A traditional Chinese medicine composition, a preparation method therefor and application thereof

Abstract

The present application provides a kind of traditional Chinese medicine composition and its preparation method and application, belong to medical field.The traditional Chinese medicine composition of the present application includes the following weight parts of raw materials: 15-30 parts of Huangqi, 15-30 parts of Maidong, 6-9 parts of Wuweizi, 9-12 parts of Jiangxiang, 12-15 parts of Yincheng.The traditional Chinese medicine composition of the present application is simple in force, can benefit heart qi, nourish heart yin to support healthy, can also resolve blood stasis, unblock heart vessel to drive evil, supplement and pass through to be used to supplement as main, so that qi yin is supplemented, blood stasis is removed, and the effect of benefiting qi and nourishing yin, promoting blood circulation to remove blood stasis is achieved together.It has significant clinical effect on chronic stable exertional angina pectoris with qi yin deficiency and heart vessel stasis.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to a traditional Chinese medicine composition, its preparation method, and its application. Background Technology

[0002] Chronic stable exertional angina is the result of both increased myocardial oxygen demand and decreased myocardial oxygen supply. On the basis of coronary artery stenosis, increased myocardial oxygen demand due to exercise, overeating, emotional fluctuations, or other stimuli, or conversely, narrowing of the coronary artery lumen due to platelet aggregation, thrombus formation, or coronary artery spasm, leads to reduced myocardial oxygen supply and impaired clearance of metabolic products, thus inducing angina. Currently, there is a lack of epidemiological surveys on chronic stable exertional angina.

[0003] Studies have found that the mortality rate from coronary heart disease has been on the rise, placing a heavy burden on public health and the economy. Western medicine alone has limitations in treating chronic stable exertional angina and has significant side effects. Compared to Western medicine, traditional Chinese medicine not only has better therapeutic effects, but also provides comprehensive regulation of the body at multiple levels, through multiple pathways, and at multiple targets. Furthermore, it can significantly improve patients' symptoms, enhance their quality of life, and has better patient compliance, making it a primary means of treating chronic stable exertional angina.

[0004] There is no record of coronary heart disease in traditional Chinese medicine literature. Based on its symptoms, evolution, and complications, it falls under the category of "chest pain and heart pain" in traditional Chinese medicine. It is often caused by factors such as invasion of cold pathogens, improper diet, and emotional distress, which lead to imbalance of yin and yang and disorder of qi and blood. Its basic pathogenesis is deficiency of the root and excess of the branch. Deficiency of both qi and yin and obstruction of the heart vessels are common syndrome types. The treatment should focus on tonifying qi and nourishing yin, and promoting blood circulation and unblocking the vessels.

[0005] There are few reports on pure traditional Chinese medicine preparations for treating angina pectoris caused by coronary heart disease with deficiency of both qi and yin and obstruction of the heart vessels. Moreover, most traditional Chinese medicines for treating chronic stable exertional angina pectoris contain multiple medicinal ingredients, requiring the aggregation of multiple ingredients to form a finished product, making the preparation process cumbersome and complex. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a traditional Chinese medicine composition that has a significant clinical effect on chronic stable exertional angina pectoris with qi and yin deficiency and blood stasis in the heart vessels.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] A traditional Chinese medicine composition comprising the following raw materials in parts by weight: 15-30 parts of Astragalus membranaceus, 15-30 parts of Ophiopogon japonicus, 6-9 parts of Schisandra chinensis, 9-12 parts of Dalbergia odorifera, and 12-15 parts of Artemisia capillaris.

[0009] Preferably, the raw materials include the following parts by weight: 18-26 parts of Astragalus membranaceus, 18-26 parts of Ophiopogon japonicus, 7-8 parts of Schisandra chinensis, 10-11 parts of Dalbergia odorifera, and 13-14 parts of Artemisia capillaris.

[0010] Another objective of this invention is to provide a method for preparing the traditional Chinese medicine composition, comprising the following steps: weighing Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera and Artemisia capillaris in proportion, mixing the traditional Chinese medicine raw materials, soaking them in water, and then decocting them twice.

[0011] Preferably, the weight of the added water is 8-12 times that of the Chinese herbal medicine raw materials.

[0012] Preferably, the soaking time is 30 to 60 minutes.

[0013] Preferably, the simmering time is 20 to 60 minutes.

[0014] Preferably, the decoction liquid from the two decoctions is collected and concentrated under reduced pressure to form an ointment, wherein the reduced pressure concentration temperature is 60-70℃ and the pressure is -0.06 to -0.08 MPa.

[0015] Another object of the present invention is to provide the use of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the method in the preparation of a drug for treating chronic stable exertional angina pectoris.

[0016] Preferably, the chronic stable exertional angina is a chronic stable exertional angina syndrome characterized by deficiency of both Qi and Yin and obstruction of the heart vessels.

[0017] Preferably, the drug for treating chronic stable exertional angina is prepared from the traditional Chinese medicine composition by adding pharmaceutically acceptable excipients to obtain powders, decoctions, pills, capsules, tablets, granules, and oral liquids.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] Guided by the principles of traditional Chinese medicine (TCM) formulation, and considering the fundamental pathogenesis and pathological characteristics of coronary heart disease with Qi and Yin deficiency and blood stasis in the heart vessels, this invention provides a TCM compound containing Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera, and Artemisia capillaris to combat chronic stable exertional angina. This compound has the effects of tonifying Qi and nourishing Yin, promoting blood circulation and unblocking the meridians, and has the efficacy of increasing coronary blood flow, improving myocardial ischemia, and improving microcirculation, thus combating coronary heart disease. The TCM composition provided by this invention is simple and potent, effectively tonifying heart Qi and nourishing heart Yin to strengthen the body's resistance, while also resolving blood stasis and unblocking the heart vessels to expel pathogens. It combines tonification and unblocking with a focus on tonification, thus replenishing Qi and Yin and removing blood stasis, achieving the combined effects of tonifying Qi and nourishing Yin, promoting blood circulation and removing blood stasis. It has significant clinical efficacy for chronic stable exertional angina with Qi and Yin deficiency and blood stasis in the heart vessels, with no obvious toxic side effects. Compared with similar drugs, it has the characteristics of fewer ingredients, lower price, and higher efficacy, and has broad application prospects.

[0020] The traditional Chinese medicine composition of this invention is prepared according to the principle of "mechanism design for coronary heart disease angina pectoris and multi-target comprehensive intervention" to form an effective traditional Chinese medicine preparation for chronic stable exertional angina pectoris. Compared with chemical drugs, it has precise therapeutic effects such as anti-platelet aggregation, improving myocardial blood supply, inhibiting sympathetic nerves, and lowering blood lipids. It can better improve patients' discomfort symptoms, improve their quality of life, and has better compliance. Detailed Implementation

[0021] This invention provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: Astragalus membranaceus 15-30 parts, Ophiopogon japonicus 15-30 parts, Schisandra chinensis 6-9 parts, Dalbergia odorifera 9-12 parts, and Artemisia capillaris 12-15 parts. Preferably, it comprises the following raw materials in parts by weight: Astragalus membranaceus 18-26 parts, Ophiopogon japonicus 18-26 parts, Schisandra chinensis 7-8 parts, Dalbergia odorifera 10-11 parts, and Artemisia capillaris 13-14 parts. This traditional Chinese medicine composition can both invigorate the heart qi and nourish the heart yin to support the body's resistance, and also resolve blood stasis and unblock the heart vessels to expel pathogens. It combines tonification and unblocking with tonification as the primary focus, thus replenishing qi and yin and removing blood stasis, achieving the combined effects of invigorating qi and nourishing yin, and promoting blood circulation and removing blood stasis. It has significant clinical efficacy for chronic stable exertional angina pectoris with qi and yin deficiency and heart vessel obstruction.

[0022] The traditional Chinese medicine composition provided by this invention contains Astragalus membranaceus, which is sweet, has a light aroma but a strong flavor, and can both ascend and descend, making it an essential herb for tonifying Qi. It has the functions of tonifying Qi and generating blood, and tonifying Qi and generating body fluids. According to *Rihuazi Materia Medica*, it "assists Qi and tonifies blood," and according to *Bielu*, it "benefits Qi and benefits heart Qi." It is especially beneficial for those with Qi deficiency and insufficient Yin fluids. *Bencao Fengyuan* states that it "tonifies the deficiency of the five internal organs and expels stagnant blood between the five internal organs," indicating that Astragalus membranaceus, in addition to tonifying heart Qi and benefiting Yin and blood, also has the effect of resolving blood stasis. Ophiopogon japonicus, sweet and slightly bitter, is slightly cold in nature. Its sweet and cold properties are moistening and nourishing, able to nourish Yin and generate body fluids, moisten the lungs and clear the heart. It is good at clearing heat from the heart and lungs while nourishing Yin and relieving irritability, and can also clear and moisten the stomach and intestines to quench thirst and moisten dryness. *Bencao Xinbian* states that "Ophiopogon japonicus drains latent fire in the lungs, clears heat evil in the stomach, and tonifies the Qi of the heart." Ophiopogon japonicus tonifies heart Yin and benefits heart Qi, making it especially beneficial for those with both Qi and Yin deficiency. When Astragalus and Ophiopogon japonicus are used together, they have the effect of invigorating Qi and nourishing Yin. Together they are the principal herbs and play a leading role in the prescription for treating the disease.

[0023] Schisandra chinensis is sour and warm in nature, possessing astringent and consolidating properties, replenishing qi and generating fluids, tonifying the kidneys and calming the mind. The *Shennong Bencao Jing* states that it "primarily replenishes qi, supplements deficiencies, and strengthens yin," while the *Bencao Huiyan* states that "Schisandra chinensis is a medicine for astringing qi and generating fluids." The *Bihua Yijing Buzhu* lists Schisandra chinensis as a powerful heart tonic. Dalbergia odorifera is pungent and warm in nature. The *Bencao Jing Shu* states that "Dalbergia odorifera is the purest and most intense fragrance, thus it can dispel all evil qi." Furthermore, the *Benjing Fengyuan* states that "Dalbergia odorifera is red in color, enters the blood and descends, therefore, when taken internally, it promotes blood circulation and breaks up stagnation." Schisandra chinensis can enhance the qi-replenishing and yin-nourishing effects of the principal herbs, its sour and sweet nature transforming into yin, preserving yin to retain yang. Dalbergia odorifera, being pungent, disperses blood stasis, regulates qi, and relieves pain, thus enhancing the qi-replenishing and blood-activating effects of Astragalus membranaceus and Ophiopogon japonicus. Schisandra chinensis and Dalbergia odorifera together serve as assistant herbs in the formula.

[0024] Artemisia capillaris has a bitter and pungent taste, and is slightly cold in nature. It has the effects of clearing heat and promoting diuresis. The *Shennong Bencao Jing* states, "Artemisia capillaris sprouts in spring from old seedlings, because it possesses the vitality of spring growth due to the cold water of winter." The *Yixue Zhongzhong Canxi Lu* states, "Its nature is quite similar to Bupleurum chinense, but its power is gentler. For those who wish to expel pathogenic factors from the Lesser Yang, but whose constitution is weak and Yin deficient and cannot withstand the dispersing effect of Bupleurum chinense, Artemisia capillaris can be used instead." This shows that this herb is fragrant and primarily dispersing, capable of dispersing pathogenic heat and also possessing liver-soothing properties without the drawback of damaging the liver and depleting Yin. "Liver Qi resides in the heart," and Artemisia capillaris excels at clearing heat and soothing the liver, harmonizing heart Qi and promoting blood circulation. When used with Ophiopogon japonicus, it clears heat without harming Yin, addressing both the root cause and the symptoms, making it an adjuvant in formulas.

[0025] The formula is simple yet potent, capable of both nourishing the heart qi and yin to strengthen the body's resistance, and also dispelling blood stasis and clearing the heart vessels to expel pathogens. It combines tonification and unblocking, with tonification as the main focus, so that qi and yin are replenished and blood stasis is removed, thus achieving the combined effects of tonifying qi and nourishing yin, and promoting blood circulation and removing blood stasis.

[0026] This invention also provides a method for preparing the aforementioned traditional Chinese medicine composition, comprising the following steps: weighing Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera, and Artemisia capillaris according to a specified ratio; mixing the raw materials and soaking them in water; and then decocting twice. This invention has found that the preparation method of the traditional Chinese medicine composition directly affects the content of effective components in the prepared composition.

[0027] In this invention, the weight of the added water is 8 to 12 times that of the Chinese herbal raw materials, preferably 9 to 11 times; the soaking time is 30 to 60 minutes, preferably 45 to 55 minutes. This invention allows the Chinese herbal raw materials to fully absorb water through soaking, thereby promoting the dissolution of active ingredients in the water. As an implementable method, this invention uses cold water soaking.

[0028] In this invention, the decoction time is 20-60 minutes. Preferably, the decoction is performed in two stages. For the first stage, 11-12 times the weight of the medicinal materials are added to water, and the decoction is simmered for 50-60 minutes. After collecting the decoction, 8-10 times the weight of the medicinal materials are added to water, and the decoction is simmered for another 20-30 minutes. As an alternative method, the medicinal materials are soaked in water, brought to a boil over high heat, and then simmered over low heat. The terms "high heat" and "low heat" are terms used in traditional Chinese medicine and can be applied using conventional methods in this field.

[0029] In this invention, the decoction liquid from two decoctions is collected and concentrated under reduced pressure to form an ointment. The concentration temperature is 60–70°C, and the pressure is -0.06–-0.08 MPa. These concentration conditions effectively improve the transfer rate of the active ingredients in traditional Chinese medicine. As one feasible method, the decoction liquid from two decoctions is collected and concentrated under reduced pressure to form an ointment with a relative density of 1.1–1.2 g / mL.

[0030] The concentrated ointment obtained by this invention can be dried to obtain a dry ointment powder. As one feasible method, this invention employs spray drying, wherein the drying conditions are an inlet air temperature of 120–140°C and an outlet air temperature of 45–90°C. After drying, the ointment powder is sieved to obtain the dry ointment powder. The dry ointment powder of this invention can be further processed into pills, tablets, and powders using conventional methods in the art.

[0031] Another object of the present invention is to provide the use of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the method in the preparation of a drug for treating chronic stable exertional angina pectoris.

[0032] Preferably, the chronic stable exertional angina is a chronic stable exertional angina syndrome characterized by deficiency of both Qi and Yin and obstruction of the heart vessels.

[0033] Preferably, the drug for treating chronic stable exertional angina further includes pharmaceutically acceptable excipients, and different dosage forms are prepared by adding excipients, including powders, decoctions, pills, capsules, tablets, granules and oral liquids.

[0034] As one feasible method, the ointment of the present invention is prepared into granules. The ointment and dextrin are mixed and then granulated by fluidized spraying at a spray rate of 100-300 r / min to form granules. The mass ratio of the ointment to dextrin is 1-1.3:1-1.5.

[0035] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0036] Example 1

[0037] A traditional Chinese medicine composition, the raw materials of which are the following traditional Chinese medicines in parts by weight: Astragalus membranaceus 15g, Ophiopogon japonicus 15g, Schisandra chinensis 6g, Dalbergia odorifera 9g, and Artemisia capillaris 12g.

[0038] The preparation method is as follows:

[0039] Weigh out Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera and Artemisia capillaris according to the proportions. Add 12 times the total weight of the Chinese medicinal materials to water, soak for 40 minutes, bring to a boil over high heat and then simmer over low heat for 60 minutes. Filter the decoction, then add 10 times the total weight of the Chinese medicinal materials to water, bring to a boil over high heat and simmer over low heat for 30 minutes. Filter the decoction.

[0040] After combining the decoction liquids, the liquids were concentrated under reduced pressure at 60–65°C and -0.06–-0.08 MPa. The concentrated paste was then spray-dried at an inlet air temperature of 140°C and an outlet air temperature of 60°C. The paste was then sieved to obtain a dry powder.

[0041] Example 2

[0042] A traditional Chinese medicine composition, the raw materials of which are the following traditional Chinese medicines in parts by weight: Astragalus membranaceus 30g, Ophiopogon japonicus 30g, Schisandra chinensis 9g, Dalbergia odorifera 12g, and Artemisia capillaris 15g.

[0043] The preparation method is the same as in Example 1.

[0044] Example 3

[0045] A traditional Chinese medicine composition, the raw materials of which are the following traditional Chinese medicines in parts by weight: Astragalus membranaceus 20g, Ophiopogon japonicus 25g, Schisandra chinensis 8g, Dalbergia odorifera 10g, and Artemisia capillaris 13g.

[0046] The preparation method is the same as in Example 1.

[0047] Example 4

[0048] A traditional Chinese medicine composition

[0049] The difference between this embodiment and Embodiment 1 is that the vacuum concentration conditions are 65-70℃ and -0.06--0.08MPa.

[0050] Example 5

[0051] A granule

[0052] The ointment obtained by vacuum concentration in Example 1 was mixed with dextrin at a mass ratio of 1:1, and granulated by fluidized spray granulation at a spray rate of 200 r / min to produce granules.

[0053] Comparative Example 1

[0054] A traditional Chinese medicine composition differs from Example 1 in that it does not contain Astragalus membranaceus.

[0055] Comparative Example 2

[0056] A traditional Chinese medicine composition differs from Example 1 in that Ophiopogon japonicus is replaced with Polygonatum odoratum.

[0057] Comparative Example 3

[0058] The preparation method of a traditional Chinese medicine composition differs from that in Example 1 in that the vacuum concentration conditions are 70-75℃ and -0.06--0.08MPa.

[0059] Comparative Example 4

[0060] A method for preparing a traditional Chinese medicine composition

[0061] Weigh out Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera and Artemisia capillaris according to the proportions, add water equal to 10 times the total weight of the Chinese medicinal materials, heat and reflux for 1 hour, and collect the filtrate.

[0062] Example 6

[0063] This example compares the effects of different concentration conditions.

[0064] Weigh out 15g of Astragalus membranaceus, 15g of Ophiopogon japonicus, 6g of Schisandra chinensis, 9g of Dalbergia odorifera, and 12g of Artemisia capillaris. Weigh out three portions in total. Using the methods in Example 1, Example 4, and Comparative Example 3, concentrate the decoction under reduced pressure to 1.5g of crude drug / mL. Calculate the component transfer rate of astragaloside A (based on the content of astragaloside A in the water extract being 100%). Repeat the calculation three times to obtain the average value. The results are shown in Table 1.

[0065] Table 1. Effects of different vacuum concentration conditions on the transfer rate of astragaloside A component.

[0066]

[0067] The results showed that different vacuum concentration conditions had a certain impact on the transfer rate of astragaloside A. The higher the temperature, the lower the transfer rate of astragaloside A. The concentration conditions of the present invention are low in cost, easy to operate, and have a high transfer rate of astragaloside A.

[0068] Example 7

[0069] This embodiment compares the effects of different preparation methods on the active ingredients.

[0070] Weigh out 15g of Astragalus membranaceus, 15g of Ophiopogon japonicus, 6g of Schisandra chinensis, 9g of Dalbergia odorifera, and 12g of Artemisia capillaris. Weigh out two portions. One portion is prepared by the method in Example 1 to obtain a combined decoction of the two decoctions. The other portion is prepared by the method in Comparative Example 4 to obtain a filtrate. Concentrate the combined decoction and the filtrate under reduced pressure (60-65℃, -0.06--0.08MPa) to 30mL. Detect the astragaloside A content in the concentrated decoction. Repeat the test three times and calculate the average value. The results are shown in Table 2.

[0071] Table 2 Results of process comparison and verification tests (n=3)

[0072]

[0073] The preparation method provided by this invention effectively increases the content of astragaloside A in the extract.

[0074] Example 8

[0075] Clinical studies on the treatment of chronic stable exertional angina.

[0076] 1. Case source and method

[0077] 1.1 Source of Cases

[0078] All cases were hospitalized patients with chronic stable exertional angina pectoris who met the criteria of Qi and Yin deficiency and blood stasis in the Department of Cardiology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, from January 2018 to March 2023.

[0079] 1.2 Western Medicine Diagnostic Criteria

[0080] According to the "Guidelines for the Diagnosis and Treatment of Stable Coronary Artery Disease at the Primary Care Level (Practical Edition, 2020)," the following conditions must be met:

[0081] 1.2.1 Symptoms:

[0082] ① Location: Chest discomfort caused by myocardial ischemia is usually located behind the sternum, but can also be in the precordial region, pharynx, jaw, etc., covering an area the size of a palm or fist, or even spanning the entire chest, with indistinct boundaries. It often radiates to the left shoulder, the inner side of the left arm reaching the ring and little fingers, or to the neck, pharynx, or jaw. The location of symptoms may vary from patient to patient, but the location of symptoms in the same patient is often fixed. Migratory and changeable chest symptoms are often not angina.

[0083] ② Nature: Chest pain is often described as a feeling of pressure, tightness, constriction, or heaviness in the chest, sometimes described as a choking sensation in the neck or a burning sensation behind the sternum, but it is not a sharp, stabbing or stabbing pain. It may be accompanied by shortness of breath, or symptoms similar to angina, such as fatigue or weakness. Shortness of breath may be the only clinical manifestation of stable coronary artery disease, and is sometimes difficult to distinguish from shortness of breath caused by lung disease. During a chest pain attack, patients are often forced to stop their ongoing activities until the symptoms subside.

[0084] ③ Duration: Usually lasts from several minutes to more than 10 minutes, most often 3 to 5 minutes, rarely exceeding 15 minutes. If the symptoms only last for a few seconds or are measured in hours, it is very likely not angina.

[0085] ④ Triggers: A key characteristic of angina is its association with exertion or emotional excitement. Angina is often triggered by increased workload, such as walking uphill, walking against the wind, after a large meal, or when the weather turns cold. The pain usually occurs during exertion or emotional excitement, rather than afterward. Sublingual nitrates often provide relief within 1–3 minutes.

[0086] 1.2.2 Auxiliary inspections:

[0087] If any one of the following is present, a diagnosis of coronary heart disease can be made: a previous positive electrocardiogram or coronary angiography; a positive computed tomography angiography; or a positive exercise test electrocardiogram.

[0088] 1.2.3 Angina Pectoris Classification

[0089] According to the Canadian Cardiovascular Society (CCS) classification of angina, it is divided into 4 grades.

[0090] Grade I: Normal physical activity (such as walking and climbing stairs) is not restricted, but angina occurs during strong, rapid or sustained exertion;

[0091] Grade II: Mild limitation of general physical activity; angina pectoris occurs during brisk walking, after meals, in cold or windy conditions, during mental stress, or within a few hours after waking up; generally limited ability to walk more than 200 meters on flat ground or climb more than one floor.

[0092] Level III: Physical activity is significantly limited; under normal circumstances, walking less than 200 meters on flat ground or climbing one floor will cause angina.

[0093] Grade IV: Angina pectoris can occur with slight activity or at rest.

[0094] 1.3 Traditional Chinese Medicine Diagnostic Criteria

[0095] Referring to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs," the "Diagnostic Criteria for Major Syndromes of Coronary Heart Disease and Angina Pectoris," and "Internal Medicine of Traditional Chinese Medicine," the TCM diagnostic criteria for chest pain due to deficiency of both Qi and Yin and obstruction of the heart vessels are as follows:

[0096] Main symptoms: Chest tightness, chest pain

[0097] Secondary symptoms: ① Palpitations, anxiety, and fatigue

[0098] ② Excessive sweating, dry mouth, hot palms and soles, and constipation

[0099] ③ Blue lips and dull complexion

[0100] Tongue and pulse examination: The tongue is reddish or purplish-dark, or has ecchymosis or petechiae, with little coating; the pulse is weak, thready, and rapid, or thready and hesitant. Note: If the primary symptom and two or more secondary symptoms are met, the tongue and pulse examination can support the diagnosis.

[0101] 1.4 Inclusion Criteria

[0102] (1) Meets the Western medical diagnostic criteria for chronic stable exertional angina.

[0103] (2) Those who meet the criteria of Qi and Yin deficiency and heart blood stasis according to traditional Chinese medicine diagnosis.

[0104] (3) Age between 18 and 85 years old.

[0105] 1.5 Exclusion Criteria

[0106] (1) Those who have experienced chest pain due to acute myocardial infarction, aortic dissection, valvular heart disease, cardiomyopathy, or other non-cardiac diseases in the past six months.

[0107] (2) Patients with severe hypertension, shock, severe arrhythmia, liver and kidney dysfunction, hematopoietic system disorders, or mental illness.

[0108] (3) Pregnant or lactating women; allergic constitution.

[0109] 1.6 Research Plan

[0110] 1.6.1 Grouping Method

[0111] The experimental group and the control group were each divided into 100 cases in a 1:1 ratio.

[0112] 1.6.2 Treatment Plan

[0113] 1.6.2.1 Group Treatment

[0114] ① Experimental group: Oral administration of traditional Chinese medicine Huangqi Maidong formula

[0115] The traditional Chinese medicine composition provided in Example 1 was obtained by combining two decoctions and concentrating them to 200 mL.

[0116] Dosage and administration: 200mL of medicine, taken twice a day, morning and evening, while warm.

[0117] ② Control group

[0118] Conventional Western medicine treatment: Isosorbide dinitrate, commonly used in clinical practice, 10mg each time, three times a day.

[0119] 1.6.2.2 Treatment course: The treatment course is 4 weeks.

[0120] 1.6.3 Observation Indicators

[0121] (1) Symptoms and signs: frequency, severity and duration of angina attacks

[0122] (2) Changes in TCM syndrome scores

[0123] (3) Safety indicators:

[0124] ① General items: including body temperature, heart rate, respiration, blood pressure, etc.; ② Blood and urine routine tests; ③ Liver and kidney function tests.

[0125] 1.7 Evaluation of therapeutic effect

[0126] The efficacy evaluation criteria were based on the "Guiding Principles for Clinical Research on New Traditional Chinese Medicine Drugs for the Treatment of Chest Pain".

[0127] 1.7.1 Western Medicine Efficacy Evaluation Standards

[0128] Clinical efficacy evaluation criteria for angina pectoris:

[0129] Significant effect: Angina symptoms disappear or basically disappear / the original grade III angina is reduced to the grade I standard; Effective: The frequency, intensity and duration of grade I angina attacks are significantly reduced / grade II angina is reduced to the grade I standard / grade III angina is reduced to the grade II standard; Ineffective: Angina symptoms are basically the same as before treatment.

[0130] 1.7.2 Evaluation Criteria for the Therapeutic Effect of Traditional Chinese Medicine

[0131] (1) Significant effect: Clinical symptoms and signs are significantly improved, and the syndrome score is reduced by ≥70%;

[0132] (2) Effective: Clinical symptoms and signs improved, and the syndrome score decreased by ≥30%;

[0133] (3) Ineffective: Clinical symptoms and signs do not improve significantly, or even worsen, and the syndrome score decreases by <30%;

[0134] (4) Worsening: Clinical symptoms and signs worsen, and syndrome score increases.

[0135] 1.8 Data Management and Statistical Analysis Solution

[0136] Data Management: Data is entered by two people, and patient information is collected in the form of medical records to ensure that the information is accurate, timely and complete. The medical record information is used to establish a database and the data is standardized to ensure the validity and consistency of the data.

[0137] Statistical analysis: R (3.6.3) was used for all statistical analyses. Depending on whether the data conformed to a normal distribution, continuous variables were expressed as mean ± standard deviation or median and quartiles. Independent samples t-tests and ANOVA were used for comparisons between groups. For data not conforming to a normal distribution, Wilcoxon rank-sum tests and Kruskal-Wallis rank-sum tests were used. Categorical variables were expressed as percentages or proportions, and chi-square tests or Fisher's exact tests were used. Missing data were imputed using the mice package (version 3.13.0) using multiple imputation (MI). The effects of different exposure levels on chronic stable exertional angina were analyzed using a Cox proportional hazards model, taking into account factors such as age and gender.

[0138] 1.9 Control of Bias

[0139] 1.9.1 Selection Bias

[0140] To minimize selection bias, researchers will enroll patients consecutively according to the protocol, rather than based on personal preferences.

[0141] 1.9.2 Information Bias

[0142] Because adverse reactions such as edema, gastrointestinal discomfort, and cough are listed in the drug's instructions, researchers may be biased when conducting causal assessments. To minimize such bias, efforts should be made to collect as much information as possible about these adverse reactions to make an objective determination of causality.

[0143] 2. Results

[0144] 2.1 Baseline Indicators

[0145] The demographic indicators (gender, age) and total TCM syndrome scores of the two groups of patients before treatment were compared using chi-square test and independent samples t-test, respectively. The results are shown in Table 3. There were no statistically significant differences between the two groups, indicating that they were comparable.

[0146] Table 3. Demographic Indicators and Total Score of Traditional Chinese Medicine Syndromes

[0147]

[0148] 2.2 Angina pectoris indicators

[0149] The results are shown in Table 4. After treatment, the experimental group was superior to the control group in terms of the efficacy of angina pectoris treatment, and the difference was statistically significant.

[0150] Table 4. Efficacy of Angina Pectoris Treatment

[0151]

[0152] 2.3 Therapeutic Effects of TCM Syndrome Improvement

[0153] The results are shown in Table 5. After treatment, the experimental group was better than the control group in terms of improvement of TCM syndromes, and the difference was statistically significant.

[0154] Table 5 Improvement of TCM Syndromes

[0155]

[0156] 2.4 Security

[0157] Both groups of patients underwent routine blood tests, routine urine tests, liver function tests, and kidney function tests before and after treatment. The results showed that no obvious adverse reactions related to the investigational drug were observed in either group of patients during the clinical observation period, and no patients experienced a worsening of their condition, indicating that the treatment received by both groups of patients during the clinical medication period was safe.

[0158] 2.5 Statistical table of clinical efficacy of the traditional Chinese medicine composition in Example 1 of the present invention for treating chronic stable exertional angina pectoris

[0159] Table 6. Statistical table of clinical efficacy of traditional Chinese medicine compositions in treating chronic stable exertional angina pectoris.

[0160]

[0161]

[0162] Example 9

[0163] Comparative Example 1: Clinical study of chronic stable exertional angina

[0164] 1. Selected Cases

[0165] The diagnostic criteria were the same as in Example 8. Sixty-two patients diagnosed with coronary heart disease, angina pectoris, and deficiency of both Qi and Yin with blood stasis were selected. These 62 patients were randomly divided into a traditional Chinese medicine group and a Western medicine group using a random number table, with 31 patients in each group. There were no significant differences between the two groups in terms of age, course of disease, etc. (P>0.05), making them comparable.

[0166] 2. Treatment methods

[0167] Traditional Chinese medicine group: The traditional Chinese medicine composition prepared in Comparative Example 1 of the present invention was administered, and the decoctions from the two decoctions were combined and concentrated to 200 mL. One dose was administered daily, divided into two administrations in the morning and evening.

[0168] Control group: Conventional Western medicine treatment: commonly used nitroglycerin, 10mg each time, three times a day.

[0169] Other requirements and standards are the same as in Example 8.

[0170] 3. Observation indicators

[0171] Same as Example 8.

[0172] 4. Efficacy evaluation criteria

[0173] Same as Example 8.

[0174] 5. Statistical methods

[0175] Same as Example 8.

[0176] 6. Treatment Results

[0177] 6.1 Symptom Improvement: Clinical observation showed that after taking the traditional Chinese medicine (TCM) medication, the significant efficacy, effective rate, and total effective rate for angina pectoris were 16.1%, 35.5%, and 51.6%, respectively. In the Western medicine (West China) group, the significant efficacy, effective rate, and total effective rate were 32.2%, 35.5%, and 67.7%, respectively. Statistical analysis showed that the Western medicine group had a better therapeutic effect than the TCM group (P<0.05).

[0178] 6.2 Efficacy of Traditional Chinese Medicine (TCM) Syndrome Differentiation: Clinical observation showed that after taking the TCM, the significant efficacy, effective rate, and total effective rate for angina pectoris were 29%, 48.4%, and 77.4%, respectively. In the Western medicine group, the significant efficacy, effective rate, and total effective rate were 22.6%, 48.4%, and 71%, respectively. Statistical analysis showed no statistically significant difference between the TCM and Western medicine groups in terms of improvement of TCM syndrome differentiation (P>0.05).

[0179] Example 10

[0180] Clinical study of Comparative Example 2 in the treatment of chronic stable exertional angina

[0181] 1. Selected Cases

[0182] The diagnostic criteria were the same as in Example 8. Sixty-eight patients diagnosed with coronary heart disease, angina pectoris, and qi and yin deficiency with blood stasis were selected. These 68 patients were randomly divided into a traditional Chinese medicine group and a Western medicine group using a random number table, with 34 patients in each group. There were no significant differences between the two groups in terms of age, disease duration, etc. (P>0.05), making them comparable.

[0183] 2. Treatment methods

[0184] Traditional Chinese medicine group: The traditional Chinese medicine composition prepared in Comparative Example 2 of the present invention was administered, and the decoctions from the two decoctions were combined and concentrated to 200 mL. One dose was administered daily, divided into two administrations in the morning and evening.

[0185] Control group: Conventional Western medicine treatment: commonly used nitroglycerin, 10mg each time, three times a day.

[0186] Other requirements and standards are the same as in Example 8.

[0187] 3. Observation indicators

[0188] Same as Example 8.

[0189] 4. Efficacy evaluation criteria

[0190] Same as Example 8.

[0191] 5. Statistical methods

[0192] Same as Example 8.

[0193] 6. Treatment Results

[0194] 6.1 Symptom Improvement: Clinical observation showed that after taking the traditional Chinese medicine (TCM) medication, the significant efficacy, effective rate, and total effective rate for angina pectoris were 17.6%, 58.8%, and 76.4%, respectively. In the Western medicine group, the significant efficacy, effective rate, and total effective rate were 23.5%, 41.2%, and 64.7%, respectively. Statistical analysis showed that the TCM group had a better therapeutic effect than the Western medicine group (P<0.05).

[0195] 6.2 Efficacy of Traditional Chinese Medicine (TCM) Syndrome Differentiation: Clinical observation showed that after taking the TCM, the significant efficacy, effective rate, and total effective rate for angina pectoris were 35.3%, 41.2%, and 76.5%, respectively. In the Western medicine group, the significant efficacy, effective rate, and total effective rate were 20.6%, 50%, and 70.6%, respectively. Statistical analysis showed that the TCM group had a significantly better effect on improving TCM syndrome differentiation compared to the Western medicine group (P<0.05).

[0196] Example 11

[0197] Example 2: Clinical study on the treatment of chronic stable exertional angina.

[0198] 1. Selected Cases

[0199] The diagnostic criteria were the same as in Example 8. 120 patients diagnosed with coronary heart disease, angina pectoris, and qi and yin deficiency with blood stasis were selected. These 120 patients were randomly divided into a traditional Chinese medicine group and a Western medicine group, with 60 patients in each group. There were no significant differences between the two groups in terms of age, disease duration, etc. (P>0.05), making them comparable.

[0200] 2. Treatment methods

[0201] Traditional Chinese medicine group: The traditional Chinese medicine composition prepared in Example 2 of the present invention was administered, and the decoctions from the two decoctions were combined and concentrated to 200 mL. One dose was administered daily, divided into two administrations in the morning and evening.

[0202] Control group: Conventional Western medicine treatment: commonly used nitroglycerin, 10mg each time, three times a day.

[0203] Other requirements and standards are the same as in Example 8.

[0204] 3. Observation indicators

[0205] Same as Example 8.

[0206] 4. Efficacy evaluation criteria

[0207] Same as Example 8.

[0208] 5. Statistical methods

[0209] Same as Example 8.

[0210] 6. Treatment Results

[0211] 6.1 Symptom Improvement: Clinical observation showed that after taking the traditional Chinese medicine (TCM) medication, the significant efficacy, effective rate, and total effective rate for angina pectoris were 33.3%, 53.3%, and 86.6%, respectively. In the Western medicine group, the significant efficacy, effective rate, and total effective rate were 16.7%, 45%, and 61.7%, respectively. Statistical analysis showed that the TCM group had a better therapeutic effect than the Western medicine group (P<0.05).

[0212] 6.2 Efficacy of Traditional Chinese Medicine (TCM) Syndrome Differentiation: Clinical observation showed that after taking the TCM, the significant efficacy, effective rate, and total effective rate for angina pectoris were 30%, 58.3%, and 88.3%, respectively. In the Western medicine group, the significant efficacy, effective rate, and total effective rate were 23.3%, 46.7%, and 70%, respectively. Statistical analysis showed that the TCM group had a significantly better effect on improving TCM syndrome differentiation compared to the Western medicine group (P<0.05).

[0213] In summary, the traditional Chinese medicine composition provided by this invention has significant clinical efficacy for chronic stable exertional angina pectoris with qi and yin deficiency and blood stasis in the heart vessels.

[0214] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating chronic stable exertional angina pectoris due to deficiency of both Qi and Yin and blood stasis in the heart vessels, characterized in that, It is made from the following raw materials in parts by weight: Astragalus membranaceus 15-30 parts, Ophiopogon japonicus 15-30 parts, Schisandra chinensis 6-9 parts, Dalbergia odorifera 9-12 parts, Artemisia capillaris 12-15 parts; The preparation method of the traditional Chinese medicine composition includes the following steps: weighing Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera and Artemisia capillaris according to the proportion, mixing the traditional Chinese medicine raw materials, soaking them in water, and then decocting them twice; collecting the two decoctions and concentrating them under reduced pressure to form an ointment, wherein the reduced pressure concentration temperature is 60-70℃ and the pressure is -0.06 to -0.08 MPa.

2. The traditional Chinese medicine composition according to claim 1 for treating chronic stable exertional angina pectoris due to deficiency of both qi and yin and blood stasis in the heart vessels, characterized in that, It is made from the following ingredients in parts by weight: Astragalus membranaceus 18-26 parts, Ophiopogon japonicus 18-26 parts, Schisandra chinensis 7-8 parts, Dalbergia odorifera 10-11 parts, and Artemisia capillaris 13-14 parts.

3. The method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The process includes the following steps: Weigh out Astragalus membranaceus, Ophiopogon japonicus, Schisandra chinensis, Dalbergia odorifera and Artemisia capillaris according to the proportions, mix the Chinese medicinal materials, soak them in water, and then decoct them twice.

4. The preparation method according to claim 3, characterized in that, The weight of the added water is 8-12 times that of the raw Chinese medicine.

5. The preparation method according to claim 3, characterized in that, The soaking time is 30 to 60 minutes.

6. The preparation method according to claim 3, characterized in that, The simmering time is 20 to 60 minutes.

7. The preparation method according to claim 3, characterized in that, The decoction liquid from the two decoctions was collected and concentrated under reduced pressure to form an ointment. The concentration temperature was 60-70℃ and the pressure was -0.06 to -0.08 MPa.

8. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared by adding pharmaceutically acceptable excipients to obtain powders, decoctions, pills, capsules, tablets, granules and oral liquids.

Images