A Chinese medicinal composition containing aconite root for treating unstable angina pectoris

Abstract

The invention discloses a Chinese medicine composition containing aconite for treating unstable angina pectoris, wherein the raw materials thereof are aconite, ginseng, American ginseng, pseudostellaria, yam, cassia twig, ophiopogon, schisandra, cornus officinalis, asparagus cochinchinensis, radix rehmanniae, spiny date seeds, keel, and oyster. The results of clinical efficacy observation tests confirm that the Chinese medicine composition of the invention can significantly improve the clinical symptoms of patients with unstable angina pectoris, significantly reduce the duration and frequency of their angina attacks, improve their cardiac function, resist myocardial oxidation, reduce stress response, antagonize ET‑1, and promote the recovery of vascular endothelial function.

Description

Technical Field

[0001] The invention belongs to the technical field of plant medicine application, and particularly relates to a traditional Chinese medicine composition for treating unstable angina pectoris. Background Art

[0002] Unstable angina pectoris (UAP) is a type of acute coronary syndrome, a clinical angina syndrome between stable angina pectoris and acute myocardial infarction. The disease has a high incidence and rapidly progresses. If it is not well controlled, it is very likely to progress to acute myocardial infarction or more serious cardiac events. At present, Western medicine has always been the main clinical treatment for UAP. Conventional Western medicine treatments include antiplatelet therapy, anti-myocardial ischemia therapy, anti-thrombotic therapy, and lipid-lowering therapy. However, on the one hand, its relief effect is relatively limited, and on the other hand, liver function damage and gastrointestinal reactions caused by long-term Western medicine treatment cannot be ignored.

[0003] Traditional medicine believes that UAP belongs to the category of "chest pain" and "heart pain". As early as the Han Dynasty, Zhang Zhongjing proposed the disease name of "chest pain and heart pain" and gave a detailed discussion on its etiology, pathogenesis, location, nature, symptoms and treatment.

[0004] Chinese patent CN1334121A discloses a Tongxinluo pharmaceutical composition and its application. The pharmaceutical composition of the patent includes three parts. The first part is one or more of ginseng, Radix Pseudostellariae, Rhizoma Dioscoreae, etc.; the second part is Radix Ophiopogonis, Semen Ziziphi Spinosae, Radix Aconiti Lateralis, Twig Cinnamomi, Fructus Schisandrae Chinensis; the third part is one or more of Scorpio, Periostracum Cicadae, Scolopendra. The composition can be used as an oral preparation for the clinical treatment of angina pectoris caused by coronary heart disease. Although the composition in the patent can be used to treat stable angina pectoris, it is not a drug specifically for unstable angina pectoris. Summary of the invention

[0005] The purpose of the present invention is to provide a Chinese medicine composition for treating unstable angina pectoris, which is used for improving the clinical symptoms of unstable angina pectoris.

[0006] In order to achieve the above objectives, the inventors provide the following technical solutions.

[0007] A Chinese medicinal composition containing aconite root for treating unstable angina pectoris, the raw materials of which are: aconite root, ginseng, American ginseng, pseudostellaria, yam, cassia twig, ophiopogon, schisandra chinensis, cornus officinalis, asparagus cochinchinensis, radix rehmanniae, spiny jujube seeds, dragon bones and oyster.

[0008] The above-mentioned Chinese medicine composition, measured in parts by weight, consists of the following raw materials: 0.1-2 parts of aconite, 0.1-2 parts of ginseng, 0.1-2 parts of American ginseng, 0.1-2 parts of Pseudostellariae Radix, 0.1-2 parts of yam, 0.1-2 parts of cinnamon twig, 0.1-2 parts of ophiopogon, 0.1-2 parts of schisandra, 0.1-2 parts of cornus, 0.1-2 parts of asparagus, 0.1-2 parts of rehmannia, 0.1-2 parts of spiny jujube seeds, 0.1-2 parts of dragon bones, and 0.1-2 parts of oyster.

[0009] The above-mentioned Chinese medicine composition, in terms of weight, preferably comprises the following raw materials: 0.5-1.8 parts of aconite, 0.5-1.8 parts of ginseng, 0.5-1.8 parts of American ginseng, 0.5-1.8 parts of Pseudostellariae Radix, 0.5-1.8 parts of yam, 0.5-1.8 parts of cinnamon twig, 0.5-1.8 parts of ophiopogon, 0.5-1.8 parts of schisandrae, 0.5-1.8 parts of cornus officinalis, 0.5-1.8 parts of asparagus, 0.5-1.8 parts of rehmannia, 0.5-1.8 parts of spiny jujube seeds, 0.5-1.8 parts of dragon bones, and 0.5-1.8 parts of oyster.

[0010] The above-mentioned Chinese medicine composition, in terms of weight, has a further preferred raw material composition: 0.8-1.5 parts of aconite, 0.8-1.5 parts of ginseng, 0.8-1.5 parts of American ginseng, 0.8-1.5 parts of Pseudostellariae Radix, 0.8-1.5 parts of yam, 0.8-1.5 parts of cinnamon twig, 0.8-1.5 parts of ophiopogon, 0.8-1.5 parts of schisandra, 0.8-1.5 parts of cornus, 0.8-1.5 parts of asparagus, 0.8-1.5 parts of rehmannia, 0.8-1.5 parts of spiny jujube seeds, 0.8-1.5 parts of dragon bones, and 0.8-1.5 parts of oyster.

[0011] The above-mentioned Chinese medicine composition, in terms of weight, has a further preferred raw material composition of: 1 part of aconite, 1 part of ginseng, 1 part of American ginseng, 1 part of pseudostellaria, 1 part of yam, 1 part of cinnamon twig, 1 part of ophiopogon, 1 part of schisandra, 1 part of cornus, 1 part of asparagus, 1 part of rehmannia, 1 part of spiny jujube seed, 1 part of dragon bone, and 1 part of oyster.

[0012] The Chinese medicine composition provided by the present invention can be directly taken after being boiled in water, or the decoction can be concentrated, and appropriate auxiliary materials can be added to prepare granules, capsules, tablets or oral liquids according to conventional methods.

[0013] At the same time, the present invention also provides the use of the above-mentioned Chinese medicine composition in preparing a medicine for treating unstable angina pectoris.

[0014] The Chinese medicine composition of the present invention comprises aconite and ginseng as the main drugs, which invigorate qi and warm yang; American ginseng, Pseudostellaria chinensis and Chinese yam assist ginseng in invigorating qi and consolidating defense; cinnamon twig assists aconite in invigorating defense and warming yang; ophiopogon, schisandra, cornus, asparagus, radix rehmanniae and spinosae seeds nourish yin and blood, and nourish the heart meridian; dragon bone and oyster restrain the floating and scattered weak yang. The prescription is suitable for UAP with deficiency of both yin and yang and weak meridians.

[0015] Clinical observations have shown that the Chinese medicine composition provided by the present invention can be used for UAP patients to reduce the duration and frequency of their angina attacks, improve their cardiac function, resist myocardial oxidation, reduce stress response, antagonize ET-1, and promote the recovery of vascular endothelial function. DETAILED DESCRIPTION

[0016] The present invention is further described in detail below with reference to specific embodiments.

[0017] Example 1 Preparation of decoction

[0018] Weigh 12g of aconite root, 12g of ginseng, 12g of American ginseng, 12g of pseudoginseng, 12g of yam, 12g of cinnamon twig, 12g of ophiopogon japonicus, 12g of schisandra chinensis, 12g of cornus officinalis, 12g of asparagus cochinchinensis, 12g of raw rehmannia, 12g of spiny jujube seed, 12g of dragon bone, and 12g of oyster.

[0019] Add 300 mL of water, boil for 0.5 h, filter, add 300 mL of water to the residue again, boil for 0.25 h, filter, combine the two filtrates, divide into two parts, and set aside.

[0020] This is the daily dosage for one person.

[0021] Example 2 Preparation of granules

[0022] Weigh 0.1kg of aconite root, 0.1kg of ginseng, 0.1kg of American ginseng, 0.1kg of Pseudostellariae Radix, 0.1kg of Chinese yam, 0.1kg of cinnamon twig, 0.1kg of Radix Ophiopogonis, 0.1kg of Schisandrae Chinensis, 0.1kg of Cornus officinalis, 0.1kg of Asparagus cochinchinensis, 0.1kg of Radix Rehmanniae, 0.1kg of Semen Ziziphi Spinosae, 0.1kg of Ossorum draco, and 0.1kg of Oyster. Add 3.5L of water, decoct for 0.5h, filter, add 3.5L of water to the residue again, decoct for 0.25h, filter, combine the two filtrates, and concentrate under reduced pressure to obtain an extract. Add dextrin, lactose, corn starch and other auxiliary materials to the extract to make a soft material, granulate, and dry to obtain granules.

[0023] Example 3 Preparation of capsules

[0024] Weigh 0.1kg of aconite root, 0.1kg of ginseng, 0.1kg of American ginseng, 0.1kg of Pseudostellaria heterophylla, 0.1kg of yam, 0.1kg of cinnamon twig, 0.1kg of Ophiopogon japonicus, 0.1kg of Schisandra chinensis, 0.1kg of Cornus officinalis, 0.1kg of Asparagus cochinchinensis, 0.1kg of Rehmannia glutinosa, 0.1kg of Ziziphus jujuba seed, 0.1kg of Dragon bone, and 0.1kg of oyster.

[0025] Add 3.5L of water, decoct for 0.5h, filter, add 3.5L of water to the residue again, decoct for 0.25h, filter, combine the two filtrates, and concentrate under reduced pressure to obtain an extract. Add mannitol, microcrystalline cellulose, lactose and other auxiliary materials to the extract to prepare capsules.

[0026] Example 4 Observation of therapeutic effect

[0027] In order to verify the actual efficacy of the Chinese medicine composition of the present invention in treating unstable angina, the inventors conducted efficacy observations, as follows:

[0028] 1. Data and methods

[0029] 1. Subjects

[0030] A total of 210 patients with UAP due to coronary heart disease who met the inclusion criteria and were admitted to Hebei Yiling Hospital from August 2019 to January 2020 were selected and randomly divided into a positive drug group, a control group, and an observation group according to their visit sequence, with 70 cases in each group.

[0031] There were 37 males and 33 females in the positive drug group, ranging in age from 46 to 73 years old, with an average age of (60.43±2.11) years old.

[0032] There were 35 males and 35 females in the control group, aged 46 to 74 years old, with an average age of (60.07±2.39) years old.

[0033] There were 36 males and 34 females in the observation group, ranging in age from 47 to 71 years old, with an average age of (60.17±2.13) years old.

[0034] There was no significant difference in age, gender and other general data among the three groups (P>0.05), so they were comparable.

[0035] 2. Diagnostic criteria

[0036] The Western medical diagnostic standards refer to the diagnostic standards of "Recommendations for the Diagnosis and Treatment of Unstable Angina" formulated by the Cardiovascular Disease Branch of the Chinese Medical Association and the Editorial Committee of the Chinese Cardiovascular Journal, that is, the patient has at least one angina attack within 48 hours, frequent angina attacks within 1 month, certain inducements, and prolonged pain. The electrocardiogram shows horizontal or downward depression of the ST segment ≥1mm or ST elevation (limb leads ≥1mm, chest leads ≥2mm).

[0037] The diagnostic criteria of Traditional Chinese Medicine are based on the "chest pain" criteria in the "Guidelines for Clinical Research of New Chinese Medicines", which refers to chest tightness and pain, or even chest pain that extends to the back. In mild cases, patients may feel chest tightness, shortness of breath, and difficulty breathing.

[0038] 3. Inclusion criteria

[0039] 1) Those who meet both Western medicine and traditional Chinese medicine diagnostic criteria;

[0040] 2) Angina pectoris > 2 times / week;

[0041] 3) The resting 12-lead electrocardiogram showed clear evidence of myocardial ischemia, with ST segment depression ≥ 0.05 mV in two limb leads or adjacent chest leads, or ST segment elevation or T wave inversion;

[0042] 4) The patient signs the informed consent form.

[0043] 4. Exclusion criteria

[0044] 1) Patients with stable angina pectoris or other heart diseases such as acute myocardial infarction;

[0045] 2) Patients with hypertension of grade 3 or above, cardiopulmonary insufficiency, and severe arrhythmia;

[0046] 3) Patients with severe liver and kidney damage;

[0047] 4) Pregnant or lactating women, people with allergies or those who are allergic to multiple drugs;

[0048] 5) The efficacy cannot be judged or the data are incomplete or affect the efficacy and safety.

[0049] 5. Shedding and rejection criteria

[0050] 1) Those who cannot be treated according to the established treatment plan;

[0051] 2) those whose complete follow-up was unavailable;

[0052] 3) Those who died during treatment.

[0053] 6. Treatment methods

[0054] The positive drug group received conventional western medicine treatment, taking aspirin enteric-coated tablets (Jiangsu Pingguang Pharmaceutical Co., Ltd., National Medicine Standard H20010205) 300 mg orally, once a night, for 3 consecutive days, and then 100 mg per day after 3 days; low molecular weight heparin sodium (Shenzhen Tiandao Pharmaceutical Co., Ltd., National Medicine Standard H20056845) 5000U, subcutaneous injection, twice a night; Betaloc (AstraZeneca Pharmaceutical Co., Ltd., National Medicine Standard H32025390) 12.5 mg, twice a day orally; isosorbide dinitrate (Qilu Pharmaceutical Co., Ltd., National Medicine Standard H20066717) 10 mg, 3 times a day orally; sublingual nitroglycerin (Shandong Huaxin Pharmaceutical Group Co., Ltd., National Medicine Standard H37021469) 0.5 mg when angina pectoris attacks. Patients with hypertension and hyperlipidemia were treated symptomatically.

[0055] The control group selected the composition disclosed in Chinese patent CN1334121A. The inventor selected a composition close to the composition of the present invention according to the content of the claim, which is composed of: 12g of aconite root, 12g of ginseng, 12g of Pseudostellariae Radix, 12g of yam, 12g of cinnamon twig, 12g of ophiopogon japonicus, 12g of schisandra chinensis, 12g of spiny date seed, 12g of scorpion, 12g of cicada shell, and 12g of centipede. Add water twice to decoct and extract a total of 400mL of juice, which is taken twice a day, morning and evening.

[0056] The observation group took the decoction of the Chinese medicine composition of the present invention for treatment. The test drug was the decoction prepared in reference to Example 1, 400 mL was taken and taken twice a day, morning and evening.

[0057] All three groups of patients were treated for 4 consecutive weeks.

[0058] 7. Observation indicators

[0059] 1) To observe and compare the changes in the frequency and duration of angina pectoris attacks among the three groups of patients before and after treatment.

[0060] The frequency of angina attacks is the sum of the number of angina attacks within a week; the duration is the time from the beginning of the angina attack to its disappearance, with each attack lasting 3 to 5 minutes.

[0061] 2) Observe and compare the changes of cardiac function indicators such as stroke volume (SV), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), and ratio of left atrioventricular early diastolic blood flow peak to late diastolic blood flow peak (E / A) before and after treatment.

[0062] The LDAI-7 Doppler ultrasound provided by GE was used. The detection indicators included SV, LVEDD, LVEF, and E / A, and the judgment was made based on the results of cardiac color ultrasound.

[0063] 3) Observe and compare the changes of nitric oxide (NO) and endothelin (ET-1) in vascular endothelial function before and after treatment.

[0064] 4 mL of venous blood was drawn on an empty stomach and the supernatant was collected after centrifugation for testing. NO was detected by nitrate reductase method and ET-1 was detected by radioimmunoassay.

[0065] 4) Observe and compare the changes of oxidative stress indicators such as serum superoxide dismutase (SOD), lipid peroxide (LPO), malondialdehyde (MDA), and total antioxidant capacity (TAC) before and after treatment.

[0066] 4 mL of venous blood was drawn on an empty stomach and the supernatant was collected after centrifugation for testing using enzyme-linked immunosorbent assay.

[0067] 5) Adverse reaction evaluation

[0068] The three groups of patients were compared for adverse reactions such as abdominal distension, nausea and vomiting, headache and dizziness during treatment, and symptomatic treatment was given in a timely manner.

[0069] 8. Statistical methods

[0070] SPSS2 2.0 statistical software was used for statistics, and the measurement data were expressed as mean ± standard deviation ( ) indicated that all the data in this study were in accordance with normal distribution. The t-test was used for intra-group comparison, and the variance analysis was used for inter-group comparison. The difference was considered statistically significant when P < 0.05.

[0071] 2. Results

[0072] 1. Comparison of angina pectoris frequency and duration

[0073] There was no significant difference in the frequency and duration of angina pectoris before treatment among the three groups (P>0.05). After treatment, the above indicators of the three groups were significantly lower than those before treatment (P<0.05). After treatment, the above indicators of the observation group were significantly lower than those of the control group and the positive drug group (P<0.05). See Table 1 for details.

[0074]

[0075] 2. Comparison of cardiac function indicators

[0076] There was no significant difference in SV, LVEDD, LVEF and E / A among the three groups before treatment (P>0.05); after treatment, SV, LVEF and E / A of the three groups were significantly higher than those before treatment, and LVEDD was significantly lower than those before treatment (P<0.05); after treatment, the above indicators of the observation group were significantly better than those of the control group and the positive drug group (P<0.05). See Table 2 for details.

[0077] LVEF is an indicator reflecting cardiac contractile function, and E / A is a specific indicator reflecting the peak blood flow during cardiac diastole. Both LVEF and E / A levels are positively correlated with cardiac function.

[0078]

[0079] 3. Comparison of vascular endothelial indicators

[0080] There was no significant difference in NO and ET-1 among the three groups before treatment (P>0.05); after treatment, NO of the three groups of patients increased significantly compared with before treatment, and ET-1 decreased significantly compared with before treatment (P<0.05); after treatment, the above indicators of the observation group were significantly better than those of the control group and the positive drug control group (P<0.05). See Table 3 for details.

[0081] NO and ET-1 are the most representative indicators of endothelial function. ET is currently the strongest vasoconstrictor, while NO levels are positively correlated with vascular homeostatic relaxation. When endothelial dysfunction occurs, serum NO levels drop significantly, while ET levels increase significantly.

[0082]

[0083] 4. Comparison of oxidative stress indicators

[0084] There was no significant difference in SOD, LPO, MDA and TAC among the three groups before treatment (P>0.05); after treatment, SOD and TAC of the three groups were significantly higher than those before treatment, while LPO and MDA were significantly lower than those before treatment (P<0.05); after treatment, the above indicators of the observation group were significantly better than those of the control group and the positive drug control group (P<0.05). See Table 4 for details.

[0085] After the onset of unstable angina, the patient's oxidation / antioxidation system will be disturbed, oxygen free radicals will increase, antioxidant free radical activity will decrease, and oxygen free radicals will accumulate, which will damage myocardial cells and blood vessels and accelerate the decline of cardiac function. MDA is the product of oxygen free radicals attacking biomembrane lipid peroxidation. SOD is an effective scavenger of oxygen free radicals in the body and an antioxidant enzyme that maintains the balance of oxidation / antioxidation in the body. Its level is related to the body's ability to resist lipid oxidation.

[0086]

[0087] The clinical efficacy observation results of the present invention show that after applying the Chinese medicine composition of the present invention, the NO level of patients with unstable angina pectoris is significantly increased, while the ET-1 level is significantly decreased, which indicates that the Chinese medicine composition of the present invention can significantly improve vascular endothelial function and the balance of inflammatory response substances in blood vessels, thereby improving the condition of vascular endothelial damage in patients with unstable angina pectoris, and ultimately showing a significant improvement in the frequency and duration of angina attacks.

[0088] The clinical efficacy observation results of the present invention also show that after the application of the Chinese medicine composition of the present invention, the MDA content of patients with unstable angina pectoris significantly decreased, while the SOD content significantly increased, which shows that the Chinese medicine composition of the present invention can improve the oxidative stress reaction and inhibit the damage of oxygen free radicals to the vascular endothelium. Combined with the cardiac function indicators, SV, LVEF, and E / A all increased significantly, while LVEDD decreased significantly.

[0089] In summary, the Chinese medicine composition provided by the present invention can improve the clinical symptoms of patients with unstable angina pectoris, significantly reduce the duration and frequency of angina pectoris attacks, improve cardiac function, resist myocardial oxidation, reduce stress response, antagonize ET-1, and promote the recovery of vascular endothelial function. Therefore, it can be used as a drug for the treatment of unstable angina pectoris.

Claims

1. A Chinese medicine composition containing aconite for treating unstable angina pectoris, characterized in that: The raw materials are as follows: 0.1-2 parts of aconite, 0.1-2 parts of ginseng, 0.1-2 parts of American ginseng, 0.1-2 parts of pseudoginseng, 0.1-2 parts of yam, 0.1-2 parts of cinnamon twig, 0.1-2 parts of ophiopogon, 0.1-2 parts of schisandra, 0.1-2 parts of cornus, 0.1-2 parts of asparagus, 0.1-2 parts of rehmannia, 0.1-2 parts of jujube seeds, 0.1-2 parts of dragon bones, and 0.1-2 parts of oyster.

2. The Chinese medicine composition according to claim 1, characterized in that: The raw material composition is as follows by weight: 0.5-1.8 parts of aconite, 0.5-1.8 parts of ginseng, 0.5-1.8 parts of American ginseng, 0.5-1.8 parts of Pseudostellariae pseudoginseng, 0.5-1.8 parts of yam, 0.5-1.8 parts of cinnamon twig, 0.5-1.8 parts of ophiopogon, 0.5-1.8 parts of schisandra, 0.5-1.8 parts of cornus, 0.5-1.8 parts of asparagus, 0.5-1.8 parts of rehmannia, 0.5-1.8 parts of spiny jujube seeds, 0.5-1.8 parts of dragon bones, and 0.5-1.8 parts of oyster.

3. The Chinese medicine composition according to claim 1, characterized in that The raw material composition is as follows by weight: 0.8-1.5 parts of aconite, 0.8-1.5 parts of ginseng, 0.8-1.5 parts of American ginseng, 0.8-1.5 parts of Pseudostellariae pseudoginseng, 0.8-1.5 parts of yam, 0.8-1.5 parts of cinnamon twig, 0.8-1.5 parts of ophiopogon, 0.8-1.5 parts of schisandra, 0.8-1.5 parts of cornus, 0.8-1.5 parts of asparagus, 0.8-1.5 parts of rehmannia, 0.8-1.5 parts of spiny jujube seeds, 0.8-1.5 parts of dragon bones, and 0.8-1.5 parts of oyster.

4. The Chinese medicine composition according to claim 1, characterized in that: The raw material composition is as follows by weight: 1 part of aconite root, 1 part of ginseng, 1 part of American ginseng, 1 part of pseudoginseng, 1 part of yam, 1 part of cinnamon twig, 1 part of ophiopogon japonicus, 1 part of schisandra chinensis, 1 part of cornus officinalis, 1 part of asparagus cochinchinensis, 1 part of rehmannia root, 1 part of spiny jujube seed, 1 part of dragon bone, and 1 part of oyster.

5. The preparation of the Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The preparations include granules, capsules, tablets, decoctions or oral liquids.

6. Use of the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a drug for treating unstable angina pectoris.

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