Qi-xue-bing-zhi-fang composition and its application in treating coronary heart disease combined with anxiety and depression state

Abstract

The application discloses a composition of Qixuebengzhi recipe and belongs to the field of traditional Chinese medicines; the composition is mainly prepared from bupleurum, immature fruit of citrus, persicae semen, safflower, chuanxiong and red peony root; the application is based on the concept of treating heart and body simultaneously, and through the ascending and descending of qi and the regulating of liver qi of bupleurum and immature fruit of citrus, the composition can dredge the liver and regulate qi, and through the dispersing of persicae semen and safflower, the composition can dredge the channels and remove stasis, and through the combination of chuanxiong and red peony root, the composition can regulate qi and blood, and the combination of the medicines can directly attack the core pathogenesis of qi stagnation and blood stasis; clinical verification shows that the composition can not only significantly improve the TCM syndromes such as chest pain and chest distress of patients and the frequency of angina pectoris attacks, but also quickly relieve anxiety and depression and improve sleep quality.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a formula for treating both qi and blood and its application in treating coronary heart disease complicated with anxiety and depression. Background Technology

[0002] Coronary atherosclerotic heart disease (CHD) is one of the leading causes of disability and death worldwide. With the shift in modern medical models, the phenomenon of CHD patients experiencing co-occurring psychological disorders such as anxiety and depression (clinically termed "dual heart disease") is becoming increasingly prominent. Clinical observations indicate that approximately 40% of CHD patients also experience varying degrees of anxiety or depression.

[0003] First, a clear vicious cycle exists between psychological disorders and cardiovascular events. Mental disorders can affect the prognosis of coronary heart disease through various pathophysiological mechanisms, including activation of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis (HPA axis), and induction of systemic chronic inflammatory responses. These physiological changes significantly increase the risk of adverse cardiovascular events, leading to further deterioration of the condition and forming a vicious cycle of "cardiac-psychological." Studies show that coronary heart disease patients who are in a state of severe anxiety and depression for a long time have a much higher risk of subsequent acute myocardial infarction, heart failure, or even sudden death than psychologically healthy patients.

[0004] Secondly, existing clinical interventions have limitations. Currently, treatment for these patients mainly involves secondary prevention of coronary heart disease (such as antiplatelet drugs, statins, and beta-blockers) combined with Western medicine anti-anxiety or antidepressant drugs. However, long-term combined use of Western medicine has the following problems:

[0005] Drug interaction risk: When antidepressants (such as SSRIs) are used in combination with commonly used coronary heart disease drugs (such as antiplatelet drugs), the risk of bleeding may increase or affect the metabolism of cytochrome P450 enzymes.

[0006] Added adverse reactions: Some antipsychotic drugs have potential cardiotoxicity and may cause arrhythmias (such as QT interval prolongation), which poses a safety risk to patients with coronary heart disease and myocardial damage.

[0007] Poor patient compliance: Due to concerns about the addictive nature or side effects of psychotropic drugs, some patients are resistant, leading to treatment interruption.

[0008] Furthermore, traditional Chinese medicine formulas still require further optimization and precision in clinical application. Traditional Chinese medicine theory emphasizes the unity of body and mind, believing that qi stagnation and blood stasis are the core pathogenesis leading to the coexistence of "chest pain" and "restlessness." Although classic formulas such as "Xuefu Zhuyu Decoction" are widely used clinically, they contain many ingredients, and there is still room for improvement in terms of precision and ease of preparation for this specific syndrome of stable coronary heart disease complicated by anxiety and depression.

[0009] Therefore, there is an urgent clinical need to find an intervention program that can simultaneously regulate qi and blood circulation (treating the physical symptoms) and calm the mind and relieve depression (treating the mental symptoms), while also being highly safe, having few drug interactions, and having a standardized preparation process. This invention proposes a qi and blood stagnation treatment formula for coronary heart disease with qi stagnation and blood stasis combined with anxiety and depression by carefully selecting medicinal ingredients and optimizing the proportions. The aim is to achieve holistic treatment of mind and body and break the vicious cycle between the heart and the mind. Summary of the Invention

[0010] To address the above deficiencies, this invention provides a formula composition for treating both Qi and Blood Circulation, prepared from the following raw materials in parts by weight:

[0011] 10-20 parts of Ligusticum chuanxiong, 10-20 parts of Paeonia lactiflora, 10-15 parts of Prunus persica, 10-15 parts of Carthamus tinctorius, 5-15 parts of Bupleurum chinense, and 10-15 parts of Citrus aurantium.

[0012] Furthermore, the ingredients are: 15 parts of Ligusticum chuanxiong, 15 parts of Paeonia lactiflora, 15 parts of Prunus persica, 10 parts of Carthamus tinctorius, 5 parts of Bupleurum chinense, and 10 parts of Citrus aurantium.

[0013] This invention discloses a method for preparing granules of the above-mentioned Qi and Blood Circulation Treatment Formula, comprising the following steps:

[0014] P1. Decoction: The composition is decocted twice with water to obtain two decoctions;

[0015] First, add 6 times the amount of water and boil for 30 minutes; second, add 4 times the amount of water and boil for 20 minutes. The temperature for both boilings should be 95 to 100℃.

[0016] P2. Concentration: The decoctions from the two decoctions are mixed and filtered, and then concentrated under reduced pressure at a temperature of 55 to 60°C and a vacuum degree of -0.08 to 0.09 MPa to produce a paste with a relative density of 1.10 to 1.20 at 50°C.

[0017] P3. Granulation: Add excipients to the paste, granulate in one step using a fluidized bed, and dry to obtain granules.

[0018] Furthermore, the excipient in step P3 is dextrin.

[0019] This invention also discloses the application of a Qi and Blood Treatment Formula composition, which is used to treat coronary heart disease complicated with anxiety or depression.

[0020] Furthermore, the coronary heart disease mentioned is stable coronary heart disease of the qi stagnation and blood stasis type.

[0021] Compared with the prior art, the present invention has the following advantages:

[0022] 1. This invention's Qi and Blood Regulating Formula, when used in conjunction with conventional Western secondary prevention, can significantly enhance therapeutic efficacy. Clinical trials (Example 3) show that the total effective rate of TCM syndromes in the experimental group reached 86.96%, significantly superior to the control group (70.77%) treated with conventional methods alone. Generalized Estimating Equation (GEE) analysis shows that this invention can significantly reduce TCM syndrome scores after 4 weeks of administration, demonstrating rapid onset of action. Simultaneously, the Seattle Angina Scale (SAQ) shows significantly amplified improvements in dimensions such as the degree of physical activity limitation, angina stability, and attack frequency, greatly improving patients' quality of life.

[0023] 2. The experimental group showed significantly greater reductions in depression (PHQ-9) and anxiety (GAD-7) scores and at a greater speed than the control group. At the same time, the experimental group also showed comprehensive improvements in sleep quality, sleep onset time, and sleep efficiency (PSQI), confirming that this composition can effectively eliminate the mental and psychological burden of patients through "soothing the liver and regulating qi".

[0024] 3. It can significantly downregulate the levels of pro-inflammatory factors CRP and IL-6 in serum, effectively protect vascular endothelium, inhibit the progression of atherosclerosis, and make up for the deficiency of rebound of inflammatory markers in the control group after intervention; it can significantly reduce the abnormal expression of 5-HT and adrenaline (E), effectively regulate the stress state of the hypothalamus-pituitary-adrenal axis (HPA), and break the vicious cycle of "mental stress-vasospasm / damage" from the material basis;

[0025] 4. Using only six Chinese herbs, this formula fully utilizes the classic herbal pairings of "Bupleurum-Immature Bitter Orange," "Peach Kernel-Safflower," and "Ligusticum striatum-Red Peony Root," resulting in a simple yet potent formula that avoids the metabolic burden associated with traditional large prescriptions. Complete clinical observation over a full period showed no clinically significant abnormalities in the subjects' routine blood, urine, and stool tests, liver and kidney function, coagulation indicators, and electrocardiograms, demonstrating the extremely high safety of this composition during long-term use and its suitability for widespread clinical application. Attached Figure Description

[0026] Figure 1 This is a line graph of the median in Example 3.

[0027] Figure 2 This is a line graph showing the changes in PHQ-9 scores at different time points in Example 3.

[0028] Figure 3 This is a line graph showing the changes in GAD-7 scores at different time points in Example 3. Detailed Implementation

[0029] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0030] Example 1

[0031] This embodiment provides a formula for treating coronary heart disease with qi stagnation and blood stasis complicated by anxiety and depression. The composition and weight parts of the raw materials used in this embodiment are as follows:

[0032] 15 parts of Ligusticum chuanxiong, 15 parts of Paeonia lactiflora, 15 parts of Prunus persica, 10 parts of Carthamus tinctorius, 5 parts of Bupleurum chinense, and 10 parts of Citrus aurantium.

[0033] It should be noted that the weight range is acceptable:

[0034] 10-20 parts of Ligusticum chuanxiong, 10-20 parts of Paeonia lactiflora, 10-15 parts of Prunus persica, 10-15 parts of Carthamus tinctorius, 5-15 parts of Bupleurum chinense, and 10-15 parts of Citrus aurantium.

[0035] This formula is a simplified version of Xuefu Zhuyu Decoction. Through the scientific combination of qi-regulating herbs (Bupleurum and Citrus aurantium) and blood-activating herbs (Ligusticum chuanxiong, Paeonia lactiflora, Prunus persica, and Carthamus tinctorius), it aims to achieve both physical and mental well-being and to treat both the mind and body.

[0036] Example 2

[0037] This embodiment describes a method for preparing the Qi and Blood Treatment Formula composition from Example 1 into Qi and Blood Treatment Formula granules, including the following steps:

[0038] P1. Boil the raw materials in Example 1 twice with water according to their weight proportions.

[0039] P101. First decoction: Add water with a weight of 6 times that of the raw materials, decoct for 30 minutes, and control the decoction temperature at 95-100℃.

[0040] P102. Second decoction: Add water with a weight of 4 times that of the raw materials, decoct for 20 minutes, and control the decoction temperature at 95-100℃.

[0041] P2. Combine the filtrates from both decoctions and filter.

[0042] P201. The filtrate is treated under reduced pressure concentration conditions, with the concentration temperature set at 55-60℃ and the vacuum degree controlled at -0.08 to -0.09 MPa.

[0043] P202, Concentrate to form a paste-like extract with a relative density of 1.10 to 1.20 measured at 50°C;

[0044] P3. Granules are prepared by one-step fluidized bed granulation process (with dextrin as an excipient).

[0045] It should be noted that the mimic used in the control group in Example 3 was made by combining 5% of the prescription amount with caramel and dextrin to ensure that the appearance and smell were basically the same as those of the experimental group.

[0046] Example 3

[0047] This embodiment verifies the clinical efficacy of the composition in Example 1 and the granules prepared by the method in Example 2 through a randomized controlled clinical trial.

[0048] I. Clinical Data and Trial Design

[0049] 1.1 Experimental subjects and grouping

[0050] 134 patients with stable coronary heart disease of the Qi stagnation and blood stasis type complicated with anxiety and depression, admitted between April 2024 and May 2025, were randomly divided into an experimental group (69 cases) and a control group (65 cases). Statistical analysis showed no significant differences between the two groups in baseline data such as age, gender, disease duration, and past medical history (P>0.05), making them comparable.

[0051] 1.1.1 Diagnostic Criteria

[0052] Western medicine diagnosis: meets the diagnosis of stable coronary heart disease (with typical chest pain, ST segment changes on electrocardiogram or coronary angiography stenosis ≥50%), and the scores of GAD-7 (anxiety) and PHQ-9 (depression) scales are both between 5 and 14.

[0053] Traditional Chinese Medicine Syndrome: Qi stagnation and blood stasis syndrome. Main symptoms: chest tightness and chest pain; secondary symptoms: chest and rib distension and palpitations; tongue and pulse: dark tongue, wiry or wiry and hesitant pulse.

[0054] 1.1.2 Inclusion and Exclusion Criteria

[0055] Subjects aged 18-75 years with a disease duration of more than 1 year and a history of myocardial infarction or evidence of coronary artery stenosis were included. Patients with severe arrhythmias, heart failure (LVEF <30%), and those who had taken other anti-anxiety medications in the past 4 weeks were excluded to eliminate confounding factors.

[0056] 1.2 Treatment intervention process (divided into three stages)

[0057] 1.2.1 Baseline assessment phase (week 0): TCM syndrome scoring and various scales (SAQ, PHQ-9, GAD-7, PSQI) were performed on enrolled patients, and venous blood was collected to detect cytokines;

[0058] 1.2.2 Intervention Phase (Weeks 1-8)

[0059] Control group: Received conventional Western medicine for coronary heart disease (antiplatelet drugs, statins, beta-blockers, etc.) + mimic granules (made from 5% of the prescription amount of Qi Xue Bing Zhi Fang and caramel and dextrin. Its appearance, size, color, dosage form, weight, taste, and even odor are the same as or basically similar to Qi Xue Bing Zhi Fang, and the preparation method is the same as the preparation method of Qi Xue Bing Zhi Fang granules).

[0060] Experimental group: In addition to the control group, the group was given the Qi and Blood Treatment Formula Granules prepared in Example 2 (1 sachet each time, twice a day, taken with warm water).

[0061] Mid-term follow-up was conducted in week 4 to assess medication adherence and safety;

[0062] At the end of the 8th week of treatment, all clinical assessments and laboratory tests from the baseline period were repeated.

[0063] 1.3 Observation Indicator Scoring Criteria

[0064] 1.3.1 Traditional Chinese Medicine Syndrome Scoring: Quantification of chest pain, chest tightness (0 / 2 / 4 / 6 points) and secondary symptoms (0 / 1 / 2 / 3 points):

[0065] Therapeutic effect index

[0066] Effective ),efficient( ) and invalid ( ).

[0067] 1.3.2 Seattle Angina Scale (SAQ): Assesses 5 dimensions; higher scores indicate better quality of life.

[0068] 1.3.3 Mood and Sleep Scales: PHQ-9 (Depression), GAD-7 (Anxiety), PSQI (Sleep Quality).

[0069] 1.3.4 Physicochemical indicators: inflammatory factors (CRP, IL-6, TNF-α) and neurotransmitters (5-HT, NE, E).

[0070] 1.3.5 Safety indicators: routine blood, urine and stool tests, liver and kidney function tests, coagulation tests, and electrocardiogram.

[0071] 1.4 Statistical Methods

[0072] Statistical analysis was performed using SPSS 27.0 software. For continuous data, if they conformed to a normal distribution and had homogeneity of variance, they were described using the mean ± standard deviation, and comparisons between groups were performed using the independent samples t-test; otherwise, they were described using the median (interquartile range), and comparisons between groups were performed using the Mann-Whitney U test. For categorical data, they were described using frequencies (percentages), and comparisons between groups were performed using the chi-square test. For repeated measures continuous data, if they conformed to a normal distribution, one-way repeated measures ANOVA was used; if they did not conform to a normal distribution, generalized estimating equation analysis was used. P < 0.05 was considered statistically significant.

[0073] II. Research Results

[0074] 2.1 General Information and Baseline Comparison

[0075] There were no statistically significant differences between the two groups in terms of age (63 years in the experimental group vs. 62 years in the control group), BMI, gender, smoking and drinking history, and past medical history (heart failure, stroke, peripheral arterial disease, etc.) (P>0.05), and the baselines were comparable, as shown in Table 1 below.

[0076] Table 1

[0077]

[0078]

[0079]

[0080]

[0081] Note: * indicates continuity correction.

[0082] 2.2 Comparison of TCM syndrome score ratings

[0083] Before treatment, and at 4 and 8 weeks after treatment, the TCM syndrome scores of the two groups did not conform to a normal distribution (P < 0.05). Repeated measures data analysis using the generalized estimating equation (GEE) showed a group effect: Wald x 2 = 6.583, P = 0.01, indicating a significant difference in TCM syndrome scores between the experimental group and the control group; Time effect: Wald x 2 =380.905, P<0.001, indicating that the TCM syndrome score changed significantly over time; group × time interaction effect: Wald x 2 = 6.573, P = 0.037, indicating a significant difference in the changing trends of the TCM syndrome scores between the two groups, as shown in Table 2 (parameter estimation results of the generalized estimation equation):

[0084] Table 2

[0085]

[0086] Simple time-effects analysis showed that before enrollment, the median TCM syndrome scores of both the experimental and control groups were 12 (9, 16), with no statistically significant difference between the groups (Z = -0.308, P = 0.758), indicating that the baselines of the two groups were comparable. After 4 weeks of intervention, the median TCM syndrome score of the experimental group decreased to 8 (6, 9), while that of the control group was 9 (7, 11), and the score of the experimental group was significantly lower than that of the control group, with a statistically significant difference (Z = -2.714, P = 0.007). After 8 weeks of intervention, the score of the experimental group further decreased to 4 (3, 7), while that of the control group was 6 (4, 9), and the score of the experimental group was still significantly lower than that of the control group, with a more statistically significant difference (Z = -3.147, P = 0.002), as shown in Table 3 (Comparison of TCM syndrome scores at different time points between the two groups [M(P)]). 25 P 75 As shown in the image:

[0087] Table 3

[0088]

[0089]

[0090] Combined with a median line graph (e.g.) Figure 1 As shown in Table 4 (Total Treatment Rate), the results are intuitively displayed. Analysis reveals that after 8 weeks of treatment, the total effective rate in the experimental group was 86.96%, significantly higher than the 70.77% in the control group (P < 0.05). This indicates that the composition of the present invention can significantly improve the TCM clinical symptoms of patients with Qi stagnation and blood stasis type dual-heart disease, and its efficacy is superior to conventional Western medicine treatment alone.

[0091] Table 4

[0092]

[0093] 2.3 Comparison of Seattle Angina Scale scores (SAQ score)

[0094] Before treatment, there were no statistically significant differences in the scores of any item on the SAQ scale between the two groups (P > 0.05), indicating comparability. Intra-group comparisons showed significant differences between the experimental and control groups before and after treatment in terms of physical activity limitation, angina stability, angina attack frequency, treatment satisfaction, and disease awareness (P < 0.05). Furthermore, the improvement in the experimental group was superior to that in the control group, as shown in Table 5 (Comparison of SAQ dimensions within different time points).

[0095] Table 5

[0096]

[0097]

[0098] Note: *P < 0.05.

[0099] Intergroup comparisons showed that after 8 weeks of treatment, the experimental group was significantly better than the control group in terms of physical activity limitation (Z=-2.127, P=0.033), angina stability (Z=-4.525, P<0.001), angina attack frequency (Z=-2.269, P=0.023), treatment satisfaction (Z=-2.520, P=0.012), and disease awareness (Z=-3.542, P<0.001). Further difference analysis showed that the experimental group showed significantly greater improvement in all dimensions than the control group. In conclusion, the Qi and Blood Regulating Therapy Formula has clear advantages in improving physical limitation, angina symptoms (stability and attack frequency), treatment satisfaction, and disease awareness in patients with coronary heart disease complicated by anxiety and depression, as shown in Table 6 (intergroup comparison of SAQ dimensions between the two groups).

[0100] Table 6

[0101]

[0102] Note: Δ = after 8 weeks of treatment - baseline.

[0103] 2.4 Comparison of PHQ-9 (Depression) Scores

[0104] The PHQ-9 scores of the two groups before treatment, at 4 weeks of treatment, and at 8 weeks of treatment did not conform to a normal distribution (P < 0.05). Repeated measures data analysis using GEE showed that the group effect was: Wald x 2 = 8.742, P = 0.003, indicating a significant difference in depression scores between the experimental group and the control group; time effect: Wald x 2 = 510.431, P < 0.001, indicating a significant change in depression scores over time; group × time interaction effect: Wald x 2 = 9.168, P = 0.01, indicating a significant difference in the trend of depression scores between the two groups, as shown in Table 7 (parameter estimation results of the generalized estimation equation):

[0105] Table 7

[0106]

[0107] Simple effects analysis over time showed that before enrollment, the median depression level in both the experimental and control groups was 10 (7, 12), with no statistically significant difference between the groups (Z = -0.963, P = 0.336), indicating that the baselines of the two groups were comparable. After 4 weeks of intervention, the median depression level in the experimental group decreased to 6 (4, 8), while that in the control group was 8 (5.5, 10), and the experimental group score was significantly lower than that in the control group, with a statistically significant difference (Z = -3.200, P < 0.001). After 8 weeks of intervention, the experimental group score further decreased to 4 (2.5, 6), while that in the control group was 5 (4, 9), and the experimental group score was still significantly lower than that in the control group, with an even more statistically significant difference (Z = -3.079, P = 0.002), as shown in Table 8 (Comparison of PHQ-9 scores at different time points between the two groups [M(P)]). 25 P 75 As shown in the image:

[0108] Table 8

[0109]

[0110] Combined with a median line chart (such as...) Figure 2 As shown in the figure, the experimental group experienced a greater and faster decline in depressive symptoms, suggesting that the intervention measures in the experimental group were more effective in improving depressive symptoms.

[0111] 2.5 Comparison of GAD-7 (Anxiety) Scores

[0112] The GAD-7 scores of the two groups before treatment, at 4 weeks of treatment, and at 8 weeks of treatment did not conform to a normal distribution. <0.05). Repeated measures data analysis using GEE showed that the group effect was: Wald x 2 = 4.353, P = 0.037, indicating a significant difference in anxiety scores between the experimental and control groups; time effect: Wald x 2 = 580.629, P < 0.001, indicating that anxiety scores changed significantly over time; group × time interaction effect: Wald x 2 = 21.078, P < 0.001, indicating a significant difference in the trend of anxiety scores between the two groups, as shown in Table 9 (parameter estimation results of the generalized estimation equation):

[0113] Table 9

[0114]

[0115] Simple effects analysis over time showed that before enrollment, the median anxiety level in both the experimental and control groups was 11 (6, 13), with no statistically significant difference between the groups (Z = -0.484, P = 0.628), indicating that the baselines of the two groups were comparable. After 4 weeks of intervention, the median anxiety level in the experimental group decreased to 6 (4, 8), while that in the control group was 7 (5, 10), and the experimental group's score was significantly lower than that of the control group, with a statistically significant difference (Z = -2.026, P = 0.043). After 8 weeks of intervention, the score in the experimental group further decreased to 3 (2, 5), while that in the control group was 5 (3, 7), and the experimental group's score was still significantly lower than that of the control group, with an even more statistically significant difference (Z = -3.740, P < 0.001), as shown in Table 10 (Comparison of PHQ-9 scores at different time points between the two groups [M(P)]). 25 P 75 As shown in the image:

[0116] Table 10

[0117]

[0118] Combined with a median line graph (e.g.) Figure 3 As shown in the figure, the experimental group experienced a greater and faster decrease in anxiety, suggesting that the intervention measures in the experimental group were more effective in improving anxiety.

[0119] 2.6 Analysis of Sleep Quality Improvement (PSQI Score)

[0120] Before treatment, there were no statistically significant differences in any PSQI indicators between the two groups (P > 0.05), making them comparable. After 8 weeks of treatment, the PSQI scores of all dimensions in both the experimental and control groups were significantly lower than baseline (experimental group: Z = -6.016 to -3.376, all P < 0.001; control group: Z = -5.776 to -3.809). Or P = 0.005), as shown in Table 11 (comparison of PSQI scores within different time groups):

[0121] Table 11

[0122]

[0123] After 8 weeks of treatment, intergroup comparisons showed that the experimental group was significantly better than the control group in terms of sleep quality, sleep onset time, sleep efficiency, and daytime dysfunction (P < 0.05), while there were no statistically significant differences between the two groups in terms of sleep duration, sleep disturbance, and use of hypnotic drugs (P > 0.05). Intergroup comparisons of differences showed statistically significant differences in sleep quality and sleep onset time in the experimental group (Z = -4.083, P < 0.05), while there were no statistically significant differences in the other dimensions (P > 0.05), as shown in Table 12 (intergroup comparison of PSQI scores between the two groups).

[0124] Table 12

[0125]

[0126]

[0127] Note: *P<0.05, **P<0.01, Δ=8 weeks after treatment - baseline.

[0128] 2.7 Comparison of inflammatory factor levels

[0129] The analysis of inflammatory markers was based on data from 40 subgroups (21 in the experimental group and 19 in the control group). Before treatment, there were no statistically significant differences in CRP, IL-6, and TNF-α levels between the two groups (P > 0.05). Within-group analysis showed that, compared with pre-treatment levels, CRP, IL-6, and TNF-α levels significantly decreased in the experimental group after 8 weeks of treatment (P < 0.05), while they increased in the control group (P < 0.01). Between-group analysis showed that the experimental group had better efficacy than the control group (P < 0.05), as shown in Table 13 (Comparison of inflammatory factor levels between the two groups).

[0130] Table 13

[0131]

[0132]

[0133] 2.8 Neurotransmitter Level Analysis

[0134] The correlation analysis of 5-HT, NE, and E levels was based on data from 40 subgroup subjects (21 in the experimental group and 19 in the control group). Before treatment, there were no statistically significant differences in 5-HT, NE, and E levels between the two groups (P > 0.05). Within-group analysis showed that, compared with before treatment, the levels of 5-HT, NE, and E in the experimental group decreased significantly after 8 weeks of treatment (P < 0.05), while there was no statistically significant decrease in the control group (P > 0.05). Between-group analysis showed that the experimental group had better efficacy than the control group (P < 0.05), as shown in Table 14 (Comparison of 5-HT, NE, and E levels between the two groups).

[0135] Table 14

[0136]

[0137] 2.9 Safety Indicators

[0138] There were no statistically significant differences in blood routine tests, urine and stool routine tests, liver and kidney function, coagulation tests, and electrocardiograms before and after treatment (P>0.05), and no serious adverse reactions occurred, as shown in Table 15 (safety indicators):

[0139] Table 15

[0140]

[0141] In summary, randomized controlled trials have confirmed that the Qi and Blood Circulation Treatment Formula (and the prepared granules) of this invention can significantly improve the symptoms of patients with coronary heart disease complicated by anxiety and depression. Its pharmacological mechanism is as follows:

[0142] Synergistic effects of the herbal combinations: Bupleurum and Citrus aurantium regulate Qi and soothe the liver; Peach kernel and Carthamus tinctorius promote blood circulation and remove blood stasis; Ligusticum chuanxiong and Paeonia lactiflora regulate both Qi and blood. Data mining shows that these herbal combinations have core therapeutic value for Qi stagnation and blood stasis type of dual heart disease.

[0143] Anti-inflammatory and protective effects: It exerts anti-inflammatory and anti-atherosclerotic effects by reducing IL-6 and TNF-α levels and improving blood rheology.

[0144] Neural regulation: Significantly reduces the expression of 5-HT, NE, and E, regulates stress state, alleviates anxiety and depression, and achieves synergistic effects of "body and mind as one".

[0145] It should be noted that the structure described in this invention can be implemented in many different forms and is not limited to the embodiments described. Any equivalent modifications made by those skilled in the art using this specification, or direct or indirect applications in other related technical fields, such as the loading and unloading of other items, are included within the scope of protection of this invention.

Claims

1. A formula composition for treating both Qi and Blood, characterized in that, It is prepared from the following raw materials in parts by weight: 10-20 parts of Ligusticum chuanxiong, 10-20 parts of Paeonia lactiflora, 10-15 parts of Prunus persica, 10-15 parts of Carthamus tinctorius, 5-15 parts of Bupleurum chinense, and 10-15 parts of Citrus aurantium.

2. The Qi and Blood Treatment Composition as described in claim 1, characterized in that: The ingredients were: 15 parts of Ligusticum chuanxiong, 15 parts of Paeonia lactiflora, 15 parts of Prunus persica, 10 parts of Carthamus tinctorius, 5 parts of Bupleurum chinense, and 10 parts of Citrus aurantium.

3. A method for preparing granules based on the Qi and Blood Treatment Formula composition according to any one of claims 1 or 2, characterized in that: Includes the following steps: P1. Decoction: The composition is decocted twice with water to obtain two decoctions; First, add 6 times the amount of water and boil for 30 minutes; second, add 4 times the amount of water and boil for 20 minutes. The temperature for both boilings should be 95 to 100℃. P2. Concentration: The decoctions from the two decoctions are mixed and filtered, and then concentrated under reduced pressure at a temperature of 55 to 60°C and a vacuum degree of -0.08 to 0.09 MPa to produce a paste with a relative density of 1.10 to 1.20 at 50°C. P3. Granulation: Add excipients to the paste, granulate in one step using a fluidized bed, and dry to obtain granules.

4. The preparation method according to claim 3, characterized in that: The excipient in step P3 is dextrin.

5. The application of the Qi and Blood Treatment Composition according to any one of claims 1 or 2, characterized in that: The formula for treating both Qi and Blood Circulation is used to treat coronary heart disease complicated by anxiety or depression.

6. The application as described in claim 5, characterized in that: The coronary heart disease mentioned is a stable coronary heart disease of the qi stagnation and blood stasis type.

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