A traditional Chinese medicine composition for treating atrial fibrillation

Abstract

The present invention relates to a traditional Chinese medicine composition for treating atrial fibrillation, which is prepared from the following raw materials in parts by weight: Pinellia ternata (Thunb.) Breit. processed with ginger 5 - 10 parts, Citrus reticulata Blanco 5 - 10 parts, Astragalus membranaceus (Fisch.) Bge. 15 - 30 parts, Atractylodes macrocephala Koidz. 5 - 15 parts, Poria cocos (Schw.) Wolf 5 - 15 parts, Coptis chinensis Franch. 3 - 9 parts, Cinnamomum cassia Presl 1 - 6 parts, Os Draconis 9 - 30 parts, Concha Ostreae 9 - 30 parts, Sophora flavescens Ait. 9 - 15 parts, Artemisia annua L. 9 - 30 parts, Polygala tenuifolia Willd. 3 - 9 parts, Ophiopogon japonicus (Thunb.) Ker-Gawl. 9 - 15 parts, Epimedium brevicornu Maxim. 9 - 15 parts, Cortex Moutan 9 - 15 parts, Ziziphus jujuba Mill. 9 - 15 parts. The traditional Chinese medicine composition of the present invention takes "phlegm" as the target for traditional Chinese medicine treatment, and formulates the prescription starting from the pathogenesis of qi deficiency and phlegm turbidity, which can reduce the frequency and duration of palpitations, improve the traditional Chinese medicine syndromes and total scores, reduce the duration and proportion of atrial fibrillation in dynamic electrocardiogram, improve the quality of life of patients, and has no side effects, being safe and reliable.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine composition for treating atrial fibrillation, which is a traditional Chinese medicine prescription for treating atrial fibrillation formulated for patients with the pathogenesis of "qi deficiency and phlegm turbidity" differentiated from atrial fibrillation. Background Art

[0002] With the acceleration of population aging and social urbanization in China, the incidence and prevalence of cardiovascular diseases have been continuously rising [1] , among which atrial fibrillation (AF) is one of the most common arrhythmias at present, and it is a supraventricular tachyarrhythmia characterized by rapid and disordered atrial electrical activity. Due to the extremely irregular ventricular beats, it brings great discomfort to patients and affects the quality of life of patients to varying degrees. In mild cases, it is manifested as palpitation, chest tightness, and fatigue, while in severe cases, syncope, angina pectoris occur.

[0003] As of 2015, the incidence of atrial fibrillation has increased by 20 times, and the probability of atrial fibrillation causing stroke has increased by 13 times [2] . According to statistics, in different age groups in China: 45 - 54 years old, 55 - 64 years old, 65 - 74 years old, ≥75 years old, the prevalence rates of atrial fibrillation are 6.2%, 10.0%, 16.2% respectively [3] . Domestic and foreign studies have shown that the prevalence and incidence of atrial fibrillation gradually increase with age, and it will lead to an increased risk of stroke and thromboembolism, an increased prevalence of heart failure and aggravated symptoms [4] , an increased incidence of myocardial infarction [5] , cognitive function decline, dementia, and renal function damage [6] and other hazards.

[0004] Treating the etiology, correcting the inducing factors, preventing complications, controlling the ventricular rate, and restoring sinus rhythm are the treatment goals of atrial fibrillation. The current treatment methods for atrial fibrillation mainly include drug treatment, radiofrequency ablation, left atrial appendage occlusion, and traditional Chinese medicine treatment. Common drug treatment methods include drugs for restoring sinus rhythm (such as propafenone, lidocaine, etc.), drugs for controlling the ventricular rate (such as bisoprolol, metoprolol, etc.), and anticoagulant drugs (such as warfarin, new oral anticoagulants) that need to be used in combination. The advantages are that drugs for restoring sinus rhythm can improve cardiac function, increase cardiac output, slightly improve exercise ability, reduce the occurrence of heart failure time, reduce complications, especially reduce the risk of stroke and lower the mortality rate [7] , however, with the long-term clinical application, problems such as poor efficacy and side effects gradually emerge [8] . Treating atrial fibrillation by occluding the left atrial appendage is safe, effective, simple, and less invasive, but thrombus can form on the surface of the occluder and there is residual cavity blood flow around the device in the early postoperative period, so there is a risk of thromboembolism and other complications [9]。The selective application of various ablation techniques has gradually increased the success rate of radiofrequency ablation for atrial fibrillation. However, there are many problems in the ablation process, such as high technical requirements and the need for rich experience of the operator, which have limited its clinical application to a certain extent.

[10] 。Surgical treatment of atrial fibrillation is also constantly being studied and improved. Since the initial stage until now, it has experienced surgical methods such as left atrial isolation, corridor surgery, atrial transection, and maze, type II, I, and V surgeries, etc., which can improve the quality of life and exercise tolerance of patients. The disadvantages are large surgical trauma, long recovery time, and complex and difficult operation techniques, so it cannot be popularized clinically.

[11] 。

[0005] Since modern times, traditional Chinese medicine has accumulated rich clinical experience in the treatment of atrial fibrillation. Modern experimental studies have shown that traditional Chinese medicine can reduce the occurrence of atrial fibrillation, improve myocardial ischemia, and inhibit ventricular remodeling by inhibiting left atrial fibrosis, improving left atrial conduction function, blocking ion channels, regulating the autonomic nervous system, etc., and has the advantages of stable efficacy, few adverse reactions, multiple components, and multiple targets.

[12] 。Many researchers have adopted the combined treatment of traditional Chinese and Western medicine for atrial fibrillation and achieved relatively significant results. Chen Guang et al.

[13] proposed that taking the small intestine as the starting point to dredge the qi movement of the intestine, allowing pathogenic factors to be discharged, ensuring that the qi of the heart, which is exterior-interiorly related to the small intestine, can function normally, thereby calming the mind and achieving the effect of reducing the occurrence of atrial fibrillation. Zhang Baoguo et al.

[14] treated patients with atrial fibrillation accompanied by heart failure with modified Buyang Huanwu Decoction. The results showed that modified Buyang Huanwu Decoction could relieve clinical symptoms, improve cardiac function, and control the ventricular rate to a certain extent. Different from Western medicine, traditional Chinese medicine needs to give different prescriptions to patients with atrial fibrillation of each syndrome type according to the patient's syndrome type through syndrome differentiation and treatment in order to effectively improve their clinical symptoms. Regarding the classification of atrial fibrillation, different researchers have different views. The most common ones are the syndrome of insufficient heart qi, the syndrome of deficiency of both the heart and spleen, the syndrome of deficiency of heart and kidney yang, the syndrome of blood stasis blocking the heart vessels, the syndrome of deficiency of both qi and yin, and the syndrome of phlegm turbidity obstructing the interior. Yin Kechun

[15] et al. found that among the traditional Chinese medicine classifications of atrial fibrillation, the syndrome of qi stagnation and blood stasis is the most common, accounting for 1 / 3, and the syndrome of phlegm turbidity obstruction is the second, accounting for 1 / 4. "Phlegm and retained fluid are both substances... They can reach all over the body, both inside and outside, and exist in all five zang-organs and six fu-organs." Therefore, any pathological product of phlegm and retained fluid produced by any of the five zang-organs will affect the whole body. Therefore, how to supplement qi, nourish qi, regulate qi, and how to dry dampness, resolve phlegm, and strengthen the spleen becomes particularly important. Blood stasis, phlegm turbidity, and qi stagnation are the main pathogenesis of atrial fibrillation. For blood stasis and qi stagnation, there are already symptomatic proprietary Chinese medicines such as Wenshen Granules and Shensong Yangxin Capsules. However, there is no corresponding proprietary Chinese medicine for atrial fibrillation of the qi deficiency and phlegm turbidity type, which also accounts for a relatively large proportion.

[0006] At present, the main drugs of Wenxin Keli and Shensong Yangxin Capsule on the market are targeted at patients with qi-yin deficiency and blood stasis. In the pathogenesis of atrial fibrillation, "deficiency" and "phlegm" are important pathogenic mechanisms. Due to the characteristics of population aging and dietary structure, a certain proportion of clinical patients have the combination of "deficiency" and "phlegm" in traditional Chinese medicine pathogenesis. The current western medicine and surgical treatments for atrial fibrillation patients cannot fundamentally change the trend of atrial fibrosis and the degenerative trend of the human body. In the medium and long term, drug maintenance is required and the recurrence rate is high. Western medicines such as amiodarone and sotalol have certain side effects when taken for a long time, with great limitations. Many patients cannot solve practical problems and need better treatment methods.

[0007] References:

[0008] [1] Beijing Hypertension Prevention and Control Association, Beijing Diabetes Prevention and Control Association, Beijing Chronic Disease Prevention, Control and Health Education Research Association, etc. Guidelines for Comprehensive Management of Cardiovascular Diseases at the Grassroots Level 2020 [J / CD]. Chinese Journal of the Frontiers of Medicine (Electronic Edition), 2020, 12(8): 1-73.

[0009] [2] Deng Dandan, Zhu Bei, Hou Li. Epidemiology and preventive measures of atrial fibrillation [J]. Chinese Journal of Clinical Healthcare, 2021, 24(6): 737-738.

[0010] [3] DU X, GUO L, XIA S, et al. Atrial fibrillation prevalence, awareness and management in a nationwide survey of adults in China [J]. Heart, 2021, 107(7): 535-541.

[0011] [4] Wang Zhen. Analysis of the medication rules of Professor Zhou Yabin in treating atrial fibrillation [D]. Heilongjiang University of Chinese Medicine, 2020.

[0012] [5] Huang Congxin, Zhang Shu, Huang Dejia, Hua Wei. Atrial fibrillation: current understanding and treatment recommendations - 2018 [J]. Chinese Journal of Cardiac Pacing and Electrophysiology, 2018, 32(04): 315-368.

[0013] [6]Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS)[J]. Eur Heart J, 2020, Aug 29.

[0014] [7]Wu Dan, Wang Chenxi, Tao Yang. Clinical effect of warfarin dual antiplatelet therapy in the treatment of non-valvular atrial fibrillation complicated with coronary heart disease[J]. Practical Clinical Medicine, 2020, 21(10): 18 - 20.

[0015] [8]Duan Wentao, Zhang Feng, Shi Dong, Zhang Zhaoxia. New progress in research on risk factors and drug treatment related to atrial fibrillation[J]. Journal of Wuhan University, 2020, 41(1): 166 - 167.

[0016] [9]Pang Naidong, Zhang Nan, Guo Min, Sun Meng, Wang Rui. Research progress of left atrial appendage electrical isolation in the treatment of persistent atrial fibrillation[J]. Journal of Clinical Cardiology, 2022, 38(01): 6 - 8.

[0017]

[10] Tilz RR, Sano M, Vogler J, et al. Fourth-generation cryoablation based left atrial appendage isolation for the treatment of persistent atrial fibrillation: first case report[J]. Am J Case Rep, 2019, 20: 1830 - 1836.

[0018]

[11] Zheng Daokuo, Ge Zhenwei, Wang Baocai, et al. Research progress in surgical treatment of atrial fibrillation[J]. Journal of Chinese Practical Diagnosis and Therapy, 2021, 35(1): 105 - 108.

[0019]

[12] Ma J, Yin C, Ma S, et al. Shensong Yangxin capsule reduces atrial fibrillation susceptibility by inhibiting atrial fibrosis in rats with post-myocardial infarction heart failure[J]. Drug Des Devel Ther, 2018, 12: 3407-3418

[0020]

[13] Chen G, Wang J. New theory on the differentiation and treatment of atrial fibrillation[J]. Journal of Traditional Chinese Medicine, 2016, 57(16): 1367-1370.

[0021]

[14] Su B L. Effects of Qingre Fumai Decoction on rapid atrial fibrillation of phlegm-fire disturbing the heart type[D]. Fujian University of Traditional Chinese Medicine, 2014.

[0022]

[15] Yin K C, Li X H, Chen L, Liu S J, Zhou W B, Chen W Q, Yang M. Clinical observation on the distribution law of traditional Chinese medicine syndromes of coronary heart disease with atrial fibrillation[J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2007, (12): 1163-1165. Summary of the Invention

[0023] In view of the above-mentioned deficiencies of the prior art, according to the embodiments of the present invention, it is desired to provide a traditional Chinese medicine composition for treating atrial fibrillation. Starting from the pathogenesis of qi deficiency and phlegm turbidity, with "phlegm" as the treatment target in traditional Chinese medicine, the formula can reduce the frequency and duration of palpitations, improve the traditional Chinese medicine symptoms and total scores, reduce the duration and proportion of atrial fibrillation in dynamic electrocardiogram, improve the quality of life of patients, and has no side effects, being safe and reliable.

[0024] According to the embodiment, a traditional Chinese medicine composition for treating atrial fibrillation provided by the present invention is prepared from the following raw materials in parts by weight: Pinellia ternata (processed with ginger) 5-10 parts, Citrus reticulata Blanco 5-10 parts, Astragalus membranaceus (Fisch.) Bge. 15-30 parts, Atractylodes macrocephala Koidz. 5-15 parts, Poria cocos (Schw.) Wolf 5-15 parts, Coptis chinensis Franch. 3-9 parts, Cinnamomum cassia Presl 1-6 parts, Os Draconis 9-30 parts, Concha Ostreae 9-30 parts, Sophora flavescens Ait. 9-15 parts, Artemisia annua L. 9-30 parts, Polygala tenuifolia Willd. 3-9 parts, Ophiopogon japonicus (Thunb.) Ker-Gawl. 9-15 parts, Epimedium brevicornu Maxim. 9-15 parts, Paeonia suffruticosa Andr. 9-15 parts, Ziziphus jujuba Mill. 9-15 parts. Preferably, the parts by weight of the raw materials are: Pinellia ternata (processed with ginger) 9 parts, Citrus reticulata Blanco 9 parts, Astragalus membranaceus (Fisch.) Bge. 15 parts, Atractylodes macrocephala Koidz. 9 parts, Poria cocos (Schw.) Wolf 12 parts, Coptis chinensis Franch. 6 parts, Cinnamomum cassia Presl 3 parts, Os Draconis 15 parts, Concha Ostreae 15 parts, Sophora flavescens Ait. 9 parts, Artemisia annua L. 15 parts, Polygala tenuifolia Willd. 6 parts, Ophiopogon japonicus (Thunb.) Ker-Gawl. 15 parts, Epimedium brevicornu Maxim. 15 parts, Paeonia suffruticosa Andr. 9 parts, Ziziphus jujuba Mill. 12 parts.

[0025] In the prescription of the Chinese medicine composition for treating atrial fibrillation of the present invention [hereinafter also referred to as the prescription for phlegm-resolving and palpitation-relief], the monarch drugs are: astragalus root for invigorating qi, consolidating the exterior and removing toxins, pinellia tuber for drying dampness and resolving phlegm, descending adverse qi and stopping vomiting, eliminating lumps and dispersing knots, coptis root for clearing heat and drying dampness, purging fire and detoxifying, polygala root for calming the mind and improving intelligence, and removing phlegm; the minister drugs are: tangerine peel, raw atractylodes, poria, dragon bone, oyster, artemisia annua, sophora flavescens, cinnamon bark, and epimedium; the adjuvant drugs are: ophiopogon root for nourishing yin and promoting fluid production, moistening the lungs and clearing the heart, peony bark for cooling blood and removing blood stasis, which together nourish yin, cool blood and clear the heart, and at the same time assist in controlling the dryness and heat of the phlegm-resolving drugs; the guiding drug is jujube for invigorating the spleen and harmonizing the stomach, invigorating qi and promoting fluid production, regulating the Ying and Wei, and removing toxins from drugs.

[0026] The preparation method of the Chinese medicine composition for treating atrial fibrillation of the present invention is nothing special, and the conventional process route and process conditions for preparing granules in the art are followed: Chinese medicine pieces - extraction - filtration - concentration - drying - granulation, and granules can be made [hereinafter also referred to as Huatan Dingji Granules].

[0027] The Chinese medicine composition for treating atrial fibrillation of the present invention takes "phlegm" as the target, focuses on "phlegm" for treatment, and takes the meaning of Huanglian Wendan Decoction to clear away heat and dampness, regulate qi and resolve phlegm and harmonize the stomach. In the prescription, the prepared Pinellia tuber can dry dampness and eliminate lumps, reduce adverse reactions and stop vomiting, resolve phlegm and disperse knots; Tangerine peel can dry dampness and strengthen the spleen, resolve phlegm and regulate qi; Poria can promote diuresis and penetrate dampness, strengthen the spleen and calm the heart; Huanglian can purge heart fire and detoxify; Jujube can benefit the spleen and harmonize the stomach, so as to eliminate the source of phlegm. The prescription also takes the effect of Liujunzi Decoction to invigorate qi and strengthen the spleen, and help the spleen to move and transport water and dampness, and block the generation of phlegm from the root. On the basis of Sijunzi Decoction, Atractylodes macrocephala is reused to remove dampness and benefit dryness, and the power of harmonizing the middle and benefiting qi is stronger. The combination of Huanglian and cinnamon takes the meaning of Jiaotai Pills to communicate the heart and kidney. On this basis, dragon bone and oyster are added to calm the mind, astragalus nourishes the middle and replenishes qi, ophiopogon nourishes yin and moistens dryness, clears the lungs and produces fluid, clears the heart and relieves troubles, calms the mind and soothes the mind, epimedium warms and replenishes kidney yang, artemisia annua clears deficiency heat and eliminates bone steaming, and sophora flavescens clears heat and dries dampness. The whole formula works together to replenish qi, strengthen the spleen and resolve phlegm, nourish the heart and calm the mind, connect the heart and kidney, and balance yin and yang.

[0028] Huatan Dingji Recipe uses 16 Chinese herbs including Radix Ophiopogonis, Pinellia, Radix Astragali, Pericarpium Citri Reticulatae, Atractylodes Macrocephalae, Poria, and Jujube. It protects the heart from all directions and angles, as evidenced by many pharmacological experiments. First, Huatan Dingji Recipe can antagonize oxidative stress response. According to relevant literature [1] , Ophiopogon japonicus polysaccharide MDG-1 and methyl Ophiopogon japonicus flavanone can reduce the production of nitric oxide and inhibit respiratory burst by inhibiting the IL-4 pathway to achieve antioxidant effects; Astragaloside IV [2] It can inhibit the nuclear factor-KB pathway, regulate the Bcl-2 gene, and regulate the expression of hypoxia-inducible factor-1α to inhibit oxidative reactions; the rutin and α-tocopherol contained in the fruit of Phellodendron chinense can also clear free radicals to a certain extent and reduce oxidative reactions; [3] It can also regulate the nuclear factor-KB pathway. [4]It can protect cells from oxidation by reducing the expression of factors such as TNF-α. Secondly, Huatan Dingji Recipe can alleviate the inflammatory response. The extract of Ophiopogon japonicus can reduce the production of interleukin-6, interleukin-10, interleukin-12, and vascular endothelial growth factor. Ophiopogonin D can regulate the CYP2J3 gene and increase endothelial-derived hyperpolarizing factor to inhibit the occurrence of inflammation; Pinellia ternata has the effect of glucocorticoid-like 27 hormones, and topical application of Pinellia ternata has an obvious detumescence effect, which may be related to its role in inhibiting the release of inflammatory factors [5] ; Tangerine peel has an inhibitory effect on the secretion of inflammatory factors such as nitric oxide, tumor necrosis factor α, IL-1β recombinant protein, and interleukin-6 induced by LpS, which is related to the fact that tangerine peel can inhibit the gene expression of iN OS, COX-2, and IL-1 and induce the gene expression of HO-1 [6] . Poria cocos polysaccharide can enhance the phagocytic function of mouse macrophages, regulate the release of interleukin-1β, IL-6, tumor necrosis factor-α, IL-12, and interferon-γ, and reduce the occurrence of inflammatory reactions; Finally, Huatan Dingji Recipe can comprehensively protect cardiomyocytes. Ophiopogon japonicus can enhance the function of the adrenal cortex to promote the regeneration of vascular endothelium and also weaken the influence of toxic substances; Astragalus membranaceus can protect ischemic myocardium by regulating autophagy genes and inhibit the expression of TGF-β1 and Smad4 to weaken myocardial fibrosis; Components such as hesperidin in tangerine peel can inhibit the proliferation and migration of vascular cells, reduce the production of 8-iso-PGF2α, and thus inhibit myocardial remodeling; Coptis chinensis [7] The berberine in it has a positive inotropic effect on cardiomyocytes and antagonizes heart failure; it can also promote the influx of sodium ions and reduce abnormal electrical activity; Prepared Licorice Root can improve myocardial hypertrophy and heart failure by inhibiting abnormal apoptosis of cells and weaken the damage of toxic substances to cardiomyocytes. Not only the above effects, the components contained in Huatan Dingji Recipe also have a promoting effect on lipid metabolism and glucose metabolism, can inhibit platelet aggregation, have anti-tumor effects, and have a calming and tranquilizing effect on anxiety and depression.

[0029] Based on the understanding of the traditional Chinese medicine pathogenesis of atrial fibrillation, Huatan Dingji Recipe comprehensively treats patients from multiple aspects such as qi and blood, yin and yang, which is the reason why Huatan Dingji Recipe can improve the symptoms of atrial fibrillation patients, reduce the atrial fibrillation attack time, and improve the quality of life of atrial fibrillation patients.

[0030] References:

[0031] [1] Yuan Chunli, Sun Li, Yuan Shengtao, Kou Junping, Yu Boyang. Research progress on the pharmacological activities and action mechanisms of the effective components of Ophiopogon japonicus [J]. Chinese Journal of New Drugs, 2013, 22(21): 2496-2502.

[0032] [2] Wu Hongwei, Li Donghui, Zhang Yugui, Zhang Shujuan, Xin Erdang, Si Xinlei, Niu Jiangtao, Li Yuefeng. Research Status of the Cardioprotective Effect of Astragaloside IV [J]. Chinese Journal of Clinical Pharmacology, 2021, 37(01): 81-83.

[0033] [3] Zuo Jun, Zhang Jinlong, Hu Xiaoyang. Research Progress on Chemical Constituents and Modern Pharmacological Effects of Atractylodes macrocephala Koidz [J / OL]. Journal of Liaoning University of Traditional Chinese Medicine: 1-8 [2021-05-07]. http: / / kns.cnki.net / kcms / detail / 21.1543.R.20210419.1116.007.html.

[0034] [4] Yu Jingjing, Su Jie, Lü Guiyuan. Research Progress on the Pharmacology of Pericarpium Citri Reticulatae in the Treatment of Cardiovascular and Cerebrovascular Diseases [J]. Chinese Traditional and Herbal Drugs, 2016, 47(17): 3127-3132.

[0035] [5] Wang Yiming, Wang Qiuhong. Research Progress on Chemical Constituents, Pharmacological Effects and Toxicity of Pinellia ternata (Thunb.) Breit. [J]. China Pharmacy, 2020, 31(21): 2676-2682.

[0036] [6] Mei Zhenying, Zhang Rongfei, Zhao Zhimin, Zheng Guodong, Xu Xinjun, Yang Depo. Research Progress on the Composition, Extraction, Purification and Biological Activity of Polymethoxyflavones in Pericarpium Citri Reticulatae [J]. Chinese Traditional Patent Medicine, 2020, 42(10): 2709-2715.

[0037] [7] Qiu Yanping. Research Progress on Chemical Constituents and Pharmacological Effects of Coptis chinensis Franch. [J]. Clinical Journal of Chinese Medicine, 2018, 10(22): 141-143.

[0038] Subsequent test examples will also prove that Huatan Dingji Decoction has the effects of replenishing qi and resolving phlegm, calming palpitation, reducing the frequency and duration of palpitation attacks, improving various TCM syndromes and total scores, reducing the duration and proportion of atrial fibrillation, improving the quality of life of patients, and having no side effects, being safe and reliable. Specific Embodiments

[0039] The present invention will be further described below in conjunction with specific embodiments. These embodiments should be understood as only for illustrating the present invention and not for limiting the protection scope of the present invention. After reading the content recorded in the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0040] Example 1 - Preparation of Huatan Dingji Granules

[0041] Weigh the batch feeding amount of the prescription listed in Table 1, and prepare 16.8 kg (1120 bags) of Huatan Dingji Granules according to the conventional process route and process conditions for preparing granules in this field: Chinese herbal medicine slices--extraction--filtration--concentration--drying--granulation, and set aside.

[0042] Table 1

[0043]

[0044] Test example

[0045] In order to observe the treatment effect of Huatan Dingji prescription on atrial fibrillation of qi deficiency and phlegm turbidity type, patients with palpitations diagnosed as atrial fibrillation of qi deficiency and phlegm turbidity type who were admitted to the outpatient department and inpatient department of cardiology of Longhua Hospital from May 2020 to October 2021 were randomly divided into Huatan Dingji prescription + western medicine treatment group and placebo granules + western medicine treatment group, with 30 cases in each group, and took the medicine for one month; the changes in palpitations attacks, changes in TCM symptom scores, average ventricular rate of electrocardiogram, echocardiography, pro-BNP, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and SF-36 quality of life scale results in the two groups before and after treatment were observed to evaluate the effectiveness and safety of Huatan Dingji prescription in the treatment of atrial fibrillation of qi deficiency and phlegm turbidity type.

[0046] 1. Diagnostic criteria

[0047] 1.1 Western medicine diagnostic criteria:

[0048] The diagnosis is made according to the criteria in "Atrial Fibrillation 2015: Current Knowledge and Treatment Recommendations":

[0049] (1) Clinical manifestations: palpitations, chest tightness, and decreased exercise tolerance.

[0050] (2) Cardiac auscultation: The heart rate is inconsistent, the heart sounds are of varying strengths, the rhythm is absolutely irregular, and the pulse is short.

[0051] (3) Electrocardiogram: The p wave disappears and is replaced by the f wave. The frequency is about 350 to 600 times / min, and the QRS complex rhythm is absolutely irregular.

[0052] (4) Clinical diagnosis: The diagnosis of atrial fibrillation can be confirmed based on clinical manifestations, physical examination and electrocardiogram characteristics.

[0053] 1.2 Standards for TCM Syndrome Differentiation

[0054] The guidelines were formulated based on the new version of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)" issued by the State Drug Administration in 2002 and the "National Standard of the People's Republic of China - TCM Clinical Diagnosis and Treatment Terminology Syndrome Part" issued in 1997.

[0055] Main symptoms: palpitations, chest tightness and shortness of breath.

[0056] Secondary symptoms: fatigue, coughing, sputum, and obesity.

[0057] Tongue and pulse: The tongue is dark purple or has petechiae on the edges, the tongue coating is white and greasy, and the pulse is thready and wiry.

[0058] The patient has one main symptom and two secondary symptoms; the diagnosis can be made based on one main symptom, one secondary symptom and tongue and pulse.

[0059] 2. Inclusion and Exclusion Criteria

[0060] 2.1 Inclusion criteria

[0061] (1) Patients who meet the above-mentioned diagnostic criteria of traditional Chinese medicine and Western medicine and whose main symptom is palpitations of qi deficiency and phlegm turbidity type according to traditional Chinese medicine syndrome differentiation.

[0062] (2) Age 40 ≤ ≤ 85 years old.

[0063] (3) Paroxysmal atrial fibrillation, with an attack frequency of ≥ 2 times / month or persistent atrial fibrillation (diagnosed by at least one electrocardiogram)

[0064] (4) Voluntarily accept clinical treatment and fill out the medical consent form, correctly understand the significance of the project research, and understand and comply with the researcher's follow-up observation and evaluation.

[0065] 2.2 Exclusion criteria

[0066] (1) Patients with primary diseases such as severe liver and kidney dysfunction, severe decline in lung function, hematopoietic system abnormalities, or severely declined heart function (NYHA IV grade);

[0067] (2) Atrial fibrillation caused by obvious causes, such as mental anxiety, poisoning, mood swings, hyperthyroidism, electrolyte imbalance, etc.;

[0068] (3) Those with mental illness that is not well controlled;

[0069] (4) Patients with heart rate ≤50 beats / min (such as sick sinus syndrome, high-degree atrioventricular block, etc.);

[0070] (5) Pregnant or lactating women;

[0071] (6) cachexia in the terminal stage of malignant tumors;

[0072] (7) The efficacy of the treatment cannot be determined due to various reasons or the data are incomplete.

[0073] 3. Treatment options

[0074] Patients with atrial fibrillation of Qi deficiency and phlegm turbidity type who met the criteria were randomly divided into a treatment group and a control group using a double-blind single-dummy random table method. The treatment course was 4 weeks.

[0075] Control group: Western medicine basic treatment + placebo simulation treatment was adopted. The placebo contained 10% of the Huatan Dingji prescription ingredients.

[0076] Treatment group: Western medicine basic treatment + Huatan Dingji prescription granules were used for treatment.

[0077] The Western medicine basic treatment was the Western medicine that the patients were currently taking.

[0078] 4. Observation indicators:

[0079] 4.1 General conditions

[0080] The general conditions of the patients were recorded before and after treatment, including: gender, age, weight, heart rate, heart rhythm, blood pressure, etc.;

[0081] 4.2 Efficacy indicators

[0082] Main efficacy criteria:

[0083] (1) Clinical symptoms: The average number of palpitations and the duration were recorded by scoring before and after treatment.

[0084] (2) Holter electrocardiogram: The dynamic changes of the 24-hour electrocardiogram activity of the patients were recorded, including the total number of heart beats, the average proportion of atrial fibrillation, the average duration of atrial fibrillation, the patients who converted from atrial fibrillation rhythm to sinus rhythm, etc., to evaluate the arrhythmia situation of the patients.

[0085] Secondary efficacy criteria:

[0086] (1) Traditional Chinese medicine syndromes: The changes of symptoms such as limb heaviness, fatigue, sticky phlegm in the mouth, etc. were recorded by scoring before and after treatment and during subsequent follow-up.

[0087] (2) Electrocardiogram: The resting electrocardiogram changes were recorded before and after treatment respectively.

[0088] (3) Echocardiogram: Echocardiography was used to detect indicators such as left atrial diameter, left ventricular ejection fraction, left ventricular stroke volume, etc. before and after treatment in each group.

[0089] (4) Cardiac function: pro-BNP indicators before and after treatment

[0090] (5) Hamilton Anxiety and Depression Scale Assessment: The Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) were used to evaluate the emotional state. The HAMA is commonly used in clinical psychiatry. According to the regulations of the Chinese scale cooperation group, a score of 14 indicates the certainty of anxiety; less than 7 points means no anxiety symptoms; 7 to 14 points is the dividing line, and there may be anxiety and depression. The HAMD is used to assess whether the patient is in a depressive state and is widely used clinically. Generally, a score of 20 or more is considered significant.

[0091] (6) SF-36 Assessment: The MOS item short from health survey (SF-36) was used to evaluate the changes in the quality of life of the patients. It consists of mental health and physical health.

[0092] Physical health includes 4 dimensions: Role-Physical: Measures the functional limitations caused by physical health; Physical Function: Measures whether the health status affects normal physical activities; Bodily Pain: Measures the degree of pain of the patient and the impact of pain on daily life; General Health: Measures the patient's assessment of their own health status and development trend;

[0093] Mental health includes 4 dimensions: Social Function: Measures the impact of the patient's physical and mental problems on the quality and quantity of social activities; Vitality: Measures the patient's subjective feelings about their energy and fatigue level; Mental Health: Measures the patient's four types of health items, including motivation, depression, behavior or emotion control, and psychological subjective feelings; Role-Emotional: Measures the limitations of life functions caused by emotional problems; Health Change, which is used to evaluate the overall situation of health changes within one year.

[0094] 4.3 Safety Indicators

[0095] Safety indicators: Blood and urine routine, liver and kidney functions, blood lipids, fasting blood glucose, coagulation indicators.

[0096] 5. Efficacy Evaluation

[0097] 5.1 Clinical Symptoms and Traditional Chinese Medicine Symptom Efficacy Judgment Criteria

[0098] According to the "Guiding Principles for Clinical Research of New Chinese Medicines" (2002 edition), it is divided into 4 levels: cured, markedly effective, effective, and ineffective:

[0099] Clinical cure: The original symptoms and signs basically disappear, and the total symptom score decreases by ≥90%;

[0100] Marked effectiveness: Most of the original symptoms and signs disappear or are significantly reduced, and the total score decreases by ≥70%;

[0101] Effective: The original symptoms and signs were alleviated compared with those before treatment, and the total score decreased by 70% - 30%.

[0102] Ineffective: The original symptoms and signs did not improve, and the total score decreased by less than 30%.

[0103] Note: The calculation formula (Nimodipine method) is: [(score before treatment - score after treatment) / score before treatment]*100%.

[0104] 5.2 Evaluation of Western Medicine Therapeutic Effect

[0105] The criteria for judging the efficacy of electrocardiogram refer to the 2018 version of "Atrial Fibrillation: Current Understanding and Treatment Recommendations"

[11] and "Evaluation Criteria for Coronary Heart Disease Angina Pectoris and Electrocardiogram Efficacy"

[13] :

[0106] Effective: (1) There was atrial fibrillation at baseline electrocardiogram but no atrial fibrillation attack during follow-up, and the subjective symptoms decreased by ≥50%; (2) There was no atrial fibrillation at baseline electrocardiogram but there were atrial tachycardia and premature atrial contractions, and the attacks of atrial tachycardia and premature atrial contractions decreased by >50% during follow-up, and the subjective symptoms decreased by ≥50%; (3) There was no atrial fibrillation attack at both baseline electrocardiogram and follow-up, but the subjective symptoms decreased by ≥50%.

[0107] Ineffective: (1) There was atrial fibrillation attack at both baseline electrocardiogram and follow-up; (2) There was no atrial fibrillation attack at baseline electrocardiogram but there was atrial fibrillation attack during follow-up; (3) There was or was not atrial fibrillation attack at baseline electrocardiogram, there was no atrial fibrillation attack during follow-up, and the subjective symptoms decreased by less than 50%.

[0108] 6. Statistical Processing Methods

[0109] All data were recorded in Excel sheets and analyzed by SPSS 22.0; due to the use of a third-party blinded research method, the data were entered and then unblinded by a third party for statistical analysis. For count data, Pearson's χ2 test was used; for measurement data, data that conformed to a normal distribution and had homogeneous variances were subjected to a t-test, and the data format was expressed as mean ± standard deviation; for data that did not conform to a normal distribution, a rank sum test was used, and the data were expressed as M(QR). Constituent ratio data were subjected to a chi-square test. Unidirectional ordinal data were subjected to a rank sum test. If P < 0.05, it means that the difference is statistically significant, and a two-sided test was used.

[0110] 7. Experimental Results

[0111] (1) Clinical symptoms: Before treatment, P>0.05 for both groups in terms of the frequency and duration of palpitations, indicating no statistically significant difference and comparability (see Table 1.1); after treatment, P = 0.028 for the inter-group comparison of the frequency of palpitations; P = 0.001 for the inter-group comparison of the duration of palpitations. Both P values are <0.05, showing statistically significant differences, and the treatment group is superior to the control group (see Table 1.2).

[0112] (2) Traditional Chinese medicine syndromes and overall efficacy: Before treatment, P>0.05 for both groups in terms of the total score of traditional Chinese medicine syndromes, indicating no statistically significant difference and comparability; after treatment, P = 0.000 for the inter-group comparison of the total score of traditional Chinese medicine syndromes, showing statistically significant differences, and the treatment group is superior to the control group (see Table 2.1); the effective rate of the treatment group is 74.19%, and the effective rate of the control group is 33.33%. P = 0.031 for the comparison between the two groups, showing statistically significant differences, and the efficacy of the treatment group is superior to that of the control group (see Table 2.2).

[0113] (3) Single traditional Chinese medicine symptoms: Before treatment, P>0.05 for both groups in terms of single traditional Chinese medicine symptoms, indicating no statistically significant difference and comparability; after treatment, P>0.05 for both groups in terms of spontaneous sweating, fatigue, chest tightness, heaviness of the head and body, and dull complexion, indicating no statistically significant differences; P<0.05 for both groups in terms of palpitations and sticky phlegm in the mouth, showing statistically significant differences, and the treatment group is superior to the control group (see Table 3).

[0114] (4) Holter electrocardiogram: Before treatment, P>0.05 for both groups in terms of each item of Holter electrocardiogram, indicating no statistically significant difference and comparability; after treatment, P<0.05 for both the average duration of atrial fibrillation and the proportion of atrial fibrillation, showing statistically significant differences (see Table 4).

[0115] (5) SF-36 quality of life scale: Before treatment, P>0.05 for both groups in terms of each item of the SF-36 life scale, indicating no statistically significant difference and comparability; after treatment, P>0.05 for the inter-group comparison in the five dimensions of physical function, bodily pain, general health, social function, and role-emotional, indicating no statistically significant differences; P<0.05 for the inter-group comparison in the four dimensions of role-physical, vitality, mental health, and health change, showing statistically significant differences, and the treatment group is superior to the control group (see Table 5).

[0116] (6) Safety indicators: Before treatment, P>0.05 for both groups in terms of safety indicators, indicating no statistically significant difference and comparability; before and after treatment, white blood cells, red blood cells, ALT, AST, creatinine, urea nitrogen, and INR were tested, and P>0.05 for each inter-group comparison, indicating no obvious statistically significant differences (see Table 6).

[0117] Table 1.1 Comparison of the average number of palpitations ( times / month)

[0118]

[0119] Table 1.2 Comparison of average palpitations duration ( min / month)

[0120]

[0121] Table 2.1 Analysis of total TCM syndrome scores in two groups of patients before and after treatment

[0122]

[0123] Table 2.2 Comparison of effective rates of TCM syndromes in two groups of patients after treatment

[0124]

[0125] Table 3 Comparison of individual TCM symptoms in two groups of patients after treatment

[0126]

[0127] Table 4 Comparison of 24-hour ambulatory electrocardiogram

[0128]

[0129] Table 5 Comparison of SF-36 scale

[0130]

Claims

1. A traditional Chinese medicine composition for treating atrial fibrillation, characterized in that, it is prepared from the following raw materials by weight: 5-10 parts of Pinellia ternata (processed with ginger), 5-10 parts of Citrus reticulata Blanco, 15-30 parts of Astragalus membranaceus, 5-15 parts of Atractylodes macrocephala Koidz., 5-15 parts of Poria cocos, 3-9 parts of Coptis chinensis Franch., 1-6 parts of Cinnamomum cassia Presl, 9-30 parts of Os Draconis, 9-30 parts of Concha Ostreae, 9-15 parts of Sophora flavescens Ait., 9-30 parts of Artemisia annua L., 3-9 parts of Polygala tenuifolia Willd., 9-15 parts of Ophiopogon japonicus (Thunb.) Ker-Gawl., 9-15 parts of Epimedium brevicornu Maxim., 9-15 parts of Cortex Moutan, 9-15 parts of Ziziphus jujuba Mill.

2. The traditional Chinese medicine composition for treating atrial fibrillation according to claim 1, characterized in that, the weights of the raw materials are respectively: 9 parts of Pinellia ternata (processed with ginger), 9 parts of Citrus reticulata Blanco, 15 parts of Astragalus membranaceus, 9 parts of Atractylodes macrocephala Koidz., 12 parts of Poria cocos, 6 parts of Coptis chinensis Franch., 3 parts of Cinnamomum cassia Presl, 15 parts of Os Draconis, 15 parts of Concha Ostreae, 9 parts of Sophora flavescens Ait., 15 parts of Artemisia annua L., 6 parts of Polygala tenuifolia Willd., 15 parts of Ophiopogon japonicus (Thunb.) Ker-Gawl., 15 parts of Epimedium brevicornu Maxim., 9 parts of Cortex Moutan, 12 parts of Ziziphus jujuba Mill.

3. The traditional Chinese medicine composition for treating atrial fibrillation according to claim 1 or 2, characterized in that, the dosage form of the traditional Chinese medicine composition is a granule prepared by a conventional method.

Images