An external sticking traditional Chinese medicine composition for treating coronary heart disease and application thereof

Abstract

The application relates to a kind of external sticking traditional Chinese medicine composition for treating coronary heart disease, which is made of the following raw medicinal materials by weight: 8-16 parts of chuanqiong, 5-13 parts of sandalwood, 5-13 parts of danshen, 1-5 parts of jiangxiang, 2-10 parts of olibanum, 2-10 parts of myrrh, 1-5 parts of clove, 5-13 parts of styrax, 8-16 parts of borneol and 1-5 parts of clematis. The composition can significantly relieve joint pain of patients, has a high effective rate of clinical curative effect, can improve the life quality of patients, and the traditional Chinese medicine composition of the application has reasonable compatibility, no toxic side effects and a good application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a kind of external application traditional Chinese medicine composition for treating coronary heart disease and application thereof. BACKGROUND

[0002] Coronary atherosclerotic heart disease, simply referred to as coronary heart disease, is a heart disease caused by coronary artery atherosclerosis, which leads to stenosis or obstruction of blood vessels, resulting in myocardial ischemia, hypoxia or necrosis. Due to different pathological and physiological changes, coronary heart disease has different clinical manifestations. At present, coronary heart disease is classified into two categories: acute coronary syndrome and chronic coronary disease. The former includes unstable angina pectoris, non-ST segment elevation myocardial infarction and ST segment elevation myocardial infarction (STEMI). The latter includes chronic stable angina pectoris, normal coronary angina pectoris (such as X syndrome), asymptomatic myocardial ischemia and ischemic heart failure. Unstable angina pectoris (UAP) is an acute cardiac event of coronary heart disease, an important component of acute coronary syndrome, and an intermediate clinical syndrome between chronic stable angina pectoris and acute myocardial infarction. It is called "unstable" because it is different from "stable angina pectoris" in terms of pathophysiology and clinical manifestations.

[0003] Traditional Chinese medicine believes that coronary heart disease angina pectoris belongs to the category of "chest pain" and "heart pain". Han Zhang Zhongjing proposed the name of "chest pain" in "Synopsis of Golden Chamber" and summarized the etiology and pathogenesis as "yang deficiency and yin excess", that is, deficiency of yang qi in upper jiao and excess of yin cold in lower jiao. It is believed that the disease is a deficiency in the root and excess in the branch. Deficiency of heart blood and yin and yang deficiency; Excess of blood stasis, phlegm, qi stagnation and cold accumulation. Pain due to obstruction and pain due to lack of nourishment are two important pathogenesis of coronary heart disease. Blood and qi are the changes, blood stasis, blood stasis, cold accumulation and other pathological factors. Therefore, in treatment, we should start from the whole, distinguish the deficiency and excess, cold and heat, and blood and qi. Combining disease differentiation with syndrome differentiation, taking "treating the branch in emergency and the root in slow progress" as the principle, different treatment methods are adopted and flexibly used in clinical practice.

[0004] Coronary artery disease (CAD), as a chronic illness, has three main treatment methods: ① medication; ② interventional stent implantation; and ③ surgical coronary artery bypass grafting (CABG). For unexplained atrial angina (UAP), the primary treatments are percutaneous coronary intervention (PCI) and medication. PCI can restore coronary artery patency, improve blood flow, and alleviate symptoms; however, significant surgical complications exist, such as no-reflow and reperfusion injury, which can lead to recurrent myocardial infarction, arrhythmia, and heart failure, severely impacting prognosis. Medication involves coronary artery dilation, lipid-lowering and plaque-stabilizing drugs, and antiplatelet therapy. However, long-term use of these drugs can lead to drug resistance and side effects, affecting treatment efficacy. Traditional Chinese medicine, due to its fewer side effects and lack of drug resistance, is often combined with conventional Western medicine to alleviate symptoms. Acupoint application therapy is a type of cardiac rehabilitation therapy with traditional Chinese medicine characteristics. It stimulates specific acupoints and allows for transdermal drug absorption, achieving therapeutic and health-preserving effects. While maintaining efficacy, it avoids irritation to the gastrointestinal tract and impacts on liver and kidney function, offering advantages unmatched by other drugs. It has shown good improvement in the subjective symptoms of coronary heart disease patients. Due to its simplicity, effectiveness, non-invasiveness, and painlessness, it is gradually becoming a new approach to the prevention and treatment of coronary heart disease. For example, Chinese patent CN103479712A, published on January 1, 2014, discloses a traditional Chinese medicine combination for treating angina pectoris in coronary heart disease. This combination is made from the following raw materials in parts by weight: frankincense 7-13 parts, sandalwood 17-23 parts, Panax notoginseng 7-13 parts, and borneol 2-8 parts. This invention also provides the application of this traditional Chinese medicine composition in the treatment of angina pectoris in coronary heart disease. Its formulation conforms to the principles of "principal, assistant, adjuvant, and guide" in traditional Chinese medicine. Pharmacological experiments have verified its good efficacy in treating angina pectoris in patients with coronary heart disease, providing a new method for its treatment. This traditional Chinese medicine composition, applied to acupoints, allows for transdermal absorption of the drug and stimulation of meridians and acupoints, avoiding the first-pass effect of oral medications, interference and degradation from gastrointestinal factors, and potential toxic side effects. Therefore, it has excellent application prospects. Another patent document, CN105435196A, published on March 30, 2016, discloses a topical traditional Chinese medicine ointment for treating angina pectoris in patients with qi stagnation and blood stasis type coronary heart disease and chronic gastritis, and its preparation method, for use in acupoint application therapy. This medicine is prepared from the following traditional Chinese medicine ingredients and the Western medicine mosapride tablets: Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Amber, Crataegus pinnatifida, Lycopus lucidus, Rheum palmatum (processed), Ligusticum chuanxiong, Boswellia carterii, Commiphora myrrha, Panax notoginseng, Corydalis yanhusuo (processed with vinegar), Curcuma longa, Pangolin scales, Sappanwood, Citrus reticulata peel, Aucklandia lappa, Polygonum multiflorum, Lycium barbarum, Ginseng, Acanthopanax senticosus, Cinnamomum cassia, Musk, Styrax benzoin, Zingiber officinale (dried), Clematis chinensis, Kaempferia galanga, Ziziphus jujuba var. spinosa, Platycladus orientalis seed, Acorus tatarinowii, Polygonum multiflorum, Astragalus membranaceus, Rhodiola rosea, and Glycyrrhiza uralensis. This invention treats both the symptoms and the root cause, using a combination of herbs to improve the effectiveness of treatment.

[0005] And more effective for coronary heart disease of traditional Chinese medicine composition still needs to be developed, currently about as a kind of treatment of coronary heart disease of external application of traditional Chinese medicine composition and its application has not been reported. SUMMARY

[0006] The first object of the present application is to provide a traditional Chinese medicine composition for treating coronary heart disease.

[0007] The second object of the present application is to provide an application of the traditional Chinese medicine composition.

[0008] To achieve the above first object, the technical solution adopted by the present application is:

[0009] A traditional Chinese medicine composition for treating coronary heart disease, the traditional Chinese medicine composition is made of the following raw medicinal materials by weight: Chuanxiong 8-16 parts, sandalwood 5-13 parts, Danshen 5-13 parts, Jiangxiang 1-5 parts, Olibanum 2-10 parts, Myrrh 2-10 parts, Clove 1-5 parts, Suhe Xiang 5-13 parts, Bingpian 8-16 parts, Lingxiaohua 1-5 parts.

[0010] As a preferred example, the traditional Chinese medicine composition is made of the following raw medicinal materials by weight: Chuanxiong 10-14 parts, sandalwood 7-11 parts, Danshen 7-11 parts, Jiangxiang 2-4 parts, Olibanum 4-8 parts, Myrrh 4-8 parts, Clove 2-4 parts, Suhe Xiang 7-11 parts, Bingpian 10-14 parts, Lingxiaohua 2-4 parts.

[0011] More preferably, the traditional Chinese medicine composition is made of the following raw medicinal materials by weight: Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Suhe Xiang 9 parts, Bingpian 12 parts, Lingxiaohua 3 parts.

[0012] More preferably, the traditional Chinese medicine composition is an external traditional Chinese medicine composition.

[0013] More preferably, the use method of the external traditional Chinese medicine composition is: taking the above-mentioned any weight ratio of each raw medicinal material and grinding into powder, and mixing with vaseline to form a paste, and then taking 5g of the paste and applying it to the patient's Dantian acupoint.

[0014] To achieve the above-mentioned second object, the technical solution adopted by the present application is:

[0015] The application of any of the above-mentioned traditional Chinese medicine compositions in the preparation of drugs for treating coronary heart disease, the coronary heart disease is unstable angina, and the syndrome type is qi deficiency and blood stasis.

[0016] The compatibility relationship of the traditional Chinese medicine composition in the present application:

[0017] Based on the two theories of the whole concept and meridian theory, after the medicine is pasted on the corresponding acupoint, the acupoint is stimulated, the meridian reaches the diseased part of the viscera meridian qi, and the medicine has the function and effect of "meridian returning". The medicine composition is based on the principle of aromatic warming and unblocking, and the composition characteristics are "warming is heavier than pungent, and is good at internal attack and moving inside". In the prescription, Chuanxiong and Dansheng have aromatic gas and can open the orifice, and they are both the monarch. Chuanxiong, "gas is good at moving and penetrating, although it enters the blood, it can also regulate all qi", is a blood qi medicine, and is widely used for chest pain caused by qi stagnation and blood stasis. Dansheng is a qi-regulating medicine, and is pungent and warm. It is often used for the treatment of chest pain caused by cold and qi stagnation; assisted with Danshen, Jiangxiang, Dingshang, Ruixiang, and Mo Yao, it can activate blood and resolve stasis, move qi and stop pain, and is a minister. Modern pharmacological research has also confirmed that Ruixiang, Mo Yao, and Jiangxiang have strong analgesic, anti-inflammatory, and blood lipid regulating effects; assisted with Ruixiang, it can open the orifice and awaken the spirit, warm and unblock, dispel cold and stop pain, and the ice piece can open the orifice and awaken the spirit, clear heat and stop pain, and lead the medicine into the muscle and tendon. In addition, modern research has proved that ice piece is an effective transdermal absorption promoter, which can improve the blood drug concentration and prolong the drug action time; Lingxiaohua can activate blood and cool blood, and has the effect of dispelling wind, which can prevent local skin allergic phenomena caused by pasting. BRIEF DESCRIPTION OF DRAWINGS

[0018] ATTACHMENT Figure 1 For comparison of SAQ scores of the two groups of patients, A: physical activity limitation (PL) score; B: stable state of angina pectoris (A5); C: angina pectoris attack (AF); D: treatment satisfaction (TS); E: disease recognition (DP).

[0019] ATTACHMENT Figure 2 For comparison of adverse cardiovascular events. DETAILED DESCRIPTION

[0020] The application will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the application and not to limit the scope of the application. In addition, it should be understood that after reading the content described in the application, those skilled in the art can make various modifications or modifications to the application, and these equivalent forms also fall within the scope defined by the claims attached to the present application.

[0021] Example 1: External application of traditional Chinese medicine composition for treating coronary heart disease (I)

[0022] Chuanxiong 12 parts, Dansheng 9 parts, Jiangxiang 3 parts, Ruixiang 6 parts, Mo Yao 6 parts, Dingshang 3 parts, Suheixiang 9 parts, ice piece 12 parts, and Lingxiaohua 3 parts.

[0023] Example 2: External application of traditional Chinese medicine composition for treating coronary heart disease (II)

[0024] Chuanxiong 12 parts, Dansheng 9 parts, Jiangxiang 3 parts, Ruixiang 6 parts, Mo Yao 6 parts, Dingshang 3 parts, Suheixiang 9 parts, ice piece 12 parts, and Lingxiaohua 3 parts.

[0025] Example 3 External application of Chinese medicine composition for treating coronary heart disease (three)

[0026] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0027] Example 4 External application of Chinese medicine composition for treating coronary heart disease (four)

[0028] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0029] Example 5 External application of Chinese medicine composition for treating coronary heart disease (five)

[0030] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0031] Example 6 External application of Chinese medicine composition for treating coronary heart disease (six)

[0032] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0033] Example 7 External application of Chinese medicine composition for treating coronary heart disease (seven)

[0034] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0035] Example 8 External application of Chinese medicine composition for treating coronary heart disease (eight)

[0036] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0037] Example 9 External application of Chinese medicine composition for treating coronary heart disease (nine)

[0038] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, Olibanum 6 parts, Myrrh 6 parts, Clove 3 parts, Storax 9 parts, Borneol 12 parts, Campsis 3 parts.

[0039] Example 10 External application of Chinese medicine composition for treating coronary heart disease (ten)

[0040] Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, frankincense 6 parts, myrrh 6 parts, clove 3 parts, Suhe Xiang 9 parts, Bingpian 12 parts, Lingxiaohua 3 parts.

[0041] Example 11 The external application of Chinese medicine composition of the present application for treating coronary heart disease (eleven)

[0042] Angelica 14 parts, Chuanweikeng 8 parts, Hujiacang 8 parts, Shentengcao 6 parts, safflower 10 parts, Xiangjiapi 6 parts, Suomu 4 parts, Jixueteng 12 parts, Eiyeh 6 parts, Zanthoxylum 10 parts.

[0043] Example 12 Preparation of the external application of Chinese medicine composition of the present application for treating coronary heart disease (eleven)

[0044] According to the weight ratio of any one of the Chinese medicine compositions in examples 1-11, the raw medicine is weighed and ground into powder, and then mixed with vaseline to form a paste.

[0045] Example 13 Clinical efficacy experiment

[0046] 1 Clinical data

[0047] 1.1 Case source

[0048] Select the cases that meet the inclusion criteria from the inpatient or outpatient department of the City Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine and the Department of Heart Disease of Shanghai Tenth People's Hospital.

[0049] 1.2 Diagnostic criteria

[0050] 1.2.1 Western diagnostic criteria

[0051] (1) Refer to the 2007 "Unstable angina and non-ST segment elevation myocardial infarction diagnosis and treatment guidelines [1] .

[0052] Clinical symptoms

[0053] ① Resting angina: the onset of angina is not significantly related to physical activity, and the symptoms often occur at rest, each time can last more than 20 min;

[0054] ② Initial angina: the course is within 1 month, and there has never been any before, which can occur at rest or during activity, without obvious onset regularity;

[0055] ③ Worsening angina: patients with a history of angina pectoris have a sudden increase in the number of angina pectoris, a prolonged duration, and an increased severity of pain in the past 1 month, and the number of nitroglycerin taken is significantly increased, and the activity tolerance is decreased;

[0056] ④ Variable angina: the symptoms of angina pectoris are spontaneous, and the electrocardiogram shows transient ST segment changes, most of which are self-relieving and do not develop into myocardial infarction.

[0057] (2) Electrocardiogram findings: During an angina attack, the resting electrocardiogram will show dynamic changes in the ST-T or T waves in two or more adjacent leads. The ST segment is often downshifted by more than 0.1mV from the baseline level, and the T wave changes (flattened or inverted).

[0058] (3) Had previously undergone coronary angiography (CAG) or coronary CTA, which confirmed that at least one coronary artery had a stenosis of ≥50%.

[0059] (4) Troponin I is normal or does not meet the criteria for myocardial infarction.

[0060] 1.2.2 Angina Pectoris Classification Criteria

[0061] Refer to the Canadian Cardiology Association's Classification of Exertional Angina (CCS):

[0062] Grade I: Normal daily activities do not cause angina, such as walking or climbing stairs, but tension, rapid exertion or sustained exertion can trigger an angina attack.

[0063] Level II: Mild limitation of daily physical activity, such as brisk walking, walking after meals or climbing stairs, walking in cold or windy conditions, or experiencing angina after emotional excitement. Angina attacks may occur after walking more than 200-400 meters on flat ground at a normal speed or climbing more than one floor.

[0064] Level III: Daily physical activities are significantly limited, and angina attacks occur after walking a distance of 100-400 meters or more on flat ground at a normal speed or climbing one or more floors.

[0065] Category IV: Angina pectoris can be triggered by mild activity and may also occur at rest (due to the more frequent and severe episodes in Category IV patients, they are not included in this clinical study).

[0066] 1.2.3 Traditional Chinese Medicine Diagnostic Criteria

[0067] Referencing the "Diagnostic Criteria for Syndrome Elements of Coronary Heart Disease and Angina Pectoris" (2018) published by the China Association of Traditional Chinese Medicine. [2] The "Standards for Traditional Chinese Medicine Diagnosis of Coronary Heart Disease" formulated by the Cardiovascular Society of the China Association of Integrative Medicine. [3] And the "Guiding Principles for Clinical Research of New Chinese Medicines" [4], proposed diagnostic criteria for chest pain and heart pain due to qi deficiency and blood stasis.

[0068] Qi deficiency syndrome: ① Chest tightness or pain, triggered by exertion (4 points); ② Fatigue (3 points); ③ Weakness (3 points); ④ Shortness of breath (3 points); ⑤ Spontaneous sweating (3 points); ⑥ Weak pulse (2 points); ⑦ Pale and swollen tongue or tongue with teeth marks (2 points).

[0069] (1 point); ⑧ Palpitation (1 point).

[0070] Blood stasis syndrome: ① fixed pain in chest (4 points); ② dark purple tongue or petechiae (4 points); ③ dark purple sublingual vein (3 points); ④ dark purple complexion (3 points); ⑤ body petechiae (3 points); ⑥ numbness of limbs (2 points); ⑦ dark purple or dark red lips (2 points); ⑧ pulse contraction (2 points).

[0071] ③ dark purple sublingual vein (3 points); ④ dark purple complexion (3 points); ⑤ body petechiae (3 points); ⑥ numbness of limbs (2 points); ⑦ dark purple or dark red lips (2 points); ⑧ pulse contraction (2 points).

[0072] Note: At least 1 item of Qi deficiency syndrome + at least 1 item of blood stasis syndrome, and the total score is ≥8 points and meets the tongue and pulse.

[0073] 1.3 Inclusion criteria

[0074] (1) Age 18-70 years old, gender unrestricted;

[0075] (2) With typical clinical manifestations and meet the diagnostic criteria of UAP;

[0076] (3) Patients with CCS classification I-III;

[0077] (4) Good mental state, can communicate orally and in writing;

[0078] (5) Informed consent of volunteers and strong compliance, patients who can cooperate with the investigation.

[0079] 1.4 Exclusion criteria

[0080] With any of the following:

[0081] (1) Combined with other heart disease, or severe cardiopulmonary insufficiency, severe arrhythmia patients;

[0082] (2) Combined with severe primary diseases of liver, kidney, hematopoietic system, etc;

[0083] (3) Suspected or confirmed history of alcohol or drug abuse, or other pathological conditions that may reduce the possibility of enrollment or complicate the enrollment, such as frequent changes in work environment, etc. which may cause loss;

[0084] (4) Allergic constitution or allergic to the drug patch;

[0085] (5) Patients with severe inflammatory diseases;

[0086] (6) Psychiatric patients;

[0087] (7) Pregnant or lactating women;

[0088] (8) Participants in other clinical trials;

[0089] 1.5 Exclusion criteria

[0090] (1) Subjects with poor compliance, failure to take medication as prescribed, inability to judge the efficacy or incomplete data, affecting the safety judgment and efficacy judgment should be excluded;

[0091] (2) Patients who voluntarily withdraw due to lack of efficacy, or inability to continue participating in the clinical trial, or fear, or adverse events, or for any reason are considered to be lost to follow-up;

[0092] (3) Individual cases that occur serious adverse events, complications or special physiological changes cannot continue to receive the test and the blind test are broken, and should be excluded.

[0093] 1.6 Lost cases

[0094] (1) The investigator should contact the patient as soon as possible, ask the reason, record the last medication date, and complete the current project evaluation as much as possible;

[0095] (2) If a patient withdraws from treatment due to serious adverse reactions or dissatisfaction with efficacy, appropriate treatment options should be taken based on actual circumstances;

[0096] (3) Once a random number is obtained, it becomes an observation object of the test, regardless of whether it has received treatment or not, and the patient does not need to be supplemented, and the lost case data is saved;

[0097] (4) Intention-to-treat analysis is performed on the lost patients after the end of the test.

[0098] 2 Research methods

[0099] 2.1 Grouping and administration

[0100] 100 standard cases were included in the test to evaluate the actual clinical efficacy, and the effectiveness and safety of Shuxin Pian were studied. The treatment group and the control group each had 50 cases.

[0101] Control group: 50 patients in this group were given conventional Western medicine treatment according to the treatment principles for stable angina pectoris: lipid regulation, coronary expansion, anticoagulation, and myocardial oxygen consumption reduction. According to the actual situation of the patients, nitroglycerin was given orally during the onset of angina pectoris, antihypertensive drugs were given to patients with hypertension, and effective hypoglycemic measures were given to patients with diabetes. The placebo is a vaseline patch (main ingredient is vaseline).

[0102] Observation group: 50 patients in this group were given Shuxin Pian on the basis of conventional Western medicine treatment in the control group. The main ingredient of the drug is (Example 1 of the invention), and vaseline is used as the carrier. It is pasted on the clitoris and fixed with adhesive tape, twice a day, 5 hours each time. Shuxin Pian is provided by the Chinese Medicine Pharmacy of Shanghai University of Traditional Chinese Medicine Affiliated City Hospital of Traditional Chinese Medicine.

[0103] 2.3 Experimental scheme

[0104] The treatment time is 1 week, and the treatment of patients is observed and followed up for one month after treatment, and the relevant information of the test is collected into the compliance data set for analysis.

[0105] 2.4 Clinical efficacy indicators

[0106] 2.4.1 Primary efficacy assessment

[0107] Improvement criteria for TCM syndromes: record the score changes on the first day of enrollment and 2 weeks after treatment. The number of patients with clinical control, significant effect, effectiveness and invalidity is summarized to calculate the overall effective rate; efficacy index (n) = (pre-test score - post-test score) / pre-test score x 100%;

[0108] Clinical control: symptoms disappear after treatment, n≥80%;

[0109] Significant effect: symptoms improved significantly after treatment, 50%≤n<80%

[0110] Effective: symptoms improved after treatment, 30%≤n<50%;

[0111] Invalid: no change or worsening of symptoms after treatment, n<30%.

[0112] 2.4.2 Secondary efficacy assessment

[0113] Angina pectoris efficacy criteria: before and after treatment, the Seattle Angina Pectoris Rating Scale (SAQ) was used to score to evaluate the quality of life of patients. SAQ is divided into 5 items and 19 items, including the degree of limitation of physical activity (PL, question 1), stable state of angina pectoris (AS, question 2), angina pectoris attack (AF, question 3-4), treatment satisfaction (TS, question 5-8), and disease awareness (DP, question 9-11). Score 5 items and 11 questions, then convert the score to standard score according to the following formula. The higher the score, the better the quality of life and the better the patient's physical function.

[0114] ECG symptoms: record ECG changes on the first day of enrollment and 2 weeks after treatment. The number of patients with significant effect, effectiveness and invalidity is summarized:

[0115] Significant effect: ECG returns to normal or approximately normal;

[0116] Effective: ST segment depression, post-treatment recovery > 0.05mV or more, but not to normal level, mainly inverted, T wave changes, shallower;

[0117] Invalid: no change;

[0118] Worsening: ST segment depression >= 0.05mV, mainly inverted, T wave deepened;

[0119] Angina classification: The angina classification (CCS classification) of patients was evaluated 1 day before treatment and at the 2nd week of treatment.

[0120] 2.4.3 Safety index

[0121] Clinical adverse reaction record:

[0122] Safety evaluation criteria

[0123] Grade 1: safe, no adverse reaction;

[0124] Grade 2: mild adverse reaction, no special treatment is needed, and the drug can be continued;

[0125] Grade 3: moderate adverse reaction, relevant treatment can be given, and the drug can be continued;

[0126] Grade 4: serious adverse reaction, the test must be stopped;

[0127] 3. Statistical methods

[0128] Measurement data were analyzed by t-test statistical method or non-parametric test, and count data were analyzed by X 2 test. The differences of indicators in each group in two cases were analyzed. P<0.05 indicates that there is a significant difference, and P<0.01 indicates that there is a significant difference.

[0129] 4. Research results

[0130] 4.1 Comparison of TCM syndrome score efficacy

[0131] The TCM syndrome score results are shown in Table 1. The effective rate of the treatment group was as high as 96%, and there was a statistical difference. The TCM syndrome efficacy of the treatment group was significantly better than that of the control group.

[0132] Table 1 Improvement of TCM syndrome after treatment

[0133]

[0134] Note: p=0.002<0.01.

[0135] 4.2 Angina classification efficacy

[0136] The angina classification efficacy is shown in Table 2. The effective rate of the treatment group was 94%, and there was a statistical difference compared with the control group. The angina classification efficacy of the treatment group was significantly better than that of the control group.

[0137] Table 2 Improvement of angina classification of two groups after treatment

[0138]

[0139] Note: p<0.01

[0140] 4.3 ECG efficacy

[0141] The results of ECG efficacy are shown in Table 3. The effective rate of the treatment group was 94%, which was statistically different from that of the control group. The improvement of angina pectoris score of the treatment group was significantly better than that of the control group.

[0142] Table 3 Improvement of ECG after treatment of two groups

[0143]

[0144] Note: p = 0.0021 < 0.01

[0145] 4.4 Comparison of SAQ scores of patients in two groups

[0146] The scores of patients in two groups after 1 week of treatment and 1 month of follow-up were significantly improved compared with those before treatment, P < 0.05, and the difference was statistically significant.

[0147] In terms of the degree of limitation of physical activity, stable state of angina pectoris, angina pectoris attack, treatment satisfaction, and disease recognition, the improvement of the Shuxin Paster group after 1 week of treatment and 1 month of follow-up was significantly better than that of the control group, all P < 0.05, and the difference was statistically significant. See the attached Figure 1 .

[0148] 4.4 Comparison of adverse cardiovascular events

[0149] The comparison of adverse cardiovascular events is shown in the attached Figure 2 Compared with the control group, the Shuxin Paster of the present application can reduce the incidence of long-term adverse cardiovascular events.

[0150] Example 14 Animal experiment

[0151] 1. Experimental materials

[0152] 1.1 Animals

[0153] 60 C57BL / 6J mice, half male and half female, 8 weeks old, were purchased from Shanghai Slek Animal Co., Ltd. They were bred in the SPF animal room of Shanghai Biomedicine Institute Animal Center, with a relative humidity of 70%-85% and a room temperature of 18-22℃.

[0154] 1.2 Drugs

[0155] The drug of the traditional Chinese medicine composition I in the present application: the composition of Example 1;

[0156] The drug of the traditional Chinese medicine composition II in the present application: the composition of Example 2;

[0157] The drug of the control group: Chuanxiong 12 parts, sandalwood 9 parts, Danshen 9 parts, Jiangxiang 3 parts, E Zhu 6 parts, Myrrh 6 parts, Agilawood 3 parts, Suhe Xiang 9 parts, musk 12 parts, Motherwort 3 parts.

[0158] Western medicine: nitroglycerin tablets (Beijing Yimin Pharmaceutical Co., Ltd., batch number: H11021022).

[0159] 1.3 Main reagents

[0160] Pituitrin (Anhui Hongye Pharmaceutical Co., Ltd.), NO kit (Shanghai Yian Biological Technology Co., Ltd.), ET-1 kit (Shanghai Sunway Biological Engineering Co., Ltd.).

[0161] 2 Method

[0162] 2.1 Animal modeling

[0163] After the mice were adaptively fed for one week, 8 mice were randomly selected as a blank group, and the remaining mice were modeled in combination with the disease. First, the mice were modeled with qi deficiency and blood stasis, and then intervened with "fasting + high fat" for 4 weeks. The mice were observed for signs and symptoms, and those with obvious shortness of breath, weakness, dark red eyes, loose stools, and tangled hair were considered to have been successfully modeled.

[0164] After the above modeling was completed, the mice that failed to model were removed. After fasting and water deprivation for 12 hours, myocardial ischemia modeling was performed. Each mouse was injected with pituitrin at a dose of 30 u / kg. After 10 minutes, the mice were anesthetized, and electrocardiogram was detected to observe changes in heart rate and T wave. A significant increase in heart rate and a low or inverted T wave were considered to indicate successful modeling of myocardial ischemia.

[0165] 2.2 Experimental scheme

[0166] From the successfully modeled mice, 8 mice per group were randomly selected and divided into 5 groups: the first and second groups of the present application, the first control group, the western medicine group, and the model group. The acupoints (Danzhong) of the mice were located according to the "Animal Acupuncture Atlas". The area 1 cm around the acupoint was shaved and the remaining hair was washed off. The mice were treated for 4 weeks according to the following methods.

[0167] The first group of the present application: The above-mentioned drug of the first group of the present application was ground into powder and mixed with petroleum jelly to form a paste. The paste was applied to the mouse's Danzhong, wrapped with gauze, and fixed with adhesive tape, twice a day for 2 hours each time. The paste was observed in real time to prevent it from falling off.

[0168] The second group of the present application: The above-mentioned drug of the second group of the present application was ground into powder and mixed with petroleum jelly to form a paste. The paste was applied to the mouse's Danzhong, wrapped with gauze, and fixed with adhesive tape, twice a day for 2 hours each time. The paste was observed in real time to prevent it from falling off.

[0169] Control group: The above-mentioned control group drug is ground into powder, mixed with vaseline to make paste, applied to the mouse's chest, wrapped with gauze, fixed with adhesive tape, 2 times a day, 2 hours each time, and observed in time to prevent falling off.

[0170] Western medicine group: Intragastric administration was performed at a dose of 10 mg / kg, twice a day.

[0171] Model group mice were wrapped with vaseline towels on the mouse's chest, wrapped with gauze, fixed with adhesive tape, 2 times a day, 2 hours each time, and observed in time to prevent falling off.

[0172] 2.3 Detection index

[0173] The body weight of the mice was recorded before and after administration. After the administration was completed, the mice's eyeball was removed to take the orbital venous blood, which was stored at 4°C and stood for 4 hours before low-speed centrifugation to extract serum. Then it was placed at -20°C for preservation. The content of NO in the mouse serum was determined by nitric acid reductase, and the content of ET-1 in the mouse was determined by ELISA method. The operation was carried out according to the instructions of the kit.

[0174] 3 Statistical method

[0175] SPSS was used for statistical processing of data. Measurement data was expressed by , those conforming to normal distribution were tested by t test, those not conforming to normal distribution were tested by non-parametric rank sum test; count data was expressed by cases or percentage, non-graded data was tested by chi-square test, and graded data was tested by rank sum test. P<0.05 was considered to have statistical significance.

[0176] 4 Results

[0177] The heart rate and T wave height of the mice after modeling are shown in Table 1. Compared with the heart rate and T wave height of the mice in the blank group, the heart rate of the model group was significantly higher than that of the blank group (P<0.05), and the T wave height was also significantly reduced (P<0.05), indicating that the pathological state of myocardial ischemia was reached.

[0178] Table 1 Comparison of heart rate and T wave height of mice

[0179] Group n (example) Heart rate (times / min) T wave amplitude (mV) Model group 45 75±9.69* 0.121±0.104* Blank group 8 67±8.26 0.215±0.014

[0180] Note: Compared with blank, *P<0.05

[0181] The contents of NO and ET-1 in the serum of mice are shown in Table 2. Compared with the blank group, the content of NO in the model group was significantly decreased, and the content of ET-1 was significantly increased (P<0.05). After drug intervention, compared with the model group, the NO levels of the application group, the control group and the western medicine group were significantly increased, and the application group two was equivalent to the western medicine group, and the application group increased most significantly. The ET-1 levels of the application group, the control group and the western medicine group were significantly decreased (P<0.05), and the application group one decreased most significantly (P<0.05). It can be seen that the improvement effect of the application group is better than that of the control group and the western medicine group, and the application group one is the most prominent.

[0182] Table 2 Comparison of NO and ET-1 levels in serum of mice n=8

[0183] Group n (example) NO (umol / ml) ET-1 (pg / ml) Invention group one 8 75.68 ± 4.88 2,3,4,5) ]] 38.96 ± 3.21 2,3,4,5) ]] Invention group two 8 72.63 ± 5.23 2,3) ]] 41.71 ± 4.24 2,3,4) ]] Control group 8 70.92 ± 5.32 2) ]] 48.15 ± 2.13 2) ]] Western medicine group 8 72.88 ± 4.82 2) ]]> 45.18 ± 2.88 2) <!-- 9 -->]] Model group 8 64.91 ± 2.77 1) ]] 68.02 ± 4.41 1) ]] Blank group 8 86.71±4.88 35.12±1.98

[0184] Note: compared with the blank group, 1) P<0.05; compared with the model group, 2) P<0.05; compared with the control group, 3) P<0.05; compared with the western medicine group, 4) compared with the application group two, 5) P<0.05

[0185] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled in the art, without departing from the method of the present application, a number of improvements and supplements can also be made, and these improvements and supplements should be considered as the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition for treating coronary heart disease, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 10-14 parts of Ligusticum chuanxiong, 7-11 parts of sandalwood, 7-11 parts of Salvia miltiorrhiza, 2-4 parts of Dalbergia odorifera, 4-8 parts of frankincense, 4-8 parts of myrrh, 2-4 parts of clove, 7-11 parts of styrax, 10-14 parts of borneol, and 2-4 parts of Campsis grandiflora. The herbal composition uses Ligusticum chuanxiong and sandalwood as the principal ingredients, Salvia miltiorrhiza, Dalbergia odorifera, clove, frankincense, and myrrh as the assistant ingredients, Styrax benzoin as the adjuvant ingredient, and borneol and Campsis grandiflora as the guiding ingredients.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 12 parts of Ligusticum chuanxiong, 9 parts of sandalwood, 9 parts of Salvia miltiorrhiza, 3 parts of Dalbergia odorifera, 6 parts of frankincense, 6 parts of myrrh, 3 parts of clove, 9 parts of styrax, 12 parts of borneol, and 3 parts of Campsis grandiflora.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The aforementioned traditional Chinese medicine composition is a topical traditional Chinese medicine composition.

4. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of drugs for treating coronary heart disease.

5. The application according to claim 4, characterized in that, The coronary heart disease mentioned is unstable angina pectoris, and its syndrome is qi deficiency and blood stasis syndrome.

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