A Chinese medicine combination preparation for treating angina pectoris caused by coronary heart disease and its preparation method

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations for treating coronary heart disease, and discloses a traditional Chinese medicine combination preparation for treating angina pectoris of coronary heart disease and a preparation method thereof. The traditional Chinese medicine combination preparation comprises the following raw materials in parts by weight: 5-15 parts of amber, 5-20 parts of red ginseng, 10-30 parts of honeysuckle, 30-120 parts of astragalus, 15-50 parts of figwort, 10-30 parts of ophiopogon, 5-15 parts of schisandra, 15-50 parts of salvia miltiorrhiza, 15-50 parts of kudzu root, 15-60 parts of angelica, 10-20 parts of ginkgo leaves, 5-15 parts of saffron, 5-20 parts of dragon's blood, 5-20 parts of antler slices, 5-10 parts of sophora flavescens, 10-20 parts of iris grandis, 5-20 parts of placenta and 10-50 parts of roasted liquorice. The Chinese medicinal components in this solution coordinate with each other and complement each other, and have the effects of promoting qi and blood circulation, resolving phlegm and detoxifying, invigorating qi and nourishing yin, etc., and are effective in treating coronary heart disease of qi stagnation and blood stasis, yin deficiency and toxic accumulation, and combined with qi and blood deficiency. The inventors found through long-term clinical studies that after taking the Chinese medicinal combination preparation of this solution for 4 consecutive weeks, the total effective rate of angina pectoris in patients is as high as 93.02%.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine preparations for treating coronary heart disease, and in particular to a traditional Chinese medicine combination preparation for treating angina pectoris caused by coronary heart disease and a preparation method thereof. Background Art

[0002] Coronary atherosclerotic heart disease, referred to as coronary heart disease (CHD), is a global disease that endangers human health and is one of the leading causes of death worldwide. It is mainly characterized by the formation of arterial plaques. Arterial plaques narrow the coronary artery lumen, leading to paroxysmal or persistent angina pectoris, so it is often called coronary heart disease angina pectoris. Plaque rupture leads to thrombosis, reduced blood flow, and myocardial infarction and death. The direct cause of angina pectoris is the absolute or relative insufficiency of myocardial blood supply. The main inducements are often due to physical labor, emotional excitement, full meals, fright and cold. Typical angina pectoris often occurs under similar working conditions. In severe cases, it can also occur during meals, dressing, defecation or rest. The pain occurs at the time of labor or excitement, not after a day or a period of fatigue. It is often manifested as dull pain, squeezing pain or tightness behind the sternum and throat. Some patients only have chest tightness. It can be divided into typical angina pectoris and atypical angina pectoris. Typical symptoms of angina pectoris are sudden onset of squeezing, stuffy or suffocating pain behind the upper or middle part of the sternum; atypical symptoms of angina pectoris may be located in the lower part of the sternum, the left precordial area or the upper abdomen, radiating to the neck, mandible, left scapula or right chest, etc.

[0003] At present, the treatment method of western medicine is: the treatment during the attack is mainly to rest immediately during the attack, and the patient's symptoms can be relieved after stopping the activity. At the same time, with drug treatment, sublingual nitroglycerin tablets are taken in an emergency, and they start to work in 1 to 2 minutes. The treatment of the remission period (1-6 months after discharge) is mainly nitrate preparations such as isosorbide nitrate. However, the remission period of western medicine is long, and the side effects of the drugs commonly used to treat this disease are large. Patients are afraid and often do not follow the doctor's advice. The medication is not standardized, resulting in poor long-term efficacy.

[0004] The current TCM treatment is to take Yufeng Ningxin Tablets, Ginkgo Leaf Oral Liquid, Guanxinning Injection and other drugs. However, although these drugs can relieve angina pectoris caused by coronary heart disease due to blood stasis to a certain extent, their cure rate and efficacy need to be improved.

[0005] In summary, developing a combination of Chinese medicines for treating angina pectoris caused by coronary heart disease with high cure rate, good efficacy and few side effects, and making it into a mixture (oral liquid) through a certain drug manufacturing process, which is easy to carry and simple to take, not only effectively makes up for the deficiencies of the existing technology, but also has important significance for effectively improving the cure rate of angina pectoris caused by coronary heart disease. Summary of the invention

[0006] The present invention aims to provide a Chinese medicine combination preparation for treating angina pectoris caused by coronary heart disease and a preparation method thereof, so as to solve the technical problem that the long-term therapeutic effects of existing western medicine preparations and Chinese medicine preparations on angina pectoris caused by coronary heart disease are both poor.

[0007] To achieve the above-mentioned purpose, the present invention adopts the following technical scheme: a Chinese medicine combination preparation for treating angina pectoris of coronary heart disease, comprising the following raw materials in parts by weight: 5-15 parts of amber, 5-20 parts of red ginseng, 10-30 parts of honeysuckle, 30-120 parts of astragalus, 15-50 parts of Scrophularia, 10-30 parts of Radix Ophiopogonis, 5-15 parts of Schisandrae Chinensis, 15-50 parts of Salvia miltiorrhiza, 15-50 parts of Pueraria lobata, 15-60 parts of Angelica sinensis, 10-20 parts of Ginkgo biloba leaves, 5-15 parts of saffron, 5-20 parts of Sanguisorba officinalis, 5-20 parts of antler slices, 5-10 parts of Sophora flavescens, 10-20 parts of Pleurotus eryngii, 5-20 parts of Placenta, and 10-50 parts of Radix Glycyrrhizae.

[0008] The principles and advantages of this solution are:

[0009] Compared with the poor long-term treatment effects of existing Western medicine preparations and Chinese medicine preparations, the Chinese medicine components in this scheme coordinate with each other and complement each other, and have the effects of promoting qi and blood circulation, resolving phlegm and detoxifying, invigorating qi and nourishing yin, etc., and effectively treat qi stagnation and blood stasis, yin deficiency and toxicity, and coronary heart disease with qi and blood deficiency. In the Chinese medicine combination preparation, the monarch medicine is amber, red ginseng and honeysuckle, among which amber promotes qi and blood circulation and relieves pain, red ginseng invigorates qi and restores yang, and honeysuckle detoxifies. Astragalus invigorates qi, Scrophularia, Ophiopogon japonicus, and Schisandra chinensis nourish yin, and Salvia miltiorrhiza, Pueraria root, Angelica sinensis, Ginkgo biloba, Sanguisorba officinalis, and Saffron invigorate blood circulation, which are all ministerial medicines. Deer antler slices warm yang and help qi and blood circulation, Sophora flavescens clears heat and detoxifies, White lily nourishes yin and clears heat, and placenta nourishes blood and benefits essence, which are all adjuvants. Roasted licorice harmonizes the various medicines as a messenger.

[0010] The Chinese medicine combination preparation of this scheme treats the causes of angina pectoris of coronary heart disease (eating and overwork, internal injuries caused by seven emotions, cold stagnation and heat depression, old age and physical weakness, etc., which lead to imbalance of qi and blood yin and yang in the heart blood vessels and stagnation of heart vessels), so that the symptoms of angina pectoris can be effectively relieved after taking the medicine for 1 month. The inventor found through long-term clinical research that after 4 weeks of continuous treatment with the Chinese medicine combination preparation of this scheme, the total effective rate of angina pectoris in patients is as high as 93.02%, which is significantly improved compared with the cure rate of only 76% when taking only the Western medicine isosorbide mononitrate sustained-release tablets.

[0011] Preferably, the raw materials are included in the following parts by mass: 10 parts of amber, 10 parts of red ginseng, 15 parts of honeysuckle, 30 parts of astragalus, 30 parts of Scrophularia, 15 parts of Ophiopogon japonicus, 10 parts of Schisandra chinensis, 30 parts of Salvia miltiorrhiza, 30 parts of Pueraria lobata, 30 parts of Angelica sinensis, 15 parts of Ginkgo biloba, 10 parts of Saffron, 10 parts of Sanguisorba officinalis, 10 parts of Deer Horn Slices, 10 parts of Sophora flavescens, 15 parts of Pleurotus eryngii, 10 parts of Placenta, and 30 parts of Radix Glycyrrhizae.

[0012] Preferably, the raw materials are included in the following parts by mass: 5 parts of amber, 5 parts of red ginseng, 10 parts of honeysuckle, 30 parts of astragalus, 15 parts of Scrophularia, 10 parts of Ophiopogon japonicus, 5 parts of Schisandra chinensis, 15 parts of Salvia miltiorrhiza, 15 parts of Pueraria lobata, 15 parts of Angelica sinensis, 10 parts of Ginkgo biloba leaves, 5 parts of saffron, 5 parts of Sanguisorba officinalis, 5 parts of antler slices, 5 parts of Sophora flavescens, 10 parts of Pleurotus eryngii, 5 parts of Placenta, and 10 parts of Radix Glycyrrhizae.

[0013] Preferably, the raw materials are included in the following parts by weight: 15 parts of amber, 20 parts of red ginseng, 30 parts of honeysuckle, 80 parts of astragalus, 50 parts of Scrophularia, 30 parts of Ophiopogon japonicus, 15 parts of Schisandra chinensis, 50 parts of Salvia miltiorrhiza, 50 parts of Pueraria lobata, 60 parts of Angelica sinensis, 20 parts of Ginkgo biloba leaves, 15 parts of saffron, 20 parts of Sanguisorba officinalis, 20 parts of antler slices, 10 parts of Sophora flavescens, 20 parts of Pleurotus eryngii, 20 parts of Placenta, and 50 parts of roasted Licorice.

[0014] This solution also provides a method for preparing a Chinese medicine combination preparation for treating angina pectoris caused by coronary heart disease, comprising the following steps:

[0015] S1: weigh the raw materials;

[0016] S2: The method for extracting the active ingredient is as follows:

[0017] Step (1): distilling angelica and radix dahuricae, respectively, and collecting the distillate, the aqueous solution after distillation and the medicinal residue;

[0018] Step (2): Take amber, dragon's blood and placenta, dry and grind them into fine powder, sieve and sterilize them for later use;

[0019] Step (3): mixing the residue obtained in step (1) with the remaining drugs, boiling with water, and filtering the decoction for later use;

[0020] S3: concentrating the medicinal liquid, mixing the distilled water solution obtained in step (1), the fine powder obtained in step (2) and the decoction obtained in step (3) evenly, and heating and concentrating them into a thick paste;

[0021] S4: preparing an oral liquid, adding sucrose, sorbic acid and the distillate obtained in step (1) to the thick paste, stirring and mixing, adding water to make up the volume, stirring, filtering and filling to obtain an oral liquid of a Chinese medicine combination preparation for treating angina pectoris of coronary heart disease.

[0022] Beneficial effects: This scheme can effectively improve the extraction effect of medicinal ingredients in various medicinal materials through item-by-item extraction, thereby increasing the content of medicinal ingredients in oral liquid.

[0023] Preferably, in step (1), the distillation comprises the following steps: extracting angelica and Pleurotus eryngii by steam distillation, crushing angelica and Pleurotus eryngii and mixing them evenly, adding them to a round-bottom flask, adding distilled water, and extracting at 80-100° C. for 8-10 hours.

[0024] Beneficial effects: The medicinal components of Angelica and Pleurotus eryngii are diverse. This scheme facilitates the full extraction of various medicinal components in Angelica and Pleurotus eryngii without destroying their components by distilling under the above conditions. The volatile oil determination method B of Part IV of the 2020 edition of the Chinese Pharmacopoeia is used here to extract volatile oil. The yield of Angelica volatile oil is ≥0.4%, and the yield of Pleurotus eryngii volatile oil is about 0.05%, which can ensure the quality control of the volatile components of Angelica and Pleurotus eryngii and the effective utilization of medicinal resources.

[0025] Preferably, in step (2), the sieving is through an 80-mesh sieve, and the sterilization is sterilization of the fine powder by 60Co-γ ray irradiation.

[0026] Beneficial effects: This scheme adopts 60Co-γ ray irradiation sterilization, which can effectively kill bacteria, viruses, fungi and other microorganisms in medicinal materials, and has a good sterilization effect; in addition, compared with the existing technology using steam sterilization and moist heat sterilization, which are easy to cause the loss of effective ingredients, the 60Co-γ ray irradiation sterilization of this scheme mainly uses cobalt ion beams with isotope 60, which will not cause any toxicity to medicinal materials, and will not produce harmful substances. It is harmless to the human body and effectively ensures the safety of medicinal materials.

[0027] Preferably, in step (3), water is added during the decoction to cover the medicinal materials, and after soaking, the water is heated to boiling and maintained at a slightly boiling state for 0.5-1h, filtered through a sieve or gauze, and the filtrate is preserved; the medicinal residue is decocted again according to the method for 1-2 times, and the decoctions from each time are combined for further preparation into the desired preparation.

[0028] Beneficial effects: This scheme boils the mixture of dregs of angelica sinensis and white mulberry and other medicinal materials for multiple times to fully extract the effective components of the medicinal materials.

[0029] Preferably, in S3, it further comprises adding 75% alcohol precipitation liquid to the thick paste, leaving it to stand in a cold storage at 0-10° C. for 24-48 hours, taking the supernatant, and concentrating it under reduced pressure to recover ethanol.

[0030] Beneficial effects: This scheme uses ethanol solution to dissolve the thick paste again, so that the active ingredients are soluble in ethanol and the impurities are insoluble in ethanol, thereby precipitating the impurities; the applicant has found through long-term research that if the thick paste is not redissolved with 75% alcohol precipitation solution, or if other concentrations of ethanol are used to redissolve the thick paste, the active ingredients cannot be completely dissolved or impurities such as starch, protein, and inorganic salts cannot be completely precipitated; if the standing temperature exceeds the range of 0 to 10°C, the precipitation and sedimentation rate of the precipitate will be slow, and the standing period will be extended; if the standing time of the re-dissolution is shorter than 24h, the precipitation will not be completely precipitated and the impurities will not be completely removed, and if the standing time is longer than 48h, the effective ingredients will be reduced due to the volatilization of ethanol, thereby affecting the effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The HPLC spectrum of puerarin in the oral solution obtained in Example 1 of the present invention (wherein a is the reference solution, b is all the oral solutions in Example 1, and c is the negative control solution). DETAILED DESCRIPTION

[0032] The present invention is further described in detail below in conjunction with examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following examples and comparative examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial sources.

[0033] A Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease and a preparation method thereof are presented with specific embodiments. Among them, embodiments 1 to 9 show the Chinese medicine combination preparations prepared when different raw material dosages and different parameter values ​​in the preparation method are used, and comparative examples 1 to 5 show the Chinese medicine combination preparations prepared when parameter values ​​outside the protection scope of the claims of this scheme are selected. The differences between the Chinese medicine combination preparations for treating angina pectoris due to coronary heart disease in embodiments 1 to 9 and comparative examples 1 to 5 are shown in Table 1. Taking embodiment 1 as an example, the Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease and a preparation method thereof in this scheme are described.

[0034] Example 1

[0035] This scheme provides a Chinese medicine combination preparation for treating angina pectoris of coronary heart disease, including the following raw materials by weight: 5-15 parts of amber, 5-20 parts of red ginseng, 10-30 parts of honeysuckle, 30-120 parts of astragalus, 15-50 parts of Scrophularia, 10-30 parts of Radix Ophiopogonis, 5-15 parts of Schisandrae Chinensis, 15-50 parts of Salviae Miltiorrhizae, 15-50 parts of Puerariae, 15-60 parts of Angelicae Sinensis, 10-20 parts of Ginkgo Biloba Leaves, 5-15 parts of Saffron, 5-20 parts of Dragon's Blood, 5-20 parts of Deer Horn Slices, 5-10 parts of Sophora Flavescentis, 10-20 parts of White Vine, 5-20 parts of Placenta, and 10-50 parts of Radix Glycyrrhizae. The raw material formula and implementation standards are detailed in Table 1.

[0036] This solution also provides a method for preparing a Chinese medicine combination preparation for treating angina pectoris caused by coronary heart disease, which specifically comprises the following steps:

[0037] S1: Weigh the raw materials. The specific amounts of raw materials used in this example are: 10g amber, 10g red ginseng, 15g honeysuckle, 30g astragalus, 30g Scrophularia, 15g Ophiopogon, 10g Schisandra, 30g Salvia, 30g Pueraria, 30g Angelica, 30g Ginkgo, 15g Saffron, 10g Sanguisorba, 10g antler slices, 10g Sophora flavescens, 15g Pleurotus eryngii, 10g Placenta, and 30g Radix Glycyrrhizae.

[0038] S2: Extraction of active ingredients, as follows:

[0039] Step (1): collecting the distillate, the aqueous solution after distillation (stored in a separate container) and the residue of Angelica sinensis and Pleurotus eryngii respectively;

[0040] Step (2): Take the prescribed amount of amber, dragon's blood and placenta, dry and grind them into fine powder, pass through an 80-mesh sieve and sterilize them by 60Co-γ ray irradiation (store in a separate container);

[0041] Step (3): add water (in a mass volume ratio of 8 to 10 (g / ml)) to the residue obtained in step (1) and the remaining drugs, and boil for 3 times, 2 hours for the first time, 1.5 hours for the second time, and 1 hour for the third time; filter the decoction for later use;

[0042] S3: concentrating the medicinal liquid, mixing and stirring the distilled water solution obtained in step (1), the fine powder obtained in step (2) and the decoction obtained in step (3) to uniformly concentrate to a thick paste with a relative density of 1.14 to 1.16 (60° C.);

[0043] Add ethanol to the thick paste to make the alcohol content reach 75%, let it stand in a cold storage at 0-10°C for 24-48 hours, take the supernatant, and recover the ethanol to a clear paste with a relative density of 1.05-1.08 (65°C);

[0044] S4: prepare an oral liquid. Add 150 g of sucrose, 1.5 g of sorbic acid and an appropriate amount of water to the clear paste obtained in S3, stir to dissolve the thick paste, add the distillate obtained in step (1), and then add water to make the volume 1000 ml. Stir well, filter, fill into 10 ml bottles, and sterilize to obtain a Chinese medicine combination oral liquid for treating angina pectoris of coronary heart disease (hereinafter referred to as oral liquid).

[0045] The differences between the Chinese medicine combination preparations for treating angina pectoris caused by coronary heart disease in Examples 1 to 9 and Comparative Examples 1 to 5 are shown in Table 1.

[0046]

[0047] Experimental Example 1: Oral liquid preparation results and quality inspection test

[0048] The specific testing standards are as follows (refer to the quality standards of 0181 mixture (oral solution) in the 2020 edition of the Chinese Pharmacopoeia):

[0049] [Properties] Take an appropriate amount of the oral liquid and observe it in a bright place. It is a brown clear liquid with a sweet and slightly bitter taste.

[0050] [Relative density] The relative density should not be less than 1.08 (General Rule 0601).

[0051] [pH value] The pH value should be 5.0-7.0 (General Rule 0631).

[0052] [Content determination] Determine according to high performance liquid chromatography (General Rule 0512).

[0053] 1. Chromatographic conditions and system suitability test: Octadecylsilane bonded silica gel was used as filler; methanol-water (21:79) was used as mobile phase; the detection wavelength was 250nm. The theoretical plate number calculated based on the puerarin peak should be no less than 3000.

[0054] 2. Preparation of reference solution: Take about 11 mg of puerarin reference substance, weigh it accurately, put it in a 10 ml volumetric flask, add methanol to dissolve and dilute to the scale, shake well, accurately measure 1 ml, put it in a 25 ml volumetric flask, add 30% methanol to dilute to the scale, shake well, and the solution is obtained (each 1 ml contains 44 μg of puerarin).

[0055] 3. Preparation of test solution: Accurately measure 5 ml of the product, place it in a 50 ml volumetric flask, add acetone to dilute to the scale, shake well, centrifuge, accurately aspirate 5 ml of the supernatant, place it in a 50 ml volumetric flask, add 30% methanol to dilute to the scale, shake well, and obtain.

[0056] 4. Determination method: Accurately pipette 10 μl of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0057] 5. Each 1ml of this product contains puerarin (C 21 H 20 O 9 ) shall not be less than 2.20 mg.

[0058] The oral liquids obtained in the examples and comparative examples were tested for performance. The test results are shown in Table 2. The HPLC spectrum of puerarin in the oral liquid prepared in Example 1 is shown in Figure 1 .

[0059] [Recovery Experiment] Measure the oral liquid with known content (specifically, measure the oral liquid prepared in Example 1, containing 2.7 mg / ml of puerarin, diluted to 1.35 mg / mL), accurately add a certain amount of puerarin reference substance, operate according to the above [Content Determination], operate 6 times in parallel, and calculate the recovery rate according to the following formula:

[0060] Recovery rate = (measured amount - content in sample) / added amount * 100%

[0061] The results are shown in Table 3.

[0062] Table 2 Performance test results of the oral liquids prepared in Examples 1 to 9 and Comparative Examples 1 to 5

[0063]

[0064]

[0065] The experimental data show that the puerarin content and relative density of the oral liquid prepared by the applicant within the parameter range in the claims of this scheme meet the relevant requirements of the oral liquid. Specifically, the oral liquids prepared in Examples 1-9 of this scheme are all brown clear liquids, the relative density of the oral liquids is ≥1.08, and the puerarin content in the oral liquids is higher than 2.2 mg. In Comparative Examples 1-5, due to the too low distillation temperature in S1 (such as Comparative Example 2) and the too short distillation time (such as Comparative Example 5), the extraction transfer rate of the effective ingredients in the medicinal materials will be reduced, thereby reducing the relative density and puerarin content of the oral liquid; and in S3, no alcohol solution is added to redissolve the thick paste (such as Comparative Example 3), resulting in the inability to completely dissolve the effective ingredients or impurities such as starch, protein, and inorganic salts cannot be completely precipitated, which is manifested as a relatively turbid oral liquid, and the relative density and puerarin content are both low; and the too high standing temperature in S3 (such as Comparative Example 1) slows down the precipitation and sedimentation of the precipitate, prolongs the standing period, and causes more impurities in the oral liquid, which is manifested as a relatively turbid oral liquid. In addition, too short a standing time in S3 (such as comparative example 4) will lead to incomplete precipitation of the precipitate and incomplete removal of impurities, which will lead to a decrease in the content of the medicinal ingredients in the obtained thick paste (such as puerarin, etc.) in the oral liquid and a high level of impurities, which is specifically manifested as a turbid solution of the oral liquid, and its relative density and puerarin content are both low.

[0066] In addition, the sample recovery rate of puerarin in the oral liquid prepared by this scheme is relatively high, indicating that the detection method adopted by this scheme has a high accuracy. As shown in Table 3, taking Example 1 as an example, the sample recovery rate of the oral liquid sample sampled 6 times was tested, and the obtained recovery rate was between 99.11% and 103.79% (the average recovery rate was 101.89%, and the RSD was 1.8%), which fully illustrates that the detection method adopted by this scheme has a high accuracy, and the puerarin content measured by it is accurate and reliable.

[0067] Table 3 Recovery test of puerarin

[0068]

[0069] Experimental Example 2: Oral Solution Efficacy Testing

[0070] [Patient conditions and groups] All 86 patients with angina pectoris due to coronary heart disease were randomly divided into two groups of 43 cases in each group.

[0071] Treatment group: 22 males and 21 females; age (56.6±9.4) years; disease course (6.1±3.9) years.

[0072] Control group: 23 males and 20 females; age (58.6±7.2) years; disease course (7.3±4.6) years.

[0073] Routine examinations included electrocardiogram, blood sugar, blood lipids, liver and kidney function, and coagulation indexes. There was no statistically significant difference in gender, age, body mass index, blood lipids, course of disease, classification, and angina pectoris grade between the two groups (P>0.05), indicating that the two groups were comparable.

[0074] [Diagnostic Indicators] The diagnosis of angina pectoris due to coronary heart disease refers to the diagnostic and treatment guidelines for coronary heart disease formulated by the Chinese Medical Association's Cardiovascular Disease Branch and the Editorial Committee of the Chinese Journal of Cardiovascular Diseases.

[0075] Inclusion criteria: Patients who meet the diagnostic criteria of traditional Chinese and Western medicine and the criteria of traditional Chinese medicine syndrome differentiation (35 years ≤ patient age < 70 years). Exclusion criteria: ① Those who do not meet the above criteria and the diagnostic criteria of traditional Chinese medicine syndrome; ② Those with severe hypertension; ③ Those with severe arrhythmias (persistent rapid atrial fibrillation, frequent premature ventricular heart beats, atrial flutter, ventricular tachycardia); ④ Acute myocardial infarction; ⑤ Acute heart failure; ⑥ Those with diabetic ketoacidosis; ⑦ Those with severe primary diseases such as liver, kidney, and hematopoietic system; ⑧ Pregnant or lactating women or those with allergic constitution; ⑨ Mental retardation, mental and consciousness disorders; ⑩ Those who cannot answer the questionnaire correctly and those who are considered by the researchers to have other factors that are not suitable for participating in the trial.

[0076] [Medication Method] Both groups were treated with isosorbide mononitrate sustained-release tablets (40 mg, once a day, one tablet at a time). The treatment group was given the oral solution obtained in Example 1, 10 mL each time, 3 times a day. Patients are advised to take it 30 minutes after meals. During the treatment trial, Chinese and Western medicines for lipid regulation and blood circulation and stasis removal were discontinued. All combined medications required detailed records of clinical observation for 4 weeks (two courses of treatment).

[0077]

result

[0078] 1. Analysis of the efficacy of TCM syndromes, observation indicators: The main symptoms of TCM syndromes in the two groups included angina pectoris, chest tightness and shortness of breath, palpitations, dark red lips and gums, numbness of limbs, dark circles around the eyes, purple tongue, and intermittent or deep, stringy or astringent pulse; secondary symptoms included subcutaneous ecchymosis, rough skin with thin collaterals, mental abnormalities, and emotional (stress) abnormalities. The results of the comparison of the efficacy of TCM syndromes were expressed by combining the integral method and the nimodipine method, as shown in Table 4.

[0079] Points scoring method: 0 points for absence of main symptoms, 2 points for mild symptoms, 4 points for moderate symptoms, and 6 points for severe symptoms; 0 points for absence of secondary symptoms, 1 point for mild symptoms, 2 points for moderate symptoms, and 3 points for severe symptoms.

[0080] The criterion for judging the efficacy of TCM syndromes was based on the nimodipine method (score before treatment - score after treatment) / score before treatment

[0081] ×100%. Markedly effective: all symptoms disappear, the score is 0 or the difference between the score before and after treatment is greater than or equal to 70%; effective: the difference between the score before and after treatment is greater than or equal to 30% and less than 70%; ineffective: the difference between the score before and after treatment is less than 30%; aggravated: the score after treatment exceeds that before treatment.

[0082] 2. Criteria for judging the efficacy of angina pectoris: expressed by combining the integral method and the nimodipine method. The criterion for judging the efficacy of angina pectoris is the nimodipine method (angina pectoris score before treatment - angina pectoris score after treatment) / angina pectoris score before treatment × 100%. Significant effect: angina pectoris disappears, the score is 0 or the difference between the angina pectoris score before and after treatment is greater than or equal to 70%; effective: the difference between the angina pectoris score before and after treatment is greater than or equal to 30% and less than 70%; ineffective: the difference between the angina pectoris score before and after treatment is less than 30%; aggravated: the angina pectoris score after treatment exceeds that before treatment. The results are shown in Table 5.

[0083] 3. After 4 weeks of treatment, electrocardiogram, endothelin (ET), interleukin-6 (IL-6), etc. were rechecked. Safety tests included routine blood and urine tests, heart, liver and kidney function tests, and adverse reaction tests. The above test items were tested once before and after the test and the data were recorded. Statistical methods were used to process the data: all data were expressed as mean ± standard deviation. The comparison of measurement data was performed by corresponding analysis of variance and t-test. The comparison of count data was performed by χ2 test. The rank sum test was used for rank data. P < 0.05 was considered statistically significant. The experimental data were statistically analyzed using SPSS 22.0 statistical software. The results are shown in Table 6.

[0084] Table 4 Comparison of TCM syndrome efficacy between the treatment group and the control group

[0085] Group N / sample size <![CDATA[Significant effect a > efficient invalid Aggravation <![CDATA[Total effective rate (%) b > Treatment Group 43 14 25 3 1 <![CDATA[90.70 * ]]> Control group 43 11 16 12 4 62.79

[0086] Note: * Compared with the control group, P < 0.01; a The criterion for judging the efficacy of TCM syndromes was the nimodipine method [(score before treatment - score after treatment) / score before treatment × 100%]; markedly effective: all symptoms disappeared, the score was 0 or the difference between the symptom scores before and after treatment was greater than or equal to 70%; effective: the difference between the symptom scores before and after treatment was greater than or equal to 30% and less than 70%; ineffective: the difference between the symptom scores before and after treatment was less than 30%; aggravated: the symptom scores after treatment exceeded those before treatment; b Total effective rate = (markedly effective + effective) / sample size*100%

[0087] Experimental data showed that the total effective rates of TCM symptoms in the treatment group and the control group were 90.70% and 62.79% respectively. The efficacy of TCM symptoms in the treatment group, which added the oral liquid in this regimen, was significantly better than that in the control group (P < 0.01).

[0088] Table 5 Comparison of efficacy of angina pectoris between the treatment group and the control group

[0089] Group N / sample size <![CDATA[Marked effect a > efficient invalid Aggravation <![CDATA[Total effective rate (%) b > Treatment Group 43 16 24 2 1 <![CDATA[93.02 * ]]> Control group 43 14 19 6 4 76.74

[0090] Note: * Comparison of effective rates between the two groups, P<0.05; a The angina pectoris efficacy was determined by the nimodipine method [(angina pectoris score before treatment - angina pectoris score after treatment) / angina pectoris score before treatment × 100%]: markedly effective: angina pectoris disappears, the score is 0 or the difference between the angina pectoris scores before and after treatment is greater than or equal to 70%; effective: the difference between the angina pectoris scores before and after treatment is greater than or equal to 30% and less than 70%; ineffective: the difference between the angina pectoris scores before and after treatment is less than 30%; aggravated: the angina pectoris score after treatment exceeds that before treatment; b Total effective rate = (markedly effective + effective) / sample size*100%

[0091] Experimental data show that the total effective rate of the treatment group in the angina pectoris efficacy of this regimen is as high as 93.02%, which is significantly higher than the total effective rate of the control group of 76.74% (P < 0.05).

[0092] Table 6 Results of ET and IL-6 in the treatment group and the control group

[0093]

[0094] Note: a means P<0.05 compared with the same group before treatment; b means P<0.05 compared with the control group.

[0095] Experimental data show that the Chinese medicine combination preparation obtained in this scheme has the effect of improving the patient's blood rheology and vascular endothelial function, increasing the deformability of red blood cells, reducing the inflammatory components in the patient's serum, playing an anti-inflammatory role, and improving the clinical efficacy. Specifically, compared with before treatment, ET in both the treatment group and the control group was significantly reduced (P < 0.05); while IL-6 in the treatment group was significantly reduced, while IL-6 in the control group was not significantly reduced.

[0096] Clinical trials have shown that the various medicinal ingredients in the Chinese medicine combination preparation obtained in this scheme have the characteristics of clear compatibility and synergistic effects, can significantly improve the patient's clinical symptoms, and is one of the ideal drugs for treating patients with angina pectoris due to coronary heart disease.

[0097] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A Chinese medicine combination preparation for treating angina pectoris caused by coronary heart disease, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5-15 parts of amber, 5-20 parts of red ginseng, 10-30 parts of honeysuckle, 30-120 parts of astragalus, 15-50 parts of scrophularia, 10-30 parts of ophiopogon, 5-15 parts of schisandra, 15-50 parts of salvia, 15-50 parts of kudzu root, 15-60 parts of angelica, 10-20 parts of ginkgo leaves, 5-15 parts of saffron, 5-20 parts of blood clotting, 5-20 parts of antler slices, 5-10 parts of sophora flavescens, 10-20 parts of iris grandis, 5-20 parts of placenta and 10-50 parts of roasted liquorice.

2. A Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 10 parts of amber, 10 parts of red ginseng, 15 parts of honeysuckle, 30 parts of astragalus, 30 parts of Scrophularia, 15 parts of Radix Ophiopogonis, 10 parts of Schisandrae Chinensis, 30 parts of Salviae Miltiorrhizae, 30 parts of Puerariae, 30 parts of Angelicae Sinensis, 15 parts of Ginkgo Biloba Leaves, 10 parts of Saffron, 10 parts of Sanguisorba Officinalis, 10 parts of Deer Horn Slices, 10 parts of Sophora Flavescens, 15 parts of Polygonum Multiflorum, 10 parts of Placenta, and 30 parts of Radix Glycyrrhizae Radix.

3. A Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5 parts of amber, 5 parts of red ginseng, 10 parts of honeysuckle, 30 parts of astragalus, 15 parts of Scrophularia, 10 parts of Radix Ophiopogonis, 5 parts of Schisandrae Chinensis, 15 parts of Salviae Miltiorrhizae, 15 parts of Puerariae, 15 parts of Angelicae Sinensis, 10 parts of Ginkgo Biloba Leaves, 5 parts of Saffron, 5 parts of Sanguisorba Officinalis, 5 parts of Deer Horn Slices, 5 parts of Sophora Flavescens, 10 parts of Polygonum Multiflorum, 5 parts of Placenta, and 10 parts of Radix Glycyrrhizae Radix.

4. A Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15 parts of amber, 20 parts of red ginseng, 30 parts of honeysuckle, 80 parts of astragalus, 50 parts of Scrophularia, 30 parts of Radix Ophiopogonis, 15 parts of Schisandrae Chinensis, 50 parts of Salviae Miltiorrhiza, 50 parts of Puerariae, 60 parts of Angelicae Sinensis, 20 parts of Ginkgo Biloba Leaves, 15 parts of Saffron, 20 parts of Sanguisorba Officinalis, 20 parts of Deer Horn Slices, 10 parts of Sophora Flavescens, 20 parts of Pleurotus eryngii, 20 parts of Placenta, and 50 parts of Radix Glycyrrhizae Radix.

5. A method for preparing a Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to any one of claims 1 to 4, characterized in that: The steps include: S1: Weigh the raw materials according to the above mass fractions; S2: The method for extracting the active ingredient is as follows: Step (1): Distilling angelica and radix scutellariae separately, and collecting the distillate, the aqueous solution after distillation and the medicinal residue; Step (2): Take amber, dragon's blood and placenta, dry and grind them into fine powder, sieve and sterilize them for later use; Step (3): Mix the residue obtained in step (1) with the remaining drugs, add water and boil, and filter the decoction for later use; S3: concentrating the medicinal liquid, mixing the distilled water solution obtained in step (1), the fine powder obtained in step (2) and the decoction obtained in step (3) uniformly, and concentrating them into a thick paste; adding 75% alcohol precipitation liquid to the thick paste, leaving it to stand at 0-10°C for 24-48 hours, taking the supernatant, and concentrating it under reduced pressure to recover ethanol; S4: preparing an oral liquid, adding sucrose, sorbic acid, and the distillate obtained in step (1) to the thick paste, stirring and mixing, adding water to make up the volume, stirring, filtering, and filling to obtain a Chinese medicine combination oral liquid for treating angina pectoris of coronary heart disease.

6. The method for preparing a Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to claim 5, characterized in that: In step (1), the distillation comprises the following steps: extracting angelica and Pleurotus eryngii by steam distillation, grinding angelica and Pleurotus eryngii by dry method and mixing them evenly, adding them into a round bottom flask, adding distilled water, and extracting at 80-100°C for 8-10h.

7. The method for preparing a Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to claim 6, characterized in that: In step (2), the sieving is through an 80-mesh sieve, and the sterilization is sterilization of the fine powder by 60Co-γ ray irradiation.

8. The method for preparing a Chinese medicine combination preparation for treating angina pectoris due to coronary heart disease according to claim 7, characterized in that: In step (3), water is added to cover the medicinal materials during the decoction, and after soaking, the water is heated to boiling and maintained at a slightly boiling state for 0.5-1h, filtered through a sieve or gauze, and the filtrate is preserved; the medicinal residue is decocted again according to the method for 1-2 times, and the decoctions from each time are combined for further preparation into the desired preparation.

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