.3.1 Comparison of scores on TCM syndrome scales

[0119] (1) Comparison of TCM syndrome scale scores between the two groups after treatment

[0120] Statistical analysis of the post-treatment results showed that the experimental group had significantly lower scores than the control group in terms of primary symptom scores, secondary symptom scores, and total score (P < 0.001). Specifically, the primary symptom score was 28 ± 2.31 in the experimental group and 5.71 ± 2.14 in the control group; the secondary symptom score was 10.26 ± 3.83 in the experimental group and 16.09 ± 5.37 in the control group; and the total score was 14.65 ± 4.52 in the experimental group and 22.79 ± 5.71 in the control group. This indicates that the experimental group was superior to the control group in improving TCM syndromes (see Table 13 for details).

[0121]

[0122] Note: Compared with the control group * P<0.05, ** P < 0.001.

[0123] Table 13 Comparison of TCM syndrome scale scores between the two groups after treatment

[0124] (2) Comparison of scores on the TCM syndrome scale between the two groups before and after treatment

[0125] Compared with before treatment, the control group showed a significant decrease in the scores of major symptoms, minor symptoms, and total score after treatment (see Table 14). Compared with before treatment, the experimental group showed a significant decrease in the scores of major symptoms, minor symptoms, and total score after treatment (see Table 15).

[0126]

[0127] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0128] Table 14 Comparison of TCM syndrome scale scores before and after treatment in the control group within the same group.

[0129]

[0130] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0131] Table 15 Comparison of TCM syndrome scale scores before and after treatment in the experimental group within the same group.

[0132] 5.3.2 Comparison of Cardiopulmonary Function and Exercise Tolerance Related Indicators

[0133] (1) Comparison of cardiopulmonary function and exercise tolerance-related indicators between the two groups after treatment

[0134] After treatment, the comparison of cardiopulmonary function and exercise-related indicators between the control group and the experimental group showed that there were statistically significant differences between the two groups in terms of the percentage of peak oxygen uptake to the predicted value, exercise load time, maximum oxygen pulse, peak oxygen uptake per kilogram, and heart rate recovery value at 1 minute (P < 0.05); there were no statistically significant differences between the two groups in terms of threshold power, dVO2 / dW, upper and lower limits of target heart rate for moderate-intensity exercise, and FEV1 / FVC (P > 0.05), as detailed in Table 16.

[0135]

[0136] Note: Compared with the control group * P<0.05, ** P < 0.001.

[0137] Table 16 Comparison of cardiopulmonary function and exercise tolerance-related indicators between the two groups after treatment.

[0138] (2) Intra-group comparison of cardiopulmonary function and exercise tolerance related indicators before and after treatment in the two groups

[0139] Compared with pre-treatment levels, the control group showed statistically significant differences after treatment in the percentage of peak oxygen uptake relative to predicted value, maximum oxygen pulse, peak oxygen uptake per kilogram, and 1-minute heart rate recovery value (P < 0.05), as detailed in Table 17. Compared with pre-treatment levels, the experimental group also showed statistically significant differences after treatment in the percentage of peak oxygen uptake relative to predicted value, exercise load time, maximum oxygen pulse, peak oxygen uptake per kilogram, and 1-minute heart rate recovery value (P < 0.05), as detailed in Table 18.

[0140]

[0141] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0142] Table 17 Comparison of cardiopulmonary function and exercise tolerance-related indicators before and after treatment in the control group.

[0143]

[0144] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0145] Table 18. Intra-group comparisons of cardiopulmonary function and exercise tolerance related indicators before and after treatment in the experimental group.

[0146] 5.3.3 Comparison of C-MLHFQ Quality of Life Scale Scores

[0147] (1) Comparison of C-MLHFQ quality of life scores between the two groups after treatment

[0148] Statistical analysis of the experimental and control groups after treatment revealed that the experimental group scored lower than the control group in terms of physical dimension, mental dimension, and total score, with statistically significant differences (P < 0.05); however, there were no statistically significant differences between the two groups in other dimensions (P > 0.05). This suggests that the Yiqi Qiyang Tiaoxin formula has certain advantages in improving patients' quality of life, as detailed in Table 19.

[0149]

[0150] Note: Compared with the control group * P<0.05, ** P < 0.001.

[0151] Table 19 Comparison of C-MLHFQ quality of life scores between the two groups after treatment.

[0152] (2) Intragroup comparison of C-MLHFQ quality of life scale scores before and after treatment between the two groups

[0153] After treatment, the scores of the physical dimension, mental dimension, other dimensions, and total score in the control group all decreased compared with those before treatment, and the differences were statistically significant (P<0.05), as detailed in Table 20. After treatment, the scores of all dimensions and total score in the experimental group all decreased significantly compared with those before treatment (P<0.05), as detailed in Table 21. This suggests that adding the Qi-tonifying and Yang-regulating formula to the conventional Western medicine treatment can effectively improve the quality of life of patients.

[0154]

[0155] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0156] Table 20 Comparison of C-MLHFQ quality of life scale scores before and after treatment in the control group within the same group

[0157]

[0158] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0159] Table 21 Comparison of C-MLHFQ quality of life scale scores before and after treatment in the experimental group.

[0160] 5.3.4 Comparison of Six-Minute Walk Tests

[0161] (1) Comparison of the two groups' ease of walking test after treatment

[0162] The comparison of the results after treatment between the experimental group and the control group showed that the six-minute walking distance in the experimental group was 349.76 ± 35.80 m, while that in the control group was 331.18 ± 33.97 m, and the difference was statistically significant (P < 0.05). See Table 22 for details.

[0163]

[0164] Note: Compared with the control group * P<0.05, ** P < 0.001.

[0165] Table 22 Comparison of the six-minute walk test between the two groups after treatment.

[0166] (2) Comparison of the six-minute walk test between the two groups before and after treatment

[0167] Intra-group comparisons showed that the walking distance in the six minutes after treatment was significantly increased in both groups compared to before treatment. In the control group, the distance increased from 283.24 ± 41.02 m to 331.18 ± 33.97 m, a statistically significant difference (P < 0.05), as detailed in Table 23; in the experimental group, the distance increased from 279.44 ± 50.67 m to 349.76 ± 35.80 m, also a statistically significant difference (P < 0.05), as detailed in Table 24.

[0168]

[0169] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0170] Table 23 Comparison of the six-minute walk test before and after treatment in the control group.

[0171]

[0172] Note: Compared with before treatment * P<0.05, ** P < 0.001.

[0173] Table 24 Comparison of six-minute walk test results before and after treatment in the experimental groups

[0174] 5.4 Safety Indicators

[0175] Liver function, kidney function, and complete blood count were compared between the experimental and control groups before and after treatment. Results showed no significant abnormalities in any safety indicators. There were no statistically significant differences in ALT, AST, BUN, CRE, WBC, RBC, Hb, and PLT levels before and after treatment in the control group (P > 0.05), as detailed in Table 25. Similarly, there were no statistically significant differences in the above indicators before and after treatment in the experimental group (P > 0.05), as detailed in Table 26. This suggests that the combination of Yiqi Qiyang Tiaoxin formula with conventional Western medicine treatment did not have significant adverse effects on liver and kidney function or complete blood count, demonstrating good safety.

[0176]

[0177] Table 25 Comparison of liver function, kidney function, and complete blood count before and after treatment in the control group.

[0178]

[0179] Table 26 Comparison of liver function, kidney function, and complete blood count before and after treatment in the control group.

[0180] 6. Theoretical Basis

[0181] 6.1 Basis for the Research Topic

[0182] Heart failure with reduced ejection fraction (HFrEF) is a severe clinical syndrome that progresses to the end stage of various cardiovascular diseases. Its main pathological manifestations are decreased myocardial contractility, ventricular remodeling, and reduced cardiac output. With the continuous deterioration of cardiac structure and function, patients may experience shortness of breath, fatigue, decreased exercise tolerance, and edema, severely impacting their quality of life and significantly increasing hospitalization and mortality rates. In recent years, with the accelerating aging of my country's population, the prevalence of heart failure has been on a continuous upward trend, becoming one of the most important public health issues globally. Epidemiological surveys show that heart failure is particularly common among the elderly. In people over 70 years of age, the prevalence of heart failure can reach approximately 10%, and it is also one of the most common causes of hospitalization in people over 65 years of age. According to the "2024 China Health Statistics Yearbook," people over 60 years of age account for as high as 85.1% of heart failure patients in my country, gradually becoming one of the important reasons for high mortality and hospitalization rates from cardiovascular diseases, placing a heavy burden on patients' families and the social medical security system.

[0183] Currently, modern medicine primarily treats heart failure with HFrEF using neuroendocrine antagonist therapy. In recent years, with the continuous updates to heart failure treatment guidelines, the treatment has evolved from the original "golden triangle" to the "new quadruple therapy," and now to the "five golden flowers," which can be summarized as: angiotensin-converting enzyme inhibitors (ACE-I) / angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and diuretics. The continuous updates in research on these drugs have led to a significant decrease in the mortality and readmission rates of heart failure. However, in extensive clinical practice, many patients still experience the following problems after receiving standardized treatment: 1. Patients still suffer from clinical symptoms that severely impact their quality of life, such as shortness of breath, fatigue, and decreased exercise tolerance; 2. Elderly patients often have complex conditions, including multiple underlying diseases, and long-term use of multiple Western medicines may increase the risk of adverse reactions and even lead to medication conflicts; 3. The long-term recurrent nature of the disease, along with high hospitalization rates and high costs, increases patients' anxiety, uncertainty about the disease's progression, and fear of medical treatment, creating a vicious cycle of psychological and physiological distress. Therefore, exploring safer and more effective integrated traditional Chinese and Western medicine treatment strategies is of great significance for further improving the prognosis of HFrEF patients.

[0184] Traditional Chinese medicine (TCM), as my country's traditional medical system, has a broad research foundation and rich clinical experience in treating heart failure. In the TCM theoretical system, heart failure mainly falls under the categories of "palpitation," "dyspnea," and "heart edema," with its basic pathogenesis often being "deficiency of the root and excess of the branch." The root deficiency is primarily qi deficiency and yang deficiency, while the branch excess often manifests as blood stasis, fluid retention, and phlegm turbidity. Elderly patients, due to advanced age and physical decline, experience a gradual weakening of yang qi, with insufficient heart yang being particularly common. Insufficient heart qi and yang lead to a loss of warmth in the heart vessels, hindering the normal circulation of body fluids and blood, resulting in poor qi and blood circulation, fluid retention, and excess patterns such as blood stasis, fluid retention, and phlegm turbidity, thus causing clinical symptoms such as dyspnea, palpitations, shortness of breath, and fatigue. Based on the above theoretical guidance and combined with years of clinical practice, our Department of Cardiology has developed the Yiqi Qiyang Tiaoxin Formula. This formula, with its core principle of invigorating Qi and warming Yang, is combined with herbs that promote blood circulation, diuresis, and regulate Qi and blood flow. It addresses the pathological basis of insufficient Yang Qi and blood stasis, thus treating heart failure patients from multiple angles. This formula has been used clinically for many years and has undergone preliminary basic research. Preliminary research shows that this formula can effectively improve patients' cardiac function and quality of life, but objective and standardized clinical evidence is lacking. Against this background, this study focuses on elderly patients with chronic heart failure with reduced ejection fraction (HFrEF) due to insufficient Yang Qi. In addition to standard Western medicine treatment, the Yiqi Qiyang Tiaoxin Formula was added for intervention. By observing changes in NT-proBNP levels, cardiopulmonary exercise test indicators, six-minute walk test distance, and quality of life scores, the clinical efficacy and safety of the Yiqi Qiyang Tiaoxin Formula for HFrEF patients were systematically evaluated. This aims to provide new clinical evidence and research ideas for the integrated traditional Chinese and Western medicine treatment of elderly patients with chronic heart failure with reduced ejection fraction.

[0185] 6.2 Analysis of the composition of Yiqi Qiyang Tiaoxin formula and its effect on symptoms of HFrEF patients

[0186] The "Yiqi Qiyang Tiaoxin Formula" strictly follows the principle of "principal-assistant-adjuvant-guide" in its formulation: the principal ingredient is cinnamon twig and codonopsis root to warm and invigorate the heart yang and replenish the original qi; the assistant ingredient is atractylodes macrocephala and poria cocos to strengthen the spleen, invigorate yang, and promote diuresis; the adjuvant ingredient is salvia miltiorrhiza, chuanxiong rhizome, and red peony root to invigorate blood, remove blood stasis, regulate qi, and resolve phlegm; and the guide ingredient is trichosanthes fruit and allium macrostemon to relieve chest tightness, resolve phlegm, regulate qi, and unblock the meridians.

[0187] This formula primarily uses cinnamon twig and codonopsis. The heart functions based on yang, governing blood vessels and storing the spirit. Insufficient yang qi weakens its peristaltic function, slows blood flow, and can even lead to blood stasis. This results in insufficient nourishment of the heart vessels and the spirit, causing palpitations. The vital energy (zongqi) relies on yang for transformation; yang deficiency weakens zongqi, hence shortness of breath. Yang is the body's driving force; yang deficiency deprives the body of warmth, nourishment, and invigoration, hindering the distribution of qi and blood to the limbs and bones, leading to general weakness, fatigue, and reluctance to speak. Cinnamon twig is pungent, sweet, and warm in nature, entering the heart, lung, and bladder meridians. It has the effects of inducing sweating and relieving muscle tension, warming and unblocking the meridians, assisting yang qi transformation, and calming rebellious qi. The Compendium of Materia Medica states that "Cinnamon twig is pungent and warm, and can unblock blood vessels." This formula uses cinnamon twig as the chief ingredient. Firstly, its warm nature allows it to enter the heart meridian, thus warming and unblocking the heart yang, invigorating the sovereign fire, assisting yang, restoring warmth, promoting circulation, and consolidation, improving symptoms such as aversion to cold, cold limbs, palpitations, shortness of breath, and fatigue. At the same time, it assists yang to transform qi, promotes diuresis and reduces swelling without harming the body's vital energy, relieving symptoms such as lower limb edema and shortness of breath that prevent lying flat. Secondly, because cinnamon twig is warm but not excessively hot, it can avoid depleting yin fluids and prevent the occurrence of yin and yang deficiency. It can also effectively alleviate the contraindication of elderly patients who are too weak to tolerate tonics. Furthermore, modern pharmacology has shown that various active ingredients in cinnamon twigs, such as cinnamaldehyde, can protect the heart through multiple mechanisms, including regulating autophagy, apoptosis, vasodilation, and inhibiting the release of inflammatory factors. Meanwhile, cinnamic acid plays a regulatory role in apoptosis-related proteins such as the Caspase family and Bcl-2 in cardiomyocytes, reducing apoptosis levels, inhibiting excessive proliferation of myocardial fibroblasts, lowering intracellular oxidative stress levels, and delaying the progression of heart failure. Codonopsis pilosula, a commonly used treatment for cardiovascular diseases, has long been proven to reduce ventricular hypertrophy and inhibit ventricular remodeling. According to traditional Chinese medicine texts, Codonopsis pilosula is sweet and neutral in nature, primarily affecting the spleen and lung meridians. It has the effects of tonifying the middle energizer, strengthening the spleen and lungs, nourishing blood and generating fluids. Its medicinal properties are mild, tonifying without causing dryness. The heart governs blood vessels and relies on heart qi for propulsion; qi deficiency weakens the pumping function, and qi deficiency is a gradual progression to yang deficiency. Prolonged qi deficiency inevitably affects yang. Codonopsis pilosula's qi-tonifying and spleen-strengthening effects allow qi to replenish and yang to gradually recover, enabling yang qi to circulate throughout the body. Furthermore, it can benefit the spleen to generate heart blood and strengthen spleen yang to control dampness. In summary, Cinnamomum cassia warms yang to promote qi circulation and unblock the meridians, ensuring the flow of yang qi without stagnation. Codonopsis pilosula tonifies qi to generate yang, providing a source for yang qi generation. Together, they serve as the principal herbs, one warming and the other strengthening, achieving the combined effect of tonifying qi and warming yang.

[0188] This formula uses Atractylodes macrocephala and Poria cocos as adjuvants. Atractylodes macrocephala is bitter and sweet in taste, warm in nature, and enters the spleen and stomach meridians. Its main functions are to strengthen the spleen and replenish qi, dry dampness and promote diuresis. Insufficient yang qi, primarily due to deficiency of heart yang, is followed by deficiency of both spleen and kidney, leading to impaired fluid metabolism, internal retention of dampness, and phlegm affecting the heart and lungs. Firstly, Atractylodes macrocephala is used to replenish qi and strengthen the spleen, nourishing the acquired constitution, ensuring a source for the generation of qi and blood, replenishing heart qi, and assisting heart yang to consolidate the foundation of deficiency. Secondly, Atractylodes macrocephala dries dampness and promotes diuresis. The spleen governs the transformation and transportation of dampness; spleen deficiency leads to the accumulation of dampness as water, phlegm, and fluid retention. Therefore, Atractylodes macrocephala is used as an adjuvant, its bitter and warm properties drying dampness and strengthening the spleen to control water retention and address the symptoms. Modern pharmacology shows that the active ingredient in Atractylodes macrocephala, atractylodes lactone I, has a regulatory effect on cell homeostasis, reducing apoptosis and oxidative stress to maintain cell cycle stability. Poria cocos is sweet and bland in taste, neutral in nature, and enters the heart, lung, spleen, and kidney meridians. Poria cocos has the effects of promoting diuresis and eliminating dampness, strengthening the spleen and calming the mind. When Yang Qi is deficient, Qi transformation is abnormal, and water metabolism is impaired, water retention occurs. If this water flows upwards, it can cause palpitations and shortness of breath; if it overflows, it can cause edema. On one hand, Poria cocos can gently promote diuresis, directly purging existing dampness and phlegm. On the other hand, Poria cocos is sweet and neutral, strengthening the spleen, aiding its function, and supporting the body's vital energy. It can also address the underlying deficiency. Entering the heart meridian, it can calm the mind and soothe the nerves, improving symptoms such as palpitations, shortness of breath, and insomnia caused by water retention affecting the heart. Atractylodes macrocephala dries dampness to prevent its internal generation, while Poria cocos drains dampness to guide it downwards, preventing the generation of dampness and phlegm and quickly eliminating existing water retention. The combination of these two ingredients, one drying and one draining, one tonifying and one draining, works synergistically to strengthen the spleen, replenish Qi, warm Yang, and promote diuresis. Furthermore, modern pharmacology shows that its active ingredient, Poria cocos polysaccharide, can effectively scavenge various reactive oxygen free radicals and can also act on the RASS system to treat heart failure.

[0189] This formula is supplemented with Danshen (Salvia miltiorrhiza), Chuanxiong (Ligusticum striatum), and Chishao (Paeonia lactiflora). Danshen is bitter and slightly cold in nature, and enters the heart and liver meridians. Its main functions are to invigorate blood circulation, remove blood stasis, and relieve pain. When Yang is deficient and unable to propel the heart, blood vessels become stagnant and the heart vessels are obstructed, leading to internal blood stasis and malnourishment of the heart vessels, resulting in symptoms such as palpitations, chest tightness, shortness of breath, and cyanosis of the lips. Danshen is used in this formula because it enters the blood level, effectively invigorating blood circulation, removing blood stasis, and promoting new blood production. It can clear obstructed heart vessels, promote blood flow, and relieve the obstruction of blood stasis. Furthermore, its slightly cold nature does not deplete the body's vital energy or Yin fluids, and it invigorates blood without breaking the blood stasis. Modern pharmacological studies have shown that the active ingredients of Danshen can exert anti-heart failure effects through multiple pathways and targets, primarily by reducing myocardial inflammation and oxidative stress damage, regulating myocardial cell apoptosis, and myocardial cell autophagy, and are related to multiple pathways such as PI3K / Akt, TGF-β / Smad, and AMPK-mTOR. Chuanxiong (Ligusticum striatum) has a pungent taste and enters the liver, gallbladder, and pericardium meridians. It is an essential herb for invigorating blood and promoting qi circulation, and is also a qi-regulating herb within the blood. Its warm nature allows it to invigorate blood and warm the meridians, making it a superior herb for treating blood stasis in the heart meridians. Its dispersing nature allows it to unblock qi and blood, effectively removing qi stagnation and assisting yang qi in promoting blood circulation. Entering the pericardium meridian, it directly reaches the affected area, relieving symptoms such as chest tightness and palpitations. The core active components of Chuanxiong are ligustrazine and ferulic acid, which can dilate coronary arteries, increase myocardial blood and oxygen supply, and reduce myocardial oxygen consumption. By inhibiting oxidative stress and scavenging oxygen free radicals, it reduces oxidative damage to myocardial cells and downregulates the expression of inflammatory factors, inhibiting myocardial inflammatory infiltration to treat heart failure. Chishao (Paeonia lactiflora) has a bitter taste and slightly cold nature, enters the liver meridian, and its functions include clearing heat and cooling blood, dispersing blood stasis, and relieving pain. The *Bielu* states, "It unblocks blood vessels, soothes the middle burner, disperses stagnant blood, expels harmful blood, removes water retention, and benefits the bladder, large intestine, and small intestine..." This accurately describes how red peony, being bitter and cold, enters the blood, excelling at dispersing blood stasis and promoting blood circulation, breaking up blood stasis. Furthermore, its dispersing effect is not drastic, its elimination of pathogens does not harm the body's vital energy, and its slightly cold nature does not cause excessive heat; it can also alleviate the warming and drying properties of Sichuan lovage rhizome. The main active components of red peony are paeoniflorin and paeoniflorin lactone, which have significant cardioprotective effects. They can inhibit cardiomyocyte apoptosis, upregulate the expression of the anti-apoptotic protein Bcl-2, downregulate the expression of the pro-apoptotic protein Bax, and reduce excessive cardiomyocyte death in heart failure. The combined use of these three herbs achieves the effects of promoting blood circulation without harming the body's vital energy, regulating qi without depleting it, and dispersing blood stasis without being drastic, thus removing blood stasis, unblocking the heart vessels, restoring yang qi, and harmonizing qi and blood.

[0190] This formula uses Trichosanthes kirilowii and Allium macrostemon. Trichosanthes kirilowii is sweet and slightly bitter, cold in nature, and enters the lung, stomach, and large intestine meridians. It has the effects of clearing heat and resolving phlegm, promoting qi circulation and relieving chest congestion, and dispersing nodules and reducing swelling. In cases of heart failure due to insufficient yang qi, the underlying deficiency is a lack of yang qi and weak peristalsis, while the superficial excess manifests as phlegm accumulation, chest yang obstruction, and qi stagnation. Internal phlegm retention and stagnation of qi in the upper jiao lead to chest tightness, shortness of breath, inability to lie down, and palpitations. This formula utilizes the bitter, cold, and moistening properties of Trichosanthes kirilowii, which effectively opens up phlegm accumulation in the chest and promotes qi circulation. It clears phlegm accumulation in the upper jiao and relieves chest congestion, thus resolving the superficial excess of phlegm accumulation, allowing qi to flow smoothly, assisting the heart yang in its circulation, and addressing the underlying deficiency. The *Shennong Bencao Jing* (Shennong's Classic of Materia Medica) discusses *Trichosanthes kirilowii* (Gua Lou) as "treating severe edema, swelling of the body, face, and limbs, promoting urination, killing parasites, relieving cough and shortness of breath..." Therefore, this formula also uses *Trichosanthes kirilowii* to treat edema. The active components of *Trichosanthes kirilowii* include polysaccharides, triterpenoid saponins, and flavonoids, which can regulate the Bcl-2 / Bax ratio, inhibiting excessive apoptosis of cardiomyocytes and achieving apoptosis balance. Simultaneously, it can activate the PI3K / Akt signaling pathway, downregulate the expression of inducible nitric oxide synthase (iNOS), reduce the toxic effects of excessive NO on the myocardium, improve myocardial ischemia and hypoxia, and alleviate myocardial energy metabolism disorders in heart failure. *Allium macrostemon* (Xie Bai) is pungent and bitter in taste, warm in nature, and enters the heart, lung, stomach, and large intestine meridians. Its effects are to promote yang, disperse stagnation, and regulate qi. Its pungent and warm nature specifically enters the chest, invigorating chest yang, warming and unblocking the heart vessels, dispersing phlegm and turbidity, and relieving symptoms such as chest tightness, heart pain, and shortness of breath. Allium macrostemon, for example, contains saponins that can protect myocardial cells and vascular endothelium by regulating the balance of vasomotor activity and combating oxidative stress, thereby reducing myocardial damage. When phlegm is cleared, Yang energy flows more easily; when Yang energy flows more easily, Qi flows more easily. These two substances, one cold and one warm, one moistening and one dispersing, one opening and one unblocking, work together to promote Yang energy, disperse stagnation, regulate Qi, and clear the chest and blood vessels, thus helping to expand chest Yang, resolve phlegm, smooth Qi flow, and unblock the heart vessels.

[0191] Looking at the whole formula, the nine herbs in the Qi-tonifying and Yang-regulating Heart Formula are meticulously combined, each with its own specific role and function, clearly distinguishing primary and secondary components while working synergistically. Cinnamon twig and Codonopsis pilosula warm the Yang and tonify Qi, strengthening the root cause; Atractylodes macrocephala and Poria cocos invigorate the spleen and promote diuresis, eliminating the superficial symptoms of edema; Salvia miltiorrhiza, Ligusticum chuanxiong, and Paeonia lactiflora invigorate blood circulation, remove blood stasis, and clear stagnation in the heart vessels; Trichosanthes kirilowii and Allium macrostemon invigorate Yang, eliminate phlegm, and promote the flow of Qi in the chest and diaphragm. The entire formula closely adheres to the pathogenesis of "deficiency of the root and excess of the branch," warming Yang without being overly drying, tonifying Qi without causing stagnation, invigorating blood circulation without breaking blood, promoting diuresis without harming the body's vital energy, and eliminating phlegm without depleting Qi. Together, these herbs warm the Yang, invigorate Qi, strengthen the spleen, promote diuresis, invigorate blood circulation, remove blood stasis, and clear Yang and eliminate phlegm, thus invigorating the heart Yang, promoting the flow of Qi and blood, resolving edema, eliminating phlegm, and clearing the heart vessels. It addresses both the root cause and the symptoms, precisely targeting the pathogenesis, making it an excellent formula for treating heart failure of the Yang deficiency type with deficiency of the root and excess of the branch.

[0192] 6.3 Effect of Yiqi Qiyang Tiaoxin Decoction combined with conventional Western medicine treatment on NT-proBNP in HFrEF patients

[0193] NT-proBNP is an important precursor fragment of a neuroendocrine hormone, secreted by ventricular myocytes under increased volume or pressure load. When ventricular wall tension increases or myocardial damage occurs, myocardial cells release the precursor proBNP, which cleaves to produce the biologically active brain natriuretic peptide (BNP) and the inactive NT-proBNP, both of which enter the bloodstream. NT-proBNP has a long half-life and good stability, and is therefore widely used clinically for the diagnosis, severity assessment, and prognosis of heart failure. Numerous studies have shown that NT-proBNP levels are closely related to ventricular pressure load, the degree of myocardial remodeling, and cardiac function classification; higher levels generally indicate more severe heart failure and are closely associated with an increased risk of poor prognosis. Furthermore, NT-proBNP can be used to evaluate treatment efficacy; a decrease in its level usually indicates reduced cardiac load and improved cardiac function. Therefore, NT-proBNP has been recommended as an important biomarker in domestic and international heart failure diagnosis and treatment guidelines, and has significant clinical value in the diagnosis, risk stratification, and efficacy assessment of heart failure. The results of this study showed that the addition of Qi-invigorating and Yang-regulating formula effectively reduced the NT-proBNP level in peripheral blood of patients with heart failure, with a significant difference compared to the control group. The reason for this is that the pathogenesis of chronic heart failure with HFrEF in the elderly is mainly characterized by deficiency of the root and excess of the branch, especially insufficient heart qi and deficiency of heart yang as the root, and blood stasis, fluid retention, and phlegm turbidity as the branch. In the Qi-invigorating and Yang-regulating formula, cinnamon twig and codonopsis are the chief ingredients. Cinnamon twig warms and invigorates heart yang, strengthens myocardial vitality, and can improve the energy metabolism of myocardial cells, enhance myocardial contractility, and relieve ventricular systolic load by activating the adenosine monophosphate-activated protein kinase (AMPK) pathway. Codonopsis pilosula invigorates qi and strengthens the spleen, enhancing the tolerance of myocardial cells to hypoxia, inhibiting myocardial cell apoptosis and inflammatory responses, reducing myocardial traction and damage at the root, and lowering the inducing factors for NT-proBNP synthesis. Atractylodes macrocephala and Poria cocos invigorate the spleen and promote diuresis, assisting Codonopsis pilosula in invigorating qi and reducing cardiac volume load through diuresis and dampness elimination, relieving ventricular wall tension, and directly reducing the secretion stimulation of NT-proBNP. Salvia miltiorrhiza, Ligusticum chuanxiong, and Paeonia lactiflora invigorate blood and remove blood stasis, inhibiting the TGF-β / Smad pathway, reducing collagen fibrin deposition, and delaying pathological ventricular remodeling; simultaneously, they effectively improve myocardial microcirculation function, enhance myocardial blood supply and oxygenation capacity, reduce myocardial ischemia and hypoxia damage, and prevent excessive stress-induced secretion of NT-proBNP by myocardial cells. Trichosanthes kirilowii and Allium macrostemon promote yang, disperse stagnation, regulate qi, and resolve phlegm, dilating coronary arteries, inhibiting myocardial fibrosis, and simultaneously inhibiting excessive activation of the RAAS and sympathetic nervous system, reducing the adverse stimulation of neuroendocrine factors on the myocardium.

[0194] 6.4 Effects of Qi-invigorating and Yang-regulating formula combined with conventional Western medicine treatment on cardiopulmonary function and exercise tolerance in patients with heart failure and pulmonary embolism (HFrEF)

[0195] Cardiopulmonary exercise testing (CPET) can simultaneously assess the integrated responses of the circulatory, respiratory, peripheral skeletal muscle, and metabolic systems under exercise load, making it one of the core tools for assessing exercise tolerance and cardiopulmonary reserve in heart failure patients. Compared to resting state testing, CPET is more revealing of the true physiological basis for shortness of breath and fatigue after activity in heart failure patients. Therefore, it can not only be used to explain the causes of symptoms and determine whether exercise limitation is mainly due to cardiac or pulmonary factors, but also for risk stratification, efficacy evaluation, exercise prescription, and advanced treatment decisions for patients with advanced heart failure. Peak oxygen uptake and other exercise gas exchange parameters in CPET are of great value in assessing the severity of heart failure, predicting prognosis, and determining treatment plans. Peak oxygen uptake is a classic core indicator for measuring exercise capacity and prognosis in heart failure. Peak oxygen uptake per kilogram is peak oxygen uptake adjusted for patient body weight, eliminating the influence of body weight on oxygen uptake capacity. It essentially reflects the comprehensive result of cardiac output, pulmonary gas exchange, and peripheral oxygen utilization at the end of exercise. The lower the value, the higher the patient's mortality rate, readmission rate, and risk of entering the advanced stage of heart failure. Peak oxygen uptake as a percentage of predicted value reflects the degree to which a patient's actual maximum oxygen uptake capacity decreases relative to predicted values ​​for the same age, sex, and body size. It is more useful than absolute peak oxygen uptake for cross-sectional comparisons between different populations, especially for women, younger patients, and individuals with significant body size differences. A lower value indicates poorer overall cardiopulmonary reserve and a worse prognosis. In elderly patients with heart failure, a peak oxygen uptake percentage <50% of predicted value indicates a poor prognosis. Furthermore, for women or patients aged ≤50 years and ≥70 years, peak VO2 ≤50% predicted is an important reference standard for heart transplant assessment. Exercise load duration is the most direct indicator of a patient's overall exercise tolerance. Heart failure patients often exhibit shortened exercise time due to limited cardiac output reserve, peripheral muscle deadaptation, and autonomic dysfunction. Invigorating qi and warming yang to regulate the heart can enhance myocardial contractility, increase cardiac output, and improve myocardial blood and oxygen supply, thereby improving exercise tolerance and quality of life. Maximum oxygen pulse (VO2 max) approximates the amount of oxygen delivered and utilized by tissues with each heartbeat. In heart failure patients, due to limited stroke volume, VO2 max often shows a decreasing trend, and its rise curve may be flat. Studies by Ricardo et al. have shown that VO2 max not only helps identify cardiac-related exercise limitation but also serves as an independent predictor of cardiac death and complex events, while supplementing risk stratification of peak oxygen uptake. Recovery-at-one (RAP) value primarily reflects the speed of vagal reactivation and sympathetic withdrawal after exercise termination, and is an important non-invasive indicator of autonomic function. Heart failure patients often exhibit sympathetic overactivation and decreased vagal tone; therefore, their RAP value is usually reduced.Multiple studies have shown that a 1-minute recovery heart rate (RFR) <12 beats / min significantly increases the risk of all-cause mortality, while a RFR <5.5 beats / min combined with a VE / VCO slope >33 increases cardiovascular mortality by 9.2 times. The six-minute walk test (6MWD), as a measure of exercise tolerance in heart failure patients, not only comprehensively reflects the overall function of the cardiopulmonary, circulatory, skeletal muscle, and peripheral metabolic systems, but also, because it more closely resembles the exercise intensity in patients' daily lives, has been defined by the American Thoracic Society (ATS) as one of the standardized methods for assessing functional exercise capacity. For heart failure patients, a decrease in 6MWD typically indicates reduced exercise tolerance, impaired cardiac function, and a decline in overall functional reserve. The main reasons for this are related to insufficient cardiac output reserve, peripheral skeletal muscle deadaptation, endothelial dysfunction, and neurohumoral activation. Therefore, the 6-minute walk test, to some extent, reflects the symptom burden and disease severity in heart failure patients. The results of this study indicate that the combination of Yiqi Qiyang Tiaoxin Decoction and Western medicine treatment can effectively improve patients' peak oxygen uptake per kilogram, the percentage of peak oxygen uptake to predicted value, exercise load time, maximum oxygen pulse, and 1-minute heart rate recovery value, and increase the distance of the six-minute walk test. This is beneficial in reducing cardiovascular mortality and all-cause mortality, and can also improve patients' exercise tolerance, quality of life, and long-term prognosis. From the perspective of modern medical mechanisms, Codonopsis pilosula and Cinnamomum cassia in Yiqi Qiyang Decoction can improve myocardial energy metabolism, enhance myocardial contractility, and to some extent regulate the overactivation of the RAAS, reduce cardiac preload and afterload, and improve cardiac output. Secondly, blood-activating and stasis-removing drugs such as Salvia miltiorrhiza, Ligusticum chuanxiong, and Paeonia lactiflora have the effects of dilating coronary arteries, improving myocardial microcirculation, inhibiting platelet aggregation, and anti-inflammatory and antioxidant stress, which can alleviate myocardial ischemia and ventricular remodeling. Drugs such as Trichosanthes kirilowii and Allium macrostemon can relieve chest tightness and promote Yang, improve coronary blood flow, and regulate neurohumoral factors, thereby reducing sympathetic nerve excitability and improving cardiopulmonary circulation efficiency. The combined effects of these medications increase cardiac output and oxygen delivery capacity, enhancing the body's oxygen uptake and utilization during exercise, leading to increases in peak oxygen uptake, the ratio of peak oxygen uptake to predicted value, and maximum oxygen pulse. Simultaneously, improved cardiac autonomic nerve function enhances vagal nerve reactivation after exercise, increasing the 1-minute heart rate recovery value. Furthermore, improvements in myocardial blood supply and skeletal muscle oxygen utilization also contribute to extending exercise duration and increasing the six-minute walking distance.

[0196] 6.5 The impact of Yiqi Qiyang Tiaoxin Decoction combined with conventional Western medicine treatment on the quality of life of HFrEF patients

[0197] The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a heart failure-specific health-related quality of life assessment tool developed by Rector et al. in 1987. It was later adapted to suit Chinese lifestyles and culture, resulting in the "Chinese Culture-Based Modified Minnesota Living with Heart Failure Questionnaire (C-MLHFQ)." This scale is divided into physical, psychological, and other dimensions (social dimensions), primarily used to assess the impact of heart failure symptoms on patients' daily lives, psychological state, and social activities, providing a comprehensive evaluation of the quality of life for heart failure patients. Numerous studies have demonstrated its good reliability and validity, and it has been widely used in clinical research and efficacy evaluation of heart failure, making it one of the most widely used heart failure-specific quality of life scales. The results of this study show that after treatment with a combination of a warming and invigorating formula and Western medicine, the scores of all dimensions and the total score of patients significantly decreased compared to before treatment, indicating a significant improvement in their quality of life. From a physical perspective, the Qi-tonifying and Yang-warming formula effectively improves the circulation and vaporization of Qi, blood, body fluids, and other bodily fluids through its effects of tonifying Qi, warming Yang and unblocking the meridians, promoting blood circulation and removing blood stasis, and resolving phlegm and nodules. This increases systemic blood flow and oxygen content, thereby alleviating clinical symptoms such as shortness of breath and fatigue, reducing cardiac volume load, relieving symptoms such as dyspnea and lower limb edema, improving exercise tolerance and daily activity ability, and ultimately improving the patient's physical function. From a psychological perspective, in addition to physical symptoms, heart failure patients often experience varying degrees of anxiety and depression. Studies have shown that the incidence of anxiety and depression in heart failure patients is significantly higher than in the general population. This is not only related to the long-term disease burden, decreased activity level, and reduced quality of life, but also closely related to abnormal neuroendocrine and inflammatory responses. In patients with chronic heart failure, the sympathetic nervous system and RAAS are continuously overactivated, leading to neuroendocrine disorders and promoting the release of inflammatory factors. These inflammatory factors can induce or aggravate mood disorders such as anxiety and depression by affecting the neurotransmitter metabolism and neuroregulatory network of the central nervous system, while further promoting myocardial remodeling and deterioration of cardiac function, forming a vicious cycle. The results of this study show that patients treated with Yiqi Qiyang Tiaoxin Decoction experienced significant improvement in anxiety and depression-related quality of life scores, suggesting that this formula has certain advantages in improving the psychological state of heart failure patients. The reason for this is that insufficient heart yang leads to poor blood and qi circulation, resulting in phlegm and blood stasis, which can aggravate symptoms such as chest tightness and shortness of breath, and affect emotional activity, leading to malnourishment of the heart spirit and manifestations of anxiety and depression. Yiqi Qiyang Tiaoxin Decoction, with its core principle of invigorating heart qi and warming yang, is combined with herbs that invigorate blood circulation, remove blood stasis, promote yang and dissipate stagnation, and resolve phlegm and widen the chest. By replenishing heart qi, warming and invigorating heart yang, and regulating qi, it nourishes the heart spirit and harmonizes blood and qi, thereby improving the patient's emotional state and overall quality of life.Other dimensions are highly correlated with the physical and mental dimensions. Due to the decline in patients' exercise tolerance, daily activity ability, and recurrent clinical symptoms and re-hospitalization, social withdrawal and weakened family roles are common. Therefore, effectively improving patients' physical and mental dimensions can also reduce the scores of the social dimension and alleviate the phenomenon of social disconnection.

[0198] 7. Conclusion

[0199] This study evaluated the efficacy and safety of Yiqi Wenyang Tiaoxin Formula in treating elderly patients with chronic heart failure with reduced ejection fraction from a clinical trial perspective. The results showed that Yiqi Wenyang Tiaoxin Formula combined with conventional Western medicine treatment:

[0200] (1) It can effectively improve the patient's main symptoms such as chest tightness and shortness of breath, as well as secondary symptoms such as spontaneous sweating, aversion to cold and cold limbs, and reduce the overall score of the TCM clinical syndrome scale.

[0201] (2) It can effectively reduce the level of NT-proBNP in the plasma of patients with heart failure.

[0202] (3) It can effectively improve patients’ peak oxygen uptake per kilogram, percentage of peak oxygen uptake to predicted value, exercise load time, maximum oxygen pulse and 1-minute heart rate recovery value, and increase patients’ six-minute walking test distance.

[0203] (4) It can reduce the scores of patients in the physical dimension, mental dimension and other dimensions, and improve the quality of life of patients from multiple aspects such as physical, psychological and social aspects.

[0204] (5) This formula has a high safety profile in clinical applications.

[0205] Example 2

[0206] Take the following Chinese medicinal materials in the following proportions: Cinnamon twig 7, Codonopsis pilosula 9, Atractylodes macrocephala 11, Salvia miltiorrhiza 12, Poria cocos 9, Ligusticum chuanxiong 12, Trichosanthes kirilowii 9, Allium macrostemon 12, and Paeonia lactiflora 8.

[0207] Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 35 minutes. Filter and collect the filtrate. Add water to the residue, continue heating to a boil, then simmer for 26 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain the Qi-invigorating and Yang-regulating Heart-Tonifying Herb. Prepare the Qi-invigorating and Yang-regulating Heart-Tonifying Herb into granules.

[0208] Example 3

[0209] Take the following Chinese medicinal materials in the following proportions: Cinnamon twig 5, Codonopsis pilosula 10, Atractylodes macrocephala 8, Salvia miltiorrhiza 9, Poria cocos 8, Ligusticum chuanxiong 8, Trichosanthes kirilowii 9, Allium macrostemon 8, and Paeonia lactiflora 6.

[0210] Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 22 minutes. Filter and collect the filtrate. Add water to the residue, continue heating to a boil, then simmer for 18 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain a medicine for invigorating qi, warming yang, and regulating the heart. Make the medicine into pills.

[0211] Although embodiments of this application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting this application. Those skilled in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of this application. Based on this, various substitutions and improvements can be made to this application, all of which fall within the protection scope of this application.

Claims

1. A formula for invigorating qi, warming yang, and regulating the heart, characterized in that, The components include the following parts by weight: Cinnamon twig 5-10g, Codonopsis pilosula 6-14g, Atractylodes macrocephala 5-14g Salvia miltiorrhiza 6-14g, Poria cocos 5-14g, Ligusticum chuanxiong 6-14g Trichosanthes kirilowii 5-15g, Allium macrostemon 6-15g, Paeonia lactiflora 5-10g.

2. The formula for invigorating qi and warming yang and regulating the heart according to claim 1, characterized in that, The components include the following parts by weight: Cinnamon twig 4-9g, Codonopsis pilosula 7-13g, Atractylodes macrocephala 6-13g Salvia miltiorrhiza 7-13, Poria cocos 6-14, Ligusticum chuanxiong 7-13, Trichosanthes kirilowii 6-14g, Allium macrostemon 8-13g, Paeonia lactiflora 6-9g.

3. The formula for invigorating qi and warming yang and regulating the heart according to claim 2, characterized in that, The components include the following parts by weight: Cinnamon twig 5-8g, Codonopsis pilosula 8-12g, Atractylodes macrocephala 7-12g Salvia miltiorrhiza 8-12, Poria cocos 7-12, Ligusticum chuanxiong 8-12, Trichosanthes kirilowii 7-12g, Allium macrostemon 9-12g, Paeonia lactiflora 5-8g.

4. The formula for invigorating qi and warming yang and regulating the heart according to claim 3, characterized in that, The components include the following parts by weight: Cinnamon twig 7g, Codonopsis pilosula 9g, Atractylodes macrocephala 11g Salvia miltiorrhiza 9g, Poria cocos 11g, Ligusticum chuanxiong 9g Trichosanthes kirilowii 11g, Allium macrostemon 9g, Paeonia lactiflora 7g.

5. The formula for invigorating qi and warming yang and regulating the heart according to claim 4, characterized in that, The components include the following parts by weight: Cinnamon twig 6g, Codonopsis pilosula 10g, Atractylodes macrocephala 10g Danshen 10g, Fuling 10g, Chuanxiong 10g Trichosanthes kirilowii 10g, Allium macrostemon 10g, Paeonia lactiflora 6g.

6. A method for preparing a formula for invigorating qi, warming yang, and regulating the heart, characterized in that, Includes the following steps: Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 20-40 minutes. Filter and collect the filtrate. Add water to the residue, continue heating and boiling, then simmer for 15-30 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain a warming and yang-regulating heart-tonifying medicine.

7. The preparation method of the Qi-tonifying, Qi-warming, and heart-regulating formula according to claim 6, characterized in that, Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 22-38 minutes. Filter and collect the filtrate. Add water to the residue, continue heating and boiling, then simmer for 18-28 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain a warming and yang-regulating heart-tonifying medicine.

8. The preparation method of the Qi-tonifying, Qi-warming, and heart-regulating formula according to claim 7, characterized in that, Take cinnamon twig, codonopsis root, atractylodes rhizome, salvia root, poria cocos, chuanxiong rhizome, trichosanthes fruit, allium macrostemon, and red peony root. Boil them, then simmer for 30 minutes. Filter and collect the filtrate. Add water to the residue, continue heating and boiling, then simmer for 24 minutes. Filter and retain the filtrate. Combine the two filtrates to obtain a medicine that benefits qi, warms yang, and regulates the heart.

9. The preparation method of the Qi-tonifying, Qi-warming, and heart-regulating formula according to claim 8, characterized in that, The medicine that invigorates qi, warms yang, and regulates the heart is made into granules.

10. The preparation method of the Qi-tonifying, Qi-warming, and heart-regulating formula according to claim 8, characterized in that, The medicine that invigorates qi, warms yang, and regulates the heart is made into pills.

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