Traditional Chinese medicine preparations for treating coronary atherosclerotic heart disease combined with anxiety and depression

Abstract

The present invention discloses a traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease complicated with anxiety and depression. The preparation is prepared from the following raw materials: 25-35 g of processed Chuanwu, 8-12 g of black aconite root, 25-35 g of cinnamon twig, 25-35 g of bupleurum root, 25-35 g of turmeric root, 25-35 g of cyperus rotundus, 25-35 g of immature bitter orange, 25-35 g of atractylodes macrocephala, 45-55 g of raw dragon bone, 45-55 g of raw oyster, 25-35 g of raw betel nut, 25-35 g of toosendan fruit, and 25-35 g of green tangerine peel. Clinical studies have shown that the traditional Chinese medicine preparation of the present invention significantly improves symptoms such as chest tightness and pain, palpitations, shortness of breath, insomnia, anxiety, irritability, and depression in patients after treatment, compared with a control group (taking delexin orally). The improvement in SAQ scores, HAMD scores, HAMA scores, and TCM syndrome scores is also better than that of the control group, demonstrating significant efficacy.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression, belonging to the technical field of traditional Chinese medicine preparations. Background Art

[0002] Coronary heart disease (CHD) is a common cardiovascular disease, also referred to as "coronary heart disease" (CHD) in Traditional Chinese Medicine (TCM). The acute phase of CHD presents suddenly, with plaque rupture leading to coronary artery stenosis and thrombosis, manifesting as squeezing chest pain, sweating, and other discomfort. The chronic phase presents with symptoms of unstable angina. The disease has a high incidence rate, numerous accompanying symptoms, and a poor prognosis. Anxiety and depression are typical psychological disorders, classified in TCM as "depression syndrome," with clinical manifestations including anxiety, tension, low mood, and insomnia. Currently, coexisting anxiety and depression in CHD is one of the most common dual heart conditions in clinical practice. In patients with CHD, anxiety and depression are associated with an increased incidence of adverse cardiovascular events. As a significant factor affecting prognosis, anxiety and depression can induce coronary restenosis. Therefore, effective intervention for coexisting anxiety and depression in CHD is an urgent clinical challenge.

[0003] Western medicine typically treats anxiety and depression associated with coronary artery disease (CAD) with antianginal medications combined with antidepressants and antianxiety medications. However, these medications are not always suitable for patients with CAD due to their potential cardiotoxicity. Therefore, drug interactions and the selection of appropriate medications have become key areas of concern. There are four main classes of antianxiety and depression medications: tricyclics (TCAs), tetracyclics, selective serotonin reuptake inhibitors (SSRIs), and selective serotonin norepinephrine reuptake inhibitors (SNRIs). Tricyclics are no longer recommended due to the risk of causing serious arrhythmias and hypotension, and should be avoided in patients with CAD. SSRIs, such as sertraline and citalopram, are considered first-line treatments for CAD with anxiety and depression due to their safety and efficacy. However, high doses of citalopram can prolong the QTC interval, so sertraline is recommended as the preferred treatment. Mirtazapine, a representative tetracyclic, and venlafaxine, a representative SNRI, can be used as second-line treatments. At the same time, research has shown that the new anti-anxiety and anti-depressant drug, Delexin, can effectively improve symptoms and is currently widely used in clinical practice. This suggests that effective, cost-effective, and well-adherent treatments for bipolar disorder are the future research trend. Summary of the Invention

[0004] In view of the above-mentioned prior art, the present invention provides a traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression.

[0005] The present invention is achieved through the following technical solutions:

[0006] A traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease complicated with anxiety and depression is prepared from the following raw materials: 25-35 g of processed Chuanwu, 8-12 g of black aconite root, 25-35 g of cinnamon twig, 25-35 g of bupleurum, 25-35 g of turmeric, 25-35 g of cyperus rotundus, 25-35 g of immature bitter orange, 25-35 g of white atractylodes, 45-55 g of raw dragon bone, 45-55 g of raw oyster, 25-35 g of raw betel nut, 25-35 g of toosendan fruit, and 25-35 g of green peel.

[0007] Preferably, it is made from the following raw materials: processed Chuanwu 30 g, black aconite root 10 g, cinnamon twig 30 g, bupleurum 30 g, curcuma 30 g, cyperus rotundus 30 g, immature bitter orange 30 g, atractylodes 30 g, raw dragon bone 50 g, raw oyster 50 g, raw betel nut 30 g, toosendan fruit 30 g, and green peel 30 g.

[0008] The preparation method of the traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression comprises the following steps:

[0009] (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 20-40 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 20-40 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 20-40 minutes, and set aside;

[0010] (2) Decoction of processed Chuanwu and Heifu Pian for 1-2 hours (decoction first to reduce toxicity. During the decoction process, Chuanwu converts aconitine into aconitine. Modern Chinese medicine pharmacology research shows that the toxicity of aconitine is one-five thousandth of that of aconitine. Do not add cold water during the decoction. If the water is low during the decoction, add boiling water);

[0011] (3) Decoction of raw dragon bones and raw oysters for 20-30 minutes (raw dragon bones, raw oysters, and turtle shells are hard medicinal materials such as minerals and shells, so they should be decocted first);

[0012] (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 30 to 50 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 30 to 50 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

[0013] Furthermore, in step (1), the soaking time is 30 minutes.

[0014] Furthermore, the decoction time in step (2) is 1 hour; and the decoction time in step (3) is 25 minutes.

[0015] Furthermore, the decoction time in step (4) is 40 minutes.

[0016] The present invention provides a traditional Chinese medicine preparation for treating coronary artery disease (CAD) complicated with anxiety and depression. The treatment principle is as follows: The disease is often caused by insufficient heart yang, poor functioning of the heart's blood vessels, phlegm and blood stasis blocking blood vessels, poor qi function, and liver depression and qi stagnation. The heart is a yin-yang organ that functions as yang. The heart's function as the master of the mind is an extension of its function as the master of the blood vessels, which in turn provides the material basis for the heart's function as the master of the mind. Once the blood vessels are damaged and blood fails to nourish the heart, phlegm, blood stasis, and toxins cling to each other, corrupting the veins and damaging the heart, leading to disordered qi and blood, and loss of nourishment for the mind, forming the pathological basis for the development or exacerbation of depression. Furthermore, CHD is often accompanied by long-term physical symptoms such as chest tightness and persistent chest pain. This recurring discomfort can easily trigger emotional changes due to stress, leading to constant worry and panic, poor qi function, and a sense of melancholy. It is difficult to resolve negative emotions, manifesting as a depressed and pessimistic state. The use of traditional Chinese medicine can not only relieve chest tightness and chest pain, but also effectively treat anxiety and depression, while avoiding adverse reactions such as cardiotoxicity of Western medicine. Based on the etiology and pathogenesis, a prescription for relieving depression and calming the mind was developed. The processed Chuanwu and Aconite root in the prescription are yang medicines among yang medicines, which are constantly moving and have great power to open and break through, and can pass through all meridians; there is also cinnamon twig that can promote yang and transform qi, and is good at circulating blood, circulating through the meridians and reaching ying stagnation, and calming palpitations; Atractylodes macrocephala is an important medicine for the spleen and stomach, with a warm nature that benefits yang, helps the spleen to function properly, and regulates the qi of the middle jiao; Bupleurum root is aromatic and clear, pungent and bitter, and is good at regulating liver qi and relieving stagnation; Cyperus rotundus mainly enters the qi of the liver meridian, and is aromatic and pungent. , excels at dispersing liver qi and relieving stagnation, making it a key herb for regulating the liver, promoting qi circulation, and relieving depression. Curcuma zedoaria, with its pungent, dispersing, and bitter properties, can both invigorate blood circulation and promote qi circulation, as well as relieve depression and open the orifices. It is used for symptoms of liver qi stagnation. "Compendium of Materia Medica" states: "It treats stagnation that cannot be dispersed." It soothes the liver and relieves depression, clears the heart and opens the orifices. Citrus aurantium regulates qi and relieves depression, and when combined with Bupleurum chinense, it enters the liver and gallbladder meridians, promoting yang qi and soothing the liver and relieving depression. These two herbs, one ascending and one descending, enhance the ability to relax qi and harmonize the liver and spleen. Together, the four herbs can dissipate stagnant liver qi. Raw dragon bone and raw oyster are descending in nature, effective at calming the mind and pacifying the mind. They enter the liver meridian to alleviate liver fire. Toosendan fruit clears the liver and relieves heat, effectively relieving heartache. Areca catechu is excellent at lowering turbid qi, dispelling depression and relieving fullness. Citrus aurantium enters the spleen and liver meridians, dispersing stagnant qi and guiding various herbs to the Jueyin meridian.

[0017] The present invention uniquely utilizes processed Chuanwu and Heifu Pian as the main herbal ingredients, rather than traditional Chinese medicines that soothe the liver and relieve depression. This is because the root cause of dual heart disease lies in insufficient heart yang, which leads to liver depression and qi stagnation and phlegm stasis caused by poor circulation of qi and blood. Therefore, processed Chuanwu and Heifu Pian are essential for warming the primordial yang and promoting blood circulation in the heart, thus illuminating the internal organs. Combined with cinnamon twig, they effectively promote qi and blood circulation, unblock the three burners, and relieve pain while promoting menstruation. Furthermore, combined with bupleurum, curcuma, cyperus, raw dragon bone, raw oyster, toosendan fruit, betel nut, and green peel, they strengthen the liver-soothing effect, guiding the drug into the liver meridian and promoting the smooth flow of liver qi. Simultaneously, they soothe pre-diseased internal organs, using Zhishi and Atractylodes macrocephala to invigorate the spleen and stomach, nourish the spleen to soothe the liver, promote the production of essence and blood, and nourish the heart meridians. The combined effects of these herbs achieve the effects of soothing the liver and relieving depression, warming yang and promoting menstruation, and calming the mind and relieving pain.

[0018] Modern pharmacological studies have confirmed that Chuanwu and Fupian have cardiotonic, analgesic, coronary artery dilation, and anti-myocardial ischemia and hypoxia effects. Among them, aconitine and flavonoid components can protect cardiovascular and improve energy metabolism. Cinnamon twig ethanol extract can inhibit rat aortic Ca 2+ Influx and Ca 2+ Releases vasodilators. Atractylodes lactone III can inhibit inflammatory responses and cardiomyocyte apoptosis, correct excessive autophagy, and improve cardiac function in mice with myocardial infarction, exerting a cardioprotective effect. Studies have shown that the combination of dragon bone and oyster can significantly improve sleep disorders in patients with anxiety and depression. Saikosaponins have antidepressant, antipyretic, anti-inflammatory, and immunomodulatory effects. Saikosaponin A can improve anxiety and depression caused by various causes through the mTOR signaling pathway. β-Sitosterol, a major phytosterol found in Curcuma zedoaria, can significantly increase brain levels of serotonin (5-HT) and norepinephrine in depressed mice, alleviating depressive-like behaviors in mice. Curcuma zedoaria is widely used in antidepressant combinations. Cyperus rotundus has anxiety-relieving, depression-modifying, analgesic, and neuroprotective effects. Cyperus rotundus modulates a series of signaling pathways, resulting in a multi-component, multi-target synergistic antidepressant effect. Cyperus rotundus volatile oil may improve anxiety by regulating the central cholinergic system and increasing hippocampal monoamine transmitter 5-HT levels. Citrus aurantium has antioxidant, antibacterial, anti-inflammatory, antidepressant, anxiolytic, and lipid metabolism-promoting effects. Both raw and processed Toosendan fruit have excellent anti-inflammatory and analgesic effects. The ethanol extract of stir-fried Toosendan fruit can reduce the number of Schwann cells and slow nerve conduction velocity, exerting an analgesic effect. Areca nut extract can lower triglyceride, total cholesterol levels, and the atherosclerosis index, while increasing high-density lipoprotein levels. Areca nut ethanol extract has also shown antidepressant activity in both acute and subchronic forced swim tests. Citrus aurantium can prevent and treat depression by intervening in key targets such as ESR1, CASP3, and PPARG, inhibiting pathways associated with depression-related gene expression and inflammation-related pathways.

[0019] The traditional Chinese medicine preparation of the present invention for treating coronary atherosclerotic heart disease combined with anxiety and depression has the effects of soothing the liver and relieving depression, warming yang and promoting menstruation, and calming the mind and relieving pain. Its ingredients have the effects of relieving anxiety and depression, strengthening the heart, protecting the heart, relieving pain, dilating coronary arteries, combating myocardial ischemia and hypoxia, providing antioxidant and anti-aging benefits, improving sleep, protecting the liver, and providing hypoxia tolerance. Treatment is oral (the drug exerts its therapeutic effect through absorption through the gastrointestinal mucosa), with one dose daily (the dosage of each raw material listed above is the dosage for one dose), taken in two divided doses, half an hour after breakfast and dinner. A course of treatment consists of four weeks.

[0020] Clinical studies of the present invention's traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression have shown that treatment significantly improved symptoms such as chest tightness and pain, palpitations, shortness of breath, insomnia, anxiety, irritability, and depression compared to the control group (oral Deanxit), with statistical significance (P < 0.05). Improvements in SAQ scores, HAMD scores, HAMA scores, and TCM syndrome scores were also statistically significant compared to the control group (P < 0.05). The present traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression demonstrates significant efficacy, good safety, and a low price, making it highly valuable for clinical promotion.

[0021] Various terms and phrases used herein have the general meanings that are well known to those skilled in the art. DETAILED DESCRIPTION

[0022] The present invention will be further described below in conjunction with the embodiments. However, the scope of the present invention is not limited to the following embodiments. Those skilled in the art will appreciate that various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention.

[0023] Unless otherwise specified, the instruments, reagents, and materials used in the following examples are all conventional instruments, reagents, and materials available in the prior art and can be obtained through regular commercial channels. The experimental methods and detection methods used in the following examples are all conventional experimental methods and detection methods available in the prior art, unless otherwise specified.

[0024] Example 1 Preparation of a Traditional Chinese Medicine Preparation for Treating Coronary Atherosclerotic Heart Disease Combined with Anxiety and Depression

[0025] The formula is as follows: processed Chuanwu 30 g, Heifu Pian 10 g, Guizhi 30 g, Bupleurum 30 g, Curcuma 30 g, Cyperus 30 g, Citrus aurantium 30 g, Atractylodes 30 g, Raw Dragon Bone 50 g, Raw Oyster 50 g, Raw Areca 30 g, Toosendan Fruit 30 g, and Citrus aurantium 30 g. Each raw drug is prepared from the corresponding Chinese herbal decoction pieces.

[0026] The preparation method is as follows:

[0027] (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 30 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 30 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 30 minutes, and set aside;

[0028] (2) Boil the processed Chuanwu and Heifupi root for 1 hour;

[0029] (3) Boil raw dragon bones and raw oysters for 25 minutes;

[0030] (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 40 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 40 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

[0031] Clinical research data

[0032] Preliminary research by the research group of the inventor of the present invention has shown that this prescription can significantly improve the symptoms related to coronary atherosclerotic heart disease combined with anxiety and depression in patients, can significantly improve SAQ scores, HAMA scores, HAMD scores and Traditional Chinese Medicine syndrome scores, and has good safety, fully demonstrating the advantages of traditional Chinese medicine in treating coronary atherosclerotic heart disease combined with anxiety and depression. At the same time, its preparation method is a summary of the inventor's many years of clinical experience, providing safe and effective guarantees for its clinical promotion and application.

[0033] 1. Clinical data

[0034] 1.1 Diagnostic criteria

[0035] 1.1.1 Western medicine diagnostic criteria

[0036] The diagnostic criteria for coronary heart disease are based on the "Guidelines for the Diagnosis and Treatment of Chronic Stable Angina" published by the Chinese Society of Cardiology in 2007 and the "Guidelines for the Diagnosis and Treatment of Stable Coronary Heart Disease" published in 2018. Patients with a history of chest tightness or chest pain, the presence of coronary heart disease risk factors, and any of the following conditions can be diagnosed with coronary heart disease:

[0037] (1) Electrocardiogram examination indicates typical ischemic changes or old myocardial infarction;

[0038] (2) positive electrocardiogram exercise test;

[0039] (3) Coronary angiography or coronary CT shows that the lumen of at least one coronary artery is stenosis ≥50%.

[0040] Depression is diagnosed using the Hamilton Depression Rating Scale (HAMD). No depression: 0-8 points; possible depression: 8-20 points; definitely depressed: 21-35 points; severe depression: 35 points or higher. Anxiety is diagnosed using the Hamilton Anxiety Rating Scale (HAMA). No anxiety: 0-7 points; possible anxiety: 7-14 points; definitely anxious: 14-21 points; marked anxiety: 21-29 points; severe anxiety: 29 points or higher.

[0041] 1.1.2 Traditional Chinese Medicine Diagnostic Criteria

[0042] The diagnostic standards of traditional Chinese medicine refer to the main symptoms, concomitant symptoms, tongue coating and pulse conditions of chest pain, heart pain and depression in "Internal Medicine of Traditional Chinese Medicine".

[0043] (1) Main symptoms: Pain and tightness in the tanzhong or precordial area, which may even radiate to the left shoulder, back, throat, inner side of the left upper arm, etc., and may be paroxysmal or persistent. Often accompanied by palpitations, shortness of breath, spontaneous sweating, wheezing, and inability to sleep. There may also be depression, lack of energy, chest tightness and flank distension, and sighing. Or there may be insomnia, frequent dreams, irritability, and crying.

[0044] (2) Concomitant symptoms: The relief time of chest tightness and pain varies from a few seconds to tens of minutes. In severe cases, the pain is severe and persistent, accompanied by profuse sweating, pale face, palpitations, and bluish lips and nails. In severe cases, there is a risk of sudden death. The pain is not fixed in any specific location, and there is abdominal tightness and belching.

[0045] (3) Tongue: The tongue is red or dark, with a thin and greasy coating.

[0046] (4) Pulse: wiry or slippery.

[0047] 1.2 Inclusion criteria

[0048] (1) Meet the diagnostic criteria for coronary heart disease combined with anxiety and depression;

[0049] (2) Patients developed anxiety and depression symptoms only after being diagnosed with CHD, with HAMD scores ranging from 8 to 35 points and HAMA scores ranging from 14 to 29 points;

[0050] (3) The patient gave informed consent to the study and showed good compliance;

[0051] (4) not taking other antidepressants in the past 4 weeks;

[0052] (5) The condition is stable.

[0053] 1.3 Exclusion criteria

[0054] (1) Those who are allergic to experimental drugs; (2) Those with abnormal renal function or undergoing hemodialysis; (3) Those with acute myocardial infarction or severe arrhythmia, aortic stenosis, acute myocarditis and other contraindications to exercise; (4) Those who have undergone valve replacement or repair; (5) Those with severe mental illness, impaired consciousness, cognitive impairment or other reasons who cannot cooperate with the experiment; (6) Pregnant women or breastfeeding women; (7) Those who have participated in other clinical trials in the past month.

[0055] 1.4 Suspension and Exit Criteria

[0056] (1) Those who did not take the drugs as required during the experiment;

[0057] (2) Patients experience severe adverse reactions or changes in their condition;

[0058] (3) Those who voluntarily requested to withdraw from the experiment;

[0059] (4) Those who take related drugs on their own during treatment. Those who are prone to allergies or are allergic to this drug.

[0060] 1.5 Elimination criteria

[0061] (1) Those who are found to not meet the inclusion criteria or meet the exclusion criteria after inclusion;

[0062] (2) Those who were found to have poor compliance and could not strictly follow the treatment plan after inclusion;

[0063] (3) Patients who arbitrarily use prohibited drugs during treatment after inclusion.

[0064] 1.6 Shedding Standard

[0065] (1) Poor compliance or combined use of drugs outside the prescribed range affects the efficacy and safety judgment;

[0066] (2) Those who have allergic reactions or serious adverse events and are not suitable to continue treatment;

[0067] (3) Those who cannot continue the clinical trial due to various reasons, withdraw from the trial or terminate the trial.

[0068] 1.7 General Information

[0069] Sixty patients aged 40 to 60 years diagnosed with coronary atherosclerotic heart disease and anxiety and depression who visited the outpatient clinic between January 2021 and January 2024 were enrolled. They were randomly divided into either the oral traditional Chinese medicine Jieyu Anxin Fang group or the Western medicine Deanxit group, with 30 patients in each group. There were no significant differences in age between the groups, demonstrating baseline consistency (P > 0.05).

[0070] 2. Methods

[0071] 2.1 Treatment methods

[0072] Both groups received the same basic Western medication regimen (enteric-coated aspirin tablets, rosuvastatin calcium tablets, isosorbide mononitrate tablets, and metoprolol succinate sustained-release tablets). In addition, starting from the date of enrollment in the study, participants received psychological counseling, health education, and guidance on maintaining a positive mood, improving their lifestyle, controlling their diet, and engaging in moderate exercise.

[0073] Treatment group: Oral Jieyu Anxin Formula (i.e., the Chinese medicine preparation of the present invention, prepared in Example 1), one dose per day, half an hour after breakfast and dinner, for 4 consecutive weeks.

[0074] Control group: Oral administration of Deanxit (flupentixol-melitracen tablets, Lundbeck Pharmaceuticals Ltd., Denmark, national medicine standard number H20130126, specification: 20 tablets), once a day, 1 tablet each time, before breakfast, for 4 consecutive weeks.

[0075] 2.2 Observation indicators

[0076] 2.2.1 General Data Observation

[0077] Observe and record the patient's age, disease progression, disease changes during treatment, and any adverse drug reactions during treatment.

[0078] 2.2.2 Evaluation of treatment effect (record once before and after treatment)

[0079] Seattle Angina Questionnaire (SAQ) score, HAMD score, HAMA score and Traditional Chinese Medicine syndrome score.

[0080] 2.2.3 Safety evaluation

[0081] Patients should monitor their blood pressure, heart rate and other vital signs during treatment. Blood, urine, stool, and liver and kidney function tests should be performed promptly before and after treatment.

[0082] 2.3 Criteria for determining efficacy

[0083] 2.3.1 Western medicine efficacy standards

[0084] SAQ score was used as the evaluation standard for the severity of coronary atherosclerotic heart disease; HAMD score was used as the evaluation standard for the severity of depression; HAMA score was used as the evaluation standard for the severity of anxiety.

[0085] 2.3.2 TCM efficacy standards

[0086] The Traditional Chinese Medicine (TCM) symptom score was modified and developed based on the "Clinical Disease Diagnosis Criteria for Cure and Improvement" and the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial)." The nimodipine method was used for evaluation. The efficacy index (n) = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%. Cure: n ≥ 95%; marked effect: 70% ≤ n < 95%; improvement: 30% ≤ n < 70%; ineffectiveness: n < 30%.

[0087] 2.3.3 Safety evaluation standards

[0088] Grade 1: Safe, no adverse reactions. Grade 2: Relatively safe, no impact on continued administration, and no special treatment required. Grade 3: Safety issues exist, moderate adverse reactions occur, and administration can continue after treatment. Grade 4: Severe adverse reactions occur, and the trial is terminated.

[0089] 2.3.4 Criteria for judging the severity of adverse events

[0090] Mild: Tolerable, does not affect treatment and recovery, and does not require special treatment. Moderate: Unbearable, requires immediate discontinuation of medication or special treatment, and affects recovery. Severe: Life-threatening, requires immediate discontinuation of medication or emergency treatment.

[0091] 2.4 Medical Ethics Control

[0092] When patients are enrolled in a clinical study, researchers will provide detailed information to the patient or their family regarding the patient's diagnosis using both Traditional Chinese Medicine (TCM) and Western Medicine, TCM syndrome differentiation, treatment options, anticipated treatment goals, and potential adverse reactions. The patient's address and phone number will be recorded for clinical follow-up. If symptoms worsen or discomfort develops after treatment, the patient should contact the researcher promptly to discontinue treatment, address the symptoms, and withdraw from the study. Participation and withdrawal are voluntary throughout the study.

[0093] 2.5 Statistical methods

[0094] All data were statistically analyzed using SPSS 26.0 software. Two-sided tests were generally used for statistical tests, and differences were considered statistically significant when P < 0.05. 2 For data with normality, the KS test was used to describe frequency, percentage, or ratio. For data with homogeneity of variance, the rank sum test was used to describe ratios or rates. Measurement data were first analyzed for normality using the KS test. Measurement data that conformed to a normal distribution or nearly conformed to a normal distribution were expressed as mean ± standard deviation (±S). Measurement data that did not conform to a normal distribution were expressed as median (quartile), or M (Q1, Q3). Data that conformed to normality and homogeneity of variance were analyzed using the t-test; otherwise, the rank sum test was used.

[0095] 3. Results

[0096] 3.1 SAQ Points Comparison

[0097] There was no significant difference in the SAQ scores between the two groups before treatment. After treatment, the improvement of SAQ scores in the Jieyu Anxin group was significantly better than that in the control group (P < 0.05), as shown in Table 1.

[0098] Table 1 Comparison of SAQ scores between the two groups (X±S)

[0099]

[0100] Note: * The comparison between the two groups after treatment was P < 0.05.

[0101] 3.2 Comparison of HAMD scale scores

[0102] There was no significant difference in the HAMD scale scores between the two groups before treatment. After treatment, the improvement of the HAMD scale scores in the Jieyu Anxin group was significantly better than that in the control group (P < 0.05), as shown in Table 2.

[0103] Table 2 Comparison of HAMD scores between the two groups (X±S)

[0104]

[0105] Note: * The comparison between the two groups after treatment was P < 0.05.

[0106] 3.3 Comparison of HAMA Scale Scores

[0107] There was no significant difference in the HAMA scale scores between the two groups before treatment. After treatment, the reduction in HAMA scale scores in the Jieyu Anxin group was significantly better than that in the control group (P < 0.05), as shown in Table 3.

[0108] Table 3 Comparison of HAMA scores between the two groups (X±S)

[0109]

[0110] Note: * The comparison between the two groups after treatment was P < 0.05.

[0111] 3.4 Comparison of TCM symptom scores before and after treatment

[0112] There was no significant difference in the TCM symptom scores between the two groups before treatment. After treatment, both the Jieyu Anxin group and the Deanxit group showed improvement compared with before treatment. However, after treatment, the improvement in the treatment group was significantly better than that in the control group (P < 0.05), as shown in Table 4.

[0113] Table 4 Comparison of TCM symptom scores between the two groups (X±S)

[0114]

[0115] Note: * The comparison between the two groups after treatment was P < 0.05.

[0116] 3.5 Occurrence of adverse reactions

[0117] The liver and kidney functions of patients in each group were normal before and after treatment, and no adverse reactions occurred in each group.

[0118] 4. Discussion

[0119] The ingredients of the Jieyu Anxin prescription are: processed Chuanwu 30 g, black aconite root 10 g, cinnamon twig 30 g, bupleurum 30 g, curcuma 30 g, cyperus rotundus 30 g, immature bitter orange 30 g, atractylodes 30 g, raw dragon bone 50 g, raw oyster 50 g, raw betel nut 30 g, toosendan fruit 30 g, and green peel 30 g.

[0120] CHD falls under the Traditional Chinese Medicine (TCM) category of "chest pain" and "heart pain." The acute phase of CHD presents suddenly, caused by plaque rupture leading to coronary artery stenosis and thrombosis, manifesting as squeezing pain in the chest area, sweating, and other discomfort. The chronic phase presents with symptoms similar to unstable angina, a condition with a high incidence, numerous accompanying symptoms, and a poor prognosis. Anxiety and depression are typical psychological disorders classified as "depression" in TCM, manifested by anxiety, tension, low mood, and insomnia. CHD combined with anxiety and depression is often caused by insufficient heart yang, poor heart-controlled blood circulation, phlegm and blood stasis blocking the blood vessels, poor qi flow, and liver depression and qi stagnation. The heart is an organ that functions as both yin and yang. The heart's role in governing the mind is an extension of its role in governing the blood vessels, which in turn provides the material foundation for its role in governing the mind. Once the blood vessels are damaged and blood fails to nourish the heart, phlegm, blood stasis, and toxins cling to each other, corrupting the veins and damaging the heart. This leads to disordered qi and blood, depriving the mind of its proper nourishment, and forms the pathological basis for the development or exacerbation of depression. On the other hand, CHD is often accompanied by long-term physical symptoms such as chest tightness and persistent chest pain. This recurring discomfort can easily trigger emotional changes, leading to constant worry and anxiety, poor qi flow, and a sense of melancholy. It's difficult to resolve negative emotions, resulting in a depressed and pessimistic state. Traditional Chinese medicine (TCM) not only alleviates symptoms like chest tightness and pain but also effectively treats anxiety and depression, while avoiding the adverse effects of Western medications such as cardiotoxicity. Based on this etiology, a Jieyu Anxin formula was developed. The processed Chuanwu and Fupian (Aconite root) in this formula are yang herbs with a relentless, open-hearted nature, possessing a powerful power to open and clear the meridians. Cinnamon twigs are also added to promote yang and transform qi, promoting blood circulation, and circulate through the meridians to reach stagnation, further alleviating anxiety and palpitations. Atractylodes macrocephala is a key herb for the spleen and stomach, with a warming nature that invigorates yang, supporting the spleen's healthy function and regulating qi in the middle burner. Bupleurum chinense is aromatic and refreshing, with a pungent and bitter properties, excelling at regulating liver qi and relieving stagnation. Cyperus rotundus primarily enters the liver meridian's qi division, with a fragrant and pungent nature, excelling at dispersing liver qi and relieving stagnation, making it a key herb for regulating liver qi and relieving depression. Curcuma zedoaria is pungent, dispersing, and bitter properties, activating blood circulation and promoting qi, as well as relieving stagnation and opening the orifices. It is used for symptoms of liver qi stagnation. "Compendium of Materia Medica" states: "It treats stagnation that cannot be dispersed," soothing the liver and relieving depression, clearing the heart and opening the orifices. Citrus aurantium regulates qi and relieves depression, and when combined with Bupleurum chinense, it enters the liver and gallbladder meridians, promoting yang qi and soothing the liver and relieving stagnation. The two herbs, one ascending and one descending, enhance the function of promoting qi circulation and harmonizing the liver and spleen. Together, the four herbs can relieve stagnant liver qi. Raw dragon bone and raw oyster, with their descending properties, are effective at calming the mind and entering the liver meridian to alleviate liver fire. Toosendan fruit clears the liver and relieves heat, and is good at relieving heart pain; Areca catechu is good at lowering turbidity and lowering qi, breaking up depression and relieving fullness; while Citrus aurantium enters the spleen and liver meridians, is mainly used to break up stagnant qi, and can lead various medicines to the Jueyin meridians.

[0121] Clinical research results show that the Jieyu Anxin formula is effective in treating symptoms of coronary artery atherosclerotic heart disease (CAD) combined with anxiety and depression, including chest pain, chest tightness, palpitations, shortness of breath, anxiety, depression, and insomnia. The treatment effect was statistically significant compared to the Delexin group (P < 0.05). This may be because, compared to single anti-anxiety and depression treatments, the Jieyu Anxin formula improves the relevant clinical symptoms of CAD combined with anxiety and depression in multiple aspects and at multiple levels, thus enhancing the therapeutic effect to a certain extent.

[0122] 5. Conclusion

[0123] The Jieyu Anxin prescription of the present invention has a clinical application effect that is significantly better than the commonly used clinical dextromethorphan and has good safety, thus providing a guarantee for its clinical promotion.

[0124] Example 2 Preparation of a Traditional Chinese Medicine Preparation for Treating Coronary Atherosclerotic Heart Disease Combined with Anxiety and Depression

[0125] The formula is as follows: processed Chuanwu 25 g, Heifu Pian 12 g, Guizhi 25 g, Bupleurum 25 g, Curcuma 35 g, Cyperus rotundus 25 g, Citrus aurantium 35 g, Atractylodes macrocephala 25 g, Raw Dragon Bone 55 g, Raw Oyster 45 g, Raw Areca nut 35 g, Toosendan Fructus 25 g, and Citrus aurantium 35 g. Each raw drug substance is selected from the corresponding Chinese herbal decoction pieces.

[0126] The preparation method is as follows:

[0127] (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 40 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 40 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 40 minutes, and set aside;

[0128] (2) Boil the processed Chuanwu and Heifupi root for 1 hour;

[0129] (3) Boil raw dragon bones and raw oysters for 20 minutes;

[0130] (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 30 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 50 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

[0131] Example 3 Preparation of a Traditional Chinese Medicine Preparation for Treating Coronary Atherosclerotic Heart Disease Combined with Anxiety and Depression

[0132] The formula is as follows: processed Chuanwu 35 g, Heifu Pian 8 g, Guizhi 35 g, Bupleurum 35 g, Curcuma 25 g, Cyperus 35 g, Citrus aurantium 25 g, Atractylodes 35 g, Raw Dragon Bone 45 g, Raw Oyster 55 g, Raw Areca 25 g, Toosendan Fructus 35 g, and Citrus aurantium 25 g. Each raw drug substance is selected from the corresponding Chinese herbal decoction pieces.

[0133] The preparation method is as follows:

[0134] (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 20 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 20 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 20 minutes, and set aside;

[0135] (2) Boil the processed Chuanwu and Heifupi root for 2 hours;

[0136] (3) Boil raw dragon bones and raw oysters for 30 minutes;

[0137] (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 50 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 30 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

[0138] Example 4 Preparation of a Traditional Chinese Medicine Preparation for Treating Coronary Atherosclerotic Heart Disease Combined with Anxiety and Depression

[0139] The formula is as follows: processed Chuanwu 28 g, Heifu Pian 11 g, Guizhi 28 g, Bupleurum 28 g, Curcuma 32 g, Cyperus 28 g, Citrus aurantium 32 g, Atractylodes 28 g, Raw Dragon Bone 52 g, Raw Oyster 48 g, Raw Areca 32 g, Toosendan Fructus 28 g, and Citrus aurantium 32 g. Each raw drug is prepared from the corresponding Chinese herbal decoction pieces.

[0140] The preparation method is as follows:

[0141] (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 30 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 30 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 30 minutes, and set aside;

[0142] (2) Decoction of processed Chuanwu and Heifupi root for 1.5 hours;

[0143] (3) Boil raw dragon bones and raw oysters for 25 minutes;

[0144] (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 40 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 40 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

[0145] Example 5 Preparation of a Traditional Chinese Medicine Preparation for Treating Coronary Atherosclerotic Heart Disease Combined with Anxiety and Depression

[0146] The formula is as follows: processed Chuanwu 32 g, Heifu Pian 9 g, Guizhi 32 g, Bupleurum 32 g, Curcuma 28 g, Cyperus 32 g, Citrus aurantium 28 g, Atractylodes 32 g, Raw Dragon Bone 48 g, Raw Oyster 52 g, Raw Areca 28 g, Toosendan Fructus 32 g, and Citrus aurantium 28 g. Each raw drug is prepared from the corresponding Chinese herbal decoction pieces.

[0147] The preparation method is as follows:

[0148] (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 30 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 30 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 30 minutes, and set aside;

[0149] (2) Boil the processed Chuanwu and Heifupi root for 1 hour;

[0150] (3) Boil raw dragon bones and raw oysters for 20 minutes;

[0151] (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 50 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 50 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

[0152] The above examples are provided to those skilled in the art to fully disclose and describe how to implement and use the claimed embodiments, rather than to limit the scope of the disclosure herein. Modifications that are obvious to those skilled in the art will fall within the scope of the appended claims.

Claims

1. A Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression, characterized in that: It is made from the following raw materials: processed Chuanwu 25-35 g, black aconite root 8-12 g, cinnamon twig 25-35 g, bupleurum 25-35 g, curcuma 25-35 g, cyperus rotundus 25-35 g, immature bitter orange 25-35 g, atractylodes 25-35 g, raw dragon bone 45-55 g, raw oyster 45-55 g, raw betel nut 25-35 g, toosendan fruit 25-35 g, and green peel 25-35 g.

2. The Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression according to claim 1, characterized in that: It is made from the following raw materials: processed Chuanwu 30 g, black aconite root 10 g, cinnamon twig 30 g, bupleurum 30 g, curcuma 30 g, cyperus rotundus 30 g, immature bitter orange 30 g, atractylodes 30 g, raw dragon bone 50 g, raw oyster 50 g, raw betel nut 30 g, toosendan fruit 30 g, and green peel 30 g.

3. The Chinese medicinal preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression according to claim 1, characterized in that: It is made from the following raw materials: processed Chuanwu 25 g, black aconite root 12 g, cinnamon twig 25 g, bupleurum 25 g, turmeric 35 g, cyperus rotundus 25 g, immature bitter orange 35 g, atractylodes 25 g, raw dragon bone 55 g, raw oyster 45 g, raw betel nut 35 g, toosendan fruit 25 g, and green peel 35 g.

4. The Chinese medicinal preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression according to claim 1, characterized in that: It is made from the following raw materials: processed Chuanwu 35 g, black aconite root 8 g, cinnamon twig 35 g, bupleurum 35 g, curcuma 25 g, cyperus rotundus 35 g, immature bitter orange 25 g, atractylodes 35 g, raw dragon bone 45 g, raw oyster 55 g, raw betel nut 25 g, toosendan fruit 35 g, and green peel 25 g.

5. The Chinese medicinal preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression according to claim 1, characterized in that: It is made from the following raw materials: processed Chuanwu 28 g, black aconite root 11 g, cinnamon twig 28 g, bupleurum 28 g, turmeric 32 g, cyperus rotundus 28 g, immature bitter orange 32 g, atractylodes 28 g, raw dragon bone 52 g, raw oyster 48 g, raw betel nut 32 g, toosendan fruit 28 g, and green peel 32 g.

6. The Chinese medicinal preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression according to claim 1, characterized in that: It is made from the following raw materials: processed Chuanwu 32 g, black aconite root 9 g, cinnamon twig 32 g, bupleurum 32 g, turmeric 28 g, cyperus rotundus 32 g, immature bitter orange 28 g, atractylodes 32 g, raw dragon bone 48 g, raw oyster 52 g, raw betel nut 28 g, toosendan fruit 32 g, and green peel 28 g.

7. The method for preparing the traditional Chinese medicine preparation for treating coronary atherosclerotic heart disease combined with anxiety and depression according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) Mix the processed Chuanwu and Heifu Pian, soak them in water for 20-40 minutes, and set aside; mix the raw dragon bone and raw oyster, soak them in water for 20-40 minutes, and set aside; mix the cinnamon twig, bupleurum, turmeric, cyperus, immature bitter orange, white atractylodes, raw betel nut, toosendan fruit, and green peel, soak them in water for 20-40 minutes, and set aside; (2) Boil the processed Chuanwu and Heifupi root for 1 to 2 hours; (3) Boil raw dragon bones and raw oysters for 20 to 30 minutes; (4) Mix the medicines in (2) and (3) above, then add cinnamon twig, bupleurum root, turmeric, cyperus rotundus, immature bitter orange, white atractylodes macrocephala, raw betel nut, toosendan fruit and green peel, and boil for 30 to 50 minutes. Pour out the medicine soup, which is the first decoction; add water to the medicine residue and boil for another 30 to 50 minutes. Pour out the medicine soup, which is the second decoction; mix the two decoctions together to obtain the product.

8. The preparation method according to claim 7, characterized in that: In the step (1), the soaking time is 30 minutes.

9. The preparation method according to claim 7, characterized in that: The decoction time in step (2) is 1 hour; the decoction time in step (3) is 25 minutes.

10. The preparation method according to claim 7, characterized in that: The decoction time in step (4) is 40 minutes.

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