Traditional Chinese medicine composition for treating paroxysmal atrial fibrillation and preparation method thereof

Abstract

The present invention discloses a traditional Chinese medicine composition for treating paroxysmal atrial fibrillation, comprising 9-15 parts of dalbergia odorifera, 1-5 parts of agarwood, 10-15 parts of salvia miltiorrhiza, 5-10 parts of earthworm, 3-10 parts of cypress seed, 10-25 parts of mother-of-pearl, 9-15 parts of tabulaeformis, 9-30 parts of astragalus, and 3-6 parts of angelica root bark. The present invention has the advantages of being based on the two physiological functions of "the heart governs blood vessels" and "the heart governs the mind," proposing that "poor blood vessels and restless mind" are the core pathogenesis of paroxysmal atrial fibrillation, and basing its prescription and medication on the principle of "harmony between the pulse and the mind." The combined use of multiple herbs synergistically invigorates Qi and blood circulation, quenches wind and calms palpitations, nourishes Yin and tranquilizes the mind, and calms the nerves. This simple yet potent combination effectively reduces the frequency and duration of atrial fibrillation attacks, lowers ventricular rate, atrial fibrillation symptom grade, and atrial fibrillation burden, improves quality of life, and enhances sleep. Furthermore, it exhibits certain anticoagulant and myocardial contractility effects, effectively preventing complications such as stroke caused by atrial fibrillation thrombosis and heart failure caused by increased cardiac workload. This Chinese medicine composition is highly effective in treating paroxysmal atrial fibrillation, primarily caused by Qi stagnation, blood stasis, and restlessness.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition for treating paroxysmal atrial fibrillation, and in particular to a pharmaceutical composition for treating paroxysmal atrial fibrillation and a preparation method thereof. Background Art

[0002] Paroxysmal atrial fibrillation (POAF) is a common clinical arrhythmia. It is a supraventricular tachyarrhythmia accompanied by uncoordinated atrial electrical activity, resulting in ineffective atrial contraction. It manifests as atrial fibrillation that terminates automatically or by intervention within 7 days. The attack duration is usually ≤48 hours, with the characteristics of sudden onset and cessation and irregular onset. The main symptoms during the attack are palpitations, fatigue, dizziness and dyspnea.

[0003] The first large-scale epidemiological survey of atrial fibrillation in China in 2004 revealed that the overall prevalence of atrial fibrillation in China was 0.77%, and the prevalence of paroxysmal atrial fibrillation was 0.26%. There are numerous risk factors for paroxysmal atrial fibrillation. Increasing age is a significant risk factor, but other comorbidities, including hypertension, diabetes, heart failure, coronary artery disease, chronic kidney disease, hyperthyroidism, hypothyroidism, obesity, and obstructive sleep apnea, also play a significant role in the development and progression of atrial fibrillation. A significant number of patients cannot identify a clear cause and are therefore classified as having idiopathic paroxysmal atrial fibrillation. Paroxysmal atrial fibrillation has an insidious clinical onset and is difficult to detect in its early stages. It often recurs due to various triggers. In severe cases, it can cause hemodynamic changes, mural thrombi, stroke, and even fatal cardiac embolism. Atrial fibrillation can also lead to electrical and structural remodeling of the atrial ventricle, causing left atrial enlargement and atrial fibrosis, which can compromise the myocardium, reduce cardiac function, and eventually cause heart failure. Furthermore, atrial fibrillation can lead to cognitive decline, anxiety and depression, decreased quality of life, increased hospitalizations, and even death. Improper treatment and prevention can lead to persistent atrial fibrillation, placing a significant burden on patients and healthcare systems worldwide. These issues urgently need to be addressed, and therefore, the search for new treatments for paroxysmal atrial fibrillation based on Traditional Chinese Medicine (TCM) theory is of great clinical significance.

[0004] Currently, modern medicine lacks a specific treatment for paroxysmal atrial fibrillation. The 2020 ESC / EACTS Guidelines for the Diagnosis and Management of Atrial Fibrillation outline the latest comprehensive management strategies for atrial fibrillation, including stroke prevention / anticoagulant therapy; rhythm control, ventricular rate stabilization, and symptom improvement; and treatment of comorbidities / cardiovascular risk factor management. Anticoagulants include warfarin and the novel oral anticoagulants rivaroxaban and dabigatran etexilate; antiarrhythmic drugs include amiodarone, dronedarone, sotalol, and propafenone hydrochloride; and beta-blockers are commonly used for ventricular rate stabilization. However, oral medications are associated with numerous side effects, including bleeding risk associated with anticoagulants, arrhythmia-induced arrhythmias, and extracardiac toxicity. Beta-blockers can cause atrioventricular conduction block and hypotension. Even with optimized medical therapy, some patients with atrial fibrillation still experience poor clinical control. When oral medications are ineffective, surgical treatment, such as pulmonary vein isolation, radiofrequency catheter ablation, and cryoablation, is often considered. However, non-drug treatments are expensive and have a high recurrence rate. Their use in China is often limited by factors such as patient financial constraints, willingness to accept, and technical challenges. Clinical studies have shown that the recurrence rate for patients with atrial fibrillation is 11% to 29% 1 to 5 years after a single ablation, and 7% to 24% after repeated ablations. The overall success rate of atrial fibrillation ablation in my country is 77.1%, with a recurrence rate of approximately 22.9% and a complication rate of 5.3%. Therefore, in recent years, the search for effective and minimally invasive treatments for paroxysmal atrial fibrillation has become a key focus of Traditional Chinese Medicine research. Summary of the Invention

[0005] To solve the above problems, the present invention provides a traditional Chinese medicine composition and a preparation method thereof, wherein the traditional Chinese medicine composition is used to treat paroxysmal atrial fibrillation.

[0006] A traditional Chinese medicine composition for treating paroxysmal atrial fibrillation, comprising the following components in parts by weight: 9-15 parts of dalbergia odorifera, 1-5 parts of agarwood, 10-15 parts of salvia miltiorrhiza, 5-10 parts of earthworm, 3-10 parts of cypress seeds, 10-25 parts of mother-of-pearl, 9-15 parts of tabulaeformis, 9-30 parts of astragalus, and 3-6 parts of cortex cyperi.

[0007] As a preferred embodiment, the Chinese medicine composition preferably comprises, based on weight parts: 10 parts of Dalbergia odorifera, 3 parts of Aquilaria wood, 15 parts of Salvia miltiorrhiza, 10 parts of Earthworm, 10 parts of Platycladi seed, 25 parts of Mother of Pearl, 10 parts of Pinus tabulaeformis, 30 parts of Raw Astragalus, and 6 parts of Perilla frutescens bark.

[0008] The following are the functions and effects of each component.

[0009] Dalbergia odorifera: Pungent, warm. Enters the heart and liver meridians. It has the effects of promoting blood circulation and dispersing blood stasis, stopping bleeding and relieving pain, eliminating filth and turbidity, and stopping vomiting. It is suitable for chest and flank pain caused by qi stagnation and blood stasis, as well as traumatic injuries, traumatic bleeding, internal obstruction of filth, vomiting and abdominal pain. Modern pharmacological studies have shown that Dalbergia odorifera has antioxidant and anti-myocardial ischemia effects. It reduces myocardial stiffness by reducing the ratio of collagen I / III in the non-infarcted myocardium, thereby improving ventricular remodeling. In addition, Dalbergia odorifera has antithrombotic and antiplatelet effects. Its antiplatelet activity increases with increasing concentration, but its antithrombotic activity is poor.

[0010] Agarwood: Pungent, bitter, and warm. It enters the spleen, stomach, and kidney meridians. It promotes qi circulation and relieves pain, reduces adverse reactions and regulates the middle, warms the kidneys, and absorbs qi. It is suitable for treating cold-induced qi stagnation, chest and abdominal distension and pain, stomach cold and vomiting, hiccups, lower abdominal coldness, asthma due to kidney qi deficiency, as well as cough and asthma caused by phlegm and fluid retention, and symptoms such as upper body fullness and lower body deficiency. Modern pharmacological research indicates that agarwood volatile oil can exert anxiolytic and antidepressant effects by inhibiting overactivity of corticotropin-releasing factor (CRF) and the hypothalamic-pituitary-adrenal (HPA) axis. It also has antioxidant, antimyocardial ischemic, antibacterial, and hypoglycemic properties.

[0011] Salvia miltiorrhiza (Danshen): Bitter and slightly cold, it enters the heart, pericardium, and liver meridians. It promotes blood circulation, dissipates blood stasis, cools blood, eliminates carbuncles, and clears the heart and relieves restlessness. It is suitable for treating palpitations, insomnia, and other symptoms caused by heat generated by blood stasis. Modern pharmacological research indicates that Salvia miltiorrhiza can dilate coronary arteries, increase coronary blood flow, improve microcirculation, resist thrombosis, promote tissue repair and regeneration, and lower blood lipids.

[0012] Earthworms: Salty and cold. They enter the liver, spleen, and bladder meridians. They clear heat and calm wind, relieve asthma, dredge meridians, and promote urination. They are suitable for treating high fever, convulsions, wheezing and phlegm, joint swelling, heat, pain, and difficulty flexing and extending due to heat-related arthralgia, bladder heat accumulation, urinary retention, or urinary obstruction. Modern pharmacological studies have shown that earthworm water extracts can significantly prolong the formation of platelet and fibrin clots and reduce clot length and dry weight. They possess potent anticoagulant and thrombolytic properties, making them highly effective thrombolytic agents.

[0013] Platycodon pine nuts: Sweet in flavor, neutral in nature. It enters the heart, kidney, and large intestine meridians. It nourishes the heart and calms the mind, moistens the intestines and promotes bowel movements, and relieves perspiration. It is suitable for treating Yin-blood deficiency, restlessness and insomnia, palpitations, constipation due to dry intestines, and night sweats due to Yin deficiency. Modern pharmacological research indicates that the volatile oil from Platycodon pine nuts has central nervous system inhibitory, sedative, and hypnotic properties.

[0014] Mother of pearl: Salty and cold in nature. It enters the Liver and Heart meridians. It calms the liver and suppresses yang, brightens the eyes, dispels cataracts, and calms the mind. It is suitable for treating headaches, liver heat, photophobia, dizziness, palpitations, tinnitus, insomnia, epilepsy, and metrorrhagia caused by liver yin deficiency and liver yang hyperactivity. Modern pharmacological research indicates that mother of pearl is rich in trace elements such as calcium, iron, sodium, and potassium, which can inhibit nerve and skeletal muscle excitation. It also has a calming and soothing effect on experimental mice.

[0015] Turpentine: Bitter, warm. Enters the Liver Meridian. It dispels wind and dampness, and relieves pain. It is suitable for rheumatic pain, traumatic injuries, and other conditions. Modern pharmacological research indicates that turpentine has anti-inflammatory and analgesic properties.

[0016] Astragalus: Sweet and slightly warm. It enters the spleen and lung meridians. It has the effects of tonifying qi and raising yang, strengthening the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid production and nourishing blood, relieving stagnation and relieving numbness, expelling toxins and draining pus, and healing sores and promoting tissue regeneration. It is suitable for spleen qi deficiency, lung qi deficiency, spontaneous perspiration due to exterior deficiency, edema caused by qi deficiency, sallow complexion due to blood deficiency, thirst, hemiplegia, pain and numbness. Modern pharmacological studies have shown that the astragalosides contained in Astragalus can effectively improve cardiac function and reverse ventricular remodeling in rats with heart failure.

[0017] Perennial Cortex: Pungent, bitter, warm; toxic. It enters the Liver, Kidney, and Heart meridians. It promotes diuresis, reduces swelling, dispels rheumatism, and strengthens bones and muscles. It is effective for treating edema, dysuria, pain caused by wind-cold-dampness, and soreness of the waist and knees. Modern pharmacological research indicates that Perennial Cortex contains cardiac glycosides with effects similar to digoxin, potentially improving cardiac ejection fraction.

[0018] The Chinese medicine composition of the present invention can also be added with pharmaceutically acceptable excipients to prepare conventional pharmaceutical preparations, wherein the excipients include disintegrants, lubricants, adhesives, etc., and the conventional pharmaceutical preparations preferably include oral preparations; wherein, oral preparations include decoctions, pills, powders, pastes, capsules or tablets, etc.

[0019] Another object of the present invention is to provide two methods for preparing a Chinese medicine composition for treating paroxysmal atrial fibrillation. The preparation of the decoction comprises the following steps:

[0020] (1) Weigh each Chinese medicine component according to the weight ratio;

[0021] (2) Mix the above Chinese herbal medicine components and place them in a container, add water to cover the surface of the medicine, and soak for 20 to 30 minutes;

[0022] (3) Cook until boiling and then continue to cook for 20 to 30 minutes, for a total of three times;

[0023] (4) Combine the three decoctions and filter them to obtain a decoction.

[0024] The preparation of granules includes the following steps:

[0025] (1) taking each Chinese medicinal component according to the stated weight portion;

[0026] (2) boiling the above Chinese herbal medicine components in a sealed container, adding 6 to 10 times the amount of water, boiling, and keeping warm at 80 to 95° C. for 25 to 45 minutes to obtain a decoction;

[0027] (3) Add 4 to 8 times the amount of water, boil, and keep warm at 80 to 95°C for 15 to 25 minutes to obtain the second decoction;

[0028] (4) combining the two decoctions, filtering, and concentrating under reduced pressure to form a paste;

[0029] (5) Add conventional excipients to prepare granules.

[0030] Advantages of the present invention:

[0031] 1. Based on the theories that "the heart governs blood vessels" and "the heart governs the mind," as well as the "harmonious blood vessels allow the mind to reside," as stated in the "Inner Canon of Medicine," the core pathogenesis of paroxysmal atrial fibrillation is proposed to be a dysfunctional blood vessel and a restless mind. "Pulse-mind harmony" is the basis for the diagnosis and treatment of paroxysmal atrial fibrillation. The heart houses the mind, and the mind is the heart's messenger. Patients with paroxysmal atrial fibrillation often experience episodes of stress, anxiety, or alcohol consumption. These mental activities fall under the purview of the mind and are evidence of a lack of mind control and dysfunction. The pulse is a tangible medium that supports vital activity. Arrhythmia and short pulses are common clinical manifestations of atrial fibrillation, caused by qi stagnation and blood stasis blocking the meridians, leading to impaired circulation. Pulse-regulating treatment of paroxysmal atrial fibrillation primarily focuses on regulating qi and activating blood circulation, which can both dispel tangible pathogens and regulate the meridians and replenish blood. Treating patients with paroxysmal atrial fibrillation from a mind-regulating perspective primarily focuses on calming the mind.

[0032] 2. A real-world study based on the "Pulse and Spirit Harmony" treatment method found that the total clinical efficacy of Dingchan Granules in the treatment of paroxysmal atrial fibrillation reached 90.67%, which can significantly reduce the number and duration of atrial fibrillation attacks in patients, lower the ventricular rate, reduce the atrial fibrillation symptom grade and atrial fibrillation burden, improve the quality of life, and improve sleep conditions, and the differences are statistically significant (P < 0.01); the total clinical efficacy of Dingchan Granules combined with Western medicine in the treatment of paroxysmal atrial fibrillation is 83.72%, which can reduce the frequency and duration of atrial fibrillation attacks in patients (P < 0.05) and lower the ventricular rate, but there is no statistical difference (P > 0.05).

[0033] 3. In cell experiments, Dingchan Granules' ethanol extract was administered to stably expressing HEK293 or CHO cell lines, and ion channel changes were recorded using membrane patch technology. The results showed that it had a tendency to inhibit the IKr channel, with an inhibition rate of 66.51%±3.07%, and had a strong enhancing effect on the IKs channel, with an enhancement rate of 199.28%±4.15%. This indicates that Dingchan Granules can exert an anti-arrhythmic effect by inhibiting the hERG channel and avoid the side effect of other antiarrhythmic drugs that prolong the QT interval. DETAILED DESCRIPTION

[0034] The present invention will be described in further detail below with reference to specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, these embodiments are merely exemplary and do not constitute any limitation to the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solutions of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, and such modifications and replacements fall within the scope of protection of the present invention.

[0035] Example 1

[0036] 10 grams of Dalbergia odorifera, 3 grams of Aquilaria wood, 15 grams of Salvia miltiorrhiza, 10 grams of earthworm, 10 grams of pine nut kernel, 25 grams of mother of pearl, 10 grams of Chinese pine knot, 30 grams of raw Astragalus membranaceus, and 6 grams of Cyperus rotundus bark.

[0037] Mix the above raw medicines together, put them in a casserole, add water to cover the surface of the medicine, soak for 20 to 30 minutes, then simmer with low heat, continue to simmer for 30 minutes after boiling, and simmer three times in total. Combine the three decoctions and filter to obtain a decoction. Instructions for use: Decoction, one dose per day, decocted with water, once in the morning and evening, 28 days as a course of treatment; Mix the above raw medicines in a sealed container and boil twice, add 6 to 10 times the amount of water the first time, boil and keep warm at 80 to 95°C for 25 to 45 minutes to obtain a decoction, add 4 to 8 times the amount of water the second time, boil and keep warm at 80 to 95°C for 15 to 25 minutes to obtain a second decoction, combine the two decoctions, filter, and concentrate under reduced pressure into a paste, and add conventional excipients to make granules. Instructions for use: Granules, one dose per day, taken with water, once in the morning and evening, 28 days as a course of treatment;

[0038] Example 2

[0039] 9 grams of agarwood, 2 grams of agarwood, 15 grams of salvia miltiorrhiza, 10 grams of earthworm, 9 grams of pine nuts, 25 grams of mother of pearl, 10 grams of pine knots, 30 grams of raw astragalus, and 6 grams of Cyperus rotundus.

[0040] The preparation and administration method is the same as in Example 1.

[0041] Example 3

[0042] 9 grams of agarwood, 2 grams of agarwood, 10 grams of salvia miltiorrhiza, 10 grams of earthworm, 9 grams of pine nuts, 20 grams of mother of pearl, 10 grams of pine knots, 25 grams of raw astragalus, and 6 grams of Cyperus rotundus.

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

[0044] Example 4

[0045] 10 grams of Dalbergia odorifera, 1 gram of Aquilaria wood, 15 grams of Salvia miltiorrhiza, 6 grams of earthworm, 10 grams of pine nuts, 25 grams of mother of pearl, 10 grams of Chinese pine knot, 25 grams of raw Astragalus, and 6 grams of Cyperus rotundus bark.

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

[0047] Example 5

[0048] 9 grams of agarwood, 2 grams of agarwood, 15 grams of salvia miltiorrhiza, 10 grams of earthworm, 9 grams of pine nuts, 25 grams of mother of pearl, 10 grams of pine knots, 30 grams of raw astragalus, and 6 grams of Cyperus rotundus.

[0049] The preparation and administration method is the same as in Example 1.

[0050] Example 6

[0051] 10 grams of Dalbergia odorifera, 3 grams of Aquilaria wood, 10 grams of Salvia miltiorrhiza, 6 grams of earthworm, 10 grams of cypress seed, 20 grams of mother of pearl, 9 grams of Chinese pine knot, 20 grams of raw Astragalus, and 3 grams of Cyperus rotundus bark.

[0052] The preparation and administration method is the same as in Example 1.

[0053] Example 7

[0054] 6 grams of Dalbergia odorifera, 5 grams of Aquilaria wood, 10 grams of Salvia miltiorrhiza, 10 grams of earthworm, 10 grams of pine nuts, 25 grams of mother of pearl, 10 grams of Chinese pine knot, 30 grams of raw Astragalus, and 6 grams of Cyperus rotundus bark.

[0055] The preparation and administration method is the same as in Example 1.

[0056] Example 8

[0057] 9 grams of Dalbergia odorifera, 1 gram of Aquilaria wood, 15 grams of Salvia miltiorrhiza, 6 grams of earthworm, 3 grams of pine nuts, 15 grams of mother-of-pearl, 15 grams of Chinese pine knots, 15 grams of raw Astragalus, and 3 grams of Cyperus rotundus bark.

[0058] The preparation and administration method is the same as in Example 1.

[0059] Example 9

[0060] 15 grams of agarwood, 5 grams of agarwood, 15 grams of salvia miltiorrhiza, 10 grams of earthworm, 10 grams of pine nuts, 25 grams of mother of pearl, 15 grams of pine knots, 30 grams of raw astragalus, and 3 grams of Cyperus rotundus bark.

[0061] The preparation and administration method is the same as in Example 1.

[0062] Example 10

[0063] 15 grams of agarwood, 3 grams of agarwood, 10 grams of salvia miltiorrhiza, 6 grams of earthworm, 10 grams of pine nuts, 20 grams of mother of pearl, 15 grams of pine knots, 20 grams of raw astragalus, and 6 grams of Cyperus rotundus bark.

[0064] The powder comprises the following steps:

[0065] (1) Mixing the above raw materials together;

[0066] (2) Grind the above-mentioned Chinese medicinal components after drying, and the medicinal powder is preferably 60-100 mesh;

[0067] (3) Packaging the drug powder to obtain a powder.

[0068] Example 11

[0069] 15 grams of agarwood, 5 grams of agarwood, 15 grams of salvia miltiorrhiza, 5 grams of earthworm, 9 grams of pine nuts, 15 grams of mother of pearl, 12 grams of pine knots, 12 grams of raw astragalus, and 3 grams of Cyperus rotundus bark.

[0070] The water pill preparation includes the following steps:

[0071] (1) Mixing the above raw materials together;

[0072] (2) Grind the above-mentioned Chinese medicinal components after drying, and the medicinal powder is preferably 60-100 mesh;

[0073] (3) Add appropriate amount of water to the drug powder;

[0074] (4) After mixing, the mixture is formed manually or by machine to obtain water pills.

[0075] Example 12

[0076] 15 grams of agarwood, 1 gram of agarwood, 15 grams of salvia miltiorrhiza, 6 grams of earthworm, 10 grams of pine nuts, 15 grams of mother of pearl, 10 grams of pine knots, 25 grams of raw astragalus, and 6 grams of Cyperus rotundus bark.

[0077] The paste pill preparation comprises the following steps:

[0078] (1) Mixing the above raw materials together;

[0079] (2) Grind the above-mentioned Chinese medicinal components after drying, and the medicinal powder is preferably 60-100 mesh;

[0080] (3) Add appropriate amount of starch paste or rice paste to the drug powder;

[0081] (4) After mixing, shape the mixture manually or by machine to obtain paste pills.

[0082] Example 13

[0083] 9 grams of Dalbergia odorifera, 5 grams of Aquilaria wood, 12 grams of Salvia miltiorrhiza, 6 grams of earthworm, 6 grams of pine nut kernel, 25 grams of mother-of-pearl, 12 grams of Pinus tabulaeformis, 20 grams of raw Astragalus, and 3 grams of Cyperus rotundus bark.

[0084] The capsule preparation comprises the following steps:

[0085] (1) Mixing the above raw materials together;

[0086] (2) Grind the above-mentioned Chinese medicinal components after drying, and the medicinal powder is preferably 80-100 mesh;

[0087] (3) granulating the drug powder and drying it;

[0088] (4) The granules are filled into capsules by a machine to obtain capsules.

[0089] Example 14

[0090] 9 grams of Dalbergia odorifera, 2 grams of Aquilaria wood, 12 grams of Salvia miltiorrhiza, 8 grams of earthworm, 8 grams of cypress seed, 20 grams of mother of pearl, 15 grams of Chinese pine knot, 30 grams of raw Astragalus, and 3 grams of Cyperus rotundus bark.

[0091] The honey pill process includes the following steps:

[0092] (1) Mixing the above raw materials together;

[0093] (2) Grind the above-mentioned Chinese medicinal components after drying, and the medicinal powder is preferably 60-100 mesh;

[0094] (3) Weigh honey with the weight of the medicinal powder in a ratio of 1:1 to 1.5, and boil the honey until it becomes medium-melted;

[0095] (4) After mixing the medicinal powder and the medium honey, shape them manually or by machine to obtain honey pills.

[0096] Example 15

[0097] 9 grams of Dalbergia odorifera, 5 grams of Aquilaria wood, 10 grams of Salvia miltiorrhiza, 6 grams of earthworm, 5 grams of cypress seed, 20 grams of mother-of-pearl, 15 grams of Pinus tabulaeformis, 25 grams of raw Astragalus, and 3 grams of Cyperus rotundus.

[0098] The paste recipe includes the following steps:

[0099] (1) Mix the above raw materials together, chop into appropriate pieces, segments or grind into coarse powder;

[0100] (2) Mix the above-mentioned Chinese medicinal components and place them in a decoction vessel, add water to moisten for 1 to 2 hours, then add water and decoct for 2 to 5 hours, remove the decoction and filter it with a suitable filter to obtain a filtrate;

[0101] (3) Add water to the residue and continue to boil until the decoction has a faint smell. Remove the decoction and set aside.

[0102] (4) The residue is squeezed, and the squeezed liquid is mixed with the entire decoction, left to stand for 1 to 2 hours, and filtered through a suitable filter;

[0103] (5) Take the above filtrate, place it in a suitable evaporator, and concentrate it into a thick paste to obtain a clear paste;

[0104] (6) Take honey of equal weight or multiple weight as that of the clear paste and add it to the clear paste to obtain the paste formula;

[0105] (7) Place in a sterile container and seal.

[0106] Clinical efficacy trials

[0107] To demonstrate the efficacy of the Chinese herbal composition of the present invention, a study was conducted using the Chinese herbal composition in combination with Western medicine to investigate its efficacy in patients with paroxysmal atrial fibrillation, including frequency, duration, ventricular rate, symptom classification, and atrial fibrillation burden. The results showed that the Chinese herbal composition had a total clinical efficacy of 90.67% in treating paroxysmal atrial fibrillation, significantly reduced ventricular rate (P < 0.01), atrial fibrillation symptom classification, and atrial fibrillation burden (P < 0.01), improved quality of life (P < 0.01), and improved sleep quality (P < 0.01), while exhibiting good clinical safety.

[0108] 1. Case selection: 75 patients with paroxysmal atrial fibrillation who visited the outpatient department of the Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences for a long time from June 2021 to March 2022 were included.

[0109] 2. Diagnostic criteria:

[0110] ※Western medicine diagnostic standards: formulated with reference to the relevant standards for paroxysmal atrial fibrillation in the "2020 ESC / EACTS Guidelines for the Diagnosis and Management of Atrial Fibrillation".

[0111] ※ Traditional Chinese Medicine Diagnostic Standards: Developed with reference to the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases" promulgated by the State Administration of Traditional Chinese Medicine in 1994 and the "Guiding Principles for Clinical Research of New Chinese Medicines" promulgated in 1995.

[0112] 3. Inclusion criteria: (1) Both male and female, aged 25 to 90 years; (2) Meet the above-mentioned diagnostic criteria for paroxysmal atrial fibrillation in both Chinese and Western medicine; (3) Have not received traditional Chinese medicine treatment or have discontinued traditional Chinese medicine treatment for more than one month before the start of the study; (4) Atrial fibrillation symptom grading score (EHRA) < 4 points; (5) Continuous follow-up time in the outpatient clinic for ≥ 2 months; (6) Agree and sign the informed consent form.

[0113] 4. Exclusion criteria: (1) Pregnant and lactating women; (2) Left atrial thrombus; (3) Patients with combined tachycardia syndrome; (4) Paroxysmal atrial fibrillation caused by valvular disease; (5) Paroxysmal atrial fibrillation caused by hyperthyroidism or hypothyroidism; (6) Paroxysmal atrial fibrillation caused by electrolyte imbalance or drugs; (7) Severe heart failure (NYHA grade III-IV); (8) Patients with combined severe liver and kidney dysfunction, as well as other organ damage; (9) Patients with incomplete medical records.

[0114] 5. Treatment Plan: Patients will receive both traditional Chinese and Western medicine based on their age, condition, severity, comorbidities, constitution, willingness, and the anticoagulation score (CHA2DS2-VASc). The traditional Chinese medicine composition of this invention will be added to Western medication for an 8-week treatment cycle. Western medication should include anticoagulants, beta-blockers, non-dihydropyridine calcium channel blockers, or digoxin according to the 2020 ESC / EACTS Guidelines for the Diagnosis and Management of Atrial Fibrillation. During the observation period, patients with other comorbidities should continue to take relevant Western medications.

[0115] 6. Observation indicators and methods:

[0116] The main efficacy indicators were: frequency and duration of atrial fibrillation; the secondary efficacy indicators were: ventricular rate, atrial fibrillation burden, symptom grade, life scale, sleep scale; and safety indicators.

[0117] 6.1 Frequency and duration of atrial fibrillation

[0118] Follow-up visits were conducted weekly during the first month of treatment and every two weeks during the second month. The frequency and duration of atrial fibrillation attacks were recorded. The severity of arrhythmia attacks was determined according to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines": ① Occasional: 1-2 attacks per month, each attack <1 hour, resolving with rest; ② Multiple: >2 attacks per month, each attack ≥1 hour but <24 hours, or requiring medication control; ③ Frequent: daily, brief, multiple attacks, or ≥1 attack per week, each attack ≥24 hours, or requiring medication control.

[0119] 6.2 Ventricular Rate

[0120] Before and after treatment, the two groups of patients underwent 12-lead electrocardiogram or dynamic electrocardiogram to record the patients' resting ventricular rate.

[0121] 6.3 Atrial Fibrillation Burden

[0122] Atrial fibrillation burden was calculated as follows: total duration of atrial fibrillation during the statistical period / total duration of the statistical period × 100%. A higher value indicates a heavier atrial fibrillation burden. Both groups were statistically analyzed once before and after treatment.

[0123] 6.4 Atrial Fibrillation Symptom Classification

[0124] The European Heart Rhythm Association (EHRA) Atrial Fibrillation Symptom Scale (AF Symptom Scale) assesses the impact of common AF-related symptoms (palpitations, fatigue, dizziness, dyspnea, chest pain, and anxiety) on patients' daily activities. The scale is divided into: Grade 1 (none): AF causes no symptoms; Grade 2a (mild): AF symptoms do not affect daily activities; Grade 2b (moderate): AF symptoms do not affect daily activities, but the patient is bothered by the symptoms; Grade 3 (severe): AF symptoms affect daily activities; and Grade 4 (disabling): AF symptoms have stopped daily activities. Both groups were evaluated once before and after treatment.

[0125] 6.5 Atrial Fibrillation-Specific Quality of Life Assessment Scale

[0126] Patients were asked to complete an atrial fibrillation scale assessment based on their actual conditions within one month and the impact of atrial fibrillation on their ability to perform daily activities, with evaluations conducted once before and after treatment.

[0127] 6.6 Pittsburgh Sleep Quality Index

[0128] A scale was used to evaluate the patient's sleep time and sleep quality in the past month, with evaluations conducted once before and after treatment.

[0129] 6.7 Safety Indicators

[0130] The patients' blood, urine, stool routine, liver and kidney function, and coagulation function were observed before and after treatment, and the occurrence of adverse events was recorded.

[0131] 7. Statistical analysis: All experimental data were sorted and statistically processed using SPSS 26.0 software.

[0132] 8. Results:

[0133] 8.1 Frequency and Duration of Atrial Fibrillation

[0134] Table 1. Comparison of frequency and duration of atrial fibrillation before and after treatment

[0135]

[0136] Note: According to the rank sum test, compared with week 0, P < 0.01, there is a significant difference.

[0137] In terms of the frequency and duration of atrial fibrillation: after treatment, the median frequency of atrial fibrillation decreased from 7 times / month to 1.5 times / month. Compared with week 0, the rank sum test showed a significant statistical difference of P < 0.01. Before and after treatment, the median duration of atrial fibrillation was 7.25h / month and 1h / month, respectively. The rank sum test showed that the difference was statistically significant (P < 0.01).

[0138] 8.2 Clinical Efficacy

[0139] After treatment with this Chinese medicine composition, the total clinical efficacy rate was 90.67%, including 17 cases of clinical recovery, with a cure rate of 22.67%, 18 cases of marked effect, with a marked efficacy rate of 24.00%, 33 cases of effectiveness, with an efficacy rate of 44.00%, 7 cases of ineffectiveness, with an inefficiency rate of 9.33%.

[0140] Table 2. Clinical efficacy [cases (%)]

[0141]

[0142] 8.3 Comparison of Ventricular Rate

[0143] Table 3. Comparison of ventricular rate before and after treatment

[0144]

[0145] Note: Paired t-test showed significant difference compared with week 0, P < 0.01.

[0146] From the perspective of resting ventricular rate: the ventricular rates before and after treatment were 74.09±11.95 beats / min and 68.09±6.81 beats / min, respectively. Compared with the 0-week group, the paired t-test showed that P<0.01 was statistically significant.

[0147] 8.4 Atrial Fibrillation Burden

[0148] Table 4. Atrial fibrillation burden values ​​before and after treatment

[0149]

[0150] Note: According to the rank sum test, P < 0.01, there is a significant difference.

[0151] In terms of atrial fibrillation burden, the median values ​​before and after treatment were 1.01% and 0.14%, respectively. The rank sum test showed that P < 0.01, which was a significant difference.

[0152] 8.5 Atrial Fibrillation-Specific Quality of Life Assessment Scale

[0153] Table 5. Atrial Fibrillation Quality of Life Scale Scores before and after treatment

[0154]

[0155] Note: According to paired t-test, P < 0.01 indicates significant difference.

[0156] A total of 150 atrial fibrillation-specific quality of life assessment scale questionnaires were distributed before and after treatment, 145 questionnaires were collected, 145 valid questionnaires, and 72 valid persons. The scale scores before and after treatment were 62.23±17.10 points and 81.26±10.28 points, respectively. The paired t-test showed that the difference was statistically significant (P<0.01).

[0157] 8.6 Pittsburgh Sleep Quality Index

[0158] Table 6. Sleep quality index before and after treatment

[0159]

[0160] Note: According to the rank sum test, P < 0.01 indicates a significant statistical difference.

[0161] A total of 150 Pittsburgh Sleep Quality Scale questionnaires were distributed before and after treatment, 140 questionnaires were collected, 140 valid questionnaires, and 70 valid persons. The median scores of the scale before and after treatment were 8 points and 4 points respectively. The rank sum test showed that P < 0.01, which was a significant difference.

[0162] 8.7 Safety Assessment

[0163] One patient developed abdominal distension and diarrhea after taking traditional Chinese medicine, which resolved after adjusting the dosage. Two patients developed hypotension and bradycardia after taking beta-blockers during atrial fibrillation. One patient developed thyroid disease after long-term amiodarone use. No bleeding tendency or symptoms developed while taking anticoagulants and receiving traditional Chinese medicine. No other significant adverse reactions were observed.

[0164] Clinical trials have shown that this Chinese medicine composition can effectively reduce the frequency and duration of atrial fibrillation attacks in patients, reduce ventricular rate, atrial fibrillation symptom grade, and atrial fibrillation load, improve quality of life, improve sleep conditions, and has certain anti-coagulation and myocardial contractility enhancing effects. It can effectively avoid complications such as stroke caused by atrial fibrillation thrombosis and heart failure caused by increased cardiac load, and has good safety.

[0165] Case

[0166] Case 1

[0167] Mr. Zhang, male, 45 years old, came to the hospital for treatment in October 2022 due to "intermittent palpitations for more than 13 years, aggravated for 1 month". 13 years ago, he had palpitations without obvious causes. He went to the local hospital for a checkup and the electrocardiogram showed "paroxysmal tachycardia". He was given drug treatment (specific details unknown), and the palpitation symptoms appeared intermittently. In 2020, the palpitation symptoms worsened and occurred frequently every day. He was diagnosed with "paroxysmal atrial fibrillation" at the local hospital and was treated with sotalol hydrochloride and diltiazem hydrochloride. The palpitation symptoms were relieved compared with before. One month ago, the patient's palpitation symptoms worsened again without obvious causes. He now seeks further traditional Chinese medicine treatment and comes to our department for treatment. Current symptoms: frequent attacks of palpitations, 3-4 times / week, each lasting 1 to 2 hours, chest tightness, accompanied by dull pain and distension in the precordial area, occasional dizziness, bad mood, distension and pain in both sides, good appetite, easy to get nervous, poor sleep, shallow sleep and easy awakening, and regular bowel movements. The tongue is dark red, with a thin white fur and a stringy pulse. Echocardiogram shows: left atrial diameter (LA) 58mm. Holter monitoring: atrial fibrillation, heart rate (HRav) 93 beats / min, heart rate variability (SDNN): 89ms. The patient was given the Chinese medicine composition of the present invention: 10g of Dalbergia odorifera, 3g of Aquilaria sinensis, 15g of Salvia miltiorrhiza, 10g of Earthworm, 10g of Platycladus orientalis, 10g of Pinus tabulaeformis, 30g of Mother of Pearl (pre-decocted), 30g of Astragalus, 6g of Perennial Herb, etc. One dose per day, decocted in water and taken orally, one portion each morning and evening. After taking the medicine for 3 months, the patient's above symptoms were reduced, the condition was stable, and there was no obvious discomfort. Auxiliary examinations: LA: 32mm, HRav: 67 beats / min, SDNN: 137ms.

[0168] Case 2

[0169] Mr. Liu, a 73-year-old male, was admitted to the hospital in June 2022 due to "intermittent attacks of palpitations for more than 15 years." 15 years ago, the patient experienced palpitations after exertion and was admitted to Shijingshan Hospital. He was diagnosed with "paroxysmal atrial fibrillation." His symptoms were relieved after infusion and cardioversion. He was given 12.5mg of bisoprolol twice a day to control his heart rate. Since then, he has had intermittent attacks of palpitations. In April 2020, due to frequent attacks of palpitations, he underwent radiofrequency ablation at Anzhen Hospital. After the operation, he was given 150mg of dabigatran etexilate twice a day and 0.2g of cordarone three times a day, which were discontinued after three months of use. His palpitations were intermittent, and the symptoms were relieved after rest or taking Wenxin Granules / Propionate. He now seeks further treatment with traditional Chinese medicine and is seeking treatment in our outpatient department. Current symptoms: intermittent palpitations, 2-3 times per week, each lasting 30 minutes to 1 hour, fatigue, shortness of breath, dull chest pain, a feeling of fullness and fullness below the heart, easy sweating, irritability, sullen complexion, good appetite, insomnia, difficulty falling asleep, and regular bowel movements. A dark tongue with a thin white fur coating, a stringy and slippery pulse, and an irregular rhythm. Echocardiography revealed a left atrial diameter (LA) of 32 mm. Holter monitoring revealed a heart rate (HRav) of 87 beats / min and a heart rate variability (SDNN) of 78 ms. The patient was given a Chinese herbal composition of the present invention: 30 g of raw Astragalus, 15 g of Salvia miltiorrhiza, 10 g of Dalbergia odorifera, 10 g of Pinus tabulaeformis, 15 g of stir-fried Semen Ziziphi Spinosae, 25 g of Mother of Pearl (pre-decocted), 10 g of Cuttlebone (pre-decocted), 15 g of calcined Cortex Corrugatede (pre-decocted), 6 g of Perennial Cortex, and 15 g of Acorus calamus. After taking the medicine for more than two months, the patient's symptoms were basically relieved and the condition was stable. Auxiliary examinations: echocardiogram showed: LA: 31mm, HRav: 68 beats / min; SDNN: 154ms.

[0170] Case 3

[0171] Kang, male, 68 years old, came to the hospital for treatment in August 2022 due to "intermittent palpitations for 3 years, aggravated for 2 weeks". Three years ago, the patient developed palpitations and discomfort after being angry, and was treated in the Aerospace General Hospital. He was diagnosed with "ventricular tachycardia and paroxysmal atrial fibrillation". After symptomatic treatment, the patient's symptoms were relieved and he was discharged from the hospital, taking medication regularly (specific details unknown). In May 2021, the patient underwent radiofrequency ablation at Anzhen Hospital due to palpitations. The electrocardiogram review in May 2022 showed "paroxysmal atrial fibrillation". He now comes to our outpatient department for further treatment with traditional Chinese medicine. Two weeks ago, there was no obvious cause for the aggravation of palpitations, accompanied by chest tightness and shortness of breath. He now comes to our outpatient department for further treatment with traditional Chinese medicine. Current symptoms: palpitations, 1-2 times / month, each lasting 20 minutes to 2 hours, dull pain and discomfort in the precordial area and back, fatigue, spontaneous perspiration, purple lips and nails, good appetite, difficulty falling asleep, frequent dreams, normal urination, formed stools, once / day. The tongue was pale purple with petechiae, the tongue coating was thick and greasy white, and the pulse was deep and stringy. Echocardiography showed a left atrial diameter (LA) of 45 mm. Holter monitoring revealed a heart rate (HRav) of 73 beats / min and a heart rate variability (SDNN) of 67 ms. The patient was given a Chinese herbal composition of the present invention: 10g of Dalbergia odorifera, 3g of Aquilaria sinensis, 10g of Earthworm, 15g of Salvia miltiorrhiza, 10g of Pinus tabulaeformis, 10g of Platycladus orientalis seeds, 30g of Mother of Pearl (pre-decocted), 6g of Perennial Cortex, 30g of Astragalus, 10g of Acorus calamus, and 15g of Curcuma aromatica. After taking the medicine for more than 21 days, the patient's symptoms were significantly relieved and all symptoms stabilized. Auxiliary examinations: Echocardiography showed: LA: 38 mm. Holter monitoring: heart rate (HRav): 65 beats / min, heart rate variability (SDNN): 89.

[0172] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the basic principles of the present invention, and such improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating paroxysmal atrial fibrillation, characterized in that The traditional Chinese medicine composition is composed of the following components in parts by weight: 9-15 parts of dalbergia odorifera, 1-5 parts of agarwood, 10-15 parts of salvia miltiorrhiza, 5-10 parts of earthworm, 3-10 parts of cypress seeds, 10-25 parts of mother-of-pearl, 9-15 parts of tabulaeformis, 9-30 parts of astragalus, and 3-6 parts of perilla bark.

2. The Chinese medicine composition according to claim 1, characterized in that The present invention comprises 10 parts of dalbergia wood, 3 parts of agarwood, 15 parts of salvia miltiorrhiza, 10 parts of earthworm, 10 parts of cypress seed, 25 parts of pearl mother, 10 parts of tabulaeformis, 30 parts of astragalus and 6 parts of angelica root bark.

3. Use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for treating paroxysmal atrial fibrillation.

4. The Chinese medicine composition according to claim 1 or 2, characterized in that Pharmaceutically acceptable excipients can also be added to prepare conventional pharmaceutical preparations.

5. A method for preparing the Chinese medicine composition according to claim 1 or 2, characterized in that The steps include: (1) Weigh each Chinese medicine component according to the weight ratio; (2) Mix the above Chinese herbal medicine components and place them in a container, add water to cover the surface of the medicine, and soak for 20 to 30 minutes; (3) Cook over low heat until boiling and then continue to cook for 20 to 30 minutes, three times in total; (4) Combine the three decoctions and filter them to obtain a decoction.

6. A method for preparing the Chinese medicine composition according to claim 1 or 2, characterized in that The steps include: (1) taking each Chinese medicinal component according to the stated weight portion; (2) boiling the above Chinese herbal medicine components in a sealed container, adding 6 to 10 times the amount of water, boiling, and keeping warm at 80 to 95° C. for 25 to 45 minutes to obtain a decoction; (3) Add 4 to 8 times the amount of water, boil, and keep warm at 80 to 95°C for 15 to 25 minutes to obtain the second decoction; (4) combining the two decoctions, filtering, and concentrating under reduced pressure to form a paste; (5) Add conventional excipients to prepare granules.

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